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ABSTRACT BACKGROUND: In Brazil, the right to healthcare and the incorporation of best scientific evidence in public health are universally guaranteed by law. However, the treatment offered to patients with mental disorders in custodial hospitals in this country has not been rigorously evaluated. OBJECTIVES: To analyze the psychiatric diagnoses and treatments implemented in three Brazilian custodial institutions. DESIGN AND SETTING: This was a retrospective, cross-sectional and descriptive study on patients held in custody in three Brazilian institutions, as judicially-determined safety measures due to their mental disorders, and the tools used in diagnoses and treatments. These institutions are in Rio de Janeiro and the Federal District. METHODS: The data from medical and judicial records that were made available were assessed regarding the diagnoses that were made and the instruments that were used. RESULTS: None of these inpatients were evaluated using validated tools, and only a few medical records presented clear descriptions of the cases. No patient with substance involvement had undergone laboratory toxicological assays. It was not possible to verify the adequacy of treatments because the procedures were inadequately described in the records. CONCLUSIONS: No standardized protocols or instruments for diagnosing mental health disorders or assessing use of psychoactive substances had been applied among the inpatients at these custodial institutions in Rio de Janeiro and the Federal District. The treatments that were prescribed to these inpatients consisted mainly of drugs.

ABSTRACT BACKGROUND: The numbers of cases of arboviral diseases have increased in tropical and subtropical regions while the coronavirus disease (COVID-19) pandemic overwhelms healthcare systems worldwide. The clinical manifestations of arboviral diseases, especially dengue fever, can be very similar to COVID-19, and misdiagnoses are still a reality. In the meantime, outcomes for patients and healthcare systems in situations of possible syndemic have not yet been clarified. OBJECTIVE: We set out to conduct a systematic review to understand and summarize the evidence relating to clinical manifestations, disease severity and prognoses among patients coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and arboviruses. METHODS: We conducted a rapid systematic review with meta-analysis, on prospective and retrospective cohorts, case-control studies and case series of patients with confirmed diagnoses of SARS-CoV-2 and arboviral infection. We followed the Cochrane Handbook recommendations. We searched EMBASE, MEDLINE, Cochrane Library, LILACS, Scopus and Web of Science to identify published, ongoing and unpublished studies. We planned to extract data and assess the risk of bias and the certainty of evidence of the studies included, using the Quality in Prognosis Studies tool and the Grading of Recommendations Assessment. RESULTS: We were able to retrieve 2,407 citations using the search strategy, but none of the studies fulfilled the inclusion criteria. CONCLUSION: The clinical presentations, disease severity and prognoses of patients coinfected with SARS-CoV-2 and arboviruses remain unclear. Further prospective studies are necessary in order to provide useful information for clinical decision-making processes. Protocol registration number in the PROSPERO database: CRD42020183460

ABSTRACT BACKGROUND: Use of inhaled corticosteroids for managing acute asthma exacerbations has been tested since the 1990s. OBJECTIVE: To compare high doses of inhaled ciclesonide with systemic hydrocortisone for managing acute asthma exacerbations in the emergency department. DESIGN AND SETTING: Double-blind, randomized clinical trial in the public healthcare system of the city of São Paulo. METHODS: Fifty-eight patients with moderate or severe asthma with peak flow < 50% of predicted were randomized into two groups. Over the course of four hours, one group received 1440 mcg of inhaled ciclesonide plus hydrocortisone-identical placebo (ciclesonide + placebo), while the other received 500 mg of intravenous hydrocortisone plus ciclesonide-identical placebo (hydrocortisone + placebo). Both groups received short-acting bronchodilators (fenoterol hydrobromide and ipratropium bromide). The research protocol included spirometry, clinical evaluation, vital signs and electrocardiogram monitoring. Data were obtained at 30 (baseline), 60, 90, 120, 180, and 240 minutes. We compared data from baseline to hour 4, between and within groups. RESULTS: Overall, 31 patients received ciclesonide + placebo and 27 received hydrocortisone + placebo. Inhaled ciclesonide was as effective as intravenous hydrocortisone for improving clinical parameters (Borg-scored dyspnea, P = 0.95; sternocleidomastoid muscle use, P = 0.55; wheezing, P = 0.55; respiratory effort, P = 0.95); and spirometric parameters (forced vital capacity, P = 0.50; forced expiratory volume in the first second, P = 0.83; peak expiratory flow, P = 0.51). CONCLUSIONS: Inhaled ciclesonide was not inferior to systemic hydrocortisone for managing acute asthma exacerbations, and it improved both clinical and spirometric parameters. TRIAL REGISTRATION: RBR-6XWC26 - Registro Brasileiro de Ensaios Clínicos (http://www.ensaiosclinicos.gov.br/rg/RBR-6xwc26/).

