Prognosis of polymerase epsilon (POLE) mutation in high-grade endometrioid endometrial cancer: Systematic review and meta-analysis.

BACKGROUND: POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior. OBJECTIVES: To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC. METHODS: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models. RESULTS: This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I2 = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I2 = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I2 = 68%, 18 studies). CONCLUSION: POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.

Efficacy, Effect on Mood Symptoms, and Safety of Deep Brain Stimulation in Refractory Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate efficacy, effect on mood, and safety of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) at different target sites. DATA SOURCES: Electronic records from databases MEDLINE, EMBASE, and CENTRAL up to November 2019 were searched. Search terms included OCD, depression, and DBS. STUDY SELECTION: Eight randomized controlled trials (RCTs) (n = 85) and 38 observational studies (case reports and case series) (n = 225) were included. DATA EXTRACTION: In RCTs, the differences in outcomes between sham and active stimulation for OCD and depression were evaluated and the proportion of responders was determined. In all included studies, at last follow-up, the improvement from baseline in OCD (Yale-Brown Obsessive Compulsive Scale [Y-BOCS score]) and a scale of weighted depression scores (WDS) were determined. Predictors of response (age, illness duration and severity, frequency parameters, and response in depression) were evaluated. The proportions of adverse events and dropouts were calculated. RESULTS: In RCTs, mean differences between sham and active stimulation in Y-BOCS and Hamilton Depression Rating Scale (HDRS) scores were -7.8 (95% CI = -11.2 to -4.3, I² = 40%, P = .0001) and -7.3 (95% CI = -11.5 to -3.0, I² = 0%, P = .0009), respectively. No differences between limbic and non-limbic targets were identified (χ² = 0.21, I² = 0%, P = .0006). At last follow-up, improvements in Y-BOCS and WDS were -15.0 (95% CI = -18.3 to -11.7, I² = 90%, P < .001) and -13.7 (95% CI = -20.1 to -7.3, I² = 76%, P < .001), respectively. No consistent predictors of response were found. There were 0.68 adverse events (95% CI = 0.59 to 0.78, I² = 88%), 0.32 serious adverse events (95% CI = 0.12 to 0.62, I² = 96%), and 0.13 dropouts (95% CI = 0.07 to 0.16, I² = 16%) per treated patient. CONCLUSIONS: DBS can significantly decrease Y-BOCS score and depressive symptoms in refractory OCD.

Morphine in acute coronary syndrome: systematic review and meta-analysis.

OBJECTIVE: Morphine is frequently used in acute coronary syndrome (ACS) due to its analgesic effect, it being recommended in the main cardiology guidelines in Europe and the USA. However, controversy exists regarding its routine use due to potential safety concerns. We conducted a systematic review of randomised-controlled trials (RCTs) and observational studies to synthesise the available evidence. DESIGN: Systematic review and meta-analysis. DATA SOURCES: CENTRAL, MEDLINE, EMBASE and trial registries. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included RCTs and observational studies evaluating the impact of morphine in cardiovascular outcomes or platelet reactivity measures. DATA EXTRACTION AND SYNTHESIS: Data were screened, extracted and appraised by two independent reviewers. The data were pooled results using a random-effects model. Outcomes included in-hospital mortality, major adverse cardiovascular events (MACE), platelet reactivity (using VerifyNow) and bleeding, reported as relative risk (RR) with 95% CI. We assessed the confidence in the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We followed the Meta-analysis Of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Five RCTs and 12 observational studies were included, enrolling 69 993 participants. Pooled results showed an increased risk of in-hospital mortality (RR 1.45 [95% CI 1.10 to 1.91], low GRADE confidence), MACE (RR 1.21, 95% CI 1.02 to 1.45) and an increased platelet reactivity at 1 and 2 hours (59.37 platelet reactivity units [PRU], 95% CI 36.04 to 82.71; 68.28 PRU, 95% CI 37.01 to 99.55, high GRADE confidence) associated with morphine. We found no significant difference in the risk of bleeding. We found no differences in subgroup analyses based on study design and ACS subtype. CONCLUSIONS: Morphine was associated with an increased risk of in-hospital mortality and MACE but the high risk of bias leads to low result confidence. There is high confidence that morphine decreases the antiplatelet effect of P2Y12 inhibitors. PROSPERO REGISTRATION NUMBER: CRD42016036357.

[Analysis of the Cochrane Review: Non-medical Prescribing versus Medical Prescribing for Acute and Chronic Disease Management in Primary and Secondary Care. Cochrane Database Syst Rev. 2016;11:CD011227.] / Análise da Revisão Cochrane: Prescrição Não-médica versus Prescrição Médica para a Gestão de Doenças Agudas e Crónicas em Cuidados de Saúde Primários e Secundários. Cochrane Database Syst Rev. 2016;11:CD011227.

In countries with diverse socioeconomic levels, in order to address the health care demands, the consideration of a wide array of strategies is needed; among these, non-medical prescription can be included. The objective of this revision was to ascertain whether non-medical prescription results in comparable clinical and patient-related outcomes to medical prescription. This systematic review was conducted in compliance with the standard Cochrane methodology. Clinical outcomes were compared between prescription carried out by non-medical health professionals and doctors, provided that the non-medical health professional prescribed with a high degree of autonomy, both in hospital and community practice, in countries with low, medium and high socioeconomic level. The review included 46 clinical trials, with different designs, with 37 337 participants overall. Most studies were based on the management of chronic disease in higher income countries, where the evidence supports comparable outcomes for the markers of disease relative to high blood pressure (moderate-certainty of evidence), diabetes control (high-certainty of evidence); high cholesterol (moderatecertainty of evidence), among others. Prescription by pharmacists and nurses with different levels of undergraduate, specific and postgraduate education could provide comparable outcomes to medical prescription, specifically with regards to adherence to therapy, adverse events, overall satisfaction, quality of life, and resource utilisation (hospitalisations, visits to the emergency department, and consultations). Non-medical prescribers frequently had medical support available to facilitate a collaborative practice. With appropriate training and support, non-medical prescription by nurses and pharmacists can be as effective as when carried out by doctors.

Em países com diversos níveis socioeconómicos, o assegurar dos cuidados de saúde requer a consideração de uma variedade de estratégias, nas quais pode incluir-se a prescrição não-médica. O objetivo desta revisão foi averiguar se a prescrição por profissionais de saúde não-médicos está associada a resultados (outcomes) clínicos e de relevância para o doente comparáveis à prescrição médica. Revisão sistemática de acordo com a metodologia preconizada pela Cochrane. Foram comparados os outcomes em saúde quando a prescrição médica era realizada por um qualquer profissional de saúde não médico (que prescrevesse com um alto grau de autonomia) versus por um médico, no contexto dos cuidados de saúde primários e secundários, e em países de baixo, médio e alto nível socioeconómico. Foram incluídos para análise 46 ensaios clínicos de diferentes desenhos que avaliaram um total de 37 337 indivíduos. A maioria dos estudos baseou-se na gestão da doença crónica em países de nível socioeconómico mais elevado, onde existe evidência que suporta que os outcomes são comparáveis para os marcadores substitutivos de controlo de doença relativos à hipertensão (evidência moderada), controlo de diabetes (evidência elevada) e hipercolesterolemia (evidência moderada), entre outros. A prescrição por enfermeiros e farmacêuticos com níveis variados de formação (pré-graduada, específica e pós-graduada) esteve também associada a outcomes globalmente comparáveis aos obtidos com a prescrição médica relativamente à adesão à medicação, eventos adversos, nível de satisfação global, qualidade de vida e utilização de recursos (hospitalizações, urgências hospitalares e consultas). Os prescritores não médicos frequentemente tiveram suporte médico disponível para facilitar um modelo de prática colaborativa. Com treino e suporte apropriados, a prescrição não-médica por enfermeiros e farmacêuticos é tão efetiva quanto a prescrição médica numa variedade de condições clínicas.

[Analysis of the Cochrane Review: Topical Treatments for Scalp Psoriasis. Cochrane Database Syst Rev. 2016;2:CD009687]. / Análise da Revisão Cochrane: Tratamentos Tópicos para a Psoríase do Couro-Cabeludo. Cochrane Database Syst Rev. 2016;2;CD009687.

Regardless the psoriasis subtype, up to 79% of people with this skin condition present scalp involvement, which is often the first site to show symptoms of the disease. In addition to being itchy, the red and scaly lesions are usually easy to see, and may be embarrassing. Topical therapy is usually the first line of treatment; however the wide array of available interventions can make the choice difficult, and may even lead to an inadequate treatment. The objective of this review was to evaluate the efficacy and safety of topical treatments for scalp psoriasis. A systematic review was performed according to the methodology recommended by Cochrane in order to evaluate the clinical severity of psoriasis, quality of life, and adverse events that led to treatment discontinuation. To evaluate this, 59 studies were included, with a total of 11 561 participants, and 15 comparisons were made between the various drugs and application vehicles tested. The principal conclusion is that corticosteroids of high or very high potency are more effective than vitamin D. The combination of a corticosteroid with vitamin D has only a marginal benefit over corticosteroid monotherapy, but is superior to vitamin D alone. Given the similar safety profile and only marginal benefit of the combination of corticosteroid with vitamin D over the corticosteroid alone, topical corticosteroid monotherapy appears to be fully acceptable for short-term therapy of scalp psoriasis.

Independentemente do tipo de psoríase, até 79% dos doentes com esta patologia apresentam atingimento do couro cabeludo, sendo este frequentemente o primeiro local a mostrar sintomas da doença. Para além do prurido, as lesões avermelhadas e escamosas são visíveis e muitas vezes embaraçosas. A terapêutica tópica é geralmente a primeira opção para estes doentes, no entanto a ampla gama de tratamentos disponíveis pode muitas vezes dificultar a escolha e levar a um tratamento potencialmente desadequado. O objetivo desta revisão foi avaliar a eficácia e a segurança dos tratamentos tópicos para a psoríase do couro cabeludo. Foi efetuada uma revisão sistemática de acordo com a metodologia preconizada pela Cochrane, com vista à avaliação da redução da gravidade clínica da psoríase, melhoria da qualidade de vida e efeitos adversos que motivassem a suspensão do tratamento. Para tal, foram incluídos 59 estudos, com um total de 11 561 participantes, tendo sido efetuadas 15 comparações entre os vários fármacos e veículos de aplicação testados. Os resultados obtidos sugerem que os corticosteroides de potência elevada ou muito elevada são mais eficazes que a vitamina D. A combinação de um corticosteroide com a vitamina D tem apenas um benefício marginal em relação à monoterapia com corticosteroide, mas é superior à vitamina D isolada. Dado o perfil de segurança semelhante e o benefício apenas marginal da combinação corticosteroide com vitamina D sobre o corticosteroide isolado, a monoterapia com corticosteroide tópico parece ser aceitável para a terapia a curto prazo da psoríase do couro cabeludo.