Era Cohorts Research Articles

COVID-19 and postoperative complications after plastic surgery procedures: More than just hypercoagulability

BackgroundWhile plastic surgery procedures generally demonstrate a less than 2% incidence of VTE outcomes, the post-COVID era data remains elusive. This study sought to elucidate the relationship between COVID-19 infection and the risk of VTE outcomes across plastic surgery procedures. MethodsPlastic surgery procedures were identified in the 2012-2022 National Surgical Quality Improvement Program databases. The outcomes of interest were the postoperative occurrence of VTE, defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), and the occurrence of any postoperative complication. Propensity score matching was used to 1) compare overall rates of VTE between pre-pandemic era and pandemic era cohorts, and 2) compare rates of VTE and overall postoperative complications in cases with and without COVID-19 diagnosis in years 2021-2022 (p<0.05). Results269,006 plastic surgery cases were identified, comprising largely general breast (76%) and trunk (9.4%) procedures. Non-breast free tissue transfer cases were associated with the highest rates of DVT (1.3%) and trunk procedures with the highest rates of PE (0.7%). After propensity score matching, the overall rate of VTE after the onset of the COVID-19 pandemic was not significantly different from the pre-pandemic era (p=0.40). In a separately matched cohort, COVID-19 diagnosis did not significantly predict risk of VTE (p=0.48) but did significantly predict risk of overall postoperative complications (p<0.001). ConclusionsWhile COVID-19 diagnosis itself did not predict risk of VTE upon matched analysis, it significantly predicted overall postoperative complications. Future studies may further investigate effects of COVID-19 infection over longer periods of follow up.

Paradigm Shift of Interventional Strategies and Outcomes for Acute Limb Ischemia Post-Pandemic.

We performed a large-scale comparison of patients treated for acute limb ischemia (ALI) in the pre-COVID (2017-2019) and COVID (2020-2022) eras to evaluate changes in interventional strategies and compare factors associated with adverse outcomes. We sought to characterize patient outcomes in an evolving ALI treatment algorithm in response to pandemic-associated presentation delays and rapid technological advancements in mechanical thrombectomy (MT). Using the TriNetX global research network, we conducted a multicenter query across 80 health care organizations (HCOs) spanning 4 countries for patients treated for ALI. Propensity score matching was performed to account for comorbidities. Risk of adverse outcomes within 30 days was calculated for each era, including re-intervention (RI30), major/minor amputation, and death. Patients were then stratified by initial intervention: open revascularization (OR), MT, or catheter-directed thrombolysis and adjunctive endovascular procedures alone (CDT/EP). Risk of adverse outcomes was compared between treatment groups of the same era. After propensity score matching, the pre-COVID era and COVID era cohorts included 7344 patients each. COVID era patients experienced a statistically significant higher risk of 30-day mortality (RR=1.211, p=0.027). Mechanical thrombectomy interventions were performed more frequently in the COVID era (RR=1.314, p<0.0001). Comparing outcomes between treatment groups, MT patients required RI30 more than OR patients (pre-COVID: RR=2.074, p=0.006; COVID: RR=1.600, p=0.025). Open revascularization patients had higher 30-day mortality (pre-COVID: RR=2.368, p<0.0001; COVID: RR=2.013, p<0.0001) and major amputations (pre-COVID: RR=2.432, p<0.0001; COVID: RR=2.176, p<0.0001) than CDT/EP. Pre-COVID CDT/EP patients were at higher risk for RI30 (RR=1.449, p=0.005) and minor amputations (RR=1.500, p=0.010) than OR. The MT group had higher major amputation rates than CDT/EP (pre-COVID: RR=2.043, p=0.019; COVID: RR=1.914, p=0.007). COVID-era MT patients had greater 30-day mortality (RR=1.706, p=0.031) and RI30 (RR=1.544, p=0.029) than CDT/EP. Significant shifts toward an MT-based approach have been observed in the last 3 years. Although MT required more RI30 than OR, there was no associated consequence of mortality and limb salvage. The increased mortality seen among COVID-era patients could be explained by delayed presentation, as well as poorly understood pro-thrombogenic or pro-inflammatory mechanisms related to the first waves of COVID. More research is necessary to determine an optimal treatment algorithm. Comorbid risk factors and severity of ischemia must be carefully considered before selecting an interventional strategy to prevent adverse outcomes and maximize limb salvage. Open revascularization strategies are associated with increased mortality and limb loss compared to less-invasive thrombolytic therapy alone. Mechanical thrombectomy (MT)-based approaches have been increasingly used in the last 3 years. Patients receiving MT are more likely to require reintervention within 30 days.

The Impact of the COVID-19 Pandemic on One-Year Mortality in Geriatric Hip Fracture: A Retrospective Cohort Study.

The COVID-19 pandemic has profoundly impacted global healthcare systems, necessitating substantial shifts in patient care strategies. The pandemic's onset led to drastic operational changes in hospitals, including reduced bed capacity and staffing levels, which could have further influenced the mortality outcomes for geriatric patients. The study aimed to assess the impact of the COVID-19 pandemic on 1-year mortality rates of surgically treated geriatric hip fractures. This retrospective, single-center cohort study included 346 participants aged 65 and above who underwent surgical treatment for hip fractures. We compared mortality rates between the pre-COVID and COVID eras. Data included demographics, treatment, complications, and COVID-19 status. The independent samples t test and Chi-square tests (or Fisher's exact test) were used for comparisons for era cohorts. Survival probabilities were assessed using Kaplan-Meier, while multivariate analysis identified mortality predictors. 175 patients were included in the pre-COVID era, and 171 patients were included in the COVID era. During the COVID era, the 30-day mortality rate was 11.7% (compared to 13.7% in the pre-COVID era, p = 0.573), and the 1-year mortality rate was 43.9% (compared to 49.1% in the pre-COVID era, p = 0.325). The overall 1-year mortality rate was 46.5%. Patients who underwent surgery within 48hours had a higher 1-year survival rate (60.5%) compared to those with delayed surgery (51.2%), p = 0.031. Additionally, patients not admitted to the ICU had a higher 1-year survival rate (74.7%) than those who were admitted (44.9%), p < 0.001. 70.1% of the total deaths occurred within the first 90days. Elderly patients with hip fractures experienced high mortality rates before and during the pandemic. This study demonstrates that the 1-year mortality rates of geriatric hip fractures were not significantly affected by the pandemic. The findings emphasize the importance of pandemic preparedness and prompt surgeries and attentive ICU care in reducing mortality rates.

Pneumonitis Rates Before and After Adoption of Immunotherapy Consolidation in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiation

We hypothesized that after adoption of immune checkpoint inhibitor (ICI) consolidation for patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiation therapy (cCRT), rates of symptomatic pneumonitis would increase, thereby supporting efforts to reduce lung radiation dose. This single institution, multisite retrospective study included 783 patients with LA-NSCLC treated with definitive cCRT either before introduction of ICI consolidation (pre-ICI era cohort [January 2011-September 2017]; N=448) or afterward (ICI era cohort [October 2017-December 2021]; N=335). Primary endpoint was grade ≥2 pneumonitis (G2P) and secondary endpoint was grade ≥3 pneumonitis (G3P), per Common Terminology Criteria for Adverse Events v5.0. Pneumonitis was compared between pre-ICI era and ICI era cohorts using the cumulative incidence function and Gray's test. Inverse probability of treatment weighting (IPTW)-adjusted Fine-Gray models were generated. Logistic models were developed to predict the 1-year probability of G2P as a function of lung dosimetry. G2P was higher in the ICI era than in the pre-ICI era (1-year cumulative incidence 31.4% vs 20.1%; P < .001; IPTW-adjusted multivariable subdistribution hazard ratio, 2.03; 95% confidence interval, 1.53-2.70; P < .001). There was no significant interaction between ICI era treatment and either lung volume receiving≥20 Gy (V20) or mean lung dose in Fine-Gray regression for G2P; however, the predicted probability of G2P was higher in the ICI era at clinically relevant values of lung V20 (≥24%) and mean lung dose (≥14 Gy). Cut-point analysis revealed a lung V20 threshold of 28% in the ICI era (1-year G2P rate 46.0% above vs 19.8% below; P < .001). Among patients receiving ICI consolidation, lung V5 was not associated with G2P. G3P was not higher in the ICI era (1-year cumulative incidence 7.5% vs 6.0%; P=.39; IPTW-adjusted multivariable subdistribution hazard ratio, 1.12; 95% confidence interval, 0.63-2.01; P=.70). In patients with LA-NSCLC treated with cCRT, the adoption of ICI consolidation was associated with an increase in G2P but not G3P. With ICI consolidation, stricter lung dose constraints may be warranted.

Optimizing primary total shoulder arthroplasty in the COVID era: shorter length of stay with no increase in the complication profile

BackgroundThe novel coronavirus (COVID-19) pandemic had significant impact on surgical volume of total shoulder arthroplasty (TSA) with a 55% decline during the second quarter of 2020. As restrictions eased, TSA volume recovered back to its prepandemic baseline by Q3/Q4. The purpose of this study was (1) to compare the postoperative length of stay (LOS), discharge disposition, complications, emergency department (ED) utilization, hospital readmissions, and reoperations within 90 days following TSA before and during the pandemic era and (2) to evaluate surgical trends of TSA induced by the pressures of the global pandemic. MethodsAll patients undergoing either primary anatomic or reverse TSA between January 2018 and December 2021 were included. Procedures performed before March 11, 2020 were considered the “pre-COVID” cohort while those after were considered the “COVID era” cohort. The outcome measures included postoperative LOS, discharge disposition, complications, ED utilization, hospital readmissions, and reoperations within 90 days following TSA. P < .05 was considered statistically significant. ResultsThere were 227 and 96 patients in the pre-COVID and COVID era groups, respectively. There were no differences in age (P = .6), gender (P = .06), body mass index (P = .33), Elixhauser Comorbidity Index (P = .8), TSA indication (P = .65), or arthroplasty type (P = .61) between pre-COVID and COVID cohorts. During the pandemic, there was a significant increase in same-day discharge TSA (49% vs. 28.2%, P < .001), and 37.9% of pre-COVID patients had a LOS between 1 and 2 days as compared to 18.8% in the COVID era group. Ultimately, there were no differences in any complications or frequency of 30- or 90-day ED encounters, readmissions, or reoperations between pre-COVID and COVID era cohorts (P > .05 for all). ConclusionPrimary TSA during the pandemic was associated with more frequent same-day discharge without increased postoperative complications, ED encounters, readmissions, or reoperations at up to 90-days postoperatively. Our results suggest that primary TSA, a procedure historically associated with an inpatient stay, can safely be performed expeditiously in an outpatient setting without increasing patient morbidity or mortality.

Abstract 13924: Impact of a Pandemic on Women Diagnosed With Peripartum Cardiomyopathy

Background: Peripartum cardiomyopathy (PPCM) is a dilated form of cardiomyopathy that occurs during the last month of pregnancy or up to five months postpartum. Approximately 1,100 women develop PPCM in the United States each year. The aim of our study is to compare the incidence of PPCM prior to the start of the Coronavirus Disease 2019 (COVID) pandemic to afterwards and to determine the impact of COVID on hospitalized patients with PPCM. Methods: This was a retrospective study of 2,286 patients with a diagnosis of PPCM who were admitted to a private hospital system across the United States between the year 2017 and year 2021. There was 1,790 patients in the pre-COVID cohort, and 496 patients in the COVID era cohort. Demographics of patients were collected, with t-test and chi square p-values utilization for statistical description. Results: The mean age of women was 32.13 years. In the COVID era cohort, the percentage of Hispanic patients was significantly higher than the pre-COVID era (16.84% vs. 12.34%, p=0.012). In the COVID era, patients were more likely to have preeclampsia (20.16% vs. 13.52%, p&lt;0.001), HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome (2.62% vs. 0.61%, p&lt;0.001), respiratory failure (19.56% vs. 10.57%, p&lt;0.001), and myocardial infarction (3.63% vs. 1.90%, p=0.022). There was no significant difference in troponin and d-dimer values between the two era cohorts. The average length of stay, percentage of patients admitted to the intensive care unit (ICU), and death did not significantly differ between the pre-COVID and COVID era cohorts. Conclusion: In our study, although there was no significant difference in length of stay, ICU admission, or death in the COVID era cohort, myocardial infarction, preeclampsia, HELLP syndrome, and respiratory failure were each more prevalent in women with PPCM during the COVID era. These findings might indicate suboptimal access to outpatient and inpatient medical care during the COVID pandemic, which could have led to these more serious diagnoses.

Child sexual abuse survivors: Differential complex multimodal treatment outcomes for pre-COVID and COVID era cohorts

BackgroundChild sexual abuse (CSA) is a form of early-life trauma that affects youth worldwide. In the midst of the current COVID-19 pandemic, it is imperative to investigate the potential impact of added stress on already vulnerable populations. ObjectiveThe aim of this study was to evaluate the effectiveness of a multimodal treatment program on mental health outcomes for youth CSA survivors aged 8–17. Secondary to this, we explored the potential impact of the COVID-19 on treatment outcomes. Participants and settingParticipants of this study were children and youth aged 8–17 who were engaged in a complex multimodal treatment program specifically designed for youth CSA survivors. MethodsParticipants were asked to complete self-report surveys at baseline and at the end of two subsequent treatment rounds. Surveys consisted of measures pertaining to: (1) PTSD, (2) depression, (3) anxiety, (4) quality of life, and (5) self-esteem. ResultsMedian scores improved for all groups at all timepoints for all five domains. For the pre-Covid participants, the largest improvements in the child program were reported in depression (36.6 %, p = 0.05); in the adolescent program anxiety showed the largest improvement (−35.7 %, p = 0.006). Improvements were generally maintained or increased at the end of round two. In almost every domain, the improvements of the pre-COVID group were greater than those of the COVID-I group. ConclusionsA complex multimodal treatment program specifically designed for youth CSA survivors has the capacity to improve a number of relevant determinants of mental health and well-being. The COVID-19 pandemic may have retraumatized participants, resulting in treatment resistance.

