Associations Among Sleep and Cancer Risk Behaviors: a Scoping Review of Experimental Studies in Healthy Adult Populations.

BACKGROUND: Links among poor sleep and cancer risk behaviors have been largely overlooked in the context of cancer prevention and behavioral medicine. The goal of this scoping review was to determine the extent and nature of experimental studies conducted with healthy adult populations that tested the associations among poor sleep and cancer risk behaviors. METHOD: Electronic databases and major sleep journals were searched to identify experimental studies in healthy adult samples published through January 2018. Studies examined associations among eight pairings of manipulated behaviors and outcomes ("independent variable (IV)-outcome pairs"): the impact of sleep manipulations on physical activity (PA), diet, alcohol consumption, and tobacco use outcomes; and the impact of PA, diet, alcohol consumption, and tobacco use manipulations on sleep outcomes. Studies were characterized in terms of sample characteristics; study design; IV type, dose, and duration; and outcome measurement and duration. RESULTS: Abstracts of 5697 papers and 345 full texts were screened. Eighty-eight studies describing 125 comparisons met inclusion criteria. Only two studies tested the association between tobacco use and sleep; none tested whether sleep influenced alcohol consumption. Sample sizes were typically small, most studies used crossover designs, and studies tended to include younger and more male participants. Within each IV-outcome pair, there was substantial heterogeneity in how behaviors were manipulated, outcome measurement, and type of control group. Few studies assessed mechanisms. CONCLUSION: There is a need for larger experimental studies with more representative samples. Overall, heterogeneity and limitations in study designs make it difficult to synthesize evidence across studies.

Diagnostic Methods for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm. PURPOSE: To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists. STUDY SELECTION: English-language studies describing methods of diagnosis of ME/CFS and their accuracy. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus. DATA SYNTHESIS: Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability. LIMITATIONS: Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations. CONCLUSION: Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus. DATA SYNTHESIS: Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence). LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. CONCLUSION: Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.

Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Medications to reduce risk for primary breast cancer are recommended for women at increased risk; however, use is low. PURPOSE: To update evidence about the effectiveness and adverse effects of medications to reduce breast cancer risk, patient use of such medications, and methods for identifying women at increased risk for breast cancer. DATA SOURCES: MEDLINE and Cochrane databases (through 5 December 2012), Scopus, Web of Science, clinical trial registries, and reference lists. STUDY SELECTION: English-language randomized trials of medication effectiveness and adverse effects, observational studies of adverse effects and patient use, and diagnostic accuracy studies of risk assessment. DATA EXTRACTION: Investigators independently extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability using established criteria. DATA SYNTHESIS: Seven good- and fair-quality trials indicated that tamoxifen and raloxifene reduced incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo. New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000 women. Neither reduced breast cancer-specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms. Thirteen risk-stratification models were modest predictors of breast cancer. LIMITATION: Data on mortality and adherence measures and for women who are nonwhite, are premenopausal, or have comorbid conditions were lacking. CONCLUSION: Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events. Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts. Use is limited by adverse effects and inaccurate methods to identify candidates. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Pressure ulcer treatment strategies: a systematic comparative effectiveness review.

BACKGROUND: Pressure ulcers affect as many as 3 million Americans and are major sources of morbidity, mortality, and health care costs. PURPOSE: To summarize evidence comparing the effectiveness and safety of treatment strategies for adults with pressure ulcers. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database for English- or foreign-language studies; reference lists; gray literature; and individual product packets from manufacturers (January 1985 to October 2012). STUDY SELECTION: Randomized trials and comparative observational studies of treatments for pressure ulcers in adults and noncomparative intervention series (n > 50) for surgical interventions and evaluation of harms. DATA EXTRACTION: Data were extracted and evaluated for accuracy of the extraction, quality of included studies, and strength of evidence. DATA SYNTHESIS: 174 studies met inclusion criteria and 92 evaluated complete wound healing. In comparison with standard care, placebo, or sham interventions, moderate-strength evidence showed that air-fluidized beds (5 studies [n = 908]; high consistency), protein-containing nutritional supplements (12 studies [n = 562]; high consistency), radiant heat dressings (4 studies [n = 160]; moderate consistency), and electrical stimulation (9 studies [n = 397]; moderate consistency) improved healing of pressure ulcers. Low-strength evidence showed that alternating-pressure surfaces, hydrocolloid dressings, platelet-derived growth factor, and light therapy improved healing of pressure ulcers. The evidence about harms was limited. LIMITATION: Applicability of results is limited by study quality, heterogeneity in methods and outcomes, and inadequate duration to assess complete wound healing. CONCLUSION: Moderate-strength evidence shows that healing of pressure ulcers in adults is improved with the use of air-fluidized beds, protein supplementation, radiant heat dressings, and electrical stimulation.

Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer.

BACKGROUND: Trials demonstrate the efficacy of medications to reduce the risk for invasive breast cancer. PURPOSE: To summarize benefits and harms of tamoxifen citrate, raloxifene, and tibolone to reduce the risk for primary breast cancer. DATA SOURCES: MEDLINE and Cochrane databases from inception to January 2009, Web of Science, trial registries, and manufacturer information. STUDY SELECTION: Predefined eligibility criteria were used to select articles. English-language reports of randomized, controlled trials (RCTs) for benefits and RCTs and observational studies for harms were included. DATA EXTRACTION: Two reviewers assessed study data, quality, and applicability. DATA SYNTHESIS: Seven placebo-controlled RCTs and 1 head-to-head trial provide results for main outcomes. Tamoxifen (risk ratio, 0.70 [95% CI, 0.59 to 0.82]; 4 trials), raloxifene (risk ratio, 0.44 [CI, 0.27 to 0.71]; 2 trials), and tibolone (risk ratio, 0.32 [CI, 0.13 to 0.80]; 1 trial) reduce risk for invasive breast cancer compared with placebo by 7 to 10 per 1000 women per year. Tamoxifen and raloxifene reduce estrogen receptor-positive breast cancer but not estrogen receptor-negative breast cancer, noninvasive breast cancer, or mortality. All medications reduce fractures. Tamoxifen (risk ratio, 1.93 [CI, 1.41 to 2.64]; 4 trials) and raloxifene (risk ratio, 1.60 [CI, 1.15 to 2.23]; 2 trials) increase thromboembolic events by 4 to 7 per 1000 women per year; raloxifene causes fewer events than tamoxifen. Tamoxifen increases risk for endometrial cancer (risk ratio, 2.13 [CI, 1.36 to 3.32]; 3 trials) compared with placebo by 4 per 1000 women per year and causes cataracts compared with raloxifene. Tibolone causes strokes in older women. LIMITATIONS: Bias, trial heterogeneity, and a dearth of head-to-head trials limit this review. Data are lacking on doses, duration, and timing of the medications; long-term effects; and nonwhite and premenopausal women. CONCLUSION: Three medications reduce risk for primary breast cancer but increase risk for thromboembolic events (tamoxifen, raloxifene), endometrial cancer (tamoxifen), or stroke (tibolone).

Early warning system scores for clinical deterioration in hospitalized patients: a systematic review.

RATIONALE: Early warning system (EWS) scores are used by hospital care teams to recognize early signs of clinical deterioration and trigger more intensive care. OBJECTIVE: To systematically review the evidence on the ability of early warning system scores to predict a patient's risk of clinical deterioration and the impact of early warning system implementation on health outcomes and resource utilization. METHODS: We searched the MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials databases through May 2014. We included English-language studies of early warning system scores used with adults admitted to medical or surgical wards. We abstracted study characteristics, including population, setting, sample size, duration, and criteria used for early warning system scoring. For predictive ability, the primary outcomes were modeled for discrimination on 48-hour mortality, cardiac arrest, or pulmonary arrest. Outcomes for the impact of early warning system implementation included 30-day mortality, cardiovascular events, use of vasopressors, respiratory failure, days on ventilator, and resource utilization. We assessed study quality using a modified Quality in Prognosis Studies assessment tool where applicable. MEASUREMENTS AND MAIN RESULTS: Of 11,183 citations studies reviewed, one controlled trial and 20 observational studies of 13 unique models met our inclusion criteria. In eight studies, researchers addressed the predictive ability of early warning system tools and found a strong predictive value for death (area under the receiver operating characteristic curve [AUROC], 0.88-0.93) and cardiac arrest (AUROC, 0.74-0.86) within 48 hours. In 13 studies (one controlled trial and 12 pre-post observational studies), researchers addressed the impact on health outcomes and resource utilization and had mixed results. The one controlled trial was of good quality, and the researchers found no difference in mortality, transfers to the ICU, or length of hospital stay. The pre-post designs of the remaining studies have significant methodological limitations, resulting in insufficient evidence to draw conclusions. CONCLUSIONS: Early warning system scores perform well for prediction of cardiac arrest and death within 48 hours, although the impact on health outcomes and resource utilization remains uncertain, owing to methodological limitations. Efforts to assess performance and effectiveness more rigorously will be needed as early warning system use becomes more widespread.

Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

OBJECTIVES: This systematic review summarizes research on methods of diagnosing myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and benefits and harms of multiple medical and nonmedical treatments. It identifies evidence gaps and limitations to inform future research. DATA SOURCES: Searches of electronic databases included MEDLINE® (1988 to September 2014), PsycINFO® (1988 to September 2014), and the Cochrane Library (through the third quarter of 2014). The searches were supplemented by reviewing reference lists, seeking suggestions from reviewers, and requesting scientific information from drug and device manufacturers. REVIEW METHODS: Two investigators reviewed abstracts and full-text articles for inclusion based on predefined criteria. Discrepancies were resolved through discussion and consensus, with a third investigator making the final decision. RESULTS: A total of 6,175 potentially relevant articles were identified, 1,069 were selected for full-text review, and 71 studies in 81 publications were included (36 observational studies on diagnosis and 35 trials of treatments). Eight case definitions have been used to define ME/CFS; those for ME, requiring the presence of postexertional malaise, represent a more symptomatic subset of the broader ME/CFS population. Researchers are unable to determine differences in accuracy between case definitions because there is no universally accepted reference standard for diagnosing ME/CFS. The Oxford criteria are the least restrictive and include patients who would not otherwise meet criteria for ME/CFS. Self-reported symptom scales may differentiate ME/CFS patients from healthy controls but have not been adequately evaluated to determine validity and generalizability in large populations with diagnostic uncertainty. Fourteen studies reported the consequences of diagnosis, including perceived stigma and the burden of misdiagnosis, as well as feelings of legitimacy upon receiving the diagnosis of ME/CFS.Of the 35 trials of treatment, rintatolimod compared with placebo improved measures of exercise performance; counseling therapies and graded exercise treatment (GET) compared with no treatment, relaxation, or support improved fatigue, function, and quality of life, and counseling therapies also improved employment outcomes. Other treatments either provided no benefit or results were insufficient to draw conclusions. GET was associated with higher numbers of reported adverse events compared with counseling therapies or controls. Harms were generally inadequately reported across trials. LIMITATIONS: Diagnostic methods were studied only in highly selected patient populations. Treatment trials were limited in number and had small sample sizes and methodological shortcomings. CONCLUSIONS: None of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. Rintatolimod improves exercise performance in some patients (low strength of evidence), while counseling therapies and GET have broader benefit but have not been adequately tested in more disabled populations (low to moderate strength of evidence). Other treatments and harms have been inadequately studied (insufficient evidence). More definitive studies are needed to fill the many research gaps in diagnosing and treating ME/CFS.

Treatment recommendations for the management of axial spondyloarthritis.

Clinical practice guidelines aid clinicians in providing optimal care for their patients. Over the past decade, treatment guidelines have been published for ankylosing spondylitis (AS), but there are no evidence-based recommendations for the management of axial spondyloarthritis. In 2003, Canadian rheumatologists published treatment recommendations for AS, which have been subsequently updated. More recently, in 2011, the Assessment of SpondyloArthritis international Society and the European League Against Rheumatism published recommendations for the management of AS. SPondyloArthritis Research and Treatment Network proposes an American College of Rheumatology-led effort to develop treatment recommendations for axial spondyloarthritis.

Quality varies across clinical practice guidelines for mammography screening in women aged 40-49 years as assessed by AGREE and AMSTAR instruments.

OBJECTIVE: To assess the quality of clinical practice guidelines providing recommendations on the frequency of mammography screening in asymptomatic, average-risk women 40-49 years of age. STUDY DESIGN AND SETTING: We searched the National Guideline Clearinghouse and MEDLINE for guidelines published from 2005 to 2010. Five independent assessors rated the quality of each guideline and its underlying evidence review using the Appraisal of Guidelines for Research and Evaluation (AGREE) and Assessment of Multiple Systematic Reviews (AMSTAR) instruments, respectively. RESULTS: Eleven guidelines were appraised. Ten referenced an underlying evidence review; two referenced the same review. Three reviews were rated good, one was moderate, and five were rated poor quality. On overall assessment of the quality of the guidelines, two were strongly recommended, two were recommended with provisos, and seven were either not recommended or the assessors were unsure whether to recommend it. Most guidelines clearly presented their recommendations, but the rigor of development, applicability, and stakeholder involvement varied. Seven guidelines recommended mammography screening as part of a periodic health examination and four recommended individualized screening in the target population. The latter four guidelines were based on good-quality reviews and three were recommended by the assessors. CONCLUSION: Guideline users need to be aware of the variability in quality and identify the high-quality guidelines that meet their needs.