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Regulatory agencies around the world have been using flexible requirements for approval of new drugs, especially for cancer drugs. The US Food and Drug Administration (FDA) is mostly the first agency to approve new drugs worldwide, mainly due to the faster terms of the accelerated pathway and breakthrough therapy designation. Surrogate endpoints and preliminary data (e.g. single-arm and phase 2 studies) are used for these new approvals, however larger effect sizes are expected. We aim to compare FDA Accelerated vs Regular Pathway approvals and Breakthrough therapy designations (BTD) for lung cancer treatments between 2006 and 2018 regarding study design, sample size, outcome measures and effect size. We assessed the FDA database to collect data from studies that formed the basis of approvals of new drugs or indications for lung cancer spanning from 2006 to 2018. We found that accelerated pathway approvals are based on significantly more single-arm studies with small sample sizes and surrogate primary endpoints. However, effect size was not different between the pathways. A large proportion of studies used to support regular pathway approvals also showed these characteristics that are related to low quality and uncertain evidence. Compared to other approvals, BTD were more frequently based on single-arm studies. There was no significant difference in use of surrogate endpoints or sample size. 44% of BTD were based on studies demonstrating large effect sizes, proportionally more than approvals not receiving this designation. In conclusion, based on the indicators of evidence quality we extracted, criteria's for granting accelerated approval and breakthrough therapy designation seen not clear. Faster approvals are in the majority full of uncertainties which should be viewed with caution and the patient have to be communicated to allow shared decision making. Post-marketing validation is essential., Competing Interests: The authors have declared that no competing interests exist.

Objective: This paper aims to describe the clinical and regulatory aspects of new drugs and indications that were approved for lung, breast, prostate, and colorectal cancer, from 2016 to 2018, in order to provide health technology assessment trends in oncology., Methods: Data were collected from the US Food and Drug Administration (FDA) online database for new medications and indications approved for the above-mentioned types of cancer. Data regarding clinical study characteristics and regulatory information were collected., Results: From 2016 to 2018, 53 percent of the FDA approvals of new drugs and indications for the most incident cancers were for oral protein kinase inhibitor monotherapy for advanced lung cancer. Since 2018, four drugs were approved as tumor-agnostic therapies. A biomarker was included in 72 percent of indications, and 58 percent of approvals were for targeted therapies, potentially heralding an end to research into conventional cytotoxic agents. A special designation for faster approval was granted in 78 percent of new approvals. The majority of the studies were open label randomized controlled trials (RCTs) (44 percent), followed by blind RCTs, single-arm clinical trials, and cohort studies. Only 14 percent of studies used overall survival as the primary end point; the vast majority used surrogate end points, and did not use patient-important outcomes. Three biosimilars were approved in the period., Conclusion: Advanced lung cancer therapy, mainly targeted drugs, accounted for 53 percent of approvals. Special designations for faster approval were used in 78 percent of FDA approvals, and four drugs were approved for tumor-agnostic treatment-a new form of approval.

