Contrasting male and female trends in tobacco-attributed mortality in China:evidence from successive nationwide prospective cohort studies

SummaryBackgroundChinese men now smoke more than a third of the world's cigarettes, following a large increase in urban then rural usage. Conversely, Chinese women now smoke far less than in previous generations. We assess the oppositely changing effects of tobacco on male and female mortality.MethodsTwo nationwide prospective studies 15 years apart recruited 220 000 men in about 1991 at ages 40–79 years (first study) and 210 000 men and 300 000 women in about 2006 at ages 35–74 years (second study), with follow-up during 1991–99 (mid-year 1995) and 2006–14 (mid-year 2010), respectively. Cox regression yielded sex-specific adjusted mortality rate ratios (RRs) comparing smokers (including any who had stopped because of illness, but not the other ex-smokers, who are described as having stopped by choice) versus never-smokers.FindingsTwo-thirds of the men smoked; there was little dependence of male smoking prevalence on age, but many smokers had not smoked cigarettes throughout adult life. Comparing men born before and since 1950, in the older generation, the age at which smoking had started was later and, particularly in rural areas, lifelong exclusive cigarette use was less common than in the younger generation. Comparing male mortality RRs in the first study (mid-year 1995) versus those in the second study (mid-year 2010), the proportional excess risk among smokers (RR-1) approximately doubled over this 15-year period (urban: RR 1·32 [95% CI 1·24–1·41] vs 1·65 [1·53–1·79]; rural: RR 1·13 [1·09–1·17] vs 1·22 [1·16–1·29]), as did the smoking-attributed fraction of deaths at ages 40–79 years (urban: 17% vs 26%; rural: 9% vs 14%). In the second study, urban male smokers who had started before age 20 years (which is now typical among both urban and rural young men) had twice the never-smoker mortality rate (RR 1·98, 1·79–2·19, approaching Western RRs), with substantial excess mortality from chronic obstructive pulmonary disease (COPD RR 9·09, 5·11–16·15), lung cancer (RR 3·78, 2·78–5·14), and ischaemic stroke or ischaemic heart disease (combined RR 2·03, 1·66–2·47). Ex-smokers who had stopped by choice (only 3% of ever-smokers in 1991, but 9% in 2006) had little smoking-attributed risk more than 10 years after stopping. Among Chinese women, however, there has been a tenfold intergenerational reduction in smoking uptake rates. In the second study, among women born in the 1930s, 1940s, 1950s, and since 1960 the proportions who had smoked were, respectively, 10%, 5%, 2%, and 1% (3097/30 943, 3265/62 246, 2339/97 344, and 1068/111 933). The smoker versus non-smoker RR of 1·51 (1·40–1·63) for all female mortality at ages 40–79 years accounted for 5%, 3%, 1%, and <1%, respectively, of all the female deaths in these four successive birth cohorts. In 2010, smoking caused about 1 million (840 000 male, 130 000 female) deaths in China.InterpretationSmoking will cause about 20% of all adult male deaths in China during the 2010s. The tobacco-attributed proportion is increasing in men, but low, and decreasing, in women. Although overall adult mortality rates are falling, as the adult population of China grows and the proportion of male deaths due to smoking increases, the annual number of deaths in China that are caused by tobacco will rise from about 1 million in 2010 to 2 million in 2030 and 3 million in 2050, unless there is widespread cessation.FundingWellcome Trust, MRC, BHF, CR-UK, Kadoorie Charitable Foundation, Chinese MoST and NSF

Determinants of never-treated status in rural versus urban contexts for individuals with schizophrenia in a population-based study in China

Background A goal of China’s 2012 National Mental Health Law is to improve access to services and decrease urban versus rural disparities in services. However, pre-reform data is needed for objective evaluation of these reforms’ effectiveness. Accordingly, this study compares the pre-reform utilization of medical services for the treatment of schizophrenia in rural and urban communities in China. Methods In a large community-based study in four provinces representing 12% of China’s population conducted from 2001 to 2005, we identified 326 individuals with schizophrenia (78 never treated). Comparing those living in urban (n = 86) versus rural (n = 240) contexts, we used adjusted Poisson regression models to assess the relationship of ‘never treated’ status with family-level factors (marital status, family income, and number of co-resident family members) and illness severity factors (age of onset, symptom severity and functional impairment). Results Despite similar impairments due to symptoms, rural patients were less likely to have received intensive mental health services (i.e., use psychiatric inpatient services), and appeared more likely to be ‘never treated’ or to only have received outpatient care. Among rural patients, only having more than four co-resident family members was independently associated with ‘never-treated’ status (RR = 0.34; 95% CI, 0.12–0.94; p = 0.039). Among urban patients, only older age of onset was independently associated with ‘never-treated’ status (RR = 1.06; 95% CI 1.02–1.10, p = 0.003). Conclusions Identifying differential drivers of service utilization in urban and rural communities is needed before implementing policies to improve the utilization and equity of services and to define metrics of program success

Malnutrition in early life and adult mental health: Evidence from a natural experiment

As natural experiments, famines provide a unique opportunity to test the health consequences of nutritional deprivation during the critical period of early life. Using data on 4,972 Chinese born between 1956 and 1963 who participated in a large mental health epidemiology survey conducted between 2001 and 2005, we investigated the potential impact of famine exposure in utero and during the early postnatal life on adult mental illness. The risk of mental illness was assessed with the 12-item General Health Questionnaire (GHQ-12) and eight other risk factors, and the famine impact on adult mental illness was estimated by difference-in-difference models. Results show that compared with women born in 1963, women born during the famine years (1959–1961) had higher GHQ scores (increased by 0.95 points; CI: 0.26, 1.65) and increased risk of mental illness (OR= 2.80; CI: 1.23, 6.39); those born in 1959 were the most affected and had GHQ scores 1.52 points higher (CI: 0.42, 2.63) and an OR for mental illness of 4.99 (CI: 1.68, 14.84). Compared to men in the 1963 birth cohort, men born during the famine had lower GHQ scores (decreased by 0.89 points; CI: −1.59, −0.20) and a nonsignificant decrease in the risk of mental illness (OR = 0.60; CI: 0.26, 1.40). We speculate that the long-term consequences of early-life famine exposure include both the selection of the hardiest and the enduring deleterious effects of famine on those who survive. The greater biological vulnerability and stronger natural selection in utero of male versus female fetuses during severe famine may result in a stronger selection effect among men than women, obscuring the deleterious impact of famine exposure on the risk of mental illness in men later in life

Long-Acting Heterodimeric Paclitaxel–Idebenone Prodrug-Based Nanomedicine Promotes Functional Recovery after Spinal Cord Injury

After spinal cord injury (SCI), successive systemic administration of microtubule-stabilizing agents has been shown to promote axon regeneration. However, this approach is limited by poor drug bioavailability, especially given the rapid restoration of the blood–spinal cord barrier. There is a pressing need for long-acting formulations of microtubule-stabilizing agents in treating SCI. Here, we conjugated the antioxidant idebenone with microtubule-stabilizing paclitaxel to create a heterodimeric paclitaxel–idebenone prodrug via an acid-activatable, self-immolative ketal linker and then fabricated it into chondroitin sulfate proteoglycan-binding nanomedicine, enabling drug retention within the spinal cord for at least 2 weeks and notable enhancement in hindlimb motor function and axon regeneration after a single intraspinal administration. Additional investigations uncovered that idebenone can suppress the activation of microglia and neuronal ferroptosis, thereby amplifying the therapeutic effect of paclitaxel. This prodrug-based nanomedicine simultaneously accomplishes neuroprotection and axon regeneration, offering a promising therapeutic strategy for SCI