Indirect Comparison of Tisagenlecleucel and Historical Treatments for Relapsed/Refractory Diffuse Large B-cell Lymphoma

No head-to-head trials have compared the efficacy of tisagenlecleucel versus historical treatments for adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study indirectly compared the overall survival (OS) and overall response rate (ORR) associated with tisagenlecleucel, using data from the JULIET study (NCT02445248), versus historical treatments assessed in the CORAL study follow-up population. To assess treatment effects in the treated (full analysis set [FAS]) and enrolled (intent-to-treat [ITT]) study populations, the JULIET FAS vs. the CORAL follow-up FAS and JULIET ITT vs. CORAL follow-up ITT populations were separately compared. Propensity score weighting using standardized mortality ratio weight (SMRW) and fine stratification weight (FSW) was used to compare OS and ORR, adjusting for baseline confounders. The results indicated that tisagenlecleucel was associated with a lower hazard of death among the FAS (adjusted hazard ratio [95% CI], both FSW and SMRW: 0.44 [0.32, 0.59]) and ITT populations (FSW: 0.60 [0.44, 0.77], SMRW: 0.57 [0.44, 0.73]; all p<0.001). Median OS was 12.48 months (JULIET) vs. 4.34-4.40 months (CORAL) for the FAS, and 8.25 (JULIET) vs. 4.04-4.86 (CORAL) for the ITT populations. Tisagenlecleucel was associated with a significantly higher ORR compared to historical treatments among the FAS (adjusted response rate difference [95% CI], both FSW and SMRW: 36% [22%, 0.48%]; p<0.001) and among the ITT populations after SMRW adjustment (11% [0%, 22%]; p=0.043). This analysis supports that improved response and OS are achieved in r/r DLBCL patients treated with tisagenlecleucel when compared to those treated with alternative historical treatments.

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension

Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research database, a primary care database in the UK. In this study, 53,832 and 43,106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio (SMR) weighted Cox proportional hazards model was used to estimate hazard ratios (HRs) of developing AMD. During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 and 2.2 per 1,000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (aHR: 1.07 (95% CI 0.90-1.27) and 0.87 (0.71-1.07) respectively).

Simplified Acute Physiology Score 3 Performance in Austrian COVID-19 Patients with and Without Diabetes

Background: TheSimplified Acute Physiology Score 3 (SAPS 3) is routinely used in intensive care units (ICUs) to predict in-hospital mortality. However, its predictive performance has not been widely evaluated in Coronavirus disease 19 (COVID-19) patients.This studyevaluated and comparedthe performance of SAPS 3for predicting in-hospital mortalityinCOVID-19patients with and without diabetesin Austria.Methods: This study analyzed the Austrian national public health institute (GÖG) data ofCOVID-19patients admitted to ICUs (N=5,850)fromMarch 2020 to March 2021.The SAPS 3 score was calculated and the predicted in-hospital mortality was estimatedusingthreelogit regression equations: standard equation, Central European equation, and Austrian equation recalibrated for COVID-19 patients. Concordance between observed and predicted mortalities was assessed using the standardized mortality ratio (SMR). Discrimination was assessed using the C-statistic. The DeLong test was applied to compare discrimination between diabetes and non-diabetes patients. Accuracy was assessed using the Brier score andcalibration using the calibration plot and Hosmer-Lemeshow test. Results: Theobservedin-hospital mortality was 38.9% in all patients, 42.9% in diabetes, and 37.3% innon-diabetes patients. Themean ±SD SAPS 3 score was 57.4 ±13.2 in all patients,58.8 ±12.9 in diabetes, and 56.8 ±13.2 in non-diabetes patients.The SMR was significantly greater than 1 for standard and Central European equations, while it was close to 1 for the Austrian equation in all, diabetes, and non-diabetes patients. TheC-statistics was 0.69 with aninsignificant (P=0.193) difference between diabetes (0.70)and non-diabetes (0.68)patients. The Brier score was >0.20 for all SAPS 3 equations. Calibration was unsatisfactory for both standard and Central European equations in all cohorts, whereas it was satisfactory for the Austrian equation in diabetes patients.Conclusions:The SAPS 3 score demonstratedlow discrimination and accuracy in COVID-19 patients in Austria with aninsignificant difference between diabetes and non-diabetes patients. All three equations of SAPS 3 were miscalibrated particularly in non-diabetes patients, while the Austrian equation demonstrated satisfactory calibration in diabetes patients. These findingssuggest that both uncalibrated and calibrated versions ofSAPS 3 should be used with caution in COVID-19 patients.

Performance of Pediatric Index of Mortality in a Tertiary Care PICU in India

Pediatric index of mortality-3 (PIM-3) is the latest update of one of the commonly used scoring systems in pediatric intensive care. It has free accessibility and is easy to use. However, there are some skepticisms regarding its practical usefulness in resource-limited settings. Hence, there is a need to generate region-specific data to evaluate its performance in different case mixes and resource constraints. The aim of the study is to evaluate the performance of the PIM-3 score in predicting mortality in a tertiary care PICU of a developing country. This was a retrospective cohort study. All children aged 1 month to 18 years admitted to the PICU during the study period from July 2016 to December 2018 were included. We reviewed the patient admission details and the case records of the enrolled. patients. Patient demographics, disease profile, co-morbidities, and PIM-3 scores were recorded along with the outcome. Area under receiver operating characteristics (AUROC) curves was used to determine discrimination. Standardized mortality ratio (SMR) and Hosmer Lemeshow goodness of fit were used to assess the calibration. Out of 282 children enrolled, 62 (21.9%) died. 58.5% of the patients were males, and 60% were less than 5 years of age. The principal diagnoses included respiratory and neurological conditions. The AUROC for PIM-3 was 0.961 (95% CI [0.93, 0.98]) and overall SMR was 1.28 (95% CI [0.96, 1.59]). Hosmer-Lemeshow goodness-of-fit was suggestive of poor calibration (χ 2 = 11.7, p < 0.05). We concluded that PIM-3 had good discrimination but poor calibration in our PICU setting.

Survival of Patients With Idiopathic Inflammatory Myopathies in Slovenia

Background: Idiopathic inflammatory myopathies (IIMs) are rare systemic diseases associated with significant morbidity and mortality. The aim of our study was to estimate for the first time the survival of IIM patients in Slovenia.Methods: We included IIM patients diagnosed between January 2005 and December 2020 and followed at two secondary/tertiary rheumatology centers in the country. To study survival/mortality the censor date of April 14 2021 was set. Kaplan–Meier analysis and standardized mortality ratio (SMR) were plotted using data of age and sex matched Slovenian population as a reference. Cox proportional hazards regression analysis was used to study prognostic factors for IIM mortality.Results: During the 16-year observation period, we identified 217 new IIM patients. During follow up 65 (30.0%) patients died. In the first year following IIM diagnosis the SMR was nearly 7-fold higher compared to the matched general population [SMR 6.88 (95%CI 4.41–10.24)] and remained higher also during the following 4 years. However, when excluding IIM patients with cancer, the survival outcome was, except in the first year after IIM diagnosis [SMR 5.55 (95%CI 3.10–9.15)], comparable to matched general population. In addition to cancer [HR 3.71 (95% CI 2.18–6.04)], cardiac involvement [HR 2.18 (95% CI 1.07–4.45)], fever [HR 2.13 (95% CI 1.13–4.03)], and older age [HR 1.07 (95% CI 1.04–1.09)] were extracted as prognostic factors associated with death.Conclusion: The survival of patients with IIM patients was substantially worse compared to matched general population. Cancer was the leading cause of death in our cohort.

Incidence and characteristics of death from peptic ulcer among cancer patients in the United States

Most cancer patients die of non-cancer causes, and peptic ulcer is one cause that deserves attention. To characterize the incidence and risk factors of death from peptic ulcer among cancer patients, we extracted the data of cancer patients registered in the Surveillance Epidemiology and End Results (SEER) program from 1975 to 2016. Out of the 8,471,051 patients extracted from SEER, 4,698 died from peptic ulcer, with a mortality rate of 9.08/100,000 person-years. Meanwhile, the mortality rate in the general population was 5.09/100,000 person-years, giving a standardized mortality ratio (SMR) of 1.78 (95% confidence interval, 1.73–1.84). Patients who are female, of other race, unmarried, and with distant tumor stage have greater SMRs. A higher SMR was associated with a younger age at diagnosis. Among those aged < 40 years at diagnosis, the plurality of fatal peptic ulcers occurred in patients with leukemia and lymphoma, while in patients aged > 40 years, the majority occurred in those with prostate, breast, colorectum, and lung cancer. Patients with upper digestive system malignancies had the highest SMRs and hazard ratios (HRs), which could be ascribed to radiotherapy-induced damage to the gastroduodenum. The risk declined rapidly one year after diagnosis. However, the SMRs in the upper digestive system cancer survivors increased significantly over ten years after diagnosis. Upper digestive system cancers adjacent to the gastroduodenum were associated with higher SMRs and HRs compared with other types of cancer, possibly contributing partially to the damage caused by radiotherapy on the radiosensitive gastroduodenum.

Sine scleroderma, limited cutaneous, and diffused cutaneous systemic sclerosis survival and predictors of mortality

Background Systemic sclerosis (SSc) is associated with a variability of mortality rates in the literature. Objective To determine the mortality and its predictors in a long-term follow-up of a bi-centric cohort of SSc patients. Methods A retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. Standardized Mortality Ratio (SMR), mortality at 1, 3, 5, 10, and 15 years of disease and causes of death were described. Predictors of mortality using Cox regression were assessed. Results Three hundred seventy-five patients were included: 63 with diffuse cutaneous SSc, 279 with limited cutaneous SSc, and 33 with sine scleroderma. The SMR ratio was 1.88 (95% CI 1.46–1.97). The overall survival rates were 97.6% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years, and 61.3% at 15 years. Sixty-nine deaths were recorded. 46.4% were SSc related deaths secondary to interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%), and digestive tract involvement (18.8%). 53.6% were non-related to SSc: cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified: carbon monoxide diffusing capacity (DLCO) < 70% (HR=3.01; p=0.0053), C-reactive protein (CRP) >5 mg/l (HR=2.13; p=0.0174), cardiac involvement (HR=2.86; p=0.0012), and the fact of being male (HR=3.25; p=0.0004). Conclusion Long-term data confirmed high mortality of SSc. Male sex, DLCO <70%, cardiac involvement, and CRP> 5mg/l were identified as independent predictors of mortality.

Five-Year Outcomes After Implementing a Pain, Agitation, and Delirium Protocol in a Mixed Intensive Care Unit

Objective: Assess for continued improvements in patient outcomes after updating our institutional sedation and analgesia protocol to include recommendations from the 2013 Society of Critical Care Medicine (SCCM) Pain, Agitation, and Delirium (PAD) guidelines. Methods: Retrospective before-and-after study in a mixed medical/surgical intensive care unit (ICU) at an academic medical center. Mechanically ventilated adults admitted from September 1, 2011 through August 31, 2012 (pre-implementation) and October 1, 2012 through September 30, 2017 (post-implementation) were included. Measurements included number of mechanically ventilated patients, APACHE IV scores, age, type of patient (medical or surgical), admission diagnosis, ICU length of stay (LOS), hospital LOS, ventilator days, number of self-extubations, ICU mortality, ICU standardized mortality ratio, hospital mortality, hospital standardized mortality ratio, medication data including as needed (PRN) analgesic and sedative use, and analgesic and sedative infusions, and institutional savings. Results: Ventilator days (Pre-PAD = 4.0 vs. Year 5 post = 3.2, P < .0001), ICU LOS (Pre-PAD = 4.8 days vs. Year 5 post = 4.1 days, P = .0004) and hospital LOS (Pre-PAD = 14 days vs. Year 5 post = 12 days, P < .0001) decreased after protocol implementation. Hospital standardized mortality ratio (Pre-PAD = 0.69 vs. Year 5 post = 0.66) remained constant; while, APACHE IV scores (Pre-PAD = 77 vs. Year 5 post = 89, P < .0001) and number of intubated patients (Pre-PAD = 1146 vs. Year 5 post = 1468) increased over the study period. Using the decreased ICU and hospital LOS estimates, it is projected the institution saved $4.3 million over the 5 years since implementation. Conclusions: Implementation of an updated PAD protocol in a mixed medical/surgical ICU was associated with a significant decrease in ventilator time, ICU LOS, and hospital LOS without a change in the standardized mortality ratio over a five-year period. These favorable outcomes are associated with a significant cost savings for the institution.

Comparing the Survival Outcomes of Radical Prostatectomy Versus Radiotherapy for Patients With De Novo Metastasis Prostate Cancer: A Population-Based Study

PurposeThe efficacy of local treatments (LTs) in selected patients with metastatic prostate cancer (mPCa) had been demonstrated. However, the comparative effectiveness between LTs is unclear. Here, we compared the impact of radical prostatectomy (RP) and brachytherapy (RT) on the survival outcomes of mPCa patients.Materials and MethodsmPCa patients who received RT or RP between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable Cox proportional hazards analysis was used to evaluate the comparative risk of prostate cancer-specific mortality (CSM) and all-cause mortality (ACM) between LTs. A 1:1 propensity score matching (PSM) and adjusted standardized mortality ratio weighting (SMRW) were performed to balance the clinicopathological characteristics of the groups.ResultsOf 684 mPCa patients, 481 underwent RP and 203 received RT. After PSM, both groups included 148 cases, and RT resulted in comparable CSM versus RP [CSM: hazard ratio (HR) = 0.77, p = 0.325; ACM: HR = 0.73, p = 0.138], which was consistent with the SMRW model [CSM: HR = 0.83, p = 0.138; overall survival (OS): HR = 0.75, p = 0.132]. However, RP was associated with a lower CSM in the T1–2 subgroup (HR = 0.42, p = 0.048) and a lower ACM in the T1–2 (HR = 0.55, p = 0.031) and prostate-specific antigen (PSA) ≤20ng/ml (HR = 0.48, p = 0.022) subgroups. Besides, the results showed that the mortality risk was similar between the two groups in the T3–4, Gleason score (GS) &gt;7, PSA &gt;20 ng/ml, and all metastatic subgroups (all p &gt; 0.100).ConclusionsRP could confer better survival outcomes than could RT in mPCa patients with favorable primary tumor features, but not in those with advanced primary tumor features. Moreover, the metastatic substage has limited impact on the comparative effectiveness between RP and RT. Further clinical trials are necessary to confirm the present results.