The consequences of tobacco tax on household health and fi nances in rich and poor smokers in China: an extended cost-eff ectiveness analysis

Background In China, there are more than 300 million male smokers. Tobacco taxation reduces smoking-related premature deaths and increases government revenues, but has been criticised for disproportionately aff ecting poorer people. We assess the distributional consequences (across diff erent wealth quintiles) of a specifi c excise tax on cigarettes in China in terms of both fi nancial and health outcomes. Methods We use extended cost-eff ectiveness analysis methods to estimate, across income quintiles, the health benefi ts (years of life gained), the additional tax revenues raised, the net fi nancial consequences for households, and the fi nancial risk protection provided to households, that would be caused by a 50% increase in tobacco price through excise tax fully passed onto tobacco consumers. For our modelling analysis, we used plausible values for key parameters, including an average price elasticity of demand for tobacco of –0·38, which is assumed to vary from –0·64 in the poorest quintile to –0·12 in the richest, and we considered only the male population, which constitutes the overwhelming majority of smokers in China. Findings Our modelling analysis showed that a 50% increase in tobacco price through excise tax would lead to 231 million years of life gained (95% uncertainty range 194–268 million) over 50 years (a third of which would be gained in the lowest income quintile), a gain of US$703 billion ($616–781 billion) of additional tax revenues from the excise tax (14% of which would come from the lowest income quintile, compared with 24% from the highest income quintile). The excise tax would increase overall household expenditures on tobacco by $376 billion ($232–505 billion), but decrease these expenditures by $21 billion (–$83 to $5 billion) in the lowest income quintile, and would reduce expenditures on tobacco-related disease by$24·0 billion ($17·3–26·3 billion, 28 income quintile). Finally, it would provide fi nancial risk protection worth$1·8 billion ($1·2–2·3 billion), mainly concentrated (74%) in the lowest income quintile. Interpretation Increased tobacco taxation can be a pro-poor policy instrument that brings substantial health and fi nancial benefi ts to households in China

Registered nurses' perceptions and experiences of autonomy: a descriptive phenomenological study

Background Professional autonomy is a key concept in understanding nurses’ roles in delivering patient care. Recent research exploring the role of autonomy in the nursing work environment indicated that English and American nurses had differing perceptions of autonomy. This qualitative study aimed to explore the understanding and experiences of autonomy of nurses working in England. Methods A descriptive phenomenological analysis of data from 48 semi-structured interviews with registered nurses from two National Health Service (NHS) hospitals (purposive sample) was used to explore the concept of autonomy. Results Six themes were identified: working independently; working in a team; having professional skills and knowledge; involvement in autonomy; boundaries around autonomy; and developing autonomy requires support. A key finding was that nurses related autonomy to their clinical work and to the immediate work environment of their ward, rather than to a wider professional context. Nurses also perceived that autonomy could be turned off and on rather than comprising an integrated aspect of nursing. Conclusions Findings suggest that nurses in England, as framed by the sample, had a local ward-focused view of autonomy in comparison to nurses in America, who were reported to relate autonomy to a wider involvement in hospital level committees. Findings further indicate that autonomy was practiced occasionally, rather than incorporated into practice. Findings highlight the need for nurses in England to adopt a broader perspective and actively contribute to writing hospital guidelines and policies that recognise the importance of autonomy to nurse training and practice

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

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

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

Background: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. Methods: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. Results: FDRs-BD had significantly larger ICV (d = +0.16, q <.05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = −0.12, q <.05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < −0.09, q <.05 corrected); and third ventricle was larger (d = +0.15, q <.05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. Conclusions: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct

Trends in treatment patterns and costs of care among patients with advanced stage cervical cancer.

