Association of stay-at-home orders and COVID-19 incidence and mortality in rural and urban United States: a population-based study.

OBJECTIVE: We examined the association between stay-at-home order implementation and the incidence of COVID-19 infections and deaths in rural versus urban counties of the United States. DESIGN: We used an interrupted time-series analysis using a mixed effects zero-inflated Poisson model with random intercept by county and standardised by population to examine the associations between stay-at-home orders and county-level counts of daily new COVID-19 cases and deaths in rural versus urban counties between 22 January 2020 and 10 June 2020. We secondarily examined the association between stay-at-home orders and mobility in rural versus urban counties using Google Community Mobility Reports. INTERVENTIONS: Issuance of stay-at-home orders. PRIMARY AND SECONDARY OUTCOME MEASURES: Co-primary outcomes were COVID-19 daily incidence of cases (14-day lagged) and mortality (26-day lagged). Secondary outcome was mobility. RESULTS: Stay-at-home orders were implemented later (median 30 March 2020 vs 28 March 2020) and were shorter in duration (median 35 vs 54 days) in rural compared with urban counties. Indoor mobility was, on average, 2.6%-6.9% higher in rural than urban counties both during and after stay-at-home orders. Compared with the baseline (pre-stay-at-home) period, the number of new COVID-19 cases increased under stay-at-home by incidence risk ratio (IRR) 1.60 (95% CI, 1.57 to 1.64) in rural and 1.36 (95% CI, 1.30 to 1.42) in urban counties, while the number of new COVID-19 deaths increased by IRR 14.21 (95% CI, 11.02 to 18.34) in rural and IRR 2.93 in urban counties (95% CI, 1.82 to 4.73). For each day under stay-at-home orders, the number of new cases changed by a factor of 0.982 (95% CI, 0.981 to 0.982) in rural and 0.952 (95% CI, 0.951 to 0.953) in urban counties compared with prior to stay-at-home, while number of new deaths changed by a factor of 0.977 (95% CI, 0.976 to 0.977) in rural counties and 0.935 (95% CI, 0.933 to 0.936) in urban counties. Each day after stay-at-home orders expired, the number of new cases changed by a factor of 0.995 (95% CI, 0.994 to 0.995) in rural and 0.997 (95% CI, 0.995 to 0.999) in urban counties compared with prior to stay-at-home, while number of new deaths changed by a factor of 0.969 (95% CI, 0.968 to 0.970) in rural counties and 0.928 (95% CI, 0.926 to 0.929) in urban counties. CONCLUSION: Stay-at-home orders decreased mobility, slowed the spread of COVID-19 and mitigated COVID-19 mortality, but did so less effectively in rural than in urban counties. This necessitates a critical re-evaluation of how stay-at-home orders are designed, communicated and implemented in rural areas.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

AIMS: Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy. METHODS AND RESULTS: From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively. Factors associated with CRT response were identified (defined as improvement in left ventricular ejection fraction [LVEF] ≥5% 6 months post-implant) and the associated impact on the primary outcome of death, implantation of a left ventricular assist device or cardiac transplantation was assessed. We identified 105 patients (mean age 51 ± 10 years) undergoing CRT, including 70 (67%) who underwent CRT as a CIED upgrade. The mean change in LVEF ∼6 months post-CRT was +4 ± 9%. A CRT response occurred in 40 (38%) patients and was associated with lower baseline LVEF or a high percentage of right ventricular pacing prior to CRT in patients with pre-existing CIED. In patients with a European Society of Cardiology class I guideline indication for CRT, response rates were 61%. A CRT response was evident at thresholds of LVEF ≤45% or percent pacing ≥50%. There was a 1.3 year estimated median difference in event-free survival in those who responded to CRT (p = 0.04). CONCLUSION: Systolic function improves in patients with LMNA cardiomyopathy who undergo CRT, especially with strong guideline indications for implantation. Post-CRT improvements in LVEF are associated with survival benefits in this population with otherwise limited options.

Association of Titin Variations With Late-Onset Dilated Cardiomyopathy.

IMPORTANCE: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM). OBJECTIVE: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM. DESIGN, SETTING, AND PARTICIPANTS: A population of patients with late-onset DCM who had undergone genetic testing in 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as the presence of pathogenic or likely pathogenic (P/LP) variants. MAIN OUTCOMES AND MEASURES: The study outcome was all-cause mortality. RESULTS: A total of 184 patients older than 60 years (103 female [56%]; mean [SD] age, 67 [6] years; mean [SD] left ventricular ejection fraction, 32% [10%]) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin-truncating variants were the most prevalent (present in 46 [25%] of the total population and accounting for 46 [69%] of all genotype-positive patients). During a median (interquartile range) follow-up of 42 (10-115) months, 23 patients (13%) died; 17 (25%) of these were carriers of P/LP variants, while 6 patients (5.1%) were genotype-negative. CONCLUSIONS AND RELEVANCE: Late-onset DCM might represent a distinct subgroup characterized by and a high genetic variation burden, largely due to titin-truncating variants. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in older patients.

Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A State-of-the-Art Review.

The vast majority of patients (>99%) with severe acute respiratory syndrome coronavirus 2 survive immediate infection but remain at risk for persistent and/or delayed multisystem. This review of published reports through May 31, 2021, found that manifestations of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) affect between 33% and 98% of coronavirus disease 2019 survivors and comprise a wide range of symptoms and complications in the pulmonary, cardiovascular, neurologic, psychiatric, gastrointestinal, renal, endocrine, and musculoskeletal systems in both adult and pediatric populations. Additional complications are likely to emerge and be identified over time. Although data on PASC risk factors and vulnerable populations are scarce, evidence points to a disproportionate impact on racial/ethnic minorities, older patients, patients with preexisting conditions, and rural residents. Concerted efforts by researchers, health systems, public health agencies, payers, and governments are urgently needed to better understand and mitigate the long-term effects of PASC on individual and population health.