Comparison of long‐term outcome of patients with ST‐segment elevation myocardial infarction between pre‐COVID‐19 and COVID‐19 era

AimsTo compare major cardiovascular and cerebrovascular events (MACCE ) rates between patients in the pre‐COVID‐19 era and COVID‐19 era, and to assess the impact of the presence of COVID‐19 (+) on long‐term MACCE in ST‐segment elevation myocardial infarction (STEMI) in Turkey.MethodsUsing the TURSER study (TURKISH ST‐segment elevation myocardial infarction registry) data, the current study included 1748 STEMI patients from 15 centers in Turkey. Patients were stratified into COVID‐19 era (March 11st–May 15st, 2020; n = 723) or pre‐ COVID‐19 era (March 11st–May 15st, 2019; n = 1025) cohorts. Long‐term MACCE rates were compared between groups. In addition, the effect of COVID‐19 positivity on long‐term outcomes was evaluated. The primary outcome was the occurrence of MACCE at long‐term follow‐up, and the secondary outcome was hospitalization with heart failure.ResultsThe MACCE and hospitalization with heart failure rates between pre‐COVID‐19 era and COVID‐19 era were 23% vs 22% (p = 0.841), and 12% vs %8 (p = 0.002), respectively. In the covid‐19 era, the rates of MACCE and hospitalization with heart failure COVID‐19 positive versus COVID‐19 negative patients were 40% vs 20%, (p < 0.001), and 43% vs 11% (p < 0.001), respectively.ConclusionThere was no difference between the pre‐COVID‐19 era and the COVID‐19 era in terms of MACCE and heart failure hospitalization in STEMI patients in Turkey. In the Covid‐19 era, STEMI patients positive for COVID‐19 had a higher rate of MACCE and heart failure hospitalization at the long‐term follow‐up.

SYST-08 SURVIVAL ANALYSIS OF METASTATIC MELANOMA PATIENTS WITH BRAIN METASTASIS USING SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS (SEER)

INTRODUCTION: Melanoma brain metastases (BM) are common and are historically associated with poor prognosis. In the early 2010s, the treatment paradigm for malignant metastatic melanoma shifted with the introduction of immunotherapy (IT). Recent studies suggest that IT provides survival benefits for patients with BM from melanoma primary. The goal of this study was to validate these findings in a large population cohort. METHODS: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database, version 8.3.4 (22 March 2017). Three cohorts were created based on the FDA approval date of IT: ipilimumab (2011), nivolumab (2014), and nivolumab plus ipilimumab (2015) for use in metastatic melanomas. Respectively, the cohorts are defined as the pre-IT era cohort (2010), early-IT era cohort (2011-2015) and late-IT era cohort (2016-2018). One-year overall survival (OS), 2-year OS, and median OS were assessed using a Kaplan-Meier analysis and log rank tests. RESULTS: 1,893 patients were included in this analysis (190 in the pre-IT era, 1,021 in the early-IT era, and 682 in the late-IT era) that had histologically confirmed melanoma with secondary BM at diagnosis. Median OS was significantly increased across the pre-, early-, and late-IT era cohorts, respectively, with the largest increase occurring between the early-IT and late-IT eras (1-year OS: 20.6% vs. 17.0% vs. 38.2%, 2-year OS: 10.5% vs. 14.2% vs. 27.1%, and median OS: 5 vs. 6 vs. 8 months, p < 0.001 by log-rank test). CONCLUSION: The introduction of IT for malignant melanomas has significantly improved the survival outcomes of melanoma patients with brain metastasis. Novel treatment paradigms involving IT with other adjuvant therapies need to be explored to further improve intracranial activity in melanoma patients.

Trends in diagnosis and treatment of early breast cancer (eBC) in the United States (US) during the COVID-19 era.

227 Background: Recent studies have demonstrated a decline in cancer screening and diagnosis during the COVID-19 pandemic. This study explored trends in the diagnosis and management of eBC at a sample of cancer clinics across the US early on in the pandemic. Methods: Patients were selected from the Flatiron Health Research Database (FHRD), an electronic health record-derived de-identified database comprising approximately 280 US cancer clinics (̃800 sites of care). Eligible patients had an ICD code for breast cancer, at least two clinical encounters, and a confirmed eBC (Stage I-III) diagnosis from unstructured documents. Patients were selected into two cohorts based on diagnosis date: a) COVID-19 era cohort diagnosed between February 1, 2020 through June 30, 2020 and b) pre-COVID-19 era cohort diagnosed from February 1, 2019 through June 30, 2019. Descriptive statistics were used to assess diagnosis trends in each time frame. Initial treatment received following eBC diagnosis was categorized as surgery, radiation or systemic therapy and was compared between the two cohorts. Initial treatment modalities for each cohort were further stratified by clinical stage and biomarker subtype (HER2+, HR+/HER2-, triple negative [TN] or unknown). Results: A total of 278 and 253 patients were selected for the pre-COVID-19 era and COVID-19 era cohorts, with a median age at diagnosis of 65 and 64 years, respectively. A 35% decrease in the number of eBC diagnoses was observed in April/May 2020 compared to March 2020, yet this reduction in diagnoses was not observed during the equivalent months in the pre-COVID-19 era cohort. Compared to the pre-COVID-19 era, a greater proportion of patients diagnosed with eBC during the COVID-19 era initiated systemic therapy as their first treatment modality (16.5% vs 29.6%) including patients with HER2+ (27.5% vs. 60%), HR+/HER2- (13.5% vs. 24.9%) and TN (30.8% vs. 40.0%) disease. This trend was observed in patients with stage I (11.7% vs. 24.1%) or II (55.9% vs. 73.0%) but not in patients with stage III (81.2% vs. 77.3%) eBC. Notably, among patients with HR+/HER2- eBC who received systemic therapy as their first treatment, endocrine therapy was most commonly used in keeping with recent recommendations from professional societies due to COVID-related anticipated surgical delays. Conclusions: This study demonstrates that COVID-19 was associated with a decreased incidence of eBC which could be, at least in part, attributed to previously reported delays in routine screening and pandemic healthcare utilization. Further efforts are required to understand who was affected by these delays and the impact on cancer outcomes. Follow-up data are needed to understand if the observed trends in cancer screening and treatment persist and their impact on long-term cancer outcomes.

Disease activity and damage in juvenile idiopathic arthritis: methotrexate era versus biologic era

ObjectiveTo compare the long-term disease state, in terms of activity and damage, of children with juvenile idiopathic arthritis (JIA) who had their disease onset in methotrexate (MTX) or biologic eras.MethodsPatients were included in MTX or biologic era cohort depending on whether their disease presentation occurred before or after January 2000. All patients had disease duration ≥ 5 years and underwent a prospective cross-sectional assessment, which included measurement of disease activity and damage. Inactive disease (ID) and low disease activity (LDA) states were defined according to Wallace, JADAS10, and cJADAS10 criteria. Articular and extraarticular damage was assessed with the Juvenile Arthritis Damage Index (JADI).ResultsMTX and biologic era cohorts included 239 and 269 patients, respectively. Patients were divided in the “functional phenotypes” of oligoarthritis and polyarthritis. At cross-sectional visit, patients in the biologic era cohort with either oligoarthritis or polyarthritis had consistently higher frequencies of ID and LDA by all criteria. The measurement of disease damage at cross-sectional visit revealed that the frequency of impairment of > 1 JADI-Articular items was higher in MTX than in biologic era cohort (17.6% versus 11% in oligoarthritis and 52.6% versus 21.8% in polyarthritis). Likewise, frequency of involvement of > 1 JADI-Extraarticular items was higher in the MTX than in the biologic era cohort (26.5% versus 16.2% in oligoarthritis and 31.4% versus 13.5% in polyarthritis).ConclusionOur study provides evidence of the remarkable outcome improvement obtained with the recent therapeutic advance in JIA.

The Impact of Removing the Donor Service Area (DSA) as the First Unit of Allocation for Lungs in the United States

Purpose On November 24, 2017, in an emergency action, the OPTN changed lung allocation policy by removing the donor service area (DSA) as the first unit of allocation for deceased donor lungs and replaced it with a 250 nautical mile (NM) circle around the donor hospital. Methods OPTN data on adult lung candidates and recipients was analyzed pre (11/25/2016- 8/24/2017) and post policy change (11/25/2017- 8/24/2018, 9 months). Comparisons were made to study the differences between cohorts. Results Comparison between the pre era (N=1,806) and the post era (N=1,843) cohorts revealed a significant increase in the match LAS at transplant (mean pre=47.24 vs. post=49.68, p Conclusion As expected, there was an increase in the distance traveled from transplant center to donor hospital to provide organs to candidates with a higher severity of illness. The waiting list mortality for LAS 60-70 decreased while transplant rate only decreased significantly for LAS 40-50. Lung utilization has not changed but an increase in the use of EVLP is noted. Continued evaluation is needed to understand the full effects of this policy change.

Changes in Otitis Media Episodes and Pressure Equalization Tube Insertions Among Young Children Following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine: A Birth Cohort-based Study.

The impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on the occurrence of first and subsequent otitis media (OM) episodes in early childhood is unclear. We compared the risk of OM episodes among children age <2 years before and after PCV13 introduction, accounting for the dependence between OM episodes. We identified consecutive annual (July-June) cohorts of Tennessee Medicaid-enrolled children (2006-2014) from birth through age 2 years. We identified OM episodes using coded diagnoses (we classified diagnoses <21 days apart as the same episode). We modeled adjusted hazard ratios (aHRs) for OM comparing 7-valent pneumococcal conjugate vaccine (PCV7)-era (2006-2010) and PCV13-era (2011-2014) birth cohorts, accounting for risk factors and dependence between first and subsequent episodes. Secondary analyses examined pressure equalization tube (PET) insertions and compared the risk of recurrent OM (≥3 episodes in 6 months or ≥4 episodes in 12 months) between PCV7- and PCV13-era birth cohorts. We observed 618 968 OM episodes and 24 875 PET insertions among 368 063 children. OM and PET insertion rates increased during the PCV7 years and declined after PCV13 introduction. OM and PET insertion risks were lower in the 2013-2014 cohort compared with the 2009-2010 cohort (aHRs [95% confidence interval], 0.92 [.91-.93] and 0.76 [.72-.80], respectively). PCV13 introduction was associated with declines in the risk of first, subsequent, and recurrent OM. The transition from PCV7 to PCV13 was associated with a decline of OM among children aged <2 years due to a reduction in the risk of both the first and subsequent OM episodes.

Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome.

Clinical molecular testing has been available for 22q11.2 deletion syndrome (22q11.2DS) for over two decades yet under-recognition and diagnostic delays are common. To characterize the "diagnostic odyssey" in 22q11.2DS we studied 202 well-characterized unrelated adults, none ascertained through an affected relative. We used a regression model to identify clinical and demographic factors associated with length of time to molecular diagnosis. Kaplan-Meier analysis compared time to diagnosis for the molecular testing era (since 1994) and earlier birth cohorts. The results showed that the median time to molecular diagnosis of the 22q11.2 deletion was 4.7 (range 0-20.7) years. Palatal and cardiac anomalies, but not developmental delay/intellectual disability, were associated with a shorter time to molecular diagnosis. Non-European ethnicity was associated with longer time to diagnosis. Inclusion of a cohort from another 22q11.2DS center increased power to observe a significantly earlier diagnosis for patients born in the molecular testing era. Nonetheless, only a minority were diagnosed in the first year of life. On average, patients were seen in seven (range 2-15) different clinical specialty areas prior to molecular diagnosis. The findings indicate that even for those born in the molecular testing era, individuals with 22q11.2DS and their families face a diagnostic odyssey that is often prolonged, particularly in the absence of typical physical congenital features or for those of non-European ancestry. The results support educational efforts to improve clinical recognition and testing, and ultimately newborn screening as a means of maximizing early detection that would provide the best opportunity to optimize outcomes.

Centralization of radical cystectomy for bladder cancer in a universal healthcare system: Early results from a Canadian academic center.

516 Background: Radical cystectomy for bladder cancer is a complex surgical oncology procedure. Centralization of this procedure to high volume, fellowship-trained surgeons may improve clinical outcomes. Our objective was to compare outcomes of radical cystectomy before and after centralization of care. Methods: A retrospective analysis of data from the University of Alberta Radical Cystectomy Database was performed. Eligible subjects were those with histologically proven urothelial carcinoma of the bladder (cTanyN1-3M0) undergoing curative intent surgery. Patients were classified into pre-centralization era (1994-2007; N = 523) and post-centralization era (2013-present; N = 134) cohorts for analyses. Pre-centralization era patients were treated by 1 of 11 urologic surgeons at 2 academic teaching hospitals. Post-centralization era patients were treated by 1 of 2 fellowship-trained urologic oncologists at 1 academic teaching hospital. Outcomes were overall survival, 90-day mortality rate, positive surgical margin (R1) resection rate, total number of lymph nodes evaluated, and 90-day blood product transfusion rate. The Kaplan-Meier method and multivariable regression analyses were used to analyze survival outcomes. Statistical tests were two-sided (p≤0.05). Results: The median follow-up duration in the pre- and post-centralization era was 33 months and 16 months, respectively. The predicted 2-year overall survival rate was 62% in the pre-centralization era and 84% in the post-centralization era (Log rank P = 0.0007; multivariable HR 0.40, 95% CI 0.24 to 0.68, P &lt; 0.0001). Treatment in the post-centralization era was associated with lower 90-day mortality (6.3% versus 1.5%, multivariable OR 0.23, 95% CI 0.06 to 0.99, P = 0.049), R1 resection (13.0% versus 1.5%; multivariable OR 0.07, 95% CI 0.01 to 0.51, P = 0.009), and 90-day blood product transfusion (59% versus 6%, P &lt; 0.0001) as well as higher total number of lymph nodes evaluated (7 versus 30 lymph nodes, P &lt; 0.0001). Conclusions: Surgical treatment in the post-centralization era was associated with superior survival, cancer control, and perioperative outcomes.

Changes in Oral Anticoagulant Prescribing for Stroke Prevention in Patients With Atrial Fibrillation

Suboptimal guideline adherence and underuse of anticoagulants in patients with atrial fibrillation (AF) have been reported worldwide. This study aimed to compare anticoagulation practice in Australia during the pre- and postdirect oral anticoagulant (DOAC) eras. Between January 2011 and July 2015, patients with nonvalvular AF (NVAF) admitted to the Royal Hobart Hospital, Tasmania, Australia, were retrospectively reviewed. The pre- and post-DOAC era cohorts included admissions from January 2011 to July 2013 and August 2013 to July 2015, respectively. Overall, 2,118 patients met our inclusion criteria. The overall rate of anticoagulation increased from 52.5% in the pre-DOAC era to 60.7% in the post-DOAC era (p <0.001). Moreover, prescribing of OACs among high-risk patients improved significantly (63.1% vs 55.2%, p = 0.001). OAC overprescribing in low-risk patients did not change significantly between the 2 cohorts (35.0% vs 42.9% in the pre- and post-DOAC eras, respectively, p = 0.59). In multivariate analysis, DOAC era (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.17 to 1.68 and CHA2DS2-VASc ≥2 (OR 1.95, 95% CI 1.36 to 2.80) were independent predictors of OAC prescribing in both eras and the whole study period. Conversely, aging and previous bleeding were inversely associated with OAC prescribing. In conclusion, there has been a significant increase in OAC prescribing in the post-DOAC era, potentially driven by the widespread availability of DOACs. However, OAC underuse in high-risk patients and overuse in low-risk patients was apparent throughout our study. These findings highlight the need to identify the drivers of anticoagulant underuse and overuse and address them accordingly.

Does Black Socioeconomic Mobility Explain Recent Progress Toward Black-White Residential Integration?

Studies of racial residential segregation have found that black-white segregation in U.S. metropolitan areas has declined slowly but steadily since the early 1970s. As of this writing, black-white residential segregation in the United States is approximately 25 % lower than it was in 1970. To identify the sources of this decline, we used individual-level, geocoded data from the Panel Study of Income Dynamics (PSID) to compare the residential attainment of different cohorts of blacks. We analyzed these data using Blinder-Oaxaca regression decomposition techniques that partition the decline in residential segregation among cohorts into the decline resulting from (1) changes in the social and economic characteristics of blacks and (2) changes in the association between blacks' social and economic characteristics and the level of residential segregation they experience. Our findings show that black cohorts entering adulthood prior to the civil rights movement of the 1960s experienced consistently high levels of residential segregation at middle age, but that cohorts transitioning to adulthood during and after this period of racial progress experienced significantly lower levels of residential segregation. We find that the decline in black-white residential segregation for these later cohorts reflects both their greater social and economic attainment and a strengthening of the association between socioeconomic characteristics and residential segregation. Educational gains for the post-civil rights era cohorts and improved access to integrated neighborhoods for high school graduates and college attendees in these later cohorts were the principal source of improved residential integration over this period.

Real-World Survival Outcomes and Prognostic Factors Among Patients Receiving First Targeted Therapy for Advanced Renal Cell Carcinoma: A SEER-Medicare Database Analysis.

