Application of Information Technology to Clinical Trial Evaluation and Enrollment: A Review.

IMPORTANCE: As cancer treatment has become more individualized, oncologic clinical trials have become more complex. Increasingly numerous and stringent eligibility criteria frequently include tumor molecular or genomic characteristics that may not be readily identified in medical records, rendering it difficult to best match clinical trials with clinical sites and to identify potentially eligible patients once a clinical trial has been selected and activated. Partly because of these factors, enrollment rates for cancer clinical trials remain low, creating delays and increased costs for drug development. Information technology (IT) platforms have been applied to the implementation and conduct of clinical trials to improve efficiencies in several medical fields, and these platforms have recently been introduced to oncologic studies. OBSERVATIONS: This review summarizes cancer and noncancer studies that used IT platforms for assistance with clinical trial site selection, patient recruitment, and patient screening. The review does not address the use of IT in other aspects of clinical research, such as wearable physical activity monitors or telehealth visits. A large number of IT platforms (which may be patient facing, site or investigator facing, or sponsor facing) are now commercially available. These applications use artificial intelligence and/or natural language processing to identify and summarize protocol eligibility criteria, institutional patient populations, and individual electronic health records. Although there is an expanding body of literature examining the role of this technology, relatively few studies to date have been performed in oncologic settings. CONCLUSIONS AND RELEVANCE: This review found that an increasing number and variety of IT platforms were available to assist in the planning and conduct of clinical trials. Because oncologic clinical care and clinical trial protocols are particularly complex, nuanced, and individualized, published experience with this technology in other fields may not be fully applicable to cancer settings. The extent to which these services will overcome ongoing and increasing challenges in cancer clinical research remains unclear.

Effectiveness of physical activity interventions in improving objective and patient-reported outcomes in head and neck cancer survivors: A systematic review.

OBJECTIVE: To assess the effectiveness of physical activity interventions in improving objective and patient-reported outcomes in HNC survivors. INTRODUCTION: Multiple guidelines recommend that head and neck cancer (HNC) survivors participate in regular physical activity. Physical activity is associated with improved outcomes and mortality in healthy individuals as well as in certain cancer populations. However, the effectiveness of physical activity interventions in HNC survivors is inadequately understood. METHODS AND RESULTS: Our literature search through December 2018 identified 2,392 articles. After de-duplication, title and abstract review, full-text review and bibliographic search, 20 studies met all inclusion criteria. Inclusion criteria included any full-body physical activity intervention in HNC survivors that did not target discrete organ sites or functions (e.g. swallowing). Study cohorts included 749 predominantly male participants with a mean age range of 48-63 years. At their conclusion, physical activity interventions were associated with at least one significant improvement in an objective or patient-reported outcome in 75% of studies. Aerobic capacity and fatigue were the most commonly improved outcomes. None of the included studies evaluated associations with survival or recurrence. Although traditional aerobic and resistance interventions were more common, a greater proportion of alternative physical activity (yoga and Tai Chi) interventions demonstrated improved objective and patient-reported outcomes. CONCLUSION: Physical activity interventions in HNC survivors often conferred some improvement in objective and patient-reported outcomes. Additional highly-powered, randomized controlled studies are needed to establish the optimal type, intensity, and timing of physical activity interventions as well as their impact on oncologic outcomes.

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

BACKGROUND: Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. METHODS: Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. RESULTS: One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. CONCLUSIONS: HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.

Immunotherapy Use in Patients With Lung Cancer and Comorbidities.

Immune checkpoint inhibitor (ICI) therapy is now in widespread clinical use for the treatment of lung cancer. Although patients with autoimmune disease and other comorbidities were excluded from initial clinical trials, emerging real-world experience suggests that these promising treatments may be administered safely to individuals with inactive low-risk autoimmune disease such as rheumatoid arthritis or psoriasis, mild to moderate renal and hepatic dysfunction, and certain chronic viral infections. Considerations for ICI in autoimmune disease populations include exacerbations of the underlying autoimmune disease, increased risk of ICI-induced immune-related adverse events, and potential for compromised efficacy if patients are receiving chronic immunosuppression. Immune checkpoint inhibitor use in higher-risk autoimmune conditions, such as myasthenia gravis or multiple sclerosis, requires careful evaluation on a case-by-case basis. Immune checkpoint inhibitor use in individuals with solid organ transplant carries a substantial risk of organ rejection. Ongoing research into the prediction of ICI efficacy and toxicity may help in patient selection, treatment, and monitoring.