Background: Ice-pack is widely used for alleviating postpartum perineal pain sustained after birth related perineal trauma. However, it lacks robust evidence on timing and frequency of applications, to ensure the effective and safe use of this therapy., Aims: To evaluate if a 10min ice-pack application relieved postpartum perineal pain and if the analgesic effect was maintained for up to 2h., Methods: A randomised controlled trial conducted from December 2012 to February 2013 with 69 primiparous women ≥18 years old, 6-24h postpartum, with perineal pain ≥3, who had not received anti-inflammatory medication or analgesics after childbirth, who were randomised to a single ice-pack application on the perineum for 10min or standard care. The primary and secondary outcomes were a reduction ≥30% in perineal pain intensity, immediately after the application and the maintenance of the analgesic effect for up to 2h, respectively., Findings: Immediately post-intervention, the proportion of women whose perineal pain decreased ≥30% was significantly higher in the experimental group. Within 2h, there was no significant difference in the pain levels in both groups. Within 2h, for 61.9% and 89.3% of women in the experimental and control group, respectively, the perineal pain levels remained unchanged. For the remaining participants, perineal pain was increasing after an average time of 1h 45min and 1h 56min for the experimental and control groups, respectively., Conclusion: By applying an ice-pack for 10min to the perineum, effective pain relief is achieved, that is maintained for between 1h 45min and 2h., (Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Rheumatoid arthritis primarily affects the working-age population and may cause key functional and work limitations. As the disease progresses, individuals become increasingly unable to conduct daily activities, which has a substantial personal and socioeconomic impact. Fairly recent prior studies showed that patients with RA stop working 20 years earlier than age-matched controls. Factors related to sociodemographic, clinical, care and disease profiles might affect the loss of work capacity. The purpose of this study was to assess the factors associated with the prevalence of working patients with rheumatoid arthritis in the municipality of Blumenau., Methods: A cross-sectional, population-based study was conducted between July 2014 and January 2015, with 296 individuals aged 20 years or older, male and female, living in Blumenau, Santa Catarina state, Brazil, and diagnosed with rheumatoid arthritis according to the 1987 American College of Rheumatology criteria. The prevalence of working patients with RA was assessed by employment status self-reporting during the interview. The chi-squared test, Wald test and Poisson regression analysis were used to test the possible associations between the independent variables and outcome., Results: The prevalence of working patients with rheumatoid arthritis was 44.3%. Patients aged 20 to 59 years had a 90% higher prevalence of outcome than subjects aged 60 years or older. The prevalence of working patients was 132% and 73% higher among individuals with low income and high functional disability, measured using the Health Assessment Questionnaire (HAQ), respectively., Conclusion: The prevalence of working RA patients was highest among adult patients with low income and high functional disability. The first variable is directly related to the individual characteristic, the second reflects the socioeconomic context of the patient, and the third reflects the degree of disability caused by the disease, which may be modifiable by health professionals.

Objective: To estimate the prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis., Methods: A cross-sectional study using the American College of Rheumatology diagnostic criteria in order to select patients seen at primary or secondary health care units in Blumenau, Santa Catarina, Southern Brazil, in 2014. The presence of ischemic heart disease was defined as an acute myocardial infarction with percutaneous coronary intervention or coronary artery bypass graft surgery that has occurred after diagnosis. Fischer's exact test, Wald's linear trend test, and multivariate logistic regression analysis were used to test the associations., Results: Among 296 patients (83.1% female) with a mean age of 56.6 years and a mean rheumatoid arthritis duration of 11.3 years, 13 reported having acute myocardial infarction requiring a percutaneous or surgical reperfusion procedure, a prevalence of 4.4% (95% CI 2.0-6.7). Diabetes Mellitus (odds ratio [OR] 4.9 [95% CI 1.6-13.8]) and disease duration >10 years (OR 8.2 [95% CI 1.8-39.7]) were the only factors associated with an ischemic disease that remained in the final model, after the multivariate analysis., Conclusion: The prevalence of acute myocardial infarction was similar to that observed in other studies. Among the traditional risk factors, Diabetes Mellitus, and among the factors related to rheumatoid arthritis, disease duration, were the variables associated with comorbidity., (Copyright © 2017 Elsevier Editora Ltda. All rights reserved.)

