Objectives To assess the economic impact of dengue in Latin America and the Caribbean using a systematic review that includes studies not previously considered by other reviews. Methods Cochrane methodology was used to conduct a systematic review of the cost of dengue in Latin America. PubMed Central, EMBASE, and the Biblioteca Virtual en Salud—which includes scientific, peer-reviewed journals not indexed by other databases—were searched from inception through August 2016. All articles that reported cost of illness data for countries in Latin America were included. Included studies underwent a methodological appraisal using a seven-question instrument designed for cost of illness studies. Extracted data were direct and indirect costs for outpatient and hospitalized cases and total cost of the disease. Values were adjusted to 2015 US dollars using the consumer price index. Results From a total of 848 initial references, 17 studies were included, mainly from Brazil, Colombia, Cuba, Mexico, and Puerto Rico; costs were available for 39 countries. The methodological appraisal showed that 70% of the studies met more than 70% of the evaluated items. The main economic impact of dengue was due to productivity costs. Average annual cost was more than US$ 3 billion. Direct costs represented over 70% of the total share for hospitalized cases. For outpatients, direct medical costs were low, but social costs were significant since indirect costs may account for up to 80% of the total cost. Conclusions Dengue fever has a significant economic impact in Latin America. It is essential to develop new public health interventions, such as dengue vaccination, to decrease the propagation of the disease and its total cost.

Objectives: Pen devices offer advantages compared with vial and syringe (VaS). The purpose of this article was to evaluate efficacy of pen devices compared to VaS. Methods: A systematic review of literature was performed in 8 different databases. References were independently screened and selected. Primary observational or experimental studies comparing pen devices with VaS for insulin administrations were included. Studies on specific populations were excluded. Risk of bias was evaluated using appropriate tools. Data on glycosylated hemoglobin (HbA1c), hypoglycemia, adherence, persistence, patient preference, and quality of life (QOL) were collected. Meta-analysis was performed when appropriate. Heterogeneity and risk of publication bias were evaluated. Otherwise, descriptive analyses of the available data was done. Results: In all, 10 348 articles were screened. A total of 17 studies were finally selected: 7 experimental and 10 analytical. The populations of the included articles were mainly composed of adults with type 2 diabetes mellitus. Important risk of bias was found in all of the articles, particularly experimental studies. Meta-analyses were performed for HbA1c, hypoglycemia, adherence and persistence. Pen device showed better results in mean HbA1c change, patients with hypoglycemia, adherence and persistence compared to VaS. No difference was observed in number of patients achieving <7% HbA1c. Preference studies showed a tendency favoring pen devices, however nonvalidated tools were used. One QoL study showed improvements in some subscales of SF-36. Conclusions: There is evidence that pen devices offer benefits in clinical and, less clearly, patient-reported outcomes compared to VaS for insulin administration. However, these results should be taken with caution.

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A363 life. When possible, meta-analysis was performed, evaluating the presence of heterogeneity and risk of publication bias. Otherwise, descriptive analysis of the available data was done. Results: Of the 10.348 original references scanned, 17 studies were finally selected, 7 experimental and 10 analytical. The population included was mainly adults, with type 2 diabetes. Important risk of bias was found in all of the articles, particularly the experimental ones. Meta-analysis was performed for glycemic control, hypoglycemia, adherence and persistence. Pen devices showed better results in mean HbA1c change, frequency of hypoglycemia, adherence and persistence compared to vial and syringes. No difference was observed in number of patients achieving < 7% of HbA1c. Studies regarding preference showed a clear tendency favorable to pen devices, but measurement methods were generally not well validated. One study on quality of life showed improvements in some subscales of SF-36. ConClusions: There is evidence that pen devices offer benefits regarding glycemic control, hypoglycemia, adherence, persistence, patient preference and quality of life compared to vial and syringes for insulin administration. However, data had considerable risk of bias, more methodologically sound studies are needed.

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The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib–trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF‐V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta‐analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF‐V600 mutation (NMA‐pBRAFV600) and another with mixed population (with or without the mutation: NMA‐pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA‐pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA‐pBRAFV600. Dabrafenib–trametinib was found to have a favorable effect on overall survival (OS) and progression‐free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA‐pMixed, dabrafenib–trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib–trametinib and vemurafenib–cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib–trametinib has a favorable effect on Grades 3 and 4 adverse events.

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