Applying Topical Anesthetic on Pediatric Lacerations in the Emergency Department: A Quality Improvement Project.

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.

A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.

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.

A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.

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.

Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.

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.

A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.

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.

Prevention of exacerbations in patients with stable non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis of pharmacological and non-pharmacological therapies.

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 (FEV1) (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.

Treatment Options for Hirsutism: A Systematic Review and Network Meta-Analysis.

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.

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study.

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.

Comparative Effectiveness and Safety of Cognitive Behavioral Therapy and Pharmacotherapy for Childhood Anxiety Disorders: A Systematic Review and Meta-analysis.

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.

The Association of Weight Loss and Cardiometabolic Outcomes in Obese Children: Systematic Review and Meta-regression.

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.

Treatment of Pediatric Obesity: An Umbrella Systematic Review.

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.

Clinical Features and Management of Non-HIV-Related Lipodystrophy in Children: A Systematic Review.

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.

Non-pharmacological treatment of depression: a systematic review and evidence map.

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.

The Association of Weight Loss and Cardiometabolic Outcomes in Obese Children: Systematic Review and Meta-regression.

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.

Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.

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.

Reducing the risk of transfusion-transmitted cytomegalovirus infection: a systematic review and meta-analysis.

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.

Bypass surgery versus endovascular interventions in severe or critical limb ischemia.

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.

The natural history of untreated severe or critical limb ischemia.

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.