Polysubstance Use in Pregnancy: Surveillance, Interventions, and Next Steps
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General & Internal Medicine↗
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Multivitamin Use Among Hispanic Women of Reproductive Age in the United States, 2013–2022
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General & Internal Medicine↗
On alert for Ebola: public health risk assessment of travellers from Uganda to the USA during the 2022 outbreak
Abstract Background On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. Methods From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments (‘health departments’) conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. Results Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. Conclusion Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers’ potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.
General & Internal Medicine↗
Comparison of Different Variants of the U.S. Army Occupational Physical Assessment Test
The U.S. Army Occupational Physical Assessment Test (OPAT) is a pre-enlistment physical employment screening assessment developed to place recruits and soldiers into Military Occupational Specialties (MOSs) based on their physical capabilities in order to optimize performance and limit injury. The OPAT consists of the seated power throw (SPT), strength deadlift (SDL), standing long jump, and interval aerobic run. During the scientific validation of the OPAT, two variants of the SPT and two variants of the SDL were used. Although the OPAT was validated using both variants for each test, U.S. Army scientists and policymakers have received queries regarding how these variants compare to each other. Therefore, the purpose of this study was to compare different variants of the SPT and SDL. Thirty-two participants (14 male and 18 female) between the ages of 18 and 42 years visited the laboratory on one occasion and performed two variants of the SPT (seated on the ground [the current OPAT standard] versus seated in a chair with a 35 cm seat height) and two variants of the SDL (using a hex-bar [the current OPAT standard] versus using paired dumbbells). Testing order for the different variants was randomized. The protocol was approved by the U.S. Army Medical Research and Development Command Institutional Review Board. Performing the SPT from a chair significantly (P < .05) increased performance when compared to performing the SPT from the ground (5.4 ± 1.3 m versus 5.0 ± 1.4 m, respectively). Values for the two SPT variants were correlated (tau = 0.90). Performing the SDL using the hex-bar significantly increased the maximal weight lifted when compared to performing the SDL using paired dumbbells (86.9 ± 18.4 kg versus 83.1 ± 18.0 kg, respectively). Values for the two SDL variants were correlated (tau = 0.83). Performing different variants of the SPT and SDL influenced the resulting score. Although these findings do not alter the administration or scoring of the OPAT, they do provide a valuable reference in the event of future inquiries regarding the development of the OPAT.
General & Internal Medicine↗
Impact of Blast Overpressure on the Pharmacokinetics of Various Antibiotics in Sprague Dawley Rats
ABSTRACT Introduction Combat injuries are complex and multimodal. Most injuries to the extremities occur because of explosive devices such as improvised explosive devices. Blast exposure dramatically increases the risk of infection in combat wounds, and there is limited available information on the best antibiotic treatments for these injuries. We previously demonstrated that mice exposed to blast displayed a delayed clearance of cefazolin from the plasma and liver; further semi-mechanistic modeling determined that cefazolin concentrations in the skin of these mice were reduced. Our objective was to investigate the effects of blast on the pharmacokinetics of antibiotics of different types used for the treatment of combat wounds in the rat model. Materials and Methods Male Sprague Dawley rats were exposed to blast overpressure followed by injection of a bolus of animal equivalent doses of an antibiotic (cefazolin, cefepime, ertapenem, or clindamycin) into the tail vein at 1-hour post-blast exposure. Blood was collected at predetermined time points via repeated sampling from the tail vein. Animals were also euthanized at predetermined time points, at which time liver, kidney, skin, and blood via cardiac puncture were collected. Antibiotic concentrations were determined by ultra-performance liquid chromatography–tandem mass spectrometry. Results Blast-exposed rats exhibited a similar rate of clearance compared to non-blasted rats in the blood, liver, kidney, and skin, which is inconsistent with the data regarding cefazolin in blast-exposed mice. Conclusions Our results in rats do not recapitulate our previous observation of delayed cefazolin clearance in mice following the blast overpressure exposure. Although using rats permitted us to collect multiple blood samples from the same animals, rats may not be a suitable model for measuring the pharmacokinetics of antibiotics following blast. The interpretation of the results may be challenging because of variation in data among rat subjects in the same sample groups.
