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Antenatal corticosteroid therapy (ACT) and size at birth: A population-based analysis using the Finnish Medical Birth Register

Me, 27/02/2019 - 00:00

by Alina Rodriguez, Yingbo Wang, Anohki Ali Khan, Rufus Cartwright, Mika Gissler, Marjo-Riitta Järvelin

Background

Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies.

Methods and findings

This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006–December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm −61.26 g (±SE 24.12, P < 0.01), preterm −232.90 g (±SE 17.24, P < .001), near term −171.50 g (±SE 17.52, P < .001), and at term −101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm −61.54 g (±SE 28.62, P < .03), preterm −222.78 g (±SE 19.64, P < .001), near term −159.25 g (±SE 19.14, P < .001), and at term −91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: −220.18 g (±SE 21.43, P < .001), −140.68 g (±SE 23.09, P < .001), and −89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested.

Conclusions

In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.

Correction: A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study

Ma, 26/02/2019 - 00:00

by Zuyun Liu, Pei-Lun Kuo, Steve Horvath, Eileen Crimmins, Luigi Ferrucci, Morgan Levine

The association between heatwaves and risk of hospitalization in Brazil: A nationwide time series study between 2000 and 2015

Sa, 23/02/2019 - 00:00

by Qi Zhao, Shanshan Li, Micheline S. Z. S. Coelho, Paulo H. N. Saldiva, Kejia Hu, Rachel R. Huxley, Michael J. Abramson, Yuming Guo

Background

To our knowledge, no study has assessed the association between heatwaves and risk of hospitalization and how it may change over time in Brazil. We quantified the heatwave–hospitalization association in Brazil during 2000–2015.

Methods and findings

Daily data on hospitalization and temperature were collected from 1,814 cities (>78% of the national population) in the hottest five consecutive months during 2000–2015. Twelve types of heatwaves were defined with daily mean temperatures of ≥90th, 92.5th, 95th, or 97.5th percentiles of year-round temperature and durations of ≥2, 3, or 4 consecutive days. The city-specific association was estimated using a quasi-Poisson regression with constrained distributed lag model and then pooled at the national level using random-effect meta-analysis. Stratified analyses were performed by five regions, sex, 10 age groups, and nine cause categories. The temporal change in the heatwave–hospitalization association was assessed using a time-varying constrained distributed lag model. Of the 58,400,682 hospitalizations (59% women), 24%, 34%, 21%, and 19% of cases were aged <20, 20–39, 40–59, and ≥60 years, respectively. The city-specific year-round daily mean temperatures were 23.5 ± 2.8 °C on average, varying from 26.8 ± 1.8 °C for the 90th percentile to 28.0 ± 1.6 °C for the 97.5th percentile. We observed that the risk of hospitalization was most pronounced for heatwaves characterized by high daily temperatures and long durations across Brazil, except for the minimal association in the north (the hottest region). After controlling for temperature, the association remained for severe heatwaves in the south and southeast (cold regions). Children 0–9 years, the elderly ≥70 years, and admissions for perinatal conditions were most strongly associated with heatwaves. Over the study period, the strength of the heatwave–hospitalization association declined substantially in the south, while an apparent increase was observed in the southeast. The main limitations of this study included the lack of data on individual temperature exposure and measured air pollution.

Conclusions

There are geographic, demographic, cause-specific, and temporal variations in the heatwave–hospitalization associations across the Brazilian population. Considering the projected increase in frequency, duration, and intensity of heatwaves, future strategies should be developed, such as building early warning systems, to reduce the health risk associated with heatwaves in Brazil.

COSMOS-E: Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology

Ve, 22/02/2019 - 00:00

by Olaf M. Dekkers, Jan P. Vandenbroucke, Myriam Cevallos, Andrew G. Renehan, Douglas G. Altman, Matthias Egger

Background

To our knowledge, no publication providing overarching guidance on the conduct of systematic reviews of observational studies of etiology exists.

Methods and findings

Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology (COSMOS-E) provides guidance on all steps in systematic reviews of observational studies of etiology, from shaping the research question, defining exposure and outcomes, to assessing the risk of bias and statistical analysis. The writing group included researchers experienced in meta-analyses and observational studies of etiology. Standard peer-review was performed. While the structure of systematic reviews of observational studies on etiology may be similar to that for systematic reviews of randomised controlled trials, there are specific tasks within each component that differ. Examples include assessment for confounding, selection bias, and information bias. In systematic reviews of observational studies of etiology, combining studies in meta-analysis may lead to more precise estimates, but such greater precision does not automatically remedy potential bias. Thorough exploration of sources of heterogeneity is key when assessing the validity of estimates and causality.

