How much time do emergency department physicians spend on medication-related tasks? A time- and-motion study.

BACKGROUND: Medication-related problems are an important cause of emergency department (ED) visits, and medication errors are reported in up to 60% of ED patients. Procedures such as medication reconciliation and medication review can identify and prevent medication-related problems and medication errors. However, this work is often time-consuming. In EDs without pharmacists, medication reconciliation is the physician's responsibility, in addition to the primary assignments of examining and diagnosing the patient. The aim of this study was to identify how much time ED physicians spend on medication-related tasks when no pharmacists are present in the EDs. METHODS: An observational time-and-motion study of physicians in three EDs in Northern Norway was conducted using Work Observation Method by Activity Timing (WOMBAT) to collect and time-stamp data. Observations were conducted in predefined two-hour observation sessions with a 1:1 relationship between observer and participant, during Monday to Friday between 8 am and 8 pm, from November 2020 to October 2021. RESULTS: In total, 386 h of observations were collected during 225 observation sessions. A total of 8.7% of the physicians' work time was spent on medication-related tasks, of which most time was spent on oral communication about medications with other physicians (3.0%) and medication-related documentation (3.2%). Physicians spent 2.2 min per hour on medication reconciliation tasks, which includes retrieving medication-related information directly from the patient, reading/retrieving written medication-related information, and medication-related documentation. Physicians spent 85.6% of the observed time on non-medication-related clinical or administrative tasks, and the remaining time was spent standby or moving between tasks. CONCLUSION: In three Norwegian EDs, physicians spent 8.7% of their work time on medication-related tasks, and 85.6% on other clinical or administrative tasks. Physicians spent 2.2 min per hour on tasks related to medication reconciliation. We worry that patient safety related tasks in the EDs receive little attention. Allocating dedicated resources like pharmacists to contribute with medication-related tasks could benefit both physicians and patients.

Is anticholinergic and sedative drug burden associated with postdischarge institutionalization in community-dwelling older patients acutely admitted to hospital? A Norwegian registry-based study.

PURPOSE: Investigate the association between anticholinergic (AC) and sedative (SED) drug burden before hospitalization and postdischarge institutionalization (PDI) in community-dwelling older patients acutely admitted to hospital. METHODS: A cross-sectional study using data from the Norwegian Patient Registry and the Norwegian Prescription Database. We studied acutely hospitalized community-dwelling patients ≥70 years during 2013 (N = 86 509). Patients acutely admitted to geriatric wards underwent subgroup analyses (n = 1715). We calculated drug burden by the Drug Burden Index (DBI), use of AC/SED drugs, and the number of AC/SED drugs. Piecewise linearity of DBI versus PDI and a knot point (DBI = 2.45) was identified. Statistical analyses included an adjusted multivariable logistic regression model. RESULTS: In the total population, 45.4% were exposed to at least one AC/SED drug, compared to 52.5% in the geriatric subgroup. AC/SED drugs were significantly associated with PDI. The DBI with odds ratios (ORs) of 1.11 (95% CI 1.07-1.15) for DBI < 2.45 and 1.08 (95% CI 1.04-1.13) for DBI ≥ 2.45. The number of AC/SED drugs with OR of 1.07 (95% CI 1.05-1.09). The AC component of DBI with OR 1.23 and the number of AC drugs with OR 1.13. In the subgroup, ORs were closer to 1 for AC drugs. CONCLUSIONS: The use of AC/SED drugs was highly prevalent in older patients before acute hospital admissions, and significantly associated with PDI. The number, or just using AC/SED drugs, gave similar associations with PDI compared to applying the DBI. Using AC drugs showed higher sensitivity, indicating that to reduce the risk of PDI, a clinical approach could be to reduce the number of AC drugs.

Completeness of medication information in admission notes from emergency departments.

BACKGROUND: Medication lists prepared in the emergency department (ED) form the basis for diagnosing and treating patients during hospitalization. Since incomplete medication information may lead to patient harm, it is crucial to obtain a correct and complete medication list at hospital admission. In this cross-sectional retrospective study we wanted to explore medication information completeness in admission notes from Norwegian EDs and investigate which factors were associated with level of completeness. METHODS: Medication information was assessed for completeness by applying five evaluation criteria; generic name, formulation, dose, frequency, and indication for use. A medication completeness score in percent was calculated per medication, per admission note and per criterion. Quantile regression analysis was applied to investigate which variables were associated with medication information completeness. RESULTS: Admission notes for patients admitted between October 2018 and September 2019 and using at least one medication were included. A total of 1,080 admission notes, containing 8,604 medication orders, were assessed. The individual medications had a mean medication completeness score of 88.1% (SD 16.4), while admission notes had a mean medication completeness score of 86.3% (SD 16.2). Over 90% of all individual medications had information about generic name, formulation, dose and frequency stated, while indication for use was only present in 60%. The use of an electronic tool to prepare medication information had a significantly strong positive association with completeness. Hospital visit within the last 30 days, the patient's living situation, number of medications in use, and which hospital the patient was admitted to, were also associated with information completeness. CONCLUSIONS: Medication information completeness in admission notes was high, but potential for improvement regarding documentation of indication for use was identified. Applying an electronic tool when preparing admission notes in EDs seems crucial to safeguard completeness of medication information.

Self-reported medication information needs among medication users in a general population aged 40 years and above - the Tromsø study.

PURPOSE: To determine the prevalence and associated factors of self-reported medication information needs among medication users in a general population aged 40 years and above - The Tromsø Study. METHODS: Cross-sectional study of medication users (n = 10,231) among participants in the Tromsø Study, a descriptive analysis of questionnaire data and multivariable logistic regression (n = 9,194). RESULTS: Sixteen percent of medication users expressed a need for more information about own medications. Overall, medication users agreed to a higher degree to have received information from the GP compared to the pharmacy. Concerned medication users and those disagreeing to have received information about side effects had the highest odds for needing more information (OR 5.07, 95% CI 4.43-5.81) and (OR 2.21, 95% CI 1.83-2.68), respectively. Medication users who used heart medications (e.g., nitroglycerin, antiarrhythmics, anticoagulants) (OR 1.71, 95% CI 1.46-2.01), medication for hypothyroidism (OR 1.36, 95% CI 1.13-1.64) or had moderately health anxiety had expressed need for medication information. Whereas medication users with lower education, those that never used internet to search for health advice, and medication users who disagreed to have received information about reason-for-use were associated with lower odds (OR 0.75, 95% CI 0.62-0.91), (OR 0.85, 95% CI 0.74-0.98) and (OR 0.68, 95% CI 0.53-0.88), respectively. CONCLUSION: This study demonstrated that there is need for more information about own medications in a general population aged 40 years and above and shed light on several characteristics of medication users with expressed information need which is important when tailoring the right information to the right person.

Intervention fidelity and process outcomes of the IMMENSE study, a pharmacist-led interdisciplinary intervention to improve medication safety in older hospitalized patients.

WHAT IS KNOWN AND OBJECTIVE: The majority of hospitalized older patients experience medication-related problems (MRPs), and there is a call for interventions to solve MRPs and improve clinical outcomes like medical visits. The IMMENSE study is a randomized controlled trial investigating the impact of a pharmacist-led interdisciplinary intervention on emergency medical visits. Its multistep intervention is based on the integrated medicines management methodology and includes a follow-up step with primary care. This study aims to describe how the intervention in the IMMENSE study was delivered and its process outcomes. METHODS: The study includes the 221 intervention patients in the per-protocol group of the IMMENSE study. Both intervention delivery, reasons for not performing interventions and process outcomes were registered daily by the study pharmacists in a Microsoft Access® database. Process outcomes were medication discrepancies, MRPs and how the team solved these. RESULTS AND DISCUSSION: A total of 121 (54.8%) patients received all intervention steps if appropriate. All patients received medication reconciliation (MedRec) and medication Review (MedRev) (step 1 and 2), while between 10% and 20% of patients were missed for medication list in discharge summary (step 3), patient counselling (step 4), or communication with general practitioner and nurse (step 5). A total of 437 discrepancies were identified in 159 (71.9%) patients during MedRec, and 1042 MRPs were identified in 209 (94.6%) patients during MedRev. Of these, 292 (66.8%) and 700 (67.2%), respectively, were communicated to and solved by the interdisciplinary team during the hospital stay. WHAT IS NEW AND CONCLUSION: The fidelity of the single steps of the intervention was high even though only about half of the patients received all intervention steps. The impact of the intervention may be influenced by not implementing all steps in all patients, but the many discrepancies and MRPs identified and solved for the patients could explain a potential effect of the IMMENSE study.

