The prevalence of polypharmacy in older Europeans: A multi-national database study of general practitioner prescribing.

AIMS: The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. METHODS: This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient-level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5-9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6-month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. RESULTS: Age and gender distribution was similar across the six countries (mean age 75-76 years; 54-56% female). The prevalence of polypharmacy of 5-9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. CONCLUSIONS: We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe.

Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.

PURPOSE: The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. METHODS: We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety. RESULTS: Fifty four studies were included. All DOACs were classified as 'no additional risks known' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as 'no additional risks known'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as 'unsafe' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as 'unknown' for CTP C. CONCLUSION: DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.

Maternal Benzodiazepines and Z-Drugs Use during Pregnancy and Adverse Birth and Neurodevelopmental Outcomes in Offspring: A Population-Based Cohort Study.

INTRODUCTION: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. OBJECTIVE: The aim of the study was to evaluate whether gestational benzodiazepine and/or z-drug exposure is associated with adverse birth and neurodevelopmental outcomes. METHODS: A population-based cohort including mother-child pairs from 2001 to 2018 in Hong Kong was analysed to compare gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression with a 95% confidence interval (CI). Sibling-matched analyses and negative control analyses were applied. RESULTS: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95% CI = 0.97-1.25) for preterm birth and 1.03 (95% CI = 0.76-1.39) for small for gestational age, while the weighted hazard ratio (wHR) was 1.40 (95% CI = 1.13-1.73) for ASD and 1.15 (95% CI = 0.94-1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR = 0.84, 95% CI = 0.66-1.06; small for gestational age: wOR = 1.02, 95% CI = 0.50-2.09; ASD: wHR = 1.10, 95% CI = 0.70-1.72; ADHD: wHR = 1.04, 95% CI = 0.57-1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. CONCLUSIONS: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against those of untreated anxiety and sleep problems.

One Health Determinants of Escherichia coli Antimicrobial Resistance in Humans in the Community: An Umbrella Review.

To date, the scientific literature on health variables for Escherichia coli antimicrobial resistance (AMR) has been investigated throughout several systematic reviews, often with a focus on only one aspect of the One Health variables: human, animal, or environment. The aim of this umbrella review is to conduct a systematic synthesis of existing evidence on Escherichia coli AMR in humans in the community from a One Health perspective. PubMed, EMBASE, and CINAHL were searched on "antibiotic resistance" and "systematic review" from inception until 25 March 2022 (PROSPERO: CRD42022316431). The methodological quality was assessed, and the importance of identified variables was tabulated across all included reviews. Twenty-three reviews were included in this study, covering 860 primary studies. All reviews were of (critically) low quality. Most reviews focused on humans (20), 3 on animals, and 1 on both human and environmental variables. Antibiotic use, urinary tract infections, diabetes, and international travel were identified as the most important human variables. Poultry farms and swimming in freshwater were identified as potential sources for AMR transmission from the animal and environmental perspectives. This umbrella review highlights a gap in high-quality literature investigating the time between variable exposure, AMR testing, and animal and environmental AMR variables.

A systematic literature review and meta-analysis of community pharmacist-led interventions to optimise the use of antibiotics.

AIMS: The aim of this systematic review is to assess the effects of community pharmacist-led interventions to optimise the use of antibiotics and identify which interventions are most effective. METHODS: This review was conducted according to the PRISMA guidelines (PROSPERO: CRD42020188552). PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for (randomised) controlled trials. Included interventions were required to target antibiotic use, be set in the community pharmacy context, and be pharmacist-led. Primary outcomes were quality of antibiotic supply and adverse effects while secondary outcomes included patient-reported outcomes. Risk of bias was assessed using the 'Cochrane suggested risk of bias criteria' and narrative synthesis of primary outcomes conducted. RESULTS: Seventeen studies were included covering in total 3822 patients (mean age 45.6 years, 61.9% female). Most studies used educational interventions. Three studies reported on primary outcomes, 12 on secondary outcomes and two on both. Three studies reported improvements in quality of dispensing, interventions led to more intensive symptom assessment (up to 30% more advice given) and a reduction of over-the-counter supply up to 53%. Three studies led to higher consumer satisfaction, effects on adherence from nine studies were mixed (risk difference 0.04 [-0.02, 0.10]). All studies had unclear or high risks of bias across at least one domain, with large heterogeneity between studies. CONCLUSIONS: Our review suggests some positive results from pharmacist-led interventions, but the interventions do not seem sufficiently effective as currently implemented. This review should be interpreted as exploratory research, as more high-quality research is needed.

Non-persistence to antihypertensive drug therapy in Lithuania.

PURPOSE: Poor persistence to antihypertensive therapy is an important cause of treatment failure. Investigating persistence is especially important in countries with a high cardiovascular mortality, like Lithuania. The aim of this study was to describe the antihypertensive treatment at initiation, to determine the percentage of patients not being persistent with antihypertensive treatment after 1 year and to explore factors associated with non-persistence. METHODS: In this cohort study, data on dispensed prescription medicines from the Lithuanian National Health Insurance Fund (NHIF) were used. All adult patients with a diagnosis of hypertension having first antihypertensive dispensed in 2018 were included. Descriptive statistics was used to determine the number of patients started with monotherapy and combination therapy. Treatment choice by Anatomical Therapeutic Chemical (ATC) and number of active pharmaceutical ingredient (API) was described. Non-persistence was assessed using the anniversary method. Multivariate logistic regression was used to explore factors associated with non-persistence. RESULTS: A total of 72,088 patients were included into the study, 56% started on monotherapy treatment, with 49% being dispensed an angiotensin converting enzyme inhibitor, and 44% started on combination therapy. Overall, 57% of patients were non-persistent after 1 year. Patients' gender and prescriber qualification showed no association with non-persistence. Younger patients, patients from rural area, patients started with monotherapy, and patients with no medication change had higher odds to become non-persistent. CONCLUSIONS: The majority of patients were initiated with treatment following hypertension management guidelines, but it is of concern that over half of the patients were non-persistent to antihypertensive therapy in the first year.

Understanding reasons for lack of acceptance of HIV programs among indigenous Papuans: a qualitative study in Indonesia.

BACKGROUND: Melanesians are indigenous Papuans racially and culturally different from most Indonesians. The Melanesia region is characterised by high poverty and inequalities, even though it has the highest revenue. Furthermore, Papua has the highest HIV prevalence rate, 24-fold higher than that of other regions. Therefore, this study aimed to examine the resistance of indigenous people residing in eastern Indonesia towards HIV programs. METHODS: This is a qualitative study analysed using grounded theory. Data were collected from July to September 2018 through semi-structured face-to-face interviews involving 23 Papuans. The interviews were conducted in Bahasa Indonesia, audio-recorded, summarised and transcribed for analysis. RESULTS: The results showed that being a good Papuan emerges from four interconnected categories, including culture and religion, dealing with modernisation, integrated HIV program and stigma reduction. As a substantive theory underpinning the indigenous people's experiences with HIV programs, 'Keep being a good Papuan' was a way of overcoming problems and dealing with modernism to eliminate HIV. This largely focuses on the local culture, implying any adjustment should keep their tradition and welcome modernism. CONCLUSIONS: The future of the HIV programs should be agreed upon, funded, implemented, measured and achieved by stakeholders. This could be achieved by elaborating a supportive culture and community-based interventions. Furthermore, the implementation should be prioritised to integrate and improve the programs' quality to take into account community needs and the available resources.

Identifying patients at increased risk of hypoglycaemia in primary care: Development of a machine learning-based screening tool.

INTRODUCTION: In primary care, identifying patients with type 2 diabetes (T2D) who are at increased risk of hypoglycaemia is important for the prevention of hypoglycaemic events. We aimed to develop a screening tool based on machine learning to identify such patients using routinely available demographic and medication data. METHODS: We used a cohort study design and the Groningen Initiative to ANalyse Type 2 diabetes Treatment (GIANTT) medical record database to develop models for hypoglycaemia risk. The first hypoglycaemic event in the observation period (2007-2013) was the outcome. Demographic and medication data were used as predictor variables to train machine learning models. The performance of the models was compared with a model using additional clinical data using fivefold cross validation with the area under the receiver operator characteristic curve (AUC) as a metric. RESULTS: We included 13,876 T2D patients. The best performing model including only demographic and medication data was logistic regression with least absolute shrinkage and selection operator, with an AUC of 0.71. Ten variables were included (odds ratio): male gender (0.997), age (0.990), total drug count (1.012), glucose-lowering drug count (1.039), sulfonylurea use (1.62), insulin use (1.769), pre-mixed insulin use (1.109), insulin count (1.827), insulin duration (1.193), and antidepressant use (1.05). The proposed model obtained a similar performance to the model using additional clinical data. CONCLUSION: Using demographic and medication data, a model for identifying patients at increased risk of hypoglycaemia was developed using machine learning. This model can be used as a tool in primary care to screen for patients with T2D who may need additional attention to prevent or reduce hypoglycaemic events.