Ethnic Disparities in Atherosclerotic Cardiovascular Disease Incidence and Prevalence Among Rheumatoid Arthritis Patients in the United States: a Systematic Review.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased atherosclerotic cardiovascular disease (ASCVD). General population cohorts have shown African American individuals to have greater and Hispanic Americans to have lower cardiovascular disease prevalence when compared with non-Hispanic white individuals; however, the reasons for these findings are not clear. This systematic review seeks to describe the incidence and prevalence of ASCVD stratified by race/ethnicity within the US RA population. METHODS: MEDLINE, Embase, and Cochrane databases were searched for studies that reported incidence or prevalence of ASCVD (including, but not limited to, fatal and nonfatal stroke, myocardial infarction, and cardiovascular death) in those with RA. Abstracts and full texts were screened separately for inclusion by two reviewers, with a third reviewer to resolve discrepancies. RESULTS: We screened 2625 abstracts and fully reviewed 138 manuscripts. Twenty-one were included that cited at a minimum the percentage of non-Hispanic whites in their population. No publication meeting entry criteria initially stratified ASCVD by race/ethnicity. The average prevalent ASCVD in RA is 46.9% (95% CI: 46.8-47) (range of prevalent ASCVD: 30%-47%). The average incident ASCVD is 8.2% (95% CI: 8.14-8.25) (range of incident ASCVD 1%-46%). CONCLUSION: In this systematic review, we found a paucity of data on racially/ethnically diverse RA patients and ASCVD outcomes. Future studies should report the prevalence of ASCVD in various races/ethnicities with RA in the United States. These data would help inform clinicians on how best to manage cardiovascular disease risk in RA.

A Systematic Review of Repeat Fecal Occult Blood Tests for Colorectal Cancer Screening.

Screening with fecal occult blood tests (FOBT) reduces colorectal cancer mortality. Failure to complete repeat tests may compromise screening effectiveness. We conducted a systematic review of repeat FOBT across diverse health care settings. We searched MEDLINE, Embase, and the Cochrane Library for studies published from 1997 to 2017 and reported repeat FOBT over ≥2 screening rounds. Studies (n = 27 reported in 35 articles) measured repeat FOBT as (i) proportion of Round 1 participants completing repeat FOBT in Round 2; (ii) proportion completing two, consecutive FOBT; or (iii) proportion completing ≥3 rounds. Among those who completed FOBT in Round 1, 24.6% to 89.6% completed repeat FOBT in Round 2 [median: 82.0%; interquartile range (IQR): 73.7%-84.6%]. The proportion completing FOBT in two rounds ranged from 16.4% to 80.0% (median: 46.6%; IQR: 40.5%-50.0%), and in studies examining ≥3 rounds, repeat FOBT ranged from 0.8% to 64.1% (median: 39.2%; IQR: 19.7%-49.4%). Repeat FOBT appeared higher in mailed outreach (69.1%-89.6%) compared with opportunistic screening (24.6%-48.6%). Few studies examined correlates of repeat FOBT. In summary, we observed a wide prevalence of repeat FOBT, and prevalence generally declined in successive screening rounds. Interventions that increase and maintain participation in FOBT are needed to optimize effectiveness of this screening strategy.

Do Decision Aids Benefit Patients with Chronic Musculoskeletal Pain? A Systematic Review.

