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Indian Journal of
CLINICAL PRACTICE 105-156 Pages
August 2011
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Volume 22, Number 3
Post Dengue Beau’s Lines
Dr KK Aggarwal Group Editor-in-Chief
Head Office: E - 219, Greater Kailash, Part - 1, New Delhi - 48, India. e-Mail: emedinews@gmail.com, Website: www.ijcpgroup.com
emedinews is now available online on www.emedinews.in or www.emedinews.org From the Desk of Editor in Chief Padma Shri and Dr BC Roy National Awardee
Dr KK Aggarwal President, Heart Care Foundation of India; Sr Consultant and Dean Medical Education, Moolchand Medcity; Member, Delhi Medical Council; Past President, Delhi Medical Association; Past President, IMA New Delhi Branch; Past Hony Director. IMA AKN Sinha Institute, Chairman IMA Academy of Medical Specialities & Hony Finance Secretary National IMA; Editor in Chief IJCP Group of Publications & Hony Visiting Professor (Clinical Research) DIPSAR
25th July 2011, Tuesday Barundanga – the new addition to date rape drugs Burundanga is in the news for its bad effects as it is being used for criminal activities like rape or to rob passengers. The drug is passed on to the victim through business cards, pamphlets, drink etc. Thorough touch the skin can absorb a very small quantity and can lead to adverse effects. It is a voodoo powder obtained from a Colombian local plant of the nightshade family called barrachera, or “drunkenbinge”. It is a new addition to the date rape group of drugs. Traditionally it has been used for religious ceremonies. The powder when ingested causes victims to lose their will and memory, a condition well described as chemical hypnotism. Medically the refined the powder contains scopolamine, a medical drug. It is used in the treatment of nausea, motion sickness, and gastrointestinal cramps. It is also used as a pre surgical drug for the purpose of impairing memory of surgical trauma. It provides an initial knockout effect, before the anaesthesia proper is administered, and has the added benefit of preventing long term memory formation during the period of time. At one time scopolamine was given to women during childbirth. Like any other date rape drugs, it is colorless, smell less and tasteless and can easily me mixed with any liquid. In powdered form scopolamine can be easily mixed into food or drink, or blown directly into victims’ faces, forcing them to inhale it. One ingested the victim can’t say no; has no will and becomes open to suggestion; from the moment it’s given, the victim remembers absolutely nothing of what happened (ante grade amnesia). For this reason this has been used as a “truth serum” by law enforcement agencies and knockout drug by criminals. Scopolamine has a selective effect on memory. The planning and manipulation of information remain unaffected. Victims remain active in terms of cognitive but are unable to retain information. It blocks the release of acetylcholine. It affects brain functioning amygdala, a brain area that controls aggression and anxiety. This explains the calming effect it has on the drug. Dr KK Aggarwal Editor in Chief ———————————————————————————— Soon, Tricolour to flutter high on Jaipur JAIPUR: The capital skyline is set to acquire a new dimension with the national flag being hoisted at a height of 206 feet throughout the year. An initiative of Flag Foundation of India, the flag itself would be of 48 feet wide and 72 feet in length and weigh about 27 kg. The Jaipur Development Authority (JDA) has received a letter from the state government to identify the land where a pole of the required height can be installed, said sources. A direction was given to the authorities after the Flag Foundation of India, of which Member of Parliament from Kurukshetra, Naveen Jindal is the founder president, has showed eagerness to install the flag in the city. Flag Foundation India CEO, Commander (Rtd) K V Singh, said: “The letter was written to the Government of Rajasthan in December 2010, to install national flag in the capital. FFI plans to install national flags at all the district headquarters of the country.” “The cities which have these poles installed will have national flags fly 24 hours throughout the year. The 206 feet flag mast will have a decorated crest and a high voltage light falling on the flag at night making it more beautiful.” The FFI has installed such flag poles in Kurukshetra, Orissa, Kanyakumari, and Bangalore. (Source: TOI, Jul 19, 2011) For comments and archives
Is ticagrelor approved for ACS? Antiplatelet drug ticagrelor has been approved by FDA for reducing thrombotic events in patients with acute coronary syndrome who are candidates for stenting. For comments and archives Seaweed: Rich source of nutrition for heart Scientists have identified seaweeds, that form an important element of Chinese and Japanese cuisine, as a rich new source of nutrition for the heart which could rival milk products as sources of these so–called “bioactive peptides”. Bioactive peptides, obtained mainly from milk products, not only provide nutrition, but have a drug–like effect in treating or preventing certain diseases, reports the Journal of Agricultural and Food Chemistry. Maria Hayes, chemist at the Teagasc Food Research Centre, Ireland and colleagues Ciarán Fitzgerald, Eimear Gallagher and Deniz Tasdemir turned their attention to seaweeds as a source of protein that work like bioactive peptides, according to a Teagasc statement. Their review of almost 100 scientific studies concluded that some seaweed proteins work just like milk products to reduce blood pressure, like the popular ACE inhibitor drugs. (Source: TOI, Jul 21, 2011)
For comments and archives Two metabolic defects turn ‘jolly’ fat risk Obesity is a recognized risk factor for heart disease, but it is the location of fat –– in the belly or in the liver –– that combines to drive metabolic defects that produce hypertriglyceridemia, researchers found. Between two groups of obese patients with similar BMI and visceral fat volume, patients with higher liver and subcutaneous abdominal fat were found to have increased very low density lipoprotein1 (VLDL1) levels, Jan Borén, MD, of the University of Gothenburg in Sweden, and colleagues reported. In addition, those with increased plasma levels of apolipoprotein C–III (apoC–III) were more likely to have impaired triglyceride clearance, the authors wrote in Arteriosclerosis, Thrombosis and Vascular Biology: Journal of the American Heart Association. (Source: Medpage Today) For comments and archives Lysis plus contrast okay in stroke Stroke patients treated with intravenous thrombolysis did not have an increased incidence of cerebral hemorrhage when exposed to iodinated contrast media, data from a retrospective review showed. About 4% to 6% of patients developed post–thrombolysis brain hemorrhage, regardless of whether they received intravenous iodinated contrast, Niall J.J. MacDougall, MRCP, of the University of Glasgow, in Glasgow, Scotland, and colleagues reported. (Source: Medpage Today) For comments and archives. —Dr Monica and Brahm Vasudev
Exercise helps rid the body of toxins, UNB researcher says The results of a recent study by Amelia Beaney, a nursing researcher at the University of New Brunswick, indicates an association between pre– and post–cancer treatment and physical activity. Beaney used cross–sectional surveys to document the physical activity levels of cancer patients in the Horizon Health Network who had completed acute cancer treatment. She found that those who reported being moderate to highly physically active before cancer treatment were seven times more likely to be moderate to highly active after completion of cancer treatment. —Contributed by Rajat Bhatnagar, International Sports & Fitness Distribution, LLC, http://www.isfdistribution.com
Idioms A taste of your own medicine: When you are mistreated the same way you mistreat others. —Ritu Sinha
Indian Journal of
Online Submission
Clinical Practice
Volume 22, Number 3, August 2011
Contents
An IJCP Group Publication Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor
From the Desk of Group Editor-in-Chief
Are we Ready for a Terror Attack: Bomb Blast Injuries Update
109
KK Aggarwal
Dr KK Aggarwal CMD, Publisher and Group Editor-in-Chief Dr Veena Aggarwal Joint MD & Group Executive Editor Anand Gopal Bhatnagar Editorial Anchor
Original Study
Efficacy and Safety of HiOra-SG in Stomatitis: An Open Clinical Study
111
Madhumita Majumdar, Swapan Majumdar, Suprabha Hegde
IJCP Editorial Board Dr Alka Kriplani Asian Journal of Obs & Gynae Practice Dr VP Sood Asian Journal of Ear, Nose and Throat Dr Praveen Chandra Asian Journal of Clinical Cardiology Dr Swati Y Bhave Asian Journal of Paediatric Practice
drug review
Cefaclor: A Review of Its Use in Management of Infections
117
Ramesh Hotchandani
Dr Vijay Viswanathan The Asian Journal of Diabetology Dr KMK Masthan Indian Journal of Multidisciplinary Dentistry Dr M Paul Anand, Dr SK Parashar Cardiology
review article
Treatment of Knee Osteoarthritis
123
Erika Ringdahl, Sandesh Pandit
Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty Diabetology Dr Ajay Kumar Gastroenterology Dr Hasmukh J Shroff Dermatology Dr Georgi Abraham Nephrology Dr Sidharth Kumar Das Rheumatology
original article
Bacteriological Trends in Geriatric Urinary Tract Infections in a Tertiary Care Referral Hospital in West Bengal 128 Tapan Kumar Chattopadhyay, Hirak Jyoti Raj, Arpita Dutta
Dr V Nagarajan Neurology Dr Thankam Verma, Dr Kamala Selvaraj Obs and Gyne Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions
original research
Pleural Fluid Analysis in HIV-associated Tuberculosis Patients: A Retrospective Study
132
Sunita H, GB Doddamani, Linganand L Pujari, CVB Prasad
Indian Journal of
Clinical Practice
Volume 22, Number 3, August 2011
Contents
Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Pvt. Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com
case report
Post Dengue Beau’s Lines
136
Navtej Singh, Varun Vijay Mahajan, Jyotsna Singh, Iesha Pargal, Ajit Pal Singh Gill, Kunal Chawla
Printed at IG Printers Pvt. Ltd., New Delhi E-mail: igprinter@rediffmail.com printer_ig@yahoo.com Š Copyright 2011 IJCP Publications Pvt. Ltd. All rights reserved. The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Pvt. Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.
Editorial Policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article. Note: Indian Journal of Clinical Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.
Huge Frantz Tumor in a Young Indian Female
138
Hanish Bansal, Raj Kamal Jenaw, Rajendra Mandia
photo quiz
Polypoid Skin Nodule in the Postpartum Period 141
practice guidelines
IOM Releases Report on Dietary Reference Intakes for Calcium and Vitamin D
143
research review
From the Journals ...
144
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From the Desk of Group Editor-in-Chief
Are we Ready for a Terror Attack: Bomb Blast Injuries Update Bomb blast injuries are always hollow organ injuries How do bomb blasts cause injuries? It is crucial that we know this to handle the aftermath of bomb blasts. Primary blast injuries are the injuries to the hollow gas-filled organs like the lungs, ear drum or intestines leading to their rupture. These occur as a direct result of the impact of the over pressurized blast wave on the body. Secondary blast injuries occur due to flying debris and bomb fragments leading to penetration or penetrating injuries such as to the eyes. Tertiary blast injuries occur when individuals are thrown by the blast wind leading to fractures as a result of the fall. Quaternary blast injuries are due to direct effect of burn or crush injuries.
Dr KK Aggarwal
Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)
The most important triage to manage blast injuries is not to waste energies and resources on patients with nonserious injuries. All patients exposed to a blast must have eardrum examination as the first step. If the ear drums are intact, the patient can be discharged with first-aid treatment. If ear drum is ruptured, an X-ray chest should be done immediately. All such patients should be observed for eight hours as primary blast injuries are notorious for delayed presentation. Doctors should therefore focus only on two exams: Otoscopic ear exam and pulse oximetry. Blast lung injury is unlikely without tympanic or ear membrane rupture. This is used as a screening procedure for admitting a patient. Decreased oxygen saturation on pulse oximetry signals early blast lung injury, even before symptoms become apparent. Half of all initial casualties seek medical care over first hour. Double this number after one hour and you will know the total casualties. This formula is often used by the media to predict the tolls. It is also useful to predict demand for care and resource needs. Always expect upside down triage as the most severely injured arrive after the less injured who self-transport to the closest hospitals. The Government should take all steps so that blasts do not occur. With the increasing use of explosives in terrorist events in our country in recent times, doctors, especially Emergency Doctors, should undergo orientation training every six months so that they are prepared and better equipped to manage multiple casualties at one time. There is a need for constant updation. Govt. should formulate guidelines, which should be available on their website and can be followed by all. n n n
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
109
Original Study
Efficacy and Safety of HiOra-SG in Stomatitis: An Open Clinical Study Madhumita Majumdar*, Swapan Majumdar**, Suprabha Hegde†
Abstract Aphthous mouth ulcers are painful sores that can occur anywhere inside the mouth. The purpose of this study was to evaluate the safety and efficacy of HiOra-SG, a polyherbal formulation in the management of stomatitis. This study was an open, prospective, noncomparative, phase III clinical trial conducted at Dr R Ahmed Dental College and Hospital, Kolkata, India. Sixty adult patients, both males and females presenting with stomatitis were instructed to apply the gel on affected oral ulcer 2-3 times a day. All the patients were followed up at weekly intervals for a period of two weeks, and the symptom score evaluation was done during each follow-up visit with a visual analog scale. In the present study, there was a remarkable improvement in the symptoms like pain, ulcer and swelling in the patients treated with HiOra-SG. No adverse effects were reported during the study period. Therefore, it can be concluded that HiOra-SG is effective and safe in the management of stomatitis. Key words: HiOra-SG, stomatitis
A
phthous ulcers, also known as canker sores, are painful open sores inside the mouth or upper throat characterized by a break in the mucous membrane. The etiology is unknown, but aphthous ulcers are not contagious. The condition is also known as aphthous stomatitis, especially in the case of major, multiple or recurring ulcers. Recurrent aphthous stomatitis (RAS) affects 20% of the general population and is the most common form of oral ulcerative disease. They can occur as solitary lesions or can be found in considerable numbers. The condition is more common in females, with a tendency to be seen in the upper socioeconomic classes.1,2 There is no proven etiology for RAS. However, immunecomplex-mediated vasculitis and autoantibodies against the oral mucosal membranes have been suggested due to the histopathological features. Precipitating factors include trauma, stress, chemical irritants, hormones and heredity.1 Local trauma frequently leads to nonrecurrent solitary ulcers, which is different from RAS. Emotional and physical stress have been *Head, Dept. of Oral Medicine, Diagnosis and Radiology Dr R Ahmed Dental College and Hospital, Kolkata **Consultant Orthodontist, Southern Dental Clinic, Kolkata †Research Associate R&D Center, The Himalaya Drug Company, Makali, Bangalore Address for correspondence Dr Suprabha Hegde Research Associate, R&D Center, The Himalaya Drug Company Makali, Bangalore - 562 123 E-mail: dr.suprabha@himalayahealthcare.com
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
implicated in the pathogenesis, which is supported by the observation that students and military personnel have a high incidence of oral ulcers.3 Certain foods, including coffee, chocolate, potatoes, cheese, nuts, figs, citrus fruits and gluten-containing foods, have also been implicated.2 Deficiencies in iron, folate and vitamin B12 have been noted in relation to these ulcers.4 L-forms of streptococci are most frequently isolated from aphthous ulcers. Antibody formation and complement fixation-induced by these streptococci is believed to play a major role in the pathophysiology.2 RAS has been noted in patients with systemic diseases such as inflammatory bowel disease, Crohn’s disease, HIV and AIDS and celiac sprue.5 Despite theories that implicate certain viruses such as Coxsackie virus, herpes simplex virus, Varicella-zoster virus, Epstein-Barr virus, cytomegalovirus or adenovirus, no viral associations have been proven so far.4,6,7 The development of aphthous ulcer is usually preceded by prodromal symptoms of burning, tingling, swelling or mucosal erythema approximately 24 hours prior to the onset. RAS has three clinical presentations: Minor aphthae, major aphthae and herpetiform aphthae. Minor aphthae (also called Mikulicz’s aphthae or mild aphthous ulcers) account for 75-85% of all cases of RAS.7 They can involve every nonkeratinized mucosa of the oral cavity (usually the labial and buccal mucosae, the floor of the mouth and the ventral or lateral surface of the tongue), are <8-10 mm in size 111
original Study and tend to heal within 10-14 days without scarring. Minor aphthae heal more slowly than do other oral wounds and this might be attributed to an intensive lymphocytic infiltrate.8,9 Major aphthae (sometimes referred to as periadenitis mucosa necrotica recurrens or Sutton’s disease) tend to involve mucosa overlying minor salivary glands. Approximately 10-15% of RAS cases are major aphthae.7 They are round or ovoid with clearly defined margins and usually appear after puberty. The prodromal symptoms are more intense than those of minor aphthae, and usually the ulcers are deeper and larger with raised irregular borders and last significantly longer than the minor aphthae. They are painful and tend to appear on the lips, soft palate and throat. Herpetiform ulcers are the least common variety and account for only 5-10% of cases. They appear on both nonkeratinized and keratinized mucosa.10 Stomatitis may be predisposed by local infection, systemic disease, a physical or chemical irritant, or an allergic reaction, viral infections, trauma, tobacco, chemotherapy and radiation therapy. Prevention of aphthous ulcers includes a careful review of dental and medical history. It also involves following oral hygiene and avoidance of predisposing factors mentioned. Application of topical corticosteroids may accelerate the healing process of ulcers and reduce pain. The Food and Drug Administration (FDA) has approved 1% triamcinolone dental paste for the relief of symptoms of any inflammatory condition in the mouth. Other, more potent topical corticosteroids or other related preparations may be useful, but they are not specifically approved.9,11 Various medicines are available for the management of aphthous ulcers but they are not devoid of adverse effects. Therefore, HiOra-SG, a polyherbal formulation, is evaluated for its efficacy and safety in patients suffering from stomatitis. Aim of the Study The purpose of this study was to evaluate the safety and efficacy of HiOra-SG, a polyherbal formulation, in the management of stomatitis. Material and Methods Study Design
This study was an open, prospective, noncomparative, phase III clinical trial conducted at Dr R Ahmed Dental College and Hospital, Kolkata, India. The study 112
protocol, product-related information, case report and informed consent forms were submitted to the ‘Institutional Ethics Committee’ and were approved by the same. All the volunteers who were willing to participate in the trial were screened for inclusion in the study. Sixty adult patients, both males and females, attending the OPD of Oral Medicine, Diagnosis and Radiology, with a complaint of stomatitis were included in the study. Pregnant and lactating women and patients with other oral diseases were excluded from the study. Patients who had participated in a clinical study within the previous four weeks or who had a history of poor compliance with medical treatment were also excluded. Patients who met eligibility criteria were enrolled and their informed consent was obtained. After initial examination, each subject was given a tube containing HiOra-SG gel. The investigator demonstrated the proper technique of application; all the patients were instructed to apply the gel on the oral ulcers 2-3 times a day. Primary and Secondary Endpoints
The predefined primary efficacy endpoint was a decrease in the signs and symptoms of stomatitis. The predefined secondary endpoint was safety, as assessed by the incidence of adverse events and patient compliance to therapy. Follow-up and Assessment
All the patients were followed up at weekly intervals for a period of two weeks, and the symptom score evaluation was done during each follow-up visit. The following 4-point scale was used to assess symptoms: 0-Nil, 1-Mild, 2-Moderate and 3-Severe. After two weeks, patients and investigator independently rated the overall improvement on the following 5-point scale: 0-No improvement, 1-Improvement in 0-25% cases, 2-Improvement in >26-50% cases, 3-Improvement in >51-75% cases and 4-Improvement in >76-100% cases. Adverse Events
All the adverse events, either reported or observed by the patients, were recorded with information about severity, date of onset, duration and action taken against the study drug. Relation of adverse events to study medication was predefined as ‘Unrelated ’ (a reaction that does not follow a reasonable temporal sequence from the administration of the drug), ‘Possible’ (follows Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
original study a known response pattern to the suspected drug, but could have been produced by the patient’s clinical state or other modes of therapy administered to the patient) and ‘Probable’ (follows a known response pattern to the suspected drug that could not be reasonably explained by the known characteristics of the patient’s clinical state). Patients were allowed to voluntarily withdraw from the study, if they had experienced serious discomfort or sustained serious clinical events requiring specific treatment during the study. For patients withdrawing from the study, efforts were made to ascertain the reason for dropout. Noncompliance (defined as failure to take <80% of the medication) was not regarded as treatment failure; reasons for noncompliance were noted.
one week (p < 0.005) and 0.25 ± 0.65 after two weeks (p < 0.001). Pain score reduced from 2.95 ± 0.25 to 2.25 ± 0.70 at one week and 0.30 ± 0.55 at two weeks with statistically significant results of p < 0.05 at one week and p < 0.001 at two weeks, respectively. At entry, the score for swelling was 2.25 ± 0.52, which reduced to 2.05 ± 0.70 after one week and 0.25 ± 0.44 at the end of the study with significance of p < 0.05 at one week and p < 0.001 at two weeks. Halitosis score was 2.30 ± 0.48 at entry and was reduced to 1.44 ± 0.56 at the end of the study; there was a reduction in the symptom but was not significant. The overall impression showed scores of 1.84 ± 0.32 at one week (p < 0.05) and 3.12 ± 0.33 (p < 0.05) at the end of the study, which was statistically significant.
Statistical Analysis
Discussion
Statistical analysis was carried out using repeated measures of ANOVA followed by appropriate posthoc test. Parametric repeated measures of ANOVA was analyzed using Bonferroni’s multiple comparison test and nonparametric repeated measures of ANOVA was analyzed using Friedman test followed by Dunnett’s multiple comparison tests to find out the level of significance. The minimum level of significance was fixed at p < 0.05. The severity score was expressed as mean ± SD. Signs and symptoms were evaluated using 0-4 grading scale. Statistical analysis was carried out using Graph Pad Prism Software, Version 4.01. Results
Stomatitis is a painful condition, associated with redness, swelling and occasional bleeding from the affected area. Halitosis may also accompany the condition. It is one of the most afflictive oral mucosal inflammatory ulcerative lesions and can cause pain on eating, swallowing and speaking.12,13 The treatment choices should be guided by the severity of the disease (the amount of pain), the frequency of ulceration and the potential adverse effects. In the absence of a clearly defined cause, the treatment is primarily aimed Table 1. Demographic Characteristics of Study Subjects at Entry (n = 60) Parameters
The demographic details of the study subjects at entry are listed in Table 1. All the 60 patients completed the study and their data was available for analysis. The results of this study showed that HiOra-SG significantly reduced the symptoms of stomatitis (Table 2). The initial mouth ulcer score was 2.75 ± 0.43, which reduced to 2.66 ± 0.25 after
HiOra-SG gel
Age in years (mean ± SD)
29.40 ± 5.50
Weight in kg (mean ± SD)
68 ± 6.50
Sex ratio/M:F
25:35
H/o smoking
04
H/o alcohol consumption
02
Diet (veg/nonveg)
35/25
Table 2. Effect of HiOra-SG Gel on Clinical Parameters of Stomatitis Clinical symptom score
HiOra-SG gel Initial
1 week
2 weeks
0.25a
0.25 ± 0.65b
Mouth ulcers
2.75 ± 0.43
2.66 ±
Pain
2.95 ± 0.25
2.25 ± 0.70a
0.30 ± 0.55b
Halitosis
2.30 ± 0.48
2.00 ± 0.22
1.44 ± 0.56
2.25 ± 0.52
0.70a
0.25 ± 0.44b
1.84 ± 0.32a
3.12 ± 0.33b
Swelling Overall impression ap
< 0.05;
bp
-
2.05 ±
< 0.001
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
113
original study at pain relief and the reduction of inflammation. Currently available treatment options for stomatitis are associated with adverse effects. Therefore, effective medicine without any adverse effects is the need for the day. Based on the results of this study, HiOra-SG has been found to be clinically safe and effective in the management of stomatitis. The beneficial effects of HiOra-SG can be attributed to the synergistic actions of its constituent potent herbs. HiOra-SG is a polyherbal formulation containing the extracts of the herbs, which have anti-inflammatory, antiseptic and ulcer healing properties. Jasminum grandiflorum has anti-inflammatory and antiseptic properties. The leaves are useful in odontalgia, fixing loose teeth and ulcerative stomatitis.14 Glycyrrhiza glabra has antibacterial and antiseptic properties.15 Triphala is a compounded form of three herbs like fruits of Emblica officinalis, Terminalia bellerica and Terminalia chebula. Triphala has analgesic, anti-inflammatory and wound-healing properties.16,17 Boerhaavia diffusa has anti-inflammatory, antiseptic, and laxative properties.18 Syzgium aromaticum has antifungal, antiviral, analgesic/anesthetic, antiseptic, anticoagulant and antioxidant properties. The antimicrobial activity is exhibited by volatile oil of clove.19 Nimbolide isolated from Azadirachta indica has antifungal activity.20 Bark extract reduces inflammation of stomatitis.21
4. 5. 6. 7. 8.
9.
10. 11.
12.
13.
Conclusion
14.
Stomatitis is a common oral disorder whose etiopathogenesis is unknown. As a result, only symptomatic therapy is available. Since, no diagnostic tests are available, diagnosis is made on clinical grounds alone. Preventive and treatment modalities may reduce the number of future ulcers and facilitate healing of developed lesions. In the present study, there was a remarkable improvement in the symptoms like pain, ulcer and swelling in the patients treated with HiOra-SG. No adverse effects were reported during the study period. Therefore, it can be concluded that HiOra-SG is effective and safe in the management of stomatitis.
15.
References 1. 2.
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3.
Rodu B, Mattingly G. Oral mucosal ulcers: diagnosis and management. J Am Dent Assoc 1992;123(10):83-6. Petersen MJ, Baughman RA. Recurrent aphthous stomatitis: primary care management. Nurse Pract 1996;21(5):36-40, 42, 47.
16.
17. 18. 19. 20. 21.
Fischman SL. Oral ulcerations. Semin Dermatol 1994; 13(2):74-7. Schneider LC, Schneider AE. Diagnosis of oral ulcers. Mt Sinai J Med 1998;65(5-6):383-7. MacPhail L. Topical and systemic therapy for recurrent aphthous stomatitis. Semin Cutan Med Surg 1997; 16(4):301-7. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med 1998;9(3):306-21. Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders. Semin Cutan Med Surg 1997;16(4):278-83. Eversole LR. Immunopathology of oral mucosal ulcerative, desquamative, and bullous diseases: selective review of the literature. Oral Surg Oral Med Oral Pathol 1994;77(6): 555-71. Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach. J Am Dent Assoc 2003;134(2): 200-7. Tilliss TS, McDowell JD. Differential diagnosis: is it herpes or aphthous? J Contemp Dent Pract 2002;3(1): 1-15. Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA, H채yrinen-Immonen R. Recurrent aphthous ulcers today: a review of the growing knowledge. Int J Oral Maxillofac Surg 2004;33(3):221-34. Miller MF, Ship II. A retrospective study of the prevalence and incidence of recurrent aphthous ulcers in a professional population, 1958-1971. Oral Surg Oral Med Oral Pathol 1977;43(4):532-7. Field EA, Brookes V, Tyldesley WR. Recurrent aphthous ulceration in children: a review. Int J Paediatr Dent 1992;2(1):1-10. Chunekar KC, Bhavaprakasha Nighantu. Chaukhambha Bharati Academy, 2006:491-2. Mitscher LA, Park YH, Clark D, Beal JL. Antimicrobial agents from higher plants. Antimicrobial isoflavanoids and related substances from Glycyrrhiza glabra L. var. typica. J Nat Prod 1980;43(2):259-69. Prabu D, Kirubanandan S, Ponnudurai K, Nappinnai M, Renganathan S. Preliminary evaluation of anti-inflammatory and analgesic activities of Triphala. Int J Nat Appl Sci 2007;3(4):419-24. Kumar MS, Kirubanandan S, Sripriya R, Sehgal PK. Triphala promotes healing of infected full-thickness dermal wound. J Surg Res 2008;144(1):94-101. Longman O, Indian medicinal plants, a compendium of 500 species. Volume 1, p. 281. Dorman HJ, Deans SG. Antimicrobial agents from plants: antimicrobial activity of plant volatile oils. J Appl Microbiol 2000;88(2):308-16. Murthy PS, Sirsi M. Pharmacological studies on Melia azadirachta, Linn. (n.o. Meliaceae). Indian J Psychol 1958;2(2):387-96. Lorenz HKP. Neem tree bark extract in the treatment of inflammatory stomatitis. J Praxis 1976;8: 231-3.
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
AD/52/AUG/2011
drug review
Cefaclor: A Review of Its Use in Management of Infections Ramesh Hotchandani
Abstract Cefaclor is an orally effective semisynthetic second-generation cephalosporin with a broad-spectrum activity against bacteria, including resistant strains despite widespread use, responsible for most community-acquired infections such as respiratory tract, both upper and lower, urinary tract and skin and soft tissue infections. In this article, we review the various aspects of cefaclor including antimicrobial spectrum, clinical pharmacology and clinical efficacy. Key words: Cefaclor, second-generation cephalosporin, community-acquired infections
W
hile dealing with community-acquired infections and healthcare associated infections, a broad-spectrum antibiotic is required. Patient may have co-existing infections. When prescribing antibiotics, often the competition is between second-generation cephalosporins versus ampicillin, amoxicillin plus a b-lactamase inhibitor. A second-generation cephalosporin like cefaclor often has an advantage of covering infections common in India. Besides respiratory and urinary tract infections, it takes care of enteric fever like infections. It lacks anti-TB activity, unlike fluoroquinolones, an advantage when diagnosis is in doubt. Cefaclor is the drug of choice for surgeons. Many surgeries like bypass, etc. are under cover of the second-generation cephalosporin cefaclor. Cefaclor: Balanced Antibacterial Coverage Cefaclor is 3-chloro-7-D-(2-phenylglycinamido)-3cephem-4-carboxylic acid;1 it is an orally effective semisynthetic second-generation cephalosporin with a b-lactam ring-base structure. Cefaclor has demonstrated activity against a wide range of organisms in vitro.2
Antimicrobial Spectrum
Cefaclor has antibacterial activity against large number of gram-negative and gram-positive bacteria.3 It has demonstrated activity against many gram-positive aerobes, gram-negative aerobes and some anaerobic bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae (including ampicillin-resistant strains).4 Knothe conducted a comparative study to evaluate the in vitro activity of cefaclor and other oral cephalosporins against a large number of freshly isolated clinical strains of gram-negative and gram-positive bacteria. Cefaclor has a superior action against S. pneumoniae.5 Compared to cephradine and cephalexin, cefaclor was less resistant to staphylococcal penicillinase.1 Cefaclor is the most active antibiotic against strains of H. influenzae, and is also more active than cephalexin and cephradine against non-b-lactamase producing strains of Escherichia coli, Klebsiella species and Proteus mirabilis.5 Cefaclor also has demonstrated efficacy against b-lactamase-producing H. influenzae resistant to ampicillin.3
Cefaclor is a bactericidal antibiotic, binds to penicillinbinding proteins (PBP) and inhibits synthesis of bacterial cell wall thereby causing cell lysis and death.
