Search

Objectives: The aim of this review was to summarize current evidence from the United States on the effectiveness of practices and interventions for preventing, recognizing, and controlling occupationally acquired infectious diseases in Emergency Medical Service (EMS) clinicians. Report and Methods: PubMed, Embase, CINAHL, and SCOPUS were searched from January 1, 2006 through March 15, 2022 for studies in the United States that involved EMS clinicians and firefighters, reported on one or more workplace practices or interventions that prevented or controlled infectious diseases, and included outcome measures. Eleven (11) observational studies reported on infection prevention and control (IPC) practices providing evidence that hand hygiene, standard precautions, mandatory vaccine policies, and on-site vaccine clinics are effective. Less frequent handwashing (survey-weight adjusted odds ratio [OR] 4.20; 95% confidence interval [CI], 1.02 to 17.27) and less frequent hand hygiene after glove use (survey-weight adjusted OR 10.51; 95% CI, 2.54 to 43.45) were positively correlated with nasal colonization of Methicillin-resistant Staphylococcus aureus (MRSA). Lack of personal protective equipment (PPE) or PPE breach were correlated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity (unadjusted risk ratio [RR] 4.2; 95% CI, 1.03 to 17.22). Workers were more likely to be vaccinated against influenza if their employer offered the vaccine (unadjusted OR 3.3; 95% CI, 1.3 to 8.3). Active, targeted education modules for H1N1 influenza were effective at increasing vaccination rates and the success of on-site vaccine clinics. Conclusions: Evidence from the United States exists on the effectiveness of IPC practices in EMS clinicians, including hand hygiene, standard precautions, mandatory vaccine policies, and vaccine clinics. More research is needed on the effectiveness of PPE and vaccine acceptance.

Objectives. Diagnostic errors are a known patient safety concern across all clinical settings, including the emergency department (ED). We conducted a systematic review to determine the most frequent diseases and clinical presentations associated with diagnostic errors (and resulting harms) in the ED, measure error and harm frequency, as well as assess causal factors. Methods. We searched PubMed®, Cumulative Index to Nursing and Allied Health Literature (CINAHL®), and Embase® from January 2000 through September 2021. We included research studies and targeted grey literature reporting diagnostic errors or misdiagnosis-related harms in EDs in the United States or other developed countries with ED care deemed comparable by a technical expert panel. We applied standard definitions for diagnostic errors, misdiagnosis-related harms (adverse events), and serious harms (permanent disability or death). Preventability was determined by original study authors or differences in harms across groups. Two reviewers independently screened search results for eligibility; serially extracted data regarding common diseases, error/harm rates, and causes/risk factors; and independently assessed risk of bias of included studies. We synthesized results for each question and extrapolated U.S. estimates. We present 95 percent confidence intervals (CIs) or plausible range (PR) bounds, as appropriate. Results. We identified 19,127 citations and included 279 studies. The top 15 clinical conditions associated with serious misdiagnosis-related harms (accounting for 68% [95% CI 66 to 71] of serious harms) were (1) stroke, (2) myocardial infarction, (3) aortic aneurysm and dissection, (4) spinal cord compression and injury, (5) venous thromboembolism, (6/7 – tie) meningitis and encephalitis, (6/7 – tie) sepsis, (8) lung cancer, (9) traumatic brain injury and traumatic intracranial hemorrhage, (10) arterial thromboembolism, (11) spinal and intracranial abscess, (12) cardiac arrhythmia, (13) pneumonia, (14) gastrointestinal perforation and rupture, and (15) intestinal obstruction. Average disease-specific error rates ranged from 1.5 percent (myocardial infarction) to 56 percent (spinal abscess), with additional variation by clinical presentation (e.g., missed stroke average 17%, but 4% for weakness and 40% for dizziness/vertigo). There was also wide, superimposed variation by hospital (e.g., missed myocardial infarction 0% to 29% across hospitals within a single study). An estimated 5.7 percent (95% CI 4.4 to 7.1) of all ED visits had at least one diagnostic error. Estimated preventable adverse event rates were as follows: any harm severity (2.0%, 95% CI 1.0 to 3.6), any serious harms (0.3%, PR 0.1 to 0.7), and deaths (0.2%, PR 0.1 to 0.4). While most disease-specific error rates derived from mainly U.S.-based studies, overall error and harm rates were derived from three prospective studies conducted outside the United States (in Canada, Spain, and Switzerland, with combined n=1,758). If overall rates are generalizable to all U.S. ED visits (130 million, 95% CI 116 to 144), this would translate to 7.4 million (PR 5.1 to 10.2) ED diagnostic errors annually; 2.6 million (PR 1.1 to 5.2) diagnostic adverse events with preventable harms; and 371,000 (PR 142,000 to 909,000) serious misdiagnosis-related harms, including more than 100,000 permanent, high-severity disabilities and 250,000 deaths. Although errors were often multifactorial, 89 percent (95% CI 88 to 90) of diagnostic error malpractice claims involved failures of clinical decision-making or judgment, regardless of the underlying disease present. Key process failures were errors in diagnostic assessment, test ordering, and test interpretation. Most often these were attributed to inadequate knowledge, skills, or reasoning, particularly in “atypical” or otherwise subtle case presentations. Limitations included use of malpractice claims and incident reports for distribution of diseases leading to serious harms, reliance on a small number of non-U.S. studies for overall (disease-agnostic) diagnostic error and harm rates, and methodologic variability across studies in measuring disease-specific rates, determining preventability, and assessing causal factors. Conclusions. Although estimated ED error rates are low (and comparable to those found in other clinical settings), the number of patients potentially impacted is large. Not all diagnostic errors or harms are preventable, but wide variability in diagnostic error rates across diseases, symptoms, and hospitals suggests improvement is possible. With 130 million U.S. ED visits, estimated rates for diagnostic error (5.7%), misdiagnosis-related harms (2.0%), and serious misdiagnosis-related harms (0.3%) could translate to more than 7 million errors, 2.5 million harms, and 350,000 patients suffering potentially preventable permanent disability or death. Over two-thirds of serious harms are attributable to just 15 diseases and linked to cognitive errors, particularly in cases with “atypical” manifestations. Scalable solutions to enhance bedside diagnostic processes are needed, and these should target the most commonly misdiagnosed clinical presentations of key diseases causing serious harms. New studies should confirm overall rates are representative of current U.S.-based ED practice and focus on identified evidence gaps (errors among common diseases with lower-severity harms, pediatric ED errors and harms, dynamic systems factors such as overcrowding, and false positives). Policy changes to consider based on this review include: (1) standardizing measurement and research results reporting to maximize comparability of measures of diagnostic error and misdiagnosis-related harms; (2) creating a National Diagnostic Performance Dashboard to track performance; and (3) using multiple policy levers (e.g., research funding, public accountability, payment reforms) to facilitate the rapid development and deployment of solutions to address this critically important patient safety concern.

