Erwin, Patricia J.

BACKGROUND Complete removal of melanoma is a primary goal of excision, and local recurrence is one measure to evaluate the efficacy of surgical technique. OBJECTIVE To compare published local recurrence rates for melanoma treated with Mohs micrographic surgery (MMS) or staged excision versus wide local excision (WLE). METHODS AND MATERIALS Search of 6 databases identified comparative and noncomparative studies that reported local recurrence rates after MMS, staged excision, or WLE for melanoma. Random-effects meta-analysis was used to estimate odds ratios and 95% confidence interval (CI) from comparative studies and event rates from noncomparative studies. RESULTS Of the 71 studies included (16,575 patients), 12 were comparative studies (2,683 patients) and 56 were noncomparative studies (13,698 patients). Comparative studies showed increased recurrence after WLE compared with MMS or staged excision (odds ratio [OR], 2.5; 95% CI, 1.4–4.6) and compared with MMS alone (OR, 3.3; 95% CI, 1.8–5.9). Pooled data from comparative and noncomparative studies showed a local recurrence rate of 7% after WLE (95% CI, 5%–11%), 3% after staged excision (95% CI, 2%–4%), and less than 1% after MMS (95% CI, 0%–1%). Statistical heterogeneity was moderate to high. CONCLUSION Local recurrence of melanoma is significantly lower after MMS (<1%) and staged excision (3%) compared with WLE (7%).

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.

AbstractBackgroundComprehensive 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.MethodsSearch 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.ResultsFifty‐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 < 0.001). Combination therapy including surgery, radiotherapy, and chemotherapy had a higher mortality rate (44.6%) than did combined surgery and radiotherapy (23.2%) (odds ratio, 2.688; 95% CI, 1.196–6.037; P = 0.02).ConclusionsThe treatment of Merkel cell carcinoma with surgery plus adjuvant radiotherapy may produce lower recurrence rates.

Background The association between the 9p21-3 locus and coronary heart disease (CHD) is well known. We performed a systematic review of the literature to assess whether this locus was associated with severity of coronary atherosclerosis. Data Sources Multiple relevant electronic databases were searched through September 2012 for English language studies with comparative design. Data extraction We tested the association of the 9p21-3 locus: 1) measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CHD Prognostic Index (Dc.PI)]. 2) angiographic outcomes [change in minimum lumen diameter ([[Unable to Display Character: &#8710;]]MLD) and number of new lesions at follow-up] and 3) key clinical outcomes (all-cause mortality, recurrent myocardial infarction and need for coronary revascularization). Genotypes were classified either as homozygous low risk (Lo) or homozygous high risk (Hi). Data Synthesis Relative risks (RR) were pooled using the random effects model. Seventeen distinct data sets that included 15,826 participants were analyzed. Ten studies (n=9807) reported number of diseased vessels at baseline. Hi genotype was associated with a 33.7% increased risk of triple vessel disease (95% CI 1.08-1.65; p=0.01). The Hi genotype was associated 0.27 higher baseline Gensini Score (95% CI 0.04-0.48; p=0.01) in 3787 individuals. The locus was not associated with Dc.PI [RR=0.21 (95% CI -0.14-0.55; p=0.25)]. The high risk genotype did not predict [[Unable to Display Character: &#8710;]]MLD or number of new lesions at follow-up. There was no difference between Hi and Lo genotypes in terms of all-cause mortality [RR=1.13 (95%CI 0.90-1.41;p=0.28)], recurrent myocardial infarction (95%CI 0.92-1.40; p=0.24) or frequency of coronary revascularization [RR=1.101 95% CI (0.78-1.57); p=0.56]. Conclusion An association between 9p21-3 and greater baseline severity of coronary atherosclerosis was seen in this meta-analysis. However no association was seen between 9p21-3 and adverse angiographic and clinical outcomes which may be due to diminishing genetic risk following dietary modification and statin therapy.

Abstract 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.

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.

Objective Bioprosthetic 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. Methods We 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. Results 13 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, p<0.001) with an absolute risk reduction of 9 per 1000 (95% CI 6 to 14). Heterogeneity within the included studies was low (I2=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. Conclusions Bioprosthetic 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.

SummaryBackgroundWhen 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).AimTo 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.MethodsA 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.ResultsWe 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.ConclusionsTherapeutic 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.

AbstractBackgroundNo consensus exists regarding optimal strategy for antifungal prophylaxis following lung transplant.ObjectiveTo review data regarding antifungal prophylaxis on the development of fungal infections.Study selection/AppraisalWe 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.MethodsOf 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 < 6 months and long term ≥ 6 months).ResultsWe found no difference in the odds of fungal infection with universal prophylaxis (49/101) compared to no prophylaxis (36/93) (OR 0.76, CI: 0.03‐17.98; I2 = 93%) and preemptive therapy (25/195) compared to universal prophylaxis (35/222) (OR 0.91, CI: 0.06‐13.80; I2 = 93%). The cumulative incidence of fungal infections within 12 months was not different with nebulized amphotericin (0.08, CI: 0.04‐0.13; I2 = 87%) compared to systemic triazoles (0.07, CI: 0.03‐0.11; I2 = 21%) (P = .65). Likewise, duration of prophylaxis did not impact the incidence of fungal infections (short term: 0.11, CI: 0.05‐0.17; I2 = 89%; long term: 0.06, CI: 0.03‐0.08; I2 = 51%; P = .39).ConclusionsWe have insufficient evidence to support or exclude a benefit of antifungal prophylaxis.