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Health information technology interventions and engagement in HIV care and achievement of viral suppression in publicly funded settings in the US: A cost-effectiveness analysis

Mer, 07/04/2021 - 16:00

by Starley B. Shade, Elliot Marseille, Valerie Kirby, Deepalika Chakravarty, Wayne Steward, Kimberly Koester, Adan Cajina, Janet J. Myers

Background

The US National HIV/AIDS Strategy (NHAS) emphasizes the use of technology to facilitate coordination of comprehensive care for people with HIV. We examined cost-effectiveness from the health system perspective of 6 health information technology (HIT) interventions implemented during 2008 to 2012 in a Ryan White HIV/AIDS Program (RWHAP) Special Projects of National Significance (SPNS) Program demonstration project.

Methods/findings

HIT interventions were implemented at 6 sites: Bronx, New York; Durham, North Carolina; Long Beach, California; New Orleans, Louisiana; New York, New York (2 sites); and Paterson, New Jersey. These interventions included: (1) use of HIV surveillance data to identify out-of-care individuals; (2) extension of access to electronic health records (EHRs) to support service providers; (3) use of electronic laboratory ordering and prescribing; and (4) development of a patient portal. We employed standard microcosting techniques to estimate costs (in 2018 US dollars) associated with intervention implementation. Data from a sample of electronic patient records from each demonstration site were analyzed to compare prescription of antiretroviral therapy (ART), CD4 cell counts, and suppression of viral load, before and after implementation of interventions. Markov models were used to estimate additional healthcare costs and quality-adjusted life-years saved as a result of each intervention. Overall, demonstration site interventions cost $3,913,313 (range = $287,682 to $998,201) among 3,110 individuals (range = 258 to 1,181) over 3 years. Changes in the proportion of patients prescribed ART ranged from a decrease from 87.0% to 72.7% at Site 4 to an increase from 74.6% to 94.2% at Site 6; changes in the proportion of patients with 0 to 200 CD4 cells/mm3 ranged from a decrease from 20.2% to 11.0% in Site 6 to an increase from 16.7% to 30.2% in Site 2; and changes in the proportion of patients with undetectable viral load ranged from a decrease from 84.6% to 46.0% in Site 1 to an increase from 67.0% to 69.9% in Site 5. Four of the 6 interventions—including use of HIV surveillance data to identify out-of-care individuals, use of electronic laboratory ordering and prescribing, and development of a patient portal—were not only cost-effective but also cost saving ($6.87 to $14.91 saved per dollar invested). In contrast, the 2 interventions that extended access to EHRs to support service providers were not effective and, therefore, not cost-effective. Most interventions remained either cost-saving or not cost-effective under all sensitivity analysis scenarios. The intervention that used HIV surveillance data to identify out-of-care individuals was no longer cost-saving when the effect of HIV on an individual’s health status was reduced and when the natural progression of HIV was increased. The results of this study are limited in that we did not have contemporaneous controls for each intervention; thus, we are only able to assess sites against themselves at baseline and not against standard of care during the same time period.

Conclusions

These results provide additional support for the use of HIT as a tool to enhance rapid and effective treatment of HIV to achieve sustained viral suppression. HIT has the potential to increase utilization of services, improve health outcomes, and reduce subsequent transmission of HIV.

Maternal weight change from prepregnancy to 18 months postpartum and subsequent risk of hypertension and cardiovascular disease in Danish women: A cohort study

Ven, 02/04/2021 - 16:00

by Helene Kirkegaard, Mette Bliddal, Henrik Støvring, Kathleen M. Rasmussen, Erica P. Gunderson, Lars Køber, Thorkild I. A. Sørensen, Ellen A. Nøhr

Background

One-fourth of women experience substantially higher weight years after childbirth. We examined weight change from prepregnancy to 18 months postpartum according to subsequent maternal risk of hypertension and cardiovascular disease (CVD).

Methods and findings

We conducted a cohort study of 47,966 women with a live-born singleton within the Danish National Birth Cohort (DNBC; 1997–2002). Interviews during pregnancy and 6 and 18 months postpartum provided information on height, gestational weight gain (GWG), postpartum weights, and maternal characteristics. Information on pregnancy complications, incident hypertension, and CVD was obtained from the National Patient Register. Using Cox regression, we estimated adjusted hazard ratios (HRs; 95% confidence interval [CI]) for hypertension and CVD through 16 years of follow-up. During this period, 2,011 women were diagnosed at the hospital with hypertension and 1,321 with CVD. The women were on average 32.3 years old (range 18.0–49.2) at start of follow-up, 73% had a prepregnancy BMI <25, and 27% a prepregnancy BMI ≥25. Compared with a stable weight (±1 BMI unit), weight gains from prepregnancy to 18 months postpartum of >1–2 and >2 BMI units were associated with 25% (10%–42%), P = 0.001 and 31% (14%–52%), P < 0.001 higher risks of hypertension, respectively. These risks were similar whether weight gain presented postpartum weight retention or a new gain from 6 months to 18 months postpartum and whether GWG was below, within, or above the recommendations. For CVD, findings differed according to prepregnancy BMI. In women with normal-/underweight, weight gain >2 BMI units and weight loss >1 BMI unit were associated with 48% (17%–87%), P = 0.001 and 28% (6%–55%), P = 0.01 higher risks of CVD, respectively. Further, weight loss >1 BMI unit combined with a GWG below recommended was associated with a 70% (24%–135%), P = 0.001 higher risk of CVD. No such increased risks were observed among women with overweight/obesity (interaction by prepregnancy BMI, P = 0.01, 0.03, and 0.03, respectively). The limitations of this observational study include potential confounding by prepregnancy metabolic health and self-reported maternal weights, which may lead to some misclassification.

Conclusions

Postpartum weight retention/new gain in all mothers and postpartum weight loss in mothers with normal-/underweight may be associated with later adverse cardiovascular health.

Epidemiological, clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox’s Bazar, Bangladesh, 2017 to 2019: A retrospective study

Gio, 01/04/2021 - 16:00

by Jonathan A. Polonsky, Melissa Ivey, Khadimul Anam Mazhar, Ziaur Rahman, Olivier le Polain de Waroux, Basel Karo, Katri Jalava, Sirenda Vong, Amrish Baidjoe, Janet Diaz, Flavio Finger, Zakir H. Habib, Charles Erik Halder, Christopher Haskew, Laurent Kaiser, Ali S. Khan, Lucky Sangal, Tahmina Shirin, Quazi Ahmed Zaki, Abdus Salam, Kate White

Background

Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox’s Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population.

Methods and findings

Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2–4.7) during the exponential growth phase. The median age was 10 years (range 0–85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown.

Conclusions

To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises.

Variation in HIV care and treatment outcomes by facility in South Africa, 2011–2015: A cohort study

Mer, 31/03/2021 - 16:00

by Jacob Bor, Anna Gage, Dorina Onoya, Mhairi Maskew, Yorghos Tripodis, Matthew P. Fox, Adrian Puren, Sergio Carmona, Koleka Mlisana, William MacLeod

Background

Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa’s national HIV program using routine laboratory data.

Methods and findings

Data were extracted from South Africa’s National Health Laboratory Service (NHLS) Corporate Data Warehouse. All CD4 counts, viral loads (VLs), and other laboratory tests used in HIV monitoring were linked, creating a validated patient identifier. We constructed longitudinal HIV care cascades for all patients in the national HIV program, excluding data from the Western Cape and very small facilities. We then estimated for each facility in each year (2011 to 2015) the following cascade measures identified a priori as reflecting quality of HIV care: median CD4 count among new patients; retention 12 months after presentation; 12-month retention among patients established in care; viral suppression; CD4 recovery; monitoring after an elevated VL. We used factor analysis to identify an underlying measure of quality of care, and we assessed the persistence of this quality measure over time. We then assessed spatiotemporal variation and facility and population predictors in a multivariable regression context.We analyzed data on 3,265 facilities with a median (IQR) annual size of 441 (189 to 988) lab-monitored HIV patients. Retention 12 months after presentation increased from 42% to 47% during the study period, and viral suppression increased from 66% to 79%, although there was substantial variability across facilities. We identified an underlying measure of quality of HIV care that correlated with all cascade measures except median CD4 count at presentation. Averaging across the 5 years of data, this quality score attained a reliability of 0.84. Quality was higher for clinics (versus hospitals), in rural (versus urban) areas, and for larger facilities. Quality was lower in high-poverty areas but was not independently associated with percent Black. Quality increased by 0.49 (95% CI 0.46 to 0.53) standard deviations from 2011 to 2015, and there was evidence of geospatial autocorrelation (p < 0.001). The study’s limitations include an inability to fully adjust for underlying patient risk, reliance on laboratory data which do not capture all relevant domains of quality, potential for errors in record linkage, and the omission of Western Cape.

Conclusions

We observed persistent differences in HIV care and treatment outcomes across South African facilities. Targeting low-performing facilities for additional support could reduce overall burden of disease.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews

Lun, 29/03/2021 - 16:00

by Matthew J. Page, Joanne E. McKenzie, Patrick M. Bossuyt, Isabelle Boutron, Tammy C. Hoffmann, Cynthia D. Mulrow, Larissa Shamseer, Jennifer M. Tetzlaff, Elie A. Akl, Sue E. Brennan, Roger Chou, Julie Glanville, Jeremy M. Grimshaw, Asbjørn Hróbjartsson, Manoj M. Lalu, Tianjing Li, Elizabeth W. Loder, Evan Mayo-Wilson, Steve McDonald, Luke A. McGuinness, Lesley A. Stewart, James Thomas, Andrea C. Tricco, Vivian A. Welch, Penny Whiting, David Moher

Matthew Page and co-authors describe PRISMA 2020, an updated reporting guideline for systematic reviews and meta-analyses.

Safety and tolerability of natural and synthetic cannabinoids in adults aged over 50 years: A systematic review and meta-analysis

Lun, 29/03/2021 - 16:00

by Latha Velayudhan, Katie McGoohan, Sagnik Bhattacharyya

Background

Cannabinoid-based medicines (CBMs) are being used widely in the elderly. However, their safety and tolerability in older adults remains unclear. We aimed to conduct a systematic review and meta-analysis of safety and tolerability of CBMs in adults of age ≥50 years.

Methods and findings

A systematic search was performed using MEDLINE, PubMed, EMBASE, CINAHL PsychInfo, Cochrane Library, and ClinicalTrials.gov (1 January 1990 to 3 October 2020). Randomised clinical trials (RCTs) of CBMs in those with mean age of ≥50 years for all indications, evaluating the safety/tolerability of CBMs where adverse events have been quantified, were included. Study quality was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers conducted all review stages independently. Where possible, data were pooled using random-effects meta-analysis. Effect sizes were calculated as incident rate ratio (IRR) for outcome data such as adverse events (AEs), serious AEs (SAEs), and death and risk ratio (RR) for withdrawal from study and reported separately for studies using tetrahydrocannabinol (THC), THC:cannabidiol (CBD) combination, and CBD. A total of 46 RCTs were identified as suitable for inclusion of which 31 (67%) were conducted in the United Kingdom and Europe. There were 6,216 patients (mean age 58.6 ± 7.5 years; 51% male) included in the analysis, with 3,469 receiving CBMs. Compared with controls, delta-9-tetrahydrocannabinol (THC)-containing CBMs significantly increased the incidence of all-cause and treatment-related AEs: THC alone (IRR: 1.42 [95% CI, 1.12 to 1.78]) and (IRR: 1.60 [95% CI, 1.26 to 2.04]); THC:CBD combination (IRR: 1.58 [95% CI,1.26 to 1.98]) and (IRR: 1.70 [95% CI,1.24 to 2.33]), respectively. IRRs of SAEs and deaths were not significantly greater under CBMs containing THC with or without CBD. THC:CBD combination (RR: 1.40 [95% CI, 1.08 to 1.80]) but not THC alone (RR: 1.18 [95% CI, 0.89 to 1.57]) significantly increased risk of AE-related withdrawals. CBD alone did not increase the incidence of all-cause AEs (IRR: 1.02 [95% CI, 0.90 to 1.16]) or other outcomes as per qualitative synthesis. AE-related withdrawals were significantly associated with THC dose in THC only [QM (df = 1) = 4.696, p = 0.03] and THC:CBD combination treatment ([QM (df = 1) = 4.554, p = 0.033]. THC-containing CBMs significantly increased incidence of dry mouth, dizziness/light-headedness, and somnolence/drowsiness. Study limitations include inability to fully exclude data from those <50 years of age in our primary analyses as well as limitations related to weaknesses in the included trials particularly incomplete reporting of outcomes and heterogeneity in included studies.

Conclusions

This pooled analysis, using data from RCTs with mean participant age ≥50 years, suggests that although THC-containing CBMs are associated with side effects, CBMs in general are safe and acceptable in older adults. However, THC:CBD combinations may be less acceptable in the dose ranges used and their tolerability may be different in adults over 65 or 75 years of age.

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis

Lun, 29/03/2021 - 16:00

by Jane E. Norman, John Norrie, Graeme MacLennan, David Cooper, Sonia Whyte, Sue Chowdhry, Sarah Cunningham-Burley, Xue W. Mei, Joel B. E. Smith, Andrew Shennan, Stephen C. Robson, Steven Thornton, Mark D. Kilby, Neil Marlow, Sarah J. Stock, Phillip R. Bennett, Jane Denton, on behalf of the STOPPIT-2 collaborative group

Background

Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.

