Long term outcome of primary non surgical root canal treatment by chanel lam

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Author(s)

Long term outcome of primary non-surgical root canal treatment

Lee, Hui-cheng, Angeline.; 李慧琴.

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2010

http://hdl.handle.net/10722/132330

The author retains all proprietary rights, (such as patent rights) and the right to use in future works.

Long term outcome of primary non-surgical root canal treatment

A thesis submitted to the University of Hong Kong in partial fulfillment of the requirements for the degree of

Master of Dental Surgery (Endodontics) The University of Hong Kong

LEE, Angeline Hui Cheng BDS (University of Otago, New Zealand), FRACDS 2010

Abstract

Aim To examine the long term outcome of primary non-surgical root canal treatment completed in a dental teaching hospital and specifically to: (1) compare the survival distributions of primary root canal treatment calculated by two survival analysis methods: Interval censoring versus Kaplan-Meier estimators; (2) assess the factors associated with the outcome of primary root canal treatment in terms of periapical healing and functional retention; and (3) evaluate the time and reasons for extraction after primary root canal treatment. Materials and methods A total sample of 999 teeth constituted about one-tenth of all teeth treated between January 1981 and December 1994 were included in this study. Information about the patientsâ&#x20AC;&#x2122; personal particulars and medical history, as well as the pre-operative status, treatment details and review status of the treated teeth were extracted from the treatment records and from findings of clinical and radiographic examination. When a sampled tooth had been retreated or extracted, the date and main reason for treatment were recorded. Treatment outcomes were categorized as either complete healing or post-treatment disease, and as functional retention. Reasons for extraction after primary endodontic treatment were also evaluated. The survival function was plotted against the time to an outcome event, using Kaplan-Meier (K-M) product limit estimators for various linear time estimates and using the Weilbull i

Abstract

accelerated failure time model for interval-censored data. Results Median survival time of treated teeth with complete healing and functional retention ranged from 103 to 187 months and 234 to 288 months, respectively. Survival curves generated from the date of first review with the observation of post-treatment disease or loss of functional retention closely approximated that of interval-censored curve up to approximately 120 months. Age, tooth type, pre-operative periapical status, occlusion, type of final restoration, condition of the tooth and its restoration, significantly affected both healing and survival outcomes. Overall, 29% of the sampled teeth resulted in extraction, almost half of these were due to crown or root fractures. Conclusion Among various linear estimates, date of first review with the observation of post-treatment disease or loss of functional retention could be considered as a reasonable time estimate of the actual date of event using Kaplan-Meier estimators, in short- to medium-term study. The long term healing and functional retention outcome of primary root canal-treated teeth are affected by a number of pre- and post-operative factors, including age, tooth type, pre-operative periapical status, occlusion, type and condition of final restoration. Most extractions were done in the first 150 months after treatment and root fractures were the single most common cause of extraction.

Acknowledgements

I shall take this opportunity to express my deepest gratitude to Dr. Gary Cheung for his supervision and guidance throughout this research project, particularly for his meticulous and tireless proofreading of the manuscript.

I would also like to thank Dr. Robert Ng and Dr. Irwan Soo for being the co-observers in evaluating the radiographs of this project, with further appreciation to the former for his generosity and selflessness in sharing the admirably vast knowledge and experience he possessed in endodontics.

I wish to convey my appreciation to Dr. May Wong, who had offered her time and invaluable expert advice for the statistical component of this research project. Her contribution was indeed treasurable. I am also very grateful to Dr. Rachel Tan for her kindly advice based on her own experience on a similar research project, as well as Dr. Jeffrey Chang and Dr. Choranda Praisanti for their friendly encouragement and support.

I am indebted to Ms Jane Lam, Ms. Lona Lee and Ms. Kitty Choi, as their assistance had greatly facilitated the clinical review process of the patients, an important part of this research project. I am also thankful to my friends and colleagues, Dr. Prajakta Mahindre, Dr. Catherine Chia, Dr. Helen Liang, Dr. Bonnie Chiu, Dr. Micheal Tse, Dr. Irwan Soo and Dr. Willis Wei for making the time throughout the course incredibly enjoyable and memorable.

Last but not least, I would like to give my special thanks to my husband, Eugene, for his unfailing support and understanding. iii

Table of contents

Table of contents Abstract……………………………………………………………………………… i Acknowledgement…………………………………………………………………… iii Table of contents…………………………………………………………………….. iv Chapter 1 Introduction………………………………………………………….. 1 Chapter 2 Literature review……………………………………………………. 4 2.1 Non-surgical root canal treatment……………………………………………….. 4 2.2 Healing versus Survival…………………………………………………………. 4 2.3 Histologic versus Radiographic assessment…………………………………….. 7 2.4 Survival analysis………………………………………………………………… 11 2.4.1 Direct method versus survival analysis………………………………. 11 2.4.2 Factors affecting the reliability and validity of survival analysis…….. 15 2.4.3 Life-table analysis (Actuarial approach) ……………………………....16 2.4.4 Kaplan-Meier product-limit estimator……………………………....... 17 2.4.5 Interval censoring…………………………………………………….. 20 2.5 Factors affecting the outcome of primary root canal treatment…………………. 21 2.5.1 Preoperative factors……………………………………………………21 2.5.2 Intraoperative factors…………………………………………………. 25 2.5.3 Postoperative factors………………………………………………….. 28 2.5.4 Summary……………………………………………………………… 33 Chapter 3 Materials and methods ………………………………………………35 3.1 Sample……………………………………………………………………………35 3.2 Pilot study……………………………………………………………………….. 36 3.2.1 Observations………………………………………………………….. 36 3.3 Collection of data………………………………………………………………... 37 3.4 Assessment criteria……………………………………………………………… 39 3.4.1 Periapical status………………………………………………………. 40 3.4.2 Preoperative pulp vitality…………………………………………….. 42 3.4.3 Treatment outcome…………………………………………………… 43 3.5 Statistical analysis………………………………………………………………. 43 Chapter 4 Results……………………………………………………………….. 50 4.1 Sample……………………………………………………………………………50 4.2 Survival outcome of healing and functional retention…………………………... 52 4.2.1 Median and mean survival time………………………………………. 52 4.2.2 Survival curves………………………………………………………...53 4.3 Factors affecting the outcome…………………………………………………… 57 4.3.1 Healing outcome (H) ………………………………………………… 64 4.3.2 Functional retention outcome (F) ……………………………………. 66 iv

Table of contents

4.3.3 Summary ………………………………………………………………68 4.4 Reasons for extraction……………………………………………………………68 Chapter 5 Discussion.…………………………………………………………… 71 5.1 Methodology…………………………………………………………………….. 71 5.2 Survival analysis………………………………………………………………… 74 5.3 Factors affecting the outcome of primary root canal treatment…………………. 79 5.4 Reasons for extraction……………………………………………………………89 Chapter 6 Conclusions………………………………………………………… 92 Chapter 7 References…………………………………………………………… 94 Appendix 1………………………………………………………………………….. 112 Appendix 2………………………………………………………………………….. 114

Introduction

1. Introduction

Survival analysis is a statistical method employed for analyzing the time to event occurrence, to compute the cumulative survival probability up to a certain time point. In dentistry, most of the event (of interests) may only be known to have occurred when a diagnosis is made at a dental visit. It follows the occurrence time of that event is less than or equal to the time when it is first observed. Therefore, the actual time of event needs to be estimated to enable the application of various survival analysis methods, except for patient who is reviewed at regular (and frequent or short) intervals.

Kaplan-Meier product-limit estimator is one of the most widely used statistical methods for survival analysis in dentistry. This method requires the entry of an exact event date, which is often achieved by using various linear estimates for the time interval between two dental visits, such as one-quarter point, half-way point, etc. (Cheung & Chan 2003). Another more recent advent is the use of “interval censoring” method (Lindsey & Ryan 1998), a rather more sophisticated statistical method with an “interval censor”, which contains information on the (approximate time of) event occurrence. Such data takes into account the uncertainty as to the exact time when the

Introduction

event occurs within an interval.

In endodontics, the outcome of root canal treatment is an important event of interests. From a clinician’s perspective, outcome in terms of periapical healing or post-treatment disease is probably the most important as it reflects the disease status of a treated tooth that determines whether the ultimate goal of endodontic treatment (in the prevention or curing of apical periodontitis) has been achieved or not. On the other hand, a relatively newer outcome measure, known as functional retention (Friedman & Mor 2004), is considered to be more patient-centered, and is more consistent with and comparable to that used in studies of implant success. Presumably, these two different, but somehow overlapped survival outcomes might be influenced by different sets of factors.

Studies may also be directed to the analysis of cases with post-treatment disease and/or loss of functional retention that had been extracted after root canal therapy, either for the “time to extraction”, or the “reasons of extractions”, and sometimes a combination of both. This should possibly offer some indication on the length of time a treated tooth is able to survive asymptomatically before resulting in tooth loss.

Introduction

The aim of the present study was, therefore, to examine the long term outcome of primary non-surgical root canal treatment completed in a dental teaching hospital, with the specific objectives to: 1.

Compare the survival distribution of primary root canal treatment calculated by different survival analysis methods: Interval censoring versus Kaplan-Meier estimators.

Assess the outcome of primary root canal treatment in terms of: (a) periapical healing; and (b) functional retention.

Evaluate the influence of different factors on the outcome of primary root canal treatment.

Evaluate the time and reasons for extraction after primary root canal therapy.

Literature review

2. Literature review

2.1 Non-surgical root canal treatment The aetiology of apical periodontitis is the infection that lies within the pulpal space (Kakehashi et al. 1965, Paterson 1976). The purpose of root canal treatment is the elimination of this infection, with the ultimate goal to prevent (further) periapical disease and to restore periapical health (European Society of Endodontology 2006, Ørstavik & Pitt Ford 2008). Clinical and radiographic follow-ups are essential to assess the treatment outcome; the evaluation criteria can be categorized into “strict” or “lenient” (Lewsey et al. 2001, Ng et al. 2007).

2.2 Healing versus Survival According to Strindberg (1956), treatment outcome should be based on a minimum of four years observation after the completion of root canal treatment. Successful outcome was (strictly) defined as both an absence of clinical signs or symptoms and resolution of periapical inflammation, i.e. normal presentation of periodontal ligament (PDL) space, except for areas with excess (extruded) root canal filling where widening of the PDL space may be accepted as a normal phenomenon. Treatment would be deemed to have failed when: (i) there is any clinical sign or symptom; (ii) the (preexisting) periapical rarefaction has not resolved after four years of observation; (iii) emergence of a new 4

Literature review

radiolucent area (for teeth / roots with no pre-existing lesion); or (iv) progression of root resorption that occurs at anytime after the completion of treatment (Tronstad 1988). This strict set of criteria for periapical healing is consistent with the outcome assessment criteria adopted in the quality guidelines of European Society of Endodontology (2006). The success or, more accurately, complete healing rate of primary root canal treatment was reported to range from 68% to 85% when such strict criteria were adopted (Ng et al. 2007).

Bender et al. (1966) observed that asymptomatic teeth can remain functional for many years, despite the presence of periapical radiolucent area, and thus might not be considered as treatment failure (at least, by the patient). The opinion forms the basis of a lenient set of successful treatment outcome, which includes: (i) absence of pain and swelling; (ii) disappearance of discharging sinus, if any; (iii) retention of function; (iv) no evidence of (continuous) tissue destruction, such as tooth and bone resorption; and (v) radiographic evidence of resolution or arrested area of rarefaction after 6 to 24 months. In this set of loose criteria, complete resolution of the periapical rarefaction is not a prerequisite. Seltzer et al. (1967) also suggested that a root canal treated tooth that is functioning adequately without any adverse clinical symptoms, such as pain, swelling or sinus tract, should be regarded as having been treated â&#x20AC;&#x153;successfullyâ&#x20AC;?. As a consequence, the use of loose criteria for evaluating treatment outcome results in a considerably 5

Literature review

increased success rate when compared to that of using strict criteria (Friedman et al. 1995, Lewsey et al. 2001), often 10% or higher (Ng et al. 2007).

It has been suggested that the use of the terms “success” and “failure”, as were often used in the description of root canal treatment outcome should be avoided (Ørstavik 1996). These terms have been challenged as being ambiguous and confusing, because the terms could carry a different meaning to different people (Friedman 2002, Friedman & Mor 2004). To facilitate a meaningful communication, the “treatment outcome” should refer to the progress of healing (of the apical periodontium) and thus the terms: healed, healing and post-treatment disease, are preferred (Friedman 2008). When both the clinical and radiographic appearance is normal, the tooth is classified as healed. If the periapical radiolucent area has reduced in size at a follow up of less than four years duration and the tooth is without any clinical signs or symptoms, then it is described as healing (in progress). A tooth that presents with clinical signs and symptoms, or with a radiographic radiolucency after four years or more, be it static, enlarging or reducing in size, or newly emerging, will be classified as post-treatment disease.

Friedman and Mor (2004) further proposed a new category for describing the treatment outcome, known as functional retention. This is not a measure of healing, but a term that is related to a goal of treatment, i.e. to achieve a symptom-free tooth that remains in 6

Literature review

place and functional. Accordingly, functional retention is defined as the absence of clinical signs and symptoms, regardless of the radiographical periapical status (which may be absent or present) for the treated tooth. This outcome category is said to be patient-centered, and is more consistent with and comparable to that used in studies of implant success (Friedman 2008).

Iqbal and Kim (2007) suggested that the root canal treatment outcome should be described in term of survival (of the treated tooth), as this is easier for patients to understand. Survival of a root canal treated tooth is defined as retention of the tooth in function without symptoms, and it is not affected by the time needed for the periapical healing to take place. Survival rates of teeth in functional retention were found to be very high (greater than 92%), as reported by a number of large epidemiologic studies (Lazarski et al. 2001, Salehrabi & Rotstein 2004, Chen et al. 2007).

2.3 Histologic versus Radiographic assessment In a classical study of 292 maxillary incisors on human cadavers, Brynolf (1967) demonstrated a strong correlation between radiographic and histological appearance of the periapical status (with only 7% of cases showed an absence of any aggregation of inflammatory cells). She reported that although an absence of periapical radiolucency did not necessarily reflect an absence of chronic apical inflammation upon histological 7

Literature review

examination, the presence of periapical rarefaction almost certainly indicated the presence of a chronic inflammatory lesion histologically (granuloma).

