Predicting cardiovascular disease risk using photoplethysmography and deep learning.

Cardiovascular diseases (CVDs) are responsible for a large proportion of premature deaths in low- and middle-income countries. Early CVD detection and intervention is critical in these populations, yet many existing CVD risk scores require a physical examination or lab measurements, which can be challenging in such health systems due to limited accessibility. We investigated the potential to use photoplethysmography (PPG), a sensing technology available on most smartphones that can potentially enable large-scale screening at low cost, for CVD risk prediction. We developed a deep learning PPG-based CVD risk score (DLS) to predict the probability of having major adverse cardiovascular events (MACE: non-fatal myocardial infarction, stroke, and cardiovascular death) within ten years, given only age, sex, smoking status and PPG as predictors. We compare the DLS with the office-based refit-WHO score, which adopts the shared predictors from WHO and Globorisk scores (age, sex, smoking status, height, weight and systolic blood pressure) but refitted on the UK Biobank (UKB) cohort. All models were trained on a development dataset (141,509 participants) and evaluated on a geographically separate test (54,856 participants) dataset, both from UKB. DLS's C-statistic (71.1%, 95% CI 69.9-72.4) is non-inferior to office-based refit-WHO score (70.9%, 95% CI 69.7-72.2; non-inferiority margin of 2.5%, p<0.01) in the test dataset. The calibration of the DLS is satisfactory, with a 1.8% mean absolute calibration error. Adding DLS features to the office-based score increases the C-statistic by 1.0% (95% CI 0.6-1.4). DLS predicts ten-year MACE risk comparable with the office-based refit-WHO score. Interpretability analyses suggest that the DLS-extracted features are related to PPG waveform morphology and are independent of heart rate. Our study provides a proof-of-concept and suggests the potential of a PPG-based approach strategies for community-based primary prevention in resource-limited regions.

The methylome and cell-free DNA: current applications in medicine and pediatric disease.

DNA methylation is an epigenetic mechanism that contributes to cell regulation and development, and different methylation patterns allow for the identification of cell and tissue type. Cell-free DNA (cfDNA) is composed of small circulating fragments of DNA found in plasma and urine. Total cfDNA levels correlate with the presence of inflammation and tissue injury in a variety of disease states. Unfortunately, the utility of cfDNA is limited by its lack of tissue or cell-type specificity. However, methylome analysis of cfDNA allows the identification of the tissue or cell type from which cfDNA originated. Thus, methylation patterns in cfDNA from tissues isolated from direct study may provide windows into health and disease states, thereby serving as a "liquid biopsy". This review will discuss methylation and its role in establishing cellular identity, cfDNA as a biomarker and its pathophysiologic role in the inflammatory process, and the ways cfDNA and methylomics can be jointly applied in medicine. IMPACT: Cell-free DNA (cfDNA) is increasingly being used as a noninvasive diagnostic and disease-monitoring tool in pediatric medicine. However, the lack of specificity of cfDNA limits its utility. Identification of cell type-specific methylation signatures can help overcome the limited specificity of cfDNA. As knowledge of the cfDNA methylome improves, cfDNA will be more broadly applied in medicine, such that clinicians will need to understand the methods and applications of its use.

Virtual Reality after Surgery-A Method to Decrease Pain After Surgery in Pediatric Patients.

BACKGROUND: Virtual Reality (VR) is used as an effective tool for distraction and as an adjunct for pain management. This study was conducted to compare VR to standard iPad use after surgery and examine its effect on pain score and opioid consumption. METHODS: This was a randomized controlled study, with stratification by surgery type, age group (7-12yo, 13-18yo) and gender. Pain and anxiety were assessed with validated scales (STAI, FACES, VAS, FLACC) and outcomes were compared between each group. RESULTS: 50 of the 106 enrolled patients used the VR device. After adjusting for age, gender, and STAI, patients had a decreased FLACC score while using the VR device compared to the iPad group (odds ratio 2.95, P = .021). The younger patients were found to have lower FLACC scores while using the VR device (odds ratio 1.15, p=0.044); this finding was most significant when patients used the VR device for 20-30 minutes (odds ratio 1.67, P = .0003). Additionally, after adjusting for treatment group, gender, and STAI, the younger patients had higher odds of withdrawal or exclusion from the study (odds ratio 1.18, P = .021). No significant difference in opioid consumption between the groups was found. DISCUSSION: Virtual reality was well tolerated and more effective in decreasing pain during the immediate postoperative period than iPad use. Despite a slightly higher withdrawal rate, younger patients benefited more from the intervention.

Dental disease patterns in methamphetamine users: Findings in a large urban sample.

BACKGROUND: The authors used a large community sample of methamphetamine (MA) users to verify the patterns and severity of dental disease and establish a hierarchy of caries susceptibility by tooth type and tooth surface. METHODS: Using a stratified sampling approach, 571 MA users received comprehensive oral examinations and psychosocial assessments. Three calibrated dentists characterized dental and periodontal disease by using National Health and Nutrition Examination Survey protocols. The authors also collected data on substance use history and other attributes linked to dental disease. RESULTS: On all dental outcome measures, MA users evidenced high dental and periodontal disease, with older (≥ 30 years) and moderate or heavy MA users disproportionately affected. Women had higher rates of tooth loss and caries, as well as a greater prevalence of anterior caries. Current cigarette smokers were more likely to manifest 5 or more anterior surfaces with untreated caries and 3 or more teeth with root caries. Nearly 3% were edentulous, and a significant percentage (40%) indicated embarrassment with their dental appearance. CONCLUSIONS: MA users have high rates of dental and periodontal disease and manifest a dose-response relationship, with greater levels of MA use associated with higher rates of dental disease. Women and current cigarette smokers are affected disproportionately. The intraoral patterns and hierarchy of caries susceptibility in MA users are distinctive. PRACTICAL IMPLICATIONS: The prevalence and patterns of dental and periodontal disease could be used to alert dentists to possible covert MA use and to plan treatment. Concerns about dental appearance have potential as triggers for behavioral interventions.

Utility of a salivary biosensor for objective assessment of surgery-related stress.

PURPOSE: To evaluate the clinical utility of a salivary α-amylase (sAA) biosensor for assessing oral surgery-related stress responses and the differential effect of the personality trait of pain catastrophizing. PATIENTS AND METHODS: A prospective cohort study was conducted in 76 healthy subjects who underwent elective removal of their third molars. Along with subjects' self-reports of anxiety and pain, biosensor-facilitated measurements of sAA levels were obtained at multiple time points during the preoperative consult, surgery, and postsurgical follow-up visits. In addition, subjects completed the Pain Catastrophizing Scale at baseline. Mixed-effect regression models examined changes in sAA levels and self-report ratings within and across visits and the contribution of pain catastrophizing. RESULTS: The sAA levels were lower during surgery and postsurgical follow-up compared with the consult visit (P < .01). The sAA levels decreased during the surgery visit (P < .05) and did not change during the consult or follow-up visits. Individuals who reported greater helplessness to pain manifested higher sAA levels during the surgery visit (P < .05). Self-reported anxiety ratings were highest during the surgery visit, and pain ratings were highest during the follow-up visit. CONCLUSIONS: The sAA levels did not show the predicted increases during the surgery visit compared with the consult and postsurgical follow-up visits or increases during the surgery visit. However, individuals who reported responding to pain with helplessness had higher sAA levels in anticipation of surgery, providing proof of concept for the value of point-of-care assessments of surgery-induced stresses and the differential effect of personality traits.