Pharmaceutical policies: effects of policies regulating drug marketing.

BACKGROUND: The costs of developing new treatments and bringing them to the market are substantial. The pharmaceutical industry uses drug promotion to gain a competitive market share, and drive sale volumes and industry profitability. This involves disseminating information about new treatments to relevant targets. However, conflicts of interest can arise when profits are prioritised over patient care and its benefits. Drug promotion regulations are complex interventions that aim to prevent potential harm associated with these activities. OBJECTIVES: To assess the effects of policies that regulate drug promotion on drug utilisation, coverage or access, healthcare utilisation, patient outcomes, adverse events and costs. SEARCH METHODS: We searched Epistemonikos for related reviews and their included studies. To find primary studies we searched MEDLINE, CENTRAL, Embase, EconLit, Global Index Medicus, Virtual Health Library, INRUD Bibliography, two trial registries and two sources of grey literature. All databases and sources were searched in January 2023. SELECTION CRITERIA: We planned to include studies that assessed policies regulating drug promotion to consumers, healthcare professionals or regulators and third-party payers, or any combination of these groups.In this review we defined policies as laws, rules, guidelines, codes of practice, and financial or administrative orders made by governments, non-government organisations or private insurers. One of the following outcomes had to be reported: drug utilisation, coverage or access, healthcare utilisation, patient health outcomes, any adverse effects (unintended consequences), and costs. The study had to be a randomised or non-randomised trial, an interrupted time series analysis (ITS), a repeated measures (RM) study or a controlled before-after (CBA) study. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed eligibility for inclusion of studies. When consensus was not reached, any disagreements were discussed with a third review author.  We planned to use the criteria suggested by Cochrane Effective Practice and Organisation of Care (EPOC) to assess the risk of bias of included studies. For randomised trials, non-randomised trials, and CBA studies, we planned to estimate relative effects, with 95% confidence intervals (CI). For dichotomous outcomes, we planned to report the risk ratio (RR) when possible and adjusted for baseline differences in the outcome measures. For ITS and RM, we planned to compute changes along two dimensions: change in level and change in slope. We planned to undertake a structured synthesis following EPOC guidance.  MAIN RESULTS: The search yielded 4593 citations, and 13 studies were selected for full-text review. No study met the inclusion criteria. AUTHORS' CONCLUSIONS: We sought to assess the effects of policies that regulate drug promotion on drug use, coverage or access, use of health services, patient outcomes, adverse events, and costs, however we did not find studies that met the review's inclusion criteria. As pharmaceutical policies that regulate drug promotion have untested effects, their impact, as well as their positive and negative influences, is currently only a matter of opinion, debate, informal or descriptive reporting. There is an urgent need to assess the effects of pharmaceutical policies that regulate drug promotion using well-conducted studies with high methodological rigour.

Use of second-generation antipsychotics in autism spectrum disorder: a systematic review and meta-analysis protocol.

INTRODUCTION: Atypical antipsychotics have been studied to treat autism spectrum disorder (ASD). However, like little is known about whether these drugs are effective and safe when compared in controlled and non-controlled settings. This study aims to assess the efficacy and safety of second-generation antipsychotics in ASD in randomised controlled trials (RCT) and observational studies. METHODS AND ANALYSIS: This systematic review will include RCT and prospective cohorts evaluating second-generation antipsychotics in people 5 years and older diagnosed with ASD. Searches will be conducted in Medline, Embase, Cochrane Library, Epistemonikos, Lilacs, CINAHL, PsycINFO, trial registries and grey literature databases without restriction on publication status, year of publication and language. The primary outcomes will be symptoms of aggressive behaviour, quality of life for the individual or their careers, and discontinuation or dropouts/withdrawals of antipsychotics due to adverse events. The secondary outcomes are other not serious adverse events and adherence to pharmacotherapy. Selection, data extraction, and quality assessment will be performed by pairs of reviewers, independently. The Risk of Bias 2 (RoB 2) and Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tools will be used to assess the risk of bias in the included studies. If appropriate, a meta-analysis and network meta-analysis will be conducted to synthesise the results. The overall quality of the evidence for each outcome will be determined by the Recommendation, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This study will systematically summarise the existing evidence evaluating the use of second-generation antipsychotics for treating ASD, in controlled and uncontrolled studies. The results of this review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022353795.