Introduction: An electronic healthcare record (EHR) system, when used by healthcare providers, improves the quality of care for patients and helps to lower costs. Information collected from manual or electronic health records can also be used for purposes not directly related to patient care delivery, in which case it is termed secondary use. EHR systems facilitate the collection of this secondary use data, which can be used for research purposes like observational studies, taking advantage of improvement in the structuring and retrieval of patient information. However, some of the following problems are common when conducting a research using this kind of data: (i) Over time, systems and data storage methods become obsolete; (ii) Data concerns arise since the data is being used in a context removed from its original intention; (iii) There are privacy concerns when sharing data about individual subjects; (iv) The partial availability of standard medical vocabularies and natural language processing tools for non-English language limits information extraction from structured and unstructured data in the EHR systems. A systematic approach is therefore needed to overcome these, where local data processing is performed prior to data sharing., Method: The proposed study describes a local processing method to extract cohorts of patients for observational studies in four steps: (1) data reorganization from an existing local logical schema into a common external schema over which information can be extracted; (2) cleaning of data, generation of the database profile and retrieval of indicators; (3) computation of derived variables from original variables; (4) application of study design parameters to transform longitudinal data into anonymized data sets ready for statistical analysis and sharing. Mapping from the local logical schema into a common external schema must be performed differently for each EHR and is not subject of this work, but step 2, 3 and 4 are common to all EHRs. The external schema accepts parameters that facilitate the extraction of different cohorts for different studies without having to change the extraction algorithms, and ensures that, given an immutable data set, can be done by the idempotent process. Statistical analysis is part of the process to generate the results necessary for inclusion in reports. The generation of indicators to describe the database allows description of its characteristics, highlighting study results. The set extraction/statistical processing is available in a version controlled repository and can be used at any time to reproduce results, allowing the verification of alterations and error corrections. This methodology promotes the development of reproducible studies and allows potential research problems to be tracked upon extraction algorithms and statistical methods RESULTS: This method was applied to an admissions database, SI 3 , from the InCor-HCFMUSP, a tertiary referral hospital for cardiovascular disease in the city of São Paulo, as a source of secondary data with 1116848 patients records from 1999 up to 2013. The cleaning process resulted in 313894 patients records and 27698 patients in the cohort selection, with the following criteria: study period: 2003-2013, gender: Male, Female, age:≥18years old, at least 2 outpatient encounters, diagnosis of cardiovascular disease (ICD-10 codes: I20-I25, I64-I70 and G45). An R script provided descriptive statistics of the extracted cohort., Conclusion: This method guarantees a reproducible cohort extraction for use of secondary data in observational studies with enough parameterization to support different study designs and can be used on diverse data sources. Moreover it allows observational electronic health record cohort research to be performed in a non-English language with limited international recognized medical vocabulary., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: There are few studies that carried out a descriptive and trend analysis based on available data from the Unified Health System (SUS) between pre- and post-free dispensing of pharmacological treatment of rheumatoid arthritis (RA) from the perspective of the public health system, in terms of the direct cost of the disease among adults and elderly residents of the State of Santa Catarina, Brazil. This study aims to characterize the direct cost of medical and surgical procedures before and after the dispensing of drugs in this state., Methods: This is a time series-type study with a cross-sectional survey of data from the Hospital (SIH) and Outpatient (SIA) Information System of SUS during the period from 1996 to 2009., Results: Between 1996 and 2009, the total expenditure for hospital- and outpatient pharmacological treatment of rheumatoid arthritis was R$ 26,659,127.20. After the dispensing of drug treatment by SUS a decrease of 36% in the number of hospital admissions was observed; however, an increase of 19% in clinical procedures was noted., Conclusion: During the observed period, a reduction in the number of hospital admissions for both clinical and orthopedic surgical procedures related to this disease was observed. Nevertheless, there was an increase in the cost of medical admissions., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

Introduction:: The effectiveness of the treatment of chronic diseases depends on the participation of the patient, influenced by different sociocultural factors, which are not fully recognized by the treatment routine., Objective:: To search for some of these factors that hinder or facilitate adherence to treatment and use of healthcare resources, approaching patients with ischemic heart disease., Method:: A cross-sectional study was conducted using face-to-face interviews. We applied semi-structured questionnaires to 347 individuals and recorded 141 interviews for qualitative analysis. Descriptors were selected to identify eight categories of analyses. The quantitative data were submitted to descriptive analysis of frequency., Results:: Only 2% had good medication adherence according to score on Morisky questionnaire. About 23% bought statins; the others obtained statin in the public health institution. Thirty-six speeches were selected and classified according to the following categories: knowledge about disease and medication, difficulty of acquisition, self management of treatment, difficulties of access to health services, side effect of statins, caregiver support, transportation to health services and concerns about the disease progression. However, it was noticed that about 1/3 of the care outside the research institution can be characterized as an attempt to bring rationalization to the health system., Conclusion:: The improved adherence to chronic treatment of ischemic heart disease depends on the establishment of effective flows for referral and counter-referral from one care unit to another, relevant information and clarification of the questions for the patients and the attention of health professionals to the many social and cultural factors involved in treatment adherence. New research should be focused on educational groups by integrated multidisciplinary teams in order to share treatment decisions, thereby increasing the patient's commitment to his own health.

