Sample entropy correlates with intraventricular hemorrhage and mortality in premature infants early in life.

BACKGROUND: Mortality and intraventricular hemorrhage (IVH) are common adverse outcomes in preterm infants and are challenging to predict clinically. Sample entropy (SE), a measure of heart rate variability (HRV), has shown predictive power for sepsis and other morbidities in neonates. We evaluated associations between SE and mortality and IVH in the first week of life. METHODS: Participants were 389 infants born before 32 weeks of gestation for whom bedside monitor data were available. A total of 29 infants had IVH grade 3 or 4 and 31 infants died within 2 weeks of life. SE was calculated with the PhysioNet open-source benchmark. Logistic regressions assessed associations between SE and IVH and/or mortality with and without common clinical covariates over various hour of life (HOL) censor points. RESULTS: Lower SE was associated with mortality by 4 HOL, but higher SE was very strongly associated with IVH and mortality at 24-96 HOL. Bootstrap testing confirmed SE significantly improved prediction using clinical variables at 96 HOL. CONCLUSION: SE is a significant predictor of IVH and mortality in premature infants. Given IVH typically occurs in the first 24-72 HOL, affected infants may initially have low SE followed by a sustained period of high SE. IMPACT: SE correlates with IVH and mortality in preterm infants early in life. SE combined with clinical factors yielded ROC AUCs well above 0.8 and significantly outperformed the clinical model at 96 h of life. Previous studies had not shown predictive power over clinical models. First study using the PhysioNet Cardiovascular Toolbox benchmark in young infants. Relative to the generally accepted timing of IVH in premature infants, we saw lower SE before or around the time of hemorrhage and a sustained period of higher SE after. Higher SE after acute events has not been reported previously.

Anterolateral congenital diaphragmatic hernia with omphalocele: a case report and literature review.

The combination of congenital diaphragmatic hernia (CDH) and omphalocele is quite rare but can be seen in several syndromes. We report on a female newborn with this combination that had not been diagnosed prenatally. The patient suffered respiratory failure that persisted despite intensive care support, suggesting severe secondary pulmonary hypoplasia. Autopsy revealed the combination of an anterolateral CDH and omphalocele in the absence of other anomalies. We believe this to be the first such case to be reported in the literature.

Improvements in Depression Outcomes Following a Digital Cognitive Behavioral Therapy Intervention in a Polychronic Population: Retrospective Study.

BACKGROUND: Digital mental health interventions have shown promise in reducing barriers to effective care for depression. Depression and related mental disorders are known to be highly comorbid with common chronic physical conditions, such as obesity and type 2 diabetes. While some research has explored the interaction dynamics of treating populations living with both mental and physical disorders, very little is known about such dynamics in digital care. OBJECTIVE: We aimed to examine the effectiveness of a 12-week, therapist-supported, app-based cognitive behavioral therapy program in improving symptoms of depression and anxiety. The studied population included adults with a heavy burden of chronic physical disease, including obesity and type 2 diabetes. METHODS: A total of 1512 participants with at least moderate depression were enrolled. The treatment cohort consisted of 831 (54.96%) participants who completed a follow-up assessment. The program included structured lessons and tools (ie, exercises and practices) and offered one-on-one weekly video counseling sessions with a licensed therapist for 12 weeks and monthly sessions thereafter. The clinically validated 8-item Patient Health Questionnaire (PHQ-8) and the 7-item Generalized Anxiety Disorder scale (GAD-7) were used to assess depression and anxiety, respectively. Linear mixed-effects modeling was employed to examine changes in depression and anxiety over time. Given correlation among various measures of program usage, a composite variable for depth of usage was used to analyze the correlation between usage and changes in depressive symptoms. Body weight changes from baseline were assessed primarily with digitally connected scales. RESULTS: Out of 831 participants in the treatment cohort, 74.5% (n=619) showed a clinically significant reduction in depressive symptom severity after 12 weeks, where follow-up PHQ-8 scores had shifted downward by at least one diagnostic category. In total, 67.5% (n=561) of the participants showed a reliable improvement in PHQ-8 scores as measured by the reliable change index. There was an average reduction of 5.9 (SD 5.2) points (P<.001) between baseline and follow-up. Greater program usage was correlated with greater likelihood of reliable improvement in depressive symptoms (odds ratio 1.3, 95% CI 1.1-1.5; P=.002). An exploratory analysis of body weight changes with a multilevel, mixed-effect model suggested that reliable improvement in depressive symptoms at follow-up was associated with significantly greater weight loss at 9 months (ß=-1.11, P=.002). CONCLUSIONS: The results provide further support that digital interventions can support clinically meaningful improvements in depression. Some form of synergy in treatment of comorbid depression and obesity or diabetes could be studied in future research. The study was limited by postintervention participant attrition as well as the retrospective observational study design.

HIV and placental infection modulate the appearance of drug-resistant Plasmodium falciparum in pregnant women who receive intermittent preventive treatment.

