Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor.

BACKGROUND: Pexidartinib (Turalio) is the only systemic therapy approved by the FDA for the treatment of adult patients with symptomatic tenosynovial giant-cell tumor (TGCT) associated with severe morbidity or functional limitations, and not amenable to improvement with surgery. This study assessed patient-reported treatment experiences and symptom improvement among patients receiving pexidartinib. METHODS: A cross-sectional, web-based survey collected data on demographics, disease history, pexidartinib dosing, and symptoms before and after pexidartinib use. RESULTS: Of 288 patients enrolled in the Turalio REMS program in May 2021, 83 completed the survey: mean age was 44.2 years, 62.7% were female, and most common tumor sites were in knee (61%) and ankle (12%). Mean initial dose was 622 mg/day: 29 patients reported reduction from initial dose and 8 had dose reduction after titrating up to a higher dose. At the time of survey completion, median time on pexidartinib was 6.0 months; 22 (26.5%) patients discontinued pexidartinib due to physician suggestion, abnormal laboratory results, side effect, or symptom improvement. Compared with before pexidartinib initiation, most patients reported improvement in overall TGCT symptom (78.3%) and physical function (77.2%) during pexidartinib treatment. Significant improvement was reported during pexidartinib treatment in worst stiffness numeric rating scale (NRS) (3.0 vs. 6.2, P < .05) and worst pain NRS (2.7 vs. 5.7, P < .05). CONCLUSION: Findings from this cross-sectional survey confirmed the benefit of pexidartinib in improving symptoms and functional outcomes among patients with symptomatic TGCTs from the patients' perspective. Future research is warranted to examine the long-term benefit and risk of pexidartinib.

Imaging in Pulmonary Vascular Disease-Understanding Right Ventricle-Pulmonary Artery Coupling.

The right ventricle (RV) and pulmonary arterial (PA) tree are inextricably linked, continually transferring energy back and forth in a process known as RV-PA coupling. Healthy organisms maintain this relationship in optimal balance by modulating RV contractility, pulmonary vascular resistance, and compliance to sustain RV-PA coupling through life's many physiologic challenges. Early in states of adaptation to cardiovascular disease-for example, in diastolic heart failure-RV-PA coupling is maintained via a multitude of cellular and mechanical transformations. However, with disease progression, these compensatory mechanisms fail and become maladaptive, leading to the often-fatal state of "uncoupling." Noninvasive imaging modalities, including echocardiography, magnetic resonance imaging, and computed tomography, allow us deeper insight into the state of coupling for an individual patient, providing for prognostication and potential intervention before uncoupling occurs. In this review, we discuss the physiologic foundations of RV-PA coupling, elaborate on the imaging techniques to qualify and quantify it, and correlate these fundamental principles with clinical scenarios in health and disease. © 2022 American Physiological Society. Compr Physiol 12: 1-26, 2022.

Metolazone Versus Intravenous Chlorothiazide for Decompensated Heart Failure Sequential Nephron Blockade: A Retrospective Cohort Study.

BACKGROUND: Metolazone and intravenous (IV) chlorothiazide are commonly used diuretics for sequential nephron blockade (SNB) in patients with acute decompensated heart failure (ADHF). Previous studies suggest metolazone may be comparable with chlorothiazide in terms of efficacy and safety. The objective of this study was to determine whether IV chlorothiazide is superior to metolazone in increasing net urine output (UOP) of hospitalized patients with ADHF. METHODS AND RESULTS: This retrospective cohort study included hospitalized patients with ADHF and evidence of loop diuretic resistance in a tertiary academic medical center. The primary end point was the change in net 24-hour UOP in patients treated with IV chlorothiazide compared with metolazone. The relative cost of chlorothiazide doses and metolazone doses administered during SNB was a notable secondary end point. The median change in net 24-hour UOP in the IV chlorothiazide group was -1481.9 mL (interquartile range -2696.0 to -641.0 mL) and -1780.0 mL (interquartile range -3084.5 to -853.5 mL) in the metolazone group (P = .05) across 220 hospital encounters. The median cost of chlorothiazide and metolazone doses used during SNB was $360 and $4, respectively (P < .01). CONCLUSIONS: Chlorothiazide was not superior to metolazone in changing the net 24-hour UOP of patients with ADHF and loop resistance. Preferential metolazone use in SNB is a potential cost-saving measure.

Management of Pulmonary Arterial Hypertension.

PURPOSE OF REVIEW: This review focuses on the therapeutic management and individualized approach to Group 1 pulmonary arterial hypertension (PAH), utilizing Food and Drug Administration-approved PAH-specific therapies and various interventional and surgical options for PAH. RECENT FINDINGS: The paradigm for the optimal management of PAH has shifted in recent years. Upfront combination therapy with an endothelin receptor antagonist and a phosphodiesterase 5 inhibitor is now widely accepted as standard of care. In addition, there is increasing emphasis on starting prostanoids early in order to delay time to clinical worsening. However, less is known regarding which prostanoid agent to initiate and the optimum time to do so. In order to facilitate shared decision-making, there is an increasing need for decision tools based on guidelines and collective clinical experiences to navigate between pharmacologic and interventional treatments, as well as explore innovative, therapeutic pathways for PAH. SUMMARY: The management of PAH has become increasingly complex. With a growing number of PAH-specific therapies, intimate knowledge of the therapeutics and the potential barriers to adherence are integral to providing optimal care for this high-risk patient population. While current PAH-specific therapies largely mediate their effects through pulmonary vasodilation, ongoing research efforts are focused on ways to disrupt the mechanisms leading to pulmonary vascular remodeling. By targeting aberrations identified in the metabolism and proliferative state of pulmonary vascular cells, novel PAH treatment pathways may be just on the horizon.

Empowering People Living with Heart Failure.

Heart failure is a chronic disease with a multitude of different clinical manifestations. Empowering people living with heart failure requires education, support structure, understanding the needs of patients, and reimaging the care delivery systems currently offered to patients. In this article, the authors discuss practical approaches to activate and empower people with heart failure and enable patient-provider dialogue and shared decision making.

Transitioning Between Prostanoid Therapies in Pulmonary Arterial Hypertension.

Background: New oral prostacyclin therapies and prostacyclin agonists have become available for the treatment of pulmonary arterial hypertension (PAH). However, methods for transitioning between oral, inhaled, and parenteral formulations are not well-established, except in the form of case reports and case series. Collectively, these emphasize the lack of a standardized process and approach in transitioning patients between PAH prostanoid therapies. In this case series, we report our experience at an accredited Pulmonary Hypertension center in transitioning between various oral, inhaled, and parenteral prostanoids to offer additional guidance on safe transitions in therapy. Methods: All cases of prostanoid transitions at an accredited Pulmonary Hypertension center from March 2018 to September 2019 were included in this report. The transition approach for each case was developed through a review of the literature, extrapolation of available pharmacokinetic data, and collaboration between pharmacists and clinicians. Results: This case series describes the transition of 3 patients from selexipag to parenteral treprostinil; 1 patient transitioning from parenteral treprostinil to selexipag; 1 patient transitioning from oral treprostinil to parenteral treprostinil; and 1 patient transitioning from inhaled treprostinil to selexipag. Four of the 6 patients presented here were transitioned to an alternate prostanoid on account of clinical worsening, while the remaining 2 patients transitioned due to intolerance of parenteral therapy and poor medication adherence. This case series includes patients with various etiologies of PAH including idiopathic PAH, methamphetamine-associated PAH, and scleroderma-associated PAH. All patients successfully completed each transition without serious adverse events. Conclusions: With the increasing utilization and availability of prostanoids, there is a critical need for a standardized approach in transitioning safely between different formulations without compromising treatment efficacy. In this case series, we present our clinical experiences, guided by available pharmacokinetic data, in transitioning between various prostanoid formulations.

Correction: Summary of Glaucoma Diagnostic Testing Accuracy: An Evidence-Based Meta-Analysis.

[This corrects the article DOI: 10.14740/jocmr2643w.].

Summary of Glaucoma Diagnostic Testing Accuracy: An Evidence-Based Meta-Analysis.

BACKGROUND: New glaucoma diagnostic technologies are penetrating clinical care and are changing rapidly. Having a systematic review of these technologies will help clinicians and decision makers and help identify gaps that need to be addressed. This systematic review studied five glaucoma technologies compared to the gold standard of white on white perimetry for glaucoma detection. METHODS: OVID(®) interface: MEDLINE(®) (In-Process & Other Non-Indexed Citations), EMBASE(®), BIOSIS Previews(®), CINAHL(®), PubMed, and the Cochrane Library were searched. A gray literature search was also performed. A technical expert panel, information specialists, systematic review method experts and biostatisticians were used. A PRISMA flow diagram was created and a random effect meta-analysis was performed. RESULTS: A total of 2,474 articles were screened. The greatest accuracy was found with frequency doubling technology (FDT) (diagnostic odds ratio (DOR): 57.7) followed by blue on yellow perimetry (DOR: 46.7), optical coherence tomography (OCT) (DOR: 41.8), GDx (DOR: 32.4) and Heidelberg retina tomography (HRT) (DOR: 17.8). Of greatest concern is that tests for heterogeneity were all above 50%, indicating that cutoffs used in these newer technologies were all very varied and not uniform across studies. CONCLUSIONS: Glaucoma content experts need to establish uniform cutoffs for these newer technologies, so that studies that compare these technologies can be interpreted more uniformly. Nevertheless, synthesized data at this time demonstrate that amongst the newest technologies, OCT has the highest glaucoma diagnostic accuracy followed by GDx and then HRT.

Predicting approach to homework in Primary school students / Predicción del enfoque de trabajo en los deberes escolares en estudiantes de Primaria

BACKGROUND: The goal of this research was to study the weight of student variables related to homework (intrinsic homework motivation, perceived homework instrumentality, homework attitude, time spent on homework, and homework time management) and context (teacher feedback on homework and parental homework support) in the prediction of approaches to homework. METHOD: 535 students of the last three courses of primary education participated in the study. Data were analyzed with hierarchical regression models and path analysis. RESULTS: The results obtained suggest that students' homework engagement (high or low) is related to students' level of intrinsic motivation and positive attitude towards homework. Furthermore, it was also observed that students who manage their homework time well (and not necessarily those who spend more time) are more likely to show the deepest approach to homework. CONCLUSIONS: Parental support and teacher feedback on homework affect student homework engagement through their effect on the levels of intrinsic homework motivation (directly), and on homework attitude, homework time management, and perceived homework instrumentality (indirectly). Data also indicated a strong and significant relationship between parental and teacher involvement

ANTECEDENTES: el objetivo de esta investigación fue estudiar el peso de variables del alumno relacionadas con los deberes escolares (motivación intrínseca, percepción de utilidad, actitud, tiempo dedicado y gestión de ese tiempo) y del contexto (feedback del profesor y apoyo parental) en la predicción de los enfoques de trabajo en los deberes. MÉTODO: participaron 535 estudiantes de los tres últimos cursos de Primaria. Los datos fueron analizados en base a modelos de regresión jerárquica y path analysis. RESULTADOS: los resultados sugieren que la mayor o menor implicación del alumno en la realización de sus deberes escolares está relacionado con el grado de motivación intrínseca y una actitud positiva hacia ellos. También se observa que los estudiantes que gestionan bien su tiempo dedicado a los deberes (y no necesariamente los que dedican más tiempo) son quienes más profundamente trabajan en ellos. CONCLUSIONES: el apoyo parental y el feedback del profesor inciden sobre la implicación de los estudiantes a través de su efecto sobre los niveles de motivación intrínseca (directamente), y de la actitud, gestión del tiempo y percepción de utilidad (indirectamente). También sugieren una relación fuerte y significativa entre la implicación parental y de los profesores en los deberes escolares

Multiple Goals and Homework Involvement in Elementary School Students.

This work arises from the need to investigate the role of motivational variables in homework involvement and academic achievement of elementary school students. The aims of this study are twofold: identifying the different combinations of student academic goals and analyzing the differences in homework involvement and academic achievement. The sample was composed of 535 fourth-, fifth- and sixth-grade elementary school students, between the ages of 9 and 13 years old. Findings showed three groups with different motivational profiles: a group of students with high multiple goals, another group with a learning goal orientation and a third group defined by a low multiple goals profile. Focusing on the differences between groups, it was observed that the amount of time doing homework was not associated with any motivational profile. Nevertheless, the differences were statistically significant between the motivational groups in the amount of homework (F(2, 530) = 42.59; p < .001; ηp 2 = .138), in the management of time spent on homework (F(2, 530) = 33.08; p < .001; ηp 2 = .111), and in academic achievement (F(2, 530) = 33.99; p < .001; ηp 2 = .114). The effect size was large for the amount of homework performed and was also relatively large in the case of management of time and academic achievement.

Predicting approach to homework in Primary school students.