Objective: To evaluate the effect of school-based physical activity (PA) and nutritional education (NE) interventions on children's and adolescents' body mass index., Methods: We conducted a systematic search in fourteen databases until September 2012 for randomised controlled trials on PA and NE, conducted in the school setting, and delivered to children and adolescents. Additionally, we performed a cross-reference check in related papers. The title and abstract review and the quality assessment were performed by two independent researchers. The software EPPI-Reviewer3 was used to store, manage and analyse all data. The meta-analysis was conducted using the random-effects model, and the outcomes were reported as standardised mean difference (SMD). As a secondary analysis, we pooled together the interventions that considered PA or NE alone., Results: Thirty-eight studies met the eligibility criteria. The main analysis showed a SMD between intervention and control groups of -0.03 (95% CI: -0.09, 0.04; n=28,870; I(2)=83%). When we considered all 57 trials, there was no difference between the results of the primary analysis., Conclusion: The synthesis of school-based PA and NE interventions showed no statistically significant mean reduction on children's and adolescents' body mass index. The high heterogeneity among studies requires caution in the generalisation of the results., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This study reviewed the effectiveness of school-based physical activity interventions aimed at reducing overweight, obesity and hypertension in children. We searched 14 databases and analyzed studies published between April 2009 and September 2012. Only randomized controlled trials performed at the school level that included elements of physical activity but did not include nutritional co-interventions were analyzed. Studies were assessed by two recommended tools (EPHPP and GRADE), and the standardized mean differences with 95% confidence intervals were collected for a random-effect meta-analysis. A total of 12 papers were included in the meta-analysis, and these were divided according to three outcomes: body mass index (11 trials, n = 4,273, -0.02, 95% CI: -0.13 to 0.17, p = 0.8); body weight (5 trials, n = 1,330, -0.07, 95% CI: -0.18 to 0.04, p = 0.2); and blood pressure (6 trials, n = 1,549), including systolic (0.11, 95% CI: -0.10 to 0.31, p = 0.3) and diastolic pressure (-0.00, 95% CI: -0.10 to 0.10, p = 0.9). This meta-analysis of data from 11 randomized, school-based physical activity interventions suggests that, regardless of the potential benefits of physical activity in the school environment, the interventions did not have a statistically significant effect. However, it is difficult to generalize from these results because the duration, intensity and type of physical activity used in the interventions varied greatly.