BACKGROUND: Current treatments for recurrent or metastatic cervical cancer (r/mCC) do not offer satisfactory clinical benefits, with most patients progressing beyond first-line (1L) treatment. With new treatments under investigation, understanding current treatment patterns, the impact of newly approved therapies, and total costs of care for r/mCC are important. METHODS: A retrospective analysis of a US commercial insurance claims database to identify adult patients with r/mCC between 2015 and Q1-2020; defining 1L treatment as the first administration of systemic treatment without concomitant chemoradiation or surgery. Patient characteristics, treatment regimens, duration of therapy, and total costs of care were evaluated for each line of therapy. RESULTS: 1323 women initiated 1L treatment for r/mCC (mean age, 56.1 years; mean follow-up, 16.5 months). One-third (n = 438) had evidence of second-line (2L) treatment; of these, 129 (29%) had evidence of third-line (3L) treatment. No regimen represented a majority among 2L+ treatments. The 2018 approval of pembrolizumab led to increased 2L immunotherapy use (0% in 2015, 37% in 2019/Q1-2020). However, only a small proportion of patients stayed on immunotherapy for a prolonged period. Mean per-patient-per-month total costs of care during treatment were $47,387 (1L),$77,661 (2L), and $53,609 (3L), driven primarily by outpatient costs. CONCLUSIONS: No clear standard of care was observed in 2L+. Although immunotherapy is increasingly used in 2L+, only a small subset of patients stayed on immunotherapy for a prolonged period, suggesting a need for more therapeutic options. Better understanding of disease biology and the introduction of new therapies may address these unmet needs

Effectiveness of zinc-fortified water on zinc intake, status and morbidity in Kenyan pre-school children : a randomised controlled trial

Objective: Zn deficiency and diarrhoea are prevalent and may coexist in children living in low-resource settings. Recently, a novel approach for delivering Zn via microbiologically treated, Zn-fortified water was shown to be effective in improving Zn status in West African schoolchildren. We assessed the effectiveness of Zn-fortified, microbiologically purified water delivered as a household intervention on Zn intake, status and morbidity in children aged 2–6 years from rural western Kenya. Design: Randomised controlled trial. Intervention included households assigned to water treatment device with (ZFW) or without (FW) Zn delivery capability Setting: Rural households in Kisumu, western Kenya. Subjects: Children aged 2–6 years. Results: The ZFW group had higher dietary Zn intake compared with the FW group. ZFW contributed 36 and 31 % of daily requirements for absorbable Zn in children aged 2–3 and 4–6 years, respectively, in the ZFW group. Consumption of Zn-fortified water resulted in lower prevalence of reported illness (risk ratio; 95 % CI) in the ZFW group compared with the FW group: for cold with runny nose (0·91; 0·83, 0·99; P=0·034) and abdominal pain (0·70; 0·56, 0·89; P=0·003) in the intention-to-treat analysis and for diarrhoea (0·72; 0·53, 0·96; P=0·025) in the per-protocol analysis. We did not detect an effect of treatment on plasma Zn concentration. Conclusions: Daily consumption of Zn-fortified, microbiologically treated water results in increased intake of absorbable dietary Zn and may help in preventing childhood infections in pre-school children in rural Africa.</p

Combining food-based dietary recommendations using Optifood with zinc-fortified water potentially improves nutrient adequacy among 4- to 6-year-old children in Kisumu West district, Kenya

Children in developing countries often face multiple micronutrient deficiencies. Introduction of zinc-fortified water can increase zinc intake, but additional recommendations are required to address overall diet nutrient adequacy. We developed and tested food-based recommendations (FBRs) that included zinc-fortified water for children aged between 4 and 6 years from rural Kenya to achieve the best possible nutrient adequacy. Dietary intakes of 60 children aged 4–6 years, from Kisumu West district, Kenya, were assessed using a quantitative multipass 24-hr recall. Linear programming model parameters were derived, including a list of foods consumed, median serving sizes, and distribution of frequency of consumption. By using the Optifood linear programming tool, we developed FBRs for diets including zinc-fortified water. FBRs with nutrient levels achieving ≥70% recommended nutrient intake (RNI) of the World Health Organization/Food and Agriculture Organization of the United Nations RNI for most of the 12 considered nutrients were selected as the final recommendations for the children. With no FBRs and no zinc-fortified water, percent RNI coverage range was between 40% and 76% for zinc, improving to 66–101% after introduction of zinc-fortified water. The final set of FBRs achieved nutrient adequacy for all nutrients except for vitamin A (25% RNI) and folate (68% RNI). Introduction of zinc-fortified water combined with FBRs will likely improve the nutrient adequacy of diets consumed by children in Kenya but needs to be complemented with alternative interventions to ensure dietary adequacy