The real-world survival outcomes and prognostic factors among patients receiving first-line targeted therapy for advanced renal cell carcinoma (aRCC) are not well known. Adult patients diagnosed with RCC and treated with first-line targeted therapy were identified from the Surveillance, Epidemiology, and End Results-Medicare database (January 1, 1993 to December 31, 2012). The patients were grouped into early (2006-2009) or late (2010-2012) targeted therapy era cohorts by the year of the first-line targeted therapy initiation. Overall survival (OS) was measured from first-line targeted therapy initiation and compared between the 2 cohorts using Kaplan-Meier analyses. The prognostic factors for OS were assessed using a multivariable-adjusted Cox model. A total of 604 and 641 aRCC patients (mean age, 68 years; ∼60% male in both cohorts) initiated first-line targeted therapy during the early and late targeted therapy eras, respectively. OS was significantly longer in the late than in the early targeted therapy era. Higher tumor grades (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.31-2.00) and lung (HR, 1.27; 95% CI, 1.06-1.53), bone (HR, 1.37; 95% CI, 1.13-1.66), and liver (HR, 1.42; 95% CI, 1.10-1.84) metastases were associated with significantly shorter OS. Previous nephrectomy (HR, 0.55; 95% CI, 0.42-0.72) and pazopanib as first-line targeted therapy relative to sorafenib (HR, 0.56; 95% CI, 0.37-0.85) or sunitinib (HR, 0.65; 95% CI, 0.44-0.95) were associated with significantly longer OS. The results of these real-world analyses suggest progress in aRCC management and identified positive (nephrectomy, pazopanib vs. sunitinib or sorafenib) and negative (higher tumor grade and lung, bone, or liver metastasis) prognostic factors among patients receiving first-line targeted therapy.

Multi-Center Quantification Study of Time, Effort and Resource Utilization Associated with Autologous Peripheral Blood Stem Cell Mobilization: A European Perspective

Autologous peripheral blood stem cell mobilization has demonstrated clinical benefit for improving stem cell collection prior to autologous or allogenic transplantation. With intense competition for hospital resources required to evaluate and manage patients preparing for stem cell mobilization and transplantation, resource requirements associated with varying therapeutic interventions is warranted. Plerixafor is indicated in combination with G-CSF to enhance mobilization of hematopoietic stem cells to peripheral blood (PBSC) for collection and subsequent autologous transplantation inpatients with lymphoma (Non-Hodgkin's Lymphoma (NHL)) and multiple myeloma (MM) whose cells mobilize poorly. A non-interventional two-part study using aggregated, de-identified data was initiated across three European countries to assess resource utilization associated with PBSC mobilization and apheresis in NHL patients in the era prior to and following approval of plerixafor (to the "Pre-P" era through June 1, 2009, and "P" era from July 1, 2010 onwards; "P", respectively).Adult patients aged ≥18 years, with a primary diagnosis of NHL, who underwent PBSC mobilization at 9 European centers in France, Germany and Italy were included in the study. Part I is a retrospective medical record review of 200 NHL patients. Outcomes measured in Part I included # of visits for administration of mobilizing agents and # days administered; assessment of adverse events (AEs) associated with administered mobilizing agents; # of apheresis sessions; hours of apheresis sessions; attainment of CD34+ target; and days until CD 34+ target level met. For Pre-P era patients, the peripheral CD-34+ count recorded immediately prior to the first apheresis; for P era patients, it was that recorded immediately prior to plerixafor administration. Part II is a prospective time and motion evaluation of apheresis performed at each center (5 events recorded per center; patient consent was obtained). Apheresis events were measured in consecutive patients scheduled to be candidates for PBSC mobilization. Time-motion assessments, obtained retrospectively (Part I) and prospectively (Part II), included total time to prepare the patient, perform apheresis and manage AEs. A micro-costing exercise was carried out by obtaining costs per unit of resource utilization from interviews with hospital administration staff. The study end points are the difference in mean time/effort to perform apheresis (including apheresis related AEs, if any) and total costs associated with mobilization to the hospital between patients in the Pre-P versus P eras.Evaluation of patient demographics revealed no significant differences between pre-P and P era cohorts. Analysis of the number of apheresis sessions demonstrated a statistically significant reduction (P<0.001) for the P era group, including # of sessions, total blood volume collected and total apheresis time required to reach the targeted PBSC compared with Pre-P era group. Total cost differences between cohorts was estimated based on observed clinical and resource utilization differences. In addition, more than twice as many patients who had a CD 34+ <10 were mobilized in the P era compared with patients in the Pre-P era.This study demonstrates that use of plexiafor is associated with statistically significant reductions in the # of apheresis sessions, driving both resource utilization efficiencies and cost savings for NHL patients undergoing autologous PBSC mobilization vs patients in the pre-P era. Further research to quantify the time and motion and cost-consequences of treatment approaches for stem cell mobilization in routine clinical care is warranted to optimize treatment for NHL patients. DisclosuresAzar:Sanofi: Honoraria, Research Funding. Reitan:Amgen: Research Funding; Sanofi: Research Funding; Spectrum: Research Funding. Gallagher:Sanofi: Employment, Equity Ownership.

OP0196 Obesity and Disease Activity in A Large International Rheumatoid Arthritis Cohort

BackgroundThere appears to be a paradoxical relationship between increasing body mass index (BMI) and outcome from rheumatoid arthritis (RA), with studies demonstrating less radiographic joint damage (RJD) for obese patients...