Electronic nicotine delivery systems and/or electronic non-nicotine delivery systems for tobacco smoking cessation or reduction: a systematic review and meta-analysis

Objective A systematic review and meta-analysis to investigate the impact of electronic nicotine delivery systems (ENDS) and/or electronic non-nicotine delivery systems (ENNDS) versus no smoking cessation aid, or alternative smoking cessation aids, in cigarette smokers on long-term tobacco use. Data sources Searches of MEDLINE, EMBASE, PsycInfo, CINAHL, CENTRAL and Web of Science up to December 2015. Study selection Randomised controlled trials (RCTs) and prospective cohort studies. Data extraction Three pairs of reviewers independently screened potentially eligible articles, extracted data from included studies on populations, interventions and outcomes and assessed their risk of bias. We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate overall certainty of the evidence by outcome. Data synthesis Three randomised trials including 1007 participants and nine cohorts including 13?115 participants proved eligible. Results provided by only two RCTs suggest a possible increase in tobacco smoking cessation with ENDS in comparison with ENNDS (RR 2.03, 95% CI 0.94 to 4.38; p=0.07; I2=0%, risk difference (RD) 64/1000 over 6 to 12?months, low-certainty evidence). Results from cohort studies suggested a possible reduction in quit rates with use of ENDS compared with no use of ENDS (OR 0.74, 95% CI 0.55 to 1.00; p=0.051; I2=56%, very low certainty). Conclusions There is very limited evidence regarding the impact of ENDS or ENNDS on tobacco smoking cessation, reduction or adverse effects: data from RCTs are of low certainty and observational studies of very low certainty. The limitations of the cohort studies led us to a rating of very low-certainty evidence from which no credible inferences can be drawn. Lack of usefulness with regard to address the question of e-cigarettes\u27 efficacy on smoking reduction and cessation was largely due to poor reporting. This review underlines the need to conduct well-designed trials measuring biochemically validated outcomes and adverse effects

Systematic survey of randomized trials evaluating the impact of alternative diagnostic strategies on patient-important outcomes

Objectives: To provide a perspective on the current practice of randomized clinical trials (RCTs) of diagnostic strategies focusing on patient-important outcomes. Study Design and Setting: We conducted a comprehensive search of MEDLINE and included RCTs published in full-text reports that evaluated alternative diagnostic strategies. Results: Of 56,912 unique citations, we sampled 7,500 and included 103 eligible RCTs, therefore suggesting that MEDLINE includes approximately 781 diagnostic RCTs. The 103 eligible trials reported on: mortality (n = 41; 39.8%); morbidities (n = 63; 61.2%); symptoms/quality of life/functional status (n = 14; 13.6%); and on composite end points (n = 10; 9.7%). Of the studies that reported statistically significant results (n = 12; 11.6%), we judged 7 (58.3%) as at low risk of bias with respect to missing outcome data and 4 (33.3%) as at low risk of bias regarding blinding. Of the 41 RCTs that reported on mortality, only one (2.4%) reported statistically significant results. Of 63 RCTs addressing morbidity outcomes, 11 (17.5%) reported statistically significant results, all of which reported relative effects of greater than 20%. Conclusion: RCTs of diagnostic tests are not uncommon, and sometimes suggest benefits on patient-important outcomes but often suffer from limitations in sample size and conduct. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Effectiveness and cost-effectiveness of 3D image-guided brachytherapy versus conventional (2D) brachytherapy in patients with cervical cancer

Problema: Braquiterapia (BT) é parte do tratamento padrão de pacientes com câncer do colo uterino localmente avançado (PCCU). Embora a BT guiada por imagem tridimensional (BT3D) seja potencialmente mais efetiva que a BT convencional (BT2D), seu uso requer recursos adicionais. Questões de pesquisa: 1) Quais são os efeitos clínicos da BT3D versus BT2D em PCCU? 2) Quais são as metodologias de custeio, componentes de custo, características dos modelos (quando aplicável) em avaliações econômicas sobre BT em PCCU? 3) Quais são os benefícios, danos, custos, custo-utilidade e custo-efetividade da BT3D guiada por ressonância magnética (BT3D-RM) versus BT3D guiada por tomografia computadorizada (BT3D-TC) versus BT2D em PCCU? Métodos: Conduzimos três estudos: 1) Revisão sistemática (RS) sobre efeitos clínicos da BT3D versus BT2D em PCCU, com buscas em seis bases de dados, seleção e extração de dados por revisores independentes, e meta-análises utilizando os métodos inverso da variância e Mantel-Haenszel com modelos de efeitos aleatórios. 2) RS de estudos de avaliação econômica sobre BT em PCCU, com buscas em 17 bases de dados, seleção e extração de dados por revisores independentes. Os custos foram convertidos em dólares americanos (USD) de 2022. 3) Modelo de análise de decisão (Markov) comparando desfechos clínicos e econômicos da BT3D-RM, BT3D-TC, e BT2D em PCCU FIGO IB2-IVA, sob a perspectiva do Instituto do Câncer do Estado de São Paulo (ICESP), em horizonte temporal de toda vida, com custos estimados por meio de microcusteio e macrocusteio, e taxa de desconto anual de 5%. Foram realizadas análises de sensibilidade determinística univariada e multivariada. Resultados: 1) Foram incluídos 20 estudos observacionais envolvendo 4.287 pacientes. As meta-análises demonstraram benefícios da BT3D comparada à BT2D na sobrevida global [Hazard Ratio (HR) 0,78; Intervalo de confiança (IC95%) 0,62-0,98], sobrevida livre de doença pélvica (HR 0,75; IC95% 0,62-0,90), controle local (HR 0,77; IC95% 0,59-0,99), toxicidade graus 3-4 global [diferença de risco (RD) -9%; IC95% -6% a -11%] e gastrointestinal (RD -5%; IC95% -2% a -8%). 2) Foram incluídos 11 estudos, sendo duas avaliações completas e nove parciais. As variabilidades dos custos médios da BT3D e BT2D por paciente, respectivamente USD$238-31.305 e USD$ 467-28.558, foram direcionadas por diferentes metodologias de custeio e componentes de custo. A BT3D foi dominante ou custo-efetiva em ambas as avaliações completas. 3) A expectativa de vida remanescente foi de 12,2, 11,7 e 11,2 anos, e 10, 9,4 e 8,9 anos de vida ajustados pela qualidade para cada paciente tratada com BT3D-RM, BT3D-TC e BT2D, respectivamente. Para cada 100 pacientes tratadas com BT3D-RM espera-se reduções de oito complicações grau 3, 13 doenças locais, e nove óbitos por câncer em comparação à BT2D. Espera-se uma economia de $32.732 Reais ao longo da vida de cada paciente tratada com BT3D-RM comparada à BT2D. A BT3D-RM foi dominante em comparação às alternativas nas análises de custo-utilidade e custo-efetividade. As análises de sensibilidade indicaram robustez dos resultados. Conclusão e aplicabilidade: A BT3D é mais efetiva e economiza recursos em comparação à BT2D e sugere-se sua implementação como estratégia padrão no ICESPResearch problem: Brachytherapy (BT) is part of the usual care of patients with locally advanced cervical cancer (PCC). Although three-dimensional image-guided BT (3DBT) is potentially more effective than conventional (BT2D), its use requires additional resources. Research questions: 1) What are the clinical effects of 3DBT versus 2DBT in PCC? 2) What are the costing methodologies, cost components, model characteristics (when applicable) in economic evaluations on BT for PCC? 3) What are the benefits, harms, costs, cost-utility and cost-effectiveness of magnetic resonance-guided 3DBT (MR-3DBT) versus computed tomography-guided (CT-3DBT) versus 2DBT in PCC? Methods: We conducted three studies: 1) Systematic review comparing the clinical effects of 3DBT versus 2DBT in PCC, with searches in six databases, selection and data extraction by two independent reviewers, and meta-analyses using the inverse of variance and Mantel-Haenszel methods with random effects models. 2) Systematic review of economic evaluation studies on BT in PCC, with searches in 17 databases, selection and data extraction by two independent reviewers. Cost estimates were converted to US dollars (USD) in 2022. 3) Decision analytic model (Markov) comparing clinical and economic expected values of MR-3DBT, CT-3DBT, and 2DBT in FIGO IB2-IVA PCC, from the perspective of the Instituto do Câncer do Estado de São Paulo (ICESP), in a lifetime horizon, micro-costing and macro-costing approaches to estimate costs, and annual discount rate of 5$ 238-31,305 and USD$467-28,558, were driven by different costing methodologies and cost components. 3DBT was dominant or cost-effective in both full economic evaluations. 3) The simulation resulted in a remaining life expectancy of 12.2, 11.7 and 11.2 years, and 10, 9.4 and 8.9 quality-adjusted life years for each patient treated with MR-3DBT, CT-3DBT and 2DBT, respectively. For every 100 patients treated with MR-3DBT, reductions of eight grade 3 toxicities events, 13 local diseases, and nine cancer-related deaths are expected compared to 2DBT. MR-3DBT is expected to save$32,732 Brazilian Reais compared to 2DBT during the lifetime for each patient treated. MR-3DBT was dominant compared to the other two alternatives in the cost-utility and cost-effectiveness analyses. Sensitivity analyses showed robustness of our results. Conclusion and applicability: 3DBT is more effective and cost-saving compared to 2DBT and its implementation is suggested as the standard strategy at ICES

