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.

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.

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.

Biological Mesh Implants for Abdominal Hernia Repair: US Food and Drug Administration Approval Process and Systematic Review of Its Efficacy.

IMPORTANCE: Expensive biological mesh materials are increasingly used to reinforce abdominal wall hernia repairs. The clinical and cost benefit of these materials are unknown. OBJECTIVES: To review the published evidence on the use of biological mesh materials and to examine the US Food and Drug Administration (FDA) approval history for these devices. EVIDENCE ACQUISITION: Search of multiple electronic databases (Ovid, MEDLINE, EMBASE, Cochrane Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Cochrane National Health Service Economic Evaluation Database) to identify articles published between 1948 and June 30, 2015, on the use of biological mesh materials used to reinforce abdominal wall hernia repair. Keywords searched included surgical mesh, abdominal hernia, recurrence, infection, fistula, bioprosthesis, biocompatible materials, absorbable implants, dermis, and collagen. The FDA online database for 510(k) clearances was reviewed for all commercially available biological mesh materials. The median national price for mesh materials was established by a benchmarking query through several Integrated Delivery Network and Group Purchasing Organization tools. EVIDENCE SYNTHESIS: Of 274 screened articles, 20 met the search criteria. Most were case series that reported results of convenience samples of patients at single institutions with a variety of clinical problems. Only 3 of the 20 were comparative studies. There were no randomized clinical trials. In total, outcomes for 1033 patients were described. Studies varied widely in follow-up time, operative technique, meshes used, and patient selection criteria. Reported outcomes and clinical outcomes, such as fistula formation and infection, were inconsistently reported across studies. Conflicts of interest were not reported in 16 of the 20 studies. Recurrence rates ranged from 0% to 80%. All biological mesh devices were approved by the FDA based on substantial equivalence to a group of nonbiological predicate devices that, on average, were one-third less costly. CONCLUSIONS AND RELEVANCE: There is insufficient evidence to determine the extra costs associated with or the clinical efficacy of biological mesh materials for the repair of abdominal wall hernia.

Dose-Response Relationship Between Physical Activity and Risk of Heart Failure: A Meta-Analysis.

BACKGROUND: Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose-response association between PA and HF risk has not been reported previously. METHODS AND RESULTS: Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose-response relationships between PA and HF risk were assessed with random-effects models. Generalized least-squares regression models were used to assess the quantitative relationship between PA (metabolic equivalent [MET]-min/wk) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF events among 370 460 participants (53.5% women; median follow-up, 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95% confidence interval, 0.67-0.73). Compared with participants reporting no leisure-time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET-min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled hazard ratio, 0.90; 95% confidence interval, 0.87-0.92). In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77-0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence interval, 0.58-0.73) the minimum guideline-recommended levels. CONCLUSIONS: There is an inverse dose-response relationship between PA and HF risk. Doses of PA in excess of the guideline-recommended minimum PA levels may be required for more substantial reductions in HF risk.

Pain Management for Elective Foot and Ankle Surgery: A Systematic Review of Randomized Controlled Trials.

Pain after foot and ankle surgery can significantly affect the postoperative outcomes. We performed a systematic review of randomized controlled trials assessing postoperative pain after foot and ankle surgery, because the surgery will lead to moderate-to-severe postoperative pain, but the optimal pain therapy has been controversial. A systematic review of randomized controlled trials in English reporting on pain after foot and ankle surgery in adults published from January 1946 to February 2013 was performed. The primary outcome measure was the postoperative pain scores. The secondary outcome measures included supplemental analgesic requirements and other recovery outcomes. With 953 studies identified, 45 met the inclusion criteria. The approaches improving pain relief (reduced pain scores or opioid requirements) included peripheral nerve blocks, wound infiltration, intravenous dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 selective inhibitors, and opioids. Wound instillation, intra-articular injection, and intravenous regional analgesia had variable analgesia. The lack of homogeneous study design precluded quantitative analyses. Optimal pain management strategies included locoregional analgesic techniques plus acetaminophen and nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 selective inhibitors, with opioids used for "rescue," and 1 intraoperative dose of parenteral dexamethasone. Popliteal sciatic nerve blocks would be appropriate when expecting severe postoperative pain (extensive surgical procedure), and ankle blocks and surgical incision infiltration would be appropriate when expecting moderate postoperative pain (less extensive and minimally invasive surgical procedures). Additional studies are needed to assess multimodal analgesia techniques.

Long-term follow-up after bariatric surgery: a systematic review.

IMPORTANCE: Bariatric surgery is an accepted treatment for obesity. Despite extensive literature, few studies report long-term follow-up in cohorts with adequate retention rates. OBJECTIVE: To assess the quality of evidence and treatment effectiveness 2 years after bariatric procedures for weight loss, type 2 diabetes, hypertension, and hyperlipidemia in severely obese adults. EVIDENCE REVIEW: MEDLINE and Cochrane databases were searched from 1946 through May 15, 2014. Search terms included bariatric surgery, individual bariatric procedures, and obesity. Studies were included if they described outcomes for gastric bypass, gastric band, or sleeve gastrectomy performed on patients with a body mass index of 35 or greater, had more than 2 years of outcome information, and had follow-up measures for at least 80% of the initial cohort. Two investigators reviewed each study and a third resolved study inclusion disagreements. FINDINGS: Of 7371 clinical studies reviewed, 29 studies (0.4%, 7971 patients) met inclusion criteria. All gastric bypass studies (6 prospective cohorts, 5 retrospective cohorts) and sleeve gastrectomy studies (2 retrospective cohorts) had 95% confidence intervals for the reported mean, median, or both exceeding 50% excess weight loss. This amount of excess weight loss occurred in 31% of gastric band studies (9 prospective cohorts, 5 retrospective cohorts). The mean sample-size-weighted percentage of excess weight loss for gastric bypass was 65.7% (n = 3544) vs 45.0% (n = 4109) for gastric band. Nine studies measured comorbidity improvement. For type 2 diabetes (glycated hemoglobin <6.5% without medication), sample-size-weighted remission rates were 66.7% for gastric bypass (n = 428) and 28.6% for gastric band (n = 96). For hypertension (blood pressure <140/90 mm Hg without medication), remission rates were 38.2% for gastric bypass ( n = 808) and 17.4% for gastric band (n = 247). For hyperlipidemia (cholesterol <200 mg/dL, high-density lipoprotein >40 mg/dL, low-density lipoprotein <160 mg/dL, and triglycerides <200 mg/dL), remission rates were 60.4% for gastric bypass (n = 477) and 22.7% for gastric band (n = 97). CONCLUSIONS AND RELEVANCE: Very few bariatric surgery studies report long-term results with sufficient patient follow-up to minimize biased results. Gastric bypass has better outcomes than gastric band procedures for long-term weight loss, type 2 diabetes control and remission, hypertension, and hyperlipidemia. Insufficient evidence exists regarding long-term outcomes for gastric sleeve resections.

Surrogate and clinical outcomes following ischemic postconditioning during primary percutaneous coronary intervention of ST--segment elevation myocardial infarction: a meta-analysis of 15 randomized trials.

OBJECTIVES: To conduct a meta-analysis on surrogate and clinical outcomes with myocardial ischemic postconditioning (IPoC) following revascularization with primary percutaneous intervention (PPCI) for ST-segment myocardial infarction (STEMI) compared with PPCI alone. BACKGROUND: Reperfusion injury remains an important problem following PPCI for STEMI. Trials of IPoC have mainly focused on cardiac biomarkers; the impact on clinical outcomes is unknown. METHODS: Clinical trials that randomized STEMI patients to IPoC as compared with conventional PPCI were included for analysis. RESULTS: A total of 15 randomized trials with 1,545 patients met our selection criteria (785 underwent IPoC + PPCI, 760 PPCI alone). Mean follow-up for clinical outcomes was 4.7 months. The mean ischemic time was 225 min. ST-segment resolution (Relative Risk [RR] = 0.98; 95% Confidence Intervals [CI] 0.85-1.13; P = 0.75) and infarct size (Weighted mean difference [WMD] = -2.53%, 95% CI -6.10 to 1.05; P = 0.17) were similar between the IPoC + PPCI vs. PPCI arms. Left ventricular ejection fraction at follow-up was marginally higher in the IPoC (WMD = 4.15%, 95% CI 0.19-8.12%, P = 0.04). No differences were noted in any of the clinical outcomes studied, including mortality (RR = 1.52; 95% CI 0.77-2.99; P = 0.23), recurrent MI (RR = 3.04; 95% CI 0.74-12.54; P = 0.12); stent thrombosis (RR = 1.24, 95% CI 0.51-3.04; P = 0.83) or the composite MACE outcome (RR = 1.53; 95% CI 0.89-2.63; P = 0.13). CONCLUSIONS: IPoC following PPCI is not associated with improvements in surrogate or clinical outcomes at 5 months as compared with PPCI alone. Our findings indicate no role for IPoC in the routine management of patients with STEMI.

Axillary node interventions in breast cancer: a systematic review.

IMPORTANCE: Recent data from clinical trials have challenged traditional thinking about axillary surgery in patients with breast cancer. OBJECTIVES: To summarize evidence regarding the role of axillary interventions (surgical and nonsurgical) in breast cancer treatment and to review the association of these axillary interventions with recurrence of axillary node metastases, mortality, and morbidity outcomes in patients with breast cancer. EVIDENCE REVIEW: Ovid MEDLINE (1946-July 2013), Cochrane Database of Systematic Reviews (2005-July 2013), Cochrane Database of Abstracts of Reviews of Effects (1994-July 2013), and Cochrane Central Register of Controlled Trials (1989-July 2013) were searched for publications on axillary interventions in breast cancer. Clinical trials, observational studies, and meta-analyses with at least 2-year follow-up were included. A total of 1070 publications were reviewed, 17 of which met final inclusion criteria. FINDINGS: Partial mastectomy followed by whole breast radiation is breast-conserving therapy. For women with no suspicious, palpable axillary nodes who undergo breast-conserving therapy, there is little evidence of benefit from surgical complete axillary node dissection compared with sentinel node biopsy alone. Complete axillary node dissection in patients with no palpable lymph nodes, compared with sentinel node biopsy, provides no survival benefit and is associated with a 1% to 3% reduction in recurrence of axillary lymph node metastases, but is associated with a 14% risk of lymphedema. Surgical axillary staging via sentinel node biopsy in patients with benign axillary nodes on radiological and clinical examination helps to inform decisions regarding adjuvant systemic and radiation therapy. Patients and physicians should tailor axillary lymph node interventions to maximize regional disease control and minimize morbidity. Complete axillary lymph node dissection is indicated in patients who present with palpable or needle biopsy-proven axillary metastases, patients with positive sentinel nodes undergoing mastectomy (who do not, as a standard, receive adjuvant radiation), patients with more than 3 positive sentinel nodes undergoing breast-conserving therapy, and patients not meeting eligibility criteria for recent trials establishing the safety of sentinel node biopsy alone in patients with breast cancer and metastases in their sentinel nodes. CONCLUSION AND RELEVANCE: Available evidence suggests that axillary node dissection is associated with more harm than benefit in women undergoing breast-conserving therapy who do not have palpable, suspicious lymph nodes, who have tumors 3.0 cm or smaller, and who have 3 or fewer positive nodes on sentinel node biopsy.

A case study: the evolution of a "facilitator model" liaison program in an academic medical library.

QUESTION: What type of liaison program would best utilize both librarians and other library staff to effectively promote library services and resources to campus departments? SETTING: The case is an academic medical center library serving a large, diverse campus. METHODS: The library implemented a "facilitator model" program to provide personalized service to targeted clients that allowed for maximum staff participation with limited subject familiarity. To determine success, details of liaison-contact interactions and results of liaison and department surveys were reviewed. RESULTS: Liaisons successfully recorded 595 interactions during the program's first 10 months of existence. A significant majority of departmental contact persons (82.5%) indicated they were aware of the liaison program, and 75% indicated they preferred email communication. CONCLUSION: The "facilitator model" provides a well-defined structure for assigning liaisons to departments or groups; however, training is essential to ensure that liaisons are able to communicate effectively with their clients.

Use of computers and the Internet by residents in US family medicine programmes.

Computers, personal digital assistants (PDA), and the Internet are widely used as resources in medical education and clinical care. Educators who intend to incorporate these resources effectively into residency education programmes can benefit from understanding how residents currently use these tools, their skills, and their preferences. The researchers sent questionnaires to 306 US family medicine residency programmes for all of their residents to complete. Respondents were 1177 residents from 125 (41%) programmes. Access to a computer was reported by 95% of respondents. Of these, 97% of desktop and 89% of laptop computers could access the Internet. Residents accessed various educational and clinical resources. Half felt they had 'intermediate' skills at Web searches, 23% had 'some skills,' and 27% were 'quite skilled.' Those under 30 years of age reported higher skill levels. Those who experienced a Web-based curriculum in medical school reported higher search skills and greater success in finding clinical information. Respondents preferred to use technology to supplement the didactic sessions offered in resident teaching conferences. Favourable conditions exist in family medicine residency programmes to implement a blend of traditional and technology-based learning experiences. These conditions include residents' experience, skills, and preferences.