BACKGROUND: The goal of this research was to study the weight of student variables related to homework (intrinsic homework motivation, perceived homework instrumentality, homework attitude, time spent on homework, and homework time management) and context (teacher feedback on homework and parental homework support) in the prediction of approaches to homework. METHOD: 535 students of the last three courses of primary education participated in the study. Data were analyzed with hierarchical regression models and path analysis. RESULTS: The results obtained suggest that students’ homework engagement (high or low) is related to students´ level of intrinsic motivation and positive attitude towards homework. Furthermore, it was also observed that students who manage their homework time well (and not necessarily those who spend more time) are more likely to show the deepest approach to homework. CONCLUSIONS: Parental support and teacher feedback on homework affect student homework engagement through their effect on the levels of intrinsic homework motivation (directly), and on homework attitude, homework time management, and perceived homework instrumentality (indirectly). Data also indicated a strong and significant relationship between parental and teacher involvement.

Deberes escolares y rendimiento académico en Educación Primaria / Homework and academic achievement in Primary Education

En este artículo se analiza la relación entre la realización de deberes escolares y el rendimiento académico en una muestra de estudiantes de los tres últimos cursos de Educación Primaria. Las variables vinculadas con la implicación de los alumnos en los deberes escolares fueron el número de deberes realizados, el tiempo dedicado a los deberes y el aprovechamiento del tiempo dedicado a los deberes; mientras que el rendimiento académico fue estimado en base a las notas en matemáticas y lengua extranjera (inglés). Se ha tenido en cuenta el posible efecto del curso y del género a la hora de calcular el nivel predictivo de las variables relativas a los deberes sobre el rendimiento académico. Los resultados obtenidos indican que la cantidad de deberes realizados de los prescritos y el aprovechamiento del tiempo predicen positiva y significativamente el rendimiento académico en ambas asignaturas, mientras que la cantidad de tiempo dedicado a la realización de los deberes no es relevante. Finalmente, mientras que el género no resultó significativo en la predicción del rendimiento académico, el curso sí predijo negativamente el rendimiento en matemáticas: a medida que se asciende de curso el rendimiento en matemáticas tiende a disminuir

This paper analyzes the relationship between homework behavior and academic achievement using a sample of students from the last three years of primary education. The variables associated with student involvement in homework were the amount of homework completed, the time spent on homework, and homework time optimization, while academic achievement was estimated based on the grades in mathematics and foreign language (english). The possible effect of the course and gender when calculating the level of predictive variables concerning the homework on academic achievement was analyzed. The results indicated that the amount of homework done and the optimization of the time dedicated at homework significantly and positively predicted academic performance in both subjects. However, the amount of time spent on homework was not relevant. Finally, while gender was not statistically significant in predicting academic achievement, the course itself was statistically significant: as the course advances the mathematics achievement tends to diminish

Barriers to the universal adoption of bilateral internal mammary artery grafting.

The left internal mammary artery (LIMA) graft is considered the "gold standard" of coronary artery bypass grafting (CABG). This conduit provides increased survival, symptomatic relief, increased freedom from myocardial infarction, and increased freedom from re-intervention when compared to saphenous venous grafting. It has a remarkable long term patency rate with clinical and angiographic outcomes that are unmatched by other conduits. Given the fact that patients often require more than one graft during a coronary revascularization procedure, the prospect of bilateral internal mammary artery (BIMA) grafting has been very appealing to some surgeons. BIMA grafting has been extensively studied via multiple retrospective and prospective cohort studies and findings have indicated that BIMA grafting can have an increased survival benefit when compared to LIMA grafting alone. As a result, this technique has accrued increasing popularity over the course of the last decade. Yet, questions still remain on whether BIMA grafting is the optimal treatment modality for patients in terms of long-term prognosis. There is limited data at the present time from randomized controlled trials and only 4-12% of CABGs performed today utilize BIMA grafting. Concerns regarding perioperative complications, which patient subsets are at higher risks for complications from the technique, and the technical challenges involved in utilizing and teaching the technique have limited its widespread use.

A randomized clinical trial of selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with pseudoexfoliation.

PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) versus argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension secondary to pseudoexfoliation. DESIGN: Multicentered randomized clinical trial. PARTICIPANTS: A total of 76 eyes from 60 patients with pseudoexfoliation and uncontrolled IOP were recruited from 5 Canadian academic institutions. Patients with prior laser trabeculoplasty, ocular surgery within 6 months, previous glaucoma surgery, an advanced visual field defect, current steroid use, and monocular patients were excluded. METHODS: Eyes were randomized to receive either 180-degree SLT or 180-degree ALT by a nonblocked randomization schedule stratified by center. MAIN OUTCOME MEASUREMENT: The primary outcome was the change in IOP at 6 months versus baseline and secondary outcomes included change in number of glaucoma medications after laser. Baseline variables included age, sex, angle grade, angle pigmentation, and number of glaucoma medications. RESULTS: Of the 76 eyes, 45 eyes received SLT and 31 eyes received ALT. The overall age was 72.9 years (65% females). The baseline IOPs in the SLT and ALT groups were 23.1 and 25.2 mm Hg, respectively (P=0.03). The IOP reduction 6 months after SLT was -6.8 mm Hg and post-ALT was -7.7 mm Hg (P>0.05). The SLT group had reduced glaucoma medications by 0.16 medications at 6 months and the ALT group had no decrease in medications over the same time period (P=0.59). There were no postlaser IOP spikes in either group. DISCUSSION: ALT and SLT are equivalent in lowering IOP at 6 months posttreatment in patients with PXF.

