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Globally, millions of infections that are resistant to antimicrobial agents are reported annually, leading to more than 700,000 fatalities. Among all, challenges arise particularly from nontuberculosis mycobacterial (NTM) and Gram-negative bacteria, as they exhibit limited treatment options in light of increasing reports of multi-drug resistant strains.Clofazimine (CFZ) is an antimycobacterial medication used to treat leprosy, and it is also known for its side effect of inducing skin pigmentation. The use of CFZ and its analogues against a broad range of Gram-negative bacteria has not been extensively investigated. In this study, we designed, synthesized and studied 11 CFZ analogues and identified examples with comparable or improved in vitro anti-bacterial activity relative to that of CFZ itself. This is the first report demonstrating in vitro activity of CFZ and its analogues against Neisseria species. The results of these studies may facilitate the development of CFZ analogues with limited side effects in humans.

Abstract Introduction Nutrition-related factors linked to pain chronicity and disability include weight status and dietary behaviours. Dietary patterns associated with concurrent pain episodes, however, remain poorly characterised. This paper outlines the protocol for a feasibility study that aims to characterise pain-related dietary and lifestyle behaviours in people experiencing chronic musculoskeletal pain. Methods The study will recruit participants who experience musculoskeletal pain on 5 or more days of the week for at least 3 months. Participants will attend two in-person clinic visits where physical measurements and a series of pain and lifestyle questionnaires will be completed. Visits will be conducted pre and post a 2-week self-monitoring period where participants will self-report concurrent diet, sleep, mood, and pain on four days and will wear a wrist-worn activity monitor (GENEActiv). Key feasibility metrics will evaluate participant recruitment, enrolment and retention rates, and compliance with the study data collection protocol. Discussion There remains a lack of evidence behind dietary advice as an adjunct pain management tool. Upon completion of the protocol, feasibility outcomes will identify challenges to guide the design and delivery of a dietary intervention for chronic musculoskeletal pain.

BackgroundThe relationship between adiposity and pain is complex. Excess weight increases the risk for chronic musculoskeletal pain (CMP), driven by increased biomechanical load and low-grade systemic inflammation. Pain limits physical function, impacting energy balance contributing to weight gain. The primary aims of this study were to profile pain characteristics in participants with overweight or obesity and determine if weight loss through dietary-induced energy restriction, and presence of CMP, or magnitude of weight loss, was associated with changes in adiposity, pain, functional mobility, and inflammation.MethodsThis was a secondary analysis of data from adults (25–65 years) with overweight or obesity (BMI 27.5–34.9 kg/m2) enrolled in a 3-month, 30% energy-restricted dietary intervention to induce weight loss (January 2019–March 2021). Anthropometric measures (weight, waist circumference and fat mass), pain prevalence, pain severity (McGill Pain Questionnaire, MPQ), pain intensity (Visual Analog Scale, VAS), functional mobility (timed up and go, TUG) and inflammation (high sensitivity C-Reactive Protein, hsCRP) were assessed at baseline and 3-months.ResultsOne hundred and ten participants completed the intervention and had weight and pain assessed at both baseline and 3-months. Participants lost 7.0 ± 0.3 kg, representing 7.9% ± 3.7% of body mass. At 3-months, functional mobility improved (TUG −0.2 ± 0.1 s, 95% CI −0.3, −0.1), but there was no change in hsCRP. Compared to baseline, fewer participants reported CMP at 3-months (n = 56, 51% to n = 27, 25%, p

Objectives To assess the feasibility and change in clinical outcomes associated with continuous glucose monitoring (CGM) use among a rural population in Malawi living with type 1 diabetes.Design A 2:1 open randomised controlled feasibility trial.Setting Two Partners In Health-supported Ministry of Health-run first-level district hospitals in Neno, Malawi.Participants 45 people living with type 1 diabetes (PLWT1D).Interventions Participants were randomly assigned to Dexcom G6 CGM (n=30) use or usual care (UC) (n=15) consisting of Safe-Accu glucose monitors and strips. Both arms received diabetes education.Outcomes Primary outcomes included fidelity, appropriateness and severe adverse events. Secondary outcomes included change in haemoglobin A1c (HbA1c), acceptability, time in range (CGM arm only) SD of HbA1c and quality of life.Results Participants tolerated CGM well but were unable to change their own sensors which resulted in increased clinic visits in the CGM arm. Despite the hot climate, skin rashes were uncommon but cut-out tape overpatches were needed to secure the sensors in place. Participants in the CGM arm had greater numbers of dose adjustments and lifestyle change suggestions than those in the UC arm. Participants in the CGM arm wore their CGM on average 63.8% of the time. Participants in the UC arm brought logbooks to clinic 75% of the time. There were three hospitalisations all in the CGM arm, but none were related to the intervention.Conclusions This is the first randomised controlled trial conducted on CGM in a rural region of a low-income country. CGM was feasible and appropriate among PLWT1D and providers, but inability of participants to change their own sensors is a challenge.Trial registration number PACTR202102832069874.

Introduction Non-communicable diseases (NCDs) are rising in low-income and middle-income countries, including Malawi. To inform policy-makers and planners on the preparedness of the Malawian healthcare system to respond to NCDs, we estimated NCD service readiness in publicly financed healthcare facilities in Malawi.Methods We analysed data from 564 facilities surveyed in the 2019 Harmonised Health Facility Assessment, including 512 primary healthcare (PHC) and 52 secondary and tertiary care (STC) facilities. To characterise service readiness, applying the law of minimum, we estimated the percentage of facilities with functional equipment and unexpired medicines required to provide NCD services. Further, we estimated permanently unavailable items to identify service readiness bottlenecks.Results Fewer than 40% of PHC facilities were ready to deliver services for each of the 14 NCDs analysed. Insulin and beclomethasone inhalers had the lowest stock levels at PHC facilities (6% and 8%, respectively). Only 17% of rural and community hospitals (RCHs) have liver and kidney diagnostics. STC facilities had varying service readiness, ranging from 27% for managing acute diabetes complications to 94% for chronic type 2 diabetes management. Only 38% of STC facilities were ready to manage chronic heart failure. Oral pain medicines were widely available at all levels of health facilities; however, only 22% of RCHs and 29% of STCs had injectable morphine or pethidine. Beclomethasone was never available at 74% of PHC and 29% of STC facilities.Conclusion Publicly financed facilities in Malawi are generally unprepared to provide NCD services, especially at the PHC level. Targeted investments in PHC can substantially improve service readiness for chronic NCD conditions in local communities and enable STC to respond to acute NCD complications and more complex NCD cases.

Introduction The Package of Essential Noncommunicable Disease Interventions—Plus (PEN-Plus) is a strategy decentralising care for severe non-communicable diseases (NCDs) including type 1 diabetes, rheumatic heart disease and sickle cell disease, to increase access to care. In the PEN-Plus model, mid-level clinicians in intermediary facilities in low and lower middle income countries are trained to provide integrated care for conditions where services traditionally were only available at tertiary referral facilities. For the upcoming phase of activities, 18 first-level hospitals in 9 countries and 1 state in India were selected for PEN-Plus expansion and will treat a variety of severe NCDs. Over 3 years, the countries and state are expected to: (1) establish PEN-Plus clinics in one or two district hospitals, (2) support these clinics to mature into training sites in preparation for national or state-level scale-up, and (3) work with the national or state-level stakeholders to describe, measure and advocate for PEN-Plus to support development of a national operational plan for scale-up.Methods and analysis Guided by Proctor outcomes for implementation research, we are conducting a mixed-method evaluation consisting of 10 components to understand outcomes in clinical implementation, training and policy development. Data will be collected through a mix of quantitative surveys, routine reporting, routine clinical data and qualitative interviews.Ethics and dissemination This protocol has been considered exempt or covered by central and local institutional review boards. Findings will be disseminated throughout the project’s course, including through quarterly M&E discussions, semiannual formative assessments, dashboard mapping of progress, quarterly newsletters, regular feedback loops with national stakeholders and publication in peer-reviewed journals.

Introduction Previous research has associated high dietary cholesterol intake with raised low-density lipoprotein cholesterol (LDL-C) and thus increased risk for cardiovascular disease (CVD). Emerging research suggests that it is saturated fat, not dietary cholesterol, associated with increased CVD risk. Despite being high in cholesterol, eggs, low in saturated fat, are not adversely associated with blood lipids or CVD risk. This paper describes a randomised controlled counter-balanced, cross-over trial assessing the effects of a high-cholesterol/low-saturated fat (egg) diet and a low-cholesterol/high-saturated fat diet (egg free) on blood lipids and lipoproteins, while accounting for physical activity levels which can also influence these parameters. The primary aim is to demonstrate that high cholesterol intake (from eggs) within a healthy, low-saturated fat diet does not adversely affect blood lipid levels and lipoprotein profiles. Instead, we propose that adverse effects on these parameters are mediated by saturated fat intake. The secondary aim is to explore relationships between changes in blood lutein and zeaxanthin concentrations and alterations in physical activity, examining whether changes in physical activity mediate effects on blood lipids and lipoproteins.Methods and analysis Fifty-two adults aged 18–60 years with LDL-C less than 3.5 mmol/L will be randomly allocated to three isocaloric diets for 5 weeks each: a high-cholesterol (600 mg)/low-saturated fat (6%) (egg) diet, a low-cholesterol (300 mg)/high-saturated fat (12%) (egg free) diet and a control diet that is high in both cholesterol (600 mg) and saturated fat (12%). Lipid and lipoprotein levels, lipoprotein size and concentrations, blood pressure, blood glucose, physical activity levels, and plasma lutein and zeaxanthin concentrations will be measured. Treatment effects will be analysed using linear mixed effects models.Ethics and dissemination Ethics approval was obtained from the University of South Australia Human Research Ethics Committee no. 204 327. Results will be disseminated through peer-reviewed journals and national and international presentations.Trial registration number NCT05267522

Abstract Background Noncommunicable diseases (NCDs) and mental health conditions represent a growing proportion of disease burden in low- and middle-income countries (LMICs). While past efforts have identified interventions to be delivered across health system levels to address this burden, the challenge remains of how to deliver heterogenous interventions in resource-constrained settings. One possible solution is the Integration of interventions within existing care delivery models. This study reviews and summarizes published literature on models of integrated NCD and mental health care in LMICs. Methods We searched Pubmed, African Index Medicus and reference lists to conduct a scoping review of studies describing an integrated model of NCD or neuropsychiatric conditions (NPs) implemented in a LMIC. Conditions of interest were grouped into common and severe NCDs and NPs. We identified domains of interest and types of service integration, conducting a narrative synthesis of study types. Studies were screened and characteristics were extracted for all relevant studies. Results are reported using PRISMA-ScR. Results Our search yielded 5004 studies, we included 219 models of integration from 188 studies. Most studies were conducted in middle-income countries, with the majority in sub-Saharan Africa. Health services were offered across all health system levels, with most models implemented at health centers. Common NCDs (including type 2 diabetes and hypertension) were most frequently addressed by these models, followed by common NPs (including depression and anxiety). Conditions and/or services were often integrated into existing primary healthcare, HIV, maternal and child health programs. Services provided for conditions of interest varied and frequency of these services differed across health system levels. Many models demonstrated decentralization of services to lower health system levels, and task shifting to lower cadre providers. Conclusions While integrated service design is a promising method to achieve ambitious global goals, little is known about what works, when, and why. This review characterizing care integration programs is an initial step toward developing a structured study of care integration.

Migration plays an important role in the life cycle of many insect species, allowing them to escape unfavourable seasonal conditions. The Bogong moth (Agrotis infusa) is a keystone species that undertakes a long-distance annual migration, with billions of individuals aestivating in summer in the Australian Alps. This species has undergone drastic population declines in the past five years, with steady long-term declines also recorded since the 1980s, and has recently been recognised as Endangered by the IUCN. Despite the role of Bogong moths as a keystone species in the Australian sub-alpine and alpine zones, their feeding habits during their time in the mountains remain understudied, although earlier research suggested that they do not feed during their summer aestivation. To examine whether Bogong moths visit flowers during the summer, we collected pollen from moths caught at a high elevation site in the Australia Alps over the 2021/22 summer period and then identified and counted pollen using light microscopy. We show for the first time that Bogong moths visit a broad range of plant species during their summer activity period and characterise the plant assemblage visited. Almost all the 129 moths sampled carried pollen in large quantities, with a mean of 521 grains per moth. Individual moths varied considerably in pollen load and species composition, suggesting generalist flower visitation. The pollen taxa present on moths indicates local flower feeding at high elevation sites, rather than pollen carried from the lowland origins of migrants. The presence of pollen throughout summer indicates continual flower feeding activity. These results provide important new insights into the ecology of Bogong moths and suggest they could play a previously unrecognised role in pollination in sub-alpine and alpine ecosystems.

BackgroundInfluenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.MethodsWe measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q

Purpose: Cancer survivors often make long-term dietary changes, and nutrition is important for survivorship outcomes. Many survivors experience persisting cognitive difficulties, which can impact health behaviors. This study aimed to identify perceived drivers of eating habit changes, and the barriers to making intentional dietary changes, among breast cancer survivors with persisting self-reported cancer-related cognitive impairment. Materials and Methods: A qualitative framework explored survivors' perceptions of dietary habit changes. Thirteen Australian breast cancer survivors (M.time since diagnosis: 23.6 months, standard deviation [SD] 15.3; M.time since completing primary treatment: 14.7 months, SD 15.3) completed semistructured interviews. Questions related to dietary changes since diagnosis and treatment. Major themes were identified from interview transcripts using thematic analysis. Results: While most individuals perceived their diet to be broadly similar to prediagnosis, several changes to diet and eating habits were identified, which were often meaningful to these survivors. Themes relating to survivors' eating habit changes included the following: (1) meal timing and frequency shifts, (2) more plant-based eating, and (3) less variety and more convenience. Changes in eating habits were attributed to the following: (1) persisting treatment-related changes, (2) help and support from others, (3) old treatment habits, (4) preventative health and self-care, and (5) changes to work schedule. Barriers to making intentional dietary changes included the following: (1) too much time and effort, (2) food cravings and enjoyment, and (3) lacking dietary ideas and resources. Conclusions: Many survivors reported long-term changes in dietary habits, some of which align with current recommendations. Causes of dietary habit changes, and barriers to engaging in healthier dietary habits, involved multiple biopsychosocial elements. Additional resources or strategies that assist navigating survivorship challenges and their effects on dietary habits are needed. Future studies should explore whether post-treatment nutritional review with a qualified dietary health professional is helpful for survivors who experience long-term cancer-related cognitive impairment.

The antibody response to the SARS-CoV-2 Omicron variant is not well studied in children. Here, the authors provide an age-stratified analysis of SARS-CoV-2 neutralizing capacity of sera from children with acute or convalescent COVID-19 as well as children with multisystem inflammatory syndrome.

Introduction: The ferritin–lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. Methods: We characterised the prognostic value of FLR in COVID-19 patients, as compared to established inflammatory markers. Results: In 217 study patients (69 years [IQR: 55–82]; 60% males), FLR was weakly correlated with CRP (R = 0.108, p = 0.115) and white cell count (R = −0.144; p = 0.034). On ROC analysis, an FLR cut-off of 286 achieved a sensitivity of 86% and a specificity of 30% for predicting inpatient mortality (AUC 0.60, 95% CI: 0.53–0.67). The negative predictive values of FLR for ruling out mortality, non-invasive ventilation requirement and critical illness (intubation and/or ICU admission) were 86%, 85% and 93%, respectively. FLR performed similarly to CRP (AUC 0.60 vs. 0.64; p = 0.375) for predicting mortality, but worse than CRP for predicting non-fatal outcomes (all p < 0.05). On Kaplan–Meier analysis, COVID-19 patients with FLR values > 286 had worse inpatient survival than patients with FLR ≤ 286, p = 0.041. Conclusions: FLR has prognostic value in COVID-19 patients, and appears unrelated to other inflammatory markers such as CRP and WCC. FLR exhibits high sensitivity and negative predictive values for adverse clinical outcomes in COVID-19, and may be a good “rule-out” test. Further work is needed to improve the sensitivity of FLR and validate its role in prospective studies for guiding clinical management.

IntroductionAssessment of inpatient mortality risk in COVID-19 patients is important for guiding clinical decision-making. High sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiac injury associated with a worse prognosis in COVID-19. We explored how hs-cTnT could potentially be used in clinical practice for ruling in and ruling out mortality in COVID-19.MethodWe tested the diagnostic value of hs-cTnT in laboratory-confirmed COVID-19 patients (≥18 years old) admitted to the Royal Berkshire Hospital (UK) between 1st March and 10th May 2020. A normal hs-cTnT was defined as a value within the 99th percentile of healthy individuals (≤14 ng/L), and an elevated hs-cTnT was defined as >14 ng/L. Adverse clinical outcome was defined as inpatient mortality related to COVID-19.ResultsA total of 191 COVID-19 patients (62% male; age 66±16 years) had hs-cTnT measured on admission. Of these patients, 124 (65%) had elevated hs-cTnT and 67 (35%) had normal hs-cTnT. On a group level, patients with elevated hs-cTnT had worse inpatient survival (p = 0.0014; Kaplan-Meier analysis) and higher risk of inpatient mortality (HR 5.84 [95% CI 1.29-26.4]; p = 0.02; Cox multivariate regression) compared to patients with normal hs-cTnT. On a per-patient level, a normal hs-cTnT had a negative predictive value of 94% (95% CI: 85-98%) for ruling out mortality, whilst an elevated hs-cTnT had a low positive predictive value of 38% (95% CI: 39-47%) for ruling in mortality.ConclusionsIn this study cohort of COVID-19 patients, the potential clinical utility of hs-cTnT appears to rest in ruling out inpatient mortality. This finding, if prospectively validated in a larger study, may allow hs-cTnT to become an important biomarker to facilitate admission-avoidance and early safe discharge.

Summary: Background: There has been increasing awareness about the importance of type 1 diabetes (T1D) globally. Diabetic ketoacidosis (DKA) is a life-threatening complication of T1D in low-income settings. Little is known about health system capacity to manage DKA in low- and lower-middle income countries (LLMICs). As such, we describe health system capacity to diagnose and manage DKA across nine LLMICs using data from Service Provision Assessments. Methods: In this cross-sectional study, we used data from Service Provision Assessment (SPA) surveys, which are part of the Demographic and Health Survey (DHS) Program. We defined an item set to diagnose and manage DKA in higher-level (tertiary or secondary) facilities, and a set to assess and refer patients presenting to lower-level (primary) facilities. We quantified each item's availability by service level in Bangladesh (Survey 1: May 22 2014–Jul 20 2014; Survey 2: Jul 2017–Oct 2017), the Democratic Republic of the Congo (DRC) (Oct 16 2017–Nov 24 2017 in Kinshasha; Aug 08 2018–Apr 20 2018 in rest of country), Haiti (Survey 1: Mar 05 2013–Jul 2013; Survey 2: Dec 16 2017–May 09 2018), Ethiopia (Feb 06 2014–Mar 09 2014), Malawi (Phase 1: Jun 11 2013–Aug 20 2013; Phase 2: Nov 13 2013–Feb 7 2014), Nepal (Phase 1: Apr 20 2015–Apr 25 2015; Phase 2: Jun 04 2015–Nov 05 2015), Senegal (Survey 1: Jan 2014–Oct 2014; Survey 2: Feb 09 2015–Nov 10 2015; Survey 3: Feb 2016–Nov 2016; Survey 4: Mar 13 2017–Dec 15 2017; Survey 5: Apr 15 2018–Dec 31 2018; Survey 6: Apr 15 2019–Feb 28 2020), Tanzania (Oct 20 2014–Feb 21 2015), and Afghanistan (Nov 1 2018–Jan 20 2019). Variation in secondary facilities’ capacity and trends over time were also explored. Findings: We examined data from 2028 higher-level and 7534 lower-level facilities. Of these, 1874 higher-level and 6636 lower-level facilities’ data were eligible for analysis. Availability of all item sets were low at higher-level facilities, where less than 50% had the minimal set of supplies, less than 20% had the full minimal set, and less than 15% had the ideal set needed to diagnose and manage DKA. Across countries in lower-level facilities, less than 14% had the minimal set of supplies and less than 9% the full set of supplies for diagnosis and transfer of DKA patients. No country had more than 20% of facilities with the minimal set of items needed to assess or manage DKA. Where data were available for more than one survey (Bangladesh, Senegal, and Haiti), changes in availability of the minimal set and ideal set of items did not exceed 15%. Tertiary facilities performed best in Haiti, Ethiopia, Malawi, Nepal, Senegal, Tanzania, and Afghanistan. Secondary facilities that were rural, public, and had fewer staff had lower capacity. Interpretation: Health system capacity to manage DKA was low across these nine LLMICs. Although efforts are underway to strengthen health systems, a specific focus on DKA management is still needed. Funding: Leona M. and Harry B. Helmsley Charitable Trust, and Juvenile Diabetes Research Foundation Ltd.

BackgroundRespiratory syncytial virus (RSV) can cause life-threatening respiratory failure in infants. We sought to characterize the local host response to RSV infection in the nasal mucosa of infants with critical bronchiolitis and to identify early admission gene signatures associated with clinical outcomes.MethodsNasal scrape biopsies were obtained from 33 infants admitted to the pediatric intensive care unit (PICU) with critical RSV bronchiolitis requiring non-invasive respiratory support (NIS) or invasive mechanical ventilation (IMV), and RNA sequencing (RNA-seq) was performed. Gene expression in participants who required shortened NIS ( 3 days), and IMV was compared.FindingsIncreased expression of ciliated cell genes and estimated ciliated cell abundance, but not immune cell abundance, positively correlated with duration of hospitalization in infants with critical bronchiolitis. A ciliated cell signature characterized infants who required NIS for > 3 days while a basal cell signature was present in infants who required NIS for

Background: CRB-65 (Confusion; Respiratory rate ≥ 30/min; Blood pressure ≤ 90/60 mmHg; age ≥ 65 years) is a risk score for prognosticating patients with COVID-19 pneumonia. However, a significant proportion of COVID-19 patients have normal chest X-rays (CXRs). The influence of CXR abnormalities on the prognostic value of CRB-65 is unknown, limiting its wider applicability. Methods: We assessed the influence of CXR abnormalities on the prognostic value of CRB-65 in COVID-19. Results: In 589 study patients (71 years (IQR: 57–83); 57% males), 186 (32%) had normal CXRs. On ROC analysis, CRB-65 performed similarly in patients with normal vs. abnormal CXRs for predicting inpatient mortality (AUC 0.67 ± 0.05 vs. 0.69 ± 0.03). In patients with normal CXRs, a CRB-65 of 0 ruled out mortality, NIV requirement and critical illness (intubation and/or ICU admission) with negative predictive values (NPVs) of 94%, 98% and 99%, respectively. In patients with abnormal CXRs, a CRB-65 of 0 ruled out the same endpoints with NPVs of 91%, 83% and 86%, respectively. Patients with low CRB-65 scores had better inpatient survival than patients with high CRB-65 scores, irrespective of CXR abnormalities (all p < 0.05). Conclusions: CRB-65, CXR and CRP are independent predictors of mortality in COVID-19. Adding CXR findings (dichotomised to either normal or abnormal) to CRB-65 does not improve its prognostic accuracy. A low CRB-65 score of 0 may be a good rule-out test for adverse clinical outcomes in COVID-19 patients with normal or abnormal CXRs, which deserves prospective validation.

OBJECTIVE: The commute home following a night shift is associated with an increased risk for accidents. This study investigated the relationship between food intake during the night shift and simulated driving performance post-shift. METHODS: Healthy non-shift working males (N=23) and females (N=16), aged 18–39 years (mean 24.5, standard deviation 5.0, years) participated in a seven-day laboratory study and underwent four simulated night shifts. Participants were randomly allocated to one of three conditions: meal at night (N=12; 7 males), snack at night (N=13; 7 males) or no eating at night (N=14; 9 males). During the night shift at 00:30 hours, participants either ate a large meal (meal at night condition), a snack (snack at night condition), or did not eat during the night shift (no eating at night condition). During the second simulated night shift, participants performed a 40-minute York driving simulation at 20:00, 22:30, 01:30, 04:00, and 07:30 hours (similar time to a commute from work). RESULTS: The effects of eating condition, drive time, and time-on-task, on driving performance were examined using mixed model analyses. Significant condition×time interactions were found, where at 07:30 hours, those in the meal at night condition displayed significant increases in time spent outside of the safe zone (percentage of time spent outside 10 km/hour of the speed limit and 0.8 meters of the lane center; P

The negative impact of an unhealthy diet on the shiftworker population has been well-documented. However, little evidence exists on the underlying reasons for unhealthy eating behaviours and the existing barriers to healthy eating withinshiftwork environments. This qualitative study investigated the dietary behaviours reported by shiftworkers through Facebook comments. Comments were collected if they were on public shiftworker-relevant posts pertaining to dietary news or dietary information on Facebook and were posted by self-identified shiftworkers, relatives of shiftworkers, or partners of shiftworkers. A thematic analysis of the 144 comments collected generated four categories that can be used to understand the motivations for eating behaviour on-shift: what shiftworkers eat, where food is sourced from, when food is eaten, and why certain foods are chosen. Results reveal motivations, attitudes, and both internal and external barriers to healthy eating behaviours, as well as similarities and differences across shiftwork industries. Recommendations for future research include further explorations on the link between scheduled eating (e.g., time-restricted eating) and shiftwork, the impact of a rotating shift arrangements on dietary health behaviours, and the impact of interpersonal relationships on shiftworker dietary choices. Understanding these motivations will inform strategies to promote healthy eating and help understand barriers for shiftworkers.

Summary: Background: Despite declines in deaths from rheumatic heart disease (RHD) in Africa over the past 30 years, it remains a major cause of cardiovascular morbidity and mortality on the continent. We present an investment case for interventions to prevent and manage RHD in the African Union (AU). Methods: We created a cohort state-transition model to estimate key outcomes in the disease process, including cases of pharyngitis from group A streptococcus, episodes of acute rheumatic fever (ARF), cases of RHD, heart failure, and deaths. With this model, we estimated the impact of scaling up interventions using estimates of effect sizes from published studies. We estimated the cost to scale up coverage of interventions and summarised the benefits by monetising health gains estimated in the model using a full income approach. Costs and benefits were compared using the benefit–cost ratio and the net benefits with discounted costs and benefits. Findings: Operationally achievable levels of scale-up of interventions along the disease spectrum, including primary prevention, secondary prevention, platforms for management of heart failure, and heart valve surgery could avert 74 000 (UI 50 000–104 000) deaths from RHD and ARF from 2021 to 2030 in the AU, reaching a 30·7% (21·6–39·0) reduction in the age-standardised death rate from RHD in 2030, compared with no increase in coverage of interventions. The estimated benefit–cost ratio for plausible scale-up of secondary prevention and secondary and tertiary care interventions was 4·7 (2·9–6·3) with a net benefit of $2·8 billion (1·6–3·9; 2019 US$) through 2030. The estimated benefit–cost ratio for primary prevention scale-up was low to 2030 (0·2,

BackgroundThe health of populations living in extreme poverty has been a long-standing focus of global development efforts, and continues to be a priority during the Sustainable Development Goal era. However, there has not been a systematic attempt to quantify the magnitude and causes of the burden in this specific population for almost two decades. We estimated disease rates by cause for the world's poorest billion and compared these rates to those in high-income populations.MethodsWe defined the population in extreme poverty using a multidimensional poverty index. We used national-level disease burden estimates from the 2017 Global Burden of Disease Study and adjusted these to account for within-country variation in rates. To adjust for within-country variation, we looked to the relationship between rates of extreme poverty and disease rates across countries. In our main modeling approach, we used these relationships when there was consistency with expert opinion from a survey we conducted of disease experts regarding the associations between household poverty and the incidence and fatality of conditions. Otherwise, no within-country variation was assumed. We compared results across multiple approaches for estimating the burden in the poorest billion, including aggregating national-level burden from the countries with the highest poverty rates. We examined the composition of the estimated disease burden among the poorest billion and made comparisons with estimates for high-income countries.ResultsThe composition of disease burden among the poorest billion, as measured by disability-adjusted life years (DALYs), was 65% communicable, maternal, neonatal, and nutritional (CMNN) diseases, 29% non-communicable diseases (NCDs), and 6% injuries. Age-standardized DALY rates from NCDs were 44% higher in the poorest billion (23,583 DALYs per 100,000) compared to high-income regions (16,344 DALYs per 100,000). Age-standardized DALY rates were 2,147% higher for CMNN conditions (32,334 DALYs per 100,000) and 86% higher for injuries (4,182 DALYs per 100,000) in the poorest billion, compared to high-income regions.ConclusionThe disease burden among the poorest people globally compared to that in high income countries is highly influenced by demographics as well as large disparities in burden from many conditions. The comparisons show that the largest disparities remain in communicable, maternal, neonatal, and nutritional diseases, though NCDs and injuries are an important part of the "unfinished agenda" of poor health among those living in extreme poverty.

Background Global efforts to address NCDs focus primarily on 4-by-4 interventions – interventions to prevent and treat four groups of conditions affecting mainly older adults (some cardiovascular disease and cancers, type 2 diabetes, chronic respiratory disease) and four associated risk factors (alcohol, tobacco, poor diets, and physical inactivity). However, the NCD burden in Sub-Saharan Africa (SSA) is composed of a more diverse set of conditions, driven by a more complex group of risks, and impacting all segments of the population. Objective To document the NCD priorities identified by NCD strategic plans, to characterize the proposed policy response, and to assess the alignment between the two. Methods Using a two-part conceptual framework, we undertook a descriptive study to characterize the framing and overall policy response of strategic plans from 24 low- and lower-middle-income countries across SSA. Results The national situation assessments that ground strategic plans emphasize a diversity of conditions that range in terms of severity and frequency. These assessments also highlight a wide diversity of factors that shape this burden. Most include discussions of a broad range of behavioral, structural, genetic, and infectious risk factors. Plans endorse a more narrow response to this diverse burden, with a focus on primary and secondary prevention that is generally convergent with the objectives established in global policy documents. Conclusions Broadly, we observe that plans developed by countries in SSA recognize the heterogeneity of the NCD burden in this region. However, they emphasize interventions that are consistent with global strategies focused on preventing a narrower set of cardiometabolic risk factors and their associated diseases. In comparison, relatively few countries detail plans to prevent, treat, and palliate the full scope of the needs they identify. There is a need for increased support for bottom-up planning efforts to address local priorities.

Context and objectives Non-communicable diseases and injuries (NCDIs) comprise a large share of mortality and morbidity in low-income countries (LICs), many of which occur earlier in life and with greater severity than in higher income settings. Our objective was to assess availability of essential equipment and medications required for a broad range of acute and chronic NCDI conditions.Design Secondary analysis of existing cross-sectional survey data.Setting We used data from Service Provision Assessment surveys in Bangladesh, the Democratic Republic of the Congo, Ethiopia, Haiti, Malawi, Nepal, Senegal and Tanzania, focusing on public first-referral level hospitals in each country.Outcome measures We defined sets of equipment and medications required for diagnosis and management of four acute and nine chronic NCDI conditions and determined availability of these items at the health facilities.Results Overall, 797 hospitals were included. Medication and equipment availability was highest for acute epilepsy (country estimates ranging from 40% to 95%) and stage 1–2 hypertension (28%–83%). Availability was low for type 1 diabetes (1%–70%), type 2 diabetes (3%–57%), asthma (0%–7%) and acute presentations of diabetes (0%–26%) and asthma (0%–4%). Few hospitals had equipment or medications for heart failure (0%–32%), rheumatic heart disease (0%–23%), hypertensive emergencies (0%–64%) or acute minor surgical conditions (0%–5%). Data for chronic pain were limited to only two countries. Availability of essential medications and equipment was lower than previous facility-reported service availability.Conclusions Our findings demonstrate low availability of essential equipment and medications for diverse NCDIs at first-referral level hospitals in eight LICs. There is a need for decentralisation and integration of NCDI services in existing care platforms and improved assessment and monitoring to fully achieve universal health coverage.

Cardiac function has been shown to transiently decrease following prolonged exercise, with greater durations related to increased impairment. However, the prospective assessment of exercise duration on cardiac performance is rare, and the influence of relative exercise intensity is typically not assessed in relation to these changes. The aim of this study was to determine whether progressively longer running distances over the same course would elicit greater cardiac impairment. The present investigation examined cardiac alterations in 49 athletes, following trail-running races of 25, 50, 80, and 160 km, performed on the same course on the same day. Echocardiography, including conventional and speckle tracking imaging, was performed with legs-raised to 60° to mitigate alterations in preload both pre- and post-race. Race-intensities were monitored via heart rate (HR). Following the races, mean arterial pressure (Δ−11 ± 7 mmHg, P < 0.0001), and HR (Δ19 ± 14 bpm, P < 0.0001) were altered independent of race distance. Both left and right ventricular (LV and RV) diastolic function were reduced (ΔLV E/A −0.54 ± 0.49, P < 0.0001; ΔRV A’ + 0.02 ± 0.04 m/s, P = 0.01) and RV systolic function decreased (ΔTAPSE −0.25 ± 0.9 cm, P = 0.01), independent of race distance. Cardiac impairment was not apparent using speckle tracking analysis with cubic spline interpolation. While race duration was unrelated to cardiac alterations, increased racing HR was related to greater RV base dilation (r = −0.37, P = 0.03). Increased time spent at higher exercise intensities was related to reduced LV ejection fraction following 25 km (r = −0.81, P = 0.03), LV systolic strain rate following 50 km (r = 0.59, P = 0.04), and TAPSE (r = −0.81, P = 0.03) following 80 km races. Increased running duration did not affect the extent of exercise-induced cardiac fatigue, however, intensity may be a greater driver of cardiac alterations.

Background:. Influenza virus is a major cause of acute hypoxemic respiratory failure. Early identification of patients who will suffer severe complications can help stratify patients for clinical trials and plan for resource use in case of pandemic. Objective:. We aimed to identify which clinical variables best predict prolonged acute hypoxemic respiratory failure in influenza-infected critically ill children. Acute hypoxemic respiratory failure was defined using hypoxemia cutoffs from international consensus definitions of acute respiratory distress syndrome in patients with ventilatory support. Prolonged acute hypoxemic respiratory failure was defined by acute hypoxemic respiratory failure criteria still present at PICU day 7. Derivation Cohort:. In this prospective multicenter study across 34 PICUs from November 2009 to April 2018, we included children (< 18 yr) without comorbid risk factors for severe disease. Validation Cohort:. We used a Monte Carlo cross validation method with N2 random train-test splits at a 70–30% proportion per model. Prediction Model:. Using clinical data at admission (day 1) and closest to 8 am on PICU day 2, we calculated the area under the receiver operating characteristic curve using random forests machine learning algorithms and logistic regression. Results:. We included 258 children (median age = 6.5 yr) and 11 (4.2%) died. By day 2, 65% (n = 165) had acute hypoxemic respiratory failure dropping to 26% (n = 67) with prolonged acute hypoxemic respiratory failure by day 7. Those with prolonged acute hypoxemic respiratory failure had a longer ICU stay (16.5 vs 4.0 d; p < 0.001) and higher mortality (13.4% vs 1.0%). A multivariable model using random forests with 10 admission and eight day 2 variables performed best (0.93 area under the receiver operating characteristic curve; 95 CI%: 0.90–0.95) where respiratory rate, Fio2, and pH on day 2 were the most important factors. Conclusions:. In this prospective multicentric study, most children with influenza virus–related respiratory failure with prolonged acute hypoxemic respiratory failure can be identified early in their hospital course applying machine learning onto routine clinical data. Further validation is needed prior to bedside implementation.

Introduction Epidemiological studies indicate an inverse association between nut consumption and body mass index (BMI). However, clinical trials evaluating the effects of nut consumption compared with a nut-free diet on adiposity have reported mixed findings with some studies reporting greater weight loss and others reporting no weight change. This paper describes the rationale and detailed protocol for a randomised controlled trial assessing whether the inclusion of almonds or carbohydrate-rich snacks in an otherwise nut-free energy-restricted diet will promote weight loss during 3 months of energy restriction and limit weight regain during 6 months of weight maintenance.Methods and analysis One hundred and thirty-four adults aged 25–65 years with a BMI of 27.5–34.9 kg/m2 will be recruited and randomly allocated to either the almond-enriched diet (AED) (15% energy from almonds) or a nut-free control diet (NFD) (15% energy from carbohydrate-rich snack foods). Study snack foods will be provided. Weight loss will be achieved through a 30% energy restriction over 3 months, and weight maintenance will be encouraged for 6 months by increasing overall energy intake by ~120–180 kcal/day (~500-750kJ/day) as required. Food will be self-selected, based on recommendations from the study dietitian. Body composition, resting energy expenditure, total daily energy expenditure (via doubly labelled water), physical activity, appetite regulation, cardiometabolic health, gut microbiome, liver health, inflammatory factors, eating behaviours, mood and personality, functional mobility and pain, quality of life and sleep patterns will be measured throughout the 9-month trial. The effects of intervention on the outcome measures over time will be analysed using random effects mixed models, with treatment (AED or NFD) and time (baseline, 3 months and 9 months) being the between and within factors, respectively in the analysis.Ethics and dissemination Ethics approval was obtained from the University of South Australia Human Research Ethics Committee (201436). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12618001861246).

ObjectivesAt any point in time, a person's lifetime health is the number of healthy life years they are expected to experience during their lifetime. In this article we propose an equity-relevant health metric, Health Adjusted Age at Death (HAAD), that facilitates comparison of lifetime health for individuals at the onset of different medical conditions, and allows for the assessment of which patient groups are worse off. A method for estimating HAAD is presented, and we use this method to rank four conditions in six countries according to several criteria of "worse off" as a proof of concept.MethodsFor individuals with specific conditions HAAD consists of two components: past health (before disease onset) and future expected health (after disease onset). Four conditions (acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), schizophrenia, and epilepsy) are analysed in six countries (Ethiopia, Haiti, China, Mexico, United States and Japan). Data from 2017 for all countries and for all diseases were obtained from the Global Burden of Disease Study database. In order to assess who are the worse off, we focus on four measures: the proportion of affected individuals who are expected to have HAADResultsEven in settings where aHAAD is similar for two conditions, other measures may vary. One example is AML (aHAAD = 59.3, T20 = 2.0%, Q3-Q1 = 14.8) and ALL (58.4, T20 = 4.6%, Q3-Q1 = 21.8) in the US. Many illnesses, such as epilepsy, are associated with more lifetime health in high-income settings (Q1 in Japan = 59.2) than in low-income settings (Q1 in Ethiopia = 26.3).ConclusionUsing HAAD we may estimate the distribution of lifetime health of all individuals in a population, and this distribution can be incorporated as an equity consideration in setting priorities for health interventions.

Cardiovascular disease (CVD) poses a serious health and economic burden worldwide. Modifiable lifestyle factors are a focus of research into reducing the burden of CVD, with diet as one of the most investigated factors. Specifically, the timing and regularity of food intake is an emerging research area, with approaches such as time-restricted eating (TRE) receiving much attention. TRE involves shortening the time available to eat across the day and is associated with improved CVD outcomes compared with longer eating windows. However, studies that have examined TRE have not considered the impact of sleep on CVD outcomes despite recent evidence showing that sleep duration can influence the timing and amount of food eaten. In this article, we argue that as TRE and sleep influence each other, and influence the same cardiometabolic parameters, experiencing inadequate sleep may attenuate any positive impact TRE has on CVD. We examine the relationship between TRE and CVD, with sleep as a potential mediator in this relationship, and propose a research agenda to investigate this relationship. This will provide necessary evidence to inform future interventions aimed at reducing the burden of CVD.

Chronic obstructive pulmonary disease (COPD) is a progressive disease of the airways, underpinned by inflammation and worsening lung function. Omega-3 polyunsaturated fatty acids (n-3PUFA) can modulate inflammatory mechanisms and may therefore impact lung function in people with COPD. This observational, cross-sectional study of 577 adults in the Whyalla Intergenerational Study of Health (WISH), conducted during 2008–09 in regional South Australia, explored associations between fish and PUFA intakes (from food frequency questionnaires) and lung function (spirometry). It also included a nested case-control study which compared fish and PUFA intakes and plasma phospholipid PUFA levels between 40 people with COPD and 80 age-sex matched controls. In the whole population, linear regression models adjusted for age, sex, smoking status and education demonstrated a weak negative association between lung function (FEV1% predicted) and consumption of fried fish (OR -0.12, 95% CI -0.22, −0.01, P = 0.026) but not fish prepared by other cooking methods or estimated intakes of PUFA. There was no association between fish or PUFA intakes and COPD risk. Compared to age and sex matched controls, cases had poorer lung function and a higher rate of smoking prevalence but did not differ in their intakes of fish or PUFA or their PUFA levels in plasma phospholipids. In this sub-population, we found a marginally significant association between COPD risk and total long chain n-3PUFA levels in plasma phospholipids (OR 1.22 95% CI 1.00–1.49, P = 0.046). Given the relatively small number of cases in this analysis, this finding should be interpreted with caution, especially given the lack of association with other markers of n-3PUFA intake or status. Taken together, our data suggest that n-3PUFA intake and status are not determinants of improved lung function in this regional Australian population. Keywords: Lung function, Chronic obstructive pulmonary disease, COPD, Polyunsaturated fatty acid, PUFA

Fusarium wilt of banana (also known as Panama disease) has been a problem in Australia since 1874. Race 1 of the pathogen (Fusarium oxysporum f. sp. cubense) is responsible for damage to ‘Lady Finger’ (AAB, Pome subgroup) and other less widely grown cultivars such as ‘Ducasse’ (Pisang Awak, ABB). Subtropical Race 4 (STR4) also affects these cultivars as well as Cavendish cultivars (AAA) in southern Queensland and northern New South Wales where cold temperature predisposition is involved. Tropical Race 4 (TR4) has led to the demise of the Cavendish industry in the Northern Territory, and its presence was confirmed in a North Queensland plantation in 2015, which warranted destruction of all banana plants on the property; as of this writing (April 2019), TR4 has spread to two adjacent properties. This review, which was commissioned by Biosecurity Queensland in response to the 2015 TR4 outbreak, considers the key epidemiological factors associated with the onset of a Fusarium wilt epidemic. Resistance to TR4, which is mediated by events following entry by the pathogen into the xylem, is not present in any commercially acceptable banana cultivar. Also, there is no effective chemical agent that can be used to manage the disease. Besides prevention, very early recognition and rapid containment of a disease outbreak are necessary to prevent epidemic development. A good understanding of the key factors responsible for disease development is required when devising practical protocols for the destruction of infected plants, treatment of surrounding infested soil, and reduction of inoculum in plant residues and soil.

Abstract The Office of Dietary Supplements, the National Institute on Minority Health and Health Disparities, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases, all components of the U.S. National Institutes of Health, co-sponsored an expert panel meeting to discuss the vitamin D paradox in Black Americans. The paradox is that despite markedly low (or “deficient”) measures of vitamin D status in Black Americans, the incidence of falls, fractures, or osteopenia are significantly lower compared to White American counterparts with similar vitamin D status. Six panelists were invited to engage in guided discussions on the state of the science with respect to key knowledge gaps impacting vitamin D status and bone health. They were also asked to reflect on best approaches for advancing the science. A central theme throughout the discussions was that there may be many factors that impact Vitamin D levels in Black Americans and understanding these factors may be key to understanding mechanisms for improving bone health in all populations. Data presented showed that although adiposity, skin pigmentation, vitamin D binding protein polymorphisms, and genetics all contributed to differences in 25(OH)D levels in Black vs. White Americans, no one factor alone could fully explain the vitamin D paradox in Black Americans. However, the panelists did agree that the paradox is significant and warrants further investigation. There was consensus that Black Americans gained no skeletal benefits from high doses of vitamin D supplementation, and that high levels of the biomarker of vitamin D status, serum 25-hydroxyvitamin D or 25(OH)D, in this population are almost certain to result in adverse effects. Some panelists proposed that additional studies are needed so that the Institute of Medicine (IOM) can better define the safe upper limits of vitamin D intake in this and other subpopulations. Others suggested a need for better, more generalizable biomarkers of bone health to advance the science.

Survivors of cancer frequently experience persistent and troublesome cognitive changes. Little is known about the role diet and nutrition plays in survivors’ cognition. We explored the feasibility of collecting cross-sectional online data from Australian survivors of breast and colorectal cancer to enable preliminary investigations of the relationships between cognition with fruit and vegetable intake, and the Omega-3 Index (a biomarker of long chain omega 3 fatty acid intake). A total of 76 participants completed online (and postal Omega-3 Index biomarker) data collection (62 breast and 14 colorectal cancer survivors): mean age 57.5 (±10.2) years, mean time since diagnosis 32.6 (±15.6) months. Almost all of the feasibility outcomes were met; however, technical difficulties were reported for online cognitive testing. In hierarchical linear regression models, none of the dietary variables of interest were significant predictors of self-reported or objective cognition. Age, BMI, and length of treatment predicted some of the cognitive outcomes. We demonstrated a viable online/postal data collection method, with participants reporting positive levels of engagement and satisfaction. Fruit, vegetable, and omega-3 intake were not significant predictors of cognition in this sample, however the role of BMI in survivors′ cognitive functioning should be further investigated. Future research could adapt this protocol to longitudinally monitor diet and cognition to assess the impact of diet on subsequent cognitive function, and whether cognitive changes impact dietary habits in survivors of cancer.

Unusual meal timing has been associated with a higher prevalence of chronic disease. Those at greater risk include shift workers and evening chronotypes. This study aimed to validate the content of a Chrononutrition Questionnaire for shift and non-shift workers to identify temporal patterns of eating in relation to chronotype. Content validity was determined using a Delphi study of three rounds. Experts rated the relevance of, and provided feedback on, 46 items across seven outcomes: meal regularity, times of first eating occasion, last eating occasion, largest meal, main meals/snacks, wake, and sleep, which were edited in response. Items with greater than 70% consensus of relevance were accepted. Rounds one, two, and three had 28, 26, and 24 experts, respectively. Across three rounds, no outcomes were irrelevant, but seven were merged into three for ease of usage, and two sections were added for experts to rate and comment on. In the final round, all but one of 29 items achieved greater than 70% consensus of relevance with no further changes. The Chrononutrition Questionnaire was deemed relevant to experts in circadian biology and chrononutrition, and could represent a convenient tool to assess temporal patterns of eating in relation to chronotype in future studies.

Abstract Background Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) may act as an effective adjunct therapy for chronic obstructive pulmonary disease (COPD), a condition characterised by persistent airflow limitation and inflammation. However, the nature of this illness presents challenges for evaluating potential benefits. The aim of this study was to determine the feasibility of undertaking a randomised controlled trial of LCn-3PUFA supplementation in adults with COPD. Methods A 16-week parallel, double-blind, randomised, placebo-controlled dietary supplementation trial was conducted. Participants diagnosed with COPD were randomly allocated to take six 1-g capsules of fish oil (3.6 g LCn-3PUFA) or corn oil (placebo) daily for 16 weeks. Key outcomes used to determine the feasibility of the trial included recruitment rate, participant retention rate and supplement adherence (blood biomarker and returned capsule count). An estimate of the effect size for clinical outcomes such as pulmonary function and functional exercise capacity was calculated. Results None of the key feasibility criteria were met. The enrolment target was 40 participants in 52 weeks; however, only 13 were finally enrolled, with just seven in the first 52 weeks. Eight participants completed the study (retention rate 62%). Targets for compliance were not achieved; red blood cell LCn-3PUFA content (expressed as percentage of total fatty acids) did not increase by more than 2% in the fish oil group; capsule counts were unreliable. As the target sample size was not achieved and only a small number of participants completed the study, it was not possible to use the variance in clinical outcomes to estimate a sample size for a future study. Conclusions This study highlights major difficulties, especially with recruitment, in conducting this LCn-3PUFA supplementation trial in people with COPD, rendering the protocol unfeasible by predetermined criteria. A modified approach is needed to investigate potential health benefits of fish oil in people with COPD. A multicentre study with changes to inclusion and exclusion criteria is recommended. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR), ACTRN12612000158864

Background Foods rich in nutrients, such as nitrate, nitrite, L-arginine and polyphenols, can promote the synthesis of nitric oxide (NO), which may induce ergogenic effects on endurance exercise performance. Thus, consuming foods rich in these components, such as almonds, dried grapes and dried cranberries (AGC), may improve athletic performance. Additionally, the antioxidant properties of these foods may reduce oxidative damage induced by intense exercise, thus improving recovery and reducing fatigue from strenuous physical training. Improvements in NO synthesis may also promote cerebral blood flow, which may improve cognitive function.Methods and analysis Ninety-six trained male cyclists or triathletes will be randomised to consume ~2550 kJ of either a mixture of AGC or a comparator snack food (oat bar) for 4 weeks during an overreaching endurance training protocol comprised of a 2-week heavy training phase, followed by a 2-week taper. The primary outcome is endurance exercise performance (5 min time-trial performance) and secondary outcomes include markers of NO synthesis (plasma and urinary nitrites and nitrates), muscle damage (serum creatine kinase and lactate dehydrogenase), oxidative stress (F2-isoprostanes), endurance exercise function (exercise efficiency, submaximal oxygen consumption and substrate utilisation), markers of internal training load (subjective well-being, rating of perceived exertion, maximal rate of heart rate increase and peak heart rate) and psychomotor speed (choice reaction time).Conclusion This study will evaluate whether consuming AGC improves endurance exercise performance, recovery and psychomotor speed across an endurance training programme, and evaluate the mechanisms responsible for any improvement.Trial registration number ACTRN12618000360213.