Interdisciplinary collaboration across secondary and primary care to improve medication safety in the elderly (The IMMENSE study) - a randomized controlled trial.

BACKGROUND: Suboptimal medication use contributes to a substantial proportion of hospitalizations and emergency department visits in older adults. We designed a clinical pharmacist intervention to optimize medication therapy in older hospitalized patients. Based on the integrated medicine management (IMM) model, the 5-step IMMENSE intervention comprise medication reconciliation, medication review, reconciled medication list upon discharge, patient counselling, and post discharge communication with primary care. The objective of this study was to evaluate the effects of the intervention on healthcare use and mortality. METHODS: A non-blinded parallel group randomized controlled trial was conducted in two internal medicine wards at the University Hospital of North Norway. Acutely admitted patients ≥ 70 years were randomized 1:1 to intervention or standard care (control). The primary outcome was the rate of emergency medical visits (readmissions and emergency department visits) 12 months after discharge. RESULTS: Of the 1510 patients assessed for eligibility, 662 patients were asked to participate, and 516 were enrolled. After withdrawal of consent and deaths in hospital, the modified intention-to-treat population comprised 480 patients with a mean age of 83.1 years (SD: 6.3); 244 intervention patients and 236 control patients. The number of emergency medical visits in the intervention and control group was 497 and 499, respectively, and no statistically significant difference was observed in rate of the primary outcome between the groups [adjusted incidence rate ratio of 1.02 (95% CI: 0.82-1.27)]. No statistically significant differences between groups were observed for any of the secondary outcomes, neither in subgroups, nor for the per-protocol population. CONCLUSIONS: We did not observe any statistical significant effects of the IMMENSE intervention on the rate of emergency medical visits or any other secondary outcomes after 12 months in hospitalized older adults included in this study. TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov on 28/06/2016, before enrolment started (NCT02816086).

The impact of hospitalisation to geriatric wards on the use of medications and potentially inappropriate medications - a health register study.

BACKGROUND: The use of potentially inappropriate medications (PIMs) are associated with negative health effects for older adults. The purpose of this study was to apply national register data to investigate the impact of hospitalisation to geriatric wards in Norway on the use of medications and PIMs, and to compare two explicit PIM identification tools. METHODS: We included 715 patients ≥65 years (mean 82.5, SD = 7.8) admitted to Norwegian geriatric wards in 2013 identified from The Norwegian Patient Registry, and collected their medication use from the Norwegian Prescription Database. Medication use before and after hospitalisation was compared and screened for PIMs applying a subset of the European Union (EU)(7)-PIM list and the Norwegian General Practice - Nursing Home (NORGEP-NH) list part A and B. RESULTS: The mean number of medications increased from 6.5 (SD = 3.5) before to 7.5 (SD = 3.5) (CI:1.2-0.8, p < 0.001) after hospitalisation. The proportion of patients with PIMs increased from before to after hospitalisation according to the EU(7)-PIM list (from 62.4 to 69.2%, p < 0.001), but not according to The NORGEP-NH list (from 49.9 to 50.6%, p = 0.73). The EU(7)-PIM list and the NORGEP-NH list had more than 70% agreement on the classification of patients as PIM users. CONCLUSIONS: Medication use increased after hospitalisation to geriatric wards. We did not find that geriatric hospital care leads to a general improvement in PIM use after hospitalisation. According to a subset of the EU(7)-PIM list, PIM use increased after hospitalisation. This increase was not identified by the NORGEP-NH list part A and B. It is feasible to use health register data to investigate the impact of hospitalisation to geriatric wards on medication use and PIMs.

Empirical prescribing of penicillin G/V reduces risk of readmission of hospitalized patients with community-acquired pneumonia in Norway: a retrospective observational study.