ABSTRACT BACKGROUND: This study identified and summarized all Cochrane systematic reviews (SRs) on the effects of ten integrative practices that were recently added to the Brazilian public healthcare system (SUS). DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp). METHODS: Review of Cochrane SRs on the following interventions were identified, summarized and critically assessed: apitherapy, aromatherapy, bioenergetics, family constellation, flower therapy, chromotherapy, geotherapy, hypnotherapy, hand imposition or ozone therapy. RESULTS: We included a total of 16 SRs: 4 on apitherapy, 4 on aromatherapy, 6 on hypnotherapy and 2 on ozone therapy. No Cochrane SR was found regarding bioenergetics, family constellation, chromotherapy, clay therapy, flower therapy or hand imposition. The only high-quality evidence was in relation to the potential benefit of apitherapy, specifically regarding some benefits from honey dressings for partial healing of burn wounds, for reduction of coughing among children with acute coughs and for preventing allergic reactions to insect stings. CONCLUSION: Except for some specific uses of apitherapy (honey for burn wounds and for acute coughs and bee venom for allergic reactions to insect stings), the use of ten integrative practices that have recently been incorporated into SUS does not seem to be supported by evidence from Cochrane SRs.

New evidence on the COVID-19 pandemic is being published daily. Ongoing high-quality assessment of this literature is therefore needed to enable clinical practice to be evidence-based. This review builds on a previous scoping review and aimed to identify associations between disease severity and various clinical, laboratory and radiological characteristics. We searched MEDLINE, CENTRAL, EMBASE, Scopus and LILACS for studies published between January 1, 2019 and March 22, 2020. Clinical studies including ≥10 patients with confirmed COVID-19 of any study design were eligible. Two investigators independently extracted data and assessed risk of bias. A quality effects model was used for the meta-analyses. Subgroup analysis and meta-regression identified sources of heterogeneity. For hospitalized patients, studies were ordered by overall disease severity of each population and this order was used as the modifier variable in meta-regression. Overall, 86 studies (n = 91,621) contributed data to the meta-analyses. Severe disease was strongly associated with fever, cough, dyspnea, pneumonia, any computed tomography findings, any ground glass opacity, lymphocytopenia, elevated C-reactive protein, elevated alanine aminotransferase, elevated aspartate aminotransferase, older age and male sex. These variables typically increased in prevalence by 30-73% from mild/early disease through to moderate/severe disease. Among hospitalized patients, 30-78% of heterogeneity was explained by severity of disease. Elevated white blood cell count was strongly associated with more severe disease among moderate/severe hospitalized patients. Elevated lymphocytes, low platelets, interleukin-6, erythrocyte sedimentation rate and D-dimers showed potential associations, while fatigue, gastrointestinal symptoms, consolidation and septal thickening showed non-linear association patterns. Headache and sore throat were associated with the presence of disease, but not with more severe disease. In COVID-19, more severe disease is strongly associated with several clinical, laboratory and radiological characteristics. Symptoms and other variables in early/mild disease appear non-specific and highly heterogeneous. Clinical Trial Registration: PROSPERO CRD42020170623.

PURPOSE: This article describes a clinically-diagnosed case of relapsing polychondritis (RP), attended at the Hospital São Paulo, and presents a literature review of the subject. SOURCE OF RESEARCH: The literature review was made via Medline (1990-96), Lilacs (1980-96), textbooks of rheumatology, and some articles about the history of the disease. In Medline, 113 articles from 1990 to 1996 were found, and there were 23 articles from 1980 to 1996 in Lilacs. RESEARCH PROCEDURE: We reviewed the articles available at BIREME (Biblioteca Regional de Medicina) with the primary focus being on the disease in question. SUMMARY: RP is a rare disease of unknown etiology described initially by Jackson-Wartenhorst in 1923 and characterized by a recurrent and acute inflammatory process that causes the collapse of the cartilaginous structures and their subsequent replacement by fibrous connective tissue. The cartilage most commonly attacked is that of the auricle of the ear and nasal septum, while the cartilage of the trachea, larynx, epiglottis, ribs, and articulations may also be involved. Ocular inflammations and systemic reactions with fever are also described. In 1976, McAdam presented a complete prospective study of 23 patients, reviewed the 136 cases described up until that time, and then proposed diagnostic criteria which were later expanded by Damiani and Levine. Currently, more than 500 cases have been described. CONCLUSION: Although a rare disease, better knowledge of it is needed, as RP may be lethal with tracheal collapse and obstruction of respiratory pathways, making precise diagnosis and adequate therapeutic intervention necessary.

OBJECTIVE: To define and disseminate the optimal search strategy for clinical trials in the Latin American and Caribbean Health Science Literature (LILACS). This strategy was elaborated based on the optimal search strategy for MEDLINE recommended by Cochrane Collaboration for the identification of clinical trials in electronic databases. DESIGN: Technical information. SETTING: Clinical Trials and Meta-Analysis Unit, Federal University of São Paulo, in conjunction with the Brazilian Cochrane Center, São Paulo, Brazil. (http://www.epm.br/cochrane). DATA: LILACS/CD-ROM (Latin American and Caribbean Health Science Information Database), 27th edition, January 1997, edited by BIREME (Latin American and Caribbean Health Science Information Center). LILACS Indexes 670 journals in the region, with abstracts in English, Portuguese or Spanish; only 41 overlap in the MEDLINE-EMBASE. Of the 168.902 citations since 1982, 104,016 are in human trials, and 38,261 citations are potentiality clinical trials. Search strategy was elaborated combining headings with text word in three languages, adapting the interface of the LILACS. We will be working by locating clinical trials in LILACS for Cochrane Controlled Trials Database. This effort is being coordinated by the Brazilian Cochrane Center.

ABSTRACT BACKGROUND: Osteoporosis compromises bone strength and increases the risk of fractures. Zoledronate prevents loss of bone mass and reduces the risk of fractures. OBJECTIVES: To determine the efficacy and safety of zoledronate in postmenopausal women with osteopenia and osteoporosis. DESIGN AND SETTINGS A systematic review and meta-analysis was conducted within the evidence-based health program at the Universidade Federal de São Paulo. METHODS: An electronic search of the CENTRAL, MEDLINE, Embase, and LILACS databases was performed until February 2022. Randomized controlled trials comparing zoledronate with placebo or other bisphosphonates were included. Standard methodological procedures were performed according to the Cochrane Handbook and the certainty of evidence for the Grading of Recommendations Assessment, Development, and Evaluation Working Group. Two authors assessed the risk of bias and extracted data on fractures, adverse events, bone turnover markers (BTM), and bone mineral density (BMD). RESULTS: Twelve trials from 6,652 records were included: nine compared zoledronate with placebo, two trials compared zoledronate with alendronate, and one trial compared zoledronate with ibandronate. Zoledronate reduced the incidence of fractures in osteoporotic [three years: morphometric vertebral fractures (relative risk, RR = 0.30 (95% confidence interval, CI: 0.24–0.38))] and osteopenic women [six years: morphometric vertebral fractures (RR = 0.39 (95%CI: 0.25–0.61))], increased incidence of post-dose symptoms [RR = 2.56 (95%CI: 1.80–3.65)], but not serious adverse events [RR = 0.97 (95%CI: 0.91–1.04)]. Zoledronate reduced BTM and increased BMD in osteoporotic and osteopenic women. CONCLUSION: This review supports the efficacy and safety of zoledronate in postmenopausal women with osteopenia for six years and osteoporosis for three years. PROSPERO REGISTRATION NUMBER: CRD42022309708, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309708.

ABSTRACT BACKGROUND: Grading of Recommendations Assessment, Development and Evaluation (GRADE) is a tool for assessing evidence produced in synthesis reports. OBJECTIVES: To present the translation into Portuguese of the GRADE checklist, whose original version is in English, and to describe and explain each topic, in order to provide examples to researchers and professionals who will use the tool. DESIGN AND SETTING: Descriptive study developed at Centro Universitário Tiradentes, Maceió, Alagoas, Brazil. METHODS: This was a translation of the GRADE checklist, with the addition of the Risk Of Bias In Systematic Reviews (ROBIS) tool in the checklist, with examples of its use. RESULTS: Situations of practical use of the tool were presented in order to facilitate and expand the use of assessment of the quality and strength of evidence among Portuguese speakers. CONCLUSIONS: The GRADE checklist is valuable in helping to assess the strength and quality of evidence for synthesis reports for healthcare decision-making.

ABSTRACT BACKGROUND: Tocilizumab is an anti-human interleukin 6 receptor monoclonal antibody that has been used to treat coronavirus disease 2019 (COVID-19). However, there is no consensus on its efficacy for the treatment of COVID-19. OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab for treating COVID-19. DESIGN AND SETTING: Systematic Review of randomized controlled trials (RCTs), Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil. METHODS: We searched MEDLINE via PubMed, EMBASE, CENTRAL, and IBECS for RCTs published up to March 2021. Two authors selected studies and assessed the risk of bias and the certainty of the evidence following Cochrane Recommendations. RESULTS: Eight RCTs with 6,139 participants were included. We were not able to find differences between using tocilizumab compared to standard care on mortality in hospitalized patients with COVID-19 (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.84 to 1.13; 8 trials; 5,950 participants; low-certainty evidence). However, hospitalized patients under tocilizumab plus standard care treatment seemed to present a significantly lower risk of needing mechanical ventilation (risk ratio = 0.78; 95% CI 0.64−0.94 moderate-certainty of evidence). CONCLUSIONS: To date, the best evidence available shows no difference between using tocilizumab plus standard care compared to standard care alone for reducing mortality in patients with COVID-19. However, as a finding with a practical implication, the use of tocilizumab in association to standard care probably reduces the risk of progressing to mechanical ventilation in those patients. REGISTRATION: osf.io/qe4fs.

