Pharmacokinetics of oxycodone/naloxone and its metabolites in patients with end-stage renal disease during and between haemodialysis sessions

The pharmacokinetics of oxycodone in patients with end-stage renal disease (ESRD) requiring haemodialysis are largely unknown. Therefore, we investigated the pharmacokinetics of oxycodone/naloxone prolonged release and their metabolites in patients with ESRD during and between haemodialysis sessions.; Single doses of oxycodone/naloxone (5/2.5 or 10/5 mg) were administered in nine patients with ESRD using a cross-over design on the day of dialysis and on a day between dialysis sessions. Plasma, dialysate and urine concentrations of oxycodone, naloxone and their metabolites were determined up to 48 h post-dosing using a liquid chromatography-tandem mass spectrometry system.; Haemodialysis performed 6-10 h after dosing removed ∼10% of the administered dose of oxycodone predominantly as unconjugated oxycodone and noroxycodone or conjugated oxymorphone and noroxymorphone. The haemodialysis clearance of oxycodone based on its recovery in dialysate was (mean ± SD) 8.4 ± 2.1 L/h. The geometric mean (coefficient of variation) plasma elimination half-life of oxycodone during the 4-h haemodialysis period was 3.9 h (39%) which was significantly shorter than the 5.7 h (22%) without haemodialysis. Plasma levels of the active metabolite oxymorphone in its unconjugated form were very low.; Oxycodone is removed during haemodialysis. The pharmacokinetics including the relatively short half-life of oxycodone in patients with ESRD with or without haemodialysis and the absence of unconjugated active metabolites indicate that oxycodone can be used at usual doses in patients requiring dialysis

Indirect costs in patients with coronary artery disease and mental disorders: A systematic review and meta-analysis

The aim of the present study was to systematically review the association of comorbid mental disorders with indirect health care costs in patients with coronary artery disease (CAD). A comprehensive database search was conducted for studies investigating persons with CAD and comorbid mental disorders (Medline, EMBASE, PsycINFO, Psyndex, EconLit, IBSS). All studies were included, which allowed for a comparison of indirect health care costs between CAD patients with comorbid mental disorders and CAD patients without mental disorders. The literature search revealed 4962 potentially relevant studies, out of which 13 primary studies met the inclusion criteria. Depression was investigated most often (N = 10), followed by anxiety disorders (N = 3) and any mental disorder not further specifi ed (N = 3). All studies focused on return to work as indirect cost outcome. CAD patients with depression showed diminished odds for return to work, compared to CAD patients without depression (OR = 0.37; 95% CI: 0.27-0.51). The fi ndings for comorbid anxiety and any mental disorder were inconsistent. Indirect health care costs were exclusively assessed by a patient self-report (N = 13). There is strong evidence for diminished odds of return to work in CAD patients with comorbid depression, highlighting the need for integrated CAD and depression care. With regard to other comorbid mental disorders, however, the evidence is sparse and inconclusive

Developing indicators for medication-related readmissions based on a Delphi consensus study.

BACKGROUND Medication-related readmissions challenge healthcare systems by burdening patients, increasing costs and straining resources. However, to date, there has been no consensus study on indicators for medication-related readmissions. OBJECTIVES This Delphi study aimed to develop a consensus-based set of indicators for detecting patients at risk of medication-related readmission. METHODS An expert panel of clinical pharmacists, physicians and nursing experts participated in a two-round Delphi study. In round 1, 31 indicators taken from the literature were rated for relevance on a scale from 1 to 9, with a median rating of 7 or higher suggesting relevance. The RAND/UCLA method was used to determine consensus. In round 2, indicators lacking consensus were re-rated together with a series of new indicators generated by the experts. Additional details were sought for some indicators. The main outcomes were the relevance of, consensus on, and completeness of the proposed indicators for identifying risks of 30-day medication-related readmission. RESULTS Thirty-eight experts participated in round 1. Consensus was found for all the indicators, with 25 included and 6 excluded. Thirty-four experts participated in round 2. Consensus was found for all 5 newly suggested indicators, and 4 were included. The expert panel prioritized the following indicators: (1) insufficient communication between different healthcare providers, (2) polypharmacy (≥7 medications), (3) low rates of medication adherence (twice-weekly mistakes or missing administration), (4) complex medication regimens (≥3 doses, ≥2 dosage forms and ≥2 administration routes per day), and (5) multimorbidity (≥3 chronic conditions). The final set comprised 29 indicators. CONCLUSIONS The indicator set developed for flagging potential medication-related readmissions could guide priorities for clinical pharmacy services at hospital discharge, improving patient outcomes and resource use. A validation study of these indicators is planned

Development of short form questionnaires for the assessment of work capacity in cardiovascular rehabilitation patients

Objectives: Prevention of job loss is an essential objective of cardiovascular rehabilitation. However, comprehensive and economic diagnostic instruments on work limitations are missing. The present study describes development of short form questionnaires from 2 domains of the WCIB-Cardio item banks for the assessment of work capacity in cardiovascular rehabilitation patients. Materials and Methods: 283 cardiovascular rehabilitation patients were recruited from 14 German rehabilitation clinics. Based on the WCIB-Cardio with the domains of cognitive and physical work capacity, we developed a short form for both domains. Item selection criteria were content coverage, content appropriateness, internal consistency reliability (≥ 0.8). We used correlation of person location scores of the short forms with person location scores of the full item banks to examine the extent of measurement precision. Results: For each domain of the WCIB-Cardio a short form was developed (cognitive work capacity - 14 items; physical work capacity 7 - items). In both domains psychometric properties were good (person separation index: cognitive work capacity - 0.80; physical work capacity - 0.80). Correlation measures of the short form with the full item banks showed a high accordance of person locations for both domains (cognitive work capacity: r = 0.97; physical work capacity: r = 0.95). Conclusions: The calibrated instrument WCIB-Cardio provides the possibility to develop short form questionnaires with high psychometric quality. These short forms make it possible to monitor patient's work capacity in cardiovascular rehabilitation settings in a more economical way

Prevalence of drug-drug interactions in older people before and after hospital admission: analysis from the OPERAM trial.

BACKGROUND Drug-drug interactions (DDIs) are highly prevalent in older patients but little is known about prevalence of DDIs over time. Our main objective was to assess changes in the prevalence and characteristics of drug-drug interactions (DDIs) during a one-year period after hospital admission in older people, and associated risk factors. METHODS We conducted a sub-study of the European OPERAM trial (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people), which assessed the effects of a structured medication review (experimental arm) compared to usual care (control arm) on reducing drug-related hospital readmissions. All OPERAM patients (≥70 years, with multimorbidity and polypharmacy, hospitalized in four centers in Bern, Brussels, Cork and Utrecht between December 2016 and October 2018, followed over 1 year) who were alive at hospital discharge and had full medication data during the index hospitalization (at baseline i.e., enrolment at admission, and at discharge) were included. DDIs were assessed using an international consensus list of potentially clinically significant DDIs in older people. The point-prevalence of DDIs was evaluated at baseline, discharge, and at 2, 6 and 12 months after hospitalization. Logistic regression models were performed to assess independent variables associated with changes in DDIs 2 months after baseline. RESULTS Of the 1950 patients (median age 79 years) included, 1045 (54%) had at least one potentially clinically significant DDI at baseline; point-prevalence rates were 58, 57, 56 and 57% at discharge, and 2, 6 and 12 months, respectively. The prevalence increased significantly from baseline to discharge (P < .001 [significant only in the control group]), then remained stable over time (P for trend .31). The five most common DDIs -all pharmacodynamic in nature- accounted for 80% of all DDIs and involved drugs that affect potassium concentrations, centrally-acting drugs and antithrombotics. At 2 months, DDIs had increased in 459 (27%) patients and decreased in 331 (19%). The main factor predictive of a change in the prevalence of DDIs was hyperpolypharmacy (≥10 medications). CONCLUSIONS DDIs were very common; their prevalence increased during hospitalization and tended to remain stable thereafter. Medication review may help control this increase and minimize the risk of adverse drug events

Inpatient and outpatient costs in patients with coronary artery disease and mental disorders: A systematic review

Background: To systematically review in- and outpatient costs in patients with coronary artery disease (CAD) and comorbid mental disorders. Methods: A comprehensive database search was conducted for studies investigating persons with CAD and comorbid mental disorders (Medline, EMBASE, PsycINFO, Psyndex, EconLit, IBSS). All studies were included which allowed a comparison of in- and outpatient health care costs (assessed either monetarily or in terms of health care utilization) of CAD patients with comorbid mental disorders (mood, anxiety, alcohol, eating, somatoform and personality disorders) and those without. Random effects meta-analyses were conducted and results reported using forest plots. Results: The literature search resulted in 7,275 potentially relevant studies, of which 52 met inclusion criteria. Hospital readmission rates were increased in CAD patients with any mental disorder (pooled standardized mean difference (SMD) = 0.34 [0.17;0.51]). Results for depression, anxiety and posttraumatic stress disorder pointed in the same direction with heterogeneous SMDs on a primary study level ranging from −0.44 to 1.26. Length of hospital stay was not increased in anxiety and any mental disorder, while studies on depression reported heterogeneous SMDs ranging from −0.08 to 0.82. Most studies reported increased overall and outpatient costs for patients with comorbid mental disorders. Results for invasive procedures were non-significant respectively inconclusive. Conclusions: Comorbid mental disorders in CAD patients are associated with an increased healthcare utilization in terms of higher hospital readmission rates and increased overall and outpatient health care costs. From a health care point of view, it is requisite to improve the diagnosis and treatment of comorbid mental disorders in patients with CAD to minimize incremental costs

C-Reactive Protein and Procalcitonin in Case Reports of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome

BACKGROUND: The spectrum of inflammatory marker response in DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome has not been systematically characterized. METHODS: An epidemiological biomarker study of C-reactive protein (CRP) and procalcitonin (PCT) values in patients with DRESS syndrome reported at 2 regional pharmacovigilance centers in Switzerland or published in the medical literature 2008-2016 was performed. RESULTS: Ninety-four DRESS cases were studied. All cases showed a CRP value > 10 mg/L (the upper limit of normal). The mean CRP value was 109.2 ± 79.4 mg/L. CRP values were significantly higher in 22 cases where a cause of inflammation besides DRESS could not be excluded (mean 162.1 vs. 92.9 mg/L; p = 0.003). Receiver operator characteristics curve analysis showed a moderate performance with a CRP cut-off value of 99.4 mg/L (AUC 0.717) to distinguish between patients with and without a possible additional cause of inflammation. The mean and median PCT values were 2.44 ± 5.94 and 0.69 ng/mL, respectively (n = 25 patients). Patients in whom an additional cause of inflammation besides DRESS could not be excluded showed a median PCT of 1.37 ng/mL (n = 9) versus 0.67 ng/mL (n = 16) in patients with DRESS only. PCT values were above the normal cut-off of 0.1 ng/mL, suggestive of bacterial infection in all but 1 case. Furthermore, there was a correlation between PCT values and hepatic enzyme measurements. CONCLUSIONS: Evaluating CRP and PCT values might be of use in helping physicians to distinguish between cases of DRESS syndrome with and without concurrent infection or other causes of inflammation. Further prospective investigation is required to define the use of these inflammatory markers in the management of DRESS