BACKGROUND: Norwegian guideline recommendations on first-line empirical antibiotic prescribing in hospitalised patients with community-acquired pneumonia (CAP) are penicillin G/V in monotherapy, or penicillin G in combination with gentamicin (or cefotaxime) in severely ill patients. The aim of this study was to explore how different empirical antibiotic treatments impact on length of hospital stay (LOS) and 30-day hospital readmission. A secondary aim was to describe median intravenous- and total treatment duration. METHODS: We included CAP patients (≥18 years age) hospitalised in North Norway during 2010 and 2012 in a retrospective study. Patients with negative chest x-ray, malignancies or immunosuppression or frequent readmissions were excluded. We collected data on patient characteristics, empirical antibiotic prescribing, treatment duration and clinical outcomes from electronic patient records and the hospital administrative system. We used directed acyclic graphs for statistical model selection, and analysed data with mulitvariable logistic and linear regression. RESULTS: We included 651 patients. Median age was 77 years [IQR; 64-84] and 46.5% were female. Median LOS was 4 days [IQR; 3-6], 30-day readmission rate was 14.4% and 30-day mortality rate was 6.9%. Penicillin G/V were empirically prescribed in monotherapy in 51.5% of patients, penicillin G and gentamicin in combination in 22.9% and other antibiotics in 25.6% of patients. Prescribing other antibiotics than penicillin G/V monotherapy was associated with increased risk of readmission [OR 1.9, 95% CI; 1.08-3.42]. Empirical antibiotic prescribing was not associated with LOS. Median intravenous- and total treatment duration was 3.0 [IQR; 2-5] and 11.0 [IQR; 9.8-13] days. CONCLUSIONS: Our findings show that empirical prescribing with penicillin G/V in monotherapy in hospitalised non-severe CAP-patients, without complicating factors such as malignancy, immunosuppression and frequent readmission, is associated with lower risk of 30-day readmission compared to other antibiotic treatments. Median total treatment duration exceeds treatment recommendations.

Safety aspects of antiepileptic drugs-a population-based study of adverse effects relative to changes in utilisation.

PURPOSE: Antiepileptic drugs (AEDs) are increasingly used, and knowledge about adverse effects is scarce based on clinical studies. The purpose of the present study was to characterise adverse effects reports of AEDs in Norway relative to changes in utilisation in various indications from population-based data to elucidate important safety aspects of use of AEDs. METHODS: Aggregated data of adverse effects reported for AEDs in Norway from the EudraVigilance-database (2004-2013) in addition to indication-specific use of AEDs during 2004-2015 from the Norwegian Prescription Database were used. RESULTS: The use of AEDs increased twofold the last decade due to use in psychiatry and neuropathic pain: lamotrigine, pregabalin, gabapentin, valproate, and carbamazepine. There were 1593 adverse effects reported (403 Individual Case Safety Reports, 2/3 women), 0-95 years (mean 46). Most adverse effects were reported for pregabalin (593), carbamazepine (265), lamotrigine (206), gabapentin (144), and valproate (119), where pregabalin had by far the highest reports in relation to the number of users. The most frequently reported adverse drug effects included rash, dizziness, cross-sensitivity reactions, and pyrexia. Overall, nervous system disorders constitute the largest organ class with the majority of the reports. Reporting of fatal outcomes is mandatory, and sudden unexplained death in epilepsy (SUDEP) was reported in 34 occasions. CONCLUSIONS: This study demonstrates that most adverse effects reported concerned AEDs increasingly used in non-epilepsy indications: neuropathic pain (pregabalin, gabapentin, carbamazepine) and psychiatry (lamotrigine, valproate, carbamazepine). Pregabalin had the highest prevalence of adverse effects reported in relation to number of users. This elucidates an important part of pharmacovigilance for improved safety and considerations in clinical practice.

Reported time to onset of neurological adverse drug reactions among different age and gender groups using metoclopramide: an analysis of the global database Vigibase®.

PURPOSE: Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender. METHODS: All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database Vigibase® between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis. RESULTS: Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys). CONCLUSIONS: Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.

Adverse drug reaction reporting: how can drug consumption information add to analyses using spontaneous reports?

PURPOSE: Spontaneous reporting of adverse drug reactions (ADRs) is a cornerstone in pharmacovigilance. However, information about the underlying consumption of drugs is rarely used when analysing spontaneous reports. The purpose of this study was to combine ADR reports with drug consumption data to demonstrate the additional information this gives in various scenarios, comparing different drugs, gender-stratified sub-populations and changes in reporting over time. METHODS: We combined all Norwegian ADR reports in 2004-2013 from the EudraVigilance database (n = 14.028) with dispensing data from the Norwegian Prescription Database (more than 800 million dispensed prescriptions during 2004-2013). This was done in order to calculate drug-specific consumption-adjusted adverse drug reaction reporting rates (CADRRs) by dividing the number of reports for each drug with the number of users of the drug during the same time period. RESULTS: Among the ten drugs with the highest number of ADR reports and the ten drugs with the highest CADRR, only four drugs were in both categories. This indicates that drugs with a high number of reports often also have a high number of users and that CADRR captures drugs with potentially relevant safety issues but a smaller number of users. Comparing reported ADRs in females and males using methylphenidate, we found that the two groups report different ADRs. Finally, we showed that changes in ADR reporting for simvastatin and atorvastatin during 2004-2013 were due to changes in consumption and that atorvastatin had a higher CADRR but fewer reports than simvastatin. CONCLUSIONS: CADRR provides additional information compared with number of reports alone in studies using spontaneous reports. It is important for researchers to adjust for consumption whenever possible in pharmacovigilance studies.

Persistent analgesic use and the association with chronic pain and other risk factors in the population-a longitudinal study from the Tromsø Study and the Norwegian Prescription Database.

PURPOSE: Analgesics are commonly used drugs. The long-term effectiveness is mostly unproven, while the risk of several serious adverse effects is well established. We aimed to estimate the prevalence and incidence of persistent analgesic use and the association with chronic pain and sociodemographic and comorbid risk factors. METHODS: The Tromsø Study is an epidemiological, prospective study of health and diseases. We linked the sixth wave (Tromsø 6, 2007-08, n = 12,981) with the Norwegian Prescription Database (NorPD, 2004-13). Persistent analgesic use was defined as the use of analgesics, i.e., either non-steroidal anti-inflammatory drugs, opioids or paracetamol, for ≥90 days with proportion-of-days-covered ≥40 %. The study design provided both cross-sectional and longitudinal data; a cohort of 11,905 persons was followed for 4.5 years. RESULTS: The prevalence of persistent analgesic use was 4 % in general and 10 % among those reporting chronic pain. The incidence rate of persistent analgesic use was 21 per 1000 person-years in general. Baseline chronic pain doubled the risk of incident persistent analgesic use (HR = 2.05, 95 % CI 1.80-2.33). The risk increased with increasing chronic pain severity, as measured by chronic pain duration, frequency, intensity, and number of body locations. Sociodemographic risk factors were older age, female sex, lower education, and most likely lower physical activity. Psychological distress was not a statistical significant risk factor. CONCLUSIONS: This study showed a relatively low prevalence of persistent analgesic use and that the majority of persons reporting chronic pain do not use analgesics persistently.

Persistent opioid use and socio-economic factors: a population-based study in Norway.

BACKGROUND: A growing proportion of the population is using opioids for longer time periods, but little is known about the characteristics of patients who are persistent opioid users. We therefore studied the association between socio-economic factors and persistent vs. short-term opioid use 4 years later. METHODS: The background population is the complete Norwegian population in 2001. The study population is derived from two groups aged 35 years or older in 2001 who met one of the following criteria in 2005: (1) persistent opioid users (n = 15,113) or (2) short-term opioid users (n = 214,061). The applied definition of persistent opioid use corresponds to an average daily dose indicating likely daily use of opioids during 365 consecutive days. The socio-economic factors work status, income, marital status, immigrant status and education were obtained from the Population and Housing Census of 2001, and data on opioid use in 2005 were obtained from the complete national Norwegian Prescription Database. For logistic regression analyses, the study population was stratified by gender and by age over/under 67 years. RESULTS: In the 35- to 67-year-old age group, receiving a disability pension was more common in persistent opioid users compared with short-term opioid users (48% vs. 16% for women, 36% vs. 9% for men). Adjusted odds ratios for receiving a disability pension were 6.51 and 5.77 for women and men, respectively. Being divorced/separated was associated with being a persistent opioid user (odds ratio of 1.4 for both genders). There were also negative associations between persistent opioid use and attained education level, an unemployed working status and income status. CONCLUSION: Disability pension, not working, divorce, low income and low education in 2001 were associated with persistent opioid use in 2005.

Laxative prescriptions to cancer outpatients receiving opioids: a study from the Norwegian prescription database.

BACKGROUND: During opioid treatment of cancer pain, constipation is one of the most prevalent and bothersome side effects. Guidelines suggest that treatment with laxatives should be initiated when opioid therapy is started. AIM: This study aims: (1) to determine to what extent patients, starting on opioids due to cancer pain, receive laxatives; (2) to examine the temporal relationship between initiation of opioid therapy and initiation of treatment with laxatives; and (3) to study to which extent the treatment follows current guidelines. METHODS: Data from the Norwegian prescription database (NorPD) were used to investigate dispensed prescriptions of laxatives to outpatients in Norway, who are receiving opioids for cancer pain. Data from NorPD cover all dispensed prescriptions of drugs to outpatients, making it possible to follow patients over time. The study cohort was followed from 2005 to the end of 2008. RESULTS: Of 2,982 patients who started opioid therapy directly with WHO step III opioids, 1,325 patients (44.4 %) did not receive laxatives during the study period. Only 738 patients (24.7 %) received laxatives at the same time as opioid therapy was initiated. Another 657 patients (22.0 %) received laxatives after their initiation of opioids at some time during the study period. CONCLUSION: Of those who started directly on a strong opioid, only one fourth received laxatives concomitantly with the first opioid, and nearly half did not receive laxatives at all. These findings indicate that the current guidelines are not followed.

Patient perceptions and experiences with medication-related activities in the emergency department: a qualitative study.

BACKGROUND: Emergency department (ED) pharmacists reduce medication errors and improve quality of medication use. Patient perceptions and experiences with ED pharmacists have not been studied. The aim of this study was to explore patients' perceptions of and experiences with medication-related activities in the ED, with and without an ED pharmacist present. METHODS: We conducted 24 semistructured individual interviews with patients admitted to one ED in Norway, 12 before and 12 during an intervention, where pharmacists performed medication-related tasks close to patients and in collaboration with ED staff. Interviews were transcribed and analysed applying thematic analysis. RESULTS: From our five developed themes, we identified that: (1) Our informants had low awareness and few expectations of the ED pharmacist, both with and without the pharmacist present. However, they were positive to the ED pharmacist. (2) Our informants expressed a variation of trust in the healthcare system, healthcare professionals and electronic systems, though the majority expressed a high level of trust. They believed that their medication list was automatically updated and assumed to get the correct medication. (3) Some informants felt responsible to have an overview of their medication use, while others expressed low interest in taking responsibility regarding their medication. (4) Some informants did not want involvement from healthcare professionals in medication administration, while others expressed no problems with giving up control. (5) Medication information was important for all informants to feel confident in medication use, but the need for information differed. CONCLUSION: Despite being positive to pharmacists, it did not seem important to our informants who performed the medication-related tasks, as long as they received the help they needed. The degree of trust, responsibility, control and information varied among ED patients. These dimensions can be applied by healthcare professionals to tailor medication-related activities to patients' individual needs.

Community carriage of ESBL-producing Escherichia coli and Klebsiella pneumoniae: a cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates.

The global prevalence of infections caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) is increasing, and for Escherichia coli, observations indicate that this is partly driven by community-onset cases. The ESBL-E population structure in the community is scarcely described, and data on risk factors for carriage are conflicting. Here, we report the prevalence and population structure of fecal ESBL-producing E. coli and Klebsiella pneumoniae (ESBL-Ec/Kp) in a general adult population, examine risk factors, and compare carriage isolates with contemporary clinical isolates. Fecal samples obtained from 4,999 participants (54% women) ≥40 years in the seventh survey of the population-based Tromsø Study, Norway (2015, 2016), were screened for ESBL-Ec/Kp. In addition, we included 118 ESBL-Ec clinical isolates from the Norwegian surveillance program in 2014. All isolates were whole-genome sequenced. Risk factors associated with carriage were analyzed using multivariable logistic regression. ESBL-Ec gastrointestinal carriage prevalence was 3.3% [95% confidence interval (CI) 2.8%-3.9%, no sex difference] and 0.08% (0.02%-0.20%) for ESBL-Kp. For ESBL-Ec, travel to Asia was the only independent risk factor (adjusted odds ratio 3.46, 95% CI 2.18-5.49). E. coli ST131 was most prevalent in both collections. However, the ST131 proportion was significantly lower in carriage (24%) versus clinical isolates (58%, P < 0.001). Carriage isolates were genetically more diverse with a higher proportion of phylogroup A (26%) than clinical isolates (5%, P < 0.001), indicating that ESBL gene acquisition occurs in a variety of E. coli lineages colonizing the gut. STs commonly related to extraintestinal infections were more frequent in clinical isolates also carrying a higher prevalence of antimicrobial resistance, which could indicate clone-associated pathogenicity.IMPORTANCEESBL-Ec and ESBL-Kp are major pathogens in the global burden of antimicrobial resistance. However, there is a gap in knowledge concerning the bacterial population structure of human ESBL-Ec/Kp carriage isolates in the community. We have examined ESBL-Ec/Kp isolates from a population-based study and compared these to contemporary clinical isolates. The large genetic diversity of carriage isolates indicates frequent ESBL gene acquisition, while those causing invasive infections are more clone dependent and associated with a higher prevalence of antibiotic resistance. The knowledge of factors associated with ESBL carriage helps to identify patients at risk to combat the spread of resistant bacteria within the healthcare system. Particularly, previous travel to Asia stands out as a major risk factor for carriage and should be considered in selecting empirical antibiotic treatment in critically ill patients.

Reimbursement of analgesics for chronic pain.

BACKGROUND: The prevalence of chronic non-malignant pain in Norway is between 24% and 30%. The proportion of the population using opioids for non-malignant pain on a long-term basis is around 1%. The purpose of our study was to investigate how many were prescribed analgesics on reimbursable prescription under reimbursement code -71 (chronic non-malignant pain) in 2009 and 2010, which analgesics were prescribed and whether prescribing practices were in accordance with national guidelines. MATERIAL AND METHOD: We retrieved pseudonymised data from the National Prescription Database on all those who received drugs with reimbursement code -71 in 2009 and 2010. The data contain information on drug, dosage, formulation, reimbursement code and date of issue. RESULTS: 90,731 patients received reimbursement for drugs indicated for chronic non-malignant pain in 2010. Of these, 6,875 were given opioids, 33,242 received paracetamol, 25,865 non-steroid inflammatory drugs (NSAIDs), 20,654 amitryptiline and 16,507 gabapentin. Oxycodone was the most frequently prescribed opioid, followed by buprenorphine, tramadol and codeine/paracetamol. Of those who were prescribed opioids, 4,047 (59%) received mainly slow-release opioids, 2,631 (38%) also received benzodiazepines and 2,418 (35%) received benzodiazepine-like sleep medications. CONCLUSION: The number of patients who received analgesics and opioids on reimbursable prescriptions was low compared to the proportion of the population with chronic pain and the proportion using opioids long-term. 38% of those reimbursed for opioids also used benzodiazepines, which is contrary to official Norwegian guidelines.

Association of area-level education with the regional growth trajectories of rates of antibacterial dispensing to patients under 3 years in Norway: a longitudinal retrospective study.

