scholarly journals Dialysate Calcium Levels: Do They Matter?

2018 ◽  
Vol 47 (1-3) ◽  
pp. 230-235 ◽  
Author(s):  
Frank M. van der Sande ◽  
Karlien J.A. ter Meulen ◽  
Peter Kotanko ◽  
Jeroen P. Kooman
Keyword(s):  
Vitamin D ◽  
Critical Role ◽  
Essential Element ◽  
Vascular Pathology ◽  
Phosphate Binders ◽  
Multiple Parameters ◽  
Vitamin D Analogues ◽  
Endocrine Disturbances ◽  
Increased Risk ◽  
The Difference

Background: Calcium (Ca) is an essential element that plays a critical role in many biological processes. In dialysis patients, the regulation of Ca balance is highly complex, given the absence of kidney function, endocrine disturbances and the use of drugs such as phosphate binders, vitamin D analogues, and calcimimetics. Also, the use of different dialysate Ca (DCa) baths has profound effect on Ca balance, which depends both on the difference between the Ca concentration in the bath and the serum of the patients, as on the ultrafiltration volume. Summary: The choice of DCa may have important short- and long-term consequences. While lower DCa (especially < 2.5 mEq/L) concentrations have been associated with an increased risk of sudden cardiac death in observational studies, DCa in the higher ranges (3.0 mEq/L and above) may contribute to vascular pathology. Intra-dialytic hemodynamics may also be affected by the choice of DCa. In general, lower DCa concentrations are associated with an increase, and higher DCa concentrations with a decrease in parathyroid hormone (PTH) levels. Preliminary data has suggested that a DCa of 2.75 mEq/L may help in obtaining a net zero intradialytic Ca balance in individual patients, but clinical experience is still limited. Key Message: The optimal Ca balance depends on multiple parameters including blood Ca levels, PTH and the use of phosphate binders and vitamin D analogues, as well as on the risk of hemodynamic stability and cardiac arrhythmias. Therefore, DCa prescription should be individualised. A DCa of 2.75 mEq/L may be useful adjunct for dialysis providers.

scholarly journals The Menstrual Cycle Related Hormone Variations and Breast Cancer Risk: A Novel Theory

2020 ◽  
pp. 1-6
Author(s):  
Liang Xiaohui ◽  
Liang Xiaohui ◽  
Nicholas Taylor ◽  
Vixey Fang ◽  
Xiao Zhang
Keyword(s):  
Breast Cancer ◽  
Menstrual Cycle ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Average Length ◽  
Critical Role ◽  
Age At Menarche ◽  
Increased Risk ◽  
Novel Theory ◽  
The Difference

Background: The cumulative and excessive exposures to estrogen contributing to increased risk of breast cancer may be misleading. Methods: We proposed a novel theory to highlight that exposure to unstable estrogen levels may play a critical role in determining breast cancer risk among females as the change of endocrine environment may pose a risky environment to breast tissues for carcinogenesis. Particularly, we considered the menstrual cycle related estrogen variation (MCREV) as the primary hazard to breast cancer among females. Results: To describe MCREV, its intensity was defined as the difference between the highest and the lowest levels of estrogen within a menstrual cycle; its timing was defined as age at menarche and age at pregnancies (i.e. timing of cessation of exposure to this hazard); and its frequency and duration can both be defined as the total number of menstrual cycles, which is influenced by many factors including age of menarche, age of menopause, average length of one menstrual cycle, and durations and number of pregnancies and breastfeeding. Conclusions: The proposed MCREV theory may identify women at high-risk of breast cancer at an earlier age. The development of breast cancer might be weakened if suitable techniques to reduce the MCREV become clinically available. This novel theory opens a new door in breast cancer prevention and management.

scholarly journals Vitamin D Receptor Gene Polymorphism and Vitamin D Status in Population of Patients with Cardiovascular Disease—A Preliminary Study

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3117
Author(s):  
Mohamed Abouzid ◽  
Marlena Kruszyna ◽  
Paweł Burchardt ◽  
Łukasz Kruszyna ◽  
Franciszek K. Główka ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Receptor Gene ◽  
Plasma Concentrations ◽  
Vitamin D Metabolites ◽  
Vdr Polymorphism ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D ◽  
The Difference

The association between vitamin D receptor (VDR) polymorphism and the risk of cardiovascular diseases (CVD) remains unclear. This study aimed to assess a relationship between the VDR genotypes, plasma concentrations of vitamin D metabolites, and the occurrence of cardiovascular and metabolic disorders. Fifty-eight patients treated for various cardiological afflictions were included. Identification of VDR polymorphisms: ApaI, TaqI, BsmI, and FokI were carried out using the PCR-RFLP method. Plasma concentrations of 25-hydroxyvitamin-D2, 25-hydroxyvitamin-D3, and 3-epi-25-hydroxyvitamin D3 were assessed by the UPLC-MS/MS method. Lower incidence of BsmI AA genotype in the studied patients was observed compared with healthy controls, but the difference was insignificant. Among patients with the TT genotype, frequency of hypertension was higher than among carriers of other ApaI genotypes (p < 0.01). In addition, carriers of the TT ApaI, TC TaqI, and GA BsmI genotypes had an increased risk of obesity, while the presence of the FokI TT genotype was associated with a higher incidence of heart failure and hypertension. In conclusion, the BsmI AA genotype can be protective against CVD, but this observation needs study on a larger group of patients. Particular VDR genotypes were associated with 25-hydroxyvitamin-D levels, and the mechanism of this association should be further investigated.

scholarly journals Primary Hypoparathyroidism and Chronic Kidney Disease: Is It Always Related to Treatment?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A214-A215
Author(s):  
Todor Zlatanski ◽  
Nicole Simon
Keyword(s):  
Vitamin D ◽  
Basal Ganglia ◽  
Critical Role ◽  
Phosphate Binders ◽  
Close Monitoring ◽  
Active Vitamin ◽  
Active Vitamin D ◽  
Qt Interval Prolongation ◽  
Ectopic Mineralization ◽  
Chronic Hypoparathyroidism

Abstract Background: Anterior neck surgery is the leading cause of acquired hypoparathyroidism. Renal failure is the most common complication of treatment for hypoparathyroidism with active vitamin D and calcium supplements. However, the contribution of hypoparathyroidism to development of CKD in the absence of treatment is not well studied. Clinical Case: A 70-year old woman was brought to ED after she was found on the floor at home. Medical history was significant only for a partial thyroidectomy over 20 years prior, without reported post-operative complications. She was not taking any medications. Pertinent physical findings included altered mental status, hand tremors, involuntary contractions of left arm, and ashen skin. Laboratory tests upon presentation were significant for profoundly low albumin-corrected calcium of 3.68 mg/dL (n 8.6–10.2 mg/dL); low PTH 9.9 pg/dL (n 15–65 pg/dL); elevated phosphorous 8.5 mg/dL (n 2.7–4.5 mg/dL), elevated BUN 36 mg/dL (n 8–22 mg/dL), creatinine 2.76 mg/dL (n 0.5–1.3 mg/dL) and elevated CK of 4787 U/L (n 10–225 U/L). EKG showed QT interval prolongation. Head CT revealed periventricular and basal ganglia calcifications. Renal US was normal. The patient was treated with IV and PO calcium acetate and active vitamin D with resolution of the symptoms while calcium level improved. Post hospital follow-ups were significant for persistent hyperphosphatemia, which gradually improved with calcium and non-calcium phosphate binders as well as active vitamin D. Although this patient presented with acute hypocalcemia, she had chronic hypoparathyroidism as evidenced by basal ganglia calcifications. In the absence of other medical conditions, including negative PTH antibodies, or treatment for chronic hypoparathyrodism, the most likely cause of the CKD was chronic hypoparathyroidism itself. Conclusion: Post-surgical hypoparathyroidism may develop many years after surgery and can be asymptomatic. It is essential to diagnose this condition early to avoid late complications of the disease. The kidneys are particularly affected. Conventional treatment with calcium and vitamin D analogues is associated with ectopic mineralization and can lead to CKD. Untreated hypoparathyroidism on the other hand, can also lead to CKD, posing therapeutic challenges on finding the most appropriate and balanced treatment regimen in order to prevent further renal complications. Close monitoring and optimizing therapy plays critical role in preserving renal function of patients with hypoparathyroidism.

Therapeutic options in male osteoporosis

2013 ◽  
Vol 22 (04) ◽  
pp. 271-276 ◽  
Author(s):  
P. Farahmand ◽  
J. D. Ringe
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Public Health Problem ◽  
Male Osteoporosis ◽  
Individual Risk ◽  
Modes Of Action ◽  
Increased Risk ◽  
Study Results ◽  
Long Term Treatment ◽  
Male Patients

SummaryOsteoporosis in men is increasingly recognized as an important public health problem but affected patients are still under-diagnosed and -treated. As in women the diagnostic and therapeutic strategy has to be adapted to the individual case. In the practical management it is very important to detect possible causes of secondary osteoporosis, to explain the possibilities of basic therapy counteracting individual risk factors and communicate that osteoporosis is a chronic disease and adherence to a long-term treatment is crucial. In established severe osteoporosis a careful analgesic therapy is important to avoid further bone loss related to immobility. In elderly men with increased risk of falling insufficient Vitamin D supply or impaired activation of Vitamin D due to renal insufficiency must be taken into consideration. Specific medications available today for the treatment of male osteoporosis comprise among antiresorptive drugs the bis phosphonates alendronate, risedronate and zoledronic acid. Denosumab, the first biological therapy is approved for men with androgen deprivation therapy for prostate cancer. An important advantage of this potent antiresorptive drug is the increased adherence due to the comfortable application by sixmonthly subcutaneous injections. Study results from the 2-year multi-center randomized controlled ADAMO-Study will very soon allow the use of denosumab in all types of male osteoporosis. Teriparatide, the 34 N-terminal amino acid sequence of parathyroid hormone was approved for men with osteoporosis as an anabolic agent based on proven efficacy by different studies. Among drugs with other modes of action the D-hormone pro-drug alfacalcidol can be used in men alone or in combination with the advantage of pleiotropic effects on calcium absorption, parathyroids, bone and muscle. Recently also Strontium-ranelate was approved for male patients with the limitation to exclude men with clinical relevant cardiovascular risk factors. In general the possibilities to treat male osteoporosis have considerably improved during recent years. Today there is a choice of a spectrum of drugs from mild to strong potency with different modes of action on bone turnover to design strategies for individual male patients.

Predictors of Success Using a mHealth Intervention in Adults with Prediabetes: Results of a Pilot Study (Preprint)

2019 ◽  
Author(s):  
Nestoras Mathioudakis ◽  
Estelle Everett ◽  
Noora Al-Hajri ◽  
Mohammed Abusamaan ◽  
Clare Lee ◽  
...  
Keyword(s):  
Pilot Study ◽  
Intervention Program ◽  
Area Deprivation ◽  
Inverse Association ◽  
Small Pilot Study ◽  
Mhealth Intervention ◽  
Increased Risk ◽  
Metabolic Equivalent Of Task ◽  
Mobile Intervention ◽  
The Difference

BACKGROUND About one-third of American adults have prediabetes and are at increased risk of type 2 diabetes. Mobile health (mHealth) technologies provide a scalable approach to diabetes prevention by encouraging physical activity (PA), weight loss, and adherence to a healthy diet in large numbers of patients. OBJECTIVE To identify factors associated with improvements in PA and glycated hemoglobin (A1c) measures among prediabetic adults who received a mobile intervention program (smartphone app in combination with a digital body weight scale) in a previously completed pilot study. METHODS We conducted a post hoc analysis of a 3-month prospective, single-arm, observational study using the Sweetch™ mHealth intervention among adults with prediabetes. Change in A1C was calculated as the difference between the 3-month and baseline A1C measurements and was categorized as decrease vs. no decrease. PA was evaluated using the total minutes and metabolic equivalent of task (MET)-hours per week. Change in MET-hours/week was categorized as increase vs. no increase. Age, sex, race, education, employment status, area deprivation, smartphone usage attitudes, and PA stage of change were compared between groups by outcomes of change in A1C and change in MET-hour/week. RESULTS A total of 37 adults received the final Sweetch mobile intervention and were included in the analysis. 62% were female and 81% were white, with average age of 57 years. The median [IQR] baseline A1C was 6.0% [5.8, 6.2]. A1C measure at 3-month was decreased in 24 (65%) participants when compared to baseline A1C. There was an inverse association between average MET-hours per week and change in A1C. Among participants whose A1C decreased vs. did not decrease, the MET-hours per week in last 2 weeks of study was 18.7 (8.4) and 15.0 (7.1), respectively (P=0.19), and the change in MET-hours per week was 2.1 (7.1) and 4.1(6.1), respectively (P=0.41). There were otherwise no statistically significant differences in participant factors by A1C and PA outcomes. CONCLUSIONS In this small pilot study, Sweetch mHealth intervention achieved comparable A1C response prediabetic adults with different individual, sociodemographic and anthropometric characteristics. CLINICALTRIAL ClincialTrials.gov NCT02896010; https://clinicaltrials.gov/ct2/show/NCT02896010 (Archived by WebCite at http://www.webcitation.org/6xJYxrgse)

scholarly journals DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Sasaki ◽  
Margaret E. Eng ◽  
Abigail H. Lee ◽  
Alisa Kostaki ◽  
Stephen G. Matthews
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Guinea Pigs ◽  
Critical Role ◽  
Methylation Status ◽  
Peripheral Tissues ◽  
Epigenetic Biomarkers ◽  
Differentially Methylated Genes ◽  
Increased Risk ◽  
Synthetic Glucocorticoids

AbstractSynthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

341 Acute effects of seltorexant, a selective orexin-2 antagonist (JNJ- 42847922), on driving after bedtime administration

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A136-A136
Author(s):  
S Brooks ◽  
R G J A Zuiker ◽  
G E Jacobs ◽  
I Kezic ◽  
A Savitz ◽  
...  
Keyword(s):  
Postural Stability ◽  
Driving Simulator ◽  
Motor Vehicle ◽  
Subjective Effects ◽  
Driving Ability ◽  
Post Dose ◽  
Double Blind ◽  
Increased Risk ◽  
Subjective Sleepiness ◽  
The Difference

Abstract Introduction Seltorexant (JNJ-42847922), a potent and selective antagonist of the human orexin-2 receptor, is being developed for the treatment of major depressive disorder. Seltorexant also has sleep-promoting properties. Investigating the effects of sleep-promoting medications on driving is important because some of these agents (e.g. GABAA receptor agonists) may be associated with increased risk of motor vehicle accidents. We evaluated the effect of seltorexant on driving after forced awakening at night, using a validated driving simulator. Methods This double-blind, placebo and active-controlled, randomized, 3-way cross-over study was conducted in 18 male and 18 female healthy subjects. All subjects received seltorexant 40 mg, zolpidem 10 mg, or placebo 15 minutes before bedtime. Eighteen subjects were awakened at 2- and 6-hours post-dose, and the other 18 at 4- and 8-hours post-dose. At those timepoints, pharmacokinetics, objective (standard deviation of the lateral position [SDLP]) and subjective effects (using Perceived Driving Quality and Effort Scales) on driving ability, postural stability and subjective sleepiness were assessed. Results For seltorexant, the SDLP difference from placebo (95% confidence interval) at 2-, 4-, 6- and 8-hours post-dose was 3.9 cm (1.26, 6.60), 0.9 cm (-1.08, 2.92), 1.1 cm (-0.42, 2.63), and 0.6 cm (-2.75, 1.55), respectively vs. 9.6 cm (6.97, 12.38), 6.6 cm (3.53, 9.60), 4.7 cm (1.46, 7.85), and 1.3cm (-1.16, 3.80), respectively for zolpidem. The difference from placebo was significant at 2-hours after taking seltorexant, while the difference from placebo was significant at 2, 4 and 6-hours after zolpidem. Subjective driving quality was decreased for both drugs at all time points and driving effort was increased up to 4-hours post-dose for both medications. Subjective sleepiness showed a significant increase compared to placebo 2- and 4-hours after administration of either drug. Postural stability was decreased up to 2-hours after administration of seltorexant, and up to 4-hours after administration of zolpidem. Conclusion Compared to zolpidem, objective effects on driving performance were more transient after seltorexant administration and largely normalized by 4–6 hours post-dose. Support (if any) This work was sponsored by Janssen R&D.

scholarly journals Increased risk of preeclampsia after use of paracetamol during pregnancy – causal or coincidence?

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hetti von Hellens ◽  
Leea Keski-Nisula ◽  
Heidi Sahlman
Keyword(s):  
Third Trimester ◽  
Retrospective Case ◽  
Reverse Causation ◽  
Gestational Period ◽  
The Third ◽  
Precise Data ◽  
Increased Risk ◽  
Study Population ◽  
The Difference ◽  
Risk Of Preeclampsia

Abstract Background The maternal use of paracetamol during pregnancy has been associated with the development of preeclampsia. This study aims to clarify whether the connection is causal or whether it is due to reverse causation. Methods This study is a continuation of the retrospective case cohort study examining 2,508 pregnant women using a variety of drugs and the development of preeclampsia (1,252 women with preeclampsia and 1,256 controls). For the purposes of this study, more precise data was collected from several hospital databases of the women among this cohort who had reported taking paracetamol during pregnancy (indications, gestational period etc.); this was evaluated in association with the development of preeclampsia. Results 5.5% (100 cases and 37 controls) of all the study population (2,508) had clearly reported paracetamol use. Women with preeclampsia had used significantly more often paracetamol during pregnancy compared to controls (cases 8.0%, controls 2.9%, p < 0.001). The difference was most evident in the third trimester (after the 29th GW) and the use of paracetamol was associated with both mild and severe preeclampsia. Headache and “general pain” were the most common indications for medication among all paracetamol users. Conclusions The use of paracetamol in the third trimester of pregnancy was associated with preeclampsia. This observation indicates that association between paracetamol use and preeclampsia is probably due to reverse causation, i.e. women with preeclampsia experience more headaches due to preeclampsia symptoms since this association was not detected with the use of paracetamol in earlier stages of pregnancy.

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