Objectives. To summarize current evidence on exposures to infectious pathogens in the emergency medical services (EMS) and 911 workforce, and on practices for preventing, recognizing, and controlling occupationally acquired infectious diseases and related exposures in that workforce. Review methods. We obtained advice on how to answer four Guiding Questions by recruiting a panel of external experts on EMS clinicians, State-level EMS leadership, and programs relevant to EMS personnel, and by engaging representatives of professional societies in infectious diseases and emergency medicine. We searched PubMed®, Embase®, CINAHL®, and SCOPUS from January 2006 to March 2022 for relevant studies. We also searched for reports from State and Federal Government agencies or nongovernmental organizations interested in infection prevention and control in the EMS and 911 workforce. Results. Twenty-five observational studies reported on the epidemiology of infections in the EMS and 911 workforce. They did not report demographic differences except for a higher risk of hepatitis C in older workers and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in minorities. EMS clinicians certified/licensed in Advanced Life Support have a high risk for blood and fluid exposure, and EMS clinicians had a higher risk of hospitalization or death from SARS-CoV-2 than firefighters whose roles were not primarily related to medical care. Eleven observational studies reported on infection prevention and control practices (IPC), providing some evidence that hand hygiene, standard precautions, mandatory vaccine policies, and on-site vaccine clinics are effective. Research on IPC in EMS and 911 workers has increased significantly since the SARS-CoV-2 pandemic. Conclusions. Moderate evidence exists on the epidemiology of infections and effectiveness of IPC practices in EMS and 911 workers, including hand hygiene, standard precautions, mandatory vaccine policies, and vaccine clinics. Most evidence is observational, with widely varying methods, outcomes, and reporting. More research is needed on personal protective equipment effectiveness and vaccine acceptance, and better guidance is needed for research methods in the EMS and 911 worker setting.

Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is associated with a statistically significant and/or clinically important change in macular pigment optical density (MPOD) among adults with healthy eyes. We searched Ovid MEDLINE, CENTRAL, and the Commonwealth of Agriculture Bureau for English-language studies through to July 2020. Two reviewers screened results to identify studies that evaluated supplements or dietary sources of lutein/zeaxanthin on MPOD among adults with healthy eyes. One reviewer extracted data and assessed strength of evidence, which was confirmed by a second reviewer. Two independent reviewers assessed the risk of bias. Meta-analyses were stratified by total lutein/zeaxanthin dose. We included 46 studies (N = 3189 participants; mean age = 43 y; 42% male). There was no statistically significant change in MPOD among studies evaluating, Statement of Significance: We conducted a systematic review to determine the quantities of lutein/zeaxanthin intake from either dietary or supplemental sources that are associated with macular pigment optical density (MPOD) among adults with healthy eyes. We concluded that >10 mg/d of lutein/zeaxanthin can increase MPOD, but the effects at doses

The emergency medical service (EMS) workforce is at high risk of occupationally-acquired infections. This review synthesized existing literature on the prevalence, incidence, and severity of infections in the EMS workforce.We searched PubMed, Embase, CINAHL, and SCOPUS from January 1, 2006 to March 15, 2022 for studies in the US that involved EMS clinician or firefighter populations and reported one or more health outcomes related to occupationally-acquired infections.Of the 25 studies that met the inclusion criteria, most focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with prevalence rates ranging from 1.1% to 36.2% (median 6.7%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in 4 studies ranged from 1.9% to 6.4%, and the prevalence of Hepatitis C in one study was 1.3%. Few studies reported incidence rates. The prevalence or incidence of these infections generally did not differ by age or gender, but 4 studies reported differences by race or ethnicity. In the 4 studies that compared infection rates between EMS clinicians and firefighters, EMS clinicians had a higher chance of hospitalization or death from SAR-CoV-2 (odds ratio 4.23), a higher prevalence of Hepatitis C in another study (odds ratio 1.74), and no significant difference in MRSA colonization in a separate study.More research is needed to better characterize the incidence and severity of occupationally-acquired infections in the EMS workforce.

BACKGROUND: Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy. METHODS: We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence. FINDINGS: We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas. INTERPRETATION: Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.

Refereed/Peer-reviewed Objectives: To evaluate feasibility of the Alfred Step Test Exercise Protocol (A-STEP) for the assessment of exercise capacity in adults and children with cystic fibrosis (CF); in adults to test whether demographics and/or lung function correlated with exercise capacity Methods: Adults and children with stable CF from two centres completed the A-STEP (a recently developed incremental maximal-effort step test). Feasibility was evaluated by: usefulness for exercise capacity assessment (measures of exercise capacity were: level reached, exercise-induced desaturation, and achievement of at least one maximal effort criteria); safety; operational factors; time to complete; floor and/or ceiling effects. We used multiple linear regression to test whether demographics and/or lung function correlated with exercise capacity Results: A total of 49 participants: 38 adults (18 male), percent predicted (pp) forced expiration in one second (FEV1) 29–109, aged 22–48 years and 11 children (6 male), ppFEV1 68–107, aged 10–15 years were included. Levels reached (mean (SD) [range]) were 10.2 (2.4) [6–15] (adults), 10.1 (2.5) [7–14] (children); desaturation (change between baseline and peak-exercise SpO2): was 8.4 (3.8 [0–15]% (adults), 2.0 (2.0) [0–7]% (children). A total of 8 (21%) adults and no children desaturated