OBJECTIVE: To review the effect of patient decision aids for adults making treatment decisions regarding the management of chronic musculoskeletal pain. METHODS: We performed a systematic review of randomized controlled trials of adults using patient decision aids to make treatment decisions for chronic musculoskeletal pain in the outpatient setting. RESULTS: Of 477 records screened, 17 met the inclusion criteria. Chronic musculoskeletal pain conditions included osteoarthritis of the hip, knee, or trapeziometacarpal joint and back pain. Thirteen studies evaluated the use of a decision aid for deciding between surgical and nonsurgical management. The remaining four studies evaluated decision aids for nonsurgical treatment options. Outcomes included decision quality, pain, function, and surgery utilization. The effects of decision aids on decision-making outcomes were mixed. Comparing decision aids with usual care, all five studies that examined knowledge scores found improvement in patient knowledge. None of the four studies that evaluated satisfaction with the decision-making process found a difference with use of a decision aid. There was limited and inconsistent data on other decision-related outcomes. Of the eight studies that evaluated surgery utilization, seven found no difference in surgery rates with use of a decision aid. Five studies made comparisons between different types of decision aids, and there was no clearly superior format. CONCLUSIONS: Decision aids may improve patients' knowledge about treatment options for chronic musculoskeletal pain but largely did not impact other outcomes. Future efforts should focus on improving the effectiveness of decision aids and incorporating nonpharmacologic and nonsurgical management options.

Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week.

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.

The Impact of Block Ambulatory Scheduling on Internal Medicine Residencies: a Systematic Review.

BACKGROUND: Over the past decade, nearly half of internal medicine residencies have implemented block clinic scheduling; however, the effects on residency-related outcomes are unknown. The authors systematically reviewed the impact of block versus traditional ambulatory scheduling on residency-related outcomes, including (1) resident satisfaction, (2) resident-perceived conflict between inpatient and outpatient responsibilities, (3) ambulatory training time, (4) continuity of care, (5) patient satisfaction, and (6) patient health outcomes. METHOD: The authors reviewed the following databases: Ovid MEDLINE, Ovid MEDLINE InProcess, EBSCO CINAHL, EBSCO ERIC, and the Cochrane Library from inception through March 2017 and included studies of residency programs comparing block to traditional scheduling with at least one outcome of interest. Two authors independently extracted data on setting, participants, schedule design, and the outcomes of interest. RESULTS: Of 8139 studies, 11 studies of fair to moderate methodologic quality were included in the final analysis. Overall, block scheduling was associated with marked improvements in resident satisfaction (n = 7 studies, effect size range - 0.3 to + 0.9), resident-perceived conflict between inpatient and outpatient responsibilities (n = 5, effect size range + 0.3 to + 2.6), and available ambulatory training time (n = 5). Larger improvements occurred in programs implementing short (1 week) ambulatory blocks. However, block scheduling may result in worse physician continuity (n = 4). Block scheduling had inconsistent effects on patient continuity (n = 4), satisfaction (n = 3), and health outcomes (n = 3). DISCUSSION: Although block scheduling improves resident satisfaction, conflict between inpatient and outpatient responsibilities, and ambulatory training time, there may be important tradeoffs with worse care continuity.

Effect of Exercise and Pharmacological Interventions on Visceral Adiposity: A Systematic Review and Meta-analysis of Long-term Randomized Controlled Trials.

OBJECTIVE: To assess the effectiveness of exercise and pharmacotherapy interventions in reducing visceral adipose tissue (VAT). PATIENTS AND METHODS: A systematic search of Ovid MEDLINE, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, New York Academy of Science Grey Literature Report, and OpenGrey was combined with hand searches of existing literature. A total of 2515 titles and abstracts were reviewed. Only randomized controlled trials evaluating the effectiveness of monitored exercise or pharmacological interventions in reducing VAT by using computed tomography or magnetic resonance imaging during a sustained intervention period (≥6 months) were included. Data were independently extracted by reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed for quality and risk of bias. Separate analyses for each intervention were performed using random effect models, with pooled estimates of the change in VAT area (in centimeters squared) from baseline to follow-up reported as standardized mean difference (SMD; with 95% CI). RESULTS: A total of 3602 participants from 17 randomized controlled trials were included in the final analysis. Both exercise and pharmacological interventions were associated with significant reductions in VAT: small reduction with pharmacological interventions (SMD, -0.27; 95% CI, -0.47 to -0.07; P=.02) and more substantial reductions with exercise interventions (SMD, -0.54; 95% CI, -0.63 to -0.46; P<.001). The mean absolute VAT reduction was greater in pharmacological trials than in exercise trials. Meta-regression exhibited a linear correlation between VAT and weight loss (R2=0.52 for exercise and R2=0.88 for pharmacological interventions), but VAT reduction relative to weight loss differed by intervention type. CONCLUSION: Exercise interventions resulted in greater reduction in VAT relative to weight loss than did pharmacological interventions. A preferential reduction in VAT may be clinically meaningful when monitoring success of interventions because weight loss alone may underestimate benefits.

Acute Myocardial Infarction Readmission Risk Prediction Models: A Systematic Review of Model Performance.

BACKGROUND: Hospitals are subject to federal financial penalties for excessive 30-day hospital readmissions for acute myocardial infarction (AMI). Prospectively identifying patients hospitalized with AMI at high risk for readmission could help prevent 30-day readmissions by enabling targeted interventions. However, the performance of AMI-specific readmission risk prediction models is unknown. METHODS AND RESULTS: We systematically searched the published literature through March 2017 for studies of risk prediction models for 30-day hospital readmission among adults with AMI. We identified 11 studies of 18 unique risk prediction models across diverse settings primarily in the United States, of which 16 models were specific to AMI. The median overall observed all-cause 30-day readmission rate across studies was 16.3% (range, 10.6%-21.0%). Six models were based on administrative data; 4 on electronic health record data; 3 on clinical hospital data; and 5 on cardiac registry data. Models included 7 to 37 predictors, of which demographics, comorbidities, and utilization metrics were the most frequently included domains. Most models, including the Centers for Medicare and Medicaid Services AMI administrative model, had modest discrimination (median C statistic, 0.65; range, 0.53-0.79). Of the 16 reported AMI-specific models, only 8 models were assessed in a validation cohort, limiting generalizability. Observed risk-stratified readmission rates ranged from 3.0% among the lowest-risk individuals to 43.0% among the highest-risk individuals, suggesting good risk stratification across all models. CONCLUSIONS: Current AMI-specific readmission risk prediction models have modest predictive ability and uncertain generalizability given methodological limitations. No existing models provide actionable information in real time to enable early identification and risk-stratification of patients with AMI before hospital discharge, a functionality needed to optimize the potential effectiveness of readmission reduction interventions.

Obesity is Independently Associated With Increased Risk of Hepatocellular Cancer-related Mortality: A Systematic Review and Meta-Analysis.

OBJECTIVE: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC-related mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and HCC-related mortality. MATERIALS AND METHODS: Through a systematic literature search-up to March 2016, we identified 9 observational studies (1,599,453 individuals, 5705 HCC-related deaths) reporting the association between premorbid body mass index (BMI), and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CIs), comparing obese (BMI>30 kg/m(2)) and overweight (BMI, 25 to 29.9 kg/m(2)) individuals with normal BMI individuals using random-effects model. RESULTS: On meta-analysis, compared with individuals with normal BMI, obese (aHR, 1.95; 95% CI, 1.46-2.46), but not overweight individuals (aHR, 1.08; 95% CI, 0.97-1.21), had higher HCC-related mortality, with moderate heterogeneity. On subgroup analysis, magnitude of increased mortality was higher in obese men (aHR, 2.50; 95% CI, 2.02-3.09; 3 studies) as compared with obese women (aHR, 1.45; 95% CI, 1.08-1.97; 2 studies). The impact of premorbid obesity on HCC-related mortality was observed only in western populations (aHR, 2.10; 95% CI, 1.77-2.48; 4 studies), but not Asian populations (aHR, 1.10; 95% CI, 0.63-1.92; 1 study). There was limited assessment of competing risk because of advanced liver disease. CONCLUSIONS: On the basis of this meta-analysis, premorbid obesity may be independently associated with a 2-fold risk of HCC-related mortality. This association was more pronounced in men and western populations. Strategies targeting obesity-associated metabolic abnormalities may provide novel pathways for HCC therapy.

Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting 75-100 million Americans. However, the disease burden may not be equally distributed among races or ethnicities. We conducted a systematic review and meta-analysis to characterize racial and ethnic disparities in NAFLD prevalence, severity, and prognosis. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases through August 2016 for studies that reported NAFLD prevalence in population-based or high-risk cohorts, NAFLD severity including presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis, and NAFLD prognosis including development of cirrhosis complications and mortality. Pooled relative risks, according to race and ethnicity, were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. RESULTS: We identified 34 studies comprising 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis. NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high-risk cohorts (range 47.6%-55.5%) than population-based cohorts (range, 13.0%-22.9%). Among patients with NAFLD, risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98-1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60-0.87) than Whites. However, the proportion of patients with significant fibrosis did not significantly differ among racial or ethnic groups. Data were limited and discordant on racial or ethnic disparities in outcomes of patients with NAFLD. CONCLUSIONS: In a systematic review and meta-analysis, we found significant racial and ethnic disparities in NAFLD prevalence and severity in the United States, with the highest burden in Hispanics and lowest burden in Blacks. However, data are discordant on racial or ethnic differences in outcomes of patients with NAFLD.

Medical and dietary interventions for preventing recurrent urinary stones in children.

BACKGROUND: Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium. OBJECTIVES: To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years. SEARCH METHODS: We searched multiple databases using search terms relevant to this review, including studies identified from the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 1), MEDLINE OvidSP (1946 to 14 February 2017), Embase OvidSP (1980 to 14 February 2017), International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Additionally, we handsearched renal-related journals and the proceedings of major renal conferences, and reviewed weekly current awareness alerts for selected renal journals. The date of the last search was 14 February 2017. There were no language restrictions. SELECTION CRITERIA: Randomized controlled trials of at least one year of MDI versus control for prevention of recurrent idiopathic (non-syndromic) nephrolithiasis in children. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. Titles and abstracts were identified by search criteria and then screened for relevance, and then data extraction and risk of bias assessment were carried out. We assessed the quality of evidence using GRADE. MAIN RESULTS: The search identified one study of 125 children (72 boys and 53 girls) with calcium-containing idiopathic nephrolithiasis and normal renal morphology following initial treatment with shockwave lithotripsy (SWL). Patients were randomized to oral potassium citrate 1 mEq/kg per day for 12 months versus no specific medication or preventive measure with results reported for a total of 96 patients (48 per group). This included children who were stone-free (n = 52) or had residual stone fragments (n = 44) following SWL. Primary outcomes:Medical therapy may lower rates of stone recurrence with a risk ratio (RR) of 0.19 (95% confidence interval (CI) 0.06 to 0.60; low quality evidence). This corresponds to 270 fewer stone recurrences per 1000 (133 fewer to 313 fewer) children. We downgraded the quality of evidence by two levels for very serious study limitations related to unclear allocation concealment (selection bias) and a high risk of performance, detection and attrition bias. While the data for adverse events were incomplete, they reported that six of 48 (12.5%) children receiving potassium citrate left the trial because of adverse effects. This corresponds to a RR of 13.0 (95% CI 0.75 to 224.53; very low quality evidence); an absolute effect size estimate could not be generated. We downgraded the quality of evidence for study limitations and imprecision.We found no information on retreatment rates. SECONDARY OUTCOMES: We found no evidence on serum electrolytes, 24-hour urine collection parameters or time to new stone formation.We were unable to perform any preplanned secondary analyses. AUTHORS' CONCLUSIONS: Oral potassium citrate supplementation may reduce recurrent calcium urinary stone formation in children following SWL; however, our confidence in this finding is limited. A substantial number of children stopped the medication due to adverse events. There is no trial evidence on retreatment rates. There is a critical need for additional well-designed trials in children with nephrolithiasis.

Occupational Therapy in the Intensive Care Unit: A Systematic Review.

This paper is a synthesis of the available literature on occupational therapy interventions performed in the adult intensive care unit (ICU). The databases of Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and CINAHL databases were systematically searched from inception through August 2016 for studies of adults who received occupational therapy interventions in the ICU. Of 1,938 citations reviewed, 10 studies met inclusion criteria. Only one study explicitly discussed occupational therapy interventions performed and only one study specifically tested the efficacy of occupational therapy. Future research is needed to clarify the specific interventions and role of occupational therapy in the ICU and the efficacy of these interventions.

What Do We Know About Intraoperative Teaching?: A Systematic Review.

BACKGROUND: There is increasing attention on enhancing surgical trainee performance and competency. The purpose of this review is to identify characteristics and themes related to intraoperative teaching that will better inform interventions and assessment endeavors. METHODS: A systematic search was carried out of the Ovid MEDLINE, Ovid MEDLINE InProcess, Ovid Embase, and the Cochrane Library databases to identify all studies that discussed teaching in the operating room for trainees at the resident and fellow level. Evidence for main outcome categories was evaluated with the Medical Education Research Study Quality Instrument (MERSQI). RESULTS: A total of 2101 records were identified. After screening by title, abstract, and full text, 34 studies were included. We categorized these articles into 3 groups on the basis of study methodology: perceptions, best practices, and interventions to enhance operative teaching. Overall strength of evidence for each type of study was as follows: perceptions (MERSQI: 7.5-10); best practices (6.5-11.5), and interventions (8-15). Although very few studies (n = 5) examined interventions for intraoperative teaching, these studies demonstrate the efficacy of techniques designed to enhance faculty teaching behaviors. CONCLUSIONS: Interventions have a positive impact on trainee ratings of their faculty intraoperative teaching performance. There is discordance between trainee perceptions of quantity and quality of teaching, compared with faculty perceptions of their own teaching behaviors. Frameworks and paradigms designed to provide best practices for intraoperative teaching agree that effective teaching spans 3 phases that take place before, during, and after cases.

Premorbid body mass index and mortality in patients with lung cancer: A systematic review and meta-analysis.

OBJECTIVES: We aimed to assess the association between premorbid obesity, measured using body mass index (BMI) and lung cancer-related mortality, through a systematic review and meta-analysis. MATERIALS AND METHODS: Observational studies reporting statistical measures of association between premorbid BMI categories and lung cancer-related mortality were included in our study. We estimated hazard ratios (aHR) with 95% confidence intervals (CI), comparing lung cancer-related mortality across BMI categories. The main outcome measure was lung cancer-related mortality in obese (BMI≥30kg/m2) and overweight participants (BMI 25.0-29.9kg/m2), compared with normal BMI participants. RESULTS: We included 14 studies (including 2 pooled cohort studies) comprising 3,008,137 cancer-free participants at inception, reporting 28,592 lung cancer-related deaths. On meta-analysis, we observed a significantly lower lung cancer-related mortality in overweight (aHR, 0.76; 95% CI, 0.68-0.85) and obese (aHR, 0.68, 95% CI; 0.57-0.81) participants as compared to participants with normal BMI, with considerable heterogeneity; after excluding one study with large effect size, a more conservative and consistent association was observed between BMI and lung cancer-related mortality (overweight vs. normal BMI: aHR, 0.84; 95% CI, 0.79-0.90; obese vs. normal BMI: aHR, 0.81; 95% CI, 0.75-0.87), with moderate heterogeneity. Were similar in men vs. women, non-smokers vs. smokers, and Western vs Asia-Pacific populations. CONCLUSIONS: Based on meta-analysis, we observed an independent protective association between premorbid obesity and lung cancer-related mortality. This association was observed across sex, smoking status and geographic region. Further studies are needed to prospectively study this association.

Continuous Dose-Response Association Between Sedentary Time and Risk for Cardiovascular Disease: A Meta-analysis.

