Pathophysiological Responses to Bloodstream Infection in Critically Ill Transplant Recipients Compared With Non-Transplant Recipients.

BACKGROUND: Identification of bloodstream infection (BSI) in transplant recipients may be difficult due to immunosuppression. Accordingly, we aimed to compare responses to BSI in critically ill transplant and non-transplant recipients and to modify systemic inflammatory response syndrome (SIRS) criteria for transplant recipients. METHODS: We analyzed univariate risks and developed multivariable models of BSI with 27 clinical variables from adult intensive care unit (ICU) patients at the University of Virginia (UVA) and at the University of Pittsburgh (Pitt). We used Bayesian inference to adjust SIRS criteria for transplant recipients. RESULTS: We analyzed 38.7 million hourly measurements from 41 725 patients at UVA, including 1897 transplant recipients with 193 episodes of BSI and 53 608 patients at Pitt, including 1614 transplant recipients with 768 episodes of BSI. The univariate responses to BSI were comparable in transplant and non-transplant recipients. The area under the receiver operating characteristic curve (AUC) was 0.82 (95% confidence interval [CI], .80-.83) for the model using all UVA patient data and 0.80 (95% CI, .76-.83) when using only transplant recipient data. The UVA all-patient model had an AUC of 0.77 (95% CI, .76-.79) in non-transplant recipients and 0.75 (95% CI, .71-.79) in transplant recipients at Pitt. The relative importance of the 27 predictors was similar in transplant and non-transplant models. An upper temperature of 37.5°C in SIRS criteria improved reclassification performance in transplant recipients. CONCLUSIONS: Critically ill transplant and non-transplant recipients had similar responses to BSI. An upper temperature of 37.5°C in SIRS criteria improved BSI screening in transplant recipients.

Antimalarial resistance risk in Mozambique detected by a novel quadruplex droplet digital PCR assay.

While the Plasmodium falciparum malaria parasite continues to cause severe disease globally, Mozambique is disproportionally represented in malaria case totals. Acquisition of copy number variations (CNVs) in the parasite genome contributes to antimalarial drug resistance through overexpression of drug targets. Of interest, piperaquine resistance is associated with plasmepsin 2 and 3 CNVs (pfpmp2 and pfpmp3, respectively), while CNVs in the multidrug efflux pump, multidrug resistance-1 (pfmdr1), increase resistance to amodiaquine and lumefantrine. These antimalarials are partner drugs in artemisinin combination therapies (ACTs) and therefore, CNV detection with accurate and efficient tools is necessary to track ACT resistance risk. Here, we evaluated ~300 clinically derived samples collected from three sites in Mozambique for resistance-associated CNVs. We developed a novel, medium-throughput, quadruplex droplet digital PCR (ddPCR) assay to simultaneously quantify the copy number of pfpmp3, pfpmp2, and pfmdr1 loci in these clinical samples. By using DNA from laboratory parasite lines, we show that this nanodroplet-based method is capable of detecting picogram levels of parasite DNA, which facilitates its application for low yield and human host-contaminated clinical surveillance samples. Following ddPCR and the application of quality control standards, we detected CNVs in 13 of 229 high-quality samples (prevalence of 5.7%). Overall, our study revealed a low number of resistance CNVs present in the parasite population across all three collection sites, including various combinations of pfmdr1, pfpmp2, and pfpmp3 CNVs. The potential for future ACT resistance across Mozambique emphasizes the need for continued molecular surveillance across the region.

Cadence (steps/min) and relative intensity in 61 to 85-year-olds: the CADENCE-Adults study.

BACKGROUND: We previously demonstrated that a heuristic (i.e., evidence-based, rounded yet practical) cadence threshold of ≥ 100 steps/min was associated with absolutely-defined moderate intensity physical activity (i.e., ≥ 3 metabolic equivalents [METs]) in older adults 61-85 years of age. Although it was difficult to ascertain achievement of absolutely-defined vigorous (6 METs) intensity, ≥ 130 steps/min was identified as a defensible threshold for this population. However, little evidence exists regarding cadence thresholds and relatively-defined moderate intensity indicators, including ≥ 64% heart rate [HR] maximum [HRmax = 220-age], ≥ 40% HR reserve [HRR = HRmax-HRresting], and ≥ 12 Borg Scale Rating of Perceived Exertion [RPE]; or vigorous intensity indicators including ≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE. PURPOSE: To analyze the relationship between cadence and relatively-defined physical activity intensity and identify relatively-defined moderate and vigorous heuristic cadence thresholds for older adults 61-85 years of age. METHODS: Ninety-seven ostensibly healthy adults (72.7 ± 6.9 years; 49.5% women) completed up to nine 5-min treadmill walking bouts beginning at 0.5 mph (0.8 km/h) and progressing by 0.5 mph speed increments (with 2-min rest between bouts). Directly-observed (and video-recorded) steps were hand-counted, HR was measured using a chest-strapped monitor, and in the final minute of each bout, participants self-reported RPE. Segmented mixed model regression and Receiver Operating Characteristic (ROC) curve analyses identified optimal cadence thresholds associated with relatively-defined moderate (≥ 64%HRmax, ≥ 40%HRR, and ≥ 12 RPE) and vigorous (≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE) intensities. A compromise between the two analytical methods, including Youden's Index (a sum of sensitivity and specificity), positive and negative predictive values, and overall accuracy, yielded final heuristic cadences. RESULTS: Across all relatively-defined moderate intensity indicators, segmented regression models and ROC curve analyses identified optimal cadence thresholds ranging from 105.9 to 112.8 steps/min and 102.0-104.3 steps/min, respectively. Comparable values for vigorous intensity indicators ranged between126.1-132.1 steps/min and 106.7-116.0 steps/min, respectively. Regardless of the relatively-defined intensity indicator, the overall best heuristic cadence threshold aligned with moderate intensity was ≥ 105 steps/min. Vigorous intensity varied between ≥ 115 (greater sensitivity) or ≥ 120 (greater specificity) steps/min. CONCLUSIONS: Heuristic cadence thresholds align with relatively-defined intensity indicators and can be useful for studying and prescribing older adults' physiological response to, and/or perceived experience of, ambulatory physical activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

Cadence-based classification of moderate-intensity overground walking in 41- to 85-year-old adults.

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

A scoping review on the impact of the COVID-19 pandemic on physical activity and sedentary behavior in Saudi Arabia.

BACKGROUND: In Saudi Arabia, stay-at-home orders to address the coronavirus disease 2019 (COVID-19) pandemic between March 15 and 23, 2020 and eased on May 28, 2020. We conducted a scoping review to systematically describe physical activity and sedentary behavior in Saudi Arabia associated with the timing of the lockdown. METHODS: We searched six databases on December 13, 2021 for articles published in English or Arabic from 2018 to the search date. Studies must have reported data from Saudi Arabia for any age and measured physical activity or sedentary behavior. RESULTS: Overall, 286 records were found; after excluding duplicates, 209 records were screened, and 19 studies were included in the review. Overall, 15 studies were cross-sectional, and 4 studies were prospective cohorts. Three studies included children and adolescents (age: 2-18 years), and 16 studies included adults (age: 15-99 years). Data collection periods were < = 5 months, with 17 studies collecting data in 2020 only, one study in 2020-2021, and one study in 2021. The median analytic sample size was 363 (interquartile range 262-640). Three studies of children/adolescents collected behaviors online at one time using parental reporting, with one also allowing self-reporting. All three studies found that physical activity was lower during and/or following the lockdown than before the lockdown. Two studies found screen time, television watching, and playing video games were higher during or following the lockdown than before the lockdown. Sixteen adult studies assessed physical activity, with 15 utilizing self-reporting and one using accelerometry. Physical activity, exercise, walking, and park visits were all lower during or following the lockdown than before the lockdown. Six adult studies assessed sedentary behavior using self-report. Sitting time (4 studies) and screen time (2 studies) were higher during or following the lockdown than before the lockdown. CONCLUSIONS: Among children, adolescents, and adults, studies consistently indicated that in the short-term, physical activity decreased and sedentary behavior increased in conjunction with the movement restrictions. Given the widespread impact of the pandemic on other health behaviors, it would be important to continue tracking behaviors post-lockdown and identify subpopulations that may not have returned to their physical activity and sedentary behavior to pre-pandemic levels to focus on intervention efforts.

Continuous ECG monitoring should be the heart of bedside AI-based predictive analytics monitoring for early detection of clinical deterioration.

