PSYCHOSOCIAL FACTORS AND MOBILE HEALTH INTERVENTION: IMPACT ON LONG-TERM OUTCOMES AFTER LUNG TRANSPLANTATION

Identifying and intervening on modifiable risk factors may improve outcomes in lung transplantation (LTx), which, despite recent improvements, remain suboptimal. Evidence suggests that two modifiable risk factors, psychiatric disorders and nonadherence, may improve LTx outcomes in the short-term; however, neither has been explored in the long-term. Therefore, the overarching goal of this dissertation was to determine the long-term impact of these modifiable risk factors and intervention to attenuate them. First, we examined the relationship of pre- and early post-transplant psychiatric disorders on LTx-related morbidity and mortality for up to 15 years post-LTx. Our sample included 155 1-year LTx survivors enrolled in a prospective study of mental health post- LTx. We found that depression during the first year post-LTx increased risk of BOS, mortality and graft loss by nearly twofold, and that pre-transplant depression and pre- and post-transplant anxiety were not associated with clinical outcomes. Next, we examined the impact of a mobile health intervention designed to promote adherence to the post-LTx regimen, PocketPATH, on long-term LTx-related morbidity, mortality and nonadherence. We conducted two follow-up studies to the original yearlong randomized controlled trial in which participants assigned to PocketPATH showed improved adherence to the regimen, relative to usual care. Among the 182 LTx recipients (LTxRs) who survived the original trial, we found that PocketPATH had a protective indirect effect on mortality by promoting LTxRs’ communication with the LTx team during the first year. Among the 104 LTxRs who completed the follow-up assessment, we found that PocketPATH’s adherence benefits over the first year were not sustained into the long-term, although LTxRs assigned to PocketPATH were more likely than LTxRs assigned to usual care to perform the home self-care tasks of the regimen at follow-up. Median time since LTx for participants in both follow-up studies was 4.2 years (range, 2.8-5.7 years). This dissertation presents an important first step toward identifying and intervening on modifiable risk factors to improve long-term LTx outcomes. Mobile health technologies offer limitless potential to target these risk factors and others. More work is needed to determine specific features and long-term patient engagement strategies that will optimize and sustain intervention effectiveness

Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort [version 2; referees: 1 approved, 2 approved with reservations]

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US.  Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB).   Methods:  888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier’s method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal).  Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were below the age of 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and had treatment that consisted of combining surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment in peritoneal mesothelioma is associated with improved survival compared to local therapy alone

Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort [version 1; referees: 1 approved, 2 approved with reservations]

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US.  Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB).   Methods:  888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier’s method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal).  Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were below the age of 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and had treatment that consisted of combining surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment is associated with improved survival compared to local therapy alone

Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity

IMPORTANCE: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients

Teammate Familiarity And Risk Of Injury In Emergency Medical Services

Objective: We investigated the association between teammate familiarity and workplace injury in the emergency medical services (EMS) setting. Methods: From January 2011 to November 2013, we abstracted a mean of 29 months of shift records and Occupational Safety Health Administration injury logs from 14 EMS organisations with 37 total bases located in four US Census regions. Total teammate familiarity was calculated for each dyad as the total number of times a clinician dyad worked together over the study period. We used negative binomial regression to examine differences in injury incidence rate ratios (IRRs) by familiarity. Results: We analysed 715 826 shift records, representing 4197 EMS clinicians and 60 701 unique dyads. We determined the mean shifts per dyad was (5.9, SD 19.7), and quartiles of familiarity were 1 shift worked together over the study period, 2-3 shifts, 4-9 shifts and ≥10 shifts worked together. More than half of all dyads worked one shift together (53.9%, n=32 739), 24.8% of dyads 2-3 shifts, 11.8% worked 4-9 shifts and 9.6% worked ≥10 shifts. The overall incidence rate of injury across all organisations was 17.5 per 100 full-time equivalent (FTE), range 4.7-85.6 per 100 FTE. The raw injury rate was 33.5 per 100 FTEs for dyads with one shift of total familiarity, 14.2 for 2-3 shifts, 8.3 for 4-9 shifts and 0.3 for ≥10 shifts. Negative binomial regression confirmed that dyads with ≥10 shifts had the lowest incidence of injury (IRR 0.03; 95% CI 0.02 to 0.04). Conclusions: Familiarity between teammates varies in the EMS setting, and less familiarity is associated with greater incidence of workplace injury

Teammate familiarity and risk of injury in emergency medical services

Objective: We investigated the association between teammate familiarity and workplace injury in the emergency medical services (EMS) setting. Methods: From January 2011 to November 2013, we abstracted a mean of 29 months of shift records and Occupational Safety Health Administration injury logs from 14 EMS organisations with 37 total bases located in four US Census regions. Total teammate familiarity was calculated for each dyad as the total number of times a clinician dyad worked together over the study period. We used negative binomial regression to examine differences in injury incidence rate ratios (IRRs) by familiarity. Results: We analysed 715 826 shift records, representing 4197 EMS clinicians and 60 701 unique dyads. We determined the mean shifts per dyad was (5.9, SD 19.7), and quartiles of familiarity were 1 shift worked together over the study period, 2–3 shifts, 4–9 shifts and ≥10 shifts worked together. More than half of all dyads worked one shift together (53.9%, n=32 739), 24.8% of dyads 2–3 shifts, 11.8% worked 4–9 shifts and 9.6% worked ≥10 shifts. The overall incidence rate of injury across all organisations was 17.5 per 100 full-time equivalent (FTE), range 4.7–85.6 per 100 FTE. The raw injury rate was 33.5 per 100 FTEs for dyads with one shift of total familiarity, 14.2 for 2–3 shifts, 8.3 for 4–9 shifts and 0.3 for ≥10 shifts. Negative binomial regression confirmed that dyads with ≥10 shifts had the lowest incidence of injury (IRR 0.03; 95% CI 0.02 to 0.04). Conclusions: Familiarity between teammates varies in the EMS setting, and less familiarity is associated with greater incidence of workplace injury

Association between Cognitive Decline in Older Adults and Use of Primary Care Physician Services in Pennsylvania

Objective : To assess the relationship between cognitive decline of older patients (≥ 65 y) and use of primary care physician (PCP) services over 24 months. Design : Retrospective analysis of prospectively collected data from a cluster randomized trial that took place from 2006-2010 and investigated the relationship between formal neuropsychological evaluation and patient outcomes in primary care. Setting : Twenty-four PCPs in 11 practices in southwestern Pennsylvania. Most practices were suburban and included more than 5 PCPs. Participants : A sample of 423 primary care patients 65 years old or older. Measurements : The association between the number of PCP visits and a decline in cognitive status, as determined by multivariable analyses that controlled for patient-level, physician-level, and practice-level factors (eg, patient age, comorbidities, and symptoms of depression; practice location and size; PCP age and sex) and used a linear mixed model with a random intercept to adjust for clustering. Results : Over a 2-year follow-up, 199 patients (47.0%) experienced a decline in cognitive status. Patients with a cognitive decline had a mean of 0.69 more PCP visits than did patients without a cognitive decline ( P < .05). Conclusions : Early signs of cognitive decline may be an indicator of greater use of primary care. Given the demographic trends, more PCPs are likely to be needed to meet the increasing needs of the older population

The triple variable index combines information generated over time from common monitoring variables to identify patients expressing distinct patterns of intraoperative physiology

