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Abstract Background Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called “vanishing microbiomes” potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations. Results Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the USA within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain sources. Conclusion Our findings demonstrate that by studying populations within Nepal, we can isolate an important role of lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes. Video Abstract

Abstract Pancreatic cancer is known to be the most lethal cancer. Fewer new treatments are being developed for pancreatic cancer as compared to other cancers. The bioactive lipid S1P, which is mainly regulated by sphingosine kinase 1 (SK1) and sphingosine kinase 2 (SK2) enzymes, plays significant roles in pancreatic cancer initiation and exacerbation. S1P controls many signaling pathways to modulate the progression of pancreatic cancer through the G-coupled receptor S1PR1-5. Several papers reporting amelioration of pancreatic cancer via modulation of S1P levels or downstream signaling pathways have previously been published. In this paper, for the first time, we have reviewed the results of previous studies to understand how S1P and its receptors contribute to the development of pancreatic cancer, and whether S1P can be a therapeutic target. In addition, we have also reviewed papers dealing with the effects of SK1 and SK2, which are kinases that regulate the level of S1P, on the pathogenesis of pancreatic cancer. We have also listed available drugs that particularly focus on S1P, S1PRs, SK1, and SK2 for the treatment of pancreatic cancer. Through this review, we would like to suggest that the SK/S1P/S1PR signaling system can be an important target for treating pancreatic cancer, where a new treatment target is desperately warranted.

Abstract Introduction Gastric antral vascular ectasia is an uncommon clinical disease that affects elder people and is characterized by severe chronic upper gastrointestinal bleeding mainly affecting the gastric antrum. It is generally unusual among patients undergoing maintenance hemodialysis for chronic kidney disease. Case presentation Here, we aim to present an uncommon case of incidental diagnosis of the gastric antral vascular ectasia and erosive gastritis in a 71-year-old Hindu male patient belonging to the Gurung ethnicity of Nepal undergoing maintenance hemodialysis due to chronic kidney disease. The patient presented with a history of melena and fatigue. On investigation, a low hemoglobin level of 7.3 gm% was used for blood transfusion. The patient was on regular hemodialysis after admission at our institution. Upper gastrointestinal bleeding was suspected after analyzing patient’s history and investigations. Therefore, an upper gastrointestinal endoscopy was performed that showed linear ectatic punctuate lesions radiating from the body of the stomach to the antrum, and hence, an incidental diagnosis of the gastric antral vascular ectasia was made. Initial fluid resuscitation, iron therapy, and a triple regimen were administered. Proper management with argon plasma coagulation therapy was scheduled at another institution due to lack of respective facilities in our institution. Discussion Gastric antral vascular ectasia is an unusual cause of upper gastrointestinal bleeding, primarily affecting the gastric antrum and pylorus with rare cases affecting the duodenum, jejunum, and gastric fundus. It is generally associated with other chronic disease conditions. Several hypotheses have been proposed for the pathogenesis of gastric antral vascular ectasia, especially its association with chronic kidney disease, as in our case, which is considered to be rare. Management varies from medical to endoscopic interventions to even surgery. Conclusion Prompt proper diagnosis and treatment for the gastric antral vascular ectasia should be sought, as it is frequently misdiagnosed or missed during upper gastrointestinal endoscopy. Our case report presents a case of gastric antral vascular ectasia in chronic kidney disease undergoing maintenance hemodialysis, which is quite uncommon, as literature has suggested the same point.

Abstract Background Five decades into the era of mass incarceration, a growing number of older adults have experienced criminal legal involvement (CLI) in their lifetime. Studies have shown that prior incarceration is associated with substantial disease burden, but little is known about the distinct needs and utilization patterns of middle-aged and older adults with lifetime CLI compared to those without. Using a nationally representative data set, we tested the association between lifetime CLI exposure and use of acute care services among middle-aged and older adults. Methods Our sample included 44,007 US adults (25,074 middle-aged-50-64 years; 18,709 older- ≥65 years) who participated in the National Survey of Drug Use and Health (2015–2019). The data is publicly available. Our independent variable was lifetime CLI. Using separate negative binomial regression models for middle-aged and older adults, we tested the association between lifetime CLI and acute healthcare utilization (ED visits and nights spent inpatient) controlling for relevant sociodemographic covariates. Results For middle-aged respondents, 19.1% reported lifetime CLI; for older adults, the rate of exposure was 9.6%. In multivariate models, CLI was associated with increased ED visits in middle-aged adults (IRR 1.18, 95% CI 1.06–1.31) but not older adults (IRR 0.99, 95% CI 0.85–1.16). CLI was associated with increased nights hospitalized in both groups (middle-aged: IRR 1.33, 95% CI 1.08–1.62; older adults: IRR 1.26, 95% CI 1.01, 1.57). Conclusion Middle-aged and older adults with lifetime CLI experience higher rates of acute care utilization than their peers with no lifetime CLI, even after adjustment for confounders. As the cohort of adults from the era of mass incarceration ages, understanding the mechanisms by which lifetime CLI impacts health outcomes is crucial in designing interventions to improve outcomes and reduce unnecessary acute healthcare utilization.

Abstract Background Myocardial bridging is a cardiac anomaly where a segment of epicardial coronary arteries runs through the myocardium and can rarely cause MI. Takotsubo syndrome is a stress-induced cardiomyopathy that can mimic MI. Catecholamine surge during stress can contribute to Takotsubo syndrome, but whether this surge can trigger an inconspicuous myocardial bridging to manifest symptomatically remains unclear, and alternately, whether a myocardial bridge might cause worsening of Takotsubo syndrome is also a matter that needs further research. Case presentation We report the case of a patient who initially presented with features of acute exacerbation of bronchiectasis and subsequently developed symptoms and ECG features suggestive of acute myocardial infarction. Echocardiography revealed features of takotsubo syndrome, and complete myocardial bridging was revealed via coronary angiography. The patient was managed conservatively with pharmacological treatment, and after a few days, echocardiographic features were reversed. As such, the diagnosis shifted toward Takotsubo syndrome with myocardial stunning due to co-existent myocardial bridging. Conclusion We report a rare case of a patient with acute bronchiectasis exacerbation with features suggestive of acute myocardial infarction who had findings of Takotsubo syndrome and complete myocardial bridging. In the beginning, it was difficult to determine whether the symptoms arose due to acute MI resulting from myocardial bridging or were solely due to takotsubo syndrome because of stress from bronchiectasis. Although myocardial bridging is often overlooked as an etiology for acute MI, this case highlights the importance of expanding the differential diagnosis to myocardial bridging in the work-up for the cause of acute MI and how Takotsubo syndrome can mimic acute MI and pose a diagnostic challenge.

Abstract Examining the future trajectory of the Sustainable Development Goals (SDGs) reveals that challenges persist in achieving their targets. While each SDG embodies unique aspirations, overarching challenges permeate its implementation. This paper, with its primary goal to raise awareness about the challenges of SDG 10, directs attention to the challenges surrounding SDG 10, focusing on reducing inequality within and among countries. Through a concise exploration, it identifies five major obstacles impeding progress toward this goal. Firstly, economic inequality poses a significant barrier, with disparities in income and wealth acting as major hindrances to achieving equality. Secondly, social exclusion exacerbates these inequalities, with marginalized groups such as minorities, women, and people with disabilities facing significant barriers to accessing resources and opportunities. Thirdly, political barriers, including a lack of political will and ineffective governance systems, are impeding efforts to address inequality and promote inclusive policies. The fourth challenge is unequal education and healthcare access, perpetuating social and economic disparities. Finally, global economic interdependence, driven by globalization, is exacerbating inequalities between countries, particularly in areas such as trade, finance, and technology access. By delineating these challenges within SDG 10, this paper aims to underscore the multifaceted nature of inequality and the imperative for targeted interventions to advance sustainable development. It’s important to note that addressing these challenges is not a task for one entity, but requires the collective efforts of all stakeholders. It necessitates innovative strategies and, most importantly, collaborative partnerships to foster a more equitable and inclusive world. Your involvement, as a key stakeholder, is crucial in this endeavor.