Using pharmacy dispensing data to predict falls in older individuals.

AIMS: Associations between individual medication use and falling in older individuals are well-documented. However, a comprehensive risk score that takes into account overall medication use and that can be used in daily pharmacy practice is lacking. We, therefore, aimed to determine whether pharmacy dispensing records can be used to predict falls. METHODS: A retrospective cohort study was conducted using pharmacy dispensing data and self-reported falls among 3454 Dutch individuals aged ≥65 years. Two different methods were used to classify medication exposure for each person: the drug burden index (DBI) for cumulative anticholinergic and sedative medication exposure as well as exposure to fall risk-increasing drugs (FRIDs). Multinomial regression analyses, adjusted for age and sex, were conducted to investigate the association between medication exposure and falling classified as nonfalling, single falling and recurrent falling. The predictive performances of the DBI and FRIDs exposure were estimated by the polytomous discrimination index (PDI). RESULTS: There were 521 single fallers (15%) and 485 recurrent fallers (14%). We found significant associations between a DBI ≥1 and single falling (adjusted odds ratio: 1.30 [95% confidence interval {CI}: 1.02-1.66]) and recurrent falling (adjusted odds ratio: 1.60 [95%CI: 1.25-2.04]). The PDI of the DBI model was 0.41 (95%CI: 0.39-0.42) and the PDI of the FRIDs model was 0.45 (95%CI: 0.43-0.47), indicating poor discrimination between fallers and nonfallers. CONCLUSION: The study shows significant associations between medication use and falling. However, the medication-based models were insufficient and other factors should be included to develop a risk score for pharmacy practice.

Trends in polypharmacy and potentially inappropriate medication (PIM) in older and middle-aged people treated for diabetes.

AIMS: Polypharmacy is common in people with diabetes and is associated with the use of potentially inappropriate medication (PIM). This study aimed to assess trends in the prevalence of polypharmacy and PIM in older and middle-aged people with diabetes. METHODS: A repeated cross-sectional study using the University Groningen IADB.nl prescription database was conducted. All people aged 45 years and over who were treated for diabetes registered in the period 2012-2016 were included. Polypharmacy was assessed for three age groups. PIMs were assessed using Beers criteria for people ≥65 years old, and PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria for 45-64 years old. Chi-square tests and regression analysis were applied. RESULTS: The prevalence of polypharmacy increased significantly in all age groups in the study period. In 2016, the prevalence of polypharmacy was 36.9% in patients aged 45-54 years, 50.3% in those aged 55-64 years, and 66.2% in those aged ≥65 years. The prevalence of older people with at least one PIM decreased by 3.1%, while in the middle-aged group this prevalence increased by 0.9% from 2012 to 2016. The most common PIMs in both age groups were the use of long-term high-dose proton pump inhibitors, benzodiazepines and strong opioids without laxatives. Of those, only benzodiazepines showed a decreasing trend. CONCLUSIONS: Polypharmacy increased in older and middle-aged people with diabetes. While the prevalence of PIM decreased over time in older age, this trend was not observed in middle-aged people with diabetes. Efforts are needed to decrease the use of PIMs in populations already burdened with many drugs, notably at middle age.

Older people's attitudes towards deprescribing cardiometabolic medication.

BACKGROUND: Overtreatment with cardiometabolic medication in older patients can lead to major adverse events. Timely deprescribing of these medications is therefore essential. Self-reported willingness to stop medication is usually high among older people, still overtreatment with cardiometabolic medication is common and deprescribing is rarely initiated. An important barrier for deprescribing reported by general practitioners is the patients' unwillingness to stop the medication. More insights are needed into the influence of patients' characteristics on their attitudes towards deprescribing and differences in these attitudes between cardiometabolic medication groups. METHODS: A survey in older people using cardiometabolic medication using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire was performed. Participants completed the general rPATD and an adapted version for four medication groups. Linear and ordinal logistic regression were used to assess the influence of age, sex, therapeutic area and number of medications used on the patients' general attitudes towards deprescribing. Univariate analysis was used to compare differences in deprescribing attitudes towards sulfonylureas, insulins, antihypertensive medication and statins. RESULTS: Overall, 314 out of 1143 invited participants completed the survey (median age 76 years, 54% female). Most participants (80%) were satisfied with their medication and willing to stop medications if their doctor said it was possible (88%). Age, sex and therapeutic area had no influence on the general attitudes towards deprescribing. Taking more than ten medicines was significantly associated with a higher perceived medication burden. Antihypertensive medication and insulin were considered more appropriate than statins, and insulin was considered more appropriate than sulfonylureas not favouring deprescribing. CONCLUSIONS: The majority of older people using cardiometabolic medication are willing to stop one of their medicines if their doctor said it was possible. Health care providers should take into account that patients perceive some of their medication as more appropriate than other medication when discussing deprescribing.

Type 2 diabetes patients' views on prevention of hypoglycaemia - a mixed methods study investigating self-management issues and self-identified causes of hypoglycaemia.

BACKGROUND: Hypoglycaemia is a common and potentially avoidable adverse event in people with type 2 diabetes (T2D). It can reduce quality of life, increase healthcare costs, and reduce treatment success. We investigated self-management issues associated with hypoglycaemia and self-identified causes of hypoglycaemia in these patients. METHODS: In this mixed methods study qualitative semi-structured interviews were performed, which informed a subsequent quantitative survey in T2D patients. All interviews were audio recorded, transcribed verbatim and coded independently by two coders using directed content analysis, guided by the Theoretical Domains Framework. Descriptive statistics were used to quantify the self-management issues and causes of hypoglycaemia collected in the survey for the respondents that had experienced at least one hypoglycaemic event in the past. RESULTS: Sixteen participants were interviewed, aged 59-84 years. Participants perceived difficulties in managing deviations from routine, and they sometimes lacked procedural knowledge to adjust medication, nutrition or physical activity to manage their glucose levels. Grief and loss of support due to the loss of a partner interfered with self-management and lead to hypoglycaemic events. Work ethic lead some participant to overexerting themselves, which in turn lead to hypoglycaemic events. The participants had difficulties preventing hypoglycaemic events, because they did not know the cause, suffered from impaired hypoglycaemia awareness and/or did not want to regularly measure their blood glucose. When they did recognise a cause, they identified issues with nutrition, physical activity, stress or medication. In total, 40% of respondents reported regular stress as an issue, 24% reported that they regularly overestimated their physical abilities, and 22% indicated they did not always know how to adjust their medication. Around 16% of patients could not always remember whether they took their medication, and 42% always took their medication at regular times. Among the 83 respondents with at least one hypoglycaemic event, common causes for hypoglycaemia mentioned were related to physical activity (67%), low food intake (52%), deviations from routine (35%) and emotional burden (28%). Accidental overuse of medication was reported by 10%. CONCLUSION: People with T2D experience various issues with self-managing their glucose levels. This study underlines the importance of daily routine and being able to adjust medication in relation to more physical activity or less food intake as well as the ability to reduce and manage stress to prevent hypoglycaemic events.

Healthcare professional-led interventions on lifestyle modifications for hypertensive patients - a systematic review and meta-analysis.

BACKGROUND: About 0.9 billion people in the world have hypertension. The mortality due to hypertension increased dramatically over the last decades. Healthcare professionals should support patients with hypertension to modify their lifestyle to decrease blood pressure, but an overview of effective lifestyle interventions is lacking. The aim of this study was to determine whether healthcare professional-led interventions on lifestyle modifications are effective in lowering blood pressure in patients with hypertension. METHODS: A systematic literature review following the PRISMA guidelines was conducted. PubMed, EMBASE and CINAHL databases were searched for randomized control trials (RCTs) of interventions on lifestyle modifications of hypertensive patients which were performed by healthcare professionals (physician, nurse, pharmacist) and which reported blood pressure measurements. Papers were reviewed by two reviewers and analysed using Cochrane software Revman 5.4. In a meta-analysis difference in systolic blood pressure (SBP), diastolic blood pressure (DBP) and the percentage of patients with controlled blood pressure (BP) was analysed. RESULTS: In total, 34 clinical trials reporting on 22,419 patients (mean age 58.4 years, 49.14% female, 69.9% used antihypertensive medications) were included. The mean difference SBP was - 4.41 mmHg (95% CI, - 5.52to - 3.30) and the mean difference DBP was - 1.66 mmHg (95% CI - 2.44 to - 0.88) in favor of the intervention group vs usual care. Fifty-six percent of patients achieved BP control in the intervention group vs 44% in usual care, OR = 1.87 (95% CI, 1.51 to 2.31). CONCLUSION: Healthcare professional-led interventions were effective. Patients achieved almost 5 mmHg decrease of SBP and more patients achieved BP control. The results suggest that efforts are needed for widespread implementation.

Medication safety in patients with hepatic impairment: A survey of community pharmacists' knowledge level and their practice in caring for these patients.

AIMS: To study community pharmacists' level of knowledge on medication safety in patients with hepatic impairment and their practice in caring for these patients. METHODS: Pharmacists from Dutch community pharmacies (n = 1545) were invited to participate in an online survey. The survey consisted of 27 questions covering 2 main topics: knowledge and current practice. The level of knowledge was measured by a 6-item knowledge test. Multiple linear regression was used to identify predictors of correctly answered responses. RESULTS: In total, 338 pharmacists (22%) completed the questionnaire. The mean knowledge score was 2.8 (standard deviation 1.6). Only 30.3% of respondents were able to appropriately advise on use of analgesics in severe cirrhosis. Postgraduate education on hepatic impairment, knowledge of recently developed practical guidance, and fewer years of practice were associated with a higher level of knowledge. In total, 70.4% indicated to evaluate medication safety in a patient with hepatic impairment at least once weekly. In the past 6 months, 83.3% of respondents consulted a prescriber about a patient with hepatic impairment. Frequently encountered barriers in practice were insufficient knowledge on the topic and a lack of essential patient information (i.e. diagnosis and severity of the impairment). CONCLUSION: Community pharmacists regularly evaluate the safety of medication in patients with hepatic impairment, yet their level of knowledge was insufficient and additional education is needed. Pharmacists experienced several difficulties in providing pharmaceutical care. If these issues are resolved, pharmacists can play a more active role in ensuring medication safety in their patients with hepatic impairment.

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study.

PURPOSE: To assess whether extracorporeal treatment (ECTR) improves outcome of patients with metformin-associated lactic acidosis (MALA) and to evaluate the clinical applicability of the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) criteria for starting ECTR in metformin poisoning. METHODS: Patients with metformin serum concentrations above 2 mg/l who were admitted in the Deventer Teaching Hospital between January 2000 and July 2019 and complied with the definition of MALA (pH < 7.35 and lactate concentration > 5 mmol/l) were included. Mortality and clinical parameters of patients treated with ECTR or not were compared. In addition, treatment of MALA in clinical practice was verified against the criteria of EXTRIP. RESULTS: Forty-two patients were included. Lactate (13.8 versus 10.5 mmol/l, p = 0.01), creatinine (575 versus 254 umol/l, p < 0.01)), metformin (29.4 versus 8.6 mg/l, p < 0.01) concentrations, and vasopressor requirement (72% versus 23%, p < 0.01) were significantly higher in the ECTR-group. Blood pH (7.05 versus 7.19, p = 0.03) and bicarbonate (6 versus 11 mmol/l, p < 0.01) were significantly lower. Mortality, length of hospital stay, and mechanical ventilation requirement were not statistically different. In 83% of patients, treatment of MALA was in accordance with the EXTRIP criteria. CONCLUSIONS: Although there was no statistical benefit in mortality shown from ECTR, ECTR might be lifesaving in MALA, considering the ECTR-group was significantly sicker than the non-ECTR-group. The majority of patients were treated in line with the EXTRIP criteria. Severity of lactic acidosis and renal impairment were the main indications for initiating ECTR.

Vietnamese version of the coronary artery disease education questionnaire-Short version: Translation, adaptation and validation.

WHAT IS KNOWN AND OBJECTIVE: Coronary artery disease (CAD) is the leading cause of mortality worldwide. Patient education is an essential part of cardiac patients' care targeting self-management behaviour to reduce risk factors and subsequent events. There has been no Vietnamese questionnaire to assess patient's knowledge about CAD; therefore, the purpose of this study was to translate, cross-culturally adapt and validate the Coronary Artery Disease Education Questionnaire-Short Version (CADE-Q SV) for use in Vietnam. METHODS: Translation and cross-cultural adaption of the tool were carried out in five stages: (a) two independent translations from English into Vietnamese were produced; (b) these two translations were then synthesized; (c) two translators blinded to the outcome measurements independently created separate back translations into English; (d) nine experts reached consensus on all items of the Vietnamese version of the CADE-Q SV; and (e) a pilot study was conducted on 35 patients with acute coronary syndrome (ACS). The validity and reliability of the questionnaires were then evaluated in 117 Vietnamese patients with ACS. The internal consistency and test-retest reliability were assessed by Cronbach's alpha and Cohen's kappa coefficient, respectively. Construct validity was determined by examining the relationship between knowledge scores and patient characteristics. RESULTS: The Vietnamese version of CADE-Q SV was created, including 20 items divided into two domains: medical and psychological condition, and nutrition and exercise. There was good equivalence between the original and the Vietnamese versions in all four areas: semantic, idiomatic, experiential and conceptual equivalence. Cronbach's alpha coefficients were acceptable for the questionnaire as a whole (0.78) and for the two domains: medical and psychological condition (0.71) and nutrition and exercise (0.52). All Cohen's kappa coefficients confirmed test-retest reliability (Kappa > 0.600; P < .001). Construct validity was confirmed by a significant correlation of knowledge scores with education level (P = .004). WHAT IS NEW AND CONCLUSION: The Vietnamese version of CADE-Q SV can be considered a valid and reliable questionnaire to evaluate patient's knowledge of CAD. Further studies could investigate the influence of knowledge scores on adherence to medications and clinical outcomes of patients with CAD.

Factors associated with workarounds in barcode-assisted medication administration in hospitals.

AIMS AND OBJECTIVES: To identify that workarounds (defined as "informal temporary practices for handling exceptions to normal procedures or workflow") by nurses using information technology potentially compromise medication safety. Therefore, we aimed to identify potential risk factors associated with workarounds performed by nurses in Barcode-assisted Medication Administration in hospitals. BACKGROUND: Medication errors occur during the prescribing, distribution and administration of medication. Errors could harm patients and be a tragedy for both nurses and medical doctors involved. Interventions to prevent errors have been developed, including those based on information technology. To cope with shortcomings in information technology-based interventions as Barcode-assisted Medication Administration, nurses perform workarounds. Identification of workarounds in information technology is essential to implement better-designed software and processes which fit the nurse workflow. DESIGN: We used the data from our previous prospective observational study, performed in four general hospitals in the Netherlands using Barcode techniques, to administer medication to inpatients. METHODS: Data were collected from 2014-2016. The disguised observation was used to gather information on potential risk factors and workarounds. The outcome was a medication administration with one or more workarounds. Logistic mixed models were used to determine the association between potential risk factors and workarounds. The STROBE checklist was used for reporting our data. RESULTS: We included 5,793 medication administrations among 1,230 patients given by 272 nurses. In 3,633 (62.7%) of the administrations, one or more workarounds were observed. In the multivariate analysis, factors significantly associated with workarounds were the medication round at 02 p.m.-06 p.m. (adjusted odds ratio [OR]: 1.60, 95% CI: 1.05-2.45) and 06 p.m.-10 p.m. (adjusted OR: 3.60, 95% CI: 2.11-6.14) versus the morning shift 06 a.m.-10 a.m., the workdays Monday (adjusted OR: 2.59, 95% CI: 1.51-4.44), Wednesday (adjusted OR: 1.92, 95% CI: 1.2-3.07) and Saturday (adjusted OR: 2.24, 95% CI: 1.31-3.84) versus Sunday, the route of medication, nonoral (adjusted OR: 1.28, 95% CI: 1.05-1.57) versus the oral route of drug administration, the Anatomic Therapeutic Chemical classification-coded medication "other" (consisting of the irregularly used Anatomic Therapeutic Chemical classes [D, G, H, L, P, V, Y, Z]) (adjusted OR: 1.49, 95% CI: 1.05-2.11) versus Anatomic Therapeutic Chemical class A (alimentary tract and metabolism), and the patient-nurse ratio ≥6-1 (adjusted OR: 5.61, 95% CI: 2.9-10.83) versus ≤5-1. CONCLUSIONS: We identified several potential risk factors associated with workarounds performed by nurses that could be used to target future improvement efforts in Barcode-assisted Medication Administration. RELEVANCE TO CLINICAL PRACTICE: Nurses administering medication in hospitals using Barcode-assisted Medication Administration frequently perform workarounds, which may compromise medication safety. In particular, nurse workload and the patient-nurse ratio could be the focus for improvement measures as these are the most clearly modifiable factors identified in this study.

