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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.

Single cell genomics is a rapidly advancing field; however, most techniques are designed for mammalian cells. Here, we present a single cell sequencing pipeline for the intracellular parasite, Plasmodium falciparum, which harbors a relatively small genome with an extremely skewed base content. Through optimization of a quasi-linear genome amplification method, we achieve better targeting of the parasite genome over contaminants and generate coverage levels that allow detection of relatively small copy number variations on a single cell level. These improvements are important for expanding accessibility of single cell approaches to new organisms and for improving the study of adaptive mechanisms.

Objective Readers will be able to identify the impact of the Alliance for Adolescent Pregnancy Prevention (AAPP) in improving knowledge and attitudes regarding risky sexual health behaviors. Methods Three AAPP, Be Proud! Be Responsible!(BPBR), Making Proud Choices! (MPC) and Wise Guys: Male Responsibility (Wise Guys), are assessed using 3 similar pre- and post-surveys which are designed specifically for these curricula. These surveys measure changes in knowledge and attitudes toward sexual health and risky behaviors at baseline and completion of the course. Results In Delaware, adolescents who completed any of the three AAPP programs have shown an increase in knowledge around condom usage; an increase in awareness of the factors around safe sexual health practices and healthy relationships; and, a positive change in attitude around communication – both with a partner and their parent(s)/guardian(s). Post-survey scores improved for BPBR, MPC and Wise Guys by 8%, 18% and 8%, respectively. Conclusions Reproductive health education is essential for teenagers, giving them the tools to make safer choices if they choose to have sex (Delaware Department of Health and Social Services, n.d.). In Delaware, the Youth Risk Behavior Survey (YRBS) indicates that teens continue to take risks with their sexual health. Programs like AAPP have the capacity to continue to make a positive impact on reducing the risk of STI and HIV transmission, along with potentially lowering the number of teens who become pregnant.

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.

Supplemental Digital Content is available in the text., Objectives: The Sepsis-3 taskforce defined sepsis as suspicion of infection and an acute rise in the Sequential Organ Failure Assessment score by 2 points over the preinfection baseline. Sepsis-3 studies, though, have not distinguished between acute and chronic organ failure, and may not accurately reflect the epidemiology, natural history, or impact of sepsis. Our objective was to determine the extent to which the predictive validity of Sepsis-3 is attributable to chronic rather than acute organ failure. Design: Retrospective cohort study. Setting: General medicine inpatient service at a tertiary teaching hospital. Patients: A total of 3,755 adult medical acute-care encounters (1,864 confirmed acute infections) over 1 year. Interventions: None. Measurements and Main Results: We measured the total Sequential Organ Failure Assessment score at the onset of infection and separated its components (baseline and acute rise) using case-by-case chart reviews. We compared the predictive validities of acuity-focused (acute rise in Sequential Organ Failure Assessment ≥ 2) and conventional (total Sequential Organ Failure Assessment ≥ 2) implementations of Sepsis-3 criteria. Measures of predictive validity were change in the rate of outcomes and change in the area under receiver operating characteristic curves after adding sepsis criteria to multivariate logistic regression models of baseline risk (age, sex, race, and Charlson comorbidity index). Outcomes were inhospital mortality (primary) and ICU transfer or inhospital mortality (secondary). Acuity-focused implementations of Sepsis-3 were associated with neither a change in mortality (2.2% vs 1.2%; p = 0.18) nor a rise in area under receiver operating characteristic curves compared with baseline models (0.67 vs 0.66; p = 0.75). In contrast, conventional implementations were associated with a six-fold change in mortality (2.4% vs 0.4%; p = 0.01) and a rise in area under receiver operating characteristic curves compared with baseline models (0.70 vs 0.66; p = 0.04). Results were similar for the secondary outcome. Conclusions: The evaluation of the validity of organ dysfunction-based clinical sepsis criteria is prone to bias, because acute organ dysfunction consequent to infection is difficult to separate from preexisting organ failure in large retrospective cohorts.

