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Prenatal fortified balanced energy—Protein supplementation and birth outcomes in rural Burkina Faso: A randomized controlled efficacy trial

Ve, 13/05/2022 - 16:00

by Brenda de Kok, Laeticia Celine Toe, Giles Hanley-Cook, Alemayehu Argaw, Moctar Ouédraogo, Anderson Compaoré, Katrien Vanslambrouck, Trenton Dailey-Chwalibóg, Rasmané Ganaba, Patrick Kolsteren, Lieven Huybregts, Carl Lachat

Background

Providing balanced energy–protein (BEP) supplements is a promising intervention to improve birth outcomes in low- and middle-income countries (LMICs); however, evidence is limited. We aimed to assess the efficacy of fortified BEP supplementation during pregnancy to improve birth outcomes, as compared to iron–folic acid (IFA) tablets, the standard of care.

Methods and findings

We conducted an individually randomized controlled efficacy trial (MIcronutriments pour la SAnté de la Mère et de l’Enfant [MISAME]-III) in 6 health center catchment areas in rural Burkina Faso. Pregnant women, aged 15 to 40 years with gestational age (GA) <21 completed weeks, were randomly assigned to receive either fortified BEP supplements and IFA (intervention) or IFA (control). Supplements were provided during home visits, and intake was supervised on a daily basis by trained village-based project workers. The primary outcome was prevalence of small-for-gestational age (SGA) and secondary outcomes included large-for-gestational age (LGA), low birth weight (LBW), preterm birth (PTB), gestational duration, birth weight, birth length, Rohrer’s ponderal index, head circumference, thoracic circumference, arm circumference, fetal loss, and stillbirth. Statistical analyses followed the intention-to-treat (ITT) principle. From October 2019 to December 2020, 1,897 pregnant women were randomized (960 control and 937 intervention). The last child was born in August 2021, and birth anthropometry was analyzed from 1,708 pregnancies (872 control and 836 intervention). A total of 22 women were lost to follow-up in the control group and 27 women in the intervention group. BEP supplementation led to a mean 3.1 percentage points (pp) reduction in SGA with a 95% confidence interval (CI) of −7.39 to 1.16 (P = 0.151), indicating a wide range of plausible true treatment efficacy. Adjusting for prognostic factors of SGA, and conducting complete cases (1,659/1,708, 97%) and per-protocol analysis among women with an observed BEP adherence ≥75% (1,481/1,708, 87%), did not change the results. The intervention significantly improved the duration of gestation (+0.20 weeks, 95% CI 0.05 to 0.36, P = 0.010), birth weight (50.1 g, 8.11 to 92.0, P = 0.019), birth length (0.20 cm, 0.01 to 0.40, P = 0.044), thoracic circumference (0.20 cm, 0.04 to 0.37, P = 0.016), arm circumference (0.86 mm, 0.11 to 1.62, P = 0.025), and decreased LBW prevalence (−3.95 pp, −6.83 to −1.06, P = 0.007) as secondary outcomes measures. No differences in serious adverse events [SAEs; fetal loss (21 control and 26 intervention) and stillbirth (16 control and 17 intervention)] between the study groups were found. Key limitations are the nonblinded administration of supplements and the lack of information on other prognostic factors (e.g., infection, inflammation, stress, and physical activity) to determine to which extent these might have influenced the effect on nutrient availability and birth outcomes.

Conclusions

The MISAME-III trial did not provide evidence that fortified BEP supplementation is efficacious in reducing SGA prevalence. However, the intervention had a small positive effect on other birth outcomes. Additional maternal and biochemical outcomes need to be investigated to provide further evidence on the overall clinical relevance of BEP supplementation.

Trial registration

ClinicalTrials.gov NCT03533712.

Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014–2018: A cohort study

Gi, 12/05/2022 - 16:00

by Doris K. Nyamwaya, Mark Otiende, Lilian Mwango, Symon M. Kariuki, Berrick Otieno, Donwilliams O. Omuoyo, George Githinji, Barnes S. Kitsao, Henry K. Karanja, John N. Gitonga, Zaydah R. de Laurent, Alun Davies, Salim Mwarumba, Charles N. Agoti, Samuel M. Thumbi, Mainga M. Hamaluba, Charles R. Newton, Philip Bejon, George M. Warimwe

Background

Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown and given the lack of diagnostic facilities in routine care it is possible that CHIKV is an unrecognized etiology among children with encephalitis or other neurological illness.

