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Objectives The purpose of this study was to determine if health literacy is associated with mortality, hospitalizations, or emergency department (ED) visits among patients living with heart failure (HF). Background Growing evidence suggests an association between health literacy and health-related outcomes in patients with HF. Methods We searched Embase, MEDLINE, PsycINFO, and EBSCO CINAHL from inception through January 1, 2019, with the help of a medical librarian. Eligible studies evaluated health literacy among patients with HF and assessed mortality, hospitalizations, and ED visits for all causes with no exclusion by time, geography, or language. Two reviewers independently selected studies, extracted data, and assessed the methodological quality of the identified studies. Results We included 15 studies, 11 with an overall high methodological quality. Among the observational studies, an average of 24% of patients had inadequate or marginal health literacy. Inadequate health literacy was associated with higher unadjusted risk for mortality (risk ratio [RR]: 1.67; 95% confidence interval [CI]: 1.18 to 2.36), hospitalizations (RR: 1.19; 95% CI: 1.09 to 1.29), and ED visits (RR: 1.17; 95% CI: 1.03 to 1.32). When the adjusted measurements were combined, inadequate health literacy remained statistically associated with mortality (RR: 1.41; 95% CI: 1.06 to 1.88) and hospitalizations (RR: 1.12; 95% CI: 1.01 to 1.25). Among the 4 interventional studies, 2 effectively improved outcomes among patients with inadequate health literacy. Conclusions In this study, the estimated prevalence of inadequate health literacy was high, and inadequate health literacy was associated with increased risk of death and hospitalizations. These findings have important clinical and public health implications and warrant measurement of health literacy and deployment of interventions to improve outcomes.

Background and objectives High-flow nasal cannula (HFNC) oxygen may provide tailored benefits in patients with preset treatment limitations. The objective of this study was to assess the effectiveness of HFNC oxygen in patients with do-not-intubate (DNI) and/or do-not-resuscitate (DNR) orders. Methods We conducted a systematic review of interventional and observational studies. A search was performed using MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science, from inception to October 15, 2018. Results We included six studies evaluating 293 patients. All studies had a high risk of bias. The hospital mortality rates of patients with DNI and/or DNR orders receiving HFNC oxygen were variable and ranged from 40% to 87%. In two before and after studies, the initiation of HFNC oxygen was associated with improved oxygenation and reduced respiratory rates. One comparative study found no difference in dyspnea reduction or morphine doses between patients using HFNC oxygen versus conventional oxygen. No studies evaluated quality of life in survivors or quality of death in nonsurvivors. HFNC was generally well tolerated with few adverse events identified. Conclusions While HFNC oxygen remains a viable treatment option for hospitalized patients who have acute respiratory failure and a DNI and/or DNR order, there is a paucity of high-quality, comparative, effectiveness data to guide the usage of HFNC oxygen compared with other treatments, such as noninvasive ventilation, conventional oxygen, and palliative opioids.

Objectives The authors aimed to explore whether weight loss may improve central hemodynamics in obesity. Background Hemodynamic abnormalities in obese heart failure with preserved ejection fraction patients are correlated with the amount of excess body mass, suggesting a possible causal relationship. Methods Relevant databases were systematically searched from inception to May 2018, without language restriction. Studies reporting invasive hemodynamic measures before and following therapeutic weight loss interventions in patients with obesity but no clinically overt heart failure were extracted. Results A total of 9 studies were identified, providing data for 110 patients. Six studies tested dietary intervention and 3 studies tested bariatric surgery. Over a median duration of 9.7 months (range 0.75 to 23.0 months), a median weight loss of 43 kg (range 10 to 58 kg) was associated with significant reductions in heart rate (−9 beats/min, 95% confidence interval [CI]: −12 to −6; p Conclusions Therapeutic weight loss in obese patients without HF is associated with favorable hemodynamic effects. Randomized controlled trials evaluating strategies for weight loss in obese patients with heart failure such as the obese phenotype of heart failure with preserved ejection fraction are needed.

Background and objectives Dialysis is a preference-sensitive decision where prognosis may play an important role. Although patients desire risk prediction, nephrologists are wary of sharing this information. We reviewed the performance of prognostic indices for patients starting dialysis to facilitate bedside translation. Design, setting, participants, & measurements Systematic review and meta-analysis following the PRISMA guidelines. We searched Ovid MEDLINE, Ovid Embase, Ovid Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus for eligible studies of patients starting dialysis published from inception to December 31, 2018. Selection Criteria: Articles describing validated prognostic indices predicting mortality at the start of dialysis. We excluded studies limited to prevalent dialysis patients, AKI and studies excluding mortality in the first 1–3 months. Two reviewers independently screened abstracts, performed full text assessment of inclusion criteria and extracted: study design, setting, population demographics, index performance and risk of bias. Pre-planned random effects meta-analysis was performed stratified by index and predictive window to reduce heterogeneity. Results Of 12,132 articles screened and 214 reviewed in full text, 36 studies were included describing 32 prognostic indices. Predictive windows ranged from 3 months to 10 years, cohort sizes from 46 to 52,796. Meta-analysis showed discrimination area under the curve (AUC) of 0.71 (95% confidence interval, 0.69 to 073) with high heterogeneity (I2=99.12). Meta-analysis by index showed highest AUC for The Obi, Ivory, and Charlson comorbidity index (CCI)=0.74, also CCI was the most commonly used (ten studies). Other commonly used indices were Kahn-Wright index (eight studies, AUC 0.68), Hemmelgarn modification of the CCI (six studies, AUC 0.66) and REIN index (five studies, AUC 0.69). Of the indices, ten have been validated externally, 16 internally and nine were pre-existing validated indices. Limitations include heterogeneity and exclusion of large cohort studies in prevalent patients. Conclusions Several well validated indices with good discrimination are available for predicting survival at dialysis start.

Thyroid disease is a very common condition that influences the entire human body, including cognitive function and mental health. As a result, thyroid disease has been associated with multiple neuropsychiatric conditions. However, the relationship between thyroid dysfunction and suicide is still controversial. We conducted a systematic review and meta-analysis to describe the association of thyroid function with suicidal behavior in adults. We searched four data bases (MEDLINE, EMBASE, PsycINFO, and Scopus) from their inception to 20 July 2018. Studies that reported mean values and standard deviation (SD) of thyroid hormone levels [Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3)] in patients with suicidal behavior compared with controls were included in this meta-analysis. The abstracts and papers retrieved with our search strategies were reviewed independently and in duplicate by four reviewers for assessment of inclusion criteria and data extraction, as well as for evaluation of risk of bias. Random-effects models were used in this meta-analysis to establish the mean difference on thyroid function tests between groups. Overall, 2278 articles were identified, and 13 studies met the inclusion criteria. These studies involved 2807 participants, including 826 participants identified with suicidal behavior. We found that patients with suicide behavior had lower levels of FT3 (−0.20 pg/mL; p = 0.02) and TT4 (−0.23 µg/dL; p = 0.045) compared to controls. We found no differences in either TSH, FT4, or TT3 levels among groups. With our search strategy, we did not identify studies with a comparison of overt/subclinical thyroid disease prevalence between patients with and without suicide behavior. The studies included in this meta-analysis had a low-to-moderate risk of bias. In the available literature, the evidence regarding the association of thyroid disorders and suicidal behavior is limited. We found that patients with suicidal behavior have significantly lower mean FT3 and TT4 levels when compared to patients without suicidal behavior. The clinical implications and pathophysiologic mechanisms of these differences remain unknown and further research is needed.

Introduction: This meta-analysis assessed the effect of chronic non-invasive positive airway pressure (> 6 weeks) on moderate to severe OSA with diastolic dysfunction based on echocardiographic parameters. Hypothesis: chronic use of non-invasive positive airway pressure (> 6 weeks) on moderate to severe OSA improves diastolic dysfunction based on echocardiographic parameters. Methods: We searched the databases for randomized clinical trials including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 20th, 2019. The search was not restricted to time, publication status or language. Two independent investigators screened the identified studies and extracted the data, in duplicate. Risk of bias was assessed using Cochrane collaboration tools. Results: A total of 2753 results were identified. A total of 9 studies including 808 participants were included. Results showed improvement in deceleration time (-39.49ms CI[-57.24,-21.74]; p=0.000), isovolumic relaxation time (-9.32 ms CI[-17.08, -1.57]; p=0.02) and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity (E/E’) (-1.38 CI[-2.6, -0.16]; p=0.03). However, improvement in left atrial volume index, the ratio of early to late mitral inflow velocities (E/A) was not statistically significant. The risk of bias is mild to moderate. Conclusions: Our results suggest that chronic treatment of moderate to severe OSA with non-invasive positive airway pressure is associated with improvement in diastolic dysfunction.

BACKGROUND This systematic review appraises the evidence from human clinical trials comparing postoperative pain scores and opioid consumption in patients receiving intra-articular ketamine versus other modalities of analgesia after orthopedic joint procedures. METHODS Studies were identified from Embase, Scopus, and OVID Medline databases. Included studies compared patients receiving intra-articular ketamine versus other modalities of analgesia. The primary outcome of interest was postprocedural pain score and total opioid consumption, whereas secondary outcomes included time to rescue analgesic medication request, active range of motion, time to mobilization, and adverse effects. RESULTS Seventeen studies were included. Dosage of ketamine varied widely from 0.25 to 2 mg/kg. Fifteen of 17 demonstrated decreased overall pain scores and decreased total postoperative opioid consumption in patients receiving intra-articular ketamine versus control groups. Included studies generally demonstrated reduced time to mobilization and increased latency until rescue analgesic medication in the intra-articular ketamine group. CONCLUSIONS Patients who received intra-articular ketamine generally reported lower pain scores and had lower postoperative opioid consumption after orthopedic joint procedures. This suggests that the intra-articular route of ketamine delivery may be a useful analgesic modality, although future larger-scale trials should explore its pharmacokinetics, optimal dosing, safety, and cost-effectiveness.

Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI. A comprehensive search of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study. The search identified 1670 articles; 12 met inclusion criteria. Four randomized clinical trials and eight cohort studies at high risk of bias enrolled 806 women with POI. The most common HT formulations were transdermal estradiol and oral conjugated equine estrogen combined with medroxyprogesterone acetate. Bone mineral density was the most frequent outcome, with three out of eight studies showing HT associated increase benefits. Only one study reported effects on fractures or vasomotor symptoms and none on cardiovascular mortality. Results regarding lipid profiles were inconsistent. Evidence supporting bone and cardiovascular benefits of HT in women with POI is limited by high risk of bias, reliance on surrogate outcomes, and heterogeneity of trials regarding the formulation, dose, route of administration, and regimen of HT. Further research addressing patient important outcomes such as fractures, stroke, and cardiovascular mortality are crucial to optimize benefits of this therapy.

Objective We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. Study Design and Setting We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. Results We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1–13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). Conclusion About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

Introduction The high failure rate of clinical trials in traumatic brain injury (TBI) may be attributable, in part, to the use of untested or insensitive measurement instruments. Of more than 1,000 clinical outcome assessment measures (COAs) for TBI, few have been systematically vetted to determine their performance within specific “contexts of use (COU).” As described in guidance issued by the U.S. Food and Drug Administration (FDA), the COU specifies the population of interest and the purpose for which the COA will be employed. COAs are commonly used for screening, diagnostic categorization, outcome prediction, and establishing treatment effectiveness. COA selection typically relies on expert consensus; there is no established methodology to match the appropriateness of a particular COA to a specific COU. We developed and pilot-tested the Evidence-Based Clinical Outcome assessment Platform (EB-COP) to systematically and transparently evaluate the suitability of TBI COAs for specific purposes. Methods and findings Following a review of existing literature and published guidelines on psychometric standards for COAs, we developed a 6-step, semi-automated, evidence-based assessment platform to grade COA performance for six specific purposes: diagnosis, symptom detection, prognosis, natural history, subgroup stratification and treatment effectiveness. Mandatory quality indicators (QIs) were identified for each purpose using a modified Delphi consensus-building process. The EB-COP framework was incorporated into a Qualtrics software platform and pilot-tested on the Glasgow Outcome Scale—Extended (GOSE), the most widely-used COA in TBI clinical studies. Conclusion The EB-COP provides a systematic methodology for conducting more precise, evidence-based assessment of COAs by evaluating performance within specific COUs. The EB-COP platform was shown to be feasible when applied to a TBI COA frequently used to detect treatment effects and can be modified to address other populations and COUs. Additional testing and validation of the EB-COP are warranted.

BACKGROUND: Patients with limited English proficiency (LEP) experience disparities in end-of-life decision making and advance care planning. Our objective was to conduct a systematic review to assess the literature about interventions addressing these issues. METHODS: Our search strategy was built around end-of-life (EOL), LEP, ACP, and goals of care. The databases included Ovid MEDLINE(R), and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily from 1946 to November 9, 2018, Ovid EMBASE. RESULTS: Eight studies from the US and Australia were included (7 studies in Spanish and 1 study in Greek and Italian). Interventions used trained personnel, video images, web-based programs, and written materials. Interventions were associated with increased advance directive completion and decreased preferences for some life-prolonging treatments. Interventions were deemed to be feasible and acceptable. CONCLUSION: Few interventions exist to improve end-of-life care for patients with LEP. Data are limited regarding intervention effectiveness.

