Reducing failures in daily medical practice: Healthcare failure mode and effect analysis combined with computer simulation.

This study proposes a risk analysis approach for complex healthcare processes that combines qualitative and quantitative methods to improve patient safety. We combine Healthcare Failure Mode and Effect Analysis with Computer Simulation (HFMEA-CS), to overcome widely recognised HFMEA drawbacks regarding the reproducibility and validity of the outcomes due to human interpretation, and show the application of this methodology in a complex healthcare setting. HFMEA-CS is applied to analyse drug adherence performance in the surgical admission to discharge process of pheochromocytoma patients. The multidisciplinary team identified and scored the failure modes, and the simulation model supported in prioritisation of failure modes, uncovered dependencies between failure modes, and predicted the impact of measures on system behaviour. The results show that drug adherence, defined as the percentage of required drugs received at the right time, can be significantly improved with 12%, to reach a drug adherence of 99%. We conclude that HFMEA-CS is both a viable and effective risk analysis approach, combining strengths of expert opinion and quantitative analysis, for analysing human-system interactions in socio-technical systems. Practitioner summary: We propose combining Healthcare Failure Mode and Effects Analysis with Computer Simulation (HFMEA-CS) for prospective risk analysis of complex and potentially harmful processes, to prevent critical incidents from occurring. HFMEA-CS combines expert opinions with quantitative analyses, such that the results are more reliable, reproducible, and fitting for complex healthcare settings.

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis.

Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options.

Chronic UVA (365-nm) irradiation induced scratching in hairless mice: dose-time dependency and the effect of ketanserin.

In a study on the dose-response relationship for longwave UVA (UVA1; 340-400 nm) carcinogenesis in hairless mice scratch marks appeared after months of daily exposure as an unwanted side effect. Tumor induction in the highest of the 4 tested dose groups (receiving a daily dose of 430 kJ/m2 of 365-nm radiation) could not be determined because extensive scarification occurred prior to the development of any tumors. The induction of scratch marks could be scored and quantified in all 4 dose groups tested. The UVA1 dose-dependencies for the induction of tumors and scratch marks were compared. We found that the induction of scratch marks depended mainly on the cumulative UVA1 exposure, whereas tumor induction showed a lesser dose-dependency. An attempt was made to prevent the apparent pruritogenic effect of UVA1 irradiation and to understand its mechanism. The influence of ketanserin, a serotonin/histamine antagonist, on the UVA1 induction of scratch marks was tested in groups of 8 mice daily irradiated with 430 kJ/m2. No difference was found between treated and untreated animals. Histological examination of skin biopsies from irradiated mice from the 430-kJ/m2 dose group from the UVA1 carcinogenic experiment, showed no changes in numbers of mast cells or other inflammatory features when compared to skin biopsies from unirradiated control mice. This indicated that UVA1-induced scratching is not mediated through mast cell release of serotonin and/or histamine. An adequate therapeutic treatment which can prevent UVA1-induced scratching would enable us to test tumor induction with UVA1 over a larger dose range, and may provide additional insight in how this radiation damages the skin. It remains conjectural whether there exists an analogous UVA-induced pruritus in human skin.

Transportation of rats affects behaviour of non-transported rats in the absence of physical contact (preliminary communication).

We have studied the effect of transportation stress in one rat on the behaviour of another, non-transported rat in the absence of physical contact. For this purpose an open box consisting of two adjacent small fields was used. Rats were placed in these fields and their behaviour was assessed. The control measurement involved pairs of non-transported rats and the experimental pairs consisted of a transported and a non-transported rat. The non-transported rats of the experimental pairs displayed significantly increased activities of sniffing when compared with the non-transported rats of the control pairs. It is suggested that stressed animals can influence the behaviour of nearby animals.