BACKGROUND Exercise testing is important in people with cystic fibrosis (pwCF). The aim was to develop an incremental maximal step test to assess exercise capacity across the range of pwCF, without floor or ceiling effects, within restrictions of space, and infection prevention. METHODS The step test was developed in adults with stable CF. Subjects assisted in selecting: step height, start rate, increments, stage and test duration parameters. Equipment to externally pace and time the test and measure exercise parameters were selected. Reasons for stopping, criteria for achieving a maximal test, and key outcome measures were determined. Documentation to record and standardize the test and instructions to set up the metronome and timer App were developed. Infection control practices were considered. RESULTS Eight subjects were recruited to develop the Alfred Step Test Exercise Protocol (A-STEP) on a 20 cm portable step. The A-STEP package included a pretest information sheet, clinical assessment and instructions, recording worksheet, and the metronome/timer instructions. The test started at 18 steps/min. Each level increased by two steps/min to a maximum of 48 steps (Level 16). Results were presented as mean (SD) [range] for: age 30.63 (5.89) [21-39] years; FEV1 58.13 (18.33) [32-89]%; levels: 10.31 (3.29) [6-15.5]. The A-STEP required space of 2 m2 and complied with current infection control guidelines. CONCLUSIONS The A-STEP is a new incremental maximal step test to assess exercise capacity in pwCF, without floor or ceiling effects. It addresses the issues of space restrictions and the need for strict infection prevention in the clinical setting.

We sought to systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people. We searched PubMed, Embase, and PsycINFO through June 10, 2020 for studies evaluating quality of life (QOL), depression, anxiety, and death by suicide in the context of gender-affirming hormone therapy among transgender people of any age. We excluded case studies and studies reporting on less than 3 months of follow-up. We included 20 studies reported in 22 publications. Fifteen were trials or prospective cohorts, one was a retrospective cohort, and 4 were cross-sectional. Seven assessed QOL, 12 assessed depression, 8 assessed anxiety, and 1 assessed death by suicide. Three studies included trans-feminine people only; 7 included trans-masculine people only, and 10 included both. Three studies focused on adolescents. Hormone therapy was associated with increased QOL, decreased depression, and decreased anxiety. Associations were similar across gender identity and age. Certainty in this conclusion is limited by high risk of bias in study designs, small sample sizes, and confounding with other interventions. We could not draw any conclusions about death by suicide. Future studies should investigate the psychological benefits of hormone therapy among larger and more diverse groups of transgender people using study designs that more effectively isolate the effects of hormone treatment.

Background Community Health Worker (CHW) certification has been proposed to promote the diffusion of the CHW model in healthcare organizations. However, the extent to which health outcomes vary as a function of CHW certification is unclear. There is also a need to clarify the landscape of CHW certification efforts in the United States. Objectives The objectives were to (1) determine the effects of certification on CHW recruitment, retention, scope of practice, reimbursement or employer liability; (2) ascertain the effects of certification on quality or consistency of care, health outcomes, or patient/family acceptance, trust, and use of community health workers; (3) elucidate the context of certification requirements and implementation in the United States; (4) identify potential positive and negative implications of requiring certification; and (5) identify future research needs. Methods We searched PubMed and CINAHL through October 2019 and handsearched relevant reviews. Our grey literature search focused on reports and presentations by national organizations, foundations, and institutes. We also reviewed the websites of State health departments which have CHW certification programs. We conducted interviews with Key Informants representing stakeholders in the CHW certification enterprise. We used these interviews to identify themes to contextualize findings from the published and grey literature searches. Results The evidence base for community health worker certification is sparse. Our published literature search identified a handful of studies examining correlates of certification (i.e., training, recruitment, and scope of practice) with health outcomes, but these were not linked to the broader issue of certification (n=4, 0 about asthma). We did not find any studies that evaluated the relationship between CHW certification and CHW retention, reimbursement, employer liability, or patients’ and families’ trust in and receptivity to CHWs. We did not find any studies suggesting that patients’ outcomes differ as a function of intervention from a certified versus non-certified CHW, or that certification influences the quality or consistency of CHW-delivered interventions. We identified 37 documents through our grey literature search. Interviews with Key Informants identified four overarching themes: (1) the perceived utility of certification, (2) the philosophical/ethical considerations influencing certification, (3) its potential effects, and (4) recommended components and approaches. The majority of participants asserted that certification does not affect health outcomes. There were diverging opinions about the perceived and actual impact of certification on the CHW workforce, including recruitment, retention, career advancement, composition, and the financial viability of the CHW model. Conclusions In the absence of evaluations of the relationship between certification and outcomes related to patients’ and families’ health, and dimensions of CHWs’ workforce development, the impact of CHW certification is more speculative than conclusive. Further research is needed to determine if certification is linked to improved outcomes for people with asthma and other chronic illness outcomes.

OBJECTIVE: This article describes the methodology used for Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI) Consensus Conference. DESIGN: Consensus conference of international experts in pediatric critical care and transfusion medicine, following standards set by the Institute of Medicine, using the Research And Development/University of California, Los Angeles (RAND/UCLA) appropriateness method, modeled after the Pediatric Acute Lung Injury Consensus Conference. Topics related to red blood cell transfusion (RBC) in children with or at risk for critical illness were divided into nine subgroups with a systematic review of the literature. METHODS: The panel of 38 content and 4 methodology experts met three times over the course of two years and collaborated to develop evidence-based and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children or those at risk for critical illness. Electronic searches were conducted using PubMed, Embase, and Cochrane Library (CENTRAL) databases from 1980 to May 2017. Agreement was obtained using the RAND/UCLA appropriateness method. We used a standardized data extraction form to construct evidence tables, and graded the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. MAIN RESULTS: The consensus conference resulted in 102 recommendation statements, of which 57 were clinical (20 evidence-based and 37 based on expert consensus), and 45 detailed recommendations for future research. Dissemination was done via decision tree, a primary publication listing all statements, and separate publications for each subtopic that include supporting arguments for each recommendation. CONCLUSIONS: A consensus conference of experts from around the world developed recommendations for RBC transfusions in critically ill children or children at risk for critical illness, the identification of current research gaps, and future research priorities.

