Evaluating Cardiac Lead Safety Using Observational, Real-World Data: EP PASSION Proof-of-Concept Study.

BACKGROUND: Traditional post-approval study (PAS) designs have been accepted by regulatory authorities to fulfill post-marketing requirements for cardiac leads but they have several limitations. OBJECTIVES: The authors conducted a proof-of-concept study of alternative methods that utilize real-world data (RWD) to evaluate lead safety in large patient populations. METHODS: Abbott patient device databases were linked with Medicare Fee-For-Service (FFS) claims to identify lead complications among patients implanted with Abbott Optisure™ lead. A 1:1 comparison between the PAS method and RWD method of detecting mechanical lead-related complication events was conducted in 444 PAS subjects who were enrolled in Medicare FFS. Agreement between methods was evaluated using McNemar's test and Cohen's kappa. Survival free from complications at 3 years was compared between the PAS and RWD cohorts using an equivalence acceptance criterion of ±2.5%. RESULTS: There were 1,171 PAS patients and 5,804 Medicare FFS patients who received an Optisure™ lead between August 27, 2014 - June 14, 2016. Patients were followed through December 31, 2018. Complete agreement was found between PAS-reported and claims-detected complications (McNemar's p-value=1.00, Cohen's Kappa = 1.0). Survival free from complications at 3 years using the RWD method was 98.4% (95% CL: 98.0%-98.7%), which was within the acceptable range of the PAS 98.4% (95% CL: 97.6%-99.0%). CONCLUSION: These results show a close agreement between RWD-detected and PAS-reported lead complication rates, which highlight the potential benefits of RWD-based methods to enhance the generation of clinical evidence for lead safety.

A Randomized Controlled Trial of the Korean Version of the Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS®-YA-K) With Autism Spectrum Disorder: A Pilot Study.

Evidence-based social skills interventions for young adults are limited, despite social difficulties in autism spectrum disorder (ASD) persisting after transition to adulthood. The Program for the Education and Enrichment of Relational Skills for Young Adults (PEERS®-YA) is an evidence-based intervention found to be effective in improving relational skills in young adults with ASD. To translate the original American version of the PEERS®-YA treatment manual into Korean, intensive interviews were performed. Based on results from interviews, several rules of dating etiquette and social activities were modified to be culturally sensitive and linguistically appropriate. Next, young adults diagnosed with ASD (18-35 years of age; IQ > 70) and their social coaches were recruited for the randomized controlled trial (RCT). Participants were randomly assigned either to a treatment group (TG; n = 19) or a delayed treatment group (DTG; n = 18). In the analysis of group differences in the TG and DTG, social skills knowledge was improved. The within group analyses showed positive effects of improving social skills knowledge on reducing depression and anxiety symptoms. After modest cultural adaptations focusing on dating and social activities, the implementation of the PEERS®-YA-K was found feasible for the Korean community. This is one of only a few cross-cultural validation trials establishing evidence-based treatment in young adults with ASD. Clinical Trial Registration: This trial was registered at ClinicalTrials.gov, identifier: NCT03310775.

Risk Scoring System of Mortality and Prediction Model of Hospital Stay for Critically Ill Patients Receiving Parenteral Nutrition.

Predicting the clinical progression of intensive care unit (ICU) patients is crucial for survival and prognosis. Therefore, this retrospective study aimed to develop the risk scoring system of mortality and the prediction model of ICU length of stay (LOS) among patients admitted to the ICU. Data from ICU patients aged at least 18 years who received parenteral nutrition support for ≥50% of the daily calorie requirement from February 2014 to January 2018 were collected. In-hospital mortality and log-transformed LOS were analyzed by logistic regression and linear regression, respectively. For calculating risk scores, each coefficient was obtained based on regression model. Of 445 patients, 97 patients died in the ICU; the observed mortality rate was 21.8%. Using logistic regression analysis, APACHE II score (15-29: 1 point, 30 or higher: 2 points), qSOFA score ≥ 2 (2 points), serum albumin level < 3.4 g/dL (1 point), and infectious or respiratory disease (1 point) were incorporated into risk scoring system for mortality; patients with 0, 1, 2-4, and 5-6 points had approximately 10%, 20%, 40%, and 65% risk of death. For LOS, linear regression analysis showed the following prediction equation: log(LOS) = 0.01 × (APACHE II) + 0.04 × (total bilirubin) - 0.09 × (admission diagnosis of gastrointestinal disease or injury, poisoning, or other external cause) + 0.970. Our study provides the mortality risk score and LOS prediction equation. It could help clinicians to identify those at risk and optimize ICU management.

Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000-2020).

Pharmacogenomics (PGx) is a key subset of precision medicine that relates genomic variation to individual response to pharmacotherapy. We assessed longitudinal trends in US FDA approval of new drugs labeled with PGx information. Drug labels containing PGx information were obtained from Drugs@FDA and guidelines from PharmGKB were used to compare the actionability of PGx information in drug labels across therapeutic areas. The annual proportion of new drug approvals with PGx labeling has increased by nearly threefold from 10.3% (n = 3) in 2000 to 28.2% (n = 11) in 2020. Inclusion of PGx information in drug labels has increased for all clinical areas over the last two decades but most prominently for cancer therapies, which comprise the largest proportion (75.5%) of biomarker-drug pairs for which PGx testing is required. Clinically actionable information was more frequently observed in biomarker-drug pairs associated with cancer drugs compared to those for other therapeutic areas (n = 92 (59.7%) vs. n = 62 (40.3%), p < 0.0051). These results suggest that further evidence is needed to support the clinical adoption of pharmacogenomics in non-cancer therapeutic areas.

Association between reduction in copayment and gastric cancer patient concentration to the capital area in South Korea: NHI cohort 2003-2013.

Since 2004, the South Korean government has introduced a policy that decreases copayment for cancer patients by strengthening public coverage in the National Health Insurance (NHI) system (first phase=copayment for outpatient care from 30% to 20%; second phase=copayment for total medical expenditures from 20% to 10%; third phase=copayment for total medical expenditures from 10% to 5%). We aimed to investigate the relationship between the policy introduction and patient visits to hospitals in the capital area. We used data from the NHI Cohort 2003-2013, which included all medical claims (7193 cases) filed for 2124 patients who visited the hospital due to stomach cancer, and performed a segmented Poisson regression analysis. Of all hospital visits, 40.6% of patients were from the capital area. After the introduction of the second phase of the policy, there was an increase in patient concentration in the capital area, although there were no significant effects on patient concentration during the first and third phases of the policy. In conclusion, our findings suggest that the introduction of a policy that reduces copayment for cancer patients had a substantial impact on patient concentration in the capital area. Therefore, health policymakers should consider effective alternatives including efficient allocation of medical resources or support for the more vulnerable population as flexible benefit plans to aid healthcare utilization by cancer patients.

Fluctuation of peripheral blood T, B, and NK cells during a menstrual cycle of normal healthy women.

Cyclical hormonal changes during an ovarian cycle may affect immune responses, which is crucial for the embryonic implantation. We aim to investigate whether the levels and activity of T, B, and NK cells change during a menstrual cycle. Twenty-two normally cycling women were enrolled and peripheral blood was drawn serially during a menstrual cycle. Intracellular cytokine expression of CD3(+)CD4(+) and CD3(+)CD8(+) cells, and Th1/Th2 cytokine-producing T cell ratios were determined using flow cytometric analysis. NK cell cytotoxicity was measured by flow cytometric analysis at E:T ratios of 50:1, 25:1, and 12.5:1 and also using LU at 20%. Proportions (percentage) of CD3(+) (p = 0.046) and CD3(+)CD4(+) (p = 0.002) T cells were increased in the follicular phase compared with the luteal phase. The levels of CD3(-)CD56(+) (p = 0.010) and CD3(-)CD56(dim) (p = 0.012) NK cells and NK cytotoxicity at E:T ratio of 50:1, 25:1, and 12.5:1 and LU at 20% were significantly increased in the luteal phase compared with the follicular phase. Even though IL-10-producing CD3(+)CD4(+) T cells were significantly lower in the midluteal phase as compared with the early follicular phase, proportions of CD19(+) B cells, CD3(+)CD56(+) NKT cells, Th1 cytokine-producing T cell subsets, and ratios of Th1/Th2 cytokine-producing T cells were not significantly changed during a menstrual cycle. We conclude that peripheral blood NK and T cell levels as well as NK cytotoxicity are changed during a menstrual cycle. Neuroendocrine regulation on immune responses is suggested during an ovarian cycle, which may be critical for embryonic implantation and pregnancy.