Using marginal structural models to analyze randomized clinical trials with non-adherence and lost to follow up.

BACKGROUND: In the presence of non-adherence and lost to follow up, results of an Intention to Treat (ITT) analysis may be biased as it is measuring the effect of assignment rather than the effect of treatment. Given that Marginal Structural Models (MSMs) adjust for such issues, this study examines the use of MSMs to assess the validity of ITT analyses in the presence of non-adherence and lost to follow up in an existing randomized clinical trial on asthma treatment. METHODS: Inverse probability weights were obtained from a pooled logistic regression assessing the probability of staying on assigned treatment (adherence) and of remaining uncensored (censored) for subjects at each visit by treatment arm. Weights were then pooled into a MSM analysis using a Poisson generalized estimating equation with an independent correlation matrix. RESULTS: Out of 488 participants, 174 (36%) did not adhere to the baseline assignment and 85 (17%) were lost to follow up by the end of the study. The adjusted relative risks (RR), and 95% confidence intervals (CI), obtained from the MSMs (theophylline vs. montelukast; RR=1.24; 95% CI: 0.83,1.84; theophylline vs. placebo: RR=1.01; 95% CI: 0.70,1.48; and montelukast vs. placebo: RR=0.83; 95% CI: 0.57,1.19) were nearly identical to that of the ITT analysis (theophylline vs. montelukast: RR=1.22; 95% CI: 0.82,1.86; theophylline vs. placebo: RR=0.99; 95% CI: 0.67,1.50; and montelukast vs. placebo: RR=0.82; 95% CI: 0.55,1.21). CONCLUSION: Concordance between the results of ITT and MSMs indicate adherence and censoring may not invalidate ITT analysis. However, no adherence or censorship thresholds currently exist to assist researchers in determining when MSMs may be superior to ITT in the analysis of clinical trials with non-adherence or censorship issues, and therefore, MSMs should be conducted as a sensitivity analysis to the ITT approach in clinical trials.

Prehospital hypoxemia, measured by pulse oximetry, predicts hospital outcomes during the New York City COVID-19 pandemic.

OBJECTIVE: To determine if oxygen saturation (out-of-hospital SpO2), measured by New York City (NYC) 9-1-1 Emergency Medical Services (EMS), was an independent predictor of coronavirus disease 2019 (COVID-19) in-hospital mortality and length of stay, after controlling for the competing risk of death. If so, out-of-hospital SpO2 could be useful for initial triage. METHODS: A population-based longitudinal study of adult patients transported by EMS to emergency departments (ED) between March 5 and April 30, 2020 (the NYC COVID-19 peak period). Inclusion required EMS prehospital SpO2 measurement while breathing room air, transport to emergency department, and a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction test. Multivariable logistic regression modeled mortality as a function of prehospital SpO2, controlling for covariates (age, sex, race/ethnicity, and comorbidities). A competing risk model also was performed to estimate the absolute risks of out-of-hospital SpO2 on the cumulative incidence of being discharged from the hospital alive. RESULTS: In 1673 patients, out-of-hospital SpO2 and age were independent predictors of in-hospital mortality and length of stay, after controlling for the competing risk of death. Among patients ≥66 years old, the probability of death was 26% with an out-of-hospital SpO2 >90% versus 54% with an out-of-hospital SpO2 ≤90%. Among patients <66 years old, the probability of death was 11.5% with an out-of-hospital SpO2 >90% versus 31% with an out-of-hospital SpO2 ≤ 90%. An out-of-hospital SpO2 level ≤90% was associated with over 50% decreased likelihood of being discharged alive, regardless of age. CONCLUSIONS: Out-of-hospital SpO2 and age predicted in-hospital mortality and length of stay: An out-of-hospital SpO2 ≤90% strongly supports a triage decision for immediate hospital admission. For out-of-hospital SpO2 >90%, the decision to admit depends on multiple factors, including age, resource availability (outpatient vs inpatient), and the potential impact of new treatments.

Factors Influencing the Prioritization of Injured Patients for Transfer to a Burn or Trauma Center Following a Mass Casualty Event.

