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Background: Saudi Arabia is experiencing rapid development of the built environment and implementing policy changes to promote physical activity (PA) and reduce sedentary behavior (SB) among its population. In light of these developments, this scoping review systematically summarized population levels of PA/SB in Saudi Arabia. Methods: The authors searched 6 databases on December 13, 2021, for articles published in English or Arabic from 2018 to the search date. Studies using population-based sampling in Saudi Arabia and measuring PA/SB were included. Results: Of the 1272 records found, 797 were screened, and 19 studies (9 on children/adolescents age 6–19 y and 10 on adults age 15–75 y) were included. All studies were cross-sectional in design, and 18 studies collected data at only one point in time, ranging from 2009 to 2020. A total of 18 studies relied on self-reporting to assess PA/SB using a variety of questionnaires. Among children/adolescents, approximately 80% to 90% did not attain at least 60 minutes per day of moderate to vigorous PA and 50% to 80% engaged in ≥2 hours per day of screen time or SB. Among adults, approximately 50% to 95% had low or insufficient PA (eg, less than meeting PA guidelines) and about half had a sitting time of ≥5 hours per day. Population-based studies were not found among children 75 years. Conclusions: A high proportion of participants in the reviewed studies did not meet PA recommendations and spent excessive time in SB. Ongoing surveillance efforts for all ages may help identify target populations for interventions and prioritize the national strategy on PA/SB in Saudi Arabia.

There is much evidence showing that physical activity is related to optimal health, including physical and mental function, and quality of life. Additionally, data are accumulating with regard to the detrimental health impacts of sedentary behavior. Much of the evidence related to long-term health outcomes, such as cardiovascular disease and cancer—the two leading causes of death in the United States and worldwide—comes from observational epidemiologic studies and, in particular, prospective cohort studies. Few data on these outcomes are derived from randomized controlled trials, conventionally regarded as the “gold standard” of research designs. Why is there a paucity of data from randomized trials on physical activity or sedentary behavior and long-term health outcomes? A further issue to consider is that prospective cohort studies investigating these outcomes can take a long time to accrue sufficient numbers of endpoints for robust and meaningful findings. This contrasts with the rapid pace at which technology advances. Thus, while the use of devices for measuring physical behaviors has been an important development in large-scale epidemiologic studies over the past decade, cohorts that are now publishing results on health outcomes related to accelerometer-assessed physical activity and sedentary behavior may have been initiated years ago, using “dated” technology. This paper, based on a keynote presentation at 8th International Conference on Ambulatory Monitoring of Physical Activity and Movement 2022, discusses the issues of study design and slow pace of discovery in prospective cohort studies and suggests some possible ways to maximize the utility and comparability of “dated” device data from prospective cohort studies for research investigations using the Women’s Health Study as an example.

Purpose: The purpose of this study was to develop 60-s epoch accelerometer intensity cut points for vertical axis count and vector magnitude (VM) output from hip-worn triaxial accelerometers among women 60–91 years old. We also compared these cut points against cut points derived by multiplying 15-s epoch cut points by four. Methods: Two hundred apparently healthy women wore an ActiGraph GT3X+ accelerometer on their hip while performing a variety of laboratory-based activities that were sedentary (watching television and assembling a puzzle), low light (washing/drying dishes), high light (laundry and dust mopping), or moderate-to-vigorous physical activity (400-m walk) intensity. Oxygen uptake was measured using an Oxycon portable calorimeter. Sedentary behavior and physical activity intensity cut points for vertical axis and VM counts were derived for 60-s epochs from receiver operating characteristic and by multiplying the 15-s cut points by four; both were compared with oxygen uptake. Results: The median age was 74.5 years (interquartile range 70–83). The 60-s epoch cut points for vertical counts were 0 sedentary, 1–73 low light, 74–578 high light, and ≥579 moderate-to-vigorous physical activity. The 60-s epoch cut points for VM were 0–88 sedentary, 89–663 low light, 664–1,730 high light, and ≥1,731 moderate-to-vigorous physical activity. For both sets of cut points, the receiver operating characteristic approach yielded more accurate estimates than the multiplication approach. Conclusion: The derived 60-s epoch cut points for vertical counts and VM can be applied to epidemiologic studies to define sedentary behavior and physical activity intensities in older adult populations.

The idea that we can detect subacute potentially catastrophic illness earlier by using statistical models trained on clinical data is now well-established. We review evidence that supports the role of continuous cardiorespiratory monitoring in these predictive analytics monitoring tools. In particular, we review how continuous ECG monitoring reflects the patient and not the clinician, is less likely to be biased, is unaffected by changes in practice patterns, captures signatures of illnesses that are interpretable by clinicians, and is an underappreciated and underutilized source of detailed information for new mathematical methods to reveal.

Walking cadence (steps/min) has emerged as a valid proxy of physical activity intensity, with consensus across numerous laboratory-based treadmill studies that ≥100 steps/min approximates absolutely defined moderate intensity (≥3 metabolic equivalents; METs). We recently reported that this cadence threshold had a classification accuracy of 73.3% for identifying moderate intensity during preferred pace overground walking in young adults. The purpose of this study was to evaluate and compare the performance of a cadence threshold of ≥100 steps/min for correctly classifying moderate intensity during overground walking in middle- and older-aged adults.Participants (N = 174, 48.3% female, 41-85 years of age) completed laboratory-based cross-sectional study involving an indoor 5-min overground walking trial at their preferred pace. Steps were manually counted and converted to cadence (total steps/5 min). Intensity was measured using indirect calorimetry and expressed as METs. Classification accuracy (sensitivity, specificity, accuracy) of a cadence threshold of ≥100 steps/min to identify individuals walking at ≥3 METs was calculated.The ≥100 steps/min threshold demonstrated accuracy of 74.7% for classifying moderate intensity. When comparing middle- vs. older-aged adults, similar accuracy (73.4% vs. 75.8%, respectively) and specificity (33.3% vs. 34.5%) were observed. Sensitivity was high, but was lower for middle- vs. older-aged adults (85.2% vs. 93.9%, respectively).A cadence threshold of ≥100 steps/min accurately identified moderate-intensity overground walking. Furthermore, accuracy was similar when comparing middle- and older-aged adults. These findings extend our previous analysis in younger adults and confirm the appropriateness of applying this cadence threshold across the adult lifespan.

The Compendium of Physical Activities reports that walking at 2.5 mph associates with absolutely-defined moderate intensity (i.e., ≥3 metabolic equivalents [METs]). However, it is unclear whether this speed threshold is accurate during overground walking and/or across the adult age-span. This study aimed to identify optimal and heuristic speed thresholds associated with 3 METs during overground walking across age groups. Healthy adults (n = 248, 21-85 years old, 49% women) performed a 5-minute self-paced overground walking trial. Speed was measured using an electronic gait mat, and oxygen uptake was measured using indirect calorimetry and converted to METs. Optimal and heuristic thresholds and classification accuracy metrics were determined and compared using ROC curve analyses. Speed thresholds (95% CIs) associated with 3 METs for the whole sample, young (21-40 years), middle-aged (41-60 years) and older-aged (61-85 years) groups were 1.29 (1.25, 1.33), 1.30 (1,26, 1,35), and 1.25 (1.21, 1.29) m/s, respectively. Overall, 3 mph and 5 km/h performed better than 2.5 mph and 4.5 km/h in balancing both sensitivity and specificity (higher Youden's Indices). Overground walking speeds associated with 3 METs were similar across age groups. A heuristic threshold of 3 mph or 5 km/h may better identify absolutely-defined moderate intensity overground walking.

The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This paper represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.

Step-based metrics provide simple measures of ambulatory activity, yet device software either includes undisclosed proprietary step detection algorithms or simply does not compute step-based metrics. We aimed to develop and validate a simple algorithm to accurately detect steps across various ambulatory and nonambulatory activities. Seventy-five adults (21–39 years) completed seven simulated activities of daily living (e.g., sitting, vacuuming, folding laundry) and an incremental treadmill protocol from 0.22 to 2.2 m/s. Directly observed steps were hand-tallied. Participants wore GENEActiv and ActiGraph accelerometers, one of each on their waist and on their nondominant wrist. Raw acceleration (g) signals from the anterior–posterior, medial–lateral, vertical, and vector magnitude directions were assessed separately for each device. Signals were demeaned across all activities and band-pass filtered (0.25, 2.5 Hz). Steps were detected via peak picking, with optimal thresholds (i.e., minimized absolute error from accumulated hand counted) determined by iterating minimum acceleration values to detect steps. Step counts were converted into cadence (steps/minute), and k-fold cross-validation quantified error (root mean squared error [RMSE]). We report optimal thresholds for use of either device on the waist (threshold = 0.0267g) and wrist (threshold = 0.0359g) using the vector magnitude signal. These thresholds yielded low error for the waist (RMSE

Pneumonia is among the most common causes of death worldwide. The epidemiologic and clinical heterogeneity of pneumonia results in challenges in diagnosis and treatment. There is inconsistency in the definition of the group of microorganisms that cause "atypical pneumonia." Nevertheless, the use of this term in the medical and radiologic literature is common. Among the causes of communityacquired pneumonia, atypical bacteria are responsible for approximately 15% of cases. Zoonotic and nonzoonotic bacteria, as well as viruses, have been considered among the causes of atypical pneumonia in a patient who is immunocompetent and have been associated with major community outbreaks of respiratory infection, with relevant implications in public health policies. Considering the difficulty of isolating atypical microorganisms and the significant overlap in clinical manifestations, a targeted empirical therapy is not possible. Imaging plays an important role in the diagnosis and management of atypical pneumonia, as in many cases its findings may first suggest the possibility of an atypical infection. Clarifying and unifying the definition of atypical pneumonia among the medical community, including radiologists, are of extreme importance. The prompt diagnosis and prevention of community spread of some atypical microorganisms can have a relevant impact on local, regional, and global health policies. (C) RSNA, 2021

Single-cell genomics is a rapidly advancing field; however, most techniques are designed for mammalian cells. We present a single-cell sequencing pipeline for an intracellular parasite, Plasmodium falciparum, with a small genome of extreme base content. Through optimization of a quasi-linear amplification method, we target the parasite genome over contaminants and generate coverage levels allowing detection of minor genetic variants. This work, as well as efforts that build on these findings, will enable detection of parasite heterogeneity contributing to P. falciparum adaptation. Furthermore, this study provides a framework for optimizing single-cell amplification and variant analysis in challenging genomes. Supplementary Information The online version contains supplementary material available at 10.1186/s13073-021-00889-9.

BackgroundProgressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously, but occult hypoxemia can occur in Black patients because the technique is affected by skin color. Oxygen dissociation curves allow non-invasive estimation of P/F ratios (ePFR) but this approach remains unproven.Research QuestionCan ePFRs measure overt and occult hypoxemia?Study Design and methodsWe retrospectively studied COVID-19 hospital encounters (n=5319) at two academic centers (University of Virginia [UVA] and Emory University). We measured primary outcomes (death or ICU transfer within 24 hours), ePFR, conventional hypoxemia measures, baseline predictors (age, sex, race, comorbidity), and acute predictors (National Early Warning Score (NEWS) and Sepsis-3). We updated predictors every 15 minutes. We assessed predictive validity using adjusted odds ratios (AOR) and area under receiver operating characteristics curves (AUROC). We quantified disparities (Black vs non-Black) in empirical cumulative distributions using the Kolmogorov-Smirnov (K-S) two-sample test.ResultsOvert hypoxemia (low ePFR) predicted bad outcomes (AOR for a 100-point ePFR drop: 2.7 [UVA]; 1.7 [Emory]; pInterpretationThe ePFR was a valid measure of overt hypoxemia. In COVID-19, it may outperform multi-organ dysfunction models like NEWS and Sepsis-3. By accounting for biased oximetry as well as clinicians’ real-time responses to it (supplemental oxygen adjustment), ePFRs may enable statistical modelling of racial disparities in outcomes attributable to occult hypoxemia.

Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda.This is a phase 3, multisite, open-label, randomised controlled clinical 2×2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58.This clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation.ClinicalTrials.gov (NCT04618198).

