Modifiable risk factors in women at high risk of breast cancer: a systematic review.

BACKGROUND: Modifiable risk factors (alcohol, smoking, obesity, hormone use, and physical activity) affect a woman's breast cancer (BC) risk. Whether these factors affect BC risk in women with inherited risk (family history, BRCA1/2 mutations, or familial cancer syndrome) remains unclear. METHODS: This review included studies on modifiable risk factors for BC in women with inherited risk. Pre-determined eligibility criteria were used and relevant data were extracted. RESULTS: The literature search resulted in 93 eligible studies. For women with family history, most studies indicated that modifiable risk factors had no association with BC and some indicated decreased (physical activity) or increased risk (hormonal contraception (HC)/menopausal hormone therapy (MHT), smoking, alcohol). For women with BRCA mutations, most studies reported no association between modifiable risk factors and BC; however, some observed increased (smoking, MHT/HC, body mass index (BMI)/weight) and decreased risk (alcohol, smoking, MHT/HC, BMI/weight, physical activity). However, measurements varied widely among studies, sample sizes were often small, and a limited number of studies existed. CONCLUSIONS: An increasing number of women will recognize their underlying inherited BC risk and seek to modify that risk. Due to heterogeneity and limited power of existing studies, further studies are needed to better understand how modifiable risk factors influence BC risk in women with inherited risk.

Repeated measures of mammographic density and texture to evaluate prediction and risk of breast cancer: a systematic review of the methods used in the literature.

PURPOSE: It may be important for women to have mammograms at different points in time to track changes in breast density, as fluctuations in breast density can affect breast cancer risk. This systematic review aimed to assess methods used to relate repeated mammographic images to breast cancer risk. METHODS: The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021. Eligibility criteria included published articles in English describing the relationship of change in mammographic features with risk of breast cancer. Risk of bias was assessed using the Quality in Prognostic Studies tool. RESULTS: Twenty articles were included. The Breast Imaging Reporting and Data System and Cumulus were most commonly used for classifying mammographic density and automated assessment was used on more recent digital mammograms. Time between mammograms varied from 1 year to a median of 4.1, and only nine of the studies used more than two mammograms. Several studies showed that adding change of density or mammographic features improved model performance. Variation in risk of bias of studies was highest in prognostic factor measurement and study confounding. CONCLUSION: This review provided an updated overview and revealed research gaps in assessment of the use of texture features, risk prediction, and AUC. We provide recommendations for future studies using repeated measure methods for mammogram images to improve risk classification and risk prediction for women to tailor screening and prevention strategies to level of risk.

Studies of parenchymal texture added to mammographic breast density and risk of breast cancer: a systematic review of the methods used in the literature.

This systematic review aimed to assess the methods used to classify mammographic breast parenchymal features in relation to the prediction of future breast cancer. The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021 to extract published articles in English describing the relationship of parenchymal texture features with the risk of breast cancer. Twenty-eight articles published since 2016 were included in the final review. The identification of parenchymal texture features varied from using a predefined list to machine-driven identification. A reduction in the number of features chosen for subsequent analysis in relation to cancer incidence then varied across statistical approaches and machine learning methods. The variation in approach and number of features identified for inclusion in analysis precluded generating a quantitative summary or meta-analysis of the value of these features to improve predicting risk of future breast cancers. This updated overview of the state of the art revealed research gaps; based on these, we provide recommendations for future studies using parenchymal features for mammogram images to make use of accumulating image data, and external validation of prediction models that extend to 5 and 10 years to guide clinical risk management. Following these recommendations could enhance the applicability of models, helping improve risk classification and risk prediction for women to tailor screening and prevention strategies to the level of risk.

Normative noninvasive bladder function measurements in healthy women: A systematic review and meta-analysis.

AIM: To conduct an evidence synthesis of normative reference values for bladder function parameters in women. METHODS: We conducted a systematic review and meta-analysis of studies reporting bladder function parameters obtained from noninvasive tests in healthy women. Seven databases were searched for relevant studies from inception through December 2018, with manual searching of reference lists. We included English language articles that provided quantitative data on urination frequency, voided and postvoid residual volumes, and uroflowmetry results in women without lower urinary tract symptoms. Study selection, data extraction, and quality assessment were undertaken by at least two independent reviewers. Random-effects meta-analytic models were used to derive study-level pooled mean estimates and 95% confidence intervals. RESULTS: A total of 24 studies (N = 3090 women, age range, 18-91 years) met eligibility criteria. Pooled mean estimates of bladder function parameters were: 6.6 daytime voids (95% confidence interval (95% CI), 6.2, 7.0), 0.4 nighttime voids (95% CI, 0.0, 0.8), 1577 mL for 24-hour voided volume (95% CI 1428,1725); 12 mL for postvoid residual volume (95% CI, 4, 20); and 28 mL/sec for maximum flow rate (95% CI, 27,30). Between-study heterogeneity was high for all outcomes (I2 = 61.1-99.6%), but insufficient data were available to explore reasons for this high heterogeneity (eg, differences by age). CONCLUSION: Although summary mean estimates of bladder function parameters were calculated, the wide heterogeneity across studies precludes generalization of these estimates to all healthy women. Further research is needed to determine normative reference values within specific groups, such as those defined by age.

Prophylactic negative-pressure wound therapy after cesarean is associated with reduced risk of surgical site infection: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to assess the effect of prophylactic negative-pressure wound therapy on surgical site infections and other wound complications in women after cesarean delivery. DATA SOURCES: We searched Ovid Medline, Embase, SCOPUS, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials and observational studies comparing prophylactic negative-pressure wound therapy with standard wound dressing for cesarean delivery. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was surgical site infection after cesarean delivery. Secondary outcomes were composite wound complications, wound dehiscence, wound seroma, endometritis, and hospital readmission. Heterogeneity was assessed using Higgin's I2. Relative risks with 95% confidence intervals were calculated using random-effects models. RESULTS: Six randomized controlled trials and 3 cohort studies in high-risk mostly obese women met inclusion criteria and were included in the meta-analysis. Six were full-text articles, 2 published abstracts, and 1 report of trial results in ClinicalTrials.gov. Studies were also heterogeneous in the patients included and type of negative-pressure wound therapy device. The risk of surgical site infection was significantly lower with the use of prophylactic negative-pressure wound therapy compared with standard wound dressing (7 studies: pooled risk ratio, 0.45; 95% confidence interval, 0.31-0.66; adjusted risk ratio, -6.0%, 95% confidence interval, -10.0% to -3.0%; number needed to treat, 17, 95% confidence interval, 10-34). There was no evidence of significant statistical heterogeneity (I2 = 9.9%) or publication bias (Egger P = .532). Of the secondary outcomes, only composite wound complications were significantly reduced in patients receiving prophylactic negative-pressure wound therapy compared with standard dressing (9 studies: pooled risk ratio, 0.68, 95% confidence interval, 0.49-0.94). CONCLUSION: Studies on the effectiveness of prophylactic negative-pressure wound therapy at cesarean delivery are heterogeneous but suggest a reduction in surgical site infection and overall wound complications. Larger definitive trials are needed to clarify the clinical utility of prophylactic negative-pressure wound therapy after cesarean delivery.

Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to examine the impact of antipyretic therapy on mortality in critically ill septic adults. DATA SOURCES: Literature searches were implemented in Ovid Medline, Embase, Scopus, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, and ClinicalTrials.gov through February 2016. STUDY SELECTION: Inclusion criteria were observational or randomized studies of septic patients, evaluation of antipyretic treatment, mortality reported, and English-language version available. Studies were excluded if they enrolled pediatric patients, patients with neurologic injury, or healthy volunteers. Criteria were applied by two independent reviewers. DATA EXTRACTION: Two reviewers independently extracted data and evaluated methodologic quality. Outcomes included mortality, frequency of shock reversal, acquisition of nosocomial infections, and changes in body temperature, heart rate, and minute ventilation. Randomized and observational studies were analyzed separately. DATA SYNTHESIS: Eight randomized studies (1,507 patients) and eight observational studies (17,432 patients) were analyzed. Antipyretic therapy did not reduce 28-day/hospital mortality in the randomized studies (relative risk, 0.93; 95% CI, 0.77-1.13; I = 0.0%) or observational studies (odds ratio, 0.90; 95% CI, 0.54-1.51; I = 76.1%). Shock reversal (relative risk, 1.13; 95% CI, 0.68-1.90; I = 51.6%) and acquisition of nosocomial infections (relative risk, 1.13; 95% CI, 0.61-2.09; I = 61.0%) were also unchanged. Antipyretic therapy decreased body temperature (mean difference, -0.38°C; 95% CI, -0.63 to -0.13; I = 84.0%), but not heart rate or minute ventilation. CONCLUSIONS: Antipyretic treatment does not significantly improve 28-day/hospital mortality in adult patients with sepsis.

Contralateral prophylactic mastectomy after unilateral breast cancer: a systematic review and meta-analysis.

OBJECTIVE: To examine whether contralateral prophylactic mastectomy (CPM) is associated with improved survival, incidence of contralateral breast cancer (CBC), and recurrence in patients with unilateral breast cancer (UBC). BACKGROUND: Despite conflicting data, CPM rates continue to increase. Here we present the first meta-analysis to assess post-CPM outcomes in women with UBC. METHODS: We searched 5 databases and retrieved papers' bibliographies for relevant studies published through March 2012. Fixed- and random-effects meta-analyses were conducted on the basis of tests of study heterogeneity. We examined potential confounding via stratification and meta-regression. We report pooled relative risks (RRs) and risk differences (RDs) with 95% confidence intervals (CIs) at 2-tailed P < 0.05 significance. RESULTS: Of 93 studies reviewed, 14 were included in meta-analyses. Compared with nonrecipients, CPM recipients had higher rates of overall survival [OS; RR = 1.09 (95% CI: 1.06, 1.11)] and lower rates of breast cancer-specific mortality [BCM; RR = 0.69 (95% CI: 0.56, 0.85)] but saw no absolute reduction in risk of metachronous CBC (MCBC). Among patients with elevated familial/genetic risk (FGR, ie, BRCA carrier status and/or family history of breast cancer), both relative and absolute risks of MCBC were significantly decreased among CPM recipients [RR = 0.04 (95% CI: 0.02, 0.09); RD = -24.0% (95% CI: -35.6%, -12.4%)], but there was no improvement in OS or BCM. CONCLUSIONS: CPM is associated with decreased MCBC incidence but not improved survival among patients with elevated FGR. The superior outcomes observed when comparing CPM recipients with nonrecipients in the general population are likely not attributable to a CPM-derived decrease in MCBC incidence. UBC patients without known FGR should not be advised to undergo CPM.

Geographic and temporal trends in the management of occult primary breast cancer: a systematic review and meta-analysis.