OBJECTIVES: In New York City, a multi-disciplinary Mass Casualty Consultation team is proposed to support prioritization of patients for coordinated inter-facility transfer after a large-scale mass casualty event. This study examines factors that influence consultation team prioritization decisions. METHODS: As part of a multi-hospital functional exercise, 2 teams prioritized the same set of 69 patient profiles. Prioritization decisions were compared between teams. Agreement between teams was assessed based on patient profile demographics and injury severity. An investigator interviewed team leaders to determine reasons for discordant transfer decisions. RESULTS: The 2 teams differed significantly in the total number of transfers recommended (49 vs 36; P = 0.003). However, there was substantial agreement when recommending transfer to burn centers, with 85.5% agreement and inter-rater reliability of 0.67 (confidence interval: 0.49-0.85). There was better agreement for patients with a higher acuity of injuries. Based on interviews, the most common reason for discordance was insider knowledge of the local community hospital and its capabilities. CONCLUSIONS: A multi-disciplinary Mass Casualty Consultation team was able to rapidly prioritize patients for coordinated secondary transfer using limited clinical information. Training for consultation teams should emphasize guidelines for transfer based on existing services at sending and receiving hospitals, as knowledge of local community hospital capabilities influence physician decision-making.

Factors Predicting Treatment of World Trade Center-Related Lung Injury: A Longitudinal Cohort Study.

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001-10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001-1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV1), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001-10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005-10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV1, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.

Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City.

Importance: Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined. From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19-related deaths. On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year. Objective: To describe the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC. Design, Setting, and Participants: This population-based, cross-sectional study compared patients with out-of-hospital cardiac arrest receiving resuscitation by the NYC 911 EMS system from March 1 to April 25, 2020, compared with March 1 to April 25, 2019. The NYC 911 EMS system serves more than 8.4 million people. Exposures: The COVID-19 pandemic. Main Outcomes and Measures: Characteristics associated with out-of-hospital arrests and the outcomes of out-of-hospital cardiac arrests. Results: A total of 5325 patients were included in the main analysis (2935 men [56.2%]; mean [SD] age, 71 [18] years), 3989 in the COVID-19 period and 1336 in the comparison period. The incidence of nontraumatic out-of-hospital cardiac arrests in those who underwent EMS resuscitation in 2020 was 3 times the incidence in 2019 (47.5/100 000 vs 15.9/100 000). Patients with out-of-hospital cardiac arrest during 2020 were older (mean [SD] age, 72 [18] vs 68 [19] years), less likely to be white (611 of 2992 [20.4%] vs 382 of 1161 [32.9%]), and more likely to have hypertension (2134 of 3989 [53.5%] vs 611 of 1336 [45.7%]), diabetes (1424 of 3989 [35.7%] vs 348 of 1336 [26.0%]), and physical limitations (2259 of 3989 [56.6%] vs 634 of 1336 [47.5%]). Compared with 2019, the odds of asystole increased in the COVID-19 period (odds ratio [OR], 3.50; 95% CI, 2.53-4.84; P < .001), as did the odds of pulseless electrical activity (OR, 1.99; 95% CI, 1.31-3.02; P = .001). Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (727 of 3989 patients [18.2%] vs 463 of 1336 patients [34.7%], P < .001) and sustained ROSC (423 of 3989 patients [10.6%] vs 337 of 1336 patients [25.2%], P < .001), with fatality rates exceeding 90%. These associations remained statistically significant after adjustment for potential confounders (OR for ROSC, 0.59 [95% CI, 0.50-0.70; P < .001]; OR for sustained ROSC, 0.53 [95% CI, 0.43-0.64; P < .001]). Conclusions and Relevance: In this population-based, cross-sectional study, out-of-hospital cardiac arrests and deaths during the COVID-19 pandemic significantly increased compared with the same period the previous year and were associated with older age, nonwhite race/ethnicity, hypertension, diabetes, physical limitations, and nonshockable presenting rhythms. Identifying patients with the greatest risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths.

System impacts of the COVID-19 pandemic on New York City's emergency medical services.

OBJECTIVES: To describe the impact of the COVID-19 pandemic on New York City's (NYC) 9-1-1 emergency medical services (EMS) system and assess the efficacy of pandemic planning to meet increased demands. METHODS: Longitudinal analysis of NYC 9-1-1 EMS system call volumes, call-types, and response times during the COVID-19 peak-period (March 16-April 15, 2020) and post-surge period (April 16-May 31, 2020) compared with the same 2019 periods. RESULTS: EMS system received 30,469 more calls from March 16-April 15, 2020 compared with March 16-April 15, 2019 (161,815 vs 127,962; P < 0.001). On March 30, 2020, call volume increased 60% compared with the same 2019 date. The majority were for respiratory (relative risk [RR] = 2.50; 95% confidence interval [CI] = 2.44-2.56) and cardiovascular (RR = 1.85; 95% CI = 1.82-1.89) call-types. The proportion of high-acuity, life-threatening call-types increased compared with 2019 (42.3% vs 36.4%). Planned interventions to prioritize high-acuity calls resulted in the average response time increasing by 3 minutes compared with an 11-minute increase for low low-acuity calls. Post-surge, EMS system received fewer calls compared with 2019 (154,310 vs 193,786; P < 0.001). CONCLUSIONS: COVID-19-associated NYC 9-1-1 EMS volume surge was primarily due to respiratory and cardiovascular call-types. As the pandemic stabilized, call volume declined to below pre-pandemic levels. Our results highlight the importance of EMS system-wide pandemic crisis planning.

Intra-Arrest Induction of Hypothermia via Large-Volume Ice-Cold Saline for Sudden Cardiac Arrest: The New York City Project Hypothermia Experience.

Therapeutic hypothermia, the standard for post-resuscitation care of out-of-hospital sudden cardiac arrest (SCA), is an area that the most recent resuscitation guidelines note "has not been studied adequately." We conducted a two-phase study examining the role of intra-arrest hypothermia for out-of-hospital SCA, first standardizing the resuscitation and transport of patients to resuscitation centers where post-resuscitation hypothermia was required and then initiating hypothermia during out-of-hospital resuscitation efforts. The primary end points were return of spontaneous circulation (ROSC), sustained ROSC, survival to hospital admission, and survival to discharge. Comparing the cohort of standard hospital-initiated hypothermia (Phase I) with the prehospital-initiated hypothermia via large-volume ice-cold saline (LVICS) infusion (Phase II), no difference was noted for any end point: ROSC (56.4% vs. 53.4%, p = 0.51; 95% confidence interval [CI]: -5.7 to 11.4), sustained ROSC (46.9% vs. 42.8%, p = 0.38; 95% CI: -4.7 to 12.4), hospital admission (44.7% vs. 37.7%, p = 0.13; 95% CI: -1.9 to 15.4), hospital discharge among those surviving to admission (40.0% vs. 28.0%, p = 0.08; 95% CI: -1.5 to 27.8), or neurological outcome among those surviving to discharge (76.0% vs. 71.4%, p = 0.73; 95% CI: -26.9 to 38.7). Patients presenting in ventricular fibrillation were more likely to survive to hospital discharge in both phases, although a trend toward worsened early outcomes (ROSC, sustained ROSC, and survival to admission) with intra-arrest hypothermia was noted in this subgroup. Multivariable regression analyses failed to demonstrate any survival benefit associated with the intra-arrest initiation of hypothermia via LVICS. Our study, the largest study of intra-arrest initiation of hypothermia published to date, failed to demonstrate any effect on survival for out-of-hospital SCA patients, confirming findings of previously published smaller studies. We therefore do not recommend the use of intra-arrest cooling via LVICS infusion as part of routine out-of-hospital SCA resuscitative efforts.

Race/ethnicity and all-cause mortality in US adults: revisiting the Hispanic paradox.

OBJECTIVES: We examined the association between race/ethnicity and all-cause mortality risk in US adults and whether this association differs by nativity status. METHODS: We used Cox proportional hazards regression to estimate all-cause mortality rates in 1997 through 2004 National Health Interview Survey respondents, relating the risk for Hispanic subgroup, non-Hispanic Black, and other non-Hispanic to non-Hispanic White adults before and after controlling for selected characteristics stratified by age and gender. RESULTS: We observed a Hispanic mortality advantage over non-Hispanic Whites among women that depended on nativity status: US-born Mexican Americans aged 25 to 44 years had a 90% (95% confidence interval [CI] = 0.03, 0.31) lower death rate; island- or foreign-born Cubans and other Hispanics aged 45 to 64 years were more than two times less likely to die than were their non-Hispanic White counterparts. Island- or foreign-born Puerto Rican and US-born Mexican American women aged 65 years and older exhibited at least a 25% lower rate of dying than did their non-Hispanics White counterparts. CONCLUSIONS: The "Hispanic paradox" may not be a static process and may change with this population growth and its increasing diversity over time.