Effect of methenamine hippurate shortage on antibiotic prescribing for urinary tract infections in Norway-an interrupted time series analysis.

BACKGROUND: Despite a lack of conclusive evidence of effect, methenamine hippurate is widely prescribed as preventive treatment for recurrent urinary tract infections (UTIs) in Norway. A national discontinuation of methenamine hippurate treatment due to a 4-month drug shortage in 2019 presented an opportunity to evaluate its preventive effect on UTIs among regular users. OBJECTIVE: To estimate the impact of the methenamine hippurate drug shortage on prescription frequency of UTI antibiotics. METHODS: Data from The Norwegian Prescription Database was analysed using an interrupted time series design. The time series consisted of 56 time periods of 14 days. The model included two naturally occurring interruptions: (i) the methenamine hippurate drug shortage, and (ii) reintroduction of the drug. The study population were 18 345 women ≥50 years receiving ≥2 prescriptions of methenamine hippurate in the study period before the shortage. Main outcome measure was number of prescriptions of UTI antibiotics per 1000 methenamine hippurate users. Prescription rates of antibiotics for respiratory tract infections were analysed to assess external events affecting antibiotic prescribing patterns. RESULTS: We found a significant increase of 2.41 prescriptions per 1000 methenamine hippurate users per 14-day period during the drug shortage (95%CI 1.39, 3.43, P < 0.001), followed by a significant reduction of -2.64 prescriptions after reintroduction (95%CI -3.66, -1.63, P < 0.001). CONCLUSIONS: During the methenamine hippurate drug shortage, we found a significant increase in prescribing trend for UTI antibiotics followed by a significant decrease in prescribing trend after reintroduction. This change in trend seems to reflect a preventive effect of the drug on recurrent UTIs.

Academic detailing as a method to improve general practitioners' drug prescribing in type 2 diabetes: evaluation of changes in prescribing.

OBJECTIVE: To investigate the effect of an academic detailing intervention on the utilisation of type 2 diabetes medication among general practitioners. DESIGN: We developed an academic detailing campaign based on the revised national treatment guideline for diabetes and the best available evidence. General practitioners were offered a 20-minute one-to-one visit by a trained academic detailer. SETTING AND SUBJECTS: A total of 371 general practitioners received a visit and represented the intervention group. The control group consisted of 1282 general practitioners not receiving a visit. MAIN OUTCOME MEASURES: Changes in prescribing from 12 months before to 12 months after the intervention. The primary endpoint was a change in metformin. Secondary endpoints were changes in other groups of Type 2 diabetes medication and of these drugs in total. RESULTS: Prescribing of metformin increased by 7.4% in the intervention group and 5.2% in the control group (p = .043). Sodium-glucose cotransporter-2 inhibitors increased by 27.6% in the intervention group and 33.8% in the control group (p = .019). For sulfonylureas there was a decrease of 3.6% in the intervention group vs. 8.9% in the control group (p = .026). The total amount of prescribed medications for type 2 diabetes increased by 9.1% in the intervention group and 7.3% in the control group (p = .08). CONCLUSION: Academic detailing initiated a small but statistically significant increase in the prescription of metformin. For a complex subject like type 2 diabetes, we recommend reserving more time in the visit than the 20 min our campaign aimed for.

Academic detailing is a validated method for facilitating changes in prescribing, via interactive one-to-one meetings with a trained academic detailer.General practitioners who received a 20-minute visit on the treatment of type 2 diabetes prescribed more metformin, compared to the control group.For a complex interventions like the present, we recommend setting aside more than 20 minutes, to ensure sufficient time for discussion and reflection.Academic detailing can impact prescribing, even for a complex subject like the treatment of Type 2 Diabetes.

Trends in the hospital-sector consumption of the WHO AWaRe Reserve group antibiotics in EU/EEA countries and the United Kingdom, 2010 to 2018.

BackgroundIn 2019, the World Health Organization published the 21st Model list of Essential Medicines and updated the Access, Watch Reserve (AWaRe) antibiotics classification to improve metrics and indicators for antibiotic stewardship activities. Reserve antibiotics are regarded as last-resort treatment options.AimWe investigated hospital-sector consumption quantities and trends of Reserve group antibiotics in European Union/European Economic Area countries and the United Kingdom (EU/EEA/UK).MethodsHospital-sector antimicrobial consumption data for 2010-2018 were obtained from the European Centre for Disease Prevention and Control. Antibacterials' consumption for systemic use (Anatomical Therapeutic Chemical classification (ATC) group J01) were included in the analysis and expressed as defined daily doses (DDD) per 1,000 inhabitants per day. We defined reserve antibiotics as per AWaRe classification and applied linear regression to analyse trends in consumption of reserve antibiotics throughout the study period.ResultsEU/EEA/UK average hospital-sector reserve-antibiotic consumption increased from 0.017 to 0.050 DDD per 1,000 inhabitants per day over the study period (p = 0.002). This significant increase concerned 15 countries. In 2018, four antibiotics (tigecycline, colistin, linezolid and daptomycin) constituted 91% of the consumption. Both absolute and relative (% of total hospital sector) consumption of reserve antibiotics varied considerably (up to 42-fold) between countries (from 0.004 to 0.155 DDD per 1,000 inhabitants per day and from 0.2% to 9.3%, respectively).ConclusionAn increasing trend in reserve antibiotic consumption was found in Europe. The substantial variation between countries may reflect the burden of infection with multidrug-resistant bacteria. Our results could guide national actions or optimisation of reserve antibiotic use.

Corrigendum: Can We Optimize Antibiotic Use in Norwegian Neonates? A Prospective Comparison Between a University Hospital and a District Hospital.

[This corrects the article DOI: 10.3389/fped.2019.00440.].

Antibiotic use in children before, during and after hospitalisation.

PURPOSE: To investigate ambulatory antibiotic use in children during 1 year before and 1 year after in-hospital antibiotic exposure compared to children from the general population that had not received antibiotics in-hospital. METHODS: Explorative data-linkage cohort study from Norway of children aged 3 months to 17 years. One group had received antibiotics in-Hospital (H+), and one group had not received antibiotics in-hospital (H-). The H+ group was recruited during admission in 2017. Using the Norwegian Population Registry, 10 children from the H- group were matched with one child from the H+ group according to county of residence, age and sex. We used the Norwegian Prescription Database to register antibiotic use 1 year before and 1 year after the month of hospitalisation. RESULTS: Of 187 children in the H+ group, 83 (44%) received antibiotics before hospitalisation compared to 288/1870 (15%) in the H- group, relative risk (RR) 2.88 (95% confidence interval 2.38-3.49). After hospitalisation, 86 (46%) received antibiotics in the H+ group compared to 311 (17%) in the H- group, RR 2.77 (2.30-3.33). Comorbidity-adjusted RR was 2.30 (1.84-2.86) before and 2.25 (1.81-2.79) after hospitalisation. RR after hospitalisation was 2.55 (1.99-3.26) in children 3 months-2 years, 4.03 (2.84-5.71) in children 3-12 years and 2.07 (1.33-3.20) in children 13-17 years. CONCLUSIONS: Children exposed to antibiotics in-hospital had two to three times higher risk of receiving antibiotics in ambulatory care both before and after hospitalisation. The link between in-hospital and ambulatory antibiotic exposure should be emphasised in future antibiotic stewardship programs.

Use of Statins in Kidney Transplant Recipients in Norway.

Kidney transplant recipients (KTRs) experience increased risk of cardiovascular disease. Guidelines recommend HMG-CoA reductase inhibitor (statin) therapy when tolerated. We aimed to study changes in the prescription of statins and patients' adherence to treatment over time. A population-based observational study utilizing linked data from the Norwegian Renal Registry (national coverage of 99.9%) and the Norwegian Prescription Database was performed. Data from a total of 2250 first KTRs were included (mean age-54 years, 69% men). Dispensed prescriptions of statins and immunosuppressants for the period 2004-2016 for all first KTRs engrafted in the period 2005-2015 were analyzed. Seventy-two percent received statins the first year after kidney transplantation and the proportion increased with age. The proportion receiving a statin varied according to the time frame of transplantation (77% in 2005-2010 vs. 66% in 2012-2015). Among new users of statins, 82% of the patients were adherent both the second and third year after kidney transplantation, while the corresponding figure for those already receiving statins before transplantation was 97%. Statin continuation rates in KTRs were high. In conclusion, our findings show a slightly lower overall proportion of patients receiving statins after kidney transplants than the national target level of 80%. The proportion of statin users increased with the age of the KTRs but showed a decreasing trend as time progressed.