ABSTRACT BACKGROUND: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of infection. OBJECTIVE: To assess whether patients undergoing pharmacological treatment for IMID present higher risk of worse outcomes when diagnosed with COVID-19. DESIGN AND SETTING: Rapid systematic review conducted in the medical school of the Federal University of São Paulo (SP), Brazil. METHODS: We searched CENTRAL, MEDLINE, EMBASE, LILACS, SCOPUS, Web of Science, L·OVE, ClinicalTrials.gov and WHO-ICTRP for studies evaluating patients diagnosed with COVID-19 who were undergoing pharmacological treatment for IMID. Two authors selected studies, extracted data and assessed risk of bias and certainty of evidence, following the Cochrane recommendations. RESULTS: We identified 1,498 references, from which one cohort study was included. This compared patients with and without rheumatic diseases (RD) who all had been diagnosed with COVID-19. Those with RD seemed to have higher chances of hospitalization and mortality, but no statistical difference was detected between the groups: hospitalization: odds ratio (OR) 1.17; 95% confidence interval (CI) 0.6 to 2.29; mortality rate: OR 1.53; 95% CI 0.33 to 7.11 (very low certainty of evidence). Patients with RD were three times more likely to require admission to intensive care units (ICUs), with invasive mechanical ventilation (IMV), than those without RD: OR 3.72; 95% CI 1.35 to 10.26 (for both outcomes; very low certainty of evidence). CONCLUSION: Patients undergoing pharmacological treatment for IMID seem to present higher chances of requiring admission to ICUs, with IMV. Additional high-quality studies are needed to analyze the effects of different treatments for IMID.

ABSTRACT BACKGROUND: Faced with a pandemic, all healthcare actions need to reflect best practices, in order to avoid high transmissibility, complications and even hospitalizations. For hospital environments, the products recommended and authorized by regulatory institutions for environmental cleaning and disinfection need to be highly effective. OBJECTIVE: To identify, systematically evaluate and summarize the best available scientific evidence on environmental cleaning to prevent COVID-19 infection. DESIGN AND SETTING: A systematic review of studies analyzing cleaning products that inactivate coronavirus, conducted within the evidence-based health program of a federal university in São Paulo (SP), Brazil. METHODS: A systematic search of the relevant literature was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL and LILACS databases, for articles published up to May 27, 2020, relating to studies evaluating cleaning products that inactivate coronavirus in the environment. RESULTS: Seven studies were selected. These analyzed use of 70% alcohol, detergent, detergent containing iodine, household bleach, sodium hypochlorite, hydrogen peroxide, chlorine dioxide, glutaraldehyde, ultraviolet irradiation and plasma air purifier. The effectiveness of treating sewage with sodium hypochlorite and chlorine dioxide was also evaluated. CONCLUSION: Disinfection of environments, especially those in ordinary use, such as bathrooms, needs to be done constantly. Viral inactivation was achieved using chlorine-based disinfectants, alcohol, detergents, glutaraldehyde, iodine-containing detergents, hydrogen peroxide compounds and household bleaches. Alcohol showed efficient immediate activity. In sewage, sodium hypochlorite had better action than chlorine dioxide. REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/YC5P4 in the Open Science Framework.

ABSTRACT BACKGROUND: A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS CoV-2, from nasopharyngeal swabs, is the current gold standard diagnostic test for this virus and has sensitivity of 60-70%. Some studies have demonstrated a significant number of false-negative RT-PCR tests while displaying significant tomographic findings, in the early days of symptoms of COVID-19. OBJECTIVE: To compare accuracy between RT-PCR and computed tomography (CT) for detecting COVID-19 in the first week of its symptoms during the pandemic. DESIGN AND SETTING: Systematic review of comparative studies of diagnostic accuracy within the Evidence-based Health Program of a federal university in São Paulo (SP), Brazil. METHODS: A systematic search of the relevant literature was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL and LILACS databases, for articles published up to June 6, 2020, relating to studies evaluating the diagnostic accuracy of RT-PCR and chest CT for COVID-19 diagnoses. The QUADAS 2 tool was used for methodological quality evaluation. RESULTS: In total, 1204 patients with COVID-19 were evaluated; 1045 had tomographic findings while 755 showed positive RT-PCR for COVID-19. RT-PCR demonstrated 81.4% sensitivity, 100% specificity and 92.3% accuracy. Chest CT demonstrated 95.3% sensitivity, 43.8% specificity and 63.3% accuracy. CONCLUSION: The high sensitivity and detection rates shown by CT demonstrate that this technique has a high degree of importance in the early stages of the disease. During an outbreak, the higher prevalence of the condition increases the positive predictive value of CT. REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/UNGHA in the Open Science Framework.

ABSTRACT BACKGROUND: COVID-19 infection has high transmissibility and several measures have been adopted for controlling its dissemination. OBJECTIVE: To identify and summarize the evidence from Cochrane systematic reviews (SRs) regarding measures for controlling the dissemination of COVID-19 infection. DESIGN AND SETTING: This review of Cochrane SRs was carried out in the Division of Vascular and Endovascular Surgery and in the Division of Emergency Medicine and Evidence-Based Medicine of Universidade Federal de São Paulo, Brazil. METHODS: A comprehensive search in the Cochrane Database of Systematic Reviews retrieved all Cochrane SRs directly related to measures for controlling COVID-19 dissemination. The main characteristics and results of all the SRs included were summarized and discussed. RESULTS: Three Cochrane SRs were included in the qualitative synthesis. These evaluated population-based and individual measures for controlling the dissemination of COVID-19. CONCLUSION: Low-certainty evidence shows that quarantine for people exposed to confirmed or suspected COVID-19 cases prevented 44% to 81% of incident cases and 31% to 63% of deaths, compared with situations of no measures. Moreover, the sooner the quarantine measures were implemented, the greater the cost savings were. High-confidence evidence showed that clear communication about infection control and prevention guidelines was vital for successful implementation. Low-certainty evidence showed that healthcare professionals with long gowns were less exposed to contamination than were those using coveralls. In addition, coveralls were more difficult to doff. Further SRs on controlling the dissemination of COVID-19 infection are desirable.

ABSTRACT BACKGROUND: The authors of randomized controlled trials will usually claim that they have met the randomization process criterion. However, sequence generation schemes differ and some schemes that are claimed to be randomized are not genuinely randomized. Even less well understood, and often more difficult to ascertain, is whether the allocation was really concealed. OBJECTIVE: To detect the extent of control over selection bias, in a comparison between two Cochrane groups: oral health and otorhinolaryngology; and to describe the methods used to control for this bias. DESIGN AND SETTING: Cross-sectional study conducted in a public university in São Paulo, Brazil. METHODS: The risk of selection bias in 1,714 records indexed in Medline database up to 2018 was assessed, independent of language and access. Two dimensions implicated in the allocation were considered: generation of the allocation sequence; and allocation concealment. RESULTS: We included 420 randomized controlled trials and all of them were evaluated to detect selection bias. In the sample studied, only 28 properly controlled the selection bias. Lack of control over selection bias was present in 80% of the studies evaluated in both groups. CONCLUSION: The two groups were similar regarding control over selection bias. They are also similar to the methods used. The dimension of allocation concealment appears to be a limiting factor with regard to production of randomized controlled trials with low risk of selection bias. The quality of reporting in studies on oral health and otorhinolaryngology is suboptimal and needs to be improved, in line with other fields of healthcare.

ABSTRACT BACKGROUND: The speed of the spread of coronavirus disease 2019 (COVID-19) has put enormous pressure on hospitals and other healthcare facilities. This, together with blockages in several countries, has hindered the availability and accessibility of the necessary personal protective equipment (PPE). OBJECTIVE: To identify, systematically evaluate and summarize the available scientific evidence on the efficacy, safety, safe use and reuse of PPE for healthcare professionals, for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN AND SETTING: Systematic review of studies analyzing products for disinfecting and enabling reuse of PPE for coronavirus within the evidence-based health program of a federal university in São Paulo (SP), Brazil. METHODS: A systematic search of the relevant literature was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, SCOPUS, Web of Science and LILACS databases, for articles published up to November 30, 2020. RESULTS: Ten studies were selected. These analyzed the use of N95, surgical and cotton masks, face shields, flexible enclosures with plastic covers or polycarbonate intubation boxes and plastic curtains; and also PPE disinfection using several substances. CONCLUSION: Combined use of a face shield with a N95 mask proved to be superior to other associations for protecting healthcare workers. Some products are useful for disinfecting PPE, such as 70% ethanol, 0.1% sodium hypochlorite and a mixture of quaternary ammonium and H2O2, and hydrogen peroxide. Ultraviolet light and dry heat at 70 °C can be used to decontaminate N95 masks. REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/4V5FD at the OPENSCIENCE Framework.

ObjectivesTo determine whether the generic and branded warfarins used as anticoagulants in Brazil are therapeutic equivalents based on their international normalized ratio (INR) results.MethodsThis crossover randomized controlled trial had four periods. We used the branded Marevan and two generic versions of warfarin sodium tablets, manufactured by União Química and Teuto laboratories, all purchased from retail drugstores. Eligible participants were outpatients from an anticoagulation clinic at a university hospital in São Paulo, Brazil. They had atrial fibrillation or flutter and had been using warfarin for at least 2 months with an INR therapeutic range of 2.0-3.0. Randomization was by numbered, opaque, sealed envelopes. Healthcare personnel and outcome assessors were blinded to treatments, but patients were not. The primary outcome was the variability in the INR (ΔINR) and secondary outcomes included mean INR. We accepted formulations as equivalent if the 95% confidence interval (CI) of the comparison of ΔINR between branded and generic formulations was within the limit of ±0.49.ResultsOne hundred patients were recruited and randomized to six sequences of treatment (four sequences with n = 17 and two sequences with n = 16). União Química generic warfarin had equivalent variability in the INR to Marevan (ΔINR +0.09 [95% CI -0.29 to +0.46], n = 84). Comparison between Teuto generic warfarin and Marevan was inconclusive (ΔINR +0.29 [95% CI -0.09 to +0.68], n = 84).ConclusionsMarevan and União Química warfarin had equivalent therapeutic effectiveness and both could be confidently used for anticoagulation. The comparison between Marevan and TW was inconclusive and does not warrant a statement of equivalence. Our methods are especially important for comparing generic and branded drugs that raise concerns and may be subject of future investigations by regulatory agents.Trial registrationClinicalTrials.gov NCT02017197.

BackgroundThere is ample evidence that gestational diabetes mellitus has a direct influence on urinary incontinence and pelvic floor muscles. There are no standardized pelvic floor muscle exercise programs in the literature for the physiotherapy and differ in the type of exercise, intensity, type and duration of application, and the frequency and duration of treatment sessions. The aim of this systematic review will be to investigate that Pelvic Floor Muscle Training can prevent and/or decrease the pregnancy specific urinary incontinence in women with gestational diabetes mellitus or gestational hyperglycemia.MethodsWe will perform a systematic review according to the Cochrane methodology of Randomized Controlled Trials. An overall search strategy will be developed and adapted for Embase, MEDLINE, LILACS, and CENTRAL databases, with the date of consultation until June 2020. The MeSH terms used will be "Pregnancy", "Hyperglycemia", "Diabetes Mellitus, Type 2", "Diabetes Mellitus, Type 1", "Pregnancy in Diabetics", "Diabetes, Gestational", "Urinary Incontinence", "Pelvic Floor Muscle Strength". Primary outcomes: improvement or cure of pregnancy specific urinary incontinence (which can be assessed by questionnaires, and tools such as tampon test, voiding diary, urodynamic study). Secondary outcomes: improvement of pelvic floor muscle strength (pelvic floor functional assessment, perineometer, electromyography, functional ultrasonography), improved quality of life (questionnaires), presence or absence of postpartum Urinary Incontinence and adverse effects. Quality assessment by Cochrane instrument. Metanalysis if plausible, will be performed by the software Review Manager 5.3.DiscussionThe present study will be the first to analyze the effectiveness of pelvic floor exercises in pregnant women with Gestational Diabetes Mellitus or Hyperglycemia, who suffer from pregnancy specific urinary incontinence. Randomized Controlled Trials design will be chosen because they present the highest level of evidence. It is expected to obtain robust and conclusive evidence to support clinical practice, in addition to promoting studies on the theme and contributing to new studies.Trial registrationSystematic review registration: PROSPERO CRD42017065281.

BackgroundRelapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS).Methods and findingsWe conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; PConclusionsThis retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.

In the Western world, calcified aortic valve stenosis is the most common form of valvular heart disease, affecting up to 3% of adults over the age of 75 years. It is a gradually progressive disease, characterized by a long asymptomatic phase that may last for several decades, followed by a short symptomatic phase associated with severe restriction of the valve orifice. Investigations on treatments for aortic valve stenosis are still in progress. Thus, it is believed that calcification of aortic valve stenosis is similar to the process of atherosclerosis that occurs in coronary artery disease. Recent studies have suggested that cholesterol lowering through the use of statins may have a salutary effect on the progression of aortic valve stenosis

CONTEXT AND OBJECTIVE: Poison control centers play an essential role in caring for poisoned patients, albeit without secure funding for their activities. The aim here was to investigate differences in length of hospital stay among poisoned patients, between those who received remote assistance from a poison control center and those who did not. DESIGN AND SETTING: A retrospective cohort including all poisoned patients hospitalized at an emergency service in Manaus between 2005 and 2007 was set up, and the local poison control center database was checked to see whether they received such assistance. METHODS: Patients presenting a known toxic agent, with less than 12 hours since exposure and without severe comorbidities, were selected. Their severity of poisoning was evaluated by two independent reviewers and divergences were resolved by another reviewer. RESULTS: One hundred and ninety-eight patients were included. Those who received remote assistance from a poison control center stayed in hospital on average for 3.43 days less than those without poison control center assistance (95% confidence interval, CI: -6.10 to -0.77). Severity was assessed in the cases of 90 patients: there was no statistical difference in severity between the patients with and without poison control center assistance (P > 0.5). CONCLUSION: Patients with remote assistance from a poison control center had a shorter length of stay then patients without this aid. The poison control center may have reduced the length of stay of the poisoned patients

Objective: To assess data on survival, recurrence and histological factors in positive and negative sentinel lymph nodes in thin melanoma cases. Methods: A systematic review was conducted on observational studies in four databases (Cochrane Library, Medline, Embase and Lilacs). Positive and negative micrometastases in sentinel lymph node biopsy were compared regarding the clinical outcomes – death and recurrence – and six histological factors – vertical growth phase, Breslow thickness, Clark level, ulceration, regression and mitosis rate. Results: Positive sentinel lymph node is statistically associated with greater risk of death in six studies (OR: 7.2; 95%CI [2.37-21.83]; I2 0%) and also to recurrence in three studies (OR: 30.7; 95%CI [12.58-74.92]; I2 36%). Comparing positive and negative groups, the histological factors predicting positive sentinel nodes and poor prognosis were: mitosis rate ≥ 5/mm2 (OR: 16.29; 95%CI [3.64-72.84]; I2 40%); VGP (OR: 2.93; 95%CI [1.08-7.93]; I2 59%); Breslow thickness ≥ 0.75mm (OR: 2.23; 95%CI [1.29-3.86]; I2 0%); and Clark level IV-V (OR: 1.61; 95%CI [1.06-2.44]; I2 34%). Conclusions: The statistically significant results associated with the presence of micrometastases in thin melanomas were Breslow thickness ≥ 0.75 mm, Clark level IV-V and mitoses ≥ 5/mm2, absence of regression. This histological factor of ulceration was associated, but not statistically significant.

