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IJCP Group of Publications Volume 28, Number 4, September 2017

Dr Sanjiv Chopra Group Consultant Editor

FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

305 AES Update: This is Not the Time for a “Blame Game” Dr Deepak Chopra Chief Editorial Advisor

KK Aggarwal

AMERICAN FAMILY PHYSICIAN

Dr KK Aggarwal Padma Shri Awardee Group Editor-in-Chief Dr Veena Aggarwal Group Executive Editor

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani, Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das, Dr A Ramachandran, Dr Samith A Shetty, Dr Vijay Viswanathan, Dr V Mohan, Dr V Seshiah, Dr Vijayakumar ENT Dr Jasveer Singh, Dr Chanchal Pal Dentistry Dr KMK Masthan, Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar, Dr Rajiv Khosla, Dr JS Rajkumar Dermatology Dr Hasmukh J Shroff, Dr Pasricha, Dr Koushik Lahiri, Dr Jayakar Thomas Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan, Dr Vineet Suri, Dr AV Srinivasan Oncology Dr V Shanta Orthopedics Dr J Maheshwari

Anand Gopal Bhatnagar Editorial Anchor

307 Lower Extremity Abnormalities in Children

316 Practice Guidelines 317 Photo Quiz CARDIOLOGY

321 Familial Hypercholesterolemia, a Widely Underdiagnosed and Undertreated Clinical Entity: The Physician Perspective

Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

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Harpreet Singh, Deepak Jain, Kiran B, Ruchi Jagota

COMMUNITY MEDICINE

325 Research and Publication: How is It Relevant in Today’s World?

Amar Ranjan, Iffat Jamal, Divya Sethi, Lawanya Ranjan, Meenakshi Wadhwani

DERMATOLOGY

327 Fine Needle Aspiration Cytology of Nodular Hidradenoma Presenting at an Unusual Site

Annu Nanda, Sangeeta Lamba, Divya Sethi

ENT

331 An Observational Study to Evaluate the Efficacy, Safety and Tolerability of Amoxicillin/Clavulanic Acid in Patients with Otitis Media: BEST Study

Manjula S, Krishna Kumar M

336 Septoplasty with Adenoidectomy: A Combined Procedure for Nasal Obstruction in Children

K Mallikarjuna Swamy, KP Basavaraju

INTERNAL MEDICINE

340 Incompatibility to All Blood Groups Due to Autoimmune Hemolytic Anemia in a Case of Antiphospholipid Syndrome

Advisory Bodies Heart Care Foundation of India

Caitlyn M. Rerucha, Caleb Dickison, Drew C. Baird

Tuhina Parveen Sarwala, Manish N Mehta, Ajay C Tanna, Jemima Bhaskar, Pratik K Patel

342 A Study of Antinuclear Antibodies Profile in Clinical Cases of Systemic Lupus Erythematosus

Nitish Patwardhan, Manish N Mehta, Hemang Acharya, Ajay C Tanna, Jemima Bhaskar

346 Dangerously Leaking Nose

R Umarani, K Baburaj, J Sangeetha, Jino Vincent

NEUROLOGY Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

349 Lance-Adams Syndrome: A Rare Case of Post-hypoxic Myoclonus, Developing After a Snake Bite

Meet M Thacker, Manish N Mehta

356 Neonatal Seizures

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OBSTETRICS AND GYNECOLOGY

Copyright 2017 IJCP Publications Ltd. All rights reserved.

360 Bilateral Endometriomas with Deep Infiltrating Endometriosis in Infertility: An Increasing Trend (Case Series)

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Parmjit Kaur, Ruby Bhatia, Aman Dev, Santosh Kumari

366 Obstetrical and Neonatal Outcome of Pregnancy in Women with Previous One Cesarean Section: A Prospective Study

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EXPERT’S VIEW

372 How are BP Levels and Visceral Adiposity Correlated with Kidney Disease?

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378 ADA-PAMS: Clinical Update in Diabetes-2017 AROUND THE GLOBE

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395 Lighter Side of Medicine

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Dr KK Aggarwal

Padma Shri Awardee Group Editor-in-Chief

AES Update: This is Not the Time for a “Blame Game”

T

he recent tragic deaths of children due to encephalitis in Gorakhpur Medical College have hit the headlines in the last few days. These deaths also generated a lot of debate on the issue. Unfortunately much of the debate centered on “finger pointing”. This is not the time for a “blame game”. This is not the first outbreak of acute encephalitis syndrome (AES) in the region. Many such outbreaks have been occurring for several years now and each epidemic has taken a heavy toll of lives.

By now there should have been a state of the art hospital to manage AES patients. There should have also been a research facility to examine why the area is vulnerable to AES, establish effective surveillance systems, plan a response plan, predict future outbreaks, etc.

This is the time to look to the future and not talk of the past or even the present outbreak. Drawing from the lessons of the past years, we must be able to anticipate such local outbreaks and be ready to respond to them systematically and in a timely manner to contain them. A research center focusing on AES will help to identify early warning signals for such impending outbreaks.

Anticipation and preparedness will enhance efforts to control and prevent future outbreaks of AES. All stakeholders have equally important roles to play in prevention of any epidemic.

SOME KEY POINTS ON AES ÂÂ

Encephalitis is inflammation of the brain parenchyma. It presents clinically as neurologic dysfunction (altered mental status, behavior or personality; motor or sensory deficits; speech or movement disorders; seizure).

ÂÂ

Viruses are the most commonly identified infectious causes of encephalitis. Around 10% cases may be due to Japanese encephalitis, scrub typhus and herpes simplex each. Enterovirus and other viruses also cause AES. Bacteria, fungi and parasites may also cause encephalitis. In many cases of encephalitis, the etiology remains unknown despite extensive evaluation.

ÂÂ

The WHO’s guidelines for JE surveillance recommend syndromic surveillance for JE meaning that all AES cases should be reported (NVBDCP, 2009).

ÂÂ

The NVBDCP 2009 guidelines on management of AES have recommended classification of a suspected case as follows: Laboratory-confirmed JE: A suspected case that has been laboratory-confirmed as JE. Probable JE: A suspected case that occurs in close geographic and temporal relationship to laboratoryconfirmed case of JE, in the context of an outbreak.

Acute encephalitis syndrome (due to agent other than JE): A suspected case in which diagnostic testing is performed and an etiological agent other than JE virus is identified.

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF Acute encephalitis syndrome (due to unknown agent) a suspected case in which no diagnostic testing is performed or in which testing was performed but no etiological agent was identified or in which the test results were indeterminate. ÂÂ

The incidence is highest among infants less than 1 year.

ÂÂ

Status epilepticus, cerebral edema, fluid and electrolyte disturbance and cardiorespiratory failure are some of the complications of AES.

ÂÂ

ICU care is essential for patients with severe encephalitis (i.e., those with seizures, cardiorespiratory compromise, coma or severe neurologic compromise) with close cardiorespiratory monitoring and careful attention to neurologic status, fluid balance and electrolyte status.

ÂÂ

Prognosis of viral encephalitis depends upon the age of the patient, neurologic findings at the time of presentation and the etiopathogen.

ÂÂ

The case fatality and morbidity is very high among various viral encephalitis especially in JE or enterovirus encephalitis.

ÂÂ

Survivors of childhood encephalitis should be monitored for long-term sequelae.

ÂÂ

Scrub typhus encephalitis: Curable with doxycycline or erythromycin if diagnosed early. Look for fever, rash, local black eschar in the legs with enlarged, lymph nodes.

ÂÂ

Japanese encephalitis: Mortality is 20% in the best of the centers. Preventable by vaccination.

ÂÂ

Herpes simplex encephalitis: Can be diagnosed due to temporal lobe localization and can be managed with antivirals.

ÂÂ

Lichi encephalitis is manageable with intravenous glucose.

ÂÂ

Enteroviral encephalitis has limited therapeutic options. Intravenous immunoglobulin is often administered despite a lack of convincing evidence for efficacy.

ÂÂ

All children who present with suspected encephalitis should be treated with acyclovir pending viral studies.

ÂÂ

Empiric treatment for bacterial meningitis pending bacterial cultures also may be warranted if bacterial meningitis cannot be excluded.

ÂÂ

Empiric treatment with doxycycline or erythromycin should be given till scrub typhus is ruled out.

ÂÂ

Prevention strategies include hand hygiene, appropriate management of pregnant women with active herpes simplex virus lesions, routine childhood immunizations, JE vaccine, traveling immunizations and insect control and avoidance measures. Control of culex mosquito.

ÂÂ

All children who are hospitalized with encephalitis should be placed on airborne, droplet and contact precautions at the time of admission, pending identification of a pathogen.

■■■■

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Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

AMERICAN FAMILY PHYSICIAN

Lower Extremity Abnormalities in Children CAITLYN M. RERUCHA, CALEB DICKISON, DREW C. BAIRD

ABSTRACT Leg and foot problems in childhood are common causes of parental concern. Rotational problems include intoeing and outtoeing. Intoeing is most common in infants and young children. Intoeing is caused by metatarsus adductus, internal tibial torsion, and femoral anteversion. Out-toeing is less common than intoeing and occurs more often in older children. Out-toeing is caused by external tibial torsion and femoral retroversion. Angular problems include genu varum (bowleg) and genu valgum (knock knee). With pes planus (flatfoot), the arch of the foot is usually flexible rather than rigid. A history and physical examination that include torsional profile tests and angular measurements are usually sufficient to evaluate patients with lower extremity abnormalities. Most children who present with lower extremity problems have normal rotational and angular findings (i.e., within two standard deviations of the mean). Lower extremity abnormalities that are within normal measurements resolve spontaneously as the child grows. Radiologic studies are not routinely required, except to exclude pathologic conditions.

Orthotics are not beneficial. Orthopedic referral is often not necessary. Rarely, surgery is required in patients older than eight years who have severe deformities that cause dysfunction.

Keywords: Lower extremity abnormalities, childhood, intoeing, out-toeing, angular problems

P

arents commonly seek medical advice because of concerns about the appearance of their child’s lower extremities, feet, or gait.1,2 Most concerns are normal variations of growth and development and are best managed with parental reassurance.1 Common normal variants of the lower extremities in children include rotational problems such as intoeing and outtoeing, angular problems such as genu varum (bowleg) and genu valgum (knock knee), and pes planus (flatfoot).

HISTORY AND PHYSICAL EXAMINATION A comprehensive history and physical examination (Table 13,4 and Table 24-6) are often sufficient to differentiate normal variations in limb development from pathologic abnormalities, without the need for radiography.3-5 For the physical examination, the lower extremities should be fully exposed, and the child may

need to wear shorts, a diaper, underwear, or a gown.4-6 The child’s height and weight with growth percentiles should be reviewed because normal growth reduces the likelihood of systemic conditions.5 The musculoskeletal examination should include evaluation for hip dysplasia, leg length discrepancy, and joint laxity (Figure 15); assessment of passive range of motion and rotational positioning of the lower extremities (i.e., torsional profile); and a gait analysis (Figure 25).

Torsional profile, a key component of the musculoskeletal examination, includes foot progression angle, Table 1. Pertinent History for Children with Lower Extremity Abnormalities Understand parental concerns: gait, function, appearance, duration, and progression Patient history: prenatal and birth history, developmental milestones Family history: complete orthopedic family history of pathologic rotational or angular deformities and interventions required

CAITLYN M. RERUCHA, MD, is a faculty physician at the Carl R. Darnall Army Medical Center Family Medicine Residency, Fort Hood, Tex. CALEB DICKISON, DO, is a faculty physician at the Carl R. Darnall Army Medical Center Family Medicine Residency.

DREW C. BAIRD, MD, is program director of the Carl R. Darnall Army Medical Center Family Medicine Residency.

Source: Adapted from Am Fam Physician. 2017;96(4):226-233.

Signs/symptoms: gait problems, issues wearing shoes, limping, tripping, falling Sitting habits: the W sitting position (Figure 8) is common in children with increased femoral anteversion; however, there is no evidence that sitting habits cause or worsen orthopedic lower extremity problems Information from references 3 and 4.

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AMERICAN FAMILY PHYSICIAN Table 2. Physical Examination in Children with Lower Extremity Abnormalities Component

Findings

Possible diagnosis

Height and weight

Plot on appropriate Centers for Disease Control and Prevention or World Health Organization growth chart

Abnormal measurements may suggest pathologic conditions (e.g., rickets, metabolic bone disease)

Facial appearance

Abnormal facies

Genetic disorders

Skin

Warmth or redness

Septic arthritis

Ecchymosis

Fracture, nonaccidental trauma

Masses; sacral pits, dimples, hair patch; congenital lesions (e.g., cafĂŠ au lait spots)

Spina bifida, neurofibromatosis

Screening examination

Spine

Flexion and extension of the spine

Scoliosis, lordosis, dorsal kyphosis

Neurologic

Neurologic abnormalities

Developmental delay

Focused musculoskeletal examination Torsional profile (Figure 5)

Angular measurements

External and internal hip rotation (Figure 3) Thigh-foot angle (Figure 4)

Measurements more than 2 standard deviations outside the mean may suggest femoral anteversion or retroversion, or internal or external tibial torsion

Intercondylar distance: with medial malleoli touching, measure distance between the femoral condyles

Measurements more than 2 standard deviations outside the mean may suggest genu varum or valgum

Intermalleolar distance: with femoral condyles touching, measure distance between the medial malleoli in sitting position Evaluation for limb asymmetry Measure leg lengths for asymmetry and joint laxity

Foot

Asymmetry may be due to contracture, cerebral palsy, perinatal stroke, intracranial mass, neuromuscular disorder, fracture, or septic joint

Assess range of motion (Figure 1)

Joint laxity can mimic or worsen torsional or angular deformities and contributes to pes planus, hip dysplasia, and dislocated patella

Heel bisector line (Figure 6)

Metatarsus adductus

Lateral C shape, tight heel cord Gait analysis

Observe child standing for loss of medial foot arch Pes planus Trendelenburg sign (Figure 2)

Hip dysplasia, leg length discrepancy

Observe child’s gait for intoeing and out-toeing, and measure foot progression angle: apply dusted chalk or sanitizing gel to child’s bare feet, have child walk on strips of examination paper

Internal or external tibial torsion, femoral anteversion or retroversion

Assess for W sitting position (Figure 8)

Femoral anteversion

Information from references 4 through 6.

internal and external hip rotation (Figure 37), and thighfoot angle (Figure 43,7). Figure 5 provides normal ranges for torsional profile measurements.8 Measurements outside these ranges indicate a pathologic condition.3-5,7

increased internal rotation with femoral anteversion and increased external rotation with femoral retroversion.3,4 Thigh-foot angle testing is positive for tibial torsion when the foot turns in relative to the thigh axis.9

Foot progression angle measurements will have positive values with out-toeing and negative values with intoeing.4,5 Evaluation of hip rotation shows

Evaluation of genu varum and genu valgum involves additional measurements, including intercondylar distance for genu varum and intermalleolar distance

308

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

AMERICAN FAMILY PHYSICIAN

Forefoot

Hindfoot Normal

A

Mild

Moderate

Severe

Figure 6. Heel bisector line. This line is used to evaluate for metatarsus adductus, a cause of intoeing. It is performed with the patient prone and knees flexed at 90 degrees, using an imaginary straight line from the heel to the forefoot.

Normally, the line that bisects the heel falls on the second toe. Metatarsus adductus is mild if the line falls on the third toe, moderate if it falls between the third and fourth toes, and severe if it falls between the fourth and fifth toes.

CLINICAL CONDITIONS B

Figure 3. Hip rotation. Child lying prone with knees bent for evaluation of (A) external rotation and (B) internal rotation.

External hip rotation is increased with femoral retroversion, and internal hip rotation is increased with femoral anteversion. Femoral anteversion is graded by severity of internal hip rotation: mild is 70 to 80 degrees, moderate is 80 to 90 degrees, and severe is greater than 90 degrees.

Information from reference 7.

Lower limb abnormalities in children can be grouped broadly into three categories: rotational, angular, and foot variations (eTable A).

Intoeing Intoeing, an inward pointing foot, is the most common rotational condition in children. The three major causes of intoeing are metatarsus adductus, internal tibial torsion, and femoral anteversion.11 The etiology of intoeing is suggested by the age at the onset of symptoms.12 Metatarsus Adductus

Information from references 3 and 7.

Metatarsus adductus is the most common congenital foot abnormality and usually resolves spontaneously by one year of age.13 Physical examination reveals medial deviation of the forefoot relative to a normal hindfoot, lack of a tight heel cord, a convexity or C shape of the lateral aspect of the foot, and a concave medial border of the foot3,12 (Figure 7). Severity is determined by the heel bisector line. The foot should be assessed for flexibility to rule out rigid deformities (e.g., metatarsus varus). Treatment is based on severity and age.12 Flexible metatarsus adductus does not require treatment.14,15 Severe metatarsus adductus and rigid deformities are treated with serial casting.3,5 Adjustable shoes are effective in prewalking infants who have motivated parents and are less expensive than serial casting.14,16,17

for genu valgum. The heel bisector line (Figure 6) should be assessed to evaluate for foot deformities such as metatarsus adductus.3,10

Rigid metatarsus adductus is ideally treated with serial casting. This is most feasible in children who are not yet walking. Older children or those with persistent symptomatic metatarsus adductus resistant to casting

Figure 4. Thigh-foot angle. A child lying prone with knees bent for assessment of the thigh-foot angle. The hindfoot is held in a neutral position and the axis of the thigh is compared with the axis of the foot. The normal thigh-foot angle is more than 10 to 15 degrees of external rotation and may be up to 30 degrees in young children.

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310 Usually bilateral; left sided when unilateral

Occurs in 1 out of 200 to 1,000 live births; 1 out of 20 siblings of children with metatarsus adductus are also born with the condition

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017 Charlie Chaplin appearance Likely caused by intrauterine positioning Unilateral, right sided

Affects boys and girls equally

Affects all ages, especially young infants

More common in boys

Seen most often in newborns and obese children

Usually bilateral; right sided when unilateral

Presents between 4 and 7 years of age

Femoral retroversion (increased femoral external rotation)A1,A2,A16

Toes pointed outward

Less common than intoeing

Clumsy, circumduction gait

Inward pointing feet and patellae (squinting or kissing patellae)

Children sit in a W position for comfort

Usually bilateral

Patellae facing forward and feet pointing inward

Usually bilateral; left sided when unilateral

External tibial torsionA1,A2,A16

Hereditary

More common in girls

Presents between 4 and 7 years of age

Possibly caused by intrauterine positioning

Affects boys and girls equally Frequent falls

Most common cause of intoeing, usually presenting in toddlers

Presents between 2 and 4 years of age

Out-toeingA1,A2,A16

Femoral anteversion (increased femoral internal rotationA1,A2,A14,A15

Internal tibial torsionA1,A2,A11-A14

Likely caused by intrauterine positioning

Occurs more often in boys, twins, and premature infants

2% of cases are associated with hip dysplasia

Usually diagnosed in infancy

Presents by 1 year of age

Metatarsus adductusA1-A10

Lateral C- or kidney-shaped foot

Toes pointing inward

Common features

Occurs in 2 out of 1,000 live births; more common than out-toeing

Epidemiology

IntoeingA1

Rotational

Condition

eTable A. Summary of Lower Extremity Conditions in Children

Surgery may be considered after 3 years of age

Cont'd...

Disability often results from osteoarthritis, stress fractures, and slipped capital femoral epiphysis

Typically resolves within the first year of walking; persistence after 3 years of age warrants radiography Decreased hip internal rotation and increased hip external rotation

Parental reassurance and watchful waiting Rule out slipped capital femoral epiphysis

Surgery may be considered after 10 years of age

Disability can result from patellofemoral syndrome and knee instability

May not resolve without treatment; tibia rotates laterally with normal childhood growth, worsening the condition as the child ages

Parental reassurance and watchful waiting

Surgery may be considered in patients older than 8 years with severe functional or cosmetic abnormality

Braces and other orthotics are ineffective

Radiography not recommended

Parental reassurance (usually resolves spontaneously by 8 years of age)

Thigh-foot angle

Thigh-foot angle

Positive foot progression angle

Internal and external hip rotation

Surgery may be considered in patients older than 8 years if thigh-foot angle is internally rotated more than 3 standard deviations above the mean (or greater than 15 degrees) and there is severe functional or cosmetic abnormality

Braces and other orthotics are ineffective

Radiography not recommended unless rickets, Blount disease, or skeletal dysplasia is suspected

Transmalleolar axis (copresentation of genu varum and/or patient is younger than 3 years)

Parental reassurance (usually resolves spontaneously by 5 years of age)

Foot progression angle

Surgical correction of persistent metatarsus adductus has high failure and complication rates; persistence into adulthood causes no long-term disability, thus surgery is reserved for severe, rigid metatarsus adductus that affects shoe wear and function

Adjustable shoes are as effective as casting; surgical consultation may be considered in older children if there is parental concern about compliance with adjustable shoes or casting

Adjustable shoes or serial casting is the preferred treatment for severe metatarsus adductus in children who are not yet walking; serial casting is usually biweekly for 6 to 8 weeks; full-leg and below-knee casts are equally effective

Treatment and radiography are not indicated for flexible metatarsus adductus

Parental reassurance (usually resolves spontaneously by 1 year of age)

Surgical referral needed only for deformities measuring more than 2 standard deviations outside the mean

Parental reassurance

Management

Thigh-foot angle

Flexibility assessment: holding the heel in neutral position, the forefoot should abduct to at least the neutral position, and the ankle should have normal range of motion; if the forefoot does not abduct to neutral, the foot deformity is rigid (e.g., metatarsus varus)

Heel bisector line

Negative foot progression angle

Diagnostic measurements

AMERICAN FAMILY PHYSICIAN

Athletes participating in high-impact sports Bilateral

Presents between 3 and 6 years of age

Associated with joint laxity, obesity, and wearing shoes

Hereditary Most cases are flexible and asymptomatic

Usually bilateral

All ages

More common in girls

Bilateral, symmetric

Affects boys and girls equally

Common features

Presents by 2 years of age

Epidemiology

Information from: A1. Jones S, Khandekar S, Tolessa E. Normal variants of the lower limbs in pediatric orthopedics. Int J Clin Med. 2013;4:12-17.

A2. Sass P, Hassan G. Lower extremity abnormalities in children [published correction appears in Am Fam Physician.

2004;69(5):1049]. Am Fam Physician. 2003;68(3):461-468.

A3. Staheli LT. Fundamentals of Pediatric Orthopedics. 5th ed. Philadelphia, Pa.: Wolters Kluwer; 2016.

A4. Wall EJ. Practical primary pediatric orthopedics. Nurs Clin North Am. 2000;35(1):95-113.

A5. Harris E. The intoeing child: etiology, prognosis, and current treatment options. Clin Podiatr Med Surg.

2013;30(4):531-565.

A6. Furdon SA, Donlon CR. Examination of the newborn foot: positional and structural abnormalities. Adv Neonatal Care. 2002;2(5):248-258.

A7. Katz K, David R, Soudry M. Below-knee plaster cast for the treatment of metatarsus adductus. J Pediatr Orthop.

1999;19(1):49-50.

A8. Herzenberg JE, Burghardt RD. Resistant metatarsus adductus: prospective randomized trial of casting versus orthosis. J Orthop Sci. 2014;19(2):250-256.

A9. Williams CM, James AM, Tran T. Metatarsus adductus: development of a non-surgical treatment pathway.

J Paediatr Child Health. 2013;49(9):E428-E433.

A10. Dietz FR. Intoeing—fact, fiction and opinion. Am Fam Physician. 1994;50(6):1249-1259, 1262-1264.

A11. Staheli LT, Engel GM. Tibial torsion: a method of assessment and a survey of normal children. Clin Orthop Relat Res. 1972;86:183-186.

A12. Davids JR, Davis RB, Jameson LC, Westberry DE, Hardin JW. Surgical management of persistent intoeing gait due to increased internal tibial torsion in children. J Pediatr Orthop. 2014;34(4):467-473.

A13. Lincoln TL, Suen PW. Common rotational variations in children. J Am Acad Orthop Surg. 2003;11(5):312-320.

Pes planus (flatfoot)A1,A3,A21-A26

Foot

Genu valgum (knock knee)A1,A2,A17-A20

Genu varum (bowleg)A1,A2,A17-A20

Angular

Condition

eTable A. Summary of Lower Extremity Conditions in Children

...Cont'd

Obtain imaging if there is concern for rigid pes planus or tarsal coalition based on examination findings; surgical referral is indicated for rigid pes planus and tarsal coalition

Consider referral to orthopedics or podiatry for adolescents or adults with flexible painful pes planus that does not respond to nonsurgical interventions

Flexible pes planus that causes pain should first be treated with nonsurgical interventions; although these interventions are not effective at altering the natural course of pes planus, there is limited evidence that they help to relieve pain and improve balance and function

Flexible pes planus that does not resolve by 10 years of age is usually still asymptomatic

Pes planus is usually flexible and asymptomatic, and resolves spontaneously

Usually resolves spontaneously, but surgery may be required

Surgery reserved for extreme angulation (more than 2 standard deviations outside the mean)

Nonsurgical interventions are not recommended

Parental reassurance (usually resolves spontaneously by 4 years of age)

Management

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

A26. Vulcano E, Maccario C, Myerson MS. How to approach the pediatric flatfoot. World J Orthop. 2016;7(1):1-7.

A25. Carr JB II, Yang S, Lather LA. Pediatric pes planus: a state-of-the-art review. Pediatrics. 2016;137(3):e20151230.

A24. Jane MacKenzie A, Rome K, Evans AM. The efficacy of nonsurgical interventions for pediatric flexible flat foot: a critical review.

J Pediatr Orthop. 2012;32(8):830-834.

A23. Evans AM, Rome K. A Cochrane review of the evidence for non-surgical interventions for flexible pediatric flat feet.

Eur J Phys Rehabil Med. 2011;47(1):69-89.

A22. Lee HJ, Lim KB, Yoo J, Yoon SW, Yun HJ, Jeong TH. Effect of custom-molded foot orthoses on foot pain and balance in children with symptomatic flexible flat feet. Ann Rehabil Med. 2015;39(6):905-913.

A21. Rome K, Ashford RL, Evans A. Non-surgical interventions for paediatric pes planus. Cochrane Database Syst Rev. 2010(7):CD006311.

A20. Arazi M, Oğün TC, Memik R. Normal development of the tibiofemoral angle in children: a clinical study of 590 normal subjects from 3 to 17 years of age. J Pediatr Orthop. 2001;21(2):264-267.

A19. Cheng JC, Chan PS, Chiang SC, Hui PW. Angular and rotational profile of the lower limb in 2,630 Chinese children.

J Pediatr Orthop. 1991;11(2):154-161.

A18. Heath CH, Staheli LT. Normal limits of knee angle in white children—genu varum and genu valgum. J Pediatr Orthop.

1993;13(2):259-262.

A17. Kaspiris A, Zaphiropoulou C, Vasiliadis E. Range of variation of genu valgum and association with anthropometric characteristics and physical activity: comparison between children aged 3-9 years. J Pediatr Orthop B. 2013;22(4):296-305.

A16. Mooney JF III. Lower extremity rotational and angular issues in children. Pediatr Clin North Am. 2014;61(6):1175-1183.

A15. Staheli LT, Corbett M, Wyss C, King H. Lower-extremity rotational problems in children. Normal values to guide management.

J Bone Joint Surg Am. 1985;67(1):39-47.

A14. Staheli LT. Torsion—treatment indications. Clin Orthop Relat Res. 1989;(247):61-66.

Rule out tarsal coalition in adolescents

Absence of the medial longitudinal arch on weight bearing and presence of the arch with tiptoeing

Pathologic causes include trauma, fracture, prior osteomyelitis

Intermalleolar distance

Rule out rickets, skeletal dysplasia, Blount disease

Intercondylar distance

Diagnostic measurements

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AMERICAN FAMILY PHYSICIAN may require surgery if the deformity causes significant dysfunction. Surgery for metatarsus adductus has high failure and complication rates, and thus casting or adjustable shoes are generally attempted first, before the child starts walking. Casting in older children who are walking is often not a feasible option, and surgical consultation may be appropriate to discuss risks and

Figure 7. Metatarsus adductus.

benefits of surgery. Most cases of persistent metatarsus adductus are still asymptomatic in adulthood, and surgery is rarely indicated.3,4,12,18 Internal Tibial Torsion Internal tibial torsion is a common normal rotational variant.3,19 It is the most common cause of intoeing,5,6 usually presenting in toddlers. The child walks with patellae facing forward and feet pointing inward, producing an internally rotated thigh-foot angle and negative foot progression angle on torsional profile.4,5 Internal tibial torsion usually resolves spontaneously by five years of age.4 Braces, night splints, shoe modification/wedges, other orthotics, and serial casting are not recommended for this condition.3 Residual internal tibial torsion has not been shown to cause degenerative joint disease or disability and, thus, surgery is rarely indicated.3,4 Surgery may be considered in patients older than eight years who have a severe residual deformity (thigh-foot angle more than three standard deviations above the mean [i.e., greater than 15 degrees internal rotation]) and severe functional or cosmetic abnormality that is not expected to self-correct.3,18,20 Femoral Anteversion Femoral anteversion is the most common cause of intoeing in school-aged children and is most severe between four and seven years of age.3,19,20 Physical examination focuses on assessment of internal and external rotation of the hip. Increased internal rotation (60 to 90 degrees) with reduced external rotation (10 to 15 degrees) is diagnostic of femoral anteversion.

The patellae and feet appear to point inward (known as squinting or kissing patellae), resulting in a clumsy, circumduction gait.4,5,12 Children with femoral anteversion often sit in the W position (Figure 8) for comfort rather than sitting cross-legged.4,12 Spontaneous resolution occurs in more than 80% of children by eight years of age.4,5,12 Special shoes, braces, connective bars, and other orthotics are not effective.3-5,12,21 Surgical intervention is indicated for children older than eight years with severe functional or cosmetic abnormality secondary to persistent femoral anteversion greater than 50 degrees and internal rotation greater than 80 degrees.4,12

Out-Toeing Figure 8. The W sitting position is common in children with increased femoral anteversion.

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Out-toeing, an outward pointing foot, is less common than intoeing. It is caused by external tibial torsion, femoral retroversion, and pes planus.3,5

AMERICAN FAMILY PHYSICIAN External Tibial Torsion External tibial torsion usually presents between four and seven years of age when the tibia externally rotates during normal growth and worsens into a deformity.

Physical examination reveals a positive foot progression angle and a thigh-foot angle greater than 30 degrees3,4 (Figure 9). Surgery to correct external tibial torsion is rarely recommended before 10 years of age, but may be performed to prevent disability from patellofemoral syndrome and knee joint instability. Surgery can have a high complication rate.3,4,11 Femoral Retroversion Femoral retroversion is common in newborns because of contracture of the hip from intrauterine positioning.5,9,11 It is diagnosed when the feet of a prewalking child are rotated outward by nearly 90 degrees (i.e., Charlie Chaplin appearance).5,9,11 There is a markedly decreased hip internal rotation and increased external rotation on torsional profile.3,4 Femoral retroversion typically improves during the first year of walking.9 Persistence after three years of age warrants radiography of the pelvis, hips, and lower extremities and referral to an orthopedist.11 If femoral

retroversion is diagnosed after eight years of age, it may be associated with a slipped capital femoral epiphysis.3,11 Femoral retroversion results in osteoarthritis and increased risk of lower extremity stress fracture.11 Surgical consultation should be considered for children with persistent femoral retroversion at three years of age5; however, the average age for surgical correction with osteotomy is 10 years of age.3,11 Pes Planus Pes planus, or flatfoot, is the absence of the medial longitudinal arch on weight bearing and presence of the arch with tiptoeing3 (Figure 10). Physiologic flatfoot that is flexible is a benign, normal variant.6,22,23 Pathologic flatfoot is rigid and requires orthopedic referral.6,22,23 Physiologic flatfoot is observed in nearly all infants, 45% of preschool-aged children, and about 15% of persons older than 10 years.6,24 Most children with physiologic flatfoot are asymptomatic and develop an arch before 10 years of age.3,23 Painless, flexible flatfoot does not require investigation or intervention.3,6,22,23 Orthotics such as special shoes and insoles are not effective for painless pes planus.3,6,22,23 Pes planus should be distinguished from tarsal coalition in adolescents.3,23 On examination, limited movement of the subtalar joint and absence of the medial arch with tiptoeing suggest tarsal coalition, which requires further investigation with oblique radiography or computed tomography.3,23 Surgical consultation is recommended for patients with tarsal coalition and symptomatic pes planus (rigid type and flexible type with persistent pain and dysfunction despite previous nonoperative treatments).

Nonoperative treatments for symptomatic flexible pes planus include rest, activity modification, massage, physical therapy, and a trial of a nonsteroidal antiinflammatory drug. Although orthotics are ineffective

Figure 9. External tibial torsion.

Figure 10. Pes planus (flatfoot).

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AMERICAN FAMILY PHYSICIAN participate in high-impact sports may develop genu varum.29 Pathologic genu varum may be due to rickets, skeletal dysplasia, or Blount disease (abnormal growth of medial proximal tibial physis that is associated with obesity).4,30,31 Genu Valgum Genu valgum commonly occurs between three and six years of age and is self-limited. Onset in adolescence is unusual and warrants investigation. Pathologic causes of genu valgum include trauma or fracture, prior osteomyelitis, and possibly obesity.32 Treatment of Angular Variations

Figure 11. Genu varum (bowleg).

at altering the course of flexible flatfoot, they may provide relief of pain when present and may also be tried before surgical management.22

Angular Variations During childhood, knee alignment changes with skeletal growth and development. At birth, most newborns have physiologic genu varum.4 This gradually progresses to a neutral position by two years of age and then to physiologic genu valgum between three and six years of age. By seven to 11 years, most children’s knees return to a neutral or slightly valgus position. Girls tend to have more valgus positioning than boys.25-28 Parental concerns for knee misalignment are often because of appearance, awkward gait, or clumsiness.

Normal, transient physiologic angulation should be distinguished from pathologic processes. Evaluation of standing knee alignment includes the intercondylar and intermalleolar distances, and the tibiofemoral angle measured with a goniometer.4,26 Severe deformity, unilateral or asymmetric presentation, and concerns for metabolic or endocrine disorders warrant further workup.

Genu Varum Genu varum (Figure 11) is typically bilateral, symmetric, and self-limited. Bracing, connective bars, and other orthotics are not necessary for most patients. Persistence after two years of age is unusual. Adolescents who

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Pathologic genu varum and valgum may be associated with early osteoarthritis.29,32 Surgical correction of genu varum and valgum is reserved for when the condition does not spontaneously resolve, conservative measures are ineffective, or there is extreme angulation. Surgical techniques attempt to realign the bone or reorient bone growth.33 Note: For complete article visit: www.aafp.org/afp.

REFERENCES 1. Hsu EY, Schwend RM, Julia L. How many referrals to a pediatric orthopaedic hospital specialty clinic are primary care problems? J Pediatr Orthop. 2012;32(7):732-736.

2. Molony D, Hefferman G, Dodds M, McCormack D. Normal variants in the paediatric orthopaedic population.

Ir Med J. 2006;99(1):13-14.

3. Jones S, Khandekar S, Tolessa E. Normal variants of the lower limbs in pediatric orthopedics. Int J Clin Med. 2013;4:12-17.

4. Mooney JF III. Lower extremity rotational and angular issues in children. Pediatr Clin North Am. 2014;61(6): 1175-1183.

5. Sass P, Hassan G. Lower extremity abnormalities in children [published correction appears in Am Fam Physician. 2004;69(5):1049]. Am Fam Physician.

2003;68(3):461-468.

6. Staheli LT. Fundamentals of Pediatric Orthopedics. 5th ed.

Philadelphia, Pa.: Wolters Kluwer; 2016.

7. Staheli LT, Corbett M, Wyss C, King H. Lower-extremity rotational problems in children. Normal values to guide management. J Bone Joint Surg Am. 1985;67(1):39-47.

8. Wenger DR, Rang M. The Art and Practice of Children’s Orthopaedics. New York, NY: Raven Press; 1993.

9. Wall EJ. Practical primary pediatric orthopedics. Nurs Clin North Am. 2000;35(1):95-113.

10. Bleck EE. Metatarsus adductus: classification and relationship to outcomes of treatment. J Pediatr Orthop.

1983;3(1):2-9.

AMERICAN FAMILY PHYSICIAN 11. Staheli LT. Rotational problems in children. J Bone Joint Surg Am. 1993;75(6):939-949.

12. Harris E. The intoeing child: etiology, prognosis, and current treatment options. Clin Podiatr Med Surg.

2013;30(4):531-565.

13. Dietz FR. Intoeing—fact, fiction and opinion. Am Fam Physician. 1994;50(6):1249-1259, 1262-1264.

14. Williams CM, James AM, Tran T. Metatarsus adductus: development of a non-surgical treatment pathway.

J Paediatr Child Health. 2013;49(9):E428-E433.

15. Ponseti IV, Becker JR. Congenital metatarsus adductus: the results of treatment. J Bone Joint Surg Am. 1966;48(4): 702-711.

16. Katz K, David R, Soudry M. Below-knee plaster cast for the treatment of metatarsus adductus. J Pediatr Orthop.

1999;19(1):49-50.

17. Herzenberg JE, Burghardt RD. Resistant metatarsus adductus: prospective randomized trial of casting versus orthosis. J Orthop Sci. 2014;19(2):250-256.

18. Staheli LT. Torsion—treatment indications. Clin Orthop Relat Res. 1989;(247):61-66.

19. Staheli LT. Rotational problems of the lower extremities.

Orthop Clin North Am. 1987;18(4):503-512.

20. Lincoln TL, Suen PW. Common rotational variations in children. J Am Acad Orthop Surg. 2003;11(5):312-320.

21. Uden H, Kumar S. Non-surgical management of a pediatric “intoed” gait pattern - a systematic review of the current best evidence. J Multidiscip Healthc. 2012;5: 27-35.

22. Carr JB II, Yang S, Lather LA. Pediatric pes planus: a stateof-the-art review. Pediatrics. 2016;137(3):e20151230.

24. Evans AM, Rome K. A Cochrane review of the evidence for non-surgical interventions for flexible pediatric flat feet. Eur J Phys Rehabil Med. 2011;47(1):69-89.

25. Kaspiris A, Zaphiropoulou C, Vasiliadis E. Range of variation of genu valgum and association with anthropometric characteristics and physical activity: comparison between children aged 3-9 years. J Pediatr Orthop B. 2013;22(4):296-305.

26. Heath CH, Staheli LT. Normal limits of knee angle in white children—genu varum and genu valgum. J Pediatr Orthop. 1993;13(2):259-262.

27. Cheng JC, Chan PS, Chiang SC, Hui PW. Angular and rotational profile of the lower limb in 2,630 Chinese children. J Pediatr Orthop. 1991;11(2):154-161.

28. Arazi M, Oğün TC, Memik R. Normal development of the tibiofemoral angle in children: a clinical study of 590 normal subjects from 3 to 17 years of age. J Pediatr Orthop.

2001;21(2):264-267.

29. Thijs Y, Bellemans J, Rombaut L, Witvrouw E. Is highimpact sports participation associated with bowlegs in adolescent boys? Med Sci Sports Exerc. 2012;44(6): 993-998.

30. Fabry G. Clinical practice. Static, axial, and rotational deformities of the lower extremities in children. Eur J Pediatr. 2010;169(5):529-534.

31. Gettys FK, Jackson JB, Frick SL. Obesity in pediatric orthopaedics. Orthop Clin North Am. 2011;42(1):95-105.

32. Farr S, Kranzl A, Pablik E, Kaipel M, Ganger R. Functional and radiographic consideration of lower limb malalignment in children and adolescents with idiopathic genu valgum. J Orthop Res. 2014;32(10):1362-1370.

33. Ballal MS, Bruce CE. Nayagam S. Correcting genu varum and genu valgum in children by guided growth: 23. Vulcano E, Maccario C, Myerson MS. How to approach temporary hemiepiphysiodesis using tension band plates.

J Bone Joint Surg Br. 2010;92(2):273-276. the pediatric flatfoot. World J Orthop. 2016;7(1):1-7.

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Practice Guidelines FEVER IN WELL-APPEARING CHILDREN YOUNGER THAN TWO YEARS: A CLINICAL POLICY FROM THE ACEP

followed by a family physician, or return to the emergency department for follow-up.

In one year, 15% of visits to the emergency department by persons younger than 15 years are children with fever, usually attributed to a benign, self-limited viral infection. Some fevers, however, can be a sign of serious infection, especially in infants younger than three months. Although treating those who appear ill is clear cut, it can be difficult to distinguish between a benign condition and a serious bacterial infection in those who appear well. The American College of Emergency Physicians (ACEP) has released a clinical policy addressing issues in children younger than two years who visit the emergency department with fever, but who appear well.

The need for chest radiography in children with fever who appear well can be uncertain, especially because these patients have a greater chance of having a benign viral condition with symptoms similar to bacterial pneumonia. Clinicians should balance the benefits of performing chest radiography in children with fever (e.g., making a diagnosis and starting treatment) with the harms (e.g., radiation exposure). Chest radiography should be considered in children with a fever of at least 100.4°F (38°C) with no clear infection source who have a cough, hypoxia, rales, high fever (at least 102.2°F [39°C]), fever lasting longer than two days, or who have tachycardia or tachypnea out of proportion to the fever. Chest radiography should not be performed in those with fever of at least 100.4°F and wheezing or a high chance of bronchiolitis.

Recommendations Infants One to Three Months of Age Laboratory studies, including a lumbar puncture to evaluate for meningitis, are commonly performed in the emergency department when an infant presents with fever. Routinely performing a lumbar puncture, which is invasive and has associated risks, is controversial.

On the other hand, initiating antibiotic treatment without performing a lumbar puncture can lead to incomplete treatment or late identification of meningitis.

Being able to predict which infants presenting with fever would benefit from a lumbar puncture could help lessen parent anxiety, as well as decrease costs, the use of invasive testing, exposure to antibiotics, and admissions to the hospital.

Lumbar puncture may be considered in infants 29 to 90 days of age with fever, despite that no predictors sufficiently pinpoint when cerebrospinal fluid should be obtained. Because of the lower risk of meningitis, lumbar puncture can be delayed in full-term infants diagnosed with a viral illness. Unless another source of bacteria is found, antibiotics should be withheld in infants whose lumbar puncture is delayed. These infants should be admitted to the hospital, be closely

Source: Adapted from Am Fam Physician. 2017;95(8):524-525.

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Children Two Months to Two Years of Age

Urinalysis and urine cultures to diagnose urinary tract infection should be considered in children who have a fever of at least 100.4°F, especially if they are at higher risk (i.e., girls younger than one year, uncircumcised boys, those who are not black, fever lasting longer than one day, fever of at least 102.2°F, negative results on respiratory pathogens testing, and no clear infection source). No clinical variable or absent variable has been identified to sufficiently rule out urinary tract infection or the need for testing, although the presence of a viral infection may reduce the risk.

An initial diagnosis of urinary tract infection can be made if there is a positive result on urine leukocyte esterase, nitrite, leukocyte count, or Gram stain testing.

A urine culture should be performed before starting antibiotics in these patients, as well as in those with a negative result on dipstick urinalysis but in whom urinary tract infection is still suspected. Although not addressed in this policy statement, it should be noted that the American Academy of Pediatrics recommends that urine collection be done through catheterization or suprapubic aspirate.

AMERICAN FAMILY PHYSICIAN

Photo Quiz HYPOXEMIA AND NONPRODUCTIVE COUGH A 47-year-old man presented with general fatigue, chills, dyspnea, dry cough, and occasional subjective fever that began two months earlier. He had an unprovoked deep venous thrombosis about one year before presentation that was treated with rivaroxaban for six months. His medical history was also notable for spinal stenosis and gastroesophageal reflux.

He was not taking any medications. He had no history of smoking or substance abuse. He quit chewing tobacco and drinking alcohol one year before presentation.

He was divorced and sexually active.

He had a regular pulse of 122 beats per minute, unlabored respirations at 21 breaths per minute, oxygen saturation of 78% on room air, and a body temperature of 100.8˚F (38.2˚C). Physical examination revealed a new oily and scaly erythematous rash on his forehead, nose, and cheeks. Pulmonary examination showed good air movement but diffuse rales bilaterally. Arterial blood gas measurements showed partial pressure of oxygen was 50 mm Hg and partial pressure of carbon dioxide was 26 mm Hg. Other laboratory testing showed a white blood cell count of 11,000 per μL (11.0 × 109 per L) and hemoglobin level of 11 g per dL (110 g per L). Chest radiography demonstrated diffuse hazy opacities (Figures 1 and 2). A high-resolution computed tomography (CT) scan of the chest also showed diffuse opacities, some with haziness or groundglass appearance. Limited bedside echocardiography showed no evidence of left ventricular dysfunction or right ventricular strain.

Figure 1.

Question Based on the patient’s history, physical examination, and other findings, which one of the following is the most likely diagnosis?

Figure 2.

A. Miliary tuberculosis with pulmonary involvement.

C. Pneumocystis jiroveci pneumonia.

B. Mycoplasma (atypical) pneumonia.

D. Pulmonary embolism.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2017;96(2):121-122.

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AMERICAN FAMILY PHYSICIAN Discussion

Summary Table

The answer is C: Pneumocystis jiroveci pneumonia, previously known as Pneumocystis carinii pneumonia.

It is the second most common AIDS-defining opportunistic infection after esophageal candidiasis.1 It is an atypical fungal infection that is uncommon in patients without human immunodeficiency virus (HIV) infection. Bronchoscopic lavage and biopsy confirmed the diagnosis, with a methenamine silver stain highlighting the fungal cyst walls. An HIV antibody test was positive. His viral load was 914,000 copies per mL, and his CD4 cell count was severely depressed at 25 per mm3.

The incidence of P. jiroveci pneumonia among patients with HIV has been reported at 3.9 cases per year.1 The infection typically manifests as subacute dyspnea and nonproductive cough. Findings on chest radiography include bilateral interstitial infiltrates, and chest CT findings include nonspecific ground-glass opacities.2 An additional clue in this patient was new-onset seborrheic dermatitis, which is common in patients with HIV.1,3 First-line treatment for P. jiroveci pneumonia with moderate to severe hypoxemia (arterial partial pressure of oxygen less than 70 mm Hg) is high-dose trimethoprim/sulfamethoxazole and glucocorticoids.4 Miliary tuberculosis that involves the lung can manifest as fever, cough, dyspnea, and hypoxemia. Findings on chest radiography include diffuse reticulonodular infiltrates, whereas CT may show diffuse 2- to 3-mm nodules or nonspecific ground-glass opacities. Because of the nonspecific findings on radiography, diagnosis must be confirmed with histopathology, acid-fast stain, and molecular tests demonstrating the presence of Mycobacterium tuberculosis.5 Mycoplasma (atypical) pneumonia manifests as fever, cough, wheezing, and occasionally dyspnea. Findings on chest radiography may include airspace opacities, reticular opacities, and bronchial thickening. CT findings include airspace consolidations, peribronchial and interstitial thickening, and centrilobular nodules.6 Pulmonary embolism is an important consideration in this patient, especially given his history of deep venous thrombosis. Typical symptoms and signs of pulmonary embolism include dyspnea, cough, chest pain, tachycardia, and hypoxemia. Findings on chest

Condition

Imaging findings

Miliary tuberculosis

Diffuse reticulonodular infiltrates on chest radiography; diffuse 2- to 3-mm nodules or nonspecific ground-glass opacities on CT

Mycoplasma (atypical) pneumonia

Airspace opacities, reticular opacities, and bronchial thickening on radiography; airspace consolidations, peribronchial and interstitial thickening, and centrilobular nodules on CT

Pneumocystis jiroveci Bilateral interstitial infiltrates on chest pneumonia radiography; nonspecific ground-glass opacities on CT Pulmonary embolism

Nonspecific radiographic findings; arterial embolus on CT

CT = Computed tomography.

radiography are usually nonspecific but may include atelectasis. In this case, CT angiography was negative for embolus, the chest radiograph showed bilateral interstitial infiltrates, and a bedside echocardiogram showed no sign of right heart strain, making pulmonary embolism unlikely.

REFERENCES 1. Buchacz K, Baker RK, Palella FJ Jr., et al. AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study. AIDS. 2010;24(10):1549-1559.

2. Huang L, Cattamanchi A, Davis JL, et al. HIV-associated pneumocystis pneumonia. Proc Am Thorac Soc. 2011;8(3):294-300.

3. Eisenstat BA, Wormser GP. Seborrheic dermatitis and butterfly rash in AIDS. N Engl J Med. 1984;311(3):189.

4. Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1-207.

5. Sharma SK, Mohan A, Sharma A, Mitra DK. Miliary tuberculosis: new insights into an old disease. Lancet Infect Dis. 2005;5(7):415-430.

6. Reittner P, Muller NL, Heyneman L, et al. Mycoplasma pneumoniae pneumonia: radiographic and high-resolution CT features in 28 patients. AJR Am J Roentgenol.

2000;174(1):37-41.

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CARDIOLOGY

Familial Hypercholesterolemia, a Widely Underdiagnosed and Undertreated Clinical Entity: The Physician Perspective HARPREET SINGH*, DEEPAK JAIN†, KIRAN B‡, RUCHI JAGOTA‡

ABSTRACT Familial hypercholesterolemia (FH) is the most common autosomal dominant genetic disease. The clinical syndrome (phenotype) is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and a propensity to early-onset atherosclerotic cardiovascular disease. Homozygous FH is of rare occurrence in which approximately 1 in 1 million persons in the general population are affected. Here we report a case of a 30-year-old male who presented with xanthomas since the age of 10 years and elevated serum LDL-C and after investigations of the patient and his family members, the diagnosis of FH was made. Healthcare providers should recommend lipid profiles for all first-degree relatives of patients with FH in order to identify other individuals at risk. Early diagnosis and early initiation of treatment will save the affected individual and the other family members from catastrophic cardiac events. Aggressive treatment of hypercholesterolemia including diet control, lipidlowering drugs, exercise and control of risk factors will help to reduce the morbidity and mortality associated with this disease.

Keywords: Familial hypercholesterolemia, autosomal dominant genetic disease, atherosclerotic cardiovascular disease, xanthomas, lipid profiles

F

amilial hypercholesterolemia (FH), also known as autosomal dominant hypercholesterolemia (ADH) type 1, is an autosomal co-dominant disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) in the absence of hypertriglyceridemia, tendon xanthomas and the development of symptomatic cardiovascular disease.1 There are two types of FH: the heterozygous form which has an incidence of 1 out of 500 and in which the patient has one normal allele and one mutated allele, whereas the homozygous form in which the patient has two mutated alleles, considered an autosomal co-dominant disorder is much rarer than

heterozygous form with an incidence of approximately 1 in a million.2 FH patients need aggressive treatment to lower plasma levels of LDL-C, that includes initiation of a diet low in saturated and trans fats and drug therapy for effective control of their LDL-C levels.3,4 If medical treatment is inefficient then LDL-C apheresis and liver transplantation are needed.5 Due to the rare prevalence of the condition and the life-threatening complications and the fact that timely aggressive treatment can delay the onset and progression of coronary vascular disease, this article aims to report a case of a 30-year-old male patient who developed xanthomas since the age of 10 years and raised serum LDL-C levels.

CASE REPORT

*Senior Professor and Head Dept. of Medicine IV †Associate Professor ‡Resident Dept. of Medicine Pt BD Sharma University of Health Sciences, Rohtak, Haryana Address for correspondence Dr Deepak Jain Associate Professor Dept. of Medicine Pt BD Sharma University of Health Sciences, Rohtak - 124001, Haryana E-mail: jaindeepakdr@gmail.com

The patient, a 30-year-old male, presented to the Dept. of Medicine, PGIMS, Rohtak with chief complaints of multiple nodular swellings over bilateral hands, both elbow and knee joints, nodular swelling over right fibular head and right fifth metatarsophalangeal joint for 20 years. There was no history of coronary artery disease (CAD), stroke, hypertension, hypothyroidism and diabetes mellitus. Patient’s sister and parents were healthy and did not have any skin lesions. Systemic

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CARDIOLOGY examination of the patient was essentially normal with no cardiovascular abnormality. Respiratory system, per abdomen and cranial nervous system revealed no abnormality.

On local examination, multiple nodular swellings over proximal interphalangeal, distal interphalangeal and metacarpophalangeal joints of both hands, elbow and knee joints were present which were soft, nontender and mobile having smooth surface with regular margins. Multiple papulonodular lesions which were yellow to skin-colored were present in right cubital fossa. Soft yellow thin plaques were seen around both eyelids (Fig. 1).

Investigations showed total cholesterol (TC) of 540 mg/dL, low-density lipoprotein (LDL) of 530 mg/dL, triglycerides (TGs) of 112 mg/dL, very low-density lipoprotein (VLDL) of 22 mg/dL and high-density lipoprotein (HDL) of 40 mg/dL. Serum apolipoprotein A-1 levels were 79 mg/dL and apolipoprotein B levels were 315 mg/dL with ApoB/ApoA1 ratio of 3.97.

Complete hemogram, blood sugar, renal function tests, liver function tests and thyroid function tests were within normal limits. Chest X-ray and electrocardiogram were normal. Echocardiography showed thickened aortic

Table 1. Lipid Profile of Family Members Fasting lipid profile

Father

Mother

Sister

TGs

131

149

121

TC

309

423

248

HDL-C

45

59

57

LDL-C

220

334

167

VLDL-C

28

34

24

valve. Bilateral carotid Doppler showed plaque of size 0.4 Ă— 0.4 cm in right carotid bulb and of size 0.6 Ă— 0.4 cm in left carotid bulb. Excision biopsy of one of the nodules showed large and small aggregates of xanthoma or foam cells with infiltration by lymphocytes, histiocytes and few polymorphs. Foreign body type and Touton giant cells were seen giving impression of aging tuberous xanthomas. Screening lipid profile of family members also revealed elevated levels of TC and LDL-C, which are shown in Table 1.

Based on the above findings, the diagnosis of FH was considered and the patient was started on low-fat, lowcholesterol diet and treatment with rosuvastatin and ezetimibe was initiated. At present, patient is under our regular follow-up along with cardiovascular clinic.

DISCUSSION

a

b

c

d

e

f

Figure 1. Cutaneous xanthomas over hands (a), papulonodular lesion in right cubital fossa (b), cutaneous xanthomas over knee (c), tuberous xanthoma over ankle joint (d), cutaneous xanthoma over feet (e) and cutaneous xanthoma over eyelids (f).

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Familial hypercholesterolemia (FH) is an autosomal dominant genetically inherited lipid disorder caused by more than 900 mutations in the LDL receptor gene present on chromosome 19, leading to the lack of functional receptors for LDL on the cell surface resulting in very high LDL-C levels and causing preventable premature cardiovascular death. FH is classified into, the heterozygous form in which the patient has one normal allele and one mutated allele; and the homozygous form in which the patient has two mutated alleles.5 FH is inherited with a gene dosing effect, in which homozygotes are more adversely affected than heterozygotes.

Patients with homozygous FH have been further classified into patients with virtually no detectable LDL receptor activity (receptor negative) and those patients with markedly reduced but detectable LDL receptor activity (receptor defective). LDL-C levels in patients with homozygous FH range from about 400 to >1,000 mg/dL, with receptor defective patients at the lower end and receptor negative patients at the higher end. TGs are usually normal.5 Untreated patients with homozygous FH rarely survive beyond

CARDIOLOGY the second decade. Patients with homozygous FH, present in childhood with cutaneous xanthomas on the hands, wrists, elbows, knees, heels or buttocks.

The devastating consequence of homozygous FH is accelerated atherosclerotic coronary vascular disease (ASCVD), which often presents in childhood or early adulthood and these patients have severe and early functional and structural cardiovascular diseases (CVDs) including clinical CAD, aortic valve disease and atherosclerotic aortic, carotid and peripheral vascular disease. Patients with heterozygous FH have hypercholesterolemia from birth but they are usually asymptomatic and the disease recognition is frequently based on detection of hypercholesterolemia on routine screening, the appearance of tendon xanthomas or the development of symptomatic CVD. Tendon, xanthomas are essentially pathognomonic for FH; however, they occur in less than half of FH patients, homozygous FH is characterized by xanthomata, particularly in age less than 10 years. They are plaques or nodules consisting of abnormal lipid deposition in foam cells (macrophages with phagocytosed lipid material) and collagen. Xanthomas develop because of lipid leakage from the vascular into the surrounding tissue, where macrophages subsequently phagocytose these lipids. But these can be seen in other rare genetic disorders (e.g., sitosterolemia and cerebrotendinous xanthomatosis).

In addition, juvenile xanthogranulomas (JXG) and other non-Langerhans cell histiocytoses have a similar appearance and may be mistaken for xanthomata.

The distribution of the lesions helps to differentiate xanthomata in FH from the lesions in JXG (in FH, xanthomata commonly occur on Achilles tendons, dorsum of the hands and extensor surfaces of the knees and elbows; whereas lesions in JXG typically occur on the head, neck and upper trunk). A definitive distinction is made on the basis of the lipid profile, which is normal in JXG. Other clinical signs include corneal arcus and xanthelasma. Arcus senilis or corneal arcus, is described as a yellowish-white ring around the cornea that is separated from the limbus by a clear zone 0.3-1 mm in width. Xanthelasma palpebrarum or simply xanthelasma, is described as plaque-like yellow lesions near the inner canthus of the eyelids that may emanate from the medial portions of the upper and lower eyelids.

A variety of approaches have been developed for diagnosing FH by applying any one of several validated sets of criteria. The best characterized are the Simon Broome Register Diagnostic Criteria for FH, the

Dutch Lipid Clinic Network Diagnostic Criteria for FH and the US Make Early Diagnosis Prevent Early Death (MEDPED) Program Diagnostic Criteria for FH.6-8 Out of these, the Simon Broome Register Diagnostic Criteria is most widely used (Table 2).

In our patient, after detailed review of literature, history, relevant investigations and clinical examination; the diagnosis of FH was made. The diagnosis of homozygous FH in our patient was based on the presence of: serum cholesterol levels >500 mg/dL with normal TG levels, appearance of xanthomas in the first decade of life (at the age of 10 years), presence of hypercholesterolemia in both parents and in the siblings and the presence of premature atherosclerosis.

He was also fulfilling the criteria for homozygous FH according to Familial Hypercholesterolemia of the European Atherosclerosis Society (Table 3).9 But due to financial constraint, nonavailability of test at our center and some technical problems, LDL receptor studies and genetic analysis could not be done in our patient. So, the differentiation into true homozygous and compound heterozygous type could not be made here. It is pertinent to mention that according to National Lipid Association, genetic screening for FH is generally not needed for diagnosis or clinical management but may be useful when the diagnosis is uncertain and moreover importantly, a negative genetic test does not exclude FH, since approximately 20% of clinically definite FH patients will not be found to have a mutation despite an exhaustive search using current methods.

Table 2. The Simon-Broome Diagnostic Criteria Definite FH a. TC >6.7 mmol/L or LDL-C above 4.0 mmol/L in a child <16 years or TC >7.5 mmol/L or LDL-C above 4.9 mmol/L in an adult (levels either pre-treatment or highest on treatment) PLUS b. Tendon xanthomas in patient, or in first-degree relative (parent, sibling, child), or in second-degree relative (grandparent, uncle, aunt) OR c. DNA-based evidence of an LDL receptor mutation or familial defective apoB-100 Possible FH Above a) PLUS One of d) or e) d. Family history of myocardial infarction: below age of 50 in second-degree relative or below age 60 in first-degree relative e. Family history of raised cholesterols: >7.5 mmol/L in adult first- or second-degree relative or >6.7 mmol/L in child or sibling under 16

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CARDIOLOGY and appropriate management of the condition is very much necessary to prevent premature deaths. The family members of the patient should also be screened for dyslipidemia.

Table 3. Criteria for the Diagnosis of Homozygous FH Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9 or LDLRAP1 gene locus* OR

REFERENCES

An untreated LDL-C >13 mmol/L (500 mg/dL) or treated LDL-C ≥8 mmol/L (300 mg/dL)* together with either

1. Nemati MH, Astaneh B. Optimal management of familial hypercholesterolemia: treatment and management strategies. Vasc Health Risk Manag. 2010;6(1):1079-88.

Cutaneous or tendon xanthoma before age 10 years OR Untreated elevated LDL-C levels consistent with heterozygous FH in both parents *These LDL-C levels are only indicative, and lower levels, especially in children or in treated patients, do not exclude history of FH.

In untreated patients of homozygous FH with markedly elevated LDL-C levels overt atherosclerosis develops before the age of 20 years, and they generally do not survive past 30 years.10 Thus, the primary goals of management are prevention of ASCVD by early and comprehensive control of hypercholesterolemia, and early detection of complications, with specific focus on ostial occlusion and aortic stenosis. Unfortunately, it is typically diagnosed when considerable coronary atherosclerosis has already developed, emphasizing the need for optimization of treatment in childhood.

Treatment consists of dietary, lifestyle modification and drugs like statins and bile acid sequestrants.3,4 New treatment options are required to decrease LDL-C levels beyond those currently achieved. The new classes of pharmacotherapy under investigation to control LDL-C levels include agents which modify LDL-C production, such as inhibitors of apolipoprotein B, or those which affect LDL-C catabolism, such as inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9), a protein which is responsible for the degradation of the LDL receptor. Therapies which raise HDL-C are also being evaluated. In nonresponsive patients to medical therapy; LDL apheresis and liver transplantation can also be considered in such patients.5 CONCLUSION Untreated FH can lead to severe atherosclerotic disease resulting in life-threatening complications. FH is both underdiagnosed and undertreated, particularly among children and deficiencies in the diagnosis and treatment of FH indicate the need for greatly increased awareness and understanding of this disease, both on the part of physician and public. Hence, early diagnosis

2. Maiorana A, Nobili V, Calandra S, Francalanci P, Bernabei S, El Hachem M, et al. Preemptive liver transplantation in a child with familial hypercholesterolemia.

Pediatr Transplant. 2011;15(2):E25-9.

3. Raal FJ, Pilcher GJ, Panz VR, van Deventer HE, Brice BC, Blom DJ, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation.

2011;124(20):2202-7.

4. Fahed AC, Nemer GM. Familial hypercholesterolemia: the lipids or the genes? Nutr Metab (Lond). 2011;8(1):23.

5. Rader DJ, Hobbs HH. Disorders of lipoprotein metabolism.

In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL (Eds.). Harrison’s Principles of Internal Medicine. Volume 2, 19th Edition. McGraw-Hill; 2015. pp.

2435-49.

6. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol.

2004;160(5):421-9.

7. Civeira F; International Panel on Management of Familial Hypercholesterolemia. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis. 2004;173(1):55-68.

8. Scientific Steering Committee on behalf of the Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. BMJ. 1991;303(6807):893-6.

9. Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, et al; European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia.

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146-57.

10. Widhalm K, Binder CB, Kreissl A, Aldover-Macasaet E, Fritsch M, Kroisboeck S, et al. Sudden death in a 4-yearold boy: a near-complete occlusion of the coronary artery caused by an aggressive low-density lipoprotein receptor mutation (W556R) in homozygous familial hypercholesterolemia. J Pediatr. 2011;158(1):167.

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COMMUNITY MEDICINE

Research and Publication: How is It Relevant in Today’s World?

AMAR RANJAN*, IFFAT JAMAL†, DIVYA SETHI‡, LAWANYA RANJAN#, MEENAKSHI WADHWANI¥

ABSTRACT In terms of research and publication in India, it is lagging far behind the western world. Presently, the Government of India is also promoting it at a large scale. Previously, the research work was used to be a part of master or PhD (Doctor of Philosophy) course only. Now its requirement is being extended amongst faculties for their career progression, although it is still limited to only the topmost level of Institutions in our country. It is also becoming a part of undergraduate students study curriculum.

Many organizations in India are promoting such programs. These are Indian Council of Medical Research, Dept. of Science and Technology, Dept. of Biotechnology, University Grants Commission, etc. Now the research profession has also become a highly paid service in our country. We are describing below in brief the importance of research and publication in the current era.

Keywords: Research, publication, medical writing

A

mong academics, the maxim “publish” or perish” (i.e., publish your research or risk losing your job) is a threatening reminder of the importance of research and publication in today’s world.1 Publishing articles, hypotheses, theories, research papers is critical for the progress of science.

The scientific community can only fulfill its roles as fact checker, visionary, whistleblower, if it has trusted information about the work of community members.

Scientists, medical doctors, research students distribute information about their ideas in many ways—informally communicating with colleagues, making presentations at conferences, writing books, etc.—but among these different modes of communication, peer reviewed journal articles are especially important.2

RESEARCH AND PUBLICATION IN INDIAN ACADEMIC CURRICULUM Research and article publication are an integral and important part of the professional activities of faculties of academic institutions. Traditionally, Doctor of Philosophy (PhD) students participate in research in their respective fields of study but in recent years students of Master course have increasingly become involved in research as well. Writing a thesis in academic Master course is the first step of learning of process of research under the guidance of an expert of a field. Student’s involvement fulfils the purpose of the Faculty’s, research activities too, because in this way students acquire new knowledge and use it in practice.

Thus, they contribute to the development of research in individual scientific discipline.

PROCESS OF GETTING RESEARCH GRANT, MEDICAL WRITING AND PUBLICATIONS

*Assistant Professor Lab Oncology Unit, Dr. BRA-IRCH-AIIMS, New Delhi †Senior Resident AIIMS, Patna, Bihar ‡Specialist ESI Hospital, Jhilmil, Delhi #Master of Engineering (Management) Royal Melbourne Institute of Technology (RMIT) University Victoria, Melbourne, Australia ¥Senior Research Officer Dr RP Center for Ophthalmic Sciences, AIIMS, New Delhi Address for correspondence Dr Amar Ranjan R. No. 422, Lab Oncology Unit, Dr. BRA-IRCH, AIIMS, New Delhi E-mail: dr.amarranjan@rediffmail.com

PhD programs incorporate various activities. Apart from studying (students take exams and have to prepare for them) and teaching (PhD students participate in teaching specialized courses), these include research and publication too. Students write a research project on one topic at their host institution with the help of their guide/guides. The project needs Ethical Clearance to be provided by the Institute’s Ethical Committee. That project is then sent for funding offered by different funding agencies. The funding

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COMMUNITY MEDICINE agencies have an interview of the Principal Investigator before a scientific committee. With successful interview, funds are offered to the candidate to start work. Timeto-time, investigators need to send progress report of that project. The duration of project may be from 1-5 years or even more.

Funding agencies in India are Dept. of Science and Technology (DST), Dept. of Biotechnology (DBT), University Grants Commission (UGC), Indian Council of Medical Research (ICMR), etc. Details of these agencies are available on internet. There are certain International funding agencies too, which provide opportunity to work at International level.

On completion of a research project, students present their works in National and International conferences.

They submit their work in the form of manuscript to journals and get it published. Such activities add points in their academic career.

These activities are related to the writing of the student’s doctoral thesis and are as important as their studying and teaching components.3 Publications are a necessary prerequisite for the student to be able to defend his doctoral thesis and for the students’ further career growth. PhD students, medical students, research fellows focus their attention on research in their respective field. The results of their research are usually presented in various publications. The common forms of publications in a journal include original article, review article, case reports, letter to the editor, etc. This may also be in the form of monograph, chapter in a book, conference paper, research report, etc.

RELEVANCE OF RESEARCH AND PUBLICATION IN TODAY’S WORLD Most of the developed European countries are actively involved in research works. They are scientifically progressing in terms of new inventions, new devices and technologies.4 RELEVANCE IN MEDICAL FIELD In medical field, the scope for research and publication is much more as here we are dealing with human body which is far more complex in its constitution than the machines. Newer genes controlling human

behavior, carcinogenesis and disease processes are being discovered that are proving useful treatment options to patients.5 These are being revealed only by thorough research and practical works. A large amount of money is being spent on the medical research and development works. Qualified doctors and scientists are being recruited for bringing new ideas and innovations in the field of science.6 SCENARIO IN INDIA In India; however, the situation is a little worse as compared to developed countries. Not much financial, educational and government aids are being provided for conducting research and development. Only few premier Indian institutes have the facilities for conducting research and publications. Much more efforts are required in this direction by the Government of India, to promote research works at all teaching Institutions in our country.

CONCLUSION Research and publications are an essential tool for progression of mankind. The developments we have achieved in medical, scientific and technological fields have been possible by only and only research and development.

REFERENCES 1. Maddux CD. Publishing in scholarly journals: A guide for beginners - Part III. Computers in the Schools.

