Reporting of paediatric osteoporotic vertebral fractures in Duchenne muscular dystrophy and potential impact on clinical management: the need for standardised and structured reporting.

BACKGROUND: In boys with Duchenne muscular dystrophy (DMD), initiation of bisphosphonate is recommended upon identification of moderate or severe vertebral fractures, even if asymptomatic. Clear radiological reporting is important for consistency of clinical interpretation and management. OBJECTIVES: To audit radiology reports of spine imaging for vertebral fracture assessment in DMD, and assess potential impact on diagnosis and management. MATERIALS AND METHODS: Lateral thoracolumbar spine imaging (71 lateral spine radiographs and 13 lateral dual energy absorptiometry spine image) in 84 boys with DMD performed across two centres. Anonymised radiology reports by paediatric radiologists were circulated to two neuromuscular clinicians and two endocrinologists. Clinicians determined if there was vertebral fracture, no vertebral fracture, or unclear interpretation. Endocrinologists also determined if bisphosphonate was indicated. A single observer (a clinician with expertise in vertebral fracture assessment) performed vertebral fracture assessment in 37 images and re-reported using a structured format. Structured reports were re-circulated to the four clinicians to re-evaluate the degree of concordance in clinical diagnosis of vertebral fracture and treatment decisions with bisphosphonate. RESULTS: The term "fracture" was used in 25/84 (30%) radiology reports and only in 8/43 (19%) with description of vertebral body abnormalities. Fracture grading was included in 7/43 (16%) radiology reports. Diagnostic concordance by the clinicians was noted in 36/84 (43%). Unclear interpretation was noted in 22% to 51% based on radiology reports. No unclear interpretation was noted with structured reports. Complete diagnostic (37/37, 100%) and treatment (37/37, 100%) concordance was noted with the structured reports, whereas complete diagnostic and treatment concordance was noted in only 16/37 (43%) and 17/37 (46%) of the radiology reports, respectively. CONCLUSION: Only a third of radiology reports of spine imaging in DMD explicitly used the terminology "fracture". Grading was only noted in a small percentage. Variability in diagnostic interpretation by clinicians may lead to differing management plans. As identification of vertebral fracture is a trigger for treatment, developing reporting guidelines for paediatric vertebral fracture assessment will improve care. A structured template should be introduced for radiological reporting of paediatric vertebral fracture assessment.

Increasing sample diversity in psychiatric genetics - Introducing a new cohort of patients with schizophrenia and controls from Vietnam - Results from a pilot study.

OBJECTIVES: Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry. METHODS: In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis. RESULTS: SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability = 4.9%, p = 6.83 × 10-8), East-Asian (R2 liability = 4.5%, p = 2.73 × 10-7) and European (R2 liability = 3.8%, p = 1.79 × 10-6) discovery samples. DISCUSSION: Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.

Assessment of dietary protein supplementation on milk productivity of commercial organic dairy farms during the grazing season.

Variability of protein and energy supply from pasture during the grazing season is a primary factor that can influence milk production of grazing organic dairy herds in the Northeast United States. This study evaluated the effects of altering the crude protein (CP) content of dietary supplements included in dairy rations fed to grazing organic dairy herds, on milk production and composition. Six commercial organic farms participated in a 6-wk trial, consisting of a 2-wk baseline period and 4-wk experimental period. Farms were paired by their summer 2017 milk urea nitrogen profile, and farms within each pair were assigned by restricted randomization to (1) continuation of their regular supplements (n = 3, control group, CON), or (2) supplement with altered CP as percentage of dry matter, formulated using an organic barley and roasted soybean mix (n = 3, treatment group, TRT). Throughout the 6-wk trial, individual milk samples were collected at 2 consecutive milkings weekly, while pasture and supplement samples, pasture measurements, and management information were collected twice weekly per farm. Data were statistically analyzed using the MIXED procedure of SAS (version 9.4, SAS Institute Inc.) for all parameters, and effects of treatment, week, and their interaction (treatment × week) were determined. The supplement CP (percentage of dry matter) during the baseline period was 13.5% for CON and 15.3% for TRT and 14.8% for CON and 19.3% for TRT during the experimental period. Milk production was 21% higher during the experimental period for TRT compared with CON (24.1 vs. 19.9 kg of milk per day, respectively). Milk production decreased for CON from wk 1 to wk 6 (23.6 vs. 20.4 kg of milk per day), whereas TRT maintained milked production from wk 1 to wk 6 (22.8 vs. 22.7 kg of milk per day). Milk composition was different between groups, with CON having higher fat percent (4.21 vs. 3.73%, respectively) and protein percent (3.15 vs. 3.05%, respectively) compared with TRT for the 6 wk. The milk urea nitrogen concentrations were similar between TRT and CON for the baseline period (11.9 vs. 12.1 mg/dL) and the final week of the experimental period (14.5 vs. 14.2 mg/dL). Although the effects of different diet CP fractions, particularly rumen undegradable protein and soluble protein, must be further delineated, these results indicate that altering the CP content of dietary supplements fed to grazing organic dairy cattle during the summer period in the Northeast US could be a useful mechanism to maintain milk production.

FDG PET versus CT radiomics to predict outcome in malignant pleural mesothelioma patients.

BACKGROUND: Careful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics-a quantitative method for image analysis-has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated. MATERIALS AND METHODS: This study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS. RESULTS: For the PFS a concordance index (c-index) of 0.67 (95% CI 0.52-0.82) and 0.66 (95% CI 0.57-0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS. CONCLUSION: We were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.

Comparative analysis of the skim milk and milk fat globule membrane proteomes produced by Jersey cows grazing pastures with different plant species diversity.

The objective of this experiment was to identify and characterize the bovine milk proteome within the skim milk fraction and milk fat globule membrane (MFGM)-associated fraction from 16 organically certified lactating Jersey cows after a short term of grazing pastures with or without annual forage crops (AFC). Cows were offered a partial mixed ration (∼60% of dry matter intake) and approximately 40% of their total dry matter intake as herbage. Eight cows were offered a cool-season grass-legume herbage (GLH), which included orchardgrass (Dactylis glomerata), timothy (Phleum pratense), Kentucky bluegrass (Poa pratensis), and white clover (Trifolium repens). The other 8 cows were offered the same GLH strip-tilled with the AFC, including oat (Avena sativa), millet (Pennisetum glaucum), teff (Eragrostis tef), buckwheat (Fagopyrum esculentum), and chickling vetch (Lathyrus sativus). Milk samples were collected from each cow during a.m. and p.m. milkings on d 19 to 21 of grazing, and composite milk samples per cow were analyzed for (1) the high-abundance milk protein profile, (2) the skim milk low-abundance protein-enriched proteome, and (3) the MFGM proteome. Of the 443 proteins identified in the skim and MFGM proteomes, 433 were included in statistical analysis, including 68 proteins identified in the skim milk fraction and 365 in the MFGM-associated fraction. Analysis of the skim and MFGM proteomes encompassed unique gene ontology profiles and proportions of functional classifications. In response to diet, αS1-casein as well as 8 low-abundance proteins were present in higher concentration or abundance in milk from cows grazing the GLH strip-tilled with the AFC compared with milk from cows grazing GLH, suggesting that even short-term grazing of pastures including some AFC may affect the milk proteome.

[Drug treatment of dementia]. / Medikamentöse Therapie demenzieller Erkrankungen.

The number of patients with dementia continues to increase worldwide, mainly due to the demographic developments. Early diagnosis and individualized therapy offers the chance of healing in secondary dementias. The therapy of the more common primary neurodegenerative forms is able to improve the course of the disease. As part of a multimodal management the therapy of dementias includes pharmacological treatment, nondrug treatment strategies, and psychosocial interventions. The treatment is administered depending on dementia form and stage. Antidementive medication and differentiated pharmacological therapy of frequent mental and behavioral symptoms corresponding to current guidelines contribute decisively to stabilize quality of life and activities of daily living, delaying the progression, and thus improving the care situation of patients and caregivers.

The relationship between oestrogen and executive functioning in ALS females with emerging Frontotemporal Lobar Degeneration (FTLD) supports a neuroendocrine model of FTLD attenuation.

OBJECTIVE: The prevalence of ALS cognitive or behavioural impairment (ci or bi) consistent with Frontotemporal Degeneration (FTLD) approachs 50%, while ∼5-10% progress to dementia. Our goal was to explore ci and bi differencs between bulbar and limb onset, as well as the neuroprotective potential of oestrogen in emerging FTLD. METHODS: We applied Mann Whitney U to evaluate differences in cognitive and behavioural profiles between site of onset in 78 female and 83 male non-demented ALS participants classified by current consensus criteria with ci. For females, we also examined differences by oestrogen level. FINDINGS: Between group analyses found significantly worse Letter Fluency (LF) for bulbar onset, and worse Category Fluency (CF) for bulbar females. Significantly worse performance was found for low oestrogen females for LF and Similarities, with significantly worse LF for low oestrogen bulbar onset. No significant differences were found for behavioural subgroups, while moderate-severe range traits were higher in occurrence for bulbar and low oestrogen bulbar onset. CONCLUSIONS: Findings support our previously published mesocortical pathway associated "bottom-up" model of FTLD emergence in ALSbi, extending it with a hierarchal hypothesis involving ascending cerebellar pathways in ALSci and ALSbi, further suggesting a role for oestrogen in mitigating female FTLD progression.

X-ray nanodiffraction analysis of stress oscillations in a W thin film on through-silicon via.

Synchrotron X-ray nanodiffraction is used to analyse residual stress distributions in a 200 nm-thick W film deposited on the scalloped inner wall of a through-silicon via. The diffraction data are evaluated using a novel dedicated methodology which allows the quantification of axial and tangential stress components under the condition that radial stresses are negligible. The results reveal oscillatory axial stresses in the range of ∼445-885 MPa, with a distribution that correlates well with the scallop wavelength and morphology, as well as nearly constant tangential stresses of ∼800 MPa. The discrepancy with larger stress values obtained from a finite-element model, as well as from a blanket W film, is attributed to the morphology and microstructural nature of the W film in the via.

Incremental amounts of ground flaxseed decrease milk yield but increase n-3 fatty acids and conjugated linoleic acids in dairy cows fed high-forage diets(1).

The objective of this study was to investigate the effect of incremental amounts of ground flaxseed (GFX) on milk yield and concentrations and yields of milk components, milk fatty acids (FA) profile, ruminal metabolism, and nutrient digestibility in dairy cows fed high-forage diets. Twelve multiparous Jersey cows averaging (mean ± SD) 112±68d in milk and 441±21kg of body weight and 8 primiparous Jersey cows averaging 98±43d in milk and 401±43kg of body weight were randomly assigned to treatment sequences in a replicated 4×4 Latin square design. Each period lasted 21d with 14d for diet adaptation and 7d for data and sample collection. Treatments were fed as a total mixed ration (63:37 forage-to-concentrate ratio) with corn meal and soybean meal replaced by incremental levels (i.e., 0, 5, 10, or 15% diet dry matter) of GFX. The ruminal molar proportions of acetate and butyrate decreased linearly with GFX supplementation, whereas the ruminal molar proportion of propionate increased linearly resulting in decreased acetate-to-propionate ratio. Apparent total-tract digestibilities of nutrients either decreased (dry matter) or tended to decrease (organic matter, neutral detergent fiber, acid detergent fiber) linearly in cows fed GFX. Milk yield decreased linearly in cows fed increasing amounts of GFX, which is explained by the linear reduction in dry matter intake. Except for the concentrations of milk protein and urea N, which decreased linearly with GFX supplementation, no other changes in the concentration of milk components were observed. However, yields of milk protein and fat decreased linearly with GFX supplementation. The linear decrease in the yields of milk fat and protein are explained by reduced milk yield, whereas that in milk urea N is explained by decreased crude protein intake. No treatment effects were observed for plasma urea N and nonesterified fatty acids, serum cortisol, and body weight change. Milk odd- and branched-chain FA and saturated FA decreased linearly with GFX supplementation. Milk trans-11 18:1, α-linolenic acid, cis-9,trans-11 18:2, and the sum of n-3 FA all increased linearly and quadratically, whereas the milk ratio of n-6 to n-3 decreased linearly in cows fed GFX. Overall, compared with the control diet (0% GFX), the diet with 15% GFX supplementation resulted in the lowest milk yield but highest milk proportions and yields (data not shown) of cis-9,trans-11 18:2 and n-3 FA.

[Ways to psychosomatic rehabilitation--differential treatment selection between psychosomatic acute care and rehabilitation]. / Wege in die psychosomatische Rehabilitation--differenzielle Indikationsstellung an der Schnittstelle zwischen Krankenhaus und psychosomatischer Rehabilitationsklinik.

Consecutive admissions to the psychosomatic departments of 5 hospital units in southwest Germany registered between October 2012 and October 2013 were asked to participate in a study investigating the treatment selection process for psychosomatic rehabilitation. 527 patients were included in the study, 269 outpatients and 258 inpatients at the end of their inpatient treatment. 52 patients (10.1%) received the recommendation for rehabilitation. 47 (90.4%) could be followed up 3 months later. 22 patients had applied for a rehabilitation treatment, 11 (50%) had obtained an approval for their rehabilitation, 5 had still no answer and for 6 patients the request was refused. 4 of the latter had objected their refusal and were still waiting for an answer. Only one patient was already admitted to a rehabilitation center. Possible reasons for the low permeability at the interface between hospital care and rehabilitation are discussed.

Incremental amounts of Ascophyllum nodosum meal do not improve animal performance but do increase milk iodine output in early lactation dairy cows fed high-forage diets.

The objective of this study was to investigate the effects of incremental amounts of Ascophyllum nodosum meal (ANOD) on milk production, milk composition including fatty acids and I, blood metabolites, and nutrient intake and digestibility in early lactation dairy cows fed high-forage diets. Twelve multiparous Jersey cows averaging (mean±standard deviation) 40±21 d in milk and 464±35 kg of body weight and 4 primiparous Jersey cows averaging 75±37 d in milk and 384±17kg of body weight were randomly assigned to treatment sequences in a replicated 4×4 Latin square design. Each period lasted 21 d with 14 d for diet adaptation and 7 d for data and sample collection. Cows were fed a total mixed ration (64:36 forage-to-concentrate ratio) supplemented (as fed) with 0, 57, 113, or 170 g/d of ANOD. Milk yield as well as concentrations and yields of milk components (fat, protein, lactose, milk urea N) were not affected by increasing dietary amounts of ANOD. Concentration (from 178 to 1,370 µg/L) and yield (from 2.8 to 20.6 mg/d) of milk I increased linearly in cows fed incremental amounts of ANOD as a result of the high concentration of I (820 mg/kg of dry matter) in ANOD. Overall, only minor changes were observed in the proportion of milk fatty acids with ANOD supplementation. Quadratic trends were observed for dry matter intake and total-tract digestibilities of organic matter and neutral detergent fiber, whereas negative linear trends were observed for serum concentration of cortisol and crude protein digestibility with ANOD supplementation. Serum concentrations of triiodothyronine and thyroxine were not affected by ANOD supplementation and averaged 1.1 and 48.4 ng/mL, respectively. However, feeding increasing amounts of ANOD linearly reduced the plasma concentration of nonesterified fatty acids (from 164 to 132 mEq/L). Quadratic effects were found for the total-tract digestibility of ADF and urinary output of purine derivatives, suggesting that ANOD supplementation may stimulate growth of ruminal cellulolytic bacteria in a dose-dependent fashion. In general, feeding incremental amounts of ANOD to early lactation dairy cows dramatically increased milk I concentration and output with no effect on animal performance.

Effect of biologics on depressive symptoms in patients with psoriasis: a systematic review.

BACKGROUND: Twenty to fifty percent of patients with psoriasis have depressive symptoms. OBJECTIVE: To describe the effects of biologics (tumour necrosis factor inhibitors [TNFi] or interleukin 12/23 inhibitors [IL-12/23i]) on depressive symptoms in patients with psoriasis. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) examining the effects of biologics on depressive symptoms in adults with psoriasis. RESULTS: Of the 305 publications identified, three RCTs were included in a systematic review. In a trial evaluating ustekinumab, mean change in Hospital and Anxiety Depression Rating Scale at 24 weeks from baseline was 3.1 with ustekinumab (P < 0.001) vs. 0.21 with placebo (not significant). In a trial evaluating adalimumab, mean change in Zung Self-Rating Depression Scale at 12 weeks from baseline was -6.7 with adalimumab vs. -1.5 with placebo. In a trial evaluating etanercept, the between-group difference at 12 weeks in Beck Depression Inventory Scale was 1.8 (95% CI: 0.6, 2.90) in favour of etanercept over placebo. Limitations are that diagnostic criteria for depression were not used and scales and data from individual RCTs could not be combined. CONCLUSION: Adalimumab, etanercept and ustekinumab were associated with statistically significant reductions in depressive symptom scores using various scales in patients with moderate-to-severe psoriasis.

Low-tube-voltage 80-kVp neck CT: evaluation of diagnostic accuracy and interobserver agreement.