Methods and findings

We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55–1.38], p = 0.54). The primary neonatal outcome—a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery—was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54–1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50–1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.

Conclusions

These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.

Trial registration

ISRCTN Registry ISRCTN 02235181.ClinicalTrials.gov NCT02235181.

Healthcare without borders: A cross-sectional study of immigrant and nonimmigrant children admitted to a large public sector hospital in the Gauteng Province of South Africa

Mar, 23/03/2021 - 16:00

by Gerhard H. Janse van Rensburg, Ute Dagmar Feucht, Jennifer Makin, Nanya le Clus, Theunis Avenant

Background

Human migration is a worldwide phenomenon that receives considerable attention from the media and healthcare authorities alike. A significant proportion of children seen at public sector health facilities in South Africa (SA) are immigrants, and gaps have previously been noted in their healthcare provision.The objective of the study was to describe the characteristics and differences between the immigrant and SA children admitted to Kalafong Provincial Tertiary Hospital (KPTH), a large public sector hospital in the urban Gauteng Province of SA.

Methods and findings

A cross-sectional study was conducted over a 4-month period during 2016 to 2017. Information was obtained through a structured questionnaire and health record review. The enrolled study participants included 508 children divided into 2 groups, namely 271 general paediatric patients and 237 neonates. Twenty-five percent of children in the neonatal group and 22.5% in the general paediatric group were immigrants. The parents/caregivers of the immigrant group had a lower educational level (p < 0.0001 neonatal and paediatric), lower income (neonatal p < 0.001; paediatric p = 0.024), difficulty communicating in English (p < 0.001 neonatal and paediatric), and were more likely residing in informal settlements (neonatal p = 0.001; paediatric p = 0.007) compared to the SA group. In the neonatal group, there was no difference in the number of antenatal care (ANC) visits, type of delivery, gestational age, and birth weight. In the general paediatric group, there was no difference in immunisation and vitamin A supplementation coverage, but when comparing growth, the immigrant group had more malnutrition compared to the SA group (p = 0.029 for wasting). There was no difference in the prevalence of maternal human immunodeficiency virus (HIV) infection, with equally good prevention of mother-to-child transmission (PMTCT) coverage. There was also no difference in reported difficulties by immigrants in terms of access to healthcare (neonatal p = 0.379; paediatric p = 0.246), although a large proportion (10%) of the neonates of immigrant mothers were born outside a medical facility.

Conclusions

Although there were health-related differences between immigrant and SA children accessing in-hospital care, these were fewer than expected. Differences were found in parental educational level and socioeconomic factors, but these did not significantly affect ANC attendance, delivery outcomes, immunisation coverage, HIV prevalence, or PMTCT coverage. The immigrant population should be viewed as a high-risk group, with potential problems including suboptimal child growth. Health workers should advocate for all children in the community they are serving and promote tolerance, respect, and equal healthcare access.

Association of genetic liability to smoking initiation with e-cigarette use in young adults: A cohort study

Gio, 18/03/2021 - 16:00

by Jasmine N. Khouja, Robyn E. Wootton, Amy E. Taylor, George Davey Smith, Marcus R. Munafò

Background

Tobacco smoking and e-cigarette use are strongly associated, but it is currently unclear whether this association is causal, or due to shared factors that influence both behaviours such as a shared genetic liability. The aim of this study was to investigate whether polygenic risk scores (PRS) for smoking initiation are associated with ever use of e-cigarettes.

Methods and findings

Smoking initiation PRS were calculated for young adults (N = 7,859, mean age = 24 years, 51% male) of European ancestry in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort study initiated in 1991. PRS were calculated using the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5 × 10−8 to 0.5 were used to calculate 5 PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and the main outcome, self-reported e-cigarette use (n = 2,894, measured between 2016 and 2017), as well as self-reported smoking initiation and 8 negative control outcomes (socioeconomic position at birth, externalising disorders in childhood, and risk-taking in young adulthood). A total of 878 young adults (30%) had ever used e-cigarettes at 24 years, and 150 (5%) were regular e-cigarette users at 24 years. We observed positive associations of similar magnitude between smoking initiation PRS (created using the p < 5 × 10−8 threshold) and both smoking initiation (odds ratio (OR) = 1.29, 95% CI 1.19 to 1.39, p < 0.001) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34, p < 0.001) by the age of 24 years, indicating that a genetic predisposition to smoking initiation is associated with an increased risk of using e-cigarettes. At lower p-value thresholds, we observed an association between smoking initiation PRS and ever e-cigarette use among never smokers. We also found evidence of associations between smoking initiation PRS and some negative control outcomes, particularly when less stringent p-value thresholds were used to create the PRS, but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth). However, this study is limited by the relatively small sample size and potential for collider bias.

Conclusions

Our results indicate that there may be a shared genetic aetiology between smoking and e-cigarette use, and also with socioeconomic position, externalising disorders in childhood, and risky behaviour more generally. This indicates that there may be a common genetic vulnerability to both smoking and e-cigarette use, which may reflect a broad risk-taking phenotype.

The “gateway” effect of e-cigarettes may be explained by a genetic liability to risk-taking

Gio, 18/03/2021 - 16:00

by Wayne Hall, Gary Chan

Wayne Hall and Gary Chan discuss Jasmine Khouja and co-workers’ accompanying study on genetic susceptibility to tobacco smoking initiation and e-cigarette use.

The potential shared role of inflammation in insulin resistance and schizophrenia: A bidirectional two-sample mendelian randomization study

Ven, 12/03/2021 - 16:00

by Benjamin I. Perry, Stephen Burgess, Hannah J. Jones, Stan Zammit, Rachel Upthegrove, Amy M. Mason, Felix R. Day, Claudia Langenberg, Nicholas J. Wareham, Peter B. Jones, Golam M. Khandaker

Background

Insulin resistance predisposes to cardiometabolic disorders, which are commonly comorbid with schizophrenia and are key contributors to the significant excess mortality in schizophrenia. Mechanisms for the comorbidity remain unclear, but observational studies have implicated inflammation in both schizophrenia and cardiometabolic disorders separately. We aimed to examine whether there is genetic evidence that insulin resistance and 7 related cardiometabolic traits may be causally associated with schizophrenia, and whether evidence supports inflammation as a common mechanism for cardiometabolic disorders and schizophrenia.

Methods and findings

We used summary data from genome-wide association studies of mostly European adults from large consortia (Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) featuring up to 108,557 participants; Diabetes Genetics Replication And Meta-analysis (DIAGRAM) featuring up to 435,387 participants; Global Lipids Genetics Consortium (GLGC) featuring up to 173,082 participants; Genetic Investigation of Anthropometric Traits (GIANT) featuring up to 339,224 participants; Psychiatric Genomics Consortium (PGC) featuring up to 105,318 participants; and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium featuring up to 204,402 participants). We conducted two-sample uni- and multivariable mendelian randomization (MR) analysis to test whether (i) 10 cardiometabolic traits (fasting insulin, high-density lipoprotein and triglycerides representing an insulin resistance phenotype, and 7 related cardiometabolic traits: low-density lipoprotein, fasting plasma glucose, glycated haemoglobin, leptin, body mass index, glucose tolerance, and type 2 diabetes) could be causally associated with schizophrenia; and (ii) inflammation could be a shared mechanism for these phenotypes. We conducted a detailed set of sensitivity analyses to test the assumptions for a valid MR analysis. We did not find statistically significant evidence in support of a causal relationship between cardiometabolic traits and schizophrenia, or vice versa. However, we report that a genetically predicted inflammation-related insulin resistance phenotype (raised fasting insulin (raised fasting insulin (Wald ratio OR = 2.95, 95% C.I, 1.38–6.34, Holm-Bonferroni corrected p-value (p) = 0.035) and lower high-density lipoprotein (Wald ratio OR = 0.55, 95% C.I., 0.36–0.84; p = 0.035)) was associated with schizophrenia. Evidence for these associations attenuated to the null in multivariable MR analyses after adjusting for C-reactive protein, an archetypal inflammatory marker: (fasting insulin Wald ratio OR = 1.02, 95% C.I, 0.37–2.78, p = 0.975), high-density lipoprotein (Wald ratio OR = 1.00, 95% C.I., 0.85–1.16; p = 0.849), suggesting that the associations could be fully explained by inflammation. One potential limitation of the study is that the full range of gene products from the genetic variants we used as proxies for the exposures is unknown, and so we are unable to comment on potential biological mechanisms of association other than inflammation, which may also be relevant.

Conclusions

Our findings support a role for inflammation as a common cause for insulin resistance and schizophrenia, which may at least partly explain why the traits commonly co-occur in clinical practice. Inflammation and immune pathways may represent novel therapeutic targets for the prevention or treatment of schizophrenia and comorbid insulin resistance. Future work is needed to understand how inflammation may contribute to the risk of schizophrenia and insulin resistance.

How will COVID-19 transform global health post-pandemic? Defining research and investment opportunities and priorities

Gio, 11/03/2021 - 16:00

by Michael Reid, Quarraisha Abdool-Karim, Elvin Geng, Eric Goosby

Michael Reid and co-authors introduce a Collection on the global health in the post-COVID-19 era.

Parental death in childhood and pathways to increased mortality across the life course in Stockholm, Sweden: A cohort study

Gio, 11/03/2021 - 16:00

by Ayako Hiyoshi, Lisa Berg, Alessandra Grotta, Ylva Almquist, Mikael Rostila

Background

Previous studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63.

Methods and findings

A cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality.Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p-value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study.

Conclusions

Our findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality.

Factors associated with suicide risk among Chinese adults: A prospective cohort study of 0.5 million individuals

Gio, 11/03/2021 - 16:00

by Rongqin Yu, Yiping Chen, Liming Li, Junshi Chen, Yu Guo, Zheng Bian, Jun Lv, Canqing Yu, Xianmin Xie, Dan Huang, Zhengming Chen, Seena Fazel

Background

Suicide is a leading cause of death in China and accounts for about one-sixth of all suicides worldwide. The objective of this study was to examine the recent distribution of suicide and risk factors for death by suicide. Identifying underlying risk factors could benefit development of evidence-based prevention and intervention programs.

Methods and findings

We conducted a prospective study, the China Kadoorie Biobank, of 512,715 individuals (41% men, mean age 52 years) from 10 (5 urban, 5 rural) areas which are diverse across China in geographic locations, social economic developmental stages, and prevalence of disease patterns. After the baseline measurements of risk factors during 2004 to 2008, participants were followed up for suicide outcomes including suicide and possible suicide deaths. Risk factors, such as sociodemographic factors and physical and mental health status, were assessed by semistructured interviews and self-report questionnaires. Suicide and possible suicide deaths were identified through linkage to the local death registries using ICD-10 codes. We conducted Cox regression to calculate hazard ratios (HRs) for suicide and for possible suicide in sensitivity analyses.During an average follow-up period of 9.9 years, 520 (101 per 100,000) people died from suicide (51.3% male), and 79.8% of them lived in rural areas. Sociodemographic factors associated with increased suicide risk were male gender (adjusted hazard ratios [aHR] = 1.6 [95% CI 1.4 to 2.0], p < 0.001), older age (1.3 [1.2 to 1.5] by each 10-yr increase, p < 0.001), rural residence (2.6 [2.1 to 3.3], p < 0.001), and single status (1.7 [1.4 to 2.2], p < 0.001). Increased hazards were found for family-related stressful life events (aHR = 1.8 [1.2 to 1.9], p < 0.001) and for major physical illnesses (1.5 [1.3 to 1.9], p < 0.001). There were strong associations of suicide with a history of lifetime mental disorders (aHR = 9.6 [5.9 to 15.6], p < 0.001) and lifetime schizophrenia-spectrum disorders (11.0 [7.1 to 17.0], p < 0.001). Links between suicide risk and depressive disorders (aHR = 2.6 [1.4 to 4.8], p = 0.002) and generalized anxiety disorders (2.6 [1.0 to 7.1], p = 0.056) in the last 12 months, and sleep disorders (1.4 [1.2 to 1.7], p < 0.001) in the past month were also found. All HRs were adjusted for sociodemographic factors including gender, age, residence, single status, education, and income. The associations with possible suicide deaths were mostly similar to those with suicide deaths, although there was no clear link between possible suicide deaths and psychiatric factors such as depression and generalized anxiety disorders. A limitation of the study is that there is likely underreporting of mental disorders due to the use of self-report information for some diagnostic categories.

Conclusions

In this study, we observed that a range of sociodemographic, lifestyle, stressful life events, physical, and mental health factors were associated with suicide in China. High-risk groups identified were elderly men in rural settings and individuals with mental disorders. These findings could form the basis of targeted approaches to reduce suicide mortality in China.

Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis

Gio, 11/03/2021 - 16:00

by Jane J. Kim, Kate T. Simms, James Killen, Megan A. Smith, Emily A. Burger, Stephen Sy, Catherine Regan, Karen Canfell

Background

A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines.

Methods and findings

We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages.

Conclusions

Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US.

Correction: Diagnostic performance of congestion score index evaluated from chest radiography for acute heart failure in the emergency department: A retrospective analysis from the PARADISE cohort

Ven, 05/03/2021 - 16:00

by Masatake Kobayashi, Amine Douair, Kevin Duarte, Déborah Jaeger, Gaetan Giacomin, Adrien Bassand, Victor Jeangeorges, Laure Abensur Vuillaume, Gregoire Preud’homme, Olivier Huttin, Faiez Zannad, Patrick Rossignol, Tahar Chouihed, Nicolas Girerd

Cardiometabolic risk factors for COVID-19 susceptibility and severity: A Mendelian randomization analysis

Gio, 04/03/2021 - 16:00

by Aaron Leong, Joanne B. Cole, Laura N. Brenner, James B. Meigs, Jose C. Florez, Josep M. Mercader

Background

Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses.

Methods and findings

We selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10−8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank: odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10−5; UK Biobank: odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10−5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null.

Conclusions

In this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.

Probabilistic seasonal dengue forecasting in Vietnam: A modelling study using superensembles

Gio, 04/03/2021 - 16:00

by Felipe J. Colón-González, Leonardo Soares Bastos, Barbara Hofmann, Alison Hopkin, Quillon Harpham, Tom Crocker, Rosanna Amato, Iacopo Ferrario, Francesca Moschini, Samuel James, Sajni Malde, Eleanor Ainscoe, Vu Sinh Nam, Dang Quang Tan, Nguyen Duc Khoa, Mark Harrison, Gina Tsarouchi, Darren Lumbroso, Oliver J. Brady, Rachel Lowe

Background

With enough advanced notice, dengue outbreaks can be mitigated. As a climate-sensitive disease, environmental conditions and past patterns of dengue can be used to make predictions about future outbreak risk. These predictions improve public health planning and decision-making to ultimately reduce the burden of disease. Past approaches to dengue forecasting have used seasonal climate forecasts, but the predictive ability of a system using different lead times in a year-round prediction system has been seldom explored. Moreover, the transition from theoretical to operational systems integrated with disease control activities is rare.

Methods and findings

We introduce an operational seasonal dengue forecasting system for Vietnam where Earth observations, seasonal climate forecasts, and lagged dengue cases are used to drive a superensemble of probabilistic dengue models to predict dengue risk up to 6 months ahead. Bayesian spatiotemporal models were fit to 19 years (2002–2020) of dengue data at the province level across Vietnam. A superensemble of these models then makes probabilistic predictions of dengue incidence at various future time points aligned with key Vietnamese decision and planning deadlines. We demonstrate that the superensemble generates more accurate predictions of dengue incidence than the individual models it incorporates across a suite of time horizons and transmission settings. Using historical data, the superensemble made slightly more accurate predictions (continuous rank probability score [CRPS] = 66.8, 95% CI 60.6–148.0) than a baseline model which forecasts the same incidence rate every month (CRPS = 79.4, 95% CI 78.5–80.5) at lead times of 1 to 3 months, albeit with larger uncertainty. The outbreak detection capability of the superensemble was considerably larger (69%) than that of the baseline model (54.5%). Predictions were most accurate in southern Vietnam, an area that experiences semi-regular seasonal dengue transmission. The system also demonstrated added value across multiple areas compared to previous practice of not using a forecast. We use the system to make a prospective prediction for dengue incidence in Vietnam for the period May to October 2020. Prospective predictions made with the superensemble were slightly more accurate (CRPS = 110, 95% CI 102–575) than those made with the baseline model (CRPS = 125, 95% CI 120–168) but had larger uncertainty. Finally, we propose a framework for the evaluation of probabilistic predictions. Despite the demonstrated value of our forecasting system, the approach is limited by the consistency of the dengue case data, as well as the lack of publicly available, continuous, and long-term data sets on mosquito control efforts and serotype-specific case data.

Conclusions

This study shows that by combining detailed Earth observation data, seasonal climate forecasts, and state-of-the-art models, dengue outbreaks can be predicted across a broad range of settings, with enough lead time to meaningfully inform dengue control. While our system omits some important variables not currently available at a subnational scale, the majority of past outbreaks could be predicted up to 3 months ahead. Over the next 2 years, the system will be prospectively evaluated and, if successful, potentially extended to other areas and other climate-sensitive disease systems.

Diagnostic accuracy of cervical cancer screening and screening–triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study

Gio, 04/03/2021 - 16:00

by Helen A. Kelly, Admire Chikandiwa, Bernard Sawadogo, Clare Gilham, Pamela Michelow, Olga Goumbri Lompo, Tanvier Omar, Souleymane Zan, Precious Magooa, Michel Segondy, Nicolas Nagot, Nicolas Meda, Sinead Delany-Moretlwe, Philippe Mayaud, for the HARP Study Group

Background

Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen–triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa.

Methods and findings

WLHIV aged 25–50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol’s iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%–52.7%) and CIN3+ (56.1%, 95% CI 43.3%–68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%–81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%–93.2%) for CIN2+ and 86.4% (95% CI 75.7%–93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%–58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%–76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%–86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28–2.32; CIN3+: 1.18, 95% CI 0.94–1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%–77.9%; CIN3+: 80.8%, 95% CI 67.5%–90.4%) and specificity (81.6%, 95% CI 77.6%–85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%–91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%–47.1%; relative specificity = 0.57, 95% CI 0.52–0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%–3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%–3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%–1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today.

Conclusions

In this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.

Applicability and cost-effectiveness of the Systolic Blood Pressure Intervention Trial (SPRINT) in the Chinese population: A cost-effectiveness modeling study

Gio, 04/03/2021 - 16:00

by Chao Li, Kangyu Chen, Victoria Cornelius, Ewan Tomeny, Yang Wang, Xiaowei Yang, Xiaodan Yuan, Rui Qin, Dahai Yu, Zhenqiang Wu, Duolao Wang, Tao Chen

Background

The Systolic Blood Pressure Intervention Trial (SPRINT) showed significant reductions in death and cardiovascular disease (CVD) risk with a systolic blood pressure (SBP) goal of <120 mm Hg compared with a SBP goal of <140 mm Hg. Our study aimed to assess the applicability of SPRINT to Chinese adults. Additionally, we sought to predict the medical and economic implications of this intensive SBP treatment among those meeting SPRINT eligibility.

Methods and findings

We used nationally representative baseline data from the China Health and Retirement Longitudinal Study (CHARLS) (2011–2012) to estimate the prevalence and number of Chinese adults aged 45 years and older who meet SPRINT criteria. A validated microsimulation model was employed to project costs, clinical outcomes, and quality-adjusted life-years (QALYs) among SPRINT-eligible adults, under 2 alternative treatment strategies (SBP goal of <120 mm Hg [intensive treatment] and SBP goal of <140 mm Hg [standard treatment]). Overall, 22.2% met the SPRINT criteria, representing 116.2 (95% CI 107.5 to 124.8) million people in China. Of these, 66.4%, representing 77.2 (95% CI 69.3 to 85.0) million, were not being treated for hypertension, and 22.9%, representing 26.6 (95% CI 22.4 to 30.7) million, had a SBP between 130 and 139 mm Hg, yet were not taking antihypertensive medication. We estimated that over 5 years, compared to standard treatment, intensive treatment would reduce heart failure incidence by 0.84 (95% CI 0.42 to 1.25) million cases, reduce CVD deaths by 2.03 (95% CI 1.44 to 2.63) million cases, and save 3.84 (95% CI 1.53 to 6.34) million life-years. Estimated reductions of 0.069 (95% CI −0.28, 0.42) million myocardial infarction cases and 0.36 (95% CI −0.10, 0.82) million stroke cases were not statistically significant. Furthermore, over a lifetime, moving from standard to intensive treatment increased the mean QALYs from 9.51 to 9.87 (an increment of 0.38 [95% CI 0.13 to 0.71]), at a cost of Int$10,997 per QALY gained. Of all 1-way sensitivity analyses, high antihypertensive drug cost and lower treatment efficacy for CVD death resulted in the 2 most unfavorable results (Int$25,291 and Int$18,995 per QALY were gained, respectively). Simulation results indicated that intensive treatment could be cost-effective (82.8% probability of being below the willingness-to-pay threshold of Int$16,782 [1× GDP per capita in China in 2017]), with a lower probability in people with SBP 130–139 mm Hg (72.9%) but a higher probability among females (91.2%). Main limitations include lack of specific SPRINT eligibility information in the CHARLS survey, uncertainty about the implications of different blood pressure measurement techniques, the use of several sources of data with large reliance on findings from SPPRINT, limited information about the serious adverse event rate, and lack of information and evidence for medication effectiveness on renal disease.

Conclusions

Although adoption of the SPRINT treatment strategy would increase the number of Chinese adults requiring SBP treatment intensification, this approach has the potential to prevent CVD events, to produce gains in life-years, and to be cost-effective under common thresholds.