Although the number of confirmed cases of spotted fever has been declining in Brazil since 2005, the mortality rate (20% to 30%) is still high in comparison to other countries. This high mortality rate is closely related to the difficulty in making the diagnosis and starting the correct treatment. Only two groups of antibiotics have proven clinical effectiveness against spotted fever: chloramphenicol and tetracyclines. Until recently, the use of tetracyclines was restricted to adults because of the associated bone and tooth changes in children. Recently, however, the American Academy of Pediatrics and various researchers have recommended the use of doxycycline in children. In more severe cases, chloramphenicol injections are often preferred in Brazil because of the lack of experience with injectable tetracycline. Since early diagnosis and the adequate drug treatment are key to a good prognosis, health care professionals must be better prepared to recognize and treat spotted fever.

Abstract

OBJECTIVE:To assess the rationality of legal suits and administrative requests requiring anticancer drugs fi led against and submitted to the São Paulo State Department of Health, in view of scientifi c evidence on effi cacy and safety. METHODS:A descriptive cross-sectional study was carried out based on information on lawsuits fi led by cancer patients requiring anticancer drugs were furnished by the Department of Health. These drugs are among those having the greatest fi nancial impact on the Brazilian Health System in 2006 and 2007. The drugs were assessed according to clinical evidence on effi cacy and safety, based on Micromedex ® categorization, on systematic reviews and meta-analyses. Indications present in the legal documentation were compared to the indications approved by regulatory agencies. RESULTS:Bevacizumab, capecitabine, cetuximab, erlotinib, rituximab, imatinib, and temozolomide accounted for expenses over R$ 40 million to meet 1220 requests and lawsuits, at an average cost of R$ 33,500 per patient. Selected studies do not recommend all the indications for the prescribed drugs. Approximately 17% of requests and lawsuits did not provide evidence for the required indication, and these amounted to inappropriate expenses of, at least, R$ 6.8 million. CONCLUSIONS:The results reinforce the need for technical expertise in dealing with legal suits and for capacity-building of health professionals in approaching the scientifi c literature, in order to appropriately select drugs and to ensure the best therapeutic decision for each clinical condition, and thus guarantee access to safe and effective health technologies and, therefore, to enhance the quality of the Brazilian pharmaceutical services model in oncology.

OBJECTIVE:To analyze judicial requests for medications that are covered by the pharmaceutical assistance components of the Sistema Único de Saúde (SUS -Brazilian Unifi ed Health System). METHODS:We analyzed 81 judicial requests for medications in the State of São Paulo between 2005 and 2009. The details of these cases were obtained electronically from the Court of Justice of the State of São Paulo. Directives that regulate pharmaceutical assistance were consulted to identify judicially requested medications that are covered by the SUS. To assess the level of evidence supporting the use of these medications to treat the clinical indications described, we consulted the Thomson Micromedex® database. RESULTS:The number of individual medications requested in each case ranged from 1 to 7; in total, 77 different pharmaceuticals agents were identifi ed. Of the medications requested, 14.3% should have been available through SUS primary care, 19.5% were classifi ed under the exceptionally dispensed medications component of the SUS, and 66.2% were not on any offi cial list. Medications of the exceptionally dispensed medications component showed better clinical evidence when indicated for the treatment of medical conditions covered by the Clinical Protocols and Therapeutic Guidelines of Brazil's Ministry of Health. CONCLUSIONS:The judicial process has been used to ensure access to medications that are covered by the SUS and to request access to those that are not covered. Our assessment of the level of available evidence reinforces the need for technical analysis in the decision-making process in cases of judicially requested medications.

OBJECTIVE: Identify and critically evaluate systematic reviews addressing the effectiveness of interventions to reduce the number of prescriptions of potentially inappropriate medication to older patients. METHODS: This is an overview of systematic reviews. The studies were searched and selected from Medline, Cochrane Library, Embase, CINAHL, Virtual Health Library, and Web of Science databases, combining the terms aged, prescriptions, inappropriate prescribing and potentially inappropriate medication list with their entry terms and other related descriptors, published by June 2017. This study included systematic reviews with or without meta-analysis that addressed the effectiveness of any intervention or combined interventions to reduce the number of prescriptions of potentially inappropriate medications to older patients, without restriction in terms of design, language or date of publication of primary studies. AMSTAR – A MeaSurement Tool to Assess systematic Reviews – was used to evaluate the methodological quality of selected systematic reviews. Study selection and the methodological quality evaluation were performed by two independent evaluators, who resolved any divergence by consensus. The main findings were grouped into thematic categories, defined after a content analysis and discussed qualitatively as narrative synthesis. RESULTS: This study analyzed 24 systematic reviews. In terms of study design and methodological quality evaluation, most were systematic reviews of randomized controlled clinical trials and studies of moderate quality, respectively. The interventions were analyzed in five thematic categories: medication review services, pharmaceutical interventions, computerized systems, educational interventions, and others. The interventions analyzed showed good results and most of them helped reduce the number of prescriptions of potentially inappropriate medication to older patients. CONCLUSIONS: The systematic reviews included in this overview showed potential benefits of different interventions. However, it was not possible to determine the most effective intervention. Combined interventions are likely to provide better results than isolated interventions.

Background: Biological agents used for the treatment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are associated with serious adverse effects (SAEs). Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to a relative lack of long-term safety data. Objective: To determine the frequency and severity of adverse effects associated with the long-term use of biologics in the treatment of PsA and RA, and possible risk factors for such events in a real-life setting. Methods: We conducted a longitudinal study in PsA and RA patients only taking long-term biological agents from 2003 to 2011. Sources of information included dispensing pharmacy data and interviews with patients. Research staff conducted telephone interviews with patients inquiring about any apparent medication-related adverse drug reactions (ADRs) or SAEs. ADR/SAE’s data was based on pharmacy reports. We conducted a multivariate analysis to identify the factors associated with the risk of ADRs. Results: Of the 305 patients identified, we interviewed 268 patients. Most of these were taking adalimumab 127 (47.4%), 52 (19.4%) etanercept, 42 (15.7%) infliximab, 25 (9.3%) rituximab, 10 (3.7%) abatacept, 9 (3.4%) efalizumab, and 3 (1.1%) tocilizumab. Of the 268 patients, 116 (43.3%) experienced one or more adverse events related to biological agents with 1.6 events per patient, and of these 29 (25%) experienced one or more SAEs, with majority subjected to hospitalizations. The most frequently reported ADRs were administration site reactions as observed in 73 patients (27.2%), infections in 30 patients (11.2%), effects on nervous system in 22 patients (8.2%), and 15 (5.6%) patients withdrew due to ADRs. The use of rituximab was related with less risk of ADR [PR 0.42, 95% CI 0.18–0.96; p = 0.04] than other agents. No other predisposing factors were associated with risk of ADR. The monitoring of patients (medical consultation and laboratory test) was only completed by 48 patients (30.4%). Conclusion: These data showed the early biological experience in Brazil that were associated with ADRs, withdrawals due to ADRs and SAEs. The quantification of adverse effects (serious or nonserious) considering close monitoring and patients’ perceptions are increasingly important for future decision-making.

BackgroundRheumatoid arthritis affects 1% of the world's population and its current treatment options are costly. There are not enough studies that evaluated the efficacy and safety of anti-inflammatory drugs medications used to reduce rheumatoid arthritis's symptoms. This study will evaluate the effectiveness and the safety of steroid and nonsteroidal anti-inflammatory drugs for the treatment of patients with rheumatoid arthritis.MethodsRandomized clinical trials eligible for our systematic review will enroll adults with rheumatoid arthritis treated with anti-inflammatory drugs compared with a control group (placebo or active control) at any dose, duration, and route of administration and double blind studies. In order to include all forms of rheumatoid arthritis and anti-inflammatory drugs, we will search the following electronic databases: Cochrane Central Register of Controlled Trials, MEDLINE (via Ovid); ExcerptaMedica Database (via Ovid); Cumulative Index to Nursing and Allied Health Literature (via Ovid); Web of Science; ClinicalTrial.gov; and WHO International Clinical Trials Registry Platform. We will not impose any language restrictions or publication status. Outcomes of interest include are pain, physical function, swelling, stiffness, grip force, radiological image of the joint, quality of life, adverse events, discontinuation due to adverse events, satisfaction with the treatment, and rescue medication for pain. A team of reviewers will independently screen search results, extract data from eligible trials, and assess risk of bias. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate overall certainty of the evidence by outcome. Dichotomous data will be summarized as risk ratios; continuous data will be given as standard average differences with 95% confidence intervals.ResultsThe evidence derived by this study will increase awareness of the effectiveness and safety of steroid and nonsteroidal anti-inflammatory drugs for the treatment of rheumatoid arthritis.ConclusionThe results could guide patients and healthcare practitioners and help facilitate evidence-based shared care decision making.

Background:The awakening and breathing coordination of daily sedation and ventilator removal trials, delirium monitoring and management, and early mobility and exercise (ABCDE) and assessment, prevent and manage pain, both spontaneous awakening and spontaneous breathing trials, choice of analgesia and sedation, assess, prevent and manage delirium, early mobility and exercise, family engagement (ABCDEF) bundles are part of the science of the liberation of the intensive care unit (ICU). There are not enough studies that have evaluated the effectiveness and safety of the implementation of these bundles. This study will analyze the implementation process, estimate their effectiveness and safety, and identify barriers, facilitators and attitudes that have influenced the implementation process.Methods:Qualitative and quantitative studies will be eligible for our systematic review with adult patients who have been exposed to the implementation of the ABCDE or ABCDEF bundles compared to the usual care in the ICU. In order to search the implementation interventions of the bundles, we will search electronically: MEDLINE (PubMed); Excerpta Medica Database (Ovid); Cumulative Index to Nursing and Allied Health Literature (EBSCO); The Cochrane Library (Wiley); Web of Science; Virtual Health Library; and OpenGrey. We will not impose any language restrictions or publication status. Outcomes of interest include ICU and hospital length of stay; mechanical ventilation time; incidence and prevalence of delirium or coma; level of agitation and sedation; early mobilization; mortality in ICU and hospital; change in perception, attitude or behavior of the stakeholders; and change in knowledge of health professionals. The team of reviewers will independently screen search results, extract data from eligible studies, and assess risk of bias. Disagreements between the reviewers will be solved through consensus or arbitration by a third-party investigator. To assess the quality and risk of bias in randomized and quasi-randomized trials we will use the domain-based evaluation recommended by The Cochrane Handbook. Studies with other methodological designs will be evaluated using the Critical Appraisal Tools developed by The Joanna Briggs Institute. Other instruments may be used, if necessary.Results:The evidence derived from this study will increase the knowledge of effectiveness and safety of the implementation process of ABCDE and ABCDEF bundles.Conclusion:The results could guide patients and healthcare practitioners by helping to facilitate evidence-based shared care decision making.Protocol registration:PROSPERO CRD42019121307.