Management and use of healthcare resources in patients with chronic lymphocytic leukemia initiating venetoclax in routine clinical practice.

Venetoclax is a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor approved as continuous monotherapy and in combination with rituximab as fixed-treatment duration for relapsed and refractory chronic lymphocytic leukemia (R/R CLL). DEVOTE was a 24-week, multicenter observational study (NCT03310190) evaluating the safety, healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) of patients initiating venetoclax for R/R CLL in Canada. Overall, 89 patients received 1 dose of venetoclax; 80% had prior exposure (42% resistant) to ibrutinib. Biochemical tumor lysis syndrome (TLS) occurred in five patients. We observed differences in hospitalization across Canadian provinces including in patients at low risk for TLS with no clear impact on TLS incidence. Additionally, a rapid and sustained improvement in several domains of HRQoL was observed during venetoclax initiation. Early adoption of venetoclax was mainly for R/R CLL patients with few treatment options; nonetheless, acceptable toxicity and a positive impact on HRQoL were observed.

Insight into prevalence, etiology, and modalities of pediatric chronic dialysis: a comprehensive nationwide analysis.

BACKGROUND: This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15 years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities. METHODS: This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities. RESULTS: The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD). CONCLUSIONS: This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries.

Friend or Foe: Draft Genome Sequence of Bradyrhizobium sp. Strain SRS-191.

We report the genomic features of Bradyrhizobium sp. strain SRS-191, which was isolated from a former nuclear legacy site in Aiken, South Carolina, USA. With a genome size of 7,621,400 bp, the strain harbored genes not only for environmentally beneficial traits (e.g., heavy metal resistance, nitrogen fixation, and aromatic biodegradation) but also for antimicrobial resistance.

The outcome of rituximab in treating steroid dependent nephrotic syndrome.: Histopathology and immunosuppressive drugs as predicting factors.

OBJECTIVES: To present our experience of treating steroid-dependent nephrotic syndrome (SDNS) in children with repeated doses of rituximab (RTX) with a relatively long follow-up, and to discuss the role of the histopathology type and previous immune-suppressor (IS) drugs on the outcome of these patients. METHODS: The patients included in this prospective study were children with SDNS who were in remission on a high-dose steroid or with additional IS drugs. All patients underwent renal biopsy before RTX treatment. Intravenous RTX was administered monthly at 375 mg/m2 for 4 doses. Response to treatment was defined as maintaining remission with no steroid-sparing agents or prednisone for one year. RESULTS: Seventeen (14 males) patients were enrolled. Approximately 76% had minimal change disease (MCD) and 3 (18%) patients had immunoglobulin M (IgM) nephropathy. Approximately 85% of MCD and 33% of IgM nephropathy showed complete response to RTX. CONCLUSION: Compared to other IS used to treat SDNS, RTX showed a significant decrease in relapse rate with fewer side effects. The dose and interval should be modified according to the patient's characteristics, such as medical history, pathology type, and previous IS agents.

Evaluation of a Telephone Version for the Montreal Cognitive Assessment: Establishing a Cutoff for Normative Data From a Cross-Sectional Study.

OBJECTIVE: Compare a telephone version and full version of the Montreal Cognitive Assessment (MoCA). METHODS: Cross-sectional analysis of a prospective study. A 20-point telephone version of MoCA (Tele-MoCA) was compared to the Full-MoCA and Mini Mental State Examination. RESULTS: Total of 140 participants enrolled. Mean scores for language were significantly lower with Tele-MoCA than with Full-MoCA (P = .003). Mean Tele-MoCA scores were significantly higher for participants with over 12 years of education (P < .001). Cutoff score of 17 for the Tele-MoCA yielded good specificity (82.2%) and negative predictive value (84.4%), while sensitivity was low (18.2%). CONCLUSIONS: Remote screening of cognition with a 20-point Tele-MoCA is as specific for defining normal cognition as the Full-MoCA. This study shows that telephone evaluation is adequate for virtual cognitive screening. Our sample did not allow accurate assessment of sensitivity for Tele-MoCA in detecting MCI or dementia. Further studies with representative populations are needed to establish sensitivity.