Background When opioid-induced constipation is treated with centrally acting opioid antagonists, there may be opioid withdrawal or aggravation of pain due to inhibition of μ-opioid analgesia. This led to the development of peripherally acting μ-opioid receptor antagonists (PAMORAs). Aim To evaluate the efficacy of available PAMORAs and other approved or experimental treatments for relieving constipation in patients with opioid-induced constipation, based on a systematic review and meta-analysis of published studies. Methods A search of MEDLINE, EMBASE and EBM Reviews Cochrane Central Register of Controlled Trials was completed in July 2019 for randomised trials compared to placebo. FDA approved doses or highest studied dose was evaluated. Efficacy was based on diverse endpoints, including continuous variables (the bowel function index, number of spontaneous bowel movements and stool consistency based on Bristol Stool Form Scale), or responder analysis (combination of >3 spontaneous bowel movements or complete spontaneous bowel movements plus 1 spontaneous bowel movement or complete spontaneous bowel movements, respectively, over baseline [so-called FDA endpoints]). Adverse effects evaluated included central opioid withdrawal, serious adverse events, abdominal pain and diarrhoea. Results We included 35 trials at low risk of bias enrolling 13 566 patients. All PAMORAs demonstrated efficacy on diverse patient response endpoints. There was greater efficacy with approved doses of the PAMORAs (methylnaltrexone, naloxegol and naldemidine), with lower efficacy or lower efficacy and greater adverse effects with combination oxycodone with naloxone, lubiprostone and linaclotide. Conclusions Therapeutic response in opioid-induced constipation is best achieved with the PAMORAs, methylnaltrexone, naloxegol and naldemidine, which are associated with low risk of serious adverse events.

BACKGROUND No consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant. OBJECTIVE To review data regarding antifungal prophylaxis on the development of fungal infections. STUDY SELECTION/APPRAISAL We searched MEDLINE, Embase, and Scopus for eligible articles through December 10, 2019. Observational or controlled trials published after January 1, 2001, that pertained to the prevention of fungal infections in adult lung recipients were reviewed independently by two reviewers for inclusion. METHODS Of 1702 articles screened, 24 were included. Data were pooled using random effects model to evaluate for the primary outcome of fungal infection. Studies were stratified by prophylactic strategy, medication, and duration (short term

INTRODUCTION: Chronic kidney disease (CKD) is widely prevalent, associated with morbidity and mortality, but may be lessened with timely implementation of evidence-based strategies including blood pressure (BP) control. Nonetheless, an evidence-practice gap persists. We synthesize the evidence for clinician-facing interventions to improve hypertension management in CKD patients in primary care. METHODS: Electronic databases and related publications were queried for relevant studies. We used a conceptual model to address heterogeneity of interventions. We conducted a quantitative synthesis of interventions on blood pressure (BP) outcomes and a narrative synthesis of other CKD relevant clinical outcomes. Planned subgroup analyses were performed by (1) study design (randomized controlled trials (RCTs) or nonrandomized studies (NRS)); (2) intervention type (guideline-concordant decision support, shared care, pharmacist-facing); and (3) use of behavioral/implementation theory. RESULTS: Of 2704 manuscripts screened, 73 underwent full-text review; 22 met inclusion criteria. BP target achievement was reported in 15 and systolic BP reduction in 6 studies. Among RCTs, all interventions had a significant effect on BP control, (pooled OR 1.21; 95% CI 1.07 to 1.38). Subgroup analysis by intervention type showed significant effects for guideline-concordant decision support (pooled OR 1.19; 95% CI 1.12 to 1.27) but not shared care (pooled OR 1.71; 95% CI 0.96 to 3.03) or pharmacist-facing interventions (pooled OR 1.04; 95% CI 0.82 to 1.34). Subgroup analysis finding was replicated with pooling of RCTs and NRS. The five contributing studies showed large and significant reduction in systolic BP (pooled WMD − 3.86; 95% CI − 7.2 to − 0.55). Use of a behavioral/implementation theory had no impact, while RCTs showed smaller effect sizes than NRS. DISCUSSION: Process-oriented implementation strategies used with guideline-concordant decision support was a promising implementation approach. Better reporting guidelines on implementation would enable more useful synthesis of the efficacy of CKD clinical interventions integrated into primary care. PROSPERO REGISTRATION NUMBER: CRD42018102441 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11606-020-06103-7) contains supplementary material, which is available to authorized users.

IntroductionThere is a considerable implementation gap in managing early stage chronic kidney disease (CKD) in primary care despite the high prevalence and risk for increased morbidity and mortality associated with CKD. This systematic review aims to synthesise the evidence of efficacy of implementation interventions aimed at primary care practitioners (PCPs) to improve CKD identification and management. We further aim to describe the interventions’ behavioural change components.Methods and analysisWe will conduct a systematic review of studies from 2000 to October 2017 that evaluate implementation interventions targeting PCPs and which include at least one clinically meaningful CKD outcome. We will search several electronic data bases and conduct reference mining of related systematic reviews and publications. An interdisciplinary team will independently and in duplicate, screen publications, extract data and assess the risk of bias. Clinical outcomes will include all clinically meaningful medical management outcomes relevant to CKD management in primary care such as blood pressure, chronic heart disease and diabetes target achievements. Quantitative evidence synthesis will be performed, where possible. Planned subgroup analyses include by (1) study design, (2) length of follow-up, (3) type of intervention, (4) type of implementation strategy, (5) whether a behavioural or implementation theory was used to guide study, (6) baseline CKD severity, (7) patient minority status, (8) study location and (9) academic setting or not.Ethics and disseminationApproval by research ethics board is not required since the review will only include published and publicly accessible data. Review findings will inform a future trial of an intervention to promote uptake of CKD diagnosis and treatment guidelines in our primary care setting and the development of complementary tools to support its successful adoption and implementation. We will publish our findings in a peer-reviewed journal and develop accessible summaries of the results.PROSPERO registration numberCRD42018102441.

The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the impact of SCH during pregnancy on maternal and neonatal outcomes, and (ii) the effect of levothyroxine replacement therapy in these patients.Ovid MEDLINE In-ProcessOther Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015. Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included. Reviewers extracted data and assessed methodological quality in duplicate. Eighteen cohort studies at low-to-moderate risk of bias were included. Compared with euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (relative risk [RR] 2.01 [confidence interval (CI) 1.66-2.44]), placental abruption (RR 2.14 [CI 1.23-3.70]), premature rupture of membranes (RR 1.43 [CI 1.04-1.95]), and neonatal death (RR 2.58 [CI 1.41-4.73]). One study at high risk of bias compared pregnant women with SCH who received levothyroxine to those who did not and found no significant decrease in the rate of pregnancy loss, preterm delivery, gestational hypertension, low birth weight, or low Apgar score.SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes. The value of levothyroxine therapy in preventing these adverse outcomes remains uncertain.

[Purpose] Ultrasound-guided ilioinguinal/iliohypogastric (II/IH) nerve and transversus abdominis plane (TAP) blocks have been increasingly utilized in patients for perioperative analgesia. We conducted this meta-analysis to evaluate the clinical efficacy of ultrasound-guided II/IH nerve or TAP blocks for perioperative analgesia in patients undergoing open inguinal surgery. [Subjects and Methods] A systematic search was conducted of 7 databases from the inception to March 5, 2015. Randomized controlled trials (RCTs) comparing the clinical efficacy of ultrasound-guided vs. landmark-based techniques to perform II/IH nerve and TAP blocks in patients with open inguinal surgery were included. We constructed random effects models to pool the standardized mean difference (SMD) for continuous outcomes and the odds ratio (OR) for dichotomized outcomes. [Results] Ultrasound-guided II/IH nerve or TAP blocks were associated with a reduced use of intraoperative additional analgesia and a significant reduction of pain scores during day-stay. The use of rescue drugs was also significantly lower in the ultrasound-guided group. [Conclusion] The use of ultrasound-guidance to perform an II/IH nerve or a TAP block was associated with improved perioperative analgesia in patients following open inguinal surgery compared to landmark-based methods.

Objetivos Se trato de una revision sistematica y metanalisis para evaluar la incidencia de eventos adversos en adultos sometidos a sedacion para procedimientos en el servicio de urgencias (SU). Metodos Se realizaron busquedas en ocho bases de datos electronicas, incluyendo MEDLINE, EMBASE, EBSCO, CINAHL, CENTRAL, la Base de datos Cochrane de Revisiones Sistematicas, Web of Science y Scopus, desde enero de 2005 hasta 2015. Se incluyeron ensayos controlados randomizados y estudios observacionales de adultos sometidos a sedacion para apoyo en procedimientos en el SU que reportaron resultados clinicos seleccionados a priori y eventos adversos. El metaanalisis se realizo utilizando un modelo de efectos aleatorios y se informo como tasas de incidencia con Intervalos de confianza (IC) de 95%. Resultados Se encontraron 2046 articulos para revision. Cincuenta y cinco articulos fueron elegidos, incluyendo 9652 sedaciones para procedimientos. El evento adverso mas frecuente fue la hipoxia, con una incidencia de 40.2 por 1000 (IC 95% = 32.5 a 47.9), seguido de vomitos con 16.4 por 1000 sedaciones (IC del 95% = 9.7 a 23.0) e hipotension con 15.2 por 1000 sedaciones (IC del 95% = 10.7 a 19.7). Los eventos adversos severos que requirieron intervencion medica de urgencia fueron raros, con un caso de aspiracion en 2370 sedaciones (1.2 por 1000), un caso de laringoespasmo en 883 sedaciones (4.2 por 1000) y dos intubaciones en 3636 sedaciones (1.6 por 1000). La incidencia de agitacion y vomitos fue mayor con Ketamina (164.1 por 1000 y 170.0 por 1000, respectivamente). La apnea fue mas frecuente con midazolam (51.4 por 1000), y la hipoxia fue menos frecuente en pacientes que recibieron Ketamina/propofol en comparacion con otras combinaciones. El caso de laringospasmo ocurrio en un paciente que recibio Ketamina, y la aspiracion y las intubaciones ocurrieron en pacientes que recibieron propofol. Cuando el propofol y la Ketamina se combinan, las incidencias de agitacion, apnea, hipoxia, bradicardia, hipersensibilidad y vomitos fueron mas bajas comparadas con cada medicacion por separado. Conclusiones Los eventos adversos graves durante sedacion para procedimientos como el laringoespasmo, aspiracion e intubacion, son extremadamente raros. Se proporcionan estimaciones cuantitativas de riesgo para facilitar la toma de decisiones compartida, la comunicacion de los riesgos y el consentimiento informado.

Background The use of mesenchymal stem cells (MSCs) in clinical applications for the treatment of musculoskeletal disease is steadily increasing in office-based practice. The so-called “first generation” of MSCs is defined as autologous stem cells that have undergone minimal manipulation and are used for a homologous purpose. Systematic reviews of the clinical trials completed to date of such MSCs enable practitioners to better understand what is currently known about the outcomes and side effects of such treatments. Study Design A systematic review of human clinical studies of office-based MSC therapy for the treatment of painful degenerative musculoskeletal conditions. Methods A search of the Ovid MEDLINE, EMBASE, and Scopus databases was conducted from 2006 through September 2016. Seven hundred sixty-one records were identified from database searching, and two records from reference review of included papers. Studies with human subjects that evaluated treatment of musculoskeletal disease with minimally manipulated MSCs were included. Results Eight studies were included in this review based on selection criteria. A total of 941 patients were included, 841 of whom received cellular products, and no significant adverse events were reported. Symptomatology generally improved, though no differences were seen over controls where present. Conclusion Support in the literature is strongest for the use of bone marrow aspirate concentrate (BMAC) injections for the treatment of knee pain, but applications of the use of BMAC and peripheral blood–derived MSCs for the treatment of hip pain, tendon pain, and disc pain have all been reported. Further research is required, with large randomized controlled trials.

This meta-analysis assessed the relationship between Obstructive Sleep Apnea (OSA) and echocardiographic parameters suggesting diastolic dysfunction, which is a well-recognized finding in Heart Failure with Preserved Ejection Fraction (HFpEF). We searched the databases including Ovid MEDLINE, Ovid

Obstructive sleep apnea (OSA) is associated with various types of cardiovascular disorders. The aim of the present meta-analysis was to investigate the relationship between OSA severity and echocardiographic measures of diastolic dysfunction (DD). We searched the databases since inception up to

Background & Aims Studies have reported a lack of association between improvements in gastric emptying (GE) and upper gastrointestinal (UGI) symptoms with promotility drugs. However, GE test methods were suboptimal in some studies. We assessed improvements in GE and UGI symptoms in patients given promotility agents in studies with optimal or moderate test methods (scintigraphy or breath test, solid meal, >2 hours duration) compared to studies with suboptimal GE test methods. Methods With an expert librarian, we completed an extensive search of publications in the Ovid MEDLINE (1946 to present), EMBASE (1988 to January 2018), and EBM Reviews Cochrane Central Register of Controlled Trials, without restrictions on language or year. Two independent reviewers evaluated the following inclusion criteria: randomized, blinded, parallel, or crossover trials of 5HT4 agonists, D2 receptor antagonist, or ghrelin agonists; trials that measured change in GE (T1/2) or composite UGI symptoms; trials of patients with functional dyspepsia and gastroparesis; and trials of GE test methods. Standardized mean differences (units expressed as SD) were used to standardize symptom assessments that were not uniform across studies. Random effects model was used to analyze data and meta-regression was used to evaluate the association between change in GE and UGI symptoms. Results Of 899 studies considered, 22 studies assessed change in GE; 23 evaluated UGI symptoms; and 14 evaluated GE and UGI symptoms. Promotility agents significantly accelerated GE (T1/2) in all studies (mean reduction in T1/2, 16.3 minutes; 95% confidence interval, –22.1 to –10.6 minutes) and in studies that used optimal GE test methods (mean reduction in T1/2, 23.6 minutes; 95% confidence interval, –32.3 to –14.9 minutes). Promotility agents also significantly reduced UGI symptoms (mean reduction, 0.25 SD; 95% confidence interval, –0.37 to –0.13 SD). Meta-regression found no significant association between change in GE and UGI symptoms. However, when only studies with optimal GE test methods were evaluated, there was a significant positive association between improvement in GE and UGI symptoms (P = .02). Conclusions In a meta-analysis of published trials, we found promotility agents to significantly accelerate GE (when optimal test methods were used) and to produce significant improvements in UGI symptoms.