Methods and findings

We estimated the incidence of CHIKV infection among children hospitalized with neurological disease in Kilifi County, coastal Kenya. We used reverse transcriptase polymerase chain reaction (RT-PCR) to systematically test for CHIKV in cerebrospinal fluid (CSF) samples from children aged <16 years hospitalized with symptoms of neurological disease at Kilifi County Hospital between January 2014 and December 2018. Clinical records were linked to the Kilifi Health and Demographic Surveillance System and population incidence rates of CHIKV infection estimated. There were 18,341 pediatric admissions for any reason during the 5-year study period, of which 4,332 (24%) had CSF collected. The most common clinical reasons for CSF collection were impaired consciousness, seizures, and coma (47%, 22%, and 21% of all collections, respectively). After acute investigations done for immediate clinical care, CSF samples were available for 3,980 admissions, of which 367 (9.2%) were CHIKV RT-PCR positive. Case fatality among CHIKV-positive children was 1.4% (95% CI 0.4, 3.2). The annual incidence of CHIKV-associated neurological disease varied between 13 to 58 episodes per 100,000 person-years among all children <16 years old. Among children aged <5 years, the incidence of CHIKV-associated neurological disease was 77 per 100,000 person-years, compared with 20 per 100,000 for cerebral malaria and 7 per 100,000 for bacterial meningitis during the study period. Because of incomplete case ascertainment due to children not presenting to hospital, or not having CSF collected, these are likely minimum estimates. Study limitations include reliance on hospital-based surveillance and limited CSF sampling in children in coma or other contraindications to lumbar puncture, both of which lead to under-ascertainment of incidence and of case fatality.

Conclusions

In this study, we observed that CHIKV infections are relatively more common than cerebral malaria and bacterial meningitis among children hospitalized with neurological disease in coastal Kenya. Given the wide distribution of CHIKV mosquito vectors, studies to determine the geographic extent of CHIKV-associated neurological disease in Africa are essential.

COVID-19 epidemiology and changes in health service utilization in Azraq and Zaatari refugee camps in Jordan: A retrospective cohort study

Ma, 10/05/2022 - 16:00

by Chiara Altare, Natalya Kostandova, Jennifer OKeeffe, Heba Hayek, Muhammad Fawad, Adam Musa Khalifa, Paul B. Spiegel

Background

The effects of the Coronavirus Disease 2019 (COVID-19) pandemic in humanitarian contexts are not well understood. Specific vulnerabilities in such settings raised concerns about the ability to respond and maintain essential health services. This study describes the epidemiology of COVID-19 in Azraq and Zaatari refugee camps in Jordan (population: 37,932 and 79,034, respectively) and evaluates changes in routine health services during the COVID-19 pandemic.

Methods and findings

We calculate the descriptive statistics of COVID-19 cases in the United Nations High Commissioner for Refugees (UNHCR)’s linelist and adjusted odds ratios (aORs) for selected outcomes. We evaluate the changes in health services using monthly routine data from UNHCR’s health information system (HIS; January 2018 to March 2021) and apply interrupted time series analysis with a generalized additive model and negative binomial (NB) distribution, accounting for long-term trends and seasonality, reporting results as incidence rate ratios (IRRs).COVID-19 cases were first reported on September 8 and September 13, 2020 in Azraq and Zaatari camps, respectively, 6 months after the first case in Jordan. Incidence rates (IRs) were lower in camps than neighboring governorates (by 37.6% in Azraq (IRR: 0.624, 95% confidence interval [CI]: [0.584 to 0.666], p-value: <0.001) and 40.2% in Zaatari (IRR: 0.598, 95% CI: [0.570, 0.629], p-value: <0.001)) and lower than Jordan (by 59.7% in Azraq (IRR: 0.403, 95% CI: [0.378 to 0.430], p-value: <0.001) and by 63.3% in Zaatari (IRR: 0.367, 95% CI: [0.350 to 0.385], p-value: <0.001)). Characteristics of cases and risk factors for negative disease outcomes were consistent with increasing COVID-19 evidence. The following health services reported an immediate decline during the first year of COVID-19: healthcare utilization (by 32% in Azraq (IRR: 0.680, 95% CI [0.549 to 0.843], p-value < 0.001) and by 24.2% in Zaatari (IRR: 0.758, 95% CI [0.577 to 0.995], p-value = 0.046)); consultations for respiratory tract infections (RTIs; by 25.1% in Azraq (IRR: 0.749, 95% CI: [0.596 to 0.940], p-value = 0.013 and by 37.5% in Zaatari (IRR: 0.625, 95% CI: [0.461 to 0.849], p-value = 0.003)); and family planning (new and repeat family planning consultations decreased by 47.4% in Azraq (IRR: 0.526, 95% CI: [0.376 to 0.736], p-value = <0.001) and 47.6% in Zaatari (IRR: 0.524, 95% CI: [0.312 to 0.878], p-value = 0.014)). Maternal and child health services as well as noncommunicable diseases did not show major changes compared to pre–COVID-19 period. Conducting interrupted time series analyses in volatile settings such refugee camps can be challenging as it may be difficult to meet some analytical assumptions and to mitigate threats to validity. The main limitation of this study relates therefore to possible unmeasured confounding.

Conclusions

COVID-19 transmission was lower in camps than outside of camps. Refugees may have been affected from external transmission, rather than driving it. Various types of health services were affected differently, but disruptions appear to have been limited in the 2 camps compared to other noncamp settings. These insights into Jordan’s refugee camps during the first year of the COVID-19 pandemic set the stage for follow-up research to investigate how infection susceptibility evolved over time, as well as which mitigation strategies were more successful and accepted.

Effect of glutamate infusion on NT-proBNP after coronary artery bypass grafting in high-risk patients (GLUTAMICS II): A randomized controlled trial

Lu, 09/05/2022 - 16:00

by Jonas Holm, Gabriele Ferrari, Anders Holmgren, Farkas Vanky, Örjan Friberg, Mårten Vidlund, Rolf Svedjeholm

Background

Animal and human data suggest that glutamate can enhance recovery of myocardial metabolism and function after ischemia. N-terminal pro-brain natriuretic peptide (NT-proBNP) reflects myocardial dysfunction after coronary artery bypass surgery (CABG). We investigated whether glutamate infusion can reduce rises of NT-proBNP in moderate- to high-risk patients after CABG.

Methods and findings

A prospective, randomized, double-blind study enrolled patients from November 15, 2015 to September 30, 2020, with a 30-day follow-up at 4 academic cardiac surgery centers in Sweden. Patients underwent CABG ± valve procedure and had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h started 10 to 20 minutes before releasing the aortic cross-clamp, then continued for another 150 minutes. Patients, staff, and investigators were blinded to the treatment. The primary endpoint was the difference between preoperative and day-3 postoperative NT-proBNP levels. Analysis was intention to treat.We studied 303 patients (age 74 ± 7 years; females 26%, diabetes 47%), 148 receiving glutamate group and 155 controls. There was no significant difference in the primary endpoint associated with glutamate administration (5,390 ± 5,396 ng/L versus 6,452 ± 5,215 ng/L; p = 0.086). One patient died ≤30 days in the glutamate group compared to 6 controls (0.7% versus 3.9%; p = 0.12). No adverse events linked to glutamate were observed.A significant interaction between glutamate and diabetes was found (p = 0.03). Among patients without diabetes the primary endpoint (mean 4,503 ± 4,846 ng/L versus 6,824 ± 5,671 ng/L; p = 0.007), and the incidence of acute kidney injury (11% versus 29%; p = 0.005) was reduced in the glutamate group. These associations remained significant after adjusting for differences in baseline data.The main limitations of the study are: (i) it relies on a surrogate marker for heart failure; and (ii) the proportion of patients with diabetes had almost doubled compared to the cohort used for the sample size estimation.

Conclusions

Infusion of glutamate did not significantly reduce postoperative rises of NT-proBNP. Diverging results in patients with and without diabetes agree with previous observations and suggest that the concept of enhancing postischemic myocardial recovery with glutamate merits further evaluation.

Trial registration

ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02592824.European Union Drug Regulating Authorities Clinical Trials Database (Eudra CT number 2011-006241-15).

Evaluation of a multicomponent intervention consisting of education and feedback to reduce benzodiazepine prescriptions by general practitioners: The BENZORED hybrid type 1 cluster randomized controlled trial

Ve, 06/05/2022 - 16:00

by Caterina Vicens, Alfonso Leiva, Ferran Bejarano, Ermengol Sempere-Verdú, Raquel María Rodríguez-Rincón, Francisca Fiol, Marta Mengual, Asunción Ajenjo-Navarro, Fernando Do Pazo, Catalina Mateu, Silvia Folch, Santiago Alegret, Jose Maria Coll, María Martín-Rabadán, Isabel Socias

Background

Current benzodiazepine (BZD) prescription guidelines recommend short-term use to minimize the risk of dependence, cognitive impairment, and falls and fractures. However, many clinicians overprescribe BZDs and chronic use by patients is common. There is limited evidence on the effectiveness of interventions delivered by general practitioners (GPs) on reducing prescriptions and long-term use of BZDs. We aimed to evaluate the effectiveness of a multicomponent intervention for GPs that seeks to reduce BZD prescriptions and the prevalence of long-term users.

Methods and findings

We conducted a multicenter two-arm, cluster randomized controlled trial in 3 health districts in Spain (primary health centers [PHCs] in Balearic Islands, Catalonia, and Valencian Community) from September 2016 to May 2018. The 81 PHCs were randomly allocated to the intervention group (n = 41; 372 GPs) or the control group (n = 40; 377 GPs). GPs were not blinded to the allocation; however, pharmacists, researchers, and trial statisticians were blinded to the allocation arm. The intervention consisted of a workshop about the appropriate prescribing of BZDs and tapering-off long-term BZD use using a tailored stepped dose reduction with monthly BZD prescription feedback and access to a support web page. The primary outcome, based on 700 GPs (351 in the control group and 349 in the intervention group), compared changes in BZD prescriptions in defined daily doses (DDDs) per 1,000 inhabitants per day after 12 months. The 2 secondary outcomes were the proportion of long-term users (≥6 months) and the proportion of long-term users over age 65 years.Intention-to-treat (ITT) analysis was used to assess all clinical outcomes.Forty-nine GPs (21 intervention group and 28 control group) were lost to follow-up. However, all GPs were included in the ITT analysis. After 12 months, there were a statistically significant decline in total BZD prescription in the intervention group compared to the control group (mean difference: −3.24 DDDs per 1,000 inhabitants per day, 95% confidence interval (CI): −4.96, −1.53, p < 0.001). The intervention group also had a smaller number of long-term users. The adjusted absolute difference overall was −0.36 (95% CI: −0.55, −0.16, p > 0.001), and the adjusted absolute difference in long-term users over age 65 years was −0.87 (95% CI: −1.44, −0.30, p = 0.003). A key limitation of this clustered design clinical trial is the imbalance of some baseline characteristics. The control groups have a higher rate of baseline BZD prescription, and more GPs in the intervention group were women, GPs with a doctorate degree, and trainers of GP residents.

Conclusions

A multicomponent intervention that targeted GPs and included educational meeting, feedback about BZD prescriptions, and a support web page led to a statistically significant reduction of BZD prescriptions and fewer long-term users. Although the effect size was small, the high prevalence of BZD use in the general population suggests that large-scale implementation of this intervention could have positive effects on the health of many patients.

Trial registration

ISRCTN ISRCTN28272199.

Correction: COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness

Me, 04/05/2022 - 16:00

by Carl A. B Pearson, Fiammetta Bozzani, Simon R. Procter, Nicholas G. Davies, Maryam Huda, Henning Tarp Jensen, Marcus Keogh-Brown, Muhammad Khalid, Sedona Sweeney, Sergio Torres-Rueda, CHiL COVID-19 Working Group , CMMID COVID-19 Working Group , Rosalind M. Eggo, Anna Vassall, Mark Jit

Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial

Lu, 02/05/2022 - 16:00

by Christopher R. Sudfeld, Lilia Bliznashka, Aichatou Salifou, Ousmane Guindo, Issaka Soumana, Irène Adehossi, Céline Langendorf, Rebecca F. Grais, Sheila Isanaka

Background

It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.

Methods and findings

We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron–folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.

Conclusions

There was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.

Trial registration

ClinicalTrials.gov NCT02145000.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

Me, 27/04/2022 - 16:00

by Benjamin Speich, Dmitry Gryaznov, Jason W. Busse, Viktoria L. Gloy, Szimonetta Lohner, Katharina Klatte, Ala Taji Heravi, Nilabh Ghosh, Hopin Lee, Anita Mansouri, Ioana R. Marian, Ramon Saccilotto, Edris Nury, Benjamin Kasenda, Elena Ojeda–Ruiz, Stefan Schandelmaier, Yuki Tomonaga, Alain Amstutz, Christiane Pauli–Magnus, Karin Bischoff, Katharina Wollmann, Laura Rehner, Joerg J. Meerpohl, Alain Nordmann, Jacqueline Wong, Ngai Chow, Patrick Jiho Hong, Kimberly Mc Cord – De Iaco, Sirintip Sricharoenchai, Arnav Agarwal, Matthias Schwenkglenks, Lars G. Hemkens, Erik von Elm, Bethan Copsey, Alexandra N. Griessbach, Christof Schönenberger, Dominik Mertz, Anette Blümle, Belinda von Niederhäusern, Sally Hopewell, Ayodele Odutayo, Matthias Briel

Background

We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs.

Methods and findings

We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment.Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%).The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations.

Conclusions

We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study

Ma, 26/04/2022 - 16:00

by Anne Lærke Spangmose, Niels Skipper, Sine Knorr, Tina Wullum Gundersen, Rikke Beck Jensen, Peter Damm, Erik Lykke Mortensen, Anja Pinborg, Jannet Svensson, Tine Clausen

Background

Conflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group.

Methods and findings

This is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were −1.59 (95% CI −2.48 to −0.71, p < 0.001) between O-mT1D and O-BP and −0.78 (95% CI −1.48 to −0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D (p = 0.16). The study’s limitation was no access to measures of glycemic control during pregnancy.

Conclusions

O-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function.

Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts

Ma, 26/04/2022 - 16:00

by Jordi Merino, Marta Guasch-Ferré, Jun Li, Wonil Chung, Yang Hu, Baoshan Ma, Yanping Li, Jae H. Kang, Peter Kraft, Liming Liang, Qi Sun, Paul W. Franks, JoAnn E. Manson, Walter C. Willet, Jose C. Florez, Frank B. Hu

Background

Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes.

Methods and findings

We analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data.

Conclusions

These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.

Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data

Ma, 26/04/2022 - 16:00

by Dian Kusuma, Petya Atanasova, Elisa Pineda, Ranjit Mohan Anjana, Laksara De Silva, Abu AM Hanif, Mehedi Hasan, Md. Mokbul Hossain, Susantha Indrawansa, Deepal Jayamanne, Sujeet Jha, Anuradhani Kasturiratne, Prasad Katulanda, Khadija I Khawaja, Balachandran Kumarendran, Malay K Mridha, Vindya Rajakaruna, John C Chambers, Gary Frost, Franco Sassi, Marisa Miraldo

Background

The global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people’s diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex.

Methods and findings

We linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant’s home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual’s home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study’s key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere.

Conclusions

Our results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.

Social justice now for an equitable tomorrow: Reflections from the Consortium of Universities for Global Health Conference 2022

Ve, 22/04/2022 - 16:00

by Beryne Odeny, Callam Davidson

PLOS Medicine editors Beryne Odeny and Callam Davidson report from the Consortium of Universities for Global Health conference.

Correction: Ethnic inequalities in COVID-19 vaccine uptake and comparison to seasonal influenza vaccine uptake in Greater Manchester, UK: A cohort study

Ve, 22/04/2022 - 16:00

by Ruth Elizabeth Watkinson, Richard Williams, Stephanie Gillibrand, Caroline Sanders, Matt Sutton

Genetic associations of adult height with risk of cardioembolic and other subtypes of ischemic stroke: A mendelian randomization study in multiple ancestries

Ve, 22/04/2022 - 16:00

by Andrew B. Linden, Robert Clarke, Imen Hammami, Jemma C. Hopewell, Yu Guo, William N. Whiteley, Kuang Lin, Iain Turnbull, Yiping Chen, Canqing Yu, Jun Lv, Alison Offer, Derrick Bennett, Robin G. Walters, Liming Li, Zhengming Chen, Sarah Parish, for the China Kadoorie Biobank Collaborative Group

Background

Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke.

Methods and findings

Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations.

Conclusions

The findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.

Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial

Ve, 22/04/2022 - 16:00

by Keerthana Deepti Karunakaran, Barry D. Kussman, Ke Peng, Lino Becerra, Robert Labadie, Rachel Bernier, Delany Berry, Stephen Green, David Zurakowski, Mark E. Alexander, David Borsook

Background

Catheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.

Methods and findings

We investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children’s Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (NadirHbO, i.e., lowest oxyhemoglobin concentration and PeakHbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater NadirHbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater PeakHbO in inferior mFPC (MD = −1.138, 95% CI = −2.062, −0.214, p = 0.002) and superior mFPC (MD = −0.999, 95% CI = −1.961, −0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher PeakHbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher NadirHbO in posterior superior S1 (Pos. SS1; MD = −0.342, 95% CI = −0.680, −0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller NadirHbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller PeakHbO in superior mFPC (MD = −0.092, 95% CI = −0.680, −0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers.

Conclusions

We observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment.

Trial registration

ClinicalTrials.gov NCT02703090

Clustering of physical health multimorbidity in people with severe mental illness: An accumulated prevalence analysis of United Kingdom primary care data

Me, 20/04/2022 - 16:00

by Naomi Launders, Joseph F Hayes, Gabriele Price, David PJ Osborn

Background

People with severe mental illness (SMI) have higher rates of a range of physical health conditions, yet little is known regarding the clustering of physical health conditions in this population. We aimed to investigate the prevalence and clustering of chronic physical health conditions in people with SMI, compared to people without SMI.

Methods and findings

We performed a cohort-nested accumulated prevalence study, using primary care data from the Clinical Practice Research Datalink (CPRD), which holds details of 39 million patients in the United Kingdom. We identified 68,783 adults with a primary care diagnosis of SMI (schizophrenia, bipolar disorder, or other psychoses) from 2000 to 2018, matched up to 1:4 to 274,684 patients without an SMI diagnosis, on age, sex, primary care practice, and year of registration at the practice. Patients had a median of 28.85 (IQR: 19.10 to 41.37) years of primary care observations. Patients with SMI had higher prevalence of smoking (27.65% versus 46.08%), obesity (24.91% versus 38.09%), alcohol misuse (3.66% versus 13.47%), and drug misuse (2.08% versus 12.84%) than comparators. We defined 24 physical health conditions derived from the Elixhauser and Charlson comorbidity indices and used logistic regression to investigate individual conditions and multimorbidity. We controlled for age, sex, region, and ethnicity and then additionally for health risk factors: smoking status, alcohol misuse, drug misuse, and body mass index (BMI). We defined multimorbidity clusters using multiple correspondence analysis (MCA) and K-means cluster analysis and described them based on the observed/expected ratio. Patients with SMI had higher odds of 19 of 24 conditions and a higher prevalence of multimorbidity (odds ratio (OR): 1.84; 95% confidence interval [CI]: 1.80 to 1.88, p < 0.001) compared to those without SMI, particularly in younger age groups (males aged 30 to 39: OR: 2.49; 95% CI: 2.27 to 2.73; p < 0.001; females aged 18 to 30: OR: 2.69; 95% CI: 2.36 to 3.07; p < 0.001). Adjusting for health risk factors reduced the OR of all conditions. We identified 7 multimorbidity clusters in those with SMI and 7 in those without SMI. A total of 4 clusters were common to those with and without SMI; while 1, heart disease, appeared as one cluster in those with SMI and 3 distinct clusters in comparators; and 2 small clusters were unique to the SMI cohort. Limitations to this study include missing data, which may have led to residual confounding, and an inability to investigate the temporal associations between SMI and physical health conditions.

Conclusions

In this study, we observed that physical health conditions cluster similarly in people with and without SMI, although patients with SMI had higher burden of multimorbidity, particularly in younger age groups. While interventions aimed at the general population may also be appropriate for those with SMI, there is a need for interventions aimed at better management of younger-age multimorbidity, and preventative measures focusing on diseases of younger age, and reduction of health risk factors.

Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19: A multinational study using the ISARIC–WHO clinical characterisation protocol

Me, 20/04/2022 - 16:00

by Marina Wainstein, Samual MacDonald, Daniel Fryer, Kyle Young, Valeria Balan, Husna Begum, Aidan Burrell, Barbara Wanjiru Citarella, J. Perren Cobb, Sadie Kelly, Kalynn Kennon, James Lee, Laura Merson, Srinivas Murthy, Alistair Nichol, Malcolm G. Semple, Samantha Strudwick, Steven A. Webb, Patrick Rossignol, Rolando Claure-Del Granado, Sally Shrapnel, the ISARIC Clinical Characterisation Group

Background

Acute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesised that an extended KDIGO (eKDIGO) definition, adapted from the International Society of Nephrology (ISN) 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI (CA-AKI) with similarly poor outcomes as previously reported in this population.

Methods and findings

All individuals recruited using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)–World Health Organization (WHO) Clinical Characterisation Protocol (CCP) and admitted to 1,609 hospitals in 54 countries with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection from February 15, 2020 to February 1, 2021 were included in the study. Data were collected and analysed for the duration of a patient’s admission. Incidence, staging, and timing of AKI were evaluated using a traditional and eKDIGO definition, which incorporated a commensurate decrease in sCr. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristics and outcomes—intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital death—were compared for all 3 groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. A total of 75,670 patients were included in the final analysis cohort. Median length of admission was 12 days (interquartile range [IQR] 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7% versus 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% versus 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% versus 23%) invasive ventilation (45% versus 15%), and increased mortality (38% versus 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted odds ratio: 1.78, 95% confidence interval: 1.71 to 1.80, p-value < 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% versus 50% death and 35% versus 70% ICU admission) but significantly higher when compared to patients with no AKI (25% versus 19% death and 35% versus 23% ICU admission) (all p-values <5 × 10−5). Limitations include ad hoc sCr sampling, exclusion of patients with less than two sCr measurements, and limited availability of sCr measurements prior to initiation of acute dialysis.

Conclusions

An extended KDIGO definition of AKI resulted in a significantly higher detection rate in this population. These additional cases of AKI occurred early in the hospital admission and were associated with worse outcomes compared to patients without AKI.

Evaluation of the Mexican warning label nutrient profile on food products marketed in Mexico in 2016 and 2017: A cross-sectional analysis

Me, 20/04/2022 - 16:00

by Alejandra Contreras-Manzano, Carlos Cruz-Casarrubias, Ana Munguía, Alejandra Jáuregui, Jorge Vargas-Meza, Claudia Nieto, Lizbeth Tolentino-Mayo, Simón Barquera

Background

Different nutrient profiles (NPs) have been developed in Latin America to assess the nutritional quality of packaged food products. Recently, the Mexican NP was developed as part of the new warning label regulation implemented in 2020, considering 5 warning octagons (calories, sugar, sodium, saturated fats, and trans fats) and 2 warning rectangles (caffeine and non-nutritive sweeteners). The objective of this cross-sectional study was to evaluate the Mexican NP and other NPs proposed or used in Latin America against the Pan American Health Organization (PAHO) model.

Methods and findings

Nutrition content data of 38,872 packaged food products available in the Mexican market were collected in 2016 and 2017. The evaluation of the Mexican NP, including its 3 implementation phases of increasing stringency (2020, 2023, and 2025), was conducted by comparing the percentage of products classified as “healthy” (without warnings) or “less healthy” (with 1 or more warnings), as well as the number and type of warnings assigned to food products, against the PAHO NP. Using the calibration method, we compared the classifications produced by the PAHO model against those produced by the NP models of Ecuador, Chile (3 phases), Peru (2 phases), Uruguay, and Brazil. Kappa coefficients and Pearson correlations were estimated, and proportion tests were performed. We found that the 3 implementation phases of the Mexican NP had near to perfect agreement in the classification of healthy foods (Mexico NP models: 19.1% to 23.8%; PAHO model: 19.7%) and a strong correlation (>91.9%) with the PAHO model. Other NPs with high agreement with the PAHO model were the Ecuador (89.8%), Uruguay (82.5%), Chile Phase 3 (82.3%), and Peru Phase 2 (84.2%) NPs. In contrast, the Peru Phase 1, Brazil, and Chile Phase 1 NP models had the highest percentage of foods classified as healthy (49.2%, 47.1%, and 46.5%, respectively) and the lowest agreement with the PAHO model (69.9%, 69.3%, and 73%, respectively). Study limitations include that warnings considered by the Mexican NP models were evaluated as if all the warnings were octagon seals, while 2 out of the 7 were rectangular warnings (caffeine and non-nutritive sweeteners), and that our data are limited by the quality of the information reported in the list of ingredients and the nutrition facts table of the products.

