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Background: The insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes., Methods: Samples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes., Results: Elevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09-2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14-2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00-2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09-2.26; P; 0.01)., Conclusions: These results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes., Trial Registration: CREDENCE; ClinicalTrials.gov Identifier: NCT02065791., (© 2023. The Author(s).)

Background: SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes., Methods and Discussion: CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020., Trial Registration: ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831)., (© 2021. The Author(s).)

Background: The role of intravenous hydration at the time of primary percutaneous intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains unclear. Guidelines are vague, supported by low level evidence, and hydration is used less often than other clinical settings.To perform a systematic review and meta-analysis of all randomized controlled trials assessing intravenous hydration compared with non-hydration for prevention of contrast induced nephropathy (CIN) and In-hospital mortality in patients with STEMI undergoing primary PCI., Methods: Medline, EMBASE and the Cochrane Register were searched to September 2018. Included studies reported the incidence of CIN, In-hospital mortality, requirement for dialysis and heart failure. Relative risks with 95% confidence intervals (CIs) for individual trials were pooled using a random effects model., Results: Three moderate quality trials were identified including 1074 patients. Overall, compared with no hydration, intravenous hydration significantly reduced the incidence of CIN by 42% (RR 0.58; 95% CI: 0.45 to 0.74, p < 0.001). The estimated effects upon all-cause mortality (RR 0.56; 95% CI: 0.30 to 1.02, p = 0.057) and the requirement for dialysis (RR 0.52, 95% CI 0.14-1.88, p = 0.462) were not statistically significant. The outcome of heart failure was not consistently reported., Conclusions: Intravenous hydration likely reduces the incidence of CIN in patients with STEMI undergoing primary PCI. However, for key clinical outcomes such as mortality, heart failure and dialysis the effect estimates were imprecise. Further high quality studies are needed to clarify the appropriate volume of fluid and effects on outcomes.

Background and Rationale: The HIV epidemic in Vietnam has from its start been concentrated among injecting drug users. Vietnam instituted the 2006 HIV/AIDS Law which includes comprehensive harm reduction measures, but these are unevenly accepted and inadequately implemented. Ward police are a major determinant of risk for IDUs, required to participate in drug control practices (especially meeting quotas for detention centres) which impede support for harm reduction. We studied influences on ward level police regarding harm reduction in Hanoi to learn how to better target education and structural change., Methods: After document review, we interviewed informants from government, NGOs, INGOs, multilateral agencies, and police, using semi-structured guides. Topics covered included perceptions of harm reduction and the police role in drug law enforcement, and harm reduction training and advocacy among police., Results: Police perceive conflicting responsibilities, but overwhelmingly see their responsibility as enforcing drug laws, identifying and knowing drug users, and selecting those for compulsory detention. Harm reduction training was very patchy, ward police not being seen as important to it; and understanding of harm reduction was limited, tending to reflect drug control priorities. Justification for methadone was as much crime prevention as HIV prevention.Competing pressures on ward police create much anxiety, with performance measures based around drug control; recourse to detention resolves competing pressures more safely. There is much recognition of the importance of discretion, and much use of it to maintain good social order. Policy dissemination approaches within the law enforcement sector were inconsistent, with little communication about harm reduction programs or approaches, and an unfounded assumption that training at senior levels would naturally reach to the street., Discussion: Ward police have not been systematically included in harm reduction advocacy or training strategies to support or operationalise legalised harm reduction interventions. The practices of street police challenge harm reduction policies, entirely understandably given the competing pressures on them. For harm reduction to be effective in Vietnam, it is essential that the ambiguities and contradictions between laws to control HIV and to control drugs be resolved for the street-level police.

Methadone maintenance therapy (MMT) was introduced in the rapidly developing semi-rural district of Tu Liem in Hanoi in December, 2009. Commune police play an integral role in determining which injecting drug users (IDUs) are eligible to commence and continue MMT. This case study highlights the importance of providing training to commune police about MMT to mitigate negative impacts drug law enforcement can have on IDU accessibility to MMT programs.

The findings of our research show that while police play multiple roles in the fight against drug-related crime, they often perceived their tasks - especially preventing and controlling drug use on the one hand, and supporting harm reduction on the other - as contradictory, and this creates tensions in their work and relations with their communities. Although they are leaders and implementers of harm reduction, not all police know about it, and some remain skeptical or perceive it as contradictory to their main task of fighting drugs. Methadone treatment is seen by some as in competition with their main task of coordinating conventional drug treatment in the rehabilitation center.The history of drug use and the evolution of discourses on drug use in Viet Nam have created these conflicting pressures on police, and thus created contradictory expectations and led to different views and attitudes of police regarding various harm reduction measures. This might aid understanding why, despite the comprehensive and progressive policies on HIV/AIDS and harm reduction in Viet Nam, it is not easy for police to actively and effectively support and be involved in harm reduction at the ground level.To promote the wider acceptance of harm reduction the concept of community safety must be expanded to include community health; harm reduction must be integrated into the "new society" movement; and laws and policies need further revision to reduce contradiction between current drug laws and HIV laws.Harm reduction guidelines for police and other actors need to be disseminated and supported, embodying better ways of working between sectors, and all sectors in the partnership require support for building capacity to contribute to the overall goal.

Background: Peritoneal dialysis-associated peritonitis (PD-peritonitis) due to Mycobacterium spp is uncommon. Non-tuberculous Mycobacterium (NTB) PD-peritonitis can present in a similar fashion to more common causes of bacterial PD-peritonitis. We describe the first reported case of multiresistant Mycobacterium fortuitum PD-peritonitis in an Australian patient., Case Presentation: A 38 year-old woman developed mild PD-peritonitis during an overseas holiday. Treatment was complicated by delayed diagnosis, requirement for special investigations, treatment with multiple antibiotics, and conversion to haemodialysis following removal of her Tenckhoff catheter., Conclusion: This case demonstrates the diagnostic yield of pursuing further investigations in cases of initially culture-negative, problematic PD-peritonitis. A systematic review of the literature identified only 17 reports of M. fortuitum PD-peritonitis. Similar to our case, a delay in microbiological diagnosis was frequently noted and the Tenckhoff catheter was commonly removed at the time of diagnosis. The type and duration of antibiotic therapy also varied widely so the optimum treatment appears to be poorly defined.

Introduction: Indigenous Australians suffer markedly higher rates of end-stage kidney disease (ESKD) but are less likely than their non-Indigenous counterparts to receive a transplant. This difference is not fully explained by measurable clinical differences. Previous work suggests that Indigenous Australian patients may be regarded by treating specialists as 'non-compliers', which may negatively impact on referral for a transplant. However, this decision-making is not well understood. The objectives of this study were to investigate: whether Indigenous patients are commonly characterised as 'non-compliers'; how estimations of patient compliance factor into Australian nephrologists' decision-making about transplant referral; and whether this may pose a particular barrier for Indigenous patients accessing transplants., Methods: Nineteen nephrologists, from eight renal units treating the majority of Indigenous Australian renal patients, were interviewed in 2005-06 as part of a larger study. Thematic analysis was undertaken to investigate how compliance factors in specialists' decision-making, and its implications for Indigenous patients' likelihood of obtaining transplants., Results: Specialists commonly identified Indigenous patients as both non-compliers and high-risk transplant candidates. Definition and assessment of 'compliance' was neither formal nor systematic. There was uncertainty about the value of compliance status in predicting post-transplant outcomes and the issue of organ scarcity permeated participants' responses. Overall, there was marked variation in how specialists weighed perceptions of compliance and risk in their decision-making., Conclusion: Reliance on notions of patient 'compliance' in decision-making for transplant referral is likely to result in continuing disadvantage for Indigenous Australian ESKD patients. In the absence of robust evidence on predictors of post-transplant outcomes, referral decision-making processes require attention and debate.