Calibration adjustments to address bias in mortality analyses due to informative sampling—a census-linked survey analysis in Switzerland

Background: Sampling bias, like survey participants' nonresponse, needs to be adequately addressed in the analysis of sampling designs. Often survey weights will be calibrated on specific covariates related to the probability of selection and nonresponse to get representative population estimates. However, such calibrated survey (CS) weights are usually constructed for cross-sectional results, but not for longitudinal analyses. For example, when the outcome of interest is time to death, and sampling selection is related to time to death and censoring, sampling is informative. Then, unweighted or CS weighted inferential statistical analyses may be biased. In 2010, Switzerland changed from a decennial full enumeration census to a yearly registry-based (i.e., data from harmonised community registries) and a survey-based census system. In the present study, we investigated the potential bias due to informative sampling when time to death is the outcome of interest, using data from the new Swiss census system. Methods: We analysed more than 6.5 million individuals aged 15 years or older from registry-based census data from years 2010 to 2013, linked with mortality records up to end of 2014. Out of this population, a target sample of 3.5% was sampled from the Swiss Federal Statistical Office (SFSO) in a stratified yearly micro census. The SFSO calculated CS weights to enable representative population estimates from the micro census. We additionally constructed inverse probability (IP) weights, where we used survival information in addition to known sampling covariates. We compared CS and IP weighted mortality rates (MR) and life expectancy (LE) with estimates from the underlying population. Additionally, we performed a simulation study under different sampling and nonresponse scenarios. Results: We found that individuals who died in 2011, had a 0.67 (95% CI [0.64-0.70]) times lower odds of participating in the 2010 micro census, using a multivariable logistic regression model with covariates age, gender, nationality, civil status, region and survival information. IP weighted MR were comparable to estimates from the total population, whereas CS weighted MR underestimated the population MR in general. The IP weighted LE estimates at age 30 years for men were 50.9 years (95% CI [50.2-51.6] years), whereas the CS weighted overestimated LE by 2.5 years. Our results from the simulation study confirmed that IP weighted models are comparable to population estimates. Conclusion: Mortality analyses based on the new Swiss survey-based census system may be biased, because of informative sampling. We conclude that mortality analyses based on census-linked survey data have to be carefully conducted, and if possible, validated by registry information to allow for unbiased interpretation and generalisation

Complement-Mediated Opsonic Activity in Normal and Infected Human Cerebrospinal Fluid: Early Response During Bacterial Meningitis

A local defense mechanism in bacterial meningitis was evaluated in humans by measuring complement-mediated opsonic activity (CMOA) in normal and infected cerebrospinal fluid (CSF) with a complement-dependent phagocytic bactericidal assay. CMOA was absent in normal untreated CSF and remained undetectable in 20 samples of CSF from patients with viral meningitis and five samples from patients with acute meningococcemia. In contrast, 15 of 27 samples of CSF from patients with acute bacterial meningitis had a measurable CMOA, which was correlated with protein concentrations (P < 0.01) and C4 hemolytic activity (P < 0.001) in the CSF. A favorable outcome of bacterial meningitis was associated with the presence of CMOA in CSF (P < 0.005). Recovery was also correlated with higher levels of C4 (P < 0.01) and C3 (P < 0.05) in CSF and with lower concentrations of microorganisms in the sample of CSF collected at the time of admission (P < 0.01). Thus, CMOA, although absent in normal CSF, can appear in CSF during acute bacterial meningitis, particularly in patients who recover completel

Re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after initial definitive radiotherapy - A systematic review and meta-analysis of recent trials.

BACKGROUND There is increasing data on re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after definitive radiotherapy for prostate cancer, with increasing evidence on prostate re-irradiation using a C-arm LINAC or an MR LINAC in recent years. We therefore conducted this systematic review and meta-analysis on prostate re-irradiation including studies published from 2020 to 2023, to serve as an update on existing meta-analysis. METHODS We searched the PubMed and Embase databases in October 2023 with queries including combinations of "repeat", "radiotherapy", "prostate", "re-irradiation", "reirradiation", "re treatment", "SBRT", "retreatment". Publication date was set to be from 2020 to 2023. There was no limitation regarding language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. After data extraction, heterogeneity testing was done by calculating the I2. A random effects model with a restricted maximum likelihood estimator was used to estimate the combined effect. Funnel plot asymmetry was assessed visually and using Egger's test to estimate the presence of publication and/or small study bias. RESULTS 14 publications were included in the systematic review. The rates of acute ≥ grade 2 (G2) genitourinary (GU) and gastrointestinal (GI) toxicities reported in the included studies ranged from 0.0-30.0 % and 0.0-25.0 % respectively. For late ≥ G2 GU and GI toxicity, the ranges are 4.0-51.8 % and 0.0-25.0 %. The pooled rate of acute GU and GI toxicity ≥ G2 were 13 % (95 % CI: 7-18 %) and 2 % (95 % CI: 0-4 %). For late GU and GI toxicity ≥ G2 the pooled rates were 25 % (95 % CI: 14-35 %) and 5 % (95 % CI: 1-9 %). The pooled 2-year biochemical recurrence-free survival was 72 % (95 % CI: 64-92 %). CONCLUSIONS SBRT in the re-irradiation of radiorecurrent prostate cancer is safe and effective. Further prospective data are warranted

Dose-Volume Histogram Parameters and Quality of Life in Patients with Prostate Cancer Treated with Surgery and High-Dose Volumetric-Intensity-Modulated Arc Therapy to the Prostate Bed.

INTRODUCTION Prostate bed radiotherapy (RT) is a major affecter of patients' long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data. METHODS Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores. RESULTS The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL. CONCLUSION Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals

Excess burden of a chronic disabling condition: life lost due to traumatic spinal cord injury in a Swiss population-based cohort study.

OBJECTIVES To estimate excess mortality and life years lost in a Swiss cohort of individuals with traumatic spinal cord injury (TSCI). METHODS This study uses population-based data collected in the Swiss Spinal Cord Injury Cohort (SwiSCI) study, which covers all specialized rehabilitation centres. Flexible parametric survival models were used to model life years remaining (LYR), potential years life lost (PYLL), relative survival and excess hazard ratios. RESULTS Men and women with TSCI and an attained age of 30 were estimated to have 42 LYR (95% CI = 37.9-45.5) and 43 LYR (95% CI = 40.1-45.5), respectively; this equates to a life expectancy (LE) of 80.6 and 76.9% of that of the Swiss general population. With respect to lesion level and completeness, persons with incomplete paraplegia had 45.1 LYR at an attained age of 30, whereas individuals with complete tetraplegia only had 28.7 LYR. This pattern was similar for PYLL. CONCLUSIONS The extended LE following TSCI, even for the most severe lesions, underscores the need for sustained follow-up to support functioning and health for individuals ageing with SCI

The role of causal inference in health services research I: tasks in health services research.

In a recent issue of the American Journal of Public Health, Herna´n and other colleagues strongly plea for causal thinking in scientific research where the research question investigates consequences of decisions and interventions (Ahern 2018; Begg and March 2018; Chiolero 2018; Glymour and Hamad 2018; Herna´n 2018a, b; Jones and Schooling 2018). Herna´n argues that causal reasoning improves quality of observational research; however, the causal terminology is often loomed by the ‘association is not causation’ argument and is viewed with skepticism (Herna´n 2018b). Health services research (HSR) supports decision making by investigating the effect of complex ‘interventions’ or ‘policies’ on different healthcare system outcomes (Glass et al. 2013). Thus, some of the research questions in HSR are inherently causal. Surprisingly, there is no consensus on how to integrate causal inference into tasks of HSR (Dowd 2011; O’Malley 2011; Pearl 2011; Herna´n et al. 2019). Typically, tasks in data science are classified into ‘description’, ‘modeling’ and ‘causal inference’ (Herna´n et al. 2019). In the present Hints and Kinks, we explain why a solidly principled causal inference framework should be integrated into the tasks of HSR