Few years later, Rud et al. (1972) similarly demonstrated a strong correlation between the lack of radiographic healing and histological inflammation for teeth receiving periapical surgery. Their results indicated that complete resolution of the periapical rarefaction would correspond to an absence of histological inflammation in 90% of cases; whereas those diagnosed radiographically as unsatisfactory healing turned out to be severely inflamed upon histological examination. Green et al. (1997) also reported that those failure cases were always associated with the presence of histological inflammation, whereas a majority of cases that appeared radiographically normal exhibited no periapical inflammation. Barthel et al. (2004) further supported a strong correlation between the presence of periapical radiolucency and histological signs of inflammation for the root canal treated teeth in human cadavers that they examined.

Radiographic assessment is not without its limitation. Bender and Seltzer (1961) demonstrated for artificially created periapical lesions (by drilling hollow cavities in the bony medulla in dried skull) that a periapical radiolucent area might not be discernible if the lesion remained in the cancellous bone, regardless of its size. Lesions only became detectable on a periapical film when the cortical bone was eroded or perforated (Bender 8

Literature review

& Seltzer 1961).

In contrast, the results of similar experiments done in the mandible of human cadavers around the roots of first and second molars showed the opposite. It was demonstrated that a great majority of lesions confined to the cancellous bone were readily detectable on the radiographs (Lee & Messer 1986, Barbat & Messer 1998). Another experiment showed that premolars were more likely to give rise to radiographic changes, even without involvement of the cortical plate, compared with molars (Shoha et al. 1974). The thickness of the cortical plate overlying the root apex seems to be a factor for the ease of detection of periapical inflammation radiographically.

For asymptomatic (chronic) apical periodontitis, radiographic assessment plays an important role in diagnosing the condition. However, as radiographs merely represent a two-dimensional image of the three-dimensional anatomical structures, they do not reflect the actual physiologic state or pathologic changes at the periapical area (Huumonen & Ă&#x2DC;rstavik 2002). In fact, many root canal treated teeth that exhibit radiographic signs of complete or partial healing have been shown to be associated with either a persistent or progressive area when examined using Cone Beam Computed Tomography (CBCT) (Wu et al. 2009).

Literature review

Accuracy of the radiographic interpretation has been a concern, too. A study by Goldman et al. (1972) on the reliability and reproducibility of radiographic assessment of periapical status between different observers indicated that the extent of disagreement was directly proportional to the number of observers involved. Two observers were found to produce the highest level of agreement (78%). Molars seemed to be the most problematic, which teeth have given rise to most disagreements (Goldman et al. 1972). To overcome the problem of inter-observer variation, many studies have included a strategy of involving the observers in a joint evaluation for those uncertain or disagreement cases to produce a common diagnosis, to minimize the variation to an acceptable level (Halse & Molven 1986, Molven et al. 2002).

There could be variations within the same examiner, if he/she was asked to repeat the examination on the same radiograph. This is known as intra-examiner variation. Reit and Hollender (1983) found that the greatest challenge to intra-observer reproducibility was the case of widening of PDL space, whereas Halse and Molven (2004) reported that many examiners would associate that with favourable healing most of the time. It is widely agreed that a well-defined set of criteria is crucial to minimize intra-observer variation when making radiographic assessment of periapical conditions. The problem with radiographic interpretation and inter- and intra-examiner variations are arguably a result of the overlapping images of the three-dimensional anatomical structures on a 10

Literature review

plain film. With the advances of CBCT (and a trend of reducing the radiation dose for similar diagnostic accuracy), it is probable that CBCT may become a replacement for intra-oral film for assessment of periapical status (Moura et al. 2009).

2.4 Survival analysis Survival analysis is a statistical method originally referred to the study of “time to death” of a population. From a mathematical point of view, it does not really matter whether one is studying the time until death or time to the occurrence of any other events (Sasieni 2005). Therefore, survival analysis has also been applied for analyzing the “time to event” data and is widely used in dentistry (especially in the study of the longevity of restorations), although its use in the endodontic outcome studies remains relatively less common.

2.4.1

Direct method versus survival analysis

Direct method (e.g. assessment of average success rate over a period of time after primary root canal treatment) is the most frequently used statistical approach to evaluate the effectiveness of dental treatments. Direct measure of the “success” or “survival” rate is done by calculating the proportion of the treated teeth that are deemed to be a success or have “survived” after a defined period of observation, but it only takes into account those cases which have been followed over the entire study period. Typically, cases lost 11

Literature review

to follow-up would be discarded from the calculation, with the condition (success or otherwise) of such cases at the last available review, if any, being ignored.

Another problem with the direct method is related to the calculation of the mean survival time, which is simply deduced by averaging the “time to failure” of those failed cases over the study period. As a consequence, cases that are successful or have “survived” will not enter into the calculation, because their “time to failure” is not yet known at the conclusion of the study. Thus, “success” or “survival” rate calculated with the direct method only reflects a snap-shot of survival experience at a certain point in time and can be misleading, because it does not reflect the change in survival pattern over a longer period of time (Thylstrup & Rölling 1975, Davies 1987). For instance, two sample populations that showed the same average “success” or “survival” rate might behave quite differently over time (Davies 1987).

Both Weiger et al. (1998) and Cheung (2002) have commented that simple calculation of a percentage value for the “success rate” does not accurately reflect the prognosis of the root canal treated teeth, due to a lack of information for the time-dependent event of healing (or failure). Simple calculation of a “success rate” (at a certain point in time) tends to result in overestimation of the rate for short-term observations, but underestimated for longer observation periods (Weiger et al. 1998). 12

Literature review

The so-called “adjusted success rate” has tried to factor the observation time into the calculation (to produce a certain percentage of failure occurrence per year) in a hope to provide a more realistic estimation of the prognosis. However, this assumption of a constant rate of deterioration of treatment effect with time could hardly reflect the truth. Cheung and Chan (2003) have shown that the long-term cumulative survival of primary root canal treatment actually declines in a nonlinear fashion; the shape of the plot would depend on how the data were manipulated. There appears to be a trend of initial rapid drop in the cumulative survival that tends to slow down in the longer term (Cheung & Chan 2003). In order to gain a more complete picture of the survival experience (of a treatment modality, or other event) over time, a survival analysis would be more appropriate (Davies 1987).

Survival analysis is a statistical method employed for analyzing the time to event occurrence (Sasieni 2005) and to compute the survival function, i.e. cumulative survival probability up to a certain time point (Davies 1987, Stoll et al. 1999). This is a rather sophisticated approach that it is able to deal with incomplete observations (i.e. patients failing to attend all follow-ups or those who attended but no “failure” have been observed), which is frequently encountered in clinical trials and longitudinal studies.

In a prospective study, it is necessary to observe the cases repeatedly over a period of 13

Literature review

time to evaluate when an event of interest occurs (usually failure to heal or recurrence of disease). Although it will be ideal to recruit all such cases at the same starting point and follow them over time, this is often impossible or impracticable. In practice, cases are commonly recruited at different times and are subsequently followed up until the conclusion of the study (Daya 2005). Survival analysis not only allows cases to be recruited at different time points, but it also takes into account any incomplete observations for those who fails to attend a recall appointment (i.e. those lost to follow up but the treatment may not have “failed” yet) and those attended but “failure” has not been diagnosed at the end of the study period. These incomplete observations are referred as a censored observation (Davies 1987, Stoll et al. 1999), which information is utilized in survival analysis. Censored observations are inevitable whenever there is a time limit to a longitudinal or cohort study; the longer the study period, the more likely the occurrence of censored observations.

Including the observation period for censored cases in the analysis offers additional information towards the estimation of “time to (failure) event” or “survival time” (Daya 2005). Adjustment is made for cases with different recruitment time, so that all recruited cases were considered as if the treatment were provided at a common time origin. Then, the end-date of the study would be regarded as the “date-last-seen” for all censored observations (Davies 1987). Survival analysis has the advantage of using all the survival 14

Literature review

information accumulated up to the end-date of the study (Cutler & Ederer 1958).

2.4.2

Factors affecting the reliability and validity of survival analysis

Survival analysis depends on a number of factors to ensure a valid estimation of the â&#x20AC;&#x153;time to eventâ&#x20AC;?, which include: (i) Existence of a well-defined time of origin; (ii) Strict adherence to the inclusion and exclusion criteria; (iii) A clearly established scale of measurement for the observation intervals; (iv) Well-defined and dichotomous outcome measures for the event of interest to allow consistent calculation and clear interpretation of results (e.g. healed versus post-treatment disease); (v) Cases of drop-out or lost to follow-up are due to reasons unrelated to the outcome itself; (vi) No systematic difference between cases recruited at different times during the study (Daya 2005).

The reliability of results from the censored survival data will improve with an increase in sample size, the completeness of observations obtained at follow-up, as well as a (relatively) small number of cases lost to follow-up at the early phase of the study (Cutler & Ederer 1958). Censored survival data is more likely to reflect the truth (i.e. higher predictive validity) for long-term survival studies, when compared to studies of shorter duration (Stoll et al. 1999). However, too great a proportion of censored observations at the early phase of long-term studies are not desirable, as it tends to underestimate the chance of survival and results in a greater degree of standard error 15

Literature review

(Davies 1987). A large amount of censored data, arising from too short a study and/or the inclusion of new cases right up to the end-date of the study, also tend to underestimate the survival time of a treatment (Davies 1987).

There are two common approaches to survival analysis: the life-table method (actuarial approach) and the Kaplan-Meier approach (Kaplan & Meier 1958). Although both methods are similar and should converge with increasing number of observations made at shorter time intervals (Daya 2005), there are some important differences.

2.4.3

Life-table analysis (Actuarial approach)

Life-table analysis, or commonly known as an actuarial approach, is the computation of a life-table with the distribution of survival grouped into equal (and arbitrary) time intervals. The probability of survival is assumed to remain constant in between the recall intervals (Cutler & Ederer 1958).

To construct a life-table, the following information is recorded at each interval: number of cases that entered the respective interval; number of cases that are censored; and the number of cases that â&#x20AC;&#x153;have not survivedâ&#x20AC;?. A survival function is calculated for each interval based on the grouped survival information, resulting in a survival curve that only changes at the end of each interval (Sasieni 2005). Assumption has to be made on 16

Literature review

the event occurrence time for lost or censored observations that they occur at the midpoint of the corresponding time intervals (Daya 2005). This actuarial estimate would therefore be somewhat dependent on the length of the time intervals (Kaplan & Meier 1958).

When compared to the direct method, survival rate computed from a life-table method tend to result in lesser degree of sample variation, because each interval contains a larger number of samples. In dental studies, it has been shown to be a reliable and useful method to measure (dichotomous) treatment outcome over time (Thylstrup & Rรถlling 1975).

A fundamental difference exists in the data structures between the grouped survival data (as in life-table analysis) and the interval-censored data (see discussion below). Simply put, the survival-time intervals of any case within a grouped interval (life-table analysis) would be completely identical and non-overlapping, whereas those of the interval-censored data may overlap. In fact, and as a result, the statistical methods for grouped survival data are relatively simpler (Zhang & Sun 2010).

2.4.4

Kaplan-Meier product-limit estimator

Another method used for the calculation of the survival function is known as 17

Literature review

Kaplan-Meier product-limit estimator, a non-parametric statistical method which was first proposed by Kaplan and Meier in 1958. In this approach, a non-parametric estimate of the survival function is produced from survival data containing either the exact time of event or right-censored data (Tomita 2007). The data is said to be right-censored if the event does not occur or the patient drops out before the end-date; that is, it is unknown when the event will occur in the future (Lesaffre et al. 2005, Sasieni 2005, Wong 2005).

Kaplan-Meier analysis has been considered as a better approach than the direct method to assess the survival function where it enables the calculation of the survival probability of subject (or treatment) as a function of time (Balkenhol et al. 2007). Weiger et al. (1998) commented that Kaplan-Meier survival analysis may be a superior method for the evaluation of prognosis for root canal treatment.

With this approach, the estimation of the survival function does not depend on the grouping of survival data into some arbitrary lengths of time, but is re-calculated every time when an event of interest occurs, with the time recorded on a continuous scale. Thus, the survival curve derived from this approach changes whenever the event (e.g. failure) occurs. It has been commented that Kaplan-Meier estimator should be the statistical method of choice for studies where no regular examination time intervals 18

Literature review

were specified (Stoll et al. 2005).

With the Kaplan-Meier estimator, both the right-censored and interval-censored observations neither require a correction factor, nor the assumption that the actual event time had occurred in the mid-point between follow-ups, as is required in life-table analysis. However, if an event (e.g. development of post-treatment disease) had occurred and the patient failed to report to the study, the exact event time would become undetermined. Owing to the lack of sophisticated statistical method, an arbitrary value of time is assigned to the exact event time, which practice might lead to bias, error and misleading result (Cheung 2002, Lesaffre et al. 2005, Wong 2005). To enter for Kaplan-Meier analysis, some studies had taken the mid-point between the last two recalls (Cheung 2002), or made an estimation based on the geometric mean (equivalent to taking the midpoint of the corresponding intervals of event occurrence time between two consecutive visits, on logarithmic scales) as the actual event time (Cheung & Chan 2003, Wang et al. 2004). Although it is reasonable to assume that a better estimate of actual event time should be generated from regular reviews of short intervals, one should consider the ethical issues that might arise if the treated teeth were to be examined radiographically in every such recall (Wang et al. 2004).

Studies using a survival analysis method for first-time, non-surgical root canal treatment 19

Literature review

performed in a dental (teaching) hospital had been reported by Cheung (2002), Cheung and Chan (2003), and Dammaschke et al. (2003). These studies have used the Kaplan-Meier approach.

2.4.5

Interval censoring

In dentistry, the occurrence of the event of interest is often observed at a dental visit (be it planned or unplanned) – one can only conclude that the event (failure) occurred during the interval between two reviews. This is especially true, because most dental diseases (or failure of dental treatment) are asymptomatic on first presentation. One only knows that the true event time is greater than the last observation time when the event has not yet occurred, but less than or equal to the observation time when the condition was first diagnosed, giving rise to an interval that contains the true event time (Zhang & Sun 2010). With advances in computational approach, survival analysis can treat this time interval as the “event time”. An “interval censor” contains information on the (approximate time of) event occurrence, as well as the length of time between two consecutive observations. Such data takes into account the uncertainty as to the exact time the event occurs within an interval.

