Prediction of Venous Thromboembolism in Diverse Populations Using Machine Learning and Structured Electronic Health Records.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide. Current risk assessment tools, such as the Caprini and Padua scores and Wells criteria, have limitations in their applicability and accuracy. This study aimed to develop machine learning models using structured electronic health record data to predict diagnosis and 1-year risk of VTE. METHODS: We trained and validated models on data from 159 001 participants in the Mount Sinai Data Warehouse. We then externally tested them on 401 723 participants in the UK Biobank and 123 039 participants in All of Us. All data sets contain populations of diverse ancestries and clinical histories. We used these data sets to develop small, medium, and large models with increasing features on a range of optimizing portability to maximizing performance. We make trained models publicly available in click-and-run format at https://doi.org/10.17632/tkwzysr4y6.6. RESULTS: In the holdout and external test sets, respectively, models achieved areas under the receiver operating characteristic curve of 0.80 to 0.83 and 0.72 to 0.82 for VTE diagnosis prediction and 0.76 to 0.78 and 0.64 to 0.69 for 1-year risk prediction, significantly outperforming the Padua score. Models also demonstrated robust performance across different VTE types and patient subsets, including ethnicity, age, and surgical and hospitalization status. Models identified both established and novel clinical features contributing to VTE risk, offering valuable insights into its underlying pathophysiology. CONCLUSIONS: Machine learning models using structured electronic health record data can significantly improve VTE diagnosis and 1-year risk prediction in diverse populations. Model probability scores exist on a continuum, affecting mortality risk in both healthy individuals and VTE cases. Integrating these models into electronic health record systems to generate real-time predictions may enhance VTE risk assessment, early detection, and preventative measures, ultimately reducing the morbidity and mortality associated with VTE.

Insects as Sustainable Feed: Enhancing Animal Nutrition and Reducing Livestock Environmental Impression.

Insects are emerging as a promising alternative source in animal nutrition, offering high protein content and a low environmental impression compared to traditional feed sources. This abstract explores the potential role of insects in reducing the environmental impact of livestock production. Insects such as black soldier fly larvae, mealworms, and crickets are rich in essential nutrients, including proteins, amino acids, fatty acids and so on. They can be efficiently farmed on organic waste streams, contributing to resource efficiency and waste lessening. Additionally, insect farming needs a small quantity of water, less land, and emits fewer greenhouse gases than conventional animal feed production. Despite these benefits, several challenges must be addressed to realize their potential, including regulatory approval, consumer acceptance, production scalability, and ensuring consistent nutritional quality. By overcoming these challenges through research, innovation, and policy support, insects can be integrated into mainstream animal feed systems, significantly reducing the environmental impact of livestock farming and contributing to a more sustainable agricultural future.

Integration of high-resolution optical and SAR satellite remote sensing datasets for aboveground biomass estimation in subtropical pine forest, Pakistan.

In this study, we investigate stand-alone and combined Pleiades high-resolution passive optical and ALOS PALSAR active Synthetic Aperture Radar (SAR) satellite imagery for aboveground biomass (AGB) estimation in subtropical mountainous Chir Pine (Pinus roxburghii) forest in Murree Forest Division, Punjab, Pakistan. Spectral vegetation indices (NDVI, SAVI, etc.) and sigma nought HV-polarization backscatter dB values are derived from processing optical and SAR datasets, respectively, and modeled against field-measured AGB values through various regression models (linear, nonlinear, multi-linear). For combination of multiple spectral indices, NDVI, TNDVI, and MSAVI2 performed the best with model R2/RMSE values of 0.86/47.3 tons/ha. AGB modeling with SAR sigma nought dB values gives low model R2 value of 0.39. The multi-linear combination of SAR sigma nought dB values with spectral indices exhibits more variability as compared with the combined spectral indices model. The Leave-One-Out-Cross-Validation (LOOCV) results follow closely the behavior of the model statistics. SAR data reaches AGB saturation at around 120-140 tons/ha, with the region of high sensitivity around 50-130 tons/ha; the SAR-derived AGB results show clear underestimation at higher AGB values. The models involving only spectral indices underestimate AGB at low values (< 60 tons/ha). This study presents biomass estimation maps of the Chir Pine forest in the study area and also the suitability of optical and SAR satellite imagery for estimating various biomass ranges. The results of this work can be utilized towards environmental monitoring and policy-level applications, including forest ecosystem management, environmental impact assessment, and performance-based REDD+ payment distribution.

Prospective randomized controlled pilot study on the effects of almond consumption on skin lipids and wrinkles.

OBJECTIVE: Almonds are a rich source of fatty acids and antioxidants, and their supplementation is known to significantly modulate serum lipids. The effects of almond on the skin's lipid barrier and the appearance of wrinkles have not yet been elucidated. The aim of this study was to investigate the effects of almond consumption on facial sebum production and wrinkles. METHODS: This was a prospective, investigator-blinded, randomized controlled trial in which subjects consumed 20% of their daily energy consumption in either almonds or a calorie-matched snack for 16 weeks. This study was completed at the UC Davis Dermatology clinic. Participants were a volunteer sample of generally healthy postmenopausal females with Fitzpatrick skin types 1 and 2. A facial photograph and image analysis system was used to obtain standardized photographs and information on wrinkle width and severity at 0, 8, and 16 weeks. Measurements of transepidermal water loss and sebum production were also completed at 0, 8, and 16 weeks. RESULTS: Fifty healthy postmenopausal females were recruited, 31 participants were enrolled, and 28 completed the study. Under photographic analysis, the almond group had significantly decreased wrinkle severity and width compared with the control group at 16 weeks (p < .02). Changes in skin barrier function were nonsignificant, measured by the transepidermal water loss (p = .65) between the almond and control groups relative to baseline after 16 weeks. No adverse effects were reported. CONCLUSION: Our study demonstrates that daily almond consumption may reduce wrinkle severity in postmenopausal females to potentially have natural antiaging benefits.

Cross-cultural validation of the Urdu translation of the Patient Health Questionnaire for Adolescents among children and adolescents at a Pakistani school.

OBJECTIVES: There is a high prevalence of depressive disorders among children and adolescents globally, accounting for 45% of disability-adjusted life years among 10- to 24-year-olds. Although it has been recognized as a major public health concern in Pakistan, there have been no studies exploring the development or cross-cultural validation of instruments for screening and assessing the severity of adolescent depression. Therefore, the present study was designed to validate the Urdu translation of the Patient Health Questionnaire for Adolescents (PHQ-A) among Pakistani children and adolescents. STUDY DESIGN: This is a cross-sectional study. METHODS: A total of 452 children and adolescents responded to a survey comprising demographic characteristics, the Urdu translation of PHQ-A, and the Urdu version of Strengths and Difficulties Questionnaire (SDQ). It was hypothesized that total scores on the PHQ-A would correlate significantly with the SDQ scores. Reliability analysis and exploratory factor analyses were carried out using SPSS v.20. Additional confirmatory factor analyses were conducted using the FACTOR program. RESULTS: No floor and ceiling effects were reported for PHQ-A total scores. Factor analysis confirmed good results for language interchangeability and unidimensionality among the sampled adolescents. Similarly, the findings showed good internal consistency (Cronbach's alpha 0.76), test-retest reliability (intraclass correlation coefficient = 0.61; 0.53-0.68), and concurrent validity. CONCLUSION: The Urdu translation of the PHQ-A is a valid and reliable instrument for assessing depression among Pakistani adolescents, based on the Diagnostic and Statistical Manual diagnosis criteria.

Association between maternal depression and risk of infant diarrhea: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the evidence for an association between maternal depression and the risk of diarrheal illness in infants. STUDY DESIGN: This study is a meta-analysis. METHODS: Nine databases were searched systematically for studies that investigated the risk of diarrheal illness in infants born to mothers with depression. RESULTS: Our search strategy yielded 10 studies of the association between maternal depression and the risk of diarrheal illness in infants: eight studies of postnatal depression, two studies of antenatal depression, and one study of perinatal depression. Our meta-analysis showed that infants born to mothers with postnatal depression were more likely to develop diarrheal illness (odds ratio [OR] = 1.902, 95% confidence interval [95% CI] = 1.385-2.612, P < 0.001, n = 18,585). A similar trend was noted for antenatal depression (OR = 2.703, 95% CI = 0.920-7.942, P = 0.071, n = 583). Only one study reported an association between perinatal depression and risk of diarrhea in infants (OR = 1.848, log OR = 0.614, standard error = 0.093, n = 107,587). CONCLUSIONS: Only a few studies so far have identified an association between maternal depression and risk of diarrhea in infants. The evidence available to date suggests that infants born to mothers with depression are more likely to develop diarrhea than infants whose mothers do not have depression.

Bone morphogenetic proteins differentially regulate pigmentation in human skin cells.

Bone morphogenetic proteins (BMPs) are a large family of multi-functional secreted signalling molecules. Previously BMP2/4 were shown to inhibit skin pigmentation by downregulating tyrosinase expression and activity in epidermal melanocytes. However, a possible role for other BMP family members and their antagonists in melanogenesis has not yet been explored. In this study we show that BMP4 and BMP6, from two different BMP subclasses, and their antagonists noggin and sclerostin were variably expressed in melanocytes and keratinocytes in human skin. We further examined their involvement in melanogenesis and melanin transfer using fully matched primary cultures of adult human melanocytes and keratinocytes. BMP6 markedly stimulated melanogenesis by upregulating tyrosinase expression and activity, and also stimulated the formation of filopodia and Myosin-X expression in melanocytes, which was associated with increased melanosome transfer from melanocytes to keratinocytes. BMP4, by contrast, inhibited melanin synthesis and transfer to below baseline levels. These findings were confirmed using siRNA knockdown of BMP receptors BMPR1A/1B or of Myosin-X, as well as by incubating cells with the antagonists noggin and sclerostin. While BMP6 was found to use the p38MAPK pathway to regulate melanogenesis in human melanocytes independently of the Smad pathway, p38MAPK, PI3-K and Smad pathways were all involved in BMP6-mediated melanin transfer. This suggests that pigment formation may be regulated independently of pigment transfer. These data reveal a complex involvement of regulation of different members of the BMP family, their antagonists and inhibitory Smads, in melanocytes behaviour.

Full genome sequence of a peste des petits ruminants virus (PPRV) from Ghana.

The full genome of a peste des petits ruminants virus (PPRV) isolated from a sheep lung sample collected in Ghana, Western Africa, in 2010, has been sequenced. Phylogenetic analysis demonstrated that the virus clustered within the lineage II clade while comparison of its full genome with those of other PPRV strains revealed the highest identity (96.6 %) at a nucleotide level with the PPRV strain Nigeria/76/1. This is the first full genome sequence generated for a PPRV lineage II isolated since 1976.

Multiple mediation analysis of a task-shared psychosocial intervention for perinatal anxiety: Exploratory findings from a randomized controlled trial in Pakistan.

BACKGROUND: The "Healthy Mother Healthy Baby" (HMHB) study is a phase three, single-blind randomized clinical trial conducted at Holy Family Hospital (HFH) in association with Rawalpindi Medical University (RMU). We aimed to examine the mediators of a specialized psychosocial approach based on Cognitive Behavioural Therapy principles, targeting pregnant women experiencing anxiety. The HMHB intervention was effective in treating perinatal anxiety symptoms and preventing future depressive episodes. METHODS: The trial randomized participants into two arms: the HMHB intervention or Enhanced Usual Care (EUC), following World Health Organization guidelines. The HMHB intervention comprised strategies to strengthen social support networks, improving mother-baby bonding and strategies to deal with interpersonal conflicts, economic challenges, and societal gender preferences using cognitive and behavioural techniques and culturally resonant illustrations. Participants underwent rigorous data collection at three pivotal timepoints: baseline, third trimester, and 6-weeks postnatal. The primary outcome was anxiety symptom severity scores using the Hospital Anxiety and Depression Scale (HADS) at 6-weeks post-childbirth. Four potential mediators - social support, behavioural activation, perceived stress, and pregnancy experience - were assessed in the third trimester of pregnancy. RESULTS: A total of 1200 participants were randomized to the HMHB and EUC arms. In the six-week follow-up time point, 379 participants remained in the EUC group, and 387 continued in the HMHB group. Post-intervention, HMHB participants displayed significant improvements in postnatal anxiety and depression scores. Mediation analyses revealed social support and pregnancy hassles as significant mediators of the intervention's effect on postnatal anxiety outcomes, while only social support emerged as a significant mediator for depression outcomes. CONCLUSION: The HMHB intervention showed promising results in improving anxiety and depression scores among pregnant women. Significant mediation effects suggest the importance of targeting social support and managing pregnancy-related hassles for optimal intervention effectiveness.

Prospective randomized double-blind comparative study of topical acetyl zingerone with tetrahexyldecyl ascorbate versus tetrahexyldecyl ascorbate alone on facial photoaging.

BACKGROUND: Tetrahexydecyl ascorbate (THDA) is a lipophilic precursor to ascorbic acid that may be stabilized by acetyl zingerone (AZ). Studies have shown that the topical application of THDA may have photoprotective effects. Similarly, AZ has been shown to mitigate oxidative and inflammatory stress, thereby improving the appearance of photoaging. AIMS: To examine the effects of THDA and AZ (THDA-AZ) on skin photoaging compared to THDA alone. PATIENTS/METHODS: In this double-blind, randomized controlled trial, healthy individuals aged 30 to 65 were included and 44 participants were randomized to receive either THDA-AZ (THDA 5% + AZ 1%) or THDA only (THDA 5%) for 8 weeks. Facial photographs were taken at 0, 4, and 8 weeks to analyze wrinkle severity, pigment intensity, and redness intensity. A skin colorimeter was used to assess infraorbital pigmentation and erythema. Self-perception of skin and tolerability were assessed through questionnaires. RESULTS: Average wrinkle severity was significantly decreased in the THDA-AZ group at Weeks 4 and 8 by 0.75% (p = 0.023) and 3.72% (p = 0.048), respectively, compared to the THDA group where wrinkle severity at Weeks 4 and 8 was increased by 7.88% and 4.48%, respectively. Facial pigment intensity was significantly decreased in the THDA-AZ group by 4.10% (p = 0.0002) at Week 8 compared to a 0.69% decrease in the THDA group. Facial redness intensity was decreased in the THDA-AZ group at Weeks 4 and 8 by 3.73% (p = 0.0162) and 14.25% (p = 0.045), respectively, compared to the THDA group where at Weeks 4 and 8 erythema increased by 27.5% and 8.34%, respectively. There were no significant differences in either group for infraorbital pigmentation or erythema. CONCLUSIONS: Daily use of combined THDA and AZ may improve facial wrinkle severity, pigment intensity, and erythema to a greater extent than THDA. While THDA alone increases facial wrinkle severity and erythema, the addition of AZ reduces both.

The Effectiveness of Exercise in Reducing Cardiovascular Risk Factors Among Adults: A Systematic Review and Meta-Analysis.

Cardiovascular disease (CVD) remains one of the major causes of sickness and death in the world. However, lifestyle modifications, such as exercise, can significantly reduce the risk of this disease. This study aimed to assess the effectiveness of various forms of physical activity in reducing CVD risk factors among adults. A comprehensive search of the databases PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and Excerpta Medica Database (EMBASE) databases was conducted between January 1, 2014, and May 31, 2024, as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs), cohort studies, and observational studies on the impact of aerobic, resistance, or combined training on cardiovascular risk factors in adults (≥18 years) were considered for inclusion. Data relating to primary outcomes, including stroke and myocardial infarction rates, BP, cholesterol levels, and BMI were collected. The Cochrane risk-of-bias tool and the Methodological Index for Non-Randomized Studies (MINORS) checklist were used for quality and bias assessment. Meta-analyses were performed using the RevMan software, with heterogeneity evaluated by I² statistics; 17 studies, including 11 RCTs and six cohort studies, met the inclusion criteria. There was a significant reduction in the mean systolic BP (SBP) by 3.32 mmHg [95% confidence interval (CI): 0.85-5.78 mmHg; p<0.0001] and mean diastolic BP (DBP) by 2.99 mmHg (95% CI: 2.34-3.64 mmHg; p < 0.00001) after exercise interventions. Moreover, cholesterol levels and BMI values improved with exercise. Those who exercised had a lower risk of stroke or heart attack compared with the controls [odds ratio (OR): 0.57; 95% CI: 0.28-1.14; p >0.0001], although there was substantial heterogeneity in effect size across the studies (I²â€Š= 98%). Different types of physical activity (i.e., aerobic, resistance, or combined exercise) can effectively reduce key cardiovascular risk factors, including BP, cholesterol levels, and BMI values. Regular physical activity is still regarded as the most effective preventive measure against CVD, despite inconsistencies in research findings. Future studies should aim to identify optimal exercise programs and their long-term effects on diverse populations.

Exome sequence analysis identifies rare coding variants associated with a machine learning-based marker for coronary artery disease.