Factors That Influence Mortality in Critically Ill Patients with SARS-CoV-2 Infection: A Multicenter Study in the Kingdom of Saudi Arabia.

BACKGROUND: SARS-CoV-2 infection has a high mortality rate and continues to be a global threat, which warrants the identification of all mortality risk factors in critically ill patients. METHODS: This is a retrospective multicenter cohort study conducted in five hospitals in the Kingdom of Saudi Arabia (KSA). We enrolled patients with confirmed SARS-COV-2 infection admitted to any of the intensive care units from the five hospitals between March 2020 and July 2020, corresponding to the peak of recorded COVID-19 cases in the KSA. RESULTS: In total, 229 critically ill patients with confirmed SARS-CoV-2 infection were included in the study. The presenting symptoms and signs of patients who died during hospitalization were not significantly different from those observed among patients who survived. The baseline comorbidities that were significantly associated with in-hospital mortality were diabetes (62% vs. 48% among patients who died and survived (p = 0.046)), underlying cardiac disease (38% vs. 19% (p = 0.001)), and underlying kidney disease (32% vs. 12% (p < 0.001)). CONCLUSION: In our cohort, the baseline comorbidities that were significantly associated with in-hospital mortality were diabetes, underlying cardiac disease, and underlying kidney disease. Additionally, the factors that independently influenced mortality among critically ill COVID-19 patients were high Activated Partial Thromboplastin Time (aPTT )and international normalization ratio (INR), acidosis, and high ferritin.

Exercise Intervention for Late-Life Depression: A Meta-Analysis.

OBJECTIVE: To quantify the association between physical exercise intervention (PEI) and reduction in depressive symptoms in older adults. DATA SOURCES: MEDLINE, PsycINFO, and EMBASE were searched from inception through December 2018 with no language restrictions using keywords related to exercise, depression, elderly adults, and randomized controlled trials. STUDY SELECTION: Randomized controlled trials comparing a sedentary control group, with no physically active intervention, to a supervised, moderate-to-vigorous PEI with participants aged ≥ 60 years and having a primary outcome of depressive symptoms were included. DATA EXTRACTION: Data on pre- and post-intervention scores on scales measuring depressive symptoms were extracted using a standard form. Random-effects models were used to pool standardized mean differences (Hedges g) in depressive symptoms across studies. DATA SYNTHESIS: Nine studies involving 1,308 participants were included; mean participant age was 82 years. Moderate-to-vigorous PEI was associated with a medium effect size of 0.64 (95% CI, 0.27 to 1.01; z = 3.38; P < .001) in reducing depressive symptoms. However, there was considerable heterogeneity (T² = 0.22, Q = 36.34, P < .0001; I² = 78.0%) in the effect of PEI across included studies. Age > 80 years, Mini-Mental State Examination (MMSE) score < 23, and no depressive symptoms at baseline contributed to heterogeneity. Fitness metrics and adherence to exercise were inconsistently reported, and 5 of 9 studies were deemed at high risk of bias. CONCLUSIONS: A moderate reduction in depressive symptoms was seen with PEI among older adults. Nevertheless, more work is needed to support PEI for late-life depression in adults over age 80 years or with MMSE scores < 23 suggestive of cognitive decline.

Androgen Deprivation Therapy for Prostate Cancer and the Risk of Rheumatoid Arthritis: A Population-Based Cohort Study.

INTRODUCTION: Two recent observational studies have investigated the association between androgen deprivation therapy (ADT) and rheumatoid arthritis (RA), but generated discrepant findings and had important methodological limitations. Thus, the objective of this study was to determine whether the use of ADT is associated with an increased risk of RA in men with prostate cancer. PATIENTS AND METHODS: We conducted a population-based cohort study using the United Kingdom Clinical Practice Research Datalink. The cohort included all men, at least 40 years of age, newly diagnosed with prostate cancer between 1 January 1988 and 31 March 2014, with follow-up until 30 September 2014. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays and latency. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of RA, comparing use of ADT with non-use. Secondary analyses were conducted to assess whether the association varied according to ADT type and cumulative duration of use. Finally, we conducted several sensitivity analyses to assess the robustness of our findings. RESULTS: The cohort included 32,302 men followed for a median of 3.3 years. During follow-up, 63 patients were newly diagnosed with RA, generating an incidence rate of 46.5/100,000 person-years. Compared with non-use, the use of ADT was not associated with an increased risk of RA (HR 0.84, 95% CI 0.49-1.45). In secondary analyses, the association did not vary according to ADT type or with cumulative duration of use (p trend = 0.53). The results remained consistent in sensitivity analyses. CONCLUSION: In this population-based study, the use of ADT was not associated with an increased risk of RA in men with prostate cancer.

Effectiveness of interventions for the implementation of thromboprophylaxis in hospitalised patients at risk of venous thromboembolism: an updated abridged Cochrane systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the effectiveness of system-wide interventions designed to increase the implementation of thromboprophylaxis and decrease the incidence of venous thromboembolism (VTE) in hospitalised medical and surgical patients at risk of VTE. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: Medline, PubMed, Embase, BIOSIS, CINAHL, Web of Science, CENTRAL, DARE, EED, LILACS and clinicaltrials.gov without language restrictions from inception to 7 January 2017, as well as the reference lists of relevant review articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RCTs that evaluated the effectiveness of system-wide interventions such as alerts, multifaceted, education, and preprinted orders when compared with no intervention, existing policy or another intervention. RESULTS: We included 13 RCTs involving 35 997 participants. Eleven RCTs had data available for meta-analysis. Compared with control, we found absolute increase in the prescription of prophylaxis associated with alerts (21% increase, 95% CI [15% to 275%]) and multifaceted interventions (4% increase, 95% CI [3% to 11%]), absolute increase in the prescription of appropriate prophylaxis associated with alerts (16% increase, 95% CI [12% to 20%]) and relative risk reductions (risk ratio 64%, 95% CI [47% to 86%]) in the incidence of symptomatic VTE associated with alerts. Computer alerts were found to be more effective than human alerts, and multifaceted interventions with an alert component appeared to be more effective than multifaceted interventions without, although comparative pooled analyses were not feasible. The quality of evidence for improvement in outcomes was judged to be low to moderate certainty. CONCLUSIONS: Alerts increased the proportion of patients who received prophylaxis and appropriate prophylaxis, and decreased the incidence of symptomatic VTE. Multifaceted interventions increased the proportion of patients who received prophylaxis but were found to be less effective than alerts interventions. TRIAL REGISTRATION NUMBER: CD008201.

External Validation of ASPECT (Algorithm for Suspected Pulmonary Embolism Confirmation and Treatment).

BACKGROUND: Administrative health care databases are increasingly being used to study pulmonary embolism (PE), but the validity of single PE codes is variable. Using data from Quebec, Canada, we developed ASPECT (Algorithm for Suspected Pulmonary Embolism Confirmation and Treatment), combining 3 components to ascertain confirmed PE: emergency department (ED) diagnoses, imaging codes, and dispensed prescriptions or hospital diagnoses. Herein, we used unrelated administrative health care databases to externally validate ASPECT. METHODS: We used ED electronic health records (ED-EHRs) to identify all residents of Calgary (Alberta, Canada) with PE codes between January and June, 2016. We applied ASPECT by identifying imaging studies in the ED-EHR, admission diagnoses in linked discharge abstract database and filled prescriptions in linked pharmacy information. Confirmed PE in ASPECT was validated against chart review in the ED-EHR. RESULTS: The cohort included 498 patients. Overall, 258 (51.9%) were managed as outpatients and 327 were adjudicated to have confirmed PE; the positive predictive value (PV) of single PE codes was 65.6%. With ASPECT the positive PV was 96.5% [95% confidence interval (CI), 94.4-98.5%] and positive likelihood ratio was 10.9 (95% CI, 6.8-15.1). The negative PV and negative likelihood ratio were 85.1% (95% CI, 80.0-90.2%) and 0.1 (95% CI, 0.0-0.1), respectively. Overall agreement of ASPECT with confirmed PE was 92.2%. Further, ASPECT was similarly robust in inpatients and outpatients and was more precise than any 2-component combination of ASPECT. CONCLUSIONS: Our findings reiterate the limitations of using single administrative codes for PE and suggest ASPECT as an acceptable tool to study PE.

Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia.

BACKGROUND: In the current study, the authors determined whether adhering to molecular monitoring guidelines in patients with chronic myeloid leukemia (CML) is associated with major molecular response (MMR) and assessed barriers to adherent monitoring. METHODS: Newly treated patients with CML from the Quebec province-wide CML registry from 2005 to 2016 were included. Timely polymerase chain reaction (tPCR) was defined as the molecular assessment of BCR-ABL1 at the 3-month, 12-month, and 18-month time points from the initiation of tyrosine kinase inhibitor (TKI) therapy. The cohort was analyzed as a nested case-control study. Cases with a first-ever MMR (BCR-ABL1 ≤0.1%, assessed at any time during follow-up) were matched to up to 5 controls by duration of TKI therapy, volume of patients with CML at the treatment center, year of cohort entry, and age. Odds ratios (ORs) for the performance of tPCR and MMR were adjusted for sex, comorbidities, type of TKI, and other important covariates. RESULTS: The cohort included 496 patients. Of 392 MMR events, 67.9% occurred before 18 months. The performance of tPCR was associated with a doubling of the MMR rate (OR, 2.23; 95% confidence interval [95% CI], 1.56-3.21) and was similar with 1 to 3 tPCRs performed (P = .67). Furthermore, tPCRs at 3 months (OR, 2.77; 95% CI, 1.81-4.23) and 12 months (OR, 3.00; 95% CI, 1.64-5.49) were associated with achieving early MMR, whereas tPCRs at 18 months were not (OR, 1.23; 95% CI, 0.80-1.89). Low-volume centers were found to have lower adherence to tPCR (OR, 0.60; 95% CI, 0.40-0.89). CONCLUSIONS: Timely molecular assessment at 3 months and 12 months appears to benefit patients with CML. Adherence to timely monitoring should be encouraged, especially in low-volume treatment centers.

Serum organochlorines and non-Hodgkin lymphoma: A case-control study in Israeli Jews and Palestinians.

Associations of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) with non-Hodgkin lymphoma are controversial. We compared serum levels of 6 OC pesticides and 38 PCBs in Israeli Jews (IJ) and Palestinian Arabs (PA) and assessed possible associations with B-cell non-Hodgkin lymphoma (B-NHL). Ninety B-NHL cases (50 IJ and 40 PA) and 120 controls (65 IJ and 55 PA) were included. Median concentrations of analytes in controls were compared across ethnic groups using quantile regression, adjusting for age and sex. We used logistic regression to derive odds ratios (OR) and 95% confidence intervals (CI) for detectable analytes and B-NHL, adjusting for age, ethnic group, faming and body mass index. Median values of PCBs and dichlorodiphenyldichloroethylene (DDE) were higher in IJ vs PA controls (P = 0.0007), as were several PCBs (74, 99, 118, 138, 146, 153, 156, 163, 170, and 180). Overall, OC pesticide and PCB exposures were comparable with reports from high-income countries. B-NHL was associated with PCB 146 (OR 1.70, 95% CI: 1.02, 2.83), PCB 156 (OR 1.75, 95% CI: 1.06, 2.89), and high-chlorinated PCBs (OR 1.55, 95% CI: 1.00, 2.40) in all study subjects. These associations were robust in quantile as well as sensitivity analyses. An association of DDE with B-NHL was noted in PA (OR 1.72, 95% CI: 1.07, 2.77), but not in IJ (OR 0.87, 95% CI: 0.59, 1.27). Although high-chlorinated PCB concentrations did not indicate high exposure levels, our findings indicate that B-NHL may be associated with this exposure.

