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The decolorization of rhodamine B was examined using the white rot fungus Coriolopsis caperata, which was isolated from the Peat Swamp Forest at CIMTROP in Sebangau, Central Kalimantan. The experiments were carried out with varying concentrations of dye (10-100 mg/L) and incubation times (2-16 days) in a modified glucose-peptone medium. During the decolorization process, the enzyme activity of laccase (EC 1.10.3.2) was monitored. The findings revealed a clear link between enzyme activity and decolorization efficiency of C. caperata. The ideal conditions for fungal laccase synthesis and decolorization occurred at a dye concentration of 60 mg/L and were achieved for 12 days. These findings suggest that the white rot fungus C. caperata, isolated from the Central Kalimantan Forest could be developed into a novel bioremediation strategy for synthetic dyes.

Alat ukur kekentalan oli SAE 10-30 telah dirancang bangun dengan menggunakan metode Falling Ball Viscometer (FBV) small tube. Tabung yang digunakan berukuran kecil dengan panjang 15 cm dan diameter 5,5 mm. Alat ukur dilengkapi dengan dua sistem sensor yaitu Light Emitting Diode (LED) infra merah dan fotodioda. Data waktu tempuh bola magnetik yang direkam oleh sistem sensor diproses oleh mikrokontroler Arduino nano untuk kemudian ditampilkan dalam bentuk nilai kekentalan pada layar Liquid Crystal Display (LCD). Temperatur pengukuran divariasikan dari 30 oC sampai 100 oC. Nilai regresi yang di peroleh saat temperatur dinaikkan yaitu 0,991. Nilai Regresi pada saat temperature diturunkan yaitu 0,977. Nilai regresi yang didapatkan menunjukkan bahwa alat yang telah dirancang bekerja dengan baik dan dapat digunakan untuk menentukan nilai kekentalan oli SAE 10-30.  Kata kunci: Falling Ball Viscometer (FBV), Arduino Nano, Kekentalan, Oli SAE 10-30, Temperatur.

Virtual reality (VR) as a distraction tool decreases anxiety and fear in children undergoing procedures, but its use has not been studied during transthoracic echocardiograms (TTEs). We hypothesized that VR in children undergoing pre-intervention TTEs decreases anxiety and fear and increases TTE study comprehensiveness and diagnostic accuracy when compared with standard distractors (television, mobile devices). Patients (6-18 years old) scheduled for pre-intervention TTEs at Lucile Packard Children's Hospital in 2021 and 2022 were prospectively enrolled and randomized to VR and non-VR groups. Patients completed pre- and post-TTE surveys using the Children's Anxiety Meter-State (CAM-S) and Children's Fear Scale (CFS). Patients, parents, and sonographers completed post-TTE experience surveys. TTEs were reviewed by pediatric cardiologists for study comprehensiveness and compared with electronic medical records for diagnostic accuracy. Among 67 enrolled patients, 6 declined VR, 31 randomized to the VR group, and 30 to the non-VR group. Anxiety (average CAM-S difference 0.78 ± 1.80, p = 0.0012) and fear (average CFS difference 0.36 ± 0.74, p = 0.0005) decreased in both groups. There was no difference between groups in the change in anxiety and fear pre- and post-TTE (p = 0.96-1.00). TTE study comprehensiveness and diagnostic accuracy were high in both groups. Procedure time (time in the echocardiography room) was less for the VR group (48.4 ± 18.1 min) than the non-VR group (58.8 ± 24.4 min), but without a statistically significant difference (p = 0.075). VR is similar to standard distractors and may decrease procedure time. Patients, parents, and sonographers rated the VR experience highly and encouraged its use with future procedures., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Caring for pediatric lacerations in the emergency department (ED) is typically painful because of irrigation and suturing. To improve this painful experience, we aimed to increase the use of a topical anesthetic, Eutectic Mixture of Local Anesthetics (EMLA) on eligible pediatric lacerations with an attainable, sustainable, and measurable goal of 60%. The baseline rate of applying topical anesthetic to eligible lacerations was 23% in our ED. We aimed to increase the use of topical anesthetics on eligible pediatric lacerations to a measurable goal of 60% within 3 months of implementing our intervention., Methods: We conducted a prospective, single-center, interrupted time series, ED quality improvement project from November 2019 to July 2020. A multidisciplinary team of physicians and nurses performed a cause-and-effect analysis identifying 2 key drivers: early placement of EMLA and physician buy-in on which we built our Plan, Do, Study, and Act (PDSA) cycles. We collected data on number of eligible patients receiving EMLA, as well as patient and physician feedback via phone calls within 2 days after encounter. Balancing measures included ED length of stay (LOS), patient and physician satisfaction with EMLA, and adverse effects of EMLA., Results: We needed 3 PDSA cycles to reach our goal of 60% in 3 months, which was also maintained for 5 months. The PDSA cycles used educational interventions, direct provider feedback about noncompliance, and patient satisfaction results obtained via phone calls. Balancing measures were minimally impacted: 75% good patient satisfaction, no adverse events but an increase in LOS of patients who received EMLA compared with those who did not (1.79 ± 0.66 vs 1.41 ± 0.83 hours, P < 0.001). The main reasons for dissatisfaction for physicians were the increased LOS and the preference for procedural sedation or intranasal medications., Conclusions: With a few simple interventions, our aim of applying EMLA to 60% of eligible pediatric lacerations was attained and maintained., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The optimal strategy for revascularization in infrainguinal chronic limb-threatening ischemia (CLTI) remains debatable. Comparative trials are scarce, and daily decisions are often made using anecdotal or low-quality evidence., Methods: We searched multiple databases through May 7, 2017, for prospective studies with at least 1-year follow-up that evaluated patient-relevant outcomes of infrainguinal revascularization procedures in adults with CLTI. Independent pairs of reviewers selected articles and extracted data. Random-effects meta-analysis was used to pool outcomes across studies., Results: We included 44 studies that enrolled 8602 patients. Periprocedural outcomes (mortality, amputation, major adverse cardiac events) were similar across treatment modalities. Overall, patients with infrapopliteal disease had higher patency rates of great saphenous vein graft at 1 and 2 years (primary: 87%, 78%; secondary: 94%, 87%, respectively) compared with all other interventions. Prosthetic bypass outcomes were notably inferior to vein bypass in terms of amputation and patency outcomes, especially for below knee targets at 2 years and beyond. Drug-eluting stents demonstrated improved patency over bare-metal stents in infrapopliteal arteries (primary patency: 73% vs 50% at 1 year), and was at least comparable to balloon angioplasty (66% primary patency). Survival, major amputation, and amputation-free survival at 2 years were broadly similar between endovascular interventions and vein bypass, with prosthetic bypass having higher rates of limb loss. Overall, the included studies were at moderate to high risk of bias and the quality of evidence was low., Conclusions: There are major limitations in the current state of evidence guiding treatment decisions in CLTI, particularly for severe anatomic patterns of disease treated via endovascular means. Periprocedural (30-day) mortality, amputation, and major adverse cardiac events are broadly similar across modalities. Patency rates are highest for saphenous vein bypass, whereas both patency and limb salvage are markedly inferior for prosthetic grafting to below the knee targets. Among endovascular interventions, percutaneous transluminal angioplasty and drug-eluting stents appear comparable for focal infrapopliteal disease, although no studies included long segment tibial lesions. Heterogeneity in patient risk, severity of limb threat, and anatomy treated renders direct comparison of outcomes from the current literature challenging. Future studies should incorporate both limb severity and anatomic staging to best guide clinical decision making in CLTI., (Copyright © 2019. Published by Elsevier B.V.)

