Adoption of new medicines in primary care: A comparison between the uptake of new oral anticoagulants and diabetes medicines.

AIMS: To gain insight in the uptake and practice variation in the prescription of 2 new medicine groups for common conditions in primary care (direct-acting oral anticoagulants [DOACs] and incretin-based therapies) from introduction, around 2007, to 2019 and the correlation between the adoption of those medicines in primary care. METHODS: Prescription data from general practices in the Dutch Nivel Primary Care Database from 2007 to 2019 were used. The percentage of patients with prescriptions for DOACs of all patients with prescriptions for DOACs and vitamin K antagonists was calculated per practice per year, as was the percentage of patients prescribed incretin-based therapies as a proportion of all patients with diabetes medication. Multilevel models were used to estimate practice variation for DOACs and incretin-based therapies, expressed as intraclass correlation coefficients. Linear regression analysis was used to study the association between the prescription of DOACs and incretin-based therapies. RESULTS: Per year, 46-424 general practices and 179 933-1 654 376 patients were included. In 2019, the mean percentage of patients per practice using DOACs or incretin-based therapies was 54.9 and 9.7%, respectively. The intraclass correlation coefficient decreased from 0.75 to 0.024 for DOACs and from 0.33 to 0.074 for incretin-based medicines during the study period. No clear correlation was found between the prescription of DOACs and incretin-based therapies. CONCLUSION: DOACs and incretin-based therapies have different adoption profiles and practice variation is large, especially in the years before these medicines were introduced in guidelines. Early adopters of both medicine classes differ.

Alignment between outcomes and minimal clinically important differences in the Dutch type 2 diabetes mellitus guideline and healthcare professionals' preferences.

To evaluate the clinical benefit of new medicines for type 2 diabetes mellitus (T2DM), the Dutch guideline committee T2DM in primary care established the importance of outcomes and minimal clinically important differences (MCIDs). The present study used an online questionnaire to investigate healthcare professionals' opinions about the importance of outcomes and preferences for MCIDs. A total of 211 physicians, pharmacists, practice nurses, diabetes nurses, nurse practitioners and physician assistants evaluated the importance of mortality, macro- and microvascular morbidity, HbA1c, body weight, quality of life, (overall) hospital admissions and severe and other hypoglycemia on a 9-point scale. All outcomes were considered critical (mean scores 7-9), except for body weight and other hypoglycemia (mean scores 4-6). Only HbA1c and hospital admissions were valued differently by the guideline committee (not critical). Other relevant outcomes according to the respondents were adverse events, ease of use and costs. Median MCIDs were 4 mmol/mol for HbA1c (guideline: 5 mmol/mol) and 3 kg for body weight (guideline: 5 kg weight gain and 2,5 kg weight loss). Healthcare professionals preferred relative risk reductions of 20% for mortality (guideline: 10%) and macrovascular morbidity (guideline: 25%) and 50% for other hypoglycaemia (guideline: 25%). The MCID of 25% for microvascular morbidity, hospital admissions and severe hypoglycaemia corresponded to the guideline-MCID. Healthcare professionals' preferences were thus comparable to the views of the guideline committee. However, healthcare professionals had a stricter view on the importance of HbA1c and hospital admissions and the MCIDs for mortality and other hypoglycemia.

Healthcare Professionals' Preferred Efficacy Endpoints and Minimal Clinically Important Differences in the Assessment of New Medicines for Chronic Obstructive Pulmonary Disease.

BACKGROUND: Registration authorities evaluate effects of new medicines for chronic obstructive pulmonary disease (COPD) on airway obstruction, dyspnea, health status and exacerbations. To establish clinical relevance, minimal clinically important differences (MCIDs) are used. The aim of this study was to investigate which efficacy endpoints and MCIDs healthcare professionals consider clinically relevant for new COPD medicines. MATERIALS AND METHODS: 7,731 Healthcare professionals received an electronic questionnaire. Participants were asked for: 1) preferred efficacy endpoints for new COPD medicines and 2) cut-off values defining clinical relevance for forced expiratory volume in 1 sec (FEV1), Transition Dyspnea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ). Those cut-off values were compared to the MCIDs used by registration authorities, namely 100 ml for FEV1, 1 unit for TDI and 4 units for SGRQ. RESULTS: 227 Healthcare professionals responded to the questionnaire. Most preferred efficacy endpoints were exacerbations (51.0%), airway obstruction (46.9%) and health status (44.9%). Mean cut-off values for TDI and SGRQ were significantly higher than the corresponding MCIDs, mean differences 1.5 (95%CI = 1.3-1.8, p < 0.001) and 7.0 (95%CI = 5.1-8.8, p < 0.001), respectively. The mean cut-off value for FEV1 was comparable to the MCID (mean difference 2.2, 95%CI = -19.9-24.3, p = 0.84). CONCLUSIONS: Healthcare professionals largely agree with efficacy endpoints used for the evaluation of new COPD medicines. However, they seem to prefer higher cut-off values for clinical relevance for TDI and SGRQ than the registration authorities. Effects of new medicines on TDI and SGRQ that are considered clinically relevant by registration authorities do, therefore, not necessarily reflect healthcare professionals' perspectives on clinical relevance.

The effect of biannual medication reviews on the appropriateness of psychotropic drug use for neuropsychiatric symptoms in patients with dementia: a randomised controlled trial.

Objective: We studied the efficacy of biannual structured medication reviews to improve the appropriateness of psychotropic drug (PD) prescriptions for neuropsychiatric symptoms (NPS) in nursing home patients with dementia. Study Design and Setting: In this randomised controlled trial, the intervention encompassed a structured multidisciplinary medication review by physician, pharmacist and nurse. During this 18-month study, the patient's medical files were assessed every 6 months. The primary outcome was the appropriateness of PD prescriptions defined by the Appropriate Psychotropic drug use In Dementia (APID) index sum score, lower scores indicating more appropriate use. Results: At baseline, 380 patients were included, of which 222 were randomised to the intervention group. Compared to the control group, the APID index sum score in the intervention group improved significantly for all PD prescriptions (-5.28, P = 0.005). Conclusion: We advise the implementation of a structured, repeated medication review with the essential roles of pharmacist, physician and nurse, into daily practice. This work was supported and funded by the Netherlands Organisation for Health Research and Development (ZonMw). Netherlands Trial Register (NTR3569).

Only 10% of the psychotropic drug use for neuropsychiatric symptoms in patients with dementia is fully appropriate. The PROPER I-study.

BACKGROUND: This study explores the appropriateness of psychotropic drug (PD) use for neuropsychiatric symptoms (NPS) in nursing home patients with dementia. METHODS: A cross-sectional study on 559 patients with dementia residing on dementia special care units in Dutch nursing homes was conducted. Appropriateness of PD use was assessed using the Appropriate Psychotropic drug use In Dementia (APID) index. The APID index score is calculated using information about individual PDs from patients' medical records. The index encompasses seven (different) domains of appropriateness, i.e. indication, evaluation, dosage, drug-drug interactions, drug-disease interactions, duplications, and therapy duration. RESULTS: A total of 578 PDs were used for NPS by 60% of the nursing home patients. Indication, evaluation, and therapy duration contributed the most to inappropriate use. Ten per cent of the PDs scored fully appropriate according to the APID index sum score, 36% scored fully appropriate for indication, 46% scored fully appropriate for evaluation, and 58% scored fully appropriate for therapy duration. Antidepressants were used the most appropriately, and antiepileptics the most inappropriately. CONCLUSIONS: The minority of the PD use was fully appropriate. The results imply that PD use for NPS in dementia can be improved; the appropriateness should be optimized with a clinical focus on the appropriate indications, evaluations, and therapy duration.

Medication management of febrile children: a qualitative study on pharmacy employees' experiences.

Background While fever is mostly self-limiting, antibiotic prescription rates for febrile children are high. Although every parent who receives a prescription visits a pharmacy, we have limited insight into pharmacy employees' experiences with these parents. Pharmacy employees do however exert an important role in ensuring children receive correct dosages and in advising parents on administration of antibiotics. Objective To describe pharmacists' and pharmacy assistants' experiences with parents contacting a pharmacy for their febrile child, and to identify ways of improving medication management of these children. Setting Community pharmacies in the Netherlands. Method A qualitative study including 24 Dutch pharmacy employees was conducted, performing four focus group discussions among pharmacy employees. Analysis was based on constant comparative technique using open and axial coding. Main outcome measure Pharmacy employees' experiences with parents contacting a pharmacy for their febrile child. Results Three categories were identified: (1) workload and general experience, (2) inconsistent information on antibiotic prescriptions, (3) improving communication and collaboration. Pharmacy employees experienced that dosing errors in antibiotic prescriptions occur frequently and doctors provide inconsistent information on prescriptions. Consequently, they have to contact doctors, resulting in a higher workload for both stakeholders. They believe this can be improved by providing the indication for antibiotics on prescriptions, especially when deviating from standard dosages. Conclusion Pharmacy employees experience a high amount of dosing errors in paediatric antibiotic prescriptions. Providing the indication for antibiotics in febrile children on prescriptions, especially when deviating from standard dosages, can potentially reduce dosage errors and miscommunication between doctors and pharmacy employees.

A reliable and valid index was developed to measure appropriate psychotropic drug use in dementia.

OBJECTIVES: The aim of this study was to develop an index derived from the Medication Appropriateness Index (MAI) items that is suited for clinical studies evaluating appropriateness of psychotropic drug use (PDU) for neuropsychiatric symptoms (NPS) in patients with dementia in nursing homes and to test its reliability and validity. STUDY DESIGN AND SETTING: An expert panel reviewed the MAI items to develop items for appropriateness of PDU; a second, independent, expert panel determined content validity of the items. An interrater reliability study was conducted (N = 54), and a summated index score, based on weighted item scores, was developed to enhance the use in clinical studies. Construct validity was explored using a representative sample of 560 medical records. RESULTS: Five existing MAI items were used, the MAI item "indication" was adjusted, a new item "evaluation" was added, and scoring rules were based on guideline recommendations, to create the Appropriate Psychotropic drugs use In Dementia (APID) index. The second expert panel concluded that all items contributed to the construct "appropriateness." All items and the summated index score had moderate to almost perfect interrater reliability (intraclass correlation coefficient for agreement, 0.577-1). The summated index score showed promising construct validity, for example, no multicollinearity issues were found. CONCLUSION: The results of this study show that the APID index is reliable and valid for measuring appropriateness of PDU for NPS in dementia in nursing homes in clinical studies.

Improving psychotropic drug prescription in nursing home patients with dementia: design of a cluster randomized controlled trial.

BACKGROUND: Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are appropriately prescribed. The aim of the PROPER (PRescription Optimization of Psychotropic drugs in Elderly nuRsing home patients with dementia) II study is to investigate the efficacy of an intervention for improving the appropriateness of psychotropic drug prescription in nursing home patients with dementia. METHODS/DESIGN: The PROPER II study is a multi-center cluster randomized controlled, pragmatic trial using parallel groups. It has a duration of eighteen months and four six-monthly assessments. Six nursing homes will participate in the intervention and six will continue care as usual. The nursing homes will be located throughout the Netherlands, each participating with two dementia special care units with an average of fifteen patients per unit, resulting in 360 patients. The intervention consists of a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. It is conducted by pharmacists, physicians, and nurses and consists of three components: 1) preparation and education, 2) conduct, and 3) evaluation/guidance. The primary outcome is the proportion of patients with appropriate psychotropic drug use. Secondary outcomes are the overall frequency of psychotropic drug use, neuropsychiatric symptoms, quality of life, activities of daily living, psychotropic drug side effects and adverse events (including cognition, comorbidity, and mortality). Besides, a process analysis on the intervention will be carried out. DISCUSSION: This study is expected to improve the appropriateness of psychotropic drug prescription for neuropsychiatric symptoms in nursing home patients with dementia by introducing a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. TRIAL REGISTRATION: Netherlands Trial Registry (NTR): NTR3569.

PROPER I: frequency and appropriateness of psychotropic drugs use in nursing home patients and its associations: a study protocol.

BACKGROUND: Nursing home patients with dementia use psychotropic drugs longer and more frequently than recommended by guidelines implying psychotropic drugs are not always prescribed appropriately. These drugs can have many side effects and effectiveness is limited. Psychotropic drug use between nursing home units varies and is not solely related to the severity of neuropsychiatric symptoms. There is growing evidence indicating that psychotropic drug use is associated with environmental factors, suggesting that the prescription of psychotropic drugs is not only related to (objective) patient factors. However, other factors related to the patient, elderly care physician, nurse and the physical environment are only partially identified. Using a mixed method of qualitative and quantitative research, this study aims to understand the nature of psychotropic drug use and its underlying factors by identifying: 1) frequency and appropriateness of psychotropic drug use for neuropsychiatric symptoms in nursing home patients with dementia, 2) factors associated with (appropriateness of) psychotropic drug use. METHODS: A cross-sectional mixed methods study. For the quantitative study, patients with dementia (n = 540), nursing staff and elderly care physicians of 36 Dementia Special Care Units of 12 nursing homes throughout the Netherlands will be recruited. Six nursing homes with high average rates and six with low average rates of psychotropic drug use, based on a national survey about frequency of psychotropic drug use on units, will be included. Psychotropic drugs include antipsychotics, anxiolytics, hypnotics, antidepressants, anticonvulsants and anti-dementia drugs. Appropriateness will be measured by an instrument based on the Medication Appropriateness Index and current guidelines for treatment of neuropsychiatric symptoms. Factors associated to psychotropic drug use, related to the patient, elderly care physician, nurse and physical environment, will be explored using multilevel regression analyses. For the qualitative study, in depth interviews with staff will be held and analyzed to identify and explore other unknown factors. DISCUSSION: This study will provide insight into factors that are associated with the frequency and appropriateness of psychotropic drug use for neuropsychiatric symptoms. Understanding psychotropic drug use and its associations may contribute to better dementia care.