Interventions for implementation of thromboprophylaxis in hospitalized patients at risk for venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. While numerous randomized controlled trials (RCTs) have shown that the appropriate use of thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective, and cost-effective, thromboprophylaxis remains underused or inappropriately used. Our previous review suggested that system-wide interventions, such as education, alerts, and multifaceted interventions were more effective at improving the prescribing of thromboprophylaxis than relying on individual providers' behaviors. However, 47 of the 55 included studies in our previous review were observational in design. Thus, an update to our systematic review, focused on the higher level of evidence of RCTs only, was warranted. OBJECTIVES: To assess the effects of system-wide interventions designed to increase the implementation of thromboprophylaxis and decrease the incidence of VTE in hospitalized adult medical and surgical patients at risk for VTE, focusing on RCTs only. SEARCH METHODS: Our research librarian conducted a systematic literature search of MEDLINE Ovid, and subsequently translated it to CENTRAL, PubMed, Embase Ovid, BIOSIS Previews Ovid, CINAHL, Web of Science, the Database of Abstracts of Reviews of Effects (DARE; in the Cochrane Library), NHS Economic Evaluation Database (EED; in the Cochrane Library), LILACS, and clinicaltrials.gov from inception to 7 January 2017. We also screened reference lists of relevant review articles. We identified 12,920 potentially relevant records. SELECTION CRITERIA: We included all types of RCTs, with random or quasi-random methods of allocation of interventions, which either randomized individuals (e.g. parallel group, cross-over, or factorial design RCTs), or groups of individuals (cluster RCTs (CRTs)), which aimed to increase the use of prophylaxis or appropriate prophylaxis, or decrease the occurrence of VTE in hospitalized adult patients. We excluded observational studies, studies in which the intervention was simply distribution of published guidelines, and studies whose interventions were not clearly described. Studies could be in any language. DATA COLLECTION AND ANALYSIS: We collected data on the following outcomes: the number of participants who received prophylaxis or appropriate prophylaxis (as defined by study authors), the occurrence of any VTE (symptomatic or asymptomatic), mortality, and safety outcomes, such as bleeding. We categorized the interventions into alerts (computer or human alerts), multifaceted interventions (combination of interventions that could include an alert component), educational interventions (e.g. grand rounds, courses), and preprinted orders (written predefined orders completed by the physician on paper or electronically). We meta-analyzed data across RCTs using a random-effects model. For CRTs, we pooled effect estimates (risk difference (RD) and risk ratio (RR), with 95% confidence interval (CI), adjusted for clustering, when possible. We pooled results if three or more trials were available for a particular intervention. We assessed the certainty of the evidence according to the GRADE approach. MAIN RESULTS: From the 12,920 records identified by our search, we included 13 RCTs (N = 35,997 participants) in our qualitative analysis and 11 RCTs (N = 33,207 participants) in our meta-analyses. PRIMARY OUTCOME: Alerts were associated with an increase in the proportion of participants who received prophylaxis (RD 21%, 95% CI 15% to 27%; three studies; 5057 participants; I² = 75%; low-certainty evidence). The substantial statistical heterogeneity may be in part explained by patient types, type of hospital, and type of alert. Subgroup analyses were not feasible due to the small number of studies included in the meta-analysis.Multifaceted interventions were associated with a small increase in the proportion of participants who received prophylaxis (cluster-adjusted RD 4%, 95% CI 2% to 6%; five studies; 9198 participants; I² = 0%; moderate-certainty evidence). Multifaceted interventions with an alert component were found to be more effective than multifaceted interventions that did not include an alert, although there were not enough studies to conduct a pooled analysis. SECONDARY OUTCOMES: Alerts were associated with an increase in the proportion of participants who received appropriate prophylaxis (RD 16%, 95% CI 12% to 20%; three studies; 1820 participants; I² = 0; moderate-certainty evidence). Alerts were also associated with a reduction in the rate of symptomatic VTE at three months (RR 64%, 95% CI 47% to 86%; three studies; 5353 participants; I² = 15%; low-certainty evidence). Computer alerts were associated with a reduction in the rate of symptomatic VTE, although there were not enough studies to pool computer alerts and human alerts results separately. AUTHORS' CONCLUSIONS: We reviewed RCTs that implemented a variety of system-wide strategies aimed at improving thromboprophylaxis in hospitalized patients. We found increased prescription of prophylaxis associated with alerts and multifaceted interventions, and increased prescription of appropriate prophylaxis associated with alerts. While multifaceted interventions were found to be less effective than alerts, a multifaceted intervention with an alert was more effective than one without an alert. Alerts, particularly computer alerts, were associated with a reduction in symptomatic VTE at three months, although there were not enough studies to pool computer alerts and human alerts results separately.Our analysis was underpowered to assess the effect on mortality and safety outcomes, such as bleeding.The incomplete reporting of relevant study design features did not allow complete assessment of the certainty of the evidence. However, the certainty of the evidence for improvement in outcomes was judged to be better than for our previous review (low- to moderate-certainty evidence, compared to very low-certainty evidence for most outcomes). The results of our updated review will help physicians, hospital administrators, and policy makers make practical decisions about adopting specific system-wide measures to improve prescription of thromboprophylaxis, and ultimately prevent VTE in hospitalized patients.

Direct Oral Anticoagulants in End-Stage Renal Disease.

Patients with end-stage renal disease (ESRD) were excluded from pivotal clinical trials with oral anticoagulants. While such patients are at an increased risk of venous and arterial thromboembolism, their risk of bleeding is also elevated. It is thus of little surprise that stroke prevention with vitamin K antagonists (VKAs) in ESRD patients with atrial fibrillation is controversial, with observational evidence ranging from beneficial to harmful. This uncertainty extends to the less studied use of VKAs for venous thromboembolism in ESRD. The direct oral anticoagulants (DOACs) apixaban and rivaroxaban have now permissive labeling in the United States for atrial fibrillation in patients with ESRD; this expanded labeling has not yet occurred either in Europe or for venous thromboembolism. This review summarizes the current evidence for the pharmacology of DOACs in ESRD as well as their utilization and safety in patients with ESRD and atrial fibrillation.

Temporal trends in outpatient management of incident pulmonary embolism and associated mortality.

INTRODUCTION: In clinical trial settings, outpatient management of pulmonary embolism (PE) is feasible and safe, but less is known on its use in routine care. We determined trends in outpatient management of PE and associated mortality in a large non-select patient population. METHODS: All residents of Quebec, Canada with a first-ever work-up for suspected PE in the emergency department (ED) over 10years were included. Patients could transition to outpatient management and from unconfirmed to confirmed PE in a time-varying fashion. Comparing the years 2005-9 with 2000-4, we assessed the odds ratio (OR) for outpatient management, and relative risk (RR) for all-cause mortality, readmissions for PE, and major bleeding in 30days. We adjusted the RR for a mortality risk score. RESULTS: Of 15,217 patients included, 7583 were outpatients (7.5% confirmed PE) and 7634 were inpatients (60.6% confirmed PE). In all, 10.9% of patients with confirmed PE were outpatients, but outpatient management of confirmed PE was more likely in the latter study period (OR 1.73, 95%CI 1.44-2.09). Among outpatients with confirmed PE, mortality (RR 0.84, 95%CI 0.15-4.61) and readmission (RR 1.25, 95%CI 0.45-3.48) rates were stable, and only 3 major bleeding events were noted. Inpatients with confirmed PE had stable mortality rates (RR 0.95, 95%CI 0.72-1.24). CONCLUSION: Outpatient PE management increased over 10years while remaining fairly uncommon. Nevertheless, stable mortality and readmission rates indicate this practice is safe in routine care, and add to the growing evidence in support of outpatient PE management.

Androgen Deprivation Therapy and the Risk of Anemia in Men with Prostate Cancer.

BACKGROUND: The use of androgen deprivation therapy in prostate cancer may be associated with an increased risk of anemia, but the evidence remains limited. This study aimed to determine if androgen deprivation is associated with increased risk of anemia in patients newly diagnosed with prostate cancer. METHODS: This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 10,364 men newly diagnosed with nonmetastatic prostate cancer between 1 April 1998 and 30 September 2015. We used time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for anemia (hemoglobin <130 g/L) associated with current and past use of androgen deprivation therapy, compared with nonuse. RESULTS: There were 3,651 incident anemia events during 31,574 person-years of follow-up (rate: 11.6/100 person-years). Current androgen deprivation therapy use was associated with a nearly three-fold increased hazard of anemia, compared with nonuse (23.5 vs. 5.9 per 100 person-years, respectively; HR: 2.90, 95% CI: 2.67, 3.16). The HR was elevated in the first 6 months of use (HR: 2.20, 95% CI: 1.95, 2.48) and continued to be elevated with longer durations of use. Past androgen deprivation therapy use was associated with a lower estimate (HR: 1.27, 95% CI: 1.12, 1.43), which returned closer to the null ≥25 months after treatment discontinuation (HR: 0.95, 95% CI: 0.79, 1.15). CONCLUSIONS: The use of androgen deprivation therapy is associated with increased risk of anemia, which reverses upon treatment discontinuation.

Prolactin-Elevating Antipsychotics and the Risk of Endometrial Cancer.

BACKGROUND: The use of antipsychotics may increase the risk of endometrial cancer through elevation of prolactin levels. We investigated the association between antipsychotics that are known to cause prolactin elevation and the risk of endometrial cancer. METHODS: In data from the United Kingdom Clinical Practice Research Datalink, all women who were newly treated with antipsychotics from 1990-2013 were identified and followed until 2014. Within this cohort of antipsychotic users, a nested case-control analysis was conducted. Main exposure was nonsporadic use of prolactin-elevating antipsychotics, and the active comparator was prolactin-sparing antipsychotics. Cases were women newly diagnosed with endometrial cancer (ICD-10) matched with up to 20 controls on age, calendar year of cohort entry, linkability to the Hospital Episode Statistics repository, and duration of follow-up. Conditional logistic regression models were used to determine the association of prolactin-elevating antipsychotics and endometrial cancer compared with prolactin-sparing antipsychotics. All analyses were adjusted for relevant potential confounders, including smoking, obesity, and diabetes mellitus. RESULTS: The cohort included 65,930 women. During 366,112 person-years of follow-up, there were 139 cases of endometrial cancer (incidence rate: 38/100,000 person-years), which were matched to 1,603 controls. Compared with the use of prolactin-sparing antipsychotics, the use of prolactin-elevating antipsychotics was not associated with an increased risk of endometrial cancer (adjusted odds ratio [aOR] = 1.00; 95% CI, 0.68-1.48). These findings remained similar with different durations of use (≤ 1 year, aOR = 1.07; 95% CI, 0.64-1.78, and > 1 year, aOR = 0.95; 95% CI, 0.58-1.54) and were robust to various sensitivity analyses. CONCLUSIONS: Prolactin-elevating antipsychotics were not associated with an increased risk of endometrial cancer.