Supplemental Digital Content is available in the text., Objectives: Bloodstream infection is associated with high mortality rates in critically ill patients but is difficult to identify clinically. This results in frequent blood culture testing, exposing patients to additional costs as well as the potential harms of unnecessary antibiotics. The purpose of this study was to assess whether the analysis of bedside physiologic monitoring data could accurately describe a pathophysiologic signature of bloodstream infection in patients admitted to the ICU. Design: Development of a statistical model using physiologic data from a retrospective observational cohort. Setting: University of Virginia Medical Center (Charlottesville, VA), a tertiary-care academic medical center. Patients: Critically ill patients consecutively admitted to either the medical or surgical/trauma ICUs with available physiologic monitoring data between February 2011 and June 2015. Interventions: None. Measurements and Main Results: We analyzed 9,954 ICU admissions with 144 patient-years of vital sign and electrocardiography waveform data, totaling 1.3 million hourly measurements. There were 15,577 blood culture instances, with 1,184 instances of bloodstream infection (8%). The multivariate pathophysiologic signature of bloodstream infection was characterized by abnormalities in 15 different physiologic features. The cross-validated area under the receiver operating characteristic curve was 0.78 (95% CI, 0.69–0.85). We also identified distinct signatures of Gram-negative and fungal bloodstream infections, but not Gram-positive bloodstream infection. Conclusions: Signatures of bloodstream infection can be identified in the routine physiologic monitoring data of critically ill adults. This may assist in identifying infected patients, maximizing diagnostic stewardship, and measuring the effect of new therapeutic modalities for sepsis.

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 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., In hospitalized HIV-infected patients in Uganda, empiric antituberculosis therapy was associated with improved survival among patients with severe sepsis.

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.

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.

The impact of malnutrition on the outcomes of hospitalized adults in resource-limited settings such as sub-Saharan Africa (SSA) is not fully described. We aimed to determine the association between malnutrition and mortality in adults admitted to hospital in the resource-limited setting of Southwestern Uganda.We performed a cohort study of adults admitted to the medical ward of Mbarara Regional Referral Hospital. Measures of nutritional status included: 1) body mass index (BMI), 2) the mini-nutritional assessment short form (MNA-sf), and 3) mid-upper arm circumference (MUAC). Subjects were followed until death or 30 days from admission. We used proportional hazards regression to assess associations between malnutrition and in-hospital and 30-day mortality.We enrolled 318 subjects. The prevalence of malnutrition was 25-59% depending on the measure used. In-hospital and 30-day mortality were 18% and 37% respectively. In the adjusted analysis, subjects with MNA-sf score 0-7 had a 2.7-fold higher risk of in-hospital mortality (95% CI: 1.3-5.9, p = 0.011) than those with a score of 8-14, and subjects with malnutrition determined by MUAC (20 cm for males, and19 cm for females) had a 1.8-fold higher risk of in-hospital mortality (95% CI: 0.98-3.4, p = 0.06) than those normally nourished. MNA-sf (HR 1.6, 95% CI: 1.02-2.6, p = 0.039) and MUAC (HR 1.6, 95% CI: 1.0-2.3, p = 0.048) were independently predictive of 30-day mortality. BMI18.5 was not associated with in-hospital or 30-day mortality.Malnutrition was common and simple measures of nutritional status predicted in-hospital and 30-day mortality. Further research is needed to understand the pathophysiology of malnutrition during acute illness and mitigate its effects.

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.

Blastomycosis is a rare fungal disease that can cause intraarticular infection and joint destruction requiring surgical reconstruction. We describe a patient who presented with destruction of the knee joint of unknown etiology. The patient was initially treated with debridement and spacer placement followed by antifungal therapy after cultures grew blastomycosis. Following adequate treatment of the infection, the patient was taken back to the operating room for reconstruction with a total knee arthroplasty. The patient had a successful outcome with no evidence of infection at two years following surgery. To our knowledge, this case report represents the first documented case in which a blastomycotic infection of a native knee was successfully treated with a two-stage total knee arthroplasty.

We validated a handheld point-of-care lactate (POCL) monitor's ability to measure lactate in cerebrospinal fluid (CSF) and diagnose bacterial meningitis in Uganda. There was a strong linear correspondence between POCL and standard laboratory lactate test results (R2 = 0.86; P < 0.001). For 145 patients with clinical meningitis, the area under the receiver operating characteristic curve for the prediction of bacterial meningitis by CSF POCL was 0.92 (95% confidence interval = 0.85–0.99, P < 0.001). A CSF POCL concentration of 7.7 mmol/L provided 88% sensitivity and 90% specificity for the diagnosis of bacterial meningitis. CSF POCL testing had excellent use in the diagnosis of bacterial meningitis, and it may be useful where CSF analyses are delayed or laboratory infrastructure is limited.

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.

Purpose. The purpose of this project was to determine if the Wise Guysprogram influences young men’s perceptions of the impact a teen birthwould have on their lives in the areas of relationships, vocation, and per-sonal life. DesignandMethods. TheWiseGuysprogramwasimplementedwith70adolescent males. The Thoughts on Teen Parenting Survey was used todetermineparticipants’perceptionsofthecostsandrewardsassociatedwithteen parenting. Results. Data, analyzed using paired t -tests, demonstrated that Wise Guyswas effective in reinforcing less positive perceptions of teen parenting. Practice Implications. Wise Guys offers an important strategy to impactyoungmen’sperceptionsabouttheteenparentingexperienceandprovidesone means to promote responsible sexual behavior in teen men. Reductions in teen pregnancy rates in the past threedecades have largely been attributed to more teenschoosingnottoengageinsexualactivityandtheuseof birth control and protection by those who do par-ticipate in sexual intercourse (Martinez, Copen, A Martinez et al., 2011).Recent federal funding initiatives emphasizingevidence-based curricula and programming, publicpolicies related to adolescent sexual health, andmediadepictions of the realities of teen childbearinghave reinforced initiatives designed to continue toreduce teen pregnancy and birth rates.Educational efforts to prevent teen pregnancystrive to enhance sexual decision making, contra-ceptive self-efficacy, abilities to negotiate, relation-ship skills, concepts of personal responsibility, andknowledgeofconsequences.Additionaleffortsfocuson youth development strategies, fostering futuregoal setting for educational and career trajectories,or on healthcare interventions that increase accessto reproductive health services and affordable birthcontrol. Although all of these interventions may becredited with contributing to the reduction in teenpregnancy rates, most efforts focus on youngwomen, young mothers, and the female role in safesexual behavior. Despite evidence that 42% of ado-lescent males are sexually active and account for alarge percentage of those with sexually transmittedinfections (Martinez et al., 2011), and the fact thatmales are obviously involved with teen pregnancy,preventionstrategiesfocusedonmenarelesspromi-nent in the literature, and comprehensive programsfocusing on the role of young men in responsiblesexualbehaviorarelimited.Sonenstein(2001)rein-forced that young men who are most vulnerable,including those of color, living in poverty, out ofschool, involved in the juvenile justice system, infostercare,whoaregayorbisexual,andmenintheirearly 20s, require the most intense efforts to con-tinue to make positive strides in teen pregnancyprevention.The lack of educational and healthcare resourcesfocused on the reproductive health of young men

Teaching pregnancy prevention to large groups offers many challenges. This article describes the use of film clips, with guided discussion, to teach pregnancy prevention. In order to analyze the costs associated with teen pregnancy, a film clip discussion session based with the film The Gloucester 18 was the keynote of a youth summit. The lesson plan, logistics, and informal evaluative data are discussed. Feedback from discussion group leaders and participants informs future implementation of this strategy. Showing film clips, with guided discussion and reflective opportunities, offers a valuable method to teach concepts of pregnancy prevention to teens.

We evaluated the association between severity of sepsis and in-hospital mortality in 150 patients with non-surgical sepsis at a regional referral hospital in Uganda. In-hospital mortality occurred in 5 of 52 (9.6%) patients with sepsis, 24 of 71 (33.8%) patients with severe sepsis, and 16 of 27 (59.3%) patients with septic shock. In the multivariate analysis, the identification of severe sepsis (adjusted hazard ratio [AHR] = 2.9, 95% confidence interval [CI] = 1.0–8.2, P = 0.04), septic shock (AHR = 5.7, 95% CI = 1.6–20.3, P = 0.007), and dysfunction of three or more organs (AHR = 2.9, 95% CI = 1.1–7.3, P = 0.03) increased the risk of in-hospital mortality. Adding aggregate organ dysfunction to the multivariate equation that included the sepsis category statistically significantly improved the model, but the opposite did not. Predictors of mortality were easily measurable and could be used to risk stratify critically ill patients in resource-constrained settings.

Dysglycemia during sepsis is associated with poor outcomes in resource-rich settings. In resource-limited settings, hypoglycemia is often diagnosed clinically without the benefit of laboratory support. We studied the utility of point-of-care glucose monitoring to predict mortality in severely septic patients in Uganda.Prospective observational study.One national and two regional referral hospitals in Uganda.We enrolled 532 patients with sepsis at three hospitals in Uganda. The analysis included 418 patients from the three sites with inhospital mortality data, a documented admission blood glucose concentration, and evidence of organ dysfunction at admission (systolic blood pressure≤100 mm Hg, lactate4 mmol/L, platelet number100,000/μL, or altered mental status).None.We evaluated the association between admission point-of-care blood glucose concentration and inhospital mortality. We also assessed the accuracy of altered mental status as a predictor of hypoglycemia. Euglycemia occurred in 33.5% (140 of 418) of patients, whereas 16.3% (68 of 418) of patients were hypoglycemic and 50.2% (210 of 418) were hyperglycemic. Univariate Cox regression analyses comparing in-hospital mortality among hypoglycemic (35.3% [24 of 68], hazard ratio 2.0, 95% confidence interval 1.2-3.6, p=.013) and hyperglycemic (29.5% [62 of 210], hazard ratio 1.5, 95% confidence interval 0.96-2.4, p=.08) patients to euglycemic (19.3% [27 of 140]) patients showed statistically significantly higher rates of inhospital mortality for patients with hypoglycemia. Hypoglycemia (adjusted hazard ratio 1.9, 95% confidence interval 1.1-3.3, p=.03) remained significantly and independently associated with inhospital mortality in the multivariate model. The sensitivity and specificity of altered mental status for hypoglycemia were 25% and 86%, respectively.Hypoglycemia is an independent risk factor for inhospital mortality in patients with severe sepsis and cannot be adequately assessed by clinical examination. Correction of hypoglycemia may improve outcomes of critically ill patients in resource-limited settings.

Blastomycosis commonly occurs following inhalation of Blastomyces dermatitidis conidia causing a pulmonary infection and can disseminate to extrapulmonary sites. Osseous involvement primarily results from hematogenous spread, but in rare cases, direct inoculation can occur. We describe a case of osseous blastomycosis without pulmonary or disseminated disease successfully treated with posaconazole.

Cadence (steps/minute) is an emerging proxy-indicator of ambulatory metabolic intensity. 100 steps/minute is a consistent threshold associated with absolutely-defined moderate intensity (i.e., 3 metabolic equivalents or METs; 1 MET=3.5 mL O2/kg/min) in adults up to 60 years of age, but its stability in older adults is not clear. Conflicting findings indicate older adults attain moderate intensity at lower, but also higher, cadences. Differences may be due to relative vs. absolute definitions of intensity with age. We present the preliminary results from CADENCE-Adults, an NIH-funded study evaluating cadence and intensity across the adult lifespan up to 85 years of age.

We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sep- sis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with neg- ative malaria smears ( N = 328 of 379), Kaplan-Meier curves revealed decreased combined inpatient and 30-day mortal- ity among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank χ 2 = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores ≤ 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank χ 2 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility.

Prediction of mortality may improve management and outcomes of patients with sepsis in resource-limited settings. Therefore, we evaluated the ability of a hand-held portable whole-blood lactate (PWBL) analyzer to predict mortality of patients who are admitted to the hospital with severe sepsis.A prospective observational study enrolled 253 patients at a national referral hospital in Uganda. Inclusion criteria required (1)or=2 systemic inflammatory response syndrome criteria or thermodysregulation, (2) hypotension, and (3) suspected infection. A subset of 72 patients had PWBL and standard laboratory serum lactate measured. The primary measured outcome was in-hospital mortality.Fifty-nine (81.9%) of 72 evaluated patients were infected with human immunodeficiency virus type 1. The in-hospital mortality rate was 25.7% (18 of 70), and the in- and outpatient mortality at 30 days was 41.6% (30 of 72). PWBL was positively associated with in-hospital but not outpatient mortality (P=.001). The receiver operating characteristic area under the curve for PWBL was 0.81 (P=.081). The optimal PWBL concentration for predicting in-hospital mortality (sensitivity, 88.3%; specificity, 71.2%) wasor=4.0 mmol/L. Patients with a PWBL concentrationor=4.0 mmol/L died while in the hospital substantially more often (50.0%) than did those with a PWBL concentration4.0 mmol/L (7.5%) (odds ratio, 12.3; 95% confidence interval, 3.5-48.9; [P=.001). Standard laboratory serum lactate results were inconsistent and less predictive of mortality than were those of PWBL in a multiple logistic regression model.A PWBL concentrationor=4.0 mmol/L predicts with 81% accuracy a 7-fold higher mortality of patients with sepsis than does a PWBL concentration4.0 mmol/L. PWBL testing would be useful in places where clinical decisions are limited by lack of laboratory infrastructure and poor reliability.

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.

Intensive Care Unit (ICU) patients have significant morbidity and mortality, often from complications that arise during the hospital stay. Severe sepsis is one of the leading causes of death among these patients. Predictive models have the potential to allow for earlier detection of severe sepsis and ultimately earlier intervention. However, current methods for identifying and predicting severe sepsis are biased and inadequate. The goal of this work is to identify a new framework for the prediction of severe sepsis and identify early predictors utilizing clinical laboratory values and vital signs collected in adult ICU patients. We explore models with logistic regression (LR), support vector machines (SVM), and logistic model trees (LMT) utilizing vital signs, laboratory values, or a combination of vital and laboratory values. When applied to a retrospective cohort of ICU patients, the SVM model using laboratory and vital signs as predictors identified 339 (65%) of the 3,446 patients as developing severe sepsis correctly. Based on this new framework and developed models, we provide a recommendation for the use in clinical decision support in ICU and non-ICU environments.