The objectives of this report are to review the assessment of patient-focused outcomes in pediatric orthopedic surgery, to describe a framework for identifying appropriate sets of measures, and to illustrate an application of the framework to a challenging orthopedic problem.A detailed framework of study design and measurement factors is described. The factors are important for selecting appropriate instruments to measure health status and health-related quality of life (HRQL) in a particular context. A study to evaluate treatment alternatives for patients with neurofibromatosis type 1 and congenital tibial dysplasia (NF1-CTD) provides a rich illustration of the application of the framework. The application involves great variability in the instrument selection factors. Furthermore, these patients and their supportive caregivers face numerous complex health challenges with long-term implications for HRQL.Detailed summaries of important generic preference-based multi-attribute measurement systems, pediatric health profile instruments, and pediatric orthopedic-specific instruments are presented. Age-appropriate generic and specific measures are identified for study of NF1-CTD patients. Selected measures include the Activities Scale for Children, Gillette Functional Assessment Questionnaire Walking Scale, Health Utilities Index, and Pediatric Inventory of Quality of Life.Reliable and valid measures for application to pediatric orthopedics are available. There are important differences among measures. The selected measures complement each other. The framework in this report provides a guide for selecting appropriate measures. Application of appropriate sets of measures will enhance the ability to describe the morbidity of pediatric orthopedic patients and to assess the effectiveness of alternative clinical interventions. The framework for measurement of health status and HRQL from a patient perspective has relevance to many other areas of orthopedic practice. Assessments of patient-focused health status and health-related quality of life (HRQL) are being recognized increasingly by clinicians, patient advocates, regulatory authorities, administrators and policy makers as primary measures of the need, efficacy, effectiveness and efficiency associated with health care services. These types of measures are commonly reported in the published literature of many health care disciplines although there are few published reports concerning orthopedic surgery. However, the orthopedic community is becoming interested in using evidence reported by patients and patients' family members to determine what is best for patients.Patient-focused evidence  refers to results from functional health status (FHS) and HRQL studies of orthopedic outcomes with measurements obtained from the perspective of patients or their non-clinician caregivers . The field of orthopedics is concerned with all musculo-skeletal problems from the top to the bottom of the human body. This broad anatomical range is associated with a wide range of functional problems. Some orthopedic problems are highly focused in regards to anatomy and associated with highly effective therapies. However, other orthopedic problems are of a diverse nature, the etiology is often poorly understood, and effective treatment strategies are sometimes elusive.The breadth and depth of some particularly challenging orthopedic problems has stimulated an interest in patient-based perspectives of their own FHS and HRQL. These types of measures will be referred to as "health measures" for the purposes of this paper. Health measures can be used to assess the burden of morbidity associated with orthopedic diagnoses, and to assess the effectiveness and efficiency of therapies. The diversity of issues also led the American Academy of Orthopedic Surgeons and the Pediatric Orthopedic Society of North America to develop the Pediatric Outcomes Data Collection Instrument (PODCI), and led other researchers to develop function-specific instruments such as the Activities Scale for Kids (ASK). However, there are a large variety of potentially appropriate health measures and there are limits to the number of these measures that can be used in any given study. The most appropriate set of health measures should be selected on the basis of underlying study objectives and design criteria .a priori specification of the comprehensive measure of health and a credible assessment viewpoint for the purposes of primary analysis of study results. Secondary study objectives may involve use of data collected from other health measures or from other assessment perspectives.Objectives and designs vary greatly across orthopedic studies. In general, orthopedic procedures and programs are undertaken to improve the health of patients. The health of patients can be measured in different ways. Conventional clinical or physiological measures are generally very useful for diagnostic and therapeutic purposes. Conventional clinical measures may, however, provide an incomplete assessment of health. For example, clinical examination and gait measures have been used to describe the quality and quantity of limitations in walking ability associated with hip flexion contracture but these types of assessments provide little information about the importance of this contracture relative to that of other serious health problems. In addition, various measures may provide conflicting results: some indicating improvement while others suggest decline in patients' health. Therefore, in the interest of scientific rigor, protocols to assess the overall effectiveness of therapy should include FHS and HRQL measures are important for a variety of reasons that complement conventional clinical measures . FHS mea"Health-related quality of life is the value assigned to duration of life as modified by the impairments, functional states, perceptions, and social opportunities that are influenced by disease, injury, treatment or policy" .It is generally accepted that a goal of therapy is to make patients feel better  and thisA series of studies from a randomized controlled clinical trial (RCT) and prospective cohort study of elective total hip arthroplasty are illustrative of these purposes. These examples, while not from a pediatric setting, are orthopedic and demonstrate how data can be used for a variety of purposes. In the RCT, Rorabeck and colleagues  undertooThere are many factors to consider when designing studies using patient-focused health measures for orthopedic patients. Among the most important factors are the study objectives, types of patients, the dimensions and FHS constructs associated with the health problem under study, the appropriateness of the questionnaire for the age range of the patients, the viewpoint of the assessors answering the questionnaire, the method of collecting questionnaire information (self-completion or interviewer-administration), the period of time respondents are asked to consider when answering the questionnaire , and measurement properties of assessment tools. Measurement properties include content and construct validity, test-retest and inter-rater reliability, responsiveness, and practical limitations of data collection. It takes many years, and often decades, for credible and relevant evidence to be accumulated about the measurement properties of instruments. Instruments with well-established measurement properties should be used whenever possible. Two prime issues for assessments of children are the developmental stage of the subjects and the most appropriate respondent for questionnaires.The methods section of the paper presents a framework of important factors for consideration in designing studies to assess FHS and HRQL for orthopedic patients. The results were generated by applying the framework in the context of developing a proposal for a comprehensive international study of patients with neurofibromatosis type 1 (NF1) and congenital tibial dysplasia (CTD). The NF1-CTD protocol provides a rich illustration because it encompasses great variability in the instrument selection factors, and these patients with their supportive caregivers face numerous complex health status challenges with long-term implications for HRQL. Furthermore, there is little information in the published literature about the comprehensive health status and HRQL of patients with NF1-CTD. The rationale and approach to studying FHS and HRQL from a patient perspective have relevance to many other areas of orthopedics.This section identifies specific study design and measurement instrument factors that should be considered in selecting measures for use in studies, and presents some background information for illustrating the application of these factors.Study design factors are specified in detailed protocols that clearly define the study objectives and conditions. Well-defined study objectives identify the study subjects, and type and number of measurements required. Study conditions describe practical issues including data collection sites, and budgets for time and resources.A highly focused, single objective study may require relatively few instruments while a broad-based, multi-faceted study will require numerous measures. For example, a RCT of efficacy for an experimental technique to achieve union of bone compared to a conventional technique might specify patients' reports from a single well-established walking ability scale as the primary outcome measure. However, an economic evaluation of the cost-effectiveness and cost-utility of the experimental technique would require at least two instruments: the single well-established walking ability scale to estimate effectiveness for the numerator in the cost-effectiveness ratio; and a utility-based scale of overall HRQL to estimate quality-adjusted life years for the numerator in the cost-utility ratio.The age of study subjects affects the choice of measurement instruments and the method of collecting data. Each instrument is valid for a specific age range and the age range is quite small for many pediatric instruments. For example, developmental changes during childhood make it difficult for single instruments to be valid from infancy through adolescence. Many instruments are valid for one or more of the following age categories: infants, pre-school children, primary-school children, adolescents, young / middle-age adults, seniors and elderly. Inability to read well , or see well , or concentrate well  inhibits use of self-complete questions. Well-designed interviewer-administered questionnaires pose clear, short, well-focused questions with readily understood and easily remembered response options .It is becoming widely accepted in many disciplines that studies of health care programs and technologies should include measures of patients' perceptions of their FHS and HRQL . MeasureThe locations and cultural characteristics of the study population will determine the language and sometimes the choice of assessors. Relatively few instruments have been carefully translated and culturally-adapted to facilitate use in a large variety of communities. Some cultures accept a variety of assessment viewpoints  while other cultures recognize only a physician viewpoint for health assessments.The literature suggests that there may be important effects due to mode of data collection  and, theFHS questionnaires should have well-specified assessment periods to help ensure that the subjects and researchers know the period of time covered by the responses. Assessment recall period refers to the period of time the assessor is asked to consider when answering the questionnaire. The period should match the objectives of the study. For instance, if a new surgical technique is thought to reduce the peri-operative burden of morbidity then frequent assessments with a brief recall period (24 hours) might be suitable. Standard assessment periods include the past 24 hours, the past 1 week, the past 2 weeks and the past 4 weeks. Short assessment periods should be used in studies of patients whose FHS varies over time and in studies involving serial assessments to ensure that there is no overlap in assessment times. Relatively long recall assessment durations may be used when it can be assumed patients' health status is fairly stable. For example, a four-week recall assessment period was used to measure the HRQL of patients in a randomized clinical trial and economic evaluation of two alternative treatment strategies for patients with knee osteoarthritis ,16.There are limits to the number and type of measures that respondents can be expected to complete without getting tired or frustrated, and/or that the study budget can afford in regards to both data collection and analysis. The evidence about the limits of respondent burden is sparse. All else being equal, studies involving serial assessments should expect to collect fewer measurements per assessment than single-assessment cross-sectional surveys. To maximize efficiency, instruments should be selected to provide complementary rather than overlapping information.There are numerous definitions of FHS and HRQL. For the purposes of the paper, a FHS measure is defined as being descriptive in terms of functional ability and HRQL is defined as involving some form of valuation of that health status.One published taxonomy  suggestsEach multi-attribute system includes a descriptive classification scheme to describe and assess health status, and a preference-based valuation system. HRQL scores for health states defined by multi-attribute systems are calculated from models fitted from directly measured preference measurements (see below). Multi-attribute systems provide descriptive information about comprehensive health status, and interval-scale preference scores of overall HRQL from a community perspective on a scale where 0.00 is the score for being dead and 1.00 is the score for being in perfect health. Several multi-attribute systems define negative scores of overall HRQL to represent preferences for states considered worse than being dead. A few systems include single-attribute preference-based scales of morbidity. Single-attribute morbidity scales are defined such that the least desirable level within an attribute  has a score of 0.00 (blind) and the most desirable level has a score of 1.00. The community perspective is most widely recommended for technology assessment and reference case economic evaluation analyses -29. InteA valid measure is "sound and sufficient" . There aA measure is reliable if it is sound and dependable . ReliabiResponsiveness is also referred to as sensitivity to change. It is an important feature for determining a measure's ability to detect effects of treatments or natural changes over time . Husted and colleagues reviewed the literature and defined two major types of responsiveness: internal and external responsiveness . InternaCeiling and floor effects are undesirable properties that reduce the validity, reliability, and responsiveness of measures. A ceiling effect may occur when a large proportion of measurement observations are close to the upper bound of the measurement scale. A ceiling effect results in a positively skewed distribution of measurements, limited ability of the measure to discriminate among subjects at the upper end of the scale, and attenuated responsiveness to improvements in health in longitudinal studies. A floor effect may occur when a large proportion of measurement observations are close to the lower bound of the measurement scale. Floor effects create a negatively skewed distribution of measurements, limited ability of the measure to discriminate among subjects at the lower end of the scale, and decreased responsiveness to decrements in health in longitudinal studies. Many generic and specific measures of HRQL may be subject to ceiling effect problems in that they may not be able to describe patients or subjects with above average  health. Some measures are subject to floor effect problems. Some are subject to both. Typically floor effect problems are more serious in clinical studies (which often involve patients with disabilities) and ceiling effect problems may be more problematic in general population studies.The limits of respondent burden depend upon many factors including the number of questions presented, how the questions are presented, the complexity of questions, the sophistication of respondents, and the respondents' interest in the questions. In general, the allowable length of questionnaire is shorter for mail and phone administration than for face-to-face interviewer administration . One setApplications of FHS and HRQL measures are greatly facilitated by expert advice, detailed instructions and other services designed to support users of a measure. Supporting documentation is usually protected by copyright and should not be used without written permission of the original developers. Documentation obtained from third-party sources should be considered suspect because it is frequently invalid. Licensing fees are used to fund high quality, readily accessible service centers. Permission to use copyright materials is typically granted one study at a time. Support services may also include consultation about the most appropriate versions of questionnaires for use in a specific study. Application packages may include data collection instruments such as questionnaires, procedure manuals, coding algorithms and scoring systems, as well as background information about the conceptual and measurement properties of the instrument.Recently there has been interest in using measures of FHS and HRQL to evaluate treatment alternatives for NF1-CTD. NF1 is one of the most common genetic disorders in childhood . It is eCTD is rare in the general population, approximately 1 per 140,000 . It has Conventional clinical measures of CTD include the Crawford classification system . These mSurveys of the published literature, experts in the fields, web sites and other sources of information were conducted to determine the dimensions of health that are affected by NF1-CTD, the types of FHS and HRQL measures that have been used, which measures should be considered as potentially useful for studies of NF1-CTD, the measurement properties of potentially useful measures, and the relative merits of various measures. A review of the on-line Quality of Life Instruments Database (QOLID) developed by Dr. Marcello Tamburini and the MAPI Research Institute , and corThere are five important research objectives of an NF1-CTD study that provide a context for applying the framework described in the Methods section:1) to document long-term health outcomes associated with the disease and its treatment;2) to measure the burden of disease and treatment during active therapy;3) to investigate the hypothesis that improved HRQL is associated with initial amputation compared with multiple limb-saving procedures;4) to determine relationships of FHS and HRQL with conventional clinical variables used in diagnosis and management; and5) to assess the measurement properties  of selected FHS and HRQL measures in NF1-CTD patients.These detailed objectives require the identification and assessment of leading FHS and HRQL measures for use in both cross-sectional and prospective longitudinal surveys.The prevalence of NF1-CTD is relatively low. Patients will need to be recruited from numerous clinical centers in North America to generate precise estimates of FHS and HRQL. Questionnaires should be available in at least 3 major languages: English, French and Spanish. The survey population ranges in age from newborn into adulthood and linking results across the study objectives requires that at least some of the assessment tools be in common across the age range of study patients. To avoid potential confounding effects, data collection techniques should be consistent across subjects and measures.The patient-focus will be represented by collecting measurements from all patients old enough to provide self-assessments, and from parents acting as proxy assessors for all children and adolescents. Self-complete questionnaires requiring minimal supervision should be used to eliminate the need for interviewers at each clinical center, to facilitate use of mail-out surveys, and to avoid potential "interviewer" effects. The number and type of measures per assessment, and the number of serial assessments per patient, should be sufficient to address all the study objectives within the limits of study resources and assessor burden. Measures of morbidity associated with NF1-CTD should be comparable with data on norms from surveys of general populations and other patient groups, and be useful for assessing the effectiveness and efficiency of health care services.The HRQL measure should be comprehensive and preference-based, to facilitate a broad variety of comparisons. A pediatric health profile measure and other specific measures will be selected to complement the selected preference-based HRQL measure. FHS measures may be focused on one or more of the following: the population of interest ; the major underlying disease ; the major human function of most interest ; the medically-defined health problem of most interest ; the medical speciality most involved with treatment of the health problem .There are six major generic preference-based HRQL utility systems , presentThe major population-specific health profiles include the Child Health Questionnaire (CHQ), Pediatric Inventory of Quality of Life (PedsQL), Pediatric Evaluation of Disability Inventory (PEI) and TNO-AZL Pre-School Children Quality of Life questionnaire (TAPQOL). The PEI is limited to children age 0.5 – 7 years of age and requires a structured parent interview or clinician observation . TAPQOL The major pediatric disease-/function-/specialty-specific instruments include the PODCI , ASK, Gillette Functional Assessment Questionnaire Walking Scale , and Wee-FIM. Wee-FIM , a populA summary of the major pediatric generic health profiles appears in Tables Table The choice of existing measures is based on a process of elimination considering the relative strengths of each instrument and the complementarities among measures. Neither the SF-36 nor the EQ-5D is valid for use in adolescent patients with orthopedic problems . A revieIn summary, there are few measures available for assessing subjects less than 5 years of age and even fewer for subjects less than 2 years of age. Most relevant measures are available in self-complete format only. Preliminary recommendations for the NF1-CTD study were that PedsQL be used as the generic health profile, HUI be the multi-attribute preference-based measure of HRQL utility scores for children age 5 years and older and that CHSCS-PS be the measure for children age 2 through 4 years, ASK be the measure of activity limitation, FAQ walking scale be the measure of walking ability, and that a small feasibility study of these instruments be completed with a convenience sample.A pilot feasibility study surveyed 8 NF1 patients using HUI and FAQ walking scale measures. Questionnaires were completed by 6 NF1 patients and 3 parents. The combined HUI and FAQ walking scale questions took respondents an average of 13 minutes  to complete. The patients were 11 to 50+ years old and had health problems ranging from mild to severe. One patient with tibial dysplasia and 2 patients with scoliosis were included.HUI data were collected from 5 patients, 2 parents and both the patient and parents in one case. Health problems were reported in 7 of the 8 HUI3 attributes . The attributes associated with the most morbidity, as assessed using HUI3 single-attribute utility scores , were paFAQ walking scale data were collected from 4 patients (1 of the 5 survey patients did not answer the question), 2 parents and both the patient and parents in one case. Five patients were reported to be at Level 10 , one patient to be at Level 8 , and one patient at Level 6 .In summary, the feasibility study showed that the HUI and FAQ walking scale questions were acceptable to patients' families and that results, especially for HUI, reflected the large variability in HRQL of the sample of patients.No single measure will provide sufficient data to address all the important study objectives. A set of measures is required. The set of measures should provide complementary data of health status and preference-based scores of HRQL. Redundancy in measurement is reduced, and efficiency of measurement is increased, by selecting the most comprehensive generic measures and then supplementing these measures with the most appropriate set of specific measures.It is recommended that HUI be selected as the comprehensive generic measure for ten reasons:a) it includes both generic health profile and preference-based scoring systems;b) the preference-based scoring systems are well-validated;c) it is the most comprehensive, compact and efficient of these types of systems;d) it includes many of the most important domains in the context of NF1-CTD;e) it is applicable for all people age 5 years and older;f) well-developed data collection questionnaires are available to match the study design criteria;g) HUI results facilitate integrating effects of morbidity and mortality, and cost-utility economic evaluations;h) it has been used successfully in a variety of studies of musculoskeletal problems;i) population norm data are available; andj) a closely-related health status system, the CHSCS-PS, is available to assess children 2 through 4 years of age.The HUI will provide a broad set of measures for comparisons with other populations and for estimating HRQL on a general scale such that dead = 0.00 and perfect health = 1.00. As a generic measure, HUI also has the ability to capture side effects and the effects of co-morbidities. However, these broad measures may not be responsive to small but important changes in health status. Therefore, HUI should be complemented by a set of instruments focused on pediatric, orthopedic and walking issues.The PedsQL 4.0, a pediatric generic health profile, should also be included in the set of measures because:a) it includes domains, social and school function, which complement HUI and CHSCS-PS domains;b) it is appropriate for children ages 2 through 18 years;c) it is not overly burdensome in terms of data collection;d) patient and parent assessment questionnaires are available; ande) it can be interviewer-administered to facilitate data collection by telephone, if necessary.Two specific measures should also be part of the set of instrumentation: the ASK and the FAQ walking scale. ASK is an orthopedic-specific instrument which has been shown to cover the most important domains in the context of musculoskeletal disorders, including the impact of limb lengthening surgery experienced by many children with tibial dysplasia. ASK is also attractive because it provides overall summary scores for both performance and capability measures, and is only moderately burdensome to complete. Walking ability is one of the most important aspects of health that is frequently compromised in NF1-CTD patients, and the FAQ walking scale is the most complete scale of functional walking ability currently available and it only requires asking one question.CHQ is not recommended because it does not add much to the set of recommended measures and it is burdensome to complete. PODCI is not recommended because it is very burdensome to complete, it has been reported to have major problems with "missing data", and the system for collapsing questionnaire responses into summary scores is not well validated.Children ages 2 to 5 years of age should be assessed by their parents using three questionnaires: the CHSCS-PS (12 questions), the PedsQL (23 questions); and the FAQ walking scale (1 question). It is expected that all three of these questionnaires can be completed in an average of 15 minutes.Children and adolescents ages 5 to 17 years of age should be assessed by their parents using four questionnaires: the HUI (15 questions), the PedsQL (23 questions), the FAQ walking scale (1 question), and the ASK (30 questions). These four questionnaires are expected to be completed in an average of 20 to 30 minutes.Children and adolescents older than 11 years should provide self-assessments using four questionnaires: the HUI (15 questions), the PedsQL (23 questions), the FAQ walking scale (1 question), and the ASK (30 questions). On average, it is expected that respondents will complete all four questionnaires in 20 to 30 minutes.This paper highlights reasons why patient-focused measures of FHS and HRQL should be considered important tools in the field of orthopedic surgery. It has also noted that there is increasing competition for scarce health-care resources, that allocation decisions about these resources are being informed by evidence based on patient-focused health measures, and that these measures are being under-utilized by the orthopedic surgery community.The orthopedic community faces numerous obstacles in utilizing FHS and HRQL measures. One major obstacle is that the multitude of existing measures makes it difficult to decide which measures may be appropriate for a specific application. A second obstacle is that most of the information about FHS and HRQL measures is not reported in the orthopedic literature. A third obstacle is that usually no one measure can capture all the important aspects associated with a specific orthopedic issue. The framework outlined in the paper provides guidance for selecting appropriate FHS and HRQL measures. The framework guides orthopedic investigators to combine their basic study criteria, including objectives and clinical context, with key criteria for FHS and HRQL measures from the published literature.The results in this paper identify some major sources of information about health measures, identify some of the most widely used measures of FHS and HRQL, and provide summaries of key characteristics for selected measures in three major taxonomical classes: generic preference-based multi-attribute systems; generic pediatric health profile systems; and orthopedic-specific systems. It is clear that there are many important differences among measures both within and across taxonomical classes. All measures are not equal. There are sound factors for making judgements about which measures are most appropriate for a given application. A process of appraisal and elimination was used to select one measure from each taxonomical class for inclusion in the NF1-CTD study illustrative example, and a pilot study of the most readily available selected measures confirmed the feasibility of their use in a small sample of NF1-CTD patients.The paper shows that a set of relevant, valid, reliable, responsive and practical patient-focused health measures for use in an orthopedic study can be readily identified and selected from the published literature and information available on the worldwide web. We encourage orthopedic researchers to use the framework to identify and select appropriate patient-focused health measures in their future studies.®) instrumentation and provides methodological advice on the use of HUI.W. Furlong and D. Feeny have a proprietary interest in Health Utilities Inc. which distributes copyright Health Utilities Index (HUIAll authors were involved in critical review of drafts for intellectual content and have given final approval to the version submitted for publication. W Furlong was responsible for much of the overall design, acquisition of data, and initial drafting. R Barr and D Feeny made important contributions to the analysis and interpretation of results. S Yandow conceived the idea of presenting the information in a published manuscript.


In various people of the Western world, gastro-oesophageal reflux (GOR) has been reported to be a common problem. Various studies have also assessed the relationship between GOR and dental erosion. The authors are not aware of such studies in Nigerians. It is therefore the aims of the present study to estimate the prevalence of GOR; to estimate the prevalence of dental erosion in patients with GORD; to document the oral findings in patients diagnosed with GORD and to compare these findings with previous studies elsewhere.A total of 225 subjects comprising of 100 volunteers and 125 patients diagnosed with GORD were involved in this study. History of gastric juice regurgitation and heartburn were recorded. Oral examination to quantify loss of tooth structure was done using the tooth wear index (TWI) designed by Smith and Knight (1984).Twenty patients with GORD presented with dental erosion in the maxillary anterior teeth with TWI scores ranging from 1–3. The prevalence of erosion was found to be statistically significant between GORD patients (16%) and control (5%) (p < 0.05), but not significant between endoscopic diagnostic groups (p > 0.05).The present study supports the consideration of dental erosion as the extra-oesophageal manifestation of GORD. However the association between GORD and burning mouth sensation needs more investigation. Gastro-oesophageal reflux (GOR) is the passage of gastric contents into the oesophagus. Once past the upper oesophageal sphincter, the gastric juice may pass into the oral cavity. The continual exposure of the teeth and other oral structures to gastric refluxate may result in dental erosion and other soft tissue symptoms . Any aciCurrent understanding of GOR and GORD is that acid reflux into the oesophagus may be caused by three possible mechanisms :(1) Transient spontaneous or inappropriate relaxations of the sphincter;(2) Transient increase in intra-abdominal or intragastric pressure;(3) Functional abnormality of the lower oesophageal sphincter (LOS).et al .To document the oral findings associated with GORD, patients referred to the Gastro-intestinal (GIT) endoscopic unit for investigation of gastro-oesophageal tract disease were also evaluated for dental erosion and other soft tissue symptoms such as non-specific burning sensation in the mouth and sensitivity in the tongue. The dental evaluation included history to determine potential eatiological factors responsible for dental erosion. Patients were also examined clinically to quantify loss of tooth structure using the tooth wear index. The oral examination was performed by one of the authors (AO), blind as to the endoscopic diagnosis of subjects. Patients with positive endoscopic findings plus the occurrence of heartburn two or more times per-week were assessed to meet the criteria for GORD. When a clear-cut endoscopic evidence of oesophageal inflammation was seen , a diagnosis of oesophagitis was made. Gastroduodenal ulcer was diagnosed through endoscopic evidence of an ulcer with a necrotic base or a clear-cut scar. This was grouped into those with gastric ulcer  and those with duodenal ulcer (ulcer in the bulbus). Only one diagnosis was given for each patient.Data collected were entered into a computer and analysed using chi-square. P value <0.05 were considered significant.Thirty-five of the 100 subjects attending the medical outpatient department had acid regurgitation and acidic taste sensation in the mouth. This occurs most of the time following a full stomach meal and is associated with belching. Table One hundred and twenty five patients were diagnosed with GORD. Twenty presented with dental erosion in the maxillary anterior teeth with TWI scores ranging from 1–3. The prevalence of erosion was found to be statistically significant between GORD patients (16%) and controls (5%) , Table The details of the orodental findings in the twenty patients who had dental erosion are shown in Table Burning mouth sensation and peppery sensation in the tongue where reported by 9 patients who had had gastrointestinal symptoms for 10–20 years.Various methods have been employed in the investigation of GOR including endoscopy with biopsy and contrast radiography. Although twenty-four hour oesophageal pH monitoring is considered the gold standard investigation of GOR , due to et al [et al [The prevalence of GOR and GORD in the present study was 35% and 11% respectively. The prevalence of GOR was much lower than the 60% reported in the U.K. and other Western societies , whereaset al . The prel [et al , and Schl [et al  respectil [et al , whereasl [et al ,25. Alsol [et al .The consumption of acidic beverages among the study population was low, hence the silence on its contribution to the overall disease level. Although this is controversial, the authors are of the opinion that intrinsic (gastric) acid results in palatally eroded sites  declare that they have no competing interests.AOO conceived of the study, participated in its design, performed the dental examination including the application of the tooth wear index (TWI), and participated in the initial draft and final write-up of the manuscript. EAA and DAN performed the endoscopic examination of patients with gastro-oesophageal reflux disease, participated in the initial draft and final write-up of the manuscript.The pre-publication history for this paper can be accessed here:


The closure of the abdomen after median laparotomy is still a matter of debate among surgeons. Further well designed and performed randomised controlled trials determining the optimal method of abdominal fascial closure are needed.This is a three armed, multi-centre, intra-operatively randomised, controlled, patient blinded trial. Over 20 surgical departments will enrol 600 patients who are planned for an elective primary abdominal operation. The objective of this study is to compare the frequency of abdominal incisional hernias between two continuous suture techniques with different, slowly absorbable monofilament materials and an interrupted suture using an absorbable braided suture material at one year postoperatively.This trial will answer the question whether the continuous abdominal wall closure with a slowly absorbable material with longitudinal elasticity is superior to the continuous suture with a material lacking elasticity and to interrupted sutures with braided thread. Median laparotomy is the most common technique of abdominal incisions because it is simple, provides adequate exposure to all four quadrants, is rapid to open and usually bloodsparing . A majorWhereas patient related factors such as age, gender, body mass index (BMI), underlying disease, co-morbidities, prior surgical procedures and life-style factors (e. g. smoking) cannot be controlled or standardised, the decisive chance to lower the incidence of incisional hernias is to optimise the surgical technique. Therefore, a great variety of suture materials and needles has been developed to provide an adequate closure of the fascia and thus the abdominal wall. Thousands of patients have been included in trials in order to answer the question which is the optimal method in abdominal fascia closure and today a number of reviews and a meta-analysis are available. However, the reliability of the existing evidence is compromised by the low number of relevant randomised controlled trials (RCT's) -8.Therefore the discussion regarding the optimal technique of abdominal fascia closure continues and most surgeons practice according to their own experience rather than acting evidence-based. This attitude resulted in an unchanged frequency of incisional hernias over the last decades . None ofWe therefore conclude that there is a lack of data from a truly well-designed long-term trial performed in the daily practice of surgery. This has led us to develop a large randomised controlled trial comparing different surgical techniques of abdominal closure after median laparotomy. INSECT is a multi-centre, intraoperatively randomised controlled trial comparing three different standardised surgical techniques with certain needle/suture combinations on the occurrence of incisional hernia in patients with elective primary midline laparotomy. Two groups will use running sutures with different longitudinal elasticity (one group PDS™ and the other MonoPlus™) combined with an atraumatic needle and one group interrupted sutures (Vicryl™) with a traumatic needle. A three-group parallel equivalence design was selected because due to the results of the latest published meta-analysis  the supeINSECT is the first large-scale trial that started after a detailed theoretical and practical training of the participating surgical centers in March 2004 in order to reduce surgical bias in the study. INSECT will provide internal valid data for an adequate surgical technique of abdominal closure. Although we are well aware that this study cannot answer all open questions, the results should help to further improve evidence based surgery.INSECT has been designed and carried out by the Study Centre of the German Surgical Society (SDGC). The SDGC is an independent research group of the German Surgical Society and the Medical School of the University of Heidelberg that has to design, conduct and analyse large randomised surgical trials in order to improve daily surgical practice. The role of the sponsor (BBD Aesculap) is limited to material supply and local first-level-support. The sponsor is not involved in the database management and has no access to the randomisation code.), database management, quality assurance including monitoring, reporting and for the scientific program of all trial related meetings.The trial is coordinated by the SDGC, which is responsible for overall trial management, trial registration , Patients will be recruited by over 20 surgical centres in Germany. All investigators are hospital-based surgeons with a focus on general surgery. In order to obtain a representative trial result hospitals of all levels of care and education  are participating in this trial.This committee consists of 3 surgeons and decides on the final diagnostic classification of critical clinical events. For all serious adverse events the documentation and relevant patient data are verified by co-ordinating personnel of each centre before submitting the data to the Adverse Events Committee for diagnostic classification.Adverse Event covers any sign, symptom, syndrome or illness that appears or worsens in a patient during the period of observation in the clinical trial and that may impair the well-being of the patient. The term also covers laboratory findings or results of other diagnostic procedures that are considered to be clinically relevant. A Serious Adverse Event is any adverse event that occurs at any time during the period of observation, that results in death, is immediately life-threatening, requires or prolongs hospitalisation, results in persistent or significant disability or incapacity.Burst abdomen, pulmonary infection and wound infection are secondary endpoints, but are also defined as Adverse Events  guidelines. The data monitoring for this trial will be performed by an independent study nurse who is not involved in the trial or in completion of the case report form (CRF). The surgical monitoring will be done by independent surgeons being not involved in conducting this trial.The final protocol was approved by the ethics committee of the University of Heidelberg, Medical School. Secondary approval is gathered from all local ethics committees responsible for the participating centres. Informed consent will be obtained from each patient in oral and written form before inclusion in the trial.INSECT focuses on hospitalised patients over 18 years of age who are planned for an elective primary abdominal operation and are eligible for a vertical abdominal incision in order to perform the planned surgical procedure. A detailed overview of all eligibility criteria is given in Table The primary objective of this study is to compare the frequency of incisional hernias between three different abdominal fascia closure methods after one year postoperatively: two continuous slowly absorbable monofilament suture materials with and without longitudinal elasticity respectively  and a interrupted suture with an absorbable braided suture material .Secondary objectives are the frequencies of early and late onset complications such as burst abdomen, postoperative pulmonary complications, wound infections and incisional hernias after three years postoperatively. Additionally a set of surgical and non-surgical parameters related to the operation will be analysed as secondary objectives such as the frequencies of various complications, the lung function and the postoperative length of hospital stay. A qualitative analysis is included in the study to assess the relevance of the primary endpoint from the patient's and the surgeon's perspective. The following aspects are ranked in a descending order from 1 (= most important) to 9 (= least important): postoperative complication, intraoperative complication, length of hospital stay, onset of enteral nutrition, death, postoperative pain, postoperative fatigue, convalescence of the complete physical maximum resilience and cosmetic result . The ranA block-randomisation-list is generated via computer system  and stratified for the individual centre. Each centre will contribute 30 patients (10 to each group). The sealed randomisation list is stored in the investigator file. Patients are randomised using sealed opaque envelopes in the operation theatre after the surgical procedure has been started and before the abdominal wall will be closed.Major challenge in this surgical trial compared to pharmaceutical trials is the standardisation of the surgical technique. All patients undergo a skin incision using electric cautery. Upon completion of the surgical procedure, closure of the abdominal wall is performed in all three groups in a standardised manner: four sharp Mikulicz-Clamps are placed at the corners of the incision and in the middle of the edges of the abdominal fascia and then the closure technique will be performed according to randomisation. Three groups are available: a continuous, all-layer closure technique with either two monofilament loops or an interrupted technique using a braided material . In all three groups suturing is initiated at both ends of the incision towards the middle, whereas the continuous suture line is overlapping at the centre for at least 2 cm to secure each other  all participating centres have been trained in the required techniques using abdominal wall models of mini-pigs. An evaluation of the investigator meeting was performed by all participants and will be published shortly. Investigators being unable to attend were trained on-site using the same training materials as in the investigator meeting. Training materials were supplemented by videos demonstrating the abdominal wall closure techniques (both continuous and interrupted) in the in vivo situation and in the animal model giving all sub-investigators good insight into the required techniques. Furthermore, a trial manager of the SDGC is available and responsible for all trial related issues and questions.In an investigator meeting before trial initiation . These are arranged for each visit time-point and contain instructions and relevant definitions. All treatments are recorded in treatment logs. Standard adverse events forms are used to document (serious) adverse events and relevant clinical procedures that have been carried out. After verification of the data entered according to "Good Clinical Practice" (GCP), one copy of each completed CRF is sent by mail to the SDGC. A concurrent database is maintained there. All incoming CRF are scanned to be electronically archived. Data are entered in a specially developed relational data base management system. The data entry module contains on-line range and logical checks. For data that are found missing, illegible or inconsistent, data clarification forms are generated which are sent to the on-site monitor for resolution.Certain events must be reported immediately by the investigator by fax on preprinted forms directly to the coordinating centre. Examples are: informed consent and randomisation form, serious adverse events and premature withdrawal form the trial. The reporting of serious adverse events complies with national regulatory requirements.Statistical methods are used to assess the quality of the data, homogeneity of treatment groups, endpoints and safety of the three different techniques.The analysis is performed on the basis of an intention to treat (ITT) population and with respect to ITT principles. A patient belongs to the ITT population after the randomisation. The primary endpoint will also be analysed on the basis of a "per protocol" population.1, R2, and R3. These hypotheses H12: R1 = R2, H13: R1 = R3, and H23: R2 = R3, are all contained in the global null hypothesis H123: R1 = R2 = R3. Sample size estimation, however, will be based on the elementary hypotheses, thus leading to sufficient power in the global test. Bauer had recommended that "sample sizes should be chosen large enough to give a high chance of jumping over the initial hurdle." [To enable multiple comparisons in this three-armed study the closed testing procedure will be used. All thrhurdle." .®, incisional hernias were seen in about 13% of patients. This number is primarily based on the four-armed trial by Wissing et al. [®, MonoPlus® or Maxon®, lower herniation rates were found, but this holds true only for continuous suturing. So far, only one trial has compared fast and slowly absorbable materials for interrupted sutures [The calculation of sample size is based on literature data, as summarised most recently by van 't Riet et al . With ing et al. . With th sutures .® groups over the first postoperative year. Smaller differences are also unlikely to be of clinical relevance.The comparison of interrupted rapidly absorbable versus continuous slowly absorbable sutures has been the aim of four previous studies. The results of these studies showed a non-significant tendency towards a lower rate of incisional hernia. Taking this data and the improved suture properties into consideration, a hernia incidence of 4% could be reasonably expected in one or both of the non-Vicryl). To account for an estimated 10% loss to follow-up and 2% surgical non-compliance with treatment allocation, sample size should be increased to 200 patients per group. In summary, the trial should recruit a total of 600 patients, with equal randomisation into the three groups. Thus a total of 720 patients have to be screened according to the CONSORT statement . We used the PS power and sample size program of Dupont and Plummer (Version 1.0.17) for sample size estimation  use the same alpha level of 0.05, because closed test procedures in three-armed designs do not require alpha level adjustment. If, however, the first global hypothesis cannot be rejected at alpha level, the family of elementary hypotheses will not be tested at all, except for exploratory reasons.In the primary intention-to-treat analysis, testing will start with the global null hypothesis HTo control for possible differences with regard to surgical procedures , centre, and surgical expertise (board-certified surgeon vs. assistant surgeon), logistic regression will be used. We expect that the use of logistic regression will not essentially comprise power assumptions when compared to univariate testing. The inclusion of time-to-event data in the primary statistical analysis (e.g. by applying Kaplan-Meier-curves or Cox-regression) does not confer specific advantages and seems unwarranted, also because an incisional hernia causes similar consequences for the patient irregardless of whether the hernia occurred after 3, 6 or 9 months.The analysis of the secondary endpoints and demographic variables will be descriptive.The description of continuous variables includes at least: numbers of observations, mean, standard deviation, median, minimum and maximum. The description of categorical variables  includes at least the number and percentage of patients belonging to the relevant categories in the trial population as well as in each treatment group.The description of the ranking of parameters of interest  and surgeon's view) includes the mean and median for each category in the trial population. There will be a listing for all measurements taken for the patients. In order to improve the presentation of the observed data, graphical methods will be applied.The clinical database including all information until 12 months after the operation will be closed six months after the last visit, complete documentation of all cases and resolution of all queries. At this time the primary endpoint of the trial will be ascertained. The information of the final follow-up three years after the operation will be added later. This database will be closed three months after the last telephone three years after the last operation.th and 6th, 2004. In June 2004, following completion of contracts and approval of local ethics committees, the first centres were initiated and the first patient was recruited in July 2004. Currently 23 centres are in an active status recruiting the required 30 patients per centre. Further 6 centres are processed and will be activated within the next months. Assuming an enrolment of 5 patients per month and centre the end of recruitment is assumed to be in October 2005.The initial idea and hypothesis for the study was developed in March 2003. After a systematic review of the literature according to Cochrane standards has been performed the study protocol was completed in October 2003. The study protocol was approved by the local ethics committee of the University of Heidelberg in December 2003. Preparation of all study and instructional materials (including video clips) was completed in February 2004 and the first investigator meeting was held in Tuttlingen, Germany on March 5The strategy to publish study protocols in surgery and thus to enhance transparency in a clinical trial might be relatively new in surgery, but has been practised in other medical fields for several years ,20. ThisINSECT is designed to help answering the question which is the optimal method for abdominal wall closure. Although there are a substantial number of randomised studies and several meta-analyses examining different techniques of abdominal fascia closure the optimal and definite method for closing the abdomen has not yet been found ,7,11. ThSeveral design features of INSECT were discussed before the trial started. A two armed or a three armed study design was debated before writing the protocol. As we wanted to compare the clinically most relevant and most evidence-based suture materials and suture techniques for closure of midline abdominal incisions the most recent and most relevant meta-analysis as a data-base for choosing the different groups in our trial was used . Two difAn important issue for a good trial is to define adequate and well designed end-points. Regarding the optimal method for abdominal closure a great variety of objectives has to be considered: wound infection, wound dehiscence, incisional hernia, suture sinus, wound pain, etc. The socio-economic and surgical most relevant objective is the incidence of incisional hernias . BecauseA major challenge in this INSECT trial compared to other studies, e. g. pharmaceutical trials, is the standardisation of the surgical technique. Lack of standardisation in surgical trials is often an argument of opponents who state that the achieved trial results would not be transferable to surgical routine. Therefore all patients in the INSECT trial undergo a standardised skin incision and opening of the abdominal cavity as well as the closure of the abdominal wall is performed in all three groups in a standardised manner. To provide an overall highly standardised surgical procedure in every study site all participating centres have been trained in the required techniques using abdominal wall models of mini-pigs during an investigator meeting before trial initiation. For investigators who were unable to attend the meeting training materials and videos demonstrating the different abdominal wall closure techniques (both continuous and interrupted) used in the study were provided. For further quality assurance there will be a regular surgical monitoring during the trial. Additionally, randomisation is stratified for each individual centre and the trial results will be therefore comparable among the different participating centres.Over the last years, surgeons' attitude towards randomised surgical trials has changed. It becomes more and more evident that surgical procedures could also be tested in randomised studies. Surgical expertise is largely a personal conviction and an apprenticeship with surgical techniques passed from one surgical generation to the next ,22. MostAWC Abdominal wall closureCRF Case Report FormGCP Good Clinical PracticeICH International Conference on Harmonisation of TechnicalRequirements for Registration of Pharmaceuticals for Human UseIEC Independent Ethics CommitteeITT Intention-to-treat-analysis® Polydioxanone PDSRCT Randomised Controlled TrialSDGC Study Centre of the German Surgical SocietyThe author(s) declare that they have no competing interests.Hanns-Peter Knaebel and Moritz Koch designed and wrote the manuscript, Stefan Sauerland prepared bio-statistics of the trial and is in charge of the data management, Markus K Diener searched and assessed the literature, Markus W Büchler sponsors the trial and provides necessary infrastructure, Christoph M Seiler searched and assessed the literature and overlooked the completion of the manuscript.The pre-publication history for this paper can be accessed here:


The relationship between the burden of uncomplicated malaria and transmission intensity is unclear and a better understanding of this relationship is important for the implementation of intervention programmes.A 6-month longitudinal study monitoring risk factors for anaemia and febrile malaria episodes was conducted among individuals aged below 20 years, residing in three villages of different altitude in areas of high, moderate and low malaria transmission intensity in North-Eastern Tanzania.Plasmodium falciparum was the only significant parasitic determinant of anaemia. Interestingly, children who carried low-density parasitaemia at the start of the study had a lower risk of contracting a febrile malaria episode but a higher risk of anaemia during the study period, than children who were slide negative at this point in time.The burden of anaemia and malarial fever fell mainly on the youngest children and was highest in the village with high transmission intensity. Although a considerable percentage of individuals in all villages carried intestinal worms, logistic regression models indicated that Young children living in the high transmission village carried a very high anaemia burden, which could be attributed to malaria. The overall incidence of febrile malaria was also highest in the high transmission village particularly among those under five years of age. These data suggest that in rolling back malaria, available resources in prevention programmes should primarily be focussed on young children, particularly those residing in areas of high malaria transmission. Plasmodium falciparum malaria remains an important public health problem in sub-Saharan Africa. To develop and assess the efficacy of control measures, it is important to obtain a better understanding of how the malaria disease burden is distributed among population groups and how this burden is affected by changes in malaria transmission intensity ) had normal haemoglobin levels during the July and September cross sectional surveys, while 44 developed anaemia during the study (mean age (years) and 95% Cl: 7.9 ). Logistic regression models correcting for age showed that the risk of developing anaemia during the study was 4.4 times (p = 0.038) higher in individuals carrying low-density parasitaemia in April than in those who were slide negative (Table This prospective longitudinal study was designed to compare the burden of uncomplicated malaria in three similar villages situated in areas of markedly different transmission intensity. Not surprisingly, the study showed that individuals living in the village with very high malaria transmission carried a markedly higher burden of both anaemia and febrile malaria episodes compared to villagers at the sites with lower transmission. This result is in agreement with results from previous studies in the area . The vilP. falciparum carriage at the beginning of the study influenced the risk of developing febrile malaria episodes or anaemia during the following study period. Interestingly, multivariate logistic regression models indicated that children carrying low-density parasitaemia during the first cross sectional survey were at a lower risk of developing a febrile malaria episode than children without detectable parasitaemia or children with higher levels of parasitaemia. This apparent protective effect of low-grade parasitaemia was recently also reported in a study from Ghana [The longitudinal design of our study allowed an exploration of whether om Ghana , but in The overall burden of malaria morbidity was found to be highest in the high-transmission area, where infants and children carried a very high malaria burden in the form of febrile episodes and anaemia. Populations in the areas of moderate and low transmission suffered a significantly lower morbidity. Therefore, in order to roll back malaria, available resources in malaria control programmes should focus on underfives residing in the high-transmission areas.JPAL and LSV participated in the planning of the study, carried out field surveys, analysed the data and drafted the manuscript. BPM participated in designing the study, carried out field surveys and managed the data. CJD participated in study planning, in the fieldwork and in editing of the manuscript. CJ participated in the planning of the study and conducted the socio-economic analysis of study villages. JA and ZXS participated in the field surveys and performed microscopy of all blood smears. AYK, MML and TGT participated in study planning, coordination, and analysis of data. All authors participated in the paper writing and approved the final manuscript.


Children with congenital hearing impairment benefit from early detection and treatment. At present, no model exists which explicitly quantifies the effectiveness of universal newborn hearing screening (UNHS) versus other programme alternatives in terms of early diagnosis. It has yet to be considered whether early diagnosis (within the first few months) of hearing impairment is of importance with regard to the further development of the child compared with effects resulting from a later diagnosis. The objective was to systematically compare two screening strategies for the early detection of new-born hearing disorders, UNHS and risk factor screening, with no systematic screening regarding their influence on early diagnosis.Design: Clinical effectiveness analysis using a Markov Model.Data Sources: Systematic literature review, empirical data survey, and expert opinion. Target Population: All newborn babies.Time scale: 6, 12 and 120 months.Perspective: Health care system.Compared Strategies: UNHS, Risk factor screening (RS), no systematic screening (NS). Outcome Measures: Quality weighted detected child months (QCM).UNHS detected 644 QCM up until the age of 6 months . RS detected 393 child months  and no systematic screening 152 child months . UNHS detected 74,3% and 86,7% weighted child months at 12 and 120 months, RS 48,4% and 73,3%, NS 23,7% and 60,6%. At the age of 6 months UNHS identified approximately 75% of all children born with hearing impairment, RS 50% and NS 25%. At the time of screening UNHS marked 10% of screened healthy children for further testing , RS 2%. UNHS demonstrated higher effectiveness even under a wide range of relevant parameters. The model was insensitive to test parameters within the assumed range but results varied along the prevalence of hearing impairment.We have shown that UNHS is able to detect hearing impairment at an earlier age and more accurately than selective RS. Further research should be carried out to establish the effects of hearing loss on the quality of life of an individual, its influence on school performance and career achievement and the differences made by early fitting of a hearing aid on these factors. Approximately one to three per 1000 children are born with at least moderate, bilateral hearing disorders . ChildreVarious tests and test combinations with acceptable sensitivity and specificity are available. Transient evoked oto-acoustic emissions (TEOAE) or brainstem evoked responses (BERA) can be measured. One common strategy consists of a two-step TEOAE with the first measurement within the first days of life and a second test a few days later   . The TasHowever, there is presently no model explicitly quantifying the effectiveness of UNHS versus other programme alternatives in terms of early diagnosis, nor has it been taken into account that diagnosis of hearing impairment within the first few months of life is more "valuable" for the child's further development than diagnosis later in life. Children identified within the developmentally sensitive time frame should therefore be given more weight compared to children with delayed diagnosis.The objective of this clinical decision analysis was to systematically compare two screening strategies for the early detection of new-born hearing disorders: UNHS and risk factor screening; with the option of no systematic screening regarding their influence on early diagnosis.Our specific objectives were to show differences between strategies expressed as the number of quality weighed detected child months (QCM), the number of true positive cases at the age of 6 and 12 months, and the number of false positive cases. We also wanted to investigate which parameters had the most influence on the reported differences and how likely these differences were.We developed a clinical decision model to compare two different screening strategies with the option of no systematic screening. Parameters were extracted from the literature, empirically derived from a representative patient survey, and estimated by experts. Univariate and multivariate sensitivity analyses were performed on all relevant parameters.The decision model was used to predict absolute and incremental effectiveness of two new-born hearing strategies compared with the option of no screening in new-born infants. For the modelling of effectiveness the recommendations of the Panel on Cost-Effectiveness in Health and Medicine were followed .Three possible strategies for neonatal hearing screening (NHS) were evaluated:- Universal neonatal hearing screening (UNHS): Every hospital-born baby is screened during the first days of life.- Risk factor screening (RS): The prevalence of hearing disorders is estimated to be higher at risk groups such as children with a positive family history, with congenital infections, cranofacial abnormalities, low APGAR-Score or low birth weight. This strategy screens all children with one or more risk factors for hearing disorders.- No systematic screening (NS): Children undergo the usual distraction test when presented to the paediatric service during the routine visit at the age of 12 weeks. Some neonates are screened in the hospital, but not in a systematic way. This reflects the present situation in Germany. UNHS is performed in some maternity hospitals and outpatient paediatric services with pilot screening projects in several regions.The target population of this analysis was all newborn infants. Health effects are expressed as quality weighed number of detected child months (QCM), and as true positive and false positive cases at certain developmentally important ages 6 and 12 months); for example, if a hearing impairment was diagnosed briefly after birth, the infant contributed six QCM at the age of six months. If the infant's hearing loss was diagnosed at the age of five months, the infant added only one detected child month at the age of six months. The term 'quality' is to reflect the idea that the early detection of impairment is a better and desired outcome, although there is no data on quality of life gained by this early detection. QCM, true positives and false positives are reported at the age of 6 and 12 months and with a time horizon of 120 months. Child months which were added up until the age of 6 months were multiplied with a weight of 1, child months added after the age of 6 months were multiplied with decreasing weighting. The derivation of this weight index is described in the section 'data and assumptions' below. We assumed that all children with hearing impairment would be detected before the age of 72 months, the age of school entry, regardless of the kind of screening strategy. In order to give outcomes in the present more weighting, compared to outcomes in the future, future effects have been discounted at an annual rate of 3%. Discounting reflects the higher value of money spent now as opposed to in the future. Similarly, discounting also weights outcomes experienced now  more heavily than those experienced in the future. Table 2 months;We developed a state-transition (Markov) model  with mon- Unknown status- Healthy (hearing) confirmed by diagnostic test and/or screening – true negative- Healthy (hearing) not confirmed by diagnostic test- Hearing impaired confirmed by diagnostic test and/or screening – true positive- Thought to be healthy (hearing) but hearing impaired – false negative- Thought to be hearing impaired but healthy (hearing) – false positive- Not compliant/not followed upThe baseline cohort consisted of infants with a certain prevalence of hearing impairment but unknown status regarding this disorder. Screened and impaired children are detected with the sensitivity of the screening test, whereas screened and healthy children are classified as healthy with the specificity of the screening test. All children with a positive screening test  undergo a second confirmatory diagnostic test, unless they did not adhere to the screening or did not present for the following tests (lost to follow-up). Impaired children who have not been screened in the first cycle can be diagnosed in the subsequent cycles according to the "natural history" of diagnosis, that is, because they don't develop speech adequately or become apparent during the routine visits to the paediatrician. In each cycle children can move to other health states according to the transition probabilities. QCM are only attributed to impaired children in whom hearing impairment is detected. Ultimately, all impaired children of the model cohort are diagnosed as impaired and all healthy children are either classified as healthy or remain unclassified.Data Professional  was used to construct and run the Markov model and Excel for Windows (Microsoft Corp.) was used to validate the model and to perform the Monte Carlo simulations.A pre-defined and externally reviewed literature search was performed on new-born hearing screening using all relevant electronic databases. Search strategy and methods have previously been reported in detail . In brieAll model parameters are shown in Table Screening procedures and diagnostic procedures are based on different biological and clinical testing principles. We therefore assumed conditional independence of screening procedures and subsequent diagnostic procedures.In order to investigate the influence of the parameter estimates on the outcome measures, one-way sensitivity analyses were performed on all relevant parameters. Ranges used for sensitivity analyses were derived from literature searches and are shown in table The decision model was validated on three levels:(i) Technical validation: The model was tested independently with two different software packages . Routine tests  yielded the expected results.(ii) Internal validation: All data used to derive model parameter values, were reproduced exactly by the model .(iii) External validation: The derived values are consistent with external projections and estimates of recently published studies which were not used in our model ,22. for Table Results of sensitivity analyses are presented in table We developed a decision-analytic Markov model for the evaluation of the effectiveness of different new-born hearing screening strategies. In our model, UNHS identified 72% of all detectable QCM at the age of 6 months, RS identified 44% QCM, the control group with no systematic screening identified 17% QCM. UNHS shows higher effectiveness even under a wide range of additional relevant parameters. QCM was introduced as a dynamic time-to-event measure which takes into account that the age of confirmation of congenital hearing impairments is important for further language development. The model results were not sensitive to test the accuracy of parameters within the assumed range but varied with the prevalence of hearing impairment. We have shown that UNHS leads to an earlier age of confirmed diagnosis compared to selective RS.The cost effectiveness of UNHS has already been modelled along secondary data ,23,24. TOur findings are consistent with study results and other projections of effectiveness. The Wessex Universal Neonatal Hearing Screening Trial Group found that 71 more babies with moderate or severe hearing loss per 100 000 target population were diagnosed before the age of 6 months during periods with neonatal screening than during periods without . We founOur study has several limitations. Firstly, it does not differentiate between bilateral and unilateral hearing loss or moderate and profound impairment. We believe, however, that even with a more refined model the differences in effectiveness would not be substantial. Variations in the degree of impairment would result in variations in sensitivity of the test, and the model was rather insensitive to changes of test parameters. Secondly, even though QCM has been weighted, it is a surrogate parameter for the actual burden of disease for the child. Preference-based utilities have not been measured and the weighting for the impact of early or late identification of hearing loss used in our analysis were estimated by experts. Sensitivity analyses, however, revealed that without weighing, the difference in effectiveness would still be substantial. Thirdly, effectiveness was measured as a function of time to diagnosis. In routine health care, adequate treatment does not necessarily start immediately after the diagnosis is made. However, as knowledge on the consequences of delayed intervention is limited, including time to intervention as another variable in the model would have resulted in decreased precision . FourthlThe value of this modelling exercise on effectiveness, lies in the facilitation and provision of information to decision makers- by quantitatively projecting available data, making explicit and transparent statements about assumptions and the degree of uncertainty involved in this area. The probability of timely intervention increases with UNHS. UNHS can reduce age of confirmation to a much greater extent than RS. In further studies, our model can be used to predict costs of real life situations to evaluate whether programme implementation costs would surpass cost-effectiveness thresholds. Policy makers can also base their decisions on the incremental effectiveness of UHNS, by introducing a screening programme. The model shows how likely an outcome is under the assumption of parameter uncertainty.In our model UNHS showed higher clinical effectiveness compared to RS and NS. The strength of our model lies in the naturalistic and generic structure, which makes it useful as a model for further evaluation. The model gives explicit, transparent and quantitative information about the effectiveness of different screening strategies for policy makers who have to decide on the potential impact of neonatal screening. The model presented here is easily adaptable to different settings. It will and should be verified and tested with longitudinal data of ongoing trials and model projects.This can be one of the first steps towards the needed transparency concerning universal new-born hearing screening.The author(s) declare that they have no competing interests.EG developed the decision model, carried out the statistical analyses and drafted the manuscript. FH designed and coordinated the study and participated in the development of the decision model and in the writing process. US participated in the statistical analyses, in the development of the decision model and in the writing process. PS-I, SK and AN performed the systematic review and data extraction. AN participated in the design of the study. JW conceived of the study and participated in its design and coordination. All authors revised the manuscript and read and approved the final version.The pre-publication history for this paper can be accessed here:


Limb-salvage is a primary objective in the management of extremity soft-tissue sarcoma in adults and children. Wide-local excision combined with radiation therapy is effective in achieving local tumor control with acceptable morbidity and good functional outcomes for most patients.Two cases of deformity after wide-local excision, brachytherapy and external beam irradiation for lower-extremity synovial cell sarcoma are presented and discussed to highlight contributing factors, time course of radiation effects and orthopedic management. In an effort to spare normal tissues from the long-term effects of radiation therapy, more focal irradiation techniques have been applied to patients with musculoskeletal tumors including brachytherapy and conformal radiation therapy. As illustrated in this report, the use of these techniques results in the asymmetric irradiation of growth plates and contributes to the development of valgus or varus deformity and leg-length discrepancies.Despite good functional outcomes, progressive deformity in both patients required epiphysiodesis more than 3 years after initial management. There is a dearth of information related to the effects of radiation therapy on the musculoskeletal system in children. Because limb-sparing approaches are to be highlighted in the next generation of cooperative group protocols for children with musculoskeletal tumors, documentation of the effects of surgery and radiation therapy will lead to improved decision making in the selection of the best treatment approach and in the follow-up of these patients. Limb-salvage is an important treatment objective for adults and children with extremity soft tissue sarcoma and often requires the use of limited surgery and irradiation . LimitinSurgery and radiation therapy both have the potential to cause significant morbidity including loss of function and deformity ,11-15. TIndividual cases of valgus and varus deformity after limited surgery and irradiation for extremity soft-tissue sarcoma are presented and discussed to identify factors that may be responsible for these treatment complications. Pre-existing orthopedic problems, multiple attempts at resection, post-operative infection, the use of chemotherapy and the addition of brachytherapy to external beam radiation therapy appear to be contributory. Because limb-sparing approaches will be an important component of the next generation of cooperative group studies for extremity soft tissue sarcoma in children, the incidence and severity of this and other treatment-related complications should be documented as well as efforts to limit the effects of these treatments and identify solutions for established problems.At the time of diagnosis, this patient was an 8 year-old male with an approximate 12–24 month history of mild pain and swelling in the left popliteal region. There was no complaint of fever or decreased range of motion. He presented to a local orthopedist (April 1995) and was found to have a palpable abnormality on the posterior aspect of the knee consistent with a Baker's cyst. Aspiration was unsuccessful and the patient was treated with ibuprofen for a 10-day course. Nearly one year later (April 1996) the family sought a second opinion and an MR study was ordered that revealed a cystic structure [Figure At the time of his evaluation after referral, he had strong popliteal pulses. There was a 7.0 × 4.5 cm area of swelling and numbness in the left popliteal region. The deep-tendon reflexes were brisk and the motor exam and gait were normal. MR showed residual abnormality consistent with tumor lateral to the joint capsule. Metastatic work-up including nuclear bone scan and CT scan of the chest was negative. Tumor bed re-excision with placement of afterloading catheters was performed in December 1996. All visible residual abnormality was removed without significant disruption of underlying ligaments and tendons. The walls of the tumor bed were biopsied to map the extent of microscopic residual disease. Microscopic residual disease was anticipated given the site of involvement and the limited ability to operate beyond the extent of the abnormal appearing tissues. Eleven afterloading catheters were placed in a parallel array to cover the tumor bed Figure . Radio-o125. The dwell time of the implant was 64 hours and the patient received a total implant dose of 2560 cGy delivered at 40 cGy/hr. Three weeks later, the patient began external beam irradiation at 180 cGy per day and received a total external beam dose of 4860 cGy using 6 MV photons with treatment delivered in a parallel-opposed beam arrangement using a CT based treatment plan [Figure Five days after surgery, the 11 catheters were loaded with a total of 135 seeds representing 408 millicuries of IA decision was made to initiate chemotherapy three weeks into the course of external beam irradiation based on the perceived high-risk nature of his case – longstanding history of symptoms, known residual tumor and size of tumor at presentation. Chemotherapy included vincristine, ifosfamide, and adriamycin was eventually administered for a total of four cycles. There was central dehiscence of the wound prior to the completion of radiation therapy. The wound was colonized with Enterococci sensitive to ampicillin and managed with antibiotics, whirlpool treatment and daily dressing changes. There was a one-week treatment break during the external beam portion of the treatment.At the completion of chemotherapy (June 1997) the patient underwent excision of scar tissue with rotation flap of gastrocnemius and skin and Z-plasty of the semi-membranous and semi-tendinous tendon for a non-healing ulcer in the operative region. There was also contracture of the knee joint without signs of abscess or cellulitis. One month later, a second procedure was required to debride and irrigate the left popliteal fossa wound at the site of previously irradiated tissue and contracture release with muscle and fasciocutaneous flap closure. One year after the completion of all therapy (June 1998) the patient reported full range of motion and softening of previously fibrotic tissue. He was actively playing baseball and had no imposed limitations.Nearly two years after completion of treatment (March 1999), the patient was noted to have Trendelenburg gait after prolonged walking ascribed to poor endurance of weakened hip abductors bilaterally. Hip hiking was also noted on the contralateral side due to leg length and ASIS height discrepancy. A difference of 2.5 cm was noted when measured from the umbilicus to the medial malleolus. He had grown 7.0 cm since the time of diagnosis. He was instructed to stretch the heel cord and strengthening his weak hip abductors. Arrangements were made to provide a shoe lift to accommodate the leg length difference. The