Evaluating the implementation of weekly rifapentine-isoniazid (3HP) for tuberculosis prevention among people living with HIV in Uganda: A qualitative evaluation of the 3HP Options Trial.

Three months of isoniazid-rifapentine (3HP) is being scaled up for tuberculosis (TB) preventive treatment (TPT) among people living with HIV (PLHIV) in high-burden settings. More evidence is needed to identify factors influencing successful 3HP delivery. We conducted a qualitative assessment of 3HP delivery nested within the 3HP Options Trial, which compared three optimized strategies for delivering 3HP: facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), and patient choice between facilitated DOT and facilitated SAT at the Mulago HIV/AIDS clinic in Kampala, Uganda. We conducted 72 in-depth interviews among PLHIV purposively selected to investigate factors influencing 3HP acceptance and completion. We conducted ten key informant interviews with healthcare providers (HCPs) involved in 3HP delivery to identify facilitators and barriers at the clinic level. We used post-trial 3HP delivery data to assess sustainability. We conducted an inductive thematic analysis and aligned the emergent themes with the RE-AIM framework dimensions to report implementation outcomes. Understanding the need for TPT, once-weekly dosing, shorter duration, and perceived 3HP safety enhanced acceptance overall. Treatment monitoring by HCPs and reduced risk of HIV status disclosure enabled DOT acceptance. Dosing autonomy enabled SAT acceptance. Switching between DOT and SAT as required enabled acceptance for patient choice. Dosing reminders, reimbursement for clinical visits, and social support enabled 3HP completion; pill burden, side effects, and COVID-19-related treatment restrictions hindered completion. All HCPs were trained and participated in 3HP delivery with high fidelity. Training, care integration, and collaboration among HCPs enabled, whereas initial concerns about 3HP safety among HCPs delayed 3HP adoption and implementation. SAT was maintained post-trial; DOT was discontinued due to inadequate ongoing financial support beyond the study period. Facilitated delivery strategies made 3HP treatment convenient for PLHIV and were feasible and implemented with high fidelity by HCPs. However, the costs of 3HP facilitation may limit wider scale-up.

Adverse events reported during weekly isoniazid-rifapentine (3HP) tuberculosis preventive treatment among people living with HIV in Uganda.

Background: Short-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AE) could differ in routine settings. Real-world data on AE type, frequency, and timing is crucial for health systems considering 3HP programmatic scale-up. Methods: We reviewed AEs among people living with HIV (PLHIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including lab tests, diagnoses made, medications prescribed, and treatment interruptions. Results: Among 1655 PLHIV treated between July 2020-September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE. Conclusions: In a routine setting, 3HP was safe with 16% of PLHIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention.

Preferences of people living with HIV for features of tuberculosis preventive treatment regimens - a discrete choice experiment.

Background: Tuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens. Methods: We conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. In nine random choice tasks, participants chose between two hypothetical TPT regimens with different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects). We analyzed preferences using hierarchical Bayesian estimation, latent class analysis, and willingness-to-trade simulations. Results: Of 400 PLHIV, 392 (median age 44, 72% female, 91% TPT-experienced) had high quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6 - 33.2), followed by frequency (20.5% [95% CI 19.7 - 21.3]), duration (19.5% [95% CI 18.6 - 20.5]), and need for ART dosage adjustment (18.2% [95% CI 17.2 - 19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N=222; 57%); another was averse to ART dosage adjustment (N=107; 27%); and the last prioritized short and tolerable regimens (N=63; 16%). All groups highly valued fewer pills per dose. Participants were willing to accept a regimen of 2.8 months' additional duration [95% CI: 2.4 - 3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4 - 4.8] months for weekly rather than daily dosing, and 2.2 [95% CI 1.3 - 3.0] months to avoid ART dosage adjustment. Conclusions: To align with preferences of PLHIV, decision-makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing, and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.

Excess Mortality With Alzheimer Disease and Related Dementias as an Underlying or Contributing Cause During the COVID-19 Pandemic in the US.

Importance: Adults with Alzheimer disease and related dementias (ADRD) are particularly vulnerable to the direct and indirect effects of the COVID-19 pandemic. Deaths associated with ADRD increased substantially in pandemic year 1. It is unclear whether mortality associated with ADRD declined when better prevention strategies, testing, and vaccines became widely available in year 2. Objective: To compare pandemic-era excess deaths associated with ADRD between year 1 and year 2 overall and by age, sex, race and ethnicity, and place of death. Design, Setting, and Participants: This time series analysis used all death certificates of US decedents 65 years and older with ADRD as an underlying or contributing cause of death from January 2014 through February 2022. Exposure: COVID-19 pandemic era. Main Outcomes and Measures: Pandemic-era excess deaths associated with ADRD were defined as the difference between deaths with ADRD as an underlying or contributing cause observed from March 2020 to February 2021 (year 1) and March 2021 to February 2022 (year 2) compared with expected deaths during this period. Expected deaths were estimated using data from January 2014 to February 2020 fitted with autoregressive integrated moving average models. Results: Overall, 2 334 101 death certificates were analyzed. A total of 94 688 (95% prediction interval [PI], 84 192-104 890) pandemic-era excess deaths with ADRD were estimated in year 1 and 21 586 (95% PI, 10 631-32 450) in year 2. Declines in ADRD-related deaths in year 2 were substantial for every age, sex, and racial and ethnic group evaluated. Pandemic-era ADRD-related excess deaths declined among nursing home/long-term care residents (from 34 259 [95% PI, 25 819-42 677] in year 1 to -22 050 [95% PI, -30 765 to -13 273] in year 2), but excess deaths at home remained high (from 34 487 [95% PI, 32 815-36 142] in year 1 to 28 804 [95% PI, 27 067-30 571] in year 2). Conclusions and Relevance: This study found that large increases in mortality with ADRD as an underlying or contributing cause of death occurred in COVID-19 pandemic year 1 but were largely mitigated in pandemic year 2. The most pronounced declines were observed for deaths in nursing home/long-term care settings. Conversely, excess deaths at home and in medical facilities remained high in year 2.

Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study.

OBJECTIVE: To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection. DESIGN: Population based, longitudinal cohort. SETTING: General population of canton of Zurich, Switzerland. PARTICIPANTS: 1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection. MAIN OUTCOME MEASURES: Trajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection. RESULTS: 22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%)). CONCLUSIONS: Up to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials. REGISTRATIONS: ISRCTN18181860, .

Best-worst scaling preferences among patients with well-controlled epilepsy: Pilot results.

Epilepsy is a common, serious condition. Fortunately, seizure risk decreases with increasing seizure-free time on antiseizure medications (ASMs). Eventually, patients may consider whether to stop ASMs, which requires weighing treatment benefit versus burden. We developed a questionnaire to quantify patient preferences relevant to ASM decision-making. Respondents rated how concerning they would finding relevant items (e.g., seizure risks, side effects, cost) on a Visual Analogue Scale (VAS, 0-100) and then repeatedly chose the most and least concerning item from subsets (best-worst scaling, BWS). We pretested with neurologists, then recruited adults with epilepsy who were seizure-free at least one year. Primary outcomes were recruitment rate, and qualitative and Likert-based feedback. Secondary outcomes included VAS ratings and best-minus-worst scores. Thirty-one of 60 (52%) contacted patients completed the study. Most patients felt VAS questions were clear (28; 90%), easy to use (27; 87%), and assessed preferences well (25; 83%). Corresponding results for BWS questions were 27 (87%), 29 (97%), and 23 (77%). Physicians suggested adding a 'warmup' question showing a completed example and simplifying terminology. Patients suggested ways to clarify instructions. Cost, inconvenience of taking medication, and laboratory monitoring were the least concerning items. Cognitive side effects and a 50% seizure risk in the next year were the most concerning items. Twelve (39%) of patients made at least one 'inconsistent choice' for example ranking a higher seizure risk as lower concern compared with a lower seizure risk, though 'inconsistent choices' represented only 3% of all question blocks. Our recruitment rate was favorable, most patients agreed the survey was clear, and we describe areas for improvement. 'Inconsistent' responses may lead us to collapse seizure probability items into a single 'seizure' category. Evidence regarding how patients weigh benefits and harms may inform care and guideline development.

COVID-19 mortality and excess mortality among working-age residents in California, USA, by occupational sector: a longitudinal cohort analysis of mortality surveillance data.

BACKGROUND: During the first year of the COVID-19 pandemic, workers in essential sectors had higher rates of SARS-CoV-2 infection and COVID-19 mortality than those in non-essential sectors. It is unknown whether disparities in pandemic-related mortality across occupational sectors have continued to occur during the periods of SARS-CoV-2 variants and vaccine availability. METHODS: In this longitudinal cohort study, we obtained data from the California Department of Public Health on all deaths occurring in the state of California, USA, from Jan 1, 2016, to Dec 31, 2021. We restricted our analysis to residents of California who were aged 18-65 years at time of death and died of natural causes. We classified the occupational sector into nine essential sectors; non-essential; or unemployed or without an occupation provided on the death certificate. We calculated the number of COVID-19 deaths in total and per capita that occurred in each occupational sector. Separately, using autoregressive integrated moving average models, we estimated total, per-capita, and relative excess natural-cause mortality by week between March 1, 2020, and Nov 30, 2021, stratifying by occupational sector. We additionally stratified analyses of occupational risk into counties with high versus low vaccine uptake, categorising high-uptake regions as counties where at least 50% of the population were fully vaccinated according to US guidelines by Aug 1, 2021. FINDINGS: From March 1, 2020, to Nov 30, 2021, 24 799 COVID-19 deaths were reported in residents of California aged 18-65 years and an estimated 28 751 (95% prediction interval 27 853-29 653) excess deaths. People working in essential sectors were associated with higher COVID-19 deaths and excess deaths than were those working in non-essential sectors, with the highest per-capita COVID-19 mortality in the agriculture (131·8 per 100 000 people), transportation or logistics (107·1 per 100 000), manufacturing (103·3 per 100 000), facilities (101·1 per 100 000), and emergency (87·8 per 100 000) sectors. Disparities were wider during periods of increased infections, including during the Nov 29, 2020, to Feb 27, 2021, surge in infections, which was driven by the delta variant (B.1.617.2) and occurred during vaccine uptake. During the June 27 to Nov 27, 2021 surge, emergency workers had higher COVID-19 mortality (113·7 per 100 000) than workers from any other sector. Workers in essential sectors had the highest COVID-19 mortality in counties with low vaccination uptake, a difference that was more pronounced during the period of the delta infection surge during Nov 29, 2020, to Feb 27, 2021. INTERPRETATION: Workers in essential sectors have continued to bear the brunt of high COVID-19 and excess mortality throughout the pandemic, particularly in the agriculture, emergency, manufacturing, facilities, and transportation or logistics sectors. This high death toll has continued during periods of vaccine availability and the delta surge. In an ongoing pandemic without widespread vaccine coverage and with anticipated threats of new variants, the USA must actively adopt policies to more adequately protect workers in essential sectors. FUNDING: US National Institute on Aging, Swiss National Science Foundation, and US National Institute on Drug Abuse.

Fingolimod versus interferon beta 1-a: Benefit-harm assessment approach based on TRANSFORMS individual patient data.

Background: Fingolimod is a disease-modifying drug approved for multiple sclerosis but its benefit-harm balance has never been assessed compared to other active treatments. Objectives: Our aim was to compare the benefits and harms of fingolimod with interferon beta-1a using individual patient data from TRial Assessing injectable interferon versus FTY720 Oral in RRMS trial. Methods: We modelled the health status of patients over time including Expanded Disability Status Scale measurements, relapses and any adverse events. We assessed the mean health status between arms and the proportion of patients whose health deteriorated or improved relatively to baseline, using a prespecified minimal important difference of 4.6. We performed sensitivity analyses to test our assumptions. Results: Main and sensitivity analyses favoured fingolimod 0.5 mg over interferon beta-1a. The average health status difference was 1.01 (95% CI 0.93-1.08). Patients on fingolimod 0.5 mg were 0.47 (95% CI: 0.35-0.63, p < 0.001) times less likely to experience a relevant decline in health status compared to interferon beta-1a patients, with a number needed to treat of 7.10 [5.18, 11.23]. Conclusions: Fingolimod's net benefit over interferon beta-1a did not reach the clinical relevance over 1 year, but the decreased risk for health status deterioration may be more pronounced more long term and patients may prefer less treatment burden associated with fingolimod.

Dynamics of racial disparities in all-cause mortality during the COVID-19 pandemic.

As research documenting disparate impacts of COVID-19 by race and ethnicity grows, little attention has been given to dynamics in mortality disparities during the pandemic and whether changes in disparities persist. We estimate age-standardized monthly all-cause mortality in the United States from January 2018 through February 2022 for seven racial/ethnic populations. Using joinpoint regression, we quantify trends in race-specific rate ratios relative to non-Hispanic White mortality to examine the magnitude of pandemic-related shifts in mortality disparities. Prepandemic disparities were stable from January 2018 through February 2020. With the start of the pandemic, relative mortality disadvantages increased for American Indian or Alaska Native (AIAN), Native Hawaiian or other Pacific Islander (NHOPI), and Black individuals, and relative mortality advantages decreased for Asian and Hispanic groups. Rate ratios generally increased during COVID-19 surges, with different patterns in the summer 2021 and winter 2021/2022 surges, when disparities approached prepandemic levels for Asian and Black individuals. However, two populations below age 65 fared worse than White individuals during these surges. For AIAN people, the observed rate ratio reached 2.25 (95% CI = 2.14, 2.37) in October 2021 vs. a prepandemic mean of 1.74 (95% CI = 1.62, 1.86), and for NHOPI people, the observed rate ratio reached 2.12 (95% CI = 1.92, 2.33) in August 2021 vs. a prepandemic mean of 1.31 (95% CI = 1.13, 1.49). Our results highlight the dynamic nature of racial/ethnic disparities in mortality and raise alarm about the exacerbation of mortality inequities for Indigenous groups due to the pandemic.

Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort.

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection.

Excess natural-cause deaths in California by cause and setting: March 2020 through February 2021.

Excess mortality has exceeded reported deaths from Covid-19 during the pandemic. This gap may be attributable to deaths that occurred among individuals with undiagnosed Covid-19 infections or indirect consequences of the pandemic response such as interruptions in medical care; distinguishing these possibilities has implications for public health responses. In the present study, we examined patterns of excess mortality over time and by setting (in-hospital or out-of-hospital) and cause of death using death certificate data from California. The estimated number of excess natural-cause deaths from 2020 March 1 to 2021 February 28 (69,182) exceeded the number of Covid-19 diagnosed deaths (53,667) by 29%. Nearly half, 47.4% (32,775), of excess natural-cause deaths occurred out of the hospital, where only 28.6% (9,366) of excess mortality was attributed to Covid-19. Over time, increases or decreases in excess natural non-Covid-19 mortality closely mirrored increases or decreases in Covid-19 mortality. The time series were positively correlated in out-of-hospital settings, particularly at time lags when excess natural-cause deaths preceded reported Covid-19 deaths; for example, when comparing Covid-19 deaths to excess natural-cause deaths in the week prior, the correlation was 0.73. The strong temporal association of reported Covid-19 deaths with excess out-of-hospital deaths from other reported natural-cause causes suggests Covid-19 deaths were undercounted during the first year of the pandemic.

Association between willingness to deprescribe and health outcome priorities among U.S. older adults: Results of a national survey.

BACKGROUND: It is not known whether older adults' willingness to deprescribe is associated with their health outcome priorities related to medications. METHODS: A cross-sectional survey was conducted from March-April 2020 using a nationally representative online panel. The survey presented two vignettes: (1) a preventive medicine; and (2) a symptom-relief medicine. Participants were asked whether they would be willing to stop each medicine if their doctor recommended it, and to rate their level of agreement with two health outcome priorities statements: "I am willing to accept the risk of future side effects … to feel better now," and "I would prefer to take fewer medicines, even if … I may not live as long or may have bothersome symptoms sometimes." Ordinal logistic regression was used to examine associations between willingness to stop each medicine, baseline characteristics and health outcome priorities. RESULTS: Of 1193 panel members ≥65 years invited to participate, 835 (70%) completed the survey. Mean (SD) age was 73 years; 496 (59%) had taken a statin and 124 (15%) a prescription sedative-hypnotic. 507 (61%) were willing to stop preventive medicines; 276 (33%) were maybe willing. 419 (50%) were willing to stop symptom-relief medicines; 380 (46%) were maybe willing. Prioritizing fewer medicines was associated with higher odds of being willing to stop symptom-relief medicines (aOR 1.43 [95% CI 1.02-2.00]) and preventive medicines (aOR 1.52 [95% CI 1.05-2.18]). Prioritizing now over future was associated with lower odds of being willing to stop symptom-relief medicines (aOR 0.62 [95% CI 0.39-1.00]). Current/prior use of statins was associated with lower willingness to stop preventive medicines (aOR 0.66 [95% CI 0.48-0.91]). CONCLUSIONS: Older adults' health outcome priorities related to medication use are associated with their willingness to consider deprescribing. Future research should determine how best to elicit patients' health outcome priorities to facilitate goal-concordant decisions about medication use.

Individual-Level Evaluation of the Exposure Notification Cascade in the SwissCovid Digital Proximity Tracing App: Observational Study.

BACKGROUND: Digital proximity tracing (DPT) aims to complement manual contact tracing (MCT) in identifying exposed contacts and preventing further transmission of SARS-CoV-2 in the population. Although several DPT apps, including SwissCovid, have shown to have promising effects on mitigating the pandemic, several challenges have impeded them from fully achieving the desired results. A key question now relates to how the effectiveness of DPT can be improved, which requires a better understanding of factors influencing its processes. OBJECTIVE: In this study, we aim to provide a detailed examination of the exposure notification (EN) cascade and to evaluate potential contextual influences for successful receipt of an EN and subsequent actions taken by cases and contacts in different exposure settings. METHODS: We used data from 285 pairs of SARS-CoV-2-infected cases and their contacts within an observational cohort study of cases and contacts identified by MCT and enrolled between August 6, 2020, and January 17, 2021, in the canton of Zurich, Switzerland. We surveyed participants with electronic questionnaires. Data were summarized descriptively and stratified by exposure setting. RESULTS: We found that only 79 (58.5%) of 135 contacts using the SwissCovid app whose corresponding cases reported to have triggered the EN also received one. Of these, 18 (22.8%) received the EN before MCT. Compared to those receiving an EN after MCT (61/79, 77.2%), we observed that a higher proportion of contacts receiving an EN before MCT were exposed in nonhousehold settings (11/18, 61.1%, vs 34/61, 55.7%) and their corresponding cases had more frequently reported mild-to-moderate symptoms (14/18, 77.8%, vs 42/61, 68.9%). Of the 18 contacts receiving an EN before MCT, 14 (77.8%) took recommended measures: 12 (66.7%) were tested for SARS-CoV-2, and 7 (38.9%) called the SwissCovid Infoline. In nonhousehold settings, the proportion of contacts taking preventive actions after receiving an EN was higher compared to same-household settings (82%, vs 67%). In addition, 1 (9%) of 11 ENs received in the nonhousehold setting before MCT led to the identification of a SARS-CoV-2-infected case by prompting the contact to get tested. This corresponds to 1 in 85 exposures of a contact to a case in a nonhousehold setting, in which both were app users and the case triggered the EN. CONCLUSIONS: Our descriptive evaluation of the DPT notification cascade provides further evidence that DPT is an important complementary tool in pandemic mitigation, especially in nonhousehold exposure settings. However, the effect of DPT apps can only be exerted if code generation processes are efficient and exposed contacts are willing to undertake preventive actions. This highlights the need to focus efforts on keeping barriers to efficient code generation as low as possible and promoting not only app adoption but also compliance with the recommended measures upon an EN. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Registry 14990068; https://doi.org/10.1186/ISRCTN14990068.

Mental health of individuals infected with SARS-CoV-2 during mandated isolation and compliance with recommendations-A population-based cohort study.

BACKGROUND: Isolation is an indispensable measure to contain the SARS-CoV-2 virus, but it may have a negative impact on mental health and overall wellbeing. Evidence on the isolation experience, facilitating and complicating factors is needed to mitigate negative effects. METHODS AND FINDINGS: This observational, population-based cohort study enrolled 1547 adults from the general population with SARS-CoV-2 infection reported to authorities between 27 February 2020 and 19 January 2021 in Zurich, Switzerland. We assessed the proportion of individuals reporting symptoms of depression and anxiety before, during and after isolation (by DASS-21), and queried worries, positive experiences, and difficulties. We analyzed the association of these outcomes with socio-demographics using ordinal regression. Additionally, we report free-text statements by participants to capture most important aspects of isolation. The proportion of participants affected by depression or anxiety increased during isolation from 10·0% to 17·1% and 9·1% to 17·6%, respectively. Ordinal regression showed that taking care of children increased the difficulty of isolation (OR 2·10, CI 1·43-3·08) and risk of non-compliance (OR 1·63, CI 1·05-2·53), especially in younger participants. A facilitating factor that individuals commonly expressed was receiving more support during isolation. CONCLUSION: Isolation due to SARS-CoV-2 presents a mental burden, especially for younger individuals and those taking care of children. Public health authorities need to train personnel and draw from community-based resources to provide targeted support, information, and guidance to individuals during isolation. Such efforts could alleviate the negative impact isolation has on the mental and physical health of individuals and ensure compliance of the population with recommendations.

Adherence and Association of Digital Proximity Tracing App Notifications With Earlier Time to Quarantine: Results From the Zurich SARS-CoV-2 Cohort Study.

Objectives: We aimed to evaluate the effectiveness of the SwissCovid digital proximity tracing (DPT) app in notifying exposed individuals and prompting them to quarantine earlier compared to individuals notified only by manual contact tracing (MCT). Methods: A population-based sample of cases and close contacts from the Zurich SARS-CoV-2 Cohort was surveyed regarding SwissCovid app use and SARS-CoV-2 exposure. We descriptively analyzed app adherence and effectiveness, and evaluated its effects on the time between exposure and quarantine among contacts using stratified multivariable time-to-event analyses. Results: We included 393 SARS-CoV-2 infected cases and 261 close contacts. 62% of cases reported using SwissCovid and among those, 88% received and uploaded a notification code. 71% of close contacts were app users, of which 38% received a warning. Non-household contacts notified by SwissCovid started quarantine 1 day earlier and were more likely to quarantine earlier than those not warned by the app (HR 1.53, 95% CI 1.15-2.03). Conclusion: These findings provide evidence that DPT may reach exposed contacts faster than MCT, with earlier quarantine and potential interruption of SARS-CoV-2 transmission chains.

Burden of post-COVID-19 syndrome and implications for healthcare service planning: A population-based cohort study.

BACKGROUND: Longer-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization. METHODS: This population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes. RESULTS: Symptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care. CONCLUSIONS: In this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care.

Assessment of Patient-Preferred Language to Achieve Goal-Aligned Deprescribing in Older Adults.

Importance: How clinicians communicate about deprescribing, the structured process of reducing or stopping unnecessary, potentially harmful, or goal-discordant medicines, may be associated with the extent to which older adults are willing to do it. Objective: To examine older adults' preferences regarding different rationales a clinician may use to explain why a patient should stop an unnecessary or potentially harmful medication. Design, Setting, and Participants: This cross-sectional survey study was conducted from March 25 to April 19, 2020, among a nationally representative, probability-based online survey panel (KnowledgePanel). KnowledgePanel members aged 65 years and older were recruited by random digit dialing and address-based sampling. Data were analyzed from May 4 to July 8, 2020. Exposures: The survey presented 2 vignettes involving hypothetical older adults. One described a statin being used for primary prevention by a person with functional impairment and polypharmacy. The second described a sedative-hypnotic, such as zolpidem, being used for insomnia by a person with good functional status. Main Outcomes and Measures: After each vignette, participants expressed preferences using a best-worst scaling method for 7 different phrases a clinician may use to explain why they should reduce or stop the medication. Conditional logistic regression was used to quantify respondents' relative preferences. Results: A total of 1193 KnowledgePanel members were invited, and 835 respondents (70.0%) completed the survey. The mean (SD) age was 73 (6) years, 414 (49.6%) were women, and 671 (80.4%) self-identified as White individuals. A total of 496 respondents (59.8%) had ever used a statin, and 124 respondents (14.9%) had ever used a sedative-hypnotic. For both medications, the most preferred phrase to explain deprescribing focused on the risk of side effects. For statins, this phrase was 5.8-fold (95% CI, 5.3-6.3) more preferred than the least preferred option, which focused on the effort (treatment burden) involved in taking the medicine. For sedative-hypnotics, the phrase about side effects was 8.6-fold (95% CI, 7.9-9.5) more preferred over the least preferred option, "This medicine is unlikely to help you function better." Conclusions and Relevance: These findings suggest that among older adults, the most preferred rationale for deprescribing both preventive and symptom-relief medicines focused on the risk of side effects. These results could be used to inform clinical practice and improve effective communications around deprescribing in older adults.