Conclusion

As many reviews of observational studies on etiology are being performed, this document may provide researchers with guidance on how to conduct and analyse such reviews.

National policies and care provision in pregnancy and childbirth for twins in Eastern and Southern Africa: A mixed-methods multi-country study

Me, 20/02/2019 - 00:00

by Claudia Hanson, Stephen Munjanja, Agnes Binagwaho, Bellington Vwalika, Andrea B. Pembe, Elsa Jacinto, George K. Chilinda, Kateri B. Donahoe, Sikolia Z. Wanyonyi, Peter Waiswa, Muchabayiwa F. Gidiri, Lenka Benova

Background

High-risk pregnancies, such as twin pregnancies, deserve particular attention as mortality is very high in this group. With a view to inform policy and national guidelines development for the Sustainable Development Goals, we reviewed national training materials, guidelines, and policies underpinning the provision of care in relation to twin pregnancies and assessed care provided to twins in 8 Eastern and Southern African countries: Kenya, Malawi, Mozambique, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe.

Methods and findings

We located policies and guidelines by reviewing national repositories and by contacting experts to systematically map country-level maternal and newborn training materials, guidelines, and policies. We extracted recommendations for care for twins spanning ante-, intra-, and postpartum care that typically should be offered during twin pregnancies and childbirth. We compared care provided for mothers of twins to that provided for mothers of singletons during the ante-, intra-, and postpartum period and computed neonatal mortality rates using the most recent Demographic and Health Surveys (DHS) data for each country. There was a paucity of guidance on care specifically for twin or multiple pregnancies: None of the countries provided clear guidance on additional number of antenatal care visits or specific antenatal content, while 7 of the 8 countries recommended twins to be delivered in a comprehensive emergency obstetric and neonatal care facility. These results were mirrored by DHS results of 73,462 live births (of which 1,360 were twin) indicating that twin pregnancies did not receive more frequent or intensified antenatal care. The percentage of twin deliveries in hospitals varied from 25.3% in Mozambique to 63.0% in Kenya, and women with twin deliveries were between 5 and 27 percentage points more likely to deliver in hospitals compared to women with singleton live births; this difference was significant in 5 of the 8 countries (t test p < 0.05). The percentage of twin deliveries by cesarean section varied from 9% in Mozambique to 36% in Rwanda. The newborn mortality rate among twins, adjusted for maternal age and parity, was 4.6 to 7.2 times higher for twins compared to singletons in all 8 countries.

Conclusions

Despite the limited sample size and the limited number of clinically relevant services evaluated, our study provided evidence that mothers of twins receive insufficient care and that mortality in twin newborns is very high in Eastern and Southern Africa. Most countries have insufficient guidelines for the care of twins. While our data do not allow us to make a causal link between insufficient guidelines and insufficient care, they call for an assessment and reconceptualisation of policies to reduce the unacceptably high mortality in twins in Eastern and Southern Africa.

The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial

Sa, 16/02/2019 - 00:00

by Lorenz von Seidlein, Thomas J. Peto, Jordi Landier, Thuy-Nhien Nguyen, Rupam Tripura, Koukeo Phommasone, Tiengkham Pongvongsa, Khin Maung Lwin, Lilly Keereecharoen, Ladda Kajeechiwa, May Myo Thwin, Daniel M. Parker, Jacher Wiladphaingern, Suphak Nosten, Stephane Proux, Vincent Corbel, Nguyen Tuong-Vy, Truong Le Phuc-Nhi, Do Hung Son, Pham Nguyen Huong-Thu, Nguyen Thi Kim Tuyen, Nguyen Thanh Tien, Le Thanh Dong, Dao Van Hue, Huynh Hong Quang, Chea Nguon, Chan Davoeung, Huy Rekol, Bipin Adhikari, Gisela Henriques, Panom Phongmany, Preyanan Suangkanarat, Atthanee Jeeyapant, Benchawan Vihokhern, Rob W. van der Pluijm, Yoel Lubell, Lisa J. White, Ricardo Aguas, Cholrawee Promnarate, Pasathorn Sirithiranont, Benoit Malleret, Laurent Rénia, Carl Onsjö, Xin Hui Chan, Jeremy Chalk, Olivo Miotto, Krittaya Patumrat, Kesinee Chotivanich, Borimas Hanboonkunupakarn, Podjanee Jittmala, Nils Kaehler, Phaik Yeong Cheah, Christopher Pell, Mehul Dhorda, Mallika Imwong, Georges Snounou, Mavuto Mukaka, Pimnara Peerawaranun, Sue J. Lee, Julie A. Simpson, Sasithon Pukrittayakamee, Pratap Singhasivanon, Martin P. Grobusch, Frank Cobelens, Frank Smithuis, Paul N. Newton, Guy E. Thwaites, Nicholas P. J. Day, Mayfong Mayxay, Tran Tinh Hien, Francois H. Nosten, Arjen M. Dondorp, Nicholas J. White