The in vitro activity of cefaclor was compared with that of cephalexin and cephradine by Gillett et al in another study. Cefaclor was the most active of the oral agents against H. influenzae (especially nonb-lactamase producing strains). It was also significantly more active against Neisseria gonorrhoeae and the Enterobacteriaceae.6
Head, Dept. of Nephrology Moolchand Medcity, New Delhi
Similar results were observed in another study where cefaclor was significantly more active than cephalexin and cephradine, against staphylococci, streptococci,
Mechanism of Action
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
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drug Review gonococci, meningococci and certain species of the Enterobacteriaceae. Cefaclor was also highly active against both b-lactamase-positive and -negative strains of H. influenzae at the recommended inoculum size.1 In the study, cefaclor was at least three times as active as cephradine at 2 µg/ml and at least one and a half times as active as cephalexin at this concentration against both penicillinase- and nonpenicillinase-producing strains of S. aureus. At 2 µg/ml, cefaclor inhibited all b-lactamase-positive and -negative strains of H. influenzae at the generally recommended inoculum of 104 CFU/ml, in contrast to cephalexin and cephradine, which required substantially greater concentrations to achieve the same order of activity and which were also considerably affected by Haemophilus b-lactamase. Cefaclor was also significantly more active against gonococci and meningococci and inhibited all strains at 0.25 µg/ml. The minimum inhibitory concentration (MIC) values of cefaclor were at least 1/16 of those of the other two cephalosporins.1 In a study, all 1,050 isolates of S. pyogenes tested were susceptible to penicillin (MIC ≤0.12 µg/ml) and cefaclor (MIC ≤0.25 µg/ml). Azithromycin, clarithromycin and erythromycin resistance rates were 15.9%, 15.4% and 15.8%, respectively. MIC90s for penicillin, cefaclor, azithromycin, clarithromycin, erythromycin and roxithromycin were found to be 0.015, 0.12, >4, 8, >1 and 16 µg/ml, respectively.7 Clinical Pharmacology
After oral administration, cefaclor is rapidly absorbed with 95% bioavailability. Peak serum levels are achieved about one hour after dosing.8 Cefaclor readily produces therapeutic plasma levels in children.9 Food does not affect its absorption. However, when taken with food, the peak concentration achieved is 50-75% of that observed in fasting subjects. Cefaclor has a half-life of one hour. After oral administration, cefaclor is excreted unchanged in the urine.8 Clinical Efficacy
Pooled data from a study in six countries in 1,493 adult and pediatric patients showed that satisfactory clinical responses were obtained in 80% of urinary tract infections, 87% of upper respiratory tract infections, 90% of cases of otitis media, 99% of lower respiratory tract infections (LRTIs) and 96% of skin and skin structure infections. Also, cefaclor was associated with a low incidence of adverse reactions.10 118
Acute otitis media: Acute otitis media (AOM) is the most frequent respiratory tract infection of infancy and childhood. S. pneumoniae, H. influenzae and Moraxella catarrhalis are the most common etiopathogens.2 Antibiotic resistance is increasing among the pathogens that commonly cause AOM.11 Cefaclor therapy is very effective for treating children aged 2-6 years affected by AOM. A study compared the clinical efficacy and tolerability of short-course therapy with cefaclor with long-term therapy for treatment of AOM in children. At the end of the treatment 95.5% of patients were cured after short-term therapy and 94.8% after long-term therapy. Short-course treatments had better compliance and tolerability.12 A multicentric prospective trial compared the efficacy and safety of cefaclor versus amoxicillin + clavulanic acid (Amoxy-Clav) in 167 children with AOM. Both cefaclor and Amoxy-Clav caused a significant improvement in all the signs and symptoms after a 10-day treatment period. However, between-the-group comparisons showed that the reduction in most of the symptoms was significantly more in cefaclor arm as compared to Amoxy-Clav arm.2 The clinical success (clinical cure + improvement) at the end of therapy was significantly more in cefaclor arm: 98% with cefaclor versus 85% with Amoxy-Clav (p < 0.05). Bacteriological eradication was seen in 95% of patients in cefaclor group and 78% of patients in Amoxy-Clav group. Based on their observations, the researchers concluded that cefaclor is a well-tolerated and effective antibiotic option for AOM in children and it is superior to the combination of Amoxy-Clav in efficacy and tolerability in acute AOM. Its expanded-spectrum of activity, ability to achieve adequate concentrations in tissues, suitability for twice-daily dosing and proven tolerability make it a good alternative to agents traditionally used in AOM.2 A total of 201 children were retrospectively studied to assess the efficacy and side effects of amoxicillin and cefaclor in the treatment of AOM. There were 456 episodes of AOM; 245 episodes were treated with amoxicillin with an efficacy of 91%, while 211 episodes were treated with cefaclor with an efficacy of 97%.13 A prospective, open-label, randomized study Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
drug Review reported that bacteriologic failure after 3-4 days of treatment with oral azithromycin and oral cefaclor in treatment of AOM occurred in a high proportion of culture-positive patients, especially in those in whom AOM was caused by H. influenzae (16 of 33 [53%] of those treated with azithromycin and 13 of 34 [52%] of those treated with cefaclor).14 Cefaclor is a better option in the chemoprophylaxis of recurrent AOM according to a retrospective study. In the 87 courses of chemoprophylaxis with cefaclor for recurrent otitis media, the efficacy was found to be 53%; while amoxicillin was found to be effective in 30% of the 33 patients studied.13 Cefaclor (40 mg/kg/day divided in three doses) was compared with cefprozil (15 mg/kg b.i.d.) and cefixime (8 mg/kg/day) for 10 days in 394 pediatric patients with otitis media. The clinical response rates observed were: 89% (cefaclor) versus 85% (cefprozil) versus 85% (cefixime). Compared with cefaclor-treated patients, cefixime-treated patients had significant increase in diarrheal episodes (15.7%), versus cefprozil (4.6%) versus cefaclor (3.1%) (p = 0.004). The relapse rates after additional two weeks were: 20.2% (cefprozil) versus 17.7% (cefixime) vs 13.3% (cefaclor).15,16 Pharyngotonsillitis: Bacteria are responsible for about 5-10% of pharyngitis cases, with Group A b-hemolytic streptococci (GABHS) being the most common bacterial etiology.17 The bacteria commonly associated with pharyngotonsillitis have developed clinically significant resistance to the traditional first-line antibiotics, creating the need for other alternative treatment modalities.18 A study was conducted to evaluate efficacy of cefaclor (20-40 mg/kg/day administered thrice-daily for one week) as treatment of pharyngotonsillitis in children aged 2-12 years. The study showed a high symptomatic response rate (cure or improvement) of 99% and minimal adverse events with cefaclor. Pre-therapy in vitro testing for antibiotic susceptibility showed that for GABHS, 37% of isolates were susceptible to cefaclor; susceptibility was less favorable for penicillin, Amoxy-Clav and erythromycin.18 In a multicenter study, overall, the clinical success (cure or improvement) with cefaclor (30 mg/kg t.i.d. Ă&#x2014; 10 days) divided into three daily doses and azithromycin (10 mg/kg o.d. Ă&#x2014; 3 days) given once-daily for three days was identical in the evaluable patients (86.3%). Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
But, bacterial eradication after completion of treatment was lower with azithromycin than with cefaclor.19 Sinusitis: In a study comparing efficacy and tolerance of cefaclor with those of cefpodoxime in patients with acute sinusitis, the overall clinical efficacy (cure + improvement) was found to be similar in the two groups with 95% (116/122) satisfactory responses in the cefpodoxime proxetil group and 93% (106/114) in the cefaclor group. Bacteriological response was similar with 95% eradication in the cefpodoxime proxetil group (55/58) versus 91% with cefaclor (63/69).20 Lower respiratory tract infections: Cefaclor is useful in the management of acute LRTIs by virtue of its excellent clinical efficacy and safety.21 Cazzola et al evaluated the efficacy and safety of cefaclor in the treatment of acute exacerbations of chronic bronchitis (AECB) in cigarette smokers (n = 106). Cefaclor (500 mg) was given orally every 8-hour for 7-16 days. H. influenzae was the most common bacterial species isolated in the sputum (in 23.6% of the total sample), followed by S. pneumoniae (18.9%), S. aureus (17.0%), Klebsiella pneumoniae (7.5%) and Branhamella catarrhalis (5.7%), while mixed forms were present in 22.6% of cases and other pathogens in 4.7%. Analysis of clinical response data showed that 75.5% of patients were cured and 17.0% improved. These findings demonstrate that the antibacterial spectrum of cefaclor covers all the most likely pathogens encountered in smokers. Because of its excellent response rate, cefaclor is of particular value in the treatment of LRTIs in cigarette smokers.22 Fifty-one patients admitted to hospital with severe exacerbations of chronic bronchitis entered a double-blind trial of treatment with cefaclor (500 mg t.d.s.; n = 26) compared with amoxicillin (500 mg t.d.s.; n = 25) for seven days in a study and at outpatient follow-up, three weeks after treatment had finished. While no significant differences between the two regimes for clinical outcome, spirometry or numbers of infecting pathogens were found, cefaclor was less damaging to normal flora than amoxycillin with a consequently reduced risk of colonization and superinfection of the respiratory tract with resistant gram-negative organisms and yeasts.23 119
drug Review In a randomized, multicenter trial, 84 patients with LRTIs were treated with cefaclor (n = 40) and amoxycillin (n = 44) in doses of 250 mg t.i.d. orally for seven days in a double-blind fashion. The clinical outcome showed 92.5% cured or improved patients on cefaclor versus 88.4% on amoxycillin.24 Cefaclor was found to be a safe and efficacious drug in the treatment of bacterial respiratory tract infections in children aged two months to 12 years. In the study, sensitivity of cefaclor for bacteria commonly seen in the respiratory tract was >90% in most of the cases. Evaluation of the 42 culture-proven cases for patients who completed the study showed that cefaclor had a 93% efficacy for indicated bacteria and 54% for nonindicated bacteria. Only 15 nonserious adverse events were observed in 160 patients, none of the cases necessitated discontinuation of drug.25 In a comparison of cefpodoxime proxetil (200 mg, b.i.d.) and cefaclor (250 mg, t.i.d.) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) in adults, no statistically significant differences between the two drug regimens in eradication of the initial pathogen (cefpodoxime 91% vs cefaclor 92%) or end-of-therapy clinical response (cure + proved; cefpodoxime 99% vs cefaclor 92%) rates for evaluable patients were observed. Both treatments were well-tolerated, with a similar incidence of drugrelated adverse events (cefpodoxime 11% vs cefaclor 12%).26 In another study in patients with acute COPD exacerbations, bacterial eradication of 87.2% isolates was achieved with azithromycin, compared with an eradication rate of 90.0% isolates with cefaclor.27 Skin and/or soft tissue infections: Cefaclor has proven effective in clinical studies of patients with skin and soft tissue infections (SSTIs). Over 90% of patients with staphylococcal bullous impetigo, streptococcal and mixed streptococcal-staphylococcal forms of pyoderma were cleared after 7-10 days courses of treatment. No significant adverse reactions were noted. Cefaclor thus is an effective orally absorbed cephalosporin for common SSTIs.28 A multicenter clinical trial in 125 outpatients (median age 32 years) with bacterial SSTIs due to bacteria compared the safety and efficacy of cefuroxime axetil and cefaclor. Patients were randomly assigned to treatment with one of three treatments: Cefuroxime axetil 250 mg b.i.d., cefuroxime axetil 500 mg b.i.d. or 120
cefaclor 250 mg t.i.d. for 10 days. Clinically, beneficial outcome was achieved for 92% (cefuroxime axetil 250 mg b.i.d.), 95% (cefuroxime axetil 500 mg b.i.d.) and 97% (cefaclor 250 mg t.i.d.) of patients.29 A comparative study of Amoxy-Clav and cefaclor recruited 64 patients. Pathogenic bacteria were recovered from 21 patients who received Amoxy-Clav and 17 patients who received cefaclor. The primary diagnoses were pyodermas and impetigo, as well as cellulitis, folliculitis, infected skin structure and infected surgical sites. Eighty-one percent of the Amoxy-Clav-treated patients were classified as successfully treated, based on clinical and bacteriologic criteria, as were 89% of the patients treated with cefaclor. Both groups reported minimal side effects.30 In a double-blind comparison of cefaclor and AmoxyClav for the outpatient treatment of soft tissue infections (abscesses, cellulitis and impetigo), patients who received Amoxy-Clav had a much higher incidence of gastrointestinal (GI) side effects than did patients who received cefaclor (34 vs 3%, p < 0.005).31 An open, multicenter comparative study evaluated the efficacy, safety and tolerability of (10 mg/kg once-daily for 3 days) or cefaclor (20 mg/kg/day in three divided doses for 10 days) oral suspensions in the treatment of children with acute SSTIs (mild-to-moderate dermatological conditions and abscesses). The clinical efficacy of both treatments was comparable: 92/98 (94%) of the evaluable azithromycin patients were cured or improved as were 93/98 (95%) of those treated with cefaclor. Before treatment, 74 pathogens were isolated from 60 of the azithromycin- and 80 pathogens from 66 of the cefaclor-treated patients. In the azithromycin group, 70/74 (95%) pathogens were eradicated, as were 79/80 (99%) pathogens in the cefaclor group. No patient in either treatment group withdrew from the study because of adverse events.32 Urinary tract infections: Insusceptibility levels of cefaclor and other commonly prescribed antibiotics were determined for 489 consecutive hospital and community-associated urinary tract isolates of E. coli. Cefaclor showed significantly greater in vitro activity than cephalexin, ampicillin and trimethoprim. Cefaclor also compared extremely well with co-amoxiclav against ampicillin-insusceptible isolates. Hence, cefaclor appears to be a useful cost-effective alternative to current therapeutic options, particularly Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
drug Review
Take Away Messages Antimicrobial resistance is a growing problem in many bacterial pathogens and is becoming increasingly prevalent in bacterial infections. β-lactamase-mediated resistance is of particular concern. Studies have demonstrated increasing resistance to most widely used antibiotics in urinary and respiratory infections such as Amoxy-Clav. Also, it is frequently associated with GI side effects such as nausea, vomiting or diarrhea, which may lead to discontinuation of treatment. Cefaclor is an orally administered second-generation cephalosporin that exhibits good activity against a range of common pathogens including S. pyogenes, S. aureus, H. influenzae, S. pneumoniae, E. coli, P. mirabilis and Klebsiella, including resistant strains despite widespread use. Cefaclor has been widely used worldwide for the management of bacterial infections of the respiratory tract (upper and lower), urinary tract and soft tissues and has shown high success rates. Its molecular stability, broad-spectrum antimicrobial activity against the most prevalent gram-positive and gram-negative pathogens, rapid absorption, >90% bioavailability are factors that contribute to the efficacy and tolerability of cefaclor. The incidence of adverse events with cefaclor is low with good patient compliance.
for long-term low-dose treatment of recurrent urinary tract infection in those geographical areas where the likelihood of resistance to other possible agents is becoming unacceptably high.33 A study performed in the USA between 1988 and 1990 (i.e., after widespread usage of cefaclor for 10 years) found that cefaclor retained microbiological activity against >95% of strains isolated from uncomplicated urinary infections, including 97.9% of the E. coli strains isolated.33 In a study, 51 patients with urinary tract infections were randomly assigned to receive cefaclor or amoxicillin 250 mg orally every eight hours for 10 days. MICs of cefaclor, amoxicillin, cephradine, and cephalexin were determined by an agar dilution technique for the 44 available pre-treatment isolates (41 E. coli and 3 P. mirabilis). Mean MICs (µg/ml ± SD) were 2.2 ± 1.4 for cefaclor, 4.4 ± 2.0 with amoxicillin, 8.1 ± 4.2 for cephradine and 5.7 ± 3.0 with cephalexin. The study showed that cefaclor is highly active in vitro against those gram-negative bacteria which are commonly isolated from urine.34
3. Derry JE. Evaluation of cefaclor. Am J Hosp Pharm 1981;38(1):54-8. 4. Rodriguez WJ, Ross S, Schwartz R, Goldenberg R, Khan W. Cefaclor in the treatment of susceptible infections in infants and children. Postgrad Med J 1979;55 Suppl 4: 35-8. 5. Knothe H. In vitro activity of cefaclor (author’s transl). Infection 1979;7 Suppl 6:518-26. 6. Gillett AP, Andrews JM, Wise R. Comparative in vitro microbiological activity and stability of cefaclor. Postgrad Med J 1979;55 Suppl 4:9-11. 7. Bandak SI, Turnak MR, Allen BS, Bolzon LD, Preston DA. Oral antimicrobial susceptibilities of Streptococcus pyogenes recently isolated in five countries. Int J Clin Pract 2000;54(9):585-8. 8. Glynne A, Goulbourn RA, Ryden R. A human pharmacology study of cefaclor. J Antimicrob Chemother 1978;4(4):343-8. 9. Spencer MJ. Cefaclor in the treatment of susceptible infections in infants and children. Infection 1979;7 Suppl 6:628-30.
References
10. Kammer RB, Short LJ. Cefaclor: summary of clinical experience. Infection 1979;7 Suppl 6:631-5.
1. Bill NJ, Washington JA 2nd. Comparison of in vitro activity of cephalexin, cephradine, and cefaclor. Antimicrob Agents Chemother 1977;11(3):470-4.
11. Pichichero ME. Acute otitis media: part II. Treatment in an era of increasing antibiotic resistance. Am Fam Physician 2000;61(8):2410-6.
2. Aggarwal M, Sinha R, Murali MV, Trihan P, Singhal PK. Comparative efficacy and safety evaluation of cefaclor vs amoxycillin + clavulanate in children with acute otitis media (AOM). Indian J Pediatr 2005;72(3):233-8.
12. Catania S, Gallo A. Clinical efficacy and tolerability of short course therapy with cefaclor compared with long-term therapy for treatment of acute otitis media in children. Infez Med 2004;12(4):259-65.
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drug Review 13. Perry BP, Zieno SA, Yonkers AJ, Moore GF. Outcomeoriented managed care comparing efficacies of cefaclor and amoxicillin in acute and recurrent acute otitis media. Ear Nose Throat J 1995;74(12):840-4. 14. Dagan R, Leibovitz E, Fliss DM, Leiberman A, Jacobs MR, Craig W, et al. Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children. Antimicrob Agents Chemother 2000;44(1):43-50. 15. Poole JM, Rosenberg R, Aronovits GM. Cefprozil vs cefixime and cefaclor in otitis media in children. Infect Med 1992;9 Suppl E: 21-32. 16. Rodman DP, McKnight JT, Anderson RL. A critical review of the new oral cephalosporins. Considerations and place in therapy. Arch Fam Med 1994;3(11): 975-80. 17. Hayes CS, Williamson H Jr. Management of Group A beta-hemolytic streptococcal pharyngitis. Am Fam Physician 2001;63(8):1557-6. 18. Siddiqui SJ, Awan A, Ekangakic A, Stocks JM, Sheikh GA, Ahmad TM, et al. An evaluation of cefaclor in Pakistani children with pharyngotonsillitis. J Pak Med Assoc 2002;52(10):451-6. 19. Cremer J, Wallrauch C, Milatovic D, Braveny I. Azithromycin versus cefaclor in the treatment of pediatric patients with acute group A beta-hemolytic streptococcal tonsillopharyngitis. Eur J Clin Microbiol Infect Dis 1998;17(4):235-9.
in acute exacerbations of bronchitis. Respir Med 1991;85(4):301-8. 24. Swedish Study Group. A randomized multicenter trial to compare the influence of cefaclor and amoxycillin on the colonization resistance of the digestive tract in patients with lower respiratory tract infection. Infection 1991;19(4):208-15. 25. Najam Y, Walla FL, Iqbal A, Khan MK, Aqil S, Sharif MW, et al. The efficacy and safety of cefaclor in respiratory infections amongst Pakistani children. J Pak Med Assoc 2000;50(9):289-93. 26. Phillips H, Van Hook CJ, Butler T, Todd WM. A comparison of cefpodoxime proxetil and cefaclor in the treatment of acute exacerbation of COPD in adults. Chest 1993;104(5):1387-92. 27. Dark D. Azithromycin versus cefaclor in the treatment of acute exacerbations of chronic obstructive pulmonary disease. Curr Ther Res 1993;53(2):203-11. 28. Dillon HC Jr, Gray BM, Ware JC. Clinical and laboratory studies with cefaclor: efficacy in skin and soft tissue infections. Postgrad Med J 1979;55 Suppl 4:77-81. 29. Parish LC, Cocchetto DM, Werner K, Jungkind DL, Witkowski J. Cefuroxime axetil in the treatment of cutaneous infections. Int J Dermatol 1987;26(6): 389-93. 30. Parish LC, Aten EM. Treatment of skin and skin structure infections: a comparative study of Augmentin and cefaclor. Cutis 1984;34(6):567-70.
20. Gehanno P, Depondt J, Barry B, Simonet M, Dewever H. Comparison of cefpodoxime proxetil with cefaclor in the treatment of sinusitis. J Antimicrob Chemother 1990;26 Suppl E: 87-91.