OBJECTIVE: To examine the association between area-level education and the local growth trajectories in antibacterial dispensing rates in Norwegian municipalities among children under 3 years old. DESIGN: Retrospective, longitudinal study using individual primary care prescription data from the Norwegian Prescription Database for the period 2006-2016. Data were collected on the date of dispensing, the type and amount of antibiotic, the patient's age, sex and municipality of residence and linked to municipality-level statistics on education available from Statistics Norway. We used multilevel growth curve modelling, with a linear trend variable modelled as a random effect and a cross-level interaction between linear trends and the proportion of the population in the municipality having received a university or college education. SETTING: The local government level in Norway. The sample includes all municipalities over the study period. OUTCOME MEASURE: Number of dispensed antibacterial prescriptions per 100 children in individual primary care by municipality and year. RESULTS: We identified a significant negative linear trend in the square root of the dispensing rate for children under 3 years old during the period. This trend varied between municipalities. A negative cross-level interaction term between population education levels and random trends showed that municipalities with an average level of population education saw a reduction in their square root dispensing rates of -0.053 (95% CI -0.066 to -0.039) prescriptions per 100 children. Each additional percentage point in population education contributed a further -0.0034 (95% CI -0.006 to -0.001) reduction to the square root dispensing rate. CONCLUSIONS: Municipalities in which a larger proportion of the local population have high educational achievements have been more successful in reducing antibacterial dispensing rates in children under 3 years old. Adopting area-level strategies and addressing local community disadvantages may help to optimise practices and prescribing patterns across local communities.

Risk factors, immune response and whole-genome sequencing of SARS-CoV-2 in a cruise ship outbreak in Norway.

OBJECTIVE: To improve understanding of SARS-CoV-2-transmission and prevention measures on cruise ships, we investigated a Norwegian cruise ship outbreak from July to August 2020 using a multidisciplinary approach after a rapid outbreak response launched by local and national health authorities. METHODS: We conducted a cross-sectional study among crew members using epidemiologic data and results from SARS-CoV-2 polymerase chain reaction (PCR) of nasopharynx-oropharynx samples, antibody analyses of blood samples, and whole-genome sequencing. RESULTS: We included 114 multinational crew members (71% participation), median age 36 years, and 69% male. The attack rate was 33%; 32 of 37 outbreak cases were seropositive 5-10 days after PCR. One PCR-negative participant was seropositive, suggesting a previous infection. Network-analysis showed clusters based on common exposures, including embarkation date, nationality, sharing a cabin with an infected cabin-mate (adjusted odds ratio [AOR] 3.27; 95% confidence interval [CI] 0.97-11.07, p = 0.057), and specific workplaces (mechanical operations: 9.17 [1.82-45.78], catering: 6.11 [1.83-20.38]). Breaches in testing, quarantine, and isolation practices before/during expeditions were reported. Whole-genome sequencing revealed lineage B.1.36, previously identified in Asia. Despite extensive sequencing, the continued transmission of B.1.36 in Norway was not detected. CONCLUSIONS: Our findings confirm the high risk of SARS-CoV-2-transmission on cruise ships related to workplace and cabin type and show that continued community transmission after the outbreak could be stopped by implementing immediate infection control measures at the final destination.

Social network analysis of Staphylococcus aureus carriage in a general youth population.

OBJECTIVES: Staphylococcus aureus carriage increases the risk of infection. We used social network analysis to evaluate whether contacts have the same S. aureus genotype indicating direct transmission or whether contagiousness is an indirect effect of contacts sharing the same lifestyle or characteristics. METHODS: The Fit Futures 1 study collected data on social contact among 1038 high school students. S. aureus carriage was determined from two nasal swab cultures and the genotype was determined by spa-typing of positive throat swabs. RESULTS: S. aureus carriage and spa-type were transmitted in the social network (P < 0.001). The probability of carriage increased by 5% for each S. aureus positive contact. Male sex was associated with a 15% lower risk of transmission compared to the female sex, although the carriage prevalence was higher for men (36% vs 24%). Students with medium physical activity levels, medium/high alcohol use, or normal weight had a higher number of contacts and an increased risk of transmission (P < 0.002). CONCLUSION: We demonstrated the direct social transmission of S. aureus. Lifestyle factors are associated with the risk of transmission, suggesting the effects of indirect social groups on S. aureus carriage, such as friends having more similar environmental exposures. The male predominance in the carriage is determined by sex-specific predisposing host characteristics as the social transmission is less frequent in males than females. Information on social networks may add to a better understanding of S. aureus epidemiology.