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Local recurrence (LR) rates of dermatofibrosarcoma protuberans (DFSP) treated with different surgical modalities are unknown.To evaluate the differences in LR rates of DFSP treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS).Pertinent studies of DFSP treated with either WLE or MMS were identified through a search of multiple databases, including Ovid MEDLINE (1946-2018), Embase (1988-2018), Web of Science (1975-2018), and Scopus (1970-2018). Comparative 2-arm and noncomparative single-arm studies were assessed through meta-analyses.Of the 517 studies identified, 88 met inclusion criteria (12 comparative studies; 76 single-arm studies). In the 12 comparative studies, 352 patients with DFSP underwent MMS and 777 patients with DFSP underwent WLE. The LR rate was 1.7% after MMS and 3.7% after WLE (odds ratio, 1.549; 95% CI, 0.710-3.381; p = .27). In the 76 noncomparative studies, 980 patients underwent MMS (LR rate, 1.5%; 95% CI, 0.9%-2.1%; p.001), and 2,215 patients underwent WLE (LR rate, 9.4%; 95% CI, 7.5%-11.3%; p.001).The LR rate of DFSP in patients treated with MMS is lower than in patients treated with WLE. Because of high rates of postoperative DFSP LR, MMS should be strongly considered when available.

Background Ketamine, a glutamate N-methyl-d-aspartate receptor antagonist, has shown rapid antidepressant effects in treatment-resistant depression. We conducted a systematic review of studies evaluating the efficacy of intravenous ketamine augmentation in treatment-resistant depression patients with bipolar disorder. Methods Major databases were searched for open-label and randomized controlled trials (RCT). Two independent reviewers screened and selected the studies that met the inclusion criteria. Studies were selected following the standard Cochrane methodology, and the findings are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Methodological quality of the included studies was assessed using standardized measures. Results A total of 1442 articles were screened. Five studies were included in the systematic review (3 RCTs and 2 open-label studies) enrolling 110 subjects (mean age, 45.54 ± 12.65 years; 68.18% female). All the RCTs and open-label studies showed improvement in depressions symptoms after receiving a single infusion of ketamine. Included studies also suggested improvement in suicidal ideation and anhedonia after ketamine infusion. Dissociation and transient increase in blood pressure were the most common reported adverse effects with ketamine. Ketamine infusions did not increase mania symptoms. Conclusions Limited data show efficacy and feasibility of intravenous racemic ketamine in treatment-resistant bipolar depression. Further studies with larger sample size are required to strengthen the evidence.

To conduct a systematic review and meta-analysis describing the association of thyroid function with posttraumatic stress disorder (PTSD) in adults.The authors conducted a comprehensive search from databases' inception to July 20, 2018. The meta-analysis included studies that reported mean values and standard deviation (SD) of thyroid hormone levels (thyroid-stimulating hormonelsqb;TSH], free thyroxinelsqb;FT4], free triiodothyroninelsqb;FT3], total T4lsqb;TT4], and total T3lsqb;TT3]) in patients with PTSD compared with controls. Five reviewers worked independently, in duplicate, to determine study inclusion, extract data, and assess risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each variable. Random-effects models for meta-analyses were applied.The meta-analysis included 10 observational studies at low-to-moderate risk of bias. Studies included 674 adults (373 PTSD, 301 controls). The meta-analytic estimates showed higher levels of FT3 (+0.28 pg/mL; P = .001) and TT3 (+18.90 ng/dL; P = .005) in patients with PTSD compared to controls. There were no differences in TSH, FT4, or TT4 levels between groups. In the subgroup analysis, patients with combat-related PTSD still had higher FT3 (+0.36 pg/mL; P = .0004) and higher TT3 (+31.62 ng/dL; P.00001) compared with controls. Conversely, patients with non-combat-related PTSD did not have differences in FT3 or TT3 levels compared with controls.There is scarce evidence regarding the association of thyroid disorders with PTSD. These findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD.

