Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths.

Methadone is an opioid that often leads to fatalities. Interpretation of toxicological findings can be challenging if no further information about the case history is available. The aims of this study were (1) to determine whether brain/blood ratios can assist in the interpretation of methadone findings in fatalities; (2) to examine whether polymorphisms in the gene encoding the P-glycoprotein (also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1)), which functions as a multispecific efflux pump in the blood-brain barrier, affect brain/blood ratios of methadone. Femoral venous blood and brain tissue (medulla oblongata and cerebellum) from 107 methadone-related deaths were analysed for methadone by gas chromatography-mass spectrometry. In addition, all the samples were genotyped for three common ABCB1 single nucleotide polymorphisms (SNPs rs1045642, rs1128503, and rs2032582) using ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry (ICEMS). In nearly all cases, methadone concentrations were higher in the brain than in the blood. Inter-individual brain/blood ratios varied (0.6-11.6); the mean ratio was 2.85 (standard deviation 1.83, median 2.35). Moreover, significant differences in mean brain/blood ratios were detected among the synonymous genotypes of rs1045642 in ABCB1 (p = 0.001). Cases with the T/T genotype had significantly higher brain/blood ratios than cases with the other genotypes (T/T vs. T/C difference (d) = 1.54, 95% CI [1.14, 2.05], p = 0.002; T/T vs. C/C d = 1.60, 95% CI [1.13, 2.29], p = 0.004). Our results suggest that the rs1045642 polymorphisms in ABCB1 may affect methadone concentrations in the brain and its site of action and may be an additional factor influencing methadone toxicity.

Costs of routine skin cancer screening in Germany: a claims data analysis.

BACKGROUND: In 2008, a routine skin cancer screening (rSCS) programme was implemented in Germany. Since then, its medical and economical effects have been evaluated and critically discussed. AIM: To compare costs for patients diagnosed with skin cancer with preceding rSCS vs. those diagnosed without rSCS. METHODS: We conducted a retrospective observational study using claims data from a large German health insurance company for the period 2013-2016. We applied entropy balancing, difference-in-differences estimation and generalized linear models to compare costs for patients with cancer with and without rSCS. We conducted sensitivity analyses to test for the robustness of results. RESULTS: In total, 12 790 patients with skin cancer were included in the analyses, of whom 6041 were diagnosed by rSCS. Treatment costs were €467 higher for patients in the control group (without rSCS). However, the screening costs were higher. For all people covered by the health insurance company, there were additional costs of €1339-1431 per patient with skin cancer diagnosed by rSCS. Thus, total costs, including costs for treatment and screening, were €872-964 higher for patients diagnosed by rSCS. CONCLUSIONS: Based on our analysis, rSCS has the potential to reduce treatment costs; however, the screening costs exceed these savings.

Cartilage calcification is associated with histological degeneration of the knee joint: a highly prevalent, age-independent systemic process.

OBJECTIVES: To investigate if cartilage calcification (CC) is a systemic process, the purpose of this study was to determine the prevalence and the amount of meniscal/hyaline CC of the knee joint in the general population by high-resolution imaging (DCR) and to evaluate the association between CC with cartilage degeneration and age. METHODS: Cross-sectional DCR-study of 180 knee joints of 90 donors (42 female/48 male, mean age 62.3y). Histological hyaline (OARSI) and meniscal (Krenn) cartilage degeneration was determined of all knees. RESULTS: CC was observed in 100% of the donors (bilaterally in 98%), hyaline cartilage calcification (HCC) in 92% and meniscal calcification (MC) in 100%. CC was detected in more than three out of six distinct cartilage areas in 84.4% of all knees. The mean amount of CC correlated between both sides of donors, the different analyzed areas of the knee joint and between the various types of cartilage structures. There was more calcification in meniscal than in hyaline cartilage (factor 5.3) and in the medial than the lateral compartment (factor 1.2). HCC/MC were already detectable with only mild cartilage lesions and the amount correlated with histological cartilage degeneration, but not with age. CONCLUSIONS: The present study provides evidence that meniscal and hyaline CC occurs in a pattern that is compatible with CC being a systemically driven process and that meniscal fibrocartilage is more prone to calcification than hyaline cartilage. Furthermore, the age-independent association between the amount of CC and the grade of degeneration in both hyaline and meniscal cartilage, suggests that CC is an obligatory early event in initiating cartilage degeneration.

Articular cartilage calcification of the hip and knee is highly prevalent, independent of age but associated with histological osteoarthritis: evidence for a systemic disorder.

OBJECTIVES: Based on the concept of a systemic predisposition for articular cartilage calcification (CC), the aim of this study was to determine the prevalence and amount of bilateral CC of hip and knee joints in an unselected sample cohort by high-resolution digital contact radiography (DCR) and to analyze the association of CC with histological OA. METHODS: Both hip and knee joints of 87 donors (48 m and 39 f; mean age 62) were analyzed by DCR in this post-mortem study of an unselected cohort of donors. Histological OA (OARSI) of the main load bearing area of femoral heads and medial femoral condyles was determined. RESULTS: The prevalence of CC of the femoral head was 96.6%, of the knee 94.3%. Bilateral calcification was detected in 79.3% of hips and 86.2% of knees. Concomitant CC of all four joints was detected in 69.0% of donors. There was no difference between the amount of CC of hips and knees (P = 0.47). The amount of CC of any given hip or knee correlated with that of the contralateral hip (rs = 0.54, P < 0.001) or knee (rs = 0.50, P < 0.001). There was a correlation between the amount of CC and histological OA (hips rs = 0.48, P < 0.001, knees rs = 0.30, P = 0.004), but not between CC and age (hips rs = -0.09, P = 0.42; knees rs = 0.10, P = 0.34). CONCLUSIONS: These data support the concept that articular CC occurs as the result of a systemic disorder. CC appears to be an early element of hip and knee OA pathogenesis independent of age.

Free flap surgery in Europe: an interdisciplinary survey.

Free flap surgery is essential for the aesthetic and functional reconstruction of various parts of the body. The aim of this study was to compare current concepts of perioperative flap management between ENT, craniomaxillofacial, and plastic surgeons. A European survey was conducted among 570 surgical departments, covering all aspects of free flap surgery. Focus was placed on antibiotic and antithrombotic drug use, aspects of osseous reconstruction, and flap monitoring strategies. One hundred and seventy-two medical units participated. A broad spectrum of anticoagulant regimens and a trend towards prolonged antibiotic prophylaxis were found. Fixation with (CAD/CAM) reconstruction plates was more popular than monocortical locking with miniplates in the mandible. Visual assessment and Doppler systems were reported to be the most common monitoring modalities. The flap loss rate was stated to be higher after osseous reconstruction. Only a few differences in perioperative flap management were identified between the different surgical fields, and osseous reconstruction appears to be the most challenging.