Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.

Outbreak of hepatitis E in urban Bangladesh resulting in maternal and perinatal mortality.

BACKGROUND: Hepatitis E virus (HEV) causes outbreaks of jaundice associated with maternal mortality. Four deaths among pregnant women with jaundice occurred in an urban community near Dhaka, Bangladesh, in late 2008 and were reported to authorities in January 2009. We investigated the etiology and risk factors for jaundice and death. METHODS: Field workers identified suspected cases, defined as acute onset of yellow eyes or skin, through house-to-house visits. A subset of persons with suspected HEV was tested for immunoglobulin M (IgM) antibodies to HEV to confirm infection. We used logistic regression analysis to identify risk factors for HEV disease and for death. We estimated the increased risk of perinatal mortality associated with jaundice during pregnancy. RESULTS: We identified 4751 suspected HEV cases during August 2008-January 2009, including 17 deaths. IgM antibodies to HEV were identified in 56 of 73 (77%) case-patients tested who were neighbors of the case-patients who died. HEV disease was significantly associated with drinking municipally supplied water. Death among persons with HEV disease was significantly associated with being female and taking paracetamol (acetaminophen). Among women who were pregnant, miscarriage and perinatal mortality was 2.7 times higher (95% confidence interval, 1.2-6.1) in pregnancies complicated by jaundice. CONCLUSIONS: This outbreak of HEV was likely caused by sewage contamination of the municipal water system. Longer-term efforts to improve access to safe water and license HEV vaccines are needed. However, securing resources and support for intervention will rely on convincing data about the endemic burden of HEV disease, particularly its role in maternal and perinatal mortality.

A systematic review and meta-analysis on the safety and efficacy of febuxostat versus allopurinol in chronic gout.

OBJECTIVE: To evaluate the safety and efficacy of febuxostat compared to allopurinol for the treatment of chronic gout. METHODS: We did a systematic review and meta-analysis of randomized and non-randomized controlled trials that compared oral febuxostat to oral allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios (RR) were calculated with random effects and were reported with corresponding 95% confidence intervals (CI). RESULTS: From 1076 potentially relevant citations, 7 studies and 25 associated publications met inclusion criteria; 5 studies were ultimately included in the analysis. Febuxostat did not reduce the risk of gout flares compared with allopurinol (RR = 1.16, 95% CI = 1.03-1.30, I(2) = 44%). Overall, the risk of any adverse event was lower in febuxostat recipients compared to allopurinol (RR = 0.94, 95% CI = 0.90-0.99, I(2) = 13%). Patients receiving febuxostat were more likely to achieve a serum uric acid of <6 mg/dl than allopurinol recipients (RR = 1.56, 95% CI = 1.22-2.00, I(2) = 92%). Subgroup analysis did not indicate any significant difference between high- and low-dose febuxostat on the risk of gout flares. CONCLUSION: Although febuxostat was associated with higher likelihood of achieving a target serum uric acid level of <6 mg/dl, there was significant heterogeneity in the pooled results. There was no evidence that febuxostat is superior to allopurinol for clinically relevant outcomes. Given its higher cost, febuxostat should not be routinely used for chronic gout.

Factors associated with initiation of chronic renal replacement therapy for patients with kidney failure.

BACKGROUND AND OBJECTIVES: Patients with kidney failure sometimes do not receive chronic renal replacement therapy (RRT), even though this may reduce their life expectancy. This study aimed to identify factors associated with initiation of chronic RRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cohort study was conducted with Albertans aged >18 years between May 2002 and March 2009, using linked data from the provincial renal programs, clinical laboratories, and provincial health ministry. This study focused on those who developed kidney failure, defined by an estimated GFR (eGFR) <15 ml/min per 1.73 m(2) at last measurement during follow-up, together with prior CKD (eGFR <60 ml/min per 1.73 m(2) at least 90 days earlier). Multivariable Cox proportional hazards models were used to determine factors significantly associated with initiation of chronic RRT. RESULTS: In total, 7901 participants had eGFR <15 ml/min per 1.73 m(2) at last measurement. After adjustment, older participants were less likely to initiate chronic RRT. Remote residence location, dementia, and metastatic cancer also decreased the likelihood of initiating RRT. The cumulative probability of initiating RRT during follow-up was 76.8% for urban-dwelling men aged <50 years without comorbidity, but was only 3.2% among remote-dwelling women aged ≥70 years with dementia and metastatic cancer. In contrast, patients with diabetes and heavy/severe proteinuria were more likely to initiate chronic RRT. CONCLUSIONS: There is substantial variability in the likelihood of RRT initiation for patients with eGFR <15 ml/min per 1.73 m(2). Further studies are needed to delineate factors that influence this outcome.

Nipah virus infection outbreak with nosocomial and corpse-to-human transmission, Bangladesh.

Active Nipah virus encephalitis surveillance identified an encephalitis cluster and sporadic cases in Faridpur, Bangladesh, in January 2010. We identified 16 case-patients; 14 of these patients died. For 1 case-patient, the only known exposure was hugging a deceased patient with a probable case, while another case-patient's exposure involved preparing the same corpse for burial by removing oral secretions and anogenital excreta with a cloth and bare hands. Among 7 persons with confirmed sporadic cases, 6 died, including a physician who had physically examined encephalitis patients without gloves or a mask. Nipah virus-infected patients were more likely than community-based controls to report drinking raw date palm sap and to have had physical contact with an encephalitis patient (29% vs. 4%, matched odds ratio undefined). Efforts to prevent transmission should focus on reducing caregivers' exposure to infected patients' bodily secretions during care and traditional burial practices.

Hospital-based prevalence of malaria and dengue in febrile patients in Bangladesh.

We conducted a nationwide study at six tertiary hospitals from December 2008 through November 2009 to investigate etiologies of febrile illnesses in Bangladesh. Febrile patients meeting a clinical case definition were enrolled from inpatient and outpatient medicine and pediatric units. We assessed 720 febrile patients over 12 months; 69 (9.6%) were positive for IgM antibodies against dengue virus by enzyme-linked immunosorbent assay, and four malaria patients (0.56%) were confirmed with immuno-chromatography and microscopic slide tests. We identified dengue cases throughout the year from rural (49%) and urban areas (51%). We followed-up 55 accessible dengue-infected patients two months after their initial enrollment: 45 (82%) patients had fully recovered, 9 (16%) reported ongoing jaundice, fever and/or joint pain, and one died. Dengue infection is widespread across Bangladesh, but malaria is sufficiently uncommon that it should not be assumed as the cause of fever without laboratory confirmation.