Diagnostics for the Real World (United States)

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality globally. Low-density lipoprotein cholesterol is a causal risk factor for atherosclerotic cardiovascular disease, with multiple classes of cholesterol-lowering therapies effective at reducing atherosclerotic cardiovascular disease risk. Despite robust efficacy data from randomized trials, real-world implementation of guideline-recommended lipid-lowering therapies is suboptimal. Barriers to the implementation of guideline lipid-lowering therapy recommendations exist at the healthcare systems level, the medical therapy level, and the patient level. A combination of strategies, including the incorporation of quality improvement and cost-effectiveness analysis among payers, pharmacist-based educational initiatives, digital health tools directed towards patients, the simplification of drug regimens via polypill, and emerging novel therapies, including PCSK9 gene silencing and editing technologies, may bridge these implementation gaps. This review highlights challenges and solutions to alleviating barriers to optimal implementation of guideline-recommended lipid-lowering therapies.

Background/Objectives: Geographical variations in outcomes and oral anticoagulant (OAC) initiation among patients with nonvalvular atrial fibrillation (NVAF) in the United States (US) have been characterized; however, regional effects on OAC persistence are unknown. The study described variation in persistence with OACs among patients with NVAF across different US regions. Methods: The Komodo Healthcare Map was used to evaluate adult patients with NVAF, elevated stroke risk, and ≥1 pharmacy claim for an OAC between 1 January 2015 and 31 August 2022. Patients initiating treatment with an OAC (treatment-naïve) and having ≥12 months continuous enrollment were included. Persistence rates were assessed at 6, 9, 12 and 18 months among OAC- and direct OAC (DOAC)-naïve patients by 3-digit zip codes. Results: Of the 260,001 (Northeast = 72,507, Midwest = 59,979, South = 83,880, West = 42,778, Other/Unknown = 857) OAC-naïve patients identified, 82.2% were DOAC-naïve while 17.8% initiated warfarin. Mean follow-up time was 1101 (median = 964) and 1073 days (median = 938) in OAC and DOAC cohorts, respectively, while mean time to discontinuation was 342 (median = 190) and 329 days (median = 181), respectively. At 12 months, persistence rates ranged from 40.3% to 78.8% for OAC-naïve patients and 40.6% to 81.4% for DOAC-naïve patients. Average OAC and DOAC 12-month persistence rates were highest in the Northeast (63.5% and 63.7%, respectively) and lowest in the South (57.1% and 56.9%, respectively). Conclusions: Variations in 12-month persistence were consistent with existing evidence on geographic variation in NVAF-related disease burden and treatment initiation. Understanding geographic trends in prescribing patterns may provide insights into differences in treatment persistence that are relevant for clinicians seeking to address real-world barriers to care.

BackgroundReal-world first-line maintenance (1LM) treatment data are limited for advanced/metastatic non-small cell lung cancer (a/mNSCLC).Materials and MethodsIn this electronic health record-derived, deidentified database study, eligible patients (≥18 years; diagnosed with stage III/IV non-small cell lung cancer [June 1, 2017-September 30, 2021]) initiated pembrolizumab-based 1LM after 4-6 cycles of first-line (1L) platinum-based chemotherapy-pembrolizumab ± pemetrexed. Study outcomes were real-world time to next treatment or death (rwTTNTD), overall survival (rwOS), and predictors of outcomes.ResultsOf 1944 patients analyzed (median follow-up, 12.2 months), 51.9% received 1LM pembrolizumab-pemetrexed and 48.1% pembrolizumab monotherapy. Median rwTTNTD and rwOS were 9.2 (95% CI: 8.5-9.8) and 18.7 (95% CI: 17.7-20.3) months, respectively. In multivariable analyses, factors significantly associated with shorter rwTTNTD included 5%-<10% (hazard ratio [HR], 1.34; 95% CI: 1.17-1.54) or ≥10% (HR, 1.69; 95% CI: 1.42-2.01) weight loss during 1L versus 0% or <5% weight loss. Programmed death-ligand 1 (PD-L1) expression 1%–49% (HR, 0.81; 95% CI: 0.71-0.93) or ≥50% (HR, 0.55; 95% CI: 0.47-0.64) and female sex (HR, 0.85; 95% CI: 0.75-0.95) were significantly associated with longer rwTTNTD. These variables were also significantly associated with shorter (weight loss 5%-<10%: HR, 1.52; 95% CI: 1.30-1.77; ≥10% HR, 2.06; 95% CI: 1.71-2.48) and longer rwOS (PD-L1 expression: 1%-49% HR, 0.84; 95% CI: 0.72-0.98; ≥ 50% HR, 0.57; 95% CI: 0.48-0.68; female sex: HR, 0.81; 95% CI: 0.71-0.92).ConclusionsPredictors of real-world clinical outcomes included 1L treatment, weight loss, PD-L1 status, and sex. Poor outcomes persisted despite immunotherapy-based 1LM availability, revealing an unmet need in this population.

We agree with the commentary that distinguishing between incident and prevalent patients with CeD is important for understanding the disease’s economic implications. However, the limited timeframe of the available data restricts our ability to accurately identify adult CeD patients who are genuinely newly diagnosed, since most individuals with CeD are diagnosed during childhood or adolescence. The available observation period for patients with CeD is not long enough to follow patients from childhood diagnosis until adulthood. Thus, there is a risk of misclassifying incident patients as prevalent cases, but it should be acceptable regarding the overall evaluation, since the probability of incident patients at older age groups is lower.Given our interest in incident patients, we are currently preparing another publication focused specifically on newly diagnosed children with CeD.

Key digested message This article explores the role of intuition in judgement and decision-making in assessment and selection and proposes that the shift towards statistically-driven approaches has led to the dismissal of intuition with negative consequences.

Influenza vaccine viruses grown in eggs may acquire egg-adaptive mutations that may reduce antigenic similarity between vaccine and circulating influenza viruses and decrease vaccine effectiveness. We compared cell- and egg-based quadrivalent influenza vaccines (QIVc and QIVe, respectively) for preventing test-confirmed influenza over 3 US influenza seasons (2017-2020). Using a retrospective test-negative design, we estimated the relative vaccine effectiveness (rVE) of QIVc vs QIVe among individuals aged 4 to 64 years who had an acute respiratory or febrile illness and were tested for influenza in routine outpatient care. Exposure, outcome, and covariate data were obtained from electronic health records linked to pharmacy and medical claims. Season-specific rVE was estimated by comparing the odds of testing positive for influenza among QIVc vs QIVe recipients. Models were adjusted for age, sex, geographic region, influenza test date, and additional unbalanced covariates. A doubly robust approach was used combining inverse probability of treatment weights with multivariable regression. The study included 31 824, 33 388, and 34 398 patients in the 2017-2018, 2018-2019, and 2019-2020 seasons, respectively; ∼10% received QIVc and ∼90% received QIVe. QIVc demonstrated superior effectiveness vs QIVe in prevention of test-confirmed influenza: rVEs were 14.8% (95% CI, 7.0%-22.0%) in 2017-2018, 12.5% (95% CI, 4.7%-19.6%) in 2018-2019, and 10.0% (95% CI, 2.7%-16.7%) in 2019-2020. This study demonstrated consistently superior effectiveness of QIVc vs QIVe in preventing test-confirmed influenza over 3 seasons characterized by different circulating viruses and degrees of egg adaptation.

The article aims to offer the contribution of a medievalist to an interdisciplinary reflection on memetics. First, memes will be identified as meta-sources, i.e. configurations that make use of new digital practices and languages. Focusing on those memes with connections to medieval history, the contribution will investigate the possible changes brought to the historian's craft by their communicative and didactic use.