IMPORTANCE: Prior studies suggest that higher sedentary time is associated with a greater risk for cardiovascular disease (CVD). However, the quantitative, dose-response association between sedentary time and CVD risk is not known. OBJECTIVE: To determine the categorical and quantitative dose-response association between sedentary time and CVD risk. DATA SOURCES: Two independent investigators searched the MEDLINE and EMBASE databases for all studies published before July 6, 2015, that evaluated the association between sedentary time and incident CVD. STUDY SELECTION: Prospective cohort studies with participants 18 years or older that reported the association between sedentary time and incident CVD were included. DATA EXTRACTION AND SYNTHESIS: Two independent investigators performed the data extraction and collection using a standardized form. The study quality was assessed using the Newcastle-Ottawa Scale. The categorical dose-response association was evaluated by comparing the pooled hazard ratio (HR) for incident CVD associated with different levels of sedentary time (vs lowest sedentary time) across studies. The continuous dose-response association was assessed using random-effects generalized least squares spline models. Data were collected from April 5 to July 6, 2015. MAIN OUTCOMES AND MEASURES: Incident CVD (coronary heart disease, including nonfatal myocardial infarction, stroke, and cardiovascular mortality). RESULTS: Nine prospective cohort studies with 720 425 unique participants (57.1% women; 42.9% men; mean age, 54.5 years) and 25 769 unique cardiovascular events and a median follow-up of 11 years were included. In categorical analyses, compared with the lowest sedentary time category (median, 2.5 h/d), participants in the highest sedentary time category (median, 12.5 h/d) had an increased risk for CVD (HR, 1.14; 95% CI, 1.09-1.19). However, no apparent risk associated with intermediate levels of sedentary time (HR for 7.5 h/d, 1.02; 95% CI, 0.96-1.08) was found. In continuous analyses, a nonlinear association between sedentary time and incident CVD was found (P for nonlinearity < .001), with an increased risk observed for more than 10 hours of sedentary time per day (pooled HR, 1.08; 95% CI, 1.00-1.14). CONCLUSIONS AND RELEVANCE: The association between sedentary time and the risk for CVD is nonlinear with an increased risk only at very high levels. These findings could have implications for guideline recommendations regarding the risks related to sedentary behavior.

Predicting the Risk of Readmission in Pneumonia. A Systematic Review of Model Performance.

RATIONALE: Predicting which patients are at highest risk for readmission after hospitalization for pneumonia could enable hospitals to proactively reallocate scarce resources to reduce 30-day readmissions. OBJECTIVES: To synthesize the available literature on readmission risk prediction models for adults who are hospitalized because of pneumonia and describe their performance. METHODS: We systematically searched Ovid MEDLINE, Embase, The Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature databases from inception through July 2015. We included studies of adults discharged with pneumonia that developed or validated a model that predicted hospital readmission. Two independent reviewers abstracted data and assessed the risk of bias. MEASUREMENTS AND MAIN RESULTS: Of 992 citations reviewed, 7 studies met inclusion criteria, which included 11 unique risk prediction models. All-cause 30-day readmission rates ranged from 11.8 to 20.8% (median, 17.3%). Model discrimination (C statistic) ranged from 0.59 to 0.77 (median, 0.63) with the highest-quality, best-validated model, the Centers for Medicare and Medicaid Services Pneumonia Administrative Model performing modestly (C Statistic of 0.63 in 4 separate multicenter cohorts). The best performing model (C statistic of 0.77) was a single-site study that lacked internal validation. The models had adequate calibration, with patients predicted as high risk for readmission having a higher average observed readmission rate than those predicted to be low risk. None of the studies included pneumonia illness severity scores, and only one included measures of in-hospital clinical trajectory and stability on discharge, robust predictors of readmission. CONCLUSIONS: We found a limited number of validated pneumonia-specific readmission models, and their predictive ability was modest. To improve predictive accuracy, future models should include measures of pneumonia illness severity, hospital complications, and stability on discharge.