Background: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies., Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method., Results: We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials., Conclusions: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women., (Copyright © 2019 Endocrine Society.)

Background: The optimal strategy for revascularization in infrainguinal chronic limb-threatening ischemia (CLTI) remains debatable. Comparative trials are scarce, and daily decisions are often made using anecdotal or low-quality evidence., Methods: We searched multiple databases through May 7, 2017, for prospective studies with at least 1-year follow-up that evaluated patient-relevant outcomes of infrainguinal revascularization procedures in adults with CLTI. Independent pairs of reviewers selected articles and extracted data. Random-effects meta-analysis was used to pool outcomes across studies., Results: We included 44 studies that enrolled 8602 patients. Periprocedural outcomes (mortality, amputation, major adverse cardiac events) were similar across treatment modalities. Overall, patients with infrapopliteal disease had higher patency rates of great saphenous vein graft at 1 and 2 years (primary: 87%, 78%; secondary: 94%, 87%, respectively) compared with all other interventions. Prosthetic bypass outcomes were notably inferior to vein bypass in terms of amputation and patency outcomes, especially for below knee targets at 2 years and beyond. Drug-eluting stents demonstrated improved patency over bare-metal stents in infrapopliteal arteries (primary patency: 73% vs 50% at 1 year), and was at least comparable to balloon angioplasty (66% primary patency). Survival, major amputation, and amputation-free survival at 2 years were broadly similar between endovascular interventions and vein bypass, with prosthetic bypass having higher rates of limb loss. Overall, the included studies were at moderate to high risk of bias and the quality of evidence was low., Conclusions: There are major limitations in the current state of evidence guiding treatment decisions in CLTI, particularly for severe anatomic patterns of disease treated via endovascular means. Periprocedural (30-day) mortality, amputation, and major adverse cardiac events are broadly similar across modalities. Patency rates are highest for saphenous vein bypass, whereas both patency and limb salvage are markedly inferior for prosthetic grafting to below the knee targets. Among endovascular interventions, percutaneous transluminal angioplasty and drug-eluting stents appear comparable for focal infrapopliteal disease, although no studies included long segment tibial lesions. Heterogeneity in patient risk, severity of limb threat, and anatomy treated renders direct comparison of outcomes from the current literature challenging. Future studies should incorporate both limb severity and anatomic staging to best guide clinical decision making in CLTI., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Several pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology., Objective: We conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations., Study Selection: Multiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model., Findings: 30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV 1 ) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD -0.90 (95% CI -1.58 to -0.22)) and improving quality of life scores assessed by the St George's Respiratory Questionnaire (WMD -6.07 (95% CI -10.7 to -1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy., Conclusions: Moderate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations., Competing Interests: Competing interests: ATH has been on advisory boards for Bayer, Griffolls and Pfizer., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