Coronary artery disease (CAD) exists on a spectrum of disease represented by a combination of risk factors and pathogenic processes. An in silico score for CAD built using machine learning and clinical data in electronic health records captures disease progression, severity and underdiagnosis on this spectrum and could enhance genetic discovery efforts for CAD. Here we tested associations of rare and ultrarare coding variants with the in silico score for CAD in the UK Biobank, All of Us Research Program and BioMe Biobank. We identified associations in 17 genes; of these, 14 show at least moderate levels of prior genetic, biological and/or clinical support for CAD. We also observed an excess of ultrarare coding variants in 321 aggregated CAD genes, suggesting more ultrarare variant associations await discovery. These results expand our understanding of the genetic etiology of CAD and illustrate how digital markers can enhance genetic association investigations for complex diseases.

Severe hypertriglyceridemia: Existing and emerging therapies.

Severe hypertriglyceridemia (sHTG), defined as a triglyceride (TG) concentration ≥ 500 mg/dL (≥ 5.7 mmol/L) is an important risk factor for acute pancreatitis. Although lifestyle, some medications, and certain conditions such as diabetes may lead to HTG, sHTG results from a combination of major and minor genetic defects in proteins that regulate TG lipolysis. Familial chylomicronemia syndrome (FCS) is a rare disorder caused by complete loss of function in lipoprotein lipase (LPL) or LPL activating proteins due to two homozygous recessive traits or compound heterozygous traits. Multifactorial chylomicronemia syndrome (MCS) and sHTG are due to the accumulation of rare heterozygous variants and polygenic defects that predispose individuals to sHTG phenotypes. Until recently, treatment of sHTG focused on lifestyle interventions, control of secondary factors, and nonselective pharmacotherapies that had modest TG-lowering efficacy and no corresponding reductions in atherosclerotic cardiovascular disease events. Genetic discoveries have allowed for the development of novel pathway-specific therapeutics targeting LPL modulating proteins. New targets directed towards inhibition of apolipoprotein C-III (apoC-III), angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like protein 4 (ANGPTL4), and fibroblast growth factor-21 (FGF21) offer far more efficacy in treating the various phenotypes of sHTG and opportunities to reduce the risk of acute pancreatitis and atherosclerotic cardiovascular disease events.

Clinical Trial Design for Lipoprotein(a)-Lowering Therapies: JACC Focus Seminar 2/3.

Lipoprotein(a) [Lp(a)] is a source of residual risk in patients with atherosclerotic cardiovascular disease (ASCVD). Clinical trials of fully human monoclonal antibodies targeting proprotein convertase subtilisin kexin 9 have shown that reductions in Lp(a) concentrations may be a predictor of event reduction with this class of cholesterol-lowering therapy. With the advent of selective therapies targeting Lp(a) such as antisense oligonucleotides, small-interfering RNA-based therapies, and gene editing, lowering of Lp(a) may lead to reduction in ASCVD. The phase 3 Lp(a)HORIZON (Assessing the Impact of Lipoprotein(a) Lowering with TQJ230 on Major Cardiovascular Events in Patients With CVD) outcomes trial is currently testing the effect of pelacarsen, an antisense oligonucleotide, on ASCVD risk. Olpasiran is a small-interfering RNA that is in a phase 3 clinical trial. As these therapies enter clinical trials, challenges in trial design will have to be addressed to optimize patient selection and outcomes.

ABCA1 Deficiency: A Rare Cause of Premature Coronary Artery Disease.

ATP-binding cassette transporter A1 (ABCA1) deficiency results in very low high-density lipoprotein cholesterol levels. Complete ABCA1 deficiency, or Tangier disease, is characterized by premature atherosclerotic cardiovascular disease, yellow-orange tonsils, hepatosplenomegaly, peripheral neuropathy, and corneal opacification. Early recognition of this condition can lead to regular monitoring for atherosclerotic cardiovascular symptoms and treatment of major modifiable risk factors. (Level of Difficulty: Beginner.).

Prospective, randomized, double-blind clinical study of split-body comparison of topical hydroquinone and hexylresorcinol for skin pigment appearance.

Dyspigmentation is a common cosmetic concern in dermatology. Currently, the first line topical medication in the United States is hydroquinone. Hydroquinone use is associated with potential safety concerns including cytotoxicity to melanocytes, systemic absorption, metabolism in distant organs, and production of potentially carcinogenic metabolites. Hexylresorcinol is an ingredient that has been used in food preservation and as antiseptic has been shown to inhibit tyrosinase in vitro and has been studied as a novel skin-lightening agent. To perform a double-blind randomized split-body investigation of comparison on topical hexylresorcinol and hydroquinone on face and hands to assess for change in the appearance of skin tone and pigmentation. Thirty-two healthy female participants ages 35-65 (50.93 ± 7.37) years old with skin type I-IV were randomized to using either topical 1% hexylresorcinol or 2% hydroquinone on the left or right side of the face and corresponding hand over 12 weeks. The topical preparation was applied twice a day to assigned areas. Standardized photos were taken of the face and colorimetric measurements were taken of both sides of the forehead, cheeks and each hand at baseline (Day 0), week 4, and week 12. Of the 32 participants, 3 were lost to follow-up and the remaining were included in the final analysis. Pigmentation measured by colorimeter and clinical grading were significantly decreased at 4 and 12 weeks relative to baseline with no difference between the HR and HQ groups. No adverse effects were noted with either intervention. Hexylresorcinol 1% is well-tolerated and equivalent to hydroquinone 2% in reducing the appearance of facial and hand pigment. Further studies with an expanded population and longer time course are warranted.Registration No.: NCT04345094.

Familial Hypercholesterolemia: Challenges for a High-Risk Population: JACC Focus Seminar 1/3.

The availability of statins, ezetimibe, and PCSK9 inhibitors has significantly improved the prognosis of familial hypercholesterolemia (FH). However, a great number of individuals with FH do not achieve guideline-recommended low-density lipoprotein (LDL) cholesterol levels despite maximal lipid-lowering therapy. Novel therapies that lower LDL independent of LDL receptor activity can help mitigate atherosclerotic cardiovascular disease risk in most homozygous FH and many heterozygous FH patients. However, access to novel therapies remains limited for heterozygous FH patients with persistent elevation of LDL cholesterol despite treatment with multiple classes of cholesterol-lowering therapies. Conduction of cardiovascular outcomes clinical trials in patients with FH can be challenging because of difficulty in recruitment and long periods of follow-up. In the future, the use of validated surrogate measures of atherosclerosis may allow for clinical trials with fewer study participants and shorter duration, thereby expediting access to novel treatments for patients with FH.

Viewing of clinical cases on social media by dentists: A cause of motivation or dissatisfaction?

Objective: To evaluate the thoughts and feelings of dentists viewing posted clinical cases (PCCs) on various social media (SM) platforms. Methods: A questionnaire was developed, validated and its reliability was established. It was distributed (in 2022) to 355 dentists who had graduated at least 2 years prior. It had three sections consisting of 20 items pertaining to general information, SM usage, and feelings. Descriptive data were reported using percentages. The chi-squared test was used for inferential analysis. P ≤ 0.05 was considered statistically significant. Results: The response rate was 92%. The majority of respondents were non-post-graduates (63%), and aged ≤40 years (90%) with clinical experience <5 years (41%). Dentists with the most clinical experience (>15 years) shared their clinical work significantly more than their counterparts (p < 0.05). Most of the dentists did not feel motivated after viewing the PCCs (41%), especially those aged >40 years (p = 0.037), and thought that viewing the PCCs was the reason for personal dissatisfaction (50%). They had a belief that they possess skills (36%) and knowledge (42%), but not the necessary equipment to replicate the PCCs (39%). Conclusions: The majority of dentists felt that viewing the PCCs on SM can cause personal dissatisfaction and lack of motivation. They had a belief that they possess the skills and knowledge to replicate the PCCs, but lack equipment. Investing resources in clinical workshops, mentorship, and the procurement of modern equipment early in the career of dentists may improve their mental well-being, satisfaction, and quality of treatment delivered to patients.

Clinical Trial Design for Triglyceride-Rich Lipoprotein-Lowering Therapies: JACC Focus Seminar 3/3.

Triglyceride-rich lipoproteins (TRLs) are a source of residual risk in patients with atherosclerotic cardiovascular disease, and are indirectly correlated with triglyceride (TG) levels. Previous clinical trials studying TG-lowering therapies have either failed to reduce major adverse cardiovascular events or shown no linkage of TG reduction with event reduction, particularly when these agents were tested on a background of statin therapy. Limitations in trial design may explain this lack of efficacy. With the advent of new RNA-silencing therapies in the TG metabolism pathway, there is renewed focus on reducing TRLs for major adverse cardiovascular event reduction. In this context, the pathophysiology of TRLs, pharmacological effects of TRL-lowering therapies, and optimal design of cardiovascular outcomes trials are major considerations.