Abstract Background Mean arterial pressure (MAP), bispectral index (BIS), and minimum alveolar concentration (MAC) represent valuable, yet dynamic intraoperative monitoring variables. They provide information related to poor outcomes when considered together, however their collective behavior across time has not been characterized. Methods We have developed the Triple Variable Index (TVI), a composite variable representing the sum of z-scores from MAP, BIS, and MAC values that occur together during surgery. We generated a TVI expression profile, defined as the sequential TVI values expressed across time, for each surgery where concurrent MAP, BIS, and MAC monitoring occurred in an adult patient (≥18 years) at the University of Pittsburgh Medical Center between January and July 2014 (n = 5296). Patterns of TVI expression were identified using k-means clustering and compared across numerous patient, procedure, and outcome characteristics. TVI and the triple low state were compared as prediction models for 30-day postoperative mortality. Results The median frequency MAP, BIS, and MAC were recorded was one measurement every 3, 5, and 5 min. Three expression patterns were identified: elevated, mixed, and depressed. The elevated pattern displayed the highest average MAP, BIS, and MAC values (86.5 mmHg, 45.3, and 0.98, respectively), while the depressed pattern displayed the lowest values (76.6 mmHg, 38.0, 0.66). Patterns (elevated, mixed, depressed) were distinct across the following characteristics: average patient age (52, 53, 54 years), American Society of Anesthesiologists Physical Status 4 (6.7, 16.1, 27.3%) and 5 (0.1, 0.6, 1.6%) categories, cardiac (2.2, 6.5, 16.1%) and emergent (5.8, 10.5, 12.8%) surgery, cardiopulmonary bypass use (0.3, 2.6, 9.8%), intraoperative medication administration including etomidate (3.0, 7.3, 12.6%), hydromorphone (47.6, 26.3, 25.2%), ketamine (11.2, 4.6, 3.0%), dexmedetomidine (18.4, 16.6, 13.6%), phenylephrine (74.0, 74.8, 83.0), epinephrine (2.0, 6.0, 18.0%), norepinephrine (2.4, 7.5, 21.2%), vasopressin (3.4, 7.6, 21.0%), succinylcholine (74.0, 69.0, 61.9%), intraoperative hypotension (28.8, 33.0, 52.3%) and the triple low state (9.4, 30.3, 80.0%) exposure, and 30-day postoperative mortality (0.8, 2.7, 5.6%). TVI was a better predictor of patients that died or survived in the 30 days following surgery compared to cumulative triple low state exposure (AUC 0.68 versus 0.62, p < 0.05). Conclusions Surgeries that share similar patterns of TVI expression display distinct patient, procedure, and outcome characteristics

Factors influencing malignant mesothelioma survival: A retrospective review of the national mesothelioma virtual bank cohort

Background: Malignant mesothelioma (MM) is a rare but deadly malignancy with about 3,000 new cases being diagnosed each year in the US. Very few studies have been performed to analyze factors associated with mesothelioma survival, especially for peritoneal presentation. The overarching aim of this study is to examine survival of the cohort of patients with malignant mesothelioma enrolled in the National Mesothelioma Virtual Bank (NMVB). Methods: 888 cases of pleural and peritoneal mesothelioma cases were selected from the NMVB database, which houses data and associated biospecimens for over 1400 cases that were diagnosed from 1990 to 2017. Kaplan Meier’s method was performed for survival analysis. The association between prognostic factors and survival was estimated using Cox Hazard Regression method and using R software for analysis. Results: The median overall survival (OS) rate of all MM patients, including pleural and peritoneal mesothelioma cases is 15 months (14 months for pleural and 31 months for peritoneal). Significant prognostic factors associated with improved survival of malignant mesothelioma cases in this NMVB cohort were younger than 45, female gender, epithelioid histological subtype, stage I, peritoneal occurrence, and having combination treatment of surgical therapy with chemotherapy. Combined surgical and chemotherapy treatment was associated with improved survival of 23 months in comparison to single line therapies. Conclusions: There has not been improvement in the overall survival for patients with malignant mesothelioma over many years with current available treatment options. Our findings show that combined surgical and chemotherapy treatment in peritoneal mesothelioma is associated with improved survival compared to local therapy alone