Statistical analysis of interval-censored data is much more complex and less well developed than their counterparts (with well-defined time points). Only few statistical 20

Literature review

models are currently available for analysis of such data (Lesaffre et al. 2005, Wong et al. 2005).

2.5 Factors affecting the outcome of primary root canal treatment Optimal treatment planning requires an accurate assessment of the outcome (of various treatment options), and this is dependent on the correct understanding of variables affecting the outcome of a treatment modality (Chugal et al. 2001). Although many studies have evaluated the influence of various factors on endodontic treatment outcome, it should be acknowledged that most factors influencing endodontic outcomes have been identified from non-randomized studies, and therefore have some degree of uncertainty associated with some of the factors showing a significant effect, such as technique of root filling.

2.5.1

Preoperative factors

Among all, the preoperative periapical status have been consistently shown to have a significant impact on the treatment outcome: the presence of periapical rarefaction will lower the chance of favourable healing (Seltzer et al. 1963, Kerekes & Tronstad 1979, Matsumoto et al. 1987, SjĂśgren et al. 1990, Friedman et al. 1995, Chugal et al. 2001, Hoskinson et al. 2002, Friedman et al. 2003, Farzaneh et al. 2004, Ă&#x2DC;rstavik et al. 2004, Imura et al. 2007, de Chevigny et al. 2008) or the survival of the treated teeth 21

Literature review

(Eckerbom et al. 1992, Cheung & Chan 2003, Dammaschke et al. 2003, Stoll et al. 2005). The success rate for those without preoperative periapical radiolucency (96% or more) is significantly greater than those with a radiolucent area (86%) (Sjรถgren et al. 1990).

Radiolucent lesions of a larger diameter (greater than 5 mm) have been implicated to result in a higher incidence of treatment failure (Weiger et al. 2000, Chugal et al. 2001, Hoskinson et al. 2002), although it has been argued that healing is a function of time and an outcome similar to smaller-sized lesions could be expected if these large lesions were allowed sufficient time for healing to take place (Sjรถgren et al. 1990, Friedman 2008).

Vital pulpectomy enjoys the best prognosis (Storms 1969, Friedman et al. 1995, Chugal et al. 2001, Hoskinson et al. 2002) and lengthier tooth survival than non-vital teeth (Stoll et al. 2005). This might be due to the fact that the root canal space of non-vital teeth is often infected (Kojima et al. 2004).

Teeth that have experienced preoperative pain have been reported to experience a lower chance of healing (Friedman et al. 1995) and length of survival (Stoll et al. 2005), although others claimined that the healing should not be affected (Pekruhn 1986, 22

Literature review

Kerekes & Tronstad 1979, SjĂśgren et al. 1990).

The presence of a preoperative sinus tract has been associated with poorer prognosis than cases without a sinus tract in teeth with a periapical lesion (Chugal et al. 2001). However, it was commented that the effect of the confounding factors, particularly the periapical lesion, would need to be better controlled to ascertain its true influence (Chugal et al. 2001).

Some studies have indicated the possibility of gender to exert an influence on treatment outcome, with females showing a higher chance of favourable healing than males (Chugal et al. 2001, Farzaneh et al. 2004). Age may also have a significant impact (Ă&#x2DC;rstavik et al. 2004). It has been shown that survival of root canal treated teeth decreases with increasing age (Caplan & Weintraub 1997, Mindiola et al. 2006).

Patients who are immuno-compromised and who suffer from diabetes pose a higher risk of persistent apical periodontitis than healthy individuals (Fouad & Burleson 2003, Segura-Egea et al. 2005, Friedman 2008). Diabetes and history of hypertension had been associated with a higher chance of tooth loss (Mindiola et al. 2006).

Single-rooted teeth appeared to enjoy a higher chance of favourable healing than 23

Literature review

multi-rooted teeth (Friedman et al. 1995, Friedman et al. 2003, Ă&#x2DC;rstavik et al. 2004, Farzaneh et al. 2004, de Chevigny et al. 2008), a possible reflection of the inherent anatomical complexity and increased difficulty faced by the clinicians to effectively disinfect the root canal system of multi-rooted teeth, as well as the proportionate increase in risk of persistent disease with increasing number of roots.

Maxillary and mandibular canines, as well as the maxillary second premolars had been associated with a higher chance of favourable healing (Kerekes & Tronstad 1979); while the reverse was true for maxillary molars and mandibular incisors (Lugi-Pegurier et al. 2002). Premolars and molars had been reported to survive for shorter time after root canal treatment (Meeuwissen & Eschen 1983, Eckerbom et al. 1992), particularly the mandibular molars (Vire 1991, Cheung 2002, Zadik et al. 2008) and all second molars (Aquilino & Caplan 2002, Caplan et al. 2002). Others had shown that mandibular premolars and all anterior teeth enjoyed a better chance of survival (Cheung & Chan 2003). In other words, anterior teeth and premolars enjoy lengthier survival than molars (Ng et al. 2010). It was suggested that heavy occlusal stresses, accessibility and technical difficulties in treating molars may be the causes of the problem (Aquilino & Caplan 2002).

Literature review

2.5.2

Intraoperative factors

Some studies have found that the apical extent of the root canal filling seems to be an important prognostic factor. Root canal filling extended to within 2 mm of the radiographic apex have frequently been associated with favourable periapical healing (Hommez et al. 2002, Lupi-Pegurier et al. 2002) and a higher chance of tooth survival (Eckerbom et al. 1992, Dammaschke et al. 2003, Stoll et al. 2005). Sjögren et al. (1990) demonstrated that such teeth enjoyed the highest success rate of 94% (after a mean observation period of 8 to 10 years, compared with short (68%) and over-extended filling (76%). Kojima et al. (2004) performed a meta-analysis and concluded that the root filling should extend to within 2mm of the radiographic apex to give the best prognosis, a conclusion supported by another systematic review reported recently (Ng et al. 2008). Extrusion of root filling materials beyond the root apex in teeth with a preoperative periapical radiolucency have been associated with less favourable healing (Ørstavik et al. 2004), possibly because the over-instrumentation has facilitated the passage of infected debris into the periapical area (Ørstavik et al. 2004, Friedman 2008).

Root canal treatment with homogenously condensed root canal fillings has a positive influence on the treatment outcome (Kerekes & Tronstad 1979, Sjögren et al. 1990, Kirkevang et al. 2000, Hommez et al. 2002, Lupi-Pegurier et al. 2002, Ørstavik et al. 25

Literature review

2004) and survival (Cheung & Chan 2003, Stoll et al. 2005). Homogeneity of root canal fillings are often assessed from the radiographs, and the limitation of this two-dimensional image should be borne in mind, owing to the impossibilities for homogeneity to be fully assessed in all planes (Wang et al. 2004, Stoll et al. 2005).

The presence of cultivable bacteria prior to root canal obturation has been shown to have a negative impact on treatment outcome. Engstrรถm et al. (1964) reported that a success rate of 76% for teeth with a positive bacteriological culture, compared with 89% for those that were tested negative. A similar, statistically significant difference in the success rate was also reported: negative culture 94% versus positive culture 68% (Sjรถgren et al. 1997).

Intraoperative complications, or procedural errors, may adversely affect the chance of healing (Friedman et al. 1995, Imura et al. 2007, de Chevigny et al. 2008). Presumably, procedural errors (such as separated instruments, canal transportation and perforation) can impede thorough disinfection or promote endodontic-periodontal communications. Caution should therefore be exercised to avoid iatrogenic mishaps (de Chevigny et al. 2008).

Operator skill is important in root canal treatment. It has been shown that primary root 26

Literature review

canal treatment delivered by endodontic specialists fares a significantly higher chance of tooth survival than those carried out by general dental practitioners (Alley et al. 2004), an observation supported by a recent systematic review (Ng et al. 2010). In contrast, others did not find this factor to be so important (Stoll et al. 2005). Notwithstanding this, it is noteworthy that endodontists tend to treat more complex cases than general dental practitioners (Lazarski et al. 2001) and, perhaps, this should be considered when one wishes to make comparison on treatment outcome between these two groups.

Systematic reviews by means of meta-analysis have shown that the success rate of single-visit treatment is not significantly different from multiple-visit treatment approach, and the former tended to enjoy a slightly more favourable outcome (Sathorn et al. 2005, Figini et al. 2008). Patients who received single-visit treatment appeared to experience a somewhat higher frequency of postoperative swelling and an increased need of taking analgesics for pain relief; these suggested a greater degree of postoperative inflammatory response after single-visit approach (Figini et al. 2008).

Calcium hydroxide is the most commonly used inter-appointment intracanal medicament. Studies have shown that non-setting calcium hydroxide can effectively disinfect the root canal system after chemo-mechanical instrumentation during the 27

Literature review

inter-appointment period (Byström et al. 1985, Sjögren et al. 1991); this should result in a higher chance of healing (Trope et al. 1999, Cheung 2002). However, some studies have challenged the beneficial effect of calcium hydroxide as intracanal medicament, due to resistant microbial strains that might be encountered in the infected root canal system (Weiger et al. 2000, Peters & Wesselink 2002).

2.5.3

Postoperative factors

Survival of root canal treated teeth is not solely dictated by the status of endodontic health (Vire 1991). Other reasons such as prosthetic failure, periodontal complication and tooth fracture (Meeuwissen & Eschen 1983, Vire 1991, Chen et al. 2008) could compromise the long-term survival of such teeth. Carious destruction that rendered a tooth non-restorable had been implicated as the main reason for extraction of root canal treated teeth (Zadik et al. 2008). However, root canal treated teeth tend to show more “early failures” if they were caused by endodontically-related factors (Vire 1991). In fact, it has been suggested that early failures usually reflect the ineffectiveness in root canal disinfection, whereas late failures are often the result of recontamination of root canal system through coronal micro-leakage caused by other failures over time (Saunders & Saunders 1994, Ørstavik 1996).

Coronal cuspal coverage has been considered to be the single, most important 28

Literature review

prognostic factors for the long-term success for root canal treated posterior teeth (Sorensen & Martinoff 1984a). Placement of a cuspal coverage restoration after root canal treatment appeared to improve the longevity of the treated tooth (Tan 2003). The provision of crowns has been shown to substantially improve the long-term survival of root canal treated teeth (Meeuwissen & Eschen 1983, Vire 1991, Aquilino & Caplan 2002, Caplan et al. 2002, Cheung & Chan 2003, Dammaschke et al. 2003, Stavropoulou et al. 2007, Ng et al. 2010), particularly for molars (Nagasiri & Chitmongkolsuk 2005). Most of the extracted root canal treated teeth had been reported to be without a cuspal coverage restoration (Salehrabi & Rotstein 2004). Aquilino and Caplan (2002) reported that root canal treated teeth without a crown were six times more likely to become extracted than crowned teeth. Root canal treated teeth also tend to be more susceptible to unfavourable, subgingival tooth fracture; therefore it is critical to consider placement of a cuspal coverage restoration to improve their long-term survival (Fennis et al. 2002).

The use of parallel-sided posts when restoring these teeth seems to be associated with a higher success rate, compared with tapered posts (Sorensen & Martinoff 1984b). It was also found that threaded posts suffered an extremely high incidence of failure due largely to vertical root fracture (Sorensen & Martinoff 1984a), resulting in greater incidence of tooth loss (Eckerbom et al. 1992). These failures are related to the structural breakdown of the restored tooth as a functional unit of the dentition. When 29

Literature review

periapical healing is concerned, studies have reported that placement of post per se did not actually affect the chance of healing (Kvist et al. 1989, Hommez et al. 2002, Friedman 2008), provided at least 3 mm of apical seal was present and intact (Kvist et al. 1989).

Cast posts and cores, per se, have a considerably better long-term survival (in terms of retention in tooth and structural integrity) than others (Creugers et al. 1993, Balkenhol et al. 2007), but experienced poorer prognosis when used in teeth serving as abutments for a removable partial denture (RPD) (Balkenhol et al. 2007). Despite their superiority in strength and fracture resistance, cast posts and cores demonstrated a greater risk of catastrophic (i.e. non-restorable) root fracture at failure, which adversely affected the chance of tooth survival (Martinez-Insua et al. 1998, Lazarski et al. 2001). Fiber-reinforced posts appeared to be more favourable in this respect, because failure did not tend to cause non-restorable tooth fracture (Newman et al. 2003). The remaining tooth structure is thus â&#x20AC;&#x153;protectedâ&#x20AC;? (Martinez-Insua et al. 1998, Newman et al. 2003) with an improved chance of survival.

Majority of the studies agreed that the best prognosis may be expected when both the coronal restoration and root canal filling are of a sound technical quality (Ray & Trope 1995, Tronstad et al. 2000, Kirkevang et al. 2000, Hommez et al. 2002, Iqbal et al. 30

Literature review

2003). Some studies even claimed that coronal leakage was the major causative factor in unfavourable treatment outcome (Ray & Trope 1995, Kirkevang et al. 2000). Root canal treated teeth restored with an inadequate or without a coronal restoration have been frequently associated histologically with apical periodontitis (Barthel et al. 2004) and lower chance of healing for primary root canal treatment (Imura et al. 2007).

Retrospective studies conducted by Ray and Trope (1995), and Kirkevang et al. (2000) based on radiographic assessment alone concluded that the quality of coronal restoration appeared to be more important than the quality of root filling in determining treatment outcome. Tronstad et al. (2000) and Segura-Egea et al. (2004) repeated the studies in different populations and found that the quality of root filling was equally, if not more important than the coronal seal in restoring and maintaining periapical health. Ricucci et al. (2000) examined root canal treated teeth with root filling exposed to the oral environment due to deep caries or displaced restoration (that were extracted due to other reasons) and concluded that the clinical importance of coronal leakage may have been unduly stressed.

Regardless of the conclusion, the profession worldwide now recognizes the importance of a coronal seal in modifying the course of periapical healing. A delay in placing the permanent restoration for root canal treated teeth would increase the susceptibility to 31

Literature review

coronal leakage. In other words, prompt and proper selection of permanent restoration would ensure a favourable outcome following root canal obturation (Safavi et al. 1987) and to prolong their survival (Mindiola et al. 2006). The need to provide a good-quality coronal restoration without delay cannot be overemphasized (Saunders & Saunders 1994).

