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

NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone

Antidepressant-Warfarin Interaction and Associated Gastrointestinal Bleeding Risk in a Case-Control Study

Bleeding is the most common and worrisome adverse effect of warfarin therapy. One of the factors that might increase bleeding risk is initiation of interacting drugs that potentiate warfarin. We sought to evaluate whether initiation of an antidepressant increases the risk of hospitalization for gastrointestinal bleeding in warfarin users.Medicaid claims data (1999-2005) were used to perform an observational case-control study nested within person-time exposed to warfarin in those ≥18 years. In total, 430,455 warfarin users contributed 407,370 person-years of warfarin use. The incidence rate of hospitalization for GI bleeding among warfarin users was 4.48 per 100 person-years (95% CI, 4.42-4.55). Each gastrointestinal bleeding cases was matched to 50 controls based on index date and state. Warfarin users had an increased odds ratio of gastrointestinal bleeding upon initiation of citalopram (OR = 1.73 [95% CI, 1.25-2.38]), fluoxetine (OR = 1.63 [95% CI, 1.11-2.38]), paroxetine (OR = 1.64 [95% CI, 1.27-2.12]), amitriptyline (OR = 1.47 [95% CI, 1.02-2.11]). Also mirtazapine, which is not believed to interact with warfarin, increased the risk of GI bleeding (OR = 1.75 [95% CI, 1.30-2.35]).Warfarin users who initiated citalopram, fluoxetine, paroxetine, amitriptyline, or mirtazapine had an increased risk of hospitalization for gastrointestinal bleeding. However, the elevated risk with mirtazapine suggests that a drug-drug interaction may not have been responsible for all of the observed increased risk

Information and feedback to improve occupational physicians’ reporting of occupational diseases: a randomised controlled trial

To assess the effectiveness of supplying occupational physicians (OPs) with targeted and stage-matched information or with feedback on reporting occupational diseases to the national registry in the Netherlands. In a randomized controlled design, 1076 OPs were divided into three groups based on previous reporting behaviour: precontemplators not considering reporting, contemplators considering reporting and actioners reporting occupational diseases. Precontemplators and contemplators were randomly assigned to receive stage-matched, stage-mismatched or general information. Actioners were randomly assigned to receive personalized or standardized feedback upon notification. Outcome measures were the number of OPs reporting and the number of reported occupational diseases in a 180-day period before and after the intervention. Precontemplators were significantly more male and self-employed compared to contemplators and actioners. There was no significant effect of stage-matched information versus stage-mismatched or general information on the percentage of reporting OPs and on the mean number of notifications in each group. Receiving any information affected reporting more in contemplators than in precontemplators. The mean number of notifications in actioners increased more after personalized feedback than after standardized feedback, but the difference was not significant. This study supports the concept that contemplators are more susceptible to receiving information but could not confirm an effect of stage-matching this information on reporting occupational diseases to the national registr

Couple’s Relationship After the Death of a Child: a Systematic Review

When a child dies, the parents must address the changes in their relationship as well as the way that these changes affect their individual adjustment. These two perspectives are addressed in this systematic review. Five databases were systematically searched for papers published in English between January 2000 and February 2014. Of the 646 publications, 24 papers met the inclusion criteria. The results suggest that a child’s death can cause cohesive as well as detrimental effects on a couple’s relationship. Variables that may produce differential outcomes for the marital relationship include situational factors, such as the cause and type of death and the child’s age at the time of death; dyad-level factors, such as surviving children, the pre-death characteristics of the relationship, communication and incongruent grieving; and individuallevel factors, such as the family of origin’s processing of trauma, social support, religious affiliation and finding meaning. Aspects such as marital quality and the couple’s interdependence were found to influence each parent’s individual adjustment. Larger, prospective, ethically conducted studies should be implemented to consolidate these findings. Mental health professionals may benefit from a deeper understanding of the risk and protective factors regarding marital adjustment after a child’s death