Are infants exposed to antimicrobials during the first 3 months of life at increased risk of recurrent use? An explorative data-linkage study.

OBJECTIVES: To investigate whether infants exposed to antimicrobials in hospital during the first 3 months of life had an increased risk of ambulatory antimicrobial use during the following year compared with infants not exposed to antimicrobials during the first 3 months of life. METHODS: Norwegian cohort study of infants less than 3 months consisting of one group exposed to antimicrobials recruited during hospitalization and one group not exposed to antimicrobials. Ten unexposed infants were matched with one exposed infant according to county of residence, birth year and month, and sex. The Norwegian Prescription Database was applied to register antimicrobial use from the month after discharge and 1 year onward. We defined comorbidity based on antimicrobials prescribed as reimbursable prescriptions due to underlying diseases. RESULTS: Of 95 infants exposed to antimicrobials during the first 3 months of life, 23% had recurrent use compared with 14% use in 950 unexposed infants [relative risk (RR) = 1.7 (95% CI = 1.1-2.5) and comorbidity-adjusted RR = 1.4 (95% CI = 0.9-2.2)]. The recurrence use rate in exposed term infants (≥37 weeks, n = 70) was 27% compared with 12% in their unexposed matches [RR 2.3 = (95% CI = 1.4-3.7) and comorbidity-adjusted RR = 1.9 (95% CI = 1.2-3.2). Of 25 exposed preterm infants, 3 (12%) had recurrent use. The total antimicrobial prescription rate was 674/1000 in the exposed group and 244/1000 in the unexposed group [incidence rate ratio = 2.8 (95% CI = 1.6-4.9)]. CONCLUSIONS: Infants exposed to antimicrobials during the first 3 months of life had an increased risk of recurrent use during the following year. This increased risk also appeared in term infants without infection-related comorbidity.

The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.

BACKGROUND: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. METHODS: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. DISCUSSION: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538550 .

Use of antibiotics during the COVID-19 pandemic. / Bruk av antibiotika under covid-19-pandemien.

BACKGROUND: Interest has been shown in the use of antibiotics during the COVID-19 pandemic. In this article we present the consumption of systemic antibiotics in Norway during the period of the pandemic. MATERIAL AND METHOD: Total sales of systemic antibiotics in defined daily doses (DDD) were retrieved from the wholesaler-based medicinal product statistics for 2019 and 2020, and sales of antibiotics for use outside of healthcare institutions were retrieved from the Norwegian prescription database. Information was retrieved on the proportion of users (prevalence), doses (measured in DDD) and prescriptions. RESULTS: Total sales of systemic antibiotics increased in March 2020, but sales to persons outside of healthcare institutions did not. Compared to previous years, both total consumption and use of antibiotics outside of institutions fell steeply in the months that followed. The reduction was greatest for antibiotics against respiratory infections and in the youngest age groups. INTERPRETATION: The significant reduction in the use of systemic antibiotics during the COVID-19 pandemic is attributed to infection control measures and reduced contact with the health service. In 2016, the Norwegian government set a goal for a 30 % reduction in antibiotic use by the end of 2020. The pandemic has contributed to the achievement of that goal.

Use of Drugs With Risk of Heart Rate-Related Problems is Common in Norwegian Dementia Patients Treated With Acetylcholinesterase Inhibitors: A Prevalence Study Based on the Norwegian Prescription Database.