OBJECTIVE: To determine whether sodium nitroprusside causes fetal death in pregnancies complicated with hypertension. DATA SOURCES: Medical Literature Analysis and Retrieval System Online (MEDLINE; 1996 to 2003), Excerpta Medica (EMBASE; 1970 to 2003), Web of Science/Institute for Scientific Information (ISI; 1945 to 2003), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS; 1982 to 2003) and the Cochrane Library. REVIEW METHODS: The medical subject headings used were "nitroprusside and pregnancy", "hypertension or eclampsia or preeclampsia" and "nitroprusside and pregnancy and hypertensive emergencies". The search was limited to humans and female gender, in all fields, publication types, languages and subsets. Articles were also identified by reviewing the references of articles and textbooks on hypertension and pregnancy. RESULTS: The search located nine studies. The sum of all the publications yielded a total of 22 patients and 24 exposed fetuses (two pairs of twins). There were no randomized clinical trials and no prospective cohorts. All of the studies were observational in nature. CONCLUSIONS: At present, there is insufficient evidence for definitive conclusions about any direct association between sodium nitroprusside use and fetal demise.

Age-related macular degeneration (AMD) is a disease that causes reduced visual acuity and blindness. The new treatment options for AMD are not provided by the Brazilian public health system.To conduct a budget impact analysis of three scenarios for the introduction of AMD treatments: all the medications (verteporfin, ranibizumab, and bevacizumab-the reference scenario), ranibizumab alone, and bevacizumab alone.The basic assumption was that the Brazilian public health system would treat the entire target population with AMD aged > 70 years between 2008 and 2011. The size of the population of interest was estimated from official population projections and the prevalence of the disease was obtained from a systematic review. Medication prices were estimated by weighting their market values with correction factors to take account of the public procurement policy. The possibility of aliquoting bevacizumab was also considered. A panel of experts was consulted to estimate the market share of the different medications for the reference scenario. The incremental costs of the ranibizumab-alone and bevacizumab-alone scenarios compared to the reference scenario were calculated. Univariate sensitivity analyses were run to check the robustness of the model.In four years, the Brazilian public health system would have treated 1,136,349 individuals with AMD. The annual costs of treating one patient would have been US$476.65 for bevacizumab, US$11,469.39 for ranibizumab, and US$4,376.28 for verteporfin. The incremental cost of the ranibizumab-alone scenario would have been US$1,878,318,056.00 in four years, while the incremental cost for the bevacizumab-alone scenario would have been a reduction of US$4,978,326,359.00 (i.e., a cost saving) in the same period. The bevacizumab-alone option was found to represent a cost saving across sensitivity analyses.The introduction of bevacizumab for the treatment of AMD is recommended for the Brazilian Public Health System.

CONTEXT: The puerperal gestational cycle is accompanied by a state of physiological hypercoagulability. Thromboembolic phenomena may occur at this time. OBJECTIVE: To report on a clinic case involving a patient that presented a family history of thromboembolism and developed deep vein thrombosis in a lower limb and vena cava thrombosis during the puerperal gestational cycle, displaying nephrotic syndrome as the main complication. DESIGN: Case report.

CONTEXT: The incidence of staphylococcal infection has been increasing during the last 20 years. OBJECTIVE: Report a case of staphylococcal endocarditis preceded by musculoskeletal manifestations, which is a rare form of clinical presentation. DESIGN: Case report. CASE REPORT: A 45-year-old-man, without addictions and without known previous cardiopathy, was diagnosed as having definitive acute bacterial endocarditis due to Staphylococcus aureus. Its etiology was community-acquired, arising from a non-apparent primary focus. In addition, the musculoskeletal symptoms preceded the infective endocarditis (IE) by about 1 month, which occurred together with other symptoms, e.g. mycotic aneurysms and petechiae. Later, the patient showed perforation of the mitral valve and moderate mitral insufficiency with clinical control.

CONTEXT AND OBJECTIVE: Cardiac resynchronization therapy (CRT) has emerged as the predominant electrical treatment strategy for patients on pharmacological therapy who present heart failure with wide QRS and low ejection fraction. The objective of this study was to investigate whether cardiac resynchronization therapy improved mortality and morbidity among patients with heart failure. METHODS: This was a systematic review using the Cochrane Collaboration's methodology. The online search strategy included the Cochrane Library, Medline (Medical Literature Analysis and Retrieval System Online), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) and cardiology congresses from 1990 to 2006. The criteria for considering studies for this review were as follows:-types of studies: randomized controlled trials; types of interventions: cardiac resynchronization therapy compared with other therapies; types of participants: patients with heart failure with low ejection fraction and wide QRS; outcomes: death or hospitalization. RESULTS: Seven trials met the selection criteria. The risk of death due to congestive heart failure was nonsignificant: relative risk (RR), 0.79; 95% confidence interval (CI): 0.60 to 1.03. There was an absolute risk reduction of 4% in all-cause mortality for the experimental group #&091;RR 0.70; CI: 0.60 to 0.83; number needed to treat (NNT) 25#&093;; sudden cardiac death showed a statistically significant difference favoring the experimental group, with absolute risk reduction of 1% (CI: 0.46 to 0.96; RR 0.67; NNT 100). There was an absolute risk reduction of 9% for hospitalization due to heart failure (RR 0.64; CI: 0.50 to 0.80; NNT 11) in the experimental group. CONCLUSIONS: Patients receiving CRT had a significantly lower risk of hospitalization due to heart failure, but death rates due to heart failure were similar.

