Banning highly hazardous pesticides saves the lives of young people, particularly females, in low- and middle-income countries.

Pesticide self-poisoning is a public health problem mostly affecting low- and middle-income countries. In Sri Lanka, India and China suicide rates have reduced among young people, particularly females, following highly hazardous pesticides (HHP) bans. This success story requires attention to encourage more research on differential effects of HHP bans.

Importance of pesticides for lethal poisoning in India during 1999 to 2018: a systematic review.

BACKGROUND: Poisoning is a major problem in India. However, there is little systematic information on the key poisons responsible for most deaths by geographical area and over time. We aimed to review the literature to identify the poison classes causing the greatest number of deaths in India over the last 20 years. METHODS: We performed a systematic literature review in Medline, Embase and Google Scholar (1999-2018), and Indian online medical journals, to find papers that reported deaths from all forms of poisoning in India, with last search 20 April 2020. We included epidemiological studies, observational studies, randomised trials, interventional studies, and case series published from 1999 to 2018 that showed the number of deaths and autopsy studies indicating the specific poisons or poison classes. Studies providing the case fatality for specific poisons or classes, which enabled calculation of the number of deaths, were also included. We excluded deaths due to animal bites and stings, ethanol or methanol poisoning, and gas inhalation as well as papers reporting a single death (case study of single patient). We grouped the papers into 5-year intervals and identified the two most common poison classes in each paper. We used descriptive statistics to summarise the findings over time based on the causative poison and the location of the study. RESULTS: We identified 186 papers reporting 16,659 poisoning deaths between 1999 and 2018. The number of publications per 5-year interval showed no clear trend over the period (48, 38, 67, and 36 for consecutive periods). Half of the deaths (n = 8338, 50.0%) were reported during the first 5 years of the study (1999-2003), the number of deaths declining thereafter (to n = 1714 in 2014-2018). Deaths due to pesticide poisoning (94.5%) were dominant across the study period compared to other classes of poison [hair dye paraphenylenediamine poisoning (2.6%), medicine overdose (1.4%) or plant poisoning (1.0%)]. Among the pesticides, aluminium phosphide was the most important lethal poison during the first 10 years before declining markedly; organophosphorus insecticides were important throughout the period, becoming dominant in the last decade as aluminium phosphide cases declined. Unfortunately, few papers identified the specific organophosphorus insecticide responsible for deaths. CONCLUSION: Use of the published literature to better understand the epidemiology of lethal poisoning in India has clear limitations, including secular variation in publishing practices and interest in poisoning. Unfortunately, there are no long-term detailed, combination hospital and community studies from India to provide this information. In their absence, our review indicates that pesticides are the most important poison in India, with organophosphorus insecticides replacing aluminium phosphide as the key lethal poison after government regulatory changes in 2001 reduced the latter's lethality. Plant and hair dye poisoning and medicines overdose caused few deaths. Aluminium phosphide deaths mostly occurred in northern Indian states, whereas deaths from organophosphorus insecticide poisoning occurred throughout India. Paraquat poisoning has become a clinical problem in the last 10 years. Lethal pesticide poisoning remains alarmingly common, emphasising the need for additional regulatory interventions to curtail the burden of pesticide poisoning deaths in India. More detailed reporting about the specific pesticide involved in lethal poisoning will be helpful to guide regulatory decisions.

Kidney function and mortality post-liver transplant in the Model for End-Stage Liver Disease era.

The Model for End-Stage Liver Disease (MELD) score incorporates serum creatinine and was introduced to facilitate allocation of orthotopic liver transplantation (LT). The objective is to determine the impact of MELD and kidney function on all-cause mortality. Among LTs performed in a tertiary referral hospital between 1995 and 2009, 419 cases were studied. Cox proportional hazards models were constructed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for death. Over mean follow-ups of 8.4 and 3.1 years during the pre-MELD and MELD era, 57 and 63 deaths were observed, respectively. Those transplanted during the MELD era had a higher likelihood of hepatorenal syndrome (8% vs 2%, P < 0.01), lower kidney function (median estimated glomerular filtration rate [eGFR] 77.8 vs 92.6 mL/ min/1.73 m(2), P < 0.01), and more pretransplantation renal replacement therapy (RRT) (5% vs 1%; P < 0.01). All-cause mortality risk was similar in the MELD vs the pre-MELD era (HR: 0.98, 95% CI: 0.58-1.65). The risk of death, however, was nearly 3-fold greater (95% CI: 1.14-6.60) among those requiring pre- transplant RRT. Similarly, eGFR < 60 mL/min/1.73 m(2) post-transplant was associated with a 2.5-fold higher mortality (95% CI: 1.48-4.11). The study suggests that MELD implementation had no impact on all-cause mortality post-LT. However, the need for pre-transplant RRT and post-transplant kidney dysfunction was associated with a more than 2-fold greater risk of subsequent death.

Safety and efficacy of sorafenib therapy in patients with metastatic kidney cancer with impaired renal function.

PURPOSE: Sorafenib is an oral Raf kinase inhibitor, approved for the treatment of advanced renal cancer. Clinical investigation of the safety and feasibility of sorafenib therapy in patients with impaired renal function was performed in this study. MATERIALS AND METHODS: The protocol was approved by the Human Investigation Committee of Wayne State University. Medical records of patients with metastatic renal cancer at Wayne State University started on sorafenib between November 2005 to January 2007 were reviewed. Patients with a calculated creatinine clearance (CrCl) of 60 mL/min or less (chronic kidney disease stage 3 or greater per Kidney Disease Outcomes Quality Initiative guidelines) were deemed to have renal insufficiency. RESULTS: A total of 32 patients who met the selection criteria were analyzed. Fourteen of 32 (44%) patients had renal insufficiency (range, 32-60 mL/min). Median age was 71 years in patients with CrCl < or = 60 mL/min and 54 years in those with > 60 mL/min. Incidence of diarrhea (57% vs. 33%) and hand-foot syndrome (86% vs. 56%) were higher in the renal-dysfunction group. Dose interruptions and dose reductions were noted in 57% and 43% of patients with renal dysfunction versus 28% and 22% in those without. No significant differences were noted in response rate, progression-free survival or overall survival. CONCLUSION: Renal insufficiency is frequently observed in patients with advanced renal cancer. Sorafenib therapy can be safely delivered in patients with mild and moderate renal dysfunction, and efficacy appears to be maintained.