Insights into the health status of the general population living near an electroplating industry zone: metal elevations and renal impairment.

A cross-sectional study was conducted in 2016 in Zhejiang Province, China, to evaluate the body burdens of metals and metalloids associated with renal dysfunction in populations living near electroplating industries. We recruited 236 subjects and performed physical examinations, determined the blood and urinary levels of arsenic (As), cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), antimony (Sb), and selenium (Se) by an inductively coupled plasma mass spectrometer (ICP-MS), and measured three renal impairment biomarkers, namely nacetyl-ß-D-glucosaminidase (NAG), retinol-binding protein (RBP), and ß2-microglobulin (BMG). The proportion of abnormal nasal symptoms in the exposure group (10.1%) was much higher than in the control group (0; p < 0.05). The blood and urinary levels of As, Cd, and Se in the exposure group were significantly higher than those in the control group (p < 0.05). The blood levels of Mn and Pb, as well as the urinary levels of Cr and Ni, were significantly higher in the exposure group than in the control group (p < 0.05). The exposure group demonstrated higher levels of NAG, RBP, and BMG than the control group (0.51 vs. 0.14 mg/g creatinine, 12.79 vs. 9.26 IU/g creatinine, and 1.39 vs. 0.78 mg/g creatinine, respectively; p < 0.05). Urinary BMG was positively correlated with urinary Cd levels (r = 0.223, p < 0.05), while urinary RBP was correlated with blood Cd levels (r = 0.151, p < 0.05) and urinary Cd, Cr, Ni, and Se levels (r = 0.220, 0.303, 0.162, and 0.306, respectively; p < 0.05). In conclusion, our study indicated that a population living in the vicinity of electroplating industries had high body burdens of certain metals and metalloids associated with non-negligible renal dysfunction.

Efficacy of Ninjin'yoeito in treating severe coronavirus disease 2019 in patients in an intensive care unit.

Coronavirus Disease-2019 (COVID-19), an infectious disease associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global emergency with high mortality. There are few effective treatments, and many severe patients are treated in an intensive care unit (ICU). The purpose of this study was to evaluate whether the Japanese Kampo medicine ninjin'yoeito (NYT) is effective in treating ICU patients with COVID-19. Nine patients with confirmed SARS-CoV-2 infection admitted to the ICU were enrolled in this study. All patients underwent respiratory management with invasive mechanical ventilation (IMV) and enteral nutrition. Four patients received NYT (7.5 g daily) from an elemental diet tube. We retrospectively examined the prognostic nutritional index (PNI), length of IMV, length of ICU stay, length of hospital stay, rate of tracheostomy, and mortality rate. The median age of the enrolled participants was 60.0 years (4 men and 5 women). The median body mass index was 27.6. The most common comorbidity was diabetes (4 patients, 44%), followed by hypertension (3 patients, 33%) and chronic kidney disease (2 patients, 22%). The median length of IMV, ICU stay, and hospital stay were all shorter in the NYT group than in the non-NYT group (IMV; 4.0 days vs 14.3 days, ICU; 5.3 days vs 14.5 days, hospital stay; 19.9 days vs 28.2 days). In the NYT and non-NYT groups, the median PNI at admission was 29.0 and 31.2, respectively. One week after admission, the PNI was 30.7 in the NYT group and 24.4 in non-NYT group. PNI was significantly (p = 0.032) increased in the NYT group (+13.6%) than in the non-NYT group (-22.0%). The Japanese Kampo medicine NYT might be useful for treating patients with severe COVID-19 in ICU. This study was conducted in a small number of cases, and further large clinical trials are necessary.

Cardiovascular and kidney outcomes of spironolactone or eplerenone in combination with ACEI/ARBs in patients with diabetic kidney disease.

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) when combined with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may provide additional benefits of cardiovascular and kidney disease risk reduction in patients with diabetic kidney disease (DKD) and hypertension. We evaluated the effectiveness of combination therapy (MRAs, either spironolactone or eplerenone, plus ACEI/ARB) compared with monotherapy (ACEI/ARB only) in patients with DKD and hypertension. METHODS: Retrospective cohort study was performed in patients (age ≥ 18 years) with hypertension, diabetes, and albuminuria between 2008 and 2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone was evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome. RESULTS: We identified 1282 patients who received MRAs with ACEI/ARBs and 5484 patients who received ACEI/ARBs alone. Median exposure time for combination therapy was 126 days. The rates per 100 person-years of cardiovascular, kidney, or all-cause mortality outcomes were 12.2 and 9.2 for combination therapy and monotherapy, respectively (hazard ratios = 1.24, 95% Confidence Interval (CI):0.94, 1.63). Patients receiving combination therapy had greater reduction in urine albumin-to-creatinine ratio compared with monotherapy (Mean reduction: 823 and 585 mg/g; p < 0.001, respectively). Hyperkalemia was more frequent in combination therapy versus monotherapy (22.3 vs. 10.9 per 100 person-years for combination and monotherapy, respectively; hazard ratios = 1.78, 95%CI: 1.42, 2.24). CONCLUSIONS: Among patients with DKD and hypertension, the short-term use of MRAs, either spironolactone or eplerenone, in combination with ACEI/ARBs, was not associated with lower risk of cardiovascular or kidney outcomes compared with ACEI/ARB monotherapy. The risk of hyperkalemia and the short duration of combination therapy may suggest a real-world clinical challenge for MRA with ACEI/ARB combination therapy.

Nephrotoxicity of Herbal Products in Europe-A Review of an Underestimated Problem.

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

Electronic health record analysis identifies kidney disease as the leading risk factor for hospitalization in confirmed COVID-19 patients.

BACKGROUND: Empirical data on conditions that increase risk of coronavirus disease 2019 (COVID-19) progression are needed to identify high risk individuals. We performed a comprehensive quantitative assessment of pre-existing clinical phenotypes associated with COVID-19-related hospitalization. METHODS: Phenome-wide association study (PheWAS) of SARS-CoV-2-positive patients from an integrated health system (Geisinger) with system-level outpatient/inpatient COVID-19 testing capacity and retrospective electronic health record (EHR) data to assess pre-COVID-19 pandemic clinical phenotypes associated with hospital admission (hospitalization). RESULTS: Of 12,971 individuals tested for SARS-CoV-2 with sufficient pre-COVID-19 pandemic EHR data at Geisinger, 1604 were SARS-CoV-2 positive and 354 required hospitalization. We identified 21 clinical phenotypes in 5 disease categories meeting phenome-wide significance (P<1.60x10-4), including: six kidney phenotypes, e.g. end stage renal disease or stage 5 CKD (OR = 11.07, p = 1.96x10-8), six cardiovascular phenotypes, e.g. congestive heart failure (OR = 3.8, p = 3.24x10-5), five respiratory phenotypes, e.g. chronic airway obstruction (OR = 2.54, p = 3.71x10-5), and three metabolic phenotypes, e.g. type 2 diabetes (OR = 1.80, p = 7.51x10-5). Additional analyses defining CKD based on estimated glomerular filtration rate, confirmed high risk of hospitalization associated with pre-existing stage 4 CKD (OR 2.90, 95% CI: 1.47, 5.74), stage 5 CKD/dialysis (OR 8.83, 95% CI: 2.76, 28.27), and kidney transplant (OR 14.98, 95% CI: 2.77, 80.8) but not stage 3 CKD (OR 1.03, 95% CI: 0.71, 1.48). CONCLUSIONS: This study provides quantitative estimates of the contribution of pre-existing clinical phenotypes to COVID-19 hospitalization and highlights kidney disorders as the strongest factors associated with hospitalization in an integrated US healthcare system.

Highly frequent utilization of outpatient services in a national health insurance system - analysis of associated factors and underlying co-morbidity.

OBJECTIVE: We aimed to identify associated factors of highly frequent use of outpatient services and explore how they were impacted to provide policy references for government and medical institutes in their efforts to seek provision of reasonable medical services, continuous care and integrated outpatient services. METHODS: The Taiwanese national health insurance database was used and 661,125 patients were identified in 2009. The patients with ≥100 internal medicine outpatient (IMO) visits were defined as the highly frequent group and they were matched at a ratio of 1:4 with patients of 1-99 IMO visits based on demographic characteristics. Multivariate logistic regression was used to estimate adjusted odds ratios with 95% confidence intervals. RESULTS: Among 1 million patients in the outpatient department, 0.05% had at least 100 visits. These patients with highly frequent IMO visits had significantly higher rates of emergency department (ED) visits, hospitalization, psychiatric disorders and possession of a catastrophic illness card as well as a significantly lower level of continuity of care index (COCI). Multivariate analysis showed that ED visits (adjusted OR [AOR] = 1.63), psychiatric disorders (AOR = 7.13), low COCI (AOR = 1.69), and several comorbidities including peripheral vascular diseases (AOR = 4.33), dementia (AOR = 0.04), chronic pulmonary disease (AOR = 3.02), peptic ulcer diseases (AOR = 3.70), diabetes mellitus (AOR = 3.45) and renal disease (AOR = 2.43) were significant associated factors. CONCLUSIONS: To rationalize use and distribution of medical resources, we suggest proper regular care and health education to those with mental disabilities and multiple chronic conditions, which may not only improve the situation of highly frequent hospital visits but also effectively control incidence of acute conditions and reduce their ED visits. In addition, improving the continuity of care is vital, and the best way to do this is to promote family medicine as the primary form of healthcare.

Treatment-resistant hypertension in the hemodialysis population: a 44-h ambulatory blood pressure monitoring-based study.

BACKGROUND: Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant hypertension (TRH), is considered as a common problem in the hemodialysis population. However, to date there is no estimate of the prevalence of this condition in hemodialysis patients. METHOD: We estimated the prevalence of TRH by 44-h ambulatory BP monitoring (ABPM) in 506 hemodialysis patients in 10 renal units in Europe included in the registry of the European Renal and Cardiovascular Medicine (EURECAm,), a working group of the European Association, European Dialysis and Transplantation Association (ERA EDTA). In a sub-group of 114 patients, we tested the relationship between fluid overload (Body Composition monitor) and TRH. RESULTS: The prevalence of hypertension with 44-h ABPM criteria was estimated at 85.6% (434 out of 506 patients). Of these, 296 (58%) patients were classified as uncontrolled hypertensive patients by 44-h ABPM criteria (≥130/80 mmHg). Two hundred and thirteen patients had uncontrolled hypertension while on treatment with less than three drugs and 210 patients were normotensive while on drug therapy (n = 138) or off drug treatment (n = 72). The prevalence of TRH was 24% (93 among 386 treated hypertensive patients). The prevalence of predialysis fluid overload was 33% among TRH patients, 34% in uncontrolled hypertensive patients and 26% in normotensive patients. The vast majority (67%) of hemodialysis patients with TRH had no fluid overload. CONCLUSION: TRH occurs in about one in four treated hypertensive patients on hemodialysis. Fluid overload per se only in part explains TRH and the 67% of these patients show no fluid overload.

Effects of bodybuilding supplements on the kidney: A population-based incidence study of biopsy pathology and clinical characteristics among middle eastern men.

BACKGROUND: The incidence of kidney diseases among bodybuilders is unknown. METHODS: Between January 2011 and December 2019, the Iraqi Kurdistan 15 to 39 year old male population averaged 1,100,000 with approximately 56,000 total participants and 25,000 regular participants (those training more than 1 year). Annual age specific incidence rates (ASIR) with (95% confidence intervals) per 100,000 bodybuilders were compared with the general age-matched male population. RESULTS: Fifteen male participants had kidney biopsies. Among regular participants, diagnoses were: focal segmental glomerulosclerosis (FSGS), 2; membranous glomerulonephritis (MGN), 2; post-infectious glomeruonephritis (PIGN), 1; tubulointerstitial nephritis (TIN), 1; and nephrocalcinosis, 2. Acute tubular necrosis (ATN) was diagnosed in 5 regular participants and 2 participants training less than 1 year. Among regular participants, anabolic steroid use was self-reported in 26% and veterinary grade vitamin D injections in 2.6%. ASIR for FSGS, MGN, PIGN, and TIN among regular participants was not statistically different than the general population. ASIR of FSGS adjusted for anabolic steroid use was 3.4 (- 1.3 to 8.1), a rate overlapping with FSGS in the general population at 2.0 (1.2 to 2.8). ATN presented as exertional muscle injury with myoglobinuria among new participants. Nevertheless, ASIR for ATN among total participants at 1.4 (0.4 to 2.4) was not significantly different than for the general population at 0.3 (0.1 to 0.5). Nephrocalcinosis was only diagnosed among bodybuilders at a 9-year cumulative rate of one per 314 vitamin D injectors. CONCLUSIONS: Kidney disease rates among bodybuilders were not significantly different than for the general population, except for nephrocalcinosis that was caused by injections of veterinary grade vitamin D compounds.

Calcium-Alkali Syndrome Associated with Hypoparathyroidism Following Total Thyroidectomy.

BACKGROUND: Patients with permanent postsurgical hypoparathyroidism, a complication of total thyroidectomy, often require high calcium supplementation with vitamin D to maintain serum calcium levels. The epidemiology of calcium-alkali syndrome (CAS) in patients with hypoparathyroidism after total thyroidectomy remains unclear. This study aimed to investigate the incidence of hypercalcemia, renal impairment, metabolic alkalosis, and CAS in patients treated for presumed hypoparathyroidism after total thyroidectomy. METHODS: Twenty-seven patients with neck cancers who underwent total thyroidectomy without parathyroid autotransplantation between January 2010 and October 2013 at our hospital were consecutively included. All patients received calcium lactate and alfacalcidol for postsurgical hypocalcemia. We defined hypercalcemia as a corrected serum calcium level (cCa) ≥10.5 mg/dL, metabolic alkalosis as a difference in serum sodium and serum chloride ([sNa-sCl]) ≥39 mEq/L, and renal impairment as a ≥50% increase in serum creatine and/or ≥35% decrease in estimated glomerular filtration rate (eGFR) compared to baseline. RESULTS: cCa peaked (11.1 ± 1.5 mg/dL) at a median of 326 days (interquartile range 78-869) after surgery. At peak cCa, [sNa-sCl] was significantly higher (p < 0.01), and eGFR was significantly lower (p < 0.01) than that at baseline. Fifteen patients (55.6%) had hypercalcemia, 19 (70.3%) had alkalosis, 12 (44.4%) had renal impairment, and 9 (33.3%) had CAS. Patients with CAS (mean age 67.1 ± 10.8 years) were older than those without CAS (56.7 ± 13.6 years, p = 0.06). The mean dose of alfacalcidol in the CAS group (3.1 ± 1.2 µg/day) was significantly larger than that in the non-CAS group (2.1 ± 1.0 µg/day, p = 0.03). CONCLUSIONS: This retrospective study reveals the high incidence of CAS in patients with hypoparathyroidism after total thyroidectomy. Furthermore, these findings suggest that the serum calcium level, acid-base balance, and renal function should be closely monitored in patients with postsurgical hypoparathyroidism who receive large doses of active vitamin D.

Epidemiological study of kidney health in an area with high levels of soil cadmium and selenium: Does selenium protect against cadmium-induced kidney injury?

Chronic exposure to cadmium (Cd) can cause renal dysfunction. Studies of animals, cell cultures, and plants have found that selenium (Se) can effectively alleviate the hazard generated by Cd, but there has been little study of this in general human populations. This study recruited 313 subjects from China's Hubei Province, including 160 living in areas with high soil Cd and Se (exposure group) and 153 living in clean areas (control group). The levels of the following were detected: Cd and Se in blood (B-Cd and B-Se), urine (U-Cd and U-Se), and hair (H-Cd and H-Se); N-acetyl-ß-D-glucosaminidase (U-NAG), ß2-microglobulin (U-ß2-MG), and albumin (U-ALB) in urine; and malondialdehyde (S-MDA), superoxide dismutase (S-SOD), and glutathione peroxidase (S-GSH-Px) in serum. In addition, the interactions between Cd and Se were assessed. The median levels of B-Cd, B-Se, U-Cd, U-Se, H-Cd, H-Se, S-MDA, and S-GSH-Px of exposure group (2.60 ng/mL, 238.90 ng/mL, 3.13 µg/g Cr, 45.43 µg/g Cr, 0.06 µg/g, 0.70 µg/g, 5.22 nmol/mL, and 308.89 U, respectively) were significantly higher than of controls (0.95 ng/mL, 130.50 ng/mL, 1.08 µg/g Cr, 30.51 µg/g Cr, 0.04 µg/g, 0.49 µg/g, 4.71 nmol/mL, and 267.54 U, respectively), but there were no significant differences in U-NAG, U-ß2-MG, U-ALB, or S-SOD between the two groups. U-NAG levels were significantly negatively associated with the interaction between Cd and Se (B: -0.511, 95% CI: -0.886, -0.136). Additionally, changes in the direction of the estimated regression coefficient in the low and high H-Se groups were observed for U-Cd and S-MDA (from 0.018 to -0.090), U-Cd and S-GSH-Px (from -0.039 to 0.101). This study found that populations living in areas with high levels of soil Cd and Se did not show greater Cd-induced renal tubular and glomerular injuries than the control population, which could attribute to the protective effects of Se. The protective effects may be related to the peculiar function of Se that Se can combine with free Cd to activate the antioxidant enzyme system.

Changes in vascular calcification and bone mineral density in calcium supplement users from the Canadian Multi-center Osteoporosis Study (CaMOS).

BACKGROUND AND AIMS: Calcium supplements have been associated with increased cardiovascular events. This study investigates the relationship between calcium supplement use and the 5 year progression of abdominal aorta calcification (AAC) in participants from one center of the Canadian Multi-Centre Osteoporosis Study (CaMOS). METHODS: Participants (n = 296; 217 women and 79 men) had lateral spine X-rays and DEXA bone mineral density (BMD) scans (femoral neck, lumbar spine and total hip) taken at two time points within a 5 year interval. AAC was assessed using the Framingham Method. Calcium supplement use was assessed by a facilitated health history questionnaire and medication inventory. RESULTS: AAC significantly increased over 5 years, AAC progression was significantly greater in calcium supplement users, as compared to non-users, overall and in females. The amount of calcium was positively correlated to AAC progression. A multi-variable linear regression model was generated for women only, as there were not enough men for multivariable modelling. Calcium supplement use and amount remained significantly associated with AAC progression after adjustment for age, hypertension, diabetes and smoking history. Change in AAC score was not associated with change in BMD T-Score. In univariate analyses of males, calcium supplement use was associated with a significantly greater BMD loss at the lumbar spine, hip, and femoral neck. CONCLUSIONS: Older female calcium supplement users had significantly higher AAC progression over 5 years, but did not have any significant BMD preservation. These results suggest that vascular calcification may contribute to the cardiovascular events observed in calcium supplement users.

Preoperative Vitamin D Concentration and Cardiac, Renal, and Infectious Morbidity after Noncardiac Surgery.

BACKGROUND: Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery. METHODS: We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications. RESULTS: A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio [95% CI]: 0.93 [0.85, 1.01] per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio [95% CI]: 0.94 [0.90, 0.98] per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate [95% CI]: 0.29 [0.11, 0.48] ml min 1.73 m per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004). CONCLUSIONS: Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.

Risk factors and clinical characteristics of tacrolimus-induced acute nephrotoxicity in children with nephrotic syndrome: a retrospective case-control study.

PURPOSE: Acute nephrotoxicity is a common adverse reaction of tacrolimus therapy; however, its risk factors in pediatric nephrotic syndrome (NS) remain to be evaluated. The objective of this study was to investigate the risk factors and characteristics of tacrolimus-induced acute nephrotoxicity in children with NS. METHODS: Past records of children with NS admitted to our hospital from 2014 to 2018 were reviewed. The incidence and characteristics of nephrotoxicity were analyzed. Multivariate logistic regression analysis was used to identify the risk factors of nephrotoxicity. A clinically applicable risk score was developed and validated. RESULTS: Tacrolimus-induced nephrotoxicity occurred in 25 of 129 patients, 13 patients were grade 1, and the renal function was recovered in 22 patients. Multivariate regression analysis showed that the maximum trough concentrations (C12h) of tacrolimus (OR, 1.48; 95% CI, 1.16 to 1.88; P < 0.001), huaiqihuang granules (OR, 0.095; 95% CI, 0.014 to 0.66; P = 0.017), and diarrhea (OR, 22.00; 95% CI, 1.58 to 306.92; P = 0.022) were independently associated with tacrolimus-induced nephrotoxicity. The maximum C12h were significantly higher in patients with nephrotoxicity (median 9.0 ng/ml) and the cut-off value for acute nephrotoxicity was 6.5 ng/ml. The area under the receiver operating characteristic curve was 0.821 for the proposed model based on the observations used to create the model and 0.817 obtained from k-fold cross-validation. CONCLUSIONS: High trough concentration of tacrolimus and diarrhea can potentiate the risk of tacrolimus-induced acute nephrotoxicity in children with NS, while huaiqihuang granules can protect this condition.

Discontinuation of non-Vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation: a population-based cohort study using primary care data from The Health Improvement Network in the UK.

OBJECTIVE: To determine discontinuation rates, patterns of use and predictors of discontinuation of non-vitamin K antagonist oral anticoagulants (NOACs) among patients with non-valvular atrial fibrillation (NVAF) in the first year of therapy. DESIGN: Population-based cohort study. SETTING: UK primary care. POPULATION: 11 481 patients with NVAF and a first prescription (index date) for apixaban, dabigatran or rivaroxaban (January 2012 to December 2016) with at least 1 year of follow-up and at least one further NOAC prescription in the year following the index date were identified. 1 year rates and patterns of discontinuation were described. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcome measures were the percentage of patients who, in the first year from starting NOAC therapy, discontinued with their oral anticoagulant (OAC) therapy (discontinuation was defined as a gap in OAC therapy of >30 days); switched OAC within 30 days; discontinued and reinitiated OAC therapy. Predictors of discontinuation were also evaluated. RESULTS: 1 year discontinuation rates according to the index NOAC were 26.1% for apixaban, 40.0% for dabigatran and 29.6% for rivaroxaban. Reinitiation rates were 18.1% for apixaban, 21.7% for dabigatran and 17.3% for rivaroxaban, and switching rates were 2.8% for apixaban, 8.8% for dabigatran and 4.9% for rivaroxaban. More than 93% of reinitiations were with the index NOAC. Patients starting on dabigatran were more likely to switch OAC therapy than those starting on apixaban; ORs 4.28 (95% CI 3.24 to 5.65) for dabigatran and 1.89 (95% CI 1.49 to 2.39) for rivaroxaban. Severely reduced renal function was a predictor of any discontinuation, OR 1.77 (95% CI 1.28 to 2.44). CONCLUSION: While the majority of patients with NVAF in the UK initiating NOAC treatment received continuous therapy in the first year of treatment, a substantial proportion of patients experienced gaps in treatment leaving them less protected against thromboembolism during these periods.

Prevalence and factors associated with renal dysfunction in children admitted to two hospitals in northwestern Tanzania.

BACKGROUND: It is evident that renal dysfunction (RD) is associated with unique infectious and non-infectious causes in African children. However, little data exists about the prevalence and factors associated with RD in children admitted to African hospitals. METHODS: In this cross-sectional study, we enrolled all children admitted to pediatric wards of Bugando Medical Centre (BMC) and Sekou-Toure Regional Referral hospital (SRRH) during a 6 month time period. Socio-demographical, clinical and laboratory data were collected using a structured questionnaire. Estimated glomerular filtration rate (eGFR) was calculated using modified Schwartz equation and those with < 60 ml/min/1.73m2were considered to have RD. Data analysis was done using STATA version 13 and considered significant when p-value was < 0.05. RESULTS: A total of 513 children were enrolled, of which 297 (57.9%) were males. Median age of children with and without RD was 34 months (27-60) and 46.5 (29-72) respectively. Prevalence of RD was 16.2%. Factors associated with RD were herbal medication use (p = 0.007), history of sore throat or skin infection (p = 0.024), sickle cell disease (SCD) (p = 0.006), dehydration (p = 0.001), malaria (p = 0.01) and proteinuria (p = < 0.001). CONCLUSIONS: High prevalence of RD was observed among children admitted to referral hospitals in Mwanza. Screening for RD should be performed on admitted children, particularly those with history of herbal medication use, sore throat/skin infection, SCD, dehydration and malaria. Where creatinine measurement is not possible, screening for proteinuria is a reasonable alternative.

Cost-effectiveness of rivaroxaban versus warfarin for treatment of nonvalvular atrial fibrillation in patients with worsening renal function.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) is highly prevalent and increases the risks of cardiovascular events. In a recent subgroup analysis, treatment response was shown to vary for patients exhibiting worsening renal function (WRF) on-treatment. It is important to understand the cost-effectiveness of novel oral anticoagulant (NOAC) use in this population. METHODS: A cost-effectiveness analysis (CEA) was conducted using a Markov model to determine whether NOAC rivaroxaban treatment is cost-effective relative to warfarin in NVAF patients with on-treatment WRF. Input parameters were sourced from clinical literature including a multicenter clinical trial and subgroup analysis. We studied elderly US male patients at increased risk for stroke (CHADS2 score ≥ 2) undergoing treatment for NVAF and exhibiting WRF. Main outcome measures included total healthcare costs in 2017 US dollars (societal perspective), total quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net monetary benefits (INMB) per-patient. RESULTS: The remaining lifetime use of rivaroxaban is associated with 5.69 QALYs at a cost of $66,075 per patient, while warfarin produced 5.22 QALYs with costs of $78,504 per patient. At a willingness-to-pay (WTP) of $150,000 per QALY, incremental net monetary benefits (INMB) per patient are $83,590. In our population, treatment with warfarin was dominated by rivaroxaban in 99.4% of 10,000 simulations. CONCLUSIONS: Rivaroxaban is likely a dominant treatment over warfarin in elderly US male NVAF patients exhibiting WRF, providing increased QALYs at a decreased overall cost. Application of these findings may require healthcare providers to predict which patients are likely to exhibit WRF.

Severe vitamin D deficiency is a risk factor for renal hyperfiltration.

Background: Vitamin D deficiency is associated with renal progression in chronic kidney disease. Moreover, improvement of clinical outcomes after vitamin D supplementation has been reported in the diabetic and chronic kidney disease population. Objective: We investigated the association between renal hyperfiltration (RHF) and vitamin D status in a relatively healthy population. Design: Data were retrieved from the Korean NHANES, a nationwide population-based cross-sectional study from 2008 to 2015. Overall, 33,210 subjects with normal renal function were included in the final analysis. Severe vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentration <10 ng/mL. RHF was defined as estimated glomerular filtration rate with residual in the >95th percentile after adjustment for age, sex, height, weight, and history of hypertension or diabetes. Results: The mean ± SD age of subjects was 48.1 ± 15.9 y, and the number of women was 18,779 (56.5%). Estimated glomerular filtration rate was negatively associated with serum 25-hydroxyvitamin D concentrations in multivariable linear regression analysis (ß: -0.02; 95% CI: -0.02, -0.01; P < 0.001). Furthermore, 1637 (4.9%) subjects were categorized into the RHF group, and the prevalence of RHF was significantly higher in the severe vitamin D deficiency group than in the sufficiency group (5.8% compared with 5.0%, P < 0.001). In a multivariable logistic regression model, severe vitamin D deficiency was a significant risk factor for RHF (OR: 2.41; 95% CI, 1.72, 3.43; P < 0.001). Conclusions: Severe vitamin D deficiency is significantly associated with increasing prevalence of RHF in a relatively healthy adult population.

Salivary levels of phosphorus and urea as indices of their plasma levels in nephropathic patients.

BACKGROUND: Phosphorus and urea are measurable in saliva. Measurements of saliva phosphorus (S-Pho) and saliva urea (S-Urea) could be useful because of low invasivity. Data are limited to saliva tests methodology and to correlations between plasma and saliva compositions. S-Pho and S-Urea were investigated focusing on blind duplicates, differences between collection sites, differences between collection times, freezing-thawing effects, and plasma-saliva correlations. METHODS: Tests were performed using fresh saliva collected by synthetic swap early morning after overnight fast (standard). Methodology was investigated in fifteen healthy volunteers. Plasma-saliva correlations were investigated in thirty nephropathic outpatients. RESULTS: S-Pho and S-Urea in all measurements ranged above detection limits (0.3 mmol/L). In healthy volunteers, S-Pho and S-Urea were similar in duplicates (results for S-Pho and S-Urea: % difference between samples ≤ 4.85%; R between samples ≥ .976, P < .001), in samples from different mouth sites (≤4.24%; R ≥ .887, P < .001), and in samples of different days (≤5.61%; R ≥ .606, P < .01) but, compared to standard, were substantially lower in after-breakfast samples (-28.0% and -21.3%; R ≥ .786, P < .001) and slightly lower in frozen-thawed samples (-12.4% and -5.92%; R ≥ .742, P < .001). In nephropathic patients, S-Pho was higher than but correlated with plasma phosphorus (saliva/plasma ratio 4.80; R = .686, P < .001), whereas S-Urea and plasma urea were similar and correlated with each other (saliva/plasma ratio 0.96; R = .944, P < .001). Post-dialysis changes in S-Pho and S-Urea paralleled post-dialysis changes in plasma phosphorus and urea. CONCLUSION: S-Pho and S-Urea reflect plasma phosphorus and plasma urea. Early morning fasting fresh samples are advisable because collection time and freezing-thawing affect saliva tests.

Use of oral anticoagulants in German nursing home residents: drug use patterns and predictors for treatment choice.

AIMS: Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA. METHODS: Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years. RESULTS: Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%. CONCLUSIONS: NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.