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

Associations of steps per day and step intensity with the risk of diabetes: the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

BACKGROUND: Higher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes. METHODS: We included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008-2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% confidence intervals (CI). We further examined whether the percent of intense steps at a given accumulation of steps/day was associated with diabetes risk, and if associations were modified by specific cohort characteristics. RESULTS: The average age of cohort members was 39 years and 52% were female. Adults had an average of 8164 steps/day and spent 12 min/day in brisk ambulation (> 100 steps/min). Over 6 years of follow-up, there were 1115 cases of diabetes. There was a suggestive lower risk of diabetes with more steps/day- adults had a 2% lower risk per 1000 steps/day (HR = 0.98 (95% CI 0.95, 1.00)). Inverse associations between average steps/day and diabetes incidence were observed across many cohort characteristics, but most importantly among adults at high risk for diabetes - those who were older, or had obesity or prediabetes. Adults who accumulated 17 min/day in brisk ambulation compared to < 2 min/day had a 31% lower risk of diabetes (HR = 0.69 (95% CI 0.53, 0.89)). A greater percent of intense steps for a given accumulation of steps/day was associated with further risk reduction. CONCLUSION: Adults who accumulate more daily steps may have a lower risk of diabetes. Accumulating more steps/day and greater step intensity appear to be important targets for preventing diabetes.

A catalog of validity indices for step counting wearable technologies during treadmill walking: the CADENCE-adults study.

BACKGROUND: Standardized validation indices (i.e., accuracy, bias, and precision) provide a comprehensive comparison of step counting wearable technologies. PURPOSE: To expand a previously published child/youth catalog of validity indices to include adults (21-40, 41-60 and 61-85 years of age) assessed across a range of treadmill speeds (slow [0.8-3.2 km/h], normal [4.0-6.4 km/h], fast [7.2-8.0 km/h]) and device wear locations (ankle, thigh, waist, and wrist). METHODS: Two hundred fifty-eight adults (52.5 ± 18.7 years, 49.6% female) participated in this laboratory-based study and performed a series of 5-min treadmill bouts while wearing multiple devices; 21 devices in total were evaluated over the course of this multi-year cross-sectional study (2015-2019). The criterion measure was directly observed steps. Computed validity indices included accuracy (mean absolute percentage error, MAPE), bias (mean percentage error, MPE), and precision (correlation coefficient, r; standard deviation, SD; coefficient of variation, CoV). RESULTS: Over the range of normal speeds, 15 devices (Actical, waist-worn ActiGraph GT9X, activPAL, Apple Watch Series 1, Fitbit Ionic, Fitbit One, Fitbit Zip, Garmin vivoactive 3, Garmin vivofit 3, waist-worn GENEActiv, NL-1000, PiezoRx, Samsung Gear Fit2, Samsung Gear Fit2 Pro, and StepWatch) performed at < 5% MAPE. The wrist-worn ActiGraph GT9X displayed the worst accuracy across normal speeds (MAPE = 52%). On average, accuracy was compromised across slow walking speeds for all wearable technologies (MAPE = 40%) while all performed best across normal speeds (MAPE = 7%). When analyzing the data by wear locations, the ankle and thigh demonstrated the best accuracy (both MAPE = 1%), followed by the waist (3%) and the wrist (15%) across normal speeds. There were significant effects of speed, wear location, and age group on accuracy and bias (both p < 0.001) and precision (p ≤ 0.045). CONCLUSIONS: Standardized validation indices cataloged by speed, wear location, and age group across the adult lifespan facilitate selecting, evaluating, or comparing performance of step counting wearable technologies. Speed, wear location, and age displayed a significant effect on accuracy, bias, and precision. Overall, reduced performance was associated with very slow walking speeds (0.8 to 3.2 km/h). Ankle- and thigh-located devices logged the highest accuracy, while those located at the wrist reported the worst accuracy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

Classification of moderate-intensity overground walking speed in 21- to 85-year-old adults.

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

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern uganda by high-resolution melt analysis.

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.

A catalog of validity indices for step counting wearable technologies during treadmill walking: the CADENCE-Kids study.

