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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

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 In younger adults (i.e., those Purpose To establish heuristic (i.e., evidence-based, practical, rounded) cadence thresholds for absolutely-defined moderate (3 METs) and vigorous (6 METs) intensity in adults 41 to 60 years of age. Methods In this cross-sectional study, 80 healthy adults of middle-age (10 men and 10 women representing each 5-year age-group between 41 to 60 years; body mass index = 26.0 ± 4.0 kg/m2) walked on a treadmill for 5-min bouts beginning at 0.5 mph and increasing in 0.5 mph increments. Performance termination criteria included: 1) transitioning to running, 2) reaching 75% of age-predicted maximum heart rate, or 3) reporting a Borg rating of perceived exertion > 13. Cadence was directly observed (i.e., hand tallied). Intensity (i.e., oxygen uptake [VO2] mL/kg/min) was assessed with an indirect calorimeter and converted to METs (1 MET = 3.5 mL/kg/min). A combination of segmented regression and Receiver Operating Characteristic (ROC) modeling approaches was used to identify optimal cadence thresholds. Final heuristic thresholds were determined based on an evaluation of classification accuracy (sensitivity, specificity, positive and negative predictive value, overall accuracy). Results The regression model identified 101.7 (95% Predictive Interval [PI]: 54.9–110.6) and 132.1 (95% PI: 122.0–142.2) steps/min as optimal cadence thresholds for 3 METs and 6 METs, respectively. Corresponding values based on ROC models were 98.5 (95% Confidence Intervals [CI]: 97.1–104.9) and 117.3 (95% CI: 113.1–126.1) steps/min. Considering both modeling approaches, the selected heuristic thresholds for moderate and vigorous intensity were 100 and 130 steps/min, respectively. Conclusions Consistent with our previous report in 21 to 40-year-old adults, cadence thresholds of 100 and 130 steps/min emerged as heuristic values associated with 3 and 6 METs, respectively, in 41 to 60-year-old adults. These values were selected based on their utility for public health messaging and on the trade-offs in classification accuracy parameters from both statistical methods. Findings will need to be confirmed in older adults and in free-living settings.

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.

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.

Critical illness from tuberculosis (TB) bloodstream infection results in a high case fatality rate for people living with human immunodeficiency virus (HIV). Critical illness can lead to altered pharmacokinetics and suboptimal drug exposures. We enrolled adults living with HIV and hospitalized with sepsis, with and without meningitis, in Mbarara, Uganda that were starting first-line anti-TB therapy. Serum was collected two weeks after enrollment at 1-, 2-, 4-, and 6-h post-dose and drug concentrations quantified by validated LC-MS/MS methods. Non-compartmental analyses were used to determine total drug exposure, and population pharmacokinetic modeling and simulations were performed to determine optimal dosages. Eighty-one participants were enrolled. Forty-nine completed pharmacokinetic testing: 18 (22%) died prior to testing, 13 (16%) were lost to follow-up and one had incomplete testing. Isoniazid had the lowest serum attainment, with only 4.1% achieving a target exposure over 24 h (AUC0–24) of 52 mg·h/L despite appropriate weight-based dosing. Simulations to reach target AUC0–24 found necessary doses of rifampin of 1800 mg, pyrazinamide of 2500–3000 mg, and for isoniazid 900 mg or higher. Given the high case fatality ratio of TB-related critical illness in this population, an early higher dose anti-TB therapy should be trialed.

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.

Background Nontuberculous mycobacteria (NTM) are rare but potentially devastating causes of musculoskeletal infection and impairment in immunocompetent patients. Purpose Given the sparse body of literature surrounding these infections, we describe a series of patients with and the cost of treatment of upper extremity NTM infections. Patients and Methods In a retrospective review of seven patients with NTM infections of the upper extremity treated at a university hospital from 2010 to 2019, we assessed patient demographics, exposures, infection characteristics, management course, outcomes, and costs of treatment. Results Insidious pain and swelling were the most common clinical manifestation of infection. Despite coupled surgical and medical management, recurrence was common. Two patients required amputation, and three others had lasting functional deficits. The most common pathogen was Mycobacterium avium complex (5 of 7). The estimated median charge related to management was $85,126 with a range from $8,361 to $1,66,229. Conclusions The treatment of NTM infections is complex and expensive. Diagnosis is usually delayed, which further complicates the management of these patients who often suffer from lasting debilitation. Due to its potentially devastating course, NTM infection should be considered and tested for whenever flexor tenosynovitis is suspected. Regardless of initial presentation, our experience suggests that a protocol of serial surgical debridement immediately after tissue diagnosis is necessary for optimal outcomes. Furthermore, NTM infections require collaboration with infectious disease colleagues to guide antimicrobial regimens based on susceptibility testing and therapeutic drug monitoring for the recommended 6 to 12 months of therapy after the final operative debridement. Level of Evidence This is a Level IV, case series study.

Background Heuristic cadence (steps/min) thresholds of ≥100 and ≥ 130 steps/min correspond with absolutely-defined moderate (3 metabolic equivalents [METs]; 1 MET = 3.5 mL O2·kg− 1·min− 1) and vigorous (6 METs) intensity, respectively. Scarce evidence informs cadence thresholds for relatively-defined moderate (≥ 64% heart rate maximum [HRmax = 220-age], ≥ 40%HR reserve [HRR = HRmax -HRresting, and ≥ 12 Rating of Perceived Exertion [RPE]); or vigorous intensity (≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE). Purpose To identify heuristic cadence thresholds corresponding with relatively-defined moderate and vigorous intensity in 21–60-year-olds. Methods In this cross-sectional study, 157 adults (40.4 ± 11.5 years; 50.6% men) completed up to twelve 5-min treadmill bouts, beginning at 0.5 mph and increasing by 0.5 mph. Steps were directly observed, HR was measured with chest-worn monitors, and RPE was queried in the final minute of each bout. Segmented mixed model regression and Receiver Operating Characteristic (ROC) curve analyses identified optimal cadence thresholds, stratified by age (21–30, 31–40, 41–50, and 51–60 years). Reconciliation of the two analytical models, including trade-offs between sensitivity, specificity, positive and negative predictive values, and overall accuracy, yielded final heuristic cadences. Results Across all moderate intensity indicators, the segmented regression models estimated optimal cadence thresholds ranging from 123.8–127.5 (ages 21–30), 120.2–126.0 (ages 31–40), 117.7–122.7 (ages 41–50), and 113.3–116.1 steps/min (ages 51–60). Corresponding values for vigorous intensity were 140.3–144.1, 139.6–142.6, 139.3–143.6, and 131.6–132.8 steps/min, respectively. ROC analysis estimated chronologically-arranged age groups’ cadence thresholds ranging from 114.5–118, 113.5–114.5, 104.6–112.9, and 103.6–106.0 across all moderate intensity indicators, and 124.5, 121.5, 117.2–122.2, and 113.0 steps/min, respectively, for vigorous intensity. Conclusions Heuristic cadence thresholds corresponding to relatively-defined moderate intensity for the chronologically-arranged age groups were ≥ 120, 120, 115, and 110 steps/min, regardless of the intensity indicator (i.e., % HRmax, %HRR, or RPE). Corresponding heuristic values for vigorous intensity indicators were ≥ 135, 130, 125, and 120 steps/min. These cadences are useful for predicting/programming intensity aligned with age-associated differences in physiological response to, and perceived experiences of, moderate and/or vigorous intensity. Trial registration Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

Pelvic pain is a common complaint in female patients who present to the emergency department. Although encountered frequently, the path to a definitive diagnosis is not always a straightforward one, and imaging offers a valuable tool to aid in this diagnostic challenge. Radiologists must be familiar with the most common etiologies of female pelvic pain in the emergency setting, their imaging characteristics, and the best way to further evaluate challenging clinical presentations. This allows the radiologist to serve as a valuable asset to the treating physician, aiding in accurate diagnosis, and in guiding the course of treatment, all while ensuring the "Image Wisely" principle. A sonographic approach to female patients presenting to the emergency setting with pelvic pain has been presented in this article and some example entities along with their imaging findings have also been reviewed.

Previous research with teens raised questions on the validity of survey studies with this population. As one response, our team implemented a mixed-methods study to evaluate an evidence-based, interactive curriculum, Wise Guys, that is designed to promote healthy relationships and sexual behavior in young men 14-17 years of age. The current study included a Youth Advisory Group, focus groups, and a video-journaling project to delineate teens' thoughts on the most salient aspects of Wise Guys and we used these to develop a stakeholder-informed survey instrument. The survey was administered via REDCap, a computer-based medium via phones and mobile devices. Quantitative survey analyses revealed significant positive changes in study constructs. Qualitative interpretations provided rich data that validated the survey findings. Community engagement in the research process and mixed methods may provide the infrastructure for future research and evaluation efforts related to teens.

Objective: The ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen is a key component of the sequential organ failure assessment score that operationally defines sepsis. But, it is calculated infrequently due to the need for the acquisition of an arterial blood gas. So, we sought to find an optimal imputation strategy for the estimation of sepsis-defining hypoxemic respiratory failure using oximetry instead of an arterial blood gas. Approach: We retrospectively studied a sample of non-intubated acute-care patients with oxygen saturation recorded ⩽10 min before arterial blood sampling (N = 492 from 2013–2017). We imputed ratios of the partial pressure of arterial oxygen to the fraction of inspired oxygen and sepsis criteria from existing imputation equations (Hill, Severinghaus–Ellis, Rice, and Pandharipande) and compared them with the ratios and sepsis criteria measured from arterial blood gases. We devised a modified model-based equation to eliminate the bias of the results. Main results: Hypoxemia severity estimates from the Severinghaus–Ellis equation were more accurate than those from other existing equations, but showed significant proportional bias towards under-estimation of hypoxemia severity, especially at oxygen saturations >96%. Our modified equation eliminated bias and surpassed others on all imputation quality metrics. Significance: Our modified imputation equation, is the first one that is free of bias at all oxygen saturations. It resulted in ratios of partial pressure of arterial oxygen to fraction of inspired oxygen and sepsis respiratory criteria closest to those obtained by arterial blood gas testing and is the optimal imputation strategy for non-intubated acute-care patients.

Background Mycobacterium tuberculosis is the leading cause of bloodstream infection among human immunodeficiency virus (HIV)-infected patients with sepsis in sub-Saharan Africa and is associated with high mortality rates. Methods We conducted a retrospective study of HIV-infected adults with sepsis at the Mbarara Regional Referral Hospital in Uganda to measure the proportion who received antituberculosis therapy and to determine the relationship between antituberculosis therapy and 28-day survival. Results Of the 149 patients evaluated, 74 (50%) had severe sepsis and 48 (32%) died. Of the 55 patients (37%) who received antituberculosis therapy, 19 (35%) died, compared with 29 of 94 (31%) who did not receive such therapy (odds ratio, 1.34; 95% confidence interval [CI], .56-3.18; P = .64). The 28-day survival rates did not differ significantly between these 2 groups (log-rank test, P = .21). Among the 74 patients with severe sepsis, 9 of 26 (35%) who received antituberculosis therapy died, versus 23 of 48 (48%) who did not receive such therapy (odds ratio, 0.58; 95% CI, .21-1.52; P = .27). In patients with severe sepsis, antituberculosis therapy was associated with an improved 28-day survival rate (log-rank test P = .01), and with a reduced mortality rate in a Cox proportional hazards model (hazard ratio, 0.32; 95% CI, .13-.80; P = .03). Conclusions Empiric antituberculosis therapy was associated with improved survival rates among patients with severe sepsis, but not among all patients with sepsis.

PurposeTo provide empirically-supported thresholds for step-based intensity (i.e., peak 30-min cadence; average of the top 30 steps/min in a day) and steps/day in relation to cardiometabolic health outcomes.MethodsReceiver operating characteristic curve analysis was applied to the National Health and Nutrition Examination Survey (NHANES) 2005-2006 accelerometer-derived step data to determine steps/day and peak 30-min cadence as risk screening values (i.e., thresholds) for fasting glucose, body mass index, waist circumference, high blood pressure, triglycerides, and HDL cholesterol. Thresholds for peak 30-min cadence and steps/day were derived that, when exceeded, classify the absence of each cardiometabolic risk factor. Additionally, logistic regression models that included the influence of age and smoking were developed using the sample weights, primary sampling units (PSUs), and stratification variables provided by the NHANES survey. Finally, a decision tree analysis was performed to delineate criteria for at-risk versus healthy populations using cadence bands.ResultsPeak 30-min cadence thresholds across cardiometabolic outcomes ranged from 66-72 steps/min. Steps/day thresholds ranged from 4325-6192 steps/day. Higher thresholds were observed in men compared to women. In men, higher steps/day thresholds were observed in age ranges of 30-39, while in women, higher thresholds were observed in the age-range 50-59 years. Decision trees for classifying being at low risk for metabolic syndrome contained one risk-free leaf at higher cadence bands, specifically for any time accumulated at ≥120 steps/min.ConclusionsMinimum thresholds representing absence of cardiometabolic risk range from 4325-6192 steps/day and 66-72 steps/min for peak 30-min cadence. Any time accumulated at ≥120 steps/min was associated with an absence of cardiometabolic risk. Although based on cross-sectional data, these thresholds represent potentially important and clinically interpretable daily physical activity goals.

PROBLEM Many interventions designed to promote safe sexual behaviors in teens focus on young women. Wise Guys is one curricular intervention designed to foster safe sexual practices in young men. This study assessed knowledge, attitude, and behavioral changes as the result of Wise Guys. METHODS This pre/posttest descriptive study measured changes in knowledge, attitudes, and sexual behaviors in 159 young men. FINDINGS This study detected limited knowledge and attitude changes but yielded statistically significant differences in safe sexual behaviors and likelihood to talk with parents or guardians about sexuality and dating. CONCLUSIONS This study revealed important benefits of Wise Guys and proposed future mixed methods research to ensure that authentic teen voices inform programing. Nurses working with adolescents may find this information valuable as they address sexual health issues in their work.

Background Previous studies have reported that walking cadence (steps/min) is associated with absolutely-defined intensity (metabolic equivalents; METs), such that cadence-based thresholds could serve as reasonable proxy values for ambulatory intensities. Purpose To establish definitive heuristic (i.e., evidence-based, practical, rounded) thresholds linking cadence with absolutely-defined moderate (3 METs) and vigorous (6 METs) intensity. Methods In this laboratory-based cross-sectional study, 76 healthy adults (10 men and 10 women representing each 5-year age-group category between 21 and 40 years, BMI = 24.8 ± 3.4 kg/m2) performed a series of 5-min treadmill bouts separated by 2-min rests. Bouts began at 0.5 mph and increased in 0.5 mph increments until participants: 1) chose to run, 2) achieved 75% of their predicted maximum heart rate, or 3) reported a Borg rating of perceived exertion > 13. Cadence was hand-tallied, and intensity (METs) was measured using a portable indirect calorimeter. Optimal cadence thresholds for moderate and vigorous ambulatory intensities were identified using a segmented regression model with random coefficients, as well as Receiver Operating Characteristic (ROC) models. Positive predictive values (PPV) of candidate heuristic thresholds were assessed to determine final heuristic values. Results Optimal cadence thresholds for 3 METs and 6 METs were 102 and 129 steps/min, respectively, using the regression model, and 96 and 120 steps/min, respectively, using ROC models. Heuristic values were set at 100 steps/min (PPV of 91.4%), and 130 steps/min (PPV of 70.7%), respectively. Conclusions Cadence thresholds of 100 and 130 steps/min can serve as reasonable heuristic thresholds representative of absolutely-defined moderate and vigorous ambulatory intensity, respectively, in 21–40 year olds. These values represent useful proxy values for recommending and modulating the intensity of ambulatory behavior and/or as measurement thresholds for processing accelerometer data. Trial registration Clinicaltrials.gov (NCT02650258). Electronic supplementary material The online version of this article (10.1186/s12966-019-0769-6) contains supplementary material, which is available to authorized users.

Background The health-related quality of life (HRQoL) is an important treatment goal that could serve as low-cost prognostication tool in resource poor settings. We sought to validate the Kansas City Cardiomyopathy Questionnaire (KCCQ) and evaluate its use as a predictor of 3 months all-cause mortality among heart failure participants in rural Uganda. Methods The Mbarara Heart Failure Registry Cohort study observes heart failure patients during hospital stay and in the community in rural Uganda. Participants completed health failure evaluations and HRQoL questionnaires at enrollment, 1 and 3 months of follow-up. We used Cronbach’s alpha coefficients to define internal consistency, intraclass correlation coefficients as a reliability coefficient, and Cox proportional hazard models to predict the risk of 3 months all-cause mortality. Results Among the 195 participants who completed HRQoL questionnaires, the mean age was 52 (standard deviation (SD) 21.4) years, 68% were women and 29% reported history of hypertension. The KCCQ had excellent internal consistency (87% Cronbach alpha) but poor reliability. Independent predictors of all-cause mortality within 3 months included: worse overall KCCQ score (Adjusted Hazard ratio (AHR) 2.9, 95% confidence interval (CI) 1.1, 8.1), highest asset ownership (AHR 3.6, 95% CI 1.2, 10.8), alcoholic drinks per sitting (AHR per 1 drink 1.4, 95% CI 1.0, 1.9), New York Heart Association (NYHA) functional class IV heart failure (AHR 2.6, 95% CI 1.3, 5.4), estimated glomerular filtration rate (eGFR) 30 to 59 ml/min/1.73 m2 (AHR 3.4, 95% CI 1.1, 10.8), and eGFR less than 15 ml/min/1.73 m2 (AHR 2.7, 95% CI 1.0, 7.1), each 1 pg/mL increase in Brain Natriuretic Peptide (BNP) (AHR, 1.0, 95% CI 1.0, 1.0), and each 1 ng/mL increase in Creatine-Kinase MB isomer (CKMB) (AHR 1.0, 95% CI 1.0, 1.1). Conclusion The KCCQ showed excellent internal consistency. Worse overall KCCQ score, highest asset ownership, increasing alcoholic drink per sitting, NYHA class IV, decreased estimated glomerular filtration rate, BNP, and CKMB predicted all-cause mortality at 3 months. The KCCQ could be an additional low-cost tool to aid in the prognostication of acute heart failure patients. Electronic supplementary material The online version of this article (10.1186/s12872-018-0959-1) contains supplementary material, which is available to authorized users.

Plasmodiumprotozoan parasites undergo rounds of asexual replication inside human erythrocytes, progressing from ring stage, to trophozoites and schizonts, before egress and reinvasion. Given the discovery of ring-specific artemisinin tolerance and quiescence inPlasmodium falciparum, there is great urgency to better understand ring stage biology. However, the lack of an effective enrichment method has left rings and related parasite stages understudied compared to their late stage counterparts, which can be easily isolated due to their paramagnetic properties. Here, a method for separatingall Plasmodiuminfected erythrocytes from uninfected erythrocytes is presented. This approach takes advantage of streptolysin-O (SLO) to preferentially lyse uninfected erythrocytes as previously shown by Jackson,et al.Following lytic treatment, Percoll gradient centrifugation removes lysed cells, leaving an intact cell population enriched in infected erythrocytes. ThisSLO-Percoll (SLOPE) method is effective on stages from the entire erythrocytic cycle, including previously inaccessible forms such as circulating rings from malaria-infected patients and artemisinin-induced quiescent parasites. Furthermore, the utility of SLOPE is extended to multiple media formulations used for the propagation of two humanPlasmodiumspecies. The alteration of external cholesterol levels modulates SLOPE effectiveness, demonstrating the role of erythrocyte membrane cholesterol in lytic discrimination. Importantly, enrichment does not impact parasite viability, which establishes the non-toxic nature of SLOPE. Targeted metabolomics of SLOPE-enriched ring stage samples confirms the impact on treated samples; parasite-derived metabolites are increased and contaminating host material is reduced compared to non-enriched samples.ImportanceMalaria is caused by infection with protozoanPlasmodiumparasites and is responsible for over 400,000 deaths annually. The availability of effective antimalarial drugs is critical to the reduction of malaria-related mortality, yet widespread resistance highlights the need for the continued study ofPlasmodiumbiology. The SLOPE method is an accessible, scalable, rapid (30-40min), and non-toxic enrichment method that is broadly effective on many erythrocytic stages. This method is ideal for use upstream of a variety of sensitive analyses, which will increase experimental quality in virtually all areas of asexualPlasmodiumparasite research. Further, because the consumption of cholesterol is a common characteristic of other intracellular parasites (both bacteria and other protozoa), SLOPE holds potential for extension to other relevant pathogens.

Step length and cadence (i.e., step frequency or steps/minute) maintain an invariant proportion across a range of walking speeds, known as the walk ratio (WR = step length/cadence). While step length is a difficult parameter to manipulate, cadence is readily modifiable using rhythmic auditory cuing (RAC; e.g., synchronizing step timing to a metronome or music tempo).The purpose of this study was to determine the effects of RAC-guided cadences on enacted cadence, step length, WR, and gait speed during overground walking.Sixteen healthy young adults repeatedly crossed a GAITRite electronic walkway while attempting to synchronize step timing to RAC-guided (metronome) tempos of 80 to 140 beats per minute. Mean absolute percent error (MAPE) was used to compare RAC tempos to enacted cadence. Repeated-measures analyses of variance were performed to test for the effects of RAC on cadence, step length, WR, and gait speed. Moreover, simple linear regressions were used to determine the precise stepwise relationship between RAC conditions and each variable.Participants successfully matched their cadence to RAC beats (MAPE1.1%). Cadence increased proportionally to RAC (linear regression slope = 1.02), while step length also increased but at a slower rate (slope = 0.40). These dissimilar slopes resulted in a modified WR that systematically decreased with increasing cadence, although ultimately gait speed increased with increasing cadence (slope = 1.41). This relationship indicates that every 10 steps/minute incremental increase in cadence corresponded with a 14 cm/s increase in gait speed.Gait speed appears to increase in a predictable manner when cadence is guided by RAC during overground walking irrespective of apparent changes to the WR.

Sepsis is a dysregulated systemic response to infection that causes organ dysfunction. It is the leading cause of in-hospital mortality and is responsible for the longest, most expensive, hospital stays in the United States. Prognostic modeling of sepsis has demonstrated potential for improving treatment and outcomes for critical care patients. However, the majority of previous models have relied on an outdated definition of sepsis based on systemic inflammatory response syndrome (SIRS). Therefore, this study sought to build predictive models of sepsis using the most recent definition of sepsis, Sepsis-3. A total of three classification methods, including logistic regression (LR), support vector machines (SVM), and logistic model trees (LMT), were used to predict onset of sepsis in adult Intensive Care Unit (ICU) patients using vital signs and blood culture results. For patients who did not develop sepsis, predictor values were selected from a random 48-hour time window during the patient's ICU stay. For those who developed sepsis, a random time was selected for the patient within 48 to 6 hours prior to onset of sepsis, and the predictor values with the closest preceding time were extracted. The LMT produced superior classification performance compared with the LR and SVM. The wide time window used for data extraction improves the clinical utility of the models relative to those built in previous work. However, while the models showed similar sensitivity and specificity to previous models using the Sepsis-3 definition, they each showed a high false positive rate.

BACKGROUND: Knowledge of causes of sepsis in sub-Saharan Africa is limited. A better understanding of the microbiology of bloodstream infections could improve outcomes. METHODS: We used a quantitative polymerase chain reaction (qPCR)-based TaqMan Array Card (TAC) to directly test for 43 targets from whole blood. We analyzed 336 cryopreserved specimens from adult Ugandans with sepsis enrolled in a multisite study; 84% were infected with human immunodeficiency virus. We compared qPCR TAC results with blood culture and determined the association of qPCR with study participant outcomes using logistic regression. RESULTS: The most frequently detected targets were cytomegalovirus (CMV, n = 139, 41%), Mycobacterium tuberculosis (TB, n = 70, 21%), Plasmodium (n = 35, 10%), and Streptococcus pneumoniae (n = 31, 9%). Diagnostic performance varied by target with qPCR sensitivity averaging 61 ± 28% and specificity 98 ± 3% versus culture. In multivariable analysis, independent factors associated with in-hospital mortality included CMV viremia (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI], 1.8–5.5; p < .01) and TB qPCR-positivity, whether blood culture-positive (aOR 4.6, 95% CI, 2.1–10.0; p < .01) or blood culture-negative (aOR 2.9, 95% CI, 1.2–6.9; p = .02). CONCLUSIONS: Using qPCR TAC on direct blood specimens, CMV and TB were the most commonly identified targets and were independently associated with increased in-hospital mortality. qPCR TAC screening of blood for multiple targets may be useful to guide triage and treatment of sepsis in sub-Saharan Africa.

Microscopic diagnosis of malaria using Giemsa-stained blood smears is the standard of care in resource-limited settings. These smears represent a potential source of DNA for PCR testing to confirm Plasmodium infections or for epidemiological studies of archived samples. Therefore, we assessed the use of DNA extracts from stained blood smears for the detection of Plasmodium species using real-time PCR. We extracted DNA from archived blood smears and corresponding red blood cell pellets collected from asymptomatic children in southwestern Uganda in 2010. We then performed real-time PCR followed by high-resolution melting (HRM) to identify Plasmodium species, and we compared our results to those of microscopy. We analyzed a total of 367 blood smears and corresponding red blood cell pellets, including 185 smears (50.4%) that were positive by microscopy. Compared to microscopy, PCR-HRM analysis of smear DNA had a sensitivity of 93.0% (95% confidence interval [CI], 88.2 to 96.2%) and a specificity of 96.7% (95% CI, 93.0 to 98.8%), and PCR-HRM analysis of pellet DNA had a sensitivity of 100.0% (95% CI, 98.0 to 100.0%) and a specificity of 94.0% (95% CI, 89.4 to 96.9%). Identification of positive PCR-HRM results to the species level revealed Plasmodium falciparum (92.0%), Plasmodium ovale (5.6%), and Plasmodium malariae (2.4%). PCR-HRM analysis of DNA extracts from Giemsa-stained thick blood smears or corresponding blood pellets had high sensitivity and specificity for malaria diagnosis, compared to microscopy. Therefore, blood smears can provide an adequate source of DNA for confirmation of Plasmodium species infections and can be used for retrospective genetic studies.

Antimalarial drug resistance exacerbates the global disease burden and complicates eradication efforts. To facilitate the surveillance of resistance markers in countries of malaria endemicity, we developed a suite of TaqMan assays for known resistance markers and compartmentalized them into a single array card (TaqMan array card, TAC). We included 87 assays for species identification, for the detection of Plasmodium falciparum mutations associated with chloroquine, atovaquone, pyrimethamine, sulfadoxine, and artemisinin resistance, and for neutral single nucleotide polymorphism (SNP) genotyping. Assay performance was first optimized using DNA from common laboratory parasite lines and plasmid controls. The limit of detection was 0.1 to 10 pg of DNA and yielded 100% accuracy compared to sequencing. The tool was then evaluated on 87 clinical blood samples from around the world, and the malaria TAC once again achieved 100% accuracy compared to sequencing and in addition detected the presence of mixed infections in clinical samples. With its streamlined protocol and high accuracy, this malaria TAC should be a useful tool for large-scale antimalarial resistance surveillance.

Sepsis is the systemic response to infection complicated by organ dysfunction. It is a leading cause of in-hospital mortality, with an observed mortality of 20–40%, and is associated with significantly high costs. Furthermore, patients who survive sepsis are more likely to have permanent organ damage, cognitive impairment and physical disability. Survival from sepsis is dependent on early and targeted treatment. Accepted methods for identifying and predicting sepsis have typically been based on intensive care unit (ICU) patients and founded upon a limited and outdated definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria — one which is not clinically validated and shown to miss at least 1 out of 8 cases. Recently updated consensus guidelines on sepsis have been published and offer the possibility of improved EWS and predictive models. Our goal was to identify non-ICU ward patients with sepsis earlier and more accurately using the newly established sepsis definition and improved predictive models. Using multivariate logistic regression and routinely available physiological and laboratory data from electronic health records (EHRs), we derived an EWS that identifies at-risk ward patients 12–24 hours prior to sepsis onset with an area under the receiver operating characteristic curve (AUC) result of 74%. This model, when applied on a separate ICU population, achieved an AUC curve result of 56%, indicating the model has worse performance in this setting.

Introduction The optimal resuscitation strategy for patients with severe sepsis in resource-limited settings is unknown. Therefore, we determined the association between intravenous fluids, changes in vital signs and lactate after the first 6 hours of resuscitation from severe sepsis, and in-hospital mortality at a hospital in Uganda. Materials and methods We enrolled patients admitted with severe sepsis to Mbarara Regional Referral Hospital and obtained vital signs and point-of-care blood lactate concentration at admission and after 6 hours of resuscitation. We used logistic regression to determine predictors of in-hospital mortality. Results We enrolled 218 patients and had 6 hour postresuscitation data for 202 patients. The median (interquartile range) age was 35 (26-50) years, 49% of patients were female, and 57% were HIV infected. The in-hospital mortality was 32% and was associated with admission Glasgow Coma Score (adjusted odds ratio [aOR], 0.749; 95% confidence interval [CI], 0.642-0.875; P P = .007), and 6-hour systolic blood pressure (aOR, 0.979; 95% CI, 0.963-0.995; P = .009) but not lactate clearance of 10% or greater (aOR, 1.2; 95% CI, 0.46-3.10; P = .73). Conclusions In patients with severe sepsis in Uganda, obtundation and wasting were more closely associated with in-hospital mortality than lactate clearance of 10% or greater.

Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria ( Bartonella spp., Brucella spp., Coxiella burnetii , Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis ), and 3 protozoa ( Leishmania spp., Plasmodium spp., and Trypanosoma brucei ). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus.

There are few data regarding outcomes from severe sepsis for HIV-infected patients living in rural or semi-rural settings. We aim to describe the characteristics and predictors of mortality in HIV-infected patients admitted with severe sepsis to the University of Virginia located in semi-rural Charlottesville, Virginia, USA. We queried the University of Virginia Clinical Data Repository for cases with ICD-9 codes that included: (1) infection, (2) acute organ dysfunction, and (3) HIV infection. We reviewed each case to confirm the presence of HIV infection and severe sepsis. We recorded socio-demographic, clinical, and laboratory data. We used a generalised linear mixed-effects model to assess pre-specified predictors of mortality. We identified 74 cases of severe sepsis in HIV-infected patients admitted to University of Virginia since 2001. The median (IQR) age was 44 (36–49), 32 (43%) were women, and 56 (76%) were from ethnic minorities. The median (IQR) CD4+ T-cell count was 81 (7–281) cells/µL. In-hospital mortality was 20%. When adjusted for severity of illness and respiratory failure, patients who lived >40 miles away from care or had a CD4+ T cell count four-fold increased risk of death compared to the rest of the study population (AOR = 4.18, 95% CI: 1.09-16.07, p = 0.037; AOR = 4.33, 95% CI: 1.15–16.29, p = 0.03). In HIV-infected patients from rural and semi-rural Virginia with severe sepsis, mortality was increased in those that lived far from University of Virginia or had a low CD4+ T cell counts. Our data suggest that rural HIV-infected patients may have limited access to care, which predisposes them to critical illness and a high associated mortality.

BACKGROUND: Critical illness is a leading cause of morbidity and mortality in sub-Saharan Africa (SSA). Identifying patients with the highest risk of death could help with resource allocation and clinical decision making. Accordingly, we derived and validated a universal vital assessment (UVA) score for use in SSA.METHODS: We pooled data from hospital-based cohort studies conducted in six countries in SSA spanning the years 2009-2015. We derived and internally validated a UVA score using decision trees and linear regression and compared its performance with the modified early warning score (MEWS) and the quick sepsis-related organ failure assessment (qSOFA) score.RESULTS: Of 5573 patients included in the analysis, 2829 (50.8%) were female, the median (IQR) age was 36 (27-49) years, 2122 (38.1%) were HIV-infected and 996 (17.3%) died in-hospital. The UVA score included points for temperature, heart and respiratory rates, systolic blood pressure, oxygen saturation, Glasgow Coma Scale score and HIV serostatus, and had an area under the receiver operating characteristic curve (AUC) of 0.77 (95% CI 0.75 to 0.79), which outperformed MEWS (AUC 0.70 (95% CI 0.67 to 0.71)) and qSOFA (AUC 0.69 (95% CI 0.67 to 0.72)).CONCLUSION: We identified predictors of in-hospital mortality irrespective of the underlying condition(s) in a large population of hospitalised patients in SSA and derived and internally validated a UVA score to assist clinicians in risk-stratifying patients for in-hospital mortality. The UVA score could help improve patient triage in resource-limited environments and serve as a standard for mortality risk in future studies.

BACKGROUND:There are limited data on region-specific drug susceptibility of tuberculosis (TB) in Uganda. We performed resistance testing on specimens collected from treatment-naive patients with pulmonary TB in Southwestern Uganda for first and second line anti-TB drugs. We sought to provide data to guide regional recommendations for empiric TB therapy. METHODS:Archived isolates, obtained from patients at Mbarara Regional Referral Hospital from February 2009 to February 2013, were tested for resistance to isoniazid and rifampicin using the MTBDRplus and Xpert MTB/RIF assays. A subset of randomly selected isolates was tested for second line agents, including fluoroquinolones (FQs), aminoglycosides, cyclic peptides, and ethambutol using the MTBDRsl assay. We performed confirmatory testing for FQ resistance using repeated MTBDRsl, the Mycobacteria growth indicator tube (MGIT) assay, and sequencing of the gyrA and gyrB genes. RESULTS:We tested isolates from 190 patients. The cohort had a median age of 33 years (IQR 26-43), 69% (131/190) were male, and the HIV prevalence was 42% (80/190). No isolates (0/190) were rifampicin-resistant and only 1/190 (0.5%) was isoniazid-resistant. Among 92 isolates tested for second-line drug resistance, 71 (77%) had interpretable results, of which none were resistant to aminoglycosides, cyclic peptides or ethambutol. Although 7 (10%) initially tested as resistant to FQs by the MTBDRsl assay, they were confirmed as susceptible by repeat MTBDRsl testing as well as by MGIT and gyrase gene sequencing. CONCLUSION:We found no MDR-TB and no resistance to ethambutol, FQs, or injectable anti-TB drugs in treatment naïve patients with pulmonary TB in Southwestern Uganda. Standard treatment guidelines for susceptible TB should be adequate for most patients with TB in this population. Where possible, molecular susceptibility testing methods should be routinely validated by culture methods.

Background The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis. Methods Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A2A AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days. Results There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-α, MIP-1α, MCP-1, IFN-γ, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01). Conclusion Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.