1996(b);12(4):7-14.

2. William W. Research Methods in Education: An Introduction. 7th Edition, Boston: Allyn and Bacon; 2000. p. 27.

3. De Rond M, Miller AN. Publish or perish: Bane or boon of academic life? J Manag Inquiry. 2005;14(4):321-9.

4. Hartemink AE. Publish or perish (2) - How much we write.

Bull Inte Union Soil Sci. 1999;96:16-23.

5. Stock WG. What is a publication? On the problem of unit training in science research. In: Fuchs-Kittowski K, Laitko H, Parthey H, Umstätter W (Eds.). Science Research Yearbook 1998. Berlin: Publisher Social Studies of Science; 2000. pp. 239-82.

6. Swales JM. Genre Analysis: English in Academic and Research Settings. Cambridge: Cambridge University Press; 1993.

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DERMATOLOGY

Fine Needle Aspiration Cytology of Nodular Hidradenoma Presenting at an Unusual Site ANNU NANDA*, SANGEETA LAMBA†, DIVYA SETHI‡

ABSTRACT Nodular hidradenomas (NH) are benign adnexal tumors of eccrine origin occurring more commonly in adults on the head and neck region with a male to female ratio of 1:1.7. They are freely movable, may be pedunculated or cystic with an average size of 0.5-2 cm. While the cytomorphology of a variety of primary cutaneous neoplasms has been described, knowledge of the cytological features of hidradenomas is limited because only rare case reports have been described in the literature.

Understanding of the cytologic features of skin adnexal tumors is valuable in distinguishing benign cutaneous neoplasms from malignant ones or metastatic disease. We report cytological features of a case of benign adnexal tumor with a subsequent histological diagnosis of NH occurring at a rare site.

Keywords: Nodular hidradenoma, adnexal tumor, eccrine tumor

N

odular hidradenoma (NH) is a rare benign adnexal tumor usually presenting as a solitary, firm, slow growing intradermal nodule. Understanding of the cytologic features of skin adnexal tumors is valuable as distinguishing benign cutaneous neoplasms from malignant primaries or metastatic disease on cytology is often difficult.

While the cytomorphology of a variety of primary cutaneous neoplasms has been described knowledge of the cytological features of hidradenomas is limited because only rare case reports have been described in the literature.

We report cytological features of a case of benign adnexal tumor with a subsequent histological diagnosis of NH occurring at gluteal region being a rare site.

aspiration (FNA) yielded mucoid material. Smears were cellular and showed sheets, cohesive clusters and singly scattered epithelial cells in a myxoid background (Fig. 1). These cells showed round to oval nuclei, evenly distributed nuclear chromatin and moderate amount of eosinophilic cytoplasm (Figs. 2 and 3).

At places cellular clusters showed closely intermingled eosinophilic stromal matrix and a few mutlinucleate giant cells and histiocytes were noted in the background.

A diagnosis of benign adnexal tumor was rendered and the mass was excised. On histopathological examination, a diagnosis of NH was made (Fig. 4).

CASE REPORT A 48-year-old male presented with a 2.5 cm firm swelling in left gluteal region for the last 8 months. Fine needle

*Associate Professor †Senior Specialist ‡Specialist Dept. of Pathology ESI Hospital, Rohini, Delhi Address for correspondence Dr Annu Nanda G-506, Som Vihar, Sector 12, RK Puram, New Delhi - 110 022 E-mail: annunanda@rediffmail.com

Figure 1. FNA smears showing cohesive clusters and sheets of epithelial cells (Giemsa, 10x).

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DERMATOLOGY DISCUSSION Nodular hidradenomas (NH) are regarded as benign adnexal tumors of eccrine origin occurring more commonly in adults with a male to female ratio of 1:1.7.

They are freely movable and may have pedunculated or cystic appearance with smooth, thickened, atrophic or ulcerated overlying skin. The average size is 0.5-2 cm but larger ones have been reported and occasionally, multiple lesions can be seen. Although any site may be affected, hidradenomas are found most frequently on the head and neck. Gluteal region is an uncommon site as was seen in the present case.

Figure 2. Polygonal tumor cells with round to oval nuclei and moderate amount of cytoplasm (Giemsa, 40x).

Fine needle aspiration cytology (FNAC) is a time and cost-effective easily accessible technique for diagnosis of adnexal tumors and helps in differentiating it from other tumors. However, cytology of NH has rarely been reported as there are very few reports in the literature of the cytologic characteristics of malignant NH and NH. The cytology smears from the tumor show cohesive clusters of polygonal cells having a bland nucleus and abundant cytoplasm that may stain eosinophilic, clear or basophilic. Intranuclear cytoplasmic pseudoinclusions may be seen.

Occasional rosettes or duct like structures are noted.

Cystic degeneration represented by amorphous background material and foam cells, is a common feature in hidradenoma as was seen in the index case although the exact subtyping could not be performed prospectively.

Figure 3. Evenly distributed nuclear chromatin with mild nuclear overlapping in tumor cells. Inset shows a multinucleated giant cell (Giemsa, 40x).

Figure 4. Histological section showing tumor cells with eosinophilic to clear cytoplasm and bland nuclear chromatin forming luminae (H&E, 40x).

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To the best of our knowledge, no prospective diagnoses of hidradenoma have been made on FNA and published.

In all the cases of NH reported by Dubb et al, a diagnosis of a benign skin adnexal tumor was made on FNA. Kumar and Verma indicated that unusual cytomorphologic features and a diversity of cell types such as polygonal cells, clear cells and spindle cells should raise the suspicion of a cutaneous adnexal tumor. If amorphous background material with or without foam cells is seen in a subcutaneous mass aspirate with a biphasic staining pattern with both eosinophilic cytoplasm and cells staining clear to basophilic associated with epithelial duct like cells and tubular structures, the possibility of hidradenoma should be considered. Rekhi et al observed metachromatic stroma, intranuclear grooves and pseudoinclusions that have been uncommonly described by Khurshid et al. Eosinophilic stromal material with attached epithelial cells was noted in the present case also. On finding nuclear pleomorphism and hyperchromatism, macronucleoli, giant cells and mitotic

DERMATOLOGY activity in addition to the above-mentioned features an atypical hidradenoma with increased risk of recurrence and possible malignant behavior must be considered.

The malignant variants show high cellularity and nuclear pleomorphism on FNA. Even though NH is regarded as a benign tumor, it may recur after inadequate surgical excision. Thus, they need to be excised with adequate margins.

Although all skin adnexal tumors, even if they appear overtly benign should have histopathologic confirmation, the recognition and attention to the cytologic features described above should allow distinguishing from other lesions. Recognition that the lesion is a skin adnexal tumor and if possible, being able to subtype it will allow appropriate management.

SUGGESTED READING 1. Hernández-Pérez E, Cestoni-Parducci R. Nodular hidradenoma and hidradenocarcinoma. A 10year review. J Am Acad Dermatol. 1985;12(1 Pt 1): 15-20.

2. Stratigos AJ, Olbricht S, Kwan TH, Bowers KE. Nodular hidradenoma. A report of three cases and review of the literature. Dermatol Surg. 1998;24(3):387-91.

3. Layfield LJ, Glasgow BJ. Aspiration biopsy cytology of primary cutaneous tumors. Acta Cytol. 1993;37(5): 679-88.

4. Gottschalk-Sabag S, Glick T. Chondroid syringoma diagnosed by fine-needle aspiration: a case report.

Diagn Cytopathol. 1994;10(2):152-5.

6. Varsa EW, Jordan SW. Fine needle aspiration cytology of malignant spiradenoma arising in congenital eccrine spiradenoma. Acta Cytol. 1990;34(2):275-7.

7. Gottschalk-Sabag S, Glick T. Fine-needle aspiration of nodular hidradenoma: a case report. Diagn Cytopathol.

1996;15(5):395-7.

8. Dubb M, Michelow P. Cytologic features of hidradenoma in fine needle aspiration biopsies. Acta Cytol. 2009;53(2):179-82.

9. Rekhi B, Ingle A, Patil B, Jambhekar NA. Cytomorphological spectrum of a nodular hidradenoma in a young girl presenting with an inguinal soft tissue mass. Cytopathology.

2011;22(2):135-7.

10. Nasit JG, Dhruva G. Nodular hidradenoma of the scalp: a cytomorphological evaluation on fine needle aspiration cytology. Indian J Dermatol Venereol Leprol.

2014;80(6):569-72.

11. Ray R, Dey P. Fine needle aspiration cytology of malignant hidradenoma. Acta Cytol. 1993;37(5):842-3.

12. Garcia-Bonafe MM, Campins MM, Redecilla PH. Malignant nodular hidradenoma on the scalp: report of a case with fine needle aspiration cytology features and histologic correlation. Acta Cytol. 2009;53(5):576-80.

13. Jinnah AH, Emory CL, Mai NH, Bergman S, Salih ZT. Hidradenocarcinoma presenting as soft tissue mass: Case report with cytomorphologic description, histologic correlation, and differential diagnosis. Diagn Cytopathol.

2016;44(5):438-41.

14. Kumar N, Verma K. Clear cell hidradenoma simulating breast carcinoma: a diagnostic pitfall in fine-needle aspiration of breast. Diagn Cytopathol. 1996;15(1):70-2.

15.

5. Jain P, Nanda A, Handa U, Bal A, Mohan H, Gupta SK. FNA diagnosis of recurrent sebaceous carcinoma.

Diagn Cytopathol. 2006;34(2):124-6.

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Khurshid A, Yaqoob N, Devan HA, Pervez S. ‘Nuclear grooves’ in nodular hidradenoma: frequency and significance of an unrecognized histopatological feature. J Cutan Pathol. 2007;34(11):871-5.

Most Melanomas Arise de novo Rather Than from a Pre-existing Nevus Most melanomas arise de novo rather than from a pre-existing nevus. A systematic review and meta-analysis of 38 observational cohort and case-control studies found that while 29.1% of melanomas likely arose from a preexisting nevus, around 71% developed de novo. The study findings are published online August 29, 2017 in the Journal of the American Academy of Dermatology.

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ENT

An Observational Study to Evaluate the Efficacy, Safety and Tolerability of Amoxicillin/Clavulanic Acid in Patients with Otitis Media: BEST Study MANJULA S*, KRISHNA KUMAR M†

ABSTRACT Background: Otitis media (OM) is a leading cause of healthcare visits and antibiotic prescriptions in ENT practice. Its complications and sequelae are important causes of preventable hearing loss. An observational study was conducted to evaluate the efficacy, safety and tolerability of amoxicillin/clavulanic acid (Bactoclav) in subjects with OM. Methodology: A multicentric, open-labeled, nonrandomized, observational study was conducted to assess the efficacy, safety and tolerability of amoxicillin/ clavulanic acid in Indian subjects with OM for 7 days (Bactoclav Efficacy, Safety and Tolerability - BEST study). A signed informed consent was obtained from all the subjects who participated in the study. Amoxicillin 500 mg/clavulanic acid 125 mg (Bactoclav 625 mg) was advised thrice-daily for 7 days. Physical and systemic examination data and otological symptom score of each recruited subject were documented before initiating therapy (baseline) and at the end of 7 days (end of study).

Results: A total of 1,862 subjects completed the 1 week study. Among them, 978 (52.25%) were men and 894 (47.75%) were women. There was a significant improvement in study subjects post-treatment with amoxicillin/clavulanic acid. Overall, 1,690 study subjects had no ear discharge post-treatment with amoxicillin/clavulanic acid. The mean total otological symptom score was 5.71 ± 1.56 at baseline and there was significant reduction to 1.87 ± 1.38 after treatment with amoxicillin 500 mg/clavulanic acid 125 mg for 7 days (p < 0.01). Clinical success rate was 93.7% at the end of treatment. There were no significant drug-related adverse events reported with amoxicillin/clavulanic acid. Conclusion: In our study, amoxicillin/clavulanic acid (Bactoclav) significantly decreased the otological symptoms, and improved the clinical outcome in subjects with OM.

Keywords: Otitis media, hearing loss, amoxicillin/clavulanic acid, otological symptom score, ear discharge

O

titis media (OM) is a group of complex infective and inflammatory conditions affecting the middle ear, with a variety of subtypes differing in presentation, associated complications and treatment. OM is a leading cause of healthcare visits worldwide, and its complications are important causes of preventable hearing loss, particularly in the developing countries.1

OM is characterized by the presence of middleear effusion together with symptoms including ear discharge (otorrhea), fever, irritability and earache.2 OM is subdivided into several disease subcategories: acute otitis media (AOM), recurrent AOM (rAOM), OM with effusion (OME) and chronic suppurative OM (CSOM).2 If AOM is left untreated, it may lead to

*Vice President †Senior Manager Dept. of Medical Sciences Micro Labs Ltd., Bengaluru, Karnataka

permanent loss of hearing. AOM episodes may lead to chronic forms, such as CSOM, potentially resulting in severe complications, such as intracranial infection, hearing impairment/loss and facial paralysis.1 OME can occur during the resolution of AOM once the acute inflammation has resolved but bacteria may still be present,3 while in CSOM ongoing inflammation of the middle ear leads to perforation of the tympanic membrane and otorrhea persisting for at least 2 weeks.1 Bacteria and viruses are responsible for 35-55% and 20-30% of AOM cases, respectively.1-3 The two primary pathogens are Streptococcus pneumoniae and nontypeable Haemophilus influenzae. Other pathogens of OM include Staphylococcus aureus, Moraxella catarrhalis and Streptococcus pyogenes.4 The treatment for OM primarily depends on antibiotic therapy.5 The Indian antibiotic guideline, the American Academy of Otolaryngology (AAO) and American Academy of Family Physicians (AAFP) recommended amoxicillin/clavulanic acid as one of the preferred antibiotics for treatment for OM.4,6

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ENT Development of resistance to amoxicillin is a major clinical problem because of inactivation by plasmidmediated penicillinases. Patients with recurrent OM will be at higher risk of being infected with penicillinnonsusceptible S. pneumoniae or β-lactamase-producing strains of H. influenzae.5 Combination with a β-lactamase inhibitor, such as clavulanic acid protects amoxicillin from enzymatic hydrolysis. Combination containing amoxicillin-clavulanic acid increases its spectrum of action and restores the efficacy of amoxicillin against amoxicillin-resistant bacteria that produce β-lactamase.5 PURPOSE OF THE STUDY The present study was designed to evaluate the efficacy, safety and tolerability of amoxicillin 500 mg + clavulanic acid 125 mg (Bactoclav Efficacy, Safety and Tolerability - BEST study) in patients with OM by measuring otological symptoms, otological scoring, clinical outcome and adverse drug reactions.

METHODOLOGY This was a multicentric, open-labeled, nonrandomized, observational study to assess the efficacy, safety and tolerability of amoxicillin 500 mg + clavulanic acid 125 mg (Bactoclav) in patients with OM. The study was conducted after receiving approval from Independent Ethics Committee which is recognized by the Indian Regulatory Authority, Drug Controller General of India.

Male and female subjects aged between 18 and 60 years were included. Subjects diagnosed with OM based upon detailed history and otoscopic examination were included in the study. Subject with clinical evidence of OM who had, or were at risk for, recurrent or persistent OM were also included. The subjects with following criteria were excluded: female subjects who were pregnant or lactating were excluded. Severe cases of OM for which hospitalization or parenteral antibiotic treatment was required and subjects with otological symptom score of ≤4 and >8 were also excluded from the study. Subjects with foul smelling discharge and those who received antibiotic in the preceding 4 weeks of screening were excluded. Safety of amoxicillin 500 mg/clavulanic acid 125 mg (Bactoclav) in subjects with OM was assessed by monitoring the frequency and type of adverse events (AEs) occurring in the subjects.

Study centers were selected in this study from urban and suburban centers by convenience sampling. Two hundred centers were included in this study. Informed consent was taken from all participating subjects.

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Physical and systemic examination data of each recruited subject were collected before initiating therapy (baseline) and at the end of 7 days (post-treatment). The total otological symptom score7-9 was calculated in all the study subjects at baseline and after treatment. The total otological symptom score was cumulative score of each of the parameter viz., amount of discharge, type of discharge, tinnitus (score on the scale of 0 to 3 was given for each parameter and higher scores indicating greater severity of symptoms).7-9 Amoxicillin 500 mg/clavulanic acid 125 mg (Bactoclav 625 mg) was given thrice-daily for 7 days.

Number of subjects achieving “treatment success” was considered to be the effectiveness parameter.7-9 Treatment success was based on changes in the otological symptoms scores at Day 8 visit. It was subdivided into: (a) “clinical cure” if the otological symptom score was <3 at Day 8 visit or (b) “clinical improvement” if the otological symptom score was between 3 and 5 on Day 8 visit or (c) “treatment failure” was declared if there was no change or increase in the baseline otological symptom score on Day 8.

STATISTICS Demographic characteristics and results of otological symptom scores are summarized with descriptive statistics, including mean and standard deviation (SD) for continuous variables, and frequency and percentages for categorical variables. t-Test is used and p ≤ 0.05 is considered to be significant.

RESULTS A total of 1,987 subjects were recruited in the study; of these, 1,862 subjects completed the 1 week study.

Among them, 973 (52.25%) were men and 889 (47.75) were women. Mean age of the subjects who were recruited, was 34.28 ± 7.8 years. Mean weight was 69.1 ± 9.08 kg and mean body mass index (BMI) was 27.04 ± 4.28 kg/m2 (Table 1). The participant patient age group distribution is represented in detail in Figure 1.

At the baseline, among the recruited study subjects with OM, 58% were afebrile. Sixty percent of the subjects had a past history of OM episodes. Furthermore, 51% of the subjects had past history of antibiotic usage for OM. At the baseline data, 40% of the subjects were suffering from recurrent OM. Fifteen percent of the study subjects had >3 episodes of OM, 16% had 3 episodes, 50% of the study subjects had at least 2 episodes of OM in past 1 year, while 19% had 1 episode of OM during the past 1 year.

ENT Table 1. Demographic Characteristics of Study Subjects Mean age, years

34.28 ± 7.8

Men, N (%)

973 (52.25)

Women, N (%)

889 (47.75)

Table 2. Type of Ear Discharge Pre and Post Amoxicillin/Clavulanic Acid (Bactoclav) Treatment in Study Subjects with OM

No discharge 800

731

No. of study subjects

700 600

Baseline number of subjects, N (%)

Post-treatment number of subjects, N (%)

112 (6)

1,690 (90.76)

Mucoid

659 (35.4)

84 (4.51)

Mucopurulent

879 (47.2)

77 (4.13)

Purulent

212 (11.4)

11 (0.6)

494

500

398

400 300

239

8 5.71 ± 1.56

200 7

0 18-30

31-40

41-50

51-60

Year

Figure 1. Recruited patient age group.

Change in Ear Discharge and Type of Discharge In the BEST study, prior to the treatment with amoxicillin/clavulanic acid (Bactoclav) 35.5% (659) of the study subjects had mucoid discharge and 47.2% (879) subjects had mucopurulent discharge. Two hundred twelve subjects had purulent discharge. After treatment only 84, 77 and 11 subjects had score of 1, 2 and 2, respectively. There was a significant improvement in study subjects post-treatment with amoxicillin/ clavulanic acid (Bactoclav). Overall, 90.76% (N = 1,690) study subjects had no discharge post-treatment with amoxicillin/clavulanic acid (Bactoclav) (Table 2).

Furthermore, 1,054 (56.8%) subjects at baseline had the discharge entering into external auditory meatus (EAM) and 679 (36.3%) subjects had the discharge confined to the middle ear. After treatment with amoxicillin/ clavulanic acid (Bactoclav), only 106 subjects (5.7%) had discharge entering into EAM and 121 (6.5%) subjects had discharge confined to the middle ear.

Otological Symptom Score In BEST study, the mean total otological symptom score was 5.71 ± 1.56 at baseline and there was significant reduction in mean total otological symptom score 1.87 ± 1.38 after treatment with amoxicillin/clavulanic acid (Bactoclav) for 7 days (p < 0.01; Fig. 2).

Number of subjects achieving “treatment success” was considered to be the effectiveness parameter. Treatment

Mean total otological symptom score

100

6 5 4 1.87 ± 1.38 3 2 1 0 Baseline

Post-treatment

Figure 2. Change in total otological symptom score.

success was based on changes in the otological symptoms scores at Day 8 visit. It was seen that 81.6% (N = 1,519) study subjects had “clinical cure” and the otological symptom score was <3 on Day 8 visit, 12.1% (N = 226) of the study subjects showed “clinical improvement” with otological symptom score between 3 and 5 on Day 8. Treatment failure was observed only in 6.3% (N = 117) of subjects (Fig. 3).

Safety Profile In our study, overall the AEs reported were generally mild. The total number of AEs reported was 9.82% (N = 183) of total study population. AEs reported by subjects included nausea (1.93%), vomiting (2.25%), diarrhea (2.84%), abdominal pain (2.36%) and hypersensitivity reactions (0.42%). These were mostly transient and mild. All the subjects who had reported the AEs recovered completely without any medications

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ENT Amoxicillin/clavulanic acid shows good activity against the main pathogens associated with AOM, including penicillin-susceptible and -intermediate strains of S. pneumoniae, and β-lactamase-producing strains of H. influenzae and M. catarrhalis. It has activity against penicillin-resistant S. pneumoniae; formulation has been developed with the aim of providing better coverage for penicillin-resistant strains.12 Amoxicillin/ clavulanic acid is recommended as first- and/or secondline antibiotic choice for AOM subjects according to the recommendations of the AAO guideline and also the Indian antibiotic guideline for OM management.4,6

90 81.6 80

Clinical outcome percentage

70 60 50 40 30 20 12.1 10

6.3

0 Clinical cure

Clinical improvement

Failure

Figure 3. Clinical outcome (percentage) in study subjects after treatment with Bactoclav.

being given and none of them had any sequelae, which establishes the safety of amoxicillin/clavulanic acid (Bactoclav).

DISCUSSION Otitis media (OM) refers to an inflammation in the middle ear cleft and is accompanied by effusion of fluids into the middle ear due to infection, which may be associated with the presence or absence of tympanic membrane perforation.10 The vulnerability of OM in relation to etiopathogenesis is due to the involvement of multiple factors such as demographic, genetic, environmental and other health-related factors like infections, allergy, asthma, eustachian tube dysfunction, cleft palate and adenoid hypertrophy, etc.10 The presence of fluid in middle ear leads to longterm morbidity with varying degrees of hearing loss in children and adults.10 OM is highly prevalent worldwide and is the main cause of hearing impairment in developing countries.

The World Health Organization (WHO) has reported that hearing impairment in 42 million people in the world was mainly caused by OM.11 The prevalence of OM varies in different countries, populations and ethnic groups. Studies around the world have reported that the prevalence of AOM varies from 2.3% to 20%, chronic otitis media (COM) 4% to 33.3%.11 In our BEST study, 56% of the subjects had COM and 44% of the subjects had AOM.

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In the BEST study, prior to the treatment with amoxicillin/clavulanic acid (Bactoclav), 35.5% (659) of the study subjects had mucoid discharge, 47.2% (879) of the study subjects had mucopurulent discharge and 212 subjects had purulent discharge. After treatment only 84, 77 and 11 subjects had score of 1, 2 and 2, respectively. Overall, 90.76% (N = 1,690) study subjects had no discharge post-treatment with amoxicillin/ clavulanic acid (Bactoclav). There was a significant improvement in study subjects post-treatment with amoxicillin/clavulanic acid (Bactoclav).

Furthermore, 1,054 (56.8%) subjects at baseline had the discharge entering into EAM, while 679 (36.3%) subjects had the discharge confined to the middle ear. After treatment with amoxicillin/clavulanic acid (Bactoclav), only 106 subjects (5.7%) had discharge entering into EAM and 121 (6.5%) subjects had discharge confined to the middle ear. The results obtained from the present study demonstrate the efficacy of amoxicillin/clavulanic acid similar to the previously published studies on the role of amoxicillin-clavulanic acid in subjects with OM.12,13 In BEST study, the mean overall otological symptom score was 5.71 ± 1.56 at baseline and there was significant reduction in the otological symptom score 1.87 ± 1.38 after treatment with amoxicillin/clavulanic acid (Bactoclav) for 7 days (p < 0.01). The change in OM score is better than the results established in the comparative studies on cefpodoxime and ciprofloxacin in OM by Ghosh et al.14 The mean change in otological symptom score and clinical outcomes are better than the studies published by Yadav et al.8 Furthermore, clinical cure rate was found to be 81.6% with amoxicillin/clavulanic acid (Bactoclav) treatment, while 12.1% of the study subjects showed clinical improvement. This is higher than the previously conducted study by Vishwakarma et al9 in subjects with OM. The safety profile data obtained in this study

ENT indicates that there was no significant drug-related AE or serious event reported thus reiterating safety of amoxicillin/clavulanic acid.12 CONCLUSION Amoxicillin/clavulanic acid (Bactoclav) lowered the otological symptoms and improves the clinical outcome in OM subjects, which was clinically and statistically significant. Clinical success rate was 93.7% at the end of treatment. There were no significant drug-related AEs reported in the BEST study. Thus, amoxicillin/ clavulanic acid (Bactoclav) is safe, well-tolerated and valuable choice for the management of OM. REFERENCES 1. Qureishi A, Lee Y, Belfield K, Birchall JP, Daniel M. Update on otitis media - prevention and treatment. Infect Drug Resist. 2014;7:15-24.

2. Schilder AG, Marom T, Bhutta MF, Casselbrant ML, Coates H, Gisselsson-Solén M, et al. Panel 7: Otitis media: Treatment and complications. Otolaryngol Head Neck Surg. 2017;156(4 Suppl):S88-S105.

3. Leskinen K, Jero J. Acute complications of otitis media in adults. Clin Otolaryngol. 2005;30(6):511-6.

4. Rosenfeld RM, Shin JJ, Schwartz SR, Coggins R, Gagnon L, Hackell JM, et al. Clinical practice guideline: otitis media with effusion (Update). Otolaryngol Head Neck Surg.

2016;154(1 Suppl):S1-S41.

Available at: www.ncdc.gov.in/writereaddata/linkimages/ AMR_guideline7001495889.pdf. Accessed on 25 July 2017.

7. Al-Abbasi AM. Efficacy of povidone iodine in treatment of active chronic suppurative otitis media. J Indian Med Assoc. 2006;38:118-22.

8. Yadav L, Singh H, Chandra H. A comparative study to evaluate the effectiveness and efficacy of topical application of 1.5% acetic acid and 0.3% gentamicin sulphate in CSOM patients of tertiary care teaching hospital of North India.

IOSR J Dent Med Sci. 2015;14(8):112-8.

9. Vishwakarma K, Khan FA, Nizamuddin S, Yadav L. Role of topical acetic acid in comparison to gentamicin for the management of chronic suppurative otitis media. Int Arch BioMed Clin Res. 2015;1(1):13-6.

10. Kumari MS, Madhavi J, Bala Krishna N, Meghanadh KR, Jyothy A. Prevalence and associated risk factors of otitis media and its subtypes in South Indian population. Egypt J ENT All Sci. 2016;17(2):57-62.

11. Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, Bavcar A, et al. Burden of disease caused by otitis media: systematic review and global estimates.

PLoS One. 2012;7(4):e36226.

12. Easton J, Noble S, Perry CM. Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media. Drugs. 2003;63(3): 311-40.

13. Hoberman A, Paradise JL, Rockette HE, Shaikh N, Wald ER, Kearney DH, et al. Treatment of acute otitis media in children under 2 years of age. N Engl J Med. 2011;364(2):105-15.

14. Ghosh A, Jana U, Khaowas A, Das S, Mandal A, Das N. Comparison of the effectiveness and safety of cefpodoxime and ciprofloxacin in acute exacerbation of chronic suppurative otitis media: A randomized, Guidelines for Antimicrobial open-labeled, phase IV clinical trial. J Pharmacol Pharmacother. 2012;3(4):320-4.

Diseases. 2016; Ver 1:1-64.

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5. Harmes KM, Blackwood RA, Burrows HL, Cooke JM, Harrison RV, Passamani PP. Otitis media: diagnosis and treatment. Am Fam Physician. 2013;88(7):435-40.

6. National Use in

Treatment Infectious

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ENT

Septoplasty with Adenoidectomy: A Combined Procedure for Nasal Obstruction in Children K MALLIKARJUNA SWAMY*, KP BASAVARAJU†

ABSTRACT Nasal obstruction in children is caused by numerous and diverse factors but the symptoms are essentially snoring, mouth breathing, sleep disturbances and rhinorrhea. Commonest causes of nasal obstruction in children are septal deviation and adenoid hypertrophy. Nasal septal deviation in children is usually due to some form of injury. Performing septoplasty alone in this age group without addressing adenoid may lead to recurrence of symptom i.e., nasal obstruction may lead to failure of procedure, so we combine both procedures in single sitting. So, we have conducted a study of combined septoplasty with adenoidectomy for relief of nasal obstruction in children aged 9-15 years.

Keywords: Septoplasty in children, adenoidectomy, nasal obstruction in children, combined procedure

C

ommonest causes of nasal obstruction in children are septal deviation and adenoid hypertrophy.

Adenoids may be implicated in upper respiratory tract disease due to partial or complete obstruction of the nasal choanae. Nasal obstruction in children is caused by numerous and diverse factors but the symptoms are essentially snoring, mouth breathing, sleep disturbances and rhinorrhea.

During the development of child, mouth breathing may lead to severe physical developmental disorder (facial, oral, nasal and thoracic), which may lead to the cognitive impairment. Nasal septal deviation in children is usually due to some form of injury. There is much debate as to whether septal surgery is appropriate in the growing nose. The main nasal growth center of the nose is the contact area between quadrangular cartilage and vomer and even minor disruption here can lead to significant problems with final midfacial contour.

Furthermore, evidence is available which states that not performing surgery on children affected by nasal

*Assistant Professor †Professor Dept. of ENT JJM Medical College, Davangere, Karnataka Address for correspondence Dr K Mallikarjuna Swamy Assistant Professor Dept. of ENT JJM Medical College, Davangere, Karnataka

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septal deviation can lead to dental malocclusion, facial abnormalities and respiratory morbidity. Therefore, not performing septal surgery in children affected by septal deviation may be more detrimental. Generally, if symptoms are significant, a limited septoplasty with minimal removal of cartilage is acceptable.

Performing septoplasty alone in this age group without addressing adenoid may lead to recurrence of symptom i.e., nasal obstruction may lead to failure of procedure; so, we should combine both procedures in single sitting. Only septoplasty with adenoidectomy when done separately leads to recurrence or persistence of nasal obstruction in children. So, we have conducted a study of combined septoplasty with adenoidectomy for relief of nasal obstruction in children aged 9-15 years.

MATERIAL AND METHODS This study included 20 children between the ages of 9-15 years undergoing adenoidectomy with septoplasty for their obstructive symptoms in Chigateri General District Hospital from November 2010 to February 2012. Among this group, there were 12 boys and 8 girls. Informed written consent taken from parents/ guardians.

Children included in this study met the following criteria: ÂÂ

Continuous nasal obstruction for at least 3 months due to deviated nasal septum (DNS) (Figs. 1 and 2)

ÂÂ

Children without allergic rhinitis.

ENT Exclusion criteria: ÂÂ

Isolated adenoid hypertrophy cases

ÂÂ

Use of topical intranasal/systemic decongestants or steroids.

The patients had history of mouth breathing, snoring, headache and rhinorrhea. A lateral nasopharyngeal soft tissue X-ray was taken to evaluate the size of the adenoids (Fig. 3); all children had considerable size of adenoids.

Adenoid facies and voice were evaluated. The ear was examined to look for eustachian tube dysfunction and its effects. X-ray paranasal sinuses (PNS) was taken to rule out associated sinus infection, in cases, when required; nasal endoscopy was also done to rule out other causes like nasal polyps (Fig. 4), and then complete examination of ear, nose and throat was done.

All children were operated under general anesthesia, the septoplasty procedure was performed with minimal removal of cartilage with septal repositioning (up to 5 mm of inferior strip and posterior end of the cartilage was removed); nasal cavity was packed with vaseline gauge.

Then the children were put in Rose’s position and

Figure 1. Gross DNS to the left with caudal dislocation in a 10-year-old patient.

Figure 3. X-ray of the nasopharynx showing adenoid hypertrophy.

Figure 2. Oblique view of the same patient.

Figure 4. Endoscopic view showing DNS with adenoid in a 9-year-old patient.

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ENT traditional adenoidectomy done, using technique of curettage. Assessment of the adenoid was made digitally prior to curetting, and hemostasis achieved with gauze tamponade.

Table 3. Results of the Procedure at Follow-up Age of the child

Follow-up 1st week 2nd week 3rd week 6 months

9-15 years

10%

20%

50%

90%

The relief of nasal obstruction was assessed subjectively by follow-up of the children or parents postoperatively.

The children were discharged on third day of surgery and advised for follow-up once weekly for 2-3 weeks and once in a month up to 6 months.

adhesions and inadequate nasal douching (Table 3).

No major complications like postnasal bleeding, septal perforation or external deformity were seen.

RESULTS

DISCUSSION

All the 20 children included in the study had nasal obstruction. Mouth breathing was seen in 18 children 90%. Snoring was the associated complaint in 16 children (80%) (Table 1).

The empirical indication for adenoidectomy includes obstructive sleep apnea, recurrent rhinosinusitis and otitis media with effusion. The adenoids when diseased may act as source of infection, supporting bacteria in a biofilm with resultant inflammatory changes in the mucosa of nose, nasopharynx, PNS and middle ear.

On clinical examination, all 20 children had septal deviation of various degrees. Rhinorrhea was seen in 16 children (80%), 8 patients had adenoid facies (40%).

None of the children had caudal dislocation (Table 2).

Out of 20 children, 3 children could not be assessed for outcome of surgery since they dropped out of their follow-up, out of 17 patients, 9 children showed improvement after 1 week of surgery. The remaining 8 children showed relief of symptoms on the 2nd follow-up. Of these, 4 patients who complained of snoring and restless sleep, showed marked symptom reduction (as observed by the parents).

Overall the combined procedure of septoplasty with adenoidectomy yielded good results in terms of nasal obstruction, mouth breathing and snoring in 1st 2nd and 3rd weeks (10%, 20% and 50%, respectively). This can be explained due to postoperative blood clots, minimal Table 1. Distribution of Symptoms Among Patients Symptoms

No. of patients

Percentage (%)

Nasal obstruction

20

100

Mouth breathing

18

90

Snoring

16

80

Rhinorrhea and headache

4

20

Surgery is recommended by the American Association of Otolaryngology-Head and Neck Surgery (AAOHNS) for infective causes including adenoiditis, where two courses of antibiotics have failed and for recurrent rhinorrhea on 4 occasions. A DNS alone is rarely significant enough to be the sole cause of obstructive breathing. Adenoidectomy appears helpful as a part of management of obstructive sleep apnea syndrome (OSAS) and sleep disordered breathing (SDB), but cross-sectional studies support the benefit of adenoidectomy and tonsillectomy performed together for OSAS and SDB. Therefore, a detailed examination is advised to exclude another cause or co-existing pathology that is adenoid hypertrophy prior to considering septoplasty. During our clinical examination in outpatient basis, we have found adenoid hypertrophy even in children above 10 years of age. Septal deviations in children are very common and significantly contribute to nasal obstruction. In children having both septal deviations along with adenoid hypertrophy, either septoplasty or adenoidectomy alone may not give satisfactory results. Hence, septoplasty with adenoidectomy helps in relieving nasal obstruction in such children without any major complications.

CONCLUSION

Table 2. Findings on Clinical Examination of the Patients Sign

No. of patients

Percentage (%)

Septal deviation

20

100

Adenoid facies

08

40

Rhinorrhea

16

80

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We performed combined septoplasty with adenoidectomy in 20 children between 9-15 years of age with good results and without any major complications. Subjective and clinical assessment in these children showed significant improvement in nasal obstruction and mouth breathing. There was also

ENT marked improvement in general health and scholastic performance after long-term follow-up. Septoplasty with adenoidectomy when done separately leads to recurrence or persistence of nasal obstruction in children. So, we conclude that combined procedure septoplasty with adenoidectomy is required for relief of nasal obstruction in children aged 9-15 years.

SUGGESTED READING

2. Lawrence R. Pediatric septoplasy: a review of the literature. Int J Pediatr Otorhinolaryngol. 2012;76(8): 1078-81.

3. Cervera Escario J, Del Castillo Martín F, Gómez Campderá JA, Gras Albert JR, Pérez Piñero B, Villafruela Sanz MA. Indications for tonsillectomy and adenoidectomy: consensus document by the Spanish Society of ORL and the Spanish Society of Pediatrics. Acta Otorrinolaringol Esp. 2006;57(2):59-65.

4.

1. Verucchi F, Caropreso CA. Indications and contraindications for septoplasty in children. VI IAPO Manual of Paediatric Otorhinolaryngol.

■■■■

Adams DA, Cinnamon MJ. Pediatric otolaryngology.

In: Scott-Brown’s Otorhinolaryngology: Head and Neck Surgery. Volume 6, 6th Edition, Butterworth-Heinemann; 1997.

Nasal Cytokine Modulation by Montelukast in Allergic Children: A Pilot Study Background: Allergic rhinitis and asthma are characterized by chronic inflammation due to a Th2 cytokine polarization. Leukotrienes receptor antagonists have been shown to be effective in both diseases.

Objective: Aim of the study was to evaluate the modulation by the antileukotriene montelukast on Th2 and Th1 cytokines in allergic rhinitis. Methods: Fourteen school children affected by persistent allergic rhinitis (PAR) and exercise-induced asthma (EIA) underwent a nasal lavage before and after a 2-week treatment with montelukast.

A panel of cytokines, including IL4, IL13 and IFN-γ, was measured by immunoassay on nasal lavage samples.

Results: Montelukast treatment induced a significant decrease of IL4 and IL13 levels (p < 0.001, for both comparisons), and a significant increase of IFN-γ (p < 0.001). Conclusions: Montelukast treatment reversed a typical Th2 cytokine pattern (IL4 and IL13) toward a Th1 (IFN-γ) predominance in children with PAR and EIA. This effect could be considered relevant for long-term allergic inflammation control and of interest when treating EIA with concomitant PAR.

Quality-of-life Assessment in Patients with Moderate-to-severe Allergic Rhinitis Treated with Montelukast and/or Intranasal Steroids: A Randomized, Double-blind, Placebo-controlled Study Objective: This study investigated improvements in quality-of-life associated with 8 weeks of montelukast and/ or intranasal steroid treatment for moderate-to-severe allergic rhinitis. Methods: A single-center, prospective, randomized, double-blind, placebo-controlled study was carried out. Assessments were made using the Rhinoconjunctivitis Quality of Life Questionnaire and symptom scales. Results: A total of 128 patients (aged 1351 years) were randomly assigned to one of two groups. In the montelukast group, patients were treated with montelukast tablets and fluticasone propionate nasal spray (n = 64). In the placebo group, treatment comprised a placebo and fluticasone propionate. The results showed significant improvements in symptom scores and quality-of-life scores for both groups after 1 month and 2 months of treatment, compared with baseline values; these improvements were significantly greater for the montelukast group compared with the placebo group.

The mean number of loratadine tablets taken by each patient during the study period was only 0.73 for the montelukast group compared with 9 for the placebo group. Conclusion: The combination of montelukast tablets and fluticasone propionate nasal spray improved symptom control and overall quality-of-life for moderate-tosevere allergic rhinitis patients.

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INTERNAL MEDICINE

Incompatibility to All Blood Groups Due to Autoimmune Hemolytic Anemia in a Case of Antiphospholipid Syndrome TUHINA PARVEEN SARWALA*, MANISH N MEHTA†, AJAY C TANNA‡, JEMIMA BHASKAR#, PRATIK K PATEL¥

ABSTRACT Antiphospholipid syndrome is an autoimmune hypercoagulable acquired thrombophilia caused by antiphospholipid antibody, characterized by recurrent arterial and venous thrombosis and/or pregnancy morbidity. It occurs in 1% of general population.

Incompatibility to all blood groups due to autoimmune hemolytic anemia [direct Coombs test - negative] as its manifestation is even rarer. We report the case of a 16-year-old girl presenting with stroke and severe hemolytic anemia.

Keywords: Antiphospholipid syndrome, autoimmune hemolytic anemia, hemolysis, incompatibility, blood groups, hemiplegia

A

ntiphospholipid syndrome (APLS) may be primary - in absence of any other related disease or secondary - associated with other autoimmune (AI) diseases like systemic lupus erythematous (SLE). Rarely, it leads to rapid organ failure due to generalized thrombosis known as catastrophic APLS. APLS may manifest clinically as venous thrombosis - deep vein thrombosis (DVT) and leg ulcers; arterial thrombosis - stroke and myocardial infarction; neurological features - migraine and epilepsy; obstetric complications - eclampsia, fetal loss and hematological conditions - autoimmune hemolytic anemia (AIHA). Diagnosis is made by at least one clinical and one laboratory criteria: raising titers of 1) lupus anticoagulant, 2) anticardiolipin and 3) anti-beta 2 glycoprotein 1 (B2GP1) antibodies, on 2 occasions at least 3 months apart. Clinical features of APLS are summarized in Table 1.

*Senior Resident †Professor and HOD ‡Assistant Professor #Senior Resident ¥1st Year Resident Dept. of Medicine MP Shah Medical College and Guru Gobind Singh Hospital, Jamnagar, Gujarat Address for correspondence Dr Jemima Bhaskar No. 404 Kings Palace, Mehulnagar, Opp. BSNL Telephone Exchange Jamnagar, Gujarat E-mail: jemimabhaskar@yahoo.com

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CASE REPORT A 16-year-old female presented to Guru Gobind Singh Hospital with complaints of acute onset rightsided weakness with mouth-deviated to left side and severe pallor. On examination, patient had right hemiplegia and power was 1/5; patient was also severely anemic. Magnetic resonance imaging (MRI) brain with angiography showed infarct in left frontoparietotemporal lobes and left insular region and anomalies of carotid arteries.

Investigations were done to rule out thrombophilic states. 2D echo was normal. USG abdomen - KUB showed hepatosplenomegaly. Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT), sickling and antinuclear antibody (ANA) profile was negative.

Activated partial thromboplastin time (aPTT) was 60.9.

So, the clinical diagnosis was APLS. Her blood group was B-positive, hemoglobin (Hb) - 8.3 g/dL, unconjugated bilirubin - 0.7 mg/dL. She was transfused with one pint of packed cell volume. Inspite of the transfusion, repeat Hb had fallen to 5 g/dL and unconjugated bilirubin had risen to 3.3 mg/dL. To rule out AIHA as a cause of hemolysis, serological tests were done. Direct Coombs test (DCT) - negative, indirect Coombs test (ICT) - positive, antiphospholipid antibodies (APLA) IgM titer was 45 IU/mL (upper normal limit 18 IU/mL). Patient was given tablet aspirin and injection enoxaparin for infarct. Injection methyl prednisolone and tablet warfarin was given for APLS.

INTERNAL MEDICINE Table 1. Clinical Features of Antiphospholipid Syndrome Manifestation Venous thrombosis and related consequences Deep vein thrombosis Livedo reticularis Pulmonary embolism Superficial thrombophlebitis Thrombosis in various other sites Arterial thrombosis and related consequences Stroke Cardiac valve thickening/dysfunction and/or Libman-Sacks vegetations Transient ischemic attack

DISCUSSION % 39 24 14 12 11 20 14 11

Myocardial ischemia (infarction or angina) and coronary bypass thrombosis Leg ulcers and/or digital gangrene

10

Arterial thrombosis in the extremities Retinal artery thrombosis/amaurosis fugax Ischemia of visceral organs or avascular necrosis of bone Multi-infarct dementia

7 7 6

9

3

Neurologic manifestations of uncertain etiology Migraine

20

Epilepsy

7

Chorea

1

Cerebellar ataxia

1

Transverse myelopathy

0.5

Renal manifestations due to various reasons (renal artery/renal vein/glomerular thrombosis, fibrous intima hyperplasia) Osteoarticular manifestations

3

Arthralgia

39

Arthritis

27

Immune hemolysis is destruction of red blood cells (RBCs) as a results of antibody production with demonstrable antibodies. Immune hemolysis may be autoimmune or alloimmune. Autoimmune response is when patients immune system produces antibodies against their own RBC antigen. This patient had compensated anemia on admission due to decrease in Hb levels.

After transfusion, she developed uncompensated anemia due to acute hemolysis leading to drop in Hb levels to 5 g/dL and rise in unconjugated bilirubin to 3.5 mg/dL. Due to sudden drop in Hb, other causes of hemolysis like hemoglobinopathies were ruled out (NESTROFT and sickling negative). AIHA was confirmed by additional serological testing: DCT - negative and ICT positive. Immune hemolysis in this patient was due to APLA. Vast majorities of patients showing signs and symptoms of AIHA will have positive DCT. Minority only have negative DCT. This is because amount of immunoglobulin G (IgG) coating the RBCs is lower than the detectable limit of commercial IgG reagent. In such cases, esoteric methods are used to detect IgG. Even with esoteric methods, IgG is detectable only half the times.

In this patient, the cause of DCT negative AIHA was APLA that lysed random RBCs of most donors and their own RBCs, making her incompatible to all blood groups.

Then she was transfused with the best compatible match available under careful monitoring, after triple saline wash.

CONCLUSION

Obstetric manifestations (Referred to the number of pregnancies) Pre-eclampsia 10 Eclampsia

4

Fetal manifestations (Referred to the number of pregnancies) Early fetal loss (<10 weeks)

35

Late fetal loss (≥10 weeks)

17

Premature birth among the live births

11

Hematologic manifestations Thrombocytopenia

30

Autoimmune hemolytic anemia

10

Stroke in this young girl led to investigations to rule out thrombophilic states. APLS was diagnosed. Her incompatibility to all blood groups was diagnosed when she had the acute episode of hemolysis after transfusion, as evidenced by sudden drop in Hb levels and rise in unconjugated bilirubin levels. Serological testing showed DCT - negative AIHA to be the cause of incompatibility. The presentation of APLS as DCT negative AIHA is very rare.

SUGGESTED READING 1. Harrison’s Principles of Internal Medicine. 19th Edition, Volume 1. Kasper and Gauci. Chapter 78.

2. Harrison’s Principles of Internal Medicine. 19th Edition, Volume 2. Kasper and Gauci. Chapters - 129, 379.

3. Modern Blood Banking and Transfusion Practices.

6th Edition, Denise. M. Harmening. Chapters - 5 to 9 and 20.

4. MD Aggarwal. Hematology Today (Chap 40). 2008. p. 31.

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INTERNAL MEDICINE

A Study of Antinuclear Antibodies Profile in Clinical Cases of Systemic Lupus Erythematosus NITISH PATWARDHAN*, MANISH N MEHTA†, HEMANG ACHARYA‡, AJAY C TANNA#, JEMIMA BHASKAR¥

ABSTRACT The presence of antinuclear antibodies (ANA) in serum is characteristic of systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis and Sjogren’s syndrome. They may also be of prognostic value, such as the development of overt connective tissue disease in patients with Raynaud’s phenomenon or antiphospholipid antibodies. Testing of individual ANA specificities should be performed in the context of clinical signs that correlate with antibody disease association (e.g., anti-DNA or anti-SM in the suspicion of SLE).

Keywords: ANA test, ANA profile, SLE, systemic sclerosis, Sjogren’s disease, mixed connective tissue disease, autoantibodies

A

ntinuclear antibodies (ANA) include a diversity of autoantibodies directed against multiple intracellular antigens, classically consisting of nuclear specificities such as DNA or small nuclear ribonucleoprotein (snRNP). ANA diseases include patients who have a high prevalence of ANA by immunofluorescence namely systemic lupus erythematosus (SLE), systemic sclerosis and mixed connective tissue disease (MCTD). In polymyositis, dermatomyositis and Siogren’s syndrome, the prevalence of ANA is somewhat lower than in the other diseases. However, these autoantibodies can arise rarely in a variety of infectious and neoplastic diseases as well as in normal individuals.

CASE REPORTS Fifteen patients with ANA positivity were analyzed and were diagnosed to have different clinical diseases, which was confirmed by ANA profile.

*2nd Year Resident †Professor and HOD ‡Professor #Assistant Professor ¥Senior Resident Dept. of Medicine MP Shah Medical College and Guru Gobind Singh Hospital, Jamnagar, Gujarat Address for correspondence Dr Jemima Bhaskar No. 404 Kings Palace Mehulnagar, Opp. BSNL Telephone Exchange, Jamnagar, Gujarat E-mail: jemimabhaskar@yahoo.com

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1. Mrs N 23/F was admitted for polyarthralgia following an episode of fever and an initial diagnosis of post viral syndrome was made.

Investigations revealed normal complete blood count (CBC) and platelet count, chest X-ray (CXR) showed minimal pleural effusion (bilateral), dengue IgG/IgM negative, serum uric acid 3.6 mgm %, anti-cyclic citrullinated peptide (antiCCP) negative, erythrocyte sedimentation rate (ESR) 47 mm/hr, antistreptolysin O (ASO) titer negative, urine albumin++, ANA titer positive, anti-dsDNA positive, nucleosome positive. Final diagnosis was SLE. 2. Mrs R 40/F presented with generalized rash with polyarthralgia with diabetes mellitus. A clinical diagnosis of SLE was made. Investigations revealed normal CBC, low platelets, normal renal function tests, normal CXR, rheumatoid arthritis factor negative, ANA titer positive, ANA profile showed histone positive. Final diagnosis was SLE. 3. Mrs S 40/F presented with respiratory symptoms.

She was investigated and diagnosed to have restrictive lung disease in pulmonary function tests (PFT) and radiologically. A diagnosis of interstitial lung disease was made. ANA titer was positive and ANA profile showed PL-12 and cytoplasmic Jo-1 (anti-smooth muscle antibody [ASMA] mitochondrial ribosomal pattern) positive. It was a very rare case of antisynthetase syndrome, which presented as interstitial lung disease with myositis.

4. Mrs R 19/F presented with 5 months amenorrhea (pregnancy) with generalized purpura. A clinical

INTERNAL MEDICINE diagnosis of idiopathic thrombocytopenic purpura was made. Investigations revealed persistent low platelets (5,000-16,000 range), ANA positive and dsDNA negative. She responded well to steroids.

5. Mrs R 45/F presented with clinical features of thickened skin and Raynaud’s phenomenon and a diagnosis of systemic sclerosis was made. It was confirmed by being anti-Ro positive in ANA profile.

6. Mrs J 25/F presented with hemolytic anemia, thrombocytopenia, polyarthralgia, hypoproteinemia and persistent hematuria. She was ANA positive.

In ANA profile, U1 snRNP, SmRNP were positive and dsDNA negative. SnRNP is found to be positive in MCTD, which is an overlap of lupus, scleroderma and myositis. SnRNP predicts lack of severe renal and central nervous system (CNS) involvement.

7. Mrs G 48/F had a clinical presentation of intermittent joint pain, alopecia and abdominal pain. She had purpura and ascites with low platelet count, low serum protein and serum albumin, normal born marrow smear, 24 hours urine protein 5,735 μg/24 hours, rheumatoid factor positive, anti-CCP negative, ANA titer positive and dsDNA positive. A diagnosis of SLE nephritis was made.

8. Miss D 18/F had proximal weakness in both thighs with raised creatine phosphokinase (CPK). Nerve conduction studies and electromyography (EMG) showed generalized primary muscle disease of acquired origin. ANA test was positive. ANA profile showed specific bands for Sm, snRNP, RNP68KD/A/C antibodies. Anti-Sm is specific for SLE and antibodies to RNP is diagnostic of MCTD, which is an overlap syndrome. Her diagnosis was MCTD. 9. Miss S 18/F had pancytopenia, ESR 56 mm/hr with a history of cough, breathlessness and GTCC. There was also a history of joint pain and alopecia. ANA titer was positive. ANA profile was positive for RNP68KD/A/C, Sm, snRNP, SSA/Ro60KD, SSA/ Ro52KD, SS-B (SSB). These antibodies are associated with cutaneous lupus and MCTD. SSA/Ro60 is positive in SLE and SSA/Ro52 is positive in systemic sclerosis and Sjogren’s syndrome.

10. Mrs D 35/F presented with recurrent fever, nausea, bilateral pleural effusion, nephrotic syndrome and right third nerve palsy. Liver was of normal size. Her ESR was 60 mm/hr, urine albumin +++, USG abdomen was normal. ANA test was positive and ANA profile showed specific bands for Sm, RNP68KD/A/C, Sm/ RNP, SSA/Ro52KD, M2 recombinant, M2 native

antibodies. These autoantibodies are positive in SLE, MCTD, systemic sclerosis and Sjogren’s syndrome.

Her clinical diagnosis was MCTD. 11. Mrs D 60/F was admitted for cervical and axillary adenopathy and left internal jugular vein thrombosis. She also had hypothyroidism. Her serum homocysteine level was normal. ANA test was positive. ANA profile showed positivity for dsDNA, CENA-A/B, M2 recombinant, M2 native antibodies.

CENA-A/B antibodies are positive in systemic sclerosis, SLE, rheumatoid arthritis. Raynaud’s phenomenon is more frequent in those who are CENA positive. A diagnostic of SLE was made.

12. Mrs D 49/F presented with sudden onset of pain and bluish discoloration of right thumb, index and middle fingers with local tenderness and swelling.

She also had dry eyes and dry mouth. Patient had similar symptoms earlier also. Peripheral pulses were normal. A clinical diagnosis of Raynaud’s phenomenon with systemic sclerosis was made.

ANA profile showed specific bands for RNP 68KD/A/C, Sm/RNP, SP100, M2 native antibodies.

Arterial Doppler was normal. Rheumatoid factor positive. Liver function test (LFT) normal. It was a case of MCTD where there is an overlap of systemic sclerosis, SLE and myositis.

13. Mrs C 24/F presented with breathlessness on exertion and anemia. PFT showed mild restrictive pattern.

ANA profile was positive for SS-A/Ro 60KD, SS-A/ Ro 52KD, U1-snRNP, RA factor and anti-CCP. CKMM was negative. Direct and indirect Coomb’s test were negative. These autoantibodies are present in MCTD, SLE and systemic sclerosis.

14. Mrs S 50/F was admitted for severe joint pain in hands, fever, vomiting and diarrhea. She had active arthritis of small joints of fingers bilaterally with swan neck deformity. RA factor was negative, ESR was 126 mm/hr and ANA test was positive. ANA profile showed bands for dsDNA/Sm/RNP 68KD/ A/C and Sm/RNP. It was a case of SLE and MCTD. ÂÂ

Mrs J 36/F presented with photosensitive skin lesions, anemia and alopecia, loss of appetite and arthritis of major and minor joints. Urine albumin positive, white blood cell count was high. Blood urea and serum creatinine were normal. ANA test was positive. ANA profile showed bands for SSA/ Ro 60KD and SSA/Ro 52KD. A case of SLE and systemic sclerosis was the final diagnosis.

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INTERNAL MEDICINE Table 1. Autoantibodies in Systemic Lupus Erythematosus Antibody

Prevalence (%)

Antigen recognized

Clinical utility

Antinuclear antibodies

98

Multiple nuclear

Best screening test; repeated negative tests make SLE unlikely

Anti-dsDNA

70

DNA (double-stranded)

High titers are SLE-specific and in some patients correlate with disease activity, nephritis, vasculitis

Anti-Sm

25

Protein complexed to 6 species of nuclear U1 RNA

Specific for SLE; no definite clinical correlations; most patients also have anti-RNP; more common in blacks and Asians than whites

Anti-RNP

40

Protein complexed to U1 RNAγ

Not specific for SLE; high titers associated with syndromes that have overlap features of several rheumatic syndromes including SLE; more common in blacks than whites

Anti-Ro (SS-A)

30

Protein complexed to hY RNA, Not specific for SLE; associated with sicca primarily 60 kDa and 52 kDa syndrome, predisposes to subacute cutaneous lupus, and to neonatal lupus with congenital heart block; associated with decreased risk for nephritis

Anti-La (SS-B)

10

47-kDa protein complexed to hY RNA

Antihistone

70

Histones associated with DNA More frequent in drug-induced lupus than in SLE (in nucleosome, chromatin)

Antiphospholipid

50

Phospholipids, β2 glycoprotein 1 cofactor, prothrombin

Three tests available—ELISAs for cardiolipin and β2G1, sensitive prothrombin time (DRVVT); predisposes to clotting, fetal loss thrombocytopenia

Antierythrocyte

60

Erythrocyte membrane

Measured as direct Coombs’ test; a small proportion develops overt hemolysis

Antiplatelet

30

Surface and altered cytoplasmic antigens on platelets

Associated with thrombocytopenia but sensitivity and specificity are not good this; this is not a useful clinical test

Antineuronal (includes anti-glutamate receptor)

60

Neuronal and lymphocyte surface antigens

In some series, a positive test in CSF correlates with active CNS lupus.

Antiribosomal P

20

Protein in ribosomes

In some series, a positive test in serum correlates with depression or psychosis due to CNS lupus

Usually associated with anti-Ro; associated with decreased risk for nephritis

CNS = Central nervous system; CSF = Cerebrospinal fluid; DRVVT = Dilute Russell viper venom time; ELISA = Enzyme-linked immunosorbent assay.

DISCUSSION Testing of individual ANA specificities, (ANA profile) should be performed in the context of clinical signs that correlate with the autoimmune disease in patients who are found to be ANA positive.

Autoantibodies Specific for SLE

ÂÂ

Antiribosomal P - correlates with depression or psychosis in CNS lupus.

ÂÂ

Antineuronal - a positive test in CSF and correlates with active CNS lupus.

Analysis of Other Autoantibodies ÂÂ

Anti-Ro (SS-A) - associated with sicca syndrome.

Not specific for SLE, but associated with cutaneous and neonatal lupus.

ÂÂ

Anti-dsDNA - specific for SLE and correlate with disease activity, nephritis, vasculitis.

ÂÂ

Anti-Sm - specific for SLE but no definite clinical correlation.

ÂÂ

Anti-La (SS-B) - usually associated with anti-Ro, associated with decreased risk for nephritis.

ÂÂ

Antihistone - more frequent in drug-induced lupus then in SLE.

ÂÂ

Anticentromere (antikinetochore) - found in systemic sclerosis and may correlate with CREST

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Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

INTERNAL MEDICINE (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia) syndrome. ÂÂ

Antiphospholipid - predisposes to clotting, fetal loss and thrombocytopenia.

ÂÂ

Anti-SCL-70 and anti-RNA polymerase 3 associated with diffuse cutaneous sclerosis and pulmonary fibrosis.

ÂÂ

Anti-RNP 68KD ---

ÂÂ

Anti-SmRMP ---

ÂÂ

Anti-U1-snRMP ---

ÂÂ

Anti-PM-Scl - found in myositis systemic sclerosis overlap.

ÂÂ

Antihisitidyl tRNA synthetase (Jo-1) - found in inflammatory myositis and are associated poor prognosis.

ÂÂ

Anti-Ro/SSA and anti-LA/SSB - found in mothers of children with neonatal lupus.

Associated with MCTD

these cases of clinical SLE, in ANA profile dsDNA was positive only in 4 cases. The other cases had SSA/Ro positive in 4 cases anti-Sm in 2 cases and antihistone in 1 case. Sm RNP and RNP 60 were positive in 7 cases showing considerable overlap of SLE with MCTD. Some patients also had SSA/Ro 60 and SSARo 52 positive, which also implies overlap with systemic sclerosis.

CONCLUSION In this short study, it is concluded that clinical SLE has considerable overlap with MCTD and systemic sclerosis. The other conclusion is that autoantibodies to dsDNA is not always positive in SLE and antibodies to SSA/Ro 60 and SM are positive in many patients. In addition, due to overlap with MCTD, many patients with SLE have autoantibodies to snRNP, anti-RNP 68 and anti-SmRNP. REFERENCES

Although many autoantibodies are disease-specific, exceptions are common confounded by the observation that many autoantibodies are present in low frequencies in healthy individuals. ANA testing is insufficient to establish the diagnosis in any patient and clinical finding should be heavily relied on.

15. Kelleys Textbook of Rheumatology. 9th Edition, Vol 1; 2013.

Of these 15 patients, clinically a diagnosis of SLE was made in 11 patients; restrictive lung disease in one case and primary muscle disease in one case and others had overlap of signs. Although the ANA test was positive in

18. Harrison’s Principles of Internal Medicine. 18th Edition, Vol 2; 2012.

16. Kelley’s Textbook of Rheumatology. 9th Edition, Vol 2; 2013.

17. Harrison’s Principles of Internal Medicine. 18th Edition, Vol 1; 2012.

19. Davidson’s Principles and Practice of Medicine. 22nd Edition; 2014.

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Anti-inflammatory Therapy may Reduce Risk of Major CV Events: CANTOS In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), compared with placebo, canakinumab 150 mg every 3 months reduced high-sensitivity C-reactive protein (hs-CRP) levels by an average of 37% and also reduced risk of major cardiovascular events by 15%, independent of lipid-level lowering. These findings were presented at the European Society of Cardiology 2017 congress in Barcelona and published in the New England Journal of Medicine.

Adalimumab-adbm, the Second FDA-approved Biosimilar to Adalimumab The US Food and Drug Administration (FDA) have approved adalimumab-adbm (Cyltezo, Boehringer Ingelheim) for multiple indications as the second FDA-approved biosimilar to Humira (adalimumab). Administered by subcutaneous injection (40 mg/0.8 mL), Cyltezo, a tumor necrosis factor (TNF) blocker is approved for the treatment of adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderately to severely active Crohn's disease, moderately to severely active ulcerative colitis and moderate-to-severe plaque psoriasis.

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Dangerously Leaking Nose R UMARANI*, K BABURAJ†, J SANGEETHA‡, JINO VINCENT‡

ABSTRACT Cerebrospinal fluid (CSF) rhinorrhea is a symptom caused by the leakage of CSF into the nasal sinus, resulting from a defect in the skull base. Bacterial meningitis following CSF rhinorrhea is seen even in immunocompetent individuals. Meningeal infection with Mycobacterium tuberculosis, is an example of a form of meningitis where difficulties in diagnosis and management regularly occur. However, tubercular meningitis (TBM) is very rare and there is still no single diagnostic method, which is both sufficiently rapid and sensitive. We present a case of a 55-year-old, postmenopausal female, with chief complaints of fever for past 30 days and headache for 7 days vomiting and altered sensorium for 1 day. She had history of watery discharge from nose for past 2 months, on and off, not mucoid, not blood stained, not associated with sneezing, increased flow on bending the head forward. She was investigated and found to have TBM with CSF rhinorrhea. This case is highlighted because, it is not clear whether it’s the probable tuberculosis of nasal area causing bone erosion leading to rhinorrhea or tuberculosis meningitis causing erosion of bone.

Keywords: Cerebrospinal fluid rhinorrhea, tubercular meningitis, CT paranasal sinuses, bone erosion, antituberculous

drugs

M

eningitis still remains a disease with high mortality and morbidity even in this antibiotic era. It is mainly due to difficulties in diagnosing the specific subsets of meningitis for best possible management. An interesting case of tuberculous meningitis (TBM) with cerebrospinal fluid (CSF) rhinorrhea is presented here, with a review of investigations that can aid in diagnosis.

CASE REPORT A 55-year-old, postmenopausal female, was brought to our hospital with chief complaints of fever for past 30 days and headache for 7 days vomiting and altered sensorium for 1 day. Fever was high grade, intermittent in nature, no chills and rigor, evening rise of temperature was present and night sweats present.

History of vomiting for past 1 day, nonprojectile, watery

*Professor †Associate Professor ‡Postgraduate Dept. of Medicine Rajah Muthiah Medical College and Hospital, Chidambaram, Tamil Nadu Address for correspondence Dr J Sangeetha Postgraduate Dept. of Medicine Rajah Muthiah Medical College and Hospital, Chidambaram, Tamil Nadu E-mail: sangeetha0560116@gmail.com

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Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

in nature, not bile or blood stained with no associated blurring of vision. Complaints of watery discharge from nose for past 2 months, on and off, not mucoid, not blood stained, not associated with sneezing, increased flow on bending the head forward. She had no history of involuntary passage of urine, blurring of vision, ear discharge, weakness of limbs, seizures and head injury. No history of syncope, throat pain, cough with expectoration, loss of weight and loss of appetite.

She has no chest pain and no swelling of legs. She had no other comorbidities.

On examination, patient was drowsy and febrile. Vitals were stable. Systemic examination revealed a normal cardiovascular and respiratory system. Nervous system examination showed altered consciousness, no involvement of cranial, motor and sensory system.

Cerebellum was intact. Neck rigidity was present.

Kernig’s and Brudzinski test were negative. Pupils were equal and reacting to light. Both sides plantar response was flexor. Fundus examination was also normal.Initial evaluation revealed hemoglobin of 12.9 g/dL, total leukocyte count was 15,800 cells/mm3, erythrocyte sedimentation rate (ESR) at 30 minutes was 72 mm and 60 minutes was 140 mm. Sugars and renal functions were normal. Blood investigations for malaria, leptospira, dengue and enteric fever and human immunodeficiency virus (HIV) were negative.

In the view of increased ESR, tuberculosis skin sensitive test was done and it was positive (26 × 20 mm). Chest

INTERNAL MEDICINE

Figure 1. Clear CSF from nasal cavity.

Figure 3. CT paranasal sinuses showing probable CSF leak.

(PNS) showed bony dehiscence in cribriform plate with probable CSF leak in correlation with history of patient (Figs. 2 and 3). A diagnosis of TBM with CSF rhinorrhea was made and patient was started on antituberculous drugs and steroids. Patient started improving from the third day of medications.

DISCUSSION Bacterial meningitis following CSF rhinorrhea is seen even in immunocompetent individuals.1 Incidence of meningitis post-traumatic CSF rhinorrhea is around 0.3-2.0%.2 However, TBM is very rare and incidence is not known. During the last three decades, extrapulmonary tuberculosis (EPTB) has gained special attention because of HIV pandemic.3 Mycobacterium tuberculosis, most frequently reaches the lung and rarely involves PNS. Figure 2. CT paranasal sinuses showing cribriform plate dehiscence.

Three types of sinonasal tuberculosis: ÂÂ

Mucosal involvement

X-ray was normal. Computed tomography (CT) brain was normal.

ÂÂ

Bony involvement and fistula formation (AFB)

ÂÂ

Hyperplastic tuberculoma.4

CSF analysis showed no pus cells nor bacteria, CSF acid-fast bacilli (AFB) staining was negative. Glucose was only 38 mg/dL (blood sugar was 132 mg/dL) and cavity proteins was 34 mg/dL. CSF adenosine deaminase (ADA) was 17 U/L (normal cut-off <10 U/L). Analysis of fluid from nostril was done. It was a clear fluid with glucose of 55 mg/dL and protein was 28 mg/dL (Fig. 1).

Beta transferrin could not be done due to nonavailability in our center and cost constraints. CT paranasal sinuses

changes

with

formation

of

Meningeal infection with M. tuberculosis is an example of a form of meningitis where difficulties in diagnosis and management regularly occur. The fact remains that there is still no single diagnostic method, which is both sufficiently rapid and sensitive.

The initial clinical and laboratory picture of TBM is relatively nonspecific, resembling many other causes of subacute meningitis.

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INTERNAL MEDICINE Typically, headache, fever and meningitis progress to coma within a few days (sometimes weeks), the CSF being lymphocytic with a low glucose concentration, though many atypical presentations have been described. Many methods of laboratory confirmation of TBM is available, but each one has its own drawback.

The gold standard investigation is detection of tubercle bacilli in the CSF by microscopy and/or culture. Direct microscopic examination of the CSF, however, is sensitive to sample volume and time spent searching for acid-alcohol fast bacilli in multiple fields.

Other investigations used in patients with suspected TBM include the tuberculin skin test, but this is subject to both false positive and false negative results. The chest X-ray may show a miliary appearance in a small proportion of cases. Brain imaging by CT or magnetic resonance (MR) may reveal hydrocephalus or basal meningeal enhancement in TBM but the appearances are nonspecific, being shared by other subacute and chronic meningitides. A significant proportion of patients with TBM will have normal imaging.5 Tuberculomas are seen only in a minority.

One approach is to measure a surrogate marker such as CSF-ADA. ADA, a polymorphic enzyme involved in purine metabolism is found to be elevated in the CSF of TBM patients and gradually returns to normal values after 2-6 weeks of specific treatment. The estimation is easy, fast, in-expensive and can be done in ordinary laboratories.

In a study CSF-ADA level 6.5 IU/L as a cut-off value exhibited a sensitivity of 95.83%, specificity of 92.85%, the positive predictive value of test is 95.83% with overall accuracy being 94.73%.6 In another study done

by PGI Chandigarh, using a cut-off level of >10 U/L, CSF-ADA had a sensitivity of 92.5% and specificity of 97%, thus serving as an excellent marker to differentiate various types of meningitis.7 The detection of M. tuberculosis nucleic acid in CSF by the polymerase chain reaction (PCR) and allied techniques is more promising. But the sensitivity of PCR is probably no different from that of a carefully analyzed smear and it requires larger sample volume.

The advantage of PCR is in patients where CSF was taken after antituberculous treatment had begun, as

mycobacterial nucleic acid is likely still to be detectable, but the sensitivity of smear and culture will have fallen dramatically. But availability and cost are major constraints.8 CONCLUSION This case is highlighted because, in our patient whether it’s the probable tuberculosis of nasal area causing bone erosion leading to rhinorrhea or tuberculosis meningitis causing erosion of bone is unclear. Meningitis with rhinorrhea can present with minimal signs of meningitis due to decreased CSF pressure. CSF rhinorrhea is an important cause of recurrent meningitis, whether due to spontaneous leak or secondary to trauma or infections and it’s an understated cause of chronic orthostatic headache. Diagnosis of TBM has become easier with availability of newer markers like ADA, which is relatively cheap, rapid, easily available and has high sensitivity and specificity.

REFERENCES 1. Pappas DG Jr, Hammerschlag PE, Hammerschlag M. Cerebrospinal fluid rhinorrhea and recurrent meningitis.

Clin Infect Dis. 1993;17(3):364-8.

2. Plaisier B, Yowler C, Fallon W, Likavec M, Anderson J, Malangoni M. Post-traumatic meningitis: risk factors, clinical features, bacteriology, and outcome. Int J Neurosurg. 2004;2(1).

3. Arora VK, Gowrinath K, Rao S. Extrapulmonary involvement in HIV with special reference to tubercular cases. Indian J Tuberc. 1995;42:27-32.

4. Gleitsmann JW. Tuberculosis of accessory sinuses of the nose. Laryngoscope. 1907;17:445.

5. Lloyd KM, DelGaudio JM, Hudgins PA. Imaging of skull base cerebrospinal fluid leaks in adults. Radiology.

2008;248(3):725-36.

6. Malan C, Donald PR, Golden M, Taljaard JJ. Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculous meningitis. J Trop Med Hyg. 1984;87(1):33-40.

7. Gupta BK, Bharat A, Debapriya B, Baruah H. Adenosine Deaminase Levels in CSF of Tuberculous Meningitis Patients. J Clin Med Res. 2010;2(5):220-4.

8. Thwaites GE, Chau TT, Stepniewska K, Phu NH, Chuong LV, Sinh DX, et al. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features.

Lancet. 2002;360(9342):1287-92.

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NEUROLOGY

Lance-Adams Syndrome: A Rare Case of Posthypoxic Myoclonus, Developing After a Snake Bite MEET M THACKER*, MANISH N MEHTA†

ABSTRACT Lance-Adams syndrome (LAS) is a rare complication of a successful cardiopulmonary resuscitation (CPR) and is often accompanied by post-hypoxic action myoclonus. Less than 200 cases have been reported in medical literature till date.

A 50-year-old female presented to the Emergency Department in a state of unconsciousness. Urgent intubation and CPR resulted in stabilization of vitals over a period of few days. On regaining consciousness, the patient developed myoclonus, which was characteristically present only on activity and absent at rest or during sleep. This action myoclonus was troublesome to the patient and interfering in the day-to-day activities of the patient. Patient was started on a combination therapy with levetiracetam and clonazepam, which resulted in marked diminution of myoclonus over a period of 15-20 days. Though LAS is a rare complication, proper diagnosis and prompt management may significantly reduce the morbidity and improves the quality-of-life.

Keywords: Lance-Adams syndrome, cardiopulmonary resuscitation, myoclonus, levetiracetam, clonazepam

L

ance-Adams syndrome (LAS) is a rare complication of a successful cardiopulmonary resuscitation (CPR). LAS is known to present as action myoclonus, days to weeks after a successful CPR, due to hypoxic injury to brain. Post-hypoxic myoclonus (PHM) is divided into two types:

ÂÂ

The acute type, which is called “myoclonic status epilepticus,” occurs within 12 hours in most cases after hypoxic brain damage in patients who are deeply comatose.

ÂÂ

The chronic type, called “the Lance-Adams syndrome,” is characterized by action myoclonus beginning days to weeks after a successful CPR and persists in patients who have recovered consciousness after CPR.

LAS is a rare complication and less than 200 cases have been reported in medical literature till date. We present

*Senior Resident †Professor and Head Dept. of Medicine Shri MP Shah Govt. Medical College, Jamnagar, Gujarat Address for correspondence Dr Meet M Thacker Senior Resident Dept. of Medicine Shri MP Shah Govt. Medical College, Jamnagar, Gujarat - 361 008 E-mail: drmeetthacker@gmail.com

here a patient who was diagnosed as LAS after CPR due to cardiorespiratory arrest following a neurotoxic snake bite.

CASE REPORT A 50-year-old female reported to our Emergency Department in a state of unconsciousness. Following a snake bite, she slipped into unconsciousness, as reported by the husband accompanying her. Her oxygen saturation on admission was 40% as measured by a finger oximeter, and respiratory movements were almost absent. After 10 minutes of vigorous CPR at the Emergency Department, her vital signs started to return. She was shifted to intensive care unit (ICU), and was given 20 vials of antisnake venom in total.

She regained consciousness the next day, after being on intermittent positive pressure mechanical ventilation and vasopressor support for a day. Meanwhile, a computed tomography (CT) scan of the brain was done, which showed no significant abnormalities (Fig. 1). All routine investigations like complete blood count, liver function tests, renal function tests, urine routine and microbiological examination and serum electrolytes were within normal range as given in Table 1.

When she was tapered from sedation (midazolam) and muscle relaxation (atracurium), on the 3rd day of ICU, she developed a generalized seizure and subsequently myoclonic movements were continuously observed

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349

NEUROLOGY

Figure 1. CT scan of the brain showing no significant abnormalities.

Figure 2. T2-weighted MRI showing mild diffuse cerebral atrophy.

throughout her body, including face. At that time, the myoclonic movements were considered as generalized myoclonus secondary to hypoxic brain insult and were empirically treated with sodium valproate. However, these were not controlled with sodium valproate. The myoclonic jerks ceased with a single bolus dose of midazolam but the effect was transient. A repeat CT scan was meanwhile done, which showed no abnormalities and the T2-weighted magnetic resonance imaging (MRI) showed mild diffuse cerebral atrophy (Fig. 2). On Day 5, the patientâ&#x20AC;&#x2122;s mental status improved, she was now intermittently able to obey simple commands, but the myoclonic jerks continued. The rest of the central nervous system (CNS) examination was normal except higher functions, where the patient had dysarthria, dyscalculia and some attention deficits.

Subsequently, on Day 9, the patient was shifted to ward and started on levetiracetam (500 mg b.i.d.) and subsequently clonazepam (1 mg t.d.s.) was added. With these medications and physiotherapy, the patient started

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Table 1. Routine Investigations Test

Value

Hemoglobin

10.8 g/dL

Total WBC count

15,200 cells/mm3

Differential count (N/L/M/E/B)

66/20/12/02/00%

Platelet count PT/INR Serum bilirubin (total/direct/indirect) SGPT

1,64,000 cells/mm3 14.4 sec/1.1 1.2/0.4/0.8 mg/dL 32 IU/L

Serum creatinine

0.8 mg/dL

Blood urea

28 mg/dL

Serum

Na+

138 mEq/L

Serum

K+

4.6 mEq/L

showing improvement, in the form of reduced frequency of myoclonic jerks, and also some improvements in higher functions. Patient was discharged on Day 21 when

Every citizen of India should have the right to accessible, affordable, quality and safe heart care irrespective of his/her economical background

Sameer Malik Heart Care Foundation Fund An Initiative of Heart Care Foundation of India E-219, Greater Kailash, Part I, New Delhi - 110048 E-mail: heartcarefoundationfund@gmail.com Helpline Number: +91 - 9958771177

“No one should die of heart disease just because he/she cannot afford it” About Sameer Malik Heart Care Foundation Fund

Who is Eligible?

“Sameer Malik Heart Care Foundation Fund” it is an initiative of the Heart Care Foundation of India created with an objective to cater to the heart care needs of people.

Objectives Assist heart patients belonging to economically weaker sections of the society in getting affordable and quality treatment.

Raise awareness about the fundamental right of individuals to medical treatment irrespective of their religion or economical background.

Sensitize the central and state government about the need for a National Cardiovascular Disease Control Program.

Encourage and involve key stakeholders such as other NGOs, private institutions and individual to help reduce the number of deaths due to heart disease in the country.

To promote heart care research in India.

All heart patients who need pacemakers, valve replacement, bypass surgery, surgery for congenital heart diseases, etc. are eligible to apply for assistance from the Fund. The Application form can be downloaded from the website of the Fund. http://heartcarefoundationfund.heartcarefoundation. org and submitted in the HCFI Fund office.

Important Notes The patient must be a citizen of India with valid Voter ID Card/ Aadhaar Card/Driving License.

The patient must be needy and underprivileged, to be assessed

by Fund Committee.

The HCFI Fund reserves the right to accept/reject any application for financial assistance without assigning any reasons thereof.

The review of applications may take 4-6 weeks.

All applications are judged on merit by a Medical Advisory Board who meet every Tuesday and decide on the acceptance/rejection of applications.

The HCFI Fund is not responsible for failure of treatment/death of patient during or after the treatment has been rendered to the patient at designated hospitals.

To promote and train hands-only CPR.

Activities of the Fund Financial Assistance

The HCFI Fund reserves the right to advise/direct the beneficiary to the designated hospital for the treatment.

Financial assistance is given to eligible non emergent heart patients.

Apart from its own resources, the fund raises money through donations, aid from individuals, organizations, professional bodies, associations and other philanthropic organizations, etc.

The financial assistance granted will be given directly to the treating hospital/medical center.

After the sanction of grant, the fund members facilitate the patient in getting his/her heart intervention done at state of art heart hospitals in Delhi NCR like Medanta – The Medicity, National Heart Institute, All India Institute of Medical Sciences (AIIMS), RML Hospital, GB Pant Hospital, Jaipur Golden Hospital, etc. The money is transferred directly to the concerned hospital where surgery is to be done.

The HCFI Fund has the right to print/publish/webcast/web post details of the patient including photos, and other details. (Under taking needs to be given to the HCFI Fund to publish the medical details so that more people can be benefitted).

The HCFI Fund does not provide assistance for any emergent heart interventions.

Check List of Documents to be Submitted with Application Form Passport size photo of the patient and the family A copy of medical records

Drug Subsidy

Identity proof with proof of residence

The HCFI Fund has tied up with Helpline Pharmacy in Delhi to facilitate

BPL Card (If Card holder)

patients with medicines at highly discounted rates (up to 50%) post surgery.

Details of financial assistance taken/applied from other sources (Prime Minister’s Relief Fund, National Illness Assistance Fund Ministry of Health Govt of India, Rotary Relief Fund, Delhi Arogya Kosh, Delhi Arogya Nidhi), etc., if anyone.

Income proof (preferably given by SDM)

The HCFI Fund has also tied up for providing up to 50% discount on imaging (CT, MR, CT angiography, etc.)

Free Diagnostic Facility

Free Education and Employment Facility

The Fund has installed the latest State-of-the-Art 3 D Color Doppler EPIQ 7C Philips at E – 219, Greater Kailash, Part 1, New Delhi.

HCFI has tied up with a leading educational institution and an export house in Delhi NCR to adopt and to provide free education and employment opportunities to needy heart patients post surgery. Girls and women will be preferred.

This machine is used to screen children and adult patients for any heart disease.

Laboratory Subsidy HCFI has also tied up with leading laboratories in Delhi to give up to 50% discounts on all pathological lab tests.

About Heart Care Foundation of India

Help Us to Save Lives

The Foundation seeks support, donations and contributions from individuals, organizations and establishments both private and governmental in its endeavor to reduce the number of deaths due to heart disease in the country. All donations made towards the Heart Care Foundation Fund are exempted from tax under Section 80 G of the IT Act (1961) within India. The Fund is also eligible for overseas donations under FCRA Registration (Reg. No 231650979). The objectives and activities of the trust are charitable within the meaning of 2 (15) of the IT Act 1961.

Heart Care Foundation of India was founded in 1986 as a National Charitable Trust with the basic objective of creating awareness about all aspects of health for people from all walks of life incorporating all pathies using low-cost infotainment modules under one roof.

HCFI is the only NGO in the country on whose community-based health awareness events, the Government of India has released two commemorative national stamps (Rs 1 in 1991 on Run For The Heart and Rs 6.50 in 1993 on Heart Care Festival- First Perfect Health Mela). In February 2012, Government of Rajasthan also released one Cancellation stamp for organizing the first mega health camp at Ajmer.

Objectives Preventive Health Care Education Perfect Health Mela Providing Financial Support for Heart Care Interventions Reversal of Sudden Cardiac Death Through CPR-10 Training Workshops Research in Heart Care

Donate Now...

Heart Care Foundation Blood Donation Camps The Heart Care Foundation organizes regular blood donation camps. The blood collected is used for patients undergoing heart surgeries in various institutions across Delhi.

Committee Members

Chief Patron

President

Raghu Kataria

Dr KK Aggarwal

Entrepreneur

Padma Shri, Dr BC Roy National & DST National Science Communication Awardee

Governing Council Members Sumi Malik Vivek Kumar Karna Chopra Dr Veena Aggarwal Veena Jaju Naina Aggarwal Nilesh Aggarwal H M Bangur

Advisors Mukul Rohtagi Ashok Chakradhar

Executive Council Members Deep Malik Geeta Anand Dr Uday Kakroo Harish Malik Aarti Upadhyay Raj Kumar Daga Shalin Kataria Anisha Kataria Vishnu Sureka

This Fund is dedicated to the memory of Sameer Malik who was an unfortunate victim of sudden cardiac death at a young age.

Rishab Soni

HCFI has associated with Shree Cement Ltd. for newspaper and outdoor publicity campaign HCFI also provides Free ambulance services for adopted heart patients HCFI has also tied up with Manav Ashray to provide free/highly subsidized accommodation to heart patients & their families visiting Delhi for treatment.

http://heartcarefoundationfund.heartcarefoundation.org

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NEUROLOGY the frequency of jerks reduced to 4-9 per action, when she used to do actions slowly, but marked escalation of jerks was found on trying to speed up actions. Mild cognitive defects and dysarthria persisted though.

On regular follow-up, the patient slowly improved, though some dysarthria persisted. On 6 monthly followup, patient showed mark improvement, she could walk about 30 meters without support and there was marked diminution in the frequency of myoclonic jerks.

DISCUSSION Lance-Adams syndrome (LAS) was first described in the 1960s by Lance and Adams, who described 4 patients who developed myoclonic jerks within a few days following an episode of anoxia. After recovery of consciousness, the patients continued their abnormal clonic movements, which were triggered by intentional action or external stimuli and they were relieved at resting or during sleep. Although the pathophysiology of LAS remains undetermined, the prognosis is good.

It is important to distinguish LAS from post-hypoxic seizures, so a correct prognosis can be provided. One of the important clinical features is consciousness, in the acute type of post-hypoxic seizures, the patient’s mental status persists as comatose, but in LAS, the patient later regains consciousness. Intentional myoclonus develops several days after the hypoxic brain insult and persists thereafter, but in post-hypoxic seizures, generalized myoclonus usually occurs within 48 hours after CPR. The myoclonus in LAS has no consistent correlation with electroencephalography (EEG) abnormalities. The patient in this case had remarkable features that are consistent with LAS. Diagnostic imaging tests such as CT or MRI of the brain are not helpful to make a diagnosis of LAS. Neuroimaging, such as brain single-photon emission computed tomography (SPECT) or brain positron emission tomography (PET), has recently showed the anatomical and pathophysiological basis of LAS. Some studies have reported that compared with control groups, patients with LAS had significantly increased glucose metabolism in the pontine tegmentum, mesencephalon and ventrolateral thalamus. In our case, brain CT and brain MRI of the patient demonstrated no abnormalities and EEG was normal too.

The loss of serotonin within the inferior olive nucleus has been thought to play a certain role and GABA may interact with the serotonin system to suppress PHM. The treatment of LAS has not been established and a combination of medications based on the neurotransmitters has been reported. Studies have found that valproate, piracetam, levetiracetam, zonisamide, clonazepam, etc. are effective.

In this case, the patient was treated with clonazepam and levetiracetam, which were effective in controlling the PHM. Failure to recognize LAS may result in inappropriate anticonvulsant therapy and delayed treatment.

Therefore, when a patient develops uncontrolled myoclonus on regaining consciousness after CPR and the myoclonus is unsuccessfully treated with traditional anticonvulsants for a certain period, the possibility of LAS should be considered. This can lead to minimizing the patient’s disabilities and improving the prognosis.

SUGGESTED READING 1. Lance JW, Adams RD. The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy. Brain. 1963;86:111-36.

2. English WA, Giffin NJ, Nolan JP. Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis.

Anaesthesia. 2009;64(8):908-11.

3. Werhahn KJ, Brown P, Thompson PD, Marsden CD. The clinical features and prognosis of chronic posthypoxic myoclonus. Mov Disord. 1997;12(2):216-20.

4. Frucht SJ, Trost M, Ma Y, Eidelberg D. The metabolic topography of posthypoxic myoclonus.

Neurology. 2004;62(10):1879-81.

5. Zhang YX, Liu JR, Jiang B, Liu HQ, Ding MP, Song SJ, et al.

Lance-Adams syndrome: a report of two cases.

J Zhejiang Univ Sci B. 2007;8(10):715-20.

6. Welsh JP, Placantonakis DG, Warsetsky SI, Marquez RG, Bernstein L, Aicher SA. The serotonin hypothesis of myoclonus from the perspective of neuronal rhythmicity.

Adv Neurol. 2002;89:307-29.

7. Hallett M. Physiology of human posthypoxic myoclonus. Mov Disord. 2000;15 Suppl 1:8-13.

8. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of The neurotransmitters related to LAS are known to the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;67(2):203-10. be serotonin and gamma-aminobutyric acid (GABA).

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Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

355

NEUROLOGY

Neonatal Seizures AMIT AGRAWAL

ABSTRACT The risk for seizures is greatest in the neonatal period and the neonatal seizures are one of the few neonatal neurological conditions that require immediate medical attention. Need not to emphasize that failure to detect seizures and the resulting lack of treatment can result in brain damage and in severe cases, fatal outcome. Although the treatment of neonatal seizures has not significantly changed in the past several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. The present review includes an overview of etiopathology, clinical presentation and approaches to the diagnosis and treatment of neonatal seizures.

Keywords: Neonatal seizures, seizures, newborn, antiepileptic therapy

T

he risk for seizures is greatest in the neonatal period (the first 28 days of life)1-4 and the neonatal seizures are one of the few neonatal neurological conditions that require immediate medical attention. A significant hypoxic-ischemic insult results in a cascade of biochemical events, which result in permanent neuronal injury over a number of hours.5 Need not to emphasize that failure to detect seizures and the resulting lack of treatment can result in brain damage and in severe cases, fatal outcome.6,7 The present review includes an overview of etiopathology, clinical presentation and approaches to the diagnosis and treatment of neonatal seizures 7 ETIOLOGY Neonatal seizures are characterized by paroxysmal electroencephalograph (EEG) activity often with motor manifestations and sometimes with autonomic or behavioral clinical manifestations including change in respiration, heart rate and/or blood pressure.1,8-11 The incidence of neonatal seizures in the newborn baby

Professor Dept. of Neurosurgery Narayana Medical College and Hospital, Chinthareddypalem, Nellore, Andhra Pradesh Address for correspondence Dr Amit Agrawal Professor Dept. of Neurosurgery Narayana Medical College and Hospital, Chinthareddypalem Nellore - 524 003, Andhra Pradesh E-mail: dramitagrawal@gmail.com, dramit_in@yahoo.com

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ranges from 1.5-3.5 per 1,000 live term births1,9,10 to 10-130 per 1,000 live preterm births.1,7 Seizures are very common and occur in up to 70% of preterm infants with intraventricular hemorrhage or periventricular leukomalacia.3,12 Neonatal seizures can be a manifestation of variety of neurological dysfunctions (Table 1).1,2,6,9,10,13 Frequent or prolonged seizures may contribute to permanent brain injury.1,8-11 CLINICAL EVALUATION Neonatal seizure patterns are more fragmentary than those observed in older children because of cortical immaturity, can present in several ways and several types may be seen in the same baby (Table 2).9,10,13 A complete description of the seizure episode obtained from the parents/attendant including the day of life on which the seizures occurred, history of associated eye movements, abnormal movements of the limbs, skin mottling or cyanosis, autonomic phenomena, any loss of conscious or sleeping needs to be elicited. History suggestive of sudden increase in fetal movements, intrauterine infection, maternal diabetes and narcotic addiction should be elicited in the antenatal history.

Ask for the evidence to suspect perinatal asphyxia (fetal distress, decreased fetal movements, instrumental delivery and need for resuscitation, lower Apgar scores) as it is the commonest cause of neonatal seizures.

History of consanguinity in parents, family history of seizures or mental retardation and early fetal/neonatal deaths may suggest inborn errors of metabolism.

Suspect inborn errors of metabolism if there is history of lethargy, poor activity, drowsiness and vomiting after initiation of breastfeeding.

NEUROLOGY Table 1. Causes of Neonatal Seizures Hypoxic-ischemic encephalopathy

Table 2. Clinical Types of Seizures for a Summary of the Four Major Types

Most common cause in term infants

Type of seizure

Clinical characteristics

Most of the time poor long-term outcome

Subtle

More common in term babies particularly with severe global insult

Intracranial hemorrhage

Incidence ranges from 10% to 35%

Intraventricular hemorrhage

Eye - staring, blinking, horizontal deviation

Intracerebral hemorrhage Subdural hemorrhage

Oral - mouthing, chewing, sucking, tongue thrusting, lip smacking

Subarachnoid hemorrhage Infections

Limb - boxing, swimming movements of the arms, pedalling

Bacterial meningitis

Autonomic - apnea, tachycardia, unstable blood pressure

Viral meningitis Encephalitis Intrauterine (TORCH) infections

Clonic

50%

Perinatal stroke

More common in term babies

Metabolic

Consciousness usually preserved Rhythmic jerking (1-3/second)

Hypoglycemia

Focal - limbs or one side of face or body.

May suggest underlying focal neuropathy (e.g., cerebral artery infarction) but can occur in metabolic disturbance

Hypocalcemia Hypomagnesemia Hypo/hypernatremia

Multifocal - irregular, fragmentary, nonordered migratory pattern

Pyridoxine dependency Inborn errors of metabolism (rare cause of neonatal seizures)

Tonic

20%

Treatable: Pyridoxine-dependent epilepsy, pyridoxal phosphate responsive epilepsy, biotinidase deficiency, phenylketonuria

More common in preterm babies

Nontreatable: Nonketotic hyperglycinemia, sulfite oxidase deficiency, mitochondrial disorder, peroxisomal disorder, neuronal ceroid lipofuscinoses

Generalized extension of upper and lower limbs with opisthotonic posturing

Drug withdrawal syndromes

May involve one extremity or the whole body

Focal - sustained posturing of limb Myoclonic

Congenital disorders

5% Rapid isolated jerks (distinguish from benign neonatal myoclonus) focal (one extremity) or multifocal (several body parts) seen in drug withdrawal (especially opiates)

Chromosomal anomalies Congenital brain anomalies Neurodegenerative disorders Benign idiopathic neonatal convulsions Benign familial neonatal convulsions3 Idiopathic

Record vital signs (including heart rate, respiratory rate, blood pressure, capillary refill time and temperature in all neonates), perform examination for the presence of any obvious malformations or dysmorphic features.

Make assessment of gestational age, record birthweight and weight for age. Look for presence of hepatosplenomegaly or an abnormal urine odor (inborn error of metabolism). Look for evidence of tuberous

sclerosis (i.e., hypopigmented macules or ash-leaf spot).

Detailed neurological examination should include presence of bulging anterior fontanel (may be due to meningitis or intracranial hemorrhage), assessment of level of consciousness and muscle tone (hypotonia or hypertonia).

DIAGNOSIS Neonatal seizures can be difficult to diagnose as there are often no clinical correlates of the electrographic Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

357

NEUROLOGY Table 3. Drugs Commonly Used for Neonatal Seizures Drug

Dose

Precautions

Phenobarbital

20 mg/kg IV. If necessary, additional 10-20 mg/kg IV in 10 mg/kg aliquots

Monitor blood pressure and respiration

Maintenance - 4-6 mg/kg/24 hrs IV/PO Lorazepam

0.05-0.10 mg/kg IV in 0.05 mg/kg increments over several minutes

Monitor for respiratory depression

Phenytoin

20 mg/kg IV (diluted in 0.9% NaCl) (Maximal rate: 1 mg/kg/min monitor cardiac rate and rhythm)

Hypotension Cardiac abnormalities

Maintenance 5-10 mg/kg/24 hrs IV Lidocaine

A bolus dose of 4 mg/kg IV followed by an infusion rate of 2 mg/kg/hr

Arrhythmias, hypotension and seizures

Sodium valproate

Dose is 20-25 mg/kg/d followed by 5-10 mg/kg every 12 hours

Hepatotoxicity

Vigabatrin (for refractory seizures)

50 mg/kg/day

Should not be administered with phenytoin

Topiramate (refractory infantile spasms) Approximately 3 mg/kg Pyridoxine (reserved as a last resort in refractory seizures)

50 mg

seizures (electroclinical dissociation) and any unusual or stereotypical movement may represent a seizure.14 Normal behavior of preterm and term babies may increase suspicion of seizures i.e., stretching, nonspecific random movements that can be sudden (particularly in preterm babies), random sucking, coughing or gagging, physiological myoclonus (benign neonatal myoclonus) and Jitteriness needs to be distinguished from seizure activity.

INVESTIGATIONS Basic investigations (to exclude meningitis, hypoglycemia, hypocalcemia and hypomagnesemia) should be considered in all neonates and these include blood sugar, serum electrolytes (Na, Ca, Mg), cerebrospinal fluid (CSF) examination (to rule out meningitis), cranial ultrasound (US) and EEG. EEG should be performed when the neonate is stable. It has both diagnostic and prognostic role in neonatal seizures. A background abnormality in both term and preterm neonates indicates a higher risk for neurological complications. Cranial US can be useful to identify hemorrhages (intracranial, intraventricular, subdural or subarachnoid), infarction or hydrocephalus. Magnetic resonance imaging (MRI) in infants with neonatal seizures provides details regarding anomalies of the brain including cerebral dysgenesis and gross structural malformations, which can be associated with neonatal seizures i.e., tuberous

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Hypotension and apnea

sclerosis, hemimegalencephaly or cortical dysplasia.14 TORCH screen and venereal disease research laboratory (VDRL) should be considered when there is presence of hepatosplenomegaly, thrombocytopenia, small for gestational age, intrauterine growth restriction and/or presence of chorioretinitis.

TREATMENT The first and foremost principle of treatment of neonatal seizures is to prevent further brain injury, identify and treat the underlying cause (i.e., correction of hypoglycemia, hypocalcemia, hypomagnesemia and hypoxia) followed by the simultaneous use of anticonvulsant drug therapy. There is lack of consensus regarding the optimal treatment protocol including the choice of anticonvulsant drugs; monotherapy is the most appropriate initial strategy for the control of seizures. The choice may vary from phenytoin, carbamazepine and valproic acid (Table 3).

CONCLUSION The outcome following neonatal seizures depends primarily on the underlying pathology and the longterm neurological consequences (cognitive deficits, mental retardation and later life epilepsy) remains high ranging from 28% to 46%.9,15-20 The clinical presentation of seizures in newborns may not be as obvious as in older children. Recognition of the neonatal seizure

NEUROLOGY remains the foremost challenge to overcome and a prompt diagnosis and treatment of neonatal seizures is recommended. Refractory neonatal seizures can still be a significant clinical challenge there is not enough treatments for this condition.

REFERENCES 1. Bassan H, Bental Y, Shany E, Berger I, Froom P, Levi L, et al. Neonatal seizures: dilemmas in workup and management. Pediatr Neurol. 2008;38(6):415-21.

2. Evans D, Levene M. Neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 1998;78(1):F70-5.

3. Greisen G, Hellström-Westas L, Lou H, Rosén I, Svenningsen NW. EEG depression and germinal layer haemorrhage in the newborn. Acta Paediatr Scand.

1987;76(3):519-25.

4. Rennie JM, Boylan GB. Neonatal seizures and their treatment. Curr Opin Neurol. 2003;16(2):177-81.

5. Evans DJ, Levene MI, Tsakmakis M. Anticonvulsants for preventing mortality and morbidity in full term newborns with perinatal asphyxia. Cochrane Database Syst Rev. 2007;(3):CD001240.

6. Rennie J, Boylan G. Treatment of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 2007;92(2):F148-50.

7. Silverstein FS, Jensen FE. Neonatal seizures. Ann Neurol. 2007;62(2):112-20.

8. Clancy RR; Neurology Group on Neonatal Seizures.

The newborn drug development initiative workshop: Summary proceedings from the neurology group on neonatal seizures. Clin Ther. 2006;28(9):1342-52.

9. Glass HC, Wirrell E. Controversies in neonatal seizure management. J Child Neurol. 2009;24(5):591-9.

11. Silverstein FS, Jensen FE, Inder T, Hellstrom-Westas L, Hirtz D, Ferriero DM. Improving the treatment of neonatal seizures: National Institute of Neurological Disorders and Stroke workshop report. J Pediatr.

2008;153(1):12-5.

12. Kubota T, Okumura A, Hayakawa F, Kato T, Itomi K, Kuno K, et al.

Combination of neonatal electroencephalography and ultrasonography: sensitive means of early diagnosis of periventricular leukomalacia.

Brain Dev. 2002;24(7):698-702.

13. Clancy RR. Summary proceedings from the neurology group on neonatal seizures. Pediatrics. 2006; 117(3 Pt 2):S23-7.

14. Jensen FE. Neonatal seizures: an update on mechanisms and management. Clin Perinatol. 2009;36(4):881-900, vii.

15. Holden KR, Mellits ED, Freeman JM. Neonatal seizures. I. Correlation of prenatal and perinatal events with outcomes. Pediatrics. 1982;70(2):165-76.

16. Ronen GM, Buckley D, Penney S, Streiner DL. Longterm prognosis in children with neonatal seizures: a population-based study. Neurology. 2007;69(19):1816-22.

17. McBride MC, Laroia N, Guillet R. Electrographic seizures in neonates correlate with poor neurodevelopmental outcome. Neurology. 2000;55(4):506-13.

18. Tekgul H, Gauvreau K, Soul J, Murphy L, Robertson R, Stewart J, et al. The current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics. 2006;117(4):1270-80.

19. Miller SP, Ramaswamy V, Michelson D, Barkovich AJ, Holshouser B, Wycliffe N, et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr. 2005;146(4): 453-60.

20. Kohelet D, Shochat R, Lusky A, Reichman B; Israel Neonatal Network. Risk factors for neonatal seizures in 10. Levene M. Recognition and management of neonatal very low birthweight infants: population-based survey. seizures. Paediatr Child Health. 2008;18(4):178-82.

J Child Neurol. 2004;19(2):123-8.

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Smell Test may Signal Parkinson’s Disease up to 10 Years Before Diagnosis in Some People A simple scratch-and-sniff test may 1 day be able to help identify some people at greater risk of developing Parkinson’s disease up to 10 years before the disease could be diagnosed, according to a new study published online September 6, 2017 in the journal Neurology. Older adults with a poor sense of smell are more likely to develop Parkinson’s disease than people who perform better on the smell test.

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

359

OBSTETRICS AND GYNECOLOGY

Bilateral Endometriomas with Deep Infiltrating Endometriosis in Infertility: An Increasing Trend (Case Series) PARMJIT KAUR*, RUBY BHATIA†, AMAN DEV‡, SANTOSH KUMARI#

ABSTRACT Endometriosis affects 8-10% of women of reproductive age; in 30% of the women, the condition is associated with primary or secondary infertility. Deep infiltrating endometriosis (DIE) is a particular form of endometriosis that extends >5 mm under the peritoneal surface. These lesions develop in the form of retroperitoneal nodules that consist histologically of endometrial epithelium and stroma, surrounded by muscular hyperplasia and fibrosis. In addition to infertility, it is commonly associated with symptoms such as dyspareunia, dysmenorrhea, bladder/bowel symptoms and chronic pelvic pain. Medical therapies may temporarily alleviate painful symptoms, but recurrence rates after their discontinuation are high. Radical surgical excision of DIE lesions is the mainstay of treatment. Ovarian endometriomas, a localized form of endometriosis are large, fluid-filled cysts that form on, and may even encapsulate, the ovaries. They are highly common and may be present in up to 30-40% of women with the disease. We report a series of 5 cases with bilateral large endometriomas with DIE associated with infertility.

Keywords: Endometriosis, deep infiltrating endometriosis, endometriomas, infertility, radical surgical excision

E

ndometriosis is a clinical and pathological entity characterized by the presence of tissue resembling functioning endometrial gland and stroma outside the uterine cavity. It is 7-10 times more common in infertile women and encountered in 70% of women with chronic pelvic pain. The most common sites of endometriosis, in decreasing order, are the ovaries, anterior/posterior cul-de-sac, broad ligaments and uterosacral ligaments, uterus, fallopian tubes, sigmoid colon and appendix. The growth of the implants is dependent on ovarian produced steroids. It is a disease that most severely affects women in the age group 25-35 years.1 In addition to infertility, it is commonly associated with symptoms

*Professor †Associate Professor ‡Civil Surgeon #Postgraduate Student Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Parmjit Kaur Professor Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab E-mail: dr.parmjit.obg@gmail.com

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Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

such as dyspareunia, dysmenorrhea, bladder/bowel symptoms and chronic pelvic pain. We report a series of 5 cases with bilateral large endometriomas with deep infiltrating endometriosis (DIE) associated with infertility.

CASE REPORTS

Case 1 A 19-year-old unmarried female admitted with chief complaint of subacute pain and lower abdomen mass of 16-18 weeks size of pregnant uterus. Her menstrual cycle was 7-8/22 with excessive flow and severe congestive dysmenorrhea. She visited our OPD 7 years back with complaint of menorrhagia and dysmenorrhea.

Her USG pelvis done that time showed nulliparous uterus with 2.5 cm cyst in right ovary (Fig. 1). She was put on nonsteroidal anti-inflammatory drugs (NSAIDs) and oral contraceptives but she was lost to follow-up and had presented now with large abdominal mass. She was thin built (body mass index [BMI] 17), with depressive personality and a school dropout. Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), erythrocyte sedimentation rate (ESR), alfa-fetoprotein (AFP) and beta human chorionic gonadotropin (β-hCG) were normal. All required investigations were done.

OBSTETRICS AND GYNECOLOGY UPT was negative and cancer antigen-125 (CA-125) was 60 U/mL. Computed tomography (CT) abdomen and pelvis showed well-defined 9 × 7.2 cm smooth walled round to oval right adnexal mass with thickened and diffuse internal echoes displacing gut loops superiorly and laterally. Another small hypodense cystic lesion of 2.8 × 1.7 cm was seen adjacent to the aforementioned adnexal mass (Fig. 2). Another well-defined smoothly marginated round mass 7.5 × 5.3 cm was seen in left adnexa CT abdomen and pelvic organ (Fig. 3).

Exploratory laparotomy confirmed bilateral fetal head size endometriomas with DIE. Dense areas with peritubal and periovarian adhesions present in pelvis, bladder, bowel and ligaments attaching uterus to pelvis.

Bilateral excision of endometriomas and extensive Figure 3. CT whole abdomen and pelvis showing welldefined thin walled cystic mass 7.5 × 5.3 cm in left adnexal region (Case 1).

endometriotic implants was done. Only minimal ovarian tissue could be reserved on both sides. Histopathological examination (HPE) confirmed extensive endometriosis.

Long-term oral contraceptive pill (OCP) started after 3 weeks and continued for 1 year. On follow-up patient is comfortable with regular menstrual cycle till date.2

Case 2

Figure 1. Longitudinal and transverse USG sections of uterus showing cystic lesion of 2.5 cm in right adnexa (Case 1).

Figure 2. CT whole abdomen and pelvis showing right adnexal mass 9 × 7.2 cm (Case 1).

A 31-year-old female presented in OPD with chief complaint of primary infertility for 10 years with menorrhagia associated with passage of clots. She is a known case of hypothyroidism, took tablet eltroxin 50 μg for 6 months but stopped herself since last 1 year.

Her menstrual cycle was 7 days, heavy flow associated with clots in every 24-26 days. P/A was soft to firm in consistency with a nontender midline mass of 14 weeks size of pregnant uterus arising out of pelvis felt with regular margins and smooth surface. Bimanual pelvic examination revealed a nontender soft to firm 10 × 10 cm mass in right fornix and another mass of 6 × 5 cm of similar consistency was felt in left adnexa. Uterus was retroverted, exact size could not be made out. USG confirmed 16 × 10 cm mass in right adnexa and 15 × 10 cm cystic mass in left adnexa. CA-125 was 46 IU/mL. On exploratory laparotomy, bilateral large endometriomas 20 × 10 cm left adnexa and 7 × 5 cm right adnexa were seen with dense adhesions between uterus, transverse colon and omentum. Uterine surface was irregular and pouch of Douglas was obliterated. Dark cherrycolored chocolate fluid was aspirated from both the endometriomas. Both of the endometriomas had daughter cysts. Most of the ovarian tissue was replaced

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OBSTETRICS AND GYNECOLOGY by endometrioma. There was Grade IV endometriosis.

Conservative surgery was done with removal of the endometriomas and conservation of ovarian tissue.

Postoperatively, she was put on injection gonadotropinreleasing hormone (GnRH) agonist (injection leuprolide 3.75 mg IM monthly for 3 months) and was advised in vitro fertilization (IVF).

Case 3 A 31-year-old female was admitted with complaint of chronic lower abdomen pain and primary infertility for 10 years. All required investigations were done. CA-125 was 75 IU/mL. CT whole abdomen showed a welldefined thin walled cystic lesion 7.3 × 4.9 cm in right adnexa with septa 3 mm with right ovary 1.5 × 2.5 cm in size was seen. Left ovary was enlarged, 3.5 × 4.9 cm in size with multiple cystic lesions of variable sizes.

Within it a well-defined cystic tubular structure 6.2 × 2.7 cm was seen lying along the ovary. Uterus was normal in shape and size with endometrial thickness (ET) 8 mm, 2 well-defined hypoechoic masses 1.5 × 1.5 cm and 0.9 × 0.9 cm were seen in anterior myometrium suggestive of fibroids. Exploratory laparotomy was done after informed consent. On exploratory laparotomy, uterus was seen buried in dense adhesions along with bilateral 7 × 7 cm large endometriomas.

There were dense peritubal and periovarian adhesions along with gut specially rectum and omentum and posterior surface of uterus. Uterosacral ligament was studded with endometriotic implants. HPE: right ovarian aspirate cytology confirmed hemosiderin laden macrophages features suggestive of chocolate cyst ovary. Left ovarian cyst cytology showed degenerated cells with necrotic debris in background (Fig. 4).

Figure 4. Histopathological examination showing hemosiderin laden macrophages (Case 3).

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Case 4 A 24-year-old unmarried female was admitted with complaint of congestive dysmenorrhea for 2-3 months.

She had normal menstrual cycles with 4 days moderate flow associated with severe pain. She was a known case of hypothyroidism who had been taking tablet eltroxin 50 μg but had discontinued taking them 2 years back.

USG confirmed normal shape size uterus with ET 10 mm irregular walled cystic lesion with internal echoes and few septa 4.75 × 5.25 cm in left adnexa with another cystic lesion 2.5 × 1.93 cm with internal echoes in right adnexa suggestive of right hemorrhagic ovarian cyst.

A tubular multiseptate structure with internal echoes was seen in right adnexa suggestive of pyosalpinx or hematosalpinx. On diagnostic laparoscopy, both the ovaries were replaced by endometriomas. Posterior surface of uterus was found densely adhered to gut and omentum. Burn match stick endometriotic patches were seen over ovarian fossa, tubes and uterine surface. Conservative surgery was done with aspiration of endometriomas and adhesiolysis and fulguration of endometriotic patches. There was Grade IV endometriosis with DIE. She was put on OCP for 1 year after surgery.

Case 5 A 45-year-old P1L1 female landed up in High Dependency Unit, Obstetrics and Gynecology with chief complaint of acute abdominal pain. She was in shock, blood pressure (BP) 90/60 mmHg and pulse rate (PR) 120/min. Her USG whole abdomen and pelvic organ showed a large 20 × 10 cm cystic mass in left adnexa with uterus 14 cm in size, multiple fibroids with fluid in peritoneum and cul-de-sac. On needling, hemoperitoneum was confirmed. She was in shock.

Immediate exploratory laparotomy was done. There was rupture of right-sided large endometrioma (10 × 8 cm) with hemoperitoneum of about 3 liters with 8 × 8 × 5 cm endometrioma on left side. There were bilateral large hematosalpinx with dark tarry chocolate material pouting out of fimbrial end. There was gross picture of DIE with dense adhesions of uterus and endometriomas with bladder, gut and omentum. Total abdominal hysterectomy and removal of endometriomas with bilateral salpingectomy was done. Uterus was 10 weeks size, studded with fibroids. On cut section, uterus was also filled with dark tarry fluid.

Note is made that during the time period of this case series, though magnetic resonance imaging (MRI) which is diagnostic modality of endometriomas (characteristic hyperintensity on T1-weighted images and hypointensity on T2-weighted

OBSTETRICS AND GYNECOLOGY images) was not available in our hospital, so CT scan was done instead of MRI.

DISCUSSION Endometriosis, though traditionally is diagnosed after the 2nd or 3rd decade, approximately one-third of the patients with confirmed endometriosis experience their 1st symptom before 15 years of age.3 Women who have a first-degree relative affected by the disease have a 7 times higher risk of developing endometriosis than women who do not have a family history of the disease.4 Pelvic anatomy becomes distorted and fecundity is reduced via mechanical disruptions such as pelvic adhesions. These disruptions impair oocyte release or pick-up, alter sperm motility, cause disordered myometrial contractions, as well as impair fertilization and embryo transport.5 IVF studies have suggested that women with more advanced endometriosis have poor ovarian reserve, low oocyte and embryo quality and poor implantation.6,7 Both eutopic and ectopic endometrium have been shown to be resistant to progesterone, causing an unopposed estrogen state, which is likely not suitable for implantation.8,9 Many factors must be taken into account including but not limited to distorted pelvic anatomy, patientâ&#x20AC;&#x2122;s ovarian reserve, partner semen analysis, age, presence of endometriomas and length of infertility.10 Depending on the patient, current treatment options may include expectant management, surgical removal of implants, ovulation induction or IVF. For women with suspected stage III/IV endometriosis, IVF is recommended.

Current treatment of endometriosis-associated infertility focuses on improving fecundity by removing or reducing ectopic endometrial implants and restoring normal pelvic anatomy.11 Current research is also examining novel promising nonhormonal treatment options for endometriosis such as immunoconjugate, vascular endothelial growth factor antagonists and stem cells, which may also prove to increase fecundity by decreasing the extent of ectopic implants or improving the eutopic endometrium.12,13 Other trends in the treatment of endometriosis include the use of aromatase inhibitors, cyclooxygenase-2 inhibitors, omega-3 fatty acids and cannabinoid agonists.14 Prolonged GnRHa treatment prior to IVF may improve fertility rates in advanced endometriosis.15-17 Laparoscopic surgery is preferred to laparotomy; it is more cost-effective, has a shorter hospital stay and shorter recovery.18 A 2008 Cochrane review examined,

the current literature regarding laparoscopic ablation versus excision of endometriomas and found that excision of the cyst was associated with a subsequent increased spontaneous pregnancy rate in women who had documented prior subfertility (odds ratio [OR] 5.21; confidence interval [CI] 2.04-13.29). Resection was clearly superior when compared to drainage or ablation. IVF is currently the most effective treatment of endometriosis-associated infertility.

CONCLUSION Treatment of endometriomas with DIE-associated infertility should focus on improving fecundity by conservative laparoscopic surgery by removing or reducing ectopic endometrial implants and restoring normal pelvic anatomy followed by hormonal therapy and IVF. Early diagnosis and treatment during adolescence may decrease disease progression, prevent subsequent infertility and such catastrophic sequelae.

REFERENCES 1. Olive DL, Schwartz LB. Endometriosis. N Engl J Med. 1993;328(24):1759-69.

2. Kaur P, Bhatia R, Singh KD, Bhatia SK, Kaur S, Singh AD. Bilateral fetal head size endometriomas with deep infiltrating endometriosis in an adolescent girl. Med Res Chron. 2015;2(3):425-9.

3. Ballweg ML. Impact of endometriosis on womenâ&#x20AC;&#x2122;s health: comparative historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):201-18.

4. Simpson JL, Elias S, Malinak LR, Buttram VC Jr. Heritable aspects of endometriosis. I. Genetic studies. Am J Obstet Gynecol. 1980;137(3):327-31.

5. Holoch KJ, Lessey BA. Endometriosis and infertility.

Clin Obstet Gynecol. 2010;53(2):429-38.

6. Brosens I. Endometriosis and the outcome of in vitro fertilization. Fertil Steril. 2004;81(5):1198-200.

7. Olivennes F. Results of IVF in women with endometriosis. J Gynecol Obstet Biol Reprod (Paris).

2003;32(8 Pt 2):S45-7.

8. Lessey BA, Ilesanmi AO, Castelbaum AJ, Yuan L, Somkuti SG, Chwalisz K, et al. Characterization of the functional progesterone receptor in an endometrial adenocarcinoma cell line (Ishikawa): progesteroneinduced expression of the alpha1 integrin. J Steroid Biochem Mol Biol. 1996;59(1):31-9.

9. Lessey BA, Yeh I, Castelbaum AJ, Fritz MA, Ilesanmi AO, Korzeniowski P, et al. Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation. Fertil Steril. 1996;65(3):477-83.

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OBSTETRICS AND GYNECOLOGY 10. Senapati S, Barnhart K. Managing endometriosisClin Obstet Gynecol. associated infertility.

2011;54(4):720-6.

11. Ozkan S, Murk W, Arici A. Endometriosis and infertility: epidemiology and evidence-based treatments. Ann N Y Acad Sci. 2008;1127:92-100.

12. Taylor HS, Osteen KG, Bruner-Tran KL, Lockwood CJ, Krikun G, Sokalska A, et al. Novel therapies targeting endometriosis. Reprod Sci. 2011;18(9):814-23.

13. Petracco RG, Kong A, Grechukhina O, Krikun G, Taylor HS. Global gene expression profiling of proliferative phase endometrium reveals distinct functional subdivisions. Reprod Sci. 2012;19(10): 1138-45.

15. Guo YH, Lu N, Zhang Y, Su YC, Wang Y, Zhang YL, et al.

Comparative study on the pregnancy outcomes of in vitro fertilization-embryo transfer between long-acting gonadotropin-releasing hormone agonist combined with transvaginal ultrasound-guided cyst aspiration and longacting gonadotropin-releasing hormone agonist alone.

Contemp Clin Trials. 2012;33(6):1206-10.

16. Ozkan S, Arici A. Advances in treatment options of endometriosis. Gynecol Obstet Invest. 2009;67(2):81-91.

17. Surrey ES, Voigt B, Fournet N, Judd HL. Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone “add-back” therapy. Fertil Steril. 1995;63(4):747-55.

18.

14. Rocha AL, Reis FM, Petraglia F. New trends for the medical treatment of endometriosis. Expert Opin Investig Drugs. 2012;21(7):905-19.

■■■■

Busacca M, Fedele L, Bianchi S, Candiani M, Agnoli B, Raffaelli R, et al. Surgical treatment of recurrent endometriosis: laparotomy versus laparoscopy. Hum Reprod. 1998;13(8):2271-4.

Risk Factors for Chronic Post-traumatic Stress Disorder Development 1 Year After Vaginal Delivery: A Prospective, Observational Study A new study published in the Scientific Reports aimed to assess the prevalence of post-traumatic stress disorder (PTSD) 1 year post vaginal delivery, and to identify characteristics of women and of associated deliveries.

In this prospective study, delivery and postpartum data of 1,103 women was collected via questionnaires, 1 year after childbirth, which included a question on their experience of childbirth on day 2. PTSD was assessed a year later by the Impact of Event and Traumatic Event Scales. The findings revealed that the factors associated with higher risk of PTSD profile were previous abortion, previous postpartum hemorrhage and postpartum hemoglobin <9 g/dL. Among 56 women (10.3%) reporting bad childbirth memories at Day 2 postpartum, 11 met PTSD diagnosis and 11 met PTSD profile criteria, a year later. Whereas, among 489 (87.7%) women with good childbirth memories at Day 2, 11 were diagnosed with PTSD and 18 with PTSD profile. Thus, it was inferred that PTSD is not rare, 1 year after vaginal delivery, in a low-risk population. It was stated that a simple question at Day 2 postpartum may identify women who are at a higher risk of PTSD and help determine the necessity of an early intervention.

Outpatient Hysteroscopy may Diagnose Endometrial Pathology in Postmenopausal Women According to a retrospective analysis published online July 31, 2017 in the journal Menopause, outpatient hysteroscopy is an adequate and reliable tool for the evaluation of benign pathology in the uterine cavity. Overall visual accuracy was calculated with 93.1% sensitivity, 52.1% specificity, 90.4% positive predictive value and 61.0% negative predictive value. Directed biopsies may improve diagnostic accuracy.

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OBSTETRICS AND GYNECOLOGY

Obstetrical and Neonatal Outcome of Pregnancy in Women with Previous One Cesarean Section: A Prospective Study NAVNEET KAUR*, GURDEEP KAUR†, PARAMJIT KAUR‡, RUBY BHATIA†

ABSTRACT Objective: Rising trends in number of post cesarean pregnancies is being observed in day-to-day obstetric practice, since there is tremendous increase in primary cesarean section rates due to multifactorial reasons. The present study was conducted to observe the maternal and the neonatal outcome in women with previous one cesarean section. Material and methods: This prospective study was conducted on 100 pregnant women with previous one cesarean section admitted to emergency labor room of Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala. Patients were evaluated thoroughly by history and clinical examination. Mode of delivery was decided. Women were given TOLAC (trial of labor after cesarean section) after informed consent. Labor was continuously monitored for any complications to decrease the maternal and perinatal morbidity and mortality. Results: A total of 100 pregnant women with previous cesarean were enrolled in the study. Eighty-five (85%) women had repeat cesarean section and 15 (15%) had vaginal delivery. Sixty-five (76.47%) women had emergency cesarean section and 20 (23.53%) had an elective cesarean. Nonprogress of labor was the most common indication for repeat cesarean section (25). Birth weight of babies were ≤2,500 g in 26 (26%) women, 42 (42%) had weight of 2,600-3,000 g and 32 (32%) had >3,000 g. There was no maternal or perinatal mortality in our study. Conclusion: The trial of labor after cesarean section should be conducted in carefully selected patients after informed consent explaining all the risks with everything ready for cesarean section with availability of blood, anesthetist, neonatologist and continuous maternal and fetal monitoring. The women who don’t fit into the criteria should be kept for elective cesarean section.

Keywords: Cesarean section, vaginal birth after cesarean section, TOLAC, pregnancy, labor

C

esarean section has been a part of human culture since ancient times and there are tales in both western and eastern cultures of this procedure resulting in live mothers and offsprings.1 In today’s obstetric practice, we encounter increasing number of post cesarean pregnancies because of rise in primary cesarean due to multifactorial reasons. There is increasing concern by obstetricians for managing these cases for medical and legal point of view.2 In past 20 years, the rate of cesarean delivery has steadily increased from about 5% to more than 20%.3 With present techniques and skill, the incidence of cesarean

*Senior Resident †Associate Professor ‡Professor Dept. of Obstetrics and Gynecology Govt. Medical College and Rajindra Hospital, Patiala, Punjab Address for correspondence Dr Navneet Kaur 267, SST Nagar/Sunder Nagar Near Guru Harkrishan Public School, Patiala - 147 001, Punjab E-mail: nav_neetu8@yahoo.in

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scar rupture in subsequent pregnancies is very low.

The strength of the uterine scar and its capacity to withstand the stress of subsequent pregnancy and labor cannot be completely assessed or guaranteed in advance.3 Planned vaginal birth after cesarean (VBAC) is contraindicated in women with previous uterine rupture or classical cesarean scar and in women who have other absolute contraindications to vaginal birth that apply irrespective of the presence or absence of a scar (e.g., major placenta previa). In women with complicated uterine scars, caution should be exercised and decisions should be made on a case-by-case basis by a senior obstetrician with access to the details of previous surgery. The success rate of a trial of labor after cesarean (TOLAC) ranges between 50% and 85%.4 Vaginal delivery is associated with fewer risks, requires less anesthesia, poses a lower potential for postpartum morbidity, involves a shorter hospital stay, is more affordable and encourages earlier and better bonding between mother and infant.5 Uterine rupture is the most catastrophic complication of a trial of labor

OBSTETRICS AND GYNECOLOGY after previous cesarean delivery. Other complications include scar dehiscence, febrile illness, infections, thromboembolic events and bleeding due to morbidly adherent placenta. The incidence of uterine rupture with VBAC in a mother who has had a low transverse incision is approximately 0.2-0.5%.6 MATERIAL AND METHODS This was an observational prospective study conducted in pregnant women at ≥35 weeks with previous one cesarean section who came to labor room of Dept. of Obstetrics and Gynecology, Govt. Medical College and Rajindra Hospital, Patiala in emergency. The study included a total of 100 pregnant women at ≥35 weeks gestation with previous one cesarean section admitted in emergency labor room. Patients were evaluated thoroughly by a detailed history, general physical and local examination with special emphasis on vitals/any evidence of scar tenderness. The maternal parameters taken were name, age, obstetric history, gestation, indication for previous cesarean (recurrent/ nonrecurrent) (elective/emergency), time elapsed since previous cesarean. The place of previous cesarean section and postpartum complication if any were was also noted. The mode of delivery (TOLAC/lower segment cesarean section [LSCS]) was decided after taking into consideration the risk factors in present pregnancy.

Patients were kept for TOLAC provided they fulfilled all the desired criteria after taking the informed consent from the patient. Labor was constantly monitored by partogram and patients were immediately taken up for emergency cesarean in event of fetal distress, scar tenderness or nonprogress of labor. Patients not fulfilling the criteria were taken up for elective cesarean section as per departmental protocol. After the delivery, birth weight, Apgar score of baby and intrapartum or postpartum complications, if any were noted.

RESULTS A total of 100 pregnant women at ≥35 weeks gestation with previous one cesarean delivery were included in the study. Of these, 85 (85%) women underwent

cesarean section and 15 (15%) had TOLAC (Table 1). Out of total 85 pregnant women who had cesarean delivery, 65 (76.47%) had an emergency cesarean section due to one or other indication, while 20 (23.53%) had an elective cesarean. In 75 (88.24%) women, repeat cesarean section was done for recurrent indication, while 10 (11.76%) had nonrecurrent indication for previous cesarean section.

Five (5%) women with previous cesarean section were ≤20 years of age, out of whom 2 (40%) had vaginal delivery. Forty (40%) women were in age group of 21-25 years, 48 (48%) in 26-30 years of age group.

Seven (7%) women came at >30 years of age and they had cesarean section. Ten (10%) women came at 35-37 weeks, 75 (75%) women at 37-40 weeks of gestation and 6 (6%) came at >40 weeks. One woman with >40 weeks gestation in labor had a vaginal delivery and rest 5 (83.33%) had cesarean section. Out of a total of 25 patients who were multiparous, 5 (20%) had a vaginal delivery and 20 (80%) had cesarean section (Table 2).

In our study, total 10 patients (who fulfilled all the desired criteria for VBAC) were induced for TOLAC, only 5 (33.33%) of them had VBAC and remaining 5 had cesarean section done due to NPOL, which was otherwise the most common indication for cesarean section in the study. Fifteen (15%) patients were referred in labor and they had cesarean section due to NPOL. Fourteen (14%) women came with pregnancy-induced hypertension, 55 (55%) had severe anemia, 2 (2%) had gestational diabetes mellitus, 12 (12%) women had fetal growth restriction with oligohydramnios. One patient each came with abruptio placentae, breech in labor and transverse lie and all had cesarean section. In half of the 20 (23.53%) women who had an elective cesarean section, intraoperatively scar was thinned out. In 10 (10%) women with repeat cesarean, previous cesarean section was done due to cephalopelvic disproportion. Thirteen (13%) women had meconium-stained liquor with fetal distress for which emergency cesarean was done and 9 (9%) women had an emergency cesarean section due to scar tenderness. Four (4%) women who were admitted due to placenta previa with previous cesarean section had an elective cesarean (Table 3).

Table 1. Total Number of Cesarean Section and Vaginal Births (n = 100) Total

VBAC (n = 15) Spontaneous

100

Cesarean section (n = 85)

Induced

Elective

Emergency

Recurrent indication

Nonrecurrent indication

No.

%

No.

%

No.

%

No.

%

No.

%

No.

%

10

66.67

5

33.33

20

23.53

65

76.47

75

88.24

10

11.76

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OBSTETRICS AND GYNECOLOGY Table 2. Demographic Profile of Patients (n =100) Total

LSCS

VBAC

No.

%

No.

%

No.

%

<20

5

5

3

60

2

40

21-30

88

88

76

86.34

12

13.64

>30

7

7

7

100

0

0

â&#x2030;Ľ35

10

10

4

40

6

60

36-40

75

75

10

13.33

65

86.67

>40

6

6

5

83.33

1

16.67

Literate

88

88

66

75

22

25

Illiterate

12

12

7

58.33

5

41.67

Lower

33

33

22

66.67

11

33.33

Middle

51

51

42

82.35

9

17.65

Upper

16

16

9

56.25

7

43.75

Rural

68

68

56

82.35

12

17.65

Urban

32

32

23

71.88

9

28.12

Age (years)

Gestation (weeks)

Literacy

Socioeconomic status

Residence

Table 3. Indications of Repeat Cesarean Section (n = 85 = 100%) Indications

No.

%

CPD

10

10

MSL

13

13

Transverse lie

1

1

NPOL

25

25

Scar tenderness

10

10

FGR with oligohydramnios

12

12

Severe pre-eclampsia

14

14

Twins

1

1

Abruptio

1

1

Placenta previa

4

4

CPD = Cephalopelvic disproportion; MSL = Meconium-stained liquor; NPOL = Nonprogress of labor; FGR = Fetal growth restriction.

Forty-three (43%) women in the study came with previous cesarean in labor, out of them, 10 (66.67%) had vaginal delivery and rest all had an emergency

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cesarean section due to either scar tenderness or fetal distress. Five (33.33%) women had a vaginal delivery were augmented with Pitocin. The patients kept were continuously monitored for any complication. None of the patient with previous LSCS for TOLAC had scar rupture during our study. Two patients were referred with rupture uterus to our hospital during the study period.

Sixteen women came with scar tenderness on admission in whom cesarean section was immediately done in emergency. In 2 women, classical cesarean section was done and one had an upper segment cesarean due to very dense adhesions. Birth weight of babies were â&#x2030;¤2,500 g in 26 (26%) women, 42 (42%) had weight of 2,600-3,000 g and 32 (32%) had >3,000 g (Table 4). There was no stillbirth or neonatal death. One women in the TOLAC group with baby birth weight >3,000 g had a successful vaginal delivery. The Apgar score of newborn babies at 1 and 5 minutes were good in all patients with TOLAC except for 2 patients each with preterm vaginal delivery and pre-eclampsia with fetal growth restriction. Twenty (20%) women had atonic postpartum

OBSTETRICS AND GYNECOLOGY Table 4. Birth Weights of Babies Born to Women with Previous Cesarean Section (n = 100) Birth weight (gms)

n = 100 = 100% No.

%

LSCS

VBAC

No.

%

No.

%

<2,500

27

27

21

21

6

6

2,500-3,000

48

48

41

41

7

7

3,100-3,500

21

21

19

19

2

2

>3,500

4

4

4

4

0

0

hemorrhage, which was managed conservatively with 6 women requiring blood transfusions. No maternal mortality was reported in the study group.

DISCUSSION Good candidates for planned TOLAC are those women in whom the balance of risks (as low as possible) and chances of success (as high as possible) are acceptable to the patient and the healthcare provider.7 In our study, patients with previous LSCS fulfilling the criteria, were taken up for TOLAC after informed consent. Patients with recurring indications were taken up for repeat elective LSCS as per departmental protocol.

In our study, 85% women had cesarean section and it was similar to the study by Rahman et al (85%).1 In their study, they took 126 women and out of them, 26 dropped out. So, 100 women were studied and compared. In the study by Balachandran et al, cesarean section rate was 16.5% which was quite less.8 The high percentage in our study (85%) is because ours is a tertiary care center and percentage of high risk who are referred is quite large, so the patients are managed very vigilantly to avoid complications and without taking any undue risks. The most common indication for elective cesarean section in our study was unknown scar type as the patients donâ&#x20AC;&#x2122;t bring their previous surgery records along with them and a very limited information could be extracted from history.

The TOLAC rate in our study was 15% and in the study by Singh et al, it was 67.6%.9 The most common indication for cesarean section was NPOL (25%) as compared to the study by Bangal et al3 and Singh et al,9 where it was fetal distress (46%). In our study, 14% women came with pre-eclampsia and all had cesarean section, whereas in the study conducted by Jani et al2 only 5.26% came with pre-eclampsia. They took only 50 women and the study was conducted in a private hospital, so the number of high risk women were less in their study (Fig. 1).

30 Jani et al

Present study

25

25

20

15

14

13 10

10

10

7 5

5

4

2

2

2

1 1

1

0 NPOL

Fetal distress

CPD

Scar S PIH Abruptio Placenta tenderness previa

Figure 1. Comparison of indications of cesarean section.

Current obstetric opinion is that the LSCS is not a contraindication for the use of oxytocin for induction and augmentation of labor; however, the role of prostaglandins is controversial. To determine the impact of labor induction on both the success and safety of a trial of labor in women who were candidates for TOLAC, a prospective observational analytical study was conducted at the Medical University of South Carolina. The vaginal delivery rate was significantly higher (77.1% vs. 57.9%) in the spontaneous labor group compared with the induced labor group6 and the similar result was found in our study (66.66% vs.

33.33%). So, these studies conclude that induction of labor in women attempting VBAC is associated with a significantly reduced rate of successful vaginal delivery.

A study was conducted by Hendler et al in which effect of prior TOLAC was studied to see the obstetric outcome and it was seen that the rate of successful trial of labor was quite high in women with prior TOLAC

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OBSTETRICS AND GYNECOLOGY (93.1% vs. 70.1%),10 but such an observation was not seen in our study because we had 5 women with prior TOLAC and all had cesarean section either due to scar tenderness or severe pre-eclampsia with fetal growth restriction with fetal distress.

In one of the study by Anwar et al11 which also involved 100 women, 59 (59%) gave birth to neonates with birth weight 2.5-3 kg, while 25 (25%) had birth weight 3.1-3.5 kg and only 16 neonate (16%) had birth weight 3.6-4 kg as compared to 48 (48%), 27 (27%) and 4 (4%), respectively in our study. The chances of success of VBAC section increases with lower birth weight as seen in our study, where 100% women had cesarean section in whom birth weight of newborns were >3,500 g and it was similarly found by Birgisdottir et al in their study that the trial of labor was less likely to succeed if the infant’s birth weight was >4,000 g compared with <4,000 g.12 CONCLUSION For successful delivery after a previous cesarean section, the obstetrician requires to have the expertise to carefully select the patients, for trial of vaginal birth because rupture of scar can endanger the life of the mother and the child. The spontaneous onset of labor, average-sized babies and increasing parity are the other factors having a positive impact on the successful outcome of TOLAC. Planned TOLAC after informed consent is appropriate for and may be offered to the majority of women with a singleton pregnancy of cephalic presentation at 37+0 weeks or beyond who have had a single previous lower segment cesarean delivery, with or without a history of previous vaginal birth (RCOG).

The informed consent for VBAC should be taken before the trial of labor and it should be conducted in the institution equipped with all the facilities for emergency cesarean section with constant maternal and fetal monitoring.

Acknowledgment I am highly thankful to all my teachers and my family who encouraged me in every aspect of my life. I am thankful to Dr Paramjit Kaur, Dr Ruby Bhatia and Dr Gurdeep Kaur who helped me in collecting the material and writing on this topic. This paper has been

possible due to joint effort of my co-authors as well.

I really appreciate the work of juniors who helped me in this topic a lot. This study has been conducted prospectively and no harm has been inflicted upon the patients involved in the study.

REFERENCES 1. Rahman R, Khanam NN, Islam N, Begum KF, Pervin HH, Arifuzzaman M. The outcome of vaginal birth after caesarean section (VBAC): a descriptive study. J Med Today. 2013;25(1):14-7.

2. Jani RS, Munshi DS. Management of pregnancy with previous lower segment caesarean section in modern obstetric practice. NHL J Med Sci. 2013;7(2):59-63.

3. Bangal VB, Giri PA, Shinde KK, Gavhane SP. Vaginal birth after cesarean section. N Am J Med Sci. 2013;5(2):140-4.

4. Martel MJ, MacKinnon CJ; Clinical Practice Obstetrics Committee, Society of Obstetricians and Gynaecologists of Canada. Guidelines for vaginal birth after previous caesarean birth. J Obstet Gynaecol Can. 2005;27(2):164-88.

5. Ugwu GO, Iyoke CA, Onah HE, Egwuatu VE, Ezugwu FO. Maternal and perinatal outcomes of delivery after a previous cesarean section in Enugu, Southeast Nigeria: a prospective observational study. Int J Womens Health. 2014;6:301-5.

6. Islam A, Ehsan A, Arif S, Murtaza J, Hanif A. Evaluating trial of scar in patients with a history of caesarean section.

N Am J Med Sci. 2011;3(4):201-5.

7. American College of Obstetricians and Gynecologists.

ACOG Practice bulletin no. 115: Vaginal birth after previous cesarean delivery. Obstet Gynecol.

2010;116(2 Pt 1):450-63.

8. Balachandran L, Vaswani PR, Mogotlane R. Pregnancy outcome in women with previous one cesarean section.

J Clin Diagn Res. 2014;8(2):99-102.

9. Singh N, Tripathi R, Mala YM. Maternal and foetal outcomes in patients with previous caesarean section undergoing trial of vaginal birth at a tertiary care centre in North India. J Preg Child Health. 2014;1(1):1-5.

10. Hendler I, Bujold E. Effect of prior vaginal delivery or prior vaginal birth after cesarean delivery on obstetric outcomes in women undergoing trial of labor. Obstet Gynecol. 2004;104(2):273-7.

11. Anwar S, Ahmad S, Abbasi N, Anwar MW. Effect of birth weight on success of vaginal birth after caesarean delivery.

Gomal J Med Sci. 2015;13(1):46-8.

12. Birgisdottir BT, Hardardottir H, Bjarnadottir RI, Thorkelsson T. Vaginal birth after one previous cesarean section. Laeknabladid. 2008;94(9):591-7.

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EXPERTâ&#x20AC;&#x2122;S VIEW

How are BP Levels and Visceral Adiposity Correlated with Kidney Disease?

KK AGGARWAL

O

besity has fast become a public health problem.

It is a significant risk factor for cardiovascular disease (CVD) and several metabolic disorders, including type 2 diabetes.1 Likewise, chronic kidney disease (CKD) has also become known as a global public health problem.2

The increasing prevalence of obesity has often been held accountable for the steady increase in CKD prevalence; however, the mechanisms are not yet clearly known.3 The link between obesity and the incident cardiovascular (CV) and renal diseases is mediated by several mechanisms including hypertension, hyperglycemia, dyslipidemia, inflammation and atherosclerosis.1 These disorders often coexist, especially in patients who have excess visceral fat.1 General body obesity, which is expressed as body mass index (BMI), has been linked with the development of CKD.2 Of note, visceral obesity, rather than peripheral/ subcutaneous type, is a more accurate marker of the metabolic changes in the body.2 Visceral adiposity seems to be a better predictor of CV risk factors than the conventional clinical anthropometric measures including BMI and waist circumference.3 There seems to be a robust correlation between visceral adiposity and the two major causes of CKD - hypertension and diabetes.1 Overweight and obesity account for 65-75% of the risk for essential hypertension and type 2 diabetes is closely linked with increased visceral adiposity.

In a recent study by Xu et al,2 visceral adiposity index (VAI) was positively correlated with the albuminto-creatinine ratio and the prevalence of CKD, and inversely with estimated glomerular filtration rate (eGFR). This correlation was dependent on fasting blood glucose and BP levels. In a study by Young et al,3 both visceral (VAT) and subcutaneous adipose tissue (SAT) were associated with CKD, but only when defined as eGFR <60 mL/min/1.73 m2 as estimated by cystatin C, not creatinine.

An association has also been shown for ectopic kidney fat depots with renal dysfunction and hypertension.

Renal sinus fat has been linked with stage II hypertension and the number of antihypertensive medications required to control BP. Additionally, visceral obesity tends to increase BP, partly on account of physical compression of the kidneys.1 In the Framingham Heart Study, subjects with increased levels of perinephric fat had increased risk for hypertension, which persisted after adjusting for BMI and visceral fat.

Therefore, hypertension and diabetes, besides other disorders associated with the metabolic syndrome, act in synergy and heighten the risk of CKD and progression to end-stage renal disease (ESRD). Additionally, obesity has the potential to cause renal dysfunction and increase the risk for CKD, independent of diabetes and hypertension.1

Fatty kidney was also associated with increased risk for CKD even after adjustment for BMI and visceral adiposity.1 A cross-sectional survey assessed 1,832 individuals without decreased GFR <60 mL/ min/1.73 m2, diabetes and metabolic syndrome. Researchers intended to determine the association between serum uric acid and urinary albumin/creatinine ratio (uACR) in subjects with 0, and 1-2 metabolic syndrome components and to ascertain the modification effects of VAI, mean arterial pressure (MAP) and fasting glucose on this association.

A strong modification effect of VAI and MAP was noted on the association between uACR and uricemia, thus pointing to obesity-related hypertension as the underlying mechanism.4

Group Editor-in-Chief, IJCP Group President, Heart Care Foundation of India

Clear evidence thus exists to explain the role of obesity, particularly visceral, in the development of CKD. Obesity-associated hypertension, diabetes and dyslipidemia seem to act synergistically to heighten the risk of renal dysfunction.

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EXPERT’S VIEW REFERENCES 1. Hall ME, do Carmo JM, da Silva AA, Juncos LA, Wang Z, Hall JE. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:75-88.

3. Young JA, Hwang SJ, Sarnak MJ, Hoffmann U, Massaro JM, Levy D, et al. Association of visceral and subcutaneous adiposity with kidney function. Clin J Am Soc Nephrol.

2008;3(6):1786-91.

4.

2. Xu X, Zhao Y, Zhao Z, Zhu S, Liu X, Zhou C, et al.

Correlation of visceral adiposity index with chronic kidney disease in the People’s Republic of China: to rediscover the new clinical potential of an old indicator for visceral obesity. Ther Clin Risk Manag. 2016;12:489-94.

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Krajcoviechova A, Tremblay J, Wohlfahrt P, Bruthans J, Tahir MR, Hamet P, et al. The impact of blood pressure and visceral adiposity on the association of serum uric acid with albuminuria in adults without full metabolic syndrome. Am J Hypertens. 2016;29(12):1335-42.

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MEDILAW

No Patient can be Denied Treatment Due to Financial Constraints

This man, who works as a labourer, has filed a complaint against this hospital for denying treatment to his child who has a life-threatening illness.

The drug used for the treatment is very expensive and has to be given lifelong. The father of the child could not pay the treatment expenses.

Proceed A patient cannot be denied treatment due to financial constraints.

Lesson: Article 21 of the Constitution of India guarantees protection of life and personal liberty to every citizen. Article 14 provides for ‘Equality before law’.

In Mohd. Ahmed (Minor) vs Union Of India & Ors. on 17 April, 2014 W.P.(C) 7279/2013, the Delhi High Court held that “on account of lack of Government planning, there is ‘pricing out’ of orphan drugs for rare and chronic diseases, like Gaucher. The enzyme replacement therapy is so expensive that there is a breach of constitutional obligation of the Government to provide medical aid on fair, reasonable, equitable and affordable basis. By their inaction, the Central and the State Governments have violated Articles 14 and 21 of the Constitution. Just because someone is poor, the State cannot allow him to die. In fact, Government is bound to ensure that poor and vulnerable sections of society have access to treatment for rare and chronic diseases, like Gaucher especially when the prognosis is good and there is a likelihood of the patient leading a normal life.”

The Court also said, “By virtue of Article 21 of the Constitution, the State is under a legal obligation to ensure access to life saving drugs to patients.”

CASE SUMMARY Mr MS, filed a case on behalf of his son aged 7 years, who suffered from Gaucher’s disease, a life-threatening disease if left untreated. His three other children also had succumbed to the same illness. The treatment of Gaucher’s disease is lifelong enzyme replacement therapy to be administered every month. The cost of treatment is around Rs. 6-7 lakhs per month. The father, who is a rickshaw puller could not afford this treatment; as a result, the patient was denied treatment.

The father filed a case in the Delhi High Court seeking free treatment for his son. The patient underwent the first treatment in August 2013, with financial assistance from the Delhi Government’s Delhi Arogya Kosh

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Scheme, which provides financial assistance to the extent of Rs. 5 lakhs to needy eligible patients. Since, the patient had already received help of Rs. 4,80,000/, he could now get assistance of only Rs. 20,000/-. A hospital, a pharmaceutical company and lawyers of Delhi High Court voluntarily came forward to organise treatment for 6 months, while the petition was awaiting decision.

On 12th February, 2014, the Delhi High Court directed the Secretary (Health), Ministry of Health & Family Welfare and Secretary (Health), Govt. of NCT of Delhi along with other Government officials to decide if a policy could be framed to provide treatment. As no solution could be found at the meeting on 25th February, 2014, the Court commenced hearing final arguments on 25th March, 2014.

MEDILAW SOME SALIENT COURT OBSERVATIONS ÂÂ

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The Counsel for the father argued that AIIMS, Central Government and Govt. of NCT of Delhi were obligated under Article 21 of the Constitution of India to provide totally free treatment to the patient as well as those with similar illness as the treatment was available in India. Denying free treatment to the common man on the alleged grounds of financial constraints, while providing free treatment to government employees was “arbitrary, discriminatory and hit by Articles 14 and 21 of the Constitution.”

Delhi Govt./AIIMS/Union of India stated that because of their restricted resources they were not able to fund the treatment as the treatment was lifelong. The Counsel for the Delhi Govt. stated that “the State had an equal obligation towards all citizens and it had to use its limited resources so as to provide the maximum benefit to the maximum number of people… Provision of facilities cannot be unlimited. It has to be to the extent finances permit. If no scale or rate is fixed then in case private clinics or hospitals increase their rate to exorbitant scales, the State would be bound to reimburse the same.”

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AIIMS confirmed that the petitioner had Gaucher’s disease and that it had no fund for treatment of any of these patients. It also submitted that while it was conducting a humanitarian program wherein 16 patients were under treatment for Gaucher’s disease, the funds for their treatment were being provided by other parties.

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“37. This Court finds that the petitioner suffers from a disease/condition which affects such small numbers of individuals that drugs for these diseases/conditions are commonly referred to as ‘orphan drugs’.” While different countries have adopted different policies towards orphan drugs, India has no policy or strategy in place with regard to orphan drugs. The Court observed: “… neither any promising orphan drug will be developed nor the prohibitive cost of ‘orphan drugs’ will see a reduction unless changes are made in the applicable laws to reduce the costs of developing such drugs and to provide financial incentives to develop such drugs like in the above mentioned countries.”

The Court expressed its inability to direct the executive to frame a policy or the parliament to pass a legislation in this regard stating that the issue had to be decided in the context of the Indian Constitution.

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“49. Article 21 of the Constitution of India casts an obligation on the State to preserve life. Article 21 reads as under: 21. Protection of life and personal liberty- No personal shall be deprived of his life or personal liberty except according to procedure established by law.”

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“50. The Indian Supreme Court in a catena of cases has held that right to health and medical care is a fundamental right under Article 21 read with Articles 39(e), 41 and 43. It has further held that self-preservation of one’s life is the necessary concomitant of the right to life enshrined in Article 21, fundamental in nature, sacred, precious and inviolable.”

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The United Nations Universal Declaration of Human Rights and the International Covenant on Economic, Social and Cultural Rights have also recognised the human right to health. And, since India is a signatory to the same, Article 21 has to be interpreted in conformity with International Covenant on Civil and Political Rights.

ÂÂ

“58. Consequently, right to health and health care access are a part of Articles 21, 38 and 46 of the Constitution.

Accordingly, every person has a fundamental right to quality health care - that is affordable, accessible and compassionate.”

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Recognising the availability of finance as a relevant factor, the Court said “… courts cannot direct that all inhabitants of this country be given free medical treatment at state expense. Even if such a direction were issued it would not be implementable as there would be neither infrastructure nor finance available for compliance of the said direction.” However, the Court also recognised that core obligations under the right to health are non-derogable. It stated as follows: “By virtue of Article 21 of the Constitution, the State is under a legal obligation to ensure access to life saving drugs to patients… Government must at the bare minimum ensure that individuals have access to essential medicines even for rare diseases like enzyme replacement for Gaucher disease...”

ÂÂ

The civil society and corporates should be involved in providing health care access to the poor and underprivileged in the form of donations.

Corporates are required to donate a percentage of their average net profits on CSR activities under Section 135 of the Companies Act, 2013.

FINAL JUDGEMENT Summarising its observations, the Court said that “there is a breach of constitutional obligation of the Government to provide medical aid on fair, reasonable, equitable and

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MEDILAW affordable basis. By their inaction, the Central and the State Governments have violated Articles 14 and 21 of the Constitution.” Nobody should be denied treatment because of financial constraints. Providing access to essential medicines at affordable prices is a core obligation of the state and “Since a breach of a Constitutional right has taken place, the Court is under a duty to ensure that effective relief is granted.” Health is a state subject. So, the

Court directed the Delhi Govt. to provide the required treatment free of cost to the patient “as and when he requires it.”

REFERENCE

1. Mohd. Ahmed (Minor) vs Union Of India & Ors. on 17 April, 2014 in the High Court of Delhi at New Delhi W.P.(C) 7279/2013.

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CONFERENCE PROCEEDINGS

ADA-PAMS: Clinical Update in Diabetes-2017 In a comparative study of SGLT2i as the 5th drug

POSITIONING SULFONYLUREA TODAY

ÂÂ

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in management of T2DM in Asian Indians not controlled with at least 4 oral antidiabetic drugs (OADs), canagliflozin was found to significantly reduce glycated hemoglobin (HbA1c) as compared to dapagliflozin. All SGLT2i showed significant weight loss (3.2% with dapagliflozin, 3.4% with empagliflozin and 4.1% with canagliflozin from baseline). All 3 SGLT2i are equally effective in getting desired glycemic control even when used as 5th add-on drug along with strict lifestyle modification in patients with inadequate glycemic control despite receiving an optimum dose of at least 4 OADs.

Dr Rajeev Chawla, New Delhi Sulfonylureas (SUs) are still largely used for treatment of type 2 diabetes patients, and they still occupy a central position in many international therapy guidelines.

Many of the clinical issues associated with the use of SUs are agent-specific, and do not pertain to the class as such.

Modern SUs (glimepiride, gliclazide MR) are backed by a large body of evidence, experience and most importantly, outcome data, which supports their role in managing patients with diabetes.

Recent trials reject that SUs lead to progressive b-cell decline.

Recent large cardiovascular (CV) trials and metaanalyses support CV safety/noninferiority of SUs. All SUs are not same. Binding to different sulfonylurea receptors (SURs), and to specific sites of SUR makes the modern SUs like glimepiride and gliclazide safe.

Another analysis of SGLT2i in real world clinical

practice in India revealed that when SGLT2i are added to any stage of the disease spectrum with any of the pre-existing therapeutic agents for patients with uncontrolled T2DM, there is an improvement in glycemic control and body weight, with minimal side effects. The real world study data on Indian patients appears to be promising.

SGLT2i - FROM CLINICAL TRIALS TO REAL WORLD

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Dr Shashank R Joshi, Mumbai

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Diabetes is associated with significant loss of life years. About 40-60% of people in India with diabetes die before the age of 60.

CVD-REAL study: Lower rates of hospitalization for heart failure and all-cause death in new users of SGLT2i.

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CVD-REAL Nordic (Dapagliflozin compared with dipeptidyl peptidase-4 inhibitors (DPP-4i): Use of dapagliflozin vs. DPP-4i was associated with lower risks of hospitalization for heart failure, major adverse cardiac event (MACE), all-cause mortality and hospitalization for kidney disease.

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Indian patient is unique and difficult to treat.

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Most type 2 diabetes mellitus (T2DM) patients do not achieve their treatment goals; have poor health outcomes and high mortality.

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India is suffering from dia-besity epidemic. Women are more impacted. Almost 75% T2DM patients in India are overweight or obese. The collateral damage of weight gain during T2DM treatment is clinically dangerous.

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Every 1 kg weight gain due to T2DM treatment leads to 7.1% relative increase in the risk of heart failure.

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Every body mass index (BMI) unit increase in the 1st year of diabetes can increase cardiovascular disease (CVD) mortality risk by 12%.

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Real world trend of SGLT2 inhibitors (SGLT2i) in India

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

WHY DO WE NEED NEWER PREMIX COFORMULATION – IDegAsp? Dr AK Singh, Kolkata ÂÂ

Biphasic insulin aspart (BIAsp) is more improvised version of premixed insulin with better prandial control and lesser nocturnal hypoglycemia but daytime hypoglycemia is undesirable due to shoulder effect.

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Insulin degludec/insulin aspart (IDegAsp), a soluble co-formulation of insulin degludec and insulin aspart, looks most promising biphasic insulin formulation - better fasting plasma glucose (FPG)

CONFERENCE PROCEEDINGS control, significantly less all components of hypoglycemia and lower dose requirement.

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SUs are not associated with increased CV risk, allcause mortality.

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Once IDegAsp is better than insulin glargine (IGlar) in reducing HbA1c as expected but with numerically lesser hypoglycemia.

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SUs as add on with metformin are considered safe in terms of overall and CV mortality.

IDegAsp was found to be superior to IGlar in terms of reducing prandial PG increment at the evening meal.

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Modern SUs (glimepiride) are still an important second-line option after metformin monotherapy.

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Twice IDegAsp challenging basal-bolus therapy in first and only study (similar glucose control but with numerically less hypoglycemia) - Very exciting finding but need few more studies to reach final conclusion.

EVOLVING LANDSCAPE OF DPP-4 INHIBITORS: FOCUS ON GEMIGLIPTIN Dr SR Aravind, Bengaluru ÂÂ

Crucial triad of glycemic control: Glycemic variability, hyperglycemia and hypoglycemia.

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Plasma glycemic variability, irrespective of HbA1c level, may confer an additional risk for the development of diabetic complications.

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Gemigliptin is an optimized DPP-4i.

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There is an unmet need to make diabetes care simpler for both physicians and patients.

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DPP-4i provide a simple, safe and effective therapeutic option.

T2DM patients who have not achieved glycemic

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Gemigliptin controls the crucial triad of hyperglycemia, hypoglycemia and glycemic variability.

Greater reduction of HbA1c, FPG.

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Gemigliptin:

MODERN SULFONYLUREAS: 40 YEARS AND BEYOND Dr Neeta Deshpande, Belgaum ÂÂ

Newer SUs are important second-line agents after metformin.

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Glycemic control with newer SUs is comparable with other regimen.

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Efficacy: control with monotherapy, glimepiride with metformin combination can be preferred

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is a potent, highly selective, long-acting DPP-4i

Durability:

provides greater inhibition of DPP-4 activity

Compared to DPP-4i + metformin, newer SU

than sitagliptin

+ metformin requires less intensification in treatment and also maintains a greater reduction of HbA1c

shows strong and sustained glycemic control in

Long-term monotherapy with glimepiride

is more effective in reducing glycemic variability

patients with T2DM than sitagliptin

(5 years), improves insulin sensitivity and has minimal effects on b-cell function compared with glibenclamide monotherapy

can be used without dose adjustment in T2DM

b-cell exhaustion: SUs are b-cell friendly, enhance

shows favorable effects on albuminuria and

patients with renal impairment

b-cell secretion, correct the imbalance between insulin production and release, protect against autophagy-associated b-cell death.

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lipid profiles

shows favorable safety profile - weight neutral

and minimal hypoglycemia

Effect on body weight:

can be used at any stage of T2DM management

SUs are less associated with weight gain When SUs are used with metformin, weight

gain is not a problem with SUs

in a once-daily dose.

INTELLIGENT SU CHOICES FOR PPG MANAGEMENT

SUs and hypoglycemia: Compared to older

SUs, newer SUs (glimepiride) show lower risk of hypoglycemic events, lower binding affinity to b cells, secrete lesser amounts of insulin during fasting.

Dr AG Unnikrishnan, Pune ÂÂ

Post-meal hyperglycemia: Independent risk factor for CVD Myocardial infarction (MI) and death

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379

CONFERENCE PROCEEDINGS Nephropathy and retinopathy

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vasodilation and impaired endothelial nitric oxide release.

Vildagliptin is associated with reduced insulin resistance due to: Reduced glucose toxicity; reduced glucagon during meals and reduced lipotoxicity.

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Successful management of postprandial glucose (PPG) significantly increases chances to get closer to A1c goal.

Vildagliptin is associated with 15% lower risk of hospitalization due to heart failure compared to sitagliptin.

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Vildagliptin - Robust clinical evidence: Most studied gliptin, robust real-world evidence; >15 million patient year of experience; >15,000 patients in clinical trials before market launch in India; approved in >120 countries; significant reduction in glycemic variability; significant liver fat reduction; established CV safety; established renal safety; and established safety in elderly patients.

Rapidly suppressed endothelium-dependent

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Gliclazide restores the first peak of insulin release from b cells.

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Repaglinide exhibits glucose-dependent activity with increase in the first phase insulin secretion following pulsatile release. It offers increased burnt mass and amplitude without tampering the pulsatile secretion pattern.

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SUs work well with all agents.

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CV risk and mortality: Gliclazide+Repaglinide has shown least risk compared to other insulin secretagogues.

DPP-4 INHIBITOR WITH ROBUST CLINICAL EVIDENCE

SULFONYLUREA PLUS COMBINATIONS: INTERNATIONAL CONSENSUS STATEMENTS Dr Anantharaman R, Bengaluru ÂÂ

Early initiation of combination therapy: Quick achievement of target glycemic level; reduces risk of adverse events associated with up-titration of monotherapy; reduces risk of micro- and macrovascular complications.

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Proposed recommendations:

Dr Rakesh Sahay, Hyderabad ÂÂ

DPP-4i represent a paradigm management of T2DM.

shift

in

the

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In many ways, they have changed the way that diabetes and its management has so far been perceived by clinicians.

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Vildagliptin is not associated with an increased CV risk including the risk of congestive heart failure compared with other noninsulin antidiabetic drugs (NIADs) under real-world conditions.

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The VildaGliptin clinical Use in the reAl woRlD (GUARD) study revealed that vildagliptin + metformin provided statistically significant and clinically relevant reductions in HbA1c from baseline, irrespective of baseline HbA1c, age or obesity status.

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Vildagliptin has been shown to induce better circadian glucose control than sitagliptin with significant decrease in overall hyperglycemia, mainly driven by reduction in basal hyperglycemia.

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Vildagliptin was shown to reduce blood glucose fluctuation in T2DM patients receiving maintenance hemodialysis for end-stage renal disease (ESRD).

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Vildagliptin treatment showed significant reduction in intrahepatic triglyceride levels in 6 months. This reduction was independent of any weight change.

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SUs in oral combination therapy: As second-

line agents - Modern SUs are effective and safe second-line agents in patients who have not achieved pre-decided glycemic targets with metformin monotherapy. As initial combination - Modern SUs are effective and safe as initial therapy if used in combination with lifestyle modification and metformin in patients with a baseline HbA1c ≥7.5%. Choice of combination with SU - SUs may be considered for use in combination with all classes of OADs except glinides. As third-line agent - If not used earlier, modern SUs may be preferred as third-line agents for management of diabetes uncontrolled with dual combination therapy, owing to better safety profile than older SUs. As fixed dose combinations (FDCs) - FDCs containing SUs reduce cost, offer convenience and improve patient adherence; hence, FDCs with varying strength of SU + metformin should be made available, while SU + other drugs may be considered.

Comparative assessment as dual therapy with

metformin: SU + metformin - Compared to metformin up-titration beyond half-maximal

CONFERENCE PROCEEDINGS dose, addition of SU to metformin demonstrates better glucose-lowering efficacy, safety and tolerability. SU vs. TZD - Compared to pioglitazone, SUs demonstrate good glucoselowering efficacy with significantly lower risk of weight gain. SUs vs. DPP-4i - Compared to DPP4i, SUs demonstrate better and more durable glucose-lowering efficacy. SUs vs. SGLT2i Compared to SGLT2i, SUs show noninferior glycemic control. SUs vs. glucagon-like peptide-1 receptor agonists (GLP-1 RA) - Compared to GLP-1 RAs, SUs show similar glycemic efficacy, with acceptable safety at lower cost.

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The CANagliflozin cardioVascular Assessment Study (CANVAS) trial included patients with type 2 diabetes - HbA1c ≥7% to ≤10.5%; eGFR ≥30 mL/ min/1.73 m2; age ≥30 years and a history of prior CV event OR age ≥50 years with ≥2 CV risk factors.

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Renal outcomes: Canagliflozin compared to placebo - Induced sustained-lowering of albuminuria; prevented progression in albuminuria; induced regression in albuminuria; reduced renal function loss events. These data suggest a potential renoprotective effect of canagliflozin treatment in patients with type 2 diabetes at high CV risk on top of angiotensin-converting enzyme/angiotensin receptor blockers (ACE/ARBs).

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CANVAS Program: Clinical Pearls- Fourteen percent reduction in MACE which consists of CV death, nonfatal MI, nonfatal stroke; achieved significant reduction in MACE in spite of including two types of patient population; favorable effect in hospitalization for heart failure; canagliflozin was not associated with an increased risk of stroke; potential renoprotection; incidence of amputation was low and was majorly seen in patients with a history of amputation.

SU and insulin combination: With basal insulin -

Modern SUs may be continued, with appropriate precaution, when basal insulin is initiated. With premixed insulin OD - Modern SUs may be continued, in the antipodal meal, if premixed insulin is initiated once-daily. With premixed insulin BD - Short-acting SUs or glinides may be continued or added with the third meal with appropriate glucose monitoring if premixed insulin is initiated twice-daily.

NEXT GENERATION GLARGINE: RE-DEFINING THE INSULIN EXPERIENCE

SGLT2i – PLACE IN THERAPY

Dr Krishna G Seshadri, Chennai ÂÂ

Majority of T2DM patients in Asia-Pacific region fail to achieve glycemic targets (HbA1c <7%).

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Next generation glargine-300 aims to improve the insulin experience, through a unique pharmacokinetic/pharmacodynamic profile: >24 hours duration of action Flexibility (+3 hours)

Dr Ganapathy Bantwal, Bengaluru ÂÂ

SGLT2i have novel insulin independent mechanism of action, which enhances the excess excretion of glucose.

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SGLT2i are effective across different HbA1c levels, BMI, age and duration of diabetes.

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SGLT2i have place in the treatment of obese or overweight T2DM patients, T2DM patients with hypertension, T2DM patients with CVD, T2DM patients with CV risk factors, T2DM patients with heart failure and T2DM patients with renal disease.

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Normalization of insulin:glucagon ratio in patients with T2DM is the novel mechanism of SGLT2i.

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Significant reduction of BMI and waist circumference has been noted with canagliflozin, majorly due to loss of fat mass.

Low variability/more predictable response. ÂÂ

Twelve months data showed more sustained A1c reduction with lower hypoglycemia and weight gain than glargine-100 and lower hypoglycemia vs. other insulin therapies in a network meta-analysis.

CLINICAL IMPLICATIONS OF THE CANVAS TRIAL Dr Rajesh Rajput, Rohtak ÂÂ

SGLT2 inhibition - CV risk factor reduction: Lowers blood glucose levels; lowers BP via osmotic diuresis; increases urinary caloric loss with reductions in body weight; reduces albuminuria possibly due to alterations in tubuloglomerular feedback.

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SGLT2i in patients with T2DM + hypertension: Effective BP reduction; improvement in 24-hour ambulatory BP monitoring systolic BP/diastolic BP; treatment of choice for diabetic nondippers; reduced BP was observed in CANVAS program.

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Canagliflozin is an orally active, selective SGLT2i, with a half-life of 11-13 hours (once-daily dosing).

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SGLT2i in patients with T2DM + CVD and CV risk factors: Canagliflozin has shown reduction in

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CONFERENCE PROCEEDINGS MACE (CV death, nonfatal MI or nonfatal stroke). ÂÂ

SGLT2i in patients with T2DM + heart failure: Canagliflozin has shown reduction in hospitalization for heart failure and reduction in CV death; canagliflozin is effective in delaying the rise in serum NT-proBNP and hsTnl for over 2 years in older adults with T2DM.

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SGLT2i in patients with T2DM + renal disease: Canagliflozin reduces the progression of albuminuria.

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Adverse events observed in CANVAS program incidence of amputation was low.

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SGLT2i are recommended by American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) 2017 guidelines as the first OAD of choice in dual and triple therapy.

SHOULD SUPERIORITY IN CVOT AFFECT CHOICE OF THERAPY IN DIABETES WITHOUT HEART DISEASE? Dr Allison Goldfine, Boston ÂÂ

CVD is the leading cause of death people with T2DM.

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Metformin is the top-line therapy according to the American Diabetes Association (ADA) practice guidelines.

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Metformin effectively improves glycemia:

and established CVD or risk factors requiring intensification.

CANVAS TRIAL: HOW CAN IT CHANGE OUR PRACTICING APPROACH? A CRITICAL ANALYSIS Dr AK Singh, Kolkata ÂÂ

The results of CANVAS and EMPA-REG together suggest a beneficial class effect of SGLT2i on CV and renal risk.

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Reduction of CV and all-cause death with empagliflozin is exceptional, Both studies showed impressive renal benefit.

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In CANVAS, canagliflozin reduced the risk of albuminuria progression by 27%, and the combined renal endpoint by 40%.

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A direct comparison between canagliflozin and empagliflozin is not formally possible, given the differences between the two CVOTs in design and population.

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More clarity is required on differential effect of drugs on amputation.

ADVANCES IN LIPID MANAGEMENT Dr AG Unnikrishnan, Pune ÂÂ

The ADA 2015 guidelines advocate moderate dose statins for all patients with diabetes in the age group 40-75 years.

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Hepatic LDL receptors (LDLRs) play a central role in cholesterol homeostasis.

Excellent safety profile in those with adequate

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Not associated with hypoglycemia

PCSK9 regulates the surface expression of LDLRs by targeting for lysosomal degradation.

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Genetic variants of PCSK9 demonstrate its importance in regulating low-density lipoprotein cholesterol (LDL-C) levels.

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Long-term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM) trial:

As monotherapy and with other glucose-

lowering drugs

Well-tolerated

renal function

Inexpensive. ÂÂ

Designs of diabetes cardiovascular outcome trials (CVOTs): These trials do not address either glucose-

lowering efficacy or glucose-lowering effects on the heart per se.

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We do not know if use of agents in different classes with established CV benefits, which have different mechanisms of action for glucose-lowering, will be additive or synergistic for CV protection.

In the setting of imperfect data, we can select agents with the best safety/risk profiles for our individual patients.

This includes use of select medication with established CV benefit in patients with T2DM

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

Alirocumab is a monoclonal antibody that

inhibits PCSK9 and has been shown to reduce LDL-C levels in patients who are receiving statin therapy

Over a period of 78 weeks, a significant

reduction in the LDL-C levels was observed when alirocumab was added to statin therapy at the maximum tolerated dose

CONFERENCE PROCEEDINGS In a post hoc analysis, there was evidence

of a reduction in the rate of CV events with alirocumab.

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In Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Outcomes study, evolocumab showed a significant reduction in the risk for CV events.

APPROACH TO HYPOTHYROIDISM Dr Chitra Selvan, Bengaluru ÂÂ

Primary hypothyroidism is a common endocrine abnormality.

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Aggressive case finding is recommended, especially in patients with symptoms of hypothyroidism, history of other autoimmune disorders, family history of hypothyroidism, patients with infertility, dyslipidemia or patients on medications like amiodarone and lithium.

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Thyroid-stimulating hormone (TSH) is recommended as the first-line screening test to detect primary thyroid abnormalities.

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TSH >10 mIU/L is overt hypothyroidism and qualifies for treatment.

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Levothyroxine (LT4) in the dose of 0.6-1.7 mg/kg/day is the most widely accepted treatment for primary hypothyroidism. LT4 is advised to be taken on an empty stomach, preferably 30-60 minutes before food in the morning.

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TSH is followed up after 6-8 weeks with a treatment target of normalizing TSH values to normal range.

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Once target TSH levels are attained, same dose of LT4 is continued and TSH assessed every 6 months or annually.

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Nonadherence to therapy is a common cause of elevated TSH levels in patients on treatment.

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Many common drugs like iron and calcium supplements, antacids, proton pump inhibitors, soy ingestion can interfere with LT4 absorption.

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It is preferable to not change brands of LT4 as bioavailability may vary between brands, leading to fluctuations in TSH levels.

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It is recommended that persons over 50 years and/ or with cardiac disease be started with a low dose of LT4 and the dose may be increased gradually.

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There is insufficient evidence to recommend routine supplements of selenium or calcium in patients with hypothyroidism. However, optimal intake of calcium from diet is to be encouraged.

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There is insufficient evidence to recommend combination therapy with liothyronine (LT3)/LT4 in patients with hypothyroidism.

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Euthyroid patients with obesity or depression do not warrant replacement with LT4.

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Congenital hypothyroidism is more common in India and regular screening of all newborns

PCSK9 inhibitors show very potent LDL-C reduction with seemingly minimal adverse effects.

IS PSYCHOLOGICAL ASSESSMENT THE MISSING LINK IN DIABETES CARE? Dr Bhavana Sosale, Yeswanthpur ÂÂ

TIME Magazine, in August 2017, reports that there are 300 million individuals with depression.

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Individuals with diabetes often suffer from mental health diseases like depression, diabetes distress, anxiety, etc.

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The lack of emotional well-being leads to poor diabetes outcomes and puts individuals at a high risk of complications.

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Thus, psychological assessment at diabetes diagnosis and at periodic intervals was incorporated into the ADA Standard of Care Guidelines in 2017.

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Integrated care models that form a continuum between the diabetes care specialist and the mental health specialist must become a part of routine care in order to empower the patient with diabetes and psychological comorbidities.

NEED FOR A COMPREHENSIVE TREATMENT: SGLT2 vs. DPP-4 – A LOGICAL APPROACH Dr Binayak Sinha, Kolkata ÂÂ

Indian diabetics are at high risk due to their increased visceral fat and risk of coronary artery disease.

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Most OADs do not address the challenges posed in Indians.

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SGLT2i are effective, safe and well-tolerated with additional benefit of reducing weight, visceral fat and waist circumference along with BP. This makes gliflozins a highly effective choice for the Indian phenotype.

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After metformin, SGLT2i, if used appropriately, might have some solid advantages over DPP-4i.

Data with SGLT2i on CV and renal outcomes till now seem highly encouraging and the publication of data with all gliflozins is eagerly expected.

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CONFERENCE PROCEEDINGS between Day 3-5 with serum TSH with/without T4 is insisted upon.

CURRENT STATUS OF VACCINATION IN PATIENTS WITH DIABETES: RECOMMENDATIONS AND EVIDENCE Prof. Jayant Panda, Cuttack ÂÂ

All adults with diabetes should be educated about administering pneumococcal and influenza vaccine and those above the age of 60 years should be advised to be vaccinated.

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Children with diabetes <2 years of age can be given pneumococcal polysaccharide vaccine and children above 6 months of age, influenza vaccine.

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Other vaccines may be administered in patients with diabetes based on need.

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Irrespective of age, immunization is recommended in all patients with: Renal failure; diabetes and immune compromised state due to concomitant conditions; diabetes and chronic lung diseases, like chronic obstructive pulmonary disease (COPD), bronchial asthma; diabetes patients who smoke; poor hygienic conditions (especially slum dwellers) and those who frequently travel to high risk areas.

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Vaccination is contraindicated/postponed in patients with: Hypersensitivity to the active substances or to any of the excipients of the vaccine; history of chicken egg allergy particularly when considering flu shot; recent history of Guillain-Barré syndrome within 6 weeks of a previous influenza vaccination in the case of flu shot; postponed in patients with febrile illness or any acute infection.

BLOOD PRESSURE TARGETS IN DIABETES: A RELOOK AT THE EVIDENCE Dr Anuj Maheshwari, Lucknow ÂÂ

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The Action to Control Cardiovascular Risk in Diabetes (ACCORD) BP trial - the risk of serious adverse events was 2.6 times higher in the intensive therapy group compared with the standard therapy group, with a 17-fold increase in hypotension and a 10-fold increase in hyperkalemia.

In patients with coronary artery disease, a J-shaped curve relationship has been documented with BP (particularly diastolic) and CV events so that lower pressures are associated with increased risk of events.

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

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The principle of primum non nocere mandates that we show evidence of benefit for intensive BP control before such a treatment strategy is advocated.

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No single optimal systolic goal BP level can be identified in patients with T2DM.

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Intensive BP control (<135 mmHg) was associated with a significant reduction in macrovascular (allcause mortality and stroke) events but with an increase in serious adverse effects (SAEs) compared with standard BP control (<140 mmHg).

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The present body of evidence suggests that intensive BP control (135 mmHg) reduces the risk of macrovascular (death, stroke) events in patients with T2DM.

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A treatment goal of 130-135 mmHg, similar to the achieved BP of 133.5 mmHg in the standard therapy group of the ACCORD trial, is therefore acceptable and more aggressive goals to 120 mmHg can be considered in patients at higher risk of stroke.

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At a systolic BP <130 mmHg, there may be target organ heterogeneity, and these cerebrovascular benefits have to be balanced against an increased risk of SAEs and a lack of benefit for cardiac, renal and retinal outcomes.

RESULTS AND IMPLICATIONS OF THE DEVOTE TRIAL Dr Leigh Perreault, Colorado ÂÂ

The DEVOTE trial was a randomized, doubleblinded, active controlled, treat-to-target eventdriven trial. The primary objective was to confirm the CV safety of insulin degludec compared with that of insulin glargine.

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Additional assessment - To assess the efficacy and safety of insulin degludec in patients with type 2 diabetes at high risk of CV events.

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Degludec achieved noninferiority vs. glargine for CV safety.

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Incidence of severe hypoglycemia reduced by 27% with degludec vs. glargine.

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Occurrence of nocturnal severe hypoglycemia reduced 53% with degludec vs. glargine.

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A 40% lower rate of severe hypoglycemia was confirmed with degludec vs. glargine at similar levels of HbA1c.

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DEVOTE confirmed the CV safety of insulin degludec in comparison with insulin glargine.

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The magnitude of reduced risk for hypoglycemia is clinically meaningful and hopefully will lead to greater adherence and better outcomes for patients.

CONFERENCE PROCEEDINGS approach, less insulin is needed and a high rate of treatment to target can be achieved.

DIABETES MANAGEMENT IN SHIFT WORKERS Dr Shalini Jaggi, New Delhi ÂÂ

Shift work affects people with diabetes in different ways.

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Differing activity levels and changes to meal times adversely impact blood glucose levels.

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Changes in the circadian rhythm, sleep-wake patterns and counter-regulatory hormones ↑Insulin resistance- impact on the ability to control blood glucose.

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Management of diabetes in shift workers should be individualized.

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Avoid therapies that predispose to hypoglycemia.

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Safer options - Sensitizers, alpha-glucosidase inhibitors, glitazones, incretin -based therapies and SGLT2i.

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Short-acting/modern SUs/meglitinides may be used if needed.

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When to stop titrating basal insulin and add prandial insulin - Current opinions: The individual is not meeting glycemic targets on basal insulin and: A1c still not at goal with 0.5 U/kg/day of daily basal insulin; elevated A1c despite normal FPG with basal insulin; FPG with basal insulin is within targeted range, but PPG is persistently above goal; further increases in basal insulin result in hypoglycemia.

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The basal plus regimen allows for more gradual intensification of insulin therapy to full basal-bolus therapy. Short-acting regular human insulin or rapid-acting insulin analogs (RAIAs) can be added before main meals. RAIAs could be preferred over regular human insulin due to faster absorption and lower risk of hypoglycemia.

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Choosing appropriate patient for basal plus therapy:

Analog insulins must be preferred.

Patients on basal insulin ± oral agents with an

HbA1c between 7% and 8%: Ideal candidates; a high percentage will achieve an HbA1c ≤7%.

Patients treated with 2 or 3 oral agents and a

BASAL INSULIN INTENSIFICATION: EVIDENCEBASED INDIAN RECOMMENDATIONS – 2017 Dr SR Aravind, Bengaluru ÂÂ

Insulin therapy should mimic endogenous insulin secretion.

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On baseline oral OADs, fasting hyperglycemia dominates over a wide range of A1c levels.

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Following treatment intensification, hyperglycemia contributes >40% to hyperglycemia.

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Basal insulin is the most commonly used insulin for initiation in combination with OADs.

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When PPG remains uncontrolled by OADs, premix insulin is a suitable alternative.

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Landmark trials support an approach where insulin glargine is initiated early when HbA1c level exceeds 7.5% on OADs. With this proactive

fasting overall

high HbA1c >8.5-9%: After optimized titration of basal insulin, addition of increasing injections of prandial insulin will be necessary to reach an HbA1c ≤7%.

Patients on basal insulin ± oral agents with an

HbA1c >8.5% who are reluctant to start basalbolus therapy: Basal plus should be considered as a transitional therapy to progress steeply to basal-bolus therapy, which will be necessary for most patients in this clinical situation.

Patients previously treated with premixed

insulin twice-daily: For those with frequent hypoglycemia episodes and/or irregular glycemic profiles, basal plus will offer an alternative.

Patients starting corticoid therapy for other

concomitant diseases: May be a valuable alternative to achieve stable daily glycemic profiles, especially at lunch and dinner.

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AROUND THE GLOBE

News and Views A New PAHO Initiative to Eliminate Mother-tochild Transmission of Four Diseases To end mother-to-child transmission of these four diseases by 2020, the Pan American Health Organization (PAHO) has launched the Framework for elimination of mother-to-child transmission of HIV, syphilis, hepatitis B and Chagas (EMTCT-PLUS), a roadmap with strategies and interventions that target women before and during pregnancy, as well as new mothers and their babies to prevent transmission of HIV, syphilis, Chagas disease and hepatitis B. If not detected and treated in time, these infections can cause miscarriages, congenital malformations, neurological and heart problems, cirrhosis, liver cancer and in some cases, even deathâ&#x20AC;Ś (PAHO, August 10, 2017).

Patients with Kidney Disease are at Risk of Atrial Fibrillation A meta-analysis of the Jackson Heart Study, the MultiEthnic Study of Atherosclerosis, and the Cardiovascular Health Study published online before print in the journal Clinical Journal of the American Society of Nephrology has shown that reduced eGFR and elevated urine albuminto-creatinine ratio were significantly associated with greater risk of incident atrial fibrillation.

Study Links Job Quality to Health Compared with adults who remained unemployed, formerly unemployed adults who transitioned into poor quality jobs had greater adverse levels of biomarkers compared with their peers who remained unemployed.

The study reported August 10, 2017 in the International Journal of Epidemiology suggests that any job is not necessarily better than no job, because job quality is important.

NPPA Fixes Prices of 9 Scheduled Formulations The NPPA has fixed/revised ceiling prices/retail prices of 9 scheduled formulations (as below) of Schedule-I under Drugs (Prices Control) Order, 2013 in related notifications/orders posted on its website.

1. Midazolam tablet 7.5 mg 2. Benzyl penicillin powder for injection 10 lac units 3. Para-aminosalicylic acid granules (As licensed) 1 g 2.58

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4. Ifosfamide powder for injection 2 g 5. Cloxacillin tablet 250 mg 6. Rifabutin tablet 150 mg 7. Cloxacillin capsule 250 mg 8. Cloxacillin capsule 500 mg 9. Ibuprofen oral liquid 100 mg/5 mL. (Source: NPPA, August 11, 2017)

The First Generic of Isoproterenol Gets FDA Approval The US Food and Drug Administration (FDA) has approved the first generic version of isoproterenol hydrochloride injection (Isuprel, Hospira). It is available as a single dose vial containing 0.2 mg/1 mL or 1 mg/ 5 mL and is an AP rated generic equivalent of Isuprel.

Patients with Metabolic Syndrome at Higher Risk of Post-carotid Artery Stenting Complications Metabolic syndrome (MetS) is associated with increased risk of short-term post-procedural complications after carotid artery stenting, says a study published online August 7, 2017 in Neurological Science. MetS patients with central obesity, high fasting plasma glucose or low HDL-C have significantly increased risk of complications post-carotid artery stenting within 30 days.

Resveratrol Supplementation Improves QOL in Postmenopausal Women Compared with placebo treatment, a significant reduction in pain and an improvement in total wellbeing was observed after resveratrol supplementation in healthy postmenopausal women. Both benefits, including measures of quality-of-life (QOL), correlated with improvements in cerebrovascular function. These findings were reported in the August 2017 issue of Menopause, the journal of The North American Menopause Society.

Cerebral Embolic Protection Devices Do Not Reduce Risk of CNS Injury During SVAR In a randomized clinical trial of patients undergoing surgical aortic valve replacement reported August 8, 2017 in JAMA, cerebral embolic protection devices (suction-based extraction and intra-aortic filtration

AROUND THE GLOBE device) compared with a standard aortic cannula did not significantly reduce the risk of ischemic central nervous system (CNS) injury at the time of SAVR.

Oman Beating Noncommunicable Diseases at Souks and Bakeries From smoke-free souks to low-salt bread, businesses and communities in the Sultanate of Oman are leading the charge against noncommunicable diseases (NCDs) such as heart and lung diseases, cancer and diabetes.

Oman is one of several countries selected by WHO to receive support to fast-track progress on achieving nine global targets to prevent and control NCDs, including a reduction of premature deaths from NCDs by 25% by 2025… (WHO, August 11, 2017).

Tocilizumab Improves Hemoglobin in Patients with RA Compared with other biologic and nonbiologic DMARDs, hemoglobin (Hb) and hematocrit (Hct) levels increased significantly by 0.72 g/dL and 2.06%, respectively among rheumatoid arthritis (RA) patients with anemia treated with tocilizumab. They were also 86% more likely to increase Hb ≥1 g/dL vs. other groups combined. These findings are reported August 3, 2017 in the journal Seminars in Arthritis & Rheumatism.

Fluocinolone Acetonide Implants Delays Progression of Diabetic Retinopathy According to new research presented at the American Society of Retina Specialists meeting in Boston, fluocinolone acetonide implant 0.2 µg/day delays progression of diabetic retinopathy to proliferative diabetic retinopathy compared with eyes not treated with the steroid implant; 12.5% versus 22.3%, respectively.

Early Symptom Control in Patients with Chronic Inducible Urticaria with Omalizumab Treatment A systematic review of published evidence reported online July 24, 2017 in the Journal of Allergy and Clinical Immunology supports the use of omalizumab, recombinant anti-immunoglobulin E (IgE) monoclonal antibody, in the treatment of patients with therapyrefractory chronic inducible urticaria. The review also demonstrated early symptom control in most cases, sometimes within 24 hours indicating rapid onset of action of omalizumab.

Study Links Poor Sleep to Poor Glycemic Control in Children with Type 1 Diabetes Findings of a study published online July 18, 2017 in Sleep Medicine show an association of sleep quality with

glycemic control suggesting sleep as a modifiable factor to improve glycemic control. Compared to children with non-poor sleep quality, children with poor sleep quality were more likely to experience severe hypoglycemia (1% vs. 4%, respectively) and more likely to experience diabetic ketoacidosis.

Immediate Initiation of ART in HIV-positive Older Patients Reduces Mortality Immediate initiation of antiretroviral therapy (ART) after an HIV diagnosis reduces all-cause and non-AIDS mortality in people aged 50-70 years, suggests new research reported July 21, 2017 in the Journal of Acquired Immune Deficiency Syndromes.

Closure of Skin Incision with Poliglecaprone 25 Suture Reduces Complications in Cesarean Births Closure of the skin after cesarean delivery with poliglecaprone 25 suture decreases the rate of overall wound complications compared with polyglactin 910 suture; 8.8% vs. 14.4%, respectively, suggests a randomized comparative trial published online August 4 and in the September issue of Obstetrics & Gynecology.

Ibuprofen Found to Increase Kidney Injury in Ultramarathoners A new study reports in the Emergency Medicine Journal, online July 5, 2017 that ultramarathoners who took ibuprofen had increased rates of acute kidney injury (AKI); 52% ibuprofen users versus 34% placebo users developed AKI. The study cautions about taking NSAID during endurance running as it could exacerbate renal injury.

Reduced Risk of Acute COPD Exacerbations Post-bariatric Surgery Among obese adults with chronic obstructive pulmonary disease (COPD) who underwent bariatric surgery to lose weight, patients who needed COPD related emergency room or inpatient hospital care declined by more than 50% following the surgery, according to a study reported in the journal Chest, online July 14, 2017.

Exposure to Combination of Tenofoviremtricitabine-efavirenz Reduces Adverse Birth Outcomes in Infants Among infants exposed to antiretroviral treatment (ART) from conception, the combination of tenofovir disoproxil fumarate, emtricitabine and efavirenz (TFC-FTC-EFV) was associated with a lower risk for any adverse or severe adverse birth outcomes compared to other ART

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AROUND THE GLOBE regimens, according to a study reported online August 7, 2017 in JAMA Pediatrics.

History of Sports-related Concussion is a Risk Factor for Future Concussions A study published in the journal Medicine and Science in Sports and Exercise, online July 13, 2017 has identified five factors that significantly predict the risk of future head/neck injury in high-impact collision sports: history of sports-related concussion in the past 12 months, reduced multifidus and quadratus lumborum muscle cross-sectional areas, joint position error and increased contraction of the multifidus muscle.

Guidelines for Cardiovascular Pre-participation Screening in Young Athletes Recommendations of the Association of European Paediatric Cardiology for cardiovascular preparticipation screening in young athletes published online August 9, 2017 in the journal Cardiology in the Young suggest screening of young competitive athletes every second year to detect progressive diseases.

Screening should include personal and family history, physical examination and ECG.

Yemen’s Cholera Epidemic, Currently the Largest in the World: WHO The total number of suspected cholera cases in Yemen this year hit the half a million mark on Sunday, and nearly 2,000 people have died since the outbreak began to spread rapidly at the end of April. The overall caseload nationwide has declined since early July, particularly in the worst affected areas. But suspected cases of the deadly waterborne disease continue to rage across the country, infecting an estimated 5,000 people per day. The spread of cholera has slowed significantly in some areas compared to peak levels but the disease is still spreading fast in more recently affected districts, which are recording large numbers of cases.

Yemen’s cholera epidemic, currently the largest in the world, has spread rapidly due to deteriorating hygiene and sanitation conditions and disruptions to the water supply across the country. Millions of people are cut off from clean water, and waste collection has ceased in major cities… (WHO, August 14, 2017)

Updated ASCO Guidelines on Stage 4 NSCLC Therapy An update of the American Society of Clinical Oncology (ASCO) clinical practice guideline published August 14, 2017 in the Journal of Clinical Oncology provides

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new recommendations on the use of targeted therapies for patients with advanced non-small-cell lung cancer (NSCLC) with changes in tumor EGFR, ALK and ROS1 genes. The guidelines also clarify the role of immunotherapy in these patients.

Marijuana Associated with Increased Risk of Death from Hypertension Marijuana use is associated with a threefold higher risk of death from hypertension and a 1.04 greater risk for each year of use, according to a retrospective follow-up study of NHANES (National Health and Nutrition Examination Survey) participants aged 20 years and above published August 9, 2017 in the European Journal of Preventive Cardiology. Compared to non-users, marijuana users had a 3.42-times higher risk of death from hypertension and a 1.04 greater risk for each year of use.

Study Links Air Pollution to Cardiovascular Disease Exposure to high levels of air pollution increased stress hormone levels and negative metabolic changes in otherwise healthy, young adults. Notable changes were found in 97 blood serum metabolites after fine particulate matter exposure. Air purifiers appeared to lessen the negative effects, according to new research August 14, 2017 published in the journal Circulation.

Cancer Patients at High Risk of Arterial Thromboembolism Patients with incident cancer are at a considerable higher short-term risk of arterial thromboembolism.

In the study published in the August 2017 issue of the Journal of the American College of Cardiology, the 6-month cumulative incidence of myocardial infarction and ischemic stroke were 2.0% and 3.0%, respectively compared to 0.7% and 1.6%, respectively in controls.

Fecal Calprotectin Helps Differentiating Children with Suspected IBD According to a study reported online August 14, 2017 in JAMA Pediatrics, fecal calprotectin should be recommended for the triage of pediatric patients with symptoms suggestive of inflammatory bowel disease (IBD).

All blood markers and fecal calprotectin individually, when added to evaluation of symptoms, significantly improved the discrimination between children with suspected IBD and those without IBD.

AROUND THE GLOBE Secukinumab is Highly Effective in Psoriasis of the Scalp

Long-term Use of ICS Increase Risk of Fracture in COPD Patients

Results of a 24-week, randomized, phase 3b study published online August 2, 2017 in the Journal of the American Academy of Dermatology show that secukinumab alone without concomitant scalp psoriasis treatment is efficacious and well-tolerated in patients with extensive moderate-to-severe scalp psoriasis. Significantly, more patients achieved complete clearance of scalp psoriasis at Week 12 with secukinumab versus placebo.

According to a study published online July 14, 2017 in the journal Chest, long-term use of inhaled corticosteroids (ICS) at high doses is associated with a modest increase in the risk of hip and upper extremity fractures in patients with chronic obstructive pulmonary disease (COPD).

New Requirements for AHA Adult CPR Courses

For patients with Parkinson’s disease, seeing a neurologist by video conference from their homes may be as effective as their usual in-person care with their local physician, according to a new study published August 16, 2017 in the journal Neurology.

The American Heart Association (AHA) will now require the use of an instrumented directive feedback device in all courses that teach adult chest compression rate (CPR) skills, effective January 31, 2019. The devices provide, real-time, audiovisual and corrective evaluation and instruction on CPR depth, chest recoil and proper hand placement during CPR training. To comply with the new course requirement, feedback devices must, at a minimum, measure and provide real-time audio and/or visual feedback on compression rate and depth, allowing students to self-correct or validate their skill performance immediately during training. This new requirement impacts the Association’s Basic Life Support (BLS), Advanced Cardiovascular Life Support (ACLS), ACLS for Experienced Providers and Heartsaver adult CPR training courses taught in the United States and internationally… (AHA Press Release, August 15, 2017).

Obesity is Still a Risk Factor for CHD Regardless of Metabolic Health Regardless of metabolic health, overweight and obese people had higher risk of coronary heart disease (CHD) than lean people, according to a study reported August 14, 2017 in the European Heart Journal. Irrespective of BMI, metabolically unhealthy individuals had higher associated risk of CHD compared to their healthy counterparts.

Study Links Zika Virus to Neurologic Syndromes in Adults In a single-center cohort at a tertiary referral center in Brazil, Zika virus infection was associated with an increase in the incidence life-threatening neurologic syndromes such as meningoencephalitis or transverse myelitis. The study was published online August 14, 2017 in JAMA Neurology. Eighty-eight percent patients were found to have molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid.

Parkinson’s Care via Telemedicine is as Effective as Going to the Clinic

Workplace Exposure to Fumes and Dust Increases risk of ILD Results of the Multi-Ethnic Study of Atherosclerosis (MESA) Air-Lung study reported online July 28, 2017 in the American Journal of Respiratory and Critical Care Medicine show association of occupational exposures to vapors, gas, dust and fumes with increased risk of subclinical interstitial lung disease (ILD).

COX-2 and β-adrenergic Blockade Improves Metastatic Markers in Early Breast Cancer Patients Perioperative COX-2 and β-adrenergic blockade improves metastatic biomarkers in early-stage breast cancer patients, according to results of a phase 2 randomized trial published in the August 2017 issue of Clinical Cancer Research. The combination inhibits multiple cellular and molecular pathways related to metastasis and disease recurrence in these patients.

Less REM Sleep Tied to Greater Risk of Dementia People who get less rapid eye movement (REM) sleep may have a greater risk of developing dementia, according to a new study published online August 23, 2017 in the journal Neurology. For every percent reduction in REM sleep, a 9% increase in the risk of dementia was observed. REM sleep is the sleep stage when dreaming occurs.

Brain Activity may Predict Stress-related CV Risk The brain may have a distinctive activity pattern during stressful events that predicts bodily reactions, such as rises in blood pressure that increase risk

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AROUND THE GLOBE for cardiovascular disease (CVD). People who have exaggerated responses to stressors, like large rises in blood pressure or heart rate, are at greater risk of developing hypertension and premature death from CVD. These results were published August 23, 2017 in the Journal of the American Heart Association.

Updated ADA Position Statement on Diabetes and Hypertension

highlights that sensitivity is paramount to counseling and treating obesity in adolescents. In addition to counseling obese patients on healthy behavior changes, the Committee Opinion also recommends that physicians should be knowledgeable about both behavioral and environmental factors that may influence obesity.

Physicians should counsel overweight and obese adolescents against the use of weight loss supplements.

The American Diabetes Association (ADA) has published updated guidelines on the assessment and treatment of hypertension in people with diabetes online on August 22, 2017 in the journal Diabetes Care. BP measurement at every routine clinical visit is recommended for patients with diabetes. BP target of <140/90 mmHg is recommended for most people with diabetes and hypertension. However, a lower BP goal is suggested for some patients at high risk of cardiovascular disease.

Study Suggests Enteritis as Potential Marker for Joint Damage in Psoriatic Arthritis

AAP Cautions About Rapid Weight Changes in Young Athletes

According to a study published online on August 16, 2017 in the Journal of General Internal Medicine, the Osteoporosis Self-Assessment Tool (OST) performs better than Fracture Risk Assessment (FRAX) tool for selecting which older men to screen for osteoporosis. The OST had better discrimination (AUC: 0.68) than the FRAX (AUC: 0.62; p = 0.004) for identifying T-score-defined osteoporosis.

The American Academy of Pediatrics (AAP) recommendations caution about unhealthy ways young athletes in “weight sensitive” sports may slim down or bulk up in hopes of achieving more competitive physiques in its new clinical report titled “Promotion of Health Weight-Control Practices in Young Athletes” published online August 21 in the journal Pediatrics.

These risky weight losses or gains increase short- and long-term health problems and injury risk, and may even hurt athletic performance.

Monitoring Hepatic Fibrosis Score in Psoriatic Patients on Methotrexate Feasible with NASH FibroSure The NASH FibroSure test may be used to monitor hepatic fibrosis scores in patients with psoriasis who are taking methotrexate, although the test is not a replacement for liver biopsy, says a study reported in JAMA Dermatology online August 23, 2017. Worsening fibrosis scores can indicate the need to switch to an alternative systemic agent without performing a liver biopsy. Around 74% of the study participants were found to have elevated hepatic steatosis scores.

Discussions and Counseling About Obesity should Begin in Adolescence New guidance from the American College of Obstetricians and Gynecologists (ACOG) published in the September 2017 issue of Obstetrics & Gynecology

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The severity of sonographic enthesitis is a potential marker of radiographic peripheral and axial joint damage in psoriatic arthritis, suggests a study reported in the journal August 15, 2017 in the journal Arthritis Research & Therapy. Enthesitis is inflammation at sites where tendons or ligaments insert into bone.

Osteoporosis Self-assessment Tool Better Than FRAX in Screening Older Men for Osteoporosis

Long-term Testosterone Therapy Improves QOL in Men with Hypogonadism Long-term testosterone therapy improves urinary and sexual function and quality-of-life in men with hypogonadism, suggest results from a propensitymatched subgroup of a controlled registry study published July 18, 2017 in the Journal of Urology.

In untreated hypogonadal men, voiding and erectile functions deteriorated with continued follow-up.

Degludec Insulin Shows Comparable Efficacy and Safety as Glargine in Type 2 Diabetes Among patients with type 2 diabetes at high risk for cardiovascular events, degludec - ultralong-acting, oncedaily basal insulin - was noninferior to glargine with respect to the incidence of major cardiovascular events.

The primary outcome of a major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke) occurred in 8.5% in the degludec group versus 9.3% in the glargine group. The study is published August 24, 2017 in the New England Journal of Medicine.

AROUND THE GLOBE New Guidelines for Screening and Management of Hypertension in Children

Preventing Spread of Disease in Wake of Mudslides is Vital, Says WHO

The American Academy of Pediatrics (AAP) has published new clinical practice guideline for screening and management of high BP in children and adolescents online August 21, 2017 in the journal Pediatrics. The guidelines include new BP tables that are based on normal-weight children; hence, the new BP values are lower than those used in prior guidelines and allow for a more precise classification of BP according to body size. Lifestyle changes continue to be recommended as the first-line treatment.

The World Health Organization (WHO) is working closely with the Government of Sierra Leone to prevent the spread of infectious diseases such as malaria and cholera in the wake of last week’s mudslides and flooding in Freetown. The Organization is also working with partners to ensure ongoing healthcare for the injured and displaced, and to provide psychological aid to those coping with trauma. “The mudslides have caused extreme suffering and loss of life, and we must do all we can to protect the population from additional health risks,” said Alexander Chimbaru, Officer in Charge of WHO Sierra Leone. With damage to water and sanitation facilities, residents of affected areas are particularly vulnerable to outbreaks of pre-existing infectious diseases including malaria and diarrheal conditions such as typhoid and cholera. The most recent cholera outbreak in the country occurred in 2012…

(WHO Africa, August 21, 2017).

ASNC/SNMMI Recommendations for PET Imaging in Diagnosis of Cardiac Sarcoidosis The American Society of Nuclear Cardiology (ASNC) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) have jointly released recommendations for PET imaging to enable diagnosis of cardiac sarcoidosis.

Published online August 2, 2017 in the Journal of Nuclear Cardiology, the recommendations include proper patient preparation successful 18F-FDG PET with prolonged fasting, dietary changes and IV heparin to inhibit physiologic myocardial glucose uptake. Myocardial perfusion and cardiac 18F-FDG PET images should be interpreted in context of the clinical presentation and other imaging studies. Both visual and quantitative interpretation should be done.

Heart Failure Patients and Clinicians have Differing Perceptions of Risk Level Physicians identified a majority of patients with advanced heart failure as at high risk for transplant, left ventricular assist device (LVAD) or death while few of those patients considered themselves to be at high risk, according to a study published August 16, 2017 in JACC: Heart Failure. In the study, 69% of the patients were considered at high risk for transplant, LVAD or death by their physicians. But, only 14% of them considered themselves to be at high risk.

Switch from Bisphosphonates to Denosumab and Teriparatide Improves BMD in Women with RA Switching women with rheumatoid arthritis from oral bisphosphonates to denosumab and teriparatide group led to significant increase in bone mineral density (BMD) in lumbar spine and femoral neck compared with women who continued on oral bisphophonates, according to an observational study published August 1, 2017 in the Journal of Bone and Mineral Metabolism.

Long-term CV Events are Common in Patients with Spontaneous Coronary Dissection According to a study reported in the August 29, 2017 issue of the Journal of the American College of Cardiology, long-term cardiovascular (CV) events (myocardial infarction, stroke) are common in patients with spontaneous coronary artery dissection. Hypertension increased the risk of recurrent spontaneous coronary artery disease, whereas b-blocker therapy appeared to be protective.

The First Fixed-dose Combination for Gout gets US FDA Nod The US Food and Drug Administration (FDA) has approved Duzallo, a fixed-dose oral combination of lesinurad and allopurinol, for the treatment of hyperuricemia associated with gout in patients for whom target serum uric acid levels have not been achieved with allopurinol alone. It is not recommended for the treatment of asymptomatic hyperuricemia. Once-daily Duzallo contains lesinurad 200 mg plus allopurinol 200/300 mg.

Transitioning to Adult Care should not be Defined

by Arbitrary Age Limits: AAP The American Academy of Pediatrics (AAP) has updated its previous policy statement on the age limit of pediatrics titled “Age Limit of Pediatrics” published in the September 2017 issue of the journal Pediatrics.

The age of transition for young adults from pediatric

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AROUND THE GLOBE to adult care be based on the patients’ individual needs.

The decision should be made solely between the patient (and family, when appropriate) and the physician and consider the physical and psychosocial needs of the patient and the abilities of the pediatric provider to meet those needs.

AACAP Policy Statement on Telepsychiatry The American Academy of Child and Adolescent Psychiatry (AACAP) has released a new policy statement on the delivery of child and adolescent psychiatry services through telepsychiatry published on its website. Telepsychiatry allows psychiatrists to deliver care directly to youth and their families over geographic distance and settings. It improves quality of care and also facilitates collaboration with primary care physicians to support their skills in providing mental healthcare.

Liver Function Impairment More Common PostRYGB in NASH Patients Patients with nonalcoholic steatohepatitis (NASH) undergoing roux-en-Y gastric bypass (RYGB) are more susceptible to early transient deterioration of liver function than after sleeve gastrectomy, says a study reported August 1, 2017 in the Annals of Surgery.

While, both RYGB and sleeve gastrectomy increased international normalized ratio (INR) at 1 month, RYGB-induced significantly greater increase in INR in the whole group and NASH patients than sleeve gastrectomy.

Dr Jitendra Singh Calls for “Make in India” Health Module The Union Minister of State (Independent Charge) for Development of North Eastern Region (DoNER), MoS PMO, Personnel, Public Grievances, Pensions, Atomic Energy and Space, Dr Jitendra Singh has called for establishing a “Make in India” health module.

Addressing the CII Health Conference organized by Confederation of Indian Industry (CII), he said that this module can be based on public-private partnership as well as multicentric healthcare collaboration to meet the changing health needs of 21st century India. While on one hand, disorders like diabetes and heart disease, which were hitherto confined to urban population, are now also on the rise in rural areas, on the other hand, the access to modern modalities of treatment is confined only to cities and big towns, as a result of which 70% of rural population gets access only to onethird of country’s hospitalization facilities and over 600 million people in the country are deprived of access

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to affordable healthcare, he added… (Press Information Bureau, Ministry for Development of North-East Region, August 22, 2017).

Oral Steroids Offer No Advantages in Lower Respiratory Tract Infections Findings of a randomized clinical trial published in the August 22/29 issue of JAMA show that treatment of acute lower respiratory tract infection symptoms in adults without asthma with oral prednisolone, 40 mg/day for 5 days, compared with placebo did not significantly reduce the median duration of moderately bad or worse cough or the mean severity of symptoms between days 2 and 4.

Palliative Care can Substantially Decrease Healthcare Utilization in Patients with Advanced Cancer A new population-based study shows that palliative care substantially decreased healthcare utilization among Medicare beneficiaries with advanced cancer, resulting in less intensive care being delivered at the end of life.

This included lower rates of hospitalization, fewer invasive procedures and reduced chemotherapy administration at the end of life, along with higher rates of hospice enrollment and stays. This study was published August 22, 2017 in the Journal of Oncology Practice.

New Recommendations for Managing Menopausal Symptoms in Breast Cancer Survivors A review on approaches to management of menopausal symptoms and associated clinical issues in breast cancer survivors has been published August 22, 2017 in the Journal of Clinical Endocrinology & Metabolism.

It recommends smoking cessation, maintaining a healthy body weight, limiting or avoiding alcohol, maintaining adequate levels of vitamin D and calcium, eating a healthy diet and regular physical activity along with nonpharmacological and pharmacological therapies for symptom control.

Low-income Patients more Likely to Take BP Medicines When Doctor Involves Them in Conversation Low-income patients with high BP whose healthcare providers did not use collaborative communication styles or ask about social issues, such as employment and housing, were less likely to take their BP medications as directed. They were also least likely to take their medication when social issues were not discussed, according to a new research reported August 22, 2017 in the journal Circulation.

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In This Issue —

Emerging role of Cardiac MRI in Ischemic and Non-ischemic Cardiomyopathy

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Acute Renal Failure and Silent Myocardial Infarction Following Multiple Honey Bee Stings

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Superficial Brachial Artery: Its Embryological and Clinical Significance

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Glucose Tolerance in Nondiabetic Patients after First Attack of Acute Myocardial Infarction and its Outcome

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A Case of Left Atrial Myxoma Presenting as Severe Pulmonary Hypertension

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Double-Chambered Right Ventricle with Transient 2:1 Atrioventricular Block: A Rare Presentation

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Cornary Artery Air Embolism more...

Asian Journal of Diabetology

Volume 17, Number 5

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Volume 1, Number 1

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LIGHTER READING

FINAL COUNTDOWN A man hasn’t been feeling well, so he goes to his doctor for a complete checkup. Afterward, the doctor comes out with the results.

“I’m afraid I have some very bad news,” the doctor says. “You’re dying, and you don’t have much time left.”

“Oh, that’s terrible!” says the man. “Give it to me straight, Doc. How long have I got?”

“Ten,” the doctor says sadly.

“Ten?” the man asks. “Ten what? Months?

Weeks? What?”

The person says, “Well, there’s one door that leads to the bathroom. There’s a second door that goes into the closet. And there’s a door I haven’t tried, but it has a ‘do not disturb’ sign on it.”

PRISON VS. WORK Just in case you ever got these two mixed up, this should make things a bit more clear.

In PRISON you spend the majority of your time in an 8 × 10 cell.

At WORK you spend the majority of your time in a 6 × 8 cubicle.

In PRISON you get three meals a day.

“Nine...”

At WORK you only get a break for one meal and you pay for it.

TELL HIM I CAN’T SEE HIM

In PRISON you get time off for good behavior.

While he was talking to me, his nurse came in and said, “Doctor, there is a man here who thinks he’s invisible.”

The doctor said, “Tell him I can’t see him.”

MORE WORDS A husband looking through the paper came upon a study that said women use more words than men. It read, “Men use about 15,000 words per day, but women use 30,000.”

Excited to prove to his wife that he had been right all along when he accused her of talking too much, he showed her the study results.

The wife thought for a while, then finally she said to her husband, “It’s because we have to repeat everything we say.”

At WORK you get more work for good behavior.

In PRISON the guard locks and unlocks all the doors for you.

At WORK you must carry around a security card and open all the doors for yourself.

Dr. Good and Dr. Bad SITUATION: Type

1 diabetes in an individual was associated with impaired skeletal muscle microvasculature.

THE PATIENT SHOULD NOT DO ANY TYPE OF EXERCISE

NO, THE PATIENT SHOULD BE ADVISED APPROPRIATE EXERCISE AND PRAZOSIN THERAPY

The husband said “What?”

© IJCP Academy

HUMOR

Lighter Side of Medicine

NO EXIT A person checks into a hotel for the first time in his life, and goes up to his room. Five minutes later he calls the desk and say, “You’ve given me a room with no exit. How do I leave?”

The desk clerk says, “Sir, that’s absurd. Have you looked for the door?”

LESSON: It has been suggested that both regular exercise and prazosin treatment are likely to stimulate angiogenesis and thus help in improving comorbid microvascular complications of type 1 diabetes.

J Appl Physiol (1985). 2017;122(3):492-502.

Indian Journal of Clinical Practice, Vol. 28, No. 4, September 2017

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Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767).

Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.

The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.

Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

Covering letter –

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The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript Three complete sets of the manuscript should be – submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures).

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The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

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All pages should be numbered consecutively beginning with the title page.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

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name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

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Confidence intervals for the measurements should be provided wherever appropriate.

Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

Discussion –

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

The back of each illustration should bear the first – author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

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Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

Books

5. Special requests _____________________________

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Indian 1.____________Foreign 1.________________

Articles in Books

2.____________ 2.________________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends These should be typed double spaces on a separate – sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.

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The legend must include enough information to permit interpretation of the figure without reference to the text.

6. Suggestions for reviewers (name and postal address)

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Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

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Dr KK Aggarwal Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

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R.N.I. No. 50798/1990 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

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