Objective: The aim of this study was to evaluate the effectiveness of school-based nutrition education interventions in reducing or preventing overweight and obesity among children and adolescents., Methods: We conducted a systematic search of 14 databases until May 2010 and cross-reference check in 8 systematic reviews (SRs) for studies published that described randomized controlled trials conducted in schools to reduce or prevent overweight in children and adolescents. An additional search was carried out using PubMed for papers published through May 2012, and no further papers were identified. Body mass index (BMI) was the primary outcome. The title and abstract review and the quality assessment were performed independently by two researchers. The software EPPI-Reviewer3 was used to store, manage and analyze all data. This SR is registered at ClinicalTrials.gov (NCT00985972)., Results: From the 4888 references initially retrieved, only 8 met the eligibility criteria for a random-effects meta-analysis. The total population consisted of 8722 children and adolescents. Across the studies, there was an average treatment effect of -0.33 kg/m(2) (-0.55, -0.11 95% CI) on BMI, with 84% of this effect explained by the highest quality studies., Conclusion: This systematic review provides evidence that school-based nutrition education interventions are effective in reducing the BMI of children and adolescents., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: to identify factors associated with maternal intrapartum transfer from a freestanding birth centre to hospital., Design: case-control study with retrospective data collection., Participants and Settings: cases included all 111 women transferred from a freestanding birth centre in Sao Paulo to the referral hospital, from March 2002 to December 2009. The controls were 456 women who gave birth in the birth centre during the same period who were not transferred, randomly selected with four controls for each case., Methods: data were obtained from maternal records. Factors associated with maternal intrapartum transfers were initially analysed using a χ(2) test of association. Variables with p<0.20 were then included in multivariate analyses. A multiple logistic regression model was built using stepwise forward selection; variables which reached statistical significance at p<0.05 were considered to be independently associated with maternal transfer., Findings: during the study data collection period, 111 (4%) of 2,736 women admitted to the centre were transferred intrapartum. Variables identified as independently associated factors for intrapartum transfer included nulliparity (OR 5.1, 95% CI 2.7-9.8), maternal age ≥35 years (OR 5.4, 95% CI 2.1-13.4), not having a partner (OR 2.8, 95% CI 1.5-5.3), cervical dilation ≤3 cm on admission to the birth centre (OR 1.9, 95% CI 1.1-3.2) and between 5 and 12 antenatal appointments at the birth centre (OR 3.8, 95% CI 1.9-7.5). In contrast, a low correlation between fundal height and pregnancy gestation (OR 0.3, 95% CI 0.2-0.6) appeared to be protective against transfer., Conclusions and Implications for Practice: identifying factors associated with maternal intrapartum transfer could support decision making by women considering options for place of birth, and support the content of appropriate information about criteria for admission to a birth centre. Findings add to the evidence base to support identification of women in early labour who may experience later complications and could support timely implementation of appropriate interventions associated with reducing transfer rates., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: to evaluate the effects of low-level laser therapy for perineal pain and healing after episiotomy., Design: a double-blind, randomised, controlled clinical trial comparing perineal pain scores and episiotomy healing in women treated with low-level laser therapy (LLLT) and with the simulation of the treatment., Setting: the study was conducted in the Birth Centre and rooming-in units of Amparo Maternal, a maternity service located in the city of São Paulo, Brazil., Participants: fifty-two postpartum women who had had mediolateral episiotomies during their first normal delivery were randomly divided into two groups of 26: an experimental group and a control group., Intervention: in the experimental group, the women were treated with LLLT. Irradiation was applied at three points directly on the episiotomy after the suture and in three postpartum sessions: up to 2 hrs postpartum, between 20 and 24 hrs postpartum and between 40 and 48 hrs postpartum. The LLLT was performed with diode laser, with a wavelength of 660 nm (red light), spot size of 0.04 cm(2), energy density of 3.8 J/cm(2), radiant power of 15 mW and 10s per point, which resulted in an energy of 0.15 J per point and a total energy of 0.45 J per session. The control group participants also underwent three treatment sessions, but without the emission of radiation (simulation group), to assess the possible effects of placebo treatment., Main Outcomes: perineal pain scores, rated on a scale from 0 to 10, were evaluated before and immediately after the irradiation in the three sessions. The healing process was assessed using the REEDA scale (Redness, Edema, Echymosis, Discharge Aproximation) before each laser therapy session and 15 and 20 days after the women's discharge., Findings: comparing the pain scores before and after the LLLT sessions, the experimental group presented a significant within-group reduction in mean pain scores after the second and third sessions (p=0.003 and p<0.001, respectively), and the control group showed a significant reduction after the first treatment simulation (p=0.043). However, the comparison of the perineal pain scores between the experimental and control groups indicated no statistical difference at any of the evaluated time points. There was no significant difference in perineal healing scores between the groups. All postpartum women approved of the low-level laser therapy., Conclusions: this pilot study showed that LLLT did not accelerate episiotomy healing. Although there was a reduction in perineal pain mean scores in the experimental group, we cannot conclude that the laser relieved perineal pain. This study led to the suggestion of a new research proposal involving another irradiation protocol to evaluate LLLT's effect on perineal pain relief., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Surrogate endpoints may be used as substitutes for, but often do not predict clinically relevant events. Objective To assess the methodological quality of articles that present their conclusions based on clinically relevant or surrogate outcomes in a systematic review of randomised trials and cohort studies of patients with rheumatoid arthritis treated with antitumour necrosis factor (TNF) agents., Methods: PubMed, Embase and Cochrane databases were searched. The Jadad score, the percentage of Consolidated Standards Of Reporting Trials (CONSORT) statement items adequately reported and levels-of-evidence (Center for Evidence-based Medicine, Oxford) were used in a descriptive synthesis., Results: Among 88 articles appraised, 27 had surrogate endpoints, mainly radiographic, and 44 were duplicate publications; 74% of articles with surrogate and 39% of articles with clinical endpoints (p=0.006). Fewer articles with surrogate endpoints represented a high level of evidence (Level 1b, 33% vs 62%, p=0.037) and the mean percentage of CONSORT statement items met was also lower for articles with surrogate endpoints (62.5 vs 70.7, p=0.026). Although fewer articles with surrogate endpoints were randomised trials (63% vs 74%, p=0.307) and articles with surrogate endpoints had lower Jadad scores (3.0 vs 3.2, p=0.538), these differences were not statistically significant., Conclusion: Studies of anti-TNF agents that report surrogate outcomes are of lesser methodological quality. As such, inclusion of such studies in evidence syntheses may bias results.

