Assessing the perspective of well-being of older patients with multiple morbidities by using the LAVA tool - a person-centered approach.

BACKGROUND: Older patients with multiple morbidities are a particularly vulnerable population that is likely to face complex medical decisions at some time in their lives. A patient-centered medical care fosters the inclusion of the patients' perspectives, priorities, and complaints into clinical decision making. METHODS: This article presents a short and non-normative assessment tool to capture the priorities and problems of older patients. The so-called LAVA ("Life and Vitality Assessment") tool was developed for practical use in seniors in the general population and for residents in nursing homes in order to gain more knowledge about the patients themselves as well as to facilitate access to the patients. The LAVA tool conceptualizes well-being from the perspectives of older individuals themselves rather than from the perspectives of outside individuals. RESULTS: The LAVA tool is graphically presented and the assessment is explained in detail. Exemplarily, the outcomes of the assessments with the LAVA of three multimorbid older patients are presented and discussed. In each case, the assessment pointed out resources as well as at least one problem area, rated as very important by the patients themselves. CONCLUSIONS: The LAVA tool is a short, non-normative, and useful approach that encapsulates the perspectives of well-being of multimorbid patients and gives insights into their resources and problem areas.

[Epidemiology and prevention of heat-related adverse health effects on elderly people]. / Epidemiologie und Prävention hitzebedingter Gesundheitsschäden älterer Menschen.

Heat waves increase the morbidity and mortality in Germany, particularly of older patients in need of care. Due to climate change the number of heat waves in Germany will increase threefold by the end of the century. In addition, the proportion of patients at risk will grow due to demographic change. Therefore, the Government and the Federal States have developed recommendations for heat action plans, in which the medical profession should also participate in the prevention of heat-related damage to health. Physicians and their team should first become acquainted with the topic. In addition, they should inform patients at risk and their relatives of the risks and preventive measures. In the summer a critical check of drugs is also needed because medications impair cooling mechanisms in heat waves, the pharmacokinetics can change and unwanted side effects of drugs occur more frequently. Lastly, due to their central position in the healthcare system, physicians should participate in the coordination of a good nursing care and intensification of social contacts during heat waves.

Association of generalized anxiety symptoms and panic with health care costs in older age-Results from the ESTHER cohort study.

BACKGROUND: Little is known specifically about the association between generalized anxiety symptoms or panic and health care costs in older age. The aim of this study was to examine the association between generalized anxiety symptoms, panic and health care costs in people aged 65 and over. METHODS: Cross-sectional data from the 8-year follow-up of a large, prospective cohort study, the ESTHER study, was used. Individuals aged 65 and over, who participated in the study's home assessment, were included in this analysis (n = 2348). Total and sectoral costs were analyzed as a function of either anxiety symptoms, probable panic disorder, or a panic attack, while controlling for selected covariates, using Two Part and Generalized Linear Models. Covariates were chosen based on Andersen's Behavioral Model of Health Care Use. RESULTS: There was no significant association between either of the anxiety or panic measures and total health care costs. Stratified by health care sectors, only the occurrence of a panic attack was significantly associated with incurring costs for outpatient non-physician services (OR: 1.99; 95% CI: 1.15-3.45) and inpatient services (OR: 2.14; 95% CI: 1.07-4.28). Other illness-related factors, such as comorbidities and depressive symptoms, were associated with health care costs in several models. LIMITATIONS: This was a cross-sectional study relying on self-reported data. CONCLUSION: This study points to an association between a panic attack and sector-specific health care costs in people aged 65 and over. Further research, especially using longitudinal data, is needed.

The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics.

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.

[Which Factors Affect Out-of-pocket Payments for Health Care Services Among Elderly Germans? Results of a Longitudinal Study]. / Welche Faktoren beeinflussen die privaten Zuzahlungen zu Gesundheitsleistungen im Alter? Ergebnisse einer Längsschnittstudie.

Background: In Germany, out-of-pocket payments (OOPP) account for a large proportion of total health expenditure. However, there are only few investigations on how morbidity-related, sociodemographic and lifestyle factors affect OOPP particularly in the older population. The aim of this study was to identify factors affecting OOPP for health care services among elderly Germans in a longitudinal setting. Methods: This longitudinal study used data from 2 follow-up waves (3-year interval) from a population-based prospective cohort study (ESTHER study) collected in Saarland, Germany. At the first follow-up wave, subjects were between 57 and 84 years old. Participants provided comprehensive data including individual OOPP for the preceding 3 months. Fixed effects (FE) regressions were used to determine factors affecting OOPP. Results: Mean individual OOPP (3-month period) rose from € 119 (first wave) to € 136 (second wave). Longitudinal regressions showed that higher morbidity did not affect OOPP. Moreover, changes in sociodemographic as well as lifestyle factors were not related to changes in OOPP. Solely, exemption of OOPP reduced the dependent variable significantly. Conclusion: In contrast to cross-sectional findings for Germany, OOPP are not related to morbidity and income in this study. This underlines the complex nature of OOPP in old age and the need for longitudinal studies to gain some insight into the underlying causal factors.

