Risk of bias and certainty of evidence on the association between obesity and mortality in patients with SARS-COV-2: An umbrella review of meta-analyses.

BACKGROUND & AIMS: This umbrella review of systematic reviews with meta-analysis (SR-MAs) aimed to evaluate the risk of bias and the certainty of the evidence of SR-MAs on the association between obesity and mortality in patients with SARS-CoV-2. METHODS: We conducted a comprehensive literature search until April 22, 2022, in several databases and assessed the risk of bias of SR-MAs according to AMSTAR-2 and the certainty of evidence using the GRADE approach. The degree of overlap between meta-analyses was based on the corrected covered area (CCA) index. The results of each MA [relative risk (RR), hazard ratio (HR), or odds ratio (OR)] were extracted to evaluate the magnitude of the association between obesity and mortality. RESULTS: A total of 24 SR-MAs were eligible, and the association between obesity and mortality was not statistically significant in eight (33.3%) of them, while the OR/HR/RR ranged from 1.14 to 3.52 in the other SR-MAs. The overlap was slight (CCA = 4.82%). The majority of SR-MAs presented critically low quality according to AMSTAR-2 (66.7%), and the certainty of the evidence for most of them (83.4%) was "very low". CONCLUSIONS: Obesity was associated with an increased risk of death in patients with SARS-CoV-2 infection in most SR-MAs; however, a critical appraisal pointed to a high risk of bias, and the certainty of their evidence was not well graded. The dissemination of poor SR-MAs may limit the interpretation of findings, and we should always aspire to trustworthy scientific evidence. PROSPERO: PROSPERO 2021 CRD42021253142.

PROTOCOL: Guidance for stakeholder engagement in guideline development: A systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows: to identify, describe, and summarize existing guidance and methods for multistakeholder engagement throughout the health guideline development process.

Prevalence of hepatitis A in the capitals of the States of North, Southeast and South regions of Brazil: decrease in prevalence and some consequences.

Hepatitis A virus (HAV) infection has been considered one of the leading causes of acute hepatitis. The aim of the present study was to estimate the prevalence of HAV among children and adolescents in a population-based study in the capitals of the States of the North, Southeast and South of Brazil and identify predictive factors for the infection. A multi-stage sampling was used to select subjects aged between 5-9 and 10-19 years. Individual and household levels aside from the level of variables in the areas were collected. The outcome was the total IgG antibodies to HAV levels detected using a commercial Enzyme Immuno Assay (EIA). The associations between HAV and the independent variables were assessed using the odds ratio. A multilevel analysis was performed by GLLAMM using the Stata software. The prevalence of HAV infection in the 5-9 and 10-19 age groups was 28.7% and 67.5%, respectively for the North, 20.6% and 37.7%, for the Southeast and 18.9% and 34.5% for the South Region. The prevalence of HAV increased according to age in all sites. Variables related to education at the individual level (North and South), family and area level (South and Southeast) and family income level (Southeast and South) were independently associated with HAV infection. This emphasizes the need for individualized strategies to prevent the infection.

Adherence to treatment in collective multiprofessional activities and factors associated with adherence in a specialized center for psychosocial care

Abstract Introduction Specialized psychosocial care centers (Centros de Atenção Psicossocial [CAPS]) are mental health services focused on social rehabilitation and reducing hospitalization of patients with severe and persistent mental illness. Collective multiprofessional activities (CMPA) are the main therapeutic tools used at CAPS. This study aimed to determine rates of adherence to CMPA and identify factors associated with adherence. Methods This is a cross-sectional study in which 111 CAPS users were evaluated using questionnaires covering patient characteristics, clinical status, and treatment and incorporating the Functioning Assessment Short Test (FAST), the Clinical Global Impression - Severity scale (CGI-S), and the Clinical Global Impression - Improvement scale (CGI-I). Adherence was defined as attendance at 50% or more CMPA during the previous 3 months. Data were analyzed using descriptive statistics, bivariate analysis, and Poisson logistic regression with robust variance to estimate prevalence ratios. Results CPMA adherence was 43%. Having children aged 14 years or younger was significantly associated with non-adherence (71%, p = 0.001). Poor or partial adherence to psychotropic drugs tended to be associated (p = 0.066) with poor adherence (33% higher risk), as was the number of psychiatric hospitalizations during CAPS (p = 0.076), with a cumulative association of 5% non-adherence per hospitalization. Conclusions CMPA adherence was low in the study. It is necessary to consider the environment in which the individual lives and invest in support networks, providing patients and family members with explanations about the importance of CMPA to rehabilitation and attempting to tailor the care provided to each patient's needs. There was an association between greater number of psychiatric hospitalizations and non-adherence, suggesting that CAPS are fulfilling a preventive role.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.

Adherence to treatment in collective multiprofessional activities and factors associated with adherence in a specialized center for psychosocial care.

INTRODUCTION: Specialized psychosocial care centers (Centros de Atenção Psicossocial [CAPS]) are mental health services focused on social rehabilitation and reducing hospitalization of patients with severe and persistent mental illness. Collective multiprofessional activities (CMPA) are the main therapeutic tools used at CAPS. This study aimed to determine rates of adherence to CMPA and identify factors associated with adherence. METHODS: This is a cross-sectional study in which 111 CAPS users were evaluated using questionnaires covering patient characteristics, clinical status, and treatment and incorporating the Functioning Assessment Short Test (FAST), the Clinical Global Impression - Severity scale (CGI-S), and the Clinical Global Impression - Improvement scale (CGI-I). Adherence was defined as attendance at 50% or more CMPA during the previous 3 months. Data were analyzed using descriptive statistics, bivariate analysis, and Poisson logistic regression with robust variance to estimate prevalence ratios. RESULTS: CPMA adherence was 43%. Having children aged 14 years or younger was significantly associated with non-adherence (71%, p = 0.001). Poor or partial adherence to psychotropic drugs tended to be associated (p = 0.066) with poor adherence (33% higher risk), as was the number of psychiatric hospitalizations during CAPS (p = 0.076), with a cumulative association of 5% non-adherence per hospitalization. CONCLUSIONS: CMPA adherence was low in the study. It is necessary to consider the environment in which the individual lives and invest in support networks, providing patients and family members with explanations about the importance of CMPA to rehabilitation and attempting to tailor the care provided to each patient's needs. There was an association between greater number of psychiatric hospitalizations and non-adherence, suggesting that CAPS are fulfilling a preventive role.

Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation.

BACKGROUND: Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health.

Effect of a Multifaceted Quality Improvement Intervention on the Prescription of Evidence-Based Treatment in Patients at High Cardiovascular Risk in Brazil: The BRIDGE Cardiovascular Prevention Cluster Randomized Clinical Trial.

Importance: Studies have found that patients at high cardiovascular risk often fail to receive evidence-based therapies in community practice. Objective: To evaluate whether a multifaceted quality improvement intervention can improve the prescription of evidence-based therapies. Design, Setting, and Participants: In this 2-arm cluster randomized clinical trial, patients with established atherothrombotic disease from 40 public and private outpatient clinics (clusters) in Brazil were studied. Patients were recruited from August 2016 to August 2017, with follow-up to August 2018. Data were analyzed in September 2018. Interventions: Case management, audit and feedback reports, and distribution of educational materials (to health care professionals and patients) vs routine practice. Main Outcomes and Measures: The primary end point was prescription of evidence-based therapies (ie, statins, antiplatelet therapy, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) using the all-or-none approach at 12 months after the intervention period in patients without contraindications. Results: Of the 1619 included patients, 1029 (63.6%) were male, 1327 (82.0%) had coronary artery disease (843 [52.1%] with prior acute myocardial infarction), 355 (21.9%) had prior ischemic stroke or transient ischemic attack, and 197 (12.2%) had peripheral vascular disease, and the mean (SD) age was 65.6 (10.5) years. Among randomized clusters, 30 (75%) were cardiology sites, 6 (15%) were primary care units, and 26 (65%) were teaching institutions. Among eligible patients, those in intervention clusters were more likely to receive a prescription of evidence-based therapies than those in control clusters (73.5% [515 of 701] vs 58.7% [493 of 840]; odds ratio, 2.30; 95% CI, 1.14-4.65). There were no differences between the intervention and control groups with regards to risk factor control (ie, hyperlipidemia, hypertension, or diabetes). Rates of education for smoking cessation were higher among current smokers in the intervention group than in the control group (51.9% [364 of 701] vs 18.2% [153 of 840]; odds ratio, 11.24; 95% CI, 2.20-57.43). The rate of cardiovascular mortality, acute myocardial infarction, and stroke was 2.6% for patients from intervention clusters and 3.4% for those in the control group (hazard ratio, 0.76; 95% CI, 0.43-1.34). Conclusions and Relevance: Among Brazilian patients at high cardiovascular risk, a quality improvement intervention resulted in improved prescription of evidence-based therapies. Trial Registration: ClinicalTrials.gov identifier: NCT02851732.