31. Pien FD. Double-blind comparative study of two dosage regimens of cefaclor and amoxicillin-clavulanic acid in the outpatient treatment of soft tissue infections. Antimicrob Agents Chemother 1983;24(6):856-9.
21. Mattson K, Renkonen OV, Laitinen L, NikanderHurme R. Treatment of acute bronchitis and pneumonia with cefaclor. Postgrad Med J 1979;55 Suppl 4:59-61.
32. Montero L. A comparative study of the efficacy, safety and tolerability of azithromycin and cefaclor in the treatment of children with acute skin and/or soft tissue infections. J Antimicrob Chemother 1996;37 Suppl C:125-31.
22. Cazzola M, Franco C, Gioia V, Legnani D, Mancini V, Polverino M, et al. Cefaclor in the treatment of infective exacerbations of chronic bronchitis in cigarette smokers. J Chemother 1991;3(4):245-9. 23. Trigg CJ, Wilks M, Herdman MJ, Clague JE, Tabaqchali S, Davies RJ. A double-blind comparison of the effects of cefaclor and amoxycillin on respiratory tract and oropharyngeal flora and clinical response
33. Webster CA, Curran R, Towner KJ. Comparative in-vitro activity of cefaclor against urinary tract isolates of Escherichia coli. J Antimicrob Chemother 1996; 38(1):59-66. 34. Rotschafer J, Crossley K, Zaske D, Viste R. Comparative study of cefaclor and amoxicillin in treatment of urinary tract infection. Urology 1979;14(3):233-6.
In this article, amoxicillin + clavulanic acid has been abbreviated as Amoxy-Clav. n
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n
n
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
review article
Treatment of Knee Osteoarthritis Erika Ringdahl, Sandesh Pandit
Abstract Knee osteoarthritis is a common disabling condition that affects more than one-third of persons older than 65-years Exercise, weight loss, physical therapy, intra-articular corticosteroid injections, and the use of nonsteroidal anti inflammatory drugs and braces or heel wedges decrease pain and improve function. Acetaminophen, glucosamine, ginger, S-adenosylmethionine (SAM-e), capsaicin cream, topical nonsteroidal anti-inflammatory drugs, acupuncture, and tai chi may offer some benefit. Tramadol has a poor trade-off between risks and benefits and is not routinely recommended. Opioids are being used more often in patients with moderate to severe pain or diminished quality-of-life, but patients receiving these drugs must be carefully selected and monitored because of the inherent adverse effects. Intra-articular corticosteroid injections are effective, but evidence for injection of hyaluronic acid is mixed. Arthroscopic surgery has been shown to have no benefit in knee osteoarthritis. Total joint arthroplasty of the knee should be considered when conservative symptomatic management is ineffective. Key words: Knee osteoarthritis, nonsteroidal anti-inflammatory drugs, degenerative joint disease
O
steoarthritis is a degenerative joint disease occurring primarily in older adults. It is characterized by erosion of the articular cartilage, hypertrophy of bone at the margins (i.e., osteophytes), and subchondral sclerosis.1 Arthritis is the leading cause of disability in the United States,2 and osteoarthritis is the most common condition affecting synovial joints.3 Despite its widespread prevalence, however, the precise etiology, pathogenesis, and progression of osteoarthritis are unknown. Several factors may make a person vulnerable to the disease (Table 1). Osteoarthritis affects 33.6 percent of persons older than 65 years.4 About 80 percent of patients with knee osteoarthritis have some limitation of movement, and 25 percent cannot perform major activities of daily living.4 Approximately 11 percent of adults with knee osteoarthritis need help with personal care.4
Diagnosis of Osteoarthritis The most common presenting symptom in persons with knee osteoarthritis is pain that is worse with use and better with rest. Other presenting signs and symptoms include stiffness that generally improves after 30 minutes of activity (inactivity gelling), crepitus, swelling, and limp. In advanced cases, patients may present with instability symptoms or genu valgum (knock knee) or varum (bow-leg). Varus deformity is more common than valgus deformity because the medial compartment of the knee is more often involved. The differential diagnosis of chronic knee pain is given in Table 2. The criteria for diagnosing knee osteoarthritis are based on the presence of knee pain plus at least three of the six clinical characteristics Table 1. Common Risk Factors for Knee Osteoarthritis Female sex Inflammatory joint disease (e.g., infection, gout, rheumatoid arthritis)
ERIKA RINGDAHL, MD, is a clinical professor in the Department of Family and Community Medicine at the University of Missouri School of Medicine, Columbia. SANDESH PANDIT, MD, is a sports medicine fellow at Saint Vincent Health System in Erie, Pa. At the time this article was written, he was a resident in the Department of Family and Community Medicine at the University of Missouri School of Medicine.
Source: Adapted from Am Fam Physician. 2011;83(11):1287-1292.
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
No history of osteoporosis Obesity (strongest modifiable risk factor) Occupation requiring repetitive knee bending Older age Previous knee injury (e.g., torn meniscus, intra-articular mechanical damage)
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Review ARticle Table 2. Differential Diagnosis of Knee Pain
Table 3. Diagnosis of Knee Osteoarthritis
Conditions involving soft tissue of knee
Clinical criteria
Bursitis
Age older than 50 years
Iliotibial band syndrome
Bony enlargement
Ligamentous instability (medial and lateral collateral ligaments)
Bony tenderness
Meniscal pathology
Crepitus
Other forms of arthritis
No palpable warmth
Gout and pseudogout
Stiffness for less than 30 minutes
Rheumatoid arthritis Septic arthritis Referred pain
Laboratory criteria Erythrocyte sedimentation rate less than 40 mm per hour Rheumatoid factor less than 1:40
Neuropathy
Synovial fluid analysis: clear, viscous, white blood cell count less than 2,000 per μL (2.00 × 109 per L)
Radiculopathy
Radiographic criteria
Other
Presence of osteophytes
Avascular necrosis
Diagnostic accuracy
Patellofemoral pain syndrome
Criteria
Sensitivity Specificity (%) (%)
Tumor
listed in Table 3.5,6 The addition of laboratory and radiographic criteria enhances the diagnostic accuracy; however, these tests are not necessary for all patients. In most patients, the history, physical examination, and radiography are all that is needed. Treatment Physical Modalities and Exercise
Physical modalities for the treatment of knee pain in patients with osteoarthritis include physical therapy, exercise, weight loss, and the use of braces or heel wedges. A review of physical therapy interventions for patients with knee osteoarthritis concluded that exercise and weight loss reduce pain and improve physical function.7 Exercise should be prescribed as a treatment for knee osteoarthritis. Highand low-intensity aerobic exercises are equally effective in improving functional status, gait, pain, and aerobic capacity in persons with knee osteoarthritis8; water-based and land-based exercises reduce knee pain and physical disability9,10; and aerobic walking, quadriceps strengthening, and resistance exercise reduce pain and disability.11,12 A small randomized controlled trial (RCT) showed that performing tai chi three times per week for 12 weeks decreased pain and improved physical functioning in older women with knee osteoarthritis.13 Any activity 124
LR+
LR–
Knee pain plus at least three clinical criteria
95
69
3.1
0.07
Knee pain plus at least five clinical or laboratory criteria
92
75
3.7
0.11
Knee pain plus at least five clinical or laboratory criteria, plus osteophytes present
91
86
6.5
0.10
LR+ = Positive likelihood ratio; LR– = Negative likelihood ratio. Information from references 5 and 6.
that worsens knee pain should be discontinued. The use of braces and heel wedges may also be effective for treatment of knee osteoarthritis. There is some evidence that the use of a lateral heel wedge decreases the use of nonsteroidal anti-inflammatory drugs (NSAIDs).14 Similar evidence suggests that a brace and lateral wedge insole may have a small beneficial effect.14 Braces and heel wedges can be customized and purchased at stores specializing in orthotics. Complementary and Alternative Medicine
Many complementary and alternative medicine treatments have been used to treat knee osteoarthritis, with variable success. Glucosamine and chondroitin supplements have been marketed since the 1990s as disease-modifying options. A double-blind RCT Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
Review ARticle showed little benefit from the use of glucosamine combined with chondroitin in participants with mild knee osteoarthritis.15 However, a greater benefit was noted in persons with moderate to severe pain. Glucosamine is safe, but the benefit is variable. Chondroitin does not decrease pain from osteoarthritis of the knee or hip.15 The benefit of acupuncture is not clear. A metaanalysis did not demonstrate any clinically relevant improvement in pain or function scores with acupuncture compared with sham acupuncture.16 However, in the short term (six weeks) and in the long term (six months), patients who received either acupuncture or sham acupuncture felt better than those who received usual care. Another study showed that six months of treatment with traditional Chinese acupuncture decreased pain scores and increased functionality an average of 40 percent compared with sham acupuncture or no treatment.17 Supplementation with S-adenosylmethionine (SAM-e), ginger (Zingiber officinale), or turmeric (Curcuma longa) has also been promoted as treatment for osteoarthritis. A meta-analysis of RCTs found that SAM-e is as effective as NSAIDs in reducing pain and disability, and has a better safety profile.18 Ginger may provide some clinical benefit in patients with knee osteoarthritis; patients who took 255 mg of ginger extract twice daily had a reduction in pain (63 percent compared with 50 percent in the placebo group).19 Turmeric historically has been used to treat arthritis pain, but no clinical trials have shown it to be effective.20 Pharmacologic Treatment
Pharmacologic treatments can be categorized as topical, oral, or intra-articular. The use of topical therapies avoids many of the adverse effects associated with systemic medications. A review of placebo-controlled trials of capsaicin cream 0.025% concluded that it was statistically more effective than placebo, but less effective than topical NSAIDs.21 A meta-analysis of RCTs compared topical NSAIDs with placebo or oral NSAIDs in patients with knee osteoarthritis.22 Topical NSAIDs were superior to placebo in relieving pain, but only for the first two weeks of treatment. Topical NSAIDs were less effective than oral NSAIDs, even in the first week of treatment. Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
Many oral medications are available for managing pain from knee osteoarthritis. Acetaminophen is the preferred drug in guidelines from the American College of Rheumatology.23 It is more effective than placebo in the treatment of osteoarthritis pain.24 Liver toxicity is extremely rare, although caution should be used in patients who consume alcohol daily. Patients taking 3 to 4 g of acetaminophen per day should have regular monitoring of kidney and liver function. NSAIDs are slightly superior to acetaminophen for improving knee and hip pain in patients with osteoarthritis, especially in those with moderate to severe pain.25 There is no difference in clinical effectiveness among NSAIDs.25 Cyclooxygenase-2 (COX-2) inhibitors may have a role in the treatment of osteoarthritis. Celecoxib is the only prototype COX-2 inhibitor available because rofecoxib and valdecoxib have been withdrawn from the market because of adverse cardiovascular effects. However, celecoxib is also associated with an increased incidence of myocardial infarction and stroke.26 A systematic review showed that although the use of celecoxib results in similar symptom control as other NSAIDs and does not reduce the risk of serious adverse gastrointestinal effects, patients may be less likely to stop taking celecoxib because of gastrointestinal effects.27,28 Although there is no increased risk of adverse effects with the use of COX-2 inhibitors for treatment of osteoarthritis compared with other NSAIDs, there also may not be much benefit. Opioids also may have a beneficial role in the treatment of knee osteoarthritis. Guidelines from the American College of Rheumatology support the use of opioid therapy when other treatments have been ineffective or are inappropriate.23 Tramadol, with or without acetaminophen, decreases pain intensity, relieves symptoms, and improves function.29 Tramadol increases the risk of seizure, especially in patients who drink alcohol. A recent guideline from the American Geriatrics Society recommends that all older patients with moderate to severe pain or diminished quality of life be considered for opioid therapy.30 The risks of NSAID use in older patients, including increased cardiovascular risk and gastrointestinal toxicity, may exceed the potential for addiction in these patients. However, propoxyphene, which was taken off the market in November 2010, should be avoided because it is no more effective than acetaminophen and is associated with more adverse effects.31 125
Review ARticle Intra-articular Injections
Intra-articular corticosteroid injections may provide short-term symptomatic relief in patients with knee osteoarthritis, with low risk of adverse effects. A systematic review of 28 clinical trials found a significant short-term reduction in pain and improvement in patient self-assessment with intra-articular corticosteroid injection compared with placebo injection32; however, good evidence of long-term benefit is lacking. The precise mechanism of action is unknown, but corticosteroids are presumed to inhibit accumulation of inflammatory cell lines, reduce prostaglandin synthesis, inhibit leukocyte secretion from synovial cells, and decrease interleukin secretion by the synovium. A typical dose for knee injections is 40 mg of triamcinolone acetonide, with a number needed to treat of two or three.33 Intra-articular hyaluronic acid injections (e.g., Synvisc, Euflexxa) for osteoarthritis are minimally effective. Despite being promoted as potential diseasemodifying agents, no study has demonstrated that these drugs alter the disease course. Synovial fluid is an ultrafiltrate of plasma modified by the addition of hyaluronic acid, which is produced by the synovium. In persons with osteoarthritis, the hyaluronic acid is decreased and compromised. Exogenous supplementation of intra-articular hyaluronic acid is thought to support and restore the elastoviscous properties of synovial fluid. However, a metaanalysis showed that studies demonstrating benefit from intra-articular hyaluronic acid injections were poorly designed or industry sponsored, whereas other studies demonstrated no clinically significant improvement in function.34 Surgery
Arthroscopic surgery is not an appropriate treatment for knee osteoarthritis unless there is evidence of loose bodies or mechanical symptoms such as locking, giving way, or catching. Two well-designed RCTs of arthroscopic surgery for treatment of knee osteoarthritis showed no benefit.35,36 Total knee replacement should be considered as a last resort. According to the American Academy of Orthopedic Surgeons, the main indication for total knee arthroplasty is relief of pain associated 126
with knee osteoarthritis if nonsurgical treatment has been ineffective. The complication rate of total knee replacement is 5.4 percent of patients and 7.6 percent of knees.37 References 1. Di Cesare P, Abramson S, Samuels J. Pathogenesis of osteoarthritis. In: Firestein GS, Kelley WN, eds. Kelley’s Textbook of Rheumatology. 8th ed. Philadelphia, Pa.: Saunders Elsevier 2009:1525-1540. 2. Centers for Disease Control and Prevention. Prevalence and most common causes of disability among adults– United States, 2005. MMWR Morb Mortal Wkly Rep. 2009;58(16):421-426. 3. Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nat Med. 1998;4(11):1241-1243. 4. Centers for Disease Control and Prevention. Osteoarthritis.‑http://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed March 1, 2010. 5. Altman R, Asch E, Bloch D, et al. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Arthritis Rheum. 1986;29(8):1039-1049. 6. Wu CW, Morrell MR, Heinze E, et al. Validation of American College of Rheumatology classification criteria for knee osteoarthritis using arthroscopically defined cartilage damage scores. Semin Arthritis Rheum. 2005;35(3):197-201. 7. Jamtvedt G, Dahm KT, Christie A, et al. Physical therapy interventions for patients with osteoarthritis of the knee: an overview of systematic reviews. Phys Ther. 2008;88(1):123-136. 8. Fransen M, McConnell S. Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev. 2008;(4): CD004376. 9. Fransen M, McConnell S. Land-based exercise for osteoarthritis of the knee: a metaanalysis of randomized controlled trials. J Rheumatol 2009;36(6):1109-1117. 10. Silva LE, Valim V, Pessanha AP, et al. Hydrotherapy versus conventional land-based exercise for the management of patients with osteoarthritis of the knee: a randomized clinical trial. Phys Ther. 2008;88(1):12-21. 11. Roddy E, Zhang W, Doherty M. Aerobic walking or strengthening exercise for osteoarthritis of the knee? A systematic review. Ann Rheum Dis. 2005; 64(4):544‑548. 12. Ettinger WH Jr, Burns R, Messier SP, et al. A randomized controlled trial comparing aerobic exercise and resistance Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
Review ARticle exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST). JAMA. 1997;277(1):25-31.
Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial [published correction appears in JAMA. 2002;287(8):989]. JAMA. 2002;287(1):64-71.
13. Song R, Lee EO, Lam P, Bae SC. Effects of tai chi exercise on pain, balance, muscle strength, and perceived difficulties in physical functioning in older women with osteoarthritis: a randomized clinical trial. J Rheumatol. 2003;30(9):2039-2044.
26. White WB, West CR, Borer JS, et al. Risk of cardiovascular events in patients receiving celecoxib: a meta- analysis of randomized clinical trials. Am J Cardiol. 2007;99(1):91‑98.
14. Brouwer RW, Jakma TS, Verhagen AP, Verhaar JA, Bierma-Zeinstra SM. Braces and orthoses for treating osteoarthritis of the knee. Cochrane Database Syst Rev. 2005;(1):CD004020.
27. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA. 2000;284(10):1247-1255.
15. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795-808. 16. Manheimer E, Linde K, Lao L, Bouter LM, Berman BM. Meta-analysis: acupuncture for osteoarthritis of the knee. Ann Intern Med. 2007;146(12):868-877. 17. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med. 2004;141(12):901‑910. 18. Soeken KL, Lee WL, Bausell RB, Agelli M, Berman BM. Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis. J Fam Pract. 2002;51(5):425‑430. 19. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum. 2001;44(11):2531-2538. 20. Medline Plus. Turmeric. http://www.nlm.nih.gov/ medlineplus/druginfo/natural/662.html.‑Accessed August 20, 2010. 21. Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ. 2004;328(7446):991. 22. Lin J, Zhang W, Jones A, Doherty M. Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials. BMJ. 2004;329(7461):324. 23. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 2000;43(9):1905‑1915.
28. Deeks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. BMJ. 2002;325(7365):619. 29. Cepeda MS, Camargo F, Zea C, Valencia L. Tramadol for osteoarthritis. Cochrane Database Syst Rev. 2006;3: CD005522. 30. American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in Older Persons. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009;57(8):1331-1346. 31. Li Wan Po A, Zhang WY. Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol [published corrections appear in BMJ. 1998;316(7125):116, and BMJ. 1998;316(7132):656]. BMJ. 1997;315(7122): 1565-1571. 32. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Intraarticular corticosteroid for treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006;(2):CD005328. 33. Arroll B, Goodyear-Smith F. Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ. 2004;328(7444):869. 34. Arrich J, Piribauer F, Mad P, Schmid D, Klaushofer K, Müllner M. Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. CMAJ. 2005;172(8):1039-1043. 35. Moseley JB, O’Malley K, Petersen NJ, et al. A controlled trial of arthroscopic surgery for osteoarthritis of the knee. N Engl J Med. 2002;347(2):81-88.
24. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G. Acetaminophen for osteoarthritis. Cochrane Database Syst Rev. 2006;(1): CD004257.
36. Kirkley A, Birmingham TB, Litchfield RB, et al. A randomized trial of arthroscopic surgery for osteoarthritis of the knee [published correction appears in N Engl J Med. 2009;361(20):2004]. N Engl J Med. 2008;359(11):1097-1107.
25. Geba GP, Weaver AL, Polis AB, Dixon ME, Schnitzer TJ; Vioxx Acetaminophen; Celecoxib Trial (VACT) Group.
37. Kane RL, Saleh KJ, Wilt TJ, et al. Total knee replacement. Evid Rep Technol Assess (Summ). 2003;(86):1-8.
n Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
n
n 127
original article
Bacteriological Trends in Geriatric Urinary Tract Infections in a Tertiary Care Referral Hospital in West Bengal Tapan Kumar Chattopadhyay*, Hirak Jyoti Raj**, Arpita Dutta†
Abstract Background: Unique features of urinary tract infection (UTI) in the elderly is a subject of modern interest; seemingly a trivial infection, UTI can lead to complications like dyselectrolytemia and septicemia. With this background, present study was undertaken to know the microbiology of UTI in the elderly. Method: In this cross-sectional study, 72 urine samples from elderly (≥65 years of age) outpatients were processed during February 2009 to February 2010 following the inclusion and exclusion criteria. A semi-quantitative culture according to CLSI guidelines and sensitivity following the Kirby-Bauer disc diffusion technique was done. Results: Thirty-nine samples (54.17%) out of 72, showed culture positivity. Escherichia coli was the commonest organism to be isolated in both sexes (46.15%). Staphylococcus aureus was the predominant organism (35.71%) in elderly females between 65-70 years of age, and in males E. coli isolates (30.76%) were more in number with lone isolation of Proteus mirabilis in a male patient. Staphylococcus saprophyticus and enterococci organisms were isolated exclusively in female patients and all the isolates showed susceptibility to commonly used antimicrobials. Conclusion: Polymicrobial isolation was observed in the studied cases. Culture positivity was more in female patients than in males; in contrast to S. saprophyticus isolated in sexually active women, S. aureus, was isolated in 20.15% of female patients at this age. The maximum number of samples had been received in cold months, the symptoms being related to less water drinking. This study requires a bigger sample size for better understanding. Key words: Geriatrics UTI, obstructive uropathy, Escherichia coli, Staphylococcus aureus
T
he importance of urinary tract infection (UTI) in the elderly population and some unique features associated with it, need continuous research. Apart from polymicrobial isolation from the UTI and their growing antimicrobial resistance, there are certain anatomical and functional impairment including the vaginal estrogen deficiency in postmenopausal women, which needs changes in therapeutic stategies. Whilst it is recognized that asymptomatic bacteriuria is a very common condition in the elderly, only the positive culture patients are treated. These facts create therapeutic dilemma and challenges to the new generation clinicians. Urinary tract is the second most common site of bacterial infection found in humans.1 The infected *Associate Professor Dept. of Microbiology **2nd Year Postgraduate Trainee †1st Year Postgraduate Trainee Burdwan Medical College, Burdwan Address for correspondence Dr Tapan Kumar Chattopadhyay Indraprastha, Baburbag PO: Rajbati, Burdwan - 713 104, West Bengal E-mail: drtapanmicroprof@gmail.com
128
urinary tract is, however, the commonest source of organisms responsible for septicemia, especially in the elderly.2 According to the Internet Journal of Geriatrics and Gerontology, several factors may explain the increased prevalence of UTIs in geriatric patients, including menopause, increased age, dehydration and catheter use.3 Any impediment to the free flow of urine, tumor, stricture, stone or prostatic hypertrophy, results in hydronephrosis and a greatly increased frequency of UTI. This obstruction may lead to rapid destruction of renal tissue. When the obstruction is minor and is not progressive or associated with infection, great caution should be exercised in attempting surgical correction. The introduction of infection in such cases may be more damaging than an uncorrected minor obstruction that does not significantly impair renal function. The development of asymptomatic bacteriuria parallels that of symptomatic infection and is rare among men under 50, but common among women between 20 and 50. Asymptomatic bacteriuria is more common among elderly men and women, with rates as high as 40-50% in some studies.4 Most UTIs in geriatric age group people are caused by bacteria such as Escherichia coli, Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
original article Klebsiella pneumoniae, Proteus mirabilis, Morganella spp., etc. In a study, it has been demonstrated that about 95% of UTIs occur when bacteria ascend the urethra to the bladder and other higher structures.5 Rest of the infections are hematogenous in spread. Increased receptivity of uroepithelial cells to bacterial attachment may be a predisposing factor in the onset of UTI in the elderly. Acquired abnormalities such as outflow obstruction may interfere with the smooth flow and drainage of urine and may lead to retention of variable volume of urine, ‘the residual urine’. The residual urine acts as a permanent source of infection and if the vesicoureteric valves are incompetent, the infection may spread upwards with chances of pyelonephritis and septicemia.6 E. coli alone causes >75% of community-acquired UTIs in all age groups including elderly. Definition of significant bacteriuria was made for asymptomatic women.4,7 Though, it is uncommon in younger population, 25-33% of bacteriuria in elderly may be polymicrobial. Reasons for multiple microorganisms other than contamination include fistula, urinary retention, infected stones and in elderly, benign prostatic hyperplasia, cancer of prostate, stricture acquired due to menopausal atrophy or recurrent UTI and due to various acquired obstructive uropathies.8 Although, a number of studies have been done on every aspect of UTI in the pediatric age group and young adult women the data for acute community-acquired infection in the elderly is lacking. Therefore, the present study was conducted to detect the prevalent etiological agents of UTIs in elderly people along with their antimicrobial susceptibility patterns, in order to formulate a local guideline to manage this illness at the earliest and to prevent the dreaded complications arising out of it. Material and Methods Study design: A retrospective, cross-sectional observational study. Setting: Patients catered through Burdwan Medical College and Hospital, outdoor and indoor. Sample size: 72 urine samples within a period of one year from February 2009 to February 2010. Inclusion criteria: Persons, ≥65 years of age, having features of UTIs like flank pain, dysuria, weak flow, frequency, etc. Exclusion criteria: Any patient below the pre-scheduled age i.e. 65 years, in-patients with features of gram-negative shock or having previous Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
surgical interventions and those who had antibiotics within two weeks of attendance in the Dept. of Microbiology. No follow-up has been done in this study. Outcome measures: Following the collection of samples, they were cultured immediately by semiquantitative method. Urine samples from the geriatric patients were inoculated onto the MacConkey’s lactose bile salt Agar and incubated at 37°C under aerobic condition for 18-24 hours. Following incubation, the plates were examined for any growth of bacteria. In case of presence of growth, the growth was examined thoroughly by staining and a battery of biochemical tests to establish their identity. Once the identity of the growth were established, they were tested for antimicrobial susceptibility pattern in Mueller-Hinton Agar by Kirby-Bauer disc diffusion method.9 Results The prevalence of UTI among geriatric population is highest in the female of >70 years age group (Table 1). This is followed by females of 65-70 years age group. Surprisingly males of >70 years age group have a low prevalence of UTI. As far the etiological organisms are concerned, E. coli had overall highest prevalence in all age groups of both the sexes. However, in female patients, it shared the rank No. 1 with Staphylococcus aureus. Other pathogens included Staphylococcus saprophyticus (7.69%), K. pneumoniae (7.69%), Enterococcus faecalis (10.25%), Pseudomonas spp. (5.12%), P. mirabilis (2.56%). S. saprophyticus had been isolated from three samples; all patients were female. Four enterococcal isolates were obtained from four female patients. A seasonal trend has been observed in this study. Maximum number of samples were collected during the winter months, November, December, January; these three months provided 27 urine samples from geriatric people, which was greater in comparison to any other three months of any season. However, prevalence of culture positivity was lesser during winter months. Almost all the bacterial isolates were sensitive to amikacin (100%) and gentamicin (100%). Individually, E. coli had a good sensitivity pattern showing susceptibility to most of the commonly used antibiotics (Table 2). Klebsiella were sensitive to gatifloxacin, levofloxacin (100%), co-trimoxazole (100%). Their 129
original article Table 1. Distribution of Bacterial Isolates Amongst the Culture Positive Cases According to the Age Group (n = 39) Bacterial isolate
Male, 65-70 years (%)
Male, >70 years (%)
Female, 65-70 years (%)
Female, >70 years (%)
Total no. of isolate
Total percentage (%)
1 (8.33 )
1 (16.66)
5 (35.71)
1 (14.28)
8
20.51
S. saprophyticus
-
-
2 (14.26)
1 (14.28)
3
7.69
E. faecalis
-
-
2 (14.29)
2 (28.57)
4
10.25
E. coli
7 (58.33 )
5 (83.34 )
4 (28.57 )
2 (28.57 )
18
46.15
K. pneumoniae
2 (16.67)
-
-
1 (14.28)
3
7.69
Pseudomonas spp.
1 (8.33)
-
1 (7.14)
-
2
5.12
P. mirabilis
1 (8.33)
-
-
-
1
2.56
S. aureus
Table 2. Antibiogram: Showing Percentage of Sensitivity to Antimicrobials (Kirby-Bauer Disc Diffusion Method) Isolate
AK
GM
RC
GF
QB
RP
CF
FG
CP
BA
AG
FD
VA
LZ
SF
TE
E. coli
100
100
0
100
100
38.8
100
-
-
80
10
78.5
-
-
-
S. aureus
100
100
-
100
100
50
75
-
-
-
28.6
-
-
-
-
E. faecalis
100
100
-
66.6
33.33
-
-
-
-
0
0
-
100
100
100
S. saprophyticus
100
100
50
100
100
0
50
-
-
-
66.6
-
-
-
-
K. pneumoniae
100
100
0
66.6
66.66
0
50
-
50
100
-
0
-
-
-
Pseudomonas spp.
100
-
0
100
-
0
-
100
100
0
-
-
-
-
-
P. mirabilis
100
-
-
-
100
50
100
100
100
0
50
-
-
-
-
AK-Amikacin; GM-Gentamicin; RC-Ciprofloxacin; GF-Gatifloxacin; QB-Levofloxacin; RP-Ceftriaxone; CF-Cefotaxime; FG-Ceftazidime; CP-Cefoperazone; BA-Co-trimoxazole; AG-Co-amoxiclav; FD-Nitrofurantoin; VA-Vancomycin; LZ-Linezolid; SF-Cefixime; TE-Teicoplanin.
Table 3. Month-wise Distribution of Culture Positive Cases Month
130
sensitivity towards cephalosporins was very poor (only towards cefotaxime, Table 2). Another quinolone, ciprofloxacin had a poor response against most of the isolates. Enterococci, isolated from the urine samples, showed 100% susceptibility to vancomycin, teicoplanin, linezolid. Apart from these reserve drugs, they were seen to be remarkably sensitive to gentamicin (100%, using 120 µg discs, HI MEDIA), gatifloxacin (66.6%). Response of cephalosporin against various bacterial isolates varied. Pseudomonas spp. showed sensitivity to ceftazidime (100%) and cefoperazone (100%), where as S. aureus showed medium sensitivity to ceftriaxone (50%), cefotaxime (75%). P. mirabilis strain was sensitive to cefotaxime (100%), ceftazidime (100%) but not so to ceftriaxone (50%). Oral cephalosporin like cefixime was only moderately sensitive against a few isolates (E. coli, S. aureus, Proteus: Table 2).
No. of samples received
No. of samples having growth
% of positive culture (growth)
February ‘09
3
2
66.66
March ‘09
-
-
-
April ‘09
5
2
40
May ‘09
7
2
28.57
June ‘09
2
-
0
July ‘09
7
4
57.14
August ‘09
5
4
80
September ‘09
6
4
66.66
October ‘09
2
2
100
November ‘09
6
3
50
December ‘09
12
5
41.66
Discussion
January ‘10
9
4
44.44
February ‘10
8
7
87.5
The diagnosis of UTI cannot be made without bacteriological culture because many patients with Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
original article frequency-dysuria syndrome have sterile urine and conversely, asymptomatic bacteriuria is a common condition especially in elderly patients having a negative culture due to small number of organisms.10 UTIs are amongst the most common infections encountered in clinical practice. UTIs can be symptomatic with clinical symptoms like dysuria, urgency, painful or frequent voiding accompanied by the presence of bacteria in the normally sterile urine and asymptomatic bacteriuria or presence of bacteria in the urine without signs or symptoms. This condition often predisposes to symptomatic infection.1 Again, the UTI can be uncomplicated or complicated; uncomplicated UTI is characterized by the absence of functional or anatomical defects to urinary flow, and complicated UTI where such obstacle is present. The elderly patients often have complicated UTI due to functional and anatomical defects and they are prone to urosepsis, renal damage and bear a high mortality. In addition, due to reasons unknown the infecting organism are less susceptible to antimicrobial drugs. As UTIs are quite common in the elderly and they have atypical presentations, early etiological diagnosis is helpful to start specific therapy. Elderly people suffer from dyselectrolytemia very often, which may be exaggerated by UTIs.11 Other factors that may complicate the condition are urinary retention, hematogenous spread of infection, sepsis, gram-negative shock and ultimately multi-organ dysfunction. To prevent poor outcomes, a guideline regarding etiology and treatment of UTIs in geriatric people has been drawn in the present study. S. aureus are increasingly becoming a potent pathogen to cause UTIs unlike earlier days. S. saprophyticus is still causing infection in women even in their 7th decade. Unlike the popular belief, Proteus infection is less prevalent as disclosed in this study. Since, Proteus infection occurs mainly in stagnant urine, the finding challenges the age old consideration that in obstructive uropathy or in the condition of stasis in bladder there should be greater number of UTI with Proteus organisms. So far the antibiotics are concerned, Klebsiella, though resistant to many newer ones, are still sensitive to co-trimoxazole. The only antibiotic, applicable for all the isolates with equal reliance is amikacin. But as it is an injectable one, the ease of administration is a problem along with its adverse drug profile especially in the elderly patients. Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
The study would have been better if the sample size was larger. Besides, it is devoid of follow-up. So, a thorough follow-up with a big sample size would enrich the study. Acknowledgement The researchers are indebted towards staff, faculty and students of the Dept. of Microbiology, BMC, Burdwan for giving active co-operation and continuous help.
References 1. Borriello SP, Murray RP, Funke G. Topley Wilsonâ&#x20AC;&#x2122;s Microbiology and Microbial Infections. 10th edition, Hodder Arnold ASM Press USA, 2005. 2. Kahlmeter G. The Eco.sens Project: a prospective multinational multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract pathogens interim report. J Antimicrob Chemother 2004;46(Suppl 1):15-22; discussion 63-5. 3. Kamel HK. Managing urinary tract infections in the nursing home: myths, mysteries and realities. Internet Journal of Geriatrics and Gerontology 2004;1(2). 4. Kass EH. Bacteriuria and the diagnosis of infections of the urinary tract. Arch Intern Med 1957;100:709-14. 5. Geriatric urinary tract infections. Available at: http:// www.ehow.com/facts_5656237_geriatric-urinary-tractinfections.html. 6. Klahr S. Urinary tract obstruction. In: Diseases of the Kidney. 7th edition, Schrier RW, Gottschalk CW (Eds.), Little, Brown: Boston 2001;751-87. 7. Kouri T, Fogazzi G, Gant V, Hallander H, Hofmann W, Guder WG; ESCMID Working Party on Urinalysis. European urinalysis guidelines. Scand J Clin Lab Invest 2000;60:1-96. 8. Zeidel ML, Pirtskhalaishvili G. Urinary tract obstruction. In: Brenner and Rectorâ&#x20AC;&#x2122;s The Kidney. 7th edition, Brenner (Ed.), Saunders, Philadelphia 2004:p1867-94. 9. Greenwood David, Slack Richard CB, Peutherer John F. Barer MR (Eds.). In: Medical Microbiology: A guide to Microbial infections. 16th edition, Churchill Livingstone, 2002. 10. Performance Standards for antimicrobial susceptibility testing. Eighth informational supplement 2000. National Committee for Clinical Laboratory Standards (NCCLS) M2A7 Vol 20, No.1 and 2 Villanova, Pa. 11. Matsumotoa T, Kumazawab J. Urinary tract infection in geriatric patients. Int J Antimicrob Agents 1999;11 (3-4):269-73.
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original research
Pleural Fluid Analysis in HIV-associated Tuberculosis Patients: A Retrospective Study Sunita H*, GB Doddamani**, Linganand L Pujari†, CVB Prasad‡
Abstract Background: One of the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients is tuberculosis. Increasing spread of HIV has become a major contributor in increasing the incidence of tuberculosis. Both the problems should be dealt with simultaneously to stop the future pandemic. Method: This is a retrospective study; 30 adult patients seropositive for HIV and having tuberculosis were included. Pleural fluid was collected for cell count, cell type and for analysis of sugar, proteins and chloride levels. Results: The prevalence of the disease was more in males compared to females. The tuberculin skin test was negative in most of the cases. Pleural effusion was unilateral in all except two patients and it was confined to the right side in many. The lymphocytes were predominant cells in the fluid. The sugar and proteins were lower than the normal blood levels, and the chlorides were increased. Conclusion: Extrapulmonary tuberculosis is very common mostly in the form of pleural effusion. Tuberculin skin testing and sputum AFB do not contribute much to the diagnosis. Analysis of pleural fluid in all seropositive cases of HIV with clinical features of tuberculosis is absolutely necessary. Key words: HIV, tuberculosis, pleural effusion
H
uman immunodeficiency virus (HIV) is a fatal infection characterized by cellular immunodeficiency. It leaves the victim vulnerable to life-threatening opportunistic infections, neurological disorders or unusual malignancies.1 In the recent years it has exponentially grown into a frightening worldwide epidemic. The disease is the first great pandemic of 20th century which has claimed thousands of lives throughout the world.2 Tuberculosis is the commonest opportunistic infection and the number one cause of death in HIV patients in developing countries. It accounts for about 40% of all manifestations seen in HIV patients.3 About 25-65% of patients with HIV have tuberculosis of any organ and tuberculosis accounts for about 13% of all HIV-related deaths worldwide.4 The adverse interaction between HIV infection and tuberculosis *Associate Professor, Dept. of Biochemistry **Associate Professor, Dept. of Medicine †Professor, Dept. of Obstetrics and Gynecology S. Nijalingappa Medical College, Nava Nagar, Bagalkot ‡Assistant Professor, Dept. of Biochemistry JN Medical College, Belgaum Address for correspondence Dr Sunita H Dept. of Biochemistry Associate Professor S. Nijalingappa Medical College Nava Nagar, Bagalkot - 587 102, Karnataka E-mail: drsunitapujar@gmail.com
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poses difficult challenges to public health programs.5 HIV-infected individuals co-infected with tuberculosis have an annual risk of 5-15% of developing active tuberculosis.6 The South East Asia region of the World Health Organization (WHO) accounts for nearly 40% of all tuberculosis cases globally and 18% of world’s HIV-infected also live in this region.7 India has one of the world’s highest burdens of both tuberculosis (1.96 million cases annually) and HIV infection (2.31 million prevalent cases).8,9 The prevalence of pulmonary tuberculosis in HIV patients is 25-60% in India.10 In India there were an estimated 5.1 million people living with HIV at the end of the year 2002. Assuming that about 40% of these persons are coinfected with tuberculosis, the estimated TB-HIV co-infection figures will be around 2 million.11 In studies reported from India, extrapulmonary tuberculosis constituted 45-56% of all the cases of tuberculosis in persons with AIDS.12 HIV-associated extrapulmonary tuberculosis has got many atypical presentations. They usually have significant weight loss and fever of long duration. Cough and hemoptysis are less frequently, while pleural effusion is commonly reported in HIVassociated pulmonary tuberculosis.13 Bagalkot district is reported to have the highest number of HIV-infected population in Karnataka. The prevalence of HIV, according to a recent survey, was found to be 2.9%.14 Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
original research This study was conducted to analyze the pleural fluid contents in HIV-associated tuberculosis in adults in this area.
Material and Methods The present study was carried out jointly by the Depts. of Biochemistry and Medicine in S. Nijalingappa Medical College and HSK Hospital and Research Centre from June 2008 to July 2009. Institutional Ethics Committee approved the study and informed consent was taken from all the subjects. The study included 30 cases comprising 27 adult males and three females who were seropositive for HIV and had pulmonary tuberculosis. They were in the age group 20-40 years and belonged to low socioeconomic status. Serological examination of HIV was done by Tri-Dot method and confirmed with western blot technique.
Patients having pulmonary manifestations of rheumatoid arthritis.
Pleural fluid was analyzed for cell count and cell type by microscopic method. The readings were taken on STATFAX 2000 reader. The levels of proteins,15 sugar16 and chloride17 were also analyzed. The pleural effusion of exudative nature with lymphocyte predominance was presumed to be of tubercular etiology. Table 1. Age Distribution, Sex Distribution, Tuberculin Skin Test Status, Sputum Status and Pleural Effusion in HIV-associated Tuberculosis Patients
They were evaluated by detailed medical history and thorough clinical examination. Clinical information with special reference to weight loss, duration of fever, hemoptysis, chronic diarrhea, generalized lymphadenopathy and history of herpes zoster were noted. If three consecutive smears were negative, sputum was sent for acid-fast bacilli (AFB) culture. Tuberculin test was done in all cases. Chest X-ray and pleural fluid tapping were also done. Pleural effusion was noticed in nine patients.
Particulars
Number of patients
Percentage (%)
21-30 years
17
56.70
31-40 years
13
43.30
Male
27
90.00
Female
03
10.00
Tuberculin skin test Positive
08
26.60
Negative
22
73.40
Positive
17
56.60
Negative
13
43.40
Bilateral
02
22.20
Right
04
44.40
Left
03
33.30
Age distribution Sex distribution
AFB Pleural effusion
Exclusion Criteria
Patients with diagnosis of lung malignancy, primary or secondary congestive cardiac failure, uremia with pulmonary manifestations, high eosinophil count suggestive of tropical eosinophilia and patients with multiple pathology of pleural effusion.
Patients with renal insufficiency/liver insufficiency/ on anti-TB drugs.
Table 2. Pleural Effusion Analysis in HIV-associated Tuberculosis Patients Patient serial no
Cell type (%)
Cell count
Protein (g/dl)
Sugar (mg/dl)
Chlorides (mmol/l)
Type
P
L
1
4
96
600
5.6
98
780
Exudate
2
40
60
1560
2.6
101
680
Transudate
11
15
85
950
5.9
29
129
Hemorrhagic
12
20
73
300
3.5
40
240
Exudate
16
8
92
750
5.7
54
317
Exudate
22
0
100
30
5.0
51
100
Exudate
25
-
-
-
-
-
-
-
27
-
-
-
-
-
-
-
29
5
95
65
4.9
34
81
Exudate
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
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original research Results Table 1 shows the age distribution, sex distribution, tuberculin skin test status, sputum status and pleural effusion in HIV-associated tuberculosis patients. Among the patients, 56.7% were between 20-30 years and 43.3% between 31-40 years. The tuberculin skin test was positive in 26.6% patients. The sputum of 56.6% of patients was positive for AFB. The pleural effusion was bilateral in two patients; it was confined to right side in four and to left side in three patients. The levels of protein, sugar, chlorides, cell type and cell count in the pleural fluid of HIV-associated tuberculosis patients are shown in Table 2. Discussion HIV epidemic has the potential to worsen the tuberculosis epidemic as has happened in certain African countries. This is mainly because HIV increases the risk of disease reactivation by progressively impairing cellmediated immunity in people with latent tuberculosis and hence HIV-infected persons are more susceptible to new tuberculosis infection.18 Data from USA suggests that the annual risk of reactivation in tuberculin positive HIV-infected individual is 7.9%.19 Since, the beginning of the epidemic in 1981, the prevalence has increased exponentially with a doubling time of 6-12 months.20 In the present study, the prevalence of disease was more in the age group 20-30 years. This is in accordance with previous studies. This reflects that persons who are sexually more active are at increased risk for HIV infection and thereby for tuberculosis.21 The tuberculin skin test was positive in 26.6% of cases. Other studies have mentioned varying percentage of the positivity22 but our findings are nearly similar to the study by Houston et al.23 Although, a positive tuberculin skin test increases the likelihood of tuberculosis, a negative test reflects the immunodeficiency status and does not rule out the presence of active tuberculosis.24 So, tuberculin test is not of much value in HIV-infected persons, particularly those with advanced disease.25 The sputum AFB was positive in 56.6% of cases. The profound impairment of the immunity seen in HIV infection may permit tubercle bacilli to multiply in such a large numbers as to become visible on smear examination.26 However in Indian studies, AFB smear negativity has been reported as high as 82%.27 Pleural effusion occurs in 2-38% of all cases of pulmonary tuberculosis. It occurs on an immunological basis when 134
a subpleural focus of Mycobacterium tuberculosis grows and ruptures into the pleural space.28 It results from direct hematogenous invasion of the pleural space by M. tuberculosis and is usually unilateral.29 In our study, pleural effusion was seen in nine cases, two patients had bilateral i.e. 22.2% which is a significant finding. It is an atypical finding as previous studies have reported bilateral pleural effusion in only 13.85% cases.22 Of all patients showing pleural effusion, analysis was done in seven patients. Of these seven samples, five showed increased lymphocytes ranging from 60 to 100% cell count (300-1560 cells) and two patients showed very less count i.e., 30 and 65 cells. The polymorphs ranged from 4 to 40 cells. The differential cell count in pleural aspirates can aid in narrowing the differential diagnosis. The predominance of polymorphonuclear cells reflects an acute process.31 A lymphocytic pleural effusion is most often the result of tuberculosis.32 Pleural effusions are classified as transudates or exudates on the basis of the fluid protein level. Classically, a pleural fluid protein level >30 g/l is an exudate and <30 g/l is a transudate, in the context of a normal serum protein level.33 Applying this criteria only one sample was transudate in our study. The result is similar to another study where the pleural fluid protein 49.15 Âą 12.2 mg/dl was reported.13 The pleural fluid glucose ranged from 29 to 101 mg/dl. This is much lower compared to the normal blood glucose (FBS: 80-120 mg/dl). This may be because the diffusion of glucose into the pleural space is impaired.27 This is in contrast to the study by Light et al; they reported pleural fluid glucose level below 60 mg/dl which suggested malignancy.34 The chloride levels in the fluid ranged from 110 to 170 mmol/l, this is much higher than the reference range in serum of normal subjects (97-108 mmol/l). The findings are in accordance with previous workers, they suggest that because of impaired membrane permeability, there is diffusion of these electrolytes into the pleural space.35 Conclusion The evidence to date indicates that preventive therapy for tuberculosis in HIV-infected persons reduces the incidence of it by 50-60%. Analysis of pleural fluid can have an important contribution for investigation of tuberculous patients with pleural effusion. The study concludes that the analysis of pleural biopsy will be useful as an ultimate procedure in cases with diagnostic problems as it is a procedure which can give a definite tissue diagnosis. Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
original research References 1. Sexually transmitted diseases: a public health issue. World Health Organ Tech Rep Ser 1986;736:1-141. 2. Kumari S, et al. Screening for seroprevalence of HTLV111/HIV infection in high risk groups in Delhi. J Commun Dis 1986;18(2):77-80. 3. Pape JW. Tuberculosis and HIV in the Caribbean: approaches to diagnosis, treatment and prophylaxis. Top HIV Med 2004;12(5):144-9. 4. Sharma SK, et al. Spectrum of clinical disease in a series of 135 hospitalized HIV-infected patients from north India. BMC Infect Dis 2004;4:52. 5. Havlir DV, et al. Opportunities and challenges for HIV care in overlapping HIV and TB epidemics. JAMA 2008;300(4):423-30. 6. Rajasekaran S, et al. Trend of HIV infection in patients with tuberculosis in rural south India. Indian J Tuberc 2000;47(4):223-6. 7. Solomon S, et al. Trend of HIV infection in patients with pulmonary tuberculosis in south India. Tuber Lung Dis 1995;76:17-9. 8. World Health Organization. Global Tuberculosis control: Surveillance, planning, financing. WHO Report 2008; 393. Geneva Switzerland. 9. National AIDS Control Organization. HIV sentinel surveillance and HIV estimation in India 2007. A technical brief. New Delhi, India: Ministry of Health and Family Welfare, Government of India, 2008. 10. Sharma SK, et al. HIV-TB co-infection: epidemiology, diagnosis & management. Indian J Med Res 2005;121(4):550-67. 11. National AIDS Control Organisation (NACO), 2003. Org/guidelines/HIV-Tb guidelines.pdf. Available from: http://www.nacoonline. 12. Sharma SK, et al. Clinical presentation of tuberculosis in patients with AIDS: an Indian experience. Indian J Chest Dis Allied Sci 1997;39(4):213-20. 13. Soe Z, et al. A study on tuberculous pleural effusion. Int J Collab Res Int Med Pub Health 2010;2(3):32-48. 14. Becker ML, et al. Prevalence and determinants of HIV infections in South India: a heterogeneous rural epidemic. AIDS 2007;21(6):739â&#x20AC;&#x2018;47. 15. Kaplan A, et al. Proteins in body fluids. In: Clinical Chemistry: Interpretation and Techniques. 2nd edition, Lea and Febiger, Philadelphia 1983:147-71. 16. Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969;6:24-5. Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
17. Schoenfeld RG, et al. A colorimetric method for determination of serum chloride. Clin Chem 1964;10:533-9. 18. Sharma SK, et al. Co-infection of human immunodeficiency virus (HIV) and tuberculosis: Indian perspective. Indian J Tuberc 2004;51:5-16. 19. Selwyn PA, et al. A prospective study of the risk of tuberculosis among intravenous drug users with HIV infection. N Engl J Med 1989;320(9):545-50. 20. WHO. Guidelines on AIDS in Europe. WHO, Copenhagen; 1986. 21. Barnes PF, et al. Tuberculosis in patients with HIV infection. Med Clin North Am 1993;77(6):1369-89. 22. Ahmad Z, et al. Manifestations of tuberculosis in HIV infected patients. JIACM 2005;6(4):302-5. 23. Houston S, et al. The association of tuberculosis and HIV infection in Harare, Zimbabwe. Tuber Lung Dis 1994;75(3):220-6. 24. Prasad R, et al. A clinico-radiological study of patients of tuberculosis with HIV co-infection. Curr Med Trends 2006;10:1971-7. 25. Swaminathan S, et al. Clinical presentation and treatment of HIV-TB. Indian J Tuberc 2002;49:11-6. 26. Elliot AM, et al. Impact of HIV on tuberculosis in Zambia: a cross-sectional study. BMJ 1990;301:412-5. 27. Verma SK, et al. HIV-tuberculosis co-infection. Int J Pulmon Med 2008;10(1):1481-90. 28. Merino JM, et al. Tuberculous pleural effusion in children. Chest 1999;115(1):26-30. 29. Kim HJ, et al. The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis. Chest 2006;129(5):1253-8. 30. Light RW, et al. Cells in pleural fluid. Their value in differential diagnosis. Arch Intern Med 1973;132(6):85460. 31. Levine H, et al. Diagnosis of tuberculous pleurisy by culture of pleural biopsy specimen. Arch Intern Med 1970;126(2):269-71. 32. Light RW, et al. Pleural effusion: the diagnostic separation of transudates and exudates. Arch Intern Med 1972;77(4):507-13. 33. Good JT Jr, et al. The diagnostic value of pleural fluid pH. Chest 1980;78(1):55-9. 34. Light RW. Pleural effusions. N Engl J Med 2002;364 (25):1971-7. 35. Folaranmi OM, et al. Comparative study of plasma electrolytes (Na, K, Cl and HCO3) and urea levels in HIV/AIDS and pulmonary tuberculosis infected subjects. Biokemistri 2004;16(1):29-36.
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case report
Post Dengue Beau’s Lines Navtej Singh*, Varun Vijay Mahajan**, Jyotsna Singh†, Iesha Pargal‡, Ajit Pal Singh Gill*, Kunal Chawla†
Abstract Beau’s lines are deep grooved lines that run from side-to-side on the fingernail. They are usually bilateral and result from a temporary cessation in the growth of the nail plate during severe systemic illnesses. We present herein a patient of dengue fever who presented with Beau’s lines on the nails of both hands and toes. Key words: Dengue fever, post dengue Beau’s lines
Case Report A 40-year-old male was admitted to the emergency room for high-grade fever since last four days with severe myalgia and dehydration. The fever was associated with chills and rigors. Nausea and vomiting started in the evening of the same day the fever started and was still continuing. Patient was given empirical treatment with antibiotics and anti-emetics. But there was no relief of vomiting and fever. Fever never touched the baseline during the hospital stay. The patient was investigated for the cause of fever. Physical examination was unremarkable except for high-grade fever and signs of dehydration. On investigation, hemoglobin was 15.6 mg/dl, RBC count was 5.5 millions/mm3, TLC was 3200/mm3, DLC showed 64% polymorphs 33% lymphocytes, 3% monocytes; platelet count at the time of admission was 1.5 lac/mm3.