Serum cystatin C has been proposed as a kidney biomarker to inform drug dosing. We conducted a systematic review to synthesize available data for the association between serum cystatin C and drug pharmacokinetics, dosing, and clinical outcomes in adults (≥18 years). PubMed, Ovid MEDLINE, Ovid EMBASE, EBSCO CINAHL, and Scopus were systematically searched from 1946 to September 2017 to identify candidate studies. Studies of cystatin C as a predictor for acute kidney injury or for management of contrast-associated acute kidney injury were excluded. Also, studies were excluded if drug concentrations were unavailable and if a reference standard for drug dosing (eg, serum creatinine) was not concurrently reported. The outcomes of interest included drug clearance (L/h), concentrations (mg/L), target level achievement (%), therapeutic failure (%), and drug toxicity (%). We included 28 articles that evaluated 16 different medications in 3455 participants. Vancomycin was the most well-studied drug. Overall, cystatin C–based estimated glomerular filtration rate (eGFRCystatin C) was more predictive of drug levels and drug clearance than eGFRCreatinine. In only one study were target attainment and outcomes compared between 2 drug-dosing regimens, one based on eGFRCreatinine-Cystatin C and one dosed with the Cockcroft-Gault creatinine clearance equation. Compared with eGFRCreatinine, use of eGFRCystatin C to predict elimination of medications via the kidney was as accurate, if not superior, in most studies, but infrequently were data on target attainment or clinical outcomes reported. Drug-specific dosing protocols that use cystatin C to estimate kidney function should be tested for clinical application.

BackgroundClinicians’ satisfaction with encounter decision aids is an important component in facilitating implementation of these tools. We aimed to determine the impact of decision aids supporting shared decision making (SDM) during the clinical encounter on clinician outcomes.MethodsWe searched nine databases from inception to June 2017. Randomised clinical trials (RCTs) of decision aids used during clinical encounters with an unaided control group were eligible for inclusion. Due to heterogeneity among included studies, we used a narrative evidence synthesis approach.ResultsTwenty-five papers met inclusion criteria including 22 RCTs and 3 qualitative or mixed-methods studies nested in an RCT, together representing 23 unique trials. These trials evaluated healthcare decisions for cardiovascular prevention and treatment (n=8), treatment of diabetes mellitus (n=3), treatment of osteoporosis (n=2), treatment of depression (n=2), antibiotics to treat acute respiratory infections (n=3), cancer prevention and treatment (n=4) and prenatal diagnosis (n=1). Clinician outcomes were measured in only a minority of studies. Clinicians’ satisfaction with decision making was assessed in only 8 (and only 2 of them showed statistically significantly greater satisfaction with the decision aid); only three trials asked if clinicians would recommend the decision aid to colleagues and only five asked if clinicians would use decision aids in the future. Outpatient consultations were not prolonged when a decision aid was used in 9 out of 13 trials. The overall strength of the evidence was low, with the major risk of bias related to lack of blinding of participants and/or outcome assessors.ConclusionDecision aids can improve clinicians’ satisfaction with medical decision making and provide helpful information without affecting length of consultation time. Most SDM trials, however, omit outcomes related to clinicians’ perspective on the decision making process or the likelihood of using a decision aid in the future.

Objectives This was a systematic review and meta-analysis to evaluate the incidence of adverse events in adults undergoing procedural sedation in the emergency department (ED). Methods Eight electronic databases were searched, including MEDLINE, EMBASE, EBSCO, CINAHL, CENTRAL, Cochrane Database of Systematic Reviews, Web of Science, and Scopus, from January 2005 through 2015. Randomized controlled trials and observational studies of adults undergoing procedural sedation in the ED that reported a priori selected outcomes and adverse events were included. Meta-analysis was performed using a random-effects model and reported as incidence rates with 95% confidence intervals (CIs). Results The search yielded 2,046 titles for review. Fifty-five articles were eligible, including 9,652 procedural sedations. The most common adverse event was hypoxia, with an incidence of 40.2 per 1,000 sedations (95% CI = 32.5 to 47.9), followed by vomiting with 16.4 per 1,000 sedations (95% CI = 9.7 to 23.0) and hypotension with 15.2 per 1,000 sedations (95% CI = 10.7 to 19.7). Severe adverse events requiring emergent medical intervention were rare, with one case of aspiration in 2,370 sedations (1.2 per 1,000), one case of laryngospasm in 883 sedations (4.2 per 1,000), and two intubations in 3,636 sedations (1.6 per 1,000). The incidence of agitation and vomiting were higher with ketamine (164.1 per 1,000 and 170.0 per 1,000, respectively). Apnea was more frequent with midazolam (51.4 per 1,000), and hypoxia was less frequent in patients who received ketamine/propofol compared to other combinations. The case of laryngospasm was in a patient who received ketamine, and the aspiration and intubations were in patients who received propofol. When propofol and ketamine are combined, the incidences of agitation, apnea, hypoxia, bradycardia, hypotension, and vomiting were lower compared to each medication separately. Conclusions Serious adverse events during procedural sedation like laryngospasm, aspiration, and intubation are exceedingly rare. Quantitative risk estimates are provided to facilitate shared decision-making, risk communication, and informed consent.

To examine the evidence supporting the use of simulation-based assessments as surrogates for patient-related outcomes assessed in the workplace.The authors systematically searched MEDLINE, EMBASE, Scopus, and key journals through February 26, 2013. They included original studies that assessed health professionals and trainees using simulation and then linked those scores with patient-related outcomes assessed in the workplace. Two reviewers independently extracted information on participants, tasks, validity evidence, study quality, patient-related and simulation-based outcomes, and magnitude of correlation. All correlations were pooled using random-effects meta-analysis.Of 11,628 potentially relevant articles, the 33 included studies enrolled 1,203 participants, including postgraduate physicians (n = 24 studies), practicing physicians (n = 8), medical students (n = 6), dentists (n = 2), and nurses (n = 1). The pooled correlation for provider behaviors was 0.51 (95% confidence interval [CI], 0.38 to 0.62; n = 27 studies); for time behaviors, 0.44 (95% CI, 0.15 to 0.66; n = 7); and for patient outcomes, 0.24 (95% CI, -0.02 to 0.47; n = 5). Most reported validity evidence was favorable, though studies often included only correlational evidence. Validity evidence of internal structure (n = 13 studies), content (n = 12), response process (n = 2), and consequences (n = 1) were reported less often. Three tools showed large pooled correlations and favorable (albeit incomplete) validity evidence.Simulation-based assessments often correlate positively with patient-related outcomes. Although these surrogates are imperfect, tools with established validity evidence may replace workplace-based assessments for evaluating select procedural skills.

In the original publication, the given and family name of the author Mohammad Hassan Murad was incorrect. This has been corrected with this erratum.

Background Clinical care review is the process of retrospectively examining potential errors or gaps in medical care, aiming for future practice improvement. The objective of our systematic review is to identify the current state of care review reported in peer-reviewed publications and to identify domains that contribute to successful systems of care review. Methods A librarian designed and conducted a comprehensive literature search of eight electronic databases. We evaluated publications from January 1, 2000, through May 31, 2016, and identified common domains for care review. Sixteen domains were identified for further abstraction. Results We found that there were few publications that described a comprehensive care review system and more focus on individual pathways within the overall systems. There is inconsistent inclusion of the identified domains of care review. Conclusion While guidelines for some aspects of care review exist and have gained traction, there is no comprehensive standardized process for care review with widespread implementation. Electronic supplementary material The online version of this article (10.1186/s12245-018-0166-y) contains supplementary material, which is available to authorized users.

