Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Stakeholder Engagement as a Strategy to Enhance Palliative Care Involvement in Intensive Care Units:A Theory of Change Approach

Background Adult patients admitted to intensive care units in the terminal phase experience high symptom burden, increased costs, and diminished quality of dying. There is limited literature on palliative care engagement in ICU, especially in lower-middle-income countries. This study explores a strategy to enhance palliative care engagement in ICU through a stakeholder participatory approach. Methods Theory of Change approach was used to develop a hypothetical causal pathway for palliative care integration into ICUs in India. Four facilitated workshops and fifteen research team meetings were conducted virtually over three months. Thirteen stakeholders were purposively chosen, and three facilitators conducted the workshops. Data included workshop discussion transcripts, online chat box comments, and team meeting minutes. These were collected, analysed and represented as theory of change map. Results The desired impact of palliative care integration was good death. Potential long-term outcomes identified were fewer deaths in ICUs, discharge against medical advice, and inappropriate admissions; increased referrals to palliative care; and improved patient and family satisfaction. Twelve preconditions were identified, and eleven key interventions were developed. Five overarching assumptions related to contextual factors influencing the outcomes of interventions. Conclusion Theory of change framework facilitated the identification of proposed mechanisms and interventions underpinning palliative care integration in ICUs

MOESM1 of Comparison of the safety and efficacy of fixed-dose combination of arterolane maleate and piperaquine phosphate with chloroquine in acute, uncomplicated Plasmodium vivax malaria: a phase III, multicentric, open-label study

Additional file 1: Table S1. Adverse events

\u27Royal science\u27 and civil war in Sri Lanka : a comment on S. Goonatilake

In highlighting the relationship between the production of knowledge, the administration of government and the formation of subject&ndash;citizens in colonial systems, post-colonialism has arguably found its most fertile field of inquiry and revision in South Asia. The reasons for this are complex and relate, in part, to the nature of both colonial administration and the colonised civilisations to be found in the region, as well as to the nature of the different independence movements&mdash;many of these persisting well beyond the formal grants of independence in the late 1940s. Also important is the emerging post-colonial middle class, its transnational interconnections comprising inter alia extensive participation in knowledge/information economies, and its &lsquo;organic intellectuals&rsquo; (Gramsci 1971) whose work represents the interests of their class. In other words, the tremendous insights offered by post-colonial theory into the nature of latent or implicit power relations to be found in forms of knowledge reveal the ongoing complicity of scholarship in government. Post-colonialism, thus, raises the issue of how the nexus of knowledge and power translates into contemporary situations&mdash;the post-colonial predicament (Breckenridge and van der Veer 1993).<br /

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically