PLoS Medicine

Condividi contenuti PLOS Medicine: New Articles
A Peer-Reviewed Open-Access Journal
Aggiornato: 3 ore 43 sec fa

Potential gains in life expectancy by attaining daily ambient fine particulate matter pollution standards in mainland China: A modeling study based on nationwide data

Ven, 17/01/2020 - 23:00

by Jinlei Qi, Zengliang Ruan, Zhengmin (Min) Qian, Peng Yin, Yin Yang, Bipin Kumar Acharya, Lijun Wang, Hualiang Lin

Background

Ambient fine particulate matter pollution (PM2.5) is one leading cause of disease burden, but no study has quantified the association between daily PM2.5 exposure and life expectancy. We aimed to assess the potential benefits in life expectancy by attaining the daily PM2.5 standards in 72 cities of China during 2013–2016.

Methods and findings

We applied a two-stage approach for the analysis. At the first stage, we used a generalized additive model (GAM) with a Gaussian link to examine the city-specific short-term association between daily PM2.5 and years of life lost (YLL); at the second stage, a random-effects meta-analysis was used to generate the regional and national estimations. We further estimated the potential gains in life expectancy (PGLE) by assuming that ambient PM2.5 has met the Chinese National Ambient Air Quality Standard (NAAQS, 75 μg/m3) or the ambient air quality guideline (AQG) of the World Health Organization (WHO) (25 μg/m3). We also calculated the attributable fraction (AF), which denoted the proportion of YLL attributable to a higher-than-standards daily mean PM2.5 concentration. During the period from January 18, 2013 to December 31, 2016, we recorded 1,226,849 nonaccidental deaths in the study area. We observed significant associations between daily PM2.5 and YLL: each 10 μg/m3 increase in three-day–averaged (lag02) PM2.5 concentrations corresponded to an increment of 0.43 years of life lost (95% CI: 0.29–0.57). We estimated that 168,065.18 (95% CI: 114,144.91–221,985.45) and 68,684.95 (95% CI: 46,648.79–90,721.11) years of life lost can be avoided by achieving WHO’s AQG and Chinese NAAQS in the study area, which corresponded to 0.14 (95% CI: 0.09–0.18) and 0.06 (95% CI: 0.04–0.07) years of gain in life expectancy for each death in these cities. We observed differential regional estimates across the 7 regions, with the highest gains in the Northwest region (0.28 years of gain [95% CI: 0.06–0.49]) and the lowest in the North region (0.08 [95% CI: 0.02–0.15]). Furthermore, using WHO’s AQG and Chinese NAAQS as the references, we estimated that 1.00% (95% CI: 0.68%–1.32%) and 0.41% (95% CI: 0.28%–0.54%) of YLL could be attributable to the PM2.5 exposure at the national level. Findings from this study were mainly limited by the unavailability of data on individual PM2.5 exposure.

Conclusions

This study indicates that significantly longer life expectancy could be achieved by a reduction in the ambient PM2.5 concentrations. It also highlights the need to formulate a stricter ambient PM2.5 standard at both national and regional levels of China to protect the population’s health.

Projected costs of single-payer healthcare financing in the United States: A systematic review of economic analyses

Mer, 15/01/2020 - 23:00

by Christopher Cai, Jackson Runte, Isabel Ostrer, Kacey Berry, Ninez Ponce, Michael Rodriguez, Stefano Bertozzi, Justin S. White, James G. Kahn

Background

The United States is the only high-income nation without universal, government-funded or -mandated health insurance employing a unified payment system. The US multi-payer system leaves residents uninsured or underinsured, despite overall healthcare costs far above other nations. Single-payer (often referred to as Medicare for All), a proposed policy solution since 1990, is receiving renewed press attention and popular support. Our review seeks to assess the projected cost impact of a single-payer approach.

Methods and findings

We conducted our literature search between June 1 and December 31, 2018, without start date restriction for included studies. We surveyed an expert panel and searched PubMed, Google, Google Scholar, and preexisting lists for formal economic studies of the projected costs of single-payer plans for the US or for individual states. Reviewer pairs extracted data on methods and findings using a template. We quantified changes in total costs standardized to percentage of contemporaneous healthcare spending. Additionally, we quantified cost changes by subtype, such as costs due to increased healthcare utilization and savings due to simplified payment administration, lower drug costs, and other factors. We further examined how modeling assumptions affected results. Our search yielded economic analyses of the cost of 22 single-payer plans over the past 30 years. Exclusions were due to inadequate technical data or assuming a substantial ongoing role for private insurers. We found that 19 (86%) of the analyses predicted net savings (median net result was a savings of 3.46% of total costs) in the first year of program operation and 20 (91%) predicted savings over several years; anticipated growth rates would result in long-term net savings for all plans. The largest source of savings was simplified payment administration (median 8.8%), and the best predictors of net savings were the magnitude of utilization increase, and savings on administration and drug costs (R2 of 0.035, 0.43, and 0.62, respectively). Only drug cost savings remained significant in multivariate analysis. Included studies were heterogeneous in methods, which precluded us from conducting a formal meta-analysis.

Conclusions

In this systematic review, we found a high degree of analytic consensus for the fiscal feasibility of a single-payer approach in the US. Actual costs will depend on plan features and implementation. Future research should refine estimates of the effects of coverage expansion on utilization, evaluate provider administrative costs in varied existing single-payer systems, analyze implementation options, and evaluate US-based single-payer programs, as available.

Infectious disease pandemic planning and response: Incorporating decision analysis

Gio, 09/01/2020 - 23:00

by Freya M. Shearer, Robert Moss, Jodie McVernon, Joshua V. Ross, James M. McCaw

Freya Shearer and co-authors discuss the use of decision analysis in planning for infectious disease pandemics.

The association of depression with subsequent dementia diagnosis: A Swedish nationwide cohort study from 1964 to 2016

Gio, 09/01/2020 - 23:00

by Sofie Holmquist, Anna Nordström, Peter Nordström

Background

Depression is associated with an increased risk of dementia. However, short follow-up times and lack of adjustment for familial factors in previous studies could influence this association. The purpose of the present study was to investigate the association between depression and subsequent dementia, while controlling for familial factors and with a follow-up of over 35 years.

Methods and findings

Two cohorts were formed from all individuals aged 50 years or older living in Sweden as of 31 December 2005 (n = 3,341,010). The Swedish National Patient Register was searched from 1964 through 2016 to identify diagnosis of depression and dementia. In the first cohort, individuals diagnosed with depression (n = 119,386) were matched 1:1 with controls without depression diagnosis. The second cohort was a sibling cohort (n = 50,644) consisting of same-sex full sibling pairs with discordant depression status. In the population matched cohort study, a total of 9,802 individuals were diagnosed with dementia during a mean follow-up time of 10.41 (range 0–35) years (5.5% of those diagnosed with depression and 2.6% of those without depression diagnosis (adjusted odds ratio [aOR] 2.47, 95% CI 2.35–2.58; p < 0.001), with a stronger association for vascular dementia (aOR 2.68, 95% CI 2.44–2.95; p < 0.001) than for Alzheimer disease (aOR 1.79, 95% CI 1.68–1.92; p < 0.001). The association with dementia diagnosis was strongest in the first 6 months after depression diagnosis (aOR 15.20, 95% CI 11.85–19.50; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 1.58, 95% CI 1.27–1.98; p < 0.001). Also in the sibling cohort, the association was strongest in the first 6 months (aOR 20.85, 95% CI 9.63–45.12; p < 0.001), then decreased rapidly but persisted over follow-up of more than 20 years (aOR 2.33, 95% CI 1.32–4.11; p < 0.001). The adjusted models included sex, age at baseline, citizenship, civil status, household income, and diagnoses at baseline. The main limitation of the study methodology is the use of observational data; hence, the associations found are not proof of causal effects.

Conclusions

Depression is associated with increased odds of dementia, even more than 20 years after diagnosis of depression, and the association remains after adjustment for familial factors. Further research is needed to investigate whether successful prevention and treatment of depression decrease the risk of dementia.

Association of puberty timing with type 2 diabetes: A systematic review and meta-analysis

Lun, 06/01/2020 - 23:00

by Tuck Seng Cheng, Felix R. Day, Rajalakshmi Lakshman, Ken K. Ong

Background

Emerging studies have investigated the association between puberty timing, particularly age at menarche (AAM), and type 2 diabetes. However, whether this association is independent of adiposity is unclear. We aimed to systematically review published evidence on the association between puberty timing and type 2 diabetes (T2D) or impaired glucose tolerance (IGT), with and without adjustment for adiposity, and to estimate the potential contribution of puberty timing to the burden of T2D in the United Kingdom (UK).

Methods and findings

We searched PubMed, Medline, and Embase databases for publications until February 2019 on the timing of any secondary sexual characteristic in boys or girls in relation to T2D/IGT. Inverse-variance-weighted random-effects meta-analysis was used to pool reported estimates, and meta-regression was used to explore sources of heterogeneity. Twenty-eight observational studies were identified. All assessed AAM in women (combined N = 1,228,306); only 1 study additionally included men. In models without adjustment for adult adiposity, T2D/IGT risk was lower per year later AAM (relative risk [RR] = 0.91, 95% CI 0.89–0.93, p < 0.001, 11 estimates, n = 833,529, I2 = 85.4%) and higher for early versus later menarche (RR = 1.39, 95% CI 1.25–1.55, p < 0.001, 23 estimates, n = 1,185,444, I2 = 87.8%). Associations were weaker but still evident in models adjusted for adiposity (AAM: RR = 0.97 per year, 95% CI 0.95–0.98, p < 0.001, 12 estimates, n = 852,268, I2 = 51.8%; early menarche: RR = 1.19, 95% CI 1.11–1.28, p < 0.001, 21 estimates, n = 890,583, I2 = 68.1%). Associations were stronger among white than Asian women, and in populations with earlier average AAM. The estimated population attributable risk of T2D in white UK women due to early menarche unadjusted and adjusted for adiposity was 12.6% (95% CI 11.0–14.3) and 5.1% (95% CI 3.6–6.7), respectively. Findings in this study are limited by residual and unmeasured confounding, and self-reported AAM.

Conclusions

Earlier AAM is consistently associated with higher T2D/IGT risk, independent of adiposity. More importantly, this research has identified that a substantial proportion of T2D in women is related to early menarche, which would be expected to increase in light of global secular trends towards earlier puberty timing. These findings highlight the need to identify the underlying mechanisms linking early menarche to T2D/IGT risk.

Effectiveness of a scalable group-based education and monitoring program, delivered by health workers, to improve control of hypertension in rural India: A cluster randomised controlled trial

Gio, 02/01/2020 - 23:00

by Dilan Giguruwa Gamage, Michaela A. Riddell, Rohina Joshi, Kavumpurathu R. Thankappan, Clara K. Chow, Brian Oldenburg, Roger G. Evans, Ajay S. Mahal, Kartik Kalyanram, Kamakshi Kartik, Oduru Suresh, Nihal Thomas, Gomathyamma K. Mini, Pallab K. Maulik, Velandai K. Srikanth, Simin Arabshahi, Ravi P. Varma, Rama K. Guggilla, Fabrizio D’Esposito, Thirunavukkarasu Sathish, Mohammed Alim, Amanda G. Thrift

Background

New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)–led group-based education and monitoring intervention would improve control of blood pressure (BP).

Methods and findings

We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP ≥ 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2–2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (−5.0 mm Hg, 95% CI −7.1 to −3.0; P < 0.001) and a greater decline in diastolic BP (−2.1 mm Hg, 95% CI −3.6 to −0.6; P < 0.006), but no detectable difference in the use of BP-lowering medications between groups (OR 1.2, 95% CI 0.8–1.9; P = 0.34). Similar results were found when using imputation analyses that included those lost to follow-up. Limitations include a relatively short follow-up period and use of outcome assessors who were not blinded to the group allocation.

Conclusions

While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally.

Trial registration

The trial was registered with the Clinical Trials Registry-India (CTRI/2016/02/006678).

Personalized public health: An implementation research agenda for the HIV response and beyond

Mar, 31/12/2019 - 23:00

by Elvin H. Geng, Charles B. Holmes, Mosa Moshabela, Izukanji Sikazwe, Maya L. Petersen

Ambient particulate matter pollution and adult hospital admissions for pneumonia in urban China: A national time series analysis for 2014 through 2017

Mar, 31/12/2019 - 23:00

by Yaohua Tian, Hui Liu, Yiqun Wu, Yaqin Si, Man Li, Yao Wu, Xiaowen Wang, Mengying Wang, Libo Chen, Chen Wei, Tao Wu, Pei Gao, Yonghua Hu

Background

The effects of ambient particulate matter (PM) pollution on pneumonia in adults are inconclusive, and few scientific data on a national scale have been generated in low- or middle-income countries, despite their much higher PM concentrations. We aimed to examine the association between PM levels and hospital admissions for pneumonia in Chinese adults.

Methods and findings

A nationwide time series study was conducted in China between 2014 and 2017. Information on daily hospital admissions for pneumonia for 2014–2017 was collected from the database of Urban Employee Basic Medical Insurance (UEBMI), which covers 282.93 million adults. Associations of PM concentrations and hospital admissions for pneumonia were estimated for each city using a quasi-Poisson regression model controlling for time trend, temperature, relative humidity, day of the week, and public holiday and then pooled by random-effects meta-analysis. Meta-regression models were used to investigate potential effect modifiers, including cities’ annual-average air pollutants concentrations, temperature, relative humidity, gross domestic product (GDP) per capita, and coverage rates by the UEBMI. More than 4.2 million pneumonia admissions were identified in 184 Chinese cities during the study period. Short-term elevations in PM concentrations were associated with increased pneumonia admissions. At the national level, a 10-μg/m3 increase in 3-day moving average (lag 0–2) concentrations of PM2.5 (PM ≤2.5 μm in aerodynamic diameter) and PM10 (PM ≤10 μm in aerodynamic diameter) was associated with 0.31% (95% confidence interval [CI] 0.15%–0.46%, P < 0.001) and 0.19% (0.11%–0.30%, P < 0.001) increases in hospital admissions for pneumonia, respectively. The effects of PM10 were stronger in cities with higher temperatures (percentage increase, 0.031%; 95% CI 0.003%–0.058%; P = 0.026) and relative humidity (percentage increase, 0.011%; 95% CI 0%–0.022%; P = 0.045), as well as in the elderly (percentage increase, 0.10% [95% CI 0.02%–0.19%] for people aged 18–64 years versus 0.32% [95% CI 0.22%–0.39%] for people aged ≥75 years; P < 0.001). The main limitation of the present study was the unavailability of data on individual exposure to PM pollution.

Conclusions

Our findings suggest that there are significant short-term associations between ambient PM levels and increased hospital admissions for pneumonia in Chinese adults. These findings support the rationale that further limiting PM concentrations in China may be an effective strategy to reduce pneumonia-related hospital admissions.

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer: A retrospective cohort study

Mar, 31/12/2019 - 23:00

by Ewan Gray, Joachim Marti, Jeremy C. Wyatt, David H. Brewster, Peter S. Hall, SATURNE advisory group

Background

Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data—real world data (RWD)—and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups.

Methods and findings

Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001–2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64–0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51–0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding.

Conclusions

The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.

Opioid-related treatment, interventions, and outcomes among incarcerated persons: A systematic review

Mar, 31/12/2019 - 23:00

by Monica Malta, Thepikaa Varatharajan, Cayley Russell, Michelle Pang, Sarah Bonato, Benedikt Fischer

Background

Worldwide opioid-related overdose has become a major public health crisis. People with opioid use disorder (OUD) are overrepresented in the criminal justice system and at higher risk for opioid-related mortality. However, correctional facilities frequently adopt an abstinence-only approach, seldom offering the gold standard opioid agonist treatment (OAT) to incarcerated persons with OUD. In an attempt to inform adequate management of OUD among incarcerated persons, we conducted a systematic review of opioid-related interventions delivered before, during, and after incarceration.

Methods and findings

We systematically reviewed 8 electronic databases for original, peer-reviewed literature published between January 2008 and October 2019. Our review included studies conducted among adult participants with OUD who were incarcerated or recently released into the community (≤90 days post-incarceration). The search identified 2,356 articles, 46 of which met the inclusion criteria based on assessments by 2 independent reviewers. Thirty studies were conducted in North America, 9 in Europe, and 7 in Asia/Oceania. The systematic review included 22 randomized control trials (RCTs), 3 non-randomized clinical trials, and 21 observational studies. Eight observational studies utilized administrative data and included large sample sizes (median of 10,419 [range 2273–131,472] participants), and 13 observational studies utilized primary data, with a median of 140 (range 27–960) participants. RCTs and non-randomized clinical trials included a median of 198 (range 15–1,557) and 44 (range 27–382) participants, respectively. Twelve studies included only men, 1 study included only women, and in the remaining 33 studies, the percentage of women was below 30%. The majority of study participants were middle-aged adults (36–55 years). Participants treated at a correctional facility with methadone maintenance treatment (MMT) or buprenorphine (BPN)/naloxone (NLX) had lower rates of illicit opioid use, had higher adherence to OUD treatment, were less likely to be re-incarcerated, and were more likely to be working 1 year post-incarceration. Participants who received MMT or BPN/NLX while incarcerated had fewer nonfatal overdoses and lower mortality. The main limitation of our systematic review is the high heterogeneity of studies (different designs, settings, populations, treatments, and outcomes), precluding a meta-analysis. Other study limitations include the insufficient data about incarcerated women with OUD, and the lack of information about incarcerated populations with OUD who are not included in published research.

Conclusions

In this carefully conducted systematic review, we found that correctional facilities should scale up OAT among incarcerated persons with OUD. The strategy is likely to decrease opioid-related overdose and mortality, reduce opioid use and other risky behaviors during and after incarceration, and improve retention in addiction treatment after prison release. Immediate OAT after prison release and additional preventive strategies such as the distribution of NLX kits to at-risk individuals upon release greatly decrease the occurrence of opioid-related overdose and mortality. In an effort to mitigate the impact of the opioid-related overdose crisis, it is crucial to scale up OAT and opioid-related overdose prevention strategies (e.g., NLX) within a continuum of treatment before, during, and after incarceration.

Variability in the use of pulse oximeters with children in Kenyan hospitals: A mixed-methods analysis

Mar, 31/12/2019 - 23:00

by Abigail J. Enoch, Mike English, the Clinical Information Network , Gerald McGivern, Sasha Shepperd

Background

Pulse oximetry, a relatively inexpensive technology, has the potential to improve health outcomes by reducing incorrect diagnoses and supporting appropriate treatment decisions. There is evidence that in low- and middle-income countries, even when available, widespread uptake of pulse oximeters has not occurred, and little research has examined why. We sought to determine when and with which children pulse oximeters are used in Kenyan hospitals, how pulse oximeter use impacts treatment provision, and the barriers to pulse oximeter use.

Methods and findings

We analyzed admissions data recorded through Kenya’s Clinical Information Network (CIN) between September 2013 and February 2016. We carried out multiple imputation and generated multivariable regression models in R. We also conducted interviews with 30 healthcare workers and staff from 14 Kenyan hospitals to examine pulse oximetry adoption. We adapted the Integrative Model of Behavioural Prediction to link the results from the multivariable regression analyses to the qualitative findings. We included 27,906 child admissions from 7 hospitals in the quantitative analyses. The median age of the children was 1 year, and 55% were male. Three-quarters had a fever, over half had a cough; other symptoms/signs were difficulty breathing (34%), difficulty feeding (34%), and indrawing (32%). The most common diagnoses were pneumonia, diarrhea, and malaria: 45%, 35%, and 28% of children, respectively, had these diagnoses. Half of the children obtained a pulse oximeter reading, and of these, 10% had an oxygen saturation level below 90%. Children were more likely to receive a pulse oximeter reading if they were not alert (odds ratio [OR]: 1.30, 95% confidence interval (CI): 1.09, 1.55, p = 0.003), had chest indrawing (OR: 1.28, 95% CI: 1.17, 1.40, p < 0.001), or a very high respiratory rate (OR: 1.27, 95% CI: 1.13, 1.43, p < 0.001), as were children admitted to certain hospitals, at later time periods, and when a Paediatric Admission Record (PAR) was used (OR PAR used compared with PAR not present: 2.41, 95% CI: 1.98, 2.94, p < 0.001). Children were more likely to be prescribed oxygen if a pulse oximeter reading was obtained (OR: 1.42, 95% CI:1.25, 1.62, p < 0.001) and if this reading was below 90% (OR: 3.29, 95% CI: 2.82, 3.84, p < 0.001). The interviews indicated that the main barriers to pulse oximeter use are inadequate supply, broken pulse oximeters, and insufficient training on how, when, and why to use pulse oximeters and interpret their results. According to the interviews, variation in pulse oximeter use between hospitals is because of differences in pulse oximeter availability and the leadership of senior doctors in advocating for pulse oximeter use, whereas variation within hospitals over time is due to repair delays. Pulse oximeter use increased over time, likely because of the CIN’s feedback to hospitals. When pulse oximeters are used, they are sometimes used incorrectly and some healthcare workers lack confidence in readings that contradict clinical signs. The main limitations of the study are that children with high levels of missing data were not excluded, interview participants might not have been representative, and the interviews did not enable a detailed exploration of differences between counties or across senior management groups.

Conclusions

There remain major challenges to implementing pulse oximetry—a cheap, decades old technology—into routine care in Kenya. Implementation requires efficient and transparent procurement and repair systems to ensure adequate availability. Periodic training, structured clinical records that include prompts, the promotion of pulse oximetry by senior doctors, and monitoring and feedback might also support pulse oximeter use. Our findings can inform strategies to support the use of pulse oximeters to guide prompt and effective treatment, in line with the Sustainable Development Goals. Without effective implementation, the potential benefits of pulse oximeters and possible hospital cost-savings by targeting oxygen therapy might not be realized.

Association between gestational weight gain and severe adverse birth outcomes in Washington State, US: A population-based retrospective cohort study, 2004–2013

Lun, 30/12/2019 - 23:00

by U. Vivian Ukah, Hamideh Bayrampour, Yasser Sabr, Neda Razaz, Wee-Shian Chan, Kenneth I. Lim, Sarka Lisonkova

Background

Suboptimal weight gain during pregnancy is a potentially modifiable risk factor. We aimed to investigate the association between suboptimal gestational weight gain and severe adverse birth outcomes by pre-pregnancy body mass index (BMI) categories, including obesity class I to III.

Methods and findings

We conducted a population-based study of pregnant women with singleton hospital births in Washington State, US, between 2004 and 2013. Optimal, low, and excess weight gain in each BMI category was calculated based on weight gain by gestational age as recommended by the American College of Obstetricians and Gynecologists and the Institute of Medicine. Primary composite outcomes were (1) maternal death and/or severe maternal morbidity (SMM) and (2) perinatal death and/or severe neonatal morbidity. Logistic regression was used to obtain adjusted odds ratios (AORs) and 95% confidence intervals. Overall, 722,839 women with information on pre-pregnancy BMI were included. Of these, 3.1% of women were underweight, 48.1% had normal pre-pregnancy BMI, 25.8% were overweight, and 23.0% were obese. Only 31.5% of women achieved optimal gestational weight gain. Women who had low weight gain were more likely to be African American and have Medicaid health insurance, while women with excess weight gain were more likely to be non-Hispanic white and younger than women with optimal weight gain in each pre-pregnancy BMI category. Compared with women who had optimal weight gain, those with low gestational weight gain had a higher rate of maternal death, 7.97 versus 2.63 per 100,000 (p = 0.027). In addition, low weight gain was associated with the composite adverse maternal outcome (death/SMM) in women with normal pre-pregnancy BMI and in overweight women (AOR 1.12, 95% CI 1.04–1.21, p = 0.004, and AOR 1.17, 95% CI 1.04–1.32, p = 0.009, respectively) compared to women in the same pre-pregnancy BMI category who had optimal weight gain. Similarly, excess gestational weight gain was associated with increased rates of death/SMM among women with normal pre-pregnancy BMI (AOR 1.20, 95% CI 1.12–1.28, p < 0.001) and obese women (AOR 1.12, 95% CI 1.01–1.23, p = 0.019). Low gestational weight gain was associated with perinatal death and severe neonatal morbidity regardless of pre-pregnancy BMI, including obesity classes I, II, and III, while excess weight gain was associated with severe neonatal morbidity only in women who were underweight or had normal BMI prior to pregnancy. Study limitations include the ascertainment of pre-pregnancy BMI using self-report, and lack of data availability for the most recent years.

Conclusions

In this study, we found that most women do not achieve optimal weight gain during pregnancy. Low weight gain was associated with increased risk of severe adverse birth outcomes, and in particular with maternal death and perinatal death. Excess gestational weight gain was associated with severe adverse birth outcomes, except for women who were overweight prior to pregnancy. Weight gain recommendations for this group may need to be reassessed. It is important to counsel women during pregnancy about specific risks associated with both low and excess weight gain.

Adherence to the 2017 French dietary guidelines and adult weight gain: A cohort study

Lun, 30/12/2019 - 23:00

by Dan Chaltiel, Chantal Julia, Moufidath Adjibade, Mathilde Touvier, Serge Hercberg, Emmanuelle Kesse-Guyot

Background

The French dietary guidelines were updated in 2017, and an adherence score to the new guidelines (Programme National Nutrition Santé Guidelines Score 2 [PNNS-GS2]) has been developed and validated recently. Since overweight and obesity are key public health issues and have been related to major chronic conditions, this prospective study aimed to measure the association between PNNS-GS2 and risk of overweight and obesity, and to compare these results with those for the modified Programme National Nutrition Santé Guidelines Score (mPNNS-GS1), reflecting adherence to 2001 guidelines.

Methods and findings

Participants (N = 54,089) were recruited among French adults (≥18 years old, mean baseline age = 47.1 [SD 14.1] years, 78.3% women) in the NutriNet-Santé web-based cohort. Mean (SD) score was 1.7 (3.3) for PNNS-GS2 and 8.2 (1.6) for mPNNS-GS1. Selected participants were those included between 2009 and 2014 and followed up to September 2018 (median follow-up = 6 years). Collected data included at least three 24-hour dietary records over a 2-year period following inclusion, baseline sociodemographics, and anthropometric data over time. In Cox regression models, PNNS-GS2 was strongly and linearly associated with a lower risk of overweight and obesity (HR for quintile 5 versus quintile 1 [95% CI] = 0.48 [0.43–0.54], p < 0.001, and 0.47 [0.40–0.55], p < 0.001, for overweight and obesity, respectively). These results were much weaker for mPNNS-GS1 (HR for quintile 5 versus quintile 1 = 0.90 [0.80–0.99], p = 0.03, and 0.98 [0.84–1.15], p = 0.8, for overweight and obesity, respectively). In multilevel models, PNNS-GS2 was negatively associated with baseline BMI and BMI increase over time (β for a 1-SD increase in score [95% CI] = −0.040 [−0.041; −0.038], p < 0.001, and −0.00080 [−0.00094; −0.00066], p < 0.001, respectively). In “direct comparison” models, PNNS-GS2 was associated with a lower risk of overweight and obesity, lower baseline BMI, and lower BMI increase over time than mPNNS-GS1. Study limitations include possible selection bias, reliance on participant self-report, use of arbitrary cutoffs in data analyses, and residual confounding, but robustness was tested in sensitivity analyses.