Background Underrepresentation of racial and ethnic minorities in clinical trials remains a reality while they have disproportionately higher rates of health disparities. Objective The purpose of this study was to identify successful community-engaged interventions that included health care providers as a key strategy in addressing barriers to clinical trial enrollment of underrepresented patients. Design A systematic review of the literature on interventions addressing enrollment barriers to clinical trials for racial and ethnic minorities was performed in Ovid MEDLINE, EBSCO Megafile, and EBSCO CINAHL. The systematic review identified 360 studies, and 20 were selected using the inclusion criteria. An iterative process extracted information from the eligible studies. Results The 20 selected studies were analyzed and then grouped by first author, nature of the clinical research initiative, priority populations, key strategies, and study outcomes. Nine of the studies addressed cancer clinical trials and 11 related to chronic medical conditions, including diabetes, hypertension management, and chronic kidney disease. The key strategies employed were categorized according to their presumed impact on barriers incurred at distinct steps in study recruitment: clinical trial awareness, opportunity to participate, and acceptance of enrollment. The strategies were further categorized by whether they would address barriers associated with minority perceptions of the research process and barriers related to how studies were designed and implemented. Conclusion Multiple and flexible strategies targeting providers and participants at provider sites and within communities might be needed to enroll underrepresented populations into clinical trials.

We conducted a metaanalysis comparing early and midterm cardiovascular adverse events associated with minimally invasive direct coronary artery bypass graft surgery (MIDCABG) and percutaneous coronary intervention (PCI), with a focus on drug-eluting stents (DES).A systematic literature review (MEDLINE, EMBASE, Scopus, and so forth) yielded 12 studies (7 randomized controlled trials; 5 observational) pooling more than 2,000 patients. A random effect, inverse variance metaanalysis was conducted, and a subgroup analysis of the PCI-DES cohort was performed. Events were compared as risk ratios using a 95% confidence interval (CI). Heterogeneity of results was evaluated by Eggers I(2) test. Results are presented as early (0 to 1 year) and midterm (2 to 5 years).Midterm mortality in the PCI and MIDCABG groups (3.6% and 2.6%, respectively) was comparable (1.24, 95% CI: 0.66 to 2.33; p = 0.5; I(2) = 0%). Risk of early restenosis was lower in the MIDCABG cohort compared with PCI (0.40, 95% CI: 0.16 to 0.99; p = 0.05; I(2) = 57%). Although the early risk of recurrence of angina was comparable, over time it was 61% (43% to 74%) lower for MIDCABG patients (p0.001). Midterm results on analysis of the entire cohort demonstrated an increased risk for target vessel reinterventions (3.84, 95% CI: 2.7 to 5.5; p0.001) in the PCI cohort. Subgroup analysis revealed that the PCI-DES cohort (4 studies; 456 patients) had a higher risk of recurrent angina (risk ratio 3.4, 95% CI: 1.9 to 6.2; p0.001; I(2) = 0%) and target vessel reinterventions (risk ratio 4.16, 95% CI: 2.7 to 6.6; p 0.001; I(2) = 0%) at midterm follow-up (2 to 5 years).Survival rates are comparable after either MIDCABG or PCI for proximal LAD disease. However, even the use of DES was associated with significantly higher rates of angina recurrence and the need for target vessel reintervention as compared with MIDCABG.

ObjectivesTreatment burden is the workload of healthcare for people with long-term conditions (LTC) and its impact on well-being. A method of measurement is required to identify those experiencing high burden and to measure intervention efficacy. Our aim was to identify, examine and appraise validated patient-reported measures (PRMs) of treatment burden in stroke. Here, stroke serves as an exemplar LTC of older adults.DesignA systematic review of published studies that describe the development and validation of PRMs measuring treatment burden in stroke survivors.Data sourcesWe searched MEDLINE, Embase, CINAHL and PsycINFO electronic databases.Eligibility criteriaStudies published between January 2000 and 12 April 2019 inclusive, in English language. No restrictions were set based on clinical setting or geographical location.Data extraction and synthesisScreening, data extraction and quality appraisal were conducted by two independent reviewers. Content of the PRMs was compared with a published taxonomy of treatment burden. Quality appraisal was conducted using International Society for Quality of Life Research standards.ResultsFrom 3993 articles, 6 relevant PRMs were identified: 3 were stroke specific: The Satisfaction with Stroke Care questionnaire; The Stroke Patient-Reported Outcome Measure and The Barriers to Physical Activity after Stroke scale. Three were generic but validated in stroke: The WHO Quality of Life-100; The Patient’s Questionnaire on Participation in Discharge Planning and The Chao Perception of Continuity scale. None comprehensively measured treatment burden. Examples of omitted burdens included developing coping strategies, managing finances and returning to driving. The most notable issue regarding quality appraisal was that three PRMs lacked any underpinning qualitative research relevant to the sample.ConclusionThere is a need to develop a comprehensive PRM of treatment burden for use in stroke, with potential for use in other older populations.

Objectives We aimed to explore whether weight loss may improve central hemodynamics in obesity Hypothesis Hemodynamic abnormalities in obese HFpEF patients are correlated with the amount of excess body mass, suggesting a possible causal relationship. Methods We systematically searched relevant databases from inception to May 2018, without language restriction. Studies reporting invasive hemodynamic measures prior to and following therapeutic weight loss interventions in patients with obesity but no clinically-overt HF were extracted. Results A total of 9 studies were identified, providing data for 111 patients. Six studies tested dietary intervention and 3 studies tested bariatric surgery. Over a median duration of 9.7 months [range 0.75 to 23], median weight loss of 43 kg [range 10-58] was associated with significant reductions in heart rate [-9 bpm, 95% CI -12 to -6, p Conclusion Therapeutic weight loss in obese patients without HF is associated with favorable hemodynamic effects that could improve symptoms in patients with obesity and HF. Randomized controlled trials evaluating strategies for weight loss in obesity-related HFpEF are needed.

