Long-Term Efficacy of High-Dose Imatinib in Hispanic Patients Without Access to Second-Generation Tyrosine Kinase Inhibitors Treated in LATAM Centers.

BACKGROUND: While second-generation tyrosine kinase inhibitors (TKI) revolutionized treatment for patients with chronic myeloid leukemia (CML) who developed a suboptimal response to imatinib, many patients in developing countries are fixed to the latter due to socioeconomic barriers. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. METHODS: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to a standard dose of imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights. Our primary outcome was overall survival (OS) at 150 months. Our secondary outcomes were disease-free survival (DFS) at 150 months and adverse events. RESULTS: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. No difference was found in the 150-month overall survival risk (RR: 95% CI 0.91, 0.55-1.95, P-value = .77; RD: -0.04, -0.3 to 0.21, P-value = .78) and disease-free survival (RR: 1.02, 95% CI 0.53-2.71, P-value = .96; RD: 0.01, -0.26 to 0.22, P-value = .96). There was also no difference in the incidence of adverse events in either group. CONCLUSION: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. If impossible, however, our findings suggest that patients treated with high-dose imatinib have a similar overall survival and disease-free survival prognosis to patients receiving a second-generation TKI.

American thyroid association guidelines are inconsistent with Grading of Recommendations Assessment, Development, and Evaluations-A meta-epidemiologic study.

OBJECTIVES: The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) working group has recognized some scenarios in which strong recommendations may be supported by low-quality evidence, the so-called paradigmatic situations. The adherence to these paradigmatic situations by the American Thyroid Association (ATA) guidelines, however, remains unknown. STUDY DESIGN AND SETTING: Clinical guidelines from the ATA were retrieved and deemed eligible if created using GRADE or the American College of Physicians (ACP) system. Reviewers, independently and in duplicate, assessed all strong recommendations based on low-quality evidence and judged their alignment with GRADE paradigmatic situations. The study was conducted at KER Unit Mexico. RESULTS: A total of five clinical guidelines, one using the GRADE and four using the ACP system, were eligible for analysis. We assessed a total of 518 recommendations, of which 355 (69%) were labeled as "strong" and 163 (31%) as "weak". A total of 151 strong recommendations were based on low-quality evidence, of which 36 (24%) were congruent with one of the five GRADE paradigmatic situations, whereas 115 (76%) were not consistent with any paradigmatic situations and should have been categorized as weak (23% [26/115]) or best-practice recommendations (77% [89/115]). CONCLUSION: ATA clinical guidelines are discordant with GRADE guidance. Future guidelines should carefully evaluate the quality of evidence and recognize its limitations when developing recommendations.

Efficacy and Safety of Pirfenidone in Patients with Second-Degree Burns: A Proof-of-Concept Randomized Controlled Trial.

OBJECTIVE: Several studies suggest that pirfenidone may have a potential off-label use for wound healing. However, the effectiveness of this medication in patients with burns remains uncertain. Accordingly, investigators sought to assess wound re-epithelialization in patients with second-degree burns after adding pirfenidone to usual care. DESIGN AND SETTING: Single-center pilot, proof-of-concept, single-blind randomized controlled trial. PATIENTS AND INTERVENTION: Eight patients with second-degree burns were treated with occlusive hydrocolloid dressings and were randomly allocated to receive either no additional treatment or pirfenidone. OUTCOME MEASURES: The primary outcome of the study was to evaluate wound healing between groups based on the thickness of the re-epithelialized epidermis at day 7. Secondary outcomes were to qualitatively assess the development of fibrotic tissue in the dermis, anomalies in the basal membrane, and the development of collagen fibers by histologic analysis. Liver and renal functions were measured daily to assess the overall safety of oral pirfenidone. MAIN RESULTS: Patients treated with pirfenidone showed a remarkable improvement in wound re-epithelialization at day 7 (148.98 ± 13.64 vs 119.27 ± 15.55 µm; P = .029; 95% confidence interval, 4.14-55.29). Histologic evaluations showed less wound fibrosis in the pirfenidone group. CONCLUSIONS: A decrease in wound healing time by enhancing wound re-epithelialization was observed with pirfenidone. Larger clinical trials are needed to reach more reliable conclusions.

Endorsement of reporting guidelines and study registration by endocrine and internal medicine journals: meta-epidemiological study.

OBJECTIVES: To improve the trustworthiness of evidence, studies should be prospectively registered and research reports should adhere to existing standards. We aimed to systematically assess the degree to which endocrinology and internal medicine journals endorse study registration and reporting standards for randomised controlled trials (RCTs), systematic reviews (SRs) and observational studies (ObS). Additionally, we evaluated characteristics that predict endorsement of reporting or registration mechanism by these journals. DESIGN: Meta-epidemiological study. SETTING: Journals included in the 'Endocrinology and Metabolism' and 'General and Internal Medicine' 2017 Journal Citation Reports. PARTICIPANTS: Journals with an impact factor of ≥1.0, focused on clinical medicine, and those who publish RCTs, SRs and ObS were included. PRIMARY OUTCOMES: Requirement of adherence to reporting guideline and study registration as determined from the journals' author instructions. RESULTS: Of the 170 (82 endocrinology and 88 internal medicine) eligible journals, endorsing of reporting standards was the highest for RCTs, with 35 (43%) of endocrine journals and 55 (63%) of internal medicine journals followed by SRs, with 21 (26%) and 48 (55%), respectively, and lastly, by ObS with 41 (50%) of endocrine journals and 21 (24%) of internal medicine journals. In 78 (46%) journals RCTs were required to be registered and published in adherence to the Consolidated Standards of Reporting Trials statement. Only 11 (6%) journals required registration of SRs. Internal medicine journals were more likely to endorse reporting guidelines than endocrine journals except for Strengthening the Reporting of Observational Studies in Epidemiology. No other journal characteristic proved to be an independent predictor of reporting standard endorsement for RCTs besides trial registration. CONCLUSION: Our results highlight that study registration requirement and reporting guideline endorsement are suboptimal in internal medicine and endocrine journals. This malpractice may be further enhanced since endorsement does not imply enforcement, impairing the practice of evidence-based medicine.

Trustworthiness of randomized trials in endocrinology-A systematic survey.

BACKGROUND: Trustworthy (i.e. low risk of bias) randomized clinical trials (RCTs) play an important role in evidence-based decision making. We aimed to systematically assess the risk of bias of trials published in high-impact endocrinology journals. METHODS: We searched the MEDLINE/PubMed database between 2014 and 2016 for phase 2-4 RCTs evaluating endocrine-related therapies. Reviewers working independently and in duplicate used the Cochrane Risk of Bias Tool (CCRBT) to determine the extent to which the methods reported protected the results of each RCT from bias. RESULTS: We assessed 292 eligible RCTs, of which 40% (116) were judged to be at low risk, 43% (126) at moderate, and 17% (50) at high risk of bias. Blinding of outcome assessment was the least common domain reported 43% (125), while selective reporting of outcomes was the most common 97% (282). In multivariable analysis, RCTs with a parallel design (OR 2.4; 95% CI; 1.2-4.6) and funded by for-profit sources (OR 2.2; 95% CI; 1.3-3.6) were more likely to be at low risk of bias. CONCLUSIONS: Trustworthy evidence should ultimately shape care to improve the likelihood of desirable patient outcomes. Six out-of 10 RCTs published in top endocrine journals are at moderate/high-risk of bias. Improving this should be a priority in endocrine research.

Pirfenidone increases the epithelialization rate of skin graft donor sites.

BACKGROUND: Improving epithelialization of donor sites of split-thickness skin grafts (STSG) is extremely important in burned patients. We aimed to assess the efficacy of pirfenidone, a drug with anti-inflammatory, antifibrotic, and antioxidant effects, to accelerate wound healing. We hypothesized that pirfenidone accelerates the epithelialization rates in donor sites. METHODS: We included 28 patients requiring STSGs with donor sites of at least 7.5×10cm. After harvesting, the donor sites were randomly treated with either non-adherent gauze or topical pirfenidone and covered with non-adherent gauze. To assess epithelialization, biopsies were taken at day 7 and 10 on the pirfenidone group, and at day 10 on the control group. Percentage of epithelialization was assessed on the same days through clinical photographs. The pathologists and the clinical observer were blinded to the group and timepoint of the samples. RESULTS: 24 patients were included in the study, with a median age of 21(5-73) for control group and 28(9-61) for pirfenidone. The thickness of epithelium was 75.10±60µm at day 10 for the control group; and 98.21±6µm at day 7, and 108±22µm at day 10 for the pirfenidone group (p=<0.05). Epithelization rate was 83.58±14.09% at day 10 for the control group; and 98.7±1.8% at day 7, and 99.5±1.6% at day 10 for the pirfenidone group. CONCLUSIONS: Pirfenidone is efficient in reducing the healing times when applied in STSG donor sites, at both days 7 and 10.

Systematic review and meta-analysis of the effect of SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes: a review protocol.

INTRODUCTION: Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a relatively new drug-class of glucose-lowering medications. Several trials and systematic reviews have demonstrated their beneficial effect on some macrovascular outcomes. Their effect on microvascular outcomes has been reported as positive in several trials, however, their effect remains uncertain. Therefore, we report the protocol of a systematic review and meta-analysis aimed at determining the effect of SGLT-2 inhibitors regarding patient-important and surrogate microvascular outcomes in patients with type 2 diabetes. METHODS AND ANALYSIS: A comprehensive search will be conducted to find eligible articles from each database's earliest inception to November 2017. These databases will include Ovid, MEDLINE, EMBASE, Web of Science, and Scopus. We will search for randomized controlled trials (RCTs) that compare any of the SGLT-2 inhibitors with any other active treatment or placebo assessing microvascular outcomes in either their primary or secondary outcomes. Reviewers working independently and in duplicate will review all abstracts, and full-text manuscripts for eligibility, and will systematically extract the data and will assess the risk of bias in the included studies. Random-effects models will also be used. ETHICS AND DISSEMINATION: The results of the systematic review will be disseminated via publication in a peer-reviewed journal regardless of outcome and will be presented at relevant conferences. The data we will use do not include individual patient data, so ethical approval is not required PROSPERO REGISTRATION NUMBER: CRD42017076460.