Objective Shared decision-making (SDM) is a process of collaboration between patients and clinicians. An increasing number of educational programs to teach SDM have been developed. We aimed to summarize and evaluate the body of evidence assessing the outcomes of these programs. Methods We conducted a systematic review of studies that aimed to teach SDM to medical trainees. Reviewers worked independently and in duplicate to select studies, extract data and evaluate the risk of bias. Results Eighteen studies were included. Most studies focused on residents/fellows (61 %) and combined a didactic component with a practical experience (50 % used a standardized patient). Overall, participants reported satisfaction with the courses. The effects on knowledge, attitudes/confidence and comfort with SDM were small; no clear improvement on SDM skills was noted. Evaluation of clinical behavior and outcomes was limited (3/18 studies). Studies had moderate risk of bias. Conclusion Very low quality evidence suggests that educational programs for teaching SDM to medical trainees are viewed as satisfactory and have a small impact on knowledge and comfort with SDM. Their impact on clinical skills, behaviors and patient outcomes is less clear. Practical implications Integration of formal and systematic outcomes evaluation (effects on behavior/clinical practice) should be part of future programs.

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.

Objective: To assess the extent to which evaluations of shared decision making (SDM) assess the extent and quality of humanistic communication (i.e., respect, compassion, empathy).Methods: We systematically searched Web of Science and Scopus for prospective studies published between 2012 and February 2018 that evaluated SDM in actual clinical decisions using validated SDM measures. Two reviewers working independently and in duplicate extracted all statements from eligible studies and all items from SDM measurement instruments that referred to humanistic patient-clinician communication.Results: Of the 154 eligible studies, 14 (9%) included >= 1 statements regarding humanistic communication, either in framing the study (N = 2), measuring impact (e.g., empathy, respect, interpersonal skills; N = 9), as patients'/clinicians' accounts of SDM (N = 2), in interpreting study results (N = 3), and in discussing implications of study findings (N = 3). Of the 192 items within the 11 SDM measurement instruments deployed in the included studies, 7 (3.6%) items assessed humanistic communication.Conclusion: Assessments of the quality of SDM focus narrowly on SDM technique and rarely assess humanistic aspects of patient-clinician communication. Practice implications: Considering SDM as merely a technique may reduce SDM's patient-centeredness and undermine its' contribution to patient care. (c) 2018 Elsevier B.V. All rights reserved.

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.

BACKGROUND Comprehensive treatment recommendations for Merkel cell carcinoma are complex. We aimed to systematically review the published data on recurrence and mortality rates associated with various treatment approaches for Merkel cell carcinoma. METHODS Search of MEDLINE, Embase, Web of Science, and Scopus from inception to August 2015. Studies were included that reported comparative survival and recurrence data for two or more treatment modalities. Two reviewers independently reviewed and abstracted recurrence and mortality rates. Event rates for individual treatment arms in each study were pooled and meta-analyzed across studies using a random-effects model. RESULTS Fifty-two retrospective studies met inclusion criteria, revealing a total of 1,804 patients with primary Merkel cell carcinoma with data available for analyses. The recurrence rate was higher for surgery alone (55.0%) versus a combination of surgery and radiotherapy (39.0%) (odds ratio, 2.089; 95% CI, 1.374-3.177; P

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.