It has been shown that teeth restored with composite resin were associated with a significantly higher incidence of persistent apical periodontits than those restored with amalgam (Hommez et al. 2002). However, others have shown that root canal treated molar without cuspal overlay appeared to survive longer when direct composite was used compared to amalgam and reinforced zinc oxide and eugenol restorations, at least in the short-term (Nagasiri & Chitmongkolsuk 2005). Root canal treated premolars restored with composite and fiber posts were also found to be more effective than amalgam in protecting the tooth from root fractures (Mannocci et al. 2005). Despite so, root canal treated teeth restored with direct restorations (composite resin, amalgam, cements), in general, appeared to survive quite well but only for the short term. Their long term survival remains poorer when compared to those restored with crowns (Stavropoulou et al. 2007).

The function of the tooth seems to have an effect on the longevity of root canal 32

Literature review

treatment. It has been reported that root canal treated teeth serving as an abutment for fixed and removable partial dentures had a significantly lower success rate than those restored with a single crown, with removable abutment being the worst (Sorensen & Martinoff 1985), possibly due to increased functional stresses (Ă&#x2DC;rstavik et al. 2004). It has been commented that the use of root canal treated teeth as fixed prosthesis abutment should be avoided for improving the survival of such teeth (Ng et al. 2010). Occlusal trauma and absence of proximal contacts (i.e. lone standing tooth) had also been associated with an increased chance of treatment failure (Matsumoto et al. 1987).

Root canal treated teeth with both missing proximal contacts have been strongly associated with a greater chance of losing that tooth (Caplan & Weintraub 1997). Such teeth with one or both proximal contacts missing had a lower survival rates, some three times lower than for those with both neighbouring teeth present (Caplan et al. 2002). Apart from an increased occlusal load (possible as a result of shared occlusal loading with adjacent teeth), it was suggested that these teeth were more likely to serve as prosthetic abutment to replace the missing neighbour(s). The presence of dental prosthesis might lead to difficulty with plaque control, adverse periodontal complication, caries or tooth fracture (Caplan ,Weintraub 1997).

2.5.4

Summary 33

Literature review

In conclusion, factors that contribute positively to healing after primary root canal treatment were: pre-operative absence of periapical radiolucency, root filling with no voids, root filling extending to 2mm within the radiographic apex and satisfactory coronal restoration (Friedman & Mor 2004, Ng et al. 2008). Factors that influence the chance of tooth survival were: definitive restoration with crown, maintenance of both proximal contacts, tooth not serving as an abutment and non-molar teeth (Ng et al. 2010). However, most of the conclusions regarding factors influencing outcomes were based on retrospective, non-randomized studies with low recall, and hence would probably need to be accepted with caution.

Materials and methods

3. Materials and methods

3.1 Sample A total sample of 999 teeth which represent a stratified random sample of patients treated in a dental teaching hospital, from three previous endodontic studies (Cheung 2002, Cheung & Chan 2003, and one unpublished) were included in this study (Table 3.1). The sample population constituted about one-tenth of all teeth treated between January 1981 and December 1994. That is, the root canal treatment had been provided more than 15 years ago.

Table 3.1 Summary of the sample population Sample

Sampling method

No. of patients

No. of teeth

Cheung and Chan (2003)

Random (stratified)

568

607

Cheung (2002)

Systematic

248

250

142

(according to record number) Internal Survey

Systematic

(extension of Cheung (2002)) Total

950

(8)*

999

*Note: ( ) indicated number of patients recruited concomitantly across the studies. The total number of teeth did not include those duplicates, and were counted as one occurrence only.

Materials and methods

3.2 Pilot study A random selection of 10 patients (i.e. 10 teeth) from the sample population was recalled to estimate the response rate, time required for each patient, and the validity of the data collection form.

3.2.1 Observations In the pilot study, 7 out of 10 patients attended the recall. On average, 10 to 15 minutes were required to review each patient. Operation with multiple chairs worked well to reduce time delay and to enhance the flow between seeing patients.

A few issues were observed while extracting information from the patientsâ&#x20AC;&#x2122; treatment records. Information about parafunctional habit and pre-operative periodontal probing depth(s) of the treated teeth were often not documented. Thus, these items were removed from the data collection form. The restoration type, its function and occlusion status of some teeth presented at the review had changed from those previously recorded. Data collection form was then improvised to accommodate information on these changes over time (Appendix 1).

Some radiographs were found to be either missing from the treatment record or of a poor quality due to technical or processing faults. To obtain the necessary information, 36

Materials and methods

all the supplemental radiographs available in the record were screened for their usefulness. Written record of the relevant radiographic findings often had to be referred to in conjunction with, or even in the absence of some radiographs.

3.3 Collection of data A data collection form was used to collate information about the patientsâ&#x20AC;&#x2122; personal particulars and medical history, as well as the pre-operative status, treatment details and review status of the treated teeth (Appendix 1). Information was extracted from the treatment records of findings from clinical and radiographic examination.

When a sampled tooth has been retreated or extracted, the date for treatment was recorded. Such information was obtained from the patientâ&#x20AC;&#x2122;s record if the treatment had been performed in PPDH, or by questioning the patient over the telephone for relevant details. Attempt was made to contact the dental practitioner who provided the (remedial) treatment for the necessary information, if required, after obtaining consent from the patient for information release (Appendix 2). Those who received further endodontic surgery as part of the primary treatment plan, was also excluded.

Of all samples, 277 teeth had been recorded from the previous studies (Cheung 2002, Cheung & Chan 2003, and one unpublished) as either been extracted or retreated. In 37

Materials and methods

addition, 32 teeth had shown clinical signs or symptoms of failure without receiving further treatment. The primary treatment of these 309 teeth was deemed to have â&#x20AC;&#x153;failedâ&#x20AC;?. The remaining 690 teeth in 653 patients that had neither shown any clinical signs or symptoms at the recall, nor undergone extraction or retreatment were identified (Table 3.2).

Table 3.2 Number of samples needed to be reviewed No. of patients

No. of teeth

Total samples

950

999

Extracted or retreated

266

277

Clinical signs or symptoms

Samples needed to be reviewed

653

690

These 653 patients were invited over the telephone to return for a review appointment. All the patients who attended the review were examined by the author. These patients were assessed for the presence of any clinical signs or symptoms, which included spontaneous pain, swelling, sinus tract and temperature sensitivity, as well as tenderness to palpation, percussion or pressure. The structural integrity of the selected tooth and its coronal restoration were examined for (recurrent) caries, fracture, presence of any marginal opening and occlusal interference.

Materials and methods

Parelleling-technique periapical radiographs were taken using either one of the two methods: (i) Conventional radiography technique â&#x20AC;&#x201C; a size 2 dental X-ray film (Insight, Eastman Kodak, Rochester, NY) with the use of a positioning device (XCP holder, Rinn, Elgin, IL, USA), which was developed in an automated processing machine (Velopex Intra XE, Medivance Instruments, London, United Kingdom); (ii) Digital radiography technique â&#x20AC;&#x201C; an intraoral sensor (Gendex Visualix HDI, Gendex, Milan, Italy) with a positioning device (Endo Bite Senso, Kerr, Sybron Dental Specialties, Bioggio, Switzerland) was used to produce direct digital radiographic images.

It was confirmed that ethics approval was not required for this study because clinical and radiographic procedures were carried out in the same manner as for routine post-operative review, without exposing patients recalled to any unnecessary or additional risk(s).

For those patients who failed or were unwilling to attend the recall, as well as those who were unable to be contacted, but the sampled teeth had been reviewed on at least one occasion more than 4 years after the primary treatment, the clinical and radiographic status was evaluated based on the clinical findings and radiographs from the most recent review(s).

Materials and methods

3.4 Assessment criteria All the conventional radiographic images were evaluated over a desktop light box aided by a 2x magnification film viewer (X-ray Viewer, Directa AB, Upplands VĂ¤sby, Sweden) that would exclude the extraneous light. Digital radiography images were evaluated on a computer screen in a room with dimmed light. Contrast and brightness of the digital images were adjusted, if required, to aid visualization of image details.

All radiographs were evaluated by the author. One-fifth of the samples were re-evaluated by the author after 4 weeks. Any uncertain cases of the sample were evaluated by a second examiner independently. Any disagreement on the findings was discussed between the two examiners. If an agreement could not be reached, a third examiner (an endodontist) was invited to evaluate the radiographs in a hope to resolve the disagreement. Any disagreeable cases that remained thereafter were excluded from the study (Molven et al. 2002). The examiners were calibrated beforehand.

Radiographs were evaluated for: (i) periapical status (i.e. presence of periapical rarefaction and its size); (ii) quality of the root filling (i.e. extent, presence of voids, profile); (iii) seal apical to the post (if applicable), and (iv) marginal integrity of the coronal restoration and (recurrent) caries.

Materials and methods

3.4.1 Periapical status Given that all the treatment had been provided for more than fours years before this study, the periapical status of the selected teeth was categorized using a strict criteria (Strindberg 1956) as either: (i) no periapical rarefaction (healed); (ii) widened PDL space, which was considered to be associated with favorable outcome (Halse & Molven 2004); or (iii) presence of periapical rarefaction (post-treatment disease).

Size of the periapical lesion was measured in two dimensions: vertical (L) and horizontal (W) dimesion. Vertical dimension (L) was measured across the greatest diameter of the radiolucent area on an imaginary line that was an extension of the longitudinal axis of the apical part of the root (not the main trunk) (Figure 3.1). Horizontal dimension (W) was measured in a similar manner but along another imaginary axis drawn perpendicular to the longitudinal imaginary line (Figure 3.1). In the presence of more than one focal area of rarefaction (as is commonly associated with multi-rooted teeth), the one presented with the largest radiolucent area was selected for evaluation in this study.

Materials and methods

Figure 3.1 Schematic illustration on how the size of a periapical lesion was measured along the imaginary lines in two dimensions (W=horizontal, red line; L = vertical, blue line). Note that L was measured from point a (instead of point x or the root apex).

3.4.2 Pre-operative pulp vitality Pre-operative pulpal status was determined mainly from the result of pulp sensibility test(s), commonly in the form of electric pulp or cold test, as was entered in the patientâ&#x20AC;&#x2122;s record. In addition and when pulp test had not been performed, any pre-operative clinical signs and symptoms, presence of periapical rarefaction, as well as the clinical findings during treatment would be taken into consideration.

Materials and methods

3.4.3 Treatment outcome When there was an absence of clinical signs and symptoms, as well as periapical radiolucency, the selected tooth was deemed to have completely healed (H). Teeth that had been extracted, retreated (surgically or nonsurgically), or associated with any clinical signs, symptoms or periapical radiolucency were categorized as post-treatment disease (D). For the purpose of this study, those that did not present with any clinical signs and symptoms, regardless of their radiographic periapical status, were referred to as functional retention (F). Reasons for extractions of teeth after primary endodontic treatment had also been evaluated. Arrangement was made for patients who attended the recall and were found to require further treatment as a result of the clinical examination.

3.5 Statistical analysis In endodontics, outcomes of interest include the onset of post-treatment disease and loss of functional retention. For the latter, diagnosis would be easy, as patient would make a complaint when clinical symptoms have developed. On the other hand, post-treatment disease usually develops over time and may not be observed until a diagnosis is made on the basis of clinical and radiographic findings at a recall, or until acute symptoms or catastrophes such as tooth fracture set in (Cheung 2002, Cheung & Chan 2003). This means that the actual date of event (onset of post-treatment disease) would have occurred some time before the date of diagnosis but after the date of last recall showing 43

Materials and methods

no occurrence of such event (Cheung 2002, Cheung & Chan 2003).

For post-treatment disease, the actual date of disease onset would have occurred between the last known recorded date when such condition was not observed (denoted as Dnodisease), and the date when it was first diagnosed (denoted as Ddisease). In other words, the actual date of post-treatment disease lies between Dnodisease and Ddisease (Figure 3.2). The same applies to the measurement of the survival time of a tooth in functional retention, as it was merely known that the actual date of loss of functional retention lies between the last known date that a treated tooth remained in functional retention (denoted as Dfunction) and the date when the loss of functional retention was observed (denoted as Dnofunction), i.e. between Dfunction and Dnofunction (Figure 3.2). Notice that Ddisease does not necessarily coincide with Dnofunction, especially for asymptomatic teeth.

Materials and methods

(a)

(b)

Dnodisease

Ddisease

Dfunction

Dnofunction

Time

Figure 3.2 Schematic diagrams illustrating the survival time of a tooth from date of obturation (D0) leading up to: (a) the development of post-treatment disease; (b) loss of functional retention. Note that the actual date of post-treatment disease and loss of functional retention should lie between: (a) Dnodisease-Ddisease; (b) Dfunction-Dnofunction.

In this context, a review appointment served to update the status of the treated teeth, confirming Ddisease or Dnofunction, if such event was noted, or resetting the period up to this new date of examination, i.e. establishing new dates for Dnodisease or Dfunction. In the present analysis, date of obturation (D0) was used as the origin of time measurement (Figure 3.2).

The survival function of the treated teeth was plotted against the calculated date of post-treatment disease and loss of functional retention, using two methods: (1) Kaplan-Meier (K-M) product limit estimators (SPSS 17 Statistics for Windows); (2)

Materials and methods

Weibull accelerated failure time model (SAS version 9.2) for interval-censored data (Lindsey & Ryan 1998).

As results subjected to survival analysis using the Kaplan-Meier estimator requires the entry of a known event date, it is necessary to insert an estimated date of post-treatment disease and loss of functional retention by using various estimates for the time interval from Dnodisease - Ddisease and from Dfunction - Dnofunction, respectively. Various time estimates were used in the present analysis: (i) one-quarter point (T1); (ii) half-way point (T2); (iii) three-quarter point (T3); (iv) Ddisease or Dno function (T4), and (v) geometric mean (T5) (Wang et al. 2004), for the calculation of the Kaplan-Meier cumulative survival probability.

Cheung (2002) pointed out that an appropriate method for making such estimation should be devised. It has been indicated that an interval-censored survival time can be estimated using Weibull accelerated failure time model (Lindsey & Ryan 1998). Therefore, survival distribution curves of various linear estimates in Kaplan-Meier estimators were compared against the survival curve using this interval-censored method for similarities in trend, with the latter method being hypothesized as the benchmark for comparison in this study.

Materials and methods

Factors that were taken into consideration are listed below (Table 3.3). Differences among subgroups of each factor were examined using the log-rank test. In order to examine the possibility of confounding or interdependence of factors, the contribution of factors found to be significant (P < 0.05) in the data set of various linear estimates in Kaplan-Meier estimators (i.e. C_T1 to C_T5, R_T1 to R_T5) was examined further by Cox Regression analysis (SPSS 17 Statistics for Windows); and the contribution of factors found to be significant in the interval-censored data set were examined further by Weibull accelerated failure time model (PROC LIFEREG, SAS version 9.2), based on hazard ratio (95% CI). The selection of significant factors was based on backward stepwise method in both analytical approaches.

This study only considered single-level modeling in order to eliminate the possible systemic influence associated with the treatment of multiple teeth for a patient. Thus, only one tooth were randomly selected and included in statistical analysis for each patient.

Materials and methods Table 3.3 List of socio-demographic, pre-operative, intra-operative and post-operative factors and their subgroups examined. Socio-demographic

Pre-operative

Age (in years) < 25 25-50 > 50

Health Healthy Known systemic disease/ immunosuppressive medication/history of radiotherapy in the head and neck region

Gender Male Female

Tooth location Maxilla Mandible Tooth type Anteriors Premolars Molars Pre-operative signs +/ symptoms Absent Present Preoperative pulpal status Non-vital Vital Pre-operative periapical status No lesion < 5mm > 5mm

Intra-operative

Post-operative

Operator status Undergraduate students Qualified dentists

Function Presence of both proximal contacts Presence of < one proximal contact Cantilever/fixed-fixed/ fixed-movable bridge abutment Denture/overdenture abutment

Number of visits 1 visit 2 visits 3 visits > 4 visits

Occlusion No opposing teeth or opposing denture Opposing natural teeth Opposing fixed prosthesis

Acute flare-up during treatment Absent Present

Post

Extent of root filling Flush (0-2mm within radiographic apex) Short (>2mm from radiographic apex) Overextension (of GP or silver point)

Type of final restoration Amalgam Composite resin or GI Indirect cuspal coverage restoration Others

Absent Present

Extrusion of root filling (incl. sealant) Absent Present

Homogeneity of root filling No apparent voids Voids in apical third Voids in middle or coronal third

Materials and methods Time to the placement of final restoration < 2 months > 2-10 months > 10 months Condition of the tooth and its restoration (based on the detection of marginal discrepancy, fracture and/or recurrent caries) Satisfactory Unsatisfactory

Root filling profile Follow original canal form Sign(s) of ledging, transportation, deviation, broken instrument or perforation

Results

4. Results

4.1 Sample Of the 999 teeth in 950 patients, 108 teeth in 59 patients were excluded from this study due to various reasons as presented in Table 4.1. This resulted in 891 cases being included for statistical analysis using Kaplan-Meier estimator (Table 4.2).

Table 4.1 Number and reasons of cases excluded from statistical analysis in general. Reasons for exclusion Mismatch of cases with patientsâ&#x20AC;&#x2122;

No. of cases

Remarks

treatment records

Periapical surgery planned as part of

primary RCT

Never returned for any review

Re-treatment cases

Right censoring <4 years:

Last available review date <4 years without any observation of post-treatment disease or loss of functional retention; and patient never returned again

Multiple teeth treated for a patient

Only one tooth, randomly selected, was included

Incomplete review information,

including uncertain healing

Total number of cases excluded

108

Results Table 4.2 Number of cases included for statistical analysis using Kaplan-Meier (K-M) estimators. Number of teeth

Number of patients

Initial samples

999

950

Excluded (in general; see Table 4.1)

108

Included

891

Owing to the inherent limitation of the interval censoring (Weibull accelerated failure time) model used in this study, any cases showing post-treatment disease or loss of functional retention at the first review after the completion of treatment could not be analyzed. In other words, samples with only data available on D0 to Ddisease or Dnofunction without any information on D0 to Dnodisease or Dfunction could not be used for analysis using this model (Figure 3.2). This necessitated exclusion of further samples which fell into this category (Table 4.3). Thus, the interval-censored data set contained a total of 719 and 818 samples for assessing the outcome of complete healing (H) and functional retention (F), respectively.

Table 4.3 Number of cases included in interval-censored data set for statistical analysis using Weibull accelerated failure time model in assessing complete healing (H) and functional retention (F) outcome. Complete healing (H)

Functional retention (F)

999

In general (see Table 4.1)

108

Unfit for analysis

172

719

818

Total Initial samples Excluded

Included

Results

4.2

Survival outcome of healing and functional retention

4.2.1 Median and mean survival time As far as healing was concerned, median and mean survival time of treated teeth before the onset of post-treatment disease ranged from 103 to 187 months and 151 to 169 months, respectively, when measured by an interval censor and Kaplan-Meier using different linear estimates (Table 4.4).

Table 4.4 Medians and means for survival time (in months) of treated teeth with complete healing (H) measured by an interval censor and Kaplan-Meier using various linear estimates. Linear estimates*

Median

Mean (SD)

Interval-censored

187

n/a

H_T1

103

151 (4.79)

H_T2

119

156 (4.57)

H_T3

137

162 (4.33)

H_T4

155

169 (4.21)

H_T5

113

151 (4.78)

*Note: Abbreviations of survival outcome of treated teeth with complete healing (H) measured by various linear estimates between the last known recorded date when post-treatment disease was not observed (denoted as Dnodisease), and the date when it was first diagnosed (denoted as Ddisease). Dnodisease â&#x20AC;&#x201C; Ddisease

Abbreviations

One-quarter point

H_T1

Half-way point

H_T2

Three-quarter point

H_T3

Ddisease

H_T4

Geometric mean

H_T5

Results

The median and mean survival time of these teeth in functional retention was considerably greater than those with complete healing, ranging from 234 to 288 months and 198 to 205 months, respectively (Table 4.5).

Table 4.5 Medians and means for survival time (in months) of treated teeth in functional retention (F) measured by an interval censor and Kaplan-Meier using various linear estimates. Linear estimates*

Median

Mean (SD)

Interval-censored

288

n/a

F_T1

252

198 (4.89)

F_T2

241

200 (4.79)

F_T3

234

202 (4.69)

F_T4

242

205 (4.61)

F_T5

237

199 (4.91)

*Note: Abbreviations of survival outcome of treated teeth in functional retention (F) measured by various linear estimates between the last known recorded date that a treated tooth remained in functional retention (denoted as Dfunction) and the date when loss of functional retention was observed (denoted as Dnofunction). Dfunction â&#x20AC;&#x201C; Dnofunction

Abbreviations

One-quarter point

F_T1

Half-way point

F_T2

Three-quarter point

F_T3

Dnofunction

F_T4

Geometric mean

F_T5

4.2.2

Survival curves

When survival curves of both outcomes were examined, it was observed that survival function declined in a non-linear fashion with time (Figure 4.1 and 4.2). An initial rapid drop that appeared to slow down with longer observation time was consistently identified across all curves. Among these curves, one generated from one-quarter point (T1) and geometric mean (T5) seemed to show the most rapid drop initially up to 53

Results

approximately 40 months, and slowed down thereafter; whereas those generated by Ddisease / Dnofunction (T4) and interval censor seemed to show lesser extent of such tendency, compared to others (Figures 4.1 and 4.2).

Results

In healing outcome, H_T4 curve closely approximated that of interval-censored curve up to approximately 120 months. After 280 months, H_T1 and H_T5 curves showed the tendency of closer approximation to the interval-censored curve (Figure 4.1). These trends remained more or less similar in the survival curves generated for functional retention outcome (Figure 4.2). It was apparent that F_T4 showed closer approximation to the interval-censored curve in the early phase, and such relationship shifted to F_T1 and F_T5 in the later phase at longer observation time.

Comparison between the survival curves generated for both outcomes using Kaplan-Meier estimators showed that the curves from one quarter point (T1) and geometric mean (T5) closely approximated each other throughout the entire period of observation (Figures 4.1 and 4.2). In general, more discrepancies between various linear estimates were identified in assessing the healing outcome, while such discrepancies were not as marked in functional retention outcome. All the curves gradually converged and cross over each other at approximately 200-250 months, and diverged thereafter (Figures 4.1 and 4.2).

4.3 Factors affecting the outcome Overall, there were 21 covariables being examined. They were categorized as socio-demographic, pre-operative, intra-operative and post-operative covariables. Their 57

Results

respective distributions are detailed in Tables 4.6, 4.7, 4.8 and 4.9.

Table 4.6 Distribution of socio-demographic covariables Covariables Age (in years) < 25 25-50 > 50 Gender Male Female

Percent

27.8% 50.1% 22.1%

248 446 197

40.2% 59.8%

358 533

Table 4.7 Distribution of pre-operative covariables Covariables

Percent

67.3% 32.7%

582 283

Tooth location Maxilla Mandible

57.7% 42.3%

514 377

Tooth type Anteriors Premolars Molars

37.7% 30.2% 32.1%

336 269 286

Pre-operative signs +/ symptoms Absent Present

45.0% 55.0%

401 490

Preoperative pulpal status Non-vital Vital

65.5% 34.5%

549 289

Pre-operative periapical status No lesion < 5mm > 5mm

58.1% 29.9% 12.0%

518 266 107

Health Healthy Known systemic disease/ immunosuppressive medication/history of radiotherapy in the head and neck region

No. of missing value 26

Results Table 4.8 Distribution of intra-operative covariables Covariables Operator status Undergraduate students Qualified dentists

Percent

70.7% 29.3%

630 261

Number of visits 1 visit 2 visits 3 visits > 4 visits

3.1% 33.8% 34.0% 29.1%

28 301 303 259

Acute flare-up during treatment Absent Present

93.6% 6.4%

794 54

Extent of root filling Flush (0-2mm short of radiographic apex) Short (>2mm short of radiographic apex) Overextension (of GP or silver point)

77.5% 12.3% 10.2%

676 107 89

Extrusion of root filling (incl. sealant) Absent Present

84.2% 15.8%

722 135

Homogeneity of root filling No apparent voids Voids in apical third Voids in middle or coronal third

48.8% 28.6% 22.6%

432 253 200

82.8% 18.2%

723 161

Percent

65.8% 14.6% 7.8%

577 128 68

11.8%

104

8.8% 85.3% 5.9%

76 735 51

38.8% 61.2%

344 543

22.7% 18.2% 57.3%

189 151 476

Root filling profile Follow original canal form Sign(s) of ledging, transportation, deviation, broken instrument or perforation

No. of missing value 0

43 (single-visit treatment cases inclusive) 19

Table 4.9 Distribution of post-operative covariables Covariables Function Presence of both proximal contacts Presence of < one proximal contact Cantilever/fixed-fixed/ fixed-movable bridge abutment Denture/overdenture abutment Occlusion No opposing teeth or opposing denture Opposing natural teeth Opposing fixed prosthesis

No. of missing value 14

Post

4 Absent Present

Type of final restoration Amalgam Composite resin or GI Indirect cuspal coverage restoration

Results Others

1.8%

Time to the placement of final restoration < 2 months > 2-10 months > 10 months

38.5% 40.6% 20.9%

270 284 146

Condition of the tooth and its restoration Satisfactory Unsatisfactory

76.3% 23.7%

680 211

191

Among these 21 covariables, 18 were included for further analysis as they were found to be significant (P < 0.05) when tested individually in either interval censoring method or Kaplan-Meier estimators using any linear estimates (T1 to T5; see Table 4.4 and 4.5), or both. These significant covariables are listed in Table 4.10.

Table 4.10 List of covariables that were found to be significant (P < 0.05) after analysis with interval censoring method or Kaplan-Meier estimators using any linear time estimates. Socio-demographical

Pre-operative

Intra-operative

Post-operative

Age

Health

Operator

Post

Gender

Tooth type

Function

Type of final restoration

Pre-operative pulpal

Occlusion

Time to the placement of

status Pre-operative periapical status

Number of visits Extent of root filling Extrusion of root filling

restoration Condition of the tooth and its restoration

(incl. sealant) Homogeneity of root filling Root filling profile

The contribution of these 18 covariables were examined further by Weibull accelerated failure time model (PROC LIFEBERG, SAS version 9.2) for interval-censored data set, 60

Results

and Cox regression analysis (SPSS 17 Statistics for Windows) for Kaplan-Meier estimator data set, based on backward stepwise selection method. The covariables found to be significant (P < 0.05) for healing and functional retention outcome in the first run of analysis for their respective outcome measure were selected. The analysis was rerun with only these selected covariables included to increase the number of samples considered by the final statistical models. The resultant covariables found to be significant (P < 0.05) after the rerun are listed in Tables 4.11 and 4.12, respectively.

