B\,^1\Sigma^{+}_{u} and EF\,^{1}\Sigma^{+}_{g} level energies of D2_{2}

Accurate absolute level energies of the B\,^1\Sigma^{+}_{u}, $v=0-8, N$ and EF\,^{1}\Sigma^{+}_{g}, $v=0-21, N$ rovibrational quantum states of molecular deuterium are derived by combining results from a Doppler-free two-photon laser excitation study on several lines in the $EF\,{}^{1}\Sigma_{g}^{+}-X\,{}^{1}\Sigma_{g}^{+}$ (0,0) band, with results from a Fourier-transform spectroscopic emission study on a low-pressure hydrogen discharge. Level energy uncertainties as low as 0.0005 cm$^{-1}$ are obtained for some low-lying E\,^{1}\Sigma^{+}_{g} inner-well rovibrational levels, while uncertainties for higher-lying rovibrational levels and those of the F\,^{1}\Sigma^{+}_{g} outer-well states are nominally 0.005 cm$^{-1}$. Level energies of B\,^1\Sigma^{+}_{u} rovibrational levels, for $v \leq 8$ and $N \leq 10$ are determined at an accuracy of 0.001 cm$^{-1}$. Computed wavelengths of D$_2$ Lyman transitions in the B\,^1\Sigma^{+}_{u}-X\,^{1}\Sigma^{+}_{g} ($v,0$) bands are also tabulated for future applications.Comment: appears in Journal of Molecular Spectroscopy (2014

Accurate level energies in the EF1S+g, GK1S+g, H1S+g, B1S+u, C1Pu, B'1S+u, D1Pu, I1Pg, J1Dg states of H2

International audienceBy combining results from a Doppler-free two-photon laser excitation study on several lines in the EF1g+ - X1g+ (0,0) band of H2 with results from a Fourier-transform spectroscopic study on a low-pressure discharge in hydrogen, absolute level energies, with respect to the X1g+, v=0, N=0 ground level, could be determined for 547 rovibronically excited states in H2. While for some of the levels in the EF1g+ and B1u+ states the uncertainties are as low as 0.0001 cm-1, the accuracy of other levels is less accurate. The general improvement on the accuracy for the comprehensive data set of level energies is by an order of magnitude with respect to previous measurements. An updated listing of transition wavelengths of the spectral lines in the Lyman and Werner bands is presented, based on combination differences between the presently obtained B1u+ and C1u level energies and those in the X1g+ ground state

Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis

Background: Etelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown. Methods: To investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n = 509) versus placebo (n = 514) and etelcalcetide (n = 340) versus cinacalcet (n = 343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide. Results: Etelcalcetide reduced FGF23 [median % change (quartile 1-quartile 3)] from baseline to the end of the trial significantly more than placebo [-56% (-85 to -7) versus +2% (-40 to +65); P < 0.001] and cinacalcet [-68% (-87 to -26) versus -41% (-76 to +25); P < 0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide. Conclusion: These data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium

Circulating markers of bone turnover

Renal osteodystrophy is a feature of chronic kidney disease (CKD), with increasing prevalence as CKD progresses. This bone disease is responsible for major morbidity, including fractures, and a deterioration in the quality of life and its sequelae. Circulating biomarkers of renal osteodystrophy typically indicate bone turnover, but not other features of bone, like bone volume, mineralization, quality or strength. Bone turnover can be considered to be primarily a reflection of bone cell activity, in particular that of osteoblasts and osteoclasts. Since current treatments for bone disease usually target cellular activity, biomarkers are considered to be able to contribute to the decision-making for treatment and its follow-up. In CKD, one has to consider the impact of a diminished clearance of biomarkers or their altered metabolism, both potentially limiting its clinical use. Here, several aspects of the most frequently used biomarkers of bone turnover are reviewed, with an emphasis on the specific situation represented by CKD. This review is based on the overview lecture at the symposium held in Amsterdam, September 23, 2016: "The Bone In CKD", organized by the CKD-MBD working group of ERA-EDTA

Development and validation of a self-report measure of practical barriers to medication adherence: The medication practical barriers to adherence questionnaire (MPRAQ)

AIM: This study reports the development and validation of a new self-report measure (MPRAQ) that assesses practical barriers to medication adherence. METHODS: MPRAQ comprises fifteen statements describing practical barriers. Responses are scored on a 5-point Likert scale; higher scores indicate more practical barriers. Initial face validity was evaluated by cognitive testing with patients from a diabetes support group. Following refinement, internal reliability and construct validity were assessed in two samples: patients recruited via Amazon mTurk and the Nivel Dutch Healthcare Consumer Panel (COPA). Respondents completed the Beliefs about Medicines Questionnaire (BMQ - general and specific), and Medication Adherence Report Scale (MARS-5). The mTurk sample also completed the Perceived Sensitivity to Medicines questionnaire (PSM), and repeated MPRAQ two weeks later to assess test-retest reliability. RESULTS: Face validity was evaluated in 15 patients (46% female; mean (SD) age 64(12) years). A total of 184 mTurk participants completed the questionnaire (in English) and 334 in COPA (in Dutch). Internal reliability was acceptable (mTurk α=0.89; COPA α=0.94). Construct validity was confirmed, with significant correlation between MPRAQ and BMQ-Specific Concerns (mTurk r=0.546, p<0.0001; COPA r=0.370, p<0.0001); BMQ-General Harm (mTurk r=0.504, p<0.0001; COPA r=0.219, p<0.0001); BMQ-General Overuse (mTurk, r=0.324, p<0.0001; COPA r=0.109, p=0.047), and PSM (mTurk only, r=0.463, p<0.0001), and a negative correlation with MARS-5 (mTurk r=-0.450, p<0.0001; COPA r=-0.260, p<0.0001). MPRAQ did not correlate with BMQ-Specific Necessity or BMQ-General Benefit. Correlation between MPRAQ baseline and 2-week follow-up scores confirmed test-retest reliability (r=0.745, p<0.0001; n=52). CONCLUSION: MPRAQ is a reliable and valid self-report measure of practical adherence barriers

Sucroferric oxyhydroxide for hyperphosphatemia: A review of real-world evidence

Hyperphosphatemia is a common complication in dialysis-dependent patients with chronic kidney disease. Most dialysis-dependent patients need oral phosphate binder therapy to control serum phosphorus concentrations. Most phosphate binders have a high daily pill burden, which may reduce treatment adherence and impair phosphorus control. Sucroferric oxyhydroxide is a potent iron-based phosphate binder approved for use in dialysis-dependent patients in 2013. A randomized controlled trial of sucroferric oxyhydroxide demonstrated its efficacy for reduction of serum phosphorus with a lower pill burden than sevelamer carbonate. Clinical trials carefully select patients, monitor adherence, and routinely titrate medications to a protocol-defined goal. Consequently, trials may not reflect real-world use of medications. Since its approval, we and others have performed retrospective and prospective analyses of sucroferric oxyhydroxide in real-world clinical practice in \u3e 6400 hemodialysis and approximately 500 peritoneal dialysis patients in the USA and Europe. Consistent with the clinical trial data, real-world observational studies have demonstrated that sucroferric oxyhydroxide can effectively reduce serum phosphorus with a lower daily pill burden than most other phosphate binders. These studies have also shown sucroferric oxyhydroxide provides effective serum phosphorus control in different treatment settings, including as monotherapy in phosphate binder-naïve patients, in patients switching from other phosphate binders, or when used in combination with other phosphate binders. These observational studies indicate a favorable safety and tolerability profile, and minimal, if any, systemic iron absorption. This article reviews the key results from these observational studies of sucroferric oxyhydroxide and evaluates its role in the management of hyperphosphatemia in clinical practice

Comprehensibility of a personalized medication overview compared to usual-care prescription drug labels

Poor understanding of prescription drug label (PDL) instructions can lead to medication errors, suboptimal treatment (side) effects, and non-adherence. A personalized medication hard-copy overview listing PDL instructions and visual information may support patients in their medication use. This study aimed to investigate the comprehensibility of PDL instructions on a personalized medication overview compared to usual-care PDL instructions presented on a medication box. A hypothetical-online-experiment was set up, comparing groups of respondents exposed vs not exposed to the medication overview and who received PDL instructions for three, five, or eight medications. Participants were divided randomly in six groups. Online questionnaires were sent to a stratified sample of 900 members from the Nivel Dutch Healthcare Consumer Panel. Outcome measures included comprehension of instructions for medication use, e.g. how often, dose timing, usage advice and warnings for a medication with simple use instructions (omeprazol) and more complex use instructions (levodopa/carbidopa (L/C)). To analyze differences between experimental conditions ANOVA testing was used. 604 respondents (net response 67%) completed the questionnaires. Respondents exposed (E) to the overview gave a higher proportion of correct answers compared to non-exposed (NE) respondents for usage advice (L/C: mean 0.83, SD 0.4 E; 0.03, SD 0.2 NE, p < 0.001; omeprazol: mean 0.85, SD 0.4 E; 0.10, SD 0.3 NE, p < 0.001). Both groups gave the same proportion of correct answers (mean 0.80, SD 0.4, p = 1.0) for dose timing of omeprazol. More NE respondents gave correct answers for how often (mean 0.85, SD 0.4 NE; mean 0.76, SD 0.4 E, p = 0.02) and dose timing (mean 0.92, SD 0.3 NE; mean 0.86, SD 0.4 E, p = 0.04) of L/C. No differences were found regarding number of medications nor were interaction effects found between the number of medications and information type. As a medication overview contains additional information, it can be a good addition in supporting patients in their medication use compared to usual-care PDLs. Future research should focus on identifying patient groups who might benefit more from a medication overview, by testing the effect of such overview on this group

A multidisciplinary review of the science of vitamin D receptor activation

Our understanding of the vitamin D receptor (VDR) and the effects of VDR activation has changed dramatically in recent years, with the publication of several new studies looking at selective VDR activation and effects on the cardio-renal syndrome (CRS).1 These advances have the potential to change the perspective of VDR activation beyond its role in mineral metabolism. Pleiotropic vitamin D effects have come into the focus of interest

Blueprint for a european calciphylaxis registry initiative. the european calciphylaxis network (eucalnet)

Calcific uraemic arteriolopathy (CUA) is a rare disease and continues to be a clinical challenge. The typical course of CUA is characterized by painful skin discolouration and induration evolving to necrotic ulcerations. Medial calcification of cutaneous arterioles and extensive extracellular matrix remodelling are the hallmarks of CUA. The epidemiology and risk factors associated with this disease are still not fully understood. Moreover, CUA treatment strategies vary significantly among centres and expert recommendations are heterogeneous. Registries may provide important insights and information to increase our knowledge about epidemiology and clinical aspects of CUA and may help to optimize its therapeutic management. In 2006, we established an internet-based registry in Germany (www.calciphylaxie.de) to allow online notification of patients with established or suspected CUA. The registry includes a comprehensive database with questions covering >70 parameters and items regarding patient-related and laboratory data, clinical background and presentation as well as therapeutic strategies. The next phase will be to allow international patient registration via www.calciphylaxis.net as part of the multinational EuCalNet (European Calciphylaxis Network) initiative, which is supported by the ERA-EDTA scientific working group 'CKD-MBD'. Based on the valuable experience with the previous German CUA registry, EuCalNet will be a useful tool to collect data on the rare disease CUA and may become a basis for prospective controlled trials in the near future