Abstract Background The high prevalence of osteoporosis has increased the economic burden on the health system globally. The burden of osteoporosis and its associated factors have not been adequately assessed in community settings in the Nepalese context thus far. Therefore, this study aimed to assess the prevalence of osteoporosis and its associated factors, lifestyle behaviors, and dietary calcium intake. Methods A community-based cross-sectional study was conducted among 395 people aged 50 years and older in the Madhesh Province of Nepal between July 2022 and August 2023. The Osteoporosis Self-assessment Tools for Asians (OSTA) index was used to measure osteoporosis. A structured questionnaire was used to collect sociodemographic information, anthropometric data, lifestyle behavior, daily dietary calcium intake, and frequency of calcium-rich food consumption. A food frequency questionnaire and 24-hour recall methods were used to assess dietary intake. The chi-square test, binary logistic regression and Mann‒Whitney U test were applied to measure the association between predictors and the outcome of interest. Results The prevalence of no risk, moderate risk and high risk of osteoporosis were 38.7%, 39%, and 22.3% respectively. The risk of osteoporosis was higher in females (aOR = 5.18, CI: 2.10-12.75, p

Abstract Background The steep rise in substance use and substance use disorder (SUD) shows an urgency to assess its prevalence using valid measures. This systematic review summarizes the validity of measures to assess the prevalence of substance use and SUD in the US estimated in population and sub-population-based surveys. Methods A literature search was performed using nine online databases. Studies were included in the review if they were published in English and tested the validity of substance use and SUD measures among US adults at the general or sub-population level. Independent reviews were conducted by the authors to complete data synthesis and assess the risk of bias. Results Overall, 46 studies validating substance use/SUD (n = 46) measures were included in this review, in which 63% were conducted in clinical settings and 89% assessed the validity of SUD measures. Among the studies that assessed SUD screening measures, 78% examined a generic SUD measure, and the rest screened for specific disorders. Almost every study used a different survey measure. Overall, sensitivity and specificity tests were conducted in over a third of the studies for validation, and 10 studies used receiver operating characteristics curve. Conclusion Findings suggest a lack of standardized methods in surveys measuring and reporting prevalence of substance use/SUD among US adults. It highlights a critical need to develop short measures for assessing SUD that do not require lengthy, time-consuming data collection that would be difficult to incorporate into population-based surveys assessing a multitude of health dimensions. Systematic review registration PROSPERO CRD42022298280.

Abstract Background Patients with obesity presenting in need of surgical intervention are at 2-to-sixfold higher risk of prolonged hospitalization, infectious morbidity, venous thromboembolism, and more. To mitigate some of these concerns, prescribed preoperative weight loss via very low-energy diets (VLEDs) has become a standard of care for patients with obesity undergoing bariatric surgery. While VLEDs have become standard prior to bariatric surgery, their application in other surgical settings remains limited. A large, definitive trial is required to resolve the uncertainty surrounding their use in these patients. Prior to a definitive trial to compare the efficacy of VLEDs in patients with obesity undergoing major non-bariatric surgery, we require a pilot trial. We argue a pilot trial will provide the following critical feasibility insights: (1) assessment of recruitment ability, (2) evaluation of adherence to VLED regimens, and (3) assessment of our ability follow patients completely. Methods The proposed trial will be a multi-center, surgeon, outcome assessor, and data-analyst blinded, parallel pilot randomized controlled trial (RCT). Patients older than 18 years of age with a body mass index (BMI) of greater than 30 kg/m2 undergoing major elective non-bariatric surgery will be eligible for inclusion. Consecutive patients will be allocated 1:1 according to a computer-generated randomization schedule. Randomization will be stratified by center and will employ randomly permutated blocks. All patients in the intervention group will receive standard patient counseling on weight loss and an active VLED protocol. The preoperative VLED protocol will utilize commercially available weight loss products for three weeks preoperatively. The primary outcomes (randomization percentage, recruitment rate, intervention adherence, follow-up completion, network development) will assess feasibility. Descriptive statistics will be used to characterize the study sample. Discussion The PREPARE pilot RCT will aim to provide feasibility and safety data that will allow for the successful completion of the definitive PREPARE trial that has the potential to provide practice changing data pertaining to the regular use of VLEDs as a means of pre-habilitation for patients with obesity undergoing major non-bariatric surgery. Trial registration This study was registered on ClinicalTrials.gov (reference #NCT05918471) on June 23, 2023.

Abstract Background Childhood obesity has increased and is considered one of the most serious public health challenges of the 21st century globally, and may be exacerbated by postpartum depression (PPD). The purpose of this study was to examine the association between PPD at 1st and 6th month postpartum, infant feeding practices, and body mass index (BMI) z-score of the child at one and three years of age. Methods This study used data from an ongoing prospective maternal-child birth cohort performed at the National Center for Child Health and Development (NCCHD) in suburban Tokyo, Japan with the period of recruitment from May 13, 2010 to November 28, 2013. Out of 2,309 total number of mothers, 1,279 mother–child dyads were assessed in the study. We performed multivariable linear regression analysis to examine the association between PPD and child’s BMI z-score stratified by the child’s age at 1 year and 3 years of age. Results The prevalence of PPD at 1 month postpartum (17%) was found to be higher than at 6 months (12%). In multivariable linear regression analysis we observed that children at 3 years who had mothers with PPD at 6 months had, on average, a BMI z-score 0.25 higher than children of mothers who did not have PPD at 6 months (ß coefficient 0.25, 95% CI [0.04 to 0.46], p value 0.02), holding all other covariates constant. Also, initiation of weaning food when child is at six months of age was associated with higher BMI z-score of the child at 3 years after adjusting for all covariates (ß coefficient = 0.18, 95% CI [0.03 to 0.34], p-value

Abstract Background Knee arthritis is a leading cause of limited function and long-term disability in older adults. Despite a technically successful total knee arthroplasty (TKA), around 20% of patients continue to have persisting pain with reduced function, and low quality of life. Many of them continue using opioids for pain control, which puts them at risk for potential long-term adverse effects such as dependence, overdose and risk of falls. Although persisting pain and opioid use after TKA have been recognised to be important issues, individual strategies to decrease their burden have limitations and multi-component interventions, despite their potential, have not been well studied. In this study, we propose a multi-component pathway including personalized pain management, facilitated by a pain management coordinator. The objectives of this pilot trial are to evaluate feasibility (recruitment, retention, and adherence), along with opioid-free pain control at 8 weeks after TKA. Methods This is a protocol for a multicentre pilot randomised controlled trial using a 2-arm parallel group design. Adult participants undergoing unilateral total knee arthroplasty will be considered for inclusion and randomised to control and intervention groups. Participants in the intervention group will receive support from a pain management coordinator who will facilitate a multicomponent pain management pathway including (1) preoperative education on pain and opioid use, (2) preoperative risk identification and mitigation, (3) personalized post-discharge analgesic prescriptions and (4) continued support for pain control and recovery up to 8 weeks post-op. Participants in the control group will undergo usual care. The primary outcomes of this pilot trial are to assess the feasibility of participant recruitment, retention, and adherence to the interventions, and key secondary outcomes are persisting pain and opioid use. Discussion The results of this trial will determine the feasibility of conducting a definitive trial for the implementation of a multicomponent pain pathway to improve pain control and reduce harms using a coordinated approach, while keeping an emphasis on patient centred care and shared decision making. Trial registration Prospectively registered in Clinicaltrials.gov (NCT04968132).

Abstract Background Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. Methods The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox’ proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. Discussion Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. Trial registration NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060

Abstract Background Intravenous iron is commonly used in patients with non-dialysis-dependent chronic kidney disease (CKD). Modern intravenous iron compounds (e.g. ferric derisomaltose (FDI), ferric carboxymaltose (FCM)) are increasingly utilized with similar efficacy. A differential effect in terms of hypophosphatemia has been noted following administration of FCM, which may be related to fibroblast growth factor 23 (FGF23). This study was designed to examine the comparative effects of FDI and FCM on FGF23, phosphate and other markers of bone turnover. Methods The single-center double-blind randomized controlled trial “Iron and Phosphaturia – ExplorIRON-CKD” primarily assessed the effects of FCM and FDI on intact FGF23 and phosphate, whilst also studying the impact on vitamin D, parathyroid hormone and phosphaturia. Bone markers including alkaline phosphatase, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide and carboxy-terminal collagen cross-linked telopeptide were monitored. Non-dialysis-dependent CKD patients (stage 3a-5) with iron deficiency with/without anemia (serum ferritin < 200 µg/L or transferrin saturation = 20% and serum ferritin 200-299 µg/L) were randomized to receive FDI or FCM in a 1:1 ratio. At baseline 1000 mg of intravenous iron was administered followed by 500-1000 mg at 1 month to achieve replenishment. Measurements were performed at baseline, 1–2 days following iron administration, 2 weeks, 1 month (second iron administration), 1–2 days following second administration, 2 months and 3 months following initial infusion. Results Twenty-six patients participated in the trial; 14 randomized to FDI and 12 to FCM. Intact FGF23 increased following administration of iron, and the increase was significantly higher with FCM compared to FDI (Baseline to 1–2 days following 1st administration: FDI: 3.0 (IQR: - 15.1 - 13.8) % vs. FCM: 146.1 (IQR: 108.1–203.1) %; p < 0.001 and Baseline to 1–2 days following 2nd administration: FDI: 3.2 (IQR: - 3.5 – 25.4) % vs. FCM: 235.1 (138.5–434.6) %; p = 0.001). Phosphate levels decreased in the FCM group, causing a significant difference versus FDI 2 weeks following administration of the first dose. A significantly greater decrease in 1,25 (OH)2 Vitamin D was noted with FCM. Several markers of bone turnover significantly changed following administration of FCM but not FDI. Conclusions The study suggests a differential effect on FGF23 following administration of FCM compared to FDI in non-dialysis-dependent CKD patients, similar to other patient groups. This may lead to changes consistent with hypovitaminosis D and alterations in bone turnover with potential clinical consequences. Further definitive studies are required to understand these differences of intravenous iron compounds. Trial registration European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) number: 2019–004370-26 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004370-26/GB ) (First date of trial registration: 03/12/2019).

Abstract Background Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains—health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. Methods An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. Discussion The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. Trial registration The trial has been registered prospectively in Clinical Trial Registry – India # CTRI/2021/11/037881, Registered on 08 November 2021.

Abstract Aim To synthesize available evidence on the association between change in linear growth (height for age z score, HAZ) beyond the first two years of life with later child neurodevelopment outcomes in Low- and middle-income countries (LMICs). Methods We searched PubMed, Web of Science, and EMBASE for cohort studies on the association between change in HAZ after age two and neurodevelopment outcomes in middle or late childhood. Data extraction was done independently by two reviewers. Results A total of 21 studies, that included 64,562 children from 13 LMICs were identified. Each unit increase in change in HAZ above two years is associated with a + 0.01 increase (N = 8 studies, 27,393 children) in the cognitive scores at 3.5 to 12 years of age and a + 0.05-standard deviation (SD) increase (95% CI 0.02 to 0.08, N = 3 studies, 17,830 children) in the language score at 5 to 15 years of age. No significant association of change in HAZ with motor (standardized mean difference (SMD) 0.04; 95% CI: -0.10, 0.18, N = 1 study, 966 children) or socio-emotional scores (SMD 0.00; 95% CI: -0.02, 0.01, N = 4 studies, 14,616 participants) was observed. Conclusion Changes in HAZ after the first two years of life appear to have a small or no association with child neurodevelopment outcomes in LMICs.

Abstract Background Back pain is the leading cause of disability worldwide. Despite guidelines discouraging opioids as first-line treatment, opioids remain the most prescribed drugs for back pain. There is renewed interest in exploring the potential medical applications of cannabis, and with the recent changes in national legislation there is a unique opportunity to investigate the analgesic properties of cannabis. Methods This was a multi-center survey-based study examining patient perceptions regarding cannabis for spine pain. We included patients presenting with back or neck pain to one of three Orthopedic clinics in Ontario. Our primary outcome was perceived effect of cannabis on back pain, while secondary outcomes were perceptions regarding potential applications and barriers to cannabis use. Results 259 patients participated in this study, 35.3% (90/255) stating they used cannabis medically. Average pain severity was 6.5/10 ± 0.3 (95% CI 6.2–6.8). Nearly three-quarters were prescribed opioids (73.6%, 148/201), with oxycodone/oxycontin (45.9% 68/148) being the most common, and almost half of (49.3%, 73/148) had used an opioid in the last week. Patients estimated cannabis could treat 54.3% ± 4.0 (95% CI 50.3–58.3%) of their spine pain and replace 46.2% ± 6. 6 (95% CI 39.6–52.8%) of their current analgesics. Age (β = − 0.3, CI − 0.6–0.0), higher pain severity (β = 0.4, CI 0.1–0.6) and previous cannabis use (β = 14.7, CI 5.1–24.4) were associated with a higher perceived effect of cannabis. Patients thought cannabis would be beneficial to treat pain (129/146, 88.4%), and reduce (116/146, 79.5%) or eliminate opioids (102/146, 69.9%). Not considering using cannabis for medical purposes (65/150, 43.3%) was the number one reported barrier. Conclusions Patients estimated medical cannabis could treat more than half of their spine pain, with one in three patients already using medical cannabis. 79% of patients also believe cannabis could reduce opioid usage. This data will help support more research into cannabis for musculoskeletal pain.

Abstract Background Resistance against artemisinin-based combination therapy is one of the challenges to malaria control and elimination globally. Mutations in different genes (Pfdhfr, Pfdhps, Pfk-13 and Pfmdr1) confer resistance to artesunate and sulfadoxine–pyrimethamine (AS + SP) were analysed from Mandla district, Madhya Pradesh, to assess the effectiveness of the current treatment regimen against uncomplicated Plasmodium falciparum. Methods Dried blood spots were collected during the active fever survey and mass screening and treatment activities as part of the Malaria Elimination Demonstration Project (MEDP) from 2019 to 2020. Isolated DNA samples were used to amplify the Pfdhfr, Pfdhps, Pfk13 and Pfmdr1 genes using nested PCR and sequenced for mutation analysis using the Sanger sequencing method. Results A total of 393 samples were subjected to PCR amplification, sequencing and sequence analysis; 199, 215, 235, and 141 samples were successfully sequenced for Pfdhfr, Pfdhps, Pfk13, Pfmdr1, respectively. Analysis revealed that the 53.3% double mutation (C59R, S108N) in Pfdhfr, 89.3% single mutation (G437A) in Pfdhps, 13.5% single mutants (N86Y), and 51.1% synonymous mutations in Pfmdr1 in the study area. Five different non-synonymous and two synonymous point mutations found in Pfk13, which were not associated to artemisinin resistance. Conclusion The study has found that mutations linked to SP resistance are increasing in frequency, which may reduce the effectiveness of this drug as a future partner in artemisinin-based combinations. No evidence of mutations linked to artemisinin resistance in Pfk13 was found, suggesting that parasites are sensitive to artemisinin derivatives in the study area. These findings are a baseline for routine molecular surveillance to proactively identify the emergence and spread of artemisinin-resistant parasites.

Abstract Nepal is a landlocked country with variable topography including the world’s tallest mountains, tropical forests, and Gangetic plains. This topography leads to diverse healthcare needs, from tropical diseases in plains, to road traffic accidents in hills, and to disaster-related emergencies from floods and landslides during monsoon season and unpredictable earthquakes. Emergency medicine care is underdeveloped and is currently being provided by general practitioners. The capital city Kathmandu has a few tertiary healthcare centers with emergency medicine fellowship-trained general practitioners staffing them, but most of the hospitals outside of Kathmandu are staffed by minimally trained or untrained medical officers. Even though emergency medicine is recognized as a specialty, Nepal still does not have an emergency medicine residency training program. To improve emergency care in the country, the government of Nepal should be focused on facilitating the start of emergency medicine residency in Nepal. Graphical Abstract

Abstract Background People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed ‘Studies Within A Trial’ (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. Methods Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. Results Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I 2 = 0%). There was no effect on any other outcomes. Conclusions Multimedia alongside written information did not improve trial recruitment rates. Trial registration ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.

Abstract Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full “lay” summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals.

Abstract Background Following traumatic hand injury, few studies have compared outcomes between people with and without a pre-morbid mental health diagnosis. This study aimed to compare sub-acute outcomes in a multicultural patient cohort with surgically managed traumatic hand injury with and without a pre-morbid mental health diagnosis. Methods A prospective, observational cohort study of people with traumatic hand injury presenting pre- surgically to a high-volume hand injury centre in a region of cultural and language diversity was conducted. Participants were assessed face-to-face (baseline) then via telephone (3-months post-surgery) and categorized according to a pre-morbid medically diagnosed mental health diagnosis. Baseline and follow-up assessments included global mental health, and the EuroQol (EQ) ‘Health Today’ analogue scale (0–100) and health domains. Return-to-work status, complications/symptomatic complaints, and hand function (QuickDASH) were also collected at follow-up. Adjusted analyses—accounting for covariates including cultural identity—were conducted to determine whether 3-month outcomes were associated with a pre-morbid mental health diagnosis. Results From 405 eligible patients, 386 were enrolled (76% male, mean age 38.9 (standard deviation 15.6)); 57% self-identified as Australian and 22% had a pre-morbid mental health diagnosis. Common injuries regardless of pre-morbid mental health diagnosis were skin (40%), tendon (17%) and bone (17%) injuries. None were complex mutilating injuries. Seventy-eight per cent of the cohort was followed-up. In adjusted analyses, a pre-morbid mental health diagnosis was associated with lower odds for reporting ‘good or better’ global mental health (Odds Ratio (OR) 0.23 (95% Confidence Interval (CI) 0.18, 0.47), p

Abstract Background Appropriate use of available inpatient beds is an ongoing challenge for US hospitals. Historical capacity goals of 80% to 85% may no longer serve the intended purpose of maximizing the resources of space, staff, and equipment. Numerous variables affect the input, throughput, and output of a hospital. Some of these variables include patient demand, regulatory requirements, coordination of patient flow between various systems, coordination of processes such as bed management and patient transfers, and the diversity of departments (both inpatient and outpatient) in an organization. Methods Mayo Clinic Health System in the Southwest Minnesota region of the US, a community-based hospital system primarily serving patients in rural southwestern Minnesota and part of Iowa, consists of 2 postacute care and 3 critical access hospitals. Our inpatient bed usage rates had exceeded 85%, and patient transfers from the region to other hospitals in the state (including Mayo Clinic in Rochester, Minnesota) had increased. To address these quality gaps, we used a blend of Agile project management methodology, rapid Plan-Do-Study-Act cycles, and a proactive approach to patient placement in the medical-surgical units as a quality improvement initiative. Results During 2 trial periods of the initiative, the main hub hospital (Mayo Clinic Health System hospital in Mankato) and other hospitals in the region increased inpatient bed usage while reducing total out-of-region transfers. Conclusion Our novel approach to proactively managing bed capacity in the hospital allowed the region’s only tertiary medical center to increase capacity for more complex and acute cases by optimizing the use of historically underused partner hospital beds.

Abstract Background Intimate partner violence (IPV) is an unabating public health issue that has numerous negative repercussions for women’s health. Its detrimental impact on women’s nutritional outcomes has been documented in a few studies from low- and middle-income countries; however, there is a lack of granular understanding in terms of the typology of IPV experiences and their association with nutritional outcomes. This study explores the distinct classes of IPV experience among women in India and examines how these classes are associated with their nutritional outcomes. Methods Using data of 60,622 ever-married women aged 15–49 years from the 2019-21 National Family Health Survey (NFHS-5), latent class analysis (LCA) was performed to identify distinct groups of women based on their IPV experiences. BMI was used to assess women’s nutritional status, and it was classified as:

Abstract Background Many people who menstruate in low- and middle-income countries struggle to manage their menstruation safely, hygienically, and with dignity. This is exacerbated in humanitarian settings with limited access to menstrual products and safe, private spaces for changing, washing, and disposing of menstrual products. To address these challenges, Youth Development Labs (YLabs) used a human-centered design approach to co-design the Cocoon Mini, a safe, physical structure for managing menstruation in the Bidi Bidi Refugee Settlement in Uganda. Methods The study comprised five phases, including background research, design research, rough prototyping, live prototyping, and a pilot study. A total of 340 people, including people who menstruate, male community members, and community stakeholders, participated in interviews, focus groups, and co-design sessions. Solution prototypes were created, evaluated, and iterated upon in each successive project phase. The final intervention design, the Cocoon Mini, was evaluated qualitatively for feasibility and acceptability during a three-month pilot using structured interviews with 109 people who menstruate utilizing Cocoon Mini structures, 64 other community members, and 20 Cocoon Mini supervisors. Results Results showed widespread desirability and acceptability of the Cocoon Mini among people who menstruate and other community members. Overall, 95% (104/109) of people who menstruate stated the space had made menstrual health management easier, primarily by providing designated waste bins, solar lights, and additional water sources. The Cocoon Mini provided an increased sense of physical and psychological safety in knowing where to privately manage menstruation. Furthermore, the Cocoon Mini demonstrated that an intervention could be run and maintained sustainably at the household level in humanitarian contexts, without continued external stakeholder intervention. Each Cocoon Mini structure costs approximately $360 USD to build and maintain and serves 15–20 people who menstruate, leading to a cost per person of $18-$24. Furthermore, attaching an incinerator to the structure for easier and quicker disposal of waste bin contents (compared to transporting full waste bins elsewhere) costs $2110 USD. Conclusions People who menstruate lack access to safe, private spaces for menstrual health and product disposal in humanitarian settings. The Cocoon Mini provides a solution for the safe and effective management of menstruation. Customizing and scaling up dedicated menstrual health spaces should be considered a high-priority intervention in humanitarian settings.

Abstract Background The COVID-19 pandemic has highlighted the need for global unity and timely access to healthcare for all including multilingual and intercultural societies. This study aimed to identify barriers to healthcare access due to the COVID-19 crisis among Nepalese migrants in Japan and explore ways to counter these barriers, both in routine and crisis situations. Methods This study used an exploratory sequential mixed-methods study design. The researchers conducted 11 focus group discussions including 89 participants and an online survey involving 937 respondents. The integration of focus group discussions and logistic regression analysis from the survey was reported via a ‘joint display’. Results Twenty-six themes on barriers to and six on facilitators of healthcare accessibility were identified by the focus group discussions among which 17 barriers like lack of knowledge of health insurance, language barriers, lack of hotline services, unawareness of available services, fear of discrimination etc. had significant association in our logistic regression analysis after adjusting for all confounders. Similarly, the only facilitator that had a significant impact, according to the multivariable logistic regression analysis, was receiving health information from Nepali healthcare professionals (OR = 1.36, 95% CI = (1.01 – 1.82), p-value

Abstract Introduction Adolescent girls and young women (AGYW) in Nepal have disproportionately poor reproductive and maternal health outcomes. In response, Save the Children, the Nepal government, and local partners designed and implemented Healthy Transitions for Nepali Youth, a multi-level integrated intervention. The intervention aimed to improve reproductive, maternal, and newborn health knowledge, attitudes, and behaviors among AGYW, and address gender attitudes and norms in four districts of Karnali Province, Nepal. Methods Married and unmarried AGYW aged 15–24 were engaged in a small group, curriculum-based intervention; husbands and families received home visits, using short videos to catalyze discussion; communities were engaged through dialogue-based activities; and the health system was made more adolescent-responsive through quality assessments, training, and supervision. An external organization conducted a quantitative survey with a sample of 786 AGYW intervention participants at baseline and 565 of the same AGYW at endline. Pooled linear regressions were estimated for each indicator to assess the statistical significance of differences between baseline and endline. Focus group discussions and key informant interviews were conducted with AGYW, husbands, families, community leadership, and program implementers. Data analysis was done through STATA 14th version and NVivo. Results The percentage of AGYW currently using a modern contraceptive method increased significantly, and more AGYW believed that their family was supportive of delaying marriage and motherhood at the endline. Young women’s knowledge of danger signs during labor increased, and there was a significant improvement in essential newborn care practices immediately after birth. AGYW reported shifts towards more gender equitable attitudes and behaviors, including related to decision-making about reproductive and maternal health. Conclusion Positive shifts in reproductive, maternal, and newborn health and gender knowledge, attitudes, and behavior were observed among AGYW, their male partners, and families. The results can inform the design of future interventions to effectively reach this critical population. Trail registration Not applicable.

Abstract Background Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. Methods This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. Results 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. Conclusion Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. Trial Registration NCT04872933. Registered 5th May 2021.

Abstract Background The number of breastfeeding mothers participating in a labor force to generate income has been increasing in Nepal. In this regard, the study aims to assess the survival of Under 3 children in Nepal from the mother based on their labor force participation and breastfeeding status. Methods Data for the study were obtained from the Nepal Demographic and Health Survey 2016. The sample size of the study was 2,994 live births children, born in the last three years prior to the day of the interview. The robust hazard ratio and cox proportional hazard regression were conducted between dependent and independent variables with 95% confidence intervals (CIs) to conclude. Results From a total of 2,994 live births, 85 children died within 36 months of birth. More than 80% of the non-working mothers were breastfeeding their children. The findings shows that the survival of children under-3 is positively associated with the interaction with the mother’s work and breastfeeding status (Hazard Ratio 0.428, 95% CI 0.24, 0.75), family structure (Hazard Ratio 1.511; 95% CI 1.37, 1.655), relationship with the household head (Hazard Ratio 0.452; 95% CI 0.311, 0.65), wealth quintiles (Hazard Ratio 0.390; 95% CI 0.33, 0.46), caste (Hazard Ratio 0.652; 95% CI 0.60, 0.69), and religion (Hazard Ratio 2.015; 95% CI 1.09, 3.70) with model CI 95%, Log pseudo likelihood = -521.39236, prob. χ2 = 0.005 and time at risk = 52,748. Conclusions The highest rate of child survival was from the working mothers as well as continuing breastfeeding their children followed by mothers breastfeeding the child but not working, compared to mothers working but not breastfeeding the child, and mothers who were neither working nor breastfeeding their children respectively. This study provides clear evidence that breastfeeding is very important for the probability of survival of the child aged below 36 months and work of mother also have some positive impact on child survival. Employers should be encouraged to have a breastfeeding policy in the workplace through the establishment of a breastfeeding facility, and a flexible work schedule. At the same time government should also regulate the paid maternity leave and encourage societal support for the breastfeeding mothers.

Abstract Background Bovine theileriosis caused by the eukaryotic parasite Theileria annulata is an economically important tick-borne disease. If it is not treated promptly, this lymphoproliferative disease has a significant fatality rate. Buparvaquone (BPQ) is the only chemotherapy-based treatment available right now. However, with the emergence of BPQ resistance on the rise and no backup therapy available, it is critical to identify imperative drugs and new targets against Theileria parasites. Methods Artemisinin and its derivatives artesunate (ARS), artemether (ARM), or dihydroartemisinin (DHART) are the primary defence line against malaria parasites. This study has analysed artemisinin and its derivatives for their anti-Theilerial activity and mechanism of action. Results ARS and DHART showed potent activity against the Theileria-infected cells. BPQ in combination with ARS or DHART showed a synergistic effect. The compounds act specifically on the parasitised cells and have minimal cytotoxicity against the uninfected host cells. Treatment with ARS or DHART induces ROS-mediated oxidative DNA damage leading to cell death. Further blocking intracellular ROS by its scavengers antagonised the anti-parasitic activity of the compounds. Increased ROS production induces oxidative stress and DNA damage causing p53 activation followed by caspase-dependent apoptosis in the Theileria-infected cells. Conclusions Our findings give unique insights into the previously unknown molecular pathways underpinning the anti-Theilerial action of artemisinin derivatives, which may aid in formulating new therapies against this deadly parasite. Video abstract

Abstract Background Evidence suggests that rates of occupational injuries in the US are decreasing. As several different occupational injury surveillance systems are used in the US, more detailed investigation of this trend is merited. Furthermore, studies of this decrease remain descriptive and do not use inferential statistics. The aim of this study was to provide both descriptive and inferential statistics of temporal trends of occupational injuries treated in US emergency departments (EDs) for 2012 to 2019. Methods Monthly non-fatal occupational injury rates from 2012 to 2019 were estimated using the national electronic injury surveillance system—occupational supplement (NEISS-Work) dataset, a nationally representative sample of ED-treated occupational injuries. Rates were generated for all injuries and by injury event type using monthly full-time worker equivalent (FTE) data from the US Current Population Survey as a denominator. Seasonality indices were used to detect seasonal variation in monthly injury rates. Trend analysis using linear regression adjusted for seasonality was conducted to quantify changes in injury rates from 2012 to 2019. Results Occupational injuries occurred at an average rate of 176.2 (95% CI = ± 30.9) per 10,000 FTE during the study period. Rates were highest in 2012 and declined to their lowest level in 2019. All injury event types occurred at their highest rate in summer months (July or August) apart from falls, slips, and trips, which occurred at their highest rate in January. Trend analyses indicated that total injury rates decreased significantly throughout the study period (− 18.5%; 95% CI = ± 14.5%). Significant decreases were also detected for injuries associated with contact with foreign object and equipment (− 26.9%; 95% CI = ± 10.5%), transportation incidents (− 23.2%; 95% CI = ± 14.7%), and falls, slips, and trips (− 18.1%; 95% CI = ± 8.9%). Conclusions This study supports evidence that occupational injuries treated in US EDs have decreased since 2012. Potential contributors to this decrease include increased workplace mechanization and automation, as well as changing patterns in US employment and health insurance access.

Abstract Background Plantar fasciitis (PF) is a common orthopaedic problem, with heel pain worsening the quality of life. Although steroid injection is often used if the conservative treatment fails, Platelet-Rich Plasma (PRP) injection is gaining popularity due to its safety and long-lasting effect. However, the effect of PRP versus steroid injection in PF has not been studied yet in Nepal. Therefore, this study aimed to assess the effect of PRP compared with steroid injection in the treatment of PF. Methods This study was a single-center, hospital-based, open-label, parallel-group randomized clinical trial to compare the effect of PRP injection with steroid injection in plantar fasciitis between August 2020 and March 2022. A total of 90 randomly selected participants aged 18 to 60 years suffering from plantar fasciitis with failed conservative treatment were intervened. The American Orthopaedic Foot and Ankle Society (AOFAS) and the Visual Analog Scale (VAS) scoring system were used to evaluate functional mobility and pain before and after the intervention for three and six months, respectively. Statistical analyses were performed using a Student’s two-sample t-test. P-value

Abstract Background Food insecurity is associated with worse general health rating, but little research exists investigating whether there is a dose response relationship across levels of food security and mental and physical health domains at the population level. Methods Data from the Medical Expenditure Panel Survey (2016–2017) with US adults aged 18 years and older was used. The physical component score (PCS) and mental component score (MCS) of Quality of Life, served as the outcome measures. Four categories of food insecurity (high, marginal, low, very low food security) served as the primary independent variable. Linear regression was used to run unadjusted followed by adjusted models. Separate models were run for PCS and MCS. Results In a sample of US adults, 16.1% reported some degree of food insecurity. For PCS, marginal (β = − 2.54 (p

Abstract Background Public health and clinical recommendations are established from systematic reviews and retrospective meta-analyses combining effect sizes, traditionally, from aggregate data and more recently, using individual participant data (IPD) of published studies. However, trials often have outcomes and other meta-data that are not defined and collected in a standardized way, making meta-analysis problematic. IPD meta-analysis can only partially fix the limitations of traditional, retrospective, aggregate meta-analysis; prospective meta-analysis further reduces the problems. Methods We developed an initiative including seven clinical intervention studies of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation that are being conducted (or recently concluded) in Burkina Faso, Ethiopia, India, Nepal, and Pakistan to test the effect of BEP on infant and maternal outcomes. These studies were commissioned after an expert consultation that designed recommendations for a BEP product for use among pregnant and lactating women in low- and middle-income countries. The initiative goal is to harmonize variables across studies to facilitate IPD meta-analyses on closely aligned data, commonly called prospective meta-analysis. Our objective here is to describe the process of harmonizing variable definitions and prioritizing research questions. A two-day workshop of investigators, content experts, and advisors was held in February 2020 and harmonization activities continued thereafter. Efforts included a range of activities from examining protocols and data collection plans to discussing best practices within field constraints. Prior to harmonization, there were many similar outcomes and variables across studies, such as newborn anthropometry, gestational age, and stillbirth, however, definitions and protocols differed. As well, some measurements were being conducted in several but not all studies, such as food insecurity. Through the harmonization process, we came to consensus on important shared variables, particularly outcomes, added new measurements, and improved protocols across studies. Discussion We have fostered extensive communication between investigators from different studies, and importantly, created a large set of harmonized variable definitions within a prospective meta-analysis framework. We expect this initiative will improve reporting within each study in addition to providing opportunities for a series of IPD meta-analyses.

Abstract Background The fresh-market tomato (Solanum lycopersicum) is bred for direct consumption and is selected for a high yield of large fruits. To understand the genetic variations (distinct types of DNA sequence polymorphism) that influence the yield, we collected the phenotypic variations in the yields of total fruit, extra-large-sized fruit, small-sized fruit, or red-colored fruit from 68 core inbred contemporary U.S. fresh-market tomatoes for three consecutive years and the genomic information in 8,289,741 single nucleotide polymorphism (SNP) positions from the whole-genome resequencing of these tomatoes. Results Genome-wide association (GWA) mapping using the SNP data with or without SNP filtering steps using the regularization methods, validated with quantitative trait loci (QTL) linkage mapping, identified 18 significant association signals for traits evaluated. Among them, 10 of which were not located within genomic regions previously identified as being associated with fruit size/shape. When mapping-driven association signals [558 SNPs associated with 28 yield (component) traits] were used to calculate genomic estimated breeding values (GEBVs) of evaluated traits, the prediction accuracies of the extra-large-sized fruit and small-sized fruit yields were higher than those of the total and red-colored fruit yields, as we tested the generated breeding values in inbred tomatoes and F2 populations. Improved accuracy in GEBV calculation of evaluated traits was achieved by using 364 SNPs identified using the regularization methods. Conclusions Together, these results provide an understanding of the genetic variations underlying the heritable phenotypic variability in yield in contemporary tomato breeding and the information necessary for improving such economically important and complex quantitative trait through breeding.

Abstract Background Mass screening and treatment (MSaT) aims at reducing the spread of malaria in communities by identifying and treating infected persons regardless of the symptoms. This study was conducted to identify and treat asymptomatic cases using MSaT approaches in the community. Methods Three rounds of MSaT using cluster combination approaches were carried out during September 2018 to December 2019 to identify and treat asymptomatic malaria cases in the community. All individuals who were present in the household were screened using RDT irrespective of malaria related symptoms. Simultaneously thick and thin blood smear and blood spot were collected for further analysis using microscopy and diagnostic PCR done in a subset of the samples. Results Logistic regression analysis revealed that asymptomatic malaria cases significantly less among the older age groups compared with

Abstract Background Low-density malaria infections (LDMI) are defined as infections that are missed by the rapid diagnostic test (RDT) and/or microscopy which can lead to continued transmission and poses a challenge in malaria elimination efforts. This study was conducted to investigate the prevalence of LDMI in febrile cases using species-specific nested Polymerase Chain Reaction (PCR) tests in the Malaria Elimination Demonstration Project, where routine diagnosis was conducted using RDT. Methods Every 10th fever case from a cross-sectional community based fever surveillance was tested with RDT, microscopy and nested PCR. Parasite DNA was isolated from the filter paper using Chelex based method. Molecular diagnosis by nested PCR was performed targeting 18SrRNA gene for Plasmodium species. Results The prevalence of malaria was 2.50% (436/17405) diagnosed by PCR, 1.13% (196/17405) by RDT, and 0.68% (118/ 17,405) by microscopy. Amongst 17,405 febrile samples, the prevalence of LDMI was 1.51% (263/17405) (95% CI 1.33–1.70), which were missed by conventional methods. Logistic regression analysis revealed that illness during summer season [OR = 1.90 (p

Abstract Background Adolescent girls and young women (AGYW) often experience early childbearing and have poor utilization of reproductive, maternal, and neonatal health (RMNH) services in Nepal. Involving men in such services has been increasingly recognized globally to improve gender-equitable reproductive health behaviour in husbands. This qualitative study assessed the implementation of Healthy Transitions’ male engagement interventions in Karnali Province, Nepal which were implemented to improve gender-equitable attitudes, and supportive RMNH care-seeking behaviors among the husbands of young women. Methods We conducted a summative qualitative study that included in-depth interviews with 12 AGYW as primary beneficiaries and their husbands (N = 12) and in-laws (N = 8). In addition, key informant interviews were conducted with health workers (N = 8), local government representatives (N = 4), members of Health Facility Operation and Management Committee (N = 8) and project implementers (N = 12). Due to COVID-19-related travel restrictions and lockdowns, all interviews were conducted via phone calls and online consultation. Data were analyzed using multistage coding and thematic content analysis. Results AGYW, their husbands, in-laws and health workers were receptive to the Healthy transitions’ male engagement initiatives. They perceived that the project contributed a momentum to facilitate men’s gender-responsive behaviour. Many participants reported that male engagement interventions, including home visits, community dialogues, and social events improved husbands’ support for their wives during menstruation, pregnancy, and childbirth. The activities also facilitated spousal communication and improved the couple’s decision-making for family planning use. Women reported that improved support from their husbands increased their self-confidence. Conclusions This study sheds light on the role of male engagement strategies to improve RMNH in a context where inequitable gender norms and roles are highly prevalent. Our findings highlight the potential to improve RMNH by addressing barriers to male engagement.

Abstract Background Children with low birth weight (LBW) are at risk of linear growth faltering and developmental deficits. Evidence suggests that early child stimulation and care reflected as responsive caregiving and opportunities for learning can promote development. The current analysis aimed to measure the extent to which linear growth and early child stimulation modify each other’s association with neurodevelopmental outcomes among LBW infants. Methods This is a secondary data analyses from a randomized controlled trial on the effect of community-initiated kangaroo mother care in LBW infants on their neurodevelopment at 12 months of corrected age. Bayley Scales of Infant and Toddler Development was used to assess cognitive, motor and language scores. Stimulation at home was assessed by the Pediatric Review of Children’s Environmental Support and Stimulation (PROCESS) tool. PROCESS scores were categorized into three groups: < Mean-1SD (low stimulation); Mean ± 1 SD (moderate stimulation) and > mean + 1SD (high stimulation). Results A total of 516 infants were available for neurodevelopment assessments. Interactions were observed between length for age z-score (LAZ) and PROCESS score categories. In the low stimulation group, the adjusted regression coefficients for the association between LAZ and cognitive, motor and language scores were substantially higher than in the moderate and high stimulation group. Stimulation was positively associated with neurodevelopmental outcomes in both stunted and non-stunted infants; however, the association was twice as strong in stunted than in non-stunted. Conclusion Moderate to high quality stimulation may alleviate the risk of sub-optimal development in LBW infants with linear growth deficits. Clinical trial registration The primary trial whose data are analysed is registered at clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02631343 ).

Abstract Background Protection by preventive Ebola vaccines has been demonstrated in clinical trials, but a complete picture of real-world effectiveness is lacking. Our previous study modeling the impact of preventively vaccinating healthcare workers (HCW) alone or with a proportion of the general population (GP) estimated significant reductions in incidence and mortality. The model assumed 100% vaccine efficacy, which is unlikely in the real world. We enhanced this model to account for lower vaccine efficacy and to factor in reduced infectiousness and lower case fatality rate in vaccinated individuals with breakthrough infections. Methods The previous model was enhanced to still permit a risk, although lower, for vaccinated individuals to become infected. The enhanced model, calibrated with data from epidemics in Sierra Leone (SL) and North Kivu, Democratic Republic of the Congo, helped evaluate the impact of preventive Ebola vaccination in different scenarios based on different vaccine efficacy rates (90% and 30% reductions in infection risk in the base and conservative scenarios, respectively; additionally, both scenarios with 50% reductions in infectiousness and mortality) and vaccination coverage among HCWs (30%, 90%) and GP (0%, 5%, and 10%). Results The base scenario estimated that, depending upon the proportions of vaccinated HCWs and GP, 33–85% of cases and 34–87% of deaths during the 2014 SL epidemic and 42–89% of cases and 41–89% of deaths during the 2018 North Kivu epidemic would be averted versus no vaccination. Corresponding estimates for the conservative scenario were: 23–74% of cases and 23–77% of deaths averted during the SL epidemic and 31–80% of both cases and deaths averted during the North Kivu epidemic. Conclusions Preventive vaccination targeting HCW alone or with GP may significantly reduce the size and mortality of an EVD outbreak, even with modest efficacy and coverage. Vaccines may also confer additional benefits through reduced infectiousness and mortality in breakthrough cases.

Abstract Background Approximately 1 in 10 patients with a surgically treated open fracture will develop a surgical site infection. The Aqueous-PREP trial will investigate the effect of 10% povidone-iodine versus 4% chlorhexidine in aqueous antiseptic solutions in reducing infections after open fracture surgery. The study protocol was published in April 2020. Methods and design The Aqueous-PREP trial is a pragmatic, multicenter, open-label, randomized multiple period cluster crossover trial. Each participating cluster is randomly assigned in a 1:1 ratio to provide 1 of the 2 study interventions on all eligible patients during a study period. The intervention periods are 2 months in length. After completing a 2-month period, the participating cluster crosses over to the alternative intervention. We plan to enroll a minimum of 1540 patients at 14 sites. Results The primary outcome is surgical site infection guided by the Centers for Disease Control and Prevention’s National Healthcare Safety Network reporting criteria (2017). All participants’ surgical site infection surveillance period will end 30 days after definitive fracture management surgery for superficial infections and 90 days after definitive fracture management surgery for deep incisional or organ/space infections [1]. The secondary outcome is an unplanned fracture-related reoperation within 12 months of the fracture. Conclusion This manuscript serves as the formal statistical analysis plan (version 1.0) for the Aqueous-PREP trial. The statistical analysis plan was completed on February 28, 2022.

Abstract Background Nurturing care, including adequate nutrition, responsive caregiving and early learning, is critical to early childhood development. In Nepal, national surveys highlight inequity in feeding and caregiving practices for young children. Our objective was to describe infant and young child feeding (IYCF) and cognitive and socio-emotional caregiving practices among caregivers of children under five in Dhanusha district, Nepal, and to explore socio-demographic and economic factors associated with these practices. Methods We did a cross-sectional analysis of a subset of data from the MIRA Dhanusha cluster randomised controlled trial, including mother-child dyads (N = 1360), sampled when children were median age 46 days and a follow-up survey of the same mother-child dyads (N = 1352) when children were median age 38 months. We used World Health Organization IYCF indicators and questions from the Multiple Indicator Cluster Survey-4 tool to obtain information on IYCF and cognitive and socio-emotional caregiving practices. Using multivariable logistic regression models, potential explanatory household, parental and child-level variables were tested to determine their independent associations with IYCF and caregiving indicators. Results The prevalence of feeding indicators varied. IYCF indicators, including ever breastfed (99%), exclusive breastfeeding (24-hour recall) (89%), and vegetable/fruit consumption (69%) were common. Problem areas were early initiation of breastfeeding (16%), colostrum feeding (67%), no pre-lacteal feeding (53%), timely introduction of complementary feeding (56%), minimum dietary diversity (49%) and animal-source food consumption (23%). Amongst caregiving indicators, access to 3+ children’s books (7%), early stimulation and responsive caregiving (11%), and participation in early childhood education (27%) were of particular concern, while 64% had access to 2+ toys and 71% received adequate care. According to the Early Child Development Index score, only 38% of children were developmentally on track. Younger children from poor households, whose mothers were young, had not received antenatal visits and delivered at home were at higher risk of poor IYCF and caregiving practices. Conclusions Suboptimal caregiving practices, inappropriate early breastfeeding practices, delayed introduction of complementary foods, inadequate dietary diversity and low animal-source food consumption are challenges in lowland Nepal. We call for urgent integrated nutrition and caregiving interventions, especially as interventions for child development are lacking in Nepal.

Abstract COVID-19 has had a substantial impact globally. It spreads readily, particularly in enclosed and crowded spaces, such as public transport carriages, yet there are limited studies on how this risk can be reduced. We developed a tool for exploring the potential impacts of mitigation strategies on public transport networks, called the Systems Analytics for Epidemiology in Transport (SAfE Transport). SAfE Transport combines an agent-based transit assignment model, a community-wide transmission model, and a transit disease spread model to support strategic and operational decision-making. For this simulated COVID-19 case study, the transit disease spread model incorporates both direct (person-to-person) and fomite (person-to-surface-to-person) transmission modes. We determine the probable impact of wearing face masks on trains over a seven day simulation horizon, showing substantial and statistically significant reductions in new cases when passenger mask wearing proportions are greater than 80%. The higher the level of mask coverage, the greater the reduction in the number of new infections. Also, the higher levels of mask coverage result in an earlier reduction in disease spread risk. These results can be used by decision makers to guide policy on face mask use for public transport networks.

Abstract Background The World Health Organization recommends the Maternal and Child Health Handbook (MCH-HB) to promote health service utilization from pregnancy to early childhood. Although many countries have adopted it as a national health policy, there is a paucity of research in MCH-HB’s implementation. Thus, this study aimed to evaluate the MCH-HB’s implementation status based on the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, Maintenance), and identify facilitators of, and barriers to its implementation in Angola to understand effective implementation strategies. Methods A cross-sectional survey was conducted targeting all health facilities which implemented MCH-HB, subsamples of health workers, and officers responsible for the MCH-HB at the municipality health office. Using the 14 indicators based on the RE-AIM framework, health facilities’ overall implementation statuses were assessed. This categorized health facilities into optimal-implementation and suboptimal-implementation groups. To identify barriers to and facilitators of MCH-HB implementation, semi-structured interviews were conducted among health workers and municipality health officers responsible for MCH-HB. The data were analyzed via content analysis. Results A total of 88 health facilities and 216 health workers were surveyed to evaluate the implementation status, and 155 interviews were conducted among health workers to assess the barriers to and facilitators of the implementation. The overall implementation target was achieved in 50 health facilities (56.8%). The target was achieved by more health facilities in urban than rural areas (urban 68.4%, rural 53.6%) and by more health facilities of higher facility types (hospital 83.3%, health center 59.3%, health post 52.7%). Through the interview data’s analysis, facilitators of and barriers to MCH-HB were comprehensively demonstrated. MCH-HB’s content advantage was the most widely recognized facilitator and inadequate training for health workers was the most widely recognized barrier. Conclusions Strengthening education for health workers, supervision by municipality health officers, and community sensitization were potential implementation strategies. These strategies must be intensified in rural and lower-level health facilities.

Abstract Background Femur fracture is a major burden among elderly people, leading patients to be bedridden for a long time in the hospital. The body is more likely to be in a catabolic state as a result of the prolonged fasting period required for surgery, leading to an increase in insulin resistance. Pre-operative carbohydrate loading has been shown to improve postoperative outcomes in several countries. The study aimed to evaluate the effect of pre-operative carbohydrate loading in femur fracture surgery. Methods This study was single-center, hospital-based, open-label, parallel-group randomized controlled trial conducted between August 2020 and November 2021. A total of 66 participants, aged 50 years and above having femur fractures planned for surgery were included in this study and assigned to the control (n = 33) and study (n = 33) groups through computer-generated random numbers. The control group was kept fasting from midnight to the next morning as in existence while the study group was intervened with carbohydrate loading according to the Enhanced Recovery After Surgery (ERAS) protocol. The pre-operative nutritional status was identified and the postoperative outcomes were measured using the Visual Analogue Score (VAS), Cumulative Ambulatory Score (CAS), and Modified Barthel Index (MBI) scoring systems. Statistical analyses were performed using the Chi-square test and the Student’s two-sample t-test to compare the outcomes between the two groups. Results All the participants completed the study. There was a significant reduction in the average postoperative pain in the carbohydrate loading group (VAS: 4.8 (SD ± 1.8), 95% CI: 4.7–5.4) as compared to the control group (VAS: 6.1 (SD ± 2.1), 95% CI: 5.3–6.8). The average CAS showed a significant improvement in regaining the mobility function of participants in the study group (CAS: 8.1 (SD ± 2.8), 95% CI: 7.1–9.1) than that of the control group (CAS: 6.8 (SD ± 2.8), 95% CI: 5.8–7.8). The mean MBI score of the participants at the time of discharge from the hospital was higher in the study group (MBI:13.1 (SD ± 2.3), 95% CI: 12.2–13.9) compared to the control group (MBI: 11.8 (SD ± 3.1), 95% CI:10.6–12.9). Similarly, the length of hospital stay after surgery had decreased in the study group than in the control group. Conclusions The uptake of carbohydrate loading showed reduced post-operative pain, enhanced functional mobility, and decreased length of hospital stay. This study warrants larger trials to show the effect of pre-operative carbohydrate loading in a clinical setting. Trial registration NCT04838366, first registered on 09/042021 ( https://clinicaltrials.gov/ct2/show/NCT04838366 ).

Abstract Background Advances in hematopoietic cell transplantation (HCT) have led to marked improvements in survival. However, adolescents and young adults (AYAs) who undergo HCT are at high risk of developing sarcopenia (loss of skeletal muscle mass) due to the impact of HCT-related exposures on the developing musculoskeletal system. HCT survivors who have sarcopenia also have excess lifetime risk of non-relapse mortality. Therefore, interventions that increase skeletal muscle mass, metabolism, strength, and function are needed to improve health in AYA HCT survivors. Skeletal muscle is highly reliant on mitochondrial energy production, as reflected by oxidative phosphorylation (OXPHOS) capacity. Exercise is one approach to target skeletal muscle mitochondrial OXPHOS, and in turn improve muscle function and strength. Another approach is to use “exercise enhancers”, such as nicotinamide riboside (NR), a safe and well-tolerated precursor of nicotinamide adenine dinucleotide (NAD+), a cofactor that in turn impacts muscle energy production. Interventions combining exercise with exercise enhancers like NR hold promise, but have not yet been rigorously tested in AYA HCT survivors. Methods/design We will perform a randomized controlled trial testing 16 weeks of in-home aerobic and resistance exercise and NR in AYA HCT survivors, with a primary outcome of muscle strength via dynamometry and a key secondary outcome of cardiovascular fitness via cardiopulmonary exercise testing. We will also test the effects of these interventions on i) muscle mass via dual energy x-ray absorptiometry; ii) muscle mitochondrial OXPHOS via an innovative non-invasive MRI-based technique, and iii) circulating correlates of NAD+ metabolism via metabolomics. Eighty AYAs (ages 15-30y) will be recruited 6–24 months post-HCT and randomized to 1 of 4 arms: exercise + NR, exercise alone, NR alone, or control. Outcomes will be collected at baseline and after the 16-week intervention. Discussion We expect that exercise with NR will produce larger changes than exercise alone in key outcomes, and that changes will be mediated by increases in muscle OXPHOS. We will apply the insights gained from this trial to develop individualized, evidence-supported precision initiatives that will reduce chronic disease burden in high-risk cancer survivors. Trial registration ClinicalTrials.gov, NCT05194397. Registered January 18, 2022, https://clinicaltrials.gov/ct2/show/NCT05194397 {2a}.

Abstract Background Timely tracking of health outcomes is difficult in low- and middle-income countries without comprehensive vital registration systems. Community health workers (CHWs) are increasingly collecting vital events data while delivering routine care in low-resource settings. It is necessary, however, to assess whether routine programmatic data collected by CHWs are sufficiently reliable for timely monitoring and evaluation of health interventions. To study this, we assessed the consistency of vital events data recorded by CHWs using two methodologies—routine data collected while delivering an integrated maternal and child health intervention, and data from a birth history census approach at the same site in rural Nepal. Methods We linked individual records from routine programmatic data from June 2017 to May 2018 with those from census data, both collected by CHWs at the same site using a mobile platform. We categorized each vital event over a one-year period as ‘recorded by both methods,’ ‘census alone,’ or ‘programmatic alone.’ We further assessed whether vital events data recorded by both methods were classified consistently. Results From June 2017 to May 2018, we identified a total of 713 unique births collectively from the census (birth history) and programmatic maternal ‘post-delivery’ data. Three-fourths of these births (n = 526) were identified by both. There was high consistency in birth location classification among the 526 births identified by both methods. Upon including additional programmatic ‘child registry’ data, we identified 746 total births, of which 572 births were identified by both census and programmatic methods. Programmatic data (maternal ‘post-delivery’ and ‘child registry’ combined) captured more births than census data (723 vs. 595). Both methods consistently classified most infants as ‘living,’ while infant deaths and stillbirths were largely classified inconsistently or recorded by only one method. Programmatic data identified five infant deaths and five stillbirths not recorded in census data. Conclusions Our findings suggest that data collected by CHWs from routinely tracking pregnancies, births, and deaths are promising for timely program monitoring and evaluation. Despite some limitations, programmatic data may be more sensitive in detecting vital events than cross-sectional census surveys asking women to recall these events.

Abstract Background Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. Methods This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3–4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. Results Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) μg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. Conclusion The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. Trial registration EudraCT: 2018–000,144-25 Registered 28/01/2019.

Abstract Background The impacts of socio-demographic and environmental risk factors on child growth have been widely documented. However, it remains unclear whether the impacts of such risk factors on child growth have remained static or changed with child’s age. The present study aims to assess the underlying age heterogeneities in child growth and its potential determinants over age in under-five children. Methods Cross-sectional data on child height (measured as height-for-age z-score, i.e., HAZ) and weight (measured as weight-for-age z-score, i.e., WAZ) and potential confounding factors from India’s 2015–16 National Family Health Survey (NFHS) were used to construct anthropometric age-profiles by a number of bio-demographic and socioeconomic characteristics. Further, age-interacted multilevel regression analyses were performed to examine differential effects of such/those risk factors on child height and weight by age. Results Faltered height and weight growth during first two years of life was noticed in children of all socioeconomic groups studied, albeit with varying magnitude. In case of child’s height, factors such as short birth interval, higher birth order, maternal education, household wealth, district level mortality rate have shown strong interaction with child’s age during the first 23 months, signifying their age-varying role in different developmental stages of child growth. These factors explain the observed upward and downward shifts in height curve during first two years. Some of these variables (e.g., household wealth) have shown even stronger age interactions after the second birthday of children. For child’s weight, interactive effects of most socio-demographic risk factors attenuated parabolically with child’s age. Conclusions The impacts of several risk factors, measured at the child, mother, community, and district levels, on child growth indicators varied significantly with the child’s age. Nutritional interventions aimed at preventing poor linear growth in children in India should consider these underlying age heterogeneities for growth determinants into account.

Abstract Background We aim to develop and test performance of a semi-automated method (computerized query combined with manual review) for chart abstraction in the identification and characterization of surveillance radiology imaging for post-treatment non-small cell lung cancer patients. Methods A gold standard dataset consisting of 3011 radiology reports from 361 lung cancer patients treated at the Veterans Health Administration from 2008 to 2016 was manually created by an abstractor coding image type, image indication, and image findings. Computerized queries using a text search tool were performed to code reports. The primary endpoint of query performance was evaluated by sensitivity, positive predictive value (PPV), and F1 score. The secondary endpoint of efficiency compared semi-automated abstraction time to manual abstraction time using a separate dataset and the Wilcoxon rank-sum test. Results Query for image type demonstrated the highest sensitivity of 85%, PPV 95%, and F1 score 0.90. Query for image indication demonstrated sensitivity 72%, PPV 70%, and F1 score 0.71. The image findings queries ranged from sensitivity 75–85%, PPV 23–25%, and F1 score 0.36–0.37. Semi-automated abstraction with our best performing query (image type) improved abstraction times by 68% per patient compared to manual abstraction alone (from median 21.5 min (interquartile range 16.0) to 6.9 min (interquartile range 9.5), p

Abstract Objective The determination of the location of quantitative trait loci (QTL) (i.e., QTL mapping) is essential for identifying new genes. Various statistical methods are being incorporated into different QTL mapping functions. However, statistical errors and limitations may often occur in a QTL mapping, implying the risk of false positive errors and/or failing to detect a true positive QTL effect. We simulated the power to detect four simulated QTL in tomato using cim() and stepwiseqtl(), widely adopted QTL mapping functions, and QTL.gCIMapping(), a derivative of the composite interval mapping method. While there is general agreement that those three functions identified simulated QTL, missing or false positive QTL were observed, which were prevalent when more realistic data (such as smaller population size) were provided. Results To address this issue, we developed postQTL, a QTL mapping R workflow that incorporates (i) both cim() and stepwiseqtl(), (ii) widely used R packages developed for model selection, and (iii) automation to increase the accuracy, efficiency, and accessibility of QTL mapping. QTL mapping experiments on tomato F2 populations in which QTL effects were simulated or calculated showed advantages of postQTL in QTL detection.