Ian J Saldanha

Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Exacerbations

The natural history of cystic fibrosis lung disease is one of chronic progression with intermittent episodes of acute worsening of symptoms frequently called acute pulmonary exacerbations These exacerbations typically warrant medical intervention. It is important that appropriate therapies are recommended on the basis of available evidence of efficacy and safety. The Cystic Fibrosis Foundation therefore established a committee to define the key questions related to pulmonary exacerbations, review the clinical evidence using an evidence-based methodology, and provide recommendations to clinicians. It is hoped that these guidelines will be helpful to clinicians in the treatment of individuals with cystic fibrosis.

Prevalence and Incidence of Endocrine and Metabolic Disorders in the United States: A Comprehensive Review

CONTEXT There has not been a comprehensive compilation of data regarding the epidemiology of all endocrine and metabolic disorders in the United States. EVIDENCE ACQUISITION We included 54 disorders with clinical and public health significance. We identified population-based studies that provided U.S. prevalence and/or incidence data by searching PubMed in December 2007 for English-language reports, hand-searching reference lists of six textbooks of endocrinology, obtaining additional resources from identified experts in each subspecialty, and searching epidemiological databases and web sites of relevant organizations. When available, we selected articles with data from 1998 or later. Otherwise, we selected the article with the most recent data, broadest geographical coverage, and most stratifications by sex, ethnicity, and/or age. Ultimately, we abstracted data from 70 articles and 40 cohorts. EVIDENCE SYNTHESIS Endocrine disorders with U.S. prevalence estimates of at least 5% in adults included diabetes mellitus, impaired fasting glucose, impaired glucose tolerance, obesity, metabolic syndrome, osteoporosis, osteopenia, mild-moderate hypovitaminosis D, erectile dysfunction, dyslipidemia, and thyroiditis. Erectile dysfunction and osteopenia/osteoporosis had the highest incidence in males and females, respectively. The least prevalent conditions, affecting less than 1% of the U.S. population, were diabetes mellitus in children and pituitary adenoma. Conditions with the lowest incidence were adrenocortical carcinoma, pheochromocytoma, and pituitary adenomas. Certain disorders, such as hyperparathyroidism and thyroid disorders, were more common in females. As expected, the prevalence of diabetes mellitus was highest among ethnic minorities. Sparse data were available on pituitary, adrenal, and gonadal disorders. CONCLUSIONS The current review shows high prevalence and incidence of common endocrine and metabolic disorders. Defining the epidemiology of these conditions will provide clues to risk factors and identify areas to allocate public health and research resources.

Cost-Effectiveness of a Novel Molecular Test for Cytologically Indeterminate Thyroid Nodules

CONTEXT Determining which patients with thyroid nodules require surgery is limited by cytologically indeterminate findings. A new approach for preoperative molecular classification of cytologically indeterminate thyroid nodules has a reported sensitivity of 91% and specificity of 75%; however, its cost-effectiveness has yet to be assessed. OBJECTIVE Our objective was to evaluate the 5-yr cost-effectiveness of routine use of a molecular test in adult patients with indeterminate fine-needle aspiration biopsy results from a societal perspective. DESIGN A 16-state Markov decision model was developed. Probabilities, costs, and quality-adjusted life years (QALY) were estimated from literature review, U.S. Department of Health and Human Services data, Medicare reimbursement schedules, and expert opinion. SETTING AND SUBJECTS Decision analysis of a hypothetical group of adult patients with cytologically indeterminate thyroid nodules was conducted. MAIN OUTCOME MEASURES Incremental cost-effectiveness ratio was calculated as incremental cost (measured in U.S. dollars) divided by incremental effectiveness (measured in QALY). RESULTS Modifying current practice with use of the molecular test resulted in 74% fewer surgeries for benign nodules with no greater number of untreated cancers. Over 5 yr, mean discounted cost estimates were

Development of a framework to identify research gaps from systematic reviews.

12,172 for current practice and

Outcomes in Cochrane Systematic Reviews Addressing Four Common Eye Conditions: An Evaluation of Completeness and Comparability

10,719 with the molecular test. Current practice and molecular test use produced 4.50 and 4.57 QALY, respectively. CONCLUSIONS Use of this novel molecular test for differential diagnosis of cytologically indeterminate thyroid nodules can potentially avoid almost three fourths of currently performed surgeries in patients with benign nodules. Compared with current practice based on cytological findings alone, use of this test may result in lower overall costs and modestly improved quality of life for patients with indeterminate thyroid nodules.

Management of Infants with Cystic Fibrosis: A Summary of the Evidence for the Cystic Fibrosis Foundation Working Group on Care of Infants with Cystic Fibrosis

OBJECTIVE Our objective was to develop a framework to identify research gaps from systematic reviews. STUDY DESIGN AND SETTING We reviewed the practices of (1) evidence-based practice centers (EPCs), and (2) other organizations that conduct evidence syntheses. We developed and pilot tested a framework for identifying research gaps. RESULTS Four (33%) EPCs and three (8%) other organizations reported using an explicit framework to determine research gaps. Variations of the PICO (population, intervention, comparison, outcomes) framework were most common. We developed a framework incorporating both the characterization of the gap using PICOS elements (also including setting) and the identification of the reason(s) why the gap exists as (1) insufficient or imprecise information, (2) biased information, (3) inconsistency or unknown consistency, and (4) not the right information. We mapped each of these reasons to concepts from three common evidence-grading systems. CONCLUSION Our framework determines from systematic reviews where the current evidence falls short and why or how the evidence falls short. This explicit identification of research gaps will allow systematic reviews to maximally inform the types of questions that need to be addressed and the types of studies needed to address the research gaps.

Identification of research gaps from evidence-based guidelines: A pilot study in cystic fibrosis

Introduction Choice of outcomes is critical for clinical trialists and systematic reviewers. It is currently unclear how systematic reviewers choose and pre-specify outcomes for systematic reviews. Our objective was to assess the completeness of pre-specification and comparability of outcomes in all Cochrane reviews addressing four common eye conditions. Methods We examined protocols for all Cochrane reviews as of June 2013 that addressed glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR). We assessed completeness and comparability for each outcome that was named in ≥25% of protocols on those topics. We defined a completely-specified outcome as including information about five elements: domain, specific measurement, specific metric, method of aggregation, and time-points. For each domain, we assessed comparability in how individual elements were specified across protocols. Results We identified 57 protocols addressing glaucoma (22), cataract (16), AMD (15), and DR (4). We assessed completeness and comparability for five outcome domains: quality-of-life, visual acuity, intraocular pressure, disease progression, and contrast sensitivity. Overall, these five outcome domains appeared 145 times (instances). Only 15/145 instances (10.3%) were completely specified (all five elements) (median = three elements per outcome). Primary outcomes were more completely specified than non-primary (median = four versus two elements). Quality-of-life was least completely specified (median = one element). Due to largely incomplete outcome pre-specification, conclusive assessment of comparability in outcome usage across the various protocols per condition was not possible. Discussion Outcome pre-specification was largely incomplete; we encourage systematic reviewers to consider all five elements. This will indicate the importance of complete specification to clinical trialists, on whose work systematic reviewers depend, and will indirectly encourage comparable outcome choice to reviewers undertaking related research questions. Complete pre-specification could improve efficiency and reduce bias in data abstraction and analysis during a systematic review. Ultimately, more completely specified and comparable outcomes could make systematic reviews more useful to decision-makers.

Clinical trials and systematic reviews addressing similar interventions for the same condition do not consider similar outcomes to be important: a case study in HIV/AIDS

OBJECTIVE To inform the development of Cystic Fibrosis (CF) Foundation guidelines on the care of infants with CF, we systematically reviewed the evidence for diagnosis and assessment of pancreatic and pulmonary disorders; management of pancreatic and pulmonary function; management of nutrition and nutritional disorders; and prevention and control of infections. STUDY DESIGN In May-June 2008, we searched The Cochrane Library for existing reviews; and MEDLINE, the National Guideline Clearinghouse, the CF Foundation Clinical Practice Guidelines and Consensus Statements, and the UK CF Trust for existing guidelines. MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Excerpta Medica Database (EMBASE) were searched for primary studies in January 2008. Bibliographies of eligible articles were searched and expert input was sought. We selected English-language articles of any study design that provided original data on any of our questions on infants up to 2 years of age. RESULTS We identified 14 relevant guidelines and 3 Cochrane reviews. Fifty-nine articles (55 primary studies) were included. Only four of these were randomized controlled trials. Sample sizes of infants ranged from 2 to 768 study participants; the median sample size was 24. Of our 21 review topics, 5 topics had only one study while for 5 we identified no relevant studies. We identified one or no primary studies for 20 of 32 review questions. CONCLUSIONS There is a paucity of evidence on the care of infants diagnosed with CF. For several of the review questions no guidelines or primary studies were identified, but for other questions, studies limited by weak design and small sample sizes were the only studies identified. With increasing numbers of infants with CF being diagnosed by newborn screening there is an opportunity to study the management of infants diagnosed with CF.

Evaluating Data Abstraction Assistant, a novel software application for data abstraction during systematic reviews: protocol for a randomized controlled trial.

OBJECTIVES Evidence-based guideline committees are multidisciplinary and explicitly consider the existing evidence. They are thus in an ideal position to identify research gaps. However, gaps have not been systematically identified through guidelines. We pilot tested a method to systematically identify and classify gaps from evidence-based guidelines. METHODS We reviewed all evidence-based guidelines published by the Cystic Fibrosis Foundation. We identified research gaps as topics for which there was insufficient evidence (recommendations were not made or consensus recommendations were made) and topics specified as needing further research. We characterized gaps using a standard framework and classified them by type of management issue, specificity of target population, and age of target population. RESULTS We identified sixty-two research gaps in five guidelines (mean = 12.4/guidelines document). While thirteen gaps were topics specified as needing further research, most (n = 49) were topics with insufficient evidence. Of these forty-nine, recommendations were not made for twenty-two topics while consensus recommendations were made for twenty-seven topics. Most gaps were issues of comparative effectiveness (44/62), addressed the general cystic fibrosis population (40/62), and were specific to infants (33/62). Relevant comparisons and outcomes were explicitly stated for only 7 percent and 16 percent of gaps respectively. CONCLUSIONS Almost 80 percent of the gaps were not topics identified as future research needs in the guidelines documents but rather were topics with insufficient evidence for making recommendations. Although we used cystic fibrosis in the United States as an example, the method we developed could be applied in other settings, including other countries and for different diseases.

Comparison of clinical trial and systematic review outcomes for the 4 most prevalent eye diseases

BACKGROUND The usefulness of clinical trials and systematic reviews is compromised when they report different outcomes. We compared outcomes in reviews of HIV/AIDS and the trials included in the reviews. STUDY DESIGN AND SETTING We examined all Cochrane reviews of HIV/AIDS (as of June 2013) that included ≥1 trial and the trials that the reviews included. We compared outcomes within subgroups defined by type of intervention: clinical management, biomedical prevention, behavioral prevention, and health services. RESULTS We included 84 reviews that encompassed 524 trials. Although the median number of outcomes per trial (8) and per review (7.5) was similar, the trials reported a considerably greater number of unique outcomes than the reviews (779 vs. 218), ranging from 2.3 times greater (clinical management) to 5.4 times greater (behavioral prevention). High proportions of trial outcomes were not in any review: 68% (clinical management) to 83% (behavioral prevention). Lower proportions of review outcomes were not in any trial: 11% (clinical management) to 39% (health services). CONCLUSION Outcomes in trials and reviews are not well aligned for appropriate inclusion of trial results in reviews and meta-analyses. Differences in perspectives, goals, and constraints between trialists and reviewers may explain differences in outcomes they consider important.