Objectives This study sought to perform a meta-analysis of randomized controlled trials comparing device closure with medical therapy in the prevention of recurrent neurological events in patients with cryptogenic stroke and patent foramen ovale. Background The optimal strategy for secondary prevention of cryptogenic stroke with a patent foramen ovale is unclear. Methods Several databases were searched from their inception to March 2013, which yielded 3 eligible studies. The results were pooled as per the different patient populations defined in the studies:—intention-to-treat, per-protocol, and as-treated cohorts. A generic inverse method was used based on time-to-event outcomes in a fixed-effect model. A supplementary analysis pooled the results from only 2 trials (RESPECT [Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment] and PC Trial [Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic Embolism]) as a similar device was used in them. Results Our meta-analysis yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI]: 0.44 to 1.00, I2 = 0%) in the intention-to-treat cohort, 0.62 (95% CI: 0.40 to 0.95). I2 = 0%) in the per-protocol cohort, and 0.61 (95% CI: 0.40 to 0.95, I2 = 38%) in the as-treated cohort, showing beneficial effects of device closure. The results became more robust with pooled results from RESPECT and the PC Trial: The effect-estimate hazard ratios being 0.54 (95% CI: 0.29 to 1.01, I2 = 0%), 0.48 (95% CI: 0.24 to 0.94, I2 = 26%), and 0.42 (95% CI: 0.21 to 0.84, I2 = 26%) in the intention-to-treat, per-protocol, and as-treated populations, respectively. Conclusions Our meta-analysis suggests that PFO closure is beneficial as compared to medical therapy in the prevention of recurrent neurological events. This meta-analysis helps to further strengthen the role of device closure in cryptogenic stroke.

Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles.We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS.Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011.We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects.Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible.We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive.Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.

BACKGROUND: The use of 2 agonist as an intervention for acute lung injury (ALI) and ARDS patients is controversial, so we performed a systematic review and meta-analysis of the published randomized controlled trials of using 2 agonists to improve outcomes (mortality and ventilator free days) among patients with ALI/ARDS. METHODS: A comprehensive search of 7 major databases (Ovid MEDLINE In-Process and other non-indexed citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials (CENTRAL), Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus) for randomized controlled trials using 2 agonists for ALI from their origin to March 2013 was conducted. The effect size was measured by relative risk for dichotomous outcomes, and mean difference for continuous outcomes, with 95% CI. The statistical heterogeneity between the studies was assessed with the Cochran Q test and I 2 statistic. The heterogeneity of > 50% was considered significant for the analysis. The Cochrane risk of bias tool was used to ascertain the quality of the included studies. RESULTS: Out of 219 studies screened, 3 randomized controlled trials reported mortality and ventilator-free days, in 646 ALI/ ARDS subjects. Of the 646 subjects, 334 (51.7%) received 2 agonist and 312 (48.3%) received placebo. There was no significant decrease in 28-day mortality or hospital mortality in the 2agonist group: relative risk 1.04, 95% CI 0.50–2.16, and relative risk 1.22, 95% CI 0.95–1.56, respectively. The ventilator-free days and organ-failure-free days were significantly lower for the ALI subjects who received 2 agonists: mean difference 2.19 days (95% CI 3.68 to 1.99 d) and mean difference 2.04 days (95% CI 3.74 to 0.35 d), respectively. CONCLUSIONS: In subjects with ALI/ARDS, 2 agonists were not only nonbeneficial in improving the survival, but were harmful and increased morbidity (reduced organ-failure-free days and ventilator-free days). The current evidence discourages the use of 2 agonist in ALI/ARDS patients. (International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/prospero, 2012:CRD42012002616.)

To perform a systematic review and meta-analysis of clinical trials evaluating the efficacy and safety of midodrine in orthostatic hypotension (OH). We searched major databases and related conference proceedings through June 30, 2012. Two reviewers independently selected studies and extracted data. Random-effects meta-analysis was used to pool the outcome measures across studies. Seven trials were included in the efficacy analysis (enrolling 325 patients, mean age 53 years) and two additional trials were included in the safety analysis. Compared to placebo, the mean change in systolic blood pressure was 4.9 mmHg (p = 0.65) and the mean change in mean arterial pressure from supine to standing was −1.7 mmHg (p = 0.45). The change in standing systolic blood pressure before and after giving midodrine was 21.5 mmHg (p

Background Coronary artery bypass graft surgery is superior to percutaneous intervention in diabetic patients with multivessel disease. The use of bilateral internal thoracic arteries (BITA) may provide better long-term graft patency, but the risk of postoperative deep sternal wound infection has limited its use in diabetic patients. However, studies have reported conflicting results, and require systematic evaluation. Methods MEDLINE, EMBASE, World of Science, and the Cochrane library were searched for randomized controlled trials and observational studies comparing the incidence of deep sternal wound infection in diabetic patients undergoing either left internal thoracic artery (LITA) or BITA harvest. We used random effect models to compare risk ratios within groups. Results One randomized controlled trial and 10 observational studies (126,235 diabetic patients: 122,465 LITA, 3,770 BITA) met inclusion criteria. Deep sternal wound infection occurred in 3.1% and 1.6% for the BITA and LITA cohorts, respectively. The risk ratio for deep sternal wound infection development was 1.71 (1.37 to 2.14) for BITA compared with LITA. Patients who underwent skeletonized BITA harvest had a similar risk of deep sternal wound infection compared with LITA (0.9 [0.42 to 2.09]), although pedicled harvest demonstrated increased risk (1.77 [1.4 to 2.23]). Early mortality was comparable in the LITA cohort (2.5%) and the BITA cohort (2.3%; p = 0.8). Conclusions The risk of deep sternal wound infection can be minimized in diabetic patients undergoing coronary artery bypass graft surgery by performing ITA harvested in a skeletonized manner with meticulous attention to preserving sternal blood flow. Pedicled harvest is to be discouraged when utilizing both ITA owing to a significant increase in the risk of postoperative deep sternal wound infection.

Background Little is known about determinants of quality of life (QoL) in autosomal dominant polycystic kidney disease (ADPKD). Recent studies suggest that QoL in ADPKD is determined by more factors than mere renal function. We investigated the effect of ADPKD on QoL and evaluated how Qol is affected by disease severity markers renal function, kidney volume and liver volume. Methods We performed a systematic review, meta-analysis and meta-regression analyses of cohort studies and randomized controlled trials investigating patient-reported QoL in adult patients with ADPKD not yet on dialysis. EMBASE, MEDLINE, and Web of Science were searched to August 2015 without language restrictions. Two investigators independently reviewed title, abstracts and full text of potentially relevant citations to determine eligibility. We compared pooled QoL summary scores of ADPKD patients using a random-effects meta-analytic model. These scores were compared with mean and age-corrected reference scores of the general population. In a meta-regression analysis, we investigated the univariate effect of renal function, kidney volume and liver volume on QoL. Results We included nine studies in meta-analysis including 1623 patients who completed the SF-36 questionnaire. Pooled physical (PCS) and mental component scores (MCS) of the SF-36 of individuals with ADPKD were lower than those of the reference population (45.7 vs. 50.0 and 47.8 vs. 50.0 points, both P

Background Chronic conditions are increasingly more common and negatively impact quality of life, disability, morbidity, and mortality. Health coaching has emerged as a possible intervention to help individuals with chronic conditions adopt health supportive behaviors that improve both quality of life and health outcomes. Methods/design We planned a systematic review and meta-analysis of the contemporary health coaching literature published in the last decade to evaluate the effect of health coaching on clinically important, disease-specific, functional, and behavioral outcomes. We will include randomized controlled trials or quasi-experimental studies that compared health coaching to alternative interventions or usual care. To enable adoption of effective interventions, we aim to explore how the effect of intervention is modified by the intervention components, delivering personnel (i.e., health professionals vs trained lay or peer persons), dose, frequency, and setting. Analysis of intervention outcomes will be reported and classified using an existing theoretical framework, the Theory of Patient Capacity, to identify the areas of patients’ capacity to access and use healthcare and enact self-care where coaching may be an effective intervention. Discussion This systematic review and meta-analysis will identify and synthesize evidence to inform the practice of health coaching by providing evidence on components and characteristics of the intervention essential for success in individuals with chronic health conditions. Systematic review registration PROSPERO CRD42016039730 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0316-3) contains supplementary material, which is available to authorized users.