General & Internal Medicine↗
Comparative Performance of Three Eye-Tracking Devices in Detection of Mild Traumatic Brain Injury in Acute Versus Chronic Subject Populations
ABSTRACT Introduction Presently, traumatic brain injury (TBI) triage in field settings relies on symptom-based screening tools such as the updated Military Acute Concussion Evaluation. Objective eye-tracking may provide an alternative means of neurotrauma screening due to sensitivity to neurotrauma brain-health changes. Previously, the US Army Medical Research and Development Command Non-Invasive NeuroAssessment Devices (NINAD) Integrated Product Team identified 3 commercially available eye-tracking devices (SyncThink EYE-SYNC, Oculogica EyeBOX, NeuroKinetics IPAS) as meeting criteria toward being operationally effective in the detection of TBI in service members. We compared these devices to assess their relative performance in the classification of mild traumatic brain injury (mTBI) subjects versus normal healthy controls. Materials and Methods Participants 18 to 45 years of age were assigned to Acute mTBI, Chronic mTBI, or Control group per study criteria. Each completed a TBI assessment protocol with all 3 devices counterbalanced across participants. Acute mTBI participants were tested within 72 hours following injury whereas time since last injury for the Chronic mTBI group ranged from months to years. Discriminant analysis was undertaken to determine device classification performance in separating TBI subjects from controls. Area Under the Curves (AUCs) were calculated and used to compare the accuracy of device performance. Device-related factors including data quality, the need to repeat tests, and technical issues experienced were aggregated for reporting. Results A total of 63 participants were recruited as Acute mTBI subjects, 34 as Chronic mTBI subjects, and 119 participants without history of TBI as controls. To maximize outcomes, poorer quality data were excluded from analysis using specific criteria where possible. Final analysis utilized 49 (43 male/6 female, mean [x̅] age = 24.3 years, SD [s] = 5.1) Acute mTBI subjects, and 34 (33 male/1 female, x̅ age = 38.8 years, s = 3.9) Chronic mTBI subjects were age- and gender-matched as closely as possible with Control subjects. AUCs obtained with 80% of total dataset ranged from 0.690 to 0.950 for the Acute Group and from 0.753 to 0.811 for the Chronic mTBI group. Validation with the remaining 20% of dataset produced AUCs ranging from 0.600 to 0.750 for Acute mTBI group and 0.490 to 0.571 for the Chronic mTBI group. Conclusions Potential eye-tracking detection of mTBI, per training model outcomes, ranged from acceptable to excellent for the Acute mTBI group; however, it was less consistent for the Chronic mTBI group. The self-imposed targeted performance (AUC of 0.850) appears achievable, but further device improvements and research are necessary. Discriminant analysis models differed for the Acute versus Chronic mTBI groups, suggesting performance differences in eye-tracking. Although eye-tracking demonstrated sensitivity in the Chronic group, a more rigorous and/or longitudinal study design is required to evaluate this observation. mTBI injuries were not controlled for this study, potentially reducing eye-tracking assessment sensitivity. Overall, these findings indicate that while eye-tracking remains a viable means of mTBI screening, device-specific variability in data quality, length of testing, and ease of use must be addressed to achieve NINAD objectives and DoD implementation.
General & Internal Medicine↗
Optimization of a Lethal, Combat-Relevant Model of Sterile Inflammation in Mice for Drug Candidate Screening
ABSTRACT Introduction Extensive trauma, commonly seen in wounded military Service Members, often leads to a severe sterile inflammation termed systemic inflammatory response syndrome (SIRS), which can progress to multiple organ dysfunction syndrome (MODS) and death. MODS is a serious threat to wounded Service Members, historically causing 10% of all deaths in trauma admissions at a forward deployed combat hospital. The importance of this problem will be exacerbated in large-scale combat operations, in which evacuation will be delayed and care of complex injuries at lower echelons of care may be prolonged. The main goal of this study was to optimize an existing mouse model of lethal SIRS/MODS as a therapeutic screening platform for the evaluation of immunomodulatory drugs. Materials and Methods Male C57BL/6 mice were euthanized, and the bones and muscles were collected and blended into a paste termed tissue–bone matrix (TBX). The TBX at 12.5%–20% relative to body weight of each recipient mouse was implanted into subcutaneous pouches created on the dorsum of anesthetized animals. Mice were observed for clinical scores for up to 48 hours postimplantation and euthanized at the preset point of moribundity. To test effects of anesthetics on TBX-induced mortality, animals received isoflurane or ketamine/xylazine (K/X). In a separate set of studies, mice received TBX followed by intraperitoneal injection with 20 mg/kg or 40 mg/kg Eritoran or a placebo carrier. All Eritoran studies were performed in a blinded fashion. Results We observed that K/X anesthesia significantly increased the lethality of the implanted TBX in comparison to inhaled anesthetics. Although all the mice anesthetized with isoflurane and implanted with 12.5% TBX survived for 24 hours, 60% of mice anesthetized with K/X were moribund by 24 hours postimplantation. To mimic more closely the timing of lethal SIRS/MODS following polytrauma in human patients, we extended observation to 48 hours. We performed TBX dose–response studies and found that as low as 15%, 17.5%, and 20% TBX caused moribundity/mortality in 50%, 80%, and 100% mice, respectively, over a 48-hour time period. With 17.5% TBX, we tested if moribundity/mortality could be rescued by anti-inflammatory drug Eritoran, a toll-like receptor 4 antagonist. Neither 20 mg/kg nor 40 mg/kg doses of Eritoran were found to be effective in this model. Conclusions We optimized a TBX mouse model of SIRS/MODS for the purpose of evaluating novel therapeutic interventions to prevent trauma-related pathophysiologies in wounded Service Members. Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS.
General & Internal Medicine↗
Evaluation of Saccadic Component Measure on Smooth Pursuit Tests
ABSTRACT Introduction Despite the advancement of eye-tracking technology for smooth pursuit (SP) eye movement evaluation, qualitative observation offers much information that is not captured by computers; hence, both objective and qualitative information should be utilized to evaluate SP. This study examined the consistency among our clinicians when evaluating SP using normal (N), grossly normal (GN), mildly abnormal (MA), and abnormal (AB) as classifications. We then evaluated the effect of combining GN and MA into a single subclinical (SUBC) category. We also evaluated the computerized percent saccade (PS) metric by determining its sensitivity and specificity in classifying SP. Materials and Methods Retrospective horizontal and vertical SP test videos and numerical data for 70 participants were obtained from the Neuro Kinetics Neuro-Otologic Test Center and de-identified. From this, eye-tracking videos, time plots of eye-tracking positional data, and tables of SP eye-tracking performance data were generated for 0.1, 0.3, and 0.5 Hz in both horizontal and vertical planes, totaling 6 tests per subject. Three clinicians rated each subject’s SP performance as N, GN, MA, or AB for a total of 6 ratings (3 frequencies, horizontal and vertical). This process was repeated using N, SUBC, and AB as rating categories. Clinicians also provided an overall SP rating for each plane as follows: AB if the results were abnormal for 2 or more frequencies tested. Alternatively, if fewer than 2 frequencies presented with a rating of AB, then an overall rating of MA, GN, or N was determined at the respective clinician’s discretion. Results When the 3 clinicians were tasked with classifying SP videos using 4 clinical categories, fair overall agreement was demonstrated. However, when MA and GN categories were combined into an SUBC category, the overall agreement for the 3 clinicians improved slightly for both horizontal SP (HSP) and vertical SP (VSP). This pattern of agreement did not differ considerably when comparing HSP versus VSP, and good consistency and reliability was observed across clinicians. Again, inter-rater consistency was smaller for VSP versus HSP despite the reduction in clinical categories. Cut-off values were generated for the PS metric and demonstrated good specificity and sensitivity when they were exceeded for 2 or more frequencies in a particular plane when evaluating a subject’s SP test. Conclusions
General & Internal Medicine↗
Association of human T-cell leukemia virus type 1 with prevalent rheumatoid arthritis among atomic bomb survivors: A cross-sectional study