Introduction: This study evaluated the effectiveness of an ice pack applied for 20 minutes to alleviate perineal pain after spontaneous vaginal birth., Methods: We conducted a randomized controlled trial at the Amparo Maternal Birth Center in São Paulo, Brazil. Study participants included 114 nulliparous women divided into 3 groups (n = 38 per group): experimental (ice packs on the perineum), placebo (water packs at set temperature), and control (no treatment)., Results: A numerical scale (0 to 10) was used for pain assessment. A comparison of the average pain at the beginning and after 20 minutes showed a significant reduction of pain (P < .001) in the 3 groups, and the experimental group had a lower average score for pain compared with the control group (1.6 versus 3.3, P = .032)., Discussion: The use of ice packs for 20 minutes was effective for perineal pain relief after vaginal birth., (© 2011 by the American College of Nurse-Midwives.)

Objective: To document the relationship between physical activity, absenteeism, presenteeism, health care utilization, and morbidity among Brazilian automotive workers., Methods: Eligible employees (N = 620) completed a questionnaire. Univariate correlations, multivariate logistic regression, and Pearson's product-moment correlation coefficient were used., Results: Work absenteeism was associated with physical activity at work (OPA) (odds ratio, [OR] = 1.63, 95% confidence interval [CI] = 1.31 to 2.02) and leisure physical activity time excluding sport (OR = 0.73, 95% CI = 0.58 to 1.00). Health care utilization was associated with OPA (OR = 1.25, 95% CI = 0.99 to 1.58) and leisure physical activity time excluding sport (OR = 0.76, 95% CI = 0.57 to 1.02). Presenteeism showed an indirect relationship with OPA (r = 0.099, P = 0.014). Referred morbidity was associated with OPA (OR = 1.3, 95% CI = 1.06 to 1.61) and sports during leisure time (OR = 0.67, 95% CI = 0.54 to 0.82)., Conclusions: Physical activity components seem to have differential relationships to the studied outcomes. Associations measured indicate negative impacts of OPA on absenteeism, health care utilization, and morbidity, although overall physical activity did not show these relationships.

Context: Malignant fungating wounds (MFW) result from cutaneous infiltration by carcinogenic cells. Fetid odor, profuse exudate, pain, and infection are common symptoms that add to the physical and psychological suffering of patients with MFW. The topical treatment of MFW remains controversial., Objectives: To collect evidence about topical treatments to control the odor of MFW., Methods: Fourteen sources of data were used, without restriction in terms of language, period, or study design. The patient, intervention, comparison, and outcome strategy for the development of research questions yielded 334 descriptors related to oncology, MFW, topical treatments, medications, and symptoms of these lesions. Data from the abstracts of these articles were extracted by two independent researchers and decisions were reached by consensus among them. Through an analysis of these abstracts, studies that broached the topic of MFW odor were selected. These studies were analyzed in their entirety and were classified according to quality, levels of evidence, and grade of recommendation., Results: Of 11,111 studies identified, 325 (2.93%) made reference to the control of some symptoms of MFW by means of topical interventions: 12.4% related to odor, 16.8% to exudate, 17.8% to bleeding, 31.0% to pain, and 22.0% to MFW-related infection. Within the 59 studies that analyzed odor control, seven were clinical trials (35%), five were case series (25%), and eight (40%) were case studies. Eleven topical treatments were identified. Topical metronidazole and Mesalt dressing yielded 2b level of evidence or B grade of recommendation. Activated carbon dressing and curcumin ointment yielded 2c level of evidence or B grade of recommendation. C and D grades of recommendation were observed for seven topical treatments: topical arsenic trioxide, essential oils, green tea extract, hydropolymer dressings, antiseptic solutions, hydrogels, and debridement enzymes. The variety of interventions and of the methodological quality of the studies did not allow for meta-analysis., Conclusion: Of the 59 studies of odor, 20 fulfilled all the criteria for inclusion. Few studies of high quality were found, and the principal methodological flaws were the design of the studies, the sample size, and the absence of scales to measure odor. Grade B evidence for the treatment of MFW was found with topical metronidazole, Mesalt dressing, activated carbon dressing, and curcumin ointment., (Copyright 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Objective: to evaluate the effect of an immersion bath on pain magnitude during the first stage of labour., Design: a randomised controlled trial comparing the pain scores of bathing and non-bathing nulliparous women during birth was employed., Setting: the study was conducted at the Normal Birth Center of Amparo Maternal, São Paulo, Brazil., Participants: 108 birthing women, with 54 women randomly assigned to each group., Interventions: when the birthing women presented at 6-7 cm of cervical dilation, they were placed in an immersion bath for 60 mins., Outcome Measures: pain scores, using a behavioural pain scale and a numeric scale, were recorded at two evaluation time points: at 6-7 cm of cervical dilation and 1h after the first pain score evaluation., Findings: at the first evaluation, on the behavioural scale, the means were 2.1 for both groups (p=0.914; 95% confidence intervals (CI) 1.9-2.3 for the control group and 2.0-2.2 for the experimental group). On the numeric scale, the means were 8.7 and 8.5 for the control and experimental groups, respectively (p=0.235; 95% CI 8.2-9.2 for the control group and 8.1-8.9 for the experimental group). At the second evaluation, the pain score means for both scales were statistically higher in the control group than in the experimental group. On the behavioural scale, the scores were 2.4 vs. 1.9, respectively, for the control and experimental groups (p<0.001; 95% CI 2.2-2.6 for the control group and 1.7-2.1 for the experimental group). On the numeric scale, the scores were 9.3 vs. 8.5, respectively, for the control and experimental groups (p<0.05; 95% CI 8.9-9.7 for the control group and 8.1-8.9 for the experimental group)., Conclusions: mean labour pain scores in the control group were significantly higher than those in the experimental group. The present findings suggest that use of an immersion bath is a suitable alternative form of pain relief for women during labour.

