Dapagliflozin for the treatment of type 2 diabetes mellitus - an update.

INTRODUCTION: Diabetes is a global health concern with a prevalence of 463 million people. Importantly, despite the availability of numerous antidiabetic medications, type 2 diabetes mellitus (T2DM) is still associated with significant morbidity and mortality worldwide. One particular drug of interest is dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor that is commonly used in the treatment of Type 2 Diabetes Mellitus (T2DM). AREAS COVERED: This review outlines the current use and pharmacology of dapagliflozin, with a specific focus on recent evidence regarding benefits in patients with cardiovascular and chronic kidney disease. The article includes an overview of the efficacy and safety of this drug and provides the reader with the expert opinion and perspectives of the authors. EXPERT OPINION: Increasing evidence of the beneficial effects on morbidity and mortality in patients with Type 2 diabetes and concurrent heart failure, acute MI and renal failure are likely to see the usage of dapagliflozin in patients with these comorbidities increase over the next 5 years.

The Association Between Benzodiazepines and Survival in Patients With Cancer: A Systematic Review.

CONTEXT: Patients with cancer often experience distressing symptoms such as anxiety or dyspnea, which can be managed with benzodiazepines; however, concerns regarding the impact of these drugs on survival may dissuade prescribing and compliance. OBJECTIVES: We aimed to identify and appraise studies examining benzodiazepine use and survival in adults with cancer, to investigate the relationship and context of use. METHODS: Systematic review of the international literature prepared according to preferred reporting items for systematic reviews. Comprehensive searches of the MEDLINE, Embase, PsycINFO, Cochrane Library, and AMED databases using medical subject heading and free-text search combinations with no date or language restrictions were undertook. Handsearching of references was conducted. Risk of bias of the included studies was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Two thousand two hundred fifty-seven unique records were identified, with 18 meeting inclusion criteria, representing 4117 patients. All studies were very low quality. No study found an increase in mortality in association with benzodiazepine use, whereas two demonstrated an increase. CONCLUSION: Existing evidence shows no association between benzodiazepine use in patients with cancer and decreased survival. None of the studies evaluated the association between benzodiazepine use and survival in earlier stages of cancer, and the quality of studies retrieved signifies a need for further robust studies to draw more definitive conclusions. Further investigation in patients with cancer using well-designed, high-quality research with survival as a primary outcome should be conducted.

The Association of Benzodiazepines and z-drugs with Mortality in Patients with Cancer: a Systematic Review.

BACKGROUND: Benzodiazepines and Z-drugs are commonly used in patients with cancer for the management of symptoms such as anxiety, agitation and dyspnoea. Clinical staff, patients and relatives have concerns about the impact of these drugs on survival. This potentially decreases prescribing leading to suboptimal symptom control. The aim of this systematic review was to find and assimilate the evidence assessing the association of benzodiazepines and Z-drugs with survival in patients with cancer, to assist in clinical decision-making regarding the use of these drugs in cancer patients. METHODS: Systematic review with narrative synthesis designed and conducted according to the recommendations set out in Preferred Reporting Items for Systematic Reviews and MetaAnalyses-Protocol (PRISMA-P) and PRISMA statements. The review protocol was registered on the PROSPERO prior to commencing the searches. The electronic databases MEDLINE, EMBASE, PsychINFO, Cochrane Library, AMED were searched and hand-searches were performed. Screening, extraction and quality assessment were performed in duplicate. RESULTS: A total of 2257 unique records were identified, 116 full-text articles assessed for eligibility, 18 met the inclusion criteria. These contained data on 4117 patients with cancer. All studies were low or very-low quality. Most studies were conducted in patients in the last days/weeks of life. No study found an association between benzodiazepines and survival in patients with cancer. CONCLUSIONS: There is no evidence demonstrating an association between benzodiazepines and survival in patients with cancer. These results should be interpreted with caution as all studies were low/very low quality, most did not report or account for other medications and did not have survival as a primary outcome. No study assessed the effect of long-term benzodiazepines on survival. Therefore, definitive conclusions regarding survival impact of benzodiazepine in patients with cancer can be made. Further investigation using high-quality long-term randomised control trials with survival as a primary endpoint are needed.

Extremity pain and refusal to walk in children with invasive meningococcal disease.

OBJECTIVE: Early recognition of invasive meningococcal disease in children may be difficult. Extremity pain and refusal to walk (extremity symptoms) are uncommonly mentioned as clinical findings in children who present with this disease. We sought to determine 1) the frequency of extremity symptoms as part of the clinical presentation in children with invasive meningococcal disease and 2) whether these symptoms help identify children with otherwise unsuspected meningococcal disease. METHODS: We reviewed the medical records of patients who were younger than 20 years and had invasive meningococcal disease from 1985 to 1996 at 3 pediatric referral centers. Children with extremity symptoms were identified and described. We compared clinical and laboratory findings and frequency of adverse outcomes between these children and those with invasive meningococcal disease without extremity symptoms. RESULTS: We identified 274 children with invasive meningococcal disease, 45 (16%) of whom had either history or physical examination evidence of extremity pain (31) or refusal to walk (14) as part of their clinical presentations. Five of the 45 patients had arthritis at the time of presentation. Patients with extremity symptoms at presentation were significantly older (77.9 +/- 62.2 vs 44.0 +/- 56.9 months), had lower temperatures (38.8 +/- 1.2 degrees C vs 39.2 +/- 1.2 degrees C), and had higher band counts (28.2 +/- 15.2% vs 18.1 +/- 12.4%) than did patients without extremity symptoms. There were no significant differences, however, between groups with regard to rash, white blood cell counts, coagulation parameters, prevalence of meningitis, or adverse outcomes. Seventy-three (27%) of the 274 patients had unsuspected disease, and 5 (7%) of these had extremity symptoms at the time of diagnosis. CONCLUSIONS: Sixteen percent of children with invasive meningococcal disease have extremity symptoms at the time of diagnosis. These symptoms may help to identify some patients with otherwise unsuspected invasive meningococcal disease.