Previous studies have suggested that human T-cell leukemia virus type 1 (HTLV-1) might act as a pathogen in rheumatoid arthritis (RA), but epidemiological evidence of an association is scarce. We measured anti-HTLV-1 antibodies among Nagasaki atomic bomb survivors to determine whether HTLV-1 is related to RA and whether radiation exposure is associated with HTLV-1 and RA prevalence. This is a cross-sectional study among atomic bomb survivors who participated in biennial health examinations from 2006 to 2010. Serum levels of anti-HTLV-1 antibodies were measured using a chemiluminescent enzyme immunoassay and confirmed by Western blotting. Association between HTLV-1 and RA was analyzed by a logistic regression model. Of 2091 participants (women 61.5%; median age, 73 years), 215 (10.3%) had anti-HTLV-1 antibodies. HTLV-1 prevalence was higher among women (13.1% vs 5.8%; P<.001). Twenty-two participants (1.1%) were diagnosed with RA. HTLV-1 prevalence among RA participants was significantly higher than that among non-RA participants (27.3% vs 10.1%; P=.020). After adjustment for age, sex, and hepatitis C virus infection, HTLV-1 was significantly associated with prevalent RA (odds ratio, 2.89; 95% confidence interval, 1.06, 7.03). There was no association between radiation dose and either the prevalence of HTLV-1 or RA. This study, among a well-defined group of atomic bomb survivors, suggests that HTLV-1 is associated with RA. Abbreviations: AHS = Adult Health Study, ATL/ATLL = adult T cell leukemia/lymphoma, bioDMARDs = biological disease modifying antirheumatic drugs, CCP = cyclic citrullinated peptide, CI = confidence interval, CLEIA = chemiluminescent enzyme immunoassay, CRP = C-reactive protein, csDMARDs = conventional synthetic disease modifying antirheumatic drugs, Gy = gray, HCV = hepatitis C virus, HTLV-1 = human T-cell leukemia virus type 1, IF = immunofluorescent, RA = rheumatoid arthritis, RERF = Radiation Effects Research Foundation, RF = rheumatoid factor, SS = Sjogren syndrome.
59 BASIC BIOLOGICAL SCIENCES↗
Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status
Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock. We measured HR, SBP, and CRM in 172 human subjects (19–55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater (p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94–0.97) compared with 0.91 (0.89–0.94) for SI (p = 0.0002). Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia.
60 APPLIED LIFE SCIENCES↗
Activities and risk factors associated with fall-related injuries among US Army soldiers
Introduction Falls/near falls are the second leading cause of hospitalisation and outpatient visits among US Army soldiers. While numerous studies have evaluated fall-related or near fall-related injuries among elderly adults, few have evaluated this association among young adults. The objective of this study is to describe the characteristics and risk factors associated with fall-related or near fall-related injuries among male US Army soldiers. Methods This is a cross-sectional study of male US Army Airborne Division soldiers (n=5187). Electronic surveys captured demographic, lifestyle, physical training (PT), fitness and injury data during spring/summer of 2016. Multiple logistic regression was used to identify independent risk factors of fall-related or near fall-related injuries, adjusting for potential confounders. Results Primary findings indicated that activities and risk factors associated with fall-related or near fall-related injuries among soldiers included younger age (≤35 years), holding a job that required minimal lifting activities, slower 2-mile run times and not running during personal PT. Conclusions The findings from this study suggest that male US Army soldiers and other physically active men may benefit from (1) obtaining and/or maintaining higher aerobic endurance and muscular strength, and (2) training focused on preventing fall-related injuries during PT, road marching and sports/recreational activities. Moreover, prevention strategies and education should further target younger soldiers (≤35 years old), as younger age is not modifiable.
General & Internal Medicine↗
Drug providers’ perspectives on antibiotic misuse practices in eastern Ethiopia: a qualitative study
Objective Antibiotic misuse includes using them to treat colds and influenza, obtaining them without a prescription, not finishing the prescribed course and sharing them with others. Although drug providers are well positioned to advise clients on proper stewardship practices, antibiotic misuse continues to rise in Ethiopia. It necessitates an understanding of why drug providers failed to limit such risky behaviours. This study aimed to explore drug providers’ perspectives on antibiotic misuse practices in eastern Ethiopia. Setting The study was conducted in rural Haramaya district and Harar town, eastern Ethiopia. Design and participants An exploratory qualitative study was undertaken between March and June 2023, among the 15 drug providers. In-depth interviews were conducted using pilot-tested, semistructured questions. The interviews were transcribed verbatim, translated into English and analysed thematically. The analyses considered the entire dataset and field notes. Results The study identified self-medication pressures, non-prescribed dispensing motives, insufficient regulatory functions and a lack of specific antibiotic use policy as the key contributors to antibiotic misuse. We found previous usage experience, a desire to avoid extra costs and a lack of essential diagnostics and antibiotics in public institutions as the key drivers of non-prescribed antibiotic access from private drug suppliers. Non-prescribed antibiotic dispensing in pharmacies was driven by client satisfaction, financial gain, business survival and market competition from informal sellers. Antibiotic misuse in the setting has also been linked to traditional and ineffective dispensing audits, inadequate regulatory oversights and policy gaps. Conclusion This study highlights profits and oversimplified access to antibiotics as the main motivations for their misuse. It also identifies the traditional antibiotic dispensing audit as an inefficient regulatory operation. Hence, enforcing specific antibiotic usage policy guidance that entails an automated practice audit, a responsible office and insurance coverage for persons with financial limitations can help optimise antibiotic use while reducing resistance consequences.
