Propensity scores in the presence of effect modification: A case study using the comparison of mortality on hemodialysis versus peritoneal dialysis

Purpose. To control for confounding bias from non-random treatment assignment in observational data, both traditional multivariable models and more recently propensity score approaches have been applied. Our aim was to compare a propensity score-stratified model with a traditional multivariable-adjusted model, specifically in estimating survival of hemodialysis (HD) versus peritoneal dialysis (PD) patients. Methods. Using the Dutch End-Stage Renal Disease Registry, we constructed a propensity score, predicting PD assignment from age, gender, primary renal disease, center of dialysis, and year of first renal replacement therapy. We developed two Cox proportional hazards regression models to estimate survival on PD relative to HD, a propensity score-stratified model stratifying on the propensity score and a multivariable-adjusted model, and tested several interaction terms in both models. Results. The propensity score performed well: it showed a reasonable fit, had a good c-statistic, calibrated well and balanced the covariates. The main-effects multivariable-adjusted model and the propensity score-stratified univariable Cox model resulted in similar relative mortality risk estimates of PD compared with HD (0.99 and 0.97, respectively) with fewer significant covariates in the propensity model. After introducing the missing interaction variables for effect modification in both models, the mortality risk estimates for both main effects and interactions remained comparable, but the propensity score model had nearly as many covariates because of the additional interaction variables. Conclusion. Although the propensity score performed well, it did not alter the treatment effect in the outcome model and lost its advantage of parsimony in the presence of effect modification

Mutant Prourokinase with Adjunctive C1-Inhibitor Is an Effective and Safer Alternative to tPA in Rat Stroke

A single-site mutant (M5) of native urokinase plasminogen activator (prouPA) induces effective thrombolysis in dogs with venous or arterial thrombosis with a reduction in bleeding complications compared to tPA. This effect, related to inhibition of two-chain M5 (tcM5) by plasma C1-inhibitor (C1I), thereby preventing non-specific plasmin generation, was augmented by the addition of exogenous C1I to plasma in vitro. In the present study, tPA, M5 or placebo +/− C1I were administered in two rat stroke models. In Part-I, permanent MCA occlusion was used to evaluate intracranial hemorrhage (ICH) by the thrombolytic regimens. In Part II, thromboembolic occlusion was used with thrombolysis administered 2 h later. Infarct and edema volumes, and ICH were determined at 24 h, and neuroscore pre (2 h) and post (24 h) treatment. In Part I, fatal ICH occurred in 57% of tPA and 75% of M5 rats. Adjunctive C1I reduced this to 25% and 17% respectively. Similarly, semiquantitation of ICH by neuropathological examination showed significantly less ICH in rats given adjunctive C1I compared with tPA or M5 alone. In Part-II, tPA, M5, and M5+C1I induced comparable ischemic volume reductions (>55%) compared with the saline or C1I controls, indicating the three treatments had a similar fibrinolytic effect. ICH was seen in 40% of tPA and 50% of M5 rats, with 1 death in the latter. Only 17% of the M5+C1I rats showed ICH, and the bleeding score in this group was significantly less than that in either the tPA or M5 group. The M5+C1I group had the best Benefit Index, calculated by dividing percent brain salvaged by the ICH visual score in each group. In conclusion, adjunctive C1I inhibited bleeding by M5, induced significant neuroscore improvement and had the best Benefit Index. The C1I did not compromise fibrinolysis by M5 in contrast with tPA, consistent with previous in vitro findings

Functional outcome after sacrospinous hysteropexy for uterine descensus

The study aimed to evaluate urogenital symptoms, defecatory symptoms and quality of life before and after a sacrospinous hysteropexy for uterovaginal prolapse. Seventy-two women with symptomatic uterovaginal prolapse were treated with sacrospinous hysteropexy. Before and after surgery, urogenital and defecatory symptoms and quality of life were assessed with a validated questionnaire. Anatomical outcome was assessed by means of pelvic examination before and after surgery. The mean follow-up time was 12.7 months. Scores on all domains of urogenital symptoms and defecatory symptoms, except for the pain and fecal incontinence domain, improved significantly. Also, quality of life improved on all domains. No major complications were encountered

The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study

-1 SD) were included in the study. A final group of 13 patients (9 males and 4 females), mean age 23.7 ± 2.9 years (range 20 – 29.7) completed a 2-year treatment with GH. IQ and neuropsychological performance were assessed at pre-treatment (T1) and after one (T2) and two (T3) years. ANOVA was performed with assessment at T1, T2 and T3 as repeated measurements factor. Relations between test score changes and changes of IGF-I levels were determined by calculating the Pearson correlation coefficient. Results Scores on the cognitive tests were in the normal range. Verbal short- and long-term memory performance decreased between T1 and T2, and increased between T2 and T3. Performance at T3 was not significantly different from that at T1. Performance for sustained attention improved from T1 to T2 and from T1 to T3. Visual-spatial memory was improved after one year of GH treatment. A significant positive correlation was found for Δ IGF-I (T2-T1) with difference scores of visual-spatial memory (T2-T1 and T3-T1), indicating that IGF-I increase after one year of GH treatment is associated with increase in cognitive-perceptual performance at month 12 and 24. Conclusion Since the level of intellectual functioning of our patient cohort was in the normal range the present finding that GH treatment has negative effects on verbal memory and positive on attention and visual-spatial memory warrants similar studies in other groups of ALL survivors. Also, a lower dose of GH should be determined inducing as much IGF as needed to improve verbal as well as visual cognitive functions. The present findings indicate that more knowledge is needed before GH treatment may be recommended to enhance cognitive functions in ALL survivors

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population

Reproductive health and burn-out among female physicians: nationwide, representative study from Hungary

BACKGROUND: There is a worldwide rising tendency of women deciding to become physicians; hence, one of the most remarkable fields of investigation is the wellbeing of female doctors. The aim of this study was to describe female physicians' reproductive health in Hungary and to explore the potential correlation between their reproductive disorders and burnout symptoms. Up to our present knowledge, there have not been any studies investigating the correlation between reproductive disorders and burnout of female physicians; therefore, our study represents a unique approach. METHODS: Data in this representative cross-sectional epidemiological study were obtained from online questionnaires completed by 3039 female physicians. Participants in a representative nationwide survey (Hungarostudy, 2013) served as controls (n = 1069). Differences between physicians and the control group were disclosed by chi-square test. Correlations between certain factors of reproductive health and the three dimensions of burnout were detected by Pearson correlations and X2 test. Binary logistic regression analysis was used to determine the association between burnout and reproductive health. RESULTS: Female physicians were more often characterised by time-to-pregnancy interval longer than one year (18.4% vs. 9.8%), were bearing more high-risk pregnancies (26.3% vs.16.3%), and were more likely to be undergoing infertility therapy (8.5% vs. 3.4%) and experiencing miscarriage (20.8% vs. 14.6%) during their reproductive years, compared with the general female population. With the exception of miscarriages, the difference remained significant in all comparisons with the professional control group. Both high-risk pregnancies and miscarriages of doctors were associated with depersonalisation (p = 0.028 and p = 0.012 respectively) and personal accomplishment (p = 0.016 and p = 0.008 respectively) dimensions of burnout. Results of the multivariate analysis showed that, beside traditional risk factors, depersonalisation acted as an important explanatory factor in case of high-risk pregnancies (OR = 1.086). CONCLUSIONS: There is a circulatory causality between burnout and the development of reproductive disorders. Burnout is an important risk factor for high-risk pregnancies and miscarriages, and it has a negative effect on the outcome of pregnancies. At the same time, women suffering from reproductive disorders are more likely to develop burnout syndrome. Improvement of working conditions and prevention of burnout in female doctors are equally important tasks

Diagnostic algorithm, prognostic factors and surgical treatment of metastatic cancer diseases of the long bones and spine

Oncological management of skeletal metastases has changed dramatically in the last few decades. A significant number of patients survive for many years with their metastases.Surgeons are more active and the technical repertoire is broader, from plates to intramedullary devices to (tumour) endoprostheses.The philosophy of treatment should be different in the case of a trauma-related fracture and a pathological fracture. A proper algorithm for establishing a diagnosis and evaluation of prognostic factors helps in planning the surgical intervention.The aim of palliative surgery is usually to eliminate pain and to allow the patient to regain his/her mobility as well as to improve the quality of life through minimally invasive techniques using life-long durable devices.In a selected group of patients with an oncologically controlled primary tumour site and a solitary bone metastasis with positive prognostic factors, which meet the criteria for radical excision (approximately 10% to 15% of the cases), a promising three to five years of survival may be achieved, especially in cases of metastases from breast and kidney cancer.Spinal metastases require meticulous evaluation because decisions on treatment mostly depend on the tumour type, segmental stability, the patient's symptoms and general state of health.Advanced radiotherapy combined with minimally invasive surgical techniques (minimally invasive stabilisation and separation surgery) provides durable local control with a low complication rate in a number of patients. Cite this article: EFORT Open Rev 2017;2:372-381