Propensity Score-weighted Analysis Research Articles

Ischemic Stroke Occurs Less Frequently in Patients With COVID-19: A Multicenter Cross-Sectional Study.

The impact of coronavirus disease 2019 (COVID-19) on the occurrence of ischemic stroke has been the subject of increased speculation but has not been confirmed in large observational studies. We investigated the association between COVID-19 and stroke. We performed a cross-sectional study involving patients discharged from a healthcare system in New York State, from January to April 2020. A mixed-effects logistic regression analysis and a propensity score-weighted analysis were used to control for confounders and investigate the association of COVID-19 with ischemic stroke. Similar techniques were used to detect the impact of concurrent COVID-19 infection on unfavorable outcomes for patients with stroke. Among 24 808 discharges, 2513 (10.1%) were diagnosed with COVID-19, and 566 (0.2%) presented with acute ischemic stroke. Patients diagnosed with COVID-19 were at one-quarter the odds of stroke compared with other patients (odds ratio, 0.25 [95% CI, 0.16-0.40]). This association was consistent in all age groups. Our results were robust in sensitivity analyses, including propensity score-weighted regression models. In patients presenting with stroke, concurrent infection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was associated with higher case-fatality (odds ratio, 10.50 [95% CI, 3.54-31.18]) and a trend towards increased occurrence of discharge to rehabilitation (odds ratio, 2.45 [95% CI, 0.81-1.25]). Using a comprehensive cross-section of patients from a large NY-based healthcare system, we did not identify a positive association between ischemic stroke and COVID-19. However, patients with stroke with COVID-19 had worse outcomes compared with those without, with over a 9-fold increase in mortality. Although no definitive conclusions can be reached from our observational study, our data do not support the concerns for an epidemic of stroke in young adults with COVID-19.

Prognostic Impact of pT3 Subclassification in a Multicentre Cohort of Patients with Urothelial Carcinoma of the Renal Pelvicalyceal System Undergoing Radical Nephroureterectomy: A Propensity Score-weighted Analysis After Central Pathology Review

BackgroundThe current pathological tumour-node-metastasis (pTNM) classification for upper tract urothelial carcinoma (UTUC) does not include any risk stratification of pT3 renal pelvicalyceal tumours. ObjectiveTo assess the prognostic impact of pT3 subclassification in a multicentre cohort of patients with UTUC of the renal pelvicalyceal system undergoing radical nephroureterectomy (RNU). Design, setting, and participantsData from all consecutive patients treated with RNU for pT3 renal pelvicalyceal UTUC at 14 French centres from 1995 to 2013 were reviewed retrospectively. InterventionA central pathology review (CPR) was used to stratify pT3 patients into those with infiltration of the renal parenchyma on a microscopic level (pT3a) versus those with infiltration of the renal parenchyma visible on gross inspection of the resection specimen and/or invasion of peripelvic fat (pT3b). Outcome measurements and statistical analysisInverse probability weighting (IPW)-adjusted Cox regression analyses were used to compare recurrence-free survival (RFS) and cancer-specific survival (CSS) between pT3a and pT3b patients. Results and limitationsOverall, 202 patients were included and further stratified into pT3a (n = 98; 48.5%) and pT3b (n = 104; 51.5%) subgroups. Median time to follow-up in the weighted population was 68 (interquartile range, 50–95) mo. In IPW-adjusted Cox regression analyses, pT3b versus pT3a substage was associated with a significant adverse effect on RFS (hazard ratio [HR] = 2.02; 95% confidence interval [CI] = [1.36–3.01]; p < 0.001) and CSS (HR = 1.84; 95% CI = [1.20–2.82]; p = 0.005). The study is limited by its retrospective design. ConclusionsUsing IPW-adjusted analyses after the CPR, we observed that RNU patients with pT3b renal pelvicalyceal UTUC had adverse prognosis as compared with those with pT3a disease. As such, this subclassification could help refine the current pTNM system for UTUC. Patient summaryIn this report, we looked at the prognostic interest of stratifying patients with pT3 renal pelvicalyceal upper tract urothelial carcinoma based on the extent of local invasion. We found that those with extensive infiltration (pT3b) had adverse prognosis as compared with those with limited infiltration (pT3a). This information could be provided on pathology reports to further guide clinical decision making.

Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). This observational, population-based cohort study enrolled 53236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.