Physiotherapeutic approach to the preoperative period for the anterior cruciate ligament reconstruction: A systematic review.

INTRODUCTION: The tearing of the anterior cruciate ligament (ACL) is one of the most common type of knee injury. Current evidence show that there are specific predictors for postoperative success in ACL injuries, but there is a limited number of studies on preoperative rehabilitation. Therefore, the goals of this review were to emphasize physiotherapy approaches to the preoperative period and to verify its effectiveness at the time the athlete returns to sport. METHOD: We conducted a systematic search in these databases: Medline, Scielo, Lilacs, CINAHL, Web of Science, PeDro and Cochrane Library. RESULTS: Our searches identified 553 occurences; of these, 511 titles and abstracts underwent triage after removal of duplicates. We identified 120 full texts for a stricter screening, amongst them, three studies included in the review for complying with the elegibility criteria. CONCLUSION: Physiotherapic preoperative treatment exhibits weak evidence for strength gains and pain relief, as well as strong evidence of functional improvement compared to the control group. These results were reported 4 months after the ACLR, in average.

Sex differences and adverse events of antiretrovirals in people living with HIV/AIDS: a systematic review and meta-analysis protocol.

INTRODUCTION: Antiretroviral therapy (ART) for HIV/AIDS is associated with adverse events (AEs). However, little is known about the differences in the risk of AEs between women and men living with HIV/AIDS. This study aims to determine (1) whether there are sex differences in the risk of AEs in people with HIV/AIDS treated with ART and (2) the prevalence of AEs to the reproductive system and bone mineral density in women. METHODS AND ANALYSIS: This systematic review (SR) will include randomised trials evaluating ART in people living with HIV/AIDS with at least 12 weeks of duration follow-up. Searches will be conducted in Medline, Embase, Cochrane Library, Epistemonikos, Lilacs, trial registries and grey literature databases, without restriction on publication status, year of publication and language. The primary outcome will be the risk of ART discontinuation or drop-outs/withdrawals of ART due to AEs and the number of any treatment-emergent AE. The secondary outcomes are the incidence of serious clinic or laboratory (grade 3 and/or 4) treatment-emergent AEs, hospitalisation, death and AEs specific to the reproductive system and bone mineral density (osteoporosis, osteopenia and fractures) of women. Selection, data extraction and quality assessment will be performed by pairs of reviewers. Cochrane collaboration tools will be used to assess the risk of bias. If appropriate, a meta-analysis will be conducted to synthesise results. The overall quality of the evidence for each outcome will be determined by the Grades of Recommendation, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: The results of this SR will assist the formulation of public policies aimed at the management and monitoring of AEs of ART in people living with HIV/AIDS. A deliberative dialogue will be scheduled with the Department of Chronic Conditions and Sexually Transmitted Infections of Brazil's Ministry of Health to align the project with policymakers' interests. PROSPERO REGISTRATION NUMBER: CRD42021251051.

Use of corticoids and non-steroidal anti-inflammatories in the treatment of rheumatoid arthritis: Systematic review and network meta-analysis.

Evidence on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticoids for rheumatoid arthritis (RA) is inconclusive and is not up to date. This systematic review assessed the effectiveness and safety of these anti-inflammatories (AI) in the treatment of RA. COCHRANE (CENTRAL), MEDLINE, EMBASE, CINAHL, Web of Science and Virtual Health Library were searched to identify randomized controlled trials (RCT) with adults which used AI (dose represented in mg/day) compared with placebo or active controls and was carried out up to December of 2019. Reviewers, in pairs and independently, selected studies, performed the data extraction and assessed the risk of bias. The quality of the evidence was assessed by GRADE. Network meta-analyses were performed using the Stata v.14.2. Twenty-six articles were selected (NSAIDs = 21 and corticoids = 5). Naproxen 1,000 improved physical function, reduced pain and the number of painful joints compared to placebo. Etoricoxib 90 reduced the number of painful joints compared to placebo. Naproxen 750 reduced the number of swollen joints, except for etoricoxib 90. Naproxen 1,000, etoricoxib 90 and diclofenac 150 were better than placebo regarding patient assessment. Assessment physician showed that NSAIDs were better than placebo. Meta-analyses were not performed for prednisolone and prednisone. Naproxen 1,000 was the most effective drug and celecoxib 200 showed fewer adverse events. However, the low quality of the evidence observed for the outcomes with NSAIDs, the absence of meta-analyses to assess the outcomes with corticoids, as well as the risk of bias observed, indicate that future RCT can confirm such findings.