Prefilled Cyclic Olefin Sterilized Syringes of Norepinephrine Injection Solution Do Not Need to Be Stabilized by Antioxidants.

Norepinephrine is a potent α-sympathomimetic drug which plays an important role in the acute treatment of hypotension and shock. Commercially available norepinephrine solutions contain sodium metabisulfite (Na2S2O5) as an antioxidant. However, prefilled cyclic olefin polymer syringes are not compatible with sodium metabisulfite. The aim of this study was to develop a new formulation of 0.1-mg/mL norepinephrine solution without sodium metabisulfite which is chemically stable and sterile and can be stored in prefilled polymer syringes. Formulation studies were performed with 0.1-mg/mL norepinephrine solution with 0, 0.05, or 0.1% ascorbic acid added as antioxidant. The syringes were filled under nitrogen gassing, stored at 20 ± 5°C, and protected from daylight. Based on the formulation test results, the final formulation was defined and stability testing at 20 ± 5°C was performed measuring norepinephrine concentration, pH, clarity, color of the solution, subvisible particles, and sterility at time intervals up to 12 months. The norepinephrine concentrations at t = 22 weeks were 100.4%, 95.4%, and 92.2% for the formulations with no ascorbic acid and with 0.05% and 0.10% ascorbic acid, respectively. Three batches for the stability study were produced containing norepinephrine, sodium edetate, sodium chloride, and water for injections filled under nitrogen gassing and stored at 20 ± 5°C. Norepinephrine concentrations were respectively 98.8%, 98.6%, and 99.3% for batches 1, 2, and 3 at t = 12 months. It can be concluded that norepinephrine (0.1 mg/mL) solution without metabisulfite is stable for at least 12 months at room temperature when protected from daylight.

The Vietnamese Version of the Brief Illness Perception Questionnaire and the Beliefs about Medicines Questionnaire: Translation and Cross-cultural Adaptation.

OBJECTIVE: To translate and cross-culturally adapt the Brief Illness Perception Questionnaire (BIPQ) and the Beliefs about Medicines Questionnaire (BMQ) into Vietnamese. METHODS: We followed the guideline by Beaton et al. (2000 & 2007). Stage I: two translators (informed and uninformed) translated the questionnaires. Stage II: the translations were synthesised. Stage III: back translation was performed by two translators fluent in both Vietnamese and English but naïve to the outcome measurement. Stage IV: seven experts reached consensus on the pre-final Vietnamese version (BIPQ-V and BMQ-V). Stage V: field test of the questionnaires on 16 twelve-year-old students and 31 Vietnamese patients. In addition, we determined the internal consistency and test-retest reliability of the questionnaires in 34 Vietnamese patients with acute coronary syndrome. RESULTS: All experts agreed that there was semantic, idiomatic, experiential and conceptual equivalence between the original and pre-final Vietnamese versions of the BIPQ and BMQ. Cronbach's alpha coefficients of the internal consistency were acceptable for the BMQ-V Specific-Necessity (0.64), BMQ-V Specific-Concerns (0.62) and BMQ-V General-Harm (0.60), with the exception of BMQ-V General-Overuse (0.27). Intra-class correlation coefficients of the test-retest reliability were acceptable for the subscales of BMQ-V (range: 0.77-0.86), and BIPQ-V items (range: 0.62-0.85) with the exception of BIPQ-V 1 (0.44, 95% CI -014 to 0.72) and BIPQ-V 4 (0.57, 95% CI 0.22-0.81). CONCLUSIONS: The Vietnamese version of BIPQ and BMQ are reliable tools to assess illness perceptions and beliefs about medicines of patients with acute coronary syndrome. Psychometric properties of these questionnaires should be tested in different patient populations.

