BMC Medicine

Jackson, Sarah E.; Brown, Jamie; Notley, Caitlin; Shahab, Lion; Cox, Sharon

2024 BMC Medicine

doi: 10.1186/s12916-024-03311-4pmid: 38632570

BackgroundTobacco smoking affects women’s fertility and is associated with substantial risks of adverse pregnancy outcomes. This study explored trends by socioeconomic position in patterns of smoking, use of non-combustible nicotine products, and quitting activity among women of reproductive age in England.MethodsData come from a nationally representative monthly cross-sectional survey. Between October 2013 and October 2023, 197,266 adults (≥ 18 years) were surveyed, of whom 44,052 were women of reproductive age (18–45 years). Main outcome measures were current smoking, vaping, and use of nicotine replacement therapy (NRT), heated tobacco products (HTPs), and nicotine pouches; mainly/exclusively smoking hand-rolled cigarettes and level of dependence among current smokers; past-year quit attempts among past-year smokers; and success of quit attempts among those who tried to quit. We modelled time trends in these outcomes, overall and by occupational social grade (ABC1 = more advantaged/C2DE = less advantaged).ResultsSmoking prevalence among women of reproductive age fell from 28.7% [95%CI = 26.3–31.2%] to 22.4% [19.6–25.5%] in social grades C2DE but there was an uncertain increase from 11.7% [10.2–13.5%] to 14.9% [13.4–16.6%] in ABC1. By contrast, among all adults and among men of the same age, smoking prevalence remained relatively stable in ABC1. Vaping prevalence among women of reproductive age more than tripled, from 5.1% [4.3–6.0%] to 19.7% [18.0–21.5%], with the absolute increase more pronounced among those in social grades C2DE (reaching 26.7%; 23.3–30.3%); these changes were larger than those observed among all adults but similar to those among men of the same age. The proportion of smokers mainly/exclusively smoking hand-rolled cigarettes increased from 40.5% [36.3–44.9%] to 61.4% [56.5–66.1%] among women of reproductive age; smaller increases were observed among all adults and among men of the same age. Patterns on other outcomes were largely similar between groups.ConclusionsAmong women of reproductive age, there appears to have been a rise in smoking prevalence in the more advantaged social grades over the past decade. Across social grades, there have been substantial increases in the proportion of women of reproductive age who vape and shifts from use of manufactured to hand-rolled cigarettes among those who smoke. These changes have been more pronounced than those observed in the general adult population over the same period.

Wen, Sai; Xu, Nannan; Zhao, Lianhui; Yang, Lulu; Yang, Hui; Chang, Caiyun; Wang, Shanshan; Qu, Chunmei; Song, Li; Zou, Wenlu; He, Yishan; Wang, Gang

2024 BMC Medicine

doi: 10.1186/s12916-024-03421-zpmid: 38764059

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS.MethodsWe conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching.ResultsBetween Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported.ConclusionsOur findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed.Trail registrationChiCTR2200063759, September 16, 2022.

Dwaraka, Varun B.; Aronica, Lucia; Carreras-Gallo, Natalia; Robinson, Jennifer L.; Hennings, Tayler; Carter, Matthew M.; Corley, Michael J.; Lin, Aaron; Turner, Logan; Smith, Ryan; Mendez, Tavis L.; Went, Hannah; Ebel, Emily R.; Sonnenburg, Erica D.; Sonnenburg, Justin L.; Gardner, Christopher D.

2024 BMC Medicine

doi: 10.1186/s12916-024-03513-wpmid: 39069614

BackgroundGeroscience focuses on interventions to mitigate molecular changes associated with aging. Lifestyle modifications, medications, and social factors influence the aging process, yet the complex molecular mechanisms require an in-depth exploration of the epigenetic landscape. The specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous diet, remain underexplored despite potential impacts on aging-related outcomes.MethodsThis study examined the impact of an entirely plant-based or healthy omnivorous diet over 8 weeks on blood DNA methylation in paired twins. Various measures of epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE) were assessed, along with system-specific effects (Inflammation, Heart, Hormone, Liver, and Metabolic). Methylation surrogates of clinical, metabolite, and protein markers were analyzed to observe diet-specific shifts.ResultsDistinct responses were observed, with the vegan cohort exhibiting significant decreases in overall epigenetic age acceleration, aligning with anti-aging effects of plant-based diets. Diet-specific shifts were noted in the analysis of methylation surrogates, demonstrating the influence of diet on complex trait prediction through DNA methylation markers. An epigenome-wide analysis revealed differentially methylated loci specific to each diet, providing insights into the affected pathways.ConclusionsThis study suggests that a short-term vegan diet is associated with epigenetic age benefits and reduced calorie intake. The use of epigenetic biomarker proxies (EBPs) highlights their potential for assessing dietary impacts and facilitating personalized nutrition strategies for healthy aging. Future research should explore the long-term effects of vegan diets on epigenetic health and overall well-being, considering the importance of proper nutrient supplementation.Trial registrationClinicaltrials.gov identifier: NCT05297825

Dodd, Jodie M.; Louise, Jennie; Deussen, Andrea R.; Mitchell, Megan; Poston, Lucilla

2024 BMC Medicine

doi: 10.1186/s12916-024-03410-2pmid: 38750522

BackgroundThe aim of this study was to evaluate commonly assumed causal relationships between body mass index (BMI), gestational weight gain (GWG), and adverse pregnancy outcomes, which have formed the basis of guidelines and interventions aimed at limiting GWG in women with overweight or obesity. We explored relationships between maternal BMI, total GWG (as a continuous variable and as ‘excessive’ GWG), and pregnancy outcomes (including infant birthweight measures and caesarean birth).MethodsAnalysis of individual participant data (IPD) from the i-WIP (International Weight Management in Pregnancy) Collaboration, from randomised trials of diet and/or physical activity interventions during pregnancy reporting GWG and maternal and neonatal outcomes.Women randomised to the control arm of 20 eligible randomised trials (4370 of 8908 participants) from the i-WIP dataset of 36 randomised trials (total 12,240 women). The main research questions were to characterise the relationship between maternal BMI and (a) total GWG, (b) the risk of ‘excessive’ GWG (using the Institute of Medicine’s guidelines), and (c) adverse pregnancy outcomes as mediated via GWG versus other pathways to determine the extent to which the observed effect of maternal BMI on pregnancy outcomes is mediated via GWG. We utilised generalised linear models and regression-based mediation analyses within an IPD meta-analysis framework.ResultsMean GWG decreased linearly as maternal BMI increased; however, the risk of ‘excessive’ GWG increased markedly at BMI category thresholds (i.e. between the normal and overweight BMI category threshold and between the overweight and obese BMI category threshold). Increasing maternal BMI was associated with increased risk of all pregnancy outcomes assessed; however, there was no evidence that this effect was mediated via effects on GWG.ConclusionsThere is evidence of a meaningful relationship between maternal BMI and GWG and between maternal BMI and adverse pregnancy outcomes. There is no evidence that the effect of maternal BMI on outcomes is via an effect on GWG. Our analyses also cast doubt on the existence of a relationship between ‘excessive’ GWG and adverse pregnancy outcomes. Our findings challenge the practice of actively managing GWG throughout pregnancy.

Garchitorena, Andres; Harimanana, Aina; Irinantenaina, Judickaelle; Razanadranaivo, Hobisoa Léa; Rasoanaivo, Tsinjo Fehizoro; Sayre, Dean; Gutman, Julie R.; Mangahasimbola, Reziky Tiandraza; Ravaoarimanga, Masiarivony; Raobela, Oméga; Razafimaharo, Lala Yvette; Ralemary, Nicolas; Andrianasolomanana, Mahefa; Pontarollo, Julie; Mukerabirori, Aline; Ochieng, Walter; Dentinger, Catherine M.; Kapesa, Laurent; Steinhardt, Laura C.

2024 BMC Medicine

doi: 10.1186/s12916-024-03441-9pmid: 38853263

BackgroundGlobal progress on malaria control has stalled recently, partly due to challenges in universal access to malaria diagnosis and treatment. Community health workers (CHWs) can play a key role in improving access to malaria care for children under 5 years (CU5), but national policies rarely permit them to treat older individuals. We conducted a two-arm cluster randomized trial in rural Madagascar to assess the impact of expanding malaria community case management (mCCM) to all ages on health care access and use.MethodsThirty health centers and their associated CHWs in Farafangana District were randomized 1:1 to mCCM for all ages (intervention) or mCCM for CU5 only (control). Both arms were supported with CHW trainings on malaria case management, community sensitization on free malaria care, monthly supervision of CHWs, and reinforcement of the malaria supply chain. Cross-sectional household surveys in approximately 1600 households were conducted at baseline (Nov–Dec 2019) and endline (Nov–Dec 2021). Monthly data were collected from health center and CHW registers for 36 months (2019–2021). Intervention impact was assessed via difference-in-differences analyses for survey data and interrupted time-series analyses for health system data.ResultsRates of care-seeking for fever and malaria diagnosis nearly tripled in both arms (from less than 25% to over 60%), driven mostly by increases in CHW care. Age-expanded mCCM yielded additional improvements for individuals over 5 years in the intervention arm (rate ratio for RDTs done in 6–13-year-olds, RRRDT6–13 years = 1.65; 95% CIs 1.45–1.87), but increases were significant only in health system data analyses. Age-expanded mCCM was associated with larger increases for populations living further from health centers (RRRDT6–13 years = 1.21 per km; 95% CIs 1.19–1.23).ConclusionsExpanding mCCM to all ages can improve universal access to malaria diagnosis and treatment. In addition, strengthening supply chain systems can achieve significant improvements even in the absence of age-expanded mCCM.Trial registrationThe trial was registered at the Pan-African Clinical Trials Registry (#PACTR202001907367187).

Stuber, Josine M.; Mackenbach, Joreintje D.; de Bruijn, Gert-Jan; Gillebaart, Marleen; Hoenink, Jody C.; Middel, Cédric N. H.; de Ridder, Denise T. D.; van der Schouw, Yvonne T.; Smit, Edith G.; Velema, Elizabeth; Vos, Anne L.; Waterlander, Wilma E.; Lakerveld, Jeroen; Beulens, Joline W. J.; ,

2024 BMC Medicine

doi: 10.1186/s12916-024-03268-4pmid: 38303069

BackgroundContext-specific interventions may contribute to sustained behaviour change and improved health outcomes. We evaluated the real-world effects of supermarket nudging and pricing strategies and mobile physical activity coaching on diet quality, food-purchasing behaviour, walking behaviour, and cardiometabolic risk markers.MethodsThis parallel cluster-randomised controlled trial included supermarkets in socially disadvantaged neighbourhoods across the Netherlands with regular shoppers aged 30–80 years. Supermarkets were randomised to receive co-created nudging and pricing strategies promoting healthier purchasing (N = 6) or not (N = 6). Nudges targeted 9% of supermarket products and pricing strategies 3%. Subsequently, participants were individually randomised to a control (step counter app) or intervention arm (step counter and mobile coaching app) to promote walking. The primary outcome was the average change in diet quality (low (0) to high (150)) over all follow-up time points measured with a validated 40-item food frequency questionnaire at baseline and 3, 6, and 12 months. Secondary outcomes included healthier food purchasing (loyalty card-derived), daily step count (step counter app), cardiometabolic risk markers (lipid profile and HbA1c via finger prick, and waist circumference via measuring tape), and supermarket customer satisfaction (questionnaire-based: very unsatisfied (1) to very satisfied (7)), evaluated using linear mixed-models. Healthy supermarket sales (an exploratory outcome) were analysed via controlled interrupted time series analyses.ResultsOf 361 participants (162 intervention, 199 control), 73% were female, the average age was 58 (SD 11) years, and 42% were highly educated. Compared to the control arm, the intervention arm showed no statistically significant average changes over time in diet quality (β − 1.1 (95% CI − 3.8 to 1.7)), percentage healthy purchasing (β 0.7 ( − 2.7 to 4.0)), step count (β − 124.0 (− 723.1 to 475.1), or any of the cardiometabolic risk markers. Participants in the intervention arm scored 0.3 points (0.1 to 0.5) higher on customer satisfaction on average over time. Supermarket-level sales were unaffected (β − 0.0 (− 0.0 to 0.0)).ConclusionsCo-created nudging and pricing strategies that predominantly targeted healthy products via nudges were unable to increase healthier food purchases and intake nor improve cardiometabolic health. The mobile coaching intervention did not affect step count. Governmental policy measures are needed to ensure more impactful supermarket modifications that promote healthier purchases.Trial registrationDutch Trial Register ID NL7064, 30 May 2018, https://www.onderzoekmetmensen.nl/en/trial/20990

Øien, Henning; Gjesvik, Jonas; Skyrud, Katrine Damgaard; Rotevatn, Torill Alise; Grøsland, Mari

2024 BMC Medicine

doi: 10.1186/s12916-024-03523-8pmid: 39113056

BackgroundThis paper investigates the consequences of the COVID-19 pandemic on mortality and hospitalization among nursing home residents in Norway. While existing evidence shows that nursing home residents were overrepresented among COVID-19-related deaths, suggesting inadequate protection measures, this study argues that the observed overrepresentation in mortality and hospitalization may partly stem from the inherent frailty of this demographic. Using nationwide administrative data, we assessed excess deaths and hospitalization by comparing pandemic-era rates to those of a pre-pandemic cohort.MethodsWe compared mortality and hospitalization rates between a pandemic cohort of nursing home residents as of September 2019 (N = 30,052), and a pre-pandemic cohort as of September 2017 (N = 30,429). Both cohorts were followed monthly for two years, beginning in September 2019 and 2017, respectively. This analysis was conducted at the national level and separately for nursing home residents in areas with low, medium, and high SARS-CoV-2 community transmission. Event studies and difference-in-difference models allowed us to separate the impact of the pandemic on mortality and hospitalization from secular and seasonal changes.ResultsThe pandemic cohort experienced a non-significant 0.07 percentage points (95% confidence interval (CI): − 0.081 to 0.221) increase in all-cause mortality during the 18 months following pandemic onset, compared to the pre-pandemic cohort. Moreover, our findings indicate a substantial reduction in hospitalizations of 0.27 percentage points (95% CI: − 0.464 to − 0.135) and a non-significant decrease of 0.80 percentage points (95% CI: − 2.529 to 0.929) in the proportion of nursing home residents hospitalized before death. The effect on mortality remained consistent across regions with both high and low levels of SARS-CoV-2 community transmission.ConclusionsOur findings indicate no clear evidence of excess all-cause mortality in Norway during the pandemic, neither nationally nor in areas with high infection rates. This suggests that early implementation of nationwide and nursing home-specific infection control measures during the pandemic effectively protected nursing home residents. Furthermore, our results revealed a decrease in hospitalizations, both overall and prior to death, suggesting that nursing homes adhered to national guidelines promoting on-site treatment for residents.

Lindsay, Calum; Baruffati, David; Mackenzie, Mhairi; Ellis, David A.; Major, Michelle; O’Donnell, Catherine A.; Simpson, Sharon A.; Williamson, Andrea E.; Wong, Geoff

2024 BMC Medicine

doi: 10.1186/s12916-024-03456-2pmid: 38858690

BackgroundAlthough missed appointments in healthcare have been an area of concern for policy, practice and research, the primary focus has been on reducing single ‘situational’ missed appointments to the benefit of services. Little attention has been paid to the causes and consequences of more ‘enduring’ multiple missed appointments in primary care and the role this has in producing health inequalities.MethodsWe conducted a realist review of the literature on multiple missed appointments to identify the causes of ‘missingness.’ We searched multiple databases, carried out iterative citation-tracking on key papers on the topic of missed appointments and identified papers through searches of grey literature. We synthesised evidence from 197 papers, drawing on the theoretical frameworks of candidacy and fundamental causation.ResultsMissingness is caused by an overlapping set of complex factors, including patients not identifying a need for an appointment or feeling it is ‘for them’; appointments as sites of poor communication, power imbalance and relational threat; patients being exposed to competing demands, priorities and urgencies; issues of travel and mobility; and an absence of choice or flexibility in when, where and with whom appointments take place.ConclusionsInterventions to address missingness at policy and practice levels should be theoretically informed, tailored to patients experiencing missingness and their identified needs and barriers; be cognisant of causal domains at multiple levels and address as many as practical; and be designed to increase safety for those seeking care.

Sheng, Chang; Lu, Xin-Wu; Shi, Hong-Tao; Zhang, Lei; Wan, Sheng-Yun; Li, Hong-Pu; Li, Ke; Shi, Sen; Liu, Zhen-Jie; Luo, Yu-Xian; Chen, Guo-Dong; Liu, Mao-Rong; Kang, You-Gen; Ye, Bo; Yao, Kai; Yang, Pu; Wang, Wei; ,

2024 BMC Medicine

doi: 10.1186/s12916-024-03545-2pmid: 39113028

BackgroundA stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction.MethodsEligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures.ResultsBetween December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14–4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93–95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (− 4.30 ± 3.66) and 12 months (− 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001).ConclusionsThe 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.

Liu, Jing; Hu, Dan; Lin, Yibin; Chen, Xiaoxi; Yang, Ruowei; Li, Li; Zhan, Yanyan; Bao, Hua; Zang, LeLe; Zhu, Mingxuan; Zhu, Fei; Yan, Junrong; Zhu, Dongqin; Zhang, Huiqi; Xu, Benhua; Xu, Qin

2024 BMC Medicine

doi: 10.1186/s12916-024-03531-8pmid: 39075419

BackgroundUterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignancy with a favorable prognosis if detected early. However, there is a lack of accurate and reliable early detection tests for UCEC. This study aims to develop a precise and non-invasive diagnostic method for UCEC using circulating cell-free DNA (cfDNA) fragmentomics.MethodsPeripheral blood samples were collected from all participants, and cfDNA was extracted for analysis. Low-coverage whole-genome sequencing was performed to obtain cfDNA fragmentomics data. A robust machine learning model was developed using these features to differentiate between UCEC and healthy conditions.ResultsThe cfDNA fragmentomics-based model showed high predictive power for UCEC detection in training (n = 133; AUC 0.991) and validation cohorts (n = 89; AUC 0.994). The model manifested a specificity of 95.5% and a sensitivity of 98.5% in the training cohort, and a specificity of 95.5% and a sensitivity of 97.8% in the validation cohort. Physiological variables and preanalytical procedures had no significant impact on the classifier’s outcomes. In terms of clinical benefit, our model would identify 99% of Chinese UCEC patients at stage I, compared to 21% under standard care, potentially raising the 5-year survival rate from 84 to 95%.ConclusionThis study presents a novel approach for the early detection of UCEC using cfDNA fragmentomics and machine learning showing promising sensitivity and specificity. Using this model in clinical practice could significantly improve UCEC management and control, enabling early intervention and better patient outcomes. Further optimization and validation of this approach are warranted to establish its clinical utility.