Background: Drugs commonly prescribed for heart rate control may induce adverse drug reactions in Alzheimer patients treated with acetylcholinesterase inhibitors (AChEIs). We have studied use of drugs with a known risk of Torsades de pointes (TdP) and drugs used to treat behavioral and psychological symptoms of dementia, as well as a combination of drugs with a known risk of TdP and drugs with a known heart rate-lowering effect, before and after initiating treatment with AChEIs. Methods: The study applied data from the Norwegian Prescription Database for the period 2004-2016. Prescriptions of concomitant use of drugs in persistent users of AChEIs was studied in a follow-up period from 4 years before to 2 years after AChEI initiation in men and women of two age groups: 37-80 and 81-88 years. Results: A small number of patients were prescribed haloperidol (∼1.5% The second year after AChEI initiation), digoxin/digitoxin (∼3%), and verapamil (∼1.3%), while a substantial proportion of the patients were prescribed betablockers (∼28%) and citalopram/escitalopram (∼17%). During follow-up, up to 6% of the study population were prescribed both betablockers and citalopram/citalopram in addition to AChEIs, a combination that increased over the follow-up period and was observed most frequently in women in the oldest age group. Conclusions: A large proportion (∼44%) of patients treated with AChEIs were prescribed drugs that could cause bradycardic and prolonged time from the start of the Q wave to the end of the T wave (QT interval). Thus, action should be taken to reduce the combination of drugs with risk of bradycardia and prolonged QT interval. Medication review on a regular basis could be an option as an important risk-reducing intervention.

Ciprofloxacin usage at a local hospital. / Bruk av ciprofloksacin ved et lokalsykehus.

BACKGROUND: The use of quinolones is subject to strict conditions, in part because of their known tendency to drive antimicrobial resistance. Use of quinolones in Norwegian hospitals increased dramatically from their launch in the 1980s to a peak in 2012. Since then, usage has decreased and had almost halved by 2019. However, little information is available on whether the use of quinolones in hospitals is in accordance with national guidelines. MATERIAL AND METHOD: This study included inpatients over 12 years of age who were prescribed quinolones at a local hospital in the Central Norway Regional Health Authority in the period 1 September-31 December 2018. An expert group of infectious disease specialists evaluated the use of quinolones against the national guidelines for the use of antibiotics in hospitals. RESULTS: The use of ciprofloxacin was considered to have been inconsistent with therapeutic recommendations in 45 out of 49 (92 %) inpatient stays in the medical, surgical and orthopaedic departments. INTERPRETATION: In a local hospital, ciprofloxacin was used all too frequently for indications outside those recommended in the Norwegian guidelines.

Identifying targets for antibiotic stewardship interventions through analysis of the antibiotic prescribing process in hospitals - a multicentre observational cohort study.

BACKGROUND: In order to change antibiotic prescribing behaviour, we need to understand the prescribing process. The aim of this study was to identify targets for antibiotic stewardship interventions in hospitals through analysis of the antibiotic prescribing process from admission to discharge across five groups of infectious diseases. METHODS: We conducted a multi-centre, observational cohort study, including patients with lower respiratory tract infections, exacerbation of chronic obstructive pulmonary disease, skin- and soft tissue infections, urinary tract infections or sepsis, admitted to wards of infectious diseases, pulmonary medicine and gastroenterology at three teaching hospitals in Western Norway. Data was collected over a 5-month period and included antibiotics prescribed and administered during admission, antibiotics prescribed at discharge, length of antibiotic therapy, indication for treatment and discharge diagnoses, estimated glomerular filtration rate (eGFR) on admission, antibiotic allergies, place of initiation of therapy, admittance from an institution, patient demographics and outcome data. Primary outcome measure was antibiotic use throughout the hospital stay, analysed by WHO AWaRe-categories and adherence to guideline. Secondary outcome measures were a) antibiotic prescribing patterns by groups of diagnoses, which were analysed using descriptive statistics and b) non-adherence to the national antibiotic guidelines, analysed using multivariate logistic regression. RESULTS: Through analysis of 1235 patient admissions, we identified five key targets for antibiotic stewardship interventions in our population of hospital inpatients; 1) adherence to guideline on initiation of treatment, as this increases the use of WHO Access-group antibiotics, 2) antibiotic prescribing in the emergency room (ER), as 83.6% of antibiotic therapy was initiated there, 3) understanding prescribing for patients admitted from other institutions, as this was significantly associated with non-adherence to guideline (OR = 1.44 95% CI 1.04, 2.00), 4) understanding cultural and contextual drives of antibiotic prescribing, as non-adherent prescribing differed significantly between the sites of initiation of therapy (between hospitals and ER versus ward) and 5) length of therapy, as days of antibiotic therapy was similar across a wide range of diagnoses and with prolonged therapy after discharge. CONCLUSIONS: Analysing the process of antibiotic prescribing in hospitals with patient-level data identified important targets for antibiotic stewardship interventions in hospitals.