Objective:To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life.Methods:We searched PubMed and Cochrane Database of Systematic Reviews for systematic reviews from 2011 to October 12, 2015, and PubMed, Embase, and the Cochrane Central Register of Controlled Trials for primary studies from January 1, 2013, to May 24, 2016. We searched Clinicaltrials.gov on March 9, 2016. Two reviewers independently evaluated studies for eligibility, serially abstracted data, and independently evaluated risk of bias and graded strength of evidence (SOE).Results:We updated a recently completed systematic review of 57 eligible studies with 24 additional published studies and 25 unpublished studies. For reducing neuropathy-related pain, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate SOE), the anticonvulsants pregabalin and oxcarbazepine (low SOE), the drug classes tricyclic antidepressants (low SOE) and atypical opioids (low SOE), and botulinum toxin (low SOE) were more effective than placebo. We could not draw conclusions about quality of life due to incomplete reporting. All studies were short-term (less than 6 months), and all effective drugs had more than 9% dropouts from adverse effects.Conclusions:For reducing pain, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids, and botulinum toxin were more effective than placebo. However, quality of life was poorly reported, studies were short-term, drugs had substantial dropout rates, and opioids have significant risks. Future studies should evaluate longer-term outcomes, use methods and measures recommended by pain organizations, and assess patients' quality of life.

BACKGROUND: Cystic fibrosis is a life‐limiting genetic condition in which thick mucus builds up in the lungs, leading to infections, inflammation, and eventually, deterioration in lung function. To clear their lungs of mucus, people with cystic fibrosis perform airway clearance techniques daily. There are various airway clearance techniques, which differ in terms of the need for assistance or equipment, and cost. OBJECTIVES: To summarise the evidence from Cochrane Reviews on the effectiveness and safety of various airway clearance techniques in people with cystic fibrosis. METHODS: For this overview, we included Cochrane Reviews of randomised or quasi‐randomised controlled trials (including cross‐over trials) that evaluated an airway clearance technique (conventional chest physiotherapy, positive expiratory pressure (PEP) therapy, high‐pressure PEP therapy, active cycle of breathing techniques, autogenic drainage, airway oscillating devices, external high frequency chest compression devices and exercise) in people with cystic fibrosis. We searched the Cochrane Database of Systematic Reviews on 29 November 2018. Two review authors independently evaluated reviews for eligibility. One review author extracted data from included reviews and a second author checked the data for accuracy. Two review authors independently graded the quality of reviews using the ROBIS tool. We used the GRADE approach for assessing the overall strength of the evidence for each primary outcome (forced expiratory volume in one second (FEV(1)), individual preference and quality of life). MAIN RESULTS: We included six Cochrane Reviews, one of which compared any type of chest physiotherapy with no chest physiotherapy or coughing alone and the remaining five reviews included head‐to‐head comparisons of different airway clearance techniques. All the reviews were considered to have a low risk of bias. However, the individual trials included in the reviews often did not report sufficient information to adequately assess risk of bias. Many trials did not sufficiently report on outcome measures and had a high risk of reporting bias. We are unable to draw definitive conclusions for comparisons of airway clearance techniques in terms of FEV(1), except for reporting no difference between PEP therapy and oscillating devices after six months of treatment, mean difference ‐1.43% predicted (95% confidence interval ‐5.72 to 2.87); the quality of the body of evidence was graded as moderate. The quality of the body of evidence comparing different airway clearance techniques for other outcomes was either low or very low. AUTHORS' CONCLUSIONS: There is little evidence to support the use of one airway clearance technique over another. People with cystic fibrosis should choose the airway clearance technique that best meets their needs, after considering comfort, convenience, flexibility, practicality, cost, or some other factor. More long‐term, high‐quality randomised controlled trials comparing airway clearance techniques among people with cystic fibrosis are needed.

This systematic review of randomized trials examines benefits and harms of antipsychotics for prevention of delirium in adults.

Background We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. Method We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review’s last literature search, screened the records using the review’s eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. Results Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov’s inception date of 2000. Conclusion Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects. Electronic supplementary material The online version of this article (10.1186/s13643-018-0726-5) contains supplementary material, which is available to authorized users.

The use of negative pressure wound therapy (NPWT) is increasing in both the inpatient and outpatient settings. We conducted a systematic review on the efficacy and safety of NPWT for the treatment of chronic wounds in the home setting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature, up to June 2014. Two independent reviewers screened search results. Seven studies met our criteria for inclusion. Six of the studies compared NPWT devices to other wound care methods and one study compared two different NPWT technologies. Data were limited by variability in the types of comparator groups, methodological limitations, and poor reporting of outcomes. We were unable to draw conclusions about the efficacy or safety of NPWT for the treatment of chronic wounds in the home setting due to the insufficient evidence. Consensus is needed on the methods of conducting and reporting wound care research so that future studies are able inform decisions about the use of NPWT in the home environment for chronic wounds.