BackgroundThe relationship between delayed gastric emptying and upper GI symptoms (UGI Sx) is controversial.ObjectiveTo assess association between gastric emptying and UGI Sx, independent of treatment.DesignWe performed a systematic review and meta-analysis of the literature from 2007 to 2017, review of references and additional papers identified by content expert. We included studies evaluating the association between gastric emptying and nausea, vomiting, early satiety/postprandial fullness, abdominal pain and bloating. Covariate analyses included optimal gastric emptying test method, gastric emptying type (breath test or scintigraphy) and patient category. Meta-regression compared the differences based on type of gastric emptying tests.ResultsSystematic review included 92 gastric emptying studies (26 breath test, 62 scintigraphy, 1 ultrasound and 3 wireless motility capsule); 25 of these studies provided quantitative data for meta-analysis (15 scintigraphy studies enrolling 4056 participants and 10 breath test studies enrolling 2231 participants). Meta-regression demonstrated a significant difference between optimal and suboptimal gastric emptying test methods when comparing delayed gastric emptying with nausea and vomiting. On evaluating studies using optimal gastric emptying test methodology, there were significant associations between gastric emptying and nausea (OR 1.6, 95% CI 1.4 to 1.8), vomiting (OR 2.0, 95% CI 1.6 to 2.7), abdominal pain (OR 1.5, 95% CI 1.0 to 2.2) and early satiety/fullness (OR 1.8, 95% CI 1.2 to 2.6) for patients with UGI Sx; gastric emptying and early satiety/fullness in patients with diabetes; gastric emptying and nausea in patients with gastroparesis.ConclusionsThe systematic review and meta-analysis supports an association between optimally measured delayed gastric emptying and UGI Sx.

Background Several pharmacologic treatments for hirsutism are used in practice; however, their relative efficacy is unclear. Methods We searched MEDLINE, EMBASE, and CENTRAL through January 2017 for randomized controlled trials (RCTs) with follow-up of at least 6 months that evaluated antiandrogens, insulin sensitizers, and oral contraceptives in women with hirsutism. Independent pairs of reviewers selected and appraised trials. Random-effects network meta-analysis was used to compare individual drugs and classes. Results We included 43 trials. Estrogen-progestin oral contraceptives pills (OCPs), antiandrogens, and insulin sensitizers were superior to placebo, with standardized mean reductions (95% confidence intervals) of -0.94 (-1.49 to -0.38), -1.29 (-1.80 to -0.79), and -0.62 (-1.00 to -0.23), respectively. Antiandrogen monotherapy, the combination of OCP and antiandrogen, the combination of OCPs and insulin sensitizer, and the combination of antiandrogen and insulin sensitizer were superior to insulin sensitizer monotherapy. The combination of OCPs and antiandrogen was superior to OCPs. Antiandrogen monotherapy with flutamide, finasteride, and spironolactone were each superior to placebo but similar to each other in efficacy. OCPs containing levonorgestrel, cyproterone acetate, or drospirenone were similar in effectiveness to other OCPs or had trivial differences. The certainty in comparisons with placebo was moderate and for head-to-head comparisons was low. Conclusions Estrogen-progestin OCPs, antiandrogens, and insulin sensitizers are superior to placebo for the treatment of hirsutism.

Background Replacing sitting with standing is one of several recommendations to decrease sedentary time and increase the daily energy expenditure, but the difference in energy expenditure between standing versus sitting has been controversial. This systematic review and meta-analysis aimed to determine this difference. Designs and methods We searched Ovid MEDLINE, Ovid Embase Scopus, Web of Science and Google Scholar for observational and experimental studies that compared the energy expenditure of standing versus sitting. We calculated mean differences and 95% confidence intervals using a random effects model. We conducted different predefined subgroup analyses based on characteristics of participants and study design. Results We identified 658 studies and included 46 studies with 1184 participants for the final analysis. The mean difference in energy expenditure between sitting and standing was 0.15 kcal/min (95% confidence interval (CI) 0.12–0.17). The difference among women was 0.1 kcal/min (95% CI 0.0–0.21), and was 0.19 kcal/min (95% CI 0.05–0.33) in men. Observational studies had a lower difference in energy expenditure (0.11 kcal/min, 95% CI 0.08–0.14) compared to randomised trials (0.2 kcal/min, 95% CI 0.12–0.28). By substituting sitting with standing for 6 hours/day, a 65 kg person will expend an additional 54 kcal/day. Assuming no increase in energy intake, this difference in energy expenditure would be translated into the energy content of about 2.5 kg of body fat mass in 1 year. Conclusions The substitution of sitting with standing could be a potential solution for a sedentary lifestyle to prevent weight gain in the long term. Future studies should aim to assess the effectiveness and feasibility of this strategy.

Cell therapy based on the trophic, mitogenic, and immunomodulatory capacity of mesenchymal stem cells is a promising treatment modality for degenerative musculoskeletal conditions. Local anesthetics have been commonly used in interventional procedures for alleviating pain, but local anesthetics may have negative impact on MSC dosing because of cytotoxicity or other biological effects. Because previous studies have not reached consensus yet on the potential complications of local anesthetics in cell therapy, we reviewed 11 studies that involve in vitro experimentation with MSCs using aminoamide-type anesthetics including lidocaine, ropivacaine, mepivacaine, bupivacaine, articaine, and prilocaine. Three studies that compare the effects of different types of local anesthetic agents showed that ropivacaine has the least detrimental effects on mesenchymal stem cell populations, whereas lidocaine seems to have the most significant effects on stem cell viability. Concentration- and time-dependent effects on cell viability were reported with bupivacaine, ropivacaine, lidocaine, and mepivacaine. We conclude that local anesthetic agents have time- and concentration-dependent detrimental effects on MSCs. However, in vivo studies will be required to understand the interactions of these agents with MSCs, because in vitro studies cannot replicate the pharmacokinetics of anesthetics in vivo or the recovery of MSCs in a more physiological environment.

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.

Patients with ankylosing (AS) often do not have a satisfactory response to, or could not tolerate, non-steroidal anti-inflammatory drugs (NSAIDs). Several biologic agents are available for such patients. However, the comparative efficacy of these treatments remains unknown as head-to-head randomized controlled trials (RCTs) are not available. RCTs examining the efficacy of biologic agents in patients with AS who had inadequate response to, or could not tolerate, NSAIDs were identified. If at least two RCTs were available for a given biologic agent, the pooled odds ratio (OR) and 95% confidence interval (CI) of achieving 20% improvement according to the Ankylosing Spondylitis Assessment Study group response criteria 20 (ASAS20) across trials were calculated. The pooled OR for each biologic agent was then compared to each other using the indirect comparison technique. A total of 14 RCTs of older TNF inhibitors, two RCTs of secukinumab, one RCT of certolizumab, and one RCT of tofacitinib were identified. No significant difference in any indirect comparisons was observed with the p values ranging from 0.12 to 0.74. The likelihood of achieving the ASAS20 response in patients AS who failed or could not tolerate NSAIDs was not significantly different between older TNF inhibitors, secukinumab, certolizumab, and tofacitinib. However, the analysis is limited by the small sample size with only one RCT for certolizumab and tofacitinib.

ObjectiveBioprosthetic valves are being used with increased frequency for valve replacement, with controversy regarding risk:benefit ratio compared with mechanical valves in younger patients. However, prior studies have been too small to provide comparative estimates of less common but serious adverse events such as infective endocarditis. We aimed to compare the incidence of infective endocarditis between bioprosthetic valves and mechanical valves.MethodsWe searched PubMed, Cochrane, EMBASE, Scopus and Web of Science from inception to April 2018 for studies comparing left-sided aortic and mitral bioprosthetic to mechanical valves for randomised trials or observational studies with propensity matching. We used random-effects model for our meta-analysis. Our primary outcome of interest was the rate of infective endocarditis at follow-up.Results13 comparison groups with 43 941 patients were included. Mean age was 59±7 years with a mean follow-up of 10.4±5.0 years. Patients with bioprosthetic valves had a higher risk of infective endocarditis compared with patients receiving mechanical valves (OR 1.59, 95% CI 1.35 to 1.88, p2=0%). Exclusion of the study with maximum weight did not change the results of the analysis (OR 1.57, 95% CI 1.14 to 2.17, p=0.006). A meta-regression of follow-up time on incidence of infective endocarditis was not statistically significant (p=0.788) indicating difference in follow-up times did not alter the pooled risk of infective endocarditis.ConclusionsBioprosthetic valves may be associated with a higher risk of infective endocarditis. These data should help guide the discussion when deciding between bioprosthetic and mechanical valves in individual patients.

Study objective To summarize interventions that impact the experience of older adults in the emergency department (ED) as measured by patient experience instruments. Methods This is a systematic review to evaluate interventions aimed to improve geriatric patient experience in the ED. We searched Ovid CENTRAL, Ovid EMBASE, Ovid MEDLINE and PsycINFO from inception to January 2019. The main outcome was patient experience measured through instruments to assess patient experience or satisfaction. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the confidence in the evidence available. Results The search strategy identified 992 studies through comprehensive literature search and hand-search of reference lists. A total of 21 studies and 3163 older adults receiving an intervention strategy aimed at improve patient experience in the ED were included. Department-wide interventions, including geriatric ED and comprehensive geriatric assessment unit, focused care coordination with discharge planning and referral for community services, were associated with improved patient experience. Providing an assistive listening device to those with hearing loss and having a pharmacist reviewing the medication list showed an improved patient perception of quality of care provided. The confidence in the evidence available for the outcome of patient experience was deemed to be very low. Conclusion While all studies reported an outcome of patient experience, there was significant heterogeneity in the tools used to measure it. The very low certainty in the evidence available highlights the need for more reliable tools to measure patient experience and studies designed to measure the effect of the interventions.

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.

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.

Counseling for patients with primary hyperparathyroidism (PHPT) and mild hypercalcemia without indications for surgical intervention requires accurate estimates of the potential benefits of parathyroidectomy. We aim to summarize the available evidence regarding the benefits of parathyroidectomy that patients with mild PHPT without indications for surgery experience compared to observation. We searched multiple databases from inception to August 2015. We included randomized controlled trials (RCT) and observational studies that evaluated changes in bone health, quality of life or neuropsychiatric symptoms, or in the risk of nephrolithiasis, cardiovascular events, or death between patients undergoing parathyroidectomy or active surveillance. Eight studies were eligible. Risk differences were not significant, in part due to lack of events (fractures, nephrolithiasis, cardiovascular events, or deaths). No significant differences were observed across measures of bone health, quality of life, and neuropsychiatric symptoms. A single RCT evaluating bone mineral density (BMD) changes at 5 years found a small statistically significant effect favoring parathyroidectomy. Patients with mild PHPT without indications for surgery experience a limited number of adverse consequences during short-term follow-up limiting our ability to estimate the benefit of surgery during this timeframe. This information is helpful as these patients consider surgery versus active surveillance. Long-term data is warranted to determine who benefits in the long run from surgical intervention and the extent to which this benefit affects outcomes that matter to patients.

Patients with Turner syndrome have adverse bone and cardiovascular outcomes from chronic estrogen deficiency. Hence, long-term estrogen replacement therapy is the cornerstone treatment. The estimates of its effect and optimal use, however, remain uncertain. We aimed to summarize the benefits and harms of estrogen replacement therapy on bone, cardiovascular, vasomotor and quality of life outcomes in patients with Turner syndrome. A comprehensive search of four databases was performed from inception through January 2016. Randomized clinical trials and observational cohort studies studying the effect of estrogen replacement therapy in patients with Turner syndrome under the age of 40 were included. Independently and in duplicate reviewers selected studies, extracted data and assessed risk of bias. Subgroup analyses were based on route of administration and type of estrogen formulation. Twenty-five studies at moderate to high risk of bias (12 randomized trials, 13 cohort studies) with 771 patients were included. Using random-effects models, estrogen replacement therapy showed an increase in bone mineral density [weighted mean change from baseline 0.09 g/cm2 (0.04-0.14)] that differed by type of estrogen but not route of administration. Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [weighted mean difference 9.33 mg/dl (4.82-13.85)] with no significant effect on other lipid fractions. The current evidence suggests possible benefit of estrogen replacement therapy on bone mineral density and high density lipoprotein cholesterol. Whether this improvement translates into changes in patient important outcomes (cardiovascular events or fractures) remains uncertain. Larger randomized clinical trials with direct comparisons on patient important outcomes are necessary.

BACKGROUND Valve selection in patients with end-stage renal disease (ESRD) is uncertain. We performed a systematic review and meta-analysis to compare clinical outcome in ESRD patients undergoing valve replacement. METHODS We systematically searched multiple databases (2000–October 2015) to identify original studies comparing adverse events between mechanical and biological valve replacement in ESRD patients. End-points studied were: postoperative mortality, bleeding events, need for re-operation, and late survival. A random-effect inverse-variance weighted analysis was performed; event rates are compared as odds ratio (OR and 95% confidence interval) and hazard ratios (HR) for time-to-event data. Mechanical valve and tissue valve replacement were considered as study and control cohorts, respectively. RESULTS Fifteen retrospective studies (5523 mechanical and 1600 tissue valve) were included in our meta-analysis. Early mortality was comparable (OR 1.15 [0.77; 1.72]; p = 0.49). The mean follow-up among studies ranged from 1.6–15 years. Bleeding was significantly higher after mechanical valve replacement (OR 2.55 [1.53; 4.26]; p = 0.0003). Structural valve degeneration was present in only 0.6% patients after a tissue valve replacement. Overall survival after valve replacement was poor (median 2.61 years); valve choice did not influence this outcome (pooled HR 0.87 [0.73; 1.04]; p = 0.14). CONCLUSION Operative mortality in ESRD patients is comparable between mechanical and tissue valve replacement. Major bleeding episodes are significantly higher after mechanical valve replacement but structural degeneration in tissue valves during the follow-up period is low. Based on the findings from this meta-analysis, we would recommend using tissue valves in patients with ESRD.

Parathyroidectomy is a definitive treatment for primary hyperparathyroidism. Patients contemplating this intervention will benefit from knowledge regarding the expected outcomes and potential risks of the currently available surgical options. To appraise and summarize the available evidence regarding benefits and harms of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE). A comprehensive search of multiple databases (MEDLINE, EMBASE, and Scopus) from each database’s inception to September 2014 was performed. Eligible studies evaluated patients with primary hyperparathyroidism undergoing MIP or BNE. Reviewers working independently and in duplicate extracted data and assessed the risk of bias. We identified 82 observational studies and 6 randomized trials at moderate risk of bias. Most of them reported outcomes after MIP (n = 71). Using random-effects models to pool results across studies, the cure rate was 98 % (95 % CI 97–98 %, I 2 = 10 %) with BNE and 97 % (95 % CI 96–98 %, I 2 = 86 %) with MIP. Hypocalcemia occurred in 14 % (95 % CI 10–17 % I 2 = 93 %) of the BNE cases and in 2.3 % (95 % CI 1.6–3.1 %, I 2 = 87 %) with MIP (P

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.

Background Atypical fibroxanthoma (AFX) is a fibrohistiocytic tumor with relatively high local recurrence rates but low metastatic potential. Wide local excision (WLE) and Mohs micrographic surgery (MMS) are common treatments, although no consensus exists regarding optimal therapy. Objective To systematically review evidence of AFX recurrence and metastatic rates after different surgical modalities. Methods A comprehensive search was performed for articles published from 1946 or database inception to March 20, 2017. Studies selected included those that had 5 or more patients with atypical fibroxanthoma treated surgically. Two reviewers independently abstracted the data. Risk of bias was assessed with the Newcastle-Ottawa scale. Main outcomes and measures included recurrence and metastasis. Results In total, 23 studies were selected (907 patients and 914 tumors); 175 patients were treated with MMS (recurrence rate 2.0%, 95% confidence interval [CI] 0%-4.1%; metastatic rate 1.9%, 95% CI 0.1%-3.8%), and 732 were treated with WLE (recurrence rate 8.7%, 95% CI 5%-12.3%; metastasis rate 1%, 95% CI 0.2%-1.9%). Among immunocompromised patients, no recurrence or metastases developed in the MMS subgroup, although 4 of 10 recurred and 1 of 10 metastasized in the WLE subgroup. Limitations Low quality of the studies published. Conclusion MMS for atypical fibroxanthoma is associated with a lower recurrence rate than WLE.

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.