BACKGROUND AND PURPOSE: Low-tube-voltage acquisition has been shown to facilitate substantial dose savings for neck CT with similar image contrast compared with standard 120-kVp acquisition. However, its potential for the detection of neck pathologies is uncertain. Our aim was to evaluate the effects of low-tube-voltage 80-kV(peak) acquisitions for neck CT on diagnostic accuracy and interobserver agreement. MATERIALS AND METHODS: Three radiologists individually analyzed 80-kVp and linearly blended 120-kVp image series of 170 patients with a variety of pathologies who underwent dual-energy neck CT. Reviewers were unblinded to the clinical indication for CT but were otherwise blinded to any other data or images and were asked to state a final main diagnosis. Findings were compared with medical record charts, CT reports, and pathology results. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each observer. Interobserver agreement was evaluated by using intraclass correlation coefficients. RESULTS: Diagnoses were grouped as squamous cell carcinoma-related (n = 107, presence/absence of primary/recurrent squamous cell carcinoma), lymphoma-related (n = 40, presence/absence of primary/recurrent lymphoma), and benign (n = 23, eg, abscess). Cumulative sensitivity, specificity, positive predictive value, and negative predictive value for 80-kVp and blended 120-kVp images were 94.8%, 93.0%, 95.9%, and 91.1%, respectively. Results were also consistently high for squamous cell carcinoma-related (94.8%/95.3%, 89.1%/89.1%, 94.3%/94.4%, 90.1%/91.0%) and lymphoma-related (95.0%, 100.0%, 100.0%, 95.2%) 80-kVp/120-kVp image series. Global interobserver agreement was almost perfect (intraclass correlation coefficient, 0.82, 0.80; 95% CI, 0.76-0.74, 0.86-0.85). Calculated dose-length product was reduced by 48% with 80-kVp acquisitions compared with the standard 120-kVp scans (135.5 versus 282.2 mGy × cm). CONCLUSIONS: Low-tube-voltage 80-kVp CT of the neck provides sufficient image quality with high diagnostic accuracy in routine clinical practice and has the potential to substantially decrease radiation exposure.

Short communication: Effect of antioxidant supplementation on milk production, milk fat synthesis, and milk fatty acids in dairy cows when fed a diet designed to cause milk fat depression.

This study evaluated the effect of a blend of synthetic antioxidants on the yield of milk and milk components and milk fatty acid composition in dairy cows fed a diet designed to cause milk fat depression (MFD). We hypothesized that supplementing a synthetic antioxidant to diets with a high rumen unsaturated fatty acid load (RUFAL) would decrease the severity of MFD. Sixteen lactating Holstein cows (163 ± 47 d in milk), in a crossover design with two 21-d periods, were fed a corn silage and grass silage-based diet containing 15% distillers grains. The diet contained 34% neutral detergent fiber, 18% crude protein, 26% starch, and 4.3% total fatty acids (dry matter basis). Cows were fed the diet without supplementation (control; CON) or supplemented with 0.02% (dry matter basis) of a synthetic antioxidant (AOX; Agrado Plus, Novus International Inc., St. Charles, MO). Dry matter intake and milk yields were recorded daily. Milk samples were collected at the start of the study for baseline values and the end of each period (d 20-21) and analyzed for milk components and fatty acid composition. Dry matter intake and milk yield were unaffected by treatment and averaged 25.9 and 50.2 kg/d, respectively. Similarly, we observed no effect of treatment on yields of fat, protein, lactose, 3.5% fat-corrected milk, energy-corrected milk, feed efficiency, body weight, or body condition score. Milk fat concentration and yield were both reduced by the high RUFAL diets. We observed a tendency for AOX to increase the concentration of milk fat and decrease the concentration of milk protein. Yields of de novo and preformed fatty acids were not affected by treatment, although we detected a trend for a slight increase in the yield of 16-carbon fatty acid for AOX compared with CON. Treatment had only minor effects on individual milk fatty acids, except for the concentration and yield of linoleic acid, which were over 90% higher for AOX compared with CON. In conclusion, milk fat concentration and yield were reduced by a high RUFAL diet containing 15% distillers grains; however, supplementation with AOX did not overcome the MFD induced by this diet.

Association of dopamine-related genetic loci to dopamine D3 receptor antagonist ABT-925 clinical response.

ABT-925, a selective dopamine D3 receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics. The effect of S9G genotype on response to ABT-925 was examined. DNA samples (N=117) were collected in a proof-of-concept, double-blind, randomized, placebo-controlled study of ABT-925 (50 or 150 mg QD) in acute exacerbation of schizophrenia. A pre-specified analysis assessed impact of genotype (SS versus SG+GG) on change from baseline to final evaluation for the Positive and Negative Syndrome Scale (PANSS) total score using analysis of covariance with genotype, treatment and genotype-by-treatment interaction as factors, and baseline score as covariate. Significant genotype-by-treatment interaction (P=0.015) was observed for change from baseline to final evaluation for the PANSS total score. Within subgroup analyses showed significant improvement from placebo in the SG+GG group treated with ABT-925 150 mg. More favorable clinical outcomes were observed in patients treated with ABT-925 150 mg who carried the DRD3 G allele than in those who carried the DRD3 SS genotype.

Magnetic resonance imaging and joint outcomes in boys with severe hemophilia A treated with tailored primary prophylaxis in Canada.

BACKGROUND/OBJECTIVES: Tailored primary prophylaxis (TPP) is a reduced-intensity treatment program for hemophiliacs with the goal of preventing arthropathy. Our primary aim was to evaluate the joint outcomes of treated subjects using magnetic resonance imaging (MRI) and physical examination as outcome measures. METHODS: Ankles, elbows and knees (index joints) of 24 subjects (median [range] age at start of therapy, 1.6 [1-2.5] years) with severe hemophilia A enrolled in the Canadian Hemophilia Primary Prophylaxis Study (CHPS) were examined by MRI at a median age of 8.8 years (range 6.2-11.5 years). Subjects were treated with TPP using a recombinant factor VIII concentrate, starting once weekly and escalating in frequency and dose according to frequency of bleeding. RESULTS: Osteochondral changes (cartilage loss/subchondral bone damage) were detected in 9% (13/140) of the index joints and 50% (12/24) of study subjects. Osteochondral changes were restricted to joints with a history of clinically reported joint bleeding. Soft tissue changes were detected in 31% (20/65) of index joints with no history of clinically reported bleeding (ankles 75% (12/16); elbows 19% (6/32); and knees 12% (2/17)). In these apparently 'bleed free' index joints hemosiderin deposition was detected by MRI in 26% (17/65) of joints (ankles 63% (10/16); elbows 16% (5/32), and knees 12% (2/17)). CONCLUSION: TPP did not completely avoid the development of MRI-detected structural joint changes in hemophilic boys in this prospective study. A longer period of follow-up is required for assessment of the longitudinal course of these early changes in hemophilic arthropathy, detected using a sensitive imaging technique (MRI).

[Implementation and results of a geriatric medication database]. / Aufbau und Ergebnisse einer geriatrischen Medikamentendatenbank.

BACKGROUND: The aim of this project was to obtain information about drug therapy in geriatric units. PATIENTS AND METHODS: Members of the geriatrics in Bavaria database (GiB-DAT) collected data on discharge medication and transferred them to the database. A total of 88,840 data sets of geriatric rehabilitation clinics and acute geriatric units were evaluated according to the anatomical therapeutic chemical (ATC) system. RESULTS: Patients (mean age: 81.1 years, female 67.7%) had an average of 10.4 diagnoses and took 8.0 drugs at discharge. A peak number of prescribed drugs was reached at the age of 60-70 years with a decrease in the following decades of life. Female patients received more drugs, significantly those in the decades from 71 to 80 and 81 to 90 years old. The bulk of the drugs were from the ATC groups "Cardiovascular system" (89.9%), "Nervous system" (82.3%) and "Alimentary tract and metabolism" (78%).

Pharmacogenetics and anaesthesia: the value of genetic profiling.

Approximately 50 years ago, pharmacogenetics was described as a new field of medicine that may explain human drug action. Anaesthesia played a key role in the early investigations. An understanding of how a person's DNA influences drug metabolism and effectiveness may allow individually tailored prescriptions, improving outcomes and safety. The ultimate goal of pharmacogenetic research is to offer tailored personalised medicine to improve both the efficacy of medication and patient safety by helping to predict risk of adverse outcomes. In this review, we present a selection of historical landmarks where anaesthesia has been a catalyst for pharmacogenetic development. We examine the level of evidence and cite examples of candidate genes and common polymorphisms known to alter the response to peri-operative medication. Finally, we set forth current views and potential exciting perspectives that may arise from the application of pharmacogenetics to the daily practice of anaesthesia and pain medicine.

Acitretin revisited.

Acitretin over the last 20 years has proven useful in a number of dermatologic diseases. Evidence of efficacy, side-effect profile, and approach to its use will be reviewed.