Non-prescription purchase of antibiotics during travel abroad among a general adult population in Norway: Findings from the seventh Tromsø Study.

BACKGROUND: Non-prescription purchase of antibiotics is undesirable and has not recently been investigated in a representative population in a high-income low-use country during travel abroad. This study examined self-reported prevalence of antibiotic purchase abroad with and without prescription among participants reporting international travel in a general adult population in Norway, and the associations with socio-demographic, lifestyle and health factors. METHODS: We analysed questionnaire-data from 19995 participants (10470 women) ≥40 years in the population-based Tromsø Study 7, 2015-2016. Data from the Norwegian Prescription Database were used to examine antibiotic use in Norway. We calculated adjusted odds ratios (AOR) for "travel abroad", "any antibiotic purchase abroad", and "antibiotic purchase abroad with" and "without prescription" using multivariable logistic regression. RESULTS: Over half (55.0%, 95%CI 54.3-55.7%) participants reported travel abroad of >1 week duration in the past year. Travelers were more likely than non-travelers to be women (AOR = 2.02, 95%CI 1.42-2.88%) and report high education/income, childhood mostly lived abroad, healthy lifestyle, and good/excellent self-rated health. In total, 17904 travel episodes to 148 countries were reported. Altogether, 3.7% (95% CI 3.4%-4.1%) of travelers had purchased antibiotic abroad in the past year. Non-prescription purchase (1.5%, 95% CI 1.3-1.7) was associated with younger age, being female (AOR 1.41, 1.0-1.97), number of travels (reference: one episode, two: AOR = 1.82, 1.25-2.67, three: 2.60, 1.58-4.28, four: 3.10, 1.40-6.36 and ≥five: 4.70, 2.30-9.62), occurrences of diarrhoea (one: 2.42, 1.50-3.93 and ≥two: 3.08, 1.29-7.35), and antibiotic use in Norway in the past year (1.84, 1.29-2.62), whereas purchase with prescription (2.4%, 2.1-2.7) was associated with low income, growing-up abroad, recent hospital admission, additionally including number of travels/diarrhoea, and antibiotic use in Norway. Thailand (10.7%, 95% CI 7.8-14.3), Turkey (5.5%, 3.8-7.8) and Spain (3.6%, 3.0-4.3) were the countries most commonly associated with any antibiotic purchase. About two in five travelers who bought antibiotics in Thailand had done so without prescription, three in five in Turkey, and less than one in three in Spain. CONCLUSION: Overall, a small proportion of travelers had bought antibiotics abroad in the past year. Low prevalence of non-prescription purchase may be explained by awareness of the risks associated with self-medication, cultural views, unawareness of the non-prescription availability, and/or few infections. Divergent predictors for purchase abroad with versus without prescription may suggest different reasons for these practices.

Can We Optimize Antibiotic Use in Norwegian Neonates? A Prospective Comparison Between a University Hospital and a District Hospital.

Background: Worldwide, a large proportion of neonates are prescribed antibiotics without having infections leading to increased antimicrobial resistance, disturbance of the evolving microbiota, and increasing the risk of various chronical diseases. Comparing practice between different hospitals/settings is important in order to optimize antibiotic stewardship. Aim: To investigate and compare the potential for improved antibiotic stewardship in neonates in two Norwegian hospitals with different academic culture, with emphasis on antibiotic exposure in unconfirmed infections, treatment length/doses, CRP values and the use of broad-spectrum antibiotics (BSA). All types of infections were investigated, but the main focus was on early-onset sepsis (EOS). Methods: We conducted a prospective observational cohort study of antibiotic use in a Norwegian university hospital (UH) and a district hospital (DH), 2017. Unconfirmed infections were defined as culture negative infections that neither fulfilled the criteria for clinical infection (clinical symptoms, maximum CRP >30 mg/L, and treatment for at least 5 days). Results: Ninety-five neonates at the DH and 89 neonates at the UH treated with systemic antibiotics were included in the study. In total, 685 prescriptions (daily doses) of antibiotics were given at the DH and 903 at the UH. Among term and premature infants (≥ 28 weeks), 82% (75% at the UH and 86% at the DH, p = 0.172) of the treatments for suspected EOS were for unconfirmed infections, and average treatment length in unconfirmed infections was 3.1 days (both hospitals). Median dose for aminoglycoside was higher for term infants at the UH (5.96, 95% CI 5.02-6.89) compared to the DH (4.98, 95% CI 4.82-5.14; p < 0.001). At the UH, all prescriptions with aminoglycosides were gentamicin, while tobramycin accounted for 93% of all prescriptions with aminoglycosides at the DH. Conclusion: There is a potential for reduction in both antibiotic exposure and treatment length in these two neonatal units, and a systematic risk/observational algorithm of sepsis should be considered in both hospitals. We revealed no major differences between the UH and DH, but doses and choice of aminoglycosides varied significantly.