CONTEXT: Systemic arterial hypertension is part of the metabolic syndrome resulting from obesity. OBJECTIVE: To evaluate the effect of sibutramine on overweight and obese patients' blood pressure through a systematic review. METHODS: All the studies included needed to be randomized controlled trials. The methodological quality of the selected trials was assessed using the criteria described in the Cochrane Handbook. The participants were overweight and obese patients; the intervention was sibutramine compared with placebo. The primary outcome measurement was systolic and diastolic blood pressure and the secondary measurement was blood pressure. Studies were identified by searching the following sources: Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Medline, Cochrane reviews, manual searches, personal communication and contact with the pharmaceutical industry. There were no language, date or other restrictions. Data collection and extraction was performed by two reviewers, who independently obtained the full articles of all eligible papers. RESULTS: Three meta-analyses were produced: 1) systolic blood pressure outcome (eight studies) did not show statistical significance between sibutramine and placebo: weighted mean difference (WMD) 1.57, confidence interval (CI) -0.03 to 3.18; 2) diastolic blood pressure outcome (ten studies) did not show statistical significance between sibutramine and placebo: WMD 1.13, CI -0.49 to 2.76; 3) blood pressure outcome (two studies) also did not show statistical significance between the groups: relative risk (RR) 0.69, CI 0.07 to 7.01. CONCLUSIONS: The meta-analyses presented in this systematic review show that sibutramine does not have a statistically significant effect on blood pressure, compared with placebo.

CONTEXT AND OBJECTIVE: The initial method for evaluating the presence of pleural effusion was chest radiography. Isolated studies have shown that sonography has greater accuracy than radiography for this diagnosis; however, no systematic reviews on this matter are available in the literature. Thus, the aim of this study was to evaluate the accuracy of sonography in detecting pleural effusion, by means of a systematic review of the literature. DESIGN AND SETTING: This was a systematic review with meta-analysis on accuracy studies. This study was conducted in the Department of Diagnostic Imaging and in the Brazilian Cochrane Center, Discipline of Emergency Medicine and Evidence-Based Medicine, Department of Medicine, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil. METHOD: The following databases were searched: Cochrane Library, Medline, Web of Science, Embase and Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs). The references of relevant studies were also screened for additional citations of interest. Studies in which the accuracy of sonography for detecting pleural effusion was tested, with an acceptable reference standard (computed tomography or thoracic drainage), were included. RESULTS: Four studies were included. All of them showed that sonography had high sensitivity, specificity and accuracy for detecting pleural effusions. The mean sensitivity was 93% (95% confidence interval, CI: 89% to 96%), and specificity was 96% (95% CI: 95% to 98%). CONCLUSIONS: In different populations and clinical settings, sonography showed consistently high sensitivity, specificity and accuracy for detecting fluid in the pleural space.

ABSTRACT Objective: To describe neurological status and associated factors of survivors after cardiac arrest, upon discharge, and at 6 and 12 month follow-up. Methods: A cohort, prospective, descriptive study conducted in an emergency room. Patients who suffered cardiac arrest and survived were included. A one-year consecutive sample, comprising 285 patients and survivors (n=16) followed up for one year after discharge. Neurological status was assessed by the Cerebral Performance Category before the cardiac arrest, upon discharge, and at 6 and 12 months after discharge. The following factors were investigated: comorbidities, presence of consciousness upon admission, previous cardiac arrest, witnessed cardiac arrest, location, cause and initial rhythm of cardiac arrest, number of cardiac arrests, interval between collapse and start of cardiopulmonary resuscitation, and between collapse and end of cardiopulmonary resuscitation, and duration of cardiopulmonary resuscitation. Results: Of the patients treated, 4.5% (n=13) survived after 6 and 12 months follow-up. Upon discharge, 50% of patients remained with previous Cerebral Performance Category of the cardiac arrest and 50% had worsening of Cerebral Performance Category. After 6 months, 53.8% remained in the same Cerebral Performance Category and 46.2% improved as compared to discharge. After 12 months, all patients remained in the same Cerebral Performance Category of the previous 6 months. There was no statistically significant association between neurological outcome during follow-up and the variables assessed. Conclusion: There was neurological worsening at discharge but improvement or stabilization in the course of a year. There was no association between Cerebral Performance Category and the variables assessed.