Treatment of urinary incontinence: a critical appraisal of clinical practice guidelines with the AGREE II instrument.

INTRODUCTION AND HYPOTHESIS: This systematic review evaluated the rigor of the development of clinical practice guidelines (CPG). METHODS: The searched sources were MEDLINE, EMBASE, Web of Science, Scopus, and specific databases of CPG. Reviewers, organized in triplicate and independently, selected the studies and assessed the quality of the guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument, which contains six domains for classification. The classification of the CPGs prioritized the domain 3 (developmental rigor) considering: high (score > 60%), moderate (score 30-60%), or low quality (score < 30%). The results were checked for discrepancies and decided by consensus. The interventions were described. Descriptive statistics presented the results. RESULTS: Of the ten CPGs evaluated, five were of high methodological quality, three were of moderate quality, and two of low quality. Three documents were not recommended for use. The domains with the highest scores were scope and purpose (mean = 90.1%) and clarity of presentation (mean = 88.9%). The domains of editorial independence (mean = 41.4%) and applicability (mean = 29.3%) were those with the lowest score. The most cited interventions in CPGs were the nonpharmacological, such as lifestyle interventions, bladder training, or re-education and pelvic floor muscle training. CONCLUSION: Most guidelines showed rigor in development and were recommended for use; however, editorial independence and applicability were domains that need to be improved in these documents. Our findings can guide the choice of CPG for the treatment of urinary incontinence.

Use of IMMPACT domains in clinical trials of acupuncture for chronic pain: A methodological survey.

Acupuncture is one of the therapeutic resources used for the management of chronic pain. Variability in outcome measurements in randomized clinical trials of non-oncologic chronic pain (RCT-NOCP) generates inconsistencies in determining effects of treatments. The objective of this survey was to assess the adherence to the recommendations made by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in the measurement of RCT-NOCP of acupuncture. This methodological research made a systematic search for eligible studies from different sources of information. Eligible studies included those with number of patients ≥100, who randomized and allocated patients with chronic non-oncologic pain to be treated with acupuncture or with "sham" acupuncture, or non-acupuncture. This research included the recommendations for IMMPACT in the measurement of RCT-NOCP: presence of outcomes pain, physical function, emotional state and improvement perception of patient, the source of the outcome information pain and the tools used to measure such domains. From a total of 1,386 studies, 24 were included in this survey. Eleven studies presented low risk of bias. Pain outcome was measured in 23 studies, physical function in 22 studies, emotional state in 14 studies and improvement perception of patient in one study. As for the pain outcome, the patient was the information source in 50% of the studies. The measurement tools recommended for IMMPACT were included in eight studies (35%) that evaluated pain, one study that evaluated the emotional state (7%), and one study that evaluated the improvement perception and satisfaction of patient. It was observed that studies which did not adhere to the recommendations had more favorable results for acupuncture in the outcome pain. This study concludes that randomized clinical trials that used acupuncture to manage chronic pain failed to adhere to IMMPACT recommendations. Clinical societies and IMMPACT do not share the same recommendations. This fact reflects in the diversity of outcomes and instruments adopted in the studies, making it difficult to compare the results.

Effect of mushrooms on obesity in animal models: study protocol for a systematic review and meta-analysis.

BACKGROUND: Obesity and its consequences are worldwide epidemic problem; therefore, studies with strategies and mechanisms that favor weight loss to improve outcomes in health are necessary. Effects of mushrooms on body weight are uncertain. The aim of this systematic review is to determine the efficacy of mushrooms in weight loss in animal preclinical models. METHOD: This is a systematic review of preclinical studies of animal models of obesity (any type of non-aquatic mammal), which were exposed to edible and medicinal mushrooms orally in comparison with the control. The following databases will be used: MEDLINE (PubMed), Web of Science, BIOSIS, SCOPUS, and gray literature. There will be no restriction of language, date, or publication status. The primary outcome will be body weight loss. And the secondary outcomes include the total amount of food consumed by the animals, analysis of metabolic parameters, inflammatory mediators, mortality for any causes, and any adverse effect reported. A team of reviewers will select, in pairs and independently, the titles and abstracts, extract data from qualifying studies, and assess bias risk (using SYstematic Review Centre for Laboratory animal Experimentation SYRCLE's risk of bias tool and the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist). The standardized mean difference (SMD) will be calculated to measure treatment effect, with 95% confidence intervals (95% CI). The heterogeneity between-study will be calculated by I2 inconsistency values and Cochran's Q statistical test, where I2 > 50% and/or p < 0.10 suggest high heterogeneity meta-analyses of random effects will be conducted as possible. DISCUSSION: Although many experimental studies about the effects of mushrooms on obesity have already been published, there is still no consensus in the literature. This study will provide evidences of preclinical research on mushrooms and their relation to body weight loss in animal models of obesity, being non-aquatic mammals. Also, this systematic review will show the limitations and strengths of the studies available in the literature, as well as it will to encourage the financing of new studies by public health managers and governmental entities. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42019125299).

Critical appraisal of clinical practice guidelines for treatment of urinary incontinence: Protocol for a systematic review.

BACKGROUND: Urinary incontinence is a common complaint in all parts of the world, cause of distress, as well as significant costs for both individuals and society. The aim of this study will be to evaluate the rigor of the development of clinical practice guidelines and to identify the recommendations of interventions for urinary incontinence in adult women. METHODS: In this systematic review, clinical practice guidelines will be identified using a prospective protocol through a systematic search of: MEDLINE (via Ovid); EMBASE (Excerpt Medical Database, via Ovid); Web of Science and Virtual Health Library. Specific databases of guidelines for clinical practice will also be searched (National Institute for Health and Care Excellence, American Urological Association, and others). Reviewers, independently and in duplicate, will assess the quality of the guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE II). The results will be checked for discrepancies. Differences between the scores equal to or greater than 2 will be considered as discrepant and the final result will be decided by consensus. A comparison of the recommendations of interventions and information about the level of evidence, the degree of recommendation, the level of agreement and the level of acceptance will be described. This step will also be done independently and in duplicate, and the result will be decided by consensus. The results will be presented in tables and the descriptive statistics will be calculated for all domains of the AGREE II instrument as mean (standard deviation) and median (interquartile range). RESULTS: The results derived from this study will increase the knowledge about the development of recommendations guidelines for urinary incontinence of high methodological rigor. This study may also identify key areas for future research. CONCLUSION: This study may guide health professionals, policy makers, and health policy managers in choosing the guidelines for recommendation in clinical practice. PROTOCOL REGISTRATION: PROSPERO - CRD42018116517.

Use of IMMPACT domains in clinical trials of acupuncture for chronic pain: a protocol for a methodological survey.

INTRODUCTION: Pain is one of the most common and most debilitating complaints among patients. It affects the individual, their relationship with friends and family, their ability to function at work, and their sociability. Acupuncture is one of the therapeutic resources for managing chronic pain. Given the variability of outcome measures in controlled randomised clinical trials on non-oncologicchronic pain (CRCT-NOCP), the Initiative in Methods, Measurements and Pain Assessment in Clinical Trials (IMMPACT) recommends six domains to be covered in evaluating the effectiveness of treatments for chronic pain. OBJECTIVE: To check whether the methodological quality of outcome reporting in published trials has used IMMPACT recommendations in measuring CRCT-NOCP outcomes when acupuncture was used as a treatment. METHOD: This is a methodological study. We will systematically search for eligible studies in specific databases with a defined strategy. We will use the MeSHterms of 'acupuncture', 'chronic pain' and similar terms, without restrictions on idiom. Eligible studies will include those which are randomised and chose NOCP patients to be treated with acupuncture or control (sham acupuncture or no acupuncture), recruited after September 2004, with ≥100 patients. The measured outcomes are to be the presence of outcome domains recommended by IMMPACT, domains reported by the patient or clinician, tools used to measure such domains, as well as other features of the studies. We shall conduct a regression analysis to explore factors which can be associated with the presence of outcome domains according to IMMPACT recommendations. ETHICS AND DISSEMINATION: This survey will be submitted for presentation at congresses and for publication in a scientific journal. The findings obtained in this study will allow us to measure the quality of the evidence and provide greater transparency in decisions regarding the use of acupuncture as a viable alternative to managing chronic pain.