Background

The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People’s Democratic Republic, where artemisinin resistance is prevalent.

Methods and findings

After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.

Conclusions

Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.

Trial registration

ClinicalTrials.gov NCT01872702

Community-, facility-, and individual-level outcomes of a district mental healthcare plan in a low-resource setting in Nepal: A population-based evaluation

Ve, 15/02/2019 - 00:00

by Mark J. D. Jordans, Nagendra P. Luitel, Brandon A. Kohrt, Sujit D. Rathod, Emily C. Garman, Mary De Silva, Ivan H. Komproe, Vikram Patel, Crick Lund

Background

In low-income countries, care for people with mental, neurological, and substance use (MNS) disorders is largely absent, especially in rural settings. To increase treatment coverage, integration of mental health services into community and primary healthcare settings is recommended. While this strategy is being rolled out globally, rigorous evaluation of outcomes at each stage of the service delivery pathway from detection to treatment initiation to individual outcomes of care has been missing.

Methods and findings

A combination of methods were employed to evaluate the impact of a district mental healthcare plan for depression, psychosis, alcohol use disorder (AUD), and epilepsy as part of the Programme for Improving Mental Health Care (PRIME) in Chitwan District, Nepal. We evaluated 4 components of the service delivery pathway: (1) contact coverage of primary care mental health services, evaluated through a community study (N = 3,482 combined for all waves of community surveys) and through service utilisation data (N = 727); (2) detection of mental illness among participants presenting in primary care facilities, evaluated through a facility study (N = 3,627 combined for all waves of facility surveys); (3) initiation of minimally adequate treatment after diagnosis, evaluated through the same facility study; and (4) treatment outcomes of patients receiving primary-care-based mental health services, evaluated through cohort studies (total N = 449 depression, N = 137; AUD, N = 175; psychosis, N = 95; epilepsy, N = 42). The lack of structured diagnostic assessments (instead of screening tools), the relatively small sample size for some study components, and the uncontrolled nature of the study are among the limitations to be noted. All data collection took place between 15 January 2013 and 15 February 2017. Contact coverage increased 7.5% for AUD (from 0% at baseline), 12.2% for depression (from 0%), 11.7% for epilepsy (from 1.3%), and 50.2% for psychosis (from 3.2%) when using service utilisation data over 12 months; community survey results did not reveal significant changes over time. Health worker detection of depression increased by 15.7% (from 8.9% to 24.6%) 6 months after training, and 10.3% (from 8.9% to 19.2%) 24 months after training; for AUD the increase was 58.9% (from 1.1% to 60.0%) and 11.0% (from 1.1% to 12.1%) for 6 months and 24 months, respectively. Provision of minimally adequate treatment subsequent to diagnosis for depression was 93.9% at 6 months and 66.7% at 24 months; for AUD these values were 95.1% and 75.0%, respectively. Changes in treatment outcomes demonstrated small to moderate effect sizes (9.7-point reduction [d = 0.34] in AUD symptoms, 6.4-point reduction [d = 0.43] in psychosis symptoms, 7.2-point reduction [d = 0.58] in depression symptoms) at 12 months post-treatment.

Conclusions

These combined results make a promising case for the feasibility and impact of community- and primary-care-based services delivered through an integrated district mental healthcare plan in reducing the treatment gap and increasing effective coverage for MNS disorders. While the integrated mental healthcare approach does lead to apparent benefits in most of the outcome metrics, there are still significant areas that require further attention (e.g., no change in community-level contact coverage, attrition in AUD detection rates over time, and relatively low detection rates for depression).