Background Complications of chronic kidney disease (CKD) include weak bones and increased fracture risk. Purpose To review the benefits and harms of osteoporosis medications (bisphosphonates, teriparatide, raloxifene, and denosumab) compared with placebo, usual care, or active control in terms of bone mineral density (BMD), fractures, and safety in patients with CKD. Data sources PubMed and the Cochrane Central Register of Controlled Trials from December 2006 through December 2016. Study selection Paired reviewers independently screened abstracts and full-text articles for English-language, randomized, controlled trials that had at least 6 months of follow-up; evaluated osteoporosis medications among patients with CKD; and reported on BMD, fractures, or safety (mortality and adverse events). Data extraction Two reviewers serially abstracted data and independently assessed risk of bias and graded the strength of evidence (SOE). Data synthesis There were 13 trials (n = 9850) that included kidney transplant recipients (6 trials), patients who had stage 3 to 5 CKD or were receiving dialysis (3 trials), or postmenopausal women with CKD (4 trials). Evidence showed that bisphosphonates may slow loss of BMD among transplant recipients (moderate SOE), but their effects on fractures and safety in transplant recipients and others with CKD are unclear. Raloxifene may prevent vertebral fractures but may not improve BMD (low SOE). Effects of teriparatide and denosumab on BMD and fractures are unclear (very low SOE), and these medications may increase risk for some safety outcomes. Limitation Unclear rigor of evidence, possible reporting biases, and scant evidence among patients with stage 3 to 5 CKD. Conclusion Effects of osteoporosis medications on BMD, fracture risk, and safety among patients with CKD are not clearly established. Primary funding source Kidney Disease: Improving Global Outcomes.

Objective Chronic venous ulcers (CVUs) remain the leading causes for nonhealing wounds in the lower extremities. Although multilayer compression dressing remains the treatment gold standard, there are various surgical procedures aimed at healing CVUs with little or no evidence on the efficacy of these treatment methods. We conducted a systematic review of the effects of various surgical treatments for CVUs, in terms of ulcer healing rates, complete time to heal, recurrence rates, mortality, pain, and quality of life. Methods We searched MEDLINE, EMBASE, the Cochrane Central Register for Controlled Trials, and the Cumulative Index for Nursing and Allied Health Literature databases from January 1980 through July 2012. We included studies that compared a surgical procedure with multilayer compression therapy or another surgical procedure among patients with CVUs. We also included studies without a comparison group if they were of sufficient quality. Two independent reviewers screened titles, abstracts, and articles for eligibility. Two reviewers extracted data on study design, applicability, results, and quality. Results We identified 10,676 citations, of which 22 studies (23 publications) were included. Eight studies (six randomized controlled trials, two cohorts) compared a surgical procedure with compression. Fourteen studies evaluated different surgical interventions. Adding superficial vein ligation and stripping to compression did not improve wound-healing rate. However, the recurrence rate was 50% reduced when surgery corrected the underlying superficial venous pathology (moderate to high strength of evidence [SOE]). Adding subfascial endoscopic perforator surgery with superficial vein surgery to compression does not improve the healing rate of venous ulcers or reduce the recurrence rate except for medial and large ulcers (high SOE). The SOE was insufficient to support a conclusion about the effects of sclerotherapy when added to compression in healing CVUs. There was insufficient evidence on the surgical treatment of CVUs secondary to deep venous reflux and venous obstruction. We are unable to draw conclusions about the effects of surgical procedures on mortality, pain, and quality of life. Conclusions Our ability to draw conclusions on most surgical techniques is limited due to poorly designed and executed studies, with no uniformity of treatment methods, follow-up or reporting, and lack of randomization. We found some evidence to suggest superficial vein ligation and stripping may reduce the risk of wound recurrence, but these surgical techniques are infrequently performed. The newer minimally invasive techniques lack evidence. Randomized controlled trials for the endovenous procedures used today for treating CVUs are needed.

The purpose of this study was to systematically review the literature on the benefits and harms of advanced wound dressings on wound healing, mortality, quality of life, pain, condition of the wound bed, and adverse events for patients with chronic venous leg ulcers as compared with treatment with compression alone. We searched for primary studies in the databases of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature(®) from January 1980 through July 2012. Each study title, abstract, and full article was evaluated by two independent reviewers. Thirty-seven studies met our specific search criteria, although most evidence was of low or insufficient quality. Cellular dressings, collagen, and some antimicrobial dressings may improve healing rates of chronic venous leg ulcers vs. compression alone or other dressings. Limited data were available on other outcomes. The poor quality of the literature limits conclusions and necessitates future, well-conducted studies to evaluate the effectiveness of advanced wound dressings on chronic venous ulcers.

OBJECTIVE We performed a systematic review to identify which genetic variants predict response to diabetes medications. RESEARCH DESIGN AND METHODS We performed a search of electronic databases (PubMed, EMBASE, and Cochrane Database) and a manual search to identify original, longitudinal studies of the effect of diabetes medications on incident diabetes, HbA1c, fasting glucose, and postprandial glucose in prediabetes or type 2 diabetes by genetic variation. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated study quality independently. Quality evaluations were based on the Strengthening the Reporting of Genetic Association Studies guidelines and Human Genome Epidemiology Network guidance. RESULTS Of 7,279 citations, we included 34 articles (N = 10,407) evaluating metformin (n = 14), sulfonylureas (n = 4), repaglinide (n = 8), pioglitazone (n = 3), rosiglitazone (n = 4), and acarbose (n = 4). Studies were not standalone randomized controlled trials, and most evaluated patients with diabetes. Significant medication–gene interactions for glycemic outcomes included 1) metformin and the SLC22A1, SLC22A2, SLC47A1, PRKAB2, PRKAA2, PRKAA1, and STK11 loci; 2) sulfonylureas and the CYP2C9 and TCF7L2 loci; 3) repaglinide and the KCNJ11, SLC30A8, NEUROD1/BETA2, UCP2, and PAX4 loci; 4) pioglitazone and the PPARG2 and PTPRD loci; 5) rosiglitazone and the KCNQ1 and RBP4 loci; and 5) acarbose and the PPARA, HNF4A, LIPC, and PPARGC1A loci. Data were insufficient for meta-analysis. CONCLUSIONS We found evidence of pharmacogenetic interactions for metformin, sulfonylureas, repaglinide, thiazolidinediones, and acarbose consistent with their pharmacokinetics and pharmacodynamics. While high-quality controlled studies with prespecified analyses are still lacking, our results bring the promise of personalized medicine in diabetes one step closer to fruition.

Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear.To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults.PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up.Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group.One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias.A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use.There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes.Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures.Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Background Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear. Purpose To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults. Data sources PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up. Study selection Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group. Data extraction One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias. Data synthesis A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use. Limitations There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes. Conclusion Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures. Primary funding source Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Objective To ensure appropriate allocation of research funds, we need methods for identifying high-priority research needs. We developed and pilot tested a process to identify needs for primary clinical research using a systematic review in gestational diabetes mellitus. Study Design and Setting We conducted eight steps: abstract research gaps from a systematic review using the Population, Intervention, Comparison, Outcomes, and Settings (PICOS) framework; solicit feedback from the review authors; translate gaps into researchable questions using the PICOS framework; solicit feedback from multidisciplinary stakeholders at our institution; establish consensus among multidisciplinary external stakeholders on the importance of the research questions using the Delphi method; prioritize outcomes; develop conceptual models to highlight research needs; and evaluate the process. Results We identified 19 research questions. During the Delphi method, external stakeholders established consensus for 16 of these 19 questions (15 with “high” and 1 with “medium” clinical benefit/importance). Conclusion We pilot tested an eight-step process to identify clinically important research needs. Before wider application of this process, it should be tested using systematic reviews of other diseases. Further evaluation should include assessment of the usefulness of the research needs generated using this process for primary researchers and funders.

Objective: To examine the roles of attachment, social support, and coping as psychosocial correlates in predicting happiness in people with spinal cord injuries.Design: Quantitative descriptive research design using multiple regression and correlation techniques.Participants: 274 individuals with spinal cord injuries.Outcome Measures: Happiness as measured by the Subjective Happiness Scale.Results: Functional disability and psychosocial correlates including coping, attachment styles, and social support were found to be associated with happiness scores. Functional disability was found to have a large negative effect on happiness and the effect was significantly reduced after taking into consideration the effect of positive psychology factors.Conclusion: Positive psychology variables are important for happiness and subjective well-being, and happiness in turn is related to better quality of life. The negative relationship between functional disability and happiness can be mediated by attachment, social support, and coping. Rehabilitation professionals should deemphasize negative characteristics related to poor psychological adjustment and focus on positive human traits and positive psychology interventions for people with disabilities.

Background People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. Objectives To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. Search methods We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 25 April 2016. Selection criteria Randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. Data collection and analysis Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. Main results Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis. Included studies compared the active cycle of breathing technique with autogenic drainage, airway oscillating devices, high frequency chest compression devices, conventional chest physiotherapy, and positive expiratory pressure. Preference of technique varied: more participants preferred autogenic drainage over the active cycle of breathing technique; more preferred the active cycle of breathing technique over airway oscillating devices; and more were comfortable with the active cycle of breathing technique versus high frequency chest compression. No significant difference was seen in quality of life, sputum weight, exercise tolerance, lung function, or oxygen saturation between the active cycle of breathing technique and autogenic drainage or between the active cycle of breathing technique and airway oscillating devices. There was no significant difference in lung function and the number of pulmonary exacerbations between the active cycle of breathing technique alone or in conjunction with conventional chest physiotherapy. All other outcomes were either not measured or had insufficient data for analysis. Authors' conclusions There is insufficient evidence to support or reject the use of the active cycle of breathing technique over any other airway clearance therapy. Five studies, with data from eight different comparators, found that the active cycle of breathing technique was comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of the active cycle of breathing technique on outcomes important for people with cystic fibrosis such as quality of life and preference.

Identification of unanswered research questions about the management of gestational diabetes mellitus (GDM) is necessary to focus future research endeavors. We developed a process for elucidating the highest priority research questions on GDM.Using a systematic review on GDM as a starting point, we developed an eight-step process: (1) identification of research gaps, (2) feedback from the review's authors, (3) translation of gaps into researchable questions using population, intervention, comparators, outcomes, setting (PICOS) framework, (4) local institutions' stakeholders' refinement of research questions, (5) national stakeholders' use of Delphi method to develop consensus on the importance of research questions, (6) prioritization of outcomes, (7) conceptual framework, and (8) evaluation.We identified 15 high priority research questions for GDM. The research questions focused on medication management of GDM (e.g., various oral agents vs. insulin), delivery management for women with GDM (e.g., induction vs. expectant management), and identification of risk factors for, prevention of, and screening for type 2 diabetes in women with prior GDM. Stakeholders rated the development of chronic diseases in offspring, cesarean delivery, and birth trauma as high priority outcomes to measure in future studies.We developed an eight-step process using a multidisciplinary group of stakeholders to identify 15 research questions of high clinical importance. Researchers, policymakers, and funders can use this list to direct research efforts and resources to the highest priority areas to improve care for women with GDM.

PurposeThis study examined demographic and rehabilitation service variables affecting employment outcomes of people with spinal cord injury (SCI) receiving services from state vocational rehabilitation agencies. A secondary purpose was to determine whether there are disparities in services and outcomes between European American and Hispanic clients.MethodThe sample included 3,119 European Americans and 395 Hispanics who were closed either as rehabilitated (Status 26) or not rehabilitated (Status 28) by their state vocational rehabilitation agencies in the fiscal year 2005. The dependent variable is employment outcomes. The predictor variables include a set of personal characteristic variables and rehabilitation service variables.ResultsLogistic regression analysis results indicated that education, on-the-job training, job search assistance, job placement assistance, on-the-job support, maintenance services, assistive technology and other services were significant predictors of successful employment outcomes for individuals with SCI. European Americans were more likely to receive assistive technology services, and Hispanics were more likely to receive support services related to basic living needs.ConclusionsAssistive technology services, basic support services, and job placement support services were found to contribute significantly to successful rehabilitation outcomes. Minor disparities in case expenditures and service patterns were found between Hispanic and European American clients.

We thank Parsons et al. for their interest in our article.1 Parsons et al. indicated concern regarding our reference to reporting bias for pregabalin and note Pfizer's commitment to publishing company-sponsored research. We appreciate this and have included all available data that met eligibility criteria in our analysis. The results of our search for each drug—including counts of studies completed without available result—can be found in table e-2.1 Concerning the published pooled analysis,2 this included studies that did not meet our eligibility criteria. As a result, the pooled analysis was not included in our review.