General & Internal Medicine↗
Day-to-day reliability of basal heart rate and short-term and ultra short-term heart rate variability assessment by the Equivital eq02+ LifeMonitor in US Army soldiers
Introduction The present study determined the (1) day-to-day reliability of basal heart rate (HR) and HR variability (HRV) measured by the Equivital eq02+ LifeMonitor and (2) agreement of ultra short-term HRV compared with short-term HRV. Methods Twenty-three active-duty US Army Soldiers (5 females, 18 males) completed two experimental visits separated by >48 hours with restrictions consistent with basal monitoring (eg, exercise, dietary), with measurements after supine rest at minutes 20–21 (ultra short-term) and minutes 20–25 (short-term). HRV was assessed as the SD of R–R intervals (SDNN) and the square root of the mean squared differences between consecutive R–R intervals (RMSSD). Results The day-to-day reliability (intraclass correlation coefficient (ICC)) using linear-mixed model approach was good for HR (0.849, 95% CI: 0.689 to 0.933) and RMSSD (ICC: 0.823, 95% CI: 0.623 to 0.920). SDNN had moderate day-to-day reliability with greater variation (ICC: 0.689, 95% CI: 0.428 to 0.858). The reliability of RMSSD was slightly improved when considering the effect of respiration (ICC: 0.821, 95% CI: 0.672 to 0.944). There was no bias for HR measured for 1 min versus 5 min (p=0.511). For 1 min measurements versus 5 min, there was a very modest mean bias of −4 ms for SDNN and −1 ms for RMSSD (p≤0.023). Conclusion When preceded by a 20 min stabilisation period using restrictions consistent with basal monitoring and measuring respiration, military personnel can rely on the eq02+ for basal HR and RMSSD monitoring but should be more cautious using SDNN. These data also support using ultra short-term measurements when following these procedures.
General & Internal Medicine↗
A MUC 5 B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality
A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post–COVID-19 pneumonia were performed in MVP subjects. The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.
59 BASIC BIOLOGICAL SCIENCES↗
Vegetable intake and the risk of bladder cancer in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study
Although a potential inverse association between vegetable intake and bladder cancer risk has been reported, epidemiological evidence is inconsistent. This research aimed to elucidate the association between vegetable intake and bladder cancer risk by conducting a pooled analysis of data from prospective cohort studies. Vegetable intake in relation to bladder cancer risk was examined by pooling individual-level data from 13 cohort studies, comprising 3203 cases among a total of 555,685 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox proportional hazards regression models stratified by cohort for intakes of total vegetable, vegetable subtypes (i.e. non-starchy, starchy, green leafy and cruciferous vegetables) and individual vegetable types. In addition, a diet diversity score was used to assess the association of the varied types of vegetable intake on bladder cancer risk. The association between vegetable intake and bladder cancer risk differed by sex ( P -interaction = 0.011) and smoking status ( P -interaction = 0.038); therefore, analyses were stratified by sex and smoking status. With adjustment of age, sex, smoking, energy intake, ethnicity and other potential dietary factors, we found that higher intake of total and non-starchy vegetables were inversely associated with the risk of bladder cancer among women (comparing the highest with lowest intake tertile: HR = 0.79, 95% CI = 0.64–0.98, P = 0.037 for trend, HR per 1 SD increment = 0.89, 95% CI = 0.81–0.99; HR = 0.78, 95% CI = 0.63–0.97, P = 0.034 for trend, HR per 1 SD increment = 0.88, 95% CI = 0.79–0.98, respectively). However, no evidence of association was observed among men, and the intake of vegetable was not found to be associated with bladder cancer when stratified by smoking status. Moreover, we found no evidence of association for diet diversity with bladder cancer risk. Higher intakes of total and non-starchy vegetable are associated with reduced risk of bladder cancer for women. Further studies are needed to clarify whether these results reflect causal processes and potential underlying mechanisms.