A randomized controlled trial to assess the effect of a medication plan containing drug administration recommendations on patients' drug knowledge after 2 months.

WHAT IS KNOWN AND OBJECTIVE: Patients' drug administration errors are often promoted by poor drug knowledge resulting from inadequate oral or written information. It has previously been shown that a medication plan enhanced with graphical and textual information on drug handling (enhanced medication plan) proved to immediately increase patients' drug knowledge. This study aimed to evaluate the effect of the enhanced medication plan on drug knowledge in outpatients after 2 months (intervention group) compared to patients with a simple medication plan with standard information (control group). METHODS: We recruited patients using ≥5 drugs in four family practices in Germany. After inclusion, patients' knowledge on handling of their drugs was assessed using three questions from a standardized catalog. Thereafter, patients were randomized to the intervention or control group. After 2 months, drug knowledge was reassessed with three different questions from the same standardized catalog. RESULTS AND DISCUSSION: Of 120 enrolled patients, 75% of participants in the control group (42/60 patients) and 78% of participants in the intervention group (46/60; P = 0·71) completed the study. Baseline drug knowledge was similar in both groups (43·7% vs. 40·6% correct answers). After 2 months, patients' drug knowledge showed an absolute increase of 23·2% in the intervention group (P < 0·01) and was unchanged in the control group (46·0%; P = 0·70). WHAT IS NEW AND CONCLUSION: The enhanced medication plan outperformed the effect of a simple medication plan and persistently increased the fraction of correct answers of polypharmacy patients. This demonstrates that the enhanced medication plan may be a useful tool in promoting drug knowledge.

[Formal prescribing errors are substantially reduced in electronic prescribing and after teaching sessions]. / Formale Fehler bei der Rezeptschreibung sind bei Nutzung elektronischer Verordnung und Schulung erheblich reduziert.

INTRODUCTION: Prescription forms enable the communication between physicians and pharmacists. Hence, incorrectly issued prescriptions may result in delay of health-care delivery, additional workload, and potentially adverse patient outcomes. We aimed to evaluate the formal prescription quality in our outpatient clinics (OC) before and after performing teaching sessions and using an electronic prescription system to replace handwritten prescriptions. METHODS: All OCs of a university hospital were offered a short teaching session on how to issue prescriptions correctly and how to use the electronic prescription system. During four weeks before and after the teaching, we anonymously collected all prescriptions of the OCs in 20 surrounding community pharmacies and assessed whether they were error-free, required an intervention by the pharmacist, additional clarification by the OC, or had to be reissued. RESULTS: After the intervention, the absolute fraction of formally error-free prescriptions increased by 12.9% from 52.9% (516/976) to 65.8% (713/1084, p < 0.001; d = 12,9% 95% confidence interval [8,7%; 17,1%]). Largest improvements were seen in prescriptions requiring clarification by the OC (224/976 prescriptions at baseline versus 93/1084 post-intervention, p < 0.001). The fraction of electronic prescriptions increased from 34.9% (341/976) to 46.9% (509/1084, p < 0.001, d = 12,0% 95% confidence interval [7,8%; 16,2%]) with electronic prescriptions consistently being of higher formal quality than handwritten prescriptions. CONCLUSION: After increased use of electronic prescribing and teaching courses, formal prescription quality was significantly improved.

More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.

WHAT IS KNOWN AND OBJECTIVES: Incorrect drug preparation for patients with feeding tubes can result in harm for the patient and the preparing person. Combined intervention programs are effective tools to reduce such preparation errors. However, to date, intervention programs have been mostly tested in hospitals with computerized physician order entry (CPOE), unit-dose systems, or ward-based clinical pharmacists. Hence, the primary objective of this study was to develop and evaluate an intervention program tailored to hospitals without such preconditions. METHODS: We conducted a prospective pre-/post-intervention study on a gastroenterological intensive care unit (ICU) and a surgical ward for oral, dental and maxillofacial diseases (surgical ward). During the study periods, observers documented and evaluated drug preparation processes of all peroral drugs for patients with feeding tubes. The primary endpoint was the rate of inappropriately crushed and/or suspended solid peroral drugs in regards to all solid peroral drugs. RESULTS AND DISCUSSION: Altogether, we evaluated 775 drug preparation processes of solid peroral drugs on the ICU and 975 on the surgical ward. The intervention program significantly reduced incorrect crushing and/or suspending of solid peroral drugs for administration to patients with feeding tubes from 9·8% to 4·2% (P < 0·01) on the ICU and from 5·7% to 1·4% (P < 0·01) on the surgical ward. WHAT IS NEW AND CONCLUSION: The implementation of the newly developed intervention program significantly reduced the rate of inappropriately prepared solid peroral drugs, suggesting that it is an effective measure to enable safe drug administration for inpatients with feeding tubes.

Memorandum on the use of information technology to improve medication safety.

BACKGROUND: Information technology in health care has a clear potential to improve the quality and efficiency of health care, especially in the area of medication processes. On the other hand, existing studies show possible adverse effects on patient safety when IT for medication-related processes is developed, introduced or used inappropriately. OBJECTIVES: To summarize definitions and observations on IT usage in pharmacotherapy and to derive recommendations and future research priorities for decision makers and domain experts. METHODS: This memorandum was developed in a consensus-based iterative process that included workshops and e-mail discussions among 21 experts coordinated by the Drug Information Systems Working Group of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS). RESULTS: The recommendations address, among other things, a stepwise and comprehensive strategy for IT usage in medication processes, the integration of contextual information for alert generation, the involvement of patients, the semantic integration of information resources, usability and adaptability of IT solutions, and the need for their continuous evaluation. CONCLUSION: Information technology can help to improve medication safety. However, challenges remain regarding access to information, quality of information, and measurable benefits.

[Use and potential risks of over-the-counter analgesics]. / Gebrauch und potenzielle Risiken durch nicht verschreibungspflichtige Schmerzmittel.

BACKGROUND AND AIM: We investigated the use of prescription and non-prescription (over-the-counter, OTC) analgesics and the associated risks in elderly patients with multiple morbidities. METHODS: Pain medication use was evaluated from the baseline data (2008/2009) of the MultiCare cohort enrolling elderly patients with multiple morbidities who were treated by primary care physicians (trial registration: ISRCTN89818205). We considered opioids (N02A), other analgesics, and antipyretics (N02B) as well as nonsteroidal anti-inflammatory drugs (NSAIDs; M01A). OTC use, duplicate prescription, dosages, and interactions were examined for acetylsalicylic acid, diclofenac, (dex)ibuprofen, naproxen, and acetaminophen. RESULTS: Of 3,189 patients with multiple morbidities aged 65-85 years, 1,170 patients reported to have taken at least one prescription or non-prescription analgesic within the last 3 months (36.7 %). Of these, 289 patients (24.7 % of 1,170) took at least one OTC analgesic. Duplicate prescription was observed in 86 cases; 15 of these cases took the analgesics regularly. In two cases, the maximum daily dose of diclofenac was exceeded due to duplicate prescription. In 235 cases, patients concurrently took a drug with a potentially clinically relevant interaction. In 43 cases (18.3 % of 235) an OTC analgesic, usually ibuprofen, was involved. DISCUSSION: About one third of the elderly patients took analgesics regularly or as needed. Despite the relatively high use of OTC analgesics, the proportions of duplicate prescription, medication overdoses, and adverse interactions due to OTC products was low.

Discussion of "Attitude of physicians towards automatic alerting in computerized physician order entry systems".

With these comments on the paper "Attitude of Physicians Towards Automatic Alerting in Computerized Physician Order Entry Systems", written by Martin Jung and co-authors, with Dr. Elske Ammenwerth as senior author [1], the journal wants to stimulate a broad discussion on computerized physician order entry systems. An international group of experts have been invited by the editor of Methods to comment on this paper. Each of the invited commentaries forms one section of this paper.

A nanogram dose of the CYP3A probe substrate midazolam to evaluate drug interactions.

The objective of the study was to establish an in vivo method for assessing cytochrome P450 3A (CYP3A) activity using therapeutically inert nanogram doses of midazolam. We administered four escalating single doses of oral midazolam (0.0001-3 mg) to 12 healthy participants, stratified according to CYP3A5 carrier status, to assess pharmacokinetics linearity. We then evaluated the interactions with the CYP3A inhibitor ketoconazole (400 mg q.d.) after nanogram and regular doses of midazolam. Area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) were linear over the entire range of doses. Ketoconazole reduced midazolam oral clearance by 92.8%. AUC and C(max) increased by 1,540 and 363%, respectively. CYP3A5 carrier status had no influence on midazolam oral clearance or its inhibition by ketoconazole. This is the first study showing that midazolam pharmacokinetics is linear in a 30,000-fold concentration range, and therefore that nano- and microgram doses of midazolam can reliably predict the pharmacokinetics of midazolam in therapeutic doses and can be used to assess CYP3A activity even in the presence of strong CYP3A inhibitors.

High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia: a prospective cohort study.

The objective of this study was to assess the incidence, timing and identify pharmacogenetic, efavirenz (EFV) pharmacokinetic and biochemical predictors of EFV-based antiretroviral therapy (ART) drug-induced liver injury (DILI). ART-naïve HIV patients (n = 285) were prospectively enrolled. Pretreatment laboratory evaluations included hepatitis B surface antigen and C antibody, CD4 count and viral load. Liver tests were done at baseline, 1st, 2nd, 4th, 8th, 12th, 24th and 48th weeks during ART. Plasma EFV and 8-hydroxyefvairenz concentration was determined at week 4 using liquid chromatography-mass spectrometry. CYP2B6, CYP3A5, ABCB1 3435C/T and UGT2B7*2 genotyping was done using Taqman genotyping assay. Data were analyzed using survival analysis and Cox proportional hazards model. The incidence of DILI was 15.7% or 27.9 per 100 person-years and that of severe injury was 3.4% or 6.13 per 100 person-years. The median time for the development of DILI and severe injury was 2 and 4 weeks after initiation of ART, respectively. There was significant association of DILI with lower baseline platelet, albumin, log plasma viral load and CD4 count (P = 0.031, 0.037, 0.06 and 0.019, respectively). Elevated baseline alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, plasma EFV level and CYP2B6*6 were good predictors for the development of DILI (P = 0.03, 0.01, 0.016, 0.017 and 0.04, respectively). We report for the first time CYP2B6*6 as a putative genetic marker and high plasma EFV concentration as intermediate biomarker for vulnerability to EFV-induced liver injury in HIV patients. CYP2B6 genotyping and/or regular monitoring of EFV and lever enzymes level during early therapy is advised for early diagnosis and management of DILI.

[HeiCare®: a project aiming to improve medication communication across health care sectors]. / HeiCare® : ein Projekt zur Verbesserung der sektorenübergreifenden Arzneimittelkommunikation.

BACKGROUND AND OBJECTIVE: Changes between health care sectors represent a critical phase in long-term pharmacotherapy. The aim of the Hei CARE(®) project was to close the communication gap at the interface between primary care physicians (PCP), hospital physicians and patients, and to improve quality and safety of pharmacotherapy. METHODS: Physicians who enrolled patients with long-term pharmacotherapy were able to participate in the Hei CARE(®) project. After enrolment the patient's medication was entered in the internet-based medication knowledge data base AiD PRAXIS and checked for medication interactions and optimized if necessary. At hospitalisation medication was transferred electronically to the hospital (AiD KLINIK(®)) and on discharge integrated in the discharge letter and faxed to the primary care physician (PCP). The project was evaluated using quantitative and qualitative methods. Hei CARE(®) -cases, in which medication was transferred electronically as planned, were compared with the other cases. PCPs' experiences were collected in focus groups. RESULTS: One thousand and three chronically ill patients of 56 primary care practices participated. 259 patients were hospitalized between October 2005 and March 2009 of which entrance and discharge medication were transferred both ways via the electronic prescribing platform in 67 cases. The number of changes in medication was reduced in comparison to the other cases. Participating PCPs reported positive changes through Hei CARE(®) as well as further potential for optimizing communication across health care sectors. CONCLUSION: Use of a common internet-based medication knowledge data base (Hei CARE(®) ) in both health care sectors reduced the number of changes in pharmacotherapy. Seamless care in chronically ill patients was thereby improved. The project also demonstrated that improving communication across health care sectors is a slow process.

Determining the time course of CYP3A inhibition by potent reversible and irreversible CYP3A inhibitors using A limited sampling strategy.

We established a new limited sampling strategy to assess CYP3A activity and evaluated the time course of reversible (voriconazole) and irreversible (ritonavir) CYP3A inhibition. In this randomized trial, two groups, each with eight healthy participants, received CYP3A inhibitors voriconazole or ritonavir orally for 9 days, with 3 mg midazolam (MDZ) administered before the inhibitor treatment, on days 1, 2, 3, 5, 8, and 9 during inhibitor treatment, and on days 10, 11, and 12 (3 days) after discontinuation. Plasma MDZ area under the curve (AUC) between 2 and 4 h after oral administration in the form of a solution strongly correlated with MDZ clearance. Using this parameter, maximum inhibition of voriconazole and ritonavir was calculated to have occurred only 48 h after starting of the inhibitor (percentage of baseline MDZ clearance, voriconazole: 10.6%; ritonavir: 8.4%). Recovery of CYP3A activity occurred with a half-life of 24 h after voriconazole, whereas ritonavir inhibition was still strong 3 days after discontinuation. These findings underscore the substantial and gradual alterations in dose requirements in the first days of and after such combination therapies.

Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis.

We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction.