Arnav Agarwal

World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics

BackgroundPrevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10% and reaches 20–30% in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention.ObjectiveThe World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of probiotics in the prevention of allergy.MethodsWe identified the most relevant clinical questions and performed a systematic review of randomized controlled trials of probiotics for the prevention of allergy. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. We searched for and reviewed the evidence about health effects, patient values and preferences, and resource use (up to November 2014). We followed the GRADE evidence-to-decision framework to develop recommendations.ResultsCurrently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children. However, considering all critical outcomes in this context, the WAO guideline panel determined that there is a likely net benefit from using probiotics resulting primarily from prevention of eczema. The WAO guideline panel suggests: a) using probiotics in pregnant women at high risk for having an allergic child; b) using probiotics in women who breastfeed infants at high risk of developing allergy; and c) using probiotics in infants at high risk of developing allergy. All recommendations are conditional and supported by very low quality evidence.ConclusionsWAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding, and whether to give them to infants.

Probiotics for the prevention of allergy: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND Allergic diseases are considered a health burden because of their high and constantly increasing prevalence, high direct and indirect costs, and undesirable effects on quality of life. Probiotics have been suggested as an intervention to prevent allergic diseases. OBJECTIVE We sought to synthesize the evidence supporting use of probiotics for the prevention of allergies and inform World Allergy Organization guidelines on probiotic use. METHODS We performed a systematic review of randomized trials assessing the effects of any probiotic administered to pregnant women, breast-feeding mothers, and/or infants. RESULTS Of 2403 articles published until December 2014 identified in Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, 29 studies fulfilled a priori specified inclusion criteria for the analyses. Probiotics reduced the risk of eczema when used by women during the last trimester of pregnancy (relative risk [RR], 0.71; 95% CI, 0.60-0.84), when used by breast-feeding mothers (RR, 0.57; 95% CI, 0.47-0.69), or when given to infants (RR, 0.80; 95% CI, 0.68-0.94). Evidence did not support an effect on other allergies, nutrition status, or incidence of adverse effects. The certainty in the evidence according to the Grading of Recommendation Assessment Development and Evaluation approach is low or very low because of the risk of bias, inconsistency and imprecision of results, and indirectness of available research. CONCLUSION Probiotics used by pregnant women or breast-feeding mothers and/or given to infants reduced the risk of eczema in infants; however, the certainty in the evidence is low. No effect was observed for the prevention of other allergic conditions.

Reanalyses of Randomized Clinical Trial Data

IMPORTANCE Reanalyses of randomized clinical trial (RCT) data may help the scientific community assess the validity of reported trial results. OBJECTIVES To identify published reanalyses of RCT data, to characterize methodological and other differences between the original trial and reanalysis, to evaluate the independence of authors performing the reanalyses, and to assess whether the reanalysis changed interpretations from the original article about the types or numbers of patients who should be treated. DESIGN We completed an electronic search of MEDLINE from inception to March 9, 2014, to identify all published studies that completed a reanalysis of individual patient data from previously published RCTs addressing the same hypothesis as the original RCT. Four data extractors independently screened articles and extracted data. MAIN OUTCOMES AND MEASURES Changes in direction and magnitude of treatment effect, statistical significance, and interpretation about the types or numbers of patients who should be treated. RESULTS We identified 37 eligible reanalyses in 36 published articles, 5 of which were performed by entirely independent authors (2 based on publicly available data and 2 on data that were provided on request; data availability was unclear for 1). Reanalyses differed most commonly in statistical or analytical approaches (n = 18) and in definitions or measurements of the outcome of interest (n = 12). Four reanalyses changed the direction and 2 changed the magnitude of treatment effect, whereas 4 led to changes in statistical significance of findings. Thirteen reanalyses (35%) led to interpretations different from that of the original article, 3 (8%) showing that different patients should be treated; 1 (3%), that fewer patients should be treated; and 9 (24%), that more patients should be treated. CONCLUSIONS AND RELEVANCE A small number of reanalyses of RCTs have been published to date. Only a few were conducted by entirely independent authors. Thirty-five percent of published reanalyses led to changes in findings that implied conclusions different from those of the original article about the types and number of patients who should be treated.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials

Background: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. Methods: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks’ duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non–high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. Results: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference −0.17 mmol/L, 95% confidence interval −0.25 to −0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. Interpretation: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. Trial registration: ClinicalTrials.gov, no. NCT01594567.