BACKGROUND: Management of occult primary breast cancer (OPBC), including the role of magnetic resonance imaging (MRI), is controversial. We conducted a pooled analysis of OPBC patients and a meta-analysis of MRI accuracy in OPBC in order to elucidate current practices. METHODS: A literature search yielded 201 studies. Patient-level data for clinically/mammographically OPBC from studies published after 1993 and from our institution were pooled; logistic regression examined associations between patient/study data and outcomes, including treatments and recurrence. We report adjusted odds ratios (OR) and 95 % confidence intervals (95 % CI) significant at 2-tailed p < 0.05. Meta-analysis included data for patients who received MRIs for workup of clinically/mammographically OPBC. We report pooled sensitivity and specificity with 95 % CIs. RESULTS: The pooled analysis included 92 patients (15 studies [n = 85] plus our institution [n = 7]). Patients from Asia were more likely to receive breast surgery (OR = 5.98, 95 % CI = 2.02-17.65) but not chemotherapy (OR = 0.32, 95 % CI = 0.13-0.82); patients from the United States were more likely to receive chemotherapy (OR = 13.08, 95 % CI = 2.64-64.78). Patients from studies published after 2003 were more likely to receive radiotherapy (OR = 3.86, 95 % CI = 1.41-10.55). Chemotherapy recipients were more likely to have distant recurrence (OR = 9.77, 95 % CI = 1.10-87.21). More patients with positive MRIs received chemotherapy than patients with negative MRIs (10 of 12 [83.3 %] vs 5 of 13 [38.5 %]; p = 0.0414). In the MRI-accuracy meta-analysis (10 studies, n = 262), pooled sensitivity and specificity were 96 % (95 % CI = 91-98 %) and 63 % (95 % CI = 42-81 %), respectively. CONCLUSIONS: OPBC management varied geographically and over time. We recommend establishing an international OPBC patient registry to facilitate longitudinal study and develop global treatment standards.

Efficacy of Postpartum Pharmacologic Thromboprophylaxis: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of pharmacologic venous thromboembolism (VTE) prophylaxis in postpartum patients. DATA SOURCES: On February 21, 2022, a literature search was conducted on Embase.com , Ovid-Medline All, Cochrane Library, Scopus, and ClinicalTrials.gov using terms postpartum period AND thromboprophylaxis AND antithrombin medications including heparin and low molecular weight heparin. METHODS OF STUDY SELECTION: Studies that evaluated the outcome of VTE among postpartum patients exposed to pharmacologic VTE prophylaxis with or without a comparator group were eligible for inclusion. Studies of patients who received antepartum VTE prophylaxis, studies in which this prophylaxis could not be definitively ruled out, and studies of patients who received therapeutic dosing of anticoagulation for specific medical problems or treatment of VTE were excluded. Titles and abstracts were independently screened by two authors. Relevant full-text articles were retrieved and independently reviewed for inclusion or exclusion by two authors. TABULATION, INTEGRATION, AND RESULTS: A total of 944 studies were screened by title and abstract, and 54 full-text studies were retrieved for further evaluation after 890 studies were excluded. Fourteen studies including 11,944 patients were analyzed: eight randomized controlled trials (8,001 patients) and six observational studies (3,943 patients). Among the eight studies with a comparator group, there was no difference in the risk of VTE between patients who were exposed to postpartum pharmacologic VTE prophylaxis and those who were unexposed (pooled relative risk 1.02, 95% CI 0.29-3.51); however, six of eight studies had no events in either the exposed or unexposed group. Among the six studies without a comparator group, the pooled proportion of postpartum VTE events was 0.00, likely due to five of six studies having no events. CONCLUSION: The current literature provided an insufficient sample size to conclude whether postpartum VTE rates differ between those exposed to postpartum pharmacologic prophylaxis and those unexposed, given the rarity of VTE events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022323841.

Curbing the Cough: Multimodal Treatments for Neurogenic Cough: A Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: Neurogenic cough affects 11% of Americans and causes significant detriment to quality of life. With the advent of novel therapies, the objective of this review is to determine how procedural therapies (e.g., superior laryngeal nerve block) compare to other established pharmacologic and non-pharmacologic treatments for neurogenic cough. METHODS: With the assistance of a medical librarian, a systematic review was performed using PICOS (patients, interventions, comparator, outcome, study design) format: adults with neurogenic cough receiving any pharmacologic or non-pharmacologic treatment for neurogenic cough compared to adults with neurogenic cough receiving any other relevant interventions, or treated as single cohorts, assessed with cough-specific quality of life outcomes, in all study designs and case series with ≥ 10 cases. Case reports, review articles, non-human studies, non-English language articles, and unavailable full-text articles were excluded. RESULTS: There were 2408 patients with neurogenic cough in this review, treated with medical therapy (77%), speech therapy (19%), both medical and speech therapy (1%), and procedural therapy (3%). The included studies ranged from low to intermediate quality. Overall, most interventions demonstrated successful improvement in cough. However, the heterogeneity of included study designs precluded direct comparisons between intervention types. CONCLUSION: This meta-analysis compared various treatments for neurogenic cough. Procedural therapy should be considered in the armamentarium of neurogenic cough treatments, particularly in patients refractory to, or intolerant of, the side effects of medical therapy. Lastly, this review illuminates key areas for improving neurogenic cough diagnosis, such as strict adherence to diagnostic and treatment guidelines, sophisticated reflux testing, and standardized, consistent outcome reporting. Laryngoscope, 132:107-123, 2022.

Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation: A Systematic Review and Meta-analysis.

Importance: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice. Objective: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes. Data Sources: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance. Study Selection: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded. Data Extraction and Synthesis: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models. Main Outcomes and Measures: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission. Results: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2 = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, -0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2 (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2 (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11). Conclusions and Relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.

Non-invasive bladder function measures in healthy, asymptomatic female children and adolescents: A systematic review and meta-analysis.

BACKGROUND: Lower urinary tract symptoms (LUTS) are common in children and adolescents. Non-invasive tests evaluating bladder function are generally preferred over invasive tests, yet few studies have explored the range of normative values for these tests in healthy, asymptomatic children. OBJECTIVE: To define normative reference ranges for non-invasive tests of bladder function in healthy, asymptomatic girls and adolescents. STUDY DESIGN: A comprehensive search strategy was performed in seven electronic databases through October 2019. English-language studies reporting data on voiding frequency, voided and postvoid residual volumes (PVR) and uroflowmetry results in healthy, asymptomatic girls (mean age ≥ 5 years) were included. Two independent reviewers performed study review, data extraction, and quality assessment. Overall mean estimates and 95% confidence intervals for each bladder function parameter were calculated using random effects models, and 95% normative reference values were estimated. RESULTS: Ten studies met eligibility criteria for the meta-analysis (n = 2143 girls, age range: 3-18). Mean estimates of maximum voided volume and PVR were 233.4 ml (95% CI 204.3-262.6; n = 1 study) and 8.6 ml (95% CI 4.8-12.4; n = 2 studies) respectively. Pooled mean estimates for uroflowmetry parameters were: 21.5 ml/s (95% CI 20.5-2.5) for maximum flow rate (n = 6 studies), 12.5 ml/s (95% CI 11.2-13.8) for mean flow rate (n = 6 studies), 6.8 s (95% CI 4.4-9.3) for time to maximum flow (n = 3 studies), 15.7 s (95% CI 13.0-18.5) for flow time (n = 3 studies), and 198.7 ml (95% CI 154.2-234.2) for voided volume (n = 9 studies). No studies reported estimates of voiding frequency. Between-study heterogeneity was high (89.0-99.6%). CONCLUSIONS: Although we were able to calculate pooled mean estimates for several parameters, the small number of included studies and the wide age ranges of participants preclude generalization of reference values to all healthy girls. Further research is needed to determine normative reference values within specific age groups.

Too much or too little? A systematic review of postparetic synkinesis treatment.

Synkinesis is a negative sequela of facial nerve recovery. Despite the need for effective treatment, controversy exists regarding optimal management and outcome reporting measures. The goals of this study were to evaluate the current synkinesis literature and compare the effectiveness of treatment modalities. A search of biomedical databases was performed in May 2019. Full-text English language articles of cohort studies or randomized controlled trials on synkinesis treatment were eligible for inclusion. Reviews, animal studies, and those without assessment of treatment effect were excluded. We found 592 unique citations; 33 articles were included in the final analyses. Nine studies focused on botulinum toxin (BTX-A), 7 on surgery, 5 on physical therapy (PT), and 12 on multimodal therapy. The Sunnybrook Facial Grading System was the most frequently used outcome measure (17 studies, 51.5%). All treatment modalities improved outcomes. Chemodenervation studies showed an average improvement of 17.8% (range 11-33.3%) in the respective outcome measures after treatment. PT improved by 29.7% (range 14.6-41.2%), surgery by 16.6% (range 4.7-41%), and combination therapy by 20.4% (range 5.13-37.5%). Only 21 studies (63.6%) provided data on adverse outcomes. There is lack of high-evidence level data for robust comparisons of postparetic synkinesis treatments; however, this condition is likely effectively treated nonsurgically and requires the support of a specialized multidisciplinary team. Adoption of standardized patient evaluation and outcome reporting methods is necessary for robust comparative effectiveness studies.

The value of a second reviewer for study selection in systematic reviews.

BACKGROUND: Although dual independent review of search results by two reviewers is generally recommended for systematic reviews, there are not consistent recommendations regarding the timing of the use of the second reviewer. This study compared the use of a complete dual review approach, with two reviewers in both the title/abstract screening stage and the full-text screening stage, as compared with a limited dual review approach, with two reviewers only in the full-text stage. METHODS: This study was performed within the context of a large systematic review. Two reviewers performed a complete dual review of 15 000 search results and a limited dual review of 15 000 search results. The number of relevant studies mistakenly excluded by highly experienced reviewers in the complete dual review was compared with the number mistakenly excluded during the full-text stage of the limited dual review. RESULTS: In the complete dual review approach, an additional 6.6% to 9.1% of eligible studies were identified during the title/abstract stage by using two reviewers, and an additional 6.6% to 11.9% of eligible studies were identified during the full-text stage by using two reviewers. In the limited dual review approach, an additional 4.4% to 5.3% of eligible studies were identified with the use of two reviewers. CONCLUSIONS: Using a second reviewer throughout the entire study screening process can increase the number of relevant studies identified for use in a systematic review. Systematic review performers should consider using a complete dual review process to ensure all relevant studies are included in their review.

Letrozole Compared With Clomiphene Citrate for Unexplained Infertility: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the clinical effectiveness, as determined by positive pregnancy test, of letrozole compared with clomiphene citrate for ovarian stimulation in patients with unexplained infertility. DATA SOURCES: We conducted a systematic review and meta-analysis of data from electronic databases including Ovid-MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and ClinicalTrials.gov. METHODS: We searched for concepts of unexplained infertility, letrozole, clomiphene citrate, and clinical outcomes including pregnancy and live birth. Studies were included if they were randomized controlled trials (RCTs) comparing clomiphene citrate with letrozole in patients with unexplained infertility. Eight RCTs including 2,647 patients with unexplained infertility were included. Primary outcome was positive pregnancy test per patient. Secondary outcomes included positive pregnancy test per cycle, clinical pregnancy, live birth, spontaneous miscarriage, twin gestation, mean serum estradiol (E2), endometrial thickness, and number of dominant follicles. The Cochrane Q test and Higgin's I were used to assess heterogeneity. Random effects models were used to obtain pooled relative risks (RR) and 95% CIs. TABULATION, INTEGRATION, AND RESULTS: In analysis per patient, there was no significant difference in positive pregnancy test between patients treated with letrozole compared with clomiphene citrate (24% vs 23%, pooled RR 1.08, 95% CI 0.85-1.36). Significant heterogeneity was noted between studies (I=60.8%). There were no significant differences in clinical pregnancy (pooled RR 1.15, 95% CI 0.71-1.85), live birth (pooled RR 0.94, 95% CI 0.83-1.08), spontaneous miscarriage (pooled RR 0.92, 95% CI 0.61-1.38), or twin gestation (pooled RR 0.81, 95% CI 0.39-1.68). Mean serum E2 was significantly lower in the letrozole group than in the clomiphene citrate group. CONCLUSION: Although limited by heterogeneity, studies of ovarian stimulation in women with unexplained infertility show no difference in clinical outcomes between letrozole and clomiphene citrate.