Introduction: The present study was motivated by the need to systematically assess the research productivity of the Heart Institute (InCor), Medical School of the University of São Paulo, Brazil., Objective: To explore methodology for the assessment of institutional scientific research productivity., Materials and Methods: Bibliometric indicators based on searches for author affiliation of original scientific articles or reviews published in journals indexed in the databases Web of Science, MEDLINE, EMBASE, LILACS and SciELO from January 2000 to December 2003 were used in this study. The retrieved records were analyzed according to the index parameters of the journals and modes of access. The number of citations was used to calculate the institutional impact factor., Results: Out of 1253 records retrieved from the five databases, 604 original articles and reviews were analyzed; of these, 246 (41%) articles were published in national journals and 221 (90%) of those were in journals with free online access through SciELO or their own websites. Of the 358 articles published in international journals, 333 (93%) had controlled online access and 223 (67%) were available through the Capes Portal of Journals. The average impact of each article for InCor was 2.224 in the period studied., Conclusion: A simple and practical methodology to evaluate the scientific production of health research institutions includes searches in the LILACS database for national journals and in MEDLINE and the Web of Science for international journals. The institutional impact factor of articles indexed in the Web of Science may serve as a measure by which to assess and review the scientific productivity of a research institution.

Objective: The increasing use of opioids by patients suffering from chronic pain caused by different etiologies, and the possible effects of those substances on everyday activities, require careful evaluation of their effects. For this purpose, a systematic review was developed to assess the influence of opioids on the cognitive function in patients with chronic pain., Methods: Eleven databases were analyzed using the following descriptors: opioids, opiates, narcotics, cognitive impairment, cognitive dysfunction, cognitive disorders and pain. The inclusion criteria were: clinical trials or case reports which included patients with chronic pain in treatment with opioids, cognitive assessment by specific tests and publication in English, Spanish or Portuguese., Results: Sixteen surveys published between 1980 and 2004 met the criteria: six controlled trials, two randomized trials, and 10 studies of a lower scientific evidence level. All better quality controlled trials did not show cognitive impairment of patients under opioid therapy., Conclusion: These results must be confirmed by additional randomized trials including a greater number of patients with chronic pain.

Evidence based practice is the use of the best scientific evidence to support the clinical decision making. The identification of the best evidence requires the construction of an appropriate research question and review of the literature. This article describes the use of the PICO strategy for the construction of the research question and bibliographical search.

