Being Transparent About Brilliant Failures:An Attempt to Use Real-World Data in a Disease Model for Patients with Castration-Resistant Prostate Cancer

Background: Real-world disease models spanning multiple treatment lines can provide insight into the (cost) effectiveness of treatment sequences in clinical practice. Objective: Our objective was to explore whether a disease model based solely on real-world data (RWD) could be used to estimate the effectiveness of treatments for patients with castration-resistant prostate cancer (CRPC) that could then be suitably used in a cost-effectiveness analysis. Methods: We developed a patient-level simulation model using patient-level data from the Dutch CAPRI registry as input parameters. Time to event (TTE) and overall survival (OS) were estimated with multivariate regression models, and type of event (i.e., next treatment or death) was estimated with multivariate logistic regression models. To test internal validity, TTE and OS from the simulation model were compared with the observed outcomes in the registry. Results: Although patient characteristics and survival outcomes of the simulated data were comparable to those in the observed data (median OS 20.6 vs. 19.8 months, respectively), the disease model was less accurate in estimating differences between treatments (median OS simulated vs. observed population: 18.6 vs. 17.9 [abiraterone acetate plus prednisone], 24.0 vs. 25.0 [enzalutamide], 20.2 vs. 18.7 [docetaxel], and 20.0 vs. 23.8 months [radium-223]). Conclusions: Overall, the disease model accurately approximated the observed data in the total CRPC population. However, the disease model was unable to predict differences in survival between treatments due to unobserved differences. Therefore, the model is not suitable for cost-effectiveness analysis of CRPC treatment. Using a combination of RWD and data from randomised controlled trials to estimate treatment effectiveness may improve the model

Obesity in total hip arthroplasty—does it really matter?: A meta-analysis

Discussion persists as to whether obesity negatively influences the outcome of hip arthroplasty. We performed a meta-analysis with the primary research question of whether obesity has a negative effect on short- and long-term outcome of total hip arthroplasty. We searched the literature and included studies comparing the outcome of hip arthroplasty in different weight groups. The methodology of the studies included was scored according to the Cochrane guidelines. We extracted and pooled the data. For continuous data, we calculated a weighted mean difference and for dichotomous variables we calculated a weighted odds ratio (OR). Heterogeneity was calculated using I(2) statistics. 15 studies were eligible for data extraction. In obese patients, dislocation of the hip (OR = 0.54, 95% CI: 0.38-0.75) (10 studies, n = 8,634), aseptic loosening (OR = 0.64, CI: 0.43-0.96) (6 studies, n = 5,137), infection (OR = 0.3, CI: 0.19-0.49) (10 studies, n = 7,500), and venous thromboembolism (OR = 0.56, CI: 0.32-0.98) (7 studies, n = 3,716) occurred more often. Concerning septic loosening and intraoperative fractures, no statistically significant differences were found, possibly due to low power. Subjective outcome measurements did not allow pooling because of high heterogeneity (I(2) = 68%). Obesity appears to have a negative influence on the outcome of total hip replacemen

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer:Results from the Dutch Castration-resistant Prostate Cancer Registry

BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2). OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed. RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research. CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P. PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice

Arteriovenous fistula after anatomic all-inside anterior cruciate ligament reconstruction

\u3cp\u3eWe present the first case of an arteriovenous fistula after an all-inside anterior cruciate ligament (ACL) reconstruction. A seventeen-year-old boy had an uneventful ACL reconstruction. Four weeks after surgery, the patient was seen with a pulsating swelling at the lateral distal upper leg. Vascular consultation led to the diagnosis of pseudoaneurysm and arteriovenous fistula of the lateral superior genicular artery. Most likely, fistula is caused by the stab incision for preparation of the femoral tunnel, and no anatomical cause was found. The clinical presentation, previous cases of arteriovenous fistula after arthroscopic ACL reconstruction, possible causes, and management are discussed.\u3c/p\u3

Arteriovenous Fistula after Anatomic All-Inside Anterior Cruciate Ligament Reconstruction

We present the first case of an arteriovenous fistula after an all-inside anterior cruciate ligament (ACL) reconstruction. A seventeen-year-old boy had an uneventful ACL reconstruction. Four weeks after surgery, the patient was seen with a pulsating swelling at the lateral distal upper leg. Vascular consultation led to the diagnosis of pseudoaneurysm and arteriovenous fistula of the lateral superior genicular artery. Most likely, fistula is caused by the stab incision for preparation of the femoral tunnel, and no anatomical cause was found. The clinical presentation, previous cases of arteriovenous fistula after arthroscopic ACL reconstruction, possible causes, and management are discussed

Real-world outcomes of radium-223 dichloride for metastatic castration resistant prostate cancer

Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line ≥3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line ≥3 (HR: 3.267; 95% CI: 1.689-6.317; p < 0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014-2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events

Real-world outcomes of radium-223 dichloride for metastatic castration resistant prostate cancer

Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line >= 3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line >= 3 (HR: 3.267; 95% CI: 1.689-6.317; p <0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014-2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events

High-Intensity Care in the End-of-Life Phase of Castration-Resistant Prostate Cancer Patients: Results from the Dutch CAPRI-Registry

Background: Intensive end-of-life care (i.e., the overuse of treatments and hospital resources in the last months of life), is undesirable since it has a minimal clinical benefit with a substantial financial burden. The aim was to investigate the care in the last three months of life (end-of-life [EOL]) in castration-resistant prostate cancer (CRPC). Methods: Castration-resistant prostate cancer registry (CAPRI) is an investigator-initiated, observational multicenter cohort study in 20 hospitals retrospectively including patients diagnosed with CRPC between 2010 and 2016. High-intensity care was defined as the initiation of life-prolonging drugs (LPDs) in the last month, continuation of LPD in last 14 days, >1 admission, admission duration ≥14 days, and/or intensive care admission in last three months of life. Descriptive and binary logistic regression analyses were performed. Results: High-intensity care was experienced by 41% of 2429 patients in the EOL period. Multivariable analysis showed that age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97–0.99), performance status (OR 0.57, 95% CI 0.33–0.97), time from CRPC to EOL (OR 0.98, 95% CI 0.97–0.98), referral to a medical oncologist (OR 1.99, 95% CI 1.55–2.55), prior LPD treatment (>1 line OR 1.72, 95% CI 1.31–2.28), and opioid use (OR 1.45, 95% CI 1.08–1.95) were significantly associated with high-intensity care. Conclusions: High-intensity care in EOL is not easily justifiable due to high economic cost and little effect on life span, but further research is awaited to give insight in the effect on patients' and their caregivers' quality of life