Inappropriate prescribing in patients with kidney disease: A rapid review of prevalence, associated clinical outcomes and impact of interventions.

BACKGROUND: The prevalence of patients with chronic kidney disease (CKD) and polypharmacy is increasing and has amplified the importance of examining inappropriate prescribing (IP) in CKD. This review focuses on the latest research regarding the prevalence of IP in CKD and the related adverse clinical effects and explores new interventions against IP. METHOD: A literature search was performed using PubMed, EMBASE and the Cochrane Library searching articles published between June 2016 and March 2022. RESULTS: Twenty-seven studies were included. An IP prevalence of 12.6% to 96% and 0.3% to 66% was reported in hospital and outpatient settings, respectively. In nonhospital settings, the prevalence of IP varied between 3.9% and 60%. IP was associated with higher risk of hospitalisation (HR 1.46, 95% CI 1.17-1.81), higher bleeding rate (HR 2.34, 95% CI 1.32 to 3.37) and higher risk of all-cause mortality (OR 1.07, 95% CI 1.02 to 1.13). Three studies reported the impact of interventions on IP. CONCLUSION: This review highlights widespread IP in CKD patients across healthcare settings, with varying prevalence rates. IP is substantially linked to adverse outcomes in patients. While limited interventions show promise, urgent research is needed to develop effective strategies addressing IP and improving CKD patient care.

Burden of Disease of Duchenne Muscular Dystrophy in Denmark - A National Register-Based Study of Individuals with Duchenne Muscular Dystrophy and their Closest Relatives.

Background: Duchenne Muscular Dystrophy (DMD) is a progressive genetic disease with a prevalence of 1 per 3,600-6,000 male births. Individuals with DMD are typically diagnosed at age 4-7 years; median survival is 30 years. They require multidisciplinary care, personal assistance, and often special education. Objective: The aim was to assess the burden of disease in DMD in Denmark. This includes incidence, prevalence, use of healthcare services, labour market participation, educational outcomes, and overall attributable costs due to DMD. Impact on the closest relatives (siblings and parents) was also investigated. Methods: The comprehensive Danish national health and administrative registers were used to assess the burden of disease following individuals with DMD and closest relatives from five years before, and up to 20 years after DMD diagnosis. Individuals with DMD (and relatives) from 1994-2021 were included. All outcomes were compared to matched control groups without the disease drawn from the Danish population. Results: 213 unique individuals with DMD were identified. They had lower grades in school, required more special education and more healthcare and home care compared to their control group. The extra costs of special education summed to EUR 180,900 over the course of 11 years elementary school. They had an annual average productivity loss of EUR 20,200 between the age of 18 to 30. The extra healthcare costs of DMD in the 20 years after diagnosis were estimated to EUR 1,524,000. If an individual with DMD lives to be 30, total extra costs sum to EUR 2,365,800. Conclusions: Using national register data this study presented detailed results on the burden of disease of DMD, including impact on closest relatives. With 60 additional hospital admissions and 200 extra outpatient contacts in 20 years healthcare costs, but also costs of home care and special education, increases as disease progresses.

Acceptability of a cross-sectoral hospital pharmacist intervention for patients in transition between hospital and general practice: a mixed methods study.

Background and objective: Drug-related problems (DRPs) are often seen when a patient is transitioning from one healthcare sector to another, for example, when a patient moves from the hospital to a General Practice (GP) setting. This transition creates an opportunity for information on medication changes and follow-up plans to be lost. A cross-sectoral hospital pharmacist intervention was developed and pilot-tested in a large GP clinic. The intervention included medication history, medication reconciliation, medication review, follow-up telephone calls, identification of possible DRPs and communication with the GP. It is unknown whether the intervention is transferable to other GP clinics. The aim of the study was to explore similarities and differences between GP clinics in descriptive data and intervention acceptability. Methods: A convergent mixed methods study design was used. The intervention was tested in four GP clinics with differing characteristics. Quantitative data on the GP clinics, patients and pharmacist activities were collected. Qualitative data on the acceptability were collected through focus group interviews with general practitioners, nurses and pharmacists. The Theoretical Framework of Acceptability was used. Results: Overall, the intervention was found acceptable and relevant by all. There were differences between the GP clinics in terms of size, daily physician work form and their use of pharmacists for ad hoc tasks. There were similarities in patient characteristics across GP clinics. Therefore, the intervention was found equally relevant for all of the clinics. Shared employment with unique access to health records in both sectors was important in the identification and resolution of DRPs. Economy was a barrier for further implementation. Conclusions: The intervention was found acceptable and relevant by all; therefore, it was considered transferable to other GP clinics. Hospital pharmacists were perceived to be relevant healthcare professionals to be utilized in GP, in hospitals and in the cross-sectoral transition of patients.

Acceptability of a pharmacist activity for patients transitioning between hospital and general practice Why was the study done? Drug-related problems are often seen in patients transitioning across healthcare sectors. A pharmacist activity was developed and pilot-tested in a large General Practice (GP) clinic. It was unknown whether the activity was transferable to other GP clinics.The pharmacist activity included talking to the patients about their usual medication and adjustment of prescriptions accordingly. The pharmacist activity also included a review of their medications, a follow-up telephone call to the patients and communication with the GP in case of drug-related problems.The aim of the study was to test the activity in different GP clinics and to explore similarities and differences in descriptive data and acceptability. What did the researchers do? The activity was tested in four GP clinics within the same geographical area for three months.Descriptive data about the GP clinics, the patients and the pharmacist's activities performed were collected.Data about acceptability of the activity was collected through focus group interviews with general practitioners, nurses and hospital pharmacists.This qualitative data was combined with descriptive data to explore similarities and differences between GP clinics. What did the researchers find? Overall, the activity was found to be acceptable and relevant by all.There were differences between the GP clinics in terms of size, daily physician work form and their use of the pharmacist for ad hoc tasks.There were similarities in patients across GP clinics e.g. in terms of the number of medications or drug-related problems. The activity was found equally relevant for every clinic.Shared employment with access to health records in both sectors was important in the identification and resolution of drug-related problems. The pharmacist had the possibility to bring issues back and forth between the hospital and the GP clinic.Economy was a barrier for further implementation. What do the findings mean? The activity was found acceptable and relevant by all; therefore, it was considered transferable to other GP clinics.Hospital pharmacists were perceived to be relevant healthcare professionals to be utilised in GP, in hospitals and in the cross-sectoral transition of patients.

Developing and piloting a cross-sectoral hospital pharmacist intervention for patients in transition between hospital and general practice.

Background: Healthcare is challenged by a rapidly growing group of patients with multi-morbidity and polypharmacy. Increasing activity and specialization puts pressure on healthcare sectors. Medication errors in cross-sectoral transition of patients are often seen. The aim of the study was to explore drug-related problems (DRPs) in the transition of patients between sectors and to develop and pilot-test a cross-sectoral hospital pharmacist intervention to overcome some of these problems. Methods: DRPs in cross-sectoral transitions were explored from four perspectives; the literature, the primary and secondary healthcare sector and the patients. An intervention was developed from the findings through co-creation between pharmacists, doctors and a nurse. The intervention was piloted and evaluated from data on the included patients and the activities performed. Results: DRPs in transitions from general practice (GP) to hospital were caused by inadequate focus on updating the Shared Medication Record (SMR). For patients being discharged, DRPs were described with multiple facets; for example, missing information on medication changes, lacking patient involvement and problems with dose-dispensed medicine or electronic prescriptions. An intervention with a pharmacist in a shared employment between Hospital Pharmacy and GP was developed and piloted. The intervention included medication reconciliation and updating SMR for patients referred to hospital; and medication review, overview of medication changes and follow-up telephone calls for patients discharged from hospital. The intervention identified and solved several DRPs; in this way, medication errors were avoided. Access to health records in both sectors was important in the identification and resolution of DRPs. Conclusion: DRPs in cross-sectoral transitions are multifaceted and the experiences depend on the point of view. The cross-sectoral hospital pharmacist intervention identified and solved several DRPs and medication errors were avoided. The intervention made sense to both healthcare sectors and patients. Shared employment and unique access to health records in both sectors showed to be of importance in the identification and resolution of DRPs. Plain language summary: Development and pilot-test of a pharmacist intervention for patients in transition between hospital and general practice Background: Healthcare is challenged by a rapidly growing group of patients with multiple chronic diseases treated with several drugs at the same time. The aim of the study was to explore drug-related problems in the transition of patients between the hospital and patients' general practitioner and to develop and pilot-test a pharmacist intervention to overcome some of these problems.Methods: Drug-related problems in patient transitions were explored from the perspectives of the hospital, the general practitioner, the patients and the literature. An intervention was developed from the findings by pharmacists, doctors and a nurse. The intervention was pilot-tested and evaluated from the descriptions of the included patients and activities performed.Results: Drug-related problems in transitions from general practice to hospital were caused by inadequate focus on updating the Shared Medication Record.For patients being discharged, drug-related problems were related to for examplemissing information on medication changessparse involvement of the patient in their own treatmentproblems with medicine dispensed on a dose dispensing machine at the local pharmacy.An intervention with a pharmacist in a shared employment between Hospital Pharmacy and general practice was developed and piloted. The intervention includedtalking to the patient about their medication and updating the Shared Medication Record for patients referred to hospitalmedication review, overview of medication changes and follow-up telephone calls for patients discharged from hospital to general practice.The intervention identified and solved several drug-related problems. Access to health records in both the general practice and at the hospital was important in the identification of drug-related problems.Conclusions: Drug-related problems in cross-sectoral transitions are multifaceted. The pharmacist intervention identified and solved several drug-related problems. The intervention made sense to the general practitioner, hospital and patients. Shared employment and unique access to health records in both the general practice and at the hospital showed to be of importance in the identification of drug-related problems.

Persistence of protective anti-poliovirus antibody levels in 4-year-old children previously primed with Picovax®, a trivalent, aluminium-adjuvanted reduced dose inactivated polio vaccine.

BACKGROUND: To meet the demand for effective and affordable inactivated polio vaccines (IPVs), a reduced dose, aluminium hydroxide (Al(OH)3)-adjuvanted IPV vaccine was developed (IPV-Al, Picovax®) and evaluated in clinical trials. The present trial is an extension of two previous trials (a primary and a booster trial). The aim was to evaluate the persistence of seroprotective antibodies (poliovirus type-specific antibody titre ≥ 8) in 4-year-old children who previously received IPV-Al as primary and booster vaccine doses and to determine the potential booster response and safety profile of an additional dose of IPV-Al. METHODS: Children participating in the two previous trials were invited to receive one additional dose of IPV-Al at 4 years of age (2.5 years after the booster dose) and to have their blood samples collected to measure the pre- and post-vaccination antibody titres. Systemic adverse events (AEs) and local reactogenicity were recorded. RESULTS: At study entry, the seroprotection rates were 89.2%, 100% and 91.1% against poliovirus type 1, 2 and 3, respectively. The additional vaccination with IPV-Al boosted the level of poliovirus type 1, 2 and 3 antibodies to above the seroprotection threshold for all but one subject, i.e., 99.4% for type 1 and 100% for types 2 and 3. The additional dose induced a robust booster response of a 26.3-, 13.9- and 30.9-fold increase in titre for poliovirus types 1, 2 and 3, respectively. The vaccine was well tolerated, with only mild and transient AEs reported. CONCLUSIONS: The present trial demonstrated that the primary vaccination with an aluminium-adjuvanted reduced dose IPV induced a persistent immune memory as evidenced by the robust anamnestic response when the subjects were re-exposed to the antigen 2.5 years after the last dose. Thus, the IPV-Al is an efficient and safe addition to increase the availability of inactivated polio vaccines globally. (ClinicalTrials.gov reg no. NCT04448132).

The use of melatonin in Danish intensive care departments-A nationwide observational study.

BACKGROUND: Melatonin is widely employed as a hypnotic in various patient groups. In intensive care patients, melatonin seems to be increasingly used due to potential clinical effects and a favourable safety profile. OBJECTIVES: We aimed to investigate the extend of usage and clinical practice of melatonin therapy in intensive care departments in Denmark. DESIGN: Data from regional hospital pharmacies and the Danish Intensive Care Database were used to estimate defined daily dose and defined daily dose per 1000 ICU admission days. Also, related expenses in the period 2015-2019. Finally, a questionnaire describing the clinical practice of melatonin therapy was provided to all Danish intensive care departments. PRINCIPAL OBSERVATIONS: The usage of melatonin in intensive care departments in Denmark increased from 21,300 DDD (200.0 DDD per 1000 ICU admission days) in 2015 to 52,170 DDD (560.7 DDD per 1000 ICU admission days) in 2019. A total of 32 ICU departments participated in the study (97% of all Danish ICU departments). All included ICU departments employed melatonin as a hypnotic. Nineteen percent of included departments administered melatonin to all admitted patients, whereas 25% of departments rarely administered melatonin. Magistral melatonin 3-mg tablets was the most employed drug dose/formulation. Increased doses of melatonin were administered in selected patients. Melatonin was considered safe by prescribing clinicians. CONCLUSIONS: Melatonin is widely and increasingly used in Danish intensive care departments. The more than doubled usage of melatonin in the study period advocates for further studies employing validated outcomes of sleep and other patient-relevant outcomes. EDITORIAL COMMENT: This study documents that melatonin is frequently used as a hypnotic in Danish intensive care units during recent years despite a shortage of reliable evidence to support a recommendation to treat with melatonin in this context. These results support a need for conducting clinical trials to determine whether or not there is a beneficial effect of melatonin treatment in critically ill patients.

Cost-consequence analysis of self-administration of medication during hospitalization: a pragmatic randomized controlled trial in a Danish hospital setting.

OBJECTIVES: The objective of this study was to evaluate the costs and consequences of introducing "self-administration of medication" (SAM) during hospitalization as compared with nurse-led dispensing and administration of medication. METHODS: This pragmatic randomized controlled trial was performed in a Danish Cardiology Unit. Patients ⩾18 years old capable of self-administering medication were eligible. In the intervention group, patients self-administered their medication. In the control group, medication was dispensed and administered by nurses. The implementation of SAM was used to evaluate the cost-consequences. The micro-costing analysis used the hospital perspective and a short-term incremental costing approach. The costs for medication, materials, and nursing time were included. Consequences included the dispensing error proportion, patients' perceptions regarding medication, satisfaction, and deviations in the medication list at follow-up. In addition, the number of readmissions and general practitioner (GP) contacts within 30 days after discharge was included. RESULTS: The total cost (TC) per patient in the intervention group was 49.9€ (95% CI: 46.6-53.2) compared with 52.6€ (95% CI: 46.6-58.6) in the control group. The difference between the groups was not statistically significant (p = 0.09). Sensitivity analysis consistently showed TCs favoring the intervention. The dispensing error proportion was 9.7% (95% CI: 7.9-11.6) in the intervention group compared with 12.8% (95% CI: 10.9-15.6) in the control group. The difference was statistically significant (p = 0.02). The analysis also found changes in the perceptions regarding medication (indicating higher medication adherence), increased satisfaction, and fewer patients with deviations in the medication list at follow-up. No statistically significant differences between the groups in relation to readmissions and GP contacts within 30 days were observed. CONCLUSIONS: SAM seems to cost less although the cost difference was small and not statistically significant. As SAM had positive effects on patient outcomes, the results indicate that SAM may be cost-effective. PLAIN LANGUAGE SUMMARY: Self-administration of medication: a research study of the costs and consequences Objectives To evaluate the costs and consequences of introducing "self-administration of medication" (SAM) during hospitalization compared to medication dispensed by nurses. Methods This research study included patients ≥18 years capable of self-administering medication and was performed in a Danish cardiology unit. Patients self-administered their own medication during hospitalization in the intervention group, whereas nurses dispensed and administered the medication in the control group. Patients were allocated between groups by randomization. The costs of SAM were analyzed from a hospital perspective and included costs for medication, materials, and nursing time. The consequences included the proportion of dispensing errors, patients' perceptions regarding medication, patient satisfaction, deviations in the medication list at follow-up, the number of readmissions and general practitioner (GP) contacts within 30 days after discharge. Results The total cost per patient was 49.9€ in the intervention group compared to 52.6€ in the control group (p = 0.09). The cost difference between groups was not significant. The proportion of dispensing errors was significantly lower in the intervention group compared to the control group. In addition the research study found changes in the perceptions regarding medication, increased satisfaction, and fewer patients with deviations in the medication list at follow-up. For readmissions and GP contacts within 30 days no significant differences between groups were found. Conclusion SAM cost less or equal to medication dispensing and administration by nurse. SAM had positive impacts on patient outcomes. Therefore, SAM may be cost-effective.

Self-administration of medication during hospitalization-a randomized pilot study.

BACKGROUND: Self-administration of medication (SAM) during hospitalization is a complex intervention where patients are involved in their course of treatment. The study aim was to pilot test the SAM intervention. The objectives were to assess the feasibility of conducting a randomized controlled trial on the safety and cost-consequences of SAM during hospitalization. METHODS: The study was performed in a Danish cardiology unit.Patients ≥ 18 years capable of self-administering medication during hospitalization were eligible. Patients were excluded if they did not self-administer medication at home, were incapable of self-administering medication, were not prescribed medication suitable for self-administration, did not bring their medication, or were unable to speak Danish.Feasibility was assessed as part of the pilot study. A future randomized controlled trial was considered feasible if it was possible to recruit 60 patients within 3 months, if outcome measurement method was capable of detecting dispensing errors in both groups, and if patients in the intervention group were more satisfied with the medication management during hospitalization compared to the control group.Forty patients were recruited to gain experience about the intervention (self-administration). Additionally, 20 patients were randomized to the intervention or control group (nurse-led dispensing) to gain experience about the randomization procedure.Dispensing error proportions were based on data collected through disguised observation of patients and nurses during dispensing. The error proportion in the control group was used for the sample size calculation. Patient acceptability was assessed through telephone calls. RESULTS: Of the 60 patients recruited, one withdrew and 11 were discharged before observation resulting in analysis of 39 patients in the intervention group and nine in the control group. A dispensing error proportion of 3.4% was found in the intervention group and 16.1% in the control group. A total of 91.7% of patients in the intervention group and 66.7% in the control group were highly satisfied with the medication management during hospitalization. The overall protocol worked as planned. Minor changes in exclusion criteria, intervention, and outcome measures were considered. CONCLUSIONS: It may be feasible to perform a pragmatic randomized controlled trial of the safety and cost-consequences of self-administration of medication during hospitalization. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03541421, retrospectively registered on 30 May 2018.

Self-administration of medication: a pragmatic randomized controlled trial of the impact on dispensing errors, perceptions, and satisfaction.

BACKGROUND: Our aim was to investigate whether self-administration of medication (SAM) during hospitalization affects the number of dispensing errors, perceptions regarding medication, and participant satisfaction when compared with nurse-led medication dispensing. METHODS: A pragmatic randomized controlled trial was performed in a Danish cardiology unit. Patients aged ⩾ 18 years capable of SAM were eligible for inclusion. Patients were excluded if they did not self-administer medication at home, were not prescribed medication suitable for self-administration, or did not speak Danish.Intervention group participants self-administered their medication. In the control group, medication was dispensed and administered by nurses.The primary outcome was the proportion of dispensing errors collected through modified disguised observation of participants and nurses. Dispensing errors were divided into clinical and procedural errors.Secondary outcomes were explored through telephone calls to determine participant perceptions regarding medication and satisfaction, and finally, deviations in their medication list two weeks after discharge. RESULTS: Significantly fewer dispensing errors were observed in the intervention group, with 100 errors/1033 opportunities for error (9.7%), compared with 132 errors/1028 opportunities for error (12.8%) in the control group. The number of clinical errors was significantly reduced, whereas no difference in procedural errors was observed. At follow up, those who were self-administering medication had fewer concerns regarding their medication, found medication to be less harmful, were more satisfied, preferred this opportunity in the future, and had fewer deviations in their medication list after discharge compared with the control group. CONCLUSION: In conclusion, the reduced number of dispensing errors in the intervention group, indicate that SAM is safe. In addition, SAM had a positive impact on (a) perceptions regarding medication, thus suggesting increased medication adherence, (b) deviations in medication list after discharge, and (c) participant satisfaction related to medication management at the hospital.

Clinical Outcomes Used in Clinical Pharmacy Intervention Studies in Secondary Care.

The objective was to investigate type, frequency and result of clinical outcomes used in studies to assess the effect of clinical pharmacy interventions in inpatient care. The literature search using Pubmed.gov was performed for the period up to 2013 using the search phrases: "Intervention(s)" and "pharmacist(s)" and "controlled" and "outcome(s)" or "effect(s)". Primary research studies in English of controlled, clinical pharmacy intervention studies, including outcome evaluation, were selected. Titles, abstracts and full-text papers were assessed individually by two reviewers, and inclusion was determined by consensus. In total, 37 publications were included in the review. The publications presented similar intervention elements but differed in study design. A large variety of outcome measures (135) had been used to evaluate the effect of the interventions; most frequently clinical measures/assessments by physician and health care service use. No apparent pattern was established among primary outcome measures with significant effect in favour of the intervention, but positive effect was most frequently related to studies that included power calculations and sufficient inclusion of patients (73% vs. 25%). This review emphasizes the importance of considering the relevance of outcomes selected to assess clinical pharmacy interventions and the importance of conducting a proper power calculation.

Investigating the Relative Significance of Drug-Related Problem Categories.

The aim of the review was to investigate whether an assessment of clinical significance can be related to specific drug-related problems (DRPs) and hence may assist in prioritizing individual categories of DRP categorization systems. The literature search using Google Scholar was performed for the period 1990 to 2013 and comprised primary research studies of clinical pharmacy interventions including DRP and clinical significance assessments. Two reviewers assessed the titles, abstracts, and full-text papers individually, and inclusion was determined by consensus. A total of 27 unique publications were included in the review. They had been conducted in 14 different countries and reported a large range of DRPs (71-5948). Five existing DRP categorisation systems were frequently used, and two methods employed to assess clinical significance were frequently reported. The present review could not establish a consistent relation between the DRP categories and the level of clinical significance. However, the categories "ADR" and possibly "Drug interaction" were often associated with an assessed high clinical significance, albeit they were infrequently identified in the studies. Hence, clinical significance assessments do not seem to be useful in prioritizing individual DRPs in the DRP categorization systems. Consequently, it may be necessary to reconsider our current approach for evaluating DRPs.

The challenges of outcome research.

Cognitive pharmacy trials seek to identify interventions that benefit patients. The potential benefits of an intervention are primarily evaluated by outcome measures. The question then is: What is the optimal outcome measure? Unfortunately, the question remains unsolved. Several factors must be taken into consideration when conducting outcome research-particularly within cognitive pharmacy trials. The interventions are often complex and non-specific, and seek to improve symptom control, optimise the use of medications and reduce medication-related risks. "Hard" endpoints, such as mortality and hospital admissions, may not be the optimal outcome measures, since cognitive pharmacy interventions are unlikely to result in changes in these measures. Instead, adverse drug events or "soft" endpoints, such as quality of life, drug-related problems and patient satisfaction may be appropriate choices of outcome measures. Finally, it is not only outcome measures that may pose a challenge when conducting outcome research; other essential components include study design, type of intervention, the patient population, etc.

The Danish 22q11 research initiative.

BACKGROUND: Neurodevelopmental brain disorders such as schizophrenia, autism and attention deficit hyperactivity disorder are complex disorders with heterogeneous etiologies. Schizophrenia and autism are difficult to treat and often cause major individual suffering largely owing to our limited understanding of the disease biology. Thus our understanding of the biological pathogenesis needs to be substantiated to enable development of more targeted treatment options with improved efficacy. Insights into the pre-morbid disease dynamics, the morbid condition and the underlying biological disease mechanisms may come from studies of subjects with homogenous etiologies. Breakthroughs in psychiatric genetics have shown that several genetic anomalies predispose for neurodevelopmental brain disorders. We have established a Danish research initiative to study the common microdeletion at chromosome 22q11.2, which is one of the genetic anomalies that confer high risk of schizophrenia, autism and attention deficit hyperactivity disorder. METHODS/DESIGN: The study applies a "cause-to-outcome" strategy to identify pre-morbid pathogenesis and underlying biological disease mechanisms of psychosis and secondarily the morbid condition of autism and attention deficit hyperactivity disorder. We use a population based epidemiological design to inform on disease prevalence, environmental risk factors and familial disposition for mental health disorders and a case control study design to map the functional effects across behavioral and neurophysiological traits of the 22q11 deletion in a recruited sample of Danish individuals. DISCUSSION: Identification of predictive pre-morbid clinical, cognitive, functional and structural brain alterations in 22q11 deletion carriers may alter current clinical practice from symptomatic therapy of manifest mental illness into early intervention strategies, which may also be applicable to at risk subjects without known etiology. Hopefully new insights into the biological disease mechanisms, which are mandatory for novel drug developments, can improve the outcome of the pharmacological interventions in psychiatry.

Correlation between the use of 'over-the-counter' medicines and adherence in elderly patients on multiple medications.

BACKGROUND: Medication adherence is a multifaceted issue that is influenced by various factors. One factor may be the concurrent use of over-the-counter (OTC)medicines. The use of OTC medicine has been reported as common amongst elderly patients. OBJECTIVE: To determine if a correlation exists between the use of OTC medicines and adherence to prescribed medications in elderly patients. SETTING: Non-institutionalised elderly patients in Denmark. METHODS: Elderly unassisted patients aged ≥65 prescribed five or more prescription drugs were included in the study. Information on the use of concurrent OTC medications (herbal medicines, dietary supplements, or non-prescribed drugs) was elicited during home visit interviews. Prescription drug adherence was determined by pill counts. A patient was categorised as non-adherent if the me an adherence rate for all drugs consumed was\80 %. Different sensitivity analyses were made where adherence was defined different. MAIN OUTCOME MEASURE: Medication adherence based on pill-count. RESULTS: A total of 253 participants included 72 % who used OTC medicines and 11 % who did not adhere to their prescriptions. Users of OTC medicines, however, were significantly more likely to be adherent than were non-users (odds ratio 0.41; 95 %confidence interval 0.18­0.91). Sensitivity analyses where adherence was defined different show no relationship between adherence and use of OTC medicine. Furthermore,separate analyses of herbal medicines, dietary supplements,or non-prescribed drugs did not correlate with adherence to prescriptions. CONCLUSION: Amongst elderly patients on multiple medications a positive relationship was found between the overall use of OTC medicines and adherence to prescription drugs, in contrast to none when adherence were defined different or herbal medicines, dietary supplements, or non-prescribed drugs were analysed separately.

Impact of pharmaceutical care on adherence, hospitalisations and mortality in elderly patients.

BACKGROUND: Elderly polypharmacy patients may be more at risk of not adhering to medication. If so, the underlying reasons may be more readily disclosed during private discussions with patients. Hence pharmaceutical care discussions at home might improve treatment adherence. OBJECTIVE: The aim of this study was to investigate the impact of pharmaceutical care on medication adherence, hospitalisation and mortality in elderly patients prescribed polypharmacy. SETTING: Pharmaceutical care discussed at home. METHODS: A randomised controlled trial with two arms; pharmaceutical care (n = 315) and controls (n = 315) was designed. It involved patients aged 65+ years living in Aarhus, Denmark who used five drugs or more without assistance. Pharmacists visited the pharmaceuticalcare patients at home, once only, and followed them during the subsequent year with three telephone calls. Non-adherence was measured by a pill-count. Patients were categorised as non-adherent if their mean adherence rate for all drugs consumed was <80 %. The impact of pharmaceutical care on non-adherence and hospitalisation was analysed by 2 × 2 tables, and mortality by Cox regression. MAIN OUTCOME MEASURE: Medication adherence, hospitalisation and mortality. RESULTS: The final analyses included 517 patients (median age 74 years; females 52 %). Dropouts were more frequent for the pharmaceutical-care group than for controls. Pharmacists encountered drug-related problems amongst 72 % of pharmaceutical-care patients. Pharmaceutical-care patients (11 %) and control patients (10 %) were similarly nonadherent (Odds ratio 1.14; 95 % confidence interval 0.65-2.00), and similar with respect to hospitalisation frequency (30 vs. 28 %; Odds ratio 1.14; 95 % confidence interval 0.78-1.67) and mortality (7.5 vs. 5 %; Hazard ratio 1.41; 95 % confidence interval 0.71-2.82). CONCLUSIONS: Pharmaceutical care given to our elderly polypharmacy patients made no significant impact on medication adherence, hospitalisation or mortality, when compared to comparable control patients.

Correlation between the use of 'over-the-counter' medicines and adherence in elderly patients on multiple medications.

Background Medication adherence is a multifaceted issue that is influenced by various factors. One factor may be the concurrent use of over-the-counter (OTC) medicines. The use of OTC medicine has been reported as common amongst elderly patients. Objective To determine if a correlation exists between the use of OTC medicines and adherence to prescribed medications in elderly patients. Setting Non-institutionalised elderly patients in Denmark. Methods Elderly unassisted patients aged ≥65 prescribed five or more prescription drugs were included in the study. Information on the use of concurrent OTC medications (herbal medicines, dietary supplements, or non-prescribed drugs) was elicited during home visit interviews. Prescription drug adherence was determined by pill counts. A patient was categorised as non-adherent if the mean adherence rate for all drugs consumed was <80 %. Different sensitivity analyses were made where adherence was defined different. Main outcome measure Medication adherence based on pill-count. Results A total of 253 participants included 72 % who used OTC medicines and 11 % who did not adhere to their prescriptions. Users of OTC medicines, however, were significantly more likely to be adherent than were non-users (odds ratio 0.41; 95 % confidence interval 0.18-0.91). Sensitivity analyses where adherence was defined different show no relationship between adherence and use of OTC medicine. Furthermore, separate analyses of herbal medicines, dietary supplements, or non-prescribed drugs did not correlate with adherence to prescriptions. Conclusion Amongst elderly patients on multiple medications a positive relationship was found between the overall use of OTC medicines and adherence to prescription drugs, in contrast to none when adherence were defined different or herbal medicines, dietary supplements, or non-prescribed drugs were analysed separately.

Generic substitution does not seem to affect adherence negatively in elderly polypharmacy patients.

PURPOSE: To investigate the association between generic substitutions and medication adherence in elderly patients with prescribed polypharmacy. METHODS: Our study included 672 patients aged 65+ years, living at home in the municipality of Aarhus (Denmark), who at the time of enrolment took at least five prescription drugs daily including both short-term and long-term treatment independently of kind of administration route but without assistance. In this paper, only oral drugs for long-term treatment are included in the analysis resulting in median of three drugs per patient. Adherence was assessed by pill counts. Patients with a mean adherence rate <80% across all oral drugs consumed for long-term treatment were categorised as non-adherent. The number of generic substitutions during 1 year was retrieved from the National Health Insurance prescription database. Each change in either a drug's or a manufacturer's name was regarded as a substitution. The association between generic substitution and the mean adherence rate to all drugs was analysed by contingency table analyses and a trend test. RESULTS: During 1 year, at least one substitution was experienced by 83.6% of patients (n = 562). Patients non-adherent to long-term oral treatment (n = 46) amounted to 8% of all patients who experienced substitutions. Amongst 110 elderly patients (16.4%) who did not experience substitutions, 16% were non-adherent (odds ratio 0.46; 95% confidence interval 0.25-0.82). CONCLUSION: As generic substitution in elderly patients undergoing polypharmacy appears not to affect adherence to long-term drug treatment negatively, there seems to be no obvious reason for avoiding generic substitution in such patients.

Enhanced maternal origin of the 22q11.2 deletion in velocardiofacial and DiGeorge syndromes.

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.

Chromosome 22q11.2 duplication is rare in a population-based cohort of Danish children with cardiovascular malformations.

The prevalence of the 22q11.2 duplication is unknown in children with cardiovascular malformations (CVMs). As most individuals with the duplication are detected in the search for other conditions, especially the 22q11.2 deletion, CVMs associated with the duplication are subject to referral bias. We circumvented this bias by investigating the prevalence of the 22q11.2 duplication in a population-based cohort of children with CVMs. The study population was defined as children born in 2000-2008, who were registered in the Danish National Patient Registry with a diagnosis of CVM from one of the two national university departments of pediatric cardiology. Sensitive multiplex ligation-dependent probe amplification was performed on dried blood spot samples from each individual's neonatal screening test. The study population consisted of 2,952 children with CVMs, 2,424 of whom were eligible for genetic testing; 13 individuals (0.5% [0.3-0.9%]) carried the duplication. Nine individuals (69%) had not previously been tested for a copy number variation on chromosome 22q11.2 in the clinical setting for children with CVMs. We conclude that 22q11.2 duplication is rare in children with CVMs, and is primarily found in malformations that are also associated with the 22q11.2 deletion.

The prevalence of chromosome 22q11.2 deletions in 2,478 children with cardiovascular malformations. A population-based study.

Deletion of chromosome 22q11.2 is considered one of the most frequent genetic causes of cardiovascular malformations. It is frequently associated with conotruncal malformations, but may also be present among patients with nonconotruncal malformations. The aim of the present study was to establish the prevalence of the 22q11.2 deletion in an unselected population-based cohort of children with various cardiovascular malformations. The study population was defined as children born in 2000-2008 who were registered in the Danish National Patient Registry with a diagnosis of cardiovascular malformation from one of the two national departments of pediatric cardiology. Sensitive multiplex ligation-dependent probe amplification was performed on dried blood spot samples from each individual's neonatal screening test. Of 2,952 children with cardiovascular malformations, 2,478 were eligible for genetic testing. A total of 46 individuals (1.9% [1.4-2.5%]) carried the deletion, with the highest prevalence among individuals registered with interrupted aortic arch (22% [11-40]). The most frequent diagnoses among individuals carrying the deletion were tetralogy of Fallot (n = 15) and ventricular septal defect (n = 15). One in four cases had not been diagnosed in the usual clinical setting. The prevalence of 22q11.2 deletions in an unselected population-based cohort of children with cardiac malformations was 1.9% [1.4-2.5%]. Genetic testing of every individual registered with a conotruncal malformation would have achieved a diagnostic sensitivity of 70% in the present cohort. Prospective studies outlining testing recommendations in children with ventricular septal defect are warranted.