Background: To study the prevalence of cardiovascular risk associated to the lifestyle of school children from the 5th to 8th grade, in public and private schools., Methods: Eighty seven randomly selected school rooms were visited adding up to 2,125 students who completed the questionnaire and whose body mass index was calculated. This sample represents around 2% of students from two school districts in the city of Sao Paulo., Results: Of the 2,125 students, 24% were overweight or obese, 53.3% presented inappropriate food habits, 15.4% were sedentary, 62.6% drank alcohol, and 23.1% smoked. Between the 5th and 8th grade, the number of students who drank alcohol doubled and the number of male and female adolescents who tried out smoking increased 3-fold and 5-fold, respectively. Conversely, inappropriate food habits decreased. This situation is found in 40% of students from public schools and in 58% of those in private schools, by the time they reach the 8th grade. Overweight and obesity are more prevalent in private schools and the reduction noted as grades progress did not reach a significance level. Sedentarism is more prevalent in public schools. In private ones, sedentarism is lower among older students, contrary to public schools, where it increases with age. Female adolescents attend fewer physical education classes. Inappropriate food habits were characterized by the habits of adding more salt to pre-prepared food, lower intake of dairy products, fruit and vegetables also a higher intake of soft drinks, butter and snacks., Conclusion: Early detection of these cardiovascular risks associated to the lifestyle of these school children endorses the preventive practice of providing health education in schools.

Evidence based health care begins with a clinical question and the search on data bases to retrieve the relevant information, that was the issue of two preceding articles of this series. At present it will be discussed how to critically appraise the medical literature using the clinical epidemiological methodology. Clinical research aims to develop diagnostic and therapeutic procedures measuring association and causality between the exposure and outcome. In this case the exposures are signs, symptoms, laboratorial or image exam, and therapy intervention. It is a mistake to take surrogate end-points instead of clinical outcomes. The main types of clinical study design are diagnostic, prognostic, therapeutic and harm/etiology. Experimental, physiologic and animal studies are useful for the medical undergraduate education, but do not contribute with clinical decisions. The study designs are classified according with the presence of a control group, patient's follow-up, and therapy interventions. The evidence hierarchy was done by the previous characteristics and the presence of systematic bias. Systematic reviews are stronger than the primary observational studies and are on the top when they revised randomized clinical trial. Since 1998 the proportion of evidence based practice guidelines was increasing compared with systematic reviews or other types of practice guidelines, although the former still are in a few numbers. The article critical appraisal must answer the clinical question, and need to have consistent study design and bias under control. In conclusion we ought to offer methodological actualization to interested physicians and put the information already critically assessed on evidence-based practice guidelines.

The inadequacy of most of traditional sources for medical information, like textbook and review article, do not sustained the clinical decision based on the best evidence current available, exposing the patient to a unnecessary risk. Although not integrated around clinical problem areas in the convenient way of textbooks, current best evidence from specific studies of clinical problems can be found in an increasing number of Internet and electronic databases. The sources that have already undergone rigorous critical appraisal are classified as secondary information sources, others that provide access to original article or abstract, as primary information source, where the quality assessment of the article rely on the clinician oneself . The most useful primary information source are SciELO, the online collection of Brazilian scientific journals, and Medline, the most comprehensive database of the USA National Library of Medicine, where the search may start with use of keywords, that were obtained at the structured answer construction (P.I.C.O.), with the addition of boolean operators "AND", "OR", "NOT". Between the secondary information sources, some of them provide critically appraised articles, like ACP Journal Club, Evidence Based Medicine and InfoPOEMs, others provide evidences organized as online texts, such as "Clinical Evidence" and "UpToDate", and finally, Cochrane Library are composed by systematic reviews of randomized controlled trials. To get studies that could answer the clinical question is part of a mindful practice, that is, becoming quicker and quicker and dynamic with the use of PDAs, Palmtops and Notebooks.

Clinical decisions in daily practice, to resolve patient's problem, are usually based at the conscious use of the available information, through explicit determined rules. Evidence based clinical practice recognize the explicit and tacit knowledge, understanding that it is impossible all the aspects of professional competence become explicit. The doubt becomes part of the decision process, identifying initially the unconscious component involved and after the explicit knowledge used. When we make a structured clinical question with a possible answer, it is necessary to remember that the doubt can be related to basics and of definition aspects of the disease or related to the patient's manager, like diagnose, treatment and prognosis. Along our medical life, both types of question are present, with proportional change as the experience increase along the clinical practice. The process to find an appropriate answer to the doubt, came out at patient's care, depends on how the parts of this process will be structured. The recommended form is known by PICO abbreviation, that means: P: patient or population, I: intervention or indicator, C: comparison or control and O: outcome, or the answer expected found at the scientific information bases. This is the first basic need to a successful search, and the second need is to find the key words that better describe each of the four components of the questions. Without this caution, the search at compute databases results in absence of information or in a lot of information that it is not related to our interest.