Multiple goals and homework involvement in elementary school students

This work arises from the need to investigate the role of motivational variables in homework involvement and academic achievement of elementary school students. The aims of this study are twofold: identifying the different combinations of student academic goals and analyzing the differences in homework involvement and academic achievement. The sample was composed of 535 fourth-, fifth- and sixth-grade elementary school students, between the ages of 9 and 13 years old. Findings showed three groups with different motivational profiles: a group of students with high multiple goals, another group with a learning goal orientation and a third group defined by a low multiple goals profile. Focusing on the differences between groups, it was observed that the amount of time doing homework was not associated with any motivational profile. Nevertheless, the differences were statistically significant between the motivational groups in the amount of homework (F(2, 530) = 42.59; p < .001; ηp 2 = .138), in the management of time spent on homework (F(2, 530) = 33.08; p < .001; ηp 2 = .111), and in academic achievement (F(2, 530) = 33.99; p < .001; ηp 2 = .114). The effect size was large for the amount of homework performed and was also relatively large in the case of management of time and academic achievement (AU)

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An investigation of the relationship between cataract surgery wait times and rates of surgery.

OBJECTIVE: The relationship between cataract surgery wait times and rates of surgery was investigated to determine whether wait times correlate with rates of surgery. DESIGN: Cross-sectional study. PARTICIPANTS: We collected 2 Ontario registries for cataract surgeries: (i) Cancer Care Ontario wait time registry; and (ii) The Ontario Health Insurance Plan billing records. METHODS: Both registries were used to determine whether wait times correlated with rates of surgery, and the data were then stratified by region of the province, priority (severity) of cases, age, and sex. RESULTS: The total number of surgeries performed between April 2, 2007, and March 31, 2008, was 65,520. The overall mean number of wait days was 69.8 days; the mean patient age was 72.5 years; and the surgery rate was 540.3 per 100,000 members of the population. For high-priority cases (priorities 1 and 2), there was a very weak inverse correlation (p = -0.27 and -0.21) between wait time and surgery rate, whereas the overall correlation between wait time and surgical rate was close to zero in both databases, regardless of the region, the patients' ages, and the patients' genders. CONCLUSIONS: This study demonstrates a very weak correlation between wait times for and rates of cataract surgery, and this should be a concern for policy makers. Further study is needed to see whether this null relationship persists over time and whether it exists for other monitored wait time procedures. Reasons for this null relationship will have to be determined and remedied as the use of wait times becomes a more widespread outcome in Canadian Healthcare.

Pharmacologic management of neovascular age-related macular degeneration: systematic review of economic evidence and primary economic evaluation.

OBJECTIVE: To examine the economic implications for the Canadian health system of pharmacologic treatment of neovascular age-related macular degeneration (AMD). DESIGN: Systematic review of economic literature and a primary economic evaluation. PARTICIPANTS: Economic literature search identified 392 potentially relevant articles, 12 of which were included for final review. METHODS: Studies were included if they met the following criteria: (i) provision of a summary measure of the trade-off between costs and consequences; (ii) participants of 40 years and older with neovascular AMD; (iii) interventions and comparators: comparison of photodynamic therapy using verteporfin (V-PDT), pegaptanib, bevacizumab, ranibizumab, anecortave acetate, intravitreal triamcinolone, placebo, or clinically relevant combinations; and (iv) outcome reported as an incremental measure of the implication of moving from the comparator to the intervention. The following databases were searched through the OVID interface: MEDLINE, EMBASE, BIOSIS Previews, CINAHL, PubMed, Health Economic Evaluations Database (HEED), and the Cochrane Library. For the economic evaluation, we took a decision analytic approach and modeled a cost-utility analysis, conducting it as a microsimulation of a Markov model. RESULTS: In general, V-PDT is more cost effective than conventional macular laser, and pegaptanib is likely more cost effective than V-PDT. The primary economic analysis revealed ranibizumab to be effective but at an unacceptably high cost per quality-adjusted life year (QALY)(>$50,000 per QALY). CONCLUSIONS: Although ranibizumab is effective for wet AMD, its cost is unacceptably high based on cost-utility theory.

Endoscopic goniotomy: early clinical experience in congenital glaucoma.

PURPOSE: To review the technique and early outcomes of endoscopic goniotomy (EG) in children with opaque corneas and primary congenital glaucoma (PCG) or developmental glaucoma with ocular or systemic anomalies (DG). METHODS: EG was performed for approximately 300 degrees of the angle through temporal and superonasal corneal incisions. We retrospectively reviewed consecutive cases from 2003 to 2007. Primary outcome was intraocular pressure (IOP) change from baseline to last postoperative visit. Success was defined as IOP < or=21 mm Hg with or without medication but no further surgical intervention. RESULTS: Fourteen eyes of 8 patients (4 PCG, 4 DG) were included. Mean age at surgery was 3.88+/-3.72 months. The reduction in IOP from baseline to the last follow-up visit was -16.7+/-16.7 mm Hg. Success was achieved in 6 of the 16 eyes (Total=43%, PCG=50%, DG=30%). Corneal diameter and axial length remained stable in all eyes. Two patients with DG needed additional surgery after 8 to 9 months. Complications included cataract and zonular dialysis both in 2 patients with aniridia. CONCLUSIONS: This pilot study indicates that EG shows reasonable potential for IOP control in congenital glaucoma. The safety and efficacy of EG needs to be further studied with a larger sample size and comparison to other angle surgery techniques.

Consequences of testing for celiac disease.

Population screening studies have identified that up to two thirds of celiac disease (CD) cases are asymptomatic. The aim of this study was to conduct a systematic review of the expected consequences of testing for CD in the following populations: (1) patients with symptoms suggestive of CD, (2) asymptomatic at-risk populations, and (3) general population. Standard systematic review methodology was used. A comprehensive literature search was conducted in MEDLINE (1996-2003), EMBASE (1974-2003), CAB (1972 forward), PsychINFO (1840-2003), AGRICOLA (1970-2003), and Sociological Abstracts (1963 forward); searches were conducted in December 2003. Pooled summary estimates were not calculated. The majority of the included studies were before-after studies, case control, or retrospective cohorts. The quality of evidence for the before-after studies is weaker. The overall strength of the evidence for this issue was fair to good. This area of research is relatively new, and further high-quality studies are required. The consequences of testing for celiac disease in symptomatic individuals appears to have a positive impact on patient-relevant outcomes. The data are less clear for those with silent CD or those with lower grade histologic lesions in small bowel biopsy. The literature suggests that compliance is less than ideal in these individuals, especially if diagnosed when adults. Long-term outcomes have not been extensively studied in those with silent CD.

The diagnostic accuracy of serologic tests for celiac disease: a systematic review.

Clinicians are increasingly utilizing noninvasive serologic tests for the diagnosis and screening of celiac disease (CD). The aim of this study was to conduct a systematic review of the diagnostic performance of serologic tests for the diagnosis and screening of CD. Standard systematic review methodology was used. A literature search was conducted in MEDLINE (1966 to October 2003) and EMBASE (1974 to December 2003) databases. A weighted mean of the sensitivity and specificity along with 95% confidence intervals and summary receiver operating characteristic (ROC) curves were calculated. The pooled specificity of endomyseal antibody (EMA)-monkey esophagus (ME) or EMA-human umbilical cord (HU) was close to 100% in adults and children. The pooled specificity of transglutaminase antibody (tTG)-guinea pig (GP) and tTG-human recombinant (HR) were between 95% and 99%. IgA-EMA-ME demonstrated sensitivities of 96% and 97% in children and adults, respectively. EMA-HU demonstrated a similar sensitivity of 97% in children but 90% in adults. The pooled sensitivity of tTG-GP in adults and children was 90% and 93%, respectively. The sensitivity of tTG-HR was 98% and 96%, respectively. The performance of antigliadin antibody was inferior to that of EMA and tTG. EMA and tTG offer high sensitivity and specificity. The sensitivity of these tests appears to be lower than reported when milder histologic grades are used to define CD (below 90%). If true, the nearly perfect negative predictive value of these tests would drop. The positive predictive value of these tests is likely lower than reported when the tests are applied in low-prevalence populations.