Table 4.11 Result of analysis by Weibull accelerated failure time model (interval-censored) and Cox regression analysis for healing ou Covariables

Age <25 years 25-50 years >50 years* Post absent present* Tooth type anteriors premolars molars* Pre-operative periapical status no lesion < 5mm > 5mm* Occlusion non-opposing/opposing (denture) opposing (natural teeth) opposing (fixed prosthesis)* Extent of root filling flush short over-extended* Extrusion of root filling(incl. sealant) absent present* Homogeneity of root filling no voids, apparently homogenous voids in apical third voids in middle/coronal third* Type of final restoration amalgam* composite/GI indirect cuspal coverage restoration others Condition of the tooth and its restoration satisfactory unsatisfactory*

Interval censored Hazard ratio P-value (95% CI) NS

H_T1 Hazard ratio (95% CI)

P-value

H_T2 Hazard ratio (95% CI)

<0.001 0.48 (0.37, 0.64) 0.65 (0.51, 0.83) 1

0.007

P-value

H_T3 Hazard ratio (95% CI)

<0.001 0.50 (0.37, 0.66) 0.65 (0.51, 0.82) 1

P-value

H Hazard rati (95% CI)

<0.001 0.50 (0.38, 0.66) 0.64 (0.50, 0.82) 1

0.50 (0.38, 0 0.62 (0.49, 0 1 NS

0.63 (0.45, 0.88) 1 NS

0.007 0.71 (0.54, 0.95) 0.67 (0.52, 0.87) 1

0.001 0.54 (0.38, 0.77) 0.78 (0.54, 1.11) 1

0.010 0.74 (0.55, 0.98) 0.68 (0.52, 0.88) 1

0.001 0.62 (0.47, 0.83) 0.88 (0.65, 1.19) 1

0.001 0.63 (0.47, 0.84) 0.87 (0.64, 1.17) 1

0.043 1 1.55 (1.08, 2.23) 1.28 (0.76, 2.16)

0.015

0.001

0.045

0.023

0.65 (0.49, 0 0.89 (0.66, 1 1 0.045

1 1.56 (1.09, 2.24) 1.33 (0.79, 2.24) 0.029

0.66 (0.49, 0.91) 0.80 (0.55, 1.16) 1 NS

0.68 (0.52, 0 0.61 (0.48, 0 1

0.63 (0.47, 0.85) 0.86 (0.64, 1.16) 1

1 1.56 (1.09, 2.24) 1.33 (0.79, 2.24)

0.67 (0.49, 0.91) 0.84 (0.58, 1.22) 1

0.010 0.74 (0.56, 0.99) 0.67 (0.52, 0.88) 1

1 1.61 (1.12, 2 1.37 (0.81, 2 0.042

0.67 (0.49, 0.92) 0.77 (0.53, 1.12) 1 NS

0.69 (0.51, 0.93) 1 <0.001 0.65 (0.49, 0.86)

0.010 0.77 (0.61, 0.99)

1.12 (0.83, 1.51) 1

1.09 (0.84, 1.41) 1 0.007

1 0.76 (0.51, 1.14) 0.58 (0.43, 0.80)

0.58 (0.45, 0.75) 1

0.64 (0.52, 0.80) 1

1 0.74 (0.53, 1 0.53 (0.42, 0

1.81 (0.91, 3.56) <0.001

0.66 (0.53, 0.81) 1

1.08 (0.84, 1 1 <0.001

1 0.72 (0.51, 1.01) 0.52 (0.41, 0.66)

1.81 (0.91, 3.56) <0.001

0.76 (0.60, 0

1.07 (0.83, 1.38) 1 <0.001

1 0.72 (0.51, 1.01) 0.52 (0.41, 0.66)

1.75 (0.88, 3.46) <0.001

0.010 0.76 (0.60, 0.98)

1.08 (0.84, 1.40) 1 <0.001

1 0.72 (0.51, 1.01) 0.53 (0.42, 0.67)

1.11 (0.44, 2.81)

0.009 0.77 (0.60, 0.98)

1.85 (0.94, 3 <0.001

0.67 (0.54, 0.83) 1

0.69 (0.56, 0 1

Results

Table 4.12 Functional retention analyzed with Weibull accelerated failure time model (interval-censored) and Cox regression analysis. * Reference categories . Covariables Age <25 years 25-50 years >50 years* Tooth type anteriors premolars molars* Pre-operative periapical status no lesion < 5mm > 5mm* Occlusion non-opposing/opposing (denture) opposing (natural teeth) opposing (fixed prosthesis)* No.of visits 1 2 3 > 4* Type of final restoration amalgam composite/GI indirect cuspal coverage restoration others* Condition of the tooth and its restoration satisfactory unsatisfactory* Time to the placement of final restoration 0-2 months* >2-10 months >10 months

Interval censored Hazard ratio P-value (95% CI) <0.001 0.40 (0.28, 0.58) 0.57 (0.42, 0.77) 1 <0.001 0.61 (0.44, 0.86) 0.42 (0.30, 0.58) 1 0.004 0.65 (0.44, 0.95) 1.00 (0.67, 1.48) 1 0.014 1.36 (0.67, 2.78) 2.10 (1.16, 3.79) 1

F_T1 Hazard ratio (95% CI)

P-value

F_T2 Hazard ratio (95% CI)

<0.001 0.35 (0.24, 0.51) 0.61 (0.45, 0.83) 1

<0.001 0.36 (0.25, 0.52) 0.60 (0.44, 0.80) 1

0.002 0.78 (0.55, 1.10) 0.56 (0.40, 0.77) 1

0.004 1.05 (0.50, 2.23)

0.003 0.96 (0.45, 2.02)

1.98 (1.07, 3.66) 1

1.90 (1.03, 3.52) 1 0.043

0.001

0.002

0.003 1.85 (1.00, 3.42) 1

<0.001

2.03 (1.10, 3.75) 1 NS

<0.001

0.43 (0.33, 0.57) 1

<0.001 0.49 (0.23, 1.06) 0.32 (0.15, 0.68) 0.23 (0.11, 0.48)

1 <0.001 0.46 (0.36, 0.60) 1

0.49 (0.38, 0.63) 1

0.51 (0.39, 0.65) 1

1 <0.001

0.52 (0.40, 0.67) 1 0.013

1 0.66 (0.50, 0.88) 0.72 (0.50, 1.01)

<0.001 0.47 (0.22, 1.01) 0.29 (0.13, 0.63) 0.21 (0.10, 0.45)

1 <0.001

0.014 1 0.66 (0.50, 0.88) 0.73 (0.51, 1.03)

<0.001 0.50 (0.24, 1.07) 0.34 (0.16, 0.74) 0.24 (0.11, 0.50)

1 <0.001

0.027 1 0.69 (0.52, 0.92) 0.73 (0.51, 1.03)

<0.001 0.49 (0.23, 1.05) 0.33 (0.15, 0.70) 0.23 (0.11, 0.48)

1 <0.001

0.035 0.60 (0.27, 1.33) 0.63 (0.45, 0.87) 0.83 (0.62, 1.12) 1

0.49 (0.23, 1.05) 0.31 (0.14, 0.66) 0.23 (0.11, 0.49)

0.003 1.06 (0.50, 2.25)

0.62 (0.28, 1.37) 0.64 (0.46, 0.88) 0.86 (0.64, 1.15) 1 0.88 (0.36, 2.11) 0.58 (0.24, 1.38) 0.40 (0.17, 0.94)

<0.001 0.57 (0.40, 0.83) 1.00 (0.68, 1.46) 1

0.92 (0.44, 1.94)

1.87 (1.02, 3.46) 1 NS

0.002 0.76 (0.54, 1.08) 0.55 (0.40, 0.76) 1

0.60 (0.42, 0.88) 0.95 (0.64, 1.40) 1

0.92 (0.44, 1.94)

<0.001

P-value

0.35 (0.24, 0.51) 0.60 (0.45, 0.81) 1

0.71 (0.51, 1.00) 0.50 (0.36, 0.69) 1

0.58 (0.40, 0.83) 0.94 (0.64, 1.37) 1

F_T5 Hazard ratio (95% CI)

<0.001

P-value

0.36 (0.25, 0.53) 0.58 (0.43, 0.78) 1

0.70 (0.50, 0.99) 0.50 (0.36, 0.69) 1

0.58 (0.40, 0.83) 0.97 (0.66, 1.42) 1

F_T4 Hazard ratio (95% CI)

<0.001

P-value

0.36 (0.25, 0.52) 0.58 (0.43, 0.79) 1

0.70 (0.50, 0.98) 0.50 (0.36, 0.68) 1

0.57 (0.39, 0.82) 0.98 (0.66, 1.43) 1

P-value

F_T3 Hazard ratio (95% CI)

<0.001 0.46 (0.36, 0.59) 1

0.012 1 0.67 (0.50, 0.89) 0.70 (0.49, 0.99)

0.024 1 0.69 (0.52, 0.92) 0.72 (0.50, 1.01)

Results

4.3.1

Healing outcome (H) (Table 4.11)

Age was found to be a significant covariable among all linear estimates, i.e. H_T1 to H_T5, except when analyzed with the interval-censored model. Patients > 50 years old were consistently associated with a higher chance of post-treatment disease (i.e. higher hazard ratio), compared to younger aged group.

As far as tooth type was concerned, molars were found to suffer a significantly higher chance of post-treatment disease (i.e. higher hazard ratio), compared to anterior teeth and premolars. This was consistently shown among all linear estimates (i.e. H_T1 to H_T5), except in the interval-censored model.

Absence of pre-operative periapical lesion was associated with a higher chance of complete healing (i.e. lower hazard ratio), when it was compared to the presence of a lesion > 5mm, regardless of the statistical methods used. However, no such difference was found between small- and large-sized lesions.

Occlusion also contributed significantly towards the survival outcome according to the Kaplan-Meier estimator using various linear estimates, i.e. H_T1 to H_T5, but not with the interval-censored model. Teeth without any opposing teeth or opposing denture teeth fared a significantly lower hazard ratio, compared to those opposing natural teeth. 64

Results

Extent of root filling was found to be a significant covariable in H_T1, H_T2 and H_T5, but not in H_T4 or the interval-censored model. Among those which showed a significant difference, root filling that was â&#x20AC;&#x153;flushâ&#x20AC;? (0-2mm) with the radiographic apex were associated with a higher chance of complete healing (i.e. lower hazard ratio), compared to over-extended root filling. No such difference was found between short and over-extended root filling.

Homogeneity of root filling was found to be a significant covariable, regardless of the statistical models used. Those with radiographic (apparently) homogenous root canal filling (no voids) showed a more favorable healing outcome than those with voids in the middle/coronal third of the root. Location of the voids did not seem to be a significant factor, as no difference was found between root filling with voids in the apical third or middle/coronal third of the root.

Similar to pre-operative periapical status and homogeneity of root filling, the type of final restoration, as well as the condition of the tooth and its restoration was consistently found to contribute significantly towards the outcome, regardless of the statistical methods used. Indirect cuspal coverage restorations were associated with a higher chance of favorable healing (i.e. lower hazard ratio) than amalgam; and satisfactory condition of these teeth and its restoration was strongly associated with a lower hazard 65

Results

ratio than those considered unsatisfactory.

In the interval-censored model, presence of post and extrusion of root filling (including sealant) were also found to negatively influence the healing of treated teeth (i.e. higher hazard ratio), while no such effect was observed in the Kaplan-Meier analysis using any linear time estimates (H_T1 to H_T5).

4.3.2

Functional retention outcome (F) (Table 4.12)

Age was found to be a significant covariable in affecting the survival time of treated teeth in functional retention, regardless of the statistical methods used. Root canal treated teeth of patients > 50 years old were consistently associated with a shorter survival time in functional retention (i.e. higher hazard ratio), compared to younger aged group.

Tooth type was also found to have a significant influence over how long a tooth could survive in functional retention, as shown in any linear estimates. Although only premolars were shown to be associated with a lower hazard ratio, compared to molars in F_T1, F_T4 and F_T5, further association was also found for anterior teeth using interval-censored model, F_T2 and F_T3 (i.e. lower hazard ratio).

Results

Effect of pre-operative periapical status was similar to that shown in healing outcome, in which no lesion was associated with a lengthier retention in function (i.e. lower hazard ratio) than those with lesion > 5mm. Again, no significant difference was found between small- and large-sized lesions. This significance was consistently shown in the result of all statistical models used.

Root canal treated teeth opposing natural teeth were associated with a significantly shorter survival time in functional retention (i.e. higher hazard ratio), compared to those opposing fixed prosthesis, a finding consistently found among all linear time estimates.

As far as number of visits was concerned, Kaplan-Meier analysis using F_T1 and F_T5 time estimates showed that treatment taken more than 3 visits to complete experienced a significantly shorter survival time in functional retention (i.e. higher hazard ratio), whereas treatment completed in 2 visits was associated with a more favorable outcome (i.e. lower hazard ratio). Such effect was not observed in interval-censored model, F_T2, F_T3 and F_T4.

All findings indicated that treated teeth restored with composite/GI and indirect cuspal coverage restorations were retained longer in the mouth (i.e. lower hazard ratio), compared to others. Tooth and its restoration in a satisfactory condition were associated 67

Results

with lengthier survival (i.e. lower hazard ratio) than those considered unsatisfactory.

Time to the placement of restoration was found to be significant among all linear estimates (F_T1 to F_T5), except interval-censored model. Interestingly, according to the findings in F_T1, F_T2, F_T3 and F_T5, final restoration placed on or before 2 months after treatment completion was associated with shorter survival time in function (i.e. higher hazard ratio), compared to those restored after 2 months but not longer than 10 months. Such effect even extended beyond 10 months, a finding shown in F_T4.

4.3.3

Summary

Age, tooth type, pre-operative periapical status, occlusion, type of final restoration, condition of the tooth and its restoration, significantly affected the long term healing and functional retention of treated teeth. However, extent of root filling and homogeneity of root filling only contributed significantly towards successful healing, and did not seem to affect the survival of teeth in functional retention. On the other hand, time to the placement of restoration merely showed a significant impact towards the outcome of functional retention, but not otherwise.

4.4 Reasons for extraction Overall, 29% of the 891 sampled teeth (n = 257) ended with extraction. An initial rapid 68

Results

increase in the rate of extraction that appeared to slow down with longer observation time was identified in the cumulative proportion curve (Figure 4.3). Approximately 80% of the extraction was performed during the first 150 months after primary root canal treatment.

Among the extracted cases, almost half of these (n = 127) were due to crown or root fractures. About 30% of the extraction was related to root canal treatment failure (n = 41) or periodontal reasons (n = 33). Only a minority of these cases were attributed to caries, orthodontic and prosthodontic reasons, approximately 5-6% each (Table 4.13).

Figure 4.3 Cumulative proportion of primary root canal-treated teeth that were extracted later.

Results Table 4.13 Distribution of reasons for extracted cases (n = 257) Reasons for extraction

No. of teeth

Percent

Caries

5.8%

Failed RCT: clinical or radiographic signs +/ symptoms

16.0%

Fractures: crown

16.0%

Fractures: root (vertical/horizontal/oblique)

33.5%

Orthodontic

0.8%

Periodontal reasons

12.8%

Prosthodontic reasons (RCT not considered failed yet)

5.4%

Others (patientâ&#x20AC;&#x2122;s request, trauma or resorption)

5.1%

Unknown

4.7%

Total

257

100%

Discussion

5. Discussion

5.1 Methodology This study has the inherent limitations of any cohort clinical study design. That is, the number of dropouts tends to increase with an extended study period. A high dropout rate would make it difficult for survival analysis to generate survival estimates that are reliable and precise (Daya 2005). However, it may not cause such a major impact in this study because the statistical methods used for calculating the survival estimates can make use of information from not only complete (interval-censored), but also incomplete (right-censored) observations. Such information was quite readily available from the clinical documentation over the years in patientsâ&#x20AC;&#x2122; record.

Another consideration is the possibility of recall bias. Patients might be reluctant to attend review appointments if the treated teeth have been asymptomatic, particularly after such a long time since the primary root canal treatment was done. The reverse could also be true with patients experiencing symptoms or was informed of a guarded prognosis for their root canal treated teeth; they might be more willing to return for a recall in the hope to receive treatment. Therefore, there is a possibility that patients attending the recall might not be truly representative of the study population and a risk of underestimating the cumulative survival. 71

Discussion

The data related to the treatment details and review findings in this study was acquired to a great extent from the information recorded on the case notes. It was therefore necessary to assume that the documentation were accurate, consistent and complete for validity of the data. When some entries were missing, retrospective information provided by the patient would become the only source of data. Such self-reported data could be subjected to prevarication and recall bias.