Conclusions

Our findings suggest that adherence to the 2017 French dietary guidelines is associated with a lower risk of overweight and obesity. The magnitude of the association and the results of the direct comparison reinforced the validity of the updated recommendations.

Trial registration

The NutriNet-Santé Study ClinicalTrials.gov (NCT03335644)

Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries

Lun, 30/12/2019 - 23:00

by Julia M. Baker, Jacqueline E. Tate, Juan Leon, Michael J. Haber, Benjamin A. Lopman

Background

Despite the success of rotavirus vaccines over the last decade, rotavirus remains a leading cause of severe diarrheal disease among young children. Further progress in reducing the burden of disease is inhibited, in part, by vaccine underperformance in certain settings. Early trials suggested that oral poliovirus vaccine (OPV), when administered concomitantly with rotavirus vaccine, reduces rotavirus seroconversion rates after the first rotavirus dose with modest or nonsignificant interference after completion of the full rotavirus vaccine course. Our study aimed to identify a range of individual-level characteristics, including concomitant receipt of OPV, that affect rotavirus vaccine immunogenicity in high- and low-child-mortality settings, controlling for individual- and country-level factors. Our central hypothesis was that OPV administered concomitantly with rotavirus vaccine reduced rotavirus vaccine immunogenicity.

Methods and findings

Pooled, individual-level data from GlaxoSmithKline’s Phase II and III clinical trials of the monovalent rotavirus vaccine (RV1), Rotarix, were analyzed, including 7,280 vaccinated infants (5–17 weeks of age at first vaccine dose) from 22 trials and 33 countries/territories (5 countries/territories with high, 13 with moderately low, and 15 with very low child mortality). Two standard markers for immune response were examined including antirotavirus immunoglobulin A (IgA) seroconversion (defined as the appearance of serum antirotavirus IgA antibodies in subjects initially seronegative) and serum antirotavirus IgA titer, both collected approximately 4–12 weeks after administration of the last rotavirus vaccine dose. Mixed-effect logistic regression and mixed-effect linear regression of log-transformed data were used to identify individual- and country-level predictors of seroconversion (dichotomous) and antibody titer (continuous), respectively. Infants in high-child-mortality settings had lower odds of seroconverting compared with infants in low-child-mortality settings (odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.43–0.53, p < 0.001). Similarly, among those who seroconverted, infants in high-child-mortality settings had lower IgA titers compared with infants in low-child-mortality settings (mean difference [β] = 0.83, 95% CI 0.77–0.90, p < 0.001). Infants who received OPV concomitantly with both their first and their second doses of rotavirus vaccine had 0.63 times the odds of seroconverting (OR = 0.63, 95% CI 0.47–0.84, p = 0.002) compared with infants who received OPV but not concomitantly with either dose. In contrast, among infants who seroconverted, OPV concomitantly administered with both the first and second rotavirus vaccine doses was found to be positively associated with antirotavirus IgA titer (β = 1.28, 95% CI 1.07–1.53, p = 0.009). Our findings may have some limitations in terms of generalizability to routine use of rotavirus vaccine because the analysis was limited to healthy infants receiving RV1 in clinical trial settings.

Conclusions

Our findings suggest that OPV given concomitantly with RV1 was a substantial contributor to reduced antirotavirus IgA seroconversion, and this interference was apparent after the second vaccine dose of RV1, as with the original clinical trials that our reanalysis is based on. However, our findings do suggest that the forthcoming withdrawal of OPV from the infant immunization schedule globally has the potential to improve RV1 performance.

Nitroglycerin for treatment of retained placenta: A randomised, placebo-controlled, multicentre, double-blind trial in the UK

Lun, 30/12/2019 - 23:00

by Fiona C. Denison, Kathryn F. Carruthers, Jemma Hudson, Gladys McPherson, Gin Nie Chua, Mathilde Peace, Jane Brewin, Nina Hallowell, Graham Scotland, Julia Lawton, John Norrie, Jane E. Norman, GOT-IT investigator team

Background

Retained placenta following vaginal delivery is a major cause of postpartum haemorrhage. Currently, the only effective treatments for a retained placenta are the surgical procedures of manual removal of placenta (MROP) and uterine curettage, which are not universally available, particularly in low- and middle-income countries. The objective of the trial was to determine whether sublingual nitroglycerin spray was clinically effective and cost-effective for medical treatment of retained placenta following vaginal delivery.

Methods and findings

A randomised, placebo-controlled, double-blind trial was undertaken between October 2014 and July 2017 at 29 delivery units in the UK (Edinburgh, Glasgow, Manchester, Newcastle, Preston, Warrington, Chesterfield, Crewe, Durham, West Middlesex, Aylesbury, Furness, Southampton, Bolton, Sunderland, Oxford, Nottingham [2 units], Burnley, Chertsey, Stockton-on-Tees, Middlesborough, Chester, Darlington, York, Reading, Milton Keynes, Telford, Frimley). In total, 1,107 women with retained placenta following vaginal delivery were recruited. The intervention was self-administered 2 puffs of sublingual nitroglycerin (800 μg; intervention, N = 543) or placebo spray (control, N = 564). The primary clinical outcome was the need for MROP, assessed at 15 minutes following administration of the intervention. Analysis was based on the intention-to-treat principle. The primary safety outcome was measured blood loss between study drug administration and transfer to the postnatal ward or other clinical area. The primary patient-sided outcomes were satisfaction with treatment and side-effect profile, assessed by questionnaires pre-discharge and 6 weeks post-delivery. Secondary clinical outcomes were measured at 5 and 15 minutes after study drug administration and prior to hospital discharge. There was no statistically significant or clinically meaningful difference in need for MROP by 15 minutes (primary clinical outcome, 505 [93.3%] for nitroglycerin versus 518 [92.0%] for placebo, odds ratio [OR] 1.01 [95% CI 0.98–1.04], p = 0.393) or blood loss (<500 ml: nitroglycerin, 238 [44.3%], versus placebo, 249 [44.5%]; 500 ml–1,000 ml: nitroglycerin, 180 [33.5%], versus placebo, 224 [40.0%]; >1,000 ml: nitroglycerin, 119 [22.2%], versus placebo, 87 [15.5%]; ordinal OR 1.14 [95% CI 0.88–1.48], p = 0.314) or satisfaction with treatment (nitroglycerin, 288 [75.4%], versus placebo, 303 [78.1%]; OR 0.87 [95% CI 0.62–1.22], p = 0.411) or health service costs (mean difference [£] 55.3 [95% CI −199.20 to 309.79]). Palpitations following drug administration were reported more often in the nitroglycerin group (36 [9.8%] versus 15 [4.0%], OR 2.60 [95% CI 1.40–4.84], p = 0.003). There were 52 serious adverse events during the trial, with no statistically significant difference in likelihood between groups (nitroglycerin, 27 [5.0%], versus placebo, 26 [4.6%]; OR 1.13 [95% CI 0.54–2.38], p = 0.747). The main limitation of our study was the low return rate for the 6-week postnatal questionnaire. There were, however, no differences in questionnaire return rates between study groups or between women who did and did not have MROP, with the patient-reported use of outpatient and primary care services at 6 weeks accounting for only a small proportion (approximately 5%) of overall health service costs.

Conclusions

In this study, we found that nitroglycerin is neither clinically effective nor cost-effective as a medical treatment for retained placenta, and has increased side effects, suggesting it should not be used. Further research is required to identify an effective medical treatment for retained placenta to reduce the morbidity caused by this condition, particularly in low- and middle-income countries where surgical management is not available.

Trial registration

ISRCTN.com ISRCTN88609453ClinicalTrials.gov NCT02085213

Intensification with dipeptidyl peptidase-4 inhibitor, insulin, or thiazolidinediones and risks of all-cause mortality, cardiovascular diseases, and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy: A retrospective cohort study

Gio, 26/12/2019 - 23:00

by Carlos K. H. Wong, Kenneth K. C. Man, Margaret Shi, Esther W. Chan, Chu Wa Ho, Emily T. Y. Tse, Ian C. K. Wong, Cindy L. K. Lam

Background

Although patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication—including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)—can be added to achieve this. However, treatment effects of intensification with the medications on the risk of severe hypoglycemia (SH), cardiovascular disease (CVD), and all-cause mortality are uncertain. Study aim was to compare the risks of all-cause mortality, CVD, and SH among patients with T2DM on Met-SU dual therapy intensified with DPP4i, insulin, or TZD.

Methods and findings

We analyzed a retrospective cohort data of 17,293 patients with T2DM who were free from CVD and on Met-SU dual therapy and who were intensified with DPP4i (n = 8,248), insulin (n = 6,395), or TZD (n = 2,650) from 2006 to 2017. Propensity-score weighting was used to balance out baseline covariates across groups. Hazard ratios (HRs) for all-cause mortality, CVD, and SH were assessed using Cox proportional hazard models. Mean age of all patients was 58.56 ± 11.41 years. All baseline covariates achieved a balance across the 3 groups. Over a mean follow-up period of 34 months with 49,299 person-years, cumulative incidences of all-cause mortality, SH, and CVD were 0.061, 0.119, and 0.074, respectively. Patients intensified with insulin had higher risk of all-cause mortality (HR = 2.648, 95% confidence interval [CI] 2.367–2.963, p < 0.001; 2.352, 95% CI 2.123–2.605, p < 0.001) than those intensified with TZD and DPP4i, respectively. Insulin users had the greatest risk of SH (HR = 1.198, 95% CI 1.071–1.340, p = 0.002; 1.496, 95% CI 1.342–1.668, p < 0.001) compared with TZD and DPP4i users, respectively. Comparing between TZDs and DPP4i, TZDs were associated with a higher risk of SH (HR = 1.249, 95% CI 1.099–1.419, p < 0.001) but not all-cause mortality (HR = 0.888, 95% CI 0.776–1.016, p = 0.084) or CVD (HR = 1.005, 95% CI 0.915–1.104, p = 0.925). Limitations of this study included the lack of data regarding lifestyle, drug adherence, time-varying factors, patients’ motivation, and cost considerations. A limited duration of patients intensifying with TZD might also weaken the strength of study results.

Conclusions

Our results indicated that, for patients with T2DM who are on Met-SU dual therapy, the addition of DPP4i was a preferred third-line medication among 3 options, with the lowest risks of mortality and SH and posing no increased risk for CVD events when compared to insulin and TZD. Intensification with insulin had the greatest risk of mortality and SH events.

The 2016 California policy to eliminate nonmedical vaccine exemptions and changes in vaccine coverage: An empirical policy analysis

Lun, 23/12/2019 - 23:00

by Sindiso Nyathi, Hannah C. Karpel, Kristin L. Sainani, Yvonne Maldonado, Peter J. Hotez, Eran Bendavid, Nathan C. Lo

Background

Vaccine hesitancy, the reluctance or refusal to receive vaccination, is a growing public health problem in the United States and globally. State policies that eliminate nonmedical (“personal belief”) exemptions to childhood vaccination requirements are controversial, and their effectiveness to improve vaccination coverage remains unclear given limited rigorous policy analysis. In 2016, a California policy (Senate Bill 277) eliminated nonmedical exemptions from school entry requirements. The objective of this study was to estimate the association between California’s 2016 policy and changes in vaccine coverage.

Methods and findings

We used a quasi-experimental state-level synthetic control analysis and a county-level difference-in-differences analysis to estimate the impact of the 2016 California policy on vaccination coverage and prevalence of exemptions to vaccine requirements (nonmedical and medical). We used publicly available state-level data from the US Centers for Disease Control and Prevention on coverage of measles, mumps, and rubella (MMR) vaccination, nonmedical exemption, and medical exemption in children entering kindergarten. We used county-level data individually requested from state departments of public health on overall vaccine coverage and exemptions. Based on data availability, we included state-level data for 45 states, including California, from 2011 to 2017 and county-level data for 17 states from 2010 to 2017. The prespecified primary study outcome was MMR vaccination in the state analysis and overall vaccine coverage in the county analysis.In the state-level synthetic control analysis, MMR coverage in California increased by 3.3% relative to its synthetic control in the postpolicy period (top 2 of 43 states evaluated in the placebo tests, top 5%), nonmedical exemptions decreased by 2.4% (top 2 of 43 states evaluated in the placebo tests, top 5%), and medical exemptions increased by 0.4% (top 1 of 44 states evaluated in the placebo tests, top 2%). In the county-level analysis, overall vaccination coverage increased by 4.3% (95% confidence interval [CI] 2.9%–5.8%, p < 0.001), nonmedical exemptions decreased by 3.9% (95% CI 2.4%–5.4%, p < 0.001), and medical exemptions increased by 2.4% (95% CI 2.0%–2.9%, p < 0.001). Changes in vaccination coverage across counties after the policy implementation from 2015 to 2017 ranged from −6% to 26%, with larger increases in coverage in counties with lower prepolicy vaccine coverage. Results were robust to alternative model specifications. The limitations of the study were the exclusion of a subset of US states from the analysis and the use of only 2 years of postpolicy data based on data availability.

Conclusions

In this study, implementation of the California policy that eliminated nonmedical childhood vaccine exemptions was associated with an estimated increase in vaccination coverage and a reduction in nonmedical exemptions at state and county levels. The observed increase in medical exemptions was offset by the larger reduction in nonmedical exemptions. The largest increases in vaccine coverage were observed in the most “high-risk” counties, meaning those with the lowest prepolicy vaccine coverage. Our findings suggest that government policies removing nonmedical exemptions can be effective at increasing vaccination coverage.

Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study

Lun, 23/12/2019 - 23:00

by Elisé G. Kaboré, Charles Guenancia, Ines Vaz-Luis, Antonio Di Meglio, Barbara Pistilli, Charles Coutant, Paul Cottu, Anne Lesur, Thierry Petit, Florence Dalenc, Philippe Rouanet, Antoine Arnaud, Olivier Arsene, Mahmoud Ibrahim, Johanna Wassermann, Geneviève Boileau-Jolimoy, Anne-Laure Martin, Jérôme Lemonnier, Fabrice André, Patrick Arveux

Background

In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity.

Methods and findings

Using prospective data collected from 2012–2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction [LVEF] > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I–III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10–8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6–40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort.

Conclusions

In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498).

Trial registration

ClinicalTrials.gov NCT01993498.

Polygenic risk-tailored screening for prostate cancer: A benefit–harm and cost-effectiveness modelling study

Ven, 20/12/2019 - 23:00

by Tom Callender, Mark Emberton, Steve Morris, Ros Eeles, Zsofia Kote-Jarai, Paul D. P. Pharoah, Nora Pashayan

Background

The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55–69. Knowing how the potential benefits and harms of screening vary by an individual’s risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit–harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening.

Methods and findings

A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model’s cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval [UI]: 16,792–59,685) at the expense of 94,831 (95% UI: 84,827–105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382–72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853–15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose.

Conclusions

Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit–harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits–harms and cost-effectiveness.

Correction: Implementing a structured model for osteoarthritis care in primary healthcare: A stepped-wedge cluster-randomised trial

Gio, 19/12/2019 - 23:00

by Nina Østerås, Tuva Moseng, Leti van Bodegom-Vos, Krysia Dziedzic, Ibrahim Mdala, Bård Natvig, Jan Harald Røtterud, Unni-Berit Schjervheim, Thea Vliet Vlieland, Øyvor Andreassen, Jorun Nystuen Hansen, Kåre Birger Hagen