The natural transition from walking to running occurs in adults at ≅140 steps/min. It is unknown when this transition occurs in children and adolescents. The purpose of this study was to develop a model to predict age- and anthropometry-specific preferred transition cadences in individuals 6-20 years of age. Sixty-nine individuals performed sequentially faster 5-min treadmill walking bouts, starting at 0.22 m/s and increasing by 0.22 m/s until completion of the bout during which they freely chose to run. Steps accumulated during each bout were directly observed and converted to cadence (steps/min). A logistic regression model was developed to predict preferred transition cadences using the best subset of parameters. The resulting model, which included age, sex, height, and BMI z-score, produced preferred transition cadences that accurately classified gait behaviour (k-fold cross-validated prediction accuracy =97.02%). This transition cadence ranged from 136-161 steps/min across the developmental age range studied. The preferred transition cadence represents a simple and practical index to predict and classify gait behaviour from wearable sensors in children, adolescents, and young adults. Moreover, herein we provide an equation and an open access online R Shiny app that researchers, practitioners, or clinicians can use to predict individual-specific preferred transition cadences.

Background: The authors conducted a scoping review as a first step toward establishing harmonized (ie, consistent and compatible), empirically based best practices for validating step-counting wearable technologies. Purpose: To catalog studies validating step-counting wearable technologies during treadmill ambulation. Methods: The authors searched PubMed and SPORTDiscus in August 2019 to identify treadmill-based validation studies that employed the criterion of directly observed (including video recorded) steps and cataloged study sample characteristics, protocol details, and analytical procedures. Where reported, speed- and wear location–specific mean absolute percentage error (MAPE) values were tabulated. Weighted median MAPE values were calculated by wear location and a 0.2-m/s speed increment. Results: Seventy-seven eligible studies were identified: most had samples averaging 54% (SD = 5%) female and 27 (5) years of age, treadmill protocols consisting of 3 to 5 bouts at speeds of 0.8 (0.1) to 1.6 (0.2) m/s, and reported measures of bias. Eleven studies provided MAPE values at treadmill speeds of 1.1 to 1.8 m/s; their weighted median MAPE values were 7% to 11% for wrist-worn, 1% to 4% for waist-worn, and ≤1% for thigh-worn devices. Conclusions: Despite divergent study methodologies, the authors identified common practices and summarized MAPE values representing device step-count accuracy during treadmill walking. These initial empirical findings should be further refined to ultimately establish harmonized best practices for validating wearable technologies.

PURPOSE This study aimed to develop cadence-based metabolic equations (CME) for predicting the intensity of level walking and evaluate these CME against the widely adopted American College of Sports Medicine (ACSM) Metabolic Equation, which predicts walking intensity from speed and grade. METHODS Two hundred and thirty-five adults (21-84 yr of age) completed 5-min level treadmill walking bouts between 0.22 and 2.24 m·s, increasing by 0.22 m·s for each bout. Cadence (in steps per minute) was derived by dividing directly observed steps by bout duration. Intensity (oxygen uptake; in milliliters per kilogram per minute) was measured using indirect calorimetry. A simple CME was developed by fitting a least-squares regression to the cadence-intensity relationship, and a full CME was developed through best subsets regression with candidate predictors of age, sex, height, leg length, body mass, body mass index (BMI), and percent body fat. Predictive accuracy of each CME and the ACSM metabolic equation was evaluated at normal (0.89-1.56 m·s) and all (0.22-2.24 m·s) walking speeds through k-fold cross-validation and converted to METs (1 MET = 3.5 mL·kg·min). RESULTS On average, the simple CME predicted intensity within ~1.8 mL·kg·min (~0.5 METs) at normal walking speeds and with negligible (

Although radiologic imaging of bowel infections is often a precursor to definitive diagnosis by endoscopy, biopsy, or stool cultures, imaging can provide critical information for diagnosis and management. Many infectious entities such as viral, bacterial, and parasitic infections can be discovered on imaging. Furthermore, imaging characterizes the extent of infection, involvement of specific bowel segments, and presence of complications in the abdomen. Utilizing a multimodality approach using ultrasound, computed tomography, and magnetic resonance imaging, we describe the spectrum of imaging findings that distinguish a number of infectious etiologies that affect the bowel, as well as differentiate from ischemic and inflammatory bowel processes.

Sepsis is a significant cause of mortality among people living with human immunodeficiency virus (HIV) in sub-Saharan Africa. In the planning period prior to the start of a large multi-country clinical trial studying the efficacy of the immediate empiric addition of anti-tuberculosis therapy to standard-of-care antibiotics for sepsis in people living with HIV, we used decision analysis to assess the costs and potential health outcome impacts of the clinical trial design based on preliminary data and epidemiological parameter estimates. The purpose of this analysis was to highlight this approach as a case example where decision analysis can estimate the cost effectiveness of a proposed clinical trial design. In this case, we estimated the impact of immediate empiric anti-tuberculosis (TB) therapy versus the diagnosis-dependent standard of care using three different TB diagnostics: urine TB-LAM, sputum Xpert-MTB/RIF, and the combination of LAM/Xpert. We constructed decision analytic models comparing the two treatment strategies for each of the three diagnostic approaches. Immediate empiric-therapy demonstrated favorable cost-effectiveness compared with all three diagnosis-dependent standard of care models. In our methodological case exemplar, the proposed randomized clinical trial intervention demonstrated the most favorable outcome within this decision simulation framework. Applying the principles of decision analysis and economic evaluation can have significant impacts on study design and clinical trial planning.

Community-engagement is a key step in conducting research which is impactful for patients and communities. The Delaware Clinical and Translational Research (DE-CTR), Accelerating Clinical and Translational Research (ACCEL) program has implemented several successful approaches to engage our community, and to educate and motivate our researchers in this area. Increased participation in community-engaged research and community-based participatory research was accomplished through DE-CTR/ACCEL using multiple methods detailed in this manuscript. The community engagement infrastructure has fostered community involvement in translational research including capacity development, implementation, evaluation and dissemination. Academic-community partnerships for research, such as those implemented in ACCEL will be crucial to addressing health disparities and health priorities.

Background: A walking cadence of ≥100 steps/min corresponds to minimally moderate intensity, absolutely defined as ≥3 metabolic equivalents (METs). This threshold has primarily been calibrated during treadmill walking. There is a need to determine the classification accuracy of this cadence threshold to predict intensity during overground walking. Methods: In this laboratory-based cross-sectional investigation, participants (N = 75, 49.3% women, age 21–40 y) performed a single 5-minute overground (hallway) walking trial at a self-selected preferred pace. Steps accumulated during each trial were hand tallied and converted to cadence (steps/min). Oxygen uptake was measured using indirect calorimetry and converted to METs. The classification accuracy (sensitivity, specificity, overall accuracy, and positive predictive value) of ≥100 steps/min to predict ≥3 METs was calculated. Results: A cadence threshold of ≥100 steps/min yielded an overall accuracy (combined sensitivity and specificity) of 73.3% for predicting minimally moderate intensity. Moreover, for individuals walking at a cadence ≥100 steps/min, the probability (positive predictive value) of achieving minimally moderate intensity was 80.3%. Conclusions: Although primarily developed using treadmill-based protocols, a cadence threshold of ≥100 steps/min for young adults appears to be a valid heuristic value (evidence-based, rounded, practical) associated with minimally moderate intensity during overground walking performed at a self-selected preferred pace.

Background Wearable technologies play an important role in measuring physical activity (PA) and promoting health. Standardized validation indices (i.e., accuracy, bias, and precision) compare performance of step counting wearable technologies in young people. Purpose To produce a catalog of validity indices for step counting wearable technologies assessed during different treadmill speeds (slow [0.8–3.2 km/h], normal [4.0–6.4 km/h], fast [7.2–8.0 km/h]), wear locations (waist, wrist/arm, thigh, and ankle), and age groups (children, 6–12 years; adolescents, 13–17 years; young adults, 18–20 years). Methods One hundred seventeen individuals (13.1 ± 4.2 years, 50.4% female) participated in this cross-sectional study and completed 5-min treadmill bouts (0.8 km/h to 8.0 km/h) while wearing eight devices (Waist: Actical, ActiGraph GT3X+, NL-1000, SW-200; Wrist: ActiGraph GT3X+; Arm: SenseWear; Thigh: activPAL; Ankle: StepWatch). Directly observed steps served as the criterion measure. Accuracy (mean absolute percentage error, MAPE), bias (mean percentage error, MPE), and precision (correlation coefficient, r; standard deviation, SD; coefficient of variation, CoV) were computed. Results Five of the eight tested wearable technologies (i.e., Actical, waist-worn ActiGraph GT3X+, activPAL, StepWatch, and SW-200) performed at P P > 0.05). Age did not have any effect (P > 0.05). Conclusions Standardized validation indices focused on accuracy, bias, and precision were cataloged by speed, wear location, and age group to serve as important reference points when selecting and/or evaluating device performance in young people moving forward. Reduced performance can be expected at very slow walking speeds (0.8 to 3.2 km/h) for all devices. Ankle-worn and thigh-worn devices demonstrated the highest accuracy. Speed and wear location had a significant effect on accuracy and bias, but not precision. Trial registration Clinicaltrials.govNCT01989104. Registered November 14, 2013.

Background Neutropenic fever (NF) is associated with significant morbidity and mortality for patients receiving cancer treatment in sub-Saharan Africa (sSA). However, the antibiotic management of NF in sub-Saharan Africa has not been well described. We evaluated the timing and selection of antibiotics for patients with NF at the Uganda Cancer Institute (UCI). Methods We conducted a retrospective chart review of adults with acute leukemia admitted to UCI from 1 January 2016 to 31 May 2017, who developed NF. For each NF event, we evaluated the association of clinical presentation and demographics with antibiotic selection as well as time to both initial and guideline-recommended antibiotics. We also evaluated the association between ordered antibiotics and the in-hospital case fatality ratio (CFR). Results Forty-nine NF events occurred among 39 patients. The time to initial antibiotic order was, We examined adherence to guideline-recommended antibiotics in 49 neutropenic fever episodes among adults with acute leukemia at the Uganda Cancer Institute. Guideline-recommended antibiotics were ordered in 37 (75%) events, but median time to guideline-recommended antibiotic order was 3 days.

Background: With the popularity of step counting and feasibility of accumulating physical activity (PA) through sporadic spurts (e.g., taking the stairs), the 2018 PA Guidelines Committee called for research to inform step-based PA recommendations by quantifying relationships between patterns of stepping and health. Purpose: To examine the relationship between daily steps accumulated outside of “bouts” (sporadic steps/d) and all-cause mortality, before and after accounting for bouted steps/d. Methods: From 2011-2015, 16,732 women (mean 72 [standard deviation 6] years) wore a hip-worn accelerometer for 7 days to assess steps and met wear time criteria. Stepping bouts were defined as ≥10 consecutive minutes at ≥40 steps/min (purposeful stepping or faster), allowing for ≤20% of time and ≤5 mins at 2000 steps/d in bouts. Results: Adjusted HRs (95% confidence intervals) in increasing quartiles of SS were 1.00 (reference); 0.63 (0.52, 0.76); 0.60 (0.49, 0.74); 0.54 (0.42, 0.70). In spline analyses, initial increases in SS corresponded to the greatest mortality reductions (Figure 1), with HRs of 0.69 (0.64, 0.76) per additional 1000 SS below 3200. After further adjusting for BS, initial 1000 steps/d increases in SS were association with HRs of 0.72 (0.66, 0.78). In increasing categories of BS, HRs adjusted for SS were 1.00 (reference); 0.91 (0.76, 1.09); 0.69 (0.56, 0.84). Conclusion: Daily step counts were inversely associated with mortality, regardless of how they were accumulated. These results can help inform step-based target PA volumes that communicate the benefits of increasing everyday walking behaviors.

Background Chloroquine (CQ) resistance is conferred by mutations in the Plasmodium falciparum CQ resistance transporter (pfcrt). Following CQ withdrawal for anti-malarial treatment, studies across malaria-endemic countries have shown a range of responses. In some areas, CQ sensitive parasites re-emerge, and in others, mutant haplotypes persist. Active surveillance of resistance mutations in clinical parasites is essential to inform treatment regimens; this effort requires fast, reliable, and cost-effective methods that work on a variety of sample types with reagents accessible in malaria-endemic countries. Methods Quantitative PCR followed by High-Resolution Melt (HRM) analysis was performed in a field setting to assess pfcrt mutations in two groups of clinical samples from Southwestern Uganda. Group 1 samples (119 in total) were collected in 2010 as predominantly Giemsa-stained slides; Group 2 samples (125 in total) were collected in 2015 as blood spots on filter paper. The Rotor-Gene Q instrument was utilized to assess the impact of different PCR-HRM reagent mixes and the detection of mixed haplotypes present in the clinical samples. Finally, the prevalence of the wild type (CVMNK) and resistant pfcrt haplotypes (CVIET and SVMNT) was evaluated in this understudied Southwestern region of Uganda. Results The sample source (i.e. Giemsa-stained slides or blood spots) and type of LCGreen-based reagent mixes did not impact the success of PCR-HRM. The detection limit of 10− 5 ng and the ability to identify mixed haplotypes as low as 10 % was similar to other HRM platforms. The CVIET haplotype predominated in the clinical samples (66 %, 162/244); however, there was a large regional variation between the sample groups (94 % CVIET in Group 1 and 44 % CVIET in Group 2). Conclusions The HRM-based method exhibits the flexibility required to conduct reliable assessment of resistance alleles from various sample types generated during the clinical management of malaria. Large regional variations in CQ resistance haplotypes across Southwestern Uganda emphasizes the need for continued local parasite genotype assessment to inform anti-malarial treatment policies.

IntroductionSub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV and tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is the leading cause of sepsis. However, anti-TB therapy is often delayed and may not achieve adequate blood concentrations in patients with sepsis. Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose anti-TB therapy improves 28-day mortality for participants with HIV and sepsis in Tanzania or Uganda.Methods and analysisThis is a phase 3, multisite, open-label, randomised controlled clinical 2×2 factorial superiority trial of (1) immediate initiation of anti-TB therapy and (2) sepsis-specific dose anti-TB therapy in addition to standard of care antibacterials for adults with HIV and sepsis admitted to hospital in Tanzania or Uganda. The primary endpoint is 28-day mortality. A sample size of 436 participants will provide 80% power for testing each of the main effects of timing and dose on 28-day mortality with a two-sided significance level of 5%. The expected main effect for absolute risk reduction is 13% and the expected OR for risk reduction is 1.58.Ethics and disseminationThis clinical trial will determine the optimal content, dosing and timing of antimicrobial therapy for sepsis in high HIV and TB prevalent settings. The study is funded by the National Institutes of Health in the US. Institutional review board approval was conferred by the University of Virginia, the Tanzania National Institute for Medical Research, and the Uganda National Council for Science and Technology. Study results will be published in peer-reviewed journals and in the popular press of Tanzania and Uganda. We will also present our findings to the Community Advisory Boards that we convened during study preparation.Trial registration numberClinicalTrials.gov (NCT04618198).

Background We previously derived a Universal Vital Assessment (UVA) score to better risk-stratify hospitalized patients in sub-Saharan Africa, including those with infection. Here, we aimed to externally validate the performance of the UVA score using previously collected data from patients hospitalized with acute infection in Rwanda. Methods We performed a secondary analysis of data collected from adults ≥18 years with acute infection admitted to Gitwe District Hospital in Rwanda from 2016 until 2017. We calculated the UVA score from the time of admission and at 72 hours after admission. We also calculated quick sepsis-related organ failure assessment (qSOFA) and modified early warning scores (MEWS). We calculated amalgamated qSOFA scores by inserting UVA cut-offs into the qSOFA score, and modified UVA scores by removing the HIV criterion. The performance of each score determined by the area under the receiver operator characteristic curve (AUC) was the primary outcome measure. Results We included 573 hospitalized adult patients with acute infection of whom 40 (7%) died in-hospital. The admission AUCs (95% confidence interval [CI]) for the prediction of mortality by the scores were: UVA, 0.77 (0.68–0.85); modified UVA, 0.77 (0.68–0.85); qSOFA, 0.66 (0.56–0.75), amalgamated qSOFA, 0.71 (0.61–0.80); and MEWS, 0.74 (0.64, 0.83). The positive predictive values (95% CI) of the scores at commonly used cut-offs were: UVA >4, 0.35 (0.15–0.59); modified UVA >4, 0.35 (0.15–0.59); qSOFA >1, 0.14 (0.07–0.24); amalgamated qSOFA >1, 0.44 (0.20–0.70); and MEWS >5, 0.14 (0.08–0.22). The 72 hour (N = 236) AUC (95% CI) for the prediction of mortality by UVA was 0.59 (0.43–0.74). The Chi-Square test for linear trend did not identify an association between mortality and delta UVA score at 72 hours (p = 0.82). Conclusions The admission UVA score and amalgamated qSOFA score had good predictive ability for mortality in adult patients admitted to hospital with acute infection in Rwanda. The UVA score could be used to assist with triage decisions and clinical interventions, for baseline risk stratification in clinical studies, and in a clinical definition of sepsis in Africa.