Delivering COVID-19 Vaccine via Trusted Social Services: Program Evaluation Results from the Chicagoland CEAL Program.

To describe the reach, implementation, and sustainability of COVID-19 vaccination programs delivered by social service community organizations. Five academic institutions in the Chicagoland CEAL (Community Engagement Alliance) program partnered with 17 community organizations from September 2021-April 2022. Interviews, community organizations program implementation tracking documents, and health department vaccination data were used to conduct the evaluation. A total of 269 events were held and 5,432 COVID-19 vaccines delivered from May 2021-April 2022. Strategies that worked best included offering vaccinations in community settings with flexible and reliable hours; pairing vaccinations with ongoing social services; giving community organizations flexibility to adjust programs; offering incentives; and vaccinating staff first. These strategies and partnership structures supported vaccine uptake, community organization alignment with their missions and communities' needs, and trust. Community organizations delivering social services are local community experts and trusted messengers. Pairing social service delivery with COVID-19 vaccination built individual and community agency. Giving COs creative control over program implementation enhanced trust and vaccine delivery. When given appropriate resources and control, community organizations can quickly deliver urgently needed health services in a public health crisis.

Early hip survival after open reduction internal fixation of acetabular fracture.

PURPOSE: To estimate survival of acetabular fracture repair by tracking patients across healthcare encounters. We hypothesized that hip survival estimated this way would be lower than reported by single-surgeon or single-center series not capturing censored reoperations. METHODS: Retrospective health insurance administrative database cohort study. All claimed healthcare encounters for employer-sponsored health insurance beneficiaries aged 18-65 years without pre-existing hip pathology with a newly diagnosed acetabular fracture were identified between October 1, 2015, through December 31, 2018. The intervention was open reduction internal fixation of acetabular fracture during index admission. The primary outcome was survival of the acetabular fracture repair to subsequent reoperation by arthroscopy, arthrotomy for drainage of infection, implant removal, revision acetabular fixation, hip arthroplasty, hip resection, or arthrodesis. RESULTS: 38 reoperation procedures on the fractured acetabulum in 852 patients occurred within 2 years (incidence 4.5%). Total hip arthroplasty (2.5%) and revision internal fixation (1.5%) accounted for most early reoperations. Multivariable Cox regression identified an association between reoperation and increasing patient age (hazard ratio = 1.4 per decade, p < 0.01). The prevalence of any mental health condition was 29%. CONCLUSIONS: Non-elderly adults with employer-sponsored insurance who sustain acetabular fractures have a greater burden of mental health disease than similarly insured patients without these injuries. Survival of the native acetabulum after fracture fixation exceeded 95% at 2 years and decreased with increasing patient age. LEVEL OF EVIDENCE: Level III, Prognostic Study.

Comparing the associations between host and tumor factors with survival outcomes with anti-PD-1 immunotherapy in metastatic melanoma.

BACKGROUND: Anti-programmed death-1 (PD-1) immunotherapy has drastically improved survival for metastatic melanoma; however, 50% of patients have progression within 6 months despite treatment. In this study, we investigated host, and tumor factors for metastatic melanoma patients treated with anti-PD-1 immunotherapy. METHODS: Patients treated with the anti-PD-1 immunotherapy between 2014 and 2017 were identified in Alberta, Canada. All patients had Stage IV melanoma. Patient characteristics, investigations, treatment, and clinical outcomes were obtained from electronic medical records. RESULTS: We identified 174 patients treated with anti-PD-1 immunotherapy. At 37.1 months median follow-up time 135 (77.6%) individuals had died and 150 (86.2%) had progressed. An elevated lactate dehydrogenase (LDH) had a response rate of 21.0% versus 41.0% for those with a normal LDH (p = 0.017). Host factors associated with worse median progression-free survival (mPFS) and median overall survival (mOS) included liver metastases, >3 sites of disease, elevated LDH, thrombocytosis, neutrophilia, anemia, lymphocytopenia, and an elevated neutrophil/lymphocyte ratio. Primary ulcerated tumors had a worse mOS of 11.8 versus 19.3 months (p = 0.042). We identified four prognostic subgroups in advanced melanoma patients treated with anti-PD-1 therapy. (1) Normal LDH with <3 visceral sites, (2) normal LDH with ≥3 visceral sites, (3) LDH 1-2x upper limit of normal (ULN), (4) LDH ≥2x ULN. The mPFS each group was 14.0, 6.5, 3.3, and 1.9 months, while the mOS for each group was 33.3, 15.7, 7.9, and 3.4 months. CONCLUSION: Our study reports that host factors measuring the general immune function, markers of systemic inflammation, and tumor burden and location are the most prognostic for survival.