Figure 1. Beau’s lines in finger nails in a patient recovered from dengue fever.
Urine examination revealed 0-1 pus cells and 6-8 RBCs/HPF. Malarial antigen was negative, HBsAg and anti-HCV were also negative. Dengue serology was ordered which turned out to be positive. Ultrasonography was done and was normal. Liver *Assistant Professor **Senior Resident Dept. of Medicine †Senior Demonstrator, Dept. of Anatomy ‡Pathology, GMC Jammu Gian Sagar Medical College, Ramnagar (Banur) Address for correspondence Dr Navtej Singh Assistant Professor, Dept. of Medicine Gian Sagar Medical College, Ramnagar (Banur) H. No.: 1853, Phase - 7, Mohali, Punjab E-mail: nvjsingh@yahoo.co.in
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Figure 2. Beau’s lines in toe nails of a patient recovered from dengue fever.
function tests and renal function tests were normal. Platelet count was followed daily and on Day 3 it was 1.1 lac/mm3, on Day 4 it was 75000/mm3, Day 5 it Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
Case Report was 90,000/mm3. So, on the basis of clinical findings and investigations, a diagnosis of dengue fever was made. Course in the hospital was unremarkable and the patient was discharged on Day 5. After one and half months, the patient again reported to the OPD for the appearance of the transverse lines on the nails of both hands and toes and falling of hair. Patient was very anxious about these two. He was diagnosed to have post dengue Beau’s lines and telogen effluvium. Discussion Beau’s lines are deep grooved lines that run from side-to-side on the fingernail. They are usually bilateral and result from a temporary cessation in the growth of the nail plate during severe systemic illnesses. It is believed that there is a temporary cessation of cell division in the nail matrix.1 This may be caused by an infection or problem in the nail fold, where the nail begins to form, or it may be caused by an injury to that area.2 Although transverse grooves can occur on the nails of one extremity, this has not been a commonly reported phenomenon. An unusual case of unilateral Beau’s line associated with a metaphyseal fracture of the distal radius extending into the growth plate with wrist immobilization has been reported. They may look like indentations or ridges in the nail plate.2 There are several reasons that humans get Beau’s lines. Beau’s lines may be also a sign of malnutrition, zinc or iron deficiency, anemia, any major metabolic condition or a condition when growth at the area under the cuticle is interrupted by an injury or after a stressful event that temporarily interrupted nail formation. Beau’s lines may also be caused by an illness of the body, such as diabetes, certain drugs, such as those
used in chemotherapy or even malnutrition.3 Beau’s lines are transverse depressions of all of the nails that appear at the base of the lunula weeks after a stressful event has temporarily interrupted nail formation. The lines progress distally with normal nail growth and eventually disappear at the free edge.4 They develop in response to many diseases, such as syphilis, uncontrolled diabetes mellitus, myocarditis, peripheral vascular disease and zinc deficiency, and to illness accompanied by high fevers, such as scarlet fever, measles, mumps and pneumonia.5-6 Beau’s lines have been reported in the fingernails of 6 divers following a deep saturation dive to a pressure equal to 335 meters of sea water, and in 2 of 6 divers following a similar dive to 305 meters.7 In our patient Beau’s lines appeared weeks after discharge from the hospital and along with this he also had telogen effluvium. References 1. Wirtschafter ZT, Littmann S. Transverse furrows of the nails. Arch Derm Syphiol 1940;42(5):874-7. 2. Ward DJ, Hudson I, Jeff JV. Beau’s lines following hand trauma. J Hand Surg Br 1988;13(6):411-4. 3. Sibinga MS. Observations on growth of fingernails in health and disease. Pediatrics 1959;24(2):225-33. 4. Wolf D, Wolf R, Goldberg MD. Beau’s lines. A case report. Cutis 1982;29(2):191-4. 5. Colvett KL, Patel D, Smith JK. Multiple Beau’s lines in a patient with fever of unknown origin. South Med J 1993; 86(12):1424-6. 6. Brusch JL, Weinstein L. Fever of unknown origin. Med Clin North Am 1998;72(5):1247-61. 7. Schwartz H. Clinical observation: Beau’s lines on fingernails after deep saturation dives. Undersea Hyperb Med 2006;33(1):5-10.
n
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
n
n
137
case report
Huge Frantz Tumor in a Young Indian Female Hanish Bansal*, Raj Kamal Jenaw**, Rajendra Mandia†
Abstract Solid pseudopapillary tumor of the pancreas is a rare condition in the literature. The tumor generally affects adolescent or young adult females. Most solid pseudopapillary tumors behave in a benign or very low grade malignant fashion and the prognosis after surgical excision is excellent. Surgical excision offers the best chance for cure and should always be attempted irrespective of the magnitude of resection involved. We report such a case in a 20-year-old female in which distal pancreaticosplenectomy was performed. Not many cases have been reported from India and there is no literature mentioning the approximate number of cases reported in India. Every effort should be made to report such cases for better understanding of the disease. Key words: Pseudopapillary, Frantz tumor, benign
S
olid pseudopapillary tumors are uncommon neoplasms of low malignant potential and generally occur in young women. The diagnosis should be suspected in any adolescent or young adult female presenting with abdominal mass and radiologically cystic or partially cystic well-circumscribed pancreatic mass. Most solid pseudopapillary tumors behave in a benign or very low grade malignant fashion and the prognosis after surgical excision is excellent. Case Report A 20-year-old female presented in Dept. of Surgery with pain in epigastrium and left hypochondrium since four months. Pain was mild, nonradiating and relieved with medication. There was no history of vomiting, fever, weight loss and any other bowel or urinary complaints. On per abdomen examination, a mass (10 × 8 cm) occupying epigastrium and left hypochondrium was found. Blood tests including renal function tests, liver function tests and cancer antigen (CA) 19-9 were normal. Computed
*Postgraduate Student (3rd Year) **Professor and Unit Head †Associate Professor Surgical Unit 4, Dept. of General Surgery SMS Medical College, Jaipur Address for correspondence Dr Hanish Bansal PG Resident Dept. of General Surgery 10-B, Udham Singh Nagar Ludhiana, Punjab - 141 001 E-mail: y2khanish@rediffmail.com
138
Figure 1. CT scan depicting a mass present in the body and tail of pancreas.
tomography (CT) of the abdomen showed an ill-defined heterogeneous lesion in the body and tail of pancreas with solid component and internal septations measuring 11 × 7 cm likely mitotic (Fig. 1). On exploratory laparotomy, a huge retroperitoneal encapsulated mass located in the body and tail of pancreas was found (Fig. 2). There were no signs of peritoneal and liver metastasis. Distal pancreaticosplenectomy was done with proximal line of resection being 2 cm medial to encapsulated mass. The proximal pancreas was closed with vertical mattress sutures. Postoperative course was uneventful; patient was discharged after six days. On gross examination, a mass 10 × 8 × 5 cm with smooth and capsulated surface along with attached Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
Case Report
Figure 2. Per operative picture depicting huge Frantz tumor.
spleen and four dissected lymph nodes was found. On histopathology, the mass was a solid pseudopapillary carcinoma and all dissected lymph nodes were negative for malignancy. Discussion Solid pseudopapillary tumor of the pancreas is a rare condition in the literature. Not many cases have been reported from India and there is no literature mentioning the approximate number of cases reported in India. This tumor was first described in 1959. Also known as the Frantz tumor, named after the author who first described it, it has also been referred to as cystic tumor; papillary epithelial neoplasia; solid and papillary epithelial neoplasia; or papillary epithelial tumor.1 The origin of the solid pseudopapillary tumor has not yet been clarified. The tumor generally affects adolescent or young adult females and relationship with oral contraceptives has not been proven; this tumor rarely affects men and is characterized by a long asymptomatic course and nonspecific symptoms.2 Clinically, they appear as slowly growing masses with or without pain; however, these tumors may appear with other rare symptoms.3 Acute manifestations such as pancreatitis triggered by ischemia, distension or duct obstruction, or hemoperitoneum caused by the rupture of the tumor capsule are rare. There are usually no abnormalities in clinical laboratory tests (e.g., serum amylase levels) or in pancreatic cancer Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
markers (e.g., CA 19-9, carcinoembryonic antigen and fetoprotein).4 It is not uncommon, though, to arrive at the final diagnosis only by pathology several weeks after the operation. Pathological features include solid, cellular, hypervascular regions without gland formation, and degenerative pseudopapillae. The cells contain eosinophilic granules rich in a1-antitrypsin and the nuclei are typically grooved.5 Vascular and capsular invasion with superimposed spread into the adjacent pancreatic parenchyma and nearby structures in solid pseudopapillary tumors of the pancreas can be accurately revealed by multidetector-row computed tomography (MDCT) preoperatively. These imaging findings are predictive of the malignant potential associated with the aggressive behavior of the tumor, even in the pathologically benign cases.6 A tissue diagnosis preoperatively is not necessary; surgery can be advised on the basis of radiological imaging.7 Complete surgical excision is the best option for patients who have solid pseudopapillary neoplasm. Thus surgery should always be attempted in a suspected case of solid pseudopapillary neoplasm even if it implies that major resections have to be performed. Solid pseudopapillary tumors are the ideal pancreatic tumors for the laparoscopic approach because of their low malignancy and their excellent prognosis.8 A local recurrence rate of 6.2% is reported in cases treated by radical surgical excision, and hepatic or Krukenbergtype distant metastases develop in 5.6% of cases.9 A recent series from Memorial Sloan-Kettering Cancer Center, New York, USA, recommends complete surgical excision with even metastatectomy if required.10 Conclusion A solid pseudopapillary tumor of the pancreas is a rare condition with a low potential for malignancy and favorable prognosis. Surgical excision offers the best chance for cure and should always be attempted irrespective of the magnitude of resection involved. References 1. Mozaffar M, Abdollahi SM. Acute post-traumatic presentation of a solid pseudopapillary tumor of pancreas: a case report. Iranian J Can Prev 2008;1(1):45â&#x20AC;&#x2018;52. 2. KlĂľppel G, Morohoshi T, John HD, Oehmichen W, Opitz K, Angelkort A, et al. Solid and cystic acinar cell
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Case Report tumor of the pancreas. A tumor in young women with favourable prognosis. Virchows Arch A Pathol Anat Histol 1981;392(2):171-83. 3. Apostolidis S, Papavramidis TS, Zatagias A, Michalopoulos A, Papadopoulos VN, Paramythiotis D, et al. Hematemesis, a very rare presentation of solid pseudopapillary tumors of the pancreas: a case report. J Med Case Rep 2008;2(3):271-2. 4. Wani N, Rawa A, Iqbal A, Qayum A. 540 solid pseudopapillary tumors of pancreas causing sinistral portal hypertension. The Internet J Gastroenterol 2010 Volume 9 Number 1. 5. Klimstra DS, Wenig BM, Heffess CS. Solidpseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential. Semin Diagn Pathol 2000;17(1):66-80. 6. Wang DB, Wang QB, Chai WM, Chen KM, Deng XX. Imaging features of solid pseudopapillary tumor of the
pancreas on multi-detector row computed tomography. World J Gastroenterol 2009;15(7):829-35. 7. Patil TB, Shrikhande SV, Kanhere HA, Saoji RR, Ramadwar MR, Shukla PJ. Solid pseudopapillary neoplasm of the pancreas: a single institution experience of 14 cases. HPB (Oxford) 2006;8(2):148-50. 8. Marinis A, Anastasopoulos G, Polymenea G. A solid pseudopapillary tumor of the pancreas treated with laparoscopic distal pancreatectomy and splenectomy: a case report and review of the literature. J Med Case Reports 2010;4:387. 9. Gonzalez-Campora R, Rios Martin JJ, Villar Rodriguez JI, Otal Salaverri C, Hevia Vazquez A, Valladolid JM, et al. Papillary cystic neoplasm of the pancreas with liver metastasis coexisting with thyroid papillary carcinoma. Arch Pathol Lab Med 1995;119(3):268-73. 10. Martin RC, Klimstra DS, Brennan MF, Conlon KC. Solid-pseudopapillary tumor of the pancreas: a surgical enigma? Ann Surg Oncol 2002;9(1):35-40.
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photo quiz
Polypoid Skin Nodule in the Postpartum Period
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23-year-old woman presented to her primary care physician eight days postpartum because of a polypoid skin nodule behind the patient’s right ear. She had first noticed the nodule two months prior. The nodule initially had grown quickly, but it had not changed in size in the previous month. It was not painful, but bled easily. The patient had no history of similar lesions, trauma to the area, or other significant dermatologic history. She was otherwise healthy. Physical examination showed an erythematous, dome-shaped nodule measuring 1.2 cm × 1.2 cm with a moist, friable surface and slight scale around the base (Figures 1 and 2).
Figure 1.
Question Based on the patient’s history and physical examination, which one of the following is the most likely diagnosis? A. B. C. D. E.
Atypical fibroxanthoma. Bacillary angiomatosis. Glomus tumor. Nodular amelanotic melanoma. Pyogenic granuloma.
Discussion The answer is E: pyogenic granuloma. This is a relatively common benign, vascular tumor. It typically manifests as a solitary, red to purple, painless, friable papule or nodule with a thin collarette of hyperkeratosis that bleeds spontaneously or after trauma. The tumor commonly occurs on the head, neck, upper trunk, hands, and feet. It grows rapidly over a few weeks and typically does not exceed 2 cm. The etiology of pyogenic granuloma is unclear, but trauma, infection, microscopic arteriovenous malformations, certain medications, cytogenetic clonal deletion abnormalities, and elevated hormone levels in pregnancy are possible causes.1 Women are more often affected because of an increased risk during pregnancy. Source: Adapted from Am Fam Physician. 2011;83(9):1091-1092.
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
Figure 2.
The condition is also common in children, with prevalence decreasing linearly with age. Pyogenic granulomas occur in up to 5 percent of pregnant women.1 They may be associated with elevated hormone levels during pregnancy, which can cause the expression of angiogenic factors in inflamed tissues and vascular endothelium or the extension of angiogenic effects by decreasing apoptosis of granuloma cells.1,2 Pyogenic granulomas presenting during pregnancy typically appear during the second or third trimester and often occur on oral tissue; however, nonoral tissue also may be affected.1 Although the diagnosis of pyogenic granulomas is usually clinical, biopsy can confirm an unclear 141
photo quiz Summary Table Condition
Characteristics
Atypical fibroxanthoma
Flesh-colored, white, or erythematous dome-shaped nodule that mainly affects skin that is exposed to the sun or therapeutic radiation; usually occurs on the face, neck, ears, or scalp of older white persons
Bacillary angiomatosis
Purple papules that enlarge to form lobular, friable nodules or tumors often covered with a fine, tightly adherent scale; caused by Bartonella species; typically affects immunocompromised adults
Glomus tumor
Blue to purple papule or nodule that may blanch; paroxysmal pain associated with pressure or temperature changes (especially cold) is possible; typically affects distal extremities
Nodular amelanotic melanoma
Nonpigmented or pink, dome-shaped papule or nodule that may ulcerate or bleed easily; typically occurs on trunk and legs in middleaged persons
Pyogenic granuloma
Red to purple, painless, friable papule or nodule with a thin collarette of hyperkeratosis that bleeds spontaneously or after trauma; usually occurs on the head, neck, upper trunk, hands and feet; most common in children and pregnant women
diagnosis. Histologically, the tumor is a lobular, capillary hemangioma with each lobule separated by a fibrous connective tissue septum. The overlying epidermis often shows inward growth at the base of the tumor causing a pedunculated or â&#x20AC;&#x153;cuffedâ&#x20AC;? appearance with surface ulceration.3-5 An atypical fibroxanthoma is a flesh-colored, white, or erythematous dome-shaped nodule that mainly affects skin that is exposed to the sun or therapeutic forms of radiation. Lesions grow quickly and usually occur on the face, neck, ears, or scalp of older white persons. Many patients with atypical fibroxanthomas have a history of nonmelanoma skin cancers. Bacillary angiomatosis is characterized by one or more purple papules that
enlarge to form lobular, friable nodules or tumors often covered with a fine, tightly adherent scale. It is caused by infection with the gram-negative Bartonella species, which may be transmitted through scratches or from cat or arthropod bites. Systemic symptoms, such as fever, weight loss, and lymphadenopathy, are common. Bacillary angiomatosis has been associated with immunosuppression. A glomus tumor is a benign neoplasm caused by proliferation of glomus cells in the dermis. It is characterized by a blue to purple papule or nodule that usually affects the distal extremities. Other findings include blanching and paroxysmal pain that is often associated with pressure or temperature changes (especially cold). Nodular amelanotic melanoma is characterized by a slow-growing, nonpigmented or pink, dome-shaped papule or nodule that may ulcerate or bleed easily. It typically occurs on the trunk and legs in middle-aged persons. Because it is the most aggressive subtype of melanoma, it must be distinguished from pyogenic granuloma. References 1. Pierson JC, Tam CC. Dermatologic manifestations of pyogenic granuloma (lobular capillary hemangioma). http://emedicine.medscape.com/article/1084701overview. Accessed March 4, 2011. 2. Yuan K, Wing LY, Lin MT. Pathogenetic roles of angiogenic factors in pyogenic granulomas in pregnancy are modulated by female sex hormones. J Periodontol. 2002;73(7):701-708. 3. Weedon D. Vascular tumors. In: Weedon D, Geoffrey Strutton, eds. Skin Pathology. 2nd ed. London, United Kingdom: Churchill Livingstone; 2002:1015-1016. 4. Lever WF. Tumors of vascular tissue. In: Lever WF, Schaumburg-Lever G, eds. Histopathology of the Skin. 7th ed. Philadelphia, Pa.: Lippincott; 1990:695-696. 5. Calonje E, Fletcher CDM. Vascular tumors. In: Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd ed. Edinburgh, United Kingdom: Churchill Livingston; 2007:47.
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practice guidelines
IOM Releases Report on Dietary Reference Intakes for Calcium and Vitamin D
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alcium and vitamin D are known for their association with bone health, but there have been conflicting messages about other health benefits of these nutrients and the amounts needed. For this reason, the Institute of Medicine (IOM) assessed current information on potential health outcomes associated with calcium and vitamin D.
Current Intake
The reference values (Dietary Reference Intakes) for calcium and vitamin D were set in 1997; however, newer reference values were created based on higherquality data. A review of this data determined that evidence of benefits outside of bone health (e.g., cancer, cardiovascular disease, diabetes mellitus, falls, hypertension, immune response, metabolic syndrome, neuropsychological functioning, physical performance, preeclampsia, reproductive outcomes) was from studies that often had mixed and inconclusive results. Strong evidence confirmed the importance of calcium and vitamin D for bone growth and maintenance.
Information from national surveys indicates that girls nine to 18 years of age may not be getting enough calcium, and that postmenopausal women who take supplements may be getting too much calcium, which increases the risk of kidney stones. Although the average intake of vitamin D is below the median requirement, average serum vitamin D levels are higher than the 20 ng per mL (49.92 nmol per L) that the IOM found to be necessary for good bone health, suggesting that sun exposure contributes significant amounts of vitamin D in persons living in North America. It also implies that most persons are getting the necessary amount of vitamin D. Although some subgroups may still be at increased risk of not getting enough vitamin D, the number of persons with vitamin D deficiency may actually be overestimated because many laboratories testing serum vitamin D levels could be using cut-points that are higher than those recommended by the IOM.
Dietary Reference Intakes
Tolerable Levels
On average, children one to three years of age need 500 mg of calcium daily, and those four years and older need 800 mg daily. To support bone growth, adolescents need approximately 1,300 mg daily. Women 19 to 50 years of age need 800 mg daily, and women older than 50 years need 1,000 mg daily. Men up to 71 years of age need 800 mg daily, and men 71 years and older should get 1,000 mg daily. When determining appropriate vitamin D intake, the IOM assumed minimal sun exposure. Persons living in North America should get 400 IU of vitamin D daily; however, those 71 years and older may need upto 800 IU daily.
The IOM set upper levels of calcium and vitamin D intake to indicate the highest safe amount a person can take. These levels vary by age; however, the IOM determined that more than 2,000 mg of calcium daily and 4,000 IU of vitamin D daily increase the risk of harm. Kidney stones are associated with too much calcium supplementation, and very high levels of vitamin D (more than 10,000 IU daily) are associated with kidney and tissue damage. Evidence of risks associated with vitamin D at lower intake levels is limited; however, some studies indicate signs of adverse effects.
Health Effects
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Source: Adapted from Am Fam Physician. 2011;83(11):1352.
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research review
From the Journals ...
Rheumatoid Arthritis Patients and Rheumatologists Approach the Decision to Escalate Care Differently: Results of a Maximum Difference Scaling Experiment
Glycemic Control, Complications and Death in Older Diabetic Patients: The Diabetes and Aging Study
Objective: Antirheumatic treatment is frequently not appropriately modified, according to ACR Guidelines, in patients with active rheumatoid arthritis (RA) as defined by a DAS28 score >3.2. The objective was to determine which factors most strongly influence patients’ and rheumatologists’ decisions to escalate care. Methods: We administered a Maximum Difference Scaling survey to 106 rheumatologists and 213 RA patients. The survey included 58 factors related to the decision to escalate care in RA. Participants answered 24 choice tasks. In each task, participants were asked to choose the most important factor from a set of five. We used Hierarchical Bayes modeling to generate the mean relative importance score (RIS) for each factor. Results: For rheumatologists, the five most influential factors were: Number of swollen joints (RIS: 5.2; SD: 0.4), DAS28 score (RIS 5.2; SD 0.5), physician global assessment of disease activity (RIS 5.2. SD 0.6), worsening erosions over the last year (RIS: 5.2; SD: 0.6) and RA disease activity now compared to three months ago (RIS 5.1; SD: 0.6). For patients, the five most important factors were: Current level of physical functioning (RIS: 4.3; SD: 1.1), motivation to get better (RIS: 3.5; SD: 1.4), trust in their rheumatologist (RIS: 3.5; SD: 1.6), satisfaction with current DMARDs (RIS: 3.4; SD: 1.4) and current number of painful joints (RIS 3.4; SD: 1.4). Conclusions: Factors influencing the decision to escalate care differ between rheumatologists and patients. Better communication between patients and their physicians may improve treatment planning in RA patients with active disease.
Objective: To identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients. Research Design and Methods: We conducted a retrospective cohort study (2004-2008) of 71,092 patients with type 2 diabetes, aged ≥60 years, enrolled in Kaiser Permanente Northern California. We specified Cox proportional hazards models to evaluate the relationships between baseline glycated hemoglobin (A1C) and subsequent outcomes (nonfatal complications [acute metabolic, microvascular, and cardiovascular events] and mortality). Results: The cohort (aged 71.0 ± 7.4 years [means ± SD]) had a mean A1C of 7.0 ± 1.2%. The risk of any nonfatal complication rose monotonically for levels of A1C >6.0% (e.g., adjusted hazard ratio 1.09 [95% CI 1.02-1.16] for A1C 6.0-6.9% and 1.86 [1.632.13] for A1C ≥11.0%). Mortality had a U-shaped relationship with A1C. Compared with the risk with A1C <6.0%, mortality risk was lower for A1C levels between 6.0 and 9.0% (e.g., 0.83 [0.76-0.90] for A1C 7.0-7.9%) and higher at A1C ≥11.0% (1.31 [1.09-1.57]). Risk of any endpoint (complication or death) became significantly higher at A1C ≥8.0%. Patterns generally were consistent across age-groups (60-69, 70-79, and ≥80 years). Conclusions: Observed relationships between A1C and combined endpoints support setting a target of A1C <8.0% for older patients, with the caution that A1CS <6.0% were associated with increased mortality risk. Additional research is needed to evaluate the low A1C-mortality relationship, as well as protocols for individualizing diabetes care.
van Hulst LT, Kievit W, van Bommel R, et al. Arthritis Care Res (Hoboken) 2011 July 11. [Epub ahead of print]
Huang ES, Liu JY, Moffet HH, et al. Diabetes Care 2011;34(6):1329-36.
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conference calendar
Conference Calendar
71st International Congress of FIP September 2-8, 2011 Venue: Hyderabad International Convention Centre (HICC), Novotel and HICC Complex, (Near Hitec City) Hyderabad, India http://www.fip.org/hyderabad2011/ Medical Ethics and Legal Medicine September 5-15, 2011 Venue: 10-Night Western Mediterranean Cruise Conference, Civitavecchia, Italy Website: http://www.continuingeducation.net/ coursedetails.php?program_number=886 10th Global Conference: Making Sense of: Health, Illness and Disease September 6-8, 2011 Venue: Mansfield College, Oxford, United Kingdom Website: http://www.inter-disciplinary.net/probingthe-boundaries/making-sense-of/health-illness-anddisease/call-for-papers/ 22nd International Congress of the Israel Society of Anesthesiologists September 13-15, 2011 Venue: David InterContinental, Tel Aviv, Israel Website: http://www.icisa.co.il
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
FDI Annual World Dental Congress New Horizons in Oral Health Care September 14-17, 2011 Venue: Centro BANAMEX Convention and Exhibition Centre, Mexico City, Select One Switzerland Website: http://www.fdicongress.org/ Current Problems of Gastroenterology and Abdominal Surgery September 15-16, 2011 Venue: Congress Hall, Kiev, Ukraine Website: http://www.nbscience.com/22.html Medical Conference in Ukraine 2011 Advances in Nephrology, Dialysis, Kidney Transplantation September 29-30, 2011 Venue: Congress Hall, Odessa, Ukraine Website: http://www.nbscience.com/25.html Medical Conference in Ukraine 2011 Modern Aspects of Surgical Endocrinology. Role Physician-Endocrinologist September 29-30, 2011 Venue: Congress Hall, Kharkov, Ukraine Website: http://www.nbscience.com/24.html
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emedinews section
From eMedinewS
Pulse Pressure Change Signals Poor Hemodialysis Survival
Endovascular Stenting Helpful in Nutcracker Syndrome
Changes in pulse pressure (PP), especially decreases, in the first year of hemodialysis predict worse survival for patients. This finding held across the entire range of PPs, Len Usvyat, MS, senior database analyst at the Renal Research Institute in New York City, told delegates here at the XLVIII European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress. (Source: Medscape)
Compression of the left renal vein between the aorta and the superior mesenteric artery can cause back pain and hematuria in a phenomenon known as ‘the nutcracker syndrome’ - but a new report from China says endovascular stents are a good long-term solution. In a June 16th online paper in the Journal of Urology, the authors of the report say the incidence of the syndrome is unknown, although it is relatively rare. Dr Hongkun Zhang and colleagues at Zhejiang University, Hang Zhou note that treatment depends on symptom severity. Endovascular stenting, they say, is attractive because it’s minimally invasive. (Source: Medscape)
New CDC Advice on Postpartum Contraception The Centers for Disease Control and Prevention (CDC) has recommended further restrictions on the use of combined hormonal contraceptives those that contain both estrogen and progestin - in the postpartum period among women who are not breast feeding. Recommendations published last year had advised that combined hormonal contraceptives should not be used in the first three weeks after delivery, with no restrictions after that, according to Naomi Tepper, MD, of the CDC’s Division of Reproductive Health in Atlanta, and colleagues. The restriction was put in place because combined hormonal contraceptives carry a slightly elevated risk of venous thromboembolism in healthy women of reproductive age, which could compound the higher risk of venous thromboembolism that occurs during a normal pregnancy due to hematologic changes. After an evidence review, however, the CDC placed a further restriction - reported in the July 8 issue of Morbidity and Mortality Weekly Report - on the use of combined hormonal contraceptives from 21 to 42 days postpartum among women with risk factors for venous thromboembolism. Those risk factors include an age of 35 and older, previous venous thromboembolism, thrombophilia, immobility, transfusion at delivery, obesity, postpartum hemorrhage, pre-eclampsia, smoking or a recent cesarean delivery. Women without such risk factors generally can start taking combined hormonal contraceptives three weeks after giving birth, according to the updated guidance. (Source: Medspage Today)
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Fitness Update Children’s Physical Activity Decreases as they Age
Though many reports claim that childhood obesity rates have leveled off, childhood physical activity is still at a critical low. New research published in the journal Pediatric Exercise Science shows that a very low number of children engage in the recommended amount of exercise and/or active play. Further, the study shows that children’s activity decreases as they get older. The study included 291 children ages 5- to 6-year-old and 919 children ages 10- to 12-year-old, as well as their parents. Parents completed questionnaires about their children’s physical activity patterns, and all children wore an accelerometer for eight days. The accelerometer data showed that younger children engaged in approximately four hours of moderate- to vigorous-intensity physical activity per day, whereas older children only accumulated two hours per day. Fewer than three-quarters of 10- to 12-year-old boys and less than half of 10- to 12-year-old girls recorded 120 minutes of activity per day. The study findings show that activities that are appealing to older childrenparticularly older girls should be considered in the creation of physical activity promotion strategies. ‒Rajat Bhatnagar, International Sports and Fitness Distribution, LLC
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
clinical algorithm
Evaluation of Vertigo
Patient complains of dizziness
Does the patient have true vertigo?
Any medication taken by patient which is causing vertigo?
Stop medication, if possible
Diagnostic work-up as appropriate
Obtain detailed history regarding timing and aggravating factors and risk factors for cerebrovascular disease
Do physical examination with reference to head and neck, cardiovascular system and provocative diagnostic tests
Differential diagnosis as suggested by physical examination findings
Think about MRI in patients with focal neurologic findings, risk factors for cerebrovascular disease, or other findings suggesting a central cause of vertigo
Consider other laboratory and radiologic studies as indicated (e.g., cervical spine series in patients with findings suggesting cervical vertigo)
Consider referral to specialist of appropriate faculty
Figure. Algorithm for an initial approach for diagnosing the cause of vertigo. MRI: Magnetic resonance imaging.
Source: IJCPâ&#x20AC;&#x2122;s ENT Clinical Decision Charts.
Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
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Indian Journal of
Clinical Practice
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). –
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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departments and institutions where the work was performed, 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.
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.
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Indian Journal of Clinical Practice, Vol. 22, No. 3, August 2011
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.
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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
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Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected
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.
2. Total number of pages ________________________
Books
5. Special requests _____________________________
Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.
6. Suggestions for reviewers (name and postal address)
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 –
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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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Current Concepts in the Management of Congenital Fibrinogen Deficiency
DIABETOLOGY
Pages 16
DR KK AGGARWAL Gr. Editor-in-Chief, IJCP Group
E
D I T O R I A L
VOLUME 12, NUMBER 2
Official Voice of Doctors of India
Member The Indian Newspaper Society
Group Editor-in-Chief Dr KK Aggarwal
Padma Shri and Dr BC Roy Awardee Sr Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group Chief Editor, eMedinewS Member, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) drkk@ijcp.com
igh doses or long-term use of PPIs or proton-pump inhibitors can lead to an increased risk of bone fractures. This holds especially true for those over the age of 50, and for people on the high dose. The latest warning is based on a FDA review of several studies of the treatment. These epidemiologic studies revealed an elevated fracture risk at the hip, wrist and spine. But the studies do not, definitively prove that PPIs are the cause of the fractures.
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FDA has instructed the manufacturers of the drugs to change the labels for both the prescription and the over-the-counter versions of the PPIs. The FDA said they should only be taken for 14 days to help ease frequent heartburn and under no circumstances should over-the-counter PPIs be taken for more than three 14-day periods in a year.
Asian Journal of
Ear, Nose Throat
Most researchers believe that more fractures are due to decreased calcium absorption from the diet because of the reduced stomach acid. But, it’s also possible that these drugs interfere with bone maintenance. Notably, PPIs have previously been linked to an increased risk of contracting pneumonia and the troublesome bacterium Clostridium difficile, as well as to an increased risk of dementia.
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iddle-aged women who move around more in their daily life have lower levels of intra-abdominal fat, a risk factor for heart disease. Minor modifications in daily routine such as reducing the time watching TV or increasing the walk time to work, can make a difference in the long-term health. Visceral fat is a hot topic because of metabolic syndrome, which predisposes people to disease. Intra-abdominal fat, or the fat that wraps around the organs in the abdomen and chest, tends to accumulate at midlife and can contribute to developing diabetes, hypertension and heart disease. The fat around the organs is known to be more related to heart disease and diabetes. A woman does not need to appear outwardly heavy to have a potentially troublesome extra ‘tire’ around her organs. Exercise for long has been known to reduce the amount of intra-abdominal fat.
“ Always aim at complete harmony of thought and word and deed. Always aim at purifying your thoughts and everything will be well.
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– Mahatama Gandhi
MAKE SURE
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DURING MEDICAL PRACTICE A terminally ill patient who develops bed sores, is given only systemic antibiotics.
N
S
I
Evidence-based Medicine
Please change the position of the patient frequently and keep the skin clean and dry.
IJCP Academy
Minor Changes in Lifestyle are All That is Required for Good Health
Make sure that good nursing care and maintenance of skin hygiene is advised first to patients with bed sores, along with topical antibiotics. KK Aggarwal
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CD I
CD II
CD III
CD IV
5.5 cm W x 6.5 cm H
8.0 cm W x 6.5 H
17.0 cm W x 6.5 cm H
17.0 cm W x10.0 H
Dr KK Aggarwal Group Editor-in-Chief
Dr Praveen Chandra
Guest Editor
January-March 2010
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3
Preparing for Commonwealth Games Illnesses
9
News & Views
10
Expert’s Opinion
11
FDA Update
13
Dr Vijay Viswanathan Editor
Classified Display Rate Card Category Dimensions
April - June 2010
PPIs may Cause Bone Fractures When Used for More Than One-year or at Higher Doses: FDA
H Dr KK Aggarwal
No. of Insertions Amount (Rs.)/Advt. 1
3,575.00
2-5
3,200.00
6+
3,000.00
1
5,200.00
2-5
4,500.00
6+
4,000.00
1
11,050.00
2-5
10,500.00
6+
9,500.00
1
17,000.00
2-5
16,150.00
6+
15,300.00
Dr VP Sood
Dr KK Aggarwal
Editor
Group Editor-in-Chief
Dr KK Aggarwal
Group Editor-in-Chief
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