We conducted a systematic review to estimate benefits and harms of the choice of timing of induction or elective cesarean delivery based on estimated fetal weight or gestational age in women with gestational diabetes mellitus (GDM).An electronic literature search was performed using MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, and The Cochrane Central Register of Controlled Trials from inception to January 2007.Two investigators independently reviewed titles and abstracts, assessed article quality, and abstracted data. Maternal outcomes included cesarean delivery and operative vaginal delivery. Neonatal outcomes included birth weight, macrosomia, large for gestational age, shoulder dystocia, birth trauma, neonatal intensive care admissions, and perinatal mortality.Five studies met our inclusion criteria: one randomized controlled trial (RCT) and four observational studies. The RCT (n=200) compared the effect of labor induction at term with expectant management. The proportion of newborns with birth weight greater than the 90th percentile was significantly greater in the expectant-management group (23% compared with 10% with active induction, P=.02); there were no significant differences in rates of cesarean delivery, shoulder dystocia, neonatal hypoglycemia, or perinatal deaths. The four observational studies suggest a potential reduction in macrosomia and shoulder dystocia with labor induction and cesarean delivery for estimated fetal weight indications, but there was insufficient evidence to assess other clinical outcomes.Active rather than expectant management of labor at term for women with GDM may reduce rates of macrosomia and related complications. Further RCTs and observational studies with a broader range of outcomes are needed for sufficient evidence to inform clinical practice.

We systematically reviewed the effectiveness and safety of continuous subcutaneous insulin infusion (CSII) with insulin analogs compared with multiple daily injections (MDI) in pregnant women with diabetes mellitus. We searched Medline®, Embase®, and the Cochrane Central Register of Controlled Trials through May 2013. Studies comparing CSII with MDI in pregnant women with diabetes mellitus were included. Studies using regular insulin CSII were excluded. We conducted meta-analyses where there were two or more comparable studies based on the type of insulin used in the MDI arm. Seven cohort studies of pregnant women with type 1 diabetes reported improvement in hemoglobin A1c (HbA1c) in both groups. Meta-analysis showed no difference in maternal and fetal outcomes for CSII versus MDI. Results were similar when CSII was compared with MDI with insulin analogs or regular insulin. Studies had moderate to high risk bias with incomplete descriptions of study methodology, populations, treatments, follow up, and outcomes. We conclude that observational studies reported similar improvements in HbA1c with CSII and MDI during pregnancy, but evidence was insufficient to rule out possible important differences between CSII and MDI for maternal and fetal outcomes. This highlights the need for future studies to examine the effectiveness and safety of CSII with insulin analogs and MDI in pregnant women with diabetes mellitus.

Objective: To examine the role of spiritual well-being as a mediator and moderator between perceived uncertainty and psychosocial adaptation to multiple sclerosis (MS). Participants and Design: Fifty individuals (40 women, 10 men) diagnosed with multiple sclerosis. Main Outcome Measures: Selfreport measures on illness uncertainty, spiritual (religious and existential) well-being, and psychosocial adjustment to illness were analyzed by a series of hierarchical multiple regression analyses. Results: Both uncertainty and spiritual well-being independently predicted psychosocial adjustment to MS after the influence of demographic and disability-related variables were considered. Spiritual well-being demonstrated a mediator effect but, mostly, failed to show a moderator effect. Conclusion: Spiritual well-being exerts an appreciable influence on adaptation to MS and also acts to mitigate the impact of uncertainty on adaptation. Rehabilitation psychologists may wish to consider its beneficial role as part of their clinical work. Multiple sclerosis (MS), one of the most common disabling diseases of young adults, is an inflammatory demyelinating disorder of the central nervous system with an estimated prevalence of about 250,000‐350,000 individuals in the United States (Devins & Shnek, 2000; Kalb, 1996; Schapiro, 1998). First symptoms usually appear at the young adult age, but the disease may also become evident later in life. The course of MS is highly variable and makes studies of etiology and possible mechanisms of treatment challenging. Because of MS’s highly variable clinical course, individual outcomes cannot be reliably predicted. For many individuals, MS starts with a relapsing‐remitting pattern with episodic exacerbations of neurological dysfunction, which remit completely or partially. Over the years, for most individuals, the disease develops into the secondary progressive form with accumulated disability (Lublin & Reingold, 1996).

This study examined the relationships among four predictors (functional limitations, perceived visibility of condition, and two disability-associated affective responses— anxiety and depression), coping strategies, and two outcome measures of psychosocial adaptation to disability (disability-specific psychosocial adjustment and life satisfaction). Based on responses from 121 university students with disabilities, two models (additive and mediational) were tested to investigate the contribution of coping strategies to psychosocial adaptation to disability. The findings of this exploratory study suggest that coping strategies add significantly to the variance in both outcome measures after controlling for the contribution of disability-related factors. The role of coping strategies as mediators between the set of predictor and outcome variables was mostly unsupported in this sample, however. Reasons for the latter finding are briefly outlined, along with the implications for rehabilitation research and practice.

The use of negative pressure wound therapy (NPWT) is increasing in both the inpatient and outpatient settings. We conducted a systematic review on the efficacy and safety of NPWT for the treatment of chronic wounds in the home setting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature, up to June 2014. Two independent reviewers screened search results. Seven studies met our criteria for inclusion. Six of the studies compared NPWT devices to other wound care methods and one study compared two different NPWT technologies. Data were limited by variability in the types of comparator groups, methodological limitations, and poor reporting of outcomes. We were unable to draw conclusions about the efficacy or safety of NPWT for the treatment of chronic wounds in the home setting due to the insufficient evidence. Consensus is needed on the methods of conducting and reporting wound care research so that future studies are able inform decisions about the use of NPWT in the home environment for chronic wounds.

Vitamin D (2012) [11] 26 22 Total 143 106 It is important that guidelines are based on a transparent, systematic assessment of evidence as they are used by clinicians to inform decisions about patient management and treatment. In 2011, the Institute of Medicine (IOM) revised their definition of a clinical practice guideline emphasizing the need to use systematic reviews (SRs) in developing guidelines [1]. However, SRs often identify a lack of evidence, or find that it is conflicting or of poor quality. There are no standards for guideline panels on drafting recommendations when there is insufficient or inconclusive evidence. Some organizations opt for a non-recommendation (i.e., a neutral statement neither for nor against an intervention) [2,3]. However, this not always satisfactory and does not provide the requisite guidance to clinicians. Others may draft consensus-based recommendations. Clinicians need to be able to recognize and interpret recommendations made with insufficient evidence. We show how one organization reacted to insufficient evidence, and provide guidance on assessing the trustworthiness of a guideline. We reviewed a set of evidence-based guidelines developed by the Cystic Fibrosis Foundation (CFF) estimating the proportion of recommendations for which there was insufficient evidence and noting the subsequent actions taken by the guideline panel [4]. As of 2013, 7 of the CFF’s 31 guidelines were based on systematic reviews (evidence-based guidelines). We abstracted 143 recommendations from these 7 guidelines [5–11]. Of these 143, 37 were identified a priori as having a limited body of evidence and no SR was conducted. For the remaining 106 recommendations, the relevant guideline panel commissioned a SR to address the question (Table 1). For 75 (71%) of these 106, there was insufficient evidence from the SR to inform a recommendation (Table 2). Only one guideline, on airway

Inflectional morphology lies at the intersection of phonology, syntax and the lexicon, three language domains that are differentially impacted in the three main variants of primary progressive aphasia (PPA). To characterize spared and impaired aspects of inflectional morphology in PPA, we elicited inflectional morphemes in 48 individuals with PPA and 13 healthy age-matched controls. We varied the factors of regularity, frequency, word class, and lexicality, and used voxel-based morphometry to identify brain regions where atrophy was predictive of deficits on particular conditions. All three PPA variants showed deficits in inflectional morphology, with the specific nature of the deficits dependent on the anatomical and linguistic features of each variant. Deficits in inflecting low-frequency irregular words were associated with semantic PPA, with lexical/semantic deficits, and with left temporal atrophy. Deficits in inflecting pseudowords were associated with non-fluent/agrammatic and logopenic variants, with phonological deficits, and with left frontal and parietal atrophy.

This article begins by reviewing the literature on the concept of psychosocial adaptation to impairment among persons with epilepsy. Particular attention is devoted to those roots reasoned to lie at the base of psychosocial problems manifested by people with epilepsy. The research literature on coping with epilepsy is then reviewed in two areas: (a) general coping styles and their relationship to psychosocial adaptation, and (b) specific coping strategies and their association with adaptation to epilepsy. Next, clinical implications of these findings are briefly outlined. The article concludes with a discussion of research limitations identified in the conceptualization and measurement of coping, followed by suggestions for future research on coping and adaptation to epilepsy.

GTP cyclohydrolase I feedback regulatory protein (GFRP) mediates the feedback inhibition of GTP cyclohydrolase I activity by (6 R )- l -erythro-5,6,7,8-tetrahydrobiopterin (BH 4 ) through protein complex formation. Since guanine and BH 4 have a common pyrimidine ring structure, we examined the inhibitory effect of guanine and its analogs on the enzyme activity. Guanine, 8-hydroxyguanine, 8-methylguanine, and 8-bromoguanine inhibited the enzyme activity in a GFRP-dependent and pH-dependent manner and induced complex formation between GTP cyclohydrolase I and GFRP. The type of inhibition by this group is a mixed type. All these properties were shared with BH 4 . In striking contrast, inhibition by 8-azaguanine and 8-mercaptoguanine was GFRP-independent and pH-independent. The type of inhibition by 8-azaguanine and 8-mercaptoguanine was a competitive type. The two compounds did not induce complex formation between the enzyme and GFRP. These results demonstrate that guanine compounds of the first group bind to the BH 4 -binding site of the GTP cyclohydrolase I/GFRP complex, whereas 8-azaguanine and 8-mercaptoguanine bind to the active site of the enzyme. Finally, the possible implications in Lesch–Nyhan syndrome and Parkinson diseases of the inhibition of GTP cyclohydrolase I by guanine and 8-hydroxyguanine are discussed.

The mechanism of arsine (AsH3) toxicity is not completely understood. In this investigation, the toxicity of AsH3 and AsH3-produced hemolytic products was determined in primary culture of renal cortical epithelial cells and in the in situ isolated rat kidney. The objective of this study was to model kidney dysfunction caused by AsH3 exposure. The hypothesis was that unchanged AsH3 and AsH3-produced hemolysate that may contain arsenite (As(III)) as metabolite are both responsible for renal toxicity. Toxicity in isolated cells was determined by 2, 3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxa nilide inner salt (XTT) bioreduction, intracellular potassium (K+), and lactate dehydrogenase (LDH) leakage. Data from XTT bioreduction showed that most toxicity occurred at 1 hour and was independent of the arsenic species. At 4 hours, the observed toxicity depended on the arsenic species and was generated by As(III). In the isolated cells, the As(III)-spiked hemolysate produced similar toxicities with regard to intracellular K and LDH. The AsH3-hemolysate only affected LDH at 1 hour. Unchanged AsH3 was very toxic to the isolated rat kidney. In this system, after 10 minutes exposure to AsH3, the effects of toxicity were observed mainly in the glomerular and peritubular endothelial cells. Tubular epithelial cells also presented early signs of toxicity. The AsH3-hemolysate was not toxic after a 1 -minute exposure. These data suggested that early cytotoxicity caused by unchanged AsH3 results in kidney dysfunction, produced by AsH3, and later by the formation of a hemolysate that may contain As(III). These data may be important in understanding the renal toxic effects after AsH3 intoxication.

Objective:Mental stress has been shown to produce intestinal disease, but the effects of a mild environmental stress on intestinal physiology have not been elucidated. This study was performed to d...