OBJECTIF: Traduire en vietnamien et adapter culturellement le Bref Questionnaire sur la Perception de la Maladie (BIPQ) et le Questionnaire sur les Croyances relatives aux Médicaments (BMQ). MÉTHODES: Nous avons suivi les directives de Beaton et al. (2000 et 2007). Etape I: deux traducteurs (informés et non informés) ont traduit les questionnaires. Etape II: les traductions ont été synthétisées. Etape III: une re-traduction a été effectuée par deux traducteurs parlant couramment le vietnamien et l'anglais mais naïfs sur la mesure des résultats. Etape IV: sept experts sont parvenus à un consensus sur la version vietnamienne pré-finale (BIPQ-V et BMQ-V). Etape V: test sur le terrain des questionnaires sur 16 étudiants de 12 ans et 31 patients vietnamiens. En outre, nous avons déterminé la cohérence interne et la fiabilité du test/re-test des questionnaires chez 34 patients vietnamiens atteints de syndrome coronarien aigu. RÉSULTATS: Tous les experts ont convenu qu'il existait une équivalence sémantique, idiomatique, expérientielle et conceptuelle entre les versions originales et pré-finale vietnamiennes du BIPQ et du BMQ. Les coefficients alpha de cohérence interne de Cronbach étaient acceptables pour la nécessité spécifique du BMQ-V (0,64), les préoccupations spécifiques du BMQ-V (0,62) et la nocivité générale du BMQ-V (0,60), à l'exception de la qualité générale du BMQ-V (0,27). Les coefficients de corrélation intra-classe de la fiabilité du test/re-test étaient acceptables pour les sous-échelles de BMQ-V (plage: 0,77-0,86) et les éléments du BIPQ-V (plage: 0,62-0,85) à l'exception du BIPQ-V 1 (0,44; IC95%: −014-0,72) et du BIPQ-V 4 (0,57; IC95%: 0,22-0,81). CONCLUSIONS: Les versions vietnamiennes du BIPQ et du BMQ constituent des outils fiables pour évaluer les perceptions relatives à la maladie et les croyances concernant les médicaments destinés aux patients atteints du syndrome coronarien aigu. Les propriétés psychométriques de ces questionnaires doivent être testées dans différentes populations de patients.

A systematic review and meta-analysis of microbial contamination of parenteral medication prepared in a clinical versus pharmacy environment.

PURPOSE: Preparation of parenteral medication in hospitals is a complex process with a risk of microbial contamination of the product, especially when inappropriately prepared. Contaminated parenteral medications can cause severe complications to patients and increase morbidity in hospitals. The aim of this literature review is to systematically evaluate the contamination rate of parenteral medications in hospitals prepared in a pharmacy environment and a clinical environment. METHODS: A literature search of PubMed and EMBASE from 2000 to 2018 was performed. Two different environments where preparation may be carried out were defined. Point estimates and 95% confidence intervals for contamination rates were calculated for each environment of medication preparation. The meta-analysis was performed using a random effects model. RESULTS: The contamination rates in the clinical environment (n = 13 studies) varied between 1.09 and 20.70%. In the pharmacy environment (n = 5), all contamination rates were 0.00% except for one study (0.66%). The point estimates (random effect model) for the overall contamination rate of doses prepared in the clinical environment was 7.47% (5.16-9.79%), and 0.08% for doses prepared in the pharmacy environment. The point estimates (random effect model) for the overall contamination rate of doses prepared by nursing/ medical staff was 7.85% (5.18-10.53%), and 0.08% for doses prepared by pharmacy staff. CONCLUSIONS: Significantly higher contamination rates were found for the preparation of parenteral medication in the clinical environment compared to pharmacy environment. In accordance with recent guidance, the almost 100-fold higher changes of contamination when reconstitution is performed in the clinical environment should urge hospitals to review their reconstitution process and apply risk-reducing measures to improve patient safety of parenteral therapy.