Rationale and design for a cluster randomized quality improvement trial to increase the uptake of evidence based therapies for patients at high cardiovascular risk: The bridge cardiovascular prevention trial

BACKGROUND: Translating evidence into clinical practice in the management of high cardiovascular risk patients is challenging. Few quality improvement interventions have rigorously evaluated their impact on both patient care and clinical outcomes. OBJECTIVES: The main objectives are to evaluate the impact of a multifaceted educational intervention on adherence to local guidelines for the prescription of statins, antiplatelets and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers for high cardiovascular risk patients, as well as on the incidence of major cardiovascular events. DESIGN: We designed a pragmatic two arm cluster randomized trial involving 40 clusters. Clusters are randomized to receive a multifaceted quality improvement intervention or to routine practice (control). The multifaceted intervention includes: reminders, care algorithms, training of a case manager, audit and feedback reports, and distribution of educational materials to health care providers. The primary endpoint is the adherence to combined evidence-based therapies (statins, antiplatelet therapy and angiotensin converting enzyme inhibitors or angiotensin receptor blockers) at 12 months after the intervention period in patients without contra-indications for these medications. All analyses follow the intention-to-treat principle and take the cluster design into account using linear mixed logistic regression modeling. SUMMARY: If proven effective, this multifaceted intervention would have wide utility as a means of promoting optimal usage of evidence-based interventions for the management of high cardiovascular risk patients. (AU)

Rationale and design for a cluster randomized quality-improvement trial to increase the uptake of evidence-based therapies for patients at high cardiovascular risk: The BRIDGE-Cardiovascular Prevention trial.

BACKGROUND: Translating evidence into clinical practice in the management of high cardiovascular risk patients is challenging. Few quality improvement interventions have rigorously evaluated their impact on both patient care and clinical outcomes. OBJECTIVES: The main objectives are to evaluate the impact of a multifaceted educational intervention on adherence to local guidelines for the prescription of statins, antiplatelets and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers for high cardiovascular risk patients, as well as on the incidence of major cardiovascular events. DESIGN: We designed a pragmatic two arm cluster randomized trial involving 40 clusters. Clusters are randomized to receive a multifaceted quality improvement intervention or to routine practice (control). The multifaceted intervention includes: reminders, care algorithms, training of a case manager, audit and feedback reports, and distribution of educational materials to health care providers. The primary endpoint is the adherence to combined evidence-based therapies (statins, antiplatelet therapy and angiotensin converting enzyme inhibitors or angiotensin receptor blockers) at 12 months after the intervention period in patients without contra-indications for these medications. All analyses follow the intention-to-treat principle and take the cluster design into account using linear mixed logistic regression modeling. SUMMARY: If proven effective, this multifaceted intervention would have wide utility as a means of promoting optimal usage of evidence-based interventions for the management of high cardiovascular risk patients.

Face-to-Face and Distance Education Modalities in the Training of Healthcare Professionals: A Quasi-Experimental Study.

This study evaluates the effectiveness of an 18-month-long course in Family Health. The course was offered in two modalities, distance education and face-to-face learning. Dependent variables were as follows: self-regulation of learning, procrastination, the perception of self-efficacy, and academic performance. The course was attended by 27 health professionals (i.e., physicians, nurses, and dentists) working in the Brazilian Unified Health System. The investigation followed a quasi-experimental design. Participants in the two modalities achieved similar academic performance; and globally no statistically significant differences were found regarding the study variables. Findings, notwithstanding their importance for professional training in health, are preliminary and further research is needed on the effectiveness of training modalities distance education and face-to-face learning (e.g., focus groups, interviews, online monitoring). The educational implications of this study are discussed and analyzed considering specificities and differences of each modality.

Nonalcoholic fatty liver disease in patients with different baseline glucose status undergoing bariatric surgery: analysis of intraoperative liver biopsies and literature review.

BACKGROUND: Bariatric surgery has been investigated as a treatment option for obese patients with nonalcoholic fatty liver disease (NAFLD). Because patients with NAFLD and type 2 diabetes show accelerated progression from liver disease to cirrhosis, it has been suggested that surgery could be indicated for patients with lower degrees of obesity and type 2 diabetes. OBJECTIVE: To analyze the degree of tissue damage in liver biopsies obtained from patients undergoing bariatric surgery, correlating histopathologic findings with their baseline glucose status. SETTING: General hospital in the public health system. METHODS: Intraoperative liver biopsies were obtained from 521 obese patients undergoing bariatric surgery. Patients were divided into 3 study groups according to their preoperative glucose levels: 167 (32.05%) type 2 diabetic, 132 (25.33%) prediabetic, and 222 (42.61%) normoglycemic patients. Tissue samples were classified in accordance with Brunt and Clinical Research Network Nonalcoholic Steatohepatis criteria. RESULTS: Prevalence of NAFLD was 95%. Higher rates of hepatic fibrosis were observed in diabetic patients (56.4%) compared with prediabetic (29.2%), and normoglycemic patients (28.6%) (P<.001). Nonalcoholic steatohepatitis was diagnosed in 59.4% of the diabetics, in 49.2% of the prediabetics, and in 36% of the normoglycemic obese (P<.001). Only 1.5% of the diabetics had no histologic hepatic alterations. CONCLUSION: NAFLD is markedly more severe in diabetic patients. Our data suggest that intraoperative liver biopsy should be considered for diabetic patients undergoing bariatric surgery. Early bariatric surgery should be investigated as a means to prevent progression of NAFLD.

Considering health equity when moving from evidence-based guideline recommendations to implementation: a case study from an upper-middle income country on the GRADE approach.

The availability of evidence-based guidelines does not ensure their implementation and use in clinical practice or policy making. Inequities in health have been defined as those inequalities within or between populations that are avoidable, unnecessary and also unjust and unfair. Evidence-based clinical practice and public health guidelines ('guidelines') can be used to target health inequities experienced by disadvantaged populations, although guidelines may unintentionally increase health inequities. For this reason, there is a need for evidence-based clinical practice and public health guidelines to intentionally target health inequities experienced by disadvantaged populations. Current guideline development processes do not include steps for planned implementation of equity-focused guidelines. This article describes nine steps that provide guidance for consideration of equity during guideline implementation. A critical appraisal of the literature followed by a process to build expert consensus was undertaken to define how to include consideration of equity issues during the specific GRADE guideline development process. Using a case study from Colombia we describe nine steps that were used to implement equity-focused GRADE recommendations: (1) identification of disadvantaged groups, (2) quantification of current health inequities, (3) development of equity-sensitive recommendations, (4) identification of key actors for implementation of equity-focused recommendations, (5) identification of barriers and facilitators to the implementation of equity-focused recommendations, (6) development of an equity strategy to be included in the implementation plan, (7) assessment of resources and incentives, (8) development of a communication strategy to support an equity focus and (9) development of monitoring and evaluation strategies. This case study can be used as model for implementing clinical practice guidelines, taking into account equity issues during guideline development and implementation.

GRADE equity guidelines 2: considering health equity in GRADE guideline development: equity extension of the guideline development checklist.

OBJECTIVE: To provide guidance for guideline developers on how to consider health equity at key stages of the guideline development process. STUDY DESIGN AND SETTING: Literature review followed by group discussions and consensus building. RESULTS: The key stages at which guideline developers could consider equity include setting priorities, guideline group membership, identifying the target audience(s), generating the guideline questions, considering the importance of outcomes and interventions, deciding what evidence to include and searching for evidence, summarizing the evidence and considering additional information, wording of recommendations, and evaluation and use. We provide examples of how guidelines have actually considered equity at each of these stages. CONCLUSION: Guideline projects should consider the aforementioned suggestions for recommendations that are equity sensitive.

Twenty-four-hour ambulatory blood pressure monitoring for clinical evaluation of hypertensive patients in primary care: which groups would most benefit?

BACKGROUND: Arterial hypertension is an important risk factor for cardiovascular outcomes. Blood pressure (BP) control levels remain largely out of target among primary healthcare (PHC) patients. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) may contribute toward the identification of cardiovascular risk groups. OBJECTIVE: To assess concordance between conventional office BP measurements and 24-h ABPM of hypertension control in cardiovascular risk groups of PHC hypertensive patients. PATIENTS AND METHODS: A cross-sectional study with 569 hypertensive patients was carried out. The evaluation of BP was performed by a PHC doctor, and the 24-h ABPM was performed by a different and blinded provider. The therapeutic targets for BP followed the guidance of The Eighth Joint National Committee, the Brazilian guideline, and the 2013 European Society of Hypertension. Considering the hypertension control therapeutic targets, the guidelines were not similar and were used to evaluate differences in BP value concordances compared with BP standard measurements. RESULTS: After a multivariate logistic regression analysis, a conventional BP was used in comparison with ABPM in different cardiovascular risk groups of hypertensive patients. According to the ABPM by European Society of Hypertension guideline, the subgroup of inactive patients (P=0.006), with altered glycemia (P=0.015) and over 30 mg/dl albuminuria (P=0.001), presented discordance among methods. When a conventional BP measurement in comparison with the ABPM results according to the Brazilian ABPM guideline was used, the discordance occurred significantly in inactive (P=0.001) and microalbuminuria more than 30 mg/dl (P=0.022) subgroups. However, in this comparison, a concordance between high-density lipoprotein more than 60 mg/dl (P=0.015) and obesity (P=0.035) subgroups occurred. CONCLUSION: Uncontrolled glucose levels, a sedentary lifestyle, and the presence of microalbuminuria correspond to some cardiovascular risk groups that would particularly benefit from 24-h ABPM as a tool for the control of BP with the PHC hypertensive patients of this study.

Adjuvant platinum-based chemotherapy for early stage cervical cancer.

BACKGROUND: This is the second updated version of the original Cochrane review published in the Cochrane Library 2009, Issue 3. Most women with early cervical cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We performed this review originally because it was unclear whether cisplatin-based chemotherapy after surgery, radiotherapy or both, in women with early stage disease with risk factors for recurrence, was associated with additional survival benefits or risks. OBJECTIVES: To evaluate the effectiveness and safety of adjuvant platinum-based chemotherapy after radical hysterectomy, radiotherapy, or both in the treatment of early stage cervical cancer. SEARCH METHODS: For the original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library 2009, Issue 1), MEDLINE, Embase, LILACS, BIOLOGICAL ABSTRACTS and CancerLit, the National Research Register and Clinical Trials register, with no language restriction. We handsearched abstracts of scientific meetings and other relevant publications. We extended the database searches to November 2011 for the first update and to September 2016 for the second update. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at least one risk factor for recurrence. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. Meta-analysis was performed using a random-effects model, with death and disease progression as outcomes. MAIN RESULTS: For this second updated version we identified only one small trial reporting grade 4 toxicity results, without disease-free or overall survival data with a median follow-up of 16 months.From the first updated version, we identified three trials that were ongoing, and remain so in 2016.Four trials including 401 women with evaluable results with early cervical cancer were included in the meta-analyses. The median follow-up period in these trials ranged from 29 to 42 months. All women had undergone surgery first. Three trials compared chemotherapy combined with radiotherapy versus radiotherapy alone; and one trial compared chemotherapy followed by radiotherapy versus radiotherapy alone. It was not possible to perform subgroup analyses by stage or tumour size.Compared with adjuvant radiotherapy, chemotherapy combined with radiotherapy significantly reduced the risk of death (two trials, 297 women; hazard ratio (HR) = 0.56, 95% confidence interval (CI): 0.36 to 0.87) and disease progression (two trials, 297 women; HR = 0.47, 95% CI 0.30 to 0.74), with no heterogeneity between trials (I² = 0% for both meta-analyses). Acute grade 4 toxicity occurred significantly more frequently in the chemotherapy plus radiotherapy group than in the radiotherapy group (three trials, 321 women; risk ratio (RR) 6.26, 95% CI 2.50 to 15.67). We considered the evidence for all three outcomes to be of a moderate quality, using the GRADE approach due to small numbers and limited follow-up in the included studies. In addition, it was not possible to separate data for bulky early stage disease.In the one small trial that compared adjuvant chemotherapy followed by radiotherapy with adjuvant radiotherapy alone there was no difference in disease recurrence between the groups (one trial, 71 women; HR = 1.34; 95% CI 0.24 to 7.66) and overall survival was not reported. We considered this evidence to be of a low quality.No trials compared adjuvant platinum-based chemotherapy with no adjuvant chemotherapy after surgery for early cervical cancer with risk factors for recurrence. AUTHORS' CONCLUSIONS: The addition of platinum-based chemotherapy to adjuvant radiotherapy (chemoradiation) may improve survival in women with early stage cervical cancer (IA2-IIA) and risk factors for recurrence. Adjuvant chemoradiation is associated with an increased risk of severe acute toxicity, although it is not clear whether this toxicity is significant in the long term due to a lack of long-term data. This evidence is limited by the small numbers and low to moderate methodological quality of the included studies. We await the results of three ongoing trials, which are likely to have an important impact on our confidence in this evidence.

Laparoscopy versus laparotomy for FIGO stage I ovarian cancer.

BACKGROUND: This is an updated version of the original review that was first published in the Cochrane Database of Systematic Reviews 2008, Issue 4. Laparoscopy has become an increasingly common approach to surgical staging of apparent early-stage ovarian tumours. This review was undertaken to assess the available evidence on the benefits and risks of laparoscopy compared with laparotomy for the management of International Federation of Gynaecology and Obstetrics (FIGO) stage I ovarian cancer. OBJECTIVES: To evaluate the benefits and harms of laparoscopy in the surgical treatment of FIGO stage I ovarian cancer (stages Ia, Ib and Ic) when compared with laparotomy. SEARCH METHODS: For the original review, we searched the Cochrane Gynaecological Cancer Group Trials (CGCRG) Register, Cochrane Central Register of Controlled Trials (CENTRAL 2007, Issue 2), MEDLINE, Embase, LILACS, Biological Abstracts and CancerLit from 1 January 1990 to 30 November 2007. We also handsearched relevant journals, reference lists of identified studies and conference abstracts. For the first updated review, the search was extended to the CGCRG Specialised Register, CENTRAL, MEDLINE, Embase and LILACS to 6 December 2011. For this update we searched CENTRAL, MEDLINE, and Embase from November 2011 to September 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs and prospective cohort studies comparing laparoscopic staging with open surgery (laparotomy) in women with stage I ovarian cancer according to FIGO. DATA COLLECTION AND ANALYSIS: There were no studies to include, therefore we tabulated data from non-randomised studies (NRS) for discussion as well as important data from other meta-analyses. MAIN RESULTS: We performed no meta-analyses. AUTHORS' CONCLUSIONS: This review has found no good-quality evidence to help quantify the risks and benefits of laparoscopy for the management of early-stage ovarian cancer as routine clinical practice.

Phlebotonics for venous insufficiency.

BACKGROUND: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. OBJECTIVES: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. SEARCH METHODS: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). SELECTION CRITERIA: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in patients with CVI at any stage of the disease. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. MAIN RESULTS: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factors in the North, South, and Southeast Regions of Brazil, 10-20 Years After the Beginning of Vaccination.

A population-based hepatitis survey was carried out to estimate the prevalence of hepatitis B virus (HBV) infection and its predictive factors for the state capitals from the north, south, and southeast regions of Brazil. A multistage cluster sampling was used to select, successively, census tracts, blocks, households, and residents in the age group 10-69 years in each state capital. The prevalence of hepatitis B surface antigen (HBsAg) was lower than 1% in the north, southeast, and south regions. Socioeconomic condition was associated with HBV infection in north and south regions. Variables related to the blood route transmission were associated with HBV infection only in the south whereas those related to sexual behavior were associated with HBV infection in the north and south regions. Drug use was associated in all regions, but the type of drug differed. The findings presented herein highlight the diversity of the potential transmission routes for hepatitis B transmission in Brazil. In one hand, it reinforces the importance of national control strategies of large impact already in course (immunization of infants, adolescents, and adults up to 49 years of age and blood supply screening). On the other hand, it shows that there is still room for further control measures targeted to different groups within each region.