discrepancy improved to less than 1 cm over a three month period of time (March-June 1999). He was carefully monitored for growth discrepancy and 6 months later, nearly 3 years after the initiation of treatment, the discrepancy returned to its original value of greater than 2 cm. He also had difficulty with ambulation with slight left-sided limp. Orthopedic surgery was re-consulted. The discrepancy was followed and treated with additional shoe lift. The patient continued to engage in normal activities including sports and reported full range of motion and normal strength. More than four and a half years after initiating treatment (August 2001) Figure , x-ray sAt the time of diagnosis this patient was a 9 year-old female with a one year history of pain and swelling about her left knee. She had experienced a fall and related all symptoms to the fall. She was seen in her local emergency room by her family physician; there was no diagnosis or treatment. Approximately one month prior to her representation, she was struck in the left knee by a basketball and developed worsening pain. She was seen by an orthopedic surgeon (December 1999) and was noted to have a valgus posture of both lower extremities, exaggerated on the left by external rotation and she walked with a mild limp. The left knee had no effusion but was hypersensitive to light touch over the lateral aspect where there was soft tissue swelling just below the knee. There was no obvious mass in the area, although firm palpation was difficult because of patient discomfort. Plain films were normal and an MR was ordered that revealed an apparent meniscal cyst in the lateral aspect of the left knee Figure . Biopsy 125 . The dwell time of the implant was 62 hours and the patient received a total implant dose of 2480 cGy delivered at 40 cGy/hr. Two weeks later the patient began external beam irradiation at 180 cGy/day and received a course of treatment and total external beam dose of 5040 cGy using 6 MV photons with treatment delivered with two beams using a CT based treatment plan [Figure At the time of her evaluation after referral (January 2000), there was a well healed scar with no excessive swelling. There was mild tenderness on the lateral aspect of her left knee. Additional imaging studies showed abnormality at the site of prior surgery equivocal for residual tumor. There was no evidence of abnormality in the joint space. The tumor bed was explored. There was no physical evidence of compromise at the level of the joint space. She underwent wide local excision with placement of afterloading catheters. Six catheters were placed in a parallel array with 1 cm spacing. Radio-opaque clips were placed to delineate the tumor bed and assist in brachytherapy planning Figure . The marn Figure . RadiatiThe patient suffered moist desquamation corresponding to the radiation therapy portal that was predicted based on the treatment and the use of a tissue equivalent bolus material which was placed on the wound on alternating days during her course of external beam irradiation. She was able to return home on the last day of treatment. On routine follow-up, only 4 months after treatment, left leg appearing to be slightly longer than her right leg by less than 1 cm. No corresponding gait problems were reported. Nearly one year after treatment (January 2000) physical examination showed good range of motion at the left knee; however, there was significant valgus angulation. An MR study was reviewed by Orthopedic Surgery and was noted to show growth arrest laterally and predominantly involving the distal femoral physis Figure . Based oDue to its high propensity for local recurrence and metastasis, aggressive treatment of synovial sarcoma is imperative. While many different methods have been used in the treatment of these high-grade tumors, including mono-bloc soft part resection and amputation, the current standard includes local excision and radiation therapy when feasible . Wide loBoth patients in our study underwent two surgical procedures and were treated with brachytherapy and external beam irradiation. Brachytherapy was used to confine the highest doses to the region at risk and minimize the dose received by normal tissues. The use of brachytherapy shortens the overall treatment time and increases the rate of local control in the setting of involved margins of resection. CT-based treatment planning was used to define the volume of irradiation and to spare normal tissue structures. By reducing the amount of radiation dose delivered to normal tissues, the probability of growth deformity, radio-chemotherapy interactions, and even the hypothetical risk of second tumor formation may be lowered. No effort was made to symmetrically irradiate the physes, which would hypothetically lead to symmetrically diminished growth without the added effect of angular deformity. Because of concerns about the effects of total joint irradiation and its possible effects on functional outcome, the inhomogeneous and asymmetric approach was taken. Despite the valgus and varus deformity experienced by these children and the need for intervention, both children and parents were completely satisfied with their functional outcome and indicated that they would chose the same course of treatment if presented again with the same options.The importance of achieving local control with aggressive surgery and high-dose irradiation cannot be overemphasized. Local control is crucial to long-term survival and avoiding the morbidity of local tumor progression. Local control, even in the setting of metastatic disease, is an important endpoint. Radiation therapy is highly successful in achieving local control in soft tissue sarcoma and is standard in the care of children with high-grade tumors such as those reviewed in this report. At our institution high-grade tumors with resection margins of 1 cm has an observed local control rate of 72% (5 of 7 patients) in the absence of radiation therapy and 100% (7 of 7 patients) when radiation therapy was given postoperatively. Among 20 unirradiated high-grade tumors that were completely resected with margins > 1 cm only 15 (75%) were locally controlled for an extended period . Our polDespite efforts to achieve local control and minimize the effects of treatment on normal tissues, damage to bone and soft tissues may be unavoidable. Synovial cell sarcoma commonly arises near tendon sheaths and joint capsules of adolescents and young adults and may be in close proximity to an epiphyseal growth plate during a time of rapid growth. The situation is made worse if the tumor is located around the distal femur or proximal tibia. Among the four epiphyseal plates in the lower extremity that contribute to the growth of the limb, those around the knee make the most significant contribution, with the distal femur and proximal tibia accounting for 50–90% and 57% of limb growth, respectively depending on age . In our There are two non-congenital mechanisms that are known to interfere with growth of the physis: direct trauma and environmental change around the plate. Trauma includes acute injury to the growth plate in manner that affects all or partial growth and results in premature closure or the formation of a physeal bar. Even if the region has retained its ability to grow it is hampered by solid bone formation across the plate . EnvironParalysis is also known to cause of growth inhibition, although the mechanism is poorly understood. Proposed contributors include reduced muscle activity, which indirectly alters the blood supply, and abnormal vasomotor control . AvasculRogalski et al.  observedIt is also conceivable that repeated surgeries to the lateral aspect of the knee in both patients played a contributive role. A change in the environment surrounding the physis, such as muscle atrophy following prolonged bed rest, paralysis, or limb-sparing surgery with muscle loss, is known to cause a significant slowing of growth . AlthougThe patients included in this report had many of the above noted contributions to abnormal growth and development including a pre-existing condition, vascular compromise due to multiple surgeries, loss of muscle mass, limited use of the extremity for a defined period of time, infection and chemotherapy. Chemotherapy may temporarily reduce bone growth through systemic effects that include the direct effects of specific agents or the indirect effects resulting from systemic infections and abnormalities in metabolism and nutrition.It has been known for almost a century that radiation therapy at sufficient levels can affect growing bone. Several factors contributing to the severity of effect including the total dose, dose per fraction, dosimetry (asymmetry and inhomogeneity) and age at the time of irradiation ,30,31. PThe conclusions of Gonzalez and Breur  were sliThe epiphyseal growth plate is the area of the developing skeleton most sensitive to the effect of radiation due in part to its rapidly proliferating stem cell population. Even low doses of radiation have been shown to cause histologic changes including temporary swelling, fragmentation, and degeneration of chondrocytes . When hiCreating a treatment plan for patients with leg deformities who have undergone radiation therapy with or without chemotherapy can pose a difficult challenge. Because the osteocytes of neighboring bone are also destroyed, it may take years for the bone to revascularize and repopulate with healthy osteocytes . The absHistorically, there have been two primary treatments for patients with angular limb deformities: epiphysiodesis and stapling. Both methods seek to achieve the same result while offering different sets of advantages and disadvantages. Partial epiphysiodesis of the knee to correct angular deformity was first described by Phemister in 1933 . It has Newer radiation delivery techniques including high-dose rate brachytherapy, intraoperative radiation therapy ,40 and tLimited surgery and irradiation may result in growth abnormalities and deformity. These effects may have minimal or significant impact depending on functional outcome and the value attached to limb preservation for a particular patient. As mentioned in this report, both patients and families were queried about their decisions regarding treatment and both reported satisfaction with outcome recognizing that side effects were anticipated. Both families attached a high value to limb preservation.None declared.DTF reviewed the patient records and drafted the manuscript. WCW contributed to drafting the manuscript. MDN contributed to drafting the manuscript. TEM conceived of the study, participated in the review of the data, and helped draft the manuscript. All authors read and approved the final manuscriptThe pre-publication history for this paper can be accessed here: