Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early

Increased integrated testing for HIV, hepatitis C and sexually transmitted infections in health care facilities: results from the INTEGRATE Joint Action pilots in Lithuania, Romania and Spain

BACKGROUND: Indicator condition guided HIV testing is a proven effective strategy for increasing HIV diagnosis in health care facilities. As part of the INTEGRATE Joint Action, we conducted four pilot studies, aiming to increase integrated testing for HIV/HCV/HBV and sexually transmitted infections, by introducing and expanding existing indicator condition guided HIV testing methods. METHODS: Pilot interventions included combined HIV/HCV testing in a dermatovenerology clinic and a clinic for addictive disorders in Lithuania; Increasing HIV testing rates in a tuberculosis clinic in Romania by introducing a patient information leaflet and offering testing for HIV/HCV/sexually transmitted infections to chemsex-users in Barcelona. Methods for implementing indicator condition guided HIV testing were adapted to include integrated testing. Testing data were collected retrospectively and prospectively. Staff were trained in all settings, Plan-do-study-act cycles frequently performed and barriers to implementation reported. RESULTS: In established indicator conditions, HIV absolute testing rates increased from 10.6 to 71% in the dermatovenerology clinic over an 18 months period. HIV testing rates improved from 67.4% at baseline to 94% in the tuberculosis clinic. HCV testing was added to all individuals in the dermatovenerology clinic, eight patients of 1701 tested positive (0.47%). HBV testing was added to individuals with sexually transmitted infections with a 0.44% positivity rate (2/452 tested positive). The Indicator condition guided HIV testing strategy was expanded to offer HIV/HCV testing to people with alcohol dependency and chemsex-users. 52% of chemsex-users tested positive for ≥ 1 sexually transmitted infection and among people with alcohol dependency 0.3 and 3.7% tested positive for HIV and HCV respectively. CONCLUSIONS: The four pilot studies successfully increased integrated testing in health care settings, by introducing testing for HBV/HCV and sexually transmitted infections along with HIV testing for established indicator conditions and expanding the strategy to include new indicators; alcohol dependency and chemsex. HCV testing of individuals with alcohol abuse showed high positivity rates and calls for further implementation studies. Methods used for implementing indicator condition guided HIV Testing have proven transferable to implementation of integrated testing

Deformable image registration based automatic CT-to-CT contour propagation for head and neck adaptive radiotherapy in the routine clinical setting

To evaluate the clinical potential of deformable image registration (DIR)-based automatic propagation of physician-drawn contours from a planning CT to midtreatment CT images for head and neck (H&N) adaptive radiotherapy. Ten H&N patients, each with a planning CT (CT1) and a subsequent CT (CT2) taken approximately 3-4 week into treatment, were considered retrospectively. Clinically relevant organs and targets were manually delineated by a radiation oncologist on both sets of images. Four commercial DIR algorithms, two B-spline-based and two Demons-based, were used to deform CT1 and the relevant contour sets onto corresponding CT2 images. Agreement of the propagated contours with manually drawn contours on CT2 was visually rated by four radiation oncologists in a scale from 1 to 5, the volume overlap was quantified using Dice coefficients, and a distance analysis was done using center of mass (CoM) displacements and Hausdorff distances (HDs). Performance of these four commercial algorithms was validated using a parameter-optimized Elastix DIR algorithm. All algorithms attained Dice coefficients of >0.85 for organs with clear boundaries and those with volumes >9 cm(3). Organs with volumes <3 cm(3) and/or those with poorly defined boundaries showed Dice coefficients of ∼ 0.5-0.6. For the propagation of small organs (<3 cm(3)), the B-spline-based algorithms showed higher mean Dice values (Dice = 0.60) than the Demons-based algorithms (Dice = 0.54). For the gross and planning target volumes, the respective mean Dice coefficients were 0.8 and 0.9. There was no statistically significant difference in the Dice coefficients, CoM, or HD among investigated DIR algorithms. The mean radiation oncologist visual scores of the four algorithms ranged from 3.2 to 3.8, which indicated that the quality of transferred contours was "clinically acceptable with minor modification or major modification in a small number of contours." Use of DIR-based contour propagation in the routine clinical setting is expected to increase the efficiency of H&N replanning, reducing the amount of time needed for manual target and organ delineations

「精神医療と触法行為の死生学 : 殺人行為をめぐって」報告

国際シンポジウム「精神医療と触法行為の死生学