Continuous Deep Sedation is Not Associated with Shorter Survival in the Last Days of Life in Patients with Advanced Cancer: A Propensity Score-Weighted Analysis of a Prospective Cohort Study

Background: Continuous deep sedation (CDS) is ethically controversial with respect to whether it shortens a patient’s life. Previous studies reported no significant difference in survival from admission or enrolment into a palliative care program to death between patients treated with and without CDS. However, these baselines are too distant from the initiation of CDS to detect the effect of CDS on survival. We aimed to examine whether CDS shortens patient survival from the day of Palliative Performance Scale decline to 20 (PPS20). Methods: This study was a part of a multicenter prospective cohort study that recruited patients between Jan. and Dec. 2017 in Japan (EASED study). Consecutive Adult patients with advanced cancer admitted to 23 participating inpatient palliative care units were eligible for this analysis. We compared survival from PPS20 between those who did and did not receive CDS. We used the inverse probability of treatment weighting method to control for potential confounders of patient characteristics, complications and laboratory data at admission, and symptoms at PPS20. Findings: A total of 1926 patients were enrolled. Of these, patients discharged alive were excluded, and finally we analyzed 1625 patients of whom 156 (9.6%) received CDS. Median survival from PPS20 of 1625 patients was 3.4 days (95% CI: 3.2-3.7). CDS was not associated with a significant survival risk from PPS20 (adjusted hazard ratio: 1.06, 95% CI:0.85–1.33; p = 0.595). In exploratory subgroup analyses, a significant survival risk was not observed in any subgroup except for those with primary lung cancer and agitated delirium. Interpretation: CDS was not associated with shorter survival in the last days of life in patients with advanced cancer, and CDS had no measurable effects on survival. Our findings may relieve the concern of patients, families, and physicians that CDS might shorten survival. Funding Statement: This work was supported by Grant-in-Aid from the Japanese Hospice Palliative Care Foundation and in part by JSPS KAKENHI Grant number JP19H03869. Declaration of Interests: No relevant conflict of interest to declare. Ethics Approval Statement: This study was conducted in accordance with the ethical standards of the Helsinki Declaration and the ethical guidelines for epidemiologic research of the Ministry of Health, Labour and Welfare of Japan. The local institutional review boards of all participating institutions approved this study. Japanese law does not require individual informed consent from participants in a non-invasive observational trial such as this. Therefore, we used an opt-out method rather than acquiring written or oral informed consent.

The impact of brachytherapy boost and radiotherapy treatment duration on survival in patients with vaginal cancer treated with definitive chemoradiation

PurposeVaginal cancer is a rare tumor that is optimally treated with a combination of chemotherapy (CHT) and radiation therapy. Because of the rarity of this cancer, the benefit of a brachytherapy boost (BT) and the relevance of radiotherapy time to treatment completion (TTC) are unclear. MethodsPatients diagnosed between 2004 and 2015 with non-metastatic vaginal cancer treated with definitive CHT and external beam radiotherapy with or without BT but with no surgery were identified in the National Cancer Database. Overall survival (OS) was assessed with Kaplan-Meier curves, and differences between groups were compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders. A Cox model using a penalized spline function was constructed to evaluate how the length of radiation therapy correlated with OS among patients receiving BT. ResultsA total of 1094 patients who met the inclusion criteria were identified. The utilization of BT was associated with improved 5-year OS (62.9% vs. 49.3%, p = 0.0126) on propensity score-weighted analyses. TTC of 63 days or less was associated with improved 5-year OS (67.8% vs. 54.5%, p = 0.0031) in patients who underwent BT. Other factors associated with improved OS in patients who received CHT, external beam radiotherapy, and BT were younger age, absent comorbidity score, and negative lymph nodes. ConclusionsA brachytherapy boost and shorter TTC were associated with a survival benefit in a cohort of patients with non-metastatic vaginal cancer treated with definitive chemoradiotherapy.

Formal Finance Usage and Innovative SMEs: Evidence from ASEAN Countries

This paper provides evidence on the likelihood of formal finance usage among innovative small and medium enterprises (SMEs) operating in ASEAN countries. To this end, the SMEs are classified into four categories, namely non-innovators and product, process, and product-and-process innovator SMEs. Subsequently, a propensity score weighting (PSW) analysis is performed to adjust for diversity existing across innovative SMEs. The resulting propensity scores are further used to perform the causal effect analysis based on the average treatment effect (ATE) approach, which measures the likelihood of formal finance usage among different types of innovative SMEs. Our ATE results reveal that SMEs simultaneously engaged in product and process innovation show a higher likelihood of using formal finance than non-innovators. However, formal finance usage of SMEs perusing only product/service or process innovation is not any different from non-innovators. Furthermore, our pairwise analysis shows that product and process innovators also exhibit a higher likelihood of formal finance usage than product/service or process innovators. Besides, younger and medium-size product and process innovating SMEs are more likely to use formal finance. These results are robust for different subsamples and firm- and country-level controls.

Impact of patient, primary tumor and metastatic pattern including tumor location on survival in patients undergoing ablation or resection for colorectal liver metastases: A population-based national cohort study

IntroductionSelecting the optimal treatment strategy for patients with colorectal liver metastases (CRLM) aim to improve survival for the total cohort. Following the introduction of laparoscopic resections and ablation, localization may direct choice of method. The aim with this study was to re-evaluate prognostic factors that should be considered at the preoperative multidisciplinary tumor board, based on a national population cohort. Materials and methodsA national cohort with radically operated colorectal cancer in 2009-2013, also treated for CRLM was identified in Swedish national registries. Prognostic factors were identified and evaluated in multivariable analyses. Results1200 patients treated with resection and 125 with ablation only were included in the study cohort. Relative five-year survival was 54.7% (50.9%-58.4%) and 32.0% (22.4%-41.9%), respectively). High age, acute surgery and complications at time of primary tumor resection remained important risk factors at liver surgery, as well as the primary tumor characteristics; vascular invasion and high lymph node ratio. As for metastatic pattern; tumor size, location in segment 4, 6, 7 or 8, multiple metastatic sites and progress after preoperative chemotherapy were significant risk factors. In multivariate analyses, ablation therapy doubled the risk of death within 5 years. This strong negative impact was confirmed in a weighted propensity score analysis (HR = 2.1 (95 % CI 1.5 -3.0)). ConclusionSegmental localization and tumor size were prognostic factors but also patient and primary tumor factors significantly impacted survival after intervention for CRLM. Long-term survival was significantly lower after ablation therapy compared to surgical resection.

Venoarterial extracorporeal membrane oxygenation to rescue sepsis-induced cardiogenic shock: a retrospective, multicentre, international cohort study

Patients with sepsis-induced cardiomyopathy with cardiogenic shock have a high mortality. This study assessed venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for sepsis-induced cardiogenic shock refractory to conventional treatments. In this retrospective, multicentre, international cohort study, we compared outcomes of 82 patients (aged ≥18 years) with septic shock who received VA-ECMO at five academic ECMO centres, with 130 controls (not receiving ECMO) obtained from three large databases of septic shock. All patients had severe myocardial dysfunction (cardiac index 3 L/min per m2 or less or left ventricular ejection fraction [LVEF] 35% or less) and severe haemodynamic compromise (inotrope score at least 75 μg/kg per min or lactic acidaemia at least 4 mmol/L) at time of inclusion. The primary endpoint was survival at 90 days. A propensity score-weighted analysis was done to control for confounders. At baseline, patients treated with VA-ECMO had more severe myocardial dysfunction (mean cardiac index 1·5 L/min per m2vs 2·2 L/min per m2, LVEF 17% vs 27%), more severe haemodynamic impairment (inotrope score 279 μg/kg per min vs 145 μg/kg per min, lactataemia 8·9 mmol/L vs 6·5 mmol/L), and more severe organ failure (Sequential Organ Failure Assessment score 17 vs 13) than did controls, with p<0·0001 for each comparison. Survival at 90 days for patients treated with VA-ECMO was significantly higher than for controls (60% vs 25%, risk ratio [RR] for mortality 0·54, 95% CI [0·40-0·70]; p<0·0001). After propensity score weighting, ECMO remained associated with improved survival (51% vs 14%, adjusted RR for mortality 0·57, 95% CI [0·35-0·93]; p=0·0029). Lactate and catecholamine clearance were also significantly enhanced in patients treated with ECMO. Among the 49 survivors treated with ECMO, 32 who had been treated at the largest centre reported satisfactory Short Form-36 evaluated health-related quality of life at 1-year follow-up. Patients with severe sepsis-induced cardiogenic shock treated with VA-ECMO had a large and significant improvement in survival compared with controls not receiving ECMO. However, despite the careful propensity-weighted analysis, we cannot rule out unmeasured confounders. None.

Comparison of heart failure risk and medical costs between patients with type 2 diabetes mellitus treated with dapagliflozin and dipeptidyl peptidase-4 inhibitors: a nationwide population-based cohort study

BackgroundDapagliflozin is one of the novel glucose-lowering agents, which has recently been reported to reduce the risk of hospitalization for heart failure (hHF). The present study aimed to compare the differences between the risk of hHF after using dapagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as second-line drugs for the treatment of type 2 diabetes mellitus using the latest nationwide population data in Korea. Additionally, we aimed to examine the impact of clinical outcomes on direct medical costs in the two groups.MethodsThe present population-based, retrospective cohort study was conducted using the nationwide claims data between September 01, 2014 and June 30, 2018. New users of dapagliflozin and DPP-4i were identified from the database and the differences in patients’ characteristics between the two groups were analyzed using propensity score-weighted analysis. Cox proportional hazards regression analysis was used to estimate the risk of hHF. A simple model was used for the estimation of direct medical costs for 3 years.ResultsIn total, 23,147 patients in the dapagliflozin group and 237,187 patients in the DPP-4i group were selected for the analysis. The incidence rates of hHF were 3.86 and 6.79 per 1000 person-years in the dapagliflozin and DPP-4i groups, respectively. In the entire study population, the hazard ratio for hHF in the dapagliflozin group compared to the DPP-4i group was 0.58 (95% confidence interval 0.46–0.74), with 0.55 (95% confidence interval 0.41–0.74) among patients with underlying cardiovascular disease and 0.66 (95% confidence interval 0.46–0.95) among patients without underlying cardiovascular disease. The direct medical costs were $57,787 lower in the dapagliflozin group than in the DPP-4i group for 3 years.ConclusionsThis study showed that dapagliflozin lowers the risk for hHF and subsequently reduces direct medical costs compared to DPP-4i. The protective effect against hHF was more evident among patients with underlying cardiovascular disease.

Compassionate Use of Hydroxychloroquine in Clinical Practice for Patients With Mild to Severe COVID-19 in a French University Hospital.

BackgroundData from non-randomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against Covid-19.MethodsWe conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe Covid-19 in a French university hospital. Patients who received hydroxychloroquine (200mg tid dosage for 10 days) on a compassionate basis in addition to SOCwere compared to patients without contraindications to hydroxychloroquine who received SOCalone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, and obesity, NEWS2 score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first.ResultsData from 89 patients with laboratory-confirmed Covid-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOCalone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxycholoroquine was not associated with a significantly reduced risk of unfavorable outcome (HR 0.90 [0.38; 2.1], p = 0.81). Overall survival was not significantly different between the two groups (HR 0.89 [0.23; 3.47], p = 1)ConclusionIn hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care. Unmeasured confounders may however have persisted despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of Covid-19.

Treatment outcomes after splenectomy with gastric devascularization or balloon-occluded retrograde transvenous obliteration for gastric varices: a propensity score-weighted analysis from a single institution.

BackgroundAlthough balloon-occluded retrograde transvenous obliteration (BRTO) is often selected to treat gastric varices caused by portal hypertension, data comparing BRTO and splenectomy with gastric devascularization (Sp + Dev) are limited.MethodsFrom January 2009 to February 2018, 100 patients with gastric varices caused by portal hypertension who underwent Sp + Dev (n = 45) or BRTO (n = 55) were included. Overall survival (OS) and the rebleeding rate were calculated using the inverse probability of a treatment weighting-adjusted log-rank test. Independent risk factors were identified by Cox regression analysis. Changes in liver function and adverse events after the procedures were analyzed.ResultsPatients in the Sp + Dev group tended to have lower platelet counts than those in the BRTO group, but liver function did not differ between these groups. The 5-year OS rates for the Sp + Dev and BRTO groups were 73.4 and 50.0% (p = 0.005), respectively. There were no significant differences in rebleeding rates between the two groups. Multivariate analysis showed that serum albumin level ≤3.6 g/dL, prothrombin time% activity (PT%) ≤80%, and serum creatinine level ≥0.84 mg/dL were poor prognostic factors. Although the Sp + Dev group had more short-term complications after procedures, Sp + Dev tended to be more effective in improving liver function than BRTO.ConclusionsSp + Dev showed better OS and improvement of liver function compared with BRTO for the treatment of gastric varices caused by portal hypertension.Electronic supplementary materialThe online version of this article (10.1007/s00535-020-01693-9) contains supplementary material, which is available to authorized users.

The Association of Antibiotic Duration With Successful Treatment of Community-Acquired Pneumonia in Children.

National guidelines recommend 10 days of antibiotics for children with community-acquired pneumonia (CAP), acknowledging that the outcomes of children hospitalized with CAP who receive shorter durations of therapy have not been evaluated. We conducted a comparative effectiveness study of children aged ≥6 months hospitalized at The Johns Hopkins Hospital who received short-course (5-7 days) vs prolonged-course (8-14 days) antibiotic therapy for uncomplicated CAP between 2012 and 2018 using an inverse probability of treatment weighted propensity score analysis. Inclusion was limited to children with clinical and radiographic criteria consistent with CAP, as adjudicated by 2 infectious diseases physicians. Children with tracheostomies; healthcare-associated, hospital-acquired, or ventilator-associated pneumonia; loculated or moderate to large pleural effusion or pulmonary abscess; intensive care unit stay >48 hours; cystic fibrosis/bronchiectasis; severe immunosuppression; or unusual pathogens were excluded. The primary outcome was treatment failure, a composite of unanticipated emergency department visits, outpatient visits, hospital readmissions, or death (all determined to be likely attributable to bacterial pneumonia) within 30 days after completing antibiotic therapy. Four hundred and thirty-nine patients met eligibility criteria; 168 (38%) patients received short-course therapy (median, 6 days) and 271 (62%) received prolonged-course therapy (median, 10 days). Four percent of children experienced treatment failure, with no differences observed between patients who received short-course vs prolonged-course antibiotic therapy (odds ratio, 0.48; 95% confidence interval, .18-1.30). A short course of antibiotic therapy (approximately 5 days) does not increase the odds of 30-day treatment failure compared with longer courses for hospitalized children with uncomplicated CAP.

Comparative effectiveness of proton versus photon chemoradiotherapy for patients with private insurance.

7049 Background: Proton therapy may increase the tolerability/efficacy of concurrent chemoradiotherapy (CRT) but is controversial &amp; generally not covered by private insurers. There is little data on the comparative effectiveness (CE) of proton vs photon CRT among private insurance pts to guide payers on proton coverage policies. Methods: We conducted a CE study of adult non-metastatic cancer pts with private insurance treated with curative-intent proton vs photon CRT from 2011-2016 at Penn. The choice of radiation modality was heavily influenced by the insurer’s proton coverage policy. Data on adverse events (AEs) &amp; survival were gathered prospectively using standardized templates. Primary endpoint was 90-day AEs associated with unplanned hospitalizations (CTCAEv4 grade ≥3 AEs). Secondary endpoints included 90-day grade ≥2 AEs, decline in ECOG performance status (PS) during treatment, disease-free survival (DFS) &amp; overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were used for adverse event outcomes. Weighted Cox proportional hazards models were used for survival outcomes. Propensity scores were estimated using an ensemble machine-learning approach. P&lt;0.01 was significant. Results: 920 pts were included (178 proton/742 photon), with H&amp;N(25 proton/296 photon); CNS(44/128); lung(41/120); upper GI(34/78) &amp; lower GI/GYN(34/120). Median age was 57. Race, comorbidity score, BMI, baseline AEs &amp; baseline PS were similar (p&gt;0.05 for all). 11.2% of proton pts had grade ≥3 AE’s vs 26.8% of photon pts. On propensity score weighted-analyses, proton CRT was associated with significantly lower relative risk (RR) of 90-day grade ≥3 AEs (RR 0.51, 95%CI 0.32-0.81, p&lt;0.01). 90-day grade ≥2 AE’s (RR 0.91, 95%CI 0.83-0.99, p=0.03); decline in PS (RR 0.85, 95%CI 0.70-1.04, p=0.11); DFS (HR 0.64, 95%CI 0.27-1.52, p=0.31) &amp; OS (HR 0.53, 95%CI 0.18-1.52, p=0.24) favored protons. Sensitivity analysis showed that a substantial imbalance in an unmeasured confounder would be needed to alter the significance of the primary outcome. Proton accepting insurance status was not associated with a difference in 90-day grade ≥3 AE’s (RR 1.02, 95%CI 0.95-1.10, p=0.54) for pts treated with photon CRT (608 with non-proton accepting insurance &amp; 134 with proton-accepting insurance). Conclusions: In adults with private insurance, proton CRT was associated with significantly reduced acute grade ≥3 AE’s with similar DFS &amp; OS. Proton-accepting insurance status was not associated with better health outcomes when adjusting for RT modality.

Comparative Effectiveness of Antibiotic Treatment Duration in Children With Pyelonephritis

National guidelines recommend treating children with pyelonephritis for 7 to 14 days of antibiotic therapy, yet data are lacking to suggest a more precise treatment duration. To compare the clinical outcomes of children receiving a short-course vs a prolonged-course of antibiotic treatment for pyelonephritis. Retrospective observational study using inverse probability of treatment weighted propensity score analysis of data from 5 hospitals in Maryland between July 1, 2016, and October 1, 2018. Participants were children aged 6 months to 18 years with a urine culture growing Escherichia coli, Klebsiella species, or Proteus mirabilis with laboratory and clinical criteria for pyelonephritis. Treatment of pyelonephritis with a short-course (6 to 9 days) vs a prolonged-course (10 or more days) of antibiotics. Composite outcome of treatment failure within 30 days of completing antibiotic therapy: (a) unanticipated emergency department or outpatient visits related to urinary tract infection symptoms, (b) hospital readmission related to UTI symptoms, (c) prolongation of the planned, initial antibiotic treatment course, or (d) death. A subsequent urinary tract infection caused by a drug-resistant bacteria within 30 days was a secondary outcome. Of 791 children who met study eligibility criteria (mean [SD] age 9.2 [6.3] years; 672 [85.0%]) were girls, 297 patients (37.5%) were prescribed a short-course and 494 patients (62.5%) were prescribed a prolonged-course of antibiotics. The median duration of short-course therapy was 8 days (interquartile range, 7-8 days), and the median duration of prolonged-course therapy was 11 days (interquartile range, 11-12 days). Baseline characteristics were similar between the groups in the inverse probability of treatment weighted cohort. There were 79 children (10.1%) who experienced treatment failure. The odds of treatment failure were similar for patients prescribed a short-course vs a prolonged-course of antibiotics (11.2% vs 9.4%; odds ratio, 1.22; 95% CI, 0.75-1.98). There was no significant difference in the odds of a drug-resistant uropathogen for patients with a subsequent urinary tract infection within 30 days when prescribed a short-courses vs prolonged-course of antibiotics (40% vs 64%; odds ratio, 0.36; 95% CI, 0.09-1.43). The study findings suggest that short-course antibiotic therapy may be as effective as prolonged-courses for children with pyelonephritis, and may mitigate the risk of future drug-resistant urinary tract infections. Additional studies are needed to confirm these findings.

Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality in Patients Hospitalized for Pneumonia

Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients. To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens. Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019. Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization. Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli. Among 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]). This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.

Abstract P2-16-36: Survival benefit of neoadjuvant chemotherapy versus adjuvant chemotherapy in HER2-positive early breast cancer: A propensity score-weighted analysis

Abstract INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly being used for locally advanced breast cancers (BCs) or aggressive BC tumors. However, no survival benefit of the neoadjuvant approach over receiving chemotherapy in the adjuvant setting has been proven so far in HER2-positive early breast cancer (BC) patients. The objective of this study was to compare the prognosis of patients with an HER2-positive BC treated with NAC to patients treated with adjuvant chemotherapy (AC). MATERIALS AND METHODS: We retrospectively identified in our institutional database 203 patients with HER2-positive BCs treated with NAC plus trastuzumab and 701 patients treated with adjuvant chemotherapy. As the treatment was not randomly allocated, we used a propensity score with an Inverse probability of received treatment weighting (IPTW) to generate a pseudo-population in which each covariate combination was balanced between treatment groups. The disease free (DFS), distant metastasis free (DMFS) and overall survival (OS) were evaluated using a weighted Cox model. The interactions with poor prognosis factors (initial tumour size, tumour grade, hormone receptor status and initial clinical nodal status) were tested to evaluate the effect of the NAC in high-risk tumours. RESULTS: By construction, patients, tumor characteristics and trastuzumab use were similar between the population treated with NAC and the population treated with adjuvant CT. No difference was found regarding DFS (p=0.3) neither DMFS (p=0.4) in the global population. However, there was a significant interaction effect between the strategy and the initial clinical nodal status, with a DFS benefit of NAC over AC in the node-positive group (HR 0.53 CI95% [0.31- 0.89]), as well as for DMFS (HR 0.39 95%CI [0.20-0.77]). We found a significant benefit in OS with the neoadjuvant strategy when compared with the adjuvant strategy (HR = 0.12 95%CI [0.03-0.47], p=0.002) and this difference was significant irrespective of tumour size, initial clinical nodal status and hormone receptor status. CONCLUSION: In patients with HER2-positive BCs, receiving NAC is associated with an improved OS when compared with chemotherapy received in the adjuvant setting. Our results support the fact that NAC should become a standard of care in HER2-positive tumours. Citation Format: Enora Laas, Arnaud Bresset, Jean Guillaume Feron, Jean-Yves Pierga, Florence Coussy, Audrey Bellesoeur, Beatriz Grandal, Eléonore De Guillebon, Sonia Rozette, Clemence Evrevin, Thomas Gaillard, Marick Lae, Anne Sophie Hamy, Fabien Reyal. Survival benefit of neoadjuvant chemotherapy versus adjuvant chemotherapy in HER2-positive early breast cancer: A propensity score-weighted analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-36.

Assessment of Out-of-Pocket Costs for Robotic Cancer Surgery in US Adults

Expensive technologies-including robotic surgery-experience rapid adoption without evidence of superior outcomes. Although previous studies have examined perioperative outcomes and costs, differences in out-of-pocket costs for patients undergoing robotic surgery are not well understood. To assess out-of-pocket costs and total payments for 5 types of common oncologic procedures that can be performed using an open or robotic approach. A retrospective, cross-sectional, propensity score-weighted analysis was performed using deidentified insurance claims for 1.9 million enrollees from the MarketScan database from January 1, 2012, to December 31, 2017. The final study sample comprised 15 893 US adults aged 18 to 64 years who were enrolled in an employer-sponsored health plan. Patients underwent either an open or robotic radical prostatectomy, hysterectomy, partial colectomy, radical nephrectomy, or partial nephrectomy for a solid-organ malignant neoplasm. Statistical analysis was performed from December 18, 2018, to June 5, 2019. Type of surgical procedure-robotic vs open. The primary outcome of interest was out-of-pocket costs associated with robotic and open surgery. The secondary outcome of interest was associated total payments. Among 15 893 patients (11 102 men; mean [SD] age, 55.4 [6.6] years), 8260 underwent robotic and 7633 underwent open procedures; patients undergoing robotic hysterectomy were older than those undergoing open hysterectomy (mean [SD] age, 55.7 [6.7] vs 54.6 [7.2] years), and patients undergoing open radical nephrectomy had more comorbidities than those undergoing robotic radical nephrectomy (≥2 comorbidities, 658 of 861 [76.4%] vs 244 of 347 [70.3%]). After adjustment for baseline characteristics, the robotic approach was associated with lower out-of-pocket costs for all procedures: -$137.75 (95% CI, -$240.24 to -$38.63) for radical prostatectomy (P = .006); -$640.63 (95% CI, -$933.62 to -$368.79) for hysterectomy (P < .001); -$1140.54 (95% CI, -$1397.79 to -$896.54) for partial colectomy (P < .001); -$728.32 (95% CI, -$1126.90 to -$366.08) for radical nephrectomy (P < .001); and -$302.74 (95% CI, -$523.14 to -$97.10) for partial nephrectomy (P = .003). The robotic approach was similarly associated with lower adjusted total payments: -$3872.62 (95% CI, -$5385.49 to -$2399.04) for radical prostatectomy (P < .001); -$29 640.69 (95% CI, -$36 243.82 to -$23 465.94) for hysterectomy (P < .001); -$38 151.74 (95% CI, -$46 386.16 to -$30 346.22) for partial colectomy; (P < .001); -$33 394.15 (95% CI, -$42 603.03 to -$24 955.20) for radical nephrectomy (P < .001); and -$9162.52 (95% CI, -$12 728.33 to -$5781.99) for partial nephrectomy (P < .001). This study found significant variation in perioperative costs according to surgical technique for both patients (out-of-pocket costs) and payers (total payments); the robotic approach was associated with lower out-of-pocket costs for all studied oncologic procedures.

Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum β-Lactamase-Producing Organisms?

Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing organisms. We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain. There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09). TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Prognostic impact of pelvic and para-aortic lymphadenectomy on clinically-apparent stage I primary mucinous epithelial ovarian carcinoma: a multi-institutional study with propensity score-weighted analysis.

The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P=0.696) and recurrence-free survival (P=0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.