Effectiveness of using STOPP/START criteria to identify potentially inappropriate medication in people aged ≥ 65 years with chronic kidney disease: a randomized clinical trial.

PURPOSE: Polypharmacy and inappropriate prescribing are common in elderly with chronic kidney disease (CKD). This study identified potentially inappropriate prescriptions (PIPs) and potential prescribing omissions (PPOs) using the Screening Tool of Older Persons' Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) criteria in elderly with advanced CKD and determined the effect of a medication review on medication adherence and health-related quality of life (HRQoL). METHODS: The intervention consisted of a medication review using STOPP/START criteria with a recommendation to a nephrologist or similar review without a recommendation. End points were prevalence of PIP and PPO, medication adherence, and HRQoL. Group differences in outcomes were assessed using a generalized linear mixed model. The trial was registered under www.clinicaltrial.gov (ID: NCT02424786). RESULTS: We randomized 180 patients with advanced CKD (mean age 77 years, 23% female). The prevalence of PIPs and PPOs in the intervention group was 54% and 50%, respectively. The odds of PPOs were lower in the intervention than the control group (OR 0.42, 95% CI 0.19-0.92, p = 0.032), while there was no intergroup difference in the number of PIPs (OR 0.57, CI 0.27-1.20, p = 0.14). There was no difference in changes in medication adherence or HRQoL from baseline to 6 months between the groups. CONCLUSIONS: The intervention with the STOPP/START criteria identified a high prevalence of inappropriate medications in the elderly with advanced CKD and reduced the number of PPOs. However, there was no detectable impact of the intervention on medication adherence or HRQoL.

Medication regimen complexity and medication adherence in elderly patients with chronic kidney disease.

INTRODUCTION: Elderly patients with chronic kidney disease (CKD) stage 5 with or without dialysis treatment usually have concomitant comorbidities, which often result in multiple pharmacological therapies. This study aimed to identify factors associated with medication complexity and medication adherence, as well as the association between medication complexity and medication adherence, in elderly patients with CKD. METHODS: This prospective study involved elderly patients with CKD stage 5 (estimated glomerular filtration rate < 15 ml/min/1.73m2 ) recruited from three Norwegian hospitals. Most of the patients were receiving either hemodialysis or peritoneal dialysis. We used the Medication Regimen Complexity Index (MRCI) to assess the complexity of medication regimens, and the eight-item Morisky Medication Adherence Scale (MMAS-8) to assess medication adherence. Factors associated with the MRCI and MMAS-8 score were determined using either multivariable linear or ordinal logistic regression analysis. FINDINGS: In total, 157 patients aged 76 ± 7.2 years (mean ± SD) were included in the analysis. Their overall MRCI score was 22.8 ± 7.7. In multivariable linear regression analyses, female sex (P = 0.044), Charlson Comorbidity Index of 4 or 5 (P = 0.029) and using several categories of phosphate binders (P < 0.001 to 0.04) were associated with the MRCI. Moderate or high adherence (MMAS-8 score ≥ 6) was demonstrated by 83% of the patients. The multivariable logistic regression analyses found no association of medication complexity, age or other variables with medication adherence as assessed using the MMAS-8. DISCUSSION: Female sex, comorbidity and use of phosphate binders were associated with more-complex medication regimens in this population. No association was found between medication regimen complexity, phosphate binders or age and medication adherence. These findings are based on a homogeneous elderly group, and so future studies should test if they can be generalized to patients of all ages with CKD.

Potentially Inappropriate Medications in Elderly Haemodialysis Patients Using the STOPP Criteria.

BACKGROUND: Polypharmacy is commonly applied to elderly haemodialysis patients for treating terminal renal failure and multiple co-morbidities. Potentially inappropriate medications (PIMs) in multidrug regimens in geriatric populations can be identified using specially designed screening tools. OBJECTIVE: The aims of this study were to estimate the prevalence of PIMs by applying the Screening Tool of Older Persons' Prescriptions (STOPP) criteria and the Beers criteria to elderly haemodialysis patients and to assess the association of some risk factors with the presence of PIMs. METHODS: Fifty-one elderly haemodialysis patients participated; their median age was 74 (range 65-89) years, and 77 % of them were male. Demographic data, co-morbidity and medication lists were collected from the electronic medical records of the patients. The STOPP criteria were applied by two physicians independently to identify PIMs. The association of some risk factors with PIMs were assessed using Fisher's exact test. RESULTS: The patients used a median of 13 (range 7-21) medications per day. The overall prevalence of PIMs using the STOPP criteria was 63 %, and using the Beers criteria was 43 %. The most prevalent PIMs were proton-pump inhibitors. Benzodiazepines and first-generation antihistamines were related to side effects such as falls in the previous 3 months, and calcium-channel blockers were associated with chronic constipation. The number of PIMs was not significantly associated with number of medications, age, sex and co-morbidity. CONCLUSIONS: The STOPP criteria revealed a high prevalence of PIMs in a population of elderly patients receiving haemodialysis.

An increase in the number of admitted patients with exercise-induced rhabdomyolysis. / Økning i antall pasienter med treningsindusert rabdomyolyse?

BACKGROUND: Rhabdomyolysis may lead to serious complications, and treatment is both time-consuming and costly. The condition can be caused by many factors, including intense exercise. The purpose of this study was to investigate whether the number of hospitalisations due to exercise-induced rhabdomyolysis has changed in recent years. We describe the disease course in hospitalised patients, and compare disease course in individuals with exercise-induced rhabdomyolysis and rhabdomyolysis due to other causes. MATERIAL AND METHOD: The study is a systematic review of medical records from Akershus University Hospital for the years 2008 and 2011 ­ 14. All hospitalised patients with diagnostic codes M62.8, M62.9 and T79.6 and creatine kinase levels > 5 000 IU/l were included. The cause of the rhabdomyolysis was recorded in addition to patient characteristics and the results of various laboratory tests. RESULTS: Of 161 patients who were hospitalised with rhabdomyolysis during the study period, 44 cases (27 %) were classified as exercise-induced. In 2008 there were no admissions due to exercise-induced rhabdomyolysis; in 2011 and 2012 there were six and four admissions respectively, while in 2014 there were 22. This gives an estimated incidence of 0.8/100 000 in 2012 and 4.6/100 000 in 2014. Strength-training was the cause of hospitalisation in 35 patients (80 % of the exercise-induced cases). Three patients (7 % of the exercise-induced cases) had transient stage 1 kidney injury, but there were no cases with stage 2 or stage 3 injury. By comparison, 52 % of patients with rhabdomyolysis due to another cause had kidney injury, of which 28 % was stage 2 or 3. INTERPRETATION: The number of persons hospitalised with exercise-induced rhabdomyolysis has increased four-fold from 2011 to 2014, possibly due to changes in exercise habits in the population. None of the patients with exercise-induced rhabdomyolysis had serological signs of kidney injury upon hospital discharge.

Relationship between cytochrome P450 polymorphisms and prescribed medication in elderly haemodialysis patients.

BACKGROUND: Elderly patients on haemodialysis have a high prevalence of polypharmacy and are at risk of drug-related complications. More than 80 % of all prescribed drugs are metabolized by the cytochrome P450 (CYP) enzyme system. The aims of this study were to describe the prevalence of polymorphism in three CYP isoenzymes and the relationship between CYP polymorphism and prescribed drugs. METHODS: Fifty-one elderly haemodialysis patients aged ≥65 years were included. CYP-genotyping was carried out in whole blood by a real-time PCR method for detecting common variant alleles in CYP2C9, CYP2C19 and CYP2D6. The allele frequencies were calculated using the Hardy-Weinberg equation. RESULTS: The overall prevalence of CYP polymorphisms (heterozygous and homozygous) was 77 %. The prevalence of heterozygous carriers of variant alleles coding for defective CYP2D6, CYP2C9 and CYP2C19 was 64, 22 and 55 %, respectively; the prevalence of homozygous carriers was 6 % for each of the CYP2D6, CYP2C9 and CYP2C19 enzymes. The prevalence of the CYP2D6*6, CYP2D6*9 and CYP2D6*41 variant alleles did not differ (p = 0.31) from that in a European Caucasian reference population. Twenty-three patients (45 %) had at least one CYP mutation and used drugs that are metabolized by the CYP isoenzymes. Metoprolol and proton-pump inhibitors were the most commonly used drugs that could be affected by a heterozygous or homozygous mutation. CONCLUSIONS: Polymorphisms of CYP2C9, CYP2C19 and CYP2D6 are common in elderly haemodialysis patients. Many of these patients have a phenotype with altered CYP enzyme activity and could benefit from close drug monitoring or a drug switch.

Can deaths in police cells be prevented? Experience from Norway and death rates in other countries.

PURPOSE: To describe the changes in death rates and causes of deaths in Norwegian police cells during the last 2 decades. To review reports on death rates in police cells that have been published in medical journals and elsewhere, and discuss the difficulties of comparing death rates between countries. METHODS: Data on deaths in Norwegian police cells were collected retrospectively in 2002 and 2012 for two time periods: 1993-2001 (period 1) and 2003-2012 (period 2). Several databases were searched to find reports on deaths in police cells from as many countries as possible. RESULTS: The death rates in Norwegian police cells reduced significantly from 0.83 deaths per year per million inhabitants (DYM) in period 1 to 0.22 DYM in period 2 (p < 0.05). The most common cause of death in period 1 was alcohol intoxication including intracranial bleeding in persons with high blood alcohol levels, and the number declined from 16 persons in period 1 to 1 person in period 2 (p = 0.032). The median death rate in the surveyed Western countries was 0.44 DYM (range: 0.14-1.46 DYM). CONCLUSION: The number of deaths in Norwegian police cells reduced by about 75% over a period of approximately 10 years. This is probably mainly due to individuals with severe alcohol intoxication no longer being placed in police cells. However, there remain large methodology difficulties in comparing deaths rates between countries.

[Deaths in Norwegian police cells from 2003 to 2012]. / Dødsfall i norske politiarrester 2003-12.

BACKGROUND: In 2002 the Politiarrestprosjektet (a police custody project in Norway) examined deaths in Norwegian police cells during the period from 1993 to 2001. They found a total of 36 deaths, 16 of which were due either to acute alcohol poisoning or to head injuries suffered by people who had been detained for intoxication. A range of preventive measures were proposed. We have now reviewed deaths in the period from 2003 to 2012 and compared them with the first study. MATERIAL AND METHOD: We asked all police districts in Norway to submit information about deaths in police cells from 2003 up to and including 2012. Autopsy reports, police reports and reports from the Norwegian Bureau for the Investigation of Police Affairs were requested. RESULTS: Altogether 11 deaths were reported, i.e. an average of 1.1 deaths per year. The most usual cause of death with six fatalities was a combination of toxic substances. Three deaths were due to suicide, one was a natural death, and one was due to acute alcohol poisoning. There were no deaths due to head injuries related to intoxication. INTERPRETATION: The number of deaths in Norwegian police cells has declined considerably. It is primarily the number of alcohol-related deaths that has fallen.

Fabry disease in donor kidneys with 3- and 12-year follow-up after transplantation.

Enzyme replacement therapy (ERT) has been introduced for Fabry disease and has been reported to clear some renal cell types of accumulated glycolipids and to reduce the accumulation in other cell types. We describe two patients without Fabry disease who were transplanted with kidney allografts from a male donor with Fabry disease. Biopsies were taken at transplantation and after 3 years in the first case and after 12 years in the second case. Even though these Fabry kidney allografts for many years had been exposed to normal levels of circulating α-galactosidase A (α-gal-A), the amount of accumulated lysosomal deposits in the podocytes remained unchanged. Additionally, small deposits were also found in tubular cells and glomerular endothelial cells as long as 12 years after transplantation.

Impaired glucose homeostasis in renal transplant recipients receiving basiliximab.

BACKGROUND: The pathogenesis of new onset diabetes after transplantation (NODAT) is multifactorial. Suppression of regulatory T lymphocytes may have a negative impact on pancreatic beta-cells. Induction with basiliximab affects regulatory T-cell function and may therefore, theoretically, also affect glucose homeostasis in renal transplant recipients. METHODS: All kidney recipients > or =50 years of age without diabetes mellitus transplanted from 1 January 2005 to 31 December 2007 were included in a single-centre retrospective study. Immunosuppression consisted of steroids, mycophenolate mofetil and cyclosporine. Basiliximab was introduced as induction therapy 1 January 2007. An oral glucose tolerance test (OGTT) was performed in all patients 10 weeks post-transplant. RESULTS: A total of 264 patients were recruited. One hundred and thirty-four patients received basiliximab. In the basiliximab group, 51.5% developed NODAT, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) versus 36.9% in the group without induction therapy (P = 0.017). In recipients with normal OGTT, the mean fasting glucose at 10 weeks was 5.18 mmol/l (SD: 0.54) in the basiliximab group (n = 65) and 4.84 mmol/l (SD: 0.64) in the no induction group (n = 82) (P = 0.001). CONCLUSION: Use of basiliximab as induction therapy may be associated with impaired glucose homeostasis after kidney transplantation.

ECG-voltage in alcoholics and non-alcoholics with acute alcohol intoxication.

Alcohol intoxication is probably the most common intoxication worldwide, and may be lethal. The exact mechanism by which ethanol intoxication contributes to death is unknown, although ventricular tachyarrhythmias degenerating into fibrillation is a possible cause. Alcoholics have increased risk of sudden death and, possibly, higher risk than occasional drinkers. In 32 consecutive patients with alcohol intoxication Delta-voltage was the differences in voltage between values at admission (when patients had high blood alcohol levels) and at discharge (when the patients were assumed sober), and was calculated for QRS complexes and T-waves in precordial and bipolar leads. Delta-precordial-QRS-voltage was positive in 13/15 (87%, p=0.010) of the occasional drinkers and in 8/17 (47%, p=0.53) of the alcoholics (alcoholics vs. occasional drinkers: p=0.008). Both Delta-precordial-QRS-voltage and Delta-precordial-T-wave-voltage differed from the group of occasional drinkers to the group of alcoholics, after adjusting for age, sex and s-osmolality. Mean alcohol concentration was 0.29%. Conclusions have to be made with caution. Alcohol in potential lethal blood concentrations seems to increase ECG-voltages in occasional drinkers but not in alcoholics. This indicates that alcohol interferes with the ion channels that create the action potentials of the heart, but in alcoholics an adaptation process has occurred.

Predictors of anemia in patients on hemodialysis.

Even though the use of erythropoietin and intravenous iron has improved the treatment of anemia in hemodialysis patients, a considerable proportion of these patients still have anemia. The aim of this study was to identify predictors of anemia in a hemodialysis population. In a single-center hemodialysis unit, all patients were studied with blood tests and their medication recorded during a period of 22 months. Correlations with hemoglobin (Hb) were performed with a simple regression or a t test. Variables that reached 5% significance were entered in a multiple regression analysis. Selected variables were presented in quartiles with levels of Hb. Mean Hb was 11.3 g/dL, and 53 patients (40%) had Hb<11.0 g/dL. In the simple regression analysis Hb correlated positively with s-iron, CHr, s-albumin, and doses of sevelamer, and negatively with sedimentation rate (SR), ferritin, base excess, and doses of erythropoietin. In the multiple regression analysis erythrocytes SR was the only variable that remained significant. Elevated SR is the strongest predictor of anemia in hemodialysis patients receiving adequate treatment with erythropoietin and intravenous iron. Patients using high doses of sevelamer had higher Hb levels than patients using low doses.

Life situation and quality of life in young adult kidney transplant recipients.

BACKGROUND: Young adults, 18-35 years of age, may be more vulnerable to chronic diseases than other age groups. In this study we describe the life situation and lifestyle of young adult kidney transplant recipients and compare their health-related quality of life (HRQoL) with a general population sample. METHODS: Questionnaires, including items on life situation, lifestyle, and the SF-36 HRQoL questionnaire, were mailed to all 280 renal transplant recipients in Norway between 18 to 35 years of age at the time of investigation of whom 131 (47%) responded. For comparison, we used 2,360 respondents aged 18 to 35 years from a general population survey in one Norwegian county. SF-36 scores are presented with unadjusted scores and the mean difference between groups adjusted for age, sex and education using multiple linear regression analysis. RESULTS: The kidney transplant recipients reported high participation rates in cultural and sports activities, and the majority of them were satisfied with their work. A larger proportion of the transplant recipients had attained university education than the general population sample. However, 25% of the total group were not integrated in professional life. The transplant recipients scored lower than the general population on seven of the eight SF-36 scales and the two summary scales after adjusting for age, sex and education. CONCLUSIONS: The majority of young adult kidney recipients aged 18-35 years were well adapted in their family and professional life and satisfied with their current life situation. However, in aggregate they reported lower HRQoL on most scales of the SF-36 than a general population sample.

ECG changes in patients with acute ethanol intoxication.

OBJECTIVES: To assess how ethanol in potential lethal serum concentrations affects features of the ECG that may be associated with cardiac arrhythmias. DESIGN: We included 84 patients, who were hospitalised with assumed acute ethanol intoxication. In the emergency room resting ECG was recorded and blood was collected for serum osmolality measurement used as a proxy for ethanol level. Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients without known alcohol ingestion served as controls. ECG segment durations were compared with controls and related to intoxication level. RESULTS: In subjects with moderately elevated to high serum osmolality, the P wave and QTc intervals were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals were longer when the subjects had high blood ethanol levels (at admission) than at discharge (p-values: 0.0001, 0.0002, 0.010 and <0.0001 for P wave, PR, QRS and QTc intervals. n=32). CONCLUSIONS: Ethanol at high to very high blood concentration causes several changes in the ECG that might be associated with increased risk of arrhythmias.

Predictors of health-related quality of life in hypertensive recipients following renal transplantation.

BACKGROUND: Health-related quality of life (HRQoL) improves after renal transplantation. However, it is unclear which variables are the strongest determinants of HRQoL following renal transplantation. In this study, we wanted to assess whether antihypertensive medication, donor type, human leukocyte antigen (HLA)-compatibility or other variables could predict HRQoL 6-12 months after transplantation. METHODS: The study was a follow up of 124 patients recruited to a single center, randomized, double-blind clinical trial, comparing the effects of lisinopril and nifedipine in hypertensive renal transplant recipients. HRQoL was assessed with the Short Form 36 (SF-36) questionnaire. Bivariate and multiple linear regression analysis were used to assess the relationship between potential predictors and the physical component summary (PCS) and mental component summary (MCS) scales of the SF-36. RESULTS: Average scores 6-12 months after transplantation did not differ between patients randomized to lisinopril or nifedipine, or between cadaveric and living donor recipients on any of the eight SF-36 scales, or the two summary scales. In multivariate analyses, recipient age (p = 0.01) and cold ischemia time >14.5 h (p = 0.04) were independent predictors of the PCS score. Recipient age (p = 0.05), 2-4 HLA-AB mismatches (p = 0.05) and donor age (p = 0.03) were independent predictors of the MCS score. CONCLUSIONS: There was no evidence of differences in HRQoL according to lisinopril or nifedipine, or living vs. cadaveric donor transplantation. HRQoL was significantly reduced with longer cold ischemia time and more than one HLA-AB mismatches, after adjusting for age. These donor kidneys related issues need confirmation.