A comparison of bayesian and frequentist approaches to incorporating external information for the prediction of prostate cancer risk

We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single‐nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers. This approach ignores a substantial amount of external information concerning effect sizes for these Genome Wide Association Study (GWAS)‐replicated SNPs. The second and third methods investigated two possible approaches to incorporating meta‐analysed external SNP effect estimates – one via a weighted PCa 'risk' score based solely on the meta analysis estimates, and the other incorporating both the current and prior data via informative priors in a Bayesian logistic regression model. All methods demonstrated a slight improvement in predictive performance upon incorporation of genetics. The two methods that incorporated external information showed the greatest receiver‐operating‐characteristic AUCs increase from 0.61 to 0.64. The value of our methods comparison is likely to lie in observations of performance similarities, rather than difference, between three approaches of very different resource requirements. The two methods that included external information performed best, but only marginally despite substantial differences in complexity.     

9‐month results of polymer‐free sirolimus eluting stents in young patients compared to a septuagenarian and octogenarian all‐comer population

Objectives

To evaluate the 9‐month safety and efficacy of polymer‐free sirolimus eluting drug eluting stents in septuagenarians and octogenarians.

Methods

An all‐comer, worldwide single armed trial ( ClinicalTrials.gov Identifier NCT02629575) was conducted to demonstrate the safety and efficacy of an ultra‐thin strut, polymer‐free sirolimus eluting stent (PF‐SES). The primary endpoint was the 9‐month target revascularization rate (TLR). Secondary endpoints included the rates of major adverse cardiac events (MACE), stent thrombosis (ST) and bleeding (BARC) in septuagenarians (≥70 years, <80 years), and in octogenarians (≥80 years) to be compared to the younger patient group (<70 years).

Results

A total of 1607 patients were treated with PF‐SES in the sub‐70‐year‐old age group, 694 in septuagenarians, and 371 in the octogenarian patient group. At 9 months, the MACE rates were 7.2% in octogenarians, 5.3% in septuagenarians, and 3.0% in the younger patient group (P = 0.001). These were mostly driven by all‐cause mortality (4.4% vs 1.9% vs 0.6%, P < 0.001) while the TLR rates were only numerically lower in the younger age group (P = 0.080). BARC 1‐5 bleeding events were more frequent in the older age group (1.9% vs 2.7% vs 4.6%, P = 0.012) whereas the rates for ST were not different (0.7% vs 0.6% vs 0.6%, P = 0.970).

Conclusions

In octogenarians treated with PF‐SES, the rates for MACE, overall mortality, and bleeding are higher as compared to the younger age groups. However, the rates for TLR and ST were not significantly different across the investigated age groups. PF‐SES are safe and effective in octogenarians.

     

Evaluation of a risk-adjustment model for pressure ulcer development using the Minimum Data Set

OBJECTIVE: To validate a previously derived risk-adjustment model for pressure ulcer development in a separate sample of nursing home residents and to determine the extent to which use of this model affects judgments of nursing home performance. DESIGN: Retrospective observational study using Minimum Data Set (MDS) data from 1998. SETTING: A large, for-profit, nursing home chain. PARTICIPANTS: Twenty-nine thousand and forty observations were made on 13,457 nursing home residents who were without a pressure ulcer on an index assessment. MEASUREMENTS: We used logistic regression in our validation sample to calculate new coefficients for the 17 previously identified predictors of pressure ulcer development. Coefficients from this new sample were compared with those previously derived. Expected rates of pressure ulcer development were determined for 108 nursing homes. Unadjusted and risk-adjusted rates of pressure ulcer development from these homes were also calculated and outlier identification using these two approaches was compared. RESULTS: Predictors of pressure ulcer development in the derivation sample generally showed similar effects in the validation sample. The model c-statistic was also unchanged at 0.73, but it was not calibrated as well in the validation sample. On applying the model to the nursing homes, expected rates of ulcer development ranged from 1.1% to 3.2% (P <.001). The observed rates ranged from 0% to 12.1% (P <.001). There were 12 outliers using unadjusted rates and 15 using adjusted performance. Ten nursing homes were identified as outliers using both approaches. CONCLUSIONS: Our MDS risk-adjustment model for pressure ulcer development performed well in this new sample. Nursing homes differ significantly in their expected rates of pressure ulcer development. Outlier identification also differs depending on whether unadjusted or risk-adjusted performance is evaluated.     

Incidence and outcome of prone positioning following police use of force in a prospective, consecutive cohort of subjects

The safety of placing suspects in the prone position following police use of force has been debated extensively, particularly in the context of sudden in-custody death. The proportion of individuals who remain in the prone position following police use of force is not known, nor has the epidemiology of sudden in-custody death in any position after police restraint been documented. Using a consecutive cohort of individuals in whom police used force, we prospectively documented the number of individuals who were placed in a prone versus not-prone position, and the prevalence of sudden in-custody death in either position. Data were collected for three consecutive years, through a single urban police service, in a city of over 1.1 million citizens. Officers prospectively documented the final position of the subject, among other data points, via electronic study forms embedded in standard use of force report forms. Final resting position was available for 1255/1269 subjects. The majority of subjects are male and demonstrated one or more abnormalities at the time of the event. We found that the majority (57.2%) of subjects were left in a not-prone position; the remainder were left in prone position. One subject died in a not-prone position, no subjects died in the prone position. The sudden in-custody death rate following police use of force was low overall (0.08%, 95% confidence interval (CI) = 0.002, 0.44) and the difference in the proportion of subjects who died suddenly in either position was not significant at 0.14%, (95%CI = ?0.8, 0.9). Our results indicate that prone positioning was common and was not associated with death in our cohort of consecutive subjects following police use of force.     

Ein experimenteller Beitrag zur Frage des localen Meteorismus bei Darmocclusion

Ohne Zusammenfassung (Fortsetzung folgt.)     

The effect on wound healing of pazopanib and bevacizumab compared with corticosteroid in experimental glaucoma filtration surgery

AIM: To compare the effects of bevacizumab and pazopanib with corticosteroids on wound healing after trabeculectomy. METHODS: In the study, 35 New Zealand white rabbits were randomly divided into five groups. Apart from the first group, limbus-based trabeculectomy was performed for the eyes of rabbits. No postoperative treatment was administered for group I. Topically administered saline, prednisolone acetate (1%), bevacizumab 5 mg/mL, pazopanib 5 mg/mL for group II, III, IV and V respectively were applied for groups 6h daily for 28d. On day 28 of the experiment, eyes were enucleated and histologically and immunohistochemically analyzed. RESULTS: The fibroblast counts of groups IV and V were determined to be lower than those of groups II and III (P<0.05). In the mononuclear cell (MNC) count evaluation, no statistically significant difference was determined between the treatment groups (P>0.05). The immunohistochemical staining intensity of fibroblast growth factor β (FGF-β) and vascular endothelial growth factor (VEGF) was determined to be lower in groups IV and V than in groups II and III (P<0.05). No statistically significant difference was determined between groups IV and V in respect of fibroblast count, MNC count, FGF-β and VEGF staining intensity (P>0.05). The platelet derived growth factor β (PDGF-β) intensity was lower in group V than in groups II, III and IV (P<0.05). While the PDGF-β staining intensity was significantly lower in group IV than in group II, the difference compared with group III was not statistically significant (P>0.05). CONCLUSION: Bevacizumab and pazopanib might be good alternatives of corticosteroid treatment on delaying wound healing in glaucoma surgery.     

Relationship between pruritus and autotaxin in intrahepatic cholestasis of pregnancy

ObjectiveIntrahepatic cholestasis of pregnancy is a temporary, pregnancy-specific disease that resolves with delivery, characterized by itching (pruritus), as well as high transaminase and serum bile acid levels in the third trimester of pregnancy. Due to the effects of Autotaxin on the physiology of pregnancy, we aimed to investigate Autotaxin activity in patients with intrahepatic cholestasis of pregnancy.Patients and methodsSixty-nine patients diagnosed with intrahepatic cholestasis of pregnancy and 20 healthy pregnant women were enrolled in the study. Fasting serum bile acid, pruritus intensity, serum parameters, gestational week of the patients at the time of diagnosis were recorded, and birth week and birth weight were monitored. Autotaxin serum level was measured enzymatically.ResultsThe mean serum bile acid level (n = 69; 38.74 ± 35.92 μmol/L) in patients with intrahepatic cholestasis of pregnancy (n = 69) was detected to be higher than healthy pregnant women (n = 20; 5.05 ± 1.88 μmol/L) (p < 0.001). Weak correlation was detected between serum bile acid level and itch intensity (p = 0.014, r = 0.295), while no relation was detected between Autotaxin and itch intensity (p = 0.446, r = 0.09). Although mean Autotaxin (intrahepatic cholestasis of pregnancy: 678.10 ± 424.42 pg/mL, control: 535.16 ± 256.47 pg/mL) levels were high in patients with intrahepatic cholestasis of pregnancy, it was not statistically significant (p = 0.157).ConclusionIn our study, we observed that the serum Autotaxin level did not make a significant difference in patients with intrahepatic cholestasis of pregnancy compared to healthy pregnant women. These findings suggest that larger clinical studies are required to reveal the physio-pathological effects of Autotaxin on pregnancy.     

Immunohistochemical localisation of 3β-hydroxysteroid dehydrogenase in<Emphasis Type="Italic"> Sarcocystis</Emphasis> spp.

3-Hydroxysteroid-dehydrogenase (3-HSD) is an isoenzyme that catalyses an essential step in the synthesis of all classes of active steroid hormones. The presence of steroid hormones of the vertebrate type in invertebrates is acknowledged in addition to a group of steroid-like hormones called ecdysteroids that were present in arthropods and helminths. In the present study, 3-HSD was detected in the bradyzoites enclosed in sarcocysts of Sarcocystis spp. with immunohistochemistry. The results suggest that self-originating steroid hormones may play important roles in the development of Sarcocystis spp., and possibly in the regulation of the reciprocal immune interaction between the host and these parasites.