Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection.

BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODS: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTS: Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONS: This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

Impact of prehospital mode of transport after severe injury: a multicenter evaluation from the Resuscitation Outcomes Consortium.

BACKGROUND: There is ongoing controversy about the relative effectiveness of air medical versus ground transportation for severely injured patients. In some systems, air medical crews may provide a higher level of care but may require longer transport times. We sought to evaluate the impact of mode of transport on outcome based on analysis of data from two randomized trials of prehospital hypertonic resuscitation. METHODS: Injured patients were enrolled based on prehospital evidence of hypovolemic shock (systolic blood pressure ≤70 mm Hg or systolic blood pressure = 71-90 mm Hg with heart rate ≥108 bpm) or severe traumatic brain injury (TBI; Glasgow Coma Scale score ≤8). Patient demographics, injury severity, and physiology were compared based on mode of transport. Multivariate logistic regression was used to determine the impact of mode of transport on 24-hour and 28-day survival for all patients and 6-month extended Glasgow Outcome Scale for patients with TBI, adjusting for differences in injury severity. RESULTS: Included were 2,049 patients, of which 703 (34%) were transported by air. Patients transported by air were more severely injured (mean Injury Severity Score, 30.3 vs. 22.8; p < 0.001), more likely to be in the TBI cohort (70% vs. 55.4%; p < 0.001), and more likely blunt mechanism (94.0% vs. 78.1%; p < 0.001). Patients transported by air had higher rates of prehospital intubation (81% vs. 36%; p < 0.001), received more intravenous fluids (mean 1.3 L vs. 0.8 L; p < 0.001), and had longer prehospital times (mean 76.1 minutes vs. 43.5 minutes; p < 0.001). Adjusted analysis revealed no significant impact of mode of transport on survival or 6-month neurologic outcome (air transport-28-day survival: odds ratio, 1.11; 95% confidence interval, 0.82-1.51; 6-month extended Glasgow Outcome Scale score ≤4: odds ratio, 0.94; 95% confidence interval, 0.68-1.31). CONCLUSION: There was no difference in the adjusted clinical outcome according to mode of transport. However, air medical transported more severely injured patients with more advanced life support procedures and longer prehospital time. LEVEL OF EVIDENCE: III.

Variability in case-mix adjusted in-hospital cardiac arrest rates.

BACKGROUND: It is unknown how in-hospital cardiac arrest (IHCA) rates vary across hospitals and predictors of variability. OBJECTIVES: Measure variability in IHCA across hospitals and determine if hospital-level factors predict differences in case-mix adjusted event rates. RESEARCH DESIGN: Get with the Guidelines Resuscitation (GWTG-R) (n=433 hospitals) was used to identify IHCA events between 2003 and 2007. The American Hospital Association survey, Medicare, and US Census were used to obtain detailed information about GWTG-R hospitals. PARTICIPANTS: Adult patients with IHCA. MEASURES: Case-mix-adjusted predicted IHCA rates were calculated for each hospital and variability across hospitals was compared. A regression model was used to predict case-mix adjusted event rates using hospital measures of volume, nurse-to-bed ratio, percent intensive care unit beds, palliative care services, urban designation, volume of black patients, income, trauma designation, academic designation, cardiac surgery capability, and a patient risk score. RESULTS: We evaluated 103,117 adult IHCAs at 433 US hospitals. The case-mix adjusted IHCA event rate was highly variable across hospitals, median 1/1000 bed days (interquartile range: 0.7 to 1.3 events/1000 bed days). In a multivariable regression model, case-mix adjusted IHCA event rates were highest in urban hospitals [rate ratio (RR), 1.1; 95% confidence interval (CI), 1.0-1.3; P=0.03] and hospitals with higher proportions of black patients (RR, 1.2; 95% CI, 1.0-1.3; P=0.01) and lower in larger hospitals (RR, 0.54; 95% CI, 0.45-0.66; P<0.0001). CONCLUSIONS: Case-mix adjusted IHCA event rates varied considerably across hospitals. Several hospital factors associated with higher IHCA event rates were consistent with factors often linked with lower hospital quality of care.

Comparison of role of early (less than six hours) to later (more than six hours) or no cardiac catheterization after resuscitation from out-of-hospital cardiac arrest.

Despite reports of patients with resuscitated sudden cardiac arrest (rSCA) receiving acute cardiac catheterization, the efficacy of this strategy is largely unknown. We hypothesized that acute cardiac catheterization of patients with rSCA would improve survival to hospital discharge. A retrospective cohort of 240 patients with out-of-hospital rSCA caused by ventricular tachycardia or fibrillation was identified from 11 institutions in Seattle, Washington from 1999 through 2002. Patients were grouped into those receiving acute catheterization within 6 hours (≤6-hour group, n = 61) and those with deferred catheterization at >6 hours or no catheterization during the index hospitalization (>6-hour group, n = 179). Attention was directed to survival to hospital discharge, neurologic status, extent of coronary artery disease, presenting electrocardiographic findings, and symptoms before arrest. Propensity-score methods were used to adjust for the likelihood of receiving acute catheterization. Survival was greater in patients who underwent acute catheterization (72% in the ≤6-hour group vs 49% in the >6-hour group, p = 0.001). Percutaneous coronary intervention was performed in 38 of 61 patients (62%) in the ≤6-hour group and 13 of 170 patients (7%) in the >6-hour group (p <0.0001). Neurologic status was similar in the 2 groups. A significantly larger percentage of patients in the acute catheterization group had symptoms before cardiac arrest and had ST-segment elevation on electrocardiogram after resuscitation. Age, bystander cardiopulmonary resuscitation, daytime presentation, history of percutaneous coronary intervention or stroke, and acute ST-segment elevation were positively associated with receiving cardiac catheterization. In conclusion, in this series of patients who sustained out-of-hospital cardiac arrest, acute catheterization (<6 hours of presentation) was associated with improved survival.

Severe traumatic injury: regional variation in incidence and outcome.

OBJECTIVES: The public health implications of regional variation in incidence and outcome of severe traumatic injury remain to be analyzed. The objective of this study was to determine whether the incidence and outcome associated with severe traumatic injury differs across geographic regions of North America. METHODS: A prospective, observational study was conducted of the Resuscitation Outcomes Consortium of all patients in 9 North American sites (6 US and 3 Canadian) sustaining severe traumatic injury from April 1, 2006 to March 31, 2007 followed to hospital discharge. Eligible patients were assessed by organized emergency medical services, and had field-based physiologic criteria including systolic blood pressure 29 per minute, advanced airway procedure, or traumatic death in the field. Census data were used to determine rates adjusted for age and sex. The main outcome measures were incidence rate, mortality rate, case fatality rate, and survival to discharge for patients sustaining severe traumatic injury assessed by EMS. RESULTS: The total catchment population of 20.5 million yielded 7080 cases of severe traumatic injury. Median age was 36 years and 67% were male. The median incidence of EMS-assessed severe traumatic injury per 100,000 population across sites was 37.4 (interquartile range [IQR] = 24.6-69.6); survival ranged from 39.8% to 80.8%, with a median of 64.5% (IQR = 55.5-78.4). About 942 cases were pronounced dead at the scene and 5857 patients were transported to hospital; 4477 (63.2%) were discharged alive. The median incidence of severe trauma due to a blunt mechanism, transported to hospital, was 25.8 (IQR = 13.1-44.3); survival ranged from 52.6% to 87.3%, with a median of 78.0% (IQR = 68.4-83.5). The median incidence of severe penetrating trauma, transported to hospital, was 2.6 (IQR = 1.5-10.4); survival ranged from 37.5% to 84.7%, with a median of 67.5% (IQR = 54.1-75.9). All P values for differences across sites for incidence and survival were <0.001. CONCLUSIONS: In this study involving 9 geographic regions in North America, there were significant and important regional differences in severe traumatic injury, incidence, and outcome. These differences were sustained for patients with either isolated blunt or penetrating injury mechanisms.

Reduction in incidence and fatality of out-of-hospital cardiac arrest in females of the reproductive age.

AIMS: The aim of this study was to determine relative risk (RR) of incidence and fatality of out-of-hospital cardiac arrest (OHCA) by gender and oestrogen status. METHODS AND RESULTS: In a prospective, population-based observational study from 1998 through 2007, incidence and neurologically intact 1-month survival after OHCA were compared by gender after grouping: 0-12 years, 13-49 years, and > or =50 years according to menarche and menopause age. Among 26 940 cardiac arrests, there were 11 179 females and 15 701 males. Age-adjusted RR of females for OHCA incidence compared with males was 0.72 [95% confidence interval (CI), 0.58-0.91] in age 0-12 years, 0.39 (95% CI, 0.37-0.43) in age 13-49 years, and 0.54 (95% CI, 0.52-0.55) in age > or =50 years. Females aged 13-49 years had a significantly higher good neurological outcome than males [adjusted odds ratio (OR), 2.00 (95% CI 1.21-3.32)]. This sex difference was larger than that in the other age groups [adjusted OR, 0.82 (95% CI, 0.06-12.02) in age 0-12 years and 1.23 (95% CI, 0.98-1.54) in age > or =50 years]. CONCLUSION: Reproductive females had a lower incidence and a better outcome of OHCA than females of other ages and males, which might be explained by cardioprotective effects of endogenous oestrogen on OHCA.

Evaluation of outcome and cost-effectiveness using an FDG PET-guided approach to management of patients with coronary disease and severe left ventricular dysfunction (PARR-2): rationale, design, and methods.

Patients with severe ventricular dysfunction and coronary disease have high morbidity and mortality. They may benefit from revascularization but have significant perioperative morbidity and mortality. Positron emission tomography (PET) imaging with F-18-fluorodeoxyglucose (FDG) can detect viable myocardium that may recover from revascularization in such patients. It is unclear whether use of FDG PET in this population improves outcome or is cost-effective. The principal aim of this study is to determine whether FDG PET-guided therapy improves clinical outcome compared to standard care. Secondary objectives are to determine whether FDG PET-guided therapy improves left ventricular (LV) function, improves quality of life, and provides a cost benefit versus standard care. Included in this multicenter randomized controlled trial are patients with coronary artery disease and severe LV dysfunction who are referred for revascularization, heart failure, or cardiac transplantation or in whom FDG PET is potentially useful. Consenting subjects will be randomized to therapy directed by FDG PET or standard care. The primary outcome is the composite cardiovascular endpoint of cardiac death, myocardial infarction, transplantation, or rehospitalization for unstable angina or heart failure. Secondary outcomes include health-related quality of life, costs, mortality, cardiovascular events, and LV function. Assuming two-sided alpha=0.05, power=80%, a sample size of 206 patients per group is required to detect a 15% absolute difference in the primary outcome between PET-directed therapy compared to standard care. Analyses will be conducted on an intention-to-treat basis. To our knowledge, this is the first large trial to evaluate whether FDG PET-directed therapy is effective and provides a cost benefit in patients with severe LV dysfunction. If so, thousands of such patients can be risk-stratified to select who is likely to benefit from revascularization.

Cancer screening and life expectancy of Canadian patients with kidney failure.

BACKGROUND: Patients with end-stage renal disease (ESRD) have at least the same prevalence of breast and cervical cancer but a reduced life expectancy compared with the general population. Whereas cancer screening has been found to be effective in the general population, competing risks in ESRD patients may obviate any screening benefit in this population. The purpose of this study was to determine if patients with ESRD benefit, in terms of life expectancy, by screening for breast and cervical cancer. METHODS: The ESRD mortality data from the Canadian Organ Replacement Registry was combined with North American statistics for breast and cervical cancer mortality, incidence, and screening efficacy for 40-, 60-, and 70-year-old women. A validated method of calculating life expectancy, the declining exponential approximation of life expectancy (DEALE), was used to estimate the average life expectancy with and without screening. The benefit of screening is then the estimated difference in the life expectancy with and without mammography or PAP smears. RESULTS: Without screening, the maximum reduction in life expectancy would be 12 days for 60-year-old women with breast cancer. The maximum calculated benefit from screening was an increase in life expectancy of only 3 days with PAP smears for 60-year-old women. CONCLUSIONS: Breast and cervical cancer screening, in women with ESRD, is not associated with as large a gain in life expectancy as for women of the general population. This conclusion does not necessarily apply to the individual woman with multiple risk factors for breast or cervical cancer and few comorbidities.