Objective: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials., Methods: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables., Results: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias., Conclusion: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Importance: Childhood anxiety is common. Multiple treatment options are available, but existing guidelines provide inconsistent advice on which treatment to use., Objectives: To evaluate the comparative effectiveness and adverse events of cognitive behavioral therapy (CBT) and pharmacotherapy for childhood anxiety disorders., Data Sources: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and SciVerse Scopus from database inception through February 1, 2017., Study Selection: Randomized and nonrandomized comparative studies that enrolled children and adolescents with confirmed diagnoses of panic disorder, social anxiety disorder, specific phobias, generalized anxiety disorder, or separation anxiety and who received CBT, pharmacotherapy, or the combination., Data Extraction and Synthesis: Independent reviewers selected studies and extracted data. Random-effects meta-analysis was used to pool data., Main Outcomes and Measures: Primary anxiety symptoms (measured by child, parent, or clinician), remission, response, and adverse events., Results: A total of 7719 patients were included from 115 studies. Of these, 4290 (55.6%) were female, and the mean (range) age was 9.2 (5.4-16.1) years. Compared with pill placebo, selective serotonin reuptake inhibitors (SSRIs) significantly reduced primary anxiety symptoms and increased remission (relative risk, 2.04; 95% CI, 1.37-3.04) and response (relative risk, 1.96; 95% CI, 1.60-2.40). Serotonin-norepinephrine reuptake inhibitors (SNRIs) significantly reduced clinician-reported primary anxiety symptoms. Benzodiazepines and tricyclics were not found to significantly reduce anxiety symptoms. When CBT was compared with wait-listing/no treatment, CBT significantly improved primary anxiety symptoms, remission, and response. Cognitive behavioral therapy reduced primary anxiety symptoms more than fluoxetine and improved remission more than sertraline. The combination of sertraline and CBT significantly reduced clinician-reported primary anxiety symptoms and response more than either treatment alone. Head-to-head comparisons were sparse, and network meta-analysis estimates were imprecise. Adverse events were common with medications but not with CBT and were not severe. Studies were too small or too short to assess suicidality with SSRIs or SNRIs. One trial showed a statistically nonsignificant increase in suicidal ideation with venlafaxine. Cognitive behavioral therapy was associated with fewer dropouts than pill placebo or medications., Conclusions and Relevance: Evidence supports the effectiveness of CBT and SSRIs for reducing childhood anxiety symptoms. Serotonin-norepinephrine reuptake inhibitors also appear to be effective based on less consistent evidence. Head-to-head comparisons between various medications and comparisons with CBT represent a need for research in the field.

Objective: Multiple interventions are available to reduce excess body weight in children. We appraised the quality of evidence supporting each intervention and assessed the effectiveness on different obesity-related outcomes., Methods: We conducted a systematic search for systematic reviews of randomized controlled trials evaluating pediatric obesity interventions applied for ≥6 months. We assessed the quality of evidence for each intervention using GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach., Results: From 16 systematic reviews, we identified 133 eligible randomized controlled trials. Physical activity interventions reduced systolic blood pressure and fasting glucose (low to moderate quality of evidence). Dietary interventions with low-carbohydrate diets had a similar effect to low-fat diets in terms of body mass index (BMI) reduction (moderate quality of evidence). Educational interventions reduced waist circumference, BMI, and diastolic blood pressure (low quality of evidence). Pharmacological interventions reduced BMI (metformin, sibutramine, orlistat) and waist circumference (sibutramine, orlistat) and increased high-density lipoprotein cholesterol (sibutramine) but also raised systolic and diastolic blood pressure (sibutramine). Surgical interventions (laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy) resulted in the largest BMI reduction (moderate quality of evidence). Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education significantly reduced systolic and diastolic blood pressure, BMI, and triglycerides. Combined parent-child interventions and parent-only interventions had similar effects on BMI (low quality of evidence)., Conclusions: Several childhood obesity interventions are effective in improving metabolic and anthropometric measures. A comprehensive multicomponent intervention, however, appears to have the best overall outcomes., (Copyright © 2017 by the Endocrine Society)

Background: Excess body weight in children is associated with multiple immediate and long-term medical comorbidities. We aimed to identify the degree of reduction in excess body weight associated with cardiometabolic changes (lipid panel, liver function tests, systolic blood pressure (SBP), diastolic blood pressure, glycosylated hemoglobin, and fasting blood glucose) in overweight and obese children., Methods: We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus through February 12, 2015. We included randomized controlled trials and cohort studies that evaluated interventions to treat pediatric obesity (medication, surgery, lifestyle, and community-based interventions) with ≥ a 6-month follow-up. We used a random effects meta-regression approach to assess the association between body mass index (BMI)/weight and cardiometabolic changes., Results: We included 42 studies (37 randomized controlled trials and five cohorts) enrolling 3807 children (mean age, 12.2 years; weight, 74.7 kg; and BMI, 31.7 kg/m2). Studies had overall moderate to low risk of bias. A 1-mm Hg decrease in SBP was significantly associated with a decrease of 0.16 kg/m2 (P = .04) in BMI. A 1-mg/dL increase in HDL was significantly associated with a 0.74-kg decrease in weight (P = .02). A 1-mg/dL decrease in triglycerides was significantly associated with a 0.1-kg decrease in weight (P = .03). The remaining associations were not statistically significant., Conclusions: Weight reduction in children is associated with significant changes in several cardiometabolic outcomes, particularly HDL, SBP, and triglycerides. The magnitude of improvement may help in setting expectations and may inform shared decision-making and counseling.

