Vitamin B6 metabolites in idiopathic calcium stone formers: no evidence for a link to hyperoxaluria

Vitamin B6 metabolites and their potential correlates to urinary oxalate excretion in idiopathic calcium stone formers (ICSF) compared with healthy subjects were investigated. This clinical study was performed in a population of male ICSF with (Hyperoxalurics, n=55) or without hyperoxaluria (Normooxalurics, n=57) as well as in 100 healthy male control subjects. Pyridoxal 5'-phosphate serum concentration (S-pyridoxal 5'P) and 24-h urinary excretion of 4-pyridoxic acid (U-4pyridoxic acid) were measured using HPLC; 24-h urinary excretion of oxalate (U-oxalate) was measured concurrently. A subgroup of subjects (40 Hyperoxalurics, 15 Normooxalurics and 50 controls) underwent the same measurements before and after 7-day pyridoxine loading per os (pyridoxine hydrochloride, 300mg/d). Under usual conditions, U-4pyridoxic acid was similar in the three groups, whereas mean S-pyridoxal 5'P was significantly lower (p<0.0001) in the Hyperoxalurics (59.6±21.2nmol/L) and in the Normooxalurics (64.9±19.7nmol/L) than in the controls (86.0±31.0nmol/L). No correlation could be found between U-oxalate and U-4pyridoxic acid or S-pyridoxal 5'P. After B6 loading, S-pyridoxal 5'P was still significantly lower in the Hyperoxalurics (415±180nmol/L, p<0.001) and in the Normooxalurics (429±115nmol/L, p=0.036) than in the controls (546±180nmol/L), although there was no difference between groups for U-4pyridoxic acid. No correlation in any group could be found between changes in U-oxalate and changes in U-4pyridoxic acid or S-pyridoxal 5'P. Although there is no vitamin B6 deficiency in ICSF with or without hyperoxaluria, these patients, on average, have lower levels of S-pyridoxal 5'P than healthy subjects. However, this slight decrease does not seem to account for idiopathic hyperoxaluri

Effect of calcium-channel blockers on calcium—phosphate metabolism in patients with end-stage renal disease

Background After EDTA-induced hypocalcaemia, healthy volunteers treated with diltiazem display more severe hyperparathyroidism than subjects on felodipine studied under identical conditions. Therefore patients with end-stage renal disease (ESRD) and severe secondary hyperparathyroidism might be particularly sensitive to this side-effect. Methods To test this hypothesis, seven patients with ESRD on chronic haemodialysis (3 women and 4 men) with serum levels of intact PTH ranging from 204 to 675 pg/ml were studied both before and during the first 180 min of haemodialysis against a dialysate with low calcium concentration (0.75 mmol/1, n=6 and 1 mmol/1, n=1) under the following three experimental conditions: control, felodipine (10 mg/day) and diltiazem (120 mg b.i.d.). Results At onset of dialysis, plasma phosphorus level was higher on diltiazem (2.03±0.08 mM) than on felodipine (1.64±0.10, P<0.02), and on the latter it was lower than in control condition (1.88±0.16, P<0.02). As a probable consequence, blood ionized calcium concentration was lower on diltiazem (1.14 mM±0.02, mean±SEM) than on felodipine (1.2±0.03, P<0.05) or in control condition (1.17±0.01, NS). There was a trend for intact PTH to be higher on diltiazem (324±47 pg/ml) than on felodipine (246±55) or in control condition (305±49) and 1,25-dihydroxyvitamin D was higher indeed on diltiazem (6.70±0.92 pg/ml) than on felodipine (4.75±0.91, P<0.02) or control (3.87±0.62, P<0.05). Area under the curve PTH over the first 60 min of dialysis was higher by 16±7% on diltiazem than on felodipine (P<0.05). Conclusions While on diltiazem rather than on felodipine, patients with ESRD display higher plasma phosphorus levels, and slightly aggravate the degree of severity of hyperparathyroidism recorded during haemodialysis against low-calcium dialysate. The longterm effect of this new observation remains to be evaluate

Targeted education improves the very low recognition of vertebral fractures and osteoporosis management by general internists

Introduction: Vertebral fractures in older persons are strong predictors of subsequent fracture risk but remain largely under-recognized. To evaluate the impact of an educational intervention on the recognition of vertebral fractures and the prescription of anti-osteoporosis treatment among general internists, we conducted a prospective study in a service of general internal medicine of a large university teaching hospital in Geneva, Switzerland. During a 3.5-month observation period (phase1), all lateral spinal or chest radiographs performed on consecutive inpatients over 60 years were reviewed by two independent investigators, and vertebral fractures were graded according to their severity. Methods: Results were compared with radiology reports and general internists' discharge summaries. During the following 2-month intervention period (phase2), internists were actively educated about vertebral fracture identification by means of lectures, posters and flyers. Radiologists did not receive this educational strategy and served as controls. Results: Among 292 consecutive patients (54% men; range: 60-97 years) included in phase1, 85 (29%) were identified by investigators as having at least one vertebral fracture; radiologists detected 29 (34%), and internists detected 19 (22%). During the intervention phase, 58 (34%) of 172 patients were identified with vertebral fractures by investigators; radiologists detected 13 patients (22%) whereas among internists the detection rate almost doubled (25/58 patients, 43%; p=0.008 compared to phase1). The percentage of patients with vertebral fracture who benefitted from an osteoporosis medical management increased from 11% (phase1) to 40% (phase2, p<0.03). Conclusions: Our findings confirm the large under-recognition of vertebral fractures, irrespective of their severity, and demonstrate that a simple educational strategy can significantly improve their detection on routine radiographs and, consequently, improve osteoporosis managemen

A Risk Analysis Method to Evaluate the Impact of a Computerized Provider Order Entry System on Patient Safety

Objectives: Quantitative evaluation of safety after the implementation of a computerized provider order entry (CPOE) system, stratification of residual risks to drive future developments. Design: Comparative risk analysis of the drug prescription process before and after the implementation of CPOE system, according to the Failure Modes, Effects and Criticality Analysis (FMECA) method. Measurements: The failure modes were defined and their criticality indices calculated on the basis of the likelihood of occurrence, potential severity for patients, and detection probability. Criticality indices of handwritten and electronic prescriptions were compared, the acceptability of residual risks was discussed. Further developments were proposed and their potential impact on the safety was estimated. Results: The sum of criticality indices of 27 identified failure modes was 3813 for the handwritten prescription, 2930 (−23%) for CPOE system, and 1658 (−57%) with 14 enhancements. The major safety improvements were observed for errors due to ambiguous, incomplete or illegible orders (−245 points), wrong dose determination (−217) and interactions (−196). Implementation of targeted pop-ups to remind treatment adaptation (−189), vital signs (−140), and automatic edition of documents needed for the dispensation (−126) were the most promising proposed improvements. Conclusion: The impact of a CPOE system on patient safety strongly depends on the implemented functions and their ergonomics. The use of risk analysis helps to quantitatively evaluate the relationship between a system and patient safety and to build a strategy for continuous quality improvement, by selecting the most appropriate improvements to the syste

Characteristics of patients with venous thromboembolism and atrial fibrillation in Venezuela

<p>Abstract</p> <p>Background</p> <p>Studies describing venous thromboembolic event (VTEE) and atrial fibrillation (AF) in South American populations are limited. The aim of this cross-sectional study was to describe the characteristics of Venezuelan patients admitted and treated for these conditions.</p> <p>Methods</p> <p>A retrospective medical record review of 1397 consecutive patients admitted to three private hospitals or clinics between January 2000 and December 2005 was performed. Data was collected on demographics, anthropometrics, hospital visit, comorbidities and treatment.</p> <p>Results</p> <p>Among 401 VTEE and 996 AF patients, men were more likely to have AF (58%) while more women experienced a VTEE (58%). Most patients were admitted via the emergency room (87%) and had only one event during the study period (83%). Common comorbidities included hypertension (46%), heart failure (17%), diabetes (12%) and congestive heart failure (11%). Characteristics of Venezuelan patients with VTEE and AF are similar to that reported in the literature for other populations.</p> <p>Conclusions</p> <p>These results provide background characteristics for future studies assessing risk factors for AF and VTEE in South American populations.</p

Increased density and periosteal expansion of the tibia in young adult men following short-term arduous training

Purpose: Few human studies have reported early structural adaptations of bone to weight-bearing exercise, which provide a greater contribution to improved bone strength than increased density. This prospective study examined site- and regional-specific adaptations of the tibia during arduous training in a cohort of male military (infantry) recruits to better understand how bone responds in vivo to mechanical loading. Methods: Tibial bone density and geometry were measured in 90 British Army male recruits (ages 21 + 3 y, height 1.78 ± 0.06 m, body mass 73.9 + 9.8 kg) in weeks 1 (Baseline) and 10 of initial military training. Scans were performed at the 4%, 14%, 38% and 66% sites, measured from the distal end plate, using pQCT (XCT2000L, Stratec Pforzheim, Germany). Customised software (BAMPack, L-3 ATI) was used to examine whole bone cross-section and regional sectors. T-tests determined significant differences between time points (P<0.05). Results: Bone density of trabecular and cortical compartments increased significantly at all measured sites. Bone geometry (cortical area and thickness) and bone strength (i, MMi and BSI) at the diaphyseal sites (38 and 66%) were also significantly higher in week 10. Regional changes in density and geometry were largely observed in the anterior, medial-anterior and anterior-posterior sectors. Calf muscle density and area (66% site) increased significantly at week 10 (P<0.01). Conclusions: In vivo mechanical loading improves bone strength of the human tibia by increased density and periosteal expansion, which varies by site and region of the bone. These changes may occur in response to the nature and distribution of forces originating from bending, torsional and shear stresses of military training. These improvements are observed early in training when the osteogenic stimulus is sufficient, which may be close to the fracture threshold in some individuals

VITA-D: Cholecalciferol substitution in vitamin D deficient kidney transplant recipients: A randomized, placebo-controlled study to evaluate the post-transplant outcome

<p>Abstract</p> <p>Background</p> <p>Vitamin D does not only regulate calcium homeostasis but also plays an important role as an immune modulator. It influences the immune system through the induction of immune shifts and regulatory cells resulting in immunologic tolerance. As such, vitamin D is thought to exert beneficial effects within the transplant setting, especially in kidney transplant recipients, considering the high prevalence of vitamin D deficiency in kidney transplant recipients.</p> <p>Methods/Design</p> <p>The VITA-D study, a randomized, placebo-controlled, double-blind study with two parallel groups including a total of 200 kidney transplant recipients, is designed to investigate the immunomodulatory and renoprotective effects of cholecalciferol (vitamin D₃) within the transplant setting. Kidney transplant recipients found to have vitamin D deficiency defined as 25-hydroxyvitamin D₃< 50 nmol per liter will be randomly assigned to receive either oral cholecalciferol therapy or placebo and will be followed for one year. Cholecalciferol will be administered at a dose of 6800 International Units daily over a time period of one year.</p> <p>The objective is to evaluate the influence of vitamin D₃substitution in vitamin D deficient kidney transplant recipients on the post-transplant outcome. As a primary endpoint glomerular filtration rate calculated with the MDRD formula (modification of diet in renal disease) one year after kidney transplantation will be evaluated. Incidence of acute rejection episodes, and the number and severity of infections (analyzed by means of C-reactive protein) within the first year after transplantation will be monitored as well. As a secondary endpoint the influence of vitamin D₃on bone mineral density within the first year post-transplant will be assessed. Three DXA analyses will be performed, one within the first four weeks post-transplant, one five months and one twelve months after kidney transplantation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00752401</p

JAMA Neurol

Importance: Moderately effective therapies (METs) have been the main treatment in pediatric-onset multiple sclerosis (POMS) for years. Despite the expanding use of highly effective therapies (HETs), treatment strategies for POMS still lack consensus.Objective: To assess the real-world association of HET as an index treatment compared with MET with disease activity.Design, setting, and participants: This was a retrospective cohort study conducted from January 1, 2010, to December 8, 2022, until the last recorded visit. The median follow-up was 5.8 years. A total of 36 French MS centers participated in the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Of the total participants in OFSEP, only treatment-naive children with relapsing-remitting POMS who received a first HET or MET before adulthood and at least 1 follow-up clinical visit were included in the study. All eligible participants were included in the study, and none declined to participate.Exposure: HET or MET at treatment initiation.Main outcomes and measures: The primary outcome was the time to first relapse after treatment. Secondary outcomes were annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, time to Expanded Disability Status Scale (EDSS) progression, tertiary education attainment, and treatment safety/tolerability. An adapted statistical method was used to model the logarithm of event rate by penalized splines of time, allowing adjustment for effects of covariates that is sensitive to nonlinearity and interactions.Results: Of the 3841 children (5.2% of 74 367 total participants in OFSEP), 530 patients (mean [SD] age, 16.0 [1.8] years; 364 female [68.7%]) were included in the study. In study patients, both treatment strategies were associated with a reduced risk of first relapse within the first 2 years. HET dampened disease activity with a 54% reduction in first relapse risk (adjusted hazard ratio [HR], 0.46; 95% CI, 0.31-0.67; P < .001) sustained over 5 years, confirmed on MRI activity (adjusted odds ratio [OR], 0.34; 95% CI, 0.18-0.66; P = .001), and with a better tolerability pattern than MET. The risk of discontinuation at 2 years was 6 times higher with MET (HR, 5.97; 95% CI, 2.92-12.20). The primary reasons for treatment discontinuation were lack of efficacy and intolerance. Index treatment was not associated with EDSS progression or tertiary education attainment (adjusted OR, 0.51; 95% CI, 0.24-1.10; P = .09).Conclusions and relevance: Results of this cohort study suggest that compared with MET, initial HET in POMS was associated with a reduction in the risk of first relapse with an optimal outcome within the first 2 years and was associated with a lower rate of treatment switching and a better midterm tolerance in children. These findings suggest prioritizing initial HET in POMS, although long-term safety studies are needed.Observatoire Français de la Sclérose en Plaque

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon