Impact of Bivalent BA.4/5 BNT162b2 COVID-19 Vaccine on Acute Symptoms, Quality of Life, Work Productivity and Activity Levels among Symptomatic US Adults Testing Positive for SARS-CoV-2 at a National Retail Pharmacy.

Evidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 (BNT162b2) and these patient-reported outcomes (PROs). Symptomatic US adults testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023 (CT.gov NCT05160636). PROs were assessed using four questionnaires measuring symptoms, HRQoL and WPAI (a CDC-based symptom survey, PROMIS Fatigue, EQ-5D-5L, WPAI-GH), from pre-COVID to Week 4 following infection. Multivariable analysis using mixed models for repeated measures was conducted, adjusting for several covariates. The study included 643 participants: 316 vaccinated with BNT162b2 and 327 unvaccinated/not up-to-date. Mean (SD) age was 46.5 years (15.9), 71.2% were female, 44.2% reported prior infection, 25.7% had ≥1 comorbidity. The BNT162b2 cohort reported fewer acute symptoms through Week 4, especially systemic and respiratory symptoms. All PROs were adversely affected, especially at Week 1; however, at that time point, the BNT162b2 cohort reported better work performance, driven by less absenteeism, and fewer work hours lost. No significant differences were observed for HRQoL COVID-19 negatively impacted patient outcomes. Compared with unvaccinated/not up-to-date participants, those vaccinated with bivalent BA.4/5 BNT162b2 reported fewer and less persistent symptoms and improved work performance.

Impact of COVID-19 Infection on Health-Related Quality of Life, Work Productivity and Activity Impairment by Symptom-Based Long COVID Status and Age in the US.

COVID-19 infection adversely impacts patients' wellbeing and daily lives. This survey-based study examined differences in patient-reported COVID-19 symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) among groups of patients defined based on age and symptom-based long COVID status. Symptomatic, COVID-19-positive US outpatients were recruited from 31 January-30 April 2022. Outcomes were collected via validated instruments at pre-COVID, Day 3, Week 1, Week 4, Month 3 and Month 6 following infection, with changes assessed from pre-COVID and between groups, adjusting for covariates. EQ-5D-5L HRQoL and WPAI scores declined in all groups, especially during the first week. Long COVID patients reported significantly higher symptoms burden and larger drops in HRQoL and WPAI scores than patients without long COVID. Their HRQoL and WPAI scores did not return to levels comparable to pre-COVID through Month 6, except for absenteeism. Patients without long COVID generally recovered between Week 4 and Month 3. Older (>50) and younger adults generally reported comparable symptoms burden and drops in HRQoL and WPAI scores. During the first week of infection, COVID-19-related health issues caused loss of 14 to 26 work hours across the groups. These data further knowledge regarding the differential impacts of COVID-19 on clinically relevant patient groups.

Comparative Effectiveness of Transcutaneous Afferent Patterned Stimulation Therapy for Essential Tremor: A Randomized Pragmatic Clinical Trial.

Background: Transcutaneous afferent patterned stimulation (TAPS) is a wrist-worn, non-invasive therapy delivering calibrated stimulation to the median and radial nerves. Previous randomized controlled studies have demonstrated the efficacy and safety of TAPS therapy in some patients with essential tremor (ET), but evidence supporting therapeutic benefits of TAPS versus standard of care (SOC) is lacking. This randomized prospective study evaluated the clinical benefit of adding TAPS treatment to SOC versus SOC alone. Methods: This randomized pragmatic trial recruited patients from a large health plan's Commercially Insured and Medicare Advantage population. All 310 patients received a TAPS device and were randomized 1:1 to either one month adding TAPS therapy to usual care (TX arm) or usual care with tremor assessment only (SOC arm). The pre-specified endpoints were changes in tremor power measured by motion sensors on the device (primary) and improvement in Bain & Findley Activities of Daily Living (BF-ADL) upper limb scores (secondary) between TX and SOC in all patients who completed the one-month study. Results: 276 patients completed the one-month study (N = 133 TX, N = 143 SOC). The study met the primary and secondary endpoints, with significantly reduced tremor power in TX compared with SOC (0.017 (0.003) versus 0.08 (0.014) (m/s2)2; geometric mean (SE); p < 0.0001) and greater improvement in the BF-ADL score in TX than SOC (1.6 (0.43) vs 0.2 (0.37) points; mean (SE); p < 0.05). No serious device-related adverse events were reported. Discussion: This trial demonstrates that adding TAPS treatment to SOC significantly improves tremor power and BF-ADLs in patients with ET compared to SOC alone over one month of home use. Highlights: This study found that adding TAPS treatment to SOC significantly improves tremor power and BF-ADL scores in patients with ET compared to SOC alone over one month of home use. This real-world evidence study suggests that non-invasive TAPS therapy is a safe and valuable treatment option for patients with ET.

Assessment of retrospective collection of EQ-5D-5L in a US COVID-19 population.

BACKGROUND: It is imperative to evaluate health related quality of life (HRQoL) pre-COVID-19, but there is currently no evidence of the retrospective application of the EuroQol 5-Dimension, 5 level version (EQ-5D-5L) for COVID-19 studies. METHODS: Symptomatic patients with SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022-04/30/2022. Consented participants completed the EQ-5D-5L questionnaire twice: a modified version where all the questions were past tense to retrospectively assess pre-COVID-19 baseline QoL, and the standard version in present tense to assess current HRQoL. Duncan's new multiple range test was adopted for post analysis of variance pairwise comparisons of EQ visual analog scale (EQ VAS) means between problem levels for each of 5 domains. A linear mixed model was applied to check whether the relationship between EQ VAS and utility index (UI) was consistent pre-COVID-19 and during COVID-19. Matching-adjusted indirect comparison was used to compare pre-COVID-19 UI and EQ VAS scores with those of the US population. Lastly, Cohen's d was used to quantify the magnitude of difference in means between two groups. RESULTS: Of 676 participants, 10.2% were age 65 or more years old, 73.2% female and 71.9% white. Diabetes was reported by 4.7% participants and hypertension by 11.2%. The estimated coefficient for the interaction of UI-by-retrospective collection indicator (0 = standard prospective collection, 1 = retrospective for pre-COVID-19), -4.2 (SE: 3.2), P = 0.197, indicates that retrospective collection does not significantly alter the relationship between EQ VAS and UI. After adjusting for age, gender, diabetes, hypertension, and percent of mobility problems, the predicted means of pre-COVID-19 baseline EQ VAS and UI were 84.6 and 0.866, respectively. Both means were close to published US population norms (80.4 and 0.851) compared to those observed (87.4 and 0.924). After adjusting for age, gender, diabetes, and hypertension, the calculated ES between pre-COVID-19 and COVID-19 for UI and EQ VAS were 0.15 and 0.39, respectively. Without retrospectively collected EQ-5D-5L, using US population norms tended to underestimate the impact of COVID-19 on HRQoL. CONCLUSION: At a group level the retrospectively collected pre-COVID-19 EQ-5D-5L is adequate and makes it possible to directly evaluate the impact of COVID-19 on HRQoL. ( ClinicalTrials.gov NCT05160636).

Impact of COVID-19 and effects of booster vaccination with BNT162b2 on six-month long COVID symptoms, quality of life, work productivity and activity impairment during Omicron.

BACKGROUND: Longitudinal estimates of long COVID burden during Omicron remain limited. This study characterized long-term impacts of COVID-19 and booster vaccination on symptoms, Health-Related Quality of Life (HRQoL), and Work Productivity Activity Impairment (WPAI). METHODS: Outpatients with ≥ 1 self-reported symptom and positive SARS-CoV-2 test at CVS Health United States test sites were recruited between 01/31 and 04/30/2022. Symptoms, EQ-5D and WPAI were collected via online surveys until 6 months following infection. Both observed and model-based estimates were analyzed. Effect sizes based on Cohen's d quantified the magnitude of outcome changes over time, within and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for covariates. Logistic regression assessed odds ratio (OR) of long COVID between vaccination groups. RESULTS: At long COVID start (Week 4), 328 participants included 87 (27%) Boosted with BNT162b2, 86 (26%) with a BNT162b2 primary series (Primed), and 155 (47%) Unvaccinated. Mean age was 42.0 years, 73.8% were female, 26.5% had ≥ 1 comorbidity, 36.9% prior infection, and 39.6% reported ≥ 3 symptoms (mean: 3.1 symptoms). At Month 6, among 260 participants, Boosted reported a mean of 1.1 symptoms versus 3.4 and 2.8 in Unvaccinated and Primed, respectively (p < 0.001). Boosted had reduced risks of ≥ 3 symptoms versus Unvaccinated (observed: OR 0.22, 95% CI 0.10-0.47, p < 0.001; model-based: OR 0.36, 95% CI 0.15-0.87, p = 0.019) and Primed (observed: OR 0.29, 95% CI 0.13-0.67, p = 0.003; model-based: OR 0.59, 95% CI 0.21-1.65, p = 0.459). Results were consistent using ≥ 2 symptoms. Regarding HRQoL, among those with long COVID, Boosted had higher EQ-5D Utility Index (UI) than Unvaccinated (observed: 0.922 vs. 0.731, p = 0.014; model-based: 0.910 vs. 0.758, p-value = 0.038) and Primed (0.922 vs. 0.648, p = 0.014; model-based: 0.910 vs. 0.708, p-value = 0.008). Observed and model-based estimates for EQ-VAS and UI among Boosted were comparable with pre-COVID since Month 3. Subjects vaccinated generally reported better WPAI scores. CONCLUSIONS: Long COVID negatively impacted HRQoL and WPAI. The BNT162b2 booster could have a beneficial effect in reducing the risk and burden of long COVID. Boosted participants reported fewer and less durable symptoms, which contributed to improve HRQoL and maintain WPAI levels. Limitations included self-reported data and small sample size for WPAI.

Anxiety, Depression, and Stress Reaction/Adjustment Disorders and Their Associations with Healthcare Resource Utilization and Costs Among Newly Diagnosed Patients With Breast Cancer.

Background: Breast cancer is the most common cancer among women in the United States. Newly diagnosed patients with breast cancer often experience anxiety, depression, and stress. However, the impact of psychological distress on healthcare resource utilization (HCRU) and costs has not been adequately assessed. Objectives: To evaluate the incidence and prevalence of anxiety, depression, and stress reaction/adjustment disorder among patients newly diagnosed with breast cancer, to examine HCRU and costs, and to assess the association of these psychiatric disorders with costs. Methods: This retrospective observational cohort study was conducted using a large US administrative claims database with an index date of newly diagnosed breast cancer. Demographics and comorbidities (including anxiety, depression, and stress reaction/adjustment disorder) were assessed using data collected 12 months before and after the index date. HCRU and costs were assessed using data collected 12 months after the index date. Generalized linear regressions were performed to examine the association between healthcare costs and anxiety, depression, and stress reaction/adjustment disorder. Results: Of 6392 patients with newly diagnosed breast cancer, 38.2% were diagnosed with psychiatric disorders including anxiety (27.7%), depression (21.9%), or stress reaction/adjustment disorder (6%). The incidence of these psychiatric disorders was 15% and the prevalence was 23.2%. Patients with anxiety, depression, or stress reaction/adjustment disorder had higher rates of several types of HCRU (P < .0001) and higher total all-cause costs compared with patients without these psychiatric disorders (P < .0001). Patients with incident anxiety, depression, or stress reaction/adjustment disorder incurred higher all-cause costs in the first year following breast cancer diagnosis than those with prevalent anxiety, depression, or stress reaction/adjustment disorder (P < .0003), or those without these psychiatric disorders (P < .0001). Discussion: Of patients with anxiety, depression, or stress reaction/adjustment disorder, those with incident psychiatric disorders had higher healthcare costs, suggesting that new-onset psychological distress may contribute to higher costs incurred by the payer. Timely treatment of psychiatric disorders in this population may improve clinical outcomes and reduce HCRU and costs. Conclusions: Anxiety, depression, and stress reaction/adjustment disorder were common among patients newly diagnosed with breast cancer and were associated with increased healthcare costs in the first year following breast cancer diagnosis.

Real-world Application of Racial and Ethnic Imputation and Cohort Balancing Techniques to Deliver Equitable Clinical Trial Recruitment.

Enhancing diversity and inclusion in clinical trial recruitment, especially for historically marginalized populations including Black, Indigenous, and People of Color individuals, is essential. This practice ensures that generalizable trial results are achieved to deliver safe, effective, and equitable health and healthcare. However, recruitment is limited by two inextricably linked barriers - the inability to recruit and retain enough trial participants, and the lack of diversity amongst trial populations whereby racial and ethnic groups are underrepresented when compared to national composition. To overcome these barriers, this study describes and evaluates a framework that combines 1) probabilistic and machine learning models to accurately impute missing race and ethnicity fields in real-world data including medical and pharmacy claims for the identification of eligible trial participants, 2) randomized controlled trial experimentation to deliver an optimal patient outreach strategy, and 3) stratified sampling techniques to effectively balance cohorts to continuously improve engagement and recruitment metrics.

Impact of COVID-19 and effects of BNT162b2 on patient-reported outcomes: quality of life, symptoms, and work productivity among US adult outpatients.

BACKGROUND: Although there is extensive literature on the clinical benefits of COVID-19 vaccination, data on humanistic effects are limited. This study evaluated the impact of SARS-CoV-2 infection on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Impairment (WPAI) prior to and one month following infection between individuals vaccinated with BNT162b2 and those unvaccinated. METHODS: Subjects with ≥ 1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022 and 04/30/2022. Socio-demographics, clinical characteristics and vaccination status were evaluated. Self-reported symptoms, HRQoL, and WPAI outcomes were assessed using questionnaires and validated instruments (EQ-5D-5L, WPAI-GH) across acute COVID time points from pre-COVID to Week 4, and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for several covariates. Effect size (ES) of Cohen's d was calculated to quantify the magnitude of outcome changes within and between vaccination groups. RESULTS: The study population included 430 subjects: 197 unvaccinated and 233 vaccinated with BNT162b2. Mean (SD) age was 42.4 years (14.3), 76.0% were female, 38.8% reported prior infection and 24.2% at least one comorbidity. Statistically significant differences in outcomes were observed compared with baseline and between groups. The EQ-Visual analogue scale scores and Utility Index dropped in both cohorts at Day 3 and increased by Week 4 but did not return to pre-COVID levels. The mean changes were statistically lower in the BNT162b2 cohort at Day 3 and Week 4. The BNT162b2 cohort reported lower prevalence and fewer symptoms at index date and Week 4. At Week 1, COVID-19 had a large impact on all WPAI-GH domains: the work productivity time loss among unvaccinated and vaccinated was 65.0% and 53.8%, and the mean activity impairment was 50.2% and 43.9%, respectively. Except for absenteeism at Week 4, the BNT162b2 cohort was associated with statistically significant less worsening in all WPAI-GH scores at both Week 1 and 4. CONCLUSIONS: COVID-19 negatively impacted HRQoL and work productivity among mildly symptomatic outpatients. Compared with unvaccinated, those vaccinated with BNT162b2 were less impacted by COVID-19 infection and recovered faster.

Multimorbidity and Its Associations With Anxiety and Depression Among Newly Diagnosed Patients With Breast Cancer: A Retrospective Observational Cohort Study in a US Commercially Insured and Medicare Advantage Population.

BACKGROUND: Multimorbidity is common in patients with breast cancer, thus increasing the complexity of cancer care and economic burden, worsening their prognosis and quality of life. The prevalence of multimorbidity and its influence on psychological distress among patients with breast cancer have not been well characterized. OBJECTIVES: To examine the prevalence of multimorbidity and its associations with anxiety and depression among newly diagnosed patients with breast cancer. METHODS: We conducted a retrospective observational cohort study using a large administrative claims database. Patients with breast cancer (ICD-10-CM: C50.x) were identified during the study period (1/1/2017-12/31/2020). The index date was defined as the diagnosis date of breast cancer. Demographics and comorbid conditions were assessed using data within 12 months prior to the index date. Multimorbidity was defined as the presence of ≥2 comorbid conditions. Anxiety and depression were examined using data within 12 months after the index date. Multivariable logistic regressions were performed to examine the associations between multimorbidity and anxiety and depression, adjusting for sociodemographic factors. RESULTS: Of the 6392 patients with newly diagnosed breast cancer, 86.9% had multimorbidity at the time of breast cancer diagnosis. The median number of comorbid conditions was 5. Overall, 27.7% experienced anxiety, and 21.9% experienced depression in the first year following breast cancer diagnosis. An increased number of comorbid conditions was associated with elevated prevalence of both anxiety and depression. After adjusting for possible confounding factors, number of comorbid conditions was significantly associated with risk of anxiety (adjusted odds ratio [95% confidence interval (CI)]: 1.17 [1.15-1.19]), and depression (1.24 [1.21-1.26]); all P < .0001. CONCLUSIONS: Multimorbidity was highly prevalent among patients with breast cancer and was strongly associated with increased risk of anxiety and depression in the first year following breast cancer diagnosis. The presence of multimorbidity, anxiety, and depression should be considered in the context of clinical decision making to optimize cancer care and improve mental health and quality of life.

Multiple Comorbidities, Psychiatric Disorders, Healthcare Resource Utilization and Costs Among Adults with Essential Tremor: A Retrospective Observational Study in a Large US Commercially Insured and Medicare Advantage Population.

Background: Essential tremor (ET), the most common movement disorder, often impairs patients' ability to perform activities of daily living, mental health, and quality of life. Objectives: To assess comorbidities, psychiatric disorders, healthcare resource utilization (HCRU), and costs among patients with ET compared with patients without ET. Methods: This retrospective observational study was conducted using a large US administrative claims database. Patients with ET were identified during the study period (1/1/2017-12/31/2019). The earliest claim date with ET diagnosis was identified as the index date. An index date was assigned randomly for each non-ET patient. Patients had to be at least 22 years old and be enrolled in the health plan for at least 6 months before and at least 12 months after the index date. Patients with and those without ET were matched 1:1 on age, gender, payer type, and first 3 digits of their ZIP code. Comorbidities were assessed using data within 6 months prior to the index date. Psychiatric disorders, HCRU, and costs were examined using data within 12 months after the index date. Results: The mean (SD) age of ET patients (n = 5286) was 70.8 (11.8) years, 49.1% were female, and 82.9% were Medicare Advantage members. In the 12 months following the index date, 26.0% of patients had no insurance claims for ET-related pharmacotherapy or invasive therapies. Patients with ET had a higher number of comorbidities than non-ET patients (5.3 [3.2] vs 4.0 [3.3]); a higher prevalence of psychiatric disorders (depression: 25.6% vs 15.3%; adjusted odds ratio (AOR) [95% CI], 1.56 [1.41-1.73]; anxiety: 27.7% vs 15.5%, AOR: 1.78 [1.61-1.96]); and higher total healthcare costs: $17 560 [$39 972] vs $13 237 [$27 098], adjusted cost ratio [95% CI]: 1.11 [1.06-1.16]; all P<.0001. Discussion: Highly prevalent multiple comorbidities and psychiatric disorders should be considered in the context of clinical decision-making to optimize ET management. Conclusions: This study represents the largest observational study to report ET disease and economic burdens in a real-world setting. The data demonstrate increased comorbidity, mental health, and healthcare cost burdens among ET patients compared with matched non-ET patients. These findings underscore the need for innovative care for this complex population.

Optimizing vaccine distribution via mobile clinics: a case study on COVID-19 vaccine distribution to long-term care facilities.

BACKGROUND: People living in clustered communities with health comorbidities are highly vulnerable to COVID-19 infection. Rapid vaccination of vulnerable populations is critical to reducing fatalities and mitigating strain on healthcare systems. We present a case study on COVID-19 vaccine distribution via mobile vans to residents/staff of 47,907 long-term care facilities (LTCFs) across the United States that relied on algorithms to optimize vaccine distribution. METHODS: We developed a modeling framework for vaccine distribution to high-risk populations in a supply-constrained environment. Our framework decomposed this challenge as two separate problems: an assignment problem where we optimally mapped each LTCF to select CVS stores responsible for distributing vaccines; and a scheduling problem where we developed an algorithm to assign available resources efficiently. RESULTS: We assigned 1,214 retail stores as depots for vaccine distribution to LTCFs throughout the United States. Forty-one percent of matched depot-LTCF pairs were within 5 miles of a depot, 74% were within 20 miles, and only 8% mapped to depots farther than 50 miles away. Our two-step approach ensured that the first LTCF vaccination dose was distributed within 9 days after the program start date in 76% of states, and greater than 90% of doses were administered in the minimum amount of time. CONCLUSIONS: We demonstrate that algorithmic approaches are instrumental in maximizing vaccine distribution efficiency. Our learning and framework may be of use to other organizations, including communities where mobile clinics can be established to efficiently distribute vaccines and other healthcare resources in a variety of scenarios.