Multimorbidity in randomized controlled trials of behavioral interventions: A systematic review.

OBJECTIVE: As the population with multiple chronic conditions (MCC) increases, it is essential that randomized controlled trials (RCTs) consider MCC. Behavioral interventions have the potential to positively impact MCC patient outcomes; however, a comprehensive review of consideration of MCC in these trials has not been conducted. The purpose of this systematic review is to determine the frequency with which participants with MCC are represented in behavioral intervention RCTs targeting chronic illness published 2000-2014. METHOD: MEDLINE and EMBASE were searched from 2000 to 2014 to identify RCTs testing behavioral interventions among adults with chronic illness. A random sampling selection process was performed to identify 600 eligible studies representative of the literature. Two reviewers independently extracted information on consideration of MCC in eligibility criteria and evaluated the reporting and consideration of MCC in trial analyses. Risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool. RESULTS: In 600 behavioral intervention RCTs, targeting MCC was rare (4.3%). Exclusion of MCC was common (68.3%) and was done through general, specific, or vague exclusion criteria. 218 (36.3%) trials reported presence of MCCs through general or condition-specific measures. Comorbidities were only considered in 4.8% of all trial analyses. CONCLUSIONS: In this comprehensive systematic review of 600 studies published from 2000-2014, RCTs testing behavioral interventions rarely consider individuals with MCC, limiting generalizability. Given the public health relevance and limited evidence base, this work highlights the urgent need to improve the consideration of MCC in clinical trial research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Geriatric Assessment and Frailty Scores Predict Mortality in Myeloma: Systematic Review and Meta-analysis.

The incidence of multiple myeloma is increasing as the proportion of older adults is growing rapidly. A critical evaluation of the evidence available is needed to guide the management of older patients with myeloma. A systematic review was conducted to report the prognostic value of geriatric assessment and frailty scores in older patients with multiple myeloma. We conducted a literature search in February and August 2018. Two researchers extracted the data and assessed the quality of the studies. Geriatric assessment and frailty scores were defined as those evaluating at least 2 geriatric domains. Main outcomes were mortality or toxicity. We estimated the pooled hazard ratios (HR) with 95% confidence intervals (CIs) using a random-effects model. We screened titles and abstracts of 1672 citations for eligibility. Seven studies were included in the qualitative analysis, of which 3 were included in the meta-analysis. Two studies reported similar risks of hematologic adverse events in intermediate-fit and in frail patients compared to frail, but a significantly increased risk of nonhematologic adverse events in frail patients compared to fit patients. In meta-analysis, a significantly increased HR for death was observed in patients with activity of daily living score ≤ 4 (pooled HR = 1.576; 95% CI, 1.051-2.102; χ2 = 0.87; P = .647; I2 = 0). Patients classified as frail showed higher risk of death than fit patients (pooled HR = 2.169; 95% CI, 1.002-2.336; χ2 = 3.02; P = .221; I2 = 33.7%). GA and frailty score are effective in predicting mortality in older adults with myeloma.

A Systematic Review and Meta-analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department.

BACKGROUND: Opioids are commonly prescribed in the emergency department (ED) for the treatment of acute pain. Analgesic alternatives are being explored in response to an epidemic of opioid misuse. Low-dose ketamine (LDK) is one opioid alternative for the treatment of acute pain in the ED. OBJECTIVES: This systematic review and meta-analysis sought to quantify whether LDK is an effective and safe opioid alternative for acute pain reduction in adults in the ED setting. (PROSPERO Registration Number CRD42017065303). METHODS: This was a systematic review of randomized controlled trials comparing intravenous opioids to LDK for relief of acute pain in the ED. Studies where the control group initially received opioids prior to ketamine were excluded. A research librarian designed the electronic search strategy. Changes in visual analog scale or numeric rating scale pain scales were analyzed to determine the relative effects of LDK and opioids in the treatment of acute pain. RESULTS: Three studies met the criteria for inclusion in this meta-analysis. Compared to pain scale reduction with morphine, ketamine was not inferior (relative reduction = 0.42, 95% confidence interval = -0.70 to 1.54). No severe adverse events were reported in any study, but higher rates of nonsevere adverse events were observed with ketamine. CONCLUSIONS: Ketamine is noninferior to morphine for the control of acute pain, indicating that ketamine can be considered as an alternative to opioids for ED short-term pain control.

Barriers to mammography among inadequately screened women.

Mammography use has increased over the past 20 years, yet more than 30% of women remain inadequately screened. Structural barriers can deter individuals from screening, however, cognitive, emotional, and communication barriers may also prevent mammography use. This study sought to identify the impact of number and type of barriers on mammography screening status, and to examine whether number and type of barriers are different for never-screened and off-schedule women. A total of 182 women aged 40 years or older completed a computer kiosk facilitated survey as part of a larger patient navigator intervention. Logistic regression analysis indicated that breast cancer knowledge predicted whether a woman had ever had a mammogram (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.02-1.06, p = .0003), while the number of emotional, structural, and communication barriers predicted whether a woman was on-schedule for mammograms (OR = 0.79, 95% CI = 0.65-0.95, p = .0127). The results suggest that to increase the use of mammography at recommended regular intervals, interventions should be tailored toward current screening status.

The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003-2012.

IMPORTANCE: The prevalence of obesity and outcomes of bariatric surgery are well established. However, analyses of the surgery impact have not been updated and comprehensively investigated since 2003. OBJECTIVE: To examine the effectiveness and risks of bariatric surgery using up-to-date, comprehensive data and appropriate meta-analytic techniques. DATA SOURCES: Literature searches of Medline, Embase, Scopus, Current Contents, Cochrane Library, and Clinicaltrials.gov between 2003 and 2012 were performed. STUDY SELECTION: Exclusion criteria included publication of abstracts only, case reports, letters, comments, or reviews; animal studies; languages other than English; duplicate studies; no surgical intervention; and no population of interest. Inclusion criteria were a report of surgical procedure performed and at least 1 outcome of interest resulting from the studied surgery was reported: comorbidities, mortality, complications, reoperations, or weight loss. Of the 25,060 initially identified articles, 24,023 studies met the exclusion criteria, and 259 met the inclusion criteria. DATA EXTRACTION AND SYNTHESIS: A review protocol was followed throughout. Three reviewers independently reviewed studies, abstracted data, and resolved disagreements by consensus. Studies were evaluated for quality. MAIN OUTCOMES AND MEASURES: Mortality, complications, reoperations, weight loss, and remission of obesity-related diseases. RESULTS: A total of 164 studies were included (37 randomized clinical trials and 127 observational studies). Analyses included 161,756 patients with a mean age of 44.56 years and body mass index of 45.62. We conducted random-effects and fixed-effect meta-analyses and meta-regression. In randomized clinical trials, the mortality rate within 30 days was 0.08% (95% CI, 0.01%-0.24%); the mortality rate after 30 days was 0.31% (95% CI, 0.01%-0.75%). Body mass index loss at 5 years postsurgery was 12 to 17. The complication rate was 17% (95% CI, 11%-23%), and the reoperation rate was 7% (95% CI, 3%-12%). Gastric bypass was more effective in weight loss but associated with more complications. Adjustable gastric banding had lower mortality and complication rates; yet, the reoperation rate was higher and weight loss was less substantial than gastric bypass. Sleeve gastrectomy appeared to be more effective in weight loss than adjustable gastric banding and comparable with gastric bypass. CONCLUSIONS AND RELEVANCE: Bariatric surgery provides substantial and sustained effects on weight loss and ameliorates obesity-attributable comorbidities in the majority of bariatric patients, although risks of complication, reoperation, and death exist. Death rates were lower than those reported in previous meta-analyses.