Context: Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue., Objective: We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset, < 18 years)., Data Source: Sources included Medline, Embase, Cochrane Library, Scopus and Non-Indexed Citations from inception through January 2016., Study Selection: Search terms included lipodystrophy, and age 0 to 18 years. Patients with unambiguous diagnosis of lipodystrophy were included. Lipodystrophy secondary to HIV treatment was excluded., Data Synthesis: We identified 1141 patients from 351 studies. Generalized fat loss involving face, neck, abdomen, thorax, and upper and lower limbs was explicitly reported in 65% to 93% of patients with congenital generalized lipodystrophy (CGL) and acquired generalized lipodystrophy (AGL). In familial partial lipodystrophy (FPL), fat loss occurred from upper and lower limbs, with sparing of face and neck. In acquired partial lipodystrophy (APL), upper limbs were involved while lower limbs were spared. Other features were prominent musculature, acromegaloid, acanthosis nigricans and hepatosplenomegaly. Diabetes mellitus was diagnosed in 48% (n = 222) of patients with CGL (mean age at onset, 5.3 years). Hypertriglyceridemia was observed in CGL, AGL and FPL. Multiple interventions were used, with most patients receiving ≥ 3 interventions and being ≥ 18 years of age at the initiation of interventions., Conclusions: To our knowledge, this is the largest reported pooled database describing lipodystrophy patients with age at onset < 18 years. We have suggested core and supportive clinical features and summarized data on available interventions, outcomes and mortality., (Copyright © 2017 by the Endocrine Society)

Background: The comparative effectiveness of non-pharmacological treatments of depression remains unclear., Methods: We conducted an overview of systematic reviews to identify randomised controlled trials (RCTs) that compared the efficacy and adverse effects of non-pharmacological treatments of depression. We searched multiple electronic databases through February 2016 without language restrictions. Pairs of reviewers determined eligibility, extracted data and assessed risk of bias. Meta-analyses were conducted when appropriate., Result: We included 367 RCTs enrolling ∼20 000 patients treated with 11 treatments leading to 17 unique head-to-head comparisons. Cognitive behavioural therapy, naturopathic therapy, biological interventions and physical activity interventions reduced depression severity as measured using standardised scales. However, the relative efficacy among these non-pharmacological interventions was lacking. The effect of these interventions on clinical response and remission was unclear. Adverse events were lower than antidepressants., Limitation: The quality of evidence was low to moderate due to inconsistency and unclear or high risk of bias, limiting our confidence in findings., Conclusions: Non-pharmacological therapies of depression reduce depression symptoms and should be considered along with antidepressant therapy for the treatment of mild-to-severe depression. A shared decision-making approach is needed to choose between non-pharmacological therapies based on values, preferences, clinical and social context., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Excess body weight in children is associated with multiple immediate and long-term medical comorbidities. We aimed to identify the degree of reduction in excess body weight associated with cardiometabolic changes (lipid panel, liver function tests, systolic blood pressure (SBP), diastolic blood pressure, glycosylated hemoglobin, and fasting blood glucose) in overweight and obese children., Methods: We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus through February 12, 2015. We included randomized controlled trials and cohort studies that evaluated interventions to treat pediatric obesity (medication, surgery, lifestyle, and community-based interventions) with ≥ a 6-month follow-up. We used a random effects meta-regression approach to assess the association between body mass index (BMI)/weight and cardiometabolic changes., Results: We included 42 studies (37 randomized controlled trials and five cohorts) enrolling 3807 children (mean age, 12.2 years; weight, 74.7 kg; and BMI, 31.7 kg/m 2 ). Studies had overall moderate to low risk of bias. A 1-mm Hg decrease in SBP was significantly associated with a decrease of 0.16 kg/m 2 (P = .04) in BMI. A 1-mg/dL increase in HDL was significantly associated with a 0.74-kg decrease in weight (P = .02). A 1-mg/dL decrease in triglycerides was significantly associated with a 0.1-kg decrease in weight (P = .03). The remaining associations were not statistically significant., Conclusions: Weight reduction in children is associated with significant changes in several cardiometabolic outcomes, particularly HDL, SBP, and triglycerides. The magnitude of improvement may help in setting expectations and may inform shared decision-making and counseling.

Background: Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events., Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model., Results: We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81., Conclusions: Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.

Background: Leukoreduced (LR) or cytomegalovirus (CMV)-seronegative cellular blood components are commonly used to reduce the risk of transfusion-transmitted CMV infection in high-risk patients., Study Design and Methods: We performed a systematic review and meta-analysis to evaluate the evidence for the use of LR cellular blood components with or without concurrent CMV testing of donor units in patients undergoing chemotherapy or solid organ and hematopoietic stem cell transplantation, in pregnant women, in very-low-birthweight infants, and in patients with primary immunodeficiency. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from 1980 through February 2015. Studies were included if they had a comparison group. Two independent reviewers selected and appraised studies. Meta-analysis was performed when appropriate., Results: Of 457 studies screened, 11 were eligible. One study was excluded from the meta-analysis because the comparison performed differed significantly from the others. Meta-analysis of five studies that compared leukoreduction to transfusing CMV-untested blood components showed no significant difference in clinical CMV infection (relative risk [RR], 0.26; 95% confidence interval [CI], 0.04-1.57) or laboratory CMV infection (RR, 0.33; 95% CI, 0.08-1.37). Meta-analysis of three studies that compared leukoreduction to transfusing CMV-seronegative cellular components showed no significant difference in laboratory CMV infection (RR, 2.18; 95% CI, 0.96-4.98). Meta-analysis of two studies that compared adding CMV testing to leukoreduction (vs. leukoreduction alone) showed no significant difference in clinical or laboratory CMV infection. The certainty in estimates was low for all comparisons., Conclusion: At present, the scientific evidence does not favor a single strategy for reducing the risk of transfusion-related CMV infection in high-risk patients., (© 2016 AABB.)

Objective: Critical limb ischemia is associated with a significant morbidity and mortality. We systematically reviewed the evidence to compare bypass surgery with endovascular revascularization in patients with critical limb ischemia., Methods: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus through October 2014 for comparative studies (randomized and nonrandomized). Predefined outcomes of interest were mortality, major amputation, patency, and wound healing. We pooled odds ratios (ORs) of the outcomes of interest using the random-effects model., Results: Nine studies that enrolled 3071 subjects were included. There was no significant difference in mortality (OR, 0.72; 95% confidence interval [CI], 0.44-1.16) or amputation (OR, 1.2; 95% CI, 0.87-1.65). Bypass surgery was associated with higher primary patency (OR, 2.50; 95% CI, 1.25-4.99) and assisted primary patency (OR, 3.39; 95% CI, 1.53-7.51). The quality of evidence was low for mortality and amputation outcomes and moderate for patency outcomes., Conclusions: Low quality of evidence due to imprecision and heterogeneity suggests that bypass surgery and endovascular approaches may have similar effect on mortality and major amputations. However, better primary and primary assisted patency can be expected with surgery., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Critical limb ischemia (CLI) is associated with high morbidity and mortality. Because most patients with CLI will eventually undergo some type of revascularization, the natural history of CLI is not well defined, although it is important to know when patients decide to pursue treatment., Methods: We systematically searched multiple databases for controlled and uncontrolled studies of patients with CLI who did not receive revascularization with a minimum follow-up of ≥1 year. Predefined outcomes of interest were mortality, major amputation, and wound healing. Random-effects meta-analysis was used to pool cumulative incidence across studies., Results: We identified 13 studies enrolling 1527 patients. During a median follow-up of 12 months, all-cause mortality rate was 22% (confidence interval [CI], 12%-33%) and major amputation rate was 22% (CI, 2%-42%). Worsened wound or ulcer was found at 35% (CI, 10%-62%). There was a trend toward improvement in mortality and amputation rate in studies done after 1997. The quality of evidence was low because of increased risk of bias and inconsistency., Conclusions: Mortality and major amputations are common in patients who have untreated CLI during a median follow-up of 1 year, although these outcomes have improved in recent times., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this systematic review was to synthesize the existing evidence about various nonrevascularization-based therapies used to treat patients with severe or critical limb ischemia (CLI) who are not candidates for surgical revascularization., Methods: We systematically searched multiple databases through November 2014 for controlled randomized and nonrandomized studies comparing the effect of medical therapies (prostaglandin E1 and angiogenic growth factors) and devices (pumps and spinal cord stimulators). We report odds ratios (ORs) and 95% confidence intervals (CIs) of the outcomes of interest pooling data across studies using the random effects model., Results: We included 19 studies that enrolled 2779 patients. None of the nonrevascularization-based treatments were associated with a significant effect on mortality. Intermittent pneumatic compression (OR, 0.14; 95% CI, 0.04-0.55) and spinal cord stimulators (OR, 0.53; 95% CI, 0.36-0.79) were associated with reduced risk of amputation. A priori established subgroup analyses (combined vs single therapy; randomized vs nonrandomized) were not statistically significant., Conclusions: Very low-quality evidence, mainly due to imprecision and increased risk of bias, suggests that intermittent pneumatic compression and spinal cord stimulators may reduce the risk of amputations. Evidence supporting other medical therapies is insufficient., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the impact of interventions to support shared decision making (SDM) with pediatric patients., Objectives: To summarize the efficacy of SDM interventions in pediatrics on patient-centered outcomes., Data Sources: We searched Ovid Medline, Ovid Embase, Ovid Cochrane Library, Web of Science, Scopus, and Ovid PsycInfo from database inception to December 30, 2013, and performed an environmental scan., Study Eligibility Criteria: We included interventions designed to engage pediatric patients, parents, or both in a medical decision, regardless of study design or reported outcomes., Study Appraisal and Synthesis Methods: We reviewed all studies in duplicate for inclusion, data extraction, and risk of bias assessment. Meta-analysis was performed on 3 outcomes: knowledge, decisional conflict, and satisfaction., Results: Sixty-one citations describing 54 interventions met eligibility criteria. Fifteen studies reported outcomes such that they were eligible for inclusion in meta-analysis. Heterogeneity across studies was high. Meta-analysis revealed SDM interventions significantly improved knowledge (standardized mean difference [SMD] 1.21, 95% confidence interval [CI] 0.26 to 2.17, P = .01) and reduced decisional conflict (SMD -1.20, 95% CI -2.01 to -0.40, P = .003). Interventions showed a nonsignificant trend toward increased satisfaction (SMD 0.37, 95% CI -0.04 to 0.78, P = .08)., Limitations: Included studies were heterogeneous in nature, including their conceptions of SDM., Conclusions and Implications of Key Findings: A limited evidence base suggests that pediatric SDM interventions improve knowledge and decisional conflict, but their impact on other outcomes is unclear., Systematic Review Registration Number: PROSPERO CRD42013004761 (http://www.crd.york.ac.uk/PROSPERO/display&#95;record.asp?ID=CRD42013004761)., (Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Computed tomography (CT) and magnetic resonance imaging (MRI) are the major imaging modalities used for the localization of catecholamine-producing tumors (pheochromocytoma and paraganglioma). Functional imaging (FI) offers an alternative approach to localize, evaluate, and stage these tumors. Our objective was to describe the additive benefit of FI studies for patients with pheochromocytoma and paraganglioma (PPG) who have undergone MRI or CT scan evaluation. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from database inception through June 2012 for studies that included patients with biochemically proven PPGs who underwent CT or MRI and additional FI for the localization of PPGs. We included 32 studies enrolling a total of 1,264 patients with a mean age of 43-years old. The studies were uncontrolled and evaluated six FI modalities. FI tests provided small additive value to CT/MRI, aiding in the localization of only 24/1,445 primary cases (1.4 %) and 28/805 metastatic cases (3.5 %). In metastatic cases, 6-[F-18]fluoro-L-dihydroxyphenylalanine (DOPA) and fluorodopamine-PET (FDA) were the FI tests most successful at identifying disease missed by CT/MRI, providing additional benefit in 6/60 (10 %) and 5/78 (6.4 %) cases, respectively. No clinically significant findings were observed in any of the predefined subgroups. No study evaluated the impact of FI on the completeness of surgical resection or other patient-important outcomes. Observational evidence suggests that FI tests have a limited additional role in patients with PPGs who have undergone CT/MRI evaluation. However, the role of FI tests in specific subgroups of patients with atypical presentations (metastatic, extra-adrenal) as well as the use of hybrid FI tests should be explored. Further research should also evaluate the impact of FI tests on patient-important outcomes.

Objective: When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional fractionated radiotherapy (RT) are utilized. We conducted a systematic review and meta-analysis to synthesize the existing evidence and compare outcomes for SRS and RT in patients with acromegaly., Methods: We searched Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 2014 for studies in which SRS or RT were used in patients with acromegaly. Outcomes evaluated were serum insulin-like growth factor-I (IGF-I) and growth hormone (GH) levels, biochemical remission, all-cause mortality, hypopituitarism, headaches, and secondary malignancies. We pooled outcomes using a random-effects model., Results: The final search yielded 30 eligible studies assessing 2,464 patients. Compared to RT, SRS was associated with a nonsignificant increase in remission rate at the latest follow-up period (52% vs. 36%; P = .14) and a significantly lower follow-up IGF-I level (-409.72 μg/L vs. -102 μg/L, P = .002). SRS had a lower incidence of hypopituitarism than RT; however, the difference was not statistically significant (32% vs. 51%, respectively; P = .05)., Conclusion: SRS may be associated with better biochemical remission, and it had a lower risk of hypopituitarism with at least 1 deficient axis when compared with RT; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Objective: When patients with acromegaly have residual disease following surgery, adjuvant radiation therapy is considered. Both stereotactic radiosurgery (SRS) and conventional fractionated radiotherapy (RT) are utilized. We conducted a systematic review and meta-analysis to synthesize the existing evidence to compare outcomes with SRS and RT in patients with acromegaly., Methods: We searched Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 2014 for studies in which SRS or RT were used in patients with acromegaly. Outcomes evaluated were serum IGF-1 and GH levels, biochemical remission, all-cause mortality, hypopituitarism, headaches and secondary malignancies. We pooled outcomes using the random-effects model., Results: The final search yielded 30 eligible studies enrolling 2464 patients. When compared to RT, SRS was associated with a non-significant increase in remission rate at the latest follow-up period (52% vs. 36%; p = 0.14), and a significantly lower follow-up IGF-1 level (decline of - 409.72 μg/1 vs. -102 μg/1; p = 0.002). SRS was associated with lower incidence of hypopituitarism than RT; however the difference was not statistically significant [(32% vs.51%, respectively; p = 0.05)., Conclusions: SRS may be associated with better biochemical remission and lower risk of hypopituitarism with at least one deficient axis when compared with RT; however, the confidence in such evidence is very low due to the non-comparative nature of the studies, high heterogeneity, and imprecision.

Background: The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown., Objective: To describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations., Methods: We searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease., Results: We included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (4·6%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members., Conclusions: The frequency of germline mutations in SPPs is approximately 11-13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear., (© 2014 John Wiley & Sons Ltd.)

Context: Various drugs affect body weight as a side effect., Objective: We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change., Data Sources: MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials., Study Selection: We included randomized trials that compared an a priori selected list of drugs to placebo and measured weight change., Data Extraction: We extracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool., Results: We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence., Conclusions: Several drugs are associated with weight change of varying magnitude. Data are provided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed.

Objective: Systematic reviews (SRs) are the cornerstone of evidence-based medicine. In this study, we evaluated the effectiveness of using two computer screens on the efficiency of conducting SRs., Study Design and Setting: A cohort of reviewers before and after using dual monitors were compared with a control group that did not use dual monitors. The outcomes were time spent for abstract screening, full-text screening and data extraction, and inter-rater agreement. We adopted multivariate difference-in-differences linear regression models., Results: A total of 60 SRs conducted by 54 reviewers were included in this analysis. We found a significant reduction of 23.81 minutes per article in data extraction in the intervention group relative to the control group (95% confidence interval: -46.03, -1.58, P = 0.04), which was a 36.85% reduction in time. There was no significant difference in time spent on abstract screening, full-text screening, or inter-rater agreement between the two groups., Conclusion: Using dual monitors when conducting SRs is associated with significant reduction of time spent on data extraction. No significant difference was observed on time spent on abstract screening or full-text screening. Using dual monitors is one strategy that may improve the efficiency of conducting SRs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Acromegaly is usually treated with surgery as a first-line treatment, although medical therapy has also been used as an alternative primary treatment., Objective: We conducted a systematic review and meta-analysis to synthesize the existing evidence comparing these two approaches in treatment-naïve patients with acromegaly., Data Sources: This study performed a comprehensive search in multiple databases, including Medline, EMBASE, and Scopus from early inception through April 2014., Study Selection: The study used original controlled and uncontrolled studies that enrolled patients with acromegaly to receive either surgical treatment or medical treatment as their first-line treatment., Data Extraction: Reviewers extracted data independently and in duplicates. Because of the noncomparative nature of the available studies, we modified the Newcastle-Ottawa Scale to assess the quality of included studies. Outcomes evaluated were biochemical remission and change in IGF-1 or GH levels. We pooled outcomes using the random-effects model., Data Synthesis: The final search yielded 35 studies enrolling 2629 patients. Studies were noncomparative series with a follow-up range of 6-360 months. Compared with medical therapy, surgery was associated with a higher remission rate (67% vs 45%; P = .02). Surgery had higher remission rates at longer follow-up periods (≥ 24 mo) (66% vs 44%; P = .04) but not the shorter follow-up periods (≤ 6 mo) (37% vs 26%; P = .22) [Corrected].Surgery had higher remission rates in the follow-up levels of GH (65% vs 46%; P = .05). In one study, the IGF-1 level was reduced more with surgery compared with medical treatment (-731 μg/L vs -251 μg/L; P = .04). Studies in which surgery was performed by a single operator reported a higher remission rate than those with multiple operators (71% vs 47%; P = .002)., Conclusions: Surgery may be associated with higher remission rate; however, the confidence in such evidence is very low due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Context: Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and is thought to be associated with loss of libido and menopausal symptoms., Objective: We conducted a systematic review and meta-analysis to summarize the evidence supporting the use of systemic DHEA in postmenopausal women with normal adrenal function., Methods: We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through January 2014. Pairs of reviewers, working independently, selected studies and extracted data from eligible randomized controlled trials (RCTs). We used the random-effects model to pool across studies and evaluated heterogeneity using the I(2) statistic., Results: We included 23 RCTs with moderate to high risk of bias enrolling 1188 women. DHEA use was not associated with significant improvement in libido or sexual function (standardized mean difference, 0.35; 95% confidence interval, -0.02 to 0.73; P value = .06; I(2) = 62%). There was also no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density. This evidence warranted low confidence in the results, mostly due to imprecision, risk of bias, and inconsistency across RCTs., Conclusions: Evidence warranting low confidence suggests that DHEA administration does not significantly impact sexual symptoms or selected metabolic markers in postmenopausal women with normal adrenal function.

Context: The use of T has been suggested to improve women's health during the postmenopausal period., Objective: We conducted a systematic review and meta-analysis of randomized trials to summarize the best available evidence regarding the benefits and harms of systemic T in postmenopausal women with normal adrenal function., Methods: A comprehensive search of MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, EBSCO CINAHL, and Scopus was conducted through January 2014. We conducted study selection, data extraction, and appraisal in duplicate. Random-effects meta-analysis was used to pool results., Results: We identified 35 randomized trials (n = 5053) at a moderate risk of bias. T use was associated with statistically significant improvement in various domains of sexual function and personal distress in postmenopausal women, although the majority of the trials did not have specific or contemporary diagnostic criteria for androgen deficiency in women. T use was also associated with a reduction in total cholesterol, triglyceride, and high-density lipoprotein and an increase in low-density lipoprotein and in the incidence of acne and hirsutism. No significant effect was noted on anthropometric measures and bone density. Long-term safety data were sparse, and the quality of such evidence was low., Conclusion: Despite the improvement in sexual function associated with T use in postmenopausal women, long-term safety data are lacking.

Objective: This goal of this study was to systematically review the literature to determine if surgical intervention (open or endovascular) is superior to compression alone with respect to ulcer healing, ulcer recurrence, and time to ulcer healing in patients with lower extremity venous ulcer disease., Methods: We conducted a comprehensive search of multiple databases for randomized controlled trials (RCTs) and comparative observational studies from 1990 to December 2013. The interventions of interest were any open or endovascular surgical interventions on the venous system in the lower extremity compared with compression alone., Results: We included 11 studies (seven RCTs and four observational studies) with moderate to increased risk of bias. The meta-analysis of all studies demonstrated increased healing rate (pooled risk ratio [RR], 1.06; 95% confidence interval [CI], 1.00-1.13; I(2) = 10%) and lower risk of recurrence (RR, 0.54; 95% CI, 0.34-0.85; I(2) = 27%) with open surgical procedures compared with compression. However, the meta-analysis of only RCTs showed no difference, possibly due to imprecision. The meta-analysis of three RCTs showed no difference in time to ulcer healing, -0.41 (95% CI, -0.89 to 0.07). Two studies of endovascular surgical procedures compared with compression showed no significant difference in ulcer healing (RR, 1.65; 95% CI, 0.43-6.32). One study of open surgical venous ligation and stripping compared with endovenous laser also showed no significant difference in ulcer recurrence (RR, 0.83; 95% CI, 0.21-3.27)., Conclusions: Open surgical interventions may improve lower extremity venous ulcer healing. The quality of this evidence is low because the analysis was dominated by the results of observational studies. The current evidence does not definitively support the superiority of endovascular surgical interventions compared with compression alone., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: This was a systematic review of the literature to determine which compression method is superior in promoting ulcer healing and reducing recurrence in patients with lower extremity venous ulcer disease., Methods: We conducted a comprehensive search of multiple databases for randomized and nonrandomized comparative studies from 1990 to December 2013., Results: We identified 36 studies and two Cochrane systematic reviews. Many studies had moderate risk of bias. We found no overall difference between compression stockings vs compression bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence outcomes. When we compared stockings vs short stretch bandages, stockings were superior with respect to ulcer healing. However, stockings compared with four-layer systems showed no difference in ulcer healing outcomes. When four-layer systems were compared with compression with less than four layers, there was also no significant difference in ulcer healing outcomes. Similarly, short stretch bandages were not superior to long stretch bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence. One Cochrane review presented many additional comparisons and reported increased wound healing with compression compared with no compression, with multicomponent systems over single component systems, and compression systems with an elastic component over no elastic component. Another Cochrane review demonstrated a reduction in recurrence with compression in patients with healed ulcers., Conclusions: At least moderate-quality evidence supports compression over no compression, multicomponent systems over single component systems, and systems with an elastic component over those without. We did not find significant differences with respect to ulcer healing outcomes for other comparisons. Low-quality evidence supports the effect of compression on ulcer recurrence., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: A compelling ethical rationale supports patient engagement in healthcare research. It is also assumed that patient engagement will lead to research findings that are more pertinent to patients' concerns and dilemmas. However; it is unclear how to best conduct this process. In this systematic review we aimed to answer 4 key questions: what are the best ways to identify patient representatives? How to engage them in designing and conducting research? What are the observed benefits of patient engagement? What are the harms and barriers of patient engagement?, Methods: We searched MEDLINE, EMBASE, PsycInfo, Cochrane, EBSCO, CINAHL, SCOPUS, Web of Science, Business Search Premier, Academic Search Premier and Google Scholar. Included studies were published in English, of any size or design that described engaging patients or their surrogates in research design. We conducted an environmental scan of the grey literature and consulted with experts and patients. Data were analyzed using a non-quantitative, meta-narrative approach., Results: We included 142 studies that described a spectrum of engagement. In general, engagement was feasible in most settings and most commonly done in the beginning of research (agenda setting and protocol development) and less commonly during the execution and translation of research. We found no comparative analytic studies to recommend a particular method. Patient engagement increased study enrollment rates and aided researchers in securing funding, designing study protocols and choosing relevant outcomes. The most commonly cited challenges were related to logistics (extra time and funding needed for engagement) and to an overarching worry of a tokenistic engagement., Conclusions: Patient engagement in healthcare research is likely feasible in many settings. However, this engagement comes at a cost and can become tokenistic. Research dedicated to identifying the best methods to achieve engagement is lacking and clearly needed.

Objectives: The current evidence rating for hyperbaric oxygen therapy indications uses the American Heart Association system, which mainly depends on the study design., Study Design and Setting: We systematically reviewed the literature and applied the Grading of Evidence, Assessment, Development and Evaluation (GRADE) approach to the main patient-important outcomes in each indication., Results: We included 17 systematic reviews that synthesized 44 randomized trials and 131 observational studies enrolling 8,145 participants. The quality of evidence for seven indications with category A was high (1), moderate (2), low (2), and very low (2); for 10 indications with category B, it was moderate (1), low (5), and very low (4); and for 1 indication with category C, it was high. The quality of evidence was rated down for the risk of bias and imprecision for most indications and rated up because of large effect size for some indications. Most discrepant ratings were in the indications of decompression illness (C, high), carbon monoxide poisoning (A, very low), and later presentations of idiopathic sudden hearing loss (A, very low)., Conclusion: The GRADE approach uncovered factors affecting the quality of evidence that were otherwise implicit. Knowing these factors can influence clinicians' confidence in applying hyperbaric oxygen therapy and orient the research agenda., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The self-organization of actin filaments is a topic that links cell biology with condensed matter physics. In vitro assays allow precise manipulation of component mechanical and chemical properties, needed for rigorous tests of theoretical models. We review recent work on in vitro motility assays that documented emergence of ordered actin filament microdomains powered by myosin motor proteins at high filament densities. Motor and filament surface density and mechanochemical cycle kinetics are additional parameters under current investigation. Individual filament collisions have been studied in order to elucidate the emergent population behavior. Apolar, weak  interactions evidenced by local filament deformations during crossover events are attenuated at high motor densities. Theoretical analysis requires refinement of rigid rod filament models. In intact cells, accessory proteins modulate actin filament length, bundling or sliding and this gives rise to complex emergent structures and behaviors such as cell motility and chemotaxis. The development of generic, mechanical and biochemical frameworks with predictive power that link molecular properties with micro- and macroscopic phenomena seen in living cells requires dialogue between theoreticians and experimentalists.