During the early years, some clinical procedures performed in this teaching hospital might not be standardized. The effects of the various procedures on the survival of the treated teeth in this study would be somewhat difficult to quantify.

The present study design precluded the assessment of some factors that might have the potential to influence the survival of root canal treated teeth. Factors such as the socio-economic status, education, history of tobacco use, attitude towards maintaining teeth, level of oral hygiene and parafunctional habits were not considered and thus their effect could not be estimated. Such information were sometimes, if not often, unavailable from the patientsâ&#x20AC;&#x2122; records. On the other hand, as the dental treatments provided in the student clinic of this teaching hospital were virtually free (apart from the laboratory cost of appliances and cast restorations), the socio-economic status and education level are unlikely to have an effect here. 72

Discussion

Another limitation of the present study is related to the use of radiographs, as they only represent a two-dimensional image of the three-dimensional structures of the jaw. Homogeneity of root canal filling cannot be fully assessed with intraoral radiography in all planes (Wang et al. 2004, Stoll et al. 2005). It is commonly known that lesions limited to the cancellous bone are almost impossible to detect with conventional radiographic technique; in other words, a periapical inflammatory reaction of endodontic origin may exist without being visible on a plain film (Bender & Seltzer 1961).

Cone-beam computer tomography (CBCT) is a three-dimensional (radiological) imaging technique that is currently considered a more sensitive method for detecting periapical lesions. In fact, many root canal treated teeth that exhibited radiographic signs of complete healing have been associated with a radiolucent area when examined using CBCT (Wu et al. 2009). If the radiation dose could be controlled to a similar level as that for intraoral periapical film, CBCT may be regarded as the preferred means to evaluate the periapical status of root canal treated teeth. Having said that, presence of periapical radiolucency does not necessarily indicate the presence of periapical periodontitis, its other causes may include apical scar tissue (Nair et al. 1990).

Discussion

5.2 Survival analysis Survival analysis provides a more reliable and valid result when patients are recalled regularly and periodically, preferably at short intervals. This is practically more difficult to achieve for such a large cohort for such an extended period of observation. In addition, this might pose ethical problems because patients would be receiving (possibly unnecessary) repeated radiation exposure as part of the routine post-treatment review of the periapical status (Wang et al. 2004).

Kaplan-Meier estimator, a widely used statistical method for survival analysis requires that the exact event date is entered into the data set to produce result that is meaningful. This is only feasible if the patients were recalled continuously at short intervals. To resolve this problem, Cheung and Chan (2003) used various linear estimates in their study in an attempt to devise the most appropriate method of estimating the actual event date (i.e. date of â&#x20AC;&#x153;failuresâ&#x20AC;?). Inevitably, some inaccuracies would remain with any of the arbitrarily chosen (linear) time estimates to replace an exact event date (Wong 2005), although the extent of which would vary. Cheung and Chan (2003) compared the survival plots calculated from different arbitrarily chosen linear time estimates, but no conclusion could be drawn from the erratic trend indicated on the resultant plots.

A different approach was used in this study for this. It was done by the use of an 74

Discussion

interval censoring method (Lindsey & Ryan 1998), which was taken as the hypothetical benchmark. With the more sophisticated interval censoring method, one could expect to get a more reliable and valid result, with which other time estimates may be compared. However, this method is not without its limitations, as only a few statistical models are currently available.

In addition, the intervals between the “interval-censored” observations should not be too variable and/or too great apart. In the present study, the former problem was largely overcome by using a 'variable' interval censor (Weibull accelerated failure time model, PROC LIFEREG, SAS version 9.2), a rather sophisticated statistical model, which takes into account recall intervals of variable length of time. In future, one might also consider including only those observations which lie within a certain width of time interval, to improve the precision of the estimate generated by this interval censor.

Early “right censoring” data (i.e. last review shortly after the treatment without any observation of event and patient never returns again) tends to introduce more errors in survival analysis. This problem was largely eliminated in this study, as any right-censored cases with less than four years of review were excluded, in accordance with the strict criteria for assessment of outcome that a minimum of 4 years observation should be allowed (European Society of Endodontology 2006). 75

Discussion

A limitation associated with the interval-censored model used in this study was that it could not analyze the data for an event (i.e. post-treatment disease or loss of functional retention) observed at the first review, unlike Kaplan-Meier estimator. In this study, the statistician was not in the position to make any clinical assumption. Thus, samples that were deemed unfit had to be excluded from analysis in the interval-censored model. From a clinicianâ&#x20AC;&#x2122;s point of view, it seems quite reasonable to assume that most, if not all root canal treated teeth are able to survive for a very short time after the treatment, say for at least 2 weeks, before developing any problems. By making such assumption, last review without any observation of event could be set to this date, eliminating the need to exclude numerous samples which might contain very useful information towards the survival outcome of a study. This deserves serious consideration for future statistical analysis of such data set.

In this study, survival curve derived from the observation date of post-treatment disease (Ddisease) and loss of functional retention (Dnofunction) was shown to be very similar to that derived from the interval censoring method up to approximately 10 years (120 months). It might be reasonable to assume Ddisease or Dnofunction as a reliable and valid estimate of the actual event time when using Kaplan-Meier estimator, at least for an observation period up to 10 years. This could form the basis of our recommendation for future analysis of treatment outcome as an alternative for interval censoring approach in short76

Discussion

to medium-term study. Nevertheless, interval censoring should remain the gold standard for verification of conclusion.

Although it appeared that one-quarter point (T1) and geometric mean (T5) were closely approximating the interval-censored curve over longer period of observation, it would be difficult to extrapolate future trend of these time estimates, as they behaved in a non-linear pattern. However, one could confidently eliminate geometric mean (T5) from future consideration because it produced very similar result to that of one-quarter point (T1) and the derivation of such estimate involves a rather complicated calculation procedure.

When comparing the survival curves between the two outcomes, more discrepancies between various linear estimates were identified in the healing outcome, but not as marked in functional retention outcome. The most likely explanation for it is that assessment of functional retention was based solely on clinical normalcy and patients were more likely to make a complaint when clinical symptoms have developed, hence such information was more frequently available in patientsâ&#x20AC;&#x2122; case notes; whereas the assessment of healing requires the additional radiographical evaluation which was not (unnecessarily) repeated at every review. Furthermore, post-treatment disease usually develops over time, and may not be observed by the patients until a diagnosis was made 77

Discussion

at a recall or until obvious problems set in. As a result, time intervals between observations for healing were greater apart, led to a subsequently greater discrepancy between various linear estimates.

In this study, it was not uncommon to find cases that had been condemned as â&#x20AC;&#x153;failedâ&#x20AC;? and were subjected to retreatment and/or surgical root canal treatment less than 4 years of observation, despite no obvious signs or symptoms of disease progression. Presumably, this would result in an underestimation of the chance of survival in both outcome measures.

In a large epidemiologic study, Salehrabi and Rotstein (2004) found that 97% of treated teeth remained functional eight years after primary non-surgical root canal treatment. Similar studies by Lazarski et al. (2001) and Chen et al. (2007) also reported high functional retention rates of 94% (3.5-year follow-up) and 93% (5-year follow-up), respectively, after non-surgical root canal treatment. However, the result of the present study generally showed a lower rate of functional retention compared with the above studies. According to F_T4, the survival rates of teeth were approximately 85%, 81% and 74% at 3.5 years, 5 years and 8 years after treatment, respectively (see Fig. 4.2).

The difference in the functional retention rates found between the present study and the 78

Discussion

epidemiologic studies discussed above (Lazarski et al. 2001, Salehrabi & Rotstein 2004, Chen et al. 2007) may be due to a number of reasons: (i) variation in outcome criteria mainly the inclusion of clinical signs and/or symptoms in evaluating functional retention, as in the present study; (ii) case selection - patients in all of the epidemiologic studies were recruited from the population enrolled in dental insurance plan, which might be an indirect reflection of their attitude and awareness towards dental health and tooth retention; (iii) treatment providers - treatment for patients in the epidemiologic studies were provided by either qualified dentists or endodontists, as oppose to that by undergraduate students in the majority of cases in the present studies (see Table 4.8); and (iv) sample size.

5.3 Factors affecting the outcome of primary root canal treatment It was observed that some factors which were found to be significant (P < 0.05) after Cox regression analysis for T_1 to T_5 were not found significant in interval-censored model, and vice versa. This was most likely attributed to the systematic difference between the two data set (Tables 4.2 and 4.3). Such difference is expected to be reduced by including those unfit samples into the interval-censored model by making a just clinical assumption (as discussed earlier).

Most previous studies had not found any significant association between age and 79

Discussion

healing outcome after primary root canal treatment (Kerekes & Tronstad 1979, Hoskinson et al. 2002, de Chevigny et al. 2008). In present study, it was found that patients older than 50 years old experienced a significantly higher chance of developing post-treatment disease compared to younger patients â&#x20AC;&#x201C; this is in contrast to the finding reported by Ă&#x2DC;rstavik et al. (2004). In fact, it is quite reasonable to assume that healing process in older patients is slower and not as effective due to physiological aging process (Ă&#x2DC;rstavik et al. 2004), thus responds less favorably to treatment. In addition, there is an increased incidence of excessive secondary and/or tertiary dentine deposition, pulp stones and calcification within the pulpal space with aging, resulting in canal obliteration. This poses a great challenge to the achievement of optimal root canal treatment and therefore compromises the healing outcome.

Age also significantly affected the functional retention of root canal treated teeth, an observation in agreement with the findings of other studies (Caplan & Weintraub 1997, Mindiola et al. 2006). It has been shown that survival of root canal treated teeth decreases in older individuals. Presumably, older patients might be more likely to have received more complex restorative treatment, and years of service might also caused more fatigue of tooth structure, potentially contributing to lower tooth retention.

In this study, no significant association was found between systemic diseases and 80

Discussion

healing or functional retention. It is noteworthy that systemic diseases were generalized as one single entity for analysis, when certain conditions may have more impact than the others on treatment outcome. For example, diabetes and hypertension could have possibly been taken into separate consideration, as these were the most common conditions reported. Some studies had found a significant contribution of these conditions towards treatment outcome (Fouad & Burleson 2003, Mindiola et al. 2006).

Systematic reviews on the outcome of healing and tooth survival concluded that tooth type should not have any significant effect on healing after primary root canal treatment (Ng et al. 2008), but molars were significantly associated with a lower chance of survival (Ng et al. 2010). In present study, tooth type showed a significant impact towards both outcomes, in which molars were consistently found to be associated with the greatest risk of developing post-treatment disease and enjoyed the shortest survival time in functional retention, in agreement with Ng et al. (2010). It was suggested that heavy occlusal stresses, accessibility and technical difficulties in treating molars may be the causes of the problems (Aquilino & Caplan 2002).

A high prevalence (more than 90%) of MB2 canal in upper first molars (Vertucci 2005), and two-canal lower incisors (Benjamin & Dowson 1974) have been reported. However, these were not common findings in this study, possibly due to the lack of knowledge of 81

Discussion

such anatomic variations of root canals, or the infrequent use of magnification aids, such as dental operating microscope in locating these canals, at that time. Radiographically, centering of canal along the root should give a fairly reliable indication for the presence or absence of additional canals. Deviation of radiographic canal outline of obturated teeth could also suggest perforation or canal deviation due to transportation somewhere along the canal wall, potentially complicating the diagnosis of missed canal(s) based on plain radiographs. Advanced imaging technique, such as CBCT remains a better means for detecting any missed canal(s).

A periapical lesion tends to develop more or less concentrically around the root apex (Zones of Fish), with the apical foramen acting as the â&#x20AC;&#x153;sourceâ&#x20AC;? of irritation and situated in the centre of (radiographic) lesion. In this study, only the largest diameter perpendicular to the long axis of the apical portion of the root (i.e. mesial-distal dimension) is taken into consideration, as the development of the vertical dimension may be constrained by vital anatomic borders such as maxillary sinus and mandibular canal. Also, this would eliminate the errors due to an elongated image in the vertical dimension resulted from film distortion.

As far as pre-operative periapical status was concerned, the result obtained in this study remains consistent with that from the previous study carried out in this teaching hospital 82

Discussion

(Cheung & Chan 2003). Absence of periapical radiolucency was associated with a significantly higher rate of both complete healing and functional retention, which also corroborates the finding of other studies (Dammaschke et al. 2003, Stoll et al. 2005). Once again, it reflects the difficulties in effective disinfection of a root canal system with an established infection (Friedman 2008). Notwithstanding this, it should be realized that the lack of visible periapical radiolucency does not necessarily imply the absence of periapical pathosis (Brynolf 1967).

On the other hand, no difference was found between lesion sizes < 5mm or > 5mm in both outcome measures. It might be explained by the hypothesis that healing is a function of time â&#x20AC;&#x201C; thus, an outcome similar to smaller-sized lesions were observed in larger-sized lesions, because sufficient time (as in the present long-term study) was allowed for healing to take place (SjĂśgren et al. 1990).

It should be mentioned that teeth were counted as units instead of the roots in the study. When multi-rooted teeth were evaluated as whole units and assessed by the worst appearing root for the presence/size of periapical rarefaction, problem arises as the worst appearing root measured for other factors may not necessarily correspond with that of the periapical rarefaction. For instance, the root with a grossly over-extended root filling may not be the root associated with the largest periapical rarefaction. In 83

Discussion

conclusion, error, say, for the example above may arise as a result, confounding the true effect of a factor in association with post-treatment disease.

Some previous studies have failed to show any correlation between the vitality of the pulp and clinical signs or symptoms, electric pulp and/or thermal tests, as well as radiography, and found them rather misleading (Dummer et al. 1980, Chambers 1982). Histopathologic examination is probably the most accurate means to diagnose the vitality of the pulp, but is neither ethical nor practicable. Therefore, one had to work within the limitation by establishing the diagnosis based on an educated guess of the presentations of the histopathologic status. This became more difficult in multi-rooted teeth because partial pulpal necrosis could easily escape proper diagnosis. In this study, no significant association was found between pre-operative pulpal vitality and any of the survival outcomes.

As far as â&#x20AC;&#x153;flare-upâ&#x20AC;? was concerned, only those presented with acute or severe inter-appointment pain, or swelling was taken into account. By doing so, one had automatically excluded the single visit treatment cases from consideration. However, the number of cases in single-visit treatment group in the present study was probably too small to cause any significant impact towards the outcome of this study.

Discussion

This study further confirmed the conclusion of a recent systematic review that homogenous root filling (i.e. root filling with no apparent voids) and root filling extending within 2mm of the radiographic apex (i.e. flush) were associated with significantly better outcome as far as complete healing is concerned (Ng et al. 2008), compared to root filling with voids and over-extended root filling, respectively. However, these factors did not seem to affect the functional retention of the teeth in the mouth.

Root canal treated teeth opposing natural tooth/teeth were consistently found to be associated with a significantly lower survival rate in both outcome measures, when compared to those opposing a denture, fixed prosthesis, or without any opposing tooth/teeth. It might be related to the damaging effects of premature occlusal contacts or interferences, which often get corrected in the process of denture or fixed prosthesis construction. Also, patients might be more willing to chew on those opposing natural tooth/teeth, potentially resulting in excessive occlusal loading. It has been suggested that occlusal trauma may modulate the healing response of periapical periodontitis of root canal treated teeth (Harn et al. 2001), and had been associated with greater endodontics treatment failure (Matsumoto et al. 1987). Furthermore, it may increase the risk of tooth fracture, which may have contributed indirectly to a greater risk of tooth loss. Obviously, the same problems do not exist when there were no opposing 85

Discussion

tooth/teeth, or with those opposing a denture that was subjected to substantially smaller occlusal force.

Indirect cuspal coverage restorations were associated with more favorable healing and were shown to improve the longevity of a tooth, a finding supported by numerous studies (Meeuwissen & Eschen 1983, Vire 1991, Aquilino & Caplan 2002, Caplan et al. 2002, Cheung & Chan 2003, Dammaschke et al. 2003, Stavropoulou et al. 2007), including a recent systematic review (Ng et al. 2010). This probably reflects the importance of cuspal protection in root canal treated teeth in order to prevent cuspal flexure, as the lack of it may lead to tooth-restoration interface breakdown and subsequent microleakage which might have affected the periapical healing. It also offers protection against tooth fracture (Fennis et al. 2002), especially for molars (Nagasiri & Chitmongkolsuk 2005), which were the tooth type associated with the least favourable outcome in this study.

Among various final restorations, composite/GI was found to be associated with a longer functional retention than others, although their true effect could be confounded by the effect of tooth type; as these materials were more commonly placed in anterior teeth and premolars, which were associated with more favorable outcome in general.

Discussion

From hindsight, one should admit the choice of â&#x20AC;&#x153;othersâ&#x20AC;? as the reference category for the evaluation of the influence of different type of final restorations toward functional retention may not seemed too wise (see Table 4.12). This group was only a minority comprised a mixture of various types of restorations (such as IRM, silicate cement, etc.) which may not share any characteristics in common, and their uses as a final restoration nowadays are certainly rare. Comparison between crowns, amalgam, or composite/GI, for example, to this group appeared relatively less meaningful.

Exposure of the root canal filling to saliva and bacteria is a serious challenge to the quality of the seal (Madison & Wilcox 1988, Torabinejad et al. 1990). A bacterial-tight coronal restoration is of critical importance to ensure long term success of root canal treatment. As reflected in this

study, teeth presented with unsatisfactory

tooth/restoration margin owing to marginal defects, fractures or recurrent caries were shown to be associated with a less favourable treatment outcome than those considered satisfactory. This result is most likely due to the effects of coronal microleakage.

According to previous teaching protocol, the temporary restoration (such as IRM) would only be replaced by a final restoration after some progress in healing was being observed after a review. It had been the routine but is no longer practiced in this teaching hospital. This treatment approach is now considered inappropriate due to the 87

Discussion

high chance of coronal microleakage (Barthel et al. 1999), an important cause of post-treatment disease (Ray & Trope 1995, Kirkevang et al. 2000). It is recommended that the final restoration should be established as soon as possible (Barthel et al. 1999), as better outcome can be anticipated with such practice (Safavi et al. 1987), which is the current teaching protocol.

In this study, the final restoration was assumed to be placed or cemented on the date the first restoration was delivered (if applicable). The reasoning behind was that the function of a final restoration was to offer protection for the foundation, if any, and the remaining tooth structure, a treatment approach commonly practiced in this teaching hospital.

Surprisingly, the result of this study showed that final restoration placed on or before 2 months after root canal treatment was associated with a significantly lower functional retention compared to those placed at a later date, contradictory to the common belief (discussed above). A possible explanation is that by delaying the placement of a final restoration for teeth that showed some progress in healing would actually select for those teeth that were likely to survive in the long run.

For the purpose of this study, number of proximal contacts postoperatively and function 88

Discussion

of a tooth as an abutment was generalized into a single category as “function”. A recent systematic review on tooth survival following non-surgical root canal treatment found that teeth having both proximal contacts intact and those not functioning as a prosthetic abutment (either fixed or removable) were associated with a significantly increased survival rate (Ng et al. 2010). However, no such significance was found in the present study.

It should be acknowledged that some degree of uncertainty associated with the factors showing a significant influence towards endodontic treatment outcomes in this study remained inevitable, owing to the non-random choice of the procedures (such as “number of visits”, “type of restoration” and “time to the placement of final restorations”, etc.), small number of cases in some categories, and the large number of factors evaluated in the same population.

5.4 Reasons for extraction In this study, all extraction cases were considered as failure with the assumption that some form of “post-treatment disease” had occurred as a consequence to warrant such treatment, regardless of their primary causes. This could lead to an overestimation of the “non-healing” rate after root canal treatment, when in fact most of the teeth might have been extracted due to non-endodontic related causes (Meeuwissen & Eschen 1983, Vire 89

Discussion

1991, Chen et al. 2008). As reflected in the present study, only 16% of the extraction was due to endodontic failure (for teeth that did not suffer from root fracture, a condition that, arguably, might be related to root canal treatment).

In this study, the high rate of extraction due to root fracture (34%) could possibly be attributable to the use lateral compaction technique. Overzealous application of â&#x20AC;&#x153;lateral compactionâ&#x20AC;? forces has been shown to cause vertical root fractures (Meister et al. 1980, Tamse 1988). Another possible reason for the high amount of root fracture might be related to the use of cast post-and-core, which had been demonstrated to increase the risk of catastrophic (i.e. non-restorable) root fracture (Martinez-Insua et al. 1998, Lazarski et al. 2001). Cast metal or rigid posts had been shown to induce considerable stress and increased the incidence of vertical root fracture when excess load is applied to the overlying restoration (Obermayr et al. 1991).

Fiber posts seem promising in reducing the risk of such catastrophic fracture, and the resultant fracture is more likely to be re-restorable in contrast to the often much deeper root fractures for teeth restored with metal posts (Mannocci et al. 1999, Newman et al. 2003). However, none of the cases in this study were restored with fiber posts, perhaps due to their unavailability or unpopularity during the time these teeth were treated; hence a conclusion could not be made in this regard. One may anticipate a lower rate of 90

Discussion

root fracture with the use of this restorative technique (Ferrari et al. 2000, Ferrari et al. 2007). A randomized controlled clinical trial would be the best way to single out the effect, beneficial or otherwise, of restoration using a fibre post.

Conclusions

6. Conclusions

Median survival time of treated teeth in functional retention was considerably greater (ranged from 87 months to 149 months, depending on the linear estimate used) than those without post-treatment disease.

Median survival time of root canal-treated teeth without post-treatment disease and those maintained in functional retention was found to be at least 103 months and 234 months, respectively.

Date of first review with the observation of post-treatment disease (Ddisease) or loss of functional retention (Dnofunction) could be considered as a reasonable time estimate of the actual date of event using Kaplan-Meier estimators, in short- to medium-term study. However, interval censoring should remain the gold standard for verification of the accuracy of such estimates.

Geometric mean (T5) could be excluded from future consideration, because it produced very similar results to those from the linear estimate using one-quarter point (T1); and more importantly, it involves a rather complicated calculation to obtain a time estimate.

It was consistently shown that pre-operative periapical status, homogeneity of root filling, type of final restoration and the condition of the tooth and its restoration had significant influences toward healing outcome, regardless of which statistical 92

Conclusions

methods or linear estimates used. For functional retention, more factors were found to affect the outcome; factors that were found to be significant among all the statistical methods and linear estimates were age, tooth type, pre-operative periapical status, occlusion, type of final restoration, condition of the tooth and its restoration, and time to the placement of restoration. 6.

Age, tooth type, pre-operative periapical status, occlusion, type of final restoration, as well as condition of the tooth and its restoration, were simultaneously shown to influence both the long term healing and functional retention outcome of primary root canal-treated teeth.

Approximately 80% of the extraction was performed during the first 150 months after primary root canal treatment. Root fractures were found to be the most common cause of extraction; whereas endodontic failure only contributed 16% towards the reasons for extraction.

References

7. References

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111

Appendix 1 Survey on Treatment Outcome of RCT : Data Collection Form ( tx code: PPDH no: Medical health:

healthy known systemic disease immunosupressive medication radiotherapy-head and neck Tooth no: No. of canals: __ Treatment commencement date: (dd/mm/yy) Obturation technique and material: (dd/mm/yy)

Operator:

)

DOB: __/__/__

Date of extirpation: Obturation date: __/__/__ cold lateral compaction compaction warm lateral compaction warm vertical compaction single cone silver point sectional silver point carrier-based Gutta Percha others

Undergraduate student Specialty postgraduate student JHDO Staff

Post and core: Type: Date of placement /cementation: dd/yy/mm History of decementation: yes/no If yes, date: dd/mm/yy

Post and core: __

)

Sex:(M,F)

nil, i.e. no restorative material in pulp chamber parallel / cast parallel / prefabricated / composite core parallel / prefabricated / amalgam core tapered / cast tapered / prefabricated / composite core tapered / prefabricated / amalgam core fiber or carbon post / prefabricated / composite core fiber or carbon post / prefabricated / amalgam core coronal-radicular amalgam core others

intact void between post and root filling less than 3mm of GP apical to post perforated not applicable

Restoration type 1:

temporary amalgam bonded amalgam composite onlay full gold crown three-quarter crown ceramic metal crown labial veneer porcelain jacket crown GI others

Restoration type 2: Restoration type 3:

Date of final placement / cementation 1: (dd/mm/yy)

Date of final placement / cementation 2: (dd/mm/yy)

Preoperative Function:

Preoperative Occlusion:

Function at review 1: Date of review 1: Function at review 2: Date of review 2:

double approximal contacts last tooth in segment single tooth fixed-fixed bridge abutment cantilever bridge abutment fixed-movable bridge abutment denture abutment single proximal contact overdenture abutment

Pre-operative status (PS) Pulpal status:

non-opposing opposing (natural teeth) opposing (denture) opposing (fixed prosthesis)

Occlusion at review 1: Date of O review 1: Occlusion at review 2: Date of O review 2:

vital non-vital

Clinical signs / symptoms: Radiographic:

pain: rarefaction:

length of root:

mesial:

swelling: no yes distal: widened PDL

sinus: trauma: Size of lesion x Crestal bone level (mm from CEJ or restoration margin):

tenderness to percussion / palpation: mm mesial ___ distal ___

Furcation bone loss:

Treatment details (TD) Irrigant1: Irrigant2:

Visit #: Visit #: Visit #: Visit #: Total no. of visits:___

NaOCL Iodine Water Saline EDTA Hydrogen peroxide Others Medication: Medication: Medication: Medication:

Apical size (mesial root of lower molar): Extent of root filling: (mm from radiographic apex)

Ca(OH)2 Ledermix chlorhexidine gel iodoform gel (e.g. Vitapex) CMCP Formocreosol Ca(OH)2 / Ledermix Ca(OH)2 / chlorhexidine Ca(OH)2 / iodoform Septomixine Forte others MB one root canal two root canals three or more root canals

ML B MB DL or P

P DB

Ml or MB2

Over-extended GP / over-filled sealer:

113

Quality:

no void, apparently homogenous voids in apical third voids in middle third voids in coronal third

Canal form:

follow original canal form signs of ledging / transportation / deviation / broken instrument / perforation

Interappointment flare up:

yes no

Review status (RS)

Clinical signs / symptoms: Tooth / restoration:

pain __ open margin __

Clinical signs of tooth wear: Radiographic: __

(no;yes) no periapical rarefaction widened PDL periapical rarefaction

Exam. Date: (dd/mm/yy) swelling __ fracture / lost __

sinus __ exposed RF__

Temp. sensitivity __ Occlusal interference__

tenderness __ caries__

Date: (dd/mm/yy)

furcation bone loss: sign of root fracture:

no conclusive suggestive

Retreatment done on the tooth in question: Periapical surgery performed on tooth in question: Extracted: Reasons for extraction:

Validity indicator:

Date of retreatment: dd/mm/yy Date of periapical surgery: dd/mm/yy Date of extraction: dd/mm/yy fractures : crown (not involving root) - deemed not restorable fractures : root - vertical / horizontal / oblique failed RCT : clinical / radiographic signs and symptoms periodontal reasons e.g. periodontal abscess/mobility prosthodontic reasons (RCT not considered failed yet) caries orthodontic others (patient's request, trauma, resorption)

Y = valid N = failed appointment P = passed away U = unable to contact E = excluded due to various reasons (see remarks below)

Remarks: (1) Last clinical review ok: (dd/mm/yy) (2) Last radiographic review ok: (dd/mm/yy) (3) First review with clinical signs & symptoms of failure: (dd/mm/yy) (4) First review with radiographic signs & symptoms of failure: (dd/mm/yy) healed = those with only (1) and (2) filled in. post-treatment disease = those with (3) and/or (4) filled in. functional retention = those without (3) filled in. Clinical outcome: Radiographic outcome: PPDH no:

113

Appendix 2

Information Release Consent Form I, of PPDH no consent to the transfer of information of my treatment details and radiographs from my dental practitioner to: Associate Professor Dr. Gary Cheung (Cc: Dr. Angeline Lee) Endodontics, Comprehensive Dental Care The University of Hong Kong The Prince Philip Dental Hospital 34, Hospital Road Sai Ying Pun Hong Kong Tel: 2859-0238

Details of dental practitioner transferred from: Dr. Address:

Dates of previous appointments (if known):

I understand that information obtained will be used solely for research purpose, and confidentiality shall be preserved by the Hospital.

Signature

Date 114