Lessons Learned Establishing the Palliative Care Research Cooperative's Qualitative Data Repository.

Data sharing is increasingly an expectation in health research as part of a general move toward more open sciences. In the United States, in particular, the implementation of the 2023 National Institutes of Health Data Management and Sharing Policy has made it clear that qualitative studies are not exempt from this data sharing requirement. Recognizing this trend, the Palliative Care Research Cooperative Group (PCRC) realized the value of creating a de-identified qualitative data repository to complement its existing de-identified quantitative data repository. The PCRC Data Informatics and Statistics Core leadership partnered with the Qualitative Data Repository (QDR) to establish the first serious illness and palliative care qualitative data repository in the U.S. We describe the processes used to develop this repository, called the PCRC-QDR, as well as our outreach and education among the palliative care researcher community, which led to the first ten projects to share the data in the new repository. Specifically, we discuss how we co-designed the PCRC-QDR and created tailored guidelines for depositing and sharing qualitative data depending on the original research context, establishing uniform expectations for key components of relevant documentation, and the use of suitable access controls for sensitive data. We also describe how PCRC was able to leverage its existing community to recruit and guide early depositors and outline lessons learned in evaluating the experience. This work advances the establishment of best practices in qualitative data sharing.

Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma: An Updated Nationwide Study.

OBJECTIVE: The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). BACKGROUND: The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. METHODS: Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. RESULTS: In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. CONCLUSIONS: The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.

Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes.

BACKGROUND: Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. METHODS: From June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year. RESULTS: Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < -2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < -2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = -0.08/illness-week, P = 0.06) and febrile illness (beta = -0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone ( P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12-15 months. CONCLUSIONS: These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.

Carotid Artery Operation Delay During the Covid-19 Pandemic: Results of a Multicenter International Study.

BACKGROUND: To measure the impact of the COVID-19 pandemic on the management of patients with carotid artery stenosis. METHODS: We prospectively collected data from 25 centers (19 centers in the United States and 6 centers internationally) on postponed carotid artery operations between March 2020 and January 2022. We describe the characteristics of these patients and their planned operations, along with outcomes including mortality and neurological deterioration during the period of operative delay due to the COVID-19 pandemic. RESULTS: A total of 1,220 vascular operations were postponed during the pandemic, of them 96 patients presented with significant carotid stenosis (median stenosis of 71%; interquartile range; 70-80) and 80% of them were planned for carotid endarterectomy. Most patients were asymptomatic (69%), and 31% of patients were symptomatic (16% of patients had a stroke, 15% of patients had a transient ischemic attack, and 1% of patients experienced amaurosis fugax). The median length of surgical delay was 71 days (interquartile range: 45.5, 115.5). At the data entry time, 62% of patients had their carotid operations postponed and successfully completed. Most postponements (72%) were due to institutional policies aimed at resource conservation. During the delay, no patient decompensated or required an urgent operation. A total of 5 patients (5%) with carotid stenosis died while awaiting operations due to COVID-19. CONCLUSIONS: Our study of a cohort of patients with carotid artery stenosis who underwent a median delay of 71 days during the COVID-19 pandemic showed a disparate operation delay between US regions and internationally, most postponements were due to hospital policy, and none of the patients deteriorated or required an emergency surgery during the delay.

Preoperative risk factors and postoperative complications associated with mortality after outpatient surgery in a broad surgical population: an analysis of 2.8 million ACS-NSQIP patients.

BACKGROUND: Thirty-day mortality after outpatient surgery is unexpected and undesired. We investigated preoperative risk factors, operative variables, and postoperative complications associated with 30-day death after outpatient surgery. METHODS: Using the 2005 to 2018 American College of Surgeons National Surgical Quality Improvement Program database, we evaluated 30-day mortality rate trends over time after outpatient operations. We analyzed associations between 37 preoperative variables, operation time, hospital length of stay, and 9 postoperative complications with mortality rate using χ2 analyses for categorical data and tests for continuous data. We used forward selection logistic regression models to determine the best predictors of mortality preoperatively and postoperatively. We also separately analyzed mortality by age group. RESULTS: A total of 2,822,789 patients were included. The 30-day mortality rate did not change significantly over time (P = .34, Cochran-Armitage trend test), remaining steady at around 0.06%. The most significant preoperative predictors of mortality included the patient having disseminated cancer, decreased functional health status, increased American Society of Anesthesiology Physical Status classification, increased age, and ascites, accounting for 95.8% (0.837/0.874) of the full model c-index. The most significant postoperative complications associated with increased risk of mortality included having cardiac (26.95% yes vs 0.04% no), pulmonary (10.25% vs 0.04%), stroke (9.22% vs 0.06%), and renal (9.33% vs 0.06%) complications. Postoperative complications conferred a greater risk for mortality than preoperative variables. Mortality risk increased incrementally with age, particularly past age 80. CONCLUSION: The operative mortality rate after outpatient surgery has not changed over time. Patients over 80 years with disseminated cancer, decreased functional health status, or increased ASA class should generally be considered for inpatient surgery. However, there might be some circumstances where outpatient surgery could be considered.

Effect of Present at Time of Surgery on Unadjusted and Risk-Adjusted Postoperative Complication Rate.

BACKGROUND: Present at the time of surgery (PATOS) is an important measure to collect in postoperative complication surveillance systems because it may affect a patient's risk of a subsequent complication and the estimation of postoperative complication rates attributed to the healthcare system. The American College of Surgeons (ACS) NSQIP started collecting PATOS data for 8 postoperative complications in 2011, but no one has used these data to quantify how this may affect unadjusted and risk-adjusted postoperative complication rates. STUDY DESIGN: This study was a retrospective observational study of the ACS NSQIP database from 2012 to 2018. PATOS data were analyzed for the 8 postoperative complications of superficial, deep, and organ space surgical site infection; pneumonia; urinary tract infection; ventilator dependence; sepsis; and septic shock. Unadjusted postoperative complication rates were compared ignoring PATOS vs taking PATOS into account. Observed to expected ratios over time were also compared by calculating expected values using multiple logistic regression analyses with complication as the dependent variable and the 28 nonlaboratory preoperative variables in the ACS NSQIP database as the independent variables. RESULTS: In 5,777,108 patients, observed event rates for each outcome were reduced by between 6.1% (superficial surgical site infection) and 52.5% (sepsis) when PATOS was taken into account. The observed to expected ratios were similar each year for all outcomes, except for sepsis and septic shock in the early years. CONCLUSIONS: Taking PATOS into account is important for reporting unadjusted event rates. The effect varied by type of complication-lowest for superficial surgical site infection and highest for sepsis and septic shock. Taking PATOS into account was less important for risk-adjusted outcomes (observed to expected ratios), except for sepsis and septic shock.

Does Adding a Measure of Social Vulnerability to a Surgical Risk Calculator Improve Its Performance?

BACKGROUND: Emerging literature suggests that measures of social vulnerability should be incorporated into surgical risk calculators. The Social Vulnerability Index (SVI) is a measure designed by the CDC that encompasses 15 socioeconomic and demographic variables at the census tract level. We examined whether adding the SVI into a parsimonious surgical risk calculator would improve model performance. STUDY DESIGN: The eight-variable Surgical Risk Preoperative Assessment System (SURPAS), developed using the entire American College of Surgeons (ACS) NSQIP database, was applied to local ACS-NSQIP data from 2012 to 2018 to predict 12 postoperative outcomes. Patient addresses were geocoded and used to estimate the SVI, which was then added to the model as a ninth predictor variable. Brier scores and c-indices were compared for the models with and without the SVI. RESULTS: The analysis included 31,222 patients from five hospitals. Brier scores were identical for eight outcomes and improved by only one to two points in the fourth decimal place for four outcomes with addition of the SVI. Similarly, c-indices were not significantly different (p values ranged from 0.15 to 0.96). Of note, the SVI was associated with most of the eight SURPAS predictor variables, suggesting that SURPAS may already indirectly capture this important risk factor. CONCLUSION: The eight-variable SURPAS prediction model was not significantly improved by adding the SVI, showing that this parsimonious tool functions well without including a measure of social vulnerability.

Galectin-3 as a potential prognostic biomarker of severe COVID-19 in SARS-CoV-2 infected patients.

Severe COVID-19 is associated with a systemic hyperinflammatory response leading to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Galectin-3 is a ß-galactoside binding lectin known to drive neutrophil infiltration and the release of pro-inflammatory cytokines contributing to airway inflammation. Thus, we aimed to investigate the potential of galectin-3 as a biomarker of severe COVID-19 outcomes. We prospectively included 156 patients with RT-PCR confirmed COVID-19. A severe outcome was defined as the requirement of invasive mechanical ventilation (IMV) and/or in-hospital death. A non-severe outcome was defined as discharge without IMV requirement. We used receiver operating characteristic (ROC) and multivariable logistic regression analysis to determine the prognostic ability of serum galectin-3 for a severe outcome. Galectin-3 levels discriminated well between severe and non-severe outcomes and correlated with markers of COVID-19 severity, (CRP, NLR, D-dimer, and neutrophil count). Using a forward-stepwise logistic regression analysis we identified galectin-3 [odds ratio (OR) 3.68 (95% CI 1.47-9.20), p < 0.01] to be an independent predictor of severe outcome. Furthermore, galectin-3 in combination with CRP, albumin and CT pulmonary affection > 50%, had significantly improved ability to predict severe outcomes [AUC 0.85 (95% CI 0.79-0.91, p < 0.0001)]. Based on the evidence presented here, we recommend clinicians measure galectin-3 levels upon admission to facilitate allocation of appropriate resources in a timely manner to COVID-19 patients at highest risk of severe outcome.

Relationships between predischarge and postdischarge infectious complications, length of stay, and unplanned readmissions in the ACS NSQIP database.

BACKGROUND: Postoperative complications, length of index hospital stay, and unplanned hospital readmissions are important metrics reflecting surgical care quality. Postoperative infections represent a substantial proportion of all postoperative complications. We examined the relationships between identification of postoperative infection prehospital and posthospital discharge, length of stay, and unplanned readmissions in the American College of Surgeons National Surgical Quality Improvement Program database across nine surgical specialties. METHODS: The 30-day postoperative infectious complications including sepsis, surgical site infections, pneumonia, and urinary tract infection were analyzed in the American College of Surgeons National Surgical Quality Improvement Program inpatient data during the period from 2012 to 2017. General, gynecologic, vascular, orthopedic, otolaryngology, plastic, thoracic, urologic, and neurosurgical inpatient operations were selected. RESULTS: Postoperative infectious complications were identified in 5.2% (137,014/2,620,450) of cases; 81,929 (59.8%) were postdischarge. The percentage of specific complications identified postdischarge were 73.4% of surgical site infections (range across specialties 63.7-93.1%); 34.9% of sepsis cases (27.4-58.1%); 26.5% of pneumonia cases (18.9%-36.3%); and 53.2% of urinary tract infections (48.3%-88.0%). The relative risk of readmission among patients with postdischarge versus predischarge surgical site infection, sepsis, pneumonia, or urinary tract infection was 5.13 (95% confidence interval: 4.90-5.37), 9.63 (8.93-10.40), 10.79 (10.15-11.45), and 3.32 (3.07-3.60), respectively. Over time, mean length of stay decreased but postdischarge infections and readmission rates significantly increased. CONCLUSION: Most postoperative infectious complications were diagnosed postdischarge. These were associated with an increased risk of readmission. The trend toward shorter length of stay over time was observed along with an increase both in the percentage of infections detected after discharge and the rate of unplanned related postoperative readmissions over time. Postoperative surveillance of infections should extend beyond hospital discharge of surgical patients.

Development and Validation of a Predictive Model of the Risk of Pediatric Septic Shock Using Data Known at the Time of Hospital Arrival.

OBJECTIVE: To derive and validate a model of risk of septic shock among children with suspected sepsis, using data known in the electronic health record at hospital arrival. STUDY DESIGN: This observational cohort study at 6 pediatric emergency department and urgent care sites used a training dataset (5 sites, April 1, 2013, to December 31, 2016), a temporal test set (5 sites, January 1, 2017 to June 30, 2018), and a geographic test set (a sixth site, April 1, 2013, to December 31, 2018). Patients 60 days to 18 years of age in whom clinicians suspected sepsis were included; patients with septic shock on arrival were excluded. The outcome, septic shock, was systolic hypotension with vasoactive medication or ≥30 mL/kg of isotonic crystalloid within 24 hours of arrival. Elastic net regularization, a penalized regression technique, was used to develop a model in the training set. RESULTS: Of 2464 included visits, septic shock occurred in 282 (11.4%). The model had an area under the curve of 0.79 (0.76-0.83) in the training set, 0.75 (0.69-0.81) in the temporal test set, and 0.87 (0.73-1.00) in the geographic test set. With a threshold set to 90% sensitivity in the training set, the model yielded 82% (72%-90%) sensitivity and 48% (44%-52%) specificity in the temporal test set, and 90% (55%-100%) sensitivity and 32% (21%-46%) specificity in the geographic test set. CONCLUSIONS: This model estimated the risk of septic shock in children at hospital arrival earlier than existing models. It leveraged the predictive value of routine electronic health record data through a modern predictive algorithm and has the potential to enhance clinical risk stratification in the critical moments before deterioration.

Performance of a Mobile Phone App-Based Participatory Syndromic Surveillance System for Acute Febrile Illness and Acute Gastroenteritis in Rural Guatemala.

BACKGROUND: With their increasing availability in resource-limited settings, mobile phones may provide an important tool for participatory syndromic surveillance, in which users provide symptom data directly into a centralized database. OBJECTIVE: We studied the performance of a mobile phone app-based participatory syndromic surveillance system for collecting syndromic data (acute febrile illness and acute gastroenteritis) to detect dengue virus and norovirus on a cohort of children living in a low-resource and rural area of Guatemala. METHODS: Randomized households were provided with a mobile phone and asked to submit weekly reports using a symptom diary app (Vigilant-e). Participants reporting acute febrile illness or acute gastroenteritis answered additional questions using a decision-tree algorithm and were subsequently visited at home by a study nurse who performed a second interview and collected samples for dengue virus if confirmed acute febrile illness and norovirus if acute gastroenteritis. We analyzed risk factors associated with decreased self-reporting of syndromic data using the Vigilant-e app and evaluated strategies to improve self-reporting. We also assessed agreement between self-report and nurse-collected data obtained during home visits. RESULTS: From April 2015 to June 2016, 469 children in 207 households provided 471 person-years of observation. Mean weekly symptom reporting rate was 78% (range 58%-89%). Households with a poor (<70%) weekly reporting rate using the Vigilant-e app during the first 25 weeks of observation (n=57) had a greater number of children (mean 2.8, SD 1.5 vs mean 2.5, SD 1.3; risk ratio [RR] 1.2, 95% CI 1.1-1.4), were less likely to have used mobile phones for text messaging at study enrollment (61%, 35/57 vs 76.7%, 115/150; RR 0.6, 95% CI 0.4-0.9), and were less likely to access care at the local public clinic (35%, 20/57 vs 67.3%, 101/150; RR 0.4, 95% CI 0.2-0.6). Parents of female enrolled participants were more likely to have low response rate (57.1%, 84/147 vs 43.8%, 141/322; RR 1.4, 95% CI 1.1-1.9). Several external factors (cellular tower collapse, contentious elections) were associated with periods of decreased reporting. Poor response rate (<70%) was associated with lower case reporting of acute gastroenteritis, norovirus-associated acute gastroenteritis, acute febrile illness, and dengue virus-associated acute febrile illness (P<.001). Parent-reported syndromic data on the Vigilant-e app demonstrated agreement with nurse-collected data for fever (kappa=.57, P<.001), vomiting (kappa=.63, P<.001), and diarrhea (kappa=.61, P<.001), with decreased agreement as the time interval between parental report and nurse home visit increased (<1 day: kappa=.65-.70; ≥2 days: kappa=.08-.29). CONCLUSIONS: In a resource-limited area of rural Guatemala, a mobile phone app-based participatory syndromic surveillance system demonstrated a high reporting rate and good agreement between parental reported data and nurse-reported data during home visits. Several household-level and external factors were associated with decreased syndromic reporting. Poor reporting rate was associated with decreased syndromic and pathogen-specific case ascertainment.