Is LDL cholesterol associated with long-term mortality among primary prevention adults? A retrospective cohort study from a large healthcare system.

OBJECTIVES: Among primary prevention-type adults not on lipid-lowering therapy, conflicting results exist on the relationship between low-density lipoprotein cholesterol (LDL-C) and long-term mortality. We evaluated this relationship in a real-world evidence population of adults. DESIGN: Retrospective cohort study. SETTING: Electronic medical record data for adults, from 4 January 2000 through 31 December 2022, were extracted from the University of Pittsburgh Medical Center healthcare system. PARTICIPANTS: Adults without diabetes aged 50-89 years not on statin therapy at baseline or within 1 year and classified as primary prevention-type patients. To mitigate potential reverse causation, patients who died within 1 year or had baseline total cholesterol (T-C) ≤120 mg/dL or LDL-C <30 mg/dL were excluded. MAIN EXPOSURE MEASURE: Baseline LDL-C categories of 30-79, 80-99, 100-129, 130-159, 160-189 or ≥190 mg/dL. MAIN OUTCOME MEASURE: All-cause mortality with follow-up starting 365 days after baseline cholesterol measurement. RESULTS: 177 860 patients with a mean (SD) age of 61.1 (8.8) years and mean (SD) LDL-C of 119 (31) mg/dL were evaluated over a mean of 6.1 years of follow-up. A U-shaped relationship was observed between the six LDL-C categories and mortality with crude 10-year mortality rates of 19.8%, 14.7%, 11.7%, 10.7%, 10.1% and 14.0%, respectively. Adjusted mortality HRs as compared with the referent group of LDL-C 80-99 mg/dL were: 30-79 mg/dL (HR 1.23, 95% CI 1.17 to 1.30), 100-129 mg/dL (0.87, 0.83-0.91), 130-159 mg/dL (0.88, 0.84-0.93), 160-189 mg/dL (0.91, 0.84-0.98) and ≥190 mg/dL (1.19, 1.06-1.34), respectively. Unlike LDL-C, both T-C/HDL cholesterol (high-density lipoprotein cholesterol) and triglycerides/HDL cholesterol ratios were independently associated with long-term mortality. CONCLUSIONS: Among primary prevention-type patients aged 50-89 years without diabetes and not on statin therapy, the lowest risk for long-term mortality appears to exist in the wide LDL-C range of 100-189 mg/dL, which is much higher than current recommendations. For counselling these patients, minimal consideration should be given to LDL-C concentration.

Emotional freedom techniques for treating post traumatic stress disorder: an updated systematic review and meta-analysis.

Introduction: Clinical Emotional Freedom Techniques (EFT) is a psychophysiological intervention that includes cognitive and somatic elements, utilizing techniques from both Cognitive Behavioral Therapy (CBT) and Prolonged Exposure therapy (PE). Because only a single meta-analysis existed examining EFT for PTSD, this systematic review and meta-analysis represents an update. Method: Ten databases were searched for quantitative reviews and randomised clinical trials, and six met inclusion criteria. Results: Study quality and effect size were evaluated and the results demonstrated that treatment with Clinical EFT, when compared to wait list, usual care, or no treatment controls, resulted in significant and large effect sizes, ranging from 1.38 to 2.51. When compared to active controls, effect sizes ranged from -0.15 to 0.79, producing treatment results similar to other evidence-based therapies. Discussion: Limitations are presented and considerations for further research are proposed.

Direct Oral Anticoagulant Failures in Atrial Fibrillation With Stroke: Retrospective Admission Analysis and Novel Classification System.

Introduction: Breakthrough acute ischemic stroke (AIS) in patients with known, nonvalvular Atrial Fibrillation (AF), on Direct Oral Anticoagulants (DOAC), is an ongoing clinical conundrum. Switching anticoagulants was shown to be ineffective in preventing recurrent AIS. Systematic, patient-level chart review of so-called "DOAC failures" may offer insight into this phenomenon. Methods: We conducted an IRB-approved, 6-year, retrospective study of AIS admissions, already prescribed DOAC for known AF. We sought plausible, alternative reasons for the AIS using a novel classification schema, CLAMP: C for Compliance concerns, L for Lacunes (small-vessel disease), A for Arteriopathy (atherosclerosis, web, or vasculitis), M for Malignancy, and P for Patent Foramen Ovale (PFO). These categories were labeled as DOAC "Pseudo-failures." Conversely, absence of CLAMP variables were labeled as DOAC "Crypto-failures" conceivably from AF itself ("atriopathy") or pharmacokinetic/pharmacogenomic dysfunction (ie, altered DOAC absorption, clearance, metabolism, or genetic polymorphisms). Forward logistic regression analysis was performed on prespecified DOAC subgroups. Results: Of 4890 AIS admissions, 606 had AF, and 87 were previously prescribed DOAC (14.4% overall DOAC failure rate, 2.4% annualized over 6 years). Pseudo-failures comprised 77%: Compliance concerns (48.9%), Lacunes (5.7%), Arteriopathy (17.0%), Malignancy (26.1%), and PFO (2.3%). Crypto-failures comprised 23%, had lower CHADSVASc scores (AOR = .65, P = .013), and occurred more with rivaroxaban (41%) than apixaban (16%) or dabigatran (5.6%). Conclusion: In AIS patients with known AF, DOAC Pseudo-failures, with identified alternate etiologies, are 3 times more likely than DOAC Crypto-failures. The CLAMP schema represents a novel approach to diagnostic classification and therapeutic adjustments in patients already prescribed DOAC for AF.

Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19 : A Cohort Study.

BACKGROUND: Treatment guidelines and U.S. Food and Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. OBJECTIVE: To evaluate whether early outpatient treatment with mAbs, overall and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status, is associated with reduced risk for hospitalization or death at 28 days. DESIGN: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients with a propensity score-matched, nontreated control group. SETTING: Large U.S. health care system. PARTICIPANTS: High-risk outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from 8 December 2020 to 31 August 2022. INTERVENTION: Single-dose intravenous mAb treatment with bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or intravenous or subcutaneous casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result. MEASUREMENTS: The primary outcome was hospitalization or death at 28 days among treated patients versus a nontreated control group (no treatment or treatment ≥3 days after SARS-CoV-2 test date). RESULTS: The risk for hospitalization or death at 28 days was 4.6% in 2571 treated patients and 7.6% in 5135 nontreated control patients (risk ratio [RR], 0.61 [95% CI, 0.50 to 0.74]). In sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively. In subgroup analyses, those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71). LIMITATIONS: Observational study design, SARS-CoV-2 variant presumed by date rather than genotyping, no data on symptom severity, and partial data on vaccination status. CONCLUSION: Early mAb treatment among outpatients with COVID-19 is associated with lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants. PRIMARY FUNDING SOURCE: None.

Changes in body weight and glycemic control in association with COVID-19 Shutdown among 23,000 adults with type 2 diabetes.

AIMS: To examine the association between COVID-19 Shutdown and within-subjects changes in body weight, body mass index (BMI), and glycemic parameters using electronic health record (EHR) data from 23,000 adults with type 2 diabetes (T2DM). METHODS: Patients with T2DM with outpatient visit data on body weight, BMI, hemoglobin A1c (HbA1c), and blood glucose (≥ 2 measures before and after 3/16/2020) recorded in the EHR at the University of Pittsburgh Medical Center were included. A within-subjects analysis compared average and clinically significant changes in weight, BMI, HbA1c, and blood glucose during the year POST-Shutdown (Time 2-3) compared to the same interval during the PRE-Shutdown year (Time 0-1) using paired samples t-tests and the McNemar-Bowker test. RESULTS: We studied 23,697 adults with T2DM (51% female; 89% White; mean age = 66 ± 13 years; mean BMI = 34 ± 7 kg/m2; mean HbA1c = 7 ± 2% [53 ± 21.9 mmol/mol]). Weight and BMI decreased during both the PRE- and POST-Shutdown intervals, but the changes were statistically smaller during the year POST-Shutdown relative to PRE (0.32 kg and 0.11 units, p < 0.0001). HbA1c showed statistically greater improvements during the POST-Shutdown interval compared to PRE (- 0.18% [-2 mmol/mol], p < 0.0001), but changes in glucose did not differ for the two intervals. CONCLUSIONS: Despite widespread discussion of weight gain in association with the COVID-19 Shutdown, study data showed no evidence of adverse effects of Shutdown on body weight, BMI, HbA1C, or blood glucose in a large sample of adults with T2DM. This information may help to inform future public health decision-making.

Comparison of Accelerated Resolution Therapy for PTSD Between Veterans With and Without Prior PTSD Treatment.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is a psychiatric disorder commonly caused by a traumatic event(s) and prevalent among service members and veterans. Accelerated Resolution Therapy (ART) is an emerging "mind-body" psychotherapy for PTSD that is generally briefer and less expensive than current first-line treatments, such as cognitive processing therapy (CPT) and prolonged exposure (PE) therapy. This study examined the results of ART for treatment of military-related PTSD, with stratification by prior PTSD treatment types, including service members/veterans with reported residual PTSD symptoms following receipt of first-line recommended psychotherapy. MATERIALS AND METHODS: Four groups were constructed and compared based on self-reported prior PTSD treatment history: treatment-naïve (n = 33), pharmacotherapy only (n = 40), first-line psychotherapy (CPT and/or PE) (n = 33), and other psychotherapy (n = 42). Participants were assessed for PTSD symptoms at baseline, post-treatment, and 6-month follow-up using the 17-item Military PTSD Checklist (PCL-M), as well as assessment of depressive, anxiety, and sleep symptoms. The study was approved by the Institutional Review Board at University of South Florida. RESULTS: Among 148 veterans/service members who enrolled and started treatment with ART, 106 (71.6%) completed treatment in a mean of 3.5 treatment sessions, and 55 (51.9%) provided 6-month follow-up data. Mean age was 43.8 years, 95% were male, and 84% were of white race. Within-group standardized effect sizes for pre-to-post changes in PTSD scores (PCL-M) were large at 1.48, 1.11, 1.88, and 1.03 for the treatment-naïve, pharmacotherapy only, first-line psychotherapy, and other psychotherapy groups, respectively. Among treatment completers, the clinically significant treatment response rate (reduction of ≥10 points on the PCL-M) was highest in the treatment-naïve (83%) and first-line psychotherapy (88%) groups. Similar significant symptom reductions were observed for measures of depression and anxiety, and favorable treatment effects were generally sustained at 6-month follow-up. CONCLUSION: In a brief treatment period, ART appears to result in substantial reductions in symptoms of PTSD among veterans, including those with residual PTSD symptoms after prior treatment with first-line psychotherapies endorsed by the U.S. Department of Defense and Veterans Affairs. These results suggest that ART be considered as a potential first-line treatment modality for veterans with PTSD.

Evaluation of Bebtelovimab for Treatment of Covid-19 During the SARS-CoV-2 Omicron Variant Era.

Background: Monoclonal antibody (mAb) treatment is associated with decreased risk of hospitalization and death in high-risk outpatients with mild to moderate coronavirus disease 2019 (COVID-19) caused by early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Bebtelovimab exhibits in vitro activity against the Omicron variant and its sublineages; however, clinical data are lacking. Methods: A retrospective cohort study was conducted comparing bebtelovimab-treated patients with propensity score-adjusted and matched nontreated control groups. Participants included high-risk outpatients eligible for bebtelovimab treatment under Emergency Use Authorization with a positive SARS-CoV-2 test from March 30 to May 28, 2022. Treated patients received single-dose intravenous treatment with bebtelovimab. The primary outcome was hospitalization or death over 28 days. Results: Before matching/statistical adjustment, mAb-treated patients were, on average, 10 years older than nontreated patients (61.6 vs 51.3 years) and had higher prevalence of obstructive sleep apnea, hypertension, chronic kidney disease, cancer, organ or cell transplant, and immunocompromised status (standardized mean differences ≥0.20). The adjusted odds ratio (OR) of hospitalization or death comparing 1006 treated with 2023 nontreated patients was 0.50 (95% CI, 0.31-0.80). Among 930 treated and 930 propensity score-matched nontreated patients, the incidence of hospitalization or death was 3.1% vs 5.5%, respectively (conditional OR, 0.53; 95% CI, 0.32-0.86). The lower odds ratio of hospitalization or death associated with bebtelovimab treatment was most evident in older patients, those with immunocompromised status, and fully vaccinated patients. Conclusions: Monoclonal antibody treatment with bebtelovimab among COVID-19 outpatients is associated with lower odds of hospitalization or death, particularly among immunocompromised and older patients.

Associations between cumulative social risk, psychosocial risk, and ideal cardiovascular health: Insights from the HeartSCORE study.

Background: Limited studies have assessed the effects of psychosocial risk factors on achievement of ideal cardiovascular health (CVH). Methods: Using the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) cohort, we examined the cross-sectional associations of cumulative social risk (CSR) and three psychosocial factors (depression, stress, perceived discrimination) with ideal CVH. CSR was calculated by assigning one point for each of: low family income, low education level, minority race (Black), and single-living status. Ideal CVH was calculated by assigning one point for ideal levels of each factor in American Heart Association's Life's Simple 7. Ideal CVH was dichotomized into fewer versus higher by combining participants achieving <3 versus ≥3 factors. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of having fewer ideal CVH factors. Psychosocial factors were assessed as mediators of the association between CSR and ideal CVH. Results: We included 2000 participants (mean age 59.1 [7.5] years, 34.6% male, 42.7% Black, and 29.1% with low income), among whom 60.6% had <3 ideal CVH factors. The odds of having fewer ideal CVH factors increased significantly with increasing CSR scores from 1 to 2, to ≥3 compared to individuals with CSR score of zero, after adjusting for age and sex (OR [95% CIs]: 1.77 [1.41 - 2.22]; 2.09 [1.62 - 2.69] 2.67 [1.97 - 3.62], respectively). Taking the components of ideal CVH separately, higher CSR was directly associated with odds of being in 'non-ideal' category for six of the seven factors, but was inversely associated with probability of being in 'non-ideal' category for cholesterol. The association was modestly attenuated after adjusting for depression, stress, and perceived discrimination (corresponding OR [95% CI]: 1.69 [1.34 - 2.12], 1.96 [1.51 - 2.55], 2.34 [1.71 - 3.20]). The psychosocial factors appeared to mediate between 10% and 20% of relationship between CSR and ideal CVH. Conclusions: Increased CSR was associated with lower probability of achieving ideal CVH factors. A modest amount of the effect of CSR on ideal CVH appeared to be mediated by depression, stress and perceived discrimination. Public health strategies aimed at improving ideal cardiovascular health may benefit from including interventions targeting social and psychosocial risk factors.

A learning health system approach to the COVID-19 pandemic: System-wide changes in clinical practice and 30-day mortality among hospitalized patients.

Introduction: Rapid, continuous implementation of credible scientific findings and regulatory approvals is often slow in large, diverse health systems. The coronavirus disease 2019 (COVID-19) pandemic created a new threat to this common "slow to learn and adapt" model in healthcare. We describe how the University of Pittsburgh Medical Center (UPMC) committed to a rapid learning health system (LHS) model to respond to the COVID-19 pandemic. Methods: A treatment cohort study was conducted among 11 429 hospitalized patients (pediatric/adult) from 22 hospitals (PA, NY) with a primary diagnosis of COVID-19 infection (March 19, 2020 - June 6, 2021). Sociodemographic and clinical data were captured from UPMC electronic medical record (EMR) systems. Patients were grouped into four time-defined patient "waves" based on nadir of daily hospital admissions, with wave 3 (September 20, 2020 - March 10, 2021) split at its zenith due to high volume with steep acceleration and deceleration. Outcomes included changes in clinical practice (eg, use of corticosteroids, antivirals, and other therapies) in relation to timing of internal system analyses, scientific publications, and regulatory approvals, along with 30-day rate of mortality over time. Results: The mean (SD) daily number of admissions across hospitals was 26 (29) with a maximum 7-day moving average of 107 patients. System-wide implementation of the use of dexamethasone, remdesivir, and tocilizumab occurred within days of release of corresponding seminal publications and regulatory actions. After adjustment for differences in patient clinical profiles over time, each month of hospital admission was associated with an estimated 5% lower odds of 30-day mortality (adjusted odds ratio [OR] = 0.95, 95% confidence interval: 0.93-0.97, P < .001). Conclusions: In our large LHS, near real-time changes in clinical management of COVID-19 patients happened promptly as scientific publications and regulatory approvals occurred throughout the pandemic. Alongside these changes, patients with COVID-19 experienced lower adjusted 30-day mortality following hospital admission over time.

Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge: A Cohort Study and Randomized Comparative Effectiveness Trial.

Importance: The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. Objective: To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. Design, Setting, and Participants: This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. Exposure: For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. Main Outcomes and Measures: For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. Results: A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. Conclusions and Relevance: In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. Trial Registration: ClinicalTrials.gov Identifier: NCT04790786.

The comparative effectiveness of COVID-19 monoclonal antibodies: A learning health system randomized clinical trial.

BACKGROUND: Monoclonal antibodies (mAb) that neutralize SARS-CoV-2 decrease hospitalization and death compared to placebo in patients with mild to moderate COVID-19; however, comparative effectiveness is unknown. We report the comparative effectiveness of bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab. METHODS: A learning health system platform trial in a U.S. health system enrolled patients meeting mAb Emergency Use Authorization criteria. An electronic health record-embedded application linked local mAb inventory to patient encounters and provided random mAb allocation. Primary outcome was hospital-free days to day 28. Primary analysis was a Bayesian model adjusting for treatment location, age, sex, and time. Inferiority was defined as 99% posterior probability of an odds ratio < 1. Equivalence was defined as 95% posterior probability the odds ratio is within a given bound. FINDINGS: Between March 10 and June 25, 2021, 1935 patients received treatment. Median hospital-free days were 28 (IQR 28, 28) for each mAb. Mortality was 0.8% (1/128), 0.8% (7/885), and 0.7% (6/922) for bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab, respectively. Relative to casirivimab-imdevimab (n = 922), median adjusted odds ratios were 0.58 (95% credible interval [CI] 0.30-1.16) and 0.94 (95% CI 0.72-1.24) for bamlanivimab (n = 128) and bamlanivimab-etesevimab (n = 885), respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab-etesevimab and casirivimab-imdevimab, and an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab. INTERPRETATION: Among patients with mild to moderate COVID-19, bamlanivimab-etesevimab or casirivimab-imdevimab treatment resulted in 86% probability of equivalence. No treatment met prespecified criteria for statistical equivalence. Median hospital-free days to day 28 were 28 (IQR 28, 28) for each mAb. FUNDING AND REGISTRATION: This work received no external funding. The U.S. government provided the reported mAb. This trial is registered at ClinicalTrials.gov, NCT04790786.

Translational Genomic Research: The Association between Genetic Profiles and Cognitive Functioning or Cardiac Function Among Breast Cancer Survivors Completing Chemotherapy.

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.

Association of Subcutaneous or Intravenous Administration of Casirivimab and Imdevimab Monoclonal Antibodies With Clinical Outcomes in Adults With COVID-19.

Importance: Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19; however, only intravenous administration has been evaluated in randomized clinical trials of treatment. Subcutaneous administration may expand outpatient treatment capacity and qualified staff available to administer treatment, but the association with patient outcomes is understudied. Objectives: To evaluate whether subcutaneous casirivimab and imdevimab treatment is associated with reduced 28-day hospitalization and death compared with nontreatment among mAb-eligible patients and whether subcutaneous casirivimab and imdevimab treatment is clinically and statistically similar to intravenous casirivimab and imdevimab treatment. Design, Setting, and Participants: This prospective cohort study evaluated high-risk outpatients in a learning health system in the US with mild to moderate COVID-19 symptoms from July 14 to October 26, 2021, who were eligible for mAb treatment under emergency use authorization. A nontreated control group of eligible patients was also studied. Exposures: Subcutaneous injection or intravenous administration of the combined single dose of 600 mg of casirivimab and 600 mg of imdevimab. Main Outcomes and Measures: The primary outcome was the 28-day adjusted risk ratio or adjusted risk difference for hospitalization or death. Secondary outcomes included 28-day adjusted risk ratios and differences in hospitalization, death, a composite end point of emergency department admission and hospitalization, and rates of adverse events. Among 1959 matched adults with mild to moderate COVID-19, 969 patients (mean [SD] age, 53.8 [16.7] years; 547 women [56.4%]) who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalization or death of 3.4% (22 of 653 patients) compared with 7.0% (92 of 1306 patients) in nontreated controls (risk ratio, 0.48; 95% CI, 0.30-0.80; P = .002). Among 2185 patients treated with subcutaneous (n = 969) or intravenous (n = 1216; mean [SD] age, 54.3 [16.6] years; 672 women [54.4%]) casirivimab and imdevimab, the 28-day rate of hospitalization or death was 2.8% vs 1.7%, which resulted in an adjusted risk difference of 1.5% (95% CI, -0.6% to 3.5%; P = .16). Among all infusion patients, there was no difference in intensive care unit admission (adjusted risk difference, 0.7%; 95% CI, -3.5% to 5.0%) or need for mechanical ventilation (adjusted risk difference, 0.2%; 95% CI, -5.8% to 5.5%). Conclusions and Relevance: In this cohort study of high-risk outpatients with mild to moderate COVID-19 symptoms, subcutaneously administered casirivimab and imdevimab was associated with reduced hospitalization and death when compared with no treatment. These results provide preliminary evidence of potential expanded use of subcutaneous mAb treatment, particularly in areas that are facing treatment capacity and/or staffing shortages.

Breast cancer mortality as a function of age.

BACKGROUND: Incidence of breast cancer (BC) in US women continues to increase with age as the strongest risk factor. We aimed to compare clinical, pathological and sociological variables associated to BC diagnosis, as well as the relative mortality rates of BC patients compared to the general US population. METHODS: We performed a retrospective, single-institution study evaluating 52,509 patients diagnosed with unilateral BC at the University of Pittsburgh Medical Center (UPMC) between 1990-2020. Primary outcome was death from any cause with cancer recurrence as a secondary outcome, evaluated for 4 age groups: 20-44, 45-55, 56-69, and 70-90. A dataset of expected mortality for women in the general population over a 10-year period was constructed using the Surveillance, Epidemiology, and End Results (SEER) Program. Observed vs. expected mortality and standardized mortality ratios (SMR) for each age group were calculated. RESULTS: Youngest patients with BC demonstrated the highest SMR at 10-year follow-up from time of diagnosis compared to the general US population (SMR 9.68, 95% CI: 8.99to 10.42), and remained highest compared to other age groups when analysis was limited to Stage 0/1 disease (10-year SMR 3.11, 95% CI: 2.54 to 3.76). SMRs decreased with increasing age at diagnosis with an SMR <1.0 in patients diagnosed with stage 0/1 at ages 70-90 at 5-year follow-up. CONCLUSIONS: Younger BC patients have the highest SMR which declines gradually with age. In the elderly, lower stage 0/1 SMR's are found compared to the general population, suggesting the possibility of an associated protective effect.

Corrigendum Supports Therapeutic Contribution of Acupoint Tapping to EFTs' Observed Effects: Response to Spielmans (2021).

ABSTRACT: We published a meta-analysis of studies that examined the various components of an evidence-based therapy called emotional freedom techniques (EFTs). EFT uses elements of conventional therapies such as exposure and cognitive processing but includes the unique ingredient of acupoint stimulation using fingertip tapping. Six studies were identified, and three of these met the quality control criteria of the American Psychological Association's Division 12 Task Force for Empirically Validated Therapies. Meta-analysis found that the acupoint component of EFT was not an inert ingredient or inactive placebo but made an active contribution to the therapeutic effects noted in a research literature that now numbers over 100 clinical trials of EFT. Subsequent to publication, errors in the original analysis were identified, primarily incorrect standard deviations. A new analysis was performed by an independent statistician and found slightly greater effects than the original investigation. The results were published as a corrigendum, which was subsequently challenged by Spielmans. Here we examine the critiques of the corrigendum and original article. We find that although they may be of academic interest, they are irrelevant to the central research question of whether the acupoint component of EFT is inert or active. We reaffirm that the evidence clearly validates the contribution made by acupoint tapping to EFT's observed clinical effects.

Complicated Grief With Post-Traumatic Stress Disorder Addressed With Accelerated Resolution Therapy: Case Discussions.

Complicated grief is a significant health concern for older adults, resulting in significant psychological and physical morbidity. Elements of post traumatic stress disorder (PTSD) are often present in individuals with complicated grief. Accelerated Resolution Therapy (ART) is a brief form of psychotherapy that utilizes the techniques of imaginal exposure, rescripting of events, and lateral eye movements that may be useful in complicated grief with PTSD symptoms. Two cases where ART was used for complicated grief with PTSD are presented. Both individuals had attempted to come to terms with their loss through traditional grief therapy with an inadequate response and substantial residual grief symptoms. These cases illustrate how ART can be used to address CG and PTSD and describe situations where it may be appropriate. Clinical and research implications are also discussed.

Screening and Priority-Setting to Determine Home- and Community-Based Aging Services for Older Floridians.

The National Aging Network serves millions of older Americans seeking home- and community-based services, but places others on waitlists due to limited resources. Little is known about how states determine service delivery and waitlists. We therefore conducted a process evaluation and analyzed data from one five-county Area Agency on Aging in Florida, where an algorithm calculates clients' priority scores for service delivery. From 23,225 screenings over 5.5 years, clients with higher priority scores were older, married, living with caregivers, and had more health problems and needs for assistance. Approximately 51% received services (e.g., meals/nutrition, case management, caregiver support), 11% were eligible/being enrolled, and 38% remained on waitlists. Service status was complex due to multiple service enrollments and terminations, funding priorities, and transfers to third-party providers. More research is needed regarding how other states determine eligibility and deliver services, potentially informing national standards that promote optimal health in older Americans.

Caregivers' Loss of the Dyadic Experience after Their Care Partners' Death.

Little is known about the experience of family caregivers when their care partner dies and their dyadic relationship comes to an end. This study qualitatively examined and characterized the loss of the dyadic experience for the caregiver after the death of their care partner. Data was accrued as part of a randomized clinical trial in 29 older hospice caregivers. Iterative thematic analysis focused on dyadic processes before, during and post death. Using two relational parameters from Relational Turbulence Theory resulted in a preliminary characterization of a new concept-dyadic dissolution as a cognitive and affective process whereby a remaining member of a dyad experiences relational uncertainty and partner interference while adapting (or not) to the death of their care partner. Findings suggest that asking several open-ended questions about the dyadic relationship will enable assessment for any continuing impact of relational uncertainty and partner interference on bereaved caregivers.

Left Ventricular Ballooning Patterns in Recurrent Takotsubo Cardiomyopathy: A Systematic Review and Meta-analysis of Reported Cases.

Recurrent takotsubo cardiomyopathy (TTC) and the clinical profiles and outcomes of patients have not been fully evaluated, nor has the effect of left ventricular ballooning pattern. After searching the medical literature for reports of patients with recurrent TTC, we identified 84 articles with 101 case descriptions. We divided the cases into those with only apical left ventricular ballooning patterns at recurrence (typical, n=60), and those with at least one midventricular or basal ballooning pattern (atypical, n=41). We then compared their clinical profiles and outcomes. The groups were similar in terms of baseline demographic characteristics, presence and types of triggers, use of heart failure medications at TTC recurrence, electrocardiographic changes at presentation, initial left ventricular ejection fractions, timespans between recurrent TTC episodes, and recovery times after each event. However, patients in the atypical group had significantly fewer severe adverse events (cardiogenic shock and cardiac arrest) than did those in the typical group, with an estimated 63% lower odds (adjusted odds ratio=0.37; 95% CI, 0.14-0.97; P=0.039). Survival to hospital discharge was statistically similar but lower in the typical group (n=53; 88.3%) than in the atypical group (n=24; 96%). Our results suggest that left ventricular ballooning patterns influence clinical outcomes, and that outcomes are more favorable in patients with recurrent TTC who have atypical left ventricular ballooning patterns.