Potentially inappropriate medication in older participants of the Berlin Aging Study II (BASE-II) - Sex differences and associations with morbidity and medication use

INTRODUCTION: Multimorbidity in advanced age and the need for drug treatment may lead to polypharmacy, while pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug events (ADEs). OBJECTIVE: The aim of this study was to determine the proportion of subjects using potentially inappropriate medication (PIM) in a cohort of older and predominantly healthy adults in relation to polypharmacy and morbidity. METHODS: Cross-sectional data were available from 1,382 study participants (median age 69 years, IQR 67-71, 51.3% females) of the Berlin Aging Study II (BASE-II). PIM was classified according to the EU(7)-PIM and German PRISCUS (representing a subset of the former) list. Polypharmacy was defined as the concomitant use of at least five drugs. A morbidity index (MI) largely based on the Charlson Index was applied to evaluate the morbidity burden. RESULTS: Overall, 24.1% of the participants were affected by polypharmacy. On average, men used 2 (IQR 1-4) and women 3 drugs (IQR 1-5). According to PRISCUS and EU(7)-PIM, 5.9% and 22.6% of participants received at least one PIM, while use was significantly more prevalent in females (25.5%) compared to males (19.6%) considering EU(7)-PIM (p = 0.01). In addition, morbidity in males receiving PIM according to EU(7)-PIM was higher (median MI 1, IQR 1-3) compared to males without PIM use (median MI 1, IQR 0-2, p<0.001). CONCLUSION: PIM use occurred more frequently in women than in men, while it was associated with higher morbidity in males. As expected, EU(7)-PIM identifies more subjects as PIM users than the PRISCUS list but further studies are needed to investigate the differential impact of both lists on ADEs and outcome. KEY POINTS: We found PIM use to be associated with a higher number of regular medications and with increased morbidity. Additionally, we detected a higher prevalence of PIM use in females compared to males, suggesting that women and people needing intensive drug treatment are patient groups, who are particularly affected by PIM use

Wet Granular Materials

Most studies on granular physics have focused on dry granular media, with no liquids between the grains. However, in geology and many real world applications (e.g., food processing, pharmaceuticals, ceramics, civil engineering, constructions, and many industrial applications), liquid is present between the grains. This produces inter-grain cohesion and drastically modifies the mechanical properties of the granular media (e.g., the surface angle can be larger than 90 degrees). Here we present a review of the mechanical properties of wet granular media, with particular emphasis on the effect of cohesion. We also list several open problems that might motivate future studies in this exciting but mostly unexplored field.Comment: review article, accepted for publication in Advances in Physics; tex-style change

Assessment of ePrescription quality: an observational study at three mail-order pharmacies

<p>Abstract</p> <p>Background</p> <p>The introduction of electronic transfer of prescriptions (ETP) or ePrescriptions in ambulatory health care has been suggested to have a positive impact on the prescribing and dispensing processes. Thereby, implying that ePrescribing can improve safety, quality, efficiency, and cost-effectiveness. In December 2007, 68% of all new prescriptions were transferred electronically in Sweden. The aim of the present study was to assess the quality of ePrescriptions by comparing the proportions of ePrescriptions and non-electronic prescriptions necessitating a clarification contact (correction, completion or change) with the prescriber at the time of dispensing.</p> <p>Methods</p> <p>A direct observational study was performed at three Swedish mail-order pharmacies which were known to dispense a large proportion of ePrescriptions (38–75%). Data were gathered on all ePrescriptions dispensed at these pharmacies over a three week period in February 2006. All clarification contacts with prescribers were included in the study and were classified and assessed in comparison with all drug prescriptions dispensed at the same pharmacies over the specified period.</p> <p>Results</p> <p>Of the 31225 prescriptions dispensed during the study period, clarification contacts were made for 2.0% (147/7532) of new ePrescriptions and 1.2% (79/6833) of new non-electronic prescriptions. This represented a relative risk (RR) of 1.7 (95% CI 1.3–2.2) for new ePrescriptions compared to new non-electronic prescriptions. The increased RR was mainly due to 'Dosage and directions for use', which had an RR of 7.6 (95% CI 2.8–20.4) when compared to other clarification contacts. In all, 89.5% of the suggested pharmacist interventions were accepted by the prescriber, 77.7% (192/247) as suggested and an additional 11.7% (29/247) after a modification during contact with the prescriber.</p> <p>Conclusion</p> <p>The increased proportion of prescriptions necessitating a clarification contact for new ePrescriptions compared to new non-electronic prescriptions indicates the need for an increased focus on quality aspects in ePrescribing deployment. ETP technology should be developed towards a two-way communication between the prescriber and the pharmacist with automated checks of missing, inaccurate, or ambiguous information. This would enhance safety and quality for the patient and also improve efficiency and cost-effectiveness within the health care system.</p

Albiglutide, a Long Lasting Glucagon-Like Peptide-1 Analog, Protects the Rat Heart against Ischemia/Reperfusion Injury: Evidence for Improving Cardiac Metabolic Efficiency

BACKGROUND: The cardioprotective effects of glucagon-like peptide-1 (GLP-1) and analogs have been previously reported. We tested the hypothesis that albiglutide, a novel long half-life analog of GLP-1, may protect the heart against I/R injury by increasing carbohydrate utilization and improving cardiac energetic efficiency. METHODS/PRINCIPAL FINDINGS: Sprague-Dawley rats were treated with albiglutide and subjected to 30 min myocardial ischemia followed by 24 h reperfusion. Left ventricle infarct size, hemodynamics, function and energetics were determined. In addition, cardiac glucose disposal, carbohydrate metabolism and metabolic gene expression were assessed. Albiglutide significantly reduced infarct size and concomitantly improved post-ischemic hemodynamics, cardiac function and energetic parameters. Albiglutide markedly increased both in vivo and ex vivo cardiac glucose uptake while reducing lactate efflux. Analysis of metabolic substrate utilization directly in the heart showed that albiglutide increased the relative carbohydrate versus fat oxidation which in part was due to an increase in both glucose and lactate oxidation. Metabolic gene expression analysis indicated upregulation of key glucose metabolism genes in the non-ischemic myocardium by albiglutide. CONCLUSION/SIGNIFICANCE: Albiglutide reduced myocardial infarct size and improved cardiac function and energetics following myocardial I/R injury. The observed benefits were associated with enhanced myocardial glucose uptake and a shift toward a more energetically favorable substrate metabolism by increasing both glucose and lactate oxidation. These findings suggest that albiglutide may have direct therapeutic potential for improving cardiac energetics and function

Linkage disequilibrium pattern of the ATM gene in breast cancer patients and controls; association of SNPs and haplotypes to radio-sensitivity and post-lumpectomy local recurrence

<p>Abstract</p> <p>Background</p> <p>The ATM protein is activated as a result of ionizing radiation, and genetic variants of the <it>ATM </it>gene may therefore affect the level of radiation-induced damage. Individuals heterozygous for <it>ATM </it>mutations have been reported to have an increased risk of malignancy, especially breast cancer.</p> <p>Materials and methods</p> <p>Norwegian breast cancer patients (272) treated with radiation (252 of which were evaluated for radiation-induced adverse side effects), 95 Norwegian women with no known history of cancer and 95 American breast cancer patients treated with radiation (44 of which developed ipsilateral breast tumour recurrence, IBTR) were screened for sequence variations in all exons of the <it>ATM </it>gene as well as known intronic variants by denaturating high performance liquid chromatography (dHPLC) followed by sequencing to determine the nature of the variant.</p> <p>Results and Conclusion</p> <p>A total of 56 variants were identified in the three materials combined. A borderline significant association with breast cancer risk was found for the 1229 T>C (Val>Ala) substitution in exon 11 (P-value 0.055) between the Norwegian controls and breast cancer patients as well as a borderline significant difference in haplotype distribution (P-value 0.06). Adverse side effects, such as: development of costal fractures and telangiectasias, subcutaneous and lung fibrosis, pleural thickening and atrophy were evaluated in the Norwegian patients. Significant associations were found for several of the identified variants such as rs1800058 (Leu > Phe) where a decrease in minor allele frequency was found with increasing level of adverse side effects for the clinical end-points pleural thickening and lung fibrosis, thus giving a protective effect. Overall our results indicate a role for variation in the <it>ATM </it>gene both for risk of developing breast cancer, and in radiation induced adverse side effects. No association could be found between risk of developing ipsilateral breast tumour recurrence and any of the sequence variants found in the American patient material.</p

Osteo-Chondroprogenitor–Specific Deletion of the Selenocysteine tRNA Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development: A Putative Model for Kashin-Beck Disease

Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions of Asia. The disease has been postulated to result from a combination of different environmental factors, including contamination of barley by mold mycotoxins, iodine deficiency, presence of humic substances in drinking water, and, importantly, deficiency of selenium. This multifunctional trace element, in the form of selenocysteine, is essential for normal selenoprotein function, including attenuation of excessive oxidative stress, and for the control of redox-sensitive molecules involved in cell growth and differentiation. To investigate the effects of skeletal selenoprotein deficiency, a Cre recombinase transgenic mouse line was used to trigger Trsp gene deletions in osteo-chondroprogenitors. Trsp encodes selenocysteine tRNA[Ser]Sec, required for the incorporation of selenocysteine residues into selenoproteins. The mutant mice exhibited growth retardation, epiphyseal growth plate abnormalities, and delayed skeletal ossification, as well as marked chondronecrosis of articular, auricular, and tracheal cartilages. Phenotypically, the mice thus replicated a number of the pathological features of Kashin-Beck disease, supporting the notion that selenium deficiency is important to the development of this syndrome

Analysis of Polymorphisms and Haplotype Structure of the Human Thymidylate Synthase Genetic Region: A Tool for Pharmacogenetic Studies

5-fluorouracil (5FU), a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms). Prior studies implicated a VNTR (variable numbers of tandem repeats) polymorphism in the 5′-untranslated region (5′-UTR) of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T) repeats and novel single nucleotide polymorphisms (SNPs) flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt), polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing

Work-life conflict and musculoskeletal disorders: a cross-sectional study of an unexplored association

BACKGROUND: The health consequences of work-family or rather work-life conflict (WLC) have been studied by numerous researchers. The work-related causes of musculoskeletal disorders (MSD) are also well explored. And stress (at work) has been found to be a consequence of WLC as well as a cause of MSD. But very little is known about a potential association between WLC and MSD and the possible mediating role of stress in this relationship. METHODS: Survey data collected in 2007 among the workforces of four large companies in Switzerland were used for this study. The study population covered 6091 employees. As the exposure variable and hypothesized risk factor for MSD, WLC was measured by using a 10-item scale based on an established 18-item scale on work-family conflict. The outcome variables used as indicators of MSD were (low) back pain and neck/shoulder pain. Stress as the assumed intervening variable was assessed by a validated single-item measure of general stress perception. Correlation coefficients (r), standardized regression coefficients (beta) and multiple adjusted odds ratios (OR) were calculated as measures of association. RESULTS: WLC was found to be quite strongly associated with MSD (beta=.21). This association turned out to be substantially confounded by physical strain at work, workload and job autonomy and was considerably reduced but far from being completely eliminated after adjusting for general stress as another identified risk factor of MSD and a proven strong correlate of WLC (r=.44). A significant and relevant association still remained (beta=.10) after having controlled for all considered covariates. This association could be fully attributed to only one direction of WLC, namely the work-to-life conflict. In subsequent analyses, a clear gradient between this WLC direction and both types of MSD was found, and proved to be consistent for both men and women. Employees who were most exposed to such work-to-life conflict were also most at risk and showed a fivefold higher prevalence rate (19%-42%) and also an up to sixfold increased relative risk (OR=3.8-6.3) of suffering greatly from these types of MSD compared with the least exposed reference group showing very low WLC in this direction. Including stress in the regression models again reduced the strength of the association significantly (OR=1.9-4.1), giving an indication for a possible indirect effect of WLC on MSD mediated by stress. CONCLUSION: Future research and workplace interventions for the prevention of MSD need to consider WLC as an important stressor, and the MSD risk factor identified in this study

Bone loss and the aromatase inhibitors

The increasing use of systemic adjuvant therapies has considerably improved the prognosis from early breast cancer. However, some of these therapies affect bone metabolism, resulting in osteoporosis. Aromatase inhibitors lower circulating oestrogen levels to almost unrecordable levels in postmenopausal women, predisposing them to bone loss with an increase in fracture risk. Ongoing clinical trials are favouring the use of the aromatase inhibitors over tamoxifen and this may advocate greater use of these drugs in the future. Strategies for the identification and management of treatment-induced bone loss are currently being defined