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis

Ma, 12/02/2019 - 00:00

by Ellis Voerman, Susana Santos, Bernadeta Patro Golab, Pilar Amiano, Ferran Ballester, Henrique Barros, Anna Bergström, Marie-Aline Charles, Leda Chatzi, Cécile Chevrier, George P. Chrousos, Eva Corpeleijn, Nathalie Costet, Sarah Crozier, Graham Devereux, Merete Eggesbø, Sandra Ekström, Maria Pia Fantini, Sara Farchi, Francesco Forastiere, Vagelis Georgiu, Keith M. Godfrey, Davide Gori, Veit Grote, Wojciech Hanke, Irva Hertz-Picciotto, Barbara Heude, Daniel Hryhorczuk, Rae-Chi Huang, Hazel Inskip, Nina Iszatt, Anne M. Karvonen, Louise C. Kenny, Berthold Koletzko, Leanne K. Küpers, Hanna Lagström, Irina Lehmann, Per Magnus, Renata Majewska, Johanna Mäkelä, Yannis Manios, Fionnuala M. McAuliffe, Sheila W. McDonald, John Mehegan, Monique Mommers, Camilla S. Morgen, Trevor A. Mori, George Moschonis, Deirdre Murray, Carol Ní Chaoimh, Ellen A. Nohr, Anne-Marie Nybo Andersen, Emily Oken, Adriëtte J. J. M. Oostvogels, Agnieszka Pac, Eleni Papadopoulou, Juha Pekkanen, Costanza Pizzi, Kinga Polanska, Daniela Porta, Lorenzo Richiardi, Sheryl L. Rifas-Shiman, Luca Ronfani, Ana C. Santos, Marie Standl, Camilla Stoltenberg, Elisabeth Thiering, Carel Thijs, Maties Torrent, Suzanne C. Tough, Tomas Trnovec, Steve Turner, Lenie van Rossem, Andrea von Berg, Martine Vrijheid, Tanja G. M. Vrijkotte, Jane West, Alet Wijga, John Wright, Oleksandr Zvinchuk, Thorkild I. A. Sørensen, Debbie A. Lawlor, Romy Gaillard, Vincent W. V. Jaddoe

Background

Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.

Methods and findings

We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0–5.0 years), mid (5.0–10.0 years) and late childhood (10.0–18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.

Conclusions

In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

The effect of a programme to improve men’s sedentary time and physical activity: The European Fans in Training (EuroFIT) randomised controlled trial

Me, 06/02/2019 - 00:00

by Sally Wyke, Christopher Bunn, Eivind Andersen, Marlene N. Silva, Femke van Nassau, Paula McSkimming, Spyros Kolovos, Jason M. R. Gill, Cindy M. Gray, Kate Hunt, Annie S. Anderson, Judith Bosmans, Judith G. M. Jelsma, Sharon Kean, Nicolas Lemyre, David W. Loudon, Lisa Macaulay, Douglas J. Maxwell, Alex McConnachie, Nanette Mutrie, Maria Nijhuis-van der Sanden, Hugo V. Pereira, Matthew Philpott, Glyn C. Roberts, John Rooksby, Øystein B. Røynesdal, Naveed Sattar, Marit Sørensen, Pedro J. Teixeira, Shaun Treweek, Theo van Achterberg, Irene van de Glind, Willem van Mechelen, Hidde P. van der Ploeg

Background

Reducing sitting time as well as increasing physical activity in inactive people is beneficial for their health. This paper investigates the effectiveness of the European Fans in Training (EuroFIT) programme to improve physical activity and sedentary time in male football fans, delivered through the professional football setting.

