Adaptive Universal Principles for Real-world Observational Studies (AUPROS): an approach to designing real-world observational studies for clinical, epidemiologic, and precision oncology research.

The field of precision oncology has witnessed several advances that stimulated the development of new clinical trial designs and the emergence of real-world data (RWD) as an important resource for evidence generation in healthcare decision-making. Here, we highlight our experience with an innovative approach to a set of Adaptive, Universal Principles for Real-world Observational Studies (AUPROS). To demonstrate the utility of these principles, we used a mixed-methods approach to assess three studies that follow AUPROS at Princess Margaret Cancer Centre: (1) Molecular Epidemiology of ThorAcic Lesions (METAL), (2) Translational Head And NecK Study (THANKS), and (3) CAnadian CAncers With Rare Molecular Alterations (CARMA; NCT04151342).

Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Operative Repair of Hamstring Injuries From the Jackling Position in Rugby.

Background: The jackling position within rugby has not been previously described as a mechanism for proximal hamstring injuries.

Hypothesis: Acute surgical repair of proximal hamstring avulsion injuries sustained from the jackling contact position enables a return to a previous level of sporting activity with low risk of recurrence.

Study Design: Case series; Level of evidence, 4.

Age-related factors associated with intention to initiate pre-exposure prophylaxis among cisgender women in Washington D.C.

Background: Pre-exposure prophylaxis (PrEP) utilization among cisgender women (subsequently 'women') is low across age groups, relative to their risk of HIV acquisition. We hypothesize that age-related differences in psychosocial factors also influence women's intention to initiate oral PrEP in Washington, D.C.

Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study.

Implementation of an Educational Intervention to Improve HIV Pre-Exposure Prophylaxis Services for Women in an Urban Sexual Health Clinic.

To test the hypothesis that implementation of a multicomponent, educational HIV pre-exposure prophylaxis (PrEP) intervention to promote universal PrEP services for cisgender women (subsequently "women") in sexual and reproductive health centers would improve the proportion of women screened, offered, and prescribed PrEP, we implemented a multicomponent, educational intervention in a Washington D.C. Department of Health-sponsored sexual health clinic.

Intention to Initiate HIV Pre-exposure Prophylaxis Among Cisgender Women in a High HIV Prevalence U.S. City.

Objective: Our objective was to identify the individual, interpersonal, community, health-system, and structural factors that influence HIV pre-exposure prophylaxis (PrEP) initiation among cisgender women seeking sexual and reproductive health care in a high HIV prevalence community to inform future clinic-based PrEP interventions.

Methods: We collected anonymous, tablet-based questionnaires from a convenience sample of cisgender women in family planning and sexual health clinics in the District of Columbia. The survey used the lens of the socio-ecological model to measure individual, interpersonal, community, institutional, and structural factors surrounding intention to initiate PrEP.

Lipoprotein Apheresis: Current Recommendations for Treating Familial Hypercholesterolemia and Elevated Lipoprotein(a).

Purpose Of Review: Familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) are relatively common disorders, posing a significant health burden due to increased risk of atherosclerotic cardiovascular disease (ASCVD). Development of electronic health record-based strategies with a linkage to the genetic test results has increased awareness, detection, and control of heritable lipid disorders. This review attempts to critically examine available data to provide a summary of the current evidence for lipoprotein apheresis in FH and elevated lipoprotein(a) (Lp(a)).

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry.

Understanding Retention in the HIV Pre-Exposure Prophylaxis Cascade Among Cisgender Women.

HIV remains a significant public health concern in the United States, with 34,800 new cases diagnosed in 2019; of those, 18% were among women. Oral pre-exposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine is effective and safe, reducing HIV transmission by up to 92% in women. Though studies demonstrate low rates of PrEP adherence among cisgender women prescribed oral PrEP, little is known about the factors that shape PrEP continuation among them.

Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial.

Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations (n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations (n = 19).

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.

Background: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.

Methods: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD).

London International Consensus and Delphi study on hamstring injuries part 1: classification.

Muscle injury classification systems for hamstring injuries have evolved to use anatomy and imaging information to aid management and prognosis. However, classification systems lack reliability and validity data and are not specific to individual hamstring muscles, potentially missing parameters vital for sport-specific and activity-specific decision making. A narrative evidence review was conducted followed by a modified Delphi study to build an international consensus on best-practice decision-making for the classification of hamstring injuries.

London International Consensus and Delphi study on hamstring injuries part 2: operative management.

The key indications for surgical repair of hamstring injuries (HSIs) remain unclear in the literature due to a lack of high-level evidence and expert knowledge. The 2020 London International Hamstring Consensus meeting aimed to highlight clear surgical indications and to create a foundation for future research. A literature review was conducted followed by a modified Delphi process, with an international expert panel.

London International Consensus and Delphi study on hamstring injuries part 3: rehabilitation, running and return to sport.

Hamstring injuries (HSIs) are the most common athletic injury in running and pivoting sports, but despite large amounts of research, injury rates have not declined in the last 2 decades. HSI often recur and many areas are lacking evidence and guidance for optimal rehabilitation. This study aimed to develop an international expert consensus for the management of HSI.

Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer.

Objectives: This real-world analysis describes treatment patterns, sequencing and clinical effectiveness, toxicities, and health utility outcomes in advanced-stage, incurable ALK-positive NSCLC patients across five different ALK-TKIs.

Materials And Methods: Clinicodemographic, treatment, and toxicity data were collected retrospectively in patients with advanced-stage ALK-positive NSCLC at Princess Margaret Cancer Centre. Patient-reported symptoms, toxicities, and health utilities were collected prospectively.

Relation of red blood cell distribution width to risk of major adverse cardiovascular events, death, and effect of alirocumab after acute coronary syndromes.

Elevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment. This post hoc analysis determined whether RDW independently predicts risk of MACE and death in patients after recent ACS, whether RDW influences MACE reduction with alirocumab, and whether alirocumab treatment affects RDW.