What Is the Most Bothersome Lower Urinary Tract Symptom? Individual- and Population-level Perspectives for Both Men and Women

Background No study has compared the bothersomeness of all lower urinary tract symptoms (LUTS) using a population-based sample of adults. Despite this lack of evidence, investigators have often cited their LUTS of interest as the “most bothersome” or “one of the most bothersome.” Objective To compare the population- and individual-level burden of LUTS in men and women. Design, setting, and participants In this population-based cross-sectional study, questionnaires were mailed to 6000 individuals (18–79 yr of age) randomly identified from the Finnish Population Register. Outcome measurements and statistical analysis The validated Danish Prostatic Symptom Score questionnaire was used for assessment of bother of 12 different LUTS. The age-standardized prevalence of at least moderate bother was calculated for each symptom (population-level burden). Among symptomatic individuals, the proportion of affected individuals with at least moderate bother was calculated for each symptom (individual-level bother). Results and limitations A total of 3727 individuals (62.4%) participated (53.7% female). The LUTS with the greatest population-level burden were urgency (7.9% with at least moderate bother), stress urinary incontinence (SUI) (6.5%), nocturia (6.0%), postmicturition dribble (5.8%), and urgency urinary incontinence (UUI) (5.0%). Burden from incontinence symptoms was higher in women than men, and the opposite was true for voiding and postmicturition symptoms. At the individual level, UUI was the most bothersome for both genders. Although the response proportion was high, approximately a third did not participate. Conclusions Both men and women with UUI report moderate or major bother more frequently than individuals with other LUTS. At the population level, the most prevalent bothersome symptoms are urgency, SUI, and nocturia. Patient summary Urinary urgency was the most common troubling symptom in a large population-based study; however, for individuals, urgency incontinence was the most likely to be rated as bothersome.

There's a Pain App for That: Review of Patient-targeted Smartphone Applications for Pain Management.

Objectives:There are a growing number of pain self-management applications (apps) available for users to download on personal smartphones. The purpose of this study was to critically appraise the content and self-management functionality of currently available pain apps. Methods:An electronic search was conducted between May and June 2014 of the official stores for the 4 major operating systems. Two authors independently identified patient-focused apps with a stated goal of pain management. Discrepancies regarding selection were resolved through discussion with a third party. Metadata from all included apps were abstracted into a standard form. The content and functionality of each app as it pertained to pain self-management was rated. Results:A total of 279 apps met the inclusion criteria. Pain self-care skill support was the most common self-management function (77.4%). Apps also purported providing patients with the ability to engage in pain education (45.9%), self-monitoring (19%), social support (3.6%), and goal-setting (0.72%). No apps were comprehensive in terms of pain self-management, with the majority of apps including only a single self-management function (58.5%). In addition, only 8.2% of apps included a health care professional in their development, not a single app provided a theoretical rationale, and only 1 app underwent scientific evaluation. Discussion:Currently available pain self-management apps for patients are simplistic, lack the involvement of health care professionals in their development, and have not been rigorously tested for effectiveness on pain-related health outcomes. There is a need to develop and test theoretically and evidence-based apps to better support patients with accessible pain care self-management.

Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis

For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non‐perforated appendicitis.

Decision aids for localized prostate cancer treatment choice: Systematic review and meta-analysis.

Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user‐centered design of decision aids that promote shared decision making. CA Cancer J Clin 2015;65: 239–251.

Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta‐analysis

The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost‐effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis.

Decision aids for localized prostate cancer treatment choice

Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user‐centered design of decision aids that promote shared decision making. CA Cancer J Clin 2015;65: 239–251.