Paradoxical Association of Hyperglycemia and Surgical Complications Among Patients With and Without Diabetes.

Importance: Surgical complications associated with perioperative hyperglycemia are conventionally associated with diabetes, but, paradoxically, prior cohort studies have found that patients without diabetes have greater risk of complications at similar levels of hyperglycemia compared with patients with diabetes. Objective: To describe the association between perioperative hyperglycemia and surgical complications in a population of surgical patients without diabetes receiving routine blood glucose testing and insulin administration and to evaluate the potential correlation of perioperative hyperglycemia. Design, Setting, and Participants: This retrospective cohort study of National Surgical Quality Improvement Program-defined complications after operation took place at a single academic medical center hospital from January 2013 to October 2016. Consecutive patients undergoing general, vascular, and gynecologic operations who were expected to have at least a 48-hour admission were included. Hyperglycemia was defined as blood glucose level of 140 mg/dL or higher within 24 hours after surgery. Multivariate regression was used to assess the association of hyperglycemia and complications, stratified by hyperglycemia severity and adjusted for diabetes status. Analysis began in February 2022. Exposures: Routine blood glucose testing and insulin administration. Main Outcomes and Measures: The main outcomes are odds of experiencing perioperative hyperglycemia and postoperative complication, comparing patients with and without diabetes. Results: A total of 7634 patients (mean [SD] age, 53.5 [15.1] years; 6664 patients without diabetes [83.3%] and 970 patients with diabetes [17.7%]) underwent general (6204 [81.3%]), vascular (208 [2.7%]), and gynecologic (1222 [16%]) operations. Of these, 5868 (77%) had blood glucose testing (4899 individuals without diabetes [73.5%] and 969 [99.9%] with diabetes). Hyperglycemia occurred in 882 patients with diabetes (91%) and 2484 patients without diabetes (50.7%). Of those with blood glucose level more than 180 mg/dL, 1388 (72.7%) received insulin (658 patients with diabetes who had hyperglycemia [91%] and 680 patients without diabetes who had hyperglycemia [61%]). Adjusted odds of experiencing a complication were 83% greater for patients without vs with diabetes at blood glucose level of 140 to 179 mg/dL (odds ratio, 1.83 [95% CI, 0.93-3.6]), 49% greater for blood glucose level of 180 to 249 mg/dL (odds ratio, 1.49 [95% CI, 1.06-2.11]), and 88% greater for blood glucose level more than 250 mg/dL (odds ratio, 1.88 [95% CI, 1.11-3.17]). A similar trend was observed for serious complications. Insulin may mitigate the association of hyperglycemia and complications in patients without diabetes. Conclusions and Relevance: In this study, with near universal blood glucose testing and frequent insulin use, patients without diabetes paradoxically had worse outcomes than patients with diabetes at similar levels of hyperglycemia. Insulin may mitigate this effect and broader use may improve outcomes.

Patterns of care after cholecystostomy tube placement.

BACKGROUND: The use of cholecystostomy (c-tube) in acute cholecystitis (AC) has increased yet there is limited evidence to guide surgical decision-making after placement. As a result, there is variability in the use and timing of cholecystectomy after c-tube. We aimed to describe patient characteristics, outcomes, and biliary-related utilization in those who did and did not have cholecystectomy after c-tube. METHODS: This is a retrospective cohort study (2007-2017) using the MarketScan® claims database of patients (18-63 years) with at least 3 months of follow-up (or death). ICD-9/10 and CPT codes were used to identify AC, c-tube placement, cholecystectomy and determine Elixhauser comorbidity index. RESULTS: A total of 2386 patients (47.5% female, mean age 52.5 [SD 9.9] years) with AC underwent c-tube with an 11.2% 90-day mortality. Among survivors, by three months 57% underwent cholecystectomy (mean 34.8 days [95% CI: 33.3-36.3]). Cholecystectomy after c-tube was more common in those with fewer comorbid conditions (mean 2.41 [95% CI: 2.26-2.56] vs 4.56 [95%CI: 4.36-4.76]). Biliary episodes prior to cholecystectomy occurred in 12.5% and were associated with eventual cholecystectomy (HR 1.49 [1.32-1.68]). Biliary-specific hospital and ICU days were similar between groups. Biliary-specific ED visits were more common among patients with cholecystectomy (mean 1.39 [95% CI: 1.29-1.48] vs 0.94 [95% CI: 0.85-1.03]). CONCLUSION: More than half of patients treated with c-tube underwent cholecystectomy by three months-most within five weeks of AC diagnosis. The high frequency of use and short time to cholecystectomy after c-tube raises questions about potential overuse of c-tube in the initial period. Future work should aim to understand how patient experience and indication for c-tube influence the likelihood and timing of subsequent cholecystectomy.

Use of post-discharge heparin prophylaxis and the risk of venous thromboembolism and bleeding following bariatric surgery.

INTRODUCTION: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality after bariatric surgery. Roughly 80% of VTEs occur post-discharge. The frequency of post-discharge heparin (PDH) prophylaxis use is unknown, and evidence about benefits and risks is limited. We aimed to determine the rate of use of PDH prophylaxis and evaluate its relationship with VTE and bleeding events. METHODS: Using the Truven Health MarketScan® database, we performed a retrospective cohort study (2007-2015) of adult patients who underwent sleeve gastrectomy or gastric bypass. We determined PDH prophylaxis from outpatient pharmacy claims, and post-discharge 90-day VTE and bleeding events from outpatient and inpatient claims. We used propensity score-adjusted regression models to mitigate confounding bias. RESULTS: Among 43,493 patients (median age 45 years; 78% women; 77% laparoscopic gastric bypass, 17% laparoscopic sleeve gastrectomy, 6% open gastric bypass), 6% received PDH prophylaxis. Overall, 224 patients (0.52%) experienced VTEs, and 806 patients (1.85%) experienced bleeding. The unadjusted VTE rate did not differ between patients who did and did not receive PDH prophylaxis (0.39% vs. 0.52%, respectively; p = 0.347). The unadjusted bleeding rate was higher for the PDH prophylaxis group (2.74% vs. 1.80%, p < 0.001). In our adjusted analysis, a 23% lower risk of VTE in the PDH prophylaxis group was not statistically significant (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.41 to 1.46), whereas the 47% higher risk of bleeding was statistically significant (OR 1.47, 95% CI 1.14 to 1.88). CONCLUSIONS: PDH prophylaxis after bariatric surgery is uncommon. In our analysis, use was not associated with a lower VTE risk but was associated with a higher bleeding risk.

What Is the Survivorship After Hip Arthroscopy for Femoroacetabular Impingement? A Large-database Study.

BACKGROUND: Patients with femoroacetabular impingement (FAI) may experience lasting clinical improvement after hip arthroscopy; however, some patients will still eventually undergo early conversion to THA due to unresolved symptoms and progression of arthritis. However, the risk of this has been only incompletely characterized in prior studies. QUESTIONS/PURPOSES: Using a large healthcare claims database over a 5-year period (2011-2016), we asked: (1) What is the survivorship free from THA after arthroscopic osteoplasty performed for FAI? (2) What identifiable demographic factors and patient characteristics are associated with early conversion to THA after hip arthroscopy performed for FAI? METHODS: We included all patients who underwent hip arthroscopy for FAI, between the ages of 12 years and 63 years, with 3 months of claims data before hip arthroscopy and minimum 2-year follow-up. A total of 4730 hip arthroscopy patients from 2011 to 2014 were retrieved from a US commercial claims database. Hip arthroscopy incidence doubled over time from 1.2 to 2.1 persons per 100,000. Temporal trends, patient demographics, diagnoses at time of arthroscopy, and patient comorbidities were retrieved and logistic regression performed. Survivorship analysis on 11,323 patients (lifting the 2-year follow-up requirement) was also performed to identify independent variables associated with early risk of conversion to THA. RESULTS: In patients undergoing hip arthroscopy for FAI, the overall proportion of conversion to THA within 2 years after hip arthroscopy was 7% (338 of 4730). After controlling for confounding variables such as sex, obesity, and depression, we found the following were independently associated with increased odds of conversion to THA: older age (odds ratio 1.08 [95% CI 1.01 to 1.10]; p < 0.001), osteoarthritis (OR 2.91 [95% CI 2.27 to 3.77]; p < 0.001), joint inflammation (OR 1.89 [95% CI 1.16 to 3.09]; p = 0.01), and a history of opioid use (OR 2.17 [95% CI 1.69 to 2.79]; p < 0.001). Survivorship analysis similarly revealed that older age (hazard ratio 1.08 [95% CI 1.07 to 1.09]; p < 0.001), osteoarthritis (HR 2.53 [95% CI 2.13 to 3.01]; p < 0.001), joint inflammation (HR 1.53 [95% CI 1.10 to 2.11]; p = 0.01), a history of opioid use (HR 2.02 [95% CI 1.71 to 2.38]; p < 0.001), and smoking (HR 1.55 [95% CI 1.14 to 2.11]; p = 0.005), were independently associated with increased odds of conversion to THA within 2 years after hip arthroscopy for FAI. CONCLUSIONS: Although the findings of this study are limited and should not be taken in isolation, patients with FAI who are older, carry diagnoses of inflammatory or degenerative articular disease, or who use opioids or smoke should be counseled about a potentially increased risk of undergoing early conversion to THA after hip arthroscopy. Future studies to further examine the effect of these diagnoses in prospectively collected cohorts, incorporating radiographic and patient-reported outcome measures, are needed. LEVEL OF EVIDENCE: Level III, prognostic study.