Targets for the reduction of antibiotic use in humans in the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) partner countries.

Unnecessary and inappropriate use of antibiotics in human healthcare is a major driver for the development and spread of antimicrobial resistance; many countries are implementing measures to limit the overuse and misuse of antibiotics e.g. through the establishment of antimicrobial use reduction targets. We performed a review of antimicrobial use reduction goals in human medicine in Transatlantic Taskforce on Antimicrobial Resistance partner countries. On 31 March 2017, the European Centre for Disease Prevention and Control sent a questionnaire to National Focal Points for Antimicrobial Consumption and the National Focal Points for Antimicrobial Resistance in 28 European Union countries, Iceland and Norway. The same questionnaire was sent to the TATFAR implementers in Canada and the United States. Thirty of 32 countries replied. Only nine countries indicated that they have established targets to reduce antimicrobial use in humans. Twenty-one countries replied that no target had been established. However, 17 of these 21 countries indicated that work to establish such targets is currently underway, often in the context of developing a national action plan against antimicrobial resistance. The reported targets varied greatly between countries and can be a useful resource for countries willing to engage in the reduction of antibiotic use in humans.

Drug Use before and after Initiating Treatment with Acetylcholinesterase Inhibitors.

BACKGROUND/AIMS: The aim was to study the prevalence of use of different drugs prescribed for behavioral and psychological symptoms of dementia in persistent users of acetylcholinesterase inhibitors (AChEIs) before and after AChEI initiation, and to compare with the use in the general population. METHODS: Use of antidepressants, antipsychotics, and analgesics in the 4 years before and 2 years after AChEI initiation was studied based on data from the Norwegian Prescription Database 2004-2016. RESULTS: The prevalence of use of antidepressants and antipsychotics the year before AChEI initiation was twice the prevalence in the age-adjusted general population and continued to rise in the first 2 years after initiation of AChEIs. The prevalence of weak analgesics and antipsychotics increased strongly in the last year before AChEI initiation. The increase in the use of antidepressants started at least 4 years before initiation of AChEIs. Opioid use was generally lower than in the general population and was not influenced by AChEI initiation. CONCLUSION: Increased use of antidepressants and antipsychotics was observed both before and after initiation of AChEIs and may indicate that behavioral symptoms occur in a preclinical or early phase of Alzheimer's disease. The prescription pattern of analgesics with a low use of opioids may indicate an undertreatment of pain in people with dementia.

Using a period incidence survey to compare antibiotic use in children between a university hospital and a district hospital in a country with low antimicrobial resistance: a prospective observational study.

OBJECTIVES: To describe and compare antibiotic use in relation to indications, doses, adherence rate to guidelines and rates of broad-spectrum antibiotics (BSA) in two different paediatric departments with different academic cultures, and identify areas with room for improvement. DESIGN: Prospective observational survey of antibiotic use. SETTING: Paediatric departments in a university hospital (UH) and a district hospital (DH) in Norway, 2017. The registration period was 1 year at the DH and 4 months at the UH. PARTICIPANTS: 201 children at the DH (mean age 3.8: SD 5.1) and 137 children at the UH (mean age 2.0: SD 5.9) were treated with systemic antibiotics by a paediatrician in the study period and included in the study. OUTCOME MEASURES: Main outcome variables were prescriptions of antibiotics, treatments with antibiotics, rates of BSA, median doses and adherence rate to national guidelines. RESULTS: In total, 744 prescriptions of antibiotics were given at the UH and 638 at the DH. Total adherence rate to guidelines was 75% at the UH and 69% at the DH (p=0.244). The rate of treatments involving BSA did not differ significantly between the hospitals (p=0.263). Use of BSA was related to treatment of central nervous system (CNS) infections, patients with underlying medical conditions or targeted microbiological treatment in 92% and 86% of the treatments, at the UH and DH, respectively (p=0.217). A larger proportion of the children at the DH were treated for respiratory tract infections (p<0.01) compared with the UH. Children at the UH were treated with higher doses of ampicillin and cefotaxime (p<0.05) compared with the DH. CONCLUSION: Our results indicate that Norwegian paediatricians have a common understanding of main aspects in rational antibiotic use independently of working in a UH or DH. Variations in treatment of respiratory tract infections and in doses of antibiotics should be further studied.