59 BASIC BIOLOGICAL SCIENCES↗
Diagnosing Malaria Patients with Plasmodium falciparum and vivax Using Deep Learning for Thick Smear Images
We propose a new framework, PlasmodiumVF-Net, to analyze thick smear microscopy images for a malaria diagnosis on both image and patient-level. Our framework detects whether a patient is infected, and in case of a malarial infection, reports whether the patient is infected by Plasmodium falciparum or Plasmodium vivax. PlasmodiumVF-Net first detects candidates for Plasmodium parasites using a Mask Regional-Convolutional Neural Network (Mask R-CNN), filters out false positives using a ResNet50 classifier, and then follows a new approach to recognize parasite species based on a score obtained from the number of detected patches and their aggregated probabilities for all of the patient images. Reporting a patient-level decision is highly challenging, and therefore reported less often in the literature, due to the small size of detected parasites, the similarity to staining artifacts, the similarity of species in different development stages, and illumination or color variations on patient-level. We use a manually annotated dataset consisting of 350 patients, with about 6000 images, which we make publicly available together with this manuscript. Our framework achieves an overall accuracy above 90% on image and patient-level.
60 APPLIED LIFE SCIENCES↗
Using Ultrasound Image Augmentation and Ensemble Predictions to Prevent Machine-Learning Model Overfitting
Deep learning predictive models have the potential to simplify and automate medical imaging diagnostics by lowering the skill threshold for image interpretation. However, this requires predictive models that are generalized to handle subject variability as seen clinically. Here, we highlight methods to improve test accuracy of an image classifier model for shrapnel identification using tissue phantom image sets. Using a previously developed image classifier neural network—termed ShrapML—blind test accuracy was less than 70% and was variable depending on the training/test data setup, as determined by a leave one subject out (LOSO) holdout methodology. Introduction of affine transformations for image augmentation or MixUp methodologies to generate additional training sets improved model performance and overall accuracy improved to 75%. Further improvements were made by aggregating predictions across five LOSO holdouts. This was done by bagging confidences or predictions from all LOSOs or the top-3 LOSO confidence models for each image prediction. Top-3 LOSO confidence bagging performed best, with test accuracy improved to greater than 85% accuracy for two different blind tissue phantoms. This was confirmed by gradient-weighted class activation mapping to highlight that the image classifier was tracking shrapnel in the image sets. Overall, data augmentation and ensemble prediction approaches were suitable for creating more generalized predictive models for ultrasound image analysis, a critical step for real-time diagnostic deployment.
60 APPLIED LIFE SCIENCES↗
Development of a Colorimetric Loop-Mediated Isothermal Amplification Assay for the Detection of Trypanosoma cruzi in Low-Resource Settings
Chagas disease is an inflammatory parasitic infection caused by Trypanosoma cruzi (T. cruzi). Early diagnosis is crucial in guiding treatment and slowing disease progression; however, current diagnostic methods have insufficient detection limits and often require skilled technicians. Molecular tests, especially isothermal nucleic acid assays, are advantageous due to their excellent sensitivity, specificity, speed, and simplicity. Here, we optimized a colorimetric loop-mediated isothermal amplification (LAMP) assay for T. cruzi. We can detect as few as 2 genomic copies/reaction using three different T. cruzi strains. We examined selectivity using other parasitic protozoans and successfully detected T. cruzi DNA extracted from parasites in human whole blood down to 1.2 parasite equivalents/reaction. We also performed a blinded study using canine blood samples and established a 100% sensitivity, specificity, and accuracy for the colorimetric LAMP assay. Finally, we used a heated 3D printer bed and an insulated thermos cup to demonstrate that the LAMP incubation step could be performed with accessible, low-cost materials. Altogether, we have developed a high-performing assay for T. cruzi with a simple colorimetric output that would be ideal for rapid, low-cost screening at the point of use.
60 APPLIED LIFE SCIENCES↗