Methods and findings

A total of 1,113 men aged 30–65 with self-reported body mass index (BMI) ≥27 kg/m2 took part in a randomised controlled trial in 15 professional football clubs in England, the Netherlands, Norway, and Portugal. Recruitment was between September 19, 2015, and February 2, 2016. Participants consented to study procedures and provided usable activity monitor baseline data. They were randomised, stratified by club, to either the EuroFIT intervention or a 12-month waiting list comparison group. Follow-up measurement was post-programme and 12 months after baseline. EuroFIT is a 12-week, group-based programme delivered by coaches in football club stadia in 12 weekly 90-minute sessions. Weekly sessions aimed to improve physical activity, sedentary time, and diet and maintain changes long term. A pocket-worn device (SitFIT) allowed self-monitoring of sedentary time and daily steps, and a game-based app (MatchFIT) encouraged between-session social support. Primary outcome (objectively measured sedentary time and physical activity) measurements were obtained for 83% and 85% of intervention and comparison participants. Intention-to-treat analyses showed a baseline-adjusted mean difference in sedentary time at 12 months of −1.6 minutes/day (97.5% confidence interval [CI], −14.3–11.0; p = 0.77) and in step counts of 678 steps/day (97.5% CI, 309–1.048; p < 0.001) in favor of the intervention. There were significant improvements in diet, weight, well-being, self-esteem, vitality, and biomarkers of cardiometabolic health in favor of the intervention group, but not in quality of life. There was a 0.95 probability of EuroFIT being cost-effective compared with the comparison group if society is willing to pay £1.50 per extra step/day, a maximum probability of 0.61 if society is willing to pay £1,800 per minute less sedentary time/day, and 0.13 probability if society is willing to pay £30,000 per quality-adjusted life-year (QALY). It was not possible to blind participants to group allocation. Men attracted to the programme already had quite high levels of physical activity at baseline (8,372 steps/day), which may have limited room for improvement. Although participants came from across the socioeconomic spectrum, a majority were well educated and in paid work. There was an increase in recent injuries and in upper and lower joint pain scores post-programme. In addition, although the five-level EuroQoL questionnaire (EQ-5D-5L) is now the preferred measure for cost-effectiveness analyses across Europe, baseline scores were high (0.93), suggesting a ceiling effect for QALYs.

Conclusion

Participation in EuroFIT led to improvements in physical activity, diet, body weight, and biomarkers of cardiometabolic health, but not in sedentary time at 12 months. Within-trial analysis suggests it is not cost-effective in the short term for QALYs due to a ceiling effect in quality of life. Nevertheless, decision-makers may consider the incremental cost for increase in steps worth the investment.

Trial registration

International Standard Randomised Controlled Trials, ISRCTN-81935608.

Long-term outcomes of an educational intervention to reduce antibiotic prescribing for childhood upper respiratory tract infections in rural China: Follow-up of a cluster-randomised controlled trial

Me, 06/02/2019 - 00:00

by Xiaolin Wei, Zhitong Zhang, Joseph P. Hicks, John D. Walley, Rebecca King, James N. Newell, Jia Yin, Jun Zeng, Yan Guo, Mei Lin, Ross E. G. Upshur, Qiang Sun

Background

Inappropriate antibiotic prescribing causes widespread serious health problems. To reduce prescribing of antibiotics in Chinese primary care to children with upper respiratory tract infections (URTIs), we developed an intervention comprising clinical guidelines, monthly prescribing review meetings, doctor–patient communication skills training, and education materials for caregivers. We previously evaluated our intervention using an unblinded cluster-randomised controlled trial (cRCT) in 25 primary care facilities across two rural counties. When our trial ended at the 6-month follow-up period, we found that the intervention had reduced antibiotic prescribing for childhood URTIs by 29 percentage points (pp) (95% CI −42 to −16).

Methods and findings

In this long-term follow-up study, we collected our trial outcomes from the one county (14 facilities and 1:1 cluster randomisation ratio) that had electronic records available 12 months after the trial ended, at the 18-month follow-up period. Our primary outcome was the antibiotic prescription rate (APR)—the percentage of outpatient prescriptions containing any antibiotic(s) for children aged 2 to 14 years who had a primary diagnosis of a URTI and had no other illness requiring antibiotics. We also conducted 15 in-depth interviews to understand how interventions were sustained.In intervention facilities, the APR was 84% (1,171 out of 1,400) at baseline, 37% (515 out of 1,380) at 6 months, and 54% (2,748 out of 5,084) at 18 months, and in control facilities, it was 76% (1,063 out of 1,400), 77% (1,084 out of 1,400), and 75% (2,772 out of 3,685), respectively. After adjusting for patient and prescribing doctor covariates, compared to the baseline intervention-control difference, the difference at 6 months represented a 6-month intervention-arm reduction in the APR of −49 pp (95% CI −63 to −35; P < 0.0001), and compared to the baseline difference, the difference at 18 months represented an 18-month intervention-arm reduction in the APR of −36 pp (95% CI −55 to −17; P < 0.0001). Compared to the 6-month intervention-control difference, the difference at 18 months represented no change in the APR: 13 pp (95% CI −7 to 33; P = 0.21). Factors reported to sustain reductions in antibiotic prescribing included doctors’ improved knowledge and communication skills and focused prescription review meetings, whereas lack of supervision and monitoring may be associated with relapse. Key limitations were not including all clusters from the trial and not collecting returned visits or sepsis cases.

Conclusions

Our intervention was associated with sustained and substantial reductions in antibiotic prescribing at the end of the intervention period and 12 months later. Our intervention may be adapted to similar resource-poor settings.

Trial registration

ISRCTN registry ISRCTN14340536.

Trazodone use and risk of dementia: A population-based cohort study

Me, 06/02/2019 - 00:00

by Ruth Brauer, Wallis C. Y. Lau, Joseph F. Hayes, Kenneth K. C. Man, David P. J. Osborn, Robert Howard, Joseph Kim, Ian C. K. Wong

Background

In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice.

Methods and findings

The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ≥50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range [IQR] = 0.5–5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval [CI] 1.56–2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding.

Conclusions

In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia.

Lifetime risk and multimorbidity of non-communicable diseases and disease-free life expectancy in the general population: A population-based cohort study

Ma, 05/02/2019 - 00:00

by Silvan Licher, Alis Heshmatollah, Kimberly D. van der Willik, Bruno H. Ch. Stricker, Rikje Ruiter, Emmely W. de Roos, Lies Lahousse, Peter J. Koudstaal, Albert Hofman, Lana Fani, Guy G. O. Brusselle, Daniel Bos, Banafsheh Arshi, Maryam Kavousi, Maarten J. G. Leening, M. Kamran Ikram, M. Arfan Ikram

Background

Non-communicable diseases (NCDs) are leading causes of premature disability and death worldwide. However, the lifetime risk of developing any NCD is unknown, as are the effects of shared common risk factors on this risk.

Methods and findings

Between July 6, 1989, and January 1, 2012, we followed participants from the prospective Rotterdam Study aged 45 years and older who were free from NCDs at baseline for incident stroke, heart disease, diabetes, chronic respiratory disease, cancer, and neurodegenerative disease. We quantified occurrence/co-occurrence and remaining lifetime risk of any NCD in a competing risk framework. We additionally studied the lifetime risk of any NCD, age at onset, and overall life expectancy for strata of 3 shared risk factors at baseline: smoking, hypertension, and overweight. During 75,354 person-years of follow-up from a total of 9,061 participants (mean age 63.9 years, 60.1% women), 814 participants were diagnosed with stroke, 1,571 with heart disease, 625 with diabetes, 1,004 with chronic respiratory disease, 1,538 with cancer, and 1,065 with neurodegenerative disease. NCDs tended to co-occur substantially, with 1,563 participants (33.7% of those who developed any NCD) diagnosed with multiple diseases during follow-up. The lifetime risk of any NCD from the age of 45 years onwards was 94.0% (95% CI 92.9%–95.1%) for men and 92.8% (95% CI 91.8%–93.8%) for women. These risks remained high (>90.0%) even for those without the 3 risk factors of smoking, hypertension, and overweight. Absence of smoking, hypertension, and overweight was associated with a 9.0-year delay (95% CI 6.3–11.6) in the age at onset of any NCD. Furthermore, the overall life expectancy for participants without these risk factors was 6.0 years (95% CI 5.2–6.8) longer than for those with all 3 risk factors. Participants aged 45 years and older without the 3 risk factors of smoking, hypertension, and overweight at baseline spent 21.6% of their remaining lifetime with 1 or more NCDs, compared to 31.8% of their remaining life for participants with all of these risk factors at baseline. This difference corresponds to a 2-year compression of morbidity of NCDs. Limitations of this study include potential residual confounding, unmeasured changes in risk factor profiles during follow-up, and potentially limited generalisability to different healthcare settings and populations not of European descent.

Conclusions

Our study suggests that in this western European community, 9 out of 10 individuals aged 45 years and older develop an NCD during their remaining lifetime. Among those individuals who develop an NCD, at least a third are subsequently diagnosed with multiple NCDs. Absence of 3 common shared risk factors is associated with compression of morbidity of NCDs. These findings underscore the importance of avoidance of these common shared risk factors to reduce the premature morbidity and mortality attributable to NCDs.

Setting targets for HIV/AIDS—What lessons can be learned from other disease control programmes?

Ma, 05/02/2019 - 00:00

by Tazeem Bhatia, Jamie Enoch, Mishal Khan, Sophie Mathewson, David Heymann, Richard Hayes, Osman Dar

In a Collection Review, Richard Hayes and colleagues discuss metrics for assessing progress in control of the HIV/AIDS epidemic in the context of prior disease control programmes.