The association between adherence to national antibiotic guidelines and mortality, readmission and length of stay in hospital inpatients: results from a Norwegian multicentre, observational cohort study.

Background: Clinical antibiotic prescribing guidelines are essential in defining responsible use in the local context. Our objective was to investigate the association between adherence to national antibiotic prescribing guidelines and patient outcomes across a wide range of infectious diseases in hospital inpatients. Methods: Over five months in 2014, inpatients receiving antibiotics under the care of pulmonary medicine, infectious diseases and gastroenterology specialties across three university hospitals in Western Norway were included in this observational cohort study. Patient and antibiotic prescribing data gathered from electronic medical records included indication for antibiotics, microbiology test results, discharge diagnoses, length of stay (LOS), comorbidity, estimated glomerular filtration rate (eGFR) on admission and patient outcomes (primary: 30-day mortality; secondary: in-hospital mortality, 30-day readmission and LOS). Antibiotic prescriptions were classified as adherent or non-adherent to national guidelines according to documented indication for treatment. Patient outcomes were analysed according to status for adherence to guidelines using multivariate logistic, linear and competing risk regression analysis with adjustments made for comorbidity, age, sex, indication for treatment, seasonality and whether the patient was admitted from an institution or not. Results: In total, 1756 patients were included in the study. 30-day-mortality and in-hospital mortality were lower (OR = 0.48, p = 0.003 and OR = 0.46, p = 0.001) in the guideline adherent group, compared to the non-adherent group. Adherence to guideline did not affect 30-day readmission. In linear regression analysis there was a trend towards shorter LOS when LOS was analysed for patients discharged alive (predicted mean difference - 0.47, 95% CI (- 1.02, 0.07), p = 0.081). In competing risk analysis of LOS, the adherent group had a subdistribution hazard ratio (SHR) of 1.17 95% CI (1.02, 1.34), p = 0.025 for discharge compared to the non-adherent group. Conclusions: Adhering to antibiotic guidelines when treating infections in hospital inpatients was associated with favourable patient outcomes in terms of mortality and LOS.

Potential for More Rational Use of Antibiotics in Hospitalized Children in a Country With Low Resistance: Data From eight Point Prevalence Surveys.

BACKGROUND: Antimicrobial resistance is low in Norway, but to prevent an increase, the Norwegian Government has launched a National Strategy including a 30% reduction of broad-spectrum antibiotics (BSA) in hospitals within 2020. BSA are defined as second- and third-generation cephalosporins, carbapenems, piperacillin/tazobactam and quinolones. There are no recent studies of antibiotic use in Norwegian hospitalized children. The aim of this study was to describe the use of antibiotics with emphasis on BSA in Norwegian hospitalized children and neonates to detect possibilities for optimization. METHODS: Data were extracted from 8 national point prevalence surveys of systemic antibiotic prescriptions in Norwegian hospitals between 2015 and 2017. The choices of antibiotics were compared with the empirical recommendations given in available Norwegian guidelines. In total, 1323 prescriptions were issued for 937 patients. RESULTS: Twenty-four percent of pediatric inpatients were given antibiotics. Adherence to guidelines was 48%, and 30% (95% confidence interval: 27%-33%) of all patients on antibiotics received BSA. We identified only small variations in use of BSA between hospitals. One-third of the patients on antibiotic therapy received prophylaxis whereof 13% were given BSA. In 30% of prescriptions with BSA, no microbiologic sample was obtained before treatment. CONCLUSIONS: This study reveals an excess of prescriptions with BSA in relation to the low resistance rate in Norway. Our findings reveal areas for improvement that can be useful in the forthcoming antibiotic stewardship programs in Norwegian pediatric departments.