Effects of alveolar recruitment maneuvers in patients with acute respiratory distress syndrome: a systematic review and meta-analysis

Objetivo: Avaliar o efeito das manobras de recrutamento alveolar em desfechos clínicos de pacientes com síndrome da angústia respiratória aguda (SARA). Métodos: Busca nas bases eletrônicas MEDLINE, EMBASE, LILACS, CINAHL, CENTRAL, Scopus, and Web of Science (até Julho de 2014), sem limite de idioma, por ensaios clínicos randomizados avaliando o efeito das manobras de recrutamento alveolar versus tratamento padrão sem manobras de recrutamento em pacientes adultos com SARA. Quatro duplas de revisores avaliaram de maneira independente a elegibilidade e o risco de viés dos estudos e extraíram os dados de interesse. Realizamos metanálise dos dados por meio de modelos de efeitos aleatórios. Foi utilizada análise sequencial de trials para estabelecer limiares de significância estatística para a metanálise cumulativa considerando nosso desfecho primário (mortalidade hospitalar) para limitar o erro tipo I global por análises múltiplas. Utilizamos sistema GRADE para avaliar a qualidade da evidência. Resultados: Foram incluídos 10 ensaios clínicos randomizados (1594 pacientes, 612 eventos). O risco relativo (RR) de óbito nos pacientes tratados com manobras de recrutamento em comparação ao controle foi de 0,84 (intervalo de 95% de confiança [IC95%] 0,74-0,95; I2=0%), embora a qualidade da evidência tenha sido considerada baixa devido ao risco de viés nos estudos incluídos e à evidência indireta (ou seja, a evidência disponível não responde diretamente nosso objetivo primário, pois os pacientes no grupo experimental receberam outras intervenções ventilatórias que podem ter impactado no desfecho, além das manobras de recrutamento). Não houve diferença no risco de barotrauma (RR 1,11; IC95% 0,78-1,57; I2=0%) ou necessidade de terapia de resgate para hipoxemia (RR 0,76; IC95% 0,41-1,40; I2=56%). A maioria dos estudos não demonstrou diferenças entre os grupos nos desfechos: tempo de ventilação mecânica, tempo de internação na UTI e no hospital. A análise sequencial de ensaios clínicos demonstrou que a evidência cumulativa sobre o efeito das manobras de recrutamento na mortalidade hospitalar de pacientes com SARA é precisa quando considerado um erro tipo I de 5%, mas é imprecisa quando considerado um erro tipo I de 1%. Conclusão: A evidência atual sugere que as manobras de recrutamento alveolar reduzem o risco de óbito hospitalar em pacientes com SARA, sem aumento do risco de eventos adversos graves, entretanto, a evidência não é definitiva. Estudos adicionais são necessários para responder esta questãoPurpose: To assess the effects of alveolar recruitment maneuvers on clinical outcomes in patients with acute respiratory distress syndrome (ARDS). Methods: We searched MEDLINE, EMBASE, LILACS, CINAHL, CENTRAL, Scopus, and Web of Science (from inception to July 2014) for randomized controlled trials evaluating the effects of alveolar recruitment maneuvers versus no recruitment maneuvers in adults with ARDS. We placed no language restriction on our search. Four teams of two reviewers independently assessed eligibility and risk of bias and extracted data from the included trials. We pooled data using random-effects models. We used trial sequential analysis to establish monitoring boundaries to limit global type I error due to repetitive testing for our primary outcome (in-hospital mortality). We rated the quality of evidence using the GRADE system. Results: We included 10 trials (1594 patients, 612 events). The meta-analysis assessing the effect of alveolar recruitment maneuvers on in-hospital mortality showed a risk ratio (RR) of 0.84 (95%CI 0.74-0.95; I2=0%). However, quality of evidence was considered low due to the risk of bias in the included trials and indirectness of evidence, that is, available evidence does not address our primary outcome directly as recruitment maneuvers were usually conducted along with other ventilatory interventions that may affect the outcome of interest. There were no differences in the rates of barotrauma (RR 1.11, 95%CI 0.78-1.57; I2=0%) or need for rescue therapies (RR 0.76, 95%CI 0.41-1.40; I2=56%). Most trials found no difference between groups regarding the duration of mechanical ventilation, length of stay in ICU and in hospital. The trial sequential analysis showed that the available evidence of the effect of recruitment maneuvers on in-hospital mortality is precise when considering a type I error of 5% but not when considering a type I error of 1%. Conclusions: Although recruitment maneuvers may decrease mortality of patients with ARDS without increasing the risk for major adverse events, the current evidence is not definitive. Additional trials addressing this question may better inform clinical practic