Practice Patterns for Women With Overactive Bladder Syndrome: Time Between Medications and Third-Line Treatments.

OBJECTIVE: The aims of this study are to determine how long it takes female patients with overactive bladder (OAB) to receive third-line treatment after starting OAB medications and identify factors associated with increased time. METHODS: This was a retrospective observational cohort study of adult female patients with OAB who received third-line treatment between 2013 and 2015 using insurance claims databases. Primary outcome was time between first OAB medication and first third-line treatment. Additional variables were patient demographics, diagnostic tests, and medical comorbidities. RESULTS: Of 3232 patients included in this study, 48.8% underwent sacral neuromodulation, 31.6% percutaneous tibial nerve stimulation, and 23% intradetrusor onabotulinumtoxin A injections. Twenty-one percent of patients filled medication prescriptions for 3 or more antimuscarinic medications, 30.4% took mirabegron, and 32.3% had advanced diagnostic tests suggestive of a specialist evaluation prior to starting medications. Median time to third-line treatment was 37.7 (interquartile range, 14.9, 16.3) months. Adjusted linear regression model revealed 2 predominant predictors of time to third-line treatments: each antimuscarinic medication trial was associated with 5.3 (95% confidence interval, 4.4-6.3) more months before third-line treatment (P < 0.001), and advanced diagnostic evaluations prior to starting medications were associated with 28.2 (95% confidence interval, 21-35) fewer months before third-line treatment (P < 0.001). CONCLUSIONS: Women with OAB who undergo third-line therapy do so on average more than 3 years after starting medications. Time to third-line treatment is largely driven by the number of antimuscarinic medications tried and timing of diagnostic evaluation by a specialist. Based on these results, we suggest providers consider limiting antimuscarinic trials to 2 medications prior to moving on to other treatment options.

Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton.

Chemotaxis allows neutrophils to seek out sites of infection and inflammation. The asymmetric accumulation of filamentous actin (F-actin) at the leading edge provides the driving force for protrusion and is essential for the development and maintenance of neutrophil polarity. The mechanism that governs actin cytoskeleton dynamics and assembly in neutrophils has been extensively explored and is still not fully understood. By using neutrophil-like HL-60 cells, we describe a pivotal role for Rictor, a component of mammalian target of rapamycin complex 2 (mTORC2), in regulating assembly of the actin cytoskeleton during neutrophil chemotaxis. Depletion of mTOR and Rictor, but not Raptor, impairs actin polymerization, leading-edge establishment, and directional migration in neutrophils stimulated with chemoattractants. Of interest, depletion of mSin1, an integral component of mTORC2, causes no detectable defects in neutrophil polarity and chemotaxis. In addition, experiments with chemical inhibition and kinase-dead mutants indicate that mTOR kinase activity and AKT phosphorylation are dispensable for chemotaxis. Instead, our results suggest that the small Rho GTPases Rac and Cdc42 serve as downstream effectors of Rictor to regulate actin assembly and organization in neutrophils. Together our findings reveal an mTORC2- and mTOR kinase-independent function and mechanism of Rictor in the regulation of neutrophil chemotaxis.

The non-receptor tyrosine kinase Lyn controls neutrophil adhesion by recruiting the CrkL-C3G complex and activating Rap1 at the leading edge.

Establishing new adhesions at the extended leading edges of motile cells is essential for stable polarity and persistent motility. Despite recent identification of signaling pathways that mediate polarity and chemotaxis in neutrophils, little is known about molecular mechanisms governing cell-extracellular-matrix (ECM) adhesion in these highly polarized and rapidly migrating cells. Here, we describe a signaling pathway in neutrophils that is essential for localized integrin activation, leading edge attachment and persistent migration during chemotaxis. This pathway depends upon G(i)-protein-mediated activation and leading edge recruitment of Lyn, a non-receptor tyrosine kinase belonging to the Src kinase family. We identified the small GTPase Rap1 as a major downstream effector of Lyn to regulate neutrophil adhesion during chemotaxis. Depletion of Lyn in neutrophil-like HL-60 cells prevented chemoattractant-induced Rap1 activation at the leading edge of the cell, whereas ectopic expression of Rap1 largely rescued the defects induced by Lyn depletion. Furthermore, Lyn controls spatial activation of Rap1 by recruiting the CrkL-C3G protein complex to the leading edge. Together, these results provide novel mechanistic insights into the poorly understood signaling network that controls leading edge adhesion during chemotaxis of neutrophils, and possibly other amoeboid cells.

Effect of fresh fruit availability at worksites on the fruit and vegetable consumption of low-wage employees.

OBJECTIVE: To examine the impact of fresh fruit availability at worksites on the fruit and vegetable consumption and related psychosocial determinants of low-wage employees. DESIGN: A prospective, randomized block experimental design. SETTING: Seven apparel manufacturing and 2 food processing worksites. PARTICIPANTS: A convenience sample of 391 low-wage employees in 6 intervention worksites and 137 low-wage employees in 3 control worksites in Los Angeles, CA. INTERVENTION: Fresh fruit deliveries with enough for 1 serving per employee, 3 days a week for 12 consecutive weeks. The control worksites did not receive the fruit deliveries. MAIN OUTCOME MEASURES: Participants' fruit and vegetable consumption, fruit and vegetable purchasing habits, self-efficacy, job satisfaction, and overall health were measured at baseline, weeks 4 and 8, and following the 12-week intervention. ANALYSIS: Descriptive statistics and growth curve analysis using hierarchical linear modeling were employed to analyze the data. RESULTS: Participants in the intervention worksites showed a significant increase in fruit, vegetable, and total fruit and vegetable consumption, purchasing of fruit, family purchasing of vegetables, and self-efficacy toward eating 2 servings of fruit each day compared to the control worksites. CONCLUSIONS AND IMPLICATIONS: Improving access to fruit during the workday can improve fruit and vegetable consumption, purchasing habits, and self-efficacy of low-income employees.

A requirement for dimerization of HP1Hsalpha in suppression of breast cancer invasion.

The development and progression of cancer is controlled by gene expression, often regulated through chromatin packaging. Heterochromatin protein 1(Hsalpha) (HP1(Hsalpha)), one of three human HP1 family members, participates in heterochromatin formation and gene regulation. HP1(Hsalpha) possesses an amino-terminal chromodomain, which binds methylated lysine 9 of histone H3 (meK9 H3), and a carboxyl-terminal chromoshadow domain (CSD) that is required for dimerization and interaction with partner proteins. HP1(Hsalpha) is down-regulated in invasive metastatic breast cancer cells compared with poorly invasive nonmetastatic breast cancer cells. Expression of EGFP-HP1(Hsalpha) in highly invasive MDA-MB-231 cells causes a reduction in in vitro invasion, without affecting cell growth. Conversely, knock-down of HP1(Hsalpha) levels in the poorly invasive breast cancer cell line MCF-7 increased invasion, without affecting cell growth. To determine whether functions of the CSD were required for the regulation of invasion, mutant forms of HP1(Hsalpha) were expressed in MDA-MB-231 cells. A W174A mutation that disrupts interactions between HP1(Hsalpha) and PXVXL-containing partner proteins reduced invasion similar to that of the wild type protein. In contrast, an I165E mutation that disrupts dimerization of HP1(Hsalpha) did not decrease invasion. No gross changes in localization and abundance of HP1(Hsbeta), HP1(Hsgamma), and meK9 H3 were observed upon expression of wild type and mutant forms of HP1(Hsalpha) in MDA-MB-231 cells. Taken together, these data demonstrate that modulation of HP1(Hsalpha) alters the invasive potential of breast cancer cells through mechanisms requiring HP1 dimerization, but not interactions with PXVXL-containing proteins.

Peripheral intravenous cannulation in nursing: performance predictors.

This study examined the impact of nurses' education and experience and the characteristics of their patients on their performance of peripheral intravenous cannulation. A researcher-developed peripheral intravenous cannulation assessment tool was used to assess nurses' behavior during cannulation. Results from a hierarchical multiple regression indicated that patient demographic variables did not significantly predict overall ratings of peripheral intravenous cannulation performance. Nurses' education and experience significantly predicted overall ratings of peripheral intravenous cannulation. Educational preparation at a postgraduate level was a significant positive predictor, and the years of experience in general nursing were a significant negative predictor of overall ratings of peripheral intravenous cannulation. The results from the current study highlight the importance of applied education, such as that indicated by a graduate degree, in providing and maintaining advanced clinical skills for specialty practice.