Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls

BACKGROUND: This study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications. METHODS: Dutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between ‘all medication use’ and ‘chronic medication use’. PP was defined at three levels: use of ≥5 medications (PP), ≥10 medications [excessive PP (EPP)] and ≥15 medications [hyper PP (HPP)]. RESULTS: The PP prevalence for all medication use was 87, 93 and 95% in CKD Stage G4/G5, dialysis and kidney transplant patients, respectively. For chronic medication use, this was 66, 70 and 75%, respectively. PP and comorbidity prevalence were higher in patients than in controls. EPP was 42 times more common in young CKD Stage G4/G5 patients (ages 20–44 years) than in controls, while this ratio was 3.8 in patients ≥75 years. Older age (64–75 and ≥75 years) was a risk factor for PP in CKD Stage G4/G5 and kidney transplant patients. Dialysis patients ≥75 years of age had a lower risk of PP compared with their younger counterparts. Additional risk factors in all patients were low SES, diabetes mellitus, vascular disease, hospitalization and an emergency room visit. The most commonly dispensed medications were proton pump inhibitors (PPIs) and statins. CONCLUSIONS: CKD Stage G4/G5 patients and patients on KRT have a high medication burden, far beyond that of individuals from the general population, as a result of their kidney disease and a large burden of comorbidities. A critical approach to medication prescription in general, and of specific medications like PPIs and statins (in the dialysis population), could be a first step towards more appropriate medication use

Chronic prescription of antidepressant medication in patients with chronic kidney disease with and without kidney replacement therapy compared with matched controls in the Dutch general population

BACKGROUND: Chronic kidney disease (CKD) is associated with a higher prevalence of depression, neuropathic pain and insomnia. These conditions are often treated pharmaceutically. In this study we aimed to determine the prevalence of chronic antidepressant use among CKD patients with and without kidney replacement therapy (KRT). METHODS: By using the Dutch health claims database, we were able to determine the prevalence, type and dosage of chronic antidepressant prescriptions in patients with CKD Stage G4/G5 without KRT (n = 14 905), patients on dialysis (n = 3872) and patients living on a functioning graft (n = 8796) and compared these to age-, sex- and socio-economic status (SES)-matched controls from the general population. RESULTS: Our data show that the prevalence of chronic antidepressant prescription is 5.6%, 5.3% and 4.2% in CKD Stage G4/G5, dialysis and kidney transplant patients, respectively, which is significantly higher than in matched controls. Although our data revealed more prescriptions in female patients and in the age category 45–64 years, our data did not show any association between antidepressant prescriptions and SES. Selective serotonin reuptake inhibitors were the most prescribed drugs in all patient groups and controls. Tricyclic antidepressants were more often used in patients compared with controls. CONCLUSION: This nationwide analysis revealed that chronic antidepressant prescription in the Netherlands is higher in CKD patients with and without KRT than in controls, higher in middle-aged patients and women, unrelated to socio-economic status and lower than chronic use reported in other countries

Evidence for Thermal Equilibration in Multifragmentation Reactions probed with Bremsstrahlung Photons

The production of nuclear bremsstrahlung photons (E$_{\gamma}>$ 30 MeV) has been studied in inclusive and exclusive measurements in four heavy-ion reactions at 60{\it A} MeV. The measured photon spectra, angular distributions and multiplicities indicate that a significant part of the hard-photons are emitted in secondary nucleon-nucleon collisions from a thermally equilibrated system. The observation of the thermal component in multi-fragment $^{36}$Ar+$^{197}$Au reactions suggests that the breakup of the thermalized source produced in this system occurs on a rather long time-scale.Comment: Revised version, accepted for publication in Physical Review Letters. 4 pages, 4 fig

Alpha-decay branching ratios of near-threshold states in 19Ne and the astrophysical rate of 15O(alpha,gamma)19Ne

The 15O(alpha,gamma)19Ne reaction is one of two routes for breakout from the hot CNO cycles into the rp process in accreting neutron stars. Its astrophysical rate depends critically on the decay properties of excited states in 19Ne lying just above the 15O + alpha threshold. We have measured the alpha-decay branching ratios for these states using the p(21Ne,t)19Ne reaction at 43 MeV/u. Combining our measurements with previous determinations of the radiative widths of these states, we conclude that no significant breakout from the hot CNO cycle into the rp process in novae is possible via 15O(alpha,gamma)19Ne, assuming current models accurately represent their temperature and density conditions

Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics

The correct interpretation of copy number gains in patients with developmental delay and multiple congenital anomalies is hampered by the large number of copy number variations (CNVs) encountered in healthy individuals. The variable phenotype associated with copy number gains makes interpretation even more difficult. Literature shows that inheritence, size and presence in healthy individuals are commonly used to decide whether a certain copy number gain is pathogenic, but no general consensus has been established. We aimed to develop guidelines for interpreting gains detected by array analysis using array CGH data of 300 patients analysed with the 105K Agilent oligo array in a diagnostic setting. We evaluated the guidelines in a second, independent, cohort of 300 patients. In the first 300 patients 797 gains of four or more adjacent oligonucleotides were observed. Of these, 45.4% were de novo and 54.6% were familial. In total, 94.8% of all de novo gains and 87.1% of all familial gains were concluded to be benign CNVs. Clinically relevant gains ranged from 288 to 7912 kb in size, and were significantly larger than benign gains and gains of unknown clinical relevance (P<0.001). Our study showed that a threshold of 200 kb is acceptable in a clinical setting, whereas heritability does not exclude a pathogenic nature of a gain. Evaluation of the guidelines in the second cohort of 300 patients revealed that the interpretation guidelines were clear, easy to follow and efficient

Study protocol for a randomised controlled multicentre study:the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) in patients with cervical radiculopathy

INTRODUCTION: Cervical radiculopathy due to discogenic or spondylotic stenosis of the neuroforamen can be surgically treated by an anterior discectomy with fusion (ACDF) or a posterior foraminotomy (FOR). Most surgeons prefer ACDF, although there are indications that FOR is as effective as ACDF, has a lower complication rate and is less expensive. A head-to-head comparison of the 2 surgical techniques in a randomised controlled trial has not yet been performed. The study objectives of the Foraminotomy ACDF Cost-Effectiveness Trial (FACET) study are to compare clinical outcomes, complication rates and cost-effectiveness of FOR to ACDF. METHODS AND ANALYSIS: The FACET study is a prospective randomised controlled trial conducted in 7 medical centres in the Netherlands. The follow-up period is 2 years. The main inclusion criterion is a radiculopathy of the C4, C5, C6 or C7 nerve root, due to a single-level isolated cervical foraminal stenosis caused by a soft disc and/or osteophytic component, requiring operative decompression. A sample size of 308 patients is required to test the hypothesis of clinical non-inferiority of FOR versus ACDF. Primary outcomes are: 'operative success', the measured decrease in radiculopathy assessed by the visual analogue scale and 'patient success', assessed by the modified Odom's criteria. Secondary outcomes are: Work Ability Index (single-item WAI), quality of life (EuroQol 5 Dimensions 5 level Survey, EQ-5D-5L), Neck Disability Index (NDI) and complications. An economic evaluation will assess cost-effectiveness. In addition, a budget impact analysis will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Ethics Committee of the University Medical Center Groningen. Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. TRIAL REGISTRATION NUMBER: NTR5536, pre-results

Jacobsen syndrome

Jacobsen syndrome is a MCA/MR contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. To date, over 200 cases have been reported. The prevalence has been estimated at 1/100,000 births, with a female/male ratio 2:1. The most common clinical features include pre- and postnatal physical growth retardation, psychomotor retardation, and characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, downslanting palpebral fissures, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small ears, low set posteriorly rotated ears). Abnormal platelet function, thrombocytopenia or pancytopenia are usually present at birth. Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Ocular, hearing, immunological and hormonal problems may be also present. The deletion size ranges from ~7 to 20 Mb, with the proximal breakpoint within or telomeric to subband 11q23.3 and the deletion extending usually to the telomere. The deletion is de novo in 85% of reported cases, and in 15% of cases it results from an unbalanced segregation of a familial balanced translocation or from other chromosome rearrangements. In a minority of cases the breakpoint is at the FRA11B fragile site. Diagnosis is based on clinical findings (intellectual deficit, facial dysmorphic features and thrombocytopenia) and confirmed by cytogenetics analysis. Differential diagnoses include Turner and Noonan syndromes, and acquired thrombocytopenia due to sepsis. Prenatal diagnosis of 11q deletion is possible by amniocentesis or chorionic villus sampling and cytogenetic analysis. Management is multi-disciplinary and requires evaluation by general pediatrician, pediatric cardiologist, neurologist, ophthalmologist. Auditory tests, blood tests, endocrine and immunological assessment and follow-up should be offered to all patients. Cardiac malformations can be very severe and require heart surgery in the neonatal period. Newborns with Jacobsen syndrome may have difficulties in feeding and tube feeding may be necessary. Special attention should be devoted due to hematological problems. About 20% of children die during the first two years of life, most commonly related to complications from congenital heart disease, and less commonly from bleeding. For patients who survive the neonatal period and infancy, the life expectancy remains unknown