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 < 5% MAPE over the range of normal speeds. More generally, waist (MAPE = 4%), thigh (4%) and ankle (5%) locations displayed higher accuracy than the wrist location (23%) at normal speeds. On average, all wearable technologies displayed the lowest accuracy across slow speeds (MAPE = 50.1 ± 35.5%), and the highest accuracy across normal speeds (MAPE = 15.9 ± 21.7%). Speed and wear location had a significant effect on accuracy and bias (P < 0.001), but not on precision (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.gov NCT01989104 . Registered November 14, 2013.

Walking cadence (steps/min) and intensity in 61-85-year-old adults: the CADENCE-Adults study.

BACKGROUND: Heuristic (i.e., evidence-based, rounded) cadences of ≥100 and ≥ 130 steps/min have consistently corresponded with absolutely-defined moderate (3 metabolic equivalents [METs]) and vigorous (6 METs) physical activity intensity, respectively, in adults 21-60 years of age. There is no consensus regarding similar thresholds in older adults. PURPOSE: To provide heuristic cadence thresholds for 3, 4, 5, and 6 METs in 61-85-year-old adults. METHODS: Ninety-eight community-dwelling ambulatory and ostensibly healthy older adults (age = 72.6 ± 6.9 years; 49% women) walked on a treadmill for a series of 5-min bouts (beginning at 0.5 mph with 0.5 mph increments) in this laboratory-based cross-sectional study until: 1) transitioning to running, 2) reaching ≥75% of their age-predicted maximum heart rate, or 3) reporting a Borg rating of perceived exertion > 13. Cadence was directly observed and hand-tallied. Intensity (oxygen uptake [VO2] mL/kg/min) was assessed with indirect calorimetry and converted to METs (1 MET = 3.5 mL/kg/min). Cadence thresholds were identified via segmented mixed effects model regression and using Receiver Operating Characteristic (ROC) curves. Final heuristic cadence thresholds represented an analytical compromise based on classification accuracy (sensitivity, specificity, positive and negative predictive value, and overall accuracy). RESULTS: Cadences of 103.1 (95% Prediction Interval: 70.0-114.2), 116.4 (105.3-127.4), 129.6 (118.6-140.7), and 142.9 steps/min (131.8-148.4) were identified for 3, 4, 5, and 6 METs, respectively, based on the segmented regression. Comparable values based on ROC analysis were 100.3 (95% Confidence Intervals: 95.7-103.1), 111.5 (106.1-112.9), 116.0 (112.4-120.2), and 128.6 steps/min (128.3-136.4). Heuristic cadence thresholds of 100, 110, and 120 were associated with 3, 4, and 5 METs. Data to inform a threshold for ≥6 METs was limited, as only 6/98 (6.0%) participants achieved this intensity. CONCLUSIONS: Consistent with previous data collected from 21-40 and 41-60-year-old adults, heuristic cadence thresholds of 100, 110, and 120 steps/min were associated with 3, 4, and 5 METs, respectively, in 61-85-year-old adults. Most older adults tested did not achieve the intensity of ≥6 METs; therefore, our data do not support establishing thresholds corresponding with this intensity level. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258 . Registered 24 December 2015.

Cadence (steps/min) and relative intensity in 21 to 60-year-olds: the CADENCE-adults 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), 121.3-126.0 (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, 140.2-142.6, 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 127.5, 121.5, 117.2-123.2, 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 105 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.

Atypical Pneumonia: Definition, Causes, and Imaging Features.

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 community-acquired 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. ©RSNA, 2021.

Using Cadence to Predict the Walk-to-Run Transition in Children and Adolescents: A Logistic Regression Approach.

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.

Walking cadence (steps/min) and intensity in 41 to 60-year-old adults: the CADENCE-adults study.

BACKGROUND: In younger adults (i.e., those < 40 years of age) a walking cadence of 100 steps/min is a consistently supported threshold indicative of absolutely-defined moderate intensity ambulation (i.e., ≥ 3 metabolic equivalents; METs). Less is known about the cadence-intensity relationship in adults of middle-age. 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.

Etiology of Sepsis in Uganda Using a Quantitative Polymerase Chain Reaction-based TaqMan Array Card.

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.

Walking cadence (steps/min) and intensity in 21-40 year olds: CADENCE-adults.

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 ).

Detection of Plasmodium Species by High-Resolution Melt Analysis of DNA from Blood Smears Acquired in Southwestern Uganda.

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.