Conclusions

The 3 implementation phases of the Mexican NP were useful to identify healthy food products. In contrast, the Peru Phase 1, Brazil, and Chile Phase 1 NP models may have limited usefulness for the classification of foods according to the content of ingredients of concern. The results of this study may inform countries seeking to adapt and evaluate existing NP models for use in population-specific applications.

Evaluation of an online intervention for improving stroke survivors’ health-related quality of life: A randomised controlled trial

Ma, 19/04/2022 - 16:00

by Ashleigh Guillaumier, Neil J. Spratt, Michael Pollack, Amanda Baker, Parker Magin, Alyna Turner, Christopher Oldmeadow, Clare Collins, Robin Callister, Chris Levi, Andrew Searles, Simon Deeming, Brigid Clancy, Billie Bonevski

Background

The aim of this trial was to evaluate the effectiveness of an online health behaviour change intervention—Prevent 2nd Stroke (P2S)—at improving health-related quality of life (HRQoL) amongst stroke survivors at 6 months of follow-up.

Methods and findings

A prospective, blinded-endpoint randomised controlled trial, with stroke survivors as the unit of randomisation, was conducted between March 2018 and November 2019. Adult stroke survivors between 6 and 36 months post-stroke with capacity to use the intervention (determined by a score of ≥4 on the Modified Rankin Scale) and who had access and willingness to use the internet were recruited via mail-out invitations from 1 national and 1 regional stroke registry. Participants completed baseline (n = 399) and 6-month follow-up (n = 356; 89%) outcome assessments via computer-assisted telephone interviewing (CATI). At baseline the sample had an average age of 66 years (SD 12), and 65% were male. Randomisation occurred at the end of the baseline survey; CATI assessors and independent statisticians were blind to group allocation. The intervention group received remote access for a 12-week period to the online-only P2S program (n = 199; n = 28 lost at follow-up). The control group were emailed and posted a list of internet addresses of generic health websites (n = 200; n = 15 lost at follow-up). The primary outcome was HRQoL as measured by the EuroQol Visual Analogue Scale (EQ-VAS; self-rated global health); the outcome was assessed for differences between treatment groups at follow-up, adjusting for baseline measures. Secondary outcomes were HRQoL as measured by the EQ-5D (descriptive health state), diet quality, physical activity, alcohol consumption, smoking status, mood, physical functioning, and independent living. All outcomes included the variable ‘stroke event (stroke/transient ischaemic attack/other)’ as a covariate, and analysis was intention-to-treat. At 6 months, median EQ-VAS HRQoL score was significantly higher in the intervention group than the control group (85 vs 80, difference 5, 95% CI 0.79–9.21, p = 0.020). The results were robust to the assumption the data were missing at random; however, the results were not robust to the assumption that the difference in HRQoL between those with complete versus missing data was at least 3 points. Significantly higher proportions of people in the intervention group reported no problems with personal care (OR 2.17, 95% CI 1.05–4.48, p = 0.0359) and usual activities (OR 1.66, 95% CI 1.06–2.60, p = 0.0256) than in the control group. There were no significant differences between groups on all other secondary outcomes. The main limitation of the study is that the sample comprises mostly ‘well’ stroke survivors with limited to no disability.

Conclusions

The P2S online healthy lifestyle program improved stroke survivors’ self-reported global ratings of HRQoL (as measured by EQ-VAS) at 6-month follow-up. Online platforms represent a promising tool to engage and support some stroke survivors.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12617001205325.