BACKGROUND: Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections. METHODS: SP resistance alleles were determined in peripheral (n = 125) and placental (n = 145) P. falciparum isolates obtained from pregnant women enrolled in a randomized, placebo-controlled trial of IPTp in Manhiça, Mozambique. RESULTS: Prevalence of quintuple mutant infections was 12% (23 of 185 isolates) in pregnant women who received placebo and 24% (20 of 85 isolates) in those who received SP (P = .031). When the last IPTp dose was administered at late pregnancy, mutant infections at delivery were more prevalent in placental samples (7 [23%] of 30, samples) than in peripheral blood samples (2 [7%] of 30 samples; P = .025), more prevalent in women who received IPTp-SP than in those who received placebo (odds ratio [OR], 8.13; 95% confidence interval [CI], 1.69-39.08), and more prevalent in HIV-positive women than in HIV-negative women (OR, 5.17; 95% CI, 1.23-21.66). No association was found between mutant infections and increased parasite density or malaria-related morbidity in mothers and children. CONCLUSIONS: IPTp with SP increases the prevalence of resistance markers in the placenta and in HIV-infected women at delivery, which suggests that host immunity is key for the clearance of drug-resistant infections. However, this effect of IPTp is limited to the period when blood levels of SP are likely to be significant and does not translate into more-severe infections or adverse clinical outcomes.

Improved Glycemic Control With a Digital Health Intervention in Adults With Type 2 Diabetes: Retrospective Study.

BACKGROUND: Traditional lifestyle interventions have shown limited success in improving diabetes-related outcomes. Digital interventions with continuously available support and personalized educational content may offer unique advantages for self-management and glycemic control. OBJECTIVE: In this study, we evaluated changes in glycemic control among participants with type 2 diabetes who enrolled in a digital diabetes management program. METHODS: The study employed a single-arm, retrospective design. A total of 950 participants with a hemoglobin A1c (HbA1c) baseline value of at least 7.0% enrolled in the Vida Health Diabetes Management Program. The intervention included one-to-one remote sessions with a Vida provider and structured lessons and tools related to diabetes management. HbA1c was the primary outcome measure. Of the 950 participants, 258 (27.2%) had a follow-up HbA1c completed at least 90 days from program start. Paired t tests were used to evaluate changes in HbA1c between baseline and follow-up. Additionally, a cluster-robust multiple regression analysis was employed to evaluate the relationship between high and low program usage and HbA1c change. A repeated measures analysis of variance was used to evaluate the difference in HbA1c as a function of the measurement period (ie, pre-Vida enrollment, baseline, and postenrollment follow-up). RESULTS: We observed a significant reduction in HbA1c of -0.81 points between baseline (mean 8.68, SD 1.7) and follow-up (mean 7.88, SD 1.46; t257=7.71; P<.001). Among participants considered high risk (baseline HbA1c≥8), there was an average reduction of -1.44 points between baseline (mean 9.73, SD 1.68) and follow-up (mean 8.29, SD 1.64; t139=9.14; P<.001). Additionally, average follow-up HbA1c (mean 7.82, SD 1.41) was significantly lower than pre-enrollment HbA1c (mean 8.12, SD 1.46; F2, 210=22.90; P<.001) There was also significant effect of program usage on HbA1c change (ß=-.60; P<.001) such that high usage was associated with a greater decrease in HbA1c (mean -1.02, SD 1.60) compared to low usage (mean -.61, SD 1.72). CONCLUSIONS: The present study revealed clinically meaningful improvements in glycemic control among participants enrolled in a digital diabetes management intervention. Higher program usage was associated with greater improvements in HbA1c. The findings of the present study suggest that a digital health intervention may represent an accessible, scalable, and effective solution to diabetes management and improved HbA1c. The study was limited by a nonrandomized, observational design and limited postenrollment follow-up data.

Comparison of single-copy and multicopy real-time PCR targets for detection of Mycobacterium tuberculosis in paraffin-embedded tissue.

Real-time PCR can rapidly identify Mycobacterium tuberculosis in paraffin-embedded tissue in the absence of microbiological culture. In a comparison of single-copy and multicopy PCR targets in 70 tissue samples, the sensitivities were 26% and 54%, respectively, with 100% specificity. Sensitivity was 75% for newer samples and was not decreased for acid-fast bacillus (AFB) stain-negative specimens.

CRE recombinase-based positive-negative selection systems for genetic manipulation in Trypanosoma brucei.

The limited repertoire of drug-resistance markers imposes a serious obstacle to genetic manipulation of Trypanosoma brucei. Here we describe experiments with a fusion protein that allows positive selection for genome integration followed by CRE recombinase-mediated excision of the marker cassette that can be selected by ganciclovir, although the excision event is so efficient that selection is not strictly necessary. We describe two variants of the tetracycline-inducible pLEW100-based CRE-expression vector that reduced its toxicity when stably integrated into the genome, and we demonstrate that transient transfection of circular pLEW100-CRE is highly efficient at catalyzing marker excision. We used this approach to delete the last two enzymes of the pyrimidine synthesis pathway, creating a cell line that is resistant to fluoroorotic acid, which would allow the same enzymes (PYR6-5) to be used as an alternative negative selectable marker.