Background Life and healthcare demand work from patients, more so from patients living with multimorbidity. Patients must respond by mobilizing available abilities and resources, their so-called capacity. We sought to summarize accounts of challenges that reduce patient capacity to access or use healthcare or to enact self-care while carrying out their lives. Methods We conducted a systematic review and synthesis of the qualitative literature published since 2000 identifying from MEDLINE, EMBASE, Psychinfo, and CINAHL and retrieving selected abstracts for full text assessment for inclusion. After assessing their methodological rigor, we coded their results using a thematic synthesis approach. Results The 110 reports selected, when synthesized, showed that patient capacity is an accomplishment of interaction with (1) the process of rewriting their biographies and making meaningful lives in the face of chronic condition(s); (2) the mobilization of resources; (3) healthcare and self-care tasks, particularly, the cognitive, emotional, and experiential results of accomplishing these tasks despite competing priorities; (4) their social networks; and (5) their environment, particularly when they encountered kindness or empathy about their condition and a feasible treatment plan. Conclusion Patient capacity is a complex and dynamic construct that exceeds “resources” alone. Additional work needs to translate this emerging theory into useful practice for which we propose a clinical mnemonic (BREWS) and the ICAN Discussion Aid. Electronic supplementary material The online version of this article (doi:10.1186/s12875-016-0525-9) contains supplementary material, which is available to authorized users.

Obliterative bronchiolitis (OB) is a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Our objective was to perform a systematic review and meta-analysis of the impact of azithromycin on change in forced expiratory volume in 1 second (FEV1). We searched MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL and Scopus databases and included studies that compared azithromycin with placebo or no intervention in the treatment of OB or bronchiolitis obliterans syndrome (BOS) in patients who had undergone allogeneic HSCT. Ninety-one unique publications were identified, and 4 studies met inclusion criteria, with a total of 90 patients. Changes in FEV1 were measured between 12 and 24 weeks after initiation of treatment. The meta-analysis demonstrated a mean increase in FEV1 of 30 mL (95% confidence interval, −260 to +330 mL; P = .82) after initiation of azithromycin. One patient death was reported but not attributed to azithromycin therapy. In conclusion, current evidence can neither support nor refute the use of azithromycin in the treatment of patients who develop OB/BOS after HSCT. Further studies are needed to determine whether azithromycin is beneficial for the treatment of OB/BOS in this setting.

Objective To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. Data sources We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. Study selection Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks9 treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. Data extraction and synthesis Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. Outcomes Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δ b ) in the number of SBM/week and Δ b CSBM/week. Results Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δ b in number of SBM/week. Conclusions Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δ b in the number of SBM/week in CIC.

Objective To consolidate the evidence from the literature to evaluate the role of prazosin in the treatment of posttraumatic stress disorder (PTSD). Data sources Major databases, including PubMed, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO, and Scopus, were searched through August 2015 for studies reporting the role of prazosin in the treatment of PTSD with no language constraints. Keywords included (PTSD OR posttraumatic stress OR posttraumatic stress OR nightmares) AND prazosin. Study selection Of 402 screened articles, 6 studies were included in the systematic review and meta-analysis. Data extraction Two reviewers independently extracted relevant data (study characteristics, type of intervention, outcome measures, and follow-up) from the included studies using a standardized data extraction form. Only randomized controlled trials comparing prazosin to a placebo or control group in patients with PTSD were included. Results The patients with PTSD receiving prazosin showed significant improvement in nightmares (standardized mean difference [SMD] = 1.01; 95% CI, 0.72-1.30), overall PTSD symptoms (SMD = 0.77; 95% CI, 0.48-1.06), and clinical global improvement (SMD = 0.94; 95%, CI 0.6-1.29) compared to the placebo/control group. Prazosin improved sleep quality (SMD = 0.87; 95% CI, 0.55-1.19), hyperarousal symptoms (SMD = 1.04; 95% CI, 0.23-1.84), dream content (SMD = 1.33; 95% CI, 0.69-1.97), and total sleep time (60.98 minutes; 95% CI, 18.69-103.26). Prazosin was fairly well tolerated. Minor side effects were reported, which were similar between the prazosin and placebo groups. Conclusions This study suggests that prazosin improves nightmares and overall PTSD symptoms including hyperarousal, sleep disturbances, total sleep time, and sleep quality.

International audience; BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52*8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24*9% of deaths worldwide in 2010, down from 15*9 million (34*1%) of 46*5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2*5 to 1*4 million), lower respiratory infections (from 3*4 to 2*8 million), neonatal disorders (from 3*1 to 2*2 million), measles (from 0*63 to 0*13 million), and tetanus (from 0*27 to 0*06 million). Deaths from HIV/AIDS increased from 0*30 million in 1990 to 1*5 million in 2010, reaching a peak of 1*7 million in 2006. Malaria mortality also rose by an estimated 19*9% since 1990 to 1*17 million deaths in 2010. Tuberculosis killed 1*2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34*5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1*5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12*9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1*3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5*1 million deaths) was marginally higher in 2010 (9*6%) compared with two decades earlier (8*8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1*3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

Infectious complications of cardiac surgery are often severe and life threatening. Statins having both immunomodulatory and anti-inflammatory effects were intuitively thought to influence the development of postsurgical infections. We sought to systematically examine whether any association exists between statin use and risk of infectious complications in patients undergoing cardiac surgery. We searched Ovid MEDLINE, Ovid EMBASE, Thomson Scientific Web of Science, and Elsevier Scopus from inception through February 2011 for comparative studies examining the association between statin use and risk of postoperative infections in patients undergoing cardiac surgery. We contacted a study's author for missing information. We conducted a random-effects meta-analysis of individual studies' odds ratios (adjusted for potential confounders). We identified 6 cohort studies for inclusion, 3 of which were conducted in Canada and 3 of which were conducted in the United States. Four were single-center studies, and 2 were population based. Exposure ascertainment was based on a review of admission medication list or prescription databases. Infectious outcomes were heterogeneous and included surgical site infections within 30 days, serious infections (sepsis), or any other postoperative infection. Statin use in the preoperative period was associated with a trend toward reduction in the incidence of postoperative infections in patients who underwent cardiac surgery (odds ratio, 0.81 [95% confidence interval, 0.64–1.01];P= .06;I2= 75%). Heterogeneity was explained by country effect. Studies performed in Canada showed weaker associations than studies performed in the United States. This difference could not be attributed to study quality alone. We did not find good evidence to support an association between statin use and postoperative infectious complications. However, the trend toward statistical significance for this association indicates that further investigation is warranted.