Key factors underlying the willingness of patients with cancer to participate in medication redispensing.

BACKGROUND: Redispensing medication unused by patients to other patients could reduce the environmental burden of medication waste. Simultaneously, associated financial loss could be reduced, particularly for expensive medication such as oral anticancer drugs. An important determinant for successful medication redispensing is patient participation. OBJECTIVE(S): To identify key factors underlying the willingness of patients with cancer to participate in the redispensing of unused oral anticancer drugs. METHODS: Semi-structured interviews via telephone or video call were conducted with adult patients diagnosed with cancer from two Dutch hospitals. The interview guide was framed using the COM-B model for behavioural change, to elicit patients' capability, opportunity and motivation to participate in medication redispensing. Questions were related to patients' willingness to accept redispensed medication, reasons thereof, perceived concerns and needs. Inductive thematic analysis was applied. RESULTS: Seventeen patients (aged 38-82 years, 71% female), with nine different types of cancer participated. The majority of participants supported medication redispensing. Four categories of key factors underlying the willingness of patients with cancer to participate in medication redispensing were identified. First, the driver for participation was having positive societal impact, relating to affordability and sustainability of healthcare. Second, having trust in product quality was a requirement, influenced by preconceived beliefs, quality assurance and patients' knowledge of this process. Third, a facilitator for participating in medication redispensing was adequate provision of information. This concerned awareness of medication waste, information about medication redispensing, support from healthcare providers and other patients, and insight into medication dispensing history. Last, a convenient process for returning unused medication to pharmacies would facilitate participation in medication redispensing. CONCLUSIONS: The willingness of patients with cancer to participate in medication redispensing relates to a drive for achieving positive societal impact, provided that medication is of high quality, there is adequate information provision and a convenient process.

Safety profile of chloroquine and hydroxychloroquine: a disproportionality analysis of the FDA Adverse Event Reporting System database.

OBJECTIVE: The present study aims to identify potential safety signals of chloroquine (CQ) and hydroxychloroquine (HCQ), over the period preceding their repurpose as COVID-19 treatment options, through the analysis of safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. MATERIALS AND METHODS: We performed a disproportionality analysis of FAERS data between the first quarter of 2004 and December 2019 using the OpenVigil2.1-MedDRA software. Disproportionality was quantified using the reporting odds ratio (ROR) and its 95% confidence interval (CIs). The reported mortality of CQ and HCQ was also investigated. RESULTS: The dataset contained 6,635,356 reports. Comparison of the RORs revealed significant differences between CQ and HCQ for the following adverse events: cardiomyopathy, cardiac arrhythmias, retinal disorders, corneal disorders, hearing disorders, headache, hepatic disorders, severe cutaneous reactions, musculoskeletal disorders, and cytopenia. Only CQ was associated with psychotic disorders, suicide, self-injury, convulsions, peripheral neuropathy, and decreased appetite. In multivariable logistic regression, death was more frequently associated with CQ use, advanced age, male sex, co-reported suicide and self-injury, cardiomyopathy, cardiac arrhythmias, and decreased appetite. CONCLUSIONS: Our results confirm previously published evidence and suggest that HCQ has a safer clinical profile compared to CQ, and thus could serve as the drug of choice for future therapeutic purposes.

The effect of non-adherence to antipsychotic treatment on rehospitalization in patients with psychotic disorders.

BACKGROUND AND AIMS: Many patients with psychotic disorders are non-adherent to antipsychotic (AP) medication(s), potentially contributing to rehospitalization. It is unknown whether non-adherence in different phases of AP use is associated with rehospitalization. The aim of this study was to assess the association between non-adherence to APs and rehospitalization in patients with psychotic disorders. Non-adherence was assessed specifically for the initiation, continued drug use and early discontinuation of AP use. METHODS: A retrospective follow-up study was performed. Adult patients were included at discharge if they suffered from schizophrenia, psychotic, or bipolar I disorder; had been hospitalized in a psychiatric hospital for ⩾7 days; and were treated with oral APs. Patients discharged between January 2006 and December 2009 from Altrecht Mental Health Care were included. Non-adherence was studied in the three phases of medication use: initiation, continued drug use (implementation) and (early) discontinuation after discharge until the end of follow up or until patients were rehospitalized. Cox regression analysis was used to assess the strength of the association between non-adherence for the different phases of AP use and rehospitalization during follow up and expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS: A total of 417 patients were included. Patients who did not initiate their APs compared with those who did in the first month (RR = 1.62, 95% CI: 1.19-2.19) and between the first and third month after discharge (RR = 1.70, 95% CI: 1.04-2.79) had the highest risk for rehospitalization during follow up. Overall, patients who did not initiate their AP medication within the first year after discharge had a RR of 2.70 (95% CI: 1.97-3.68) for rehospitalization during follow up compared with those that initiated their AP. CONCLUSION: Not initiating APs right after discharge was associated with an increased risk of rehospitalization. Interventions should aim to promote the initiation of APs soon after discharge to minimize the risk of rehospitalization.

Adverse events related to biologicals used for patients with multiple sclerosis: a comparison between information originating from regulators and information originating from the scientific community.

BACKGROUND AND PURPOSE: Clinical decision making is facilitated by healthcare professionals' and patients' adequate knowledge of the adverse events. This is especially important for biologicals used for treating multiple sclerosis (MS). So far, little is known about whether different information sources report adverse events consistently. METHODS: Biologicals authorized by the European Medicines Agency for the treatment of MS were included in this study. Information on adverse events derived from phase 3 clinical trials from European Public Assessment Reports (EPARs) and from scientific publications was compared. RESULTS: In the study, eight biologicals used for the treatment of MS were included for which the EPAR and/or scientific publication reported a total of 707 adverse events. Approximately one-third of the adverse events was reported in both the EPAR and scientific publication, one-third was only reported in the EPAR and one-third only in the scientific publication. Serious adverse events and adverse events that regulators classified as 'important identified risk' were significantly more often reported in both sources compared to adverse events not classified as such (respectively, 38% vs. 30% and 49% vs. 30%). Adverse events only reported in the EPAR or in the scientific publication were, in general, not described in the benefit-risk section or abstract, which were considered to be the most important sections of the documents. CONCLUSIONS: This study showed that there is substantial discordance in the reporting of adverse events on the same phase 3 trials between EPARs and scientific publications. To support optimal clinical decision making, both documents should be considered.

Prevalence of use of erectile dysfunction medication by Dutch military personnel between 2003 and 2012.

Use of ED medication can be seen as a marker for ED. ED is associated with increasing age, exposure to traumatic events and physical injuries in military veterans. The objective of this study was to assess the prevalence of use of ED medication in Dutch military personnel in the period 2003-2012 and to assess its association with age and psychotropic medication use. Data on dispensing of ED medication, age and co-medication with psychotropic medication of all Dutch military personnel between 2003 and 2012 were collected. The prevalence of ED medication use in each year was estimated, stratified for age and use of psychotropic medication. The number of ED medication users increased a hundredfold from 0.09 to 9.29 per 1000 per year between 2003 and 2012. ED medication was more often used by men over 40 than under 40 (prevalence in 2012: 2.4% vs 0.2%, OR (2003-2012, adjusted for calendar year) 15.6, 95% CI 13.5-17.9) and by men using psychotropic medication (prevalence in 2012: 3.8% vs 0.9%, OR (2003-2012, adjusted for calendar year) 3.13, 95% CI 2.66-3.67). This study shows a strong increase between 2003 and 2012 in a number of ED medication users in male Dutch military personnel. ED medication use increases with age and with psychotropic medication use.

Medication management capacity in relation to cognition and self-management skills in older people on polypharmacy.

OBJECTIVE: To determine the medication management capacity of independently living older people (≥75 years) on polypharmacy (≥ 5 medications) in relation to their cognitive- and self-management skills. DESIGN: Cross-sectional study. SETTING: Two homecare organizations in the Netherlands. PARTICIPANTS: Homecare clients aged 75 and older on polypharmacy (N=95). MEASUREMENTS: The primary outcome measure was medication management capacity, quantified as the number of 'yes' answers (range = 0-17) on the Medication Management Capacity (MMC) questionnaire. Other measures included self-management ability (assessed with the SMAS30) and cognitive skills (assessed with the clock drawing test). RESULTS: Overall, 48.4% (n= 46) of the participants were able to manage their medication by themselves at home. About 40% of the participants were unable to state the names of their medications, even with the aid of a medication list, and about 25% reported having problems with opening medication packages. Correlations were found between self-management ability (Rs = 0.473; p < 0.001), cognitive skills (Rs = 0.372; p < 0.001), and age (Rs = 0.216; p < 0.005) and Medication Management Capacity score. Self-management ability and medication management support were significantly associated with medication management capacity. CONCLUSION: A considerable proportion of independently living older people who receive home care and regularly use five or more medications lack the knowledge and skills needed to independently manage their own medications. Cognition and self management ability were related to medication management capacity. Self-management ability and medication management support were predictors of medication management capacity.

Prevalence of medication use for somatic disease in institutionalized psychiatric patients.

INTRODUCTION: Psychiatric patients may use medications for their psychiatric condition as well as for treating concurrent somatic diseases or somatic side effects of psychiatric medicines. The objective of this study was to estimate the prevalence of use of medication for somatic disease in institutionalized psychiatric patients and changes therein during 2006-2010. METHOD: A cross-sectional study in institutionalized psychiatric patients was performed. Medication use for somatic disease on 10 time points between 2006 and 2010 was investigated and stratified by gender, age, psychiatric medication class and the number of different psychiatric medication classes used. RESULTS: The prevalence of use of medication for somatic disease increased from 67.5% in 2006 to 76.9% in 2010. The median number of medications used for somatic disease per patient was 3 between 2006 and 2010. Approximately one-third (34.1%) of the patients received ≥ 3 medications intended for treating somatic disease in 2006 which increased to 46.3% in 2010. In 2010, the prevalence of medication use for somatic disease was highest for analgesics and antirheumatics (34.0%), acid and bowel related medication (25.6%) and anticholinergic medication (24.2%). Medication use for somatic disease was highest in patients ≥ 60 years (95.3%), patients treated with more than one psychiatric medication class (87.5%) and patients treated with mood stabilizers (90.6%). DISCUSSION: Somatic medication use is high in institutionalized psychiatric patients. More attention is needed for co-use of psychiatric and somatic medications to prevent side effects, drug-disease or drug-drug interactions. More research is needed to investigate if somatic care is optimal in institutionalized psychiatric patients.

Use of serotonergic drugs and the risk of bleeding.

We assessed several classes of serotonergic drugs in order to evaluate whether they constitute a risk factor for hospitalization for bleeding (gastrointestinal, intracranial, or in the female genital tract). A case-control study was conducted using data from the PHARMO record linkage system (RLS). The study population comprised 28,289 cases and 50,786 matched controls. Current use of antidepressant drugs was associated with all three types of bleeding, whereas antipsychotic drugs were associated with an increased risk of gastrointestinal and intracranial bleeding. Current use of ergoline derivatives increased the risk of female genital tract bleeding. The risks of gastrointestinal and intracranial bleeding were higher in new users of antidepressant and antipsychotic drugs as compared with those who were already receiving these drugs. No clear association was found between the degree of affinity for the serotonin (5-HT) transporter or the 5-HT(2A) receptor and the risk of any of the three types of bleeding. The association between antipsychotic drugs and gastrointestinal bleeding may warrant further research, in view of the fact that this association was rather unexpected.

Trials assessing parmacotherapeutic management of aggression in psychiatric patients: comparability with clinical practice.

INTRODUCTION: In a previous review of randomized controlled trials (RCTs) on the pharmacotherapeutic management of aggression, it was shown that there is only weak evidence of effectiveness. In the present study we aim to determine comparability of patients included in these RCTs and patients of psychiatric long-stay wards. METHODS: Exclusion criteria that were used in at least 20% of the RCTs were applied to a sample of aggressive inpatients from clinical practice, in order to find what proportion of these patients would be eligible to participate in the reviewed, high quality RCTs. RESULTS: Only 30% of aggressive psychiatric patients as seen in clinical practice would be eligible to participate in a typical randomized controlled trial based on the most frequently applied exclusion criteria. DISCUSSION: The low comparability of patients included in RCTs with those seen in clinical practice may decrease the generalizability of the findings form RCTs to clinical practice.

Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial.

BACKGROUND: Sialorrhea affects approximately 75% of patients with Parkinson disease (PD). Sialorrhea is often treated with anticholinergics, but central side effects limit their usefulness. Glycopyrrolate (glycopyrronium bromide) is an anticholinergic drug with a quaternary ammonium structure not able to cross the blood-brain barrier in considerable amounts. Therefore, glycopyrrolate exhibits minimal central side effects, which may be an advantage in patients with PD, of whom a significant portion already experience cognitive deficits. OBJECTIVE: To determine the efficacy and safety of glycopyrrolate in the treatment of sialorrhea in patients with PD. METHODS: We conducted a 4-week, randomized, double-blind, placebo-controlled, crossover trial with oral glycopyrrolate 1 mg 3 times daily in 23 patients with PD. The severity of the sialorrhea was scored on a daily basis by the patients or a caregiver with a sialorrhea scoring scale ranging from 1 (no sialorrhea) to 9 (profuse sialorrhea). RESULTS: The mean (SD) sialorrhea score improved from 4.6 (1.7) with placebo to 3.8 (1.6) with glycopyrrolate (p = 0.011). Nine patients (39.1%) with glycopyrrolate had a clinically relevant improvement of at least 30% vs 1 patient (4.3%) with placebo (p = 0.021). There were no significant differences in adverse events between glycopyrrolate and placebo treatment. CONCLUSIONS: Oral glycopyrrolate 1 mg 3 times daily is an effective and safe therapy for sialorrhea in Parkinson disease. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that glycopyrrolate 1 mg 3 times daily is more effective than placebo in reducing sialorrhea in patients with Parkinson disease during a 4-week study.

Pharmacogenetics: from bench to byte.

Despite initial enthusiasm, the use of pharmacogenetics has remained limited to investigation in only a few clinical fields such as oncology and psychiatry. The main reason is the paucity of scientific evidence to show that pharmacogenetic testing leads to improved clinical outcomes. Moreover, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and both physicians and pharmacists might find it difficult to interpret the clinical value of pharmacogenetic test results. Guidelines that link the result of a pharmacogenetic test to therapeutic recommendations might help to overcome these problems, but such guidelines are only sparsely available. In 2001, an early step was taken to develop such guidelines for the therapeutic use of antidepressants, and these included CYP2D6-related dose recommendations drawn from pharmacokinetic study data. However, the use of such recommendations in routine clinical practice remains difficult, because they are currently outside the ambit of the clinical environment and are not accessible during the decision-making process by physicians and pharmacists, namely the prescription and dispensing of drugs.

Laxative prescribing in relation to opioid use and the influence of pharmacy-based intervention.

INTRODUCTION: Opioid-induced constipation is a common problem and can cause serious complications. It is widely advised that laxatives should be started concurrently with opiates, unless there is a clear indication not to do so. OBJECTIVE: This study was undertaken to estimate how often laxatives were started concurrently with opiates and to describe the effect of pharmacy-based interventions to promote the use of laxatives in patients starting opioids. METHODS: Twenty-six community pharmacies identified all patients who received a first prescription for a strong opioid during January and February of 1998, 1999 or 2000. Pharmacists collected information on patient, drug and prescriber characteristics (age, gender, use of opiates and laxatives). A separate questionnaire was used to collect data on pharmacy-based interventions to promote the simultaneous prescribing of laxatives with the opiates. RESULTS: Overall, 37% of the patients receiving an opioid started taking laxatives within 5 days. The percentage of patients who received laxatives simultaneously with opioids increased from 31% in 1998 to 35% in 1999 and 42% in 2000. In 117 (43%) of the opioid prescriptions, pharmacy-based intervention had taken place before the prescription date. Of these, 48.7% was accompanied by a laxative. Opioid prescriptions (n=152) without a pharmacy based intervention were accompanied in 27.6%. After adjustment for covariates (including time trends), pharmacy-based intervention increased the probability of concomitant laxative use 1.9 [95% CI 1.1-3.3] times. DISCUSSION: This study shows that the widely used guideline to start a laxative when prescribing an opioid is not always followed in daily practice. In addition, we showed that pharmacy-based intervention contributed to increasing laxative use in patients receiving opioids.

Drug-related problems in hospitalised patients.

Drug-related problems include medication errors (involving an error in the process of prescribing, dispensing, or administering a drug, whether there are adverse consequences or not) and adverse drug reactions (any response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function). Furthermore, adverse drug events can be defined as an injury--whether or not causally-related to the use of a drug. Drug-related problems are relatively common in hospitalised patients and can result in patient morbidity and mortality, and increased costs. In order to get an overview of studies on drug-related problems in hospitalised patients, with specific attention to the incidence of drug-related problems and their costs, to the possibilities of prevention and to the effect of these interventions, we performed a literature search. Incidences of medication errors reported in studies vary widely. The range of reported incidences of adverse drug reactions is even wider. These wide ranges can be largely explained by the different study methods and definitions used. Problems related to drug therapy may be averted by preventive interventions. Several possibilities for prevention exist, especially for the prevention of medication errors. Prescribing, transcription and interpretation errors can be reduced by using computerised physician order entry. Together with the use of automated dispensing systems and bar-code technology, this will aid in the reduction of both dispensing and administration errors. Education of nursing staff involved in the process of drug distribution is another important measure for preventing medication errors. Finally, the introduction of systems for the early detection of adverse drug reactions may help to reduce problems related to drug therapy. Identifying risk factors that contribute to the development of adverse drug reactions, may aid in the prevention of these reactions.

Para-methylthioamphetamine, a new amphetamine designer drug of abuse.

A case study is described of a patient who was intoxicated after the intake of so-called herbal stimulants. A visit to a physician after the intoxication prompted to this investigation and the case was examined for its direct cause. An interview with the patient revealed that the source of the herbal stimulants was a so-called 'S-5 tablet'. Information provided on the packings of the tablet only indicated the presence of natural alkaloids and vitamins. Toxicological analysis however proved that the 'S-5 tablet' contained para-methylthioamphetamine (MTA), mainly. MTA is a relative unknown amphetamine designer drug, which has only been studied as a model compound in some structure-activity relationship studies. The fact that MTA appeared in tablets was therefore completely unexpected. Not only the potential abuse of this new amphetamine designer drug is a serious matter of concern, but also the misleading information provided with the tablet.

Prophylaxis for venous thromboembolism in hip fracture surgery: total costs and cost effectiveness in The Netherlands.

Fracture of the hip is one of most significant risk factors for development of deep vein thrombosis (DVT) and its complications. A number of pharmacological prophylactic methods are currently available which can reduce the incidence of postoperative thromboembolism in patients undergoing surgery for fracture of the hip. A retrospective analysis of controlled clinical studies was performed to examine in this patient group the total cost of prevention and treatment, and the cost effectiveness in terms of lives saved, of 5 prophylactic regimens--oral anticoagulants, dextran, low dose heparin, low molecular weight (LMW)-heparin and danaparoid sodium--compared with clinical diagnosis and conventional treatment of DVT only. Our results show that the total cost, including the savings in treatment of the complications of DVT, of each prophylactic regimen is less than the total cost of no prophylaxis. Thus, prophylaxis may not only save lives but may also lead to lower costs of care (including prophylaxis costs). The total cost of the new antithrombotic danaparoid sodium is less than that of the other forms of prophylaxis considered and danaparoid sodium appears to be the most cost-effective modality. We conclude that general use of danaparoid sodium in surgery for hip fracture is the most efficient approach to decreasing the incidence of postoperative morbidity and mortality and reducing healthcare expenses for the complications of DVT.