Decreasing lifetime prevalence of diabetes-related foot ulcers in Norway: repeated cross-sectional population-based surveys from the HUNT study (1995-2019).

Background and aims: Diabetes-related foot ulcers (DFU) are a persistent healthcare challenge, impacting both patients and healthcare systems, with adverse effects on quality of life and productivity. Our primary aim was to examine the trends in lifetime prevalence of DFU, as well as other micro- and macrovascular complications in the Trøndelag Health Study (HUNT) in Norway. Methods: This study consists of individuals ≥20 years with diabetes participating in the population-based cross-sectional HUNT surveys (1995-2019). Prevalence ratios, comparing the lifetime prevalence of DFU and other relevant micro- and macrovascular complications between the HUNT surveys, were calculated using Poisson regression. Results: The lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 11.0% (9.5-12.7) in HUNT2, 7.5% (6.3-8.8) in HUNT3 and 5.3% (4.4-6.3) in HUNT4. The decrease in DFU prevalence from 1995 to 2019 was observed in both men and women, for all age groups, and for both type 1 and type 2 diabetes. The highest lifetime prevalence of DFU was found among those with type 1 diabetes. The decrease in HbA1c from HUNT2 to HUNT4 did not differ between those with and without a DFU. The prevalence of chronic kidney disease (eGFR <60 mL/min/1.73 m2 (eGFR categories G3-G5)) increased in both individuals with and without a DFU. Conclusion: Results from the HUNT surveys show a substantial decline in the lifetime prevalence of DFU from 1995 to 2019.

Socioeconomic differences in use of antiseizure medication in pregnancies with maternal epilepsy: A population-based study from Nordic universal health care systems.

OBJECTIVE: Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy. METHODS: We conducted a cross-sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006-2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%-4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference. RESULTS: Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03-1.57) to aRR = 1.66 for low education (95% CI: 1.30-2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88-2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29-2.24) and in polytherapy (aRR 2.65; 95% CI 1.66-4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08-1.26) to 1.26 (not married or cohabiting; 95% CI 1.17-1.36). SIGNIFICANCE: Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care.

GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis.

Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson's disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.

Interprofessional follow-up for people at risk of type 2 diabetes in primary healthcare - a randomized controlled trial with embedded qualitative interviews.

OBJECTIVE: To examine the effects of an empowerment-based interprofessional lifestyle intervention program among people at risk of type 2 diabetes on knowledge, skills, and confidence in self-management, health, psychological well-being, and lifestyle characteristics, and to explore the participants' perceptions of participating in the intervention. DESIGN AND METHODS: In line with the Medical Research Council complex interventions research methods framework, we conducted a randomized controlled trial with embedded qualitative interviews in primary healthcare clinics in Norway between 2019-2021. Of the patients at risk (The Finnish Diabetes Risk Score Calculator (FINDRISC) ≥15 or Body Mass Index (BMI) ≥30) 142 accepted the invitation, and 14 participants from the intervention group participated in individual interviews after the 12-month follow-up. Our primary outcome was the Patient Activation Measure (PAM-13). Secondary outcomes were EQ-5D-5L, EQ-VAS, WHO-Overall health, WHO-Overall QOL, weight, height, waist circumference, and regularity of physical activity. We used thematic analysis to analyse the qualitative data. RESULTS: There was no clinically relevant differences of neither the primary nor the secondary endpoints between intervention and control group. As to the qualitative data, we identified two distinct features: 'Meaningful perspectives on lifestyle changes' and 'Lifestyle change is not a linear process due to challenges faced along the way' putting ownership of their choices in life into picture. CONCLUSION: The negative results of the RCT stand in contrast to the findings given by the participants voices, perceiving the intervention as a key eye opener placing their health challenges in perspective. How to interpret these seemingly conflicting findings of participants being seen, heard, and understood, helping them to take more conscious ownership of their choices in life, and at the same time demonstrating no improvements in symptoms or measures, is a dilemma that needs further exploration. We should be careful to implement interventions that do not demonstrate any effects on the quantitative outcomes.

Prescribing patterns for higher dose folic acid in pregnant women with epilepsy treated with antiseizure medication.

OBJECTIVE: This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM). METHODS: In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends. RESULTS: Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid. SIGNIFICANCE: Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability.

Prenatal exposure to antiseizure medications and fetal growth: a population-based cohort study from the Nordic countries.

Background: The short- and long-term consequences of restricted fetal growth cause considerable concern, and how prenatal exposure to different antiseizure medications (ASMs) affects fetal growth remains uncertain. Methods: This was a population-based cohort study of liveborn singleton children born in Denmark, Finland, Iceland, Norway, and Sweden from 1996 to 2017. Prenatal exposure was defined as maternal filling of prescriptions for ASM during pregnancy registered in national prescription registries and primary outcomes were adjusted odds ratios (aORs) of microcephaly or being born small for gestational age. Findings: We identified 4,494,918 children (males: 51.3%, 2,306,991/4,494,918), including 38,714 (0.9%) children of mothers with epilepsy. In the overall population, prenatal monotherapy exposure with carbamazepine (aOR: 1.25 (95% CI: 1.12-1.40)), pregabalin (aOR: 1.16 (95% CI: 1.02-1.31)), oxcarbazepine (aOR: 1.48 (95% CI: 1.28-1.71)), clonazepam (aOR: 1.27 (95% CI: 1.10-1.48)), and topiramate (aOR: 1.48 (95% CI: 1.18-1.85)) was associated with risk of being born small for gestational age, and carbamazepine was associated with microcephaly (aOR: 1.43 (95% CI: 1.17-1.75)). In children of mothers with epilepsy, prenatal exposure to carbamazepine (aOR: 1.27 (95% CI: 1.11-1.47)), oxcarbazepine (aOR: 1.42 (95% CI: 1.18-1.70)), clonazepam (aOR: 1.40 (95% CI: 1.03-1.89)), and topiramate (aOR: 1.86 (95% CI: 1.36-2.54)) was associated with being born small for gestational age; carbamazepine, with microcephaly (aOR: 1.51 (95% CI: 1.17-1.95)). No associations with small for gestational age and microcephaly were identified after prenatal exposure to lamotrigine, valproate, gabapentin, levetiracetam, phenobarbital, acetazolamide, phenytoin, clobazam, primidone, zonisamide, vigabatrin, ethosuximide and lacosamide, but except for lamotrigine, valproate, gabapentin, and levetiracetam, numbers of exposed children were small. Interpretation: Prenatal exposure to carbamazepine, oxcarbazepine, clonazepam, and topiramate was associated with increased risk of being born small for gestational age in both the overall population and in children of women with epilepsy suggesting that prenatal exposure to these drugs is associated with fetal growth restriction. Funding: The NordForsk Nordic Program on Health and Welfare (83539), the Independent Research Fund Denmark (1133-00026B), the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), and the Lundbeck Foundation (R400-2022-1205).

How valid is a prescription-based multimorbidity index (Rx-risk) in predicting mortality in the Outcomes and Multimorbidity In Type 2 diabetes (OMIT) study? A nation-wide registry-based cohort study from Norway.

OBJECTIVE: The prescription-based Rx-risk index has previously been developed to measure multimorbidity. We aimed to adapt and evaluate the validity of the Rx-risk index in prediction of mortality among persons with type 2 diabetes. DESIGN: Registry-based study. SETTING: Adults with type 2 diabetes in Norway identified within the 'Outcomes and Multimorbidity In Type 2 diabetes' cohort, with linkage to prescriptions from the Norwegian Prescription Database and mortality from the Population Registry. PARTICIPANTS: We defined a calibration sample of 42 290 adults diagnosed with type 2 diabetes 1950-2013, and a temporal validation sample of 7085 adults diagnosed 2014-2016 to evaluate the index validity over time PRIMARY OUTCOME MEASURE: All-cause mortality METHODS: For the calibration sample, dispensed drug prescriptions in 2013 were used to define 44 morbidity categories. Weights were estimated using regression coefficients from a Cox regression model with 5 year mortality as the outcome and all morbidity categories, age and sex included as covariates. The Rx-risk index was computed as a weighted sum of morbidities. The validity of the index was evaluated using C-statistic and calibration plots. RESULTS: In the calibration sample, mean (SD) age at start of follow-up and duration of diabetes was 63.8 (12.4) and 10.1 (7.0) years, respectively. The overall C-statistic was 0.82 and varied from 0.74 to 0.85 when stratifying on age groups, sex, level of education and country of origin. In the validation sample, mean (SD) age and duration of diabetes was 59.7 (13.0) and 2.0 (0.8) years, respectively. Despite younger age, shorter duration of diabetes and later time period, the C-index was high both in the total sample (0.84) and separately for men (0.83) and women (0.84). CONCLUSIONS: The Rx-risk index showed good discrimination and calibration in predicting mortality and thus presents a valid tool to assess multimorbidity among persons with type 2 diabetes.

Incidence trends of adult glioma in Norway and its association with occupation and education: A registry-based cohort study.

BACKGROUND: Gliomas constitute 75 % of all malignant primary adult brain tumors. Being the most frequent histologic subtype, glioblastomas (GBMs) cause substantial morbidity and mortality worldwide and the Nordic countries have some of the highest incidence rates in the world. Therefore, we investigated the incidence of gliomas in Norway including time trends and associations with education and occupation. METHODS: We retrieved individual-level data from databases at Statistics Norway containing information on education and occupation and linked them to data on adult glioma patients diagnosed during 2004-21 from the Cancer Registry of Norway. Age-standardized incidence rates (ASIRs) (World Standard Population) were calculated and analyzed with regards to sex and morphology. Poisson regression was used to test for time-trends, and to analyze the associations between education, occupation and glioma incidence, adjusted for age, sex, and calendar year. Estimates were reported as incidence rate ratios (IRRs) with 95 % confidence intervals (CIs). RESULTS: The overall ASIR of gliomas (per 100,000 person-years) was 7.1 (95 % CI 6.9-7.3), with no specific time trend during the study period. The incidence increased with age. Compared to the other subtypes, GBMs were diagnosed at older ages. The risks of developing glioma overall and GBM were associated with occupation but not with educational level. The relative risk of glioma and GBM were respectively 1.17 (95 % CI 1.05-1.31) and 1.17 (95 % CI 1.02-1.35) among high-skilled white-collar workers compared to blue-collar workers. CONCLUSIONS: The overall and sex-specific ASIRs of gliomas and GBMs did not show any noticeable time trends. The higher risk of developing glioma overall and GBM in high-skilled white-collar workers compared to blue-collar workers calls for further investigations.

Prenatal Exposure to Antiseizure Medications and Risk of Epilepsy in Children of Mothers With Epilepsy.

Importance: Use of valproate and certain other antiseizure medications (ASMs) in pregnancy is associated with abnormal fetal brain development with potential long-term implications for the child. Objective: To examine whether use of valproate and other ASMs in pregnancy among mothers with epilepsy is associated with epilepsy risk in their children. Design, Setting, and Participants: This prospective, population-based register cohort study included singletons born to mothers with epilepsy in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Data analysis was performed from October 2022 to December 2023. Exposure: Redeemed prescription for an ASM from 30 days before pregnancy until birth. Main Outcomes and Measures: The main outcome was epilepsy in children, assessed using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses from hospital care. Adjusted hazard ratios (AHRs) and 95% CIs were estimated using Cox proportional hazards regression. Secondary analyses included dose-response analyses, analyses using children of mothers who discontinued ASM prior to pregnancy as the reference, and sibling analyses. Results: This cohort study included 38 663 children of mothers with epilepsy (19 854 [51.4%] boys). Children were followed up from birth; the mean length of follow-up was 7.2 years (range 0-22 years). Compared with 22 207 children of mothers not using an ASM in pregnancy, increased risks of epilepsy in children of mothers who used valproate in pregnancy (monotherapy: AHR, 2.18; 95% CI, 1.70-2.79; polytherapy: AHR, 2.10; 95% CI, 1.49-2.96) were observed. However, there was no dose-dependent association, and there was a similar risk of epilepsy in siblings who were exposed and unexposed to valproate (AHR, 0.95; 95% CI, 0.50-1.82). Prenatal exposure to topiramate monotherapy was associated with increased risk of epilepsy (AHR, 2.32; 95% CI, 1.30-4.16), and the risk was greater for higher doses, but the risk attenuated in comparisons with children of mothers who discontinued topiramate before pregnancy (AHR, 1.19; 95% CI, 0.26-5.44). Prenatal exposure to clonazepam monotherapy was also associated with increased epilepsy risk (AHR, 1.90; 95% CI, 1.16-3.12), but limited follow-up and low numbers precluded further analyses. No associations were observed for prenatal exposure to lamotrigine (AHR, 1.18; 95% CI, 0.95-1.47), levetiracetam (AHR, 1.28; 95% CI, 0.77-2.14), carbamazepine (AHR, 1.13; 95% CI, 0.85-1.50), or oxcarbazepine (AHR, 0.68; 95% CI, 0.44-1.05). Conclusions and Relevance: In this cohort study of children born to mothers with epilepsy, the associations found between prenatal exposure to certain ASMs and the child's risk of epilepsy did not persist in sensitivity analyses, suggesting that maternal ASM use in pregnancy may not increase epilepsy risk in children beyond that associated with the maternal epilepsy itself. These findings are reassuring for women in need of treatment with ASM in pregnancy.

Trends in cervical cancer screening in Norway 2012-2017: a comparison study of non-immigrant and immigrant women.

AIMS: Immigrant women in Norway have lower cervical cancer screening participation than non-immigrant women. Our aim in this study was to assess whether the observed increase in screening participation during 2012-2017 was different between Norwegian-born women and immigrant women. METHODS: Data were collected from three national registries. The study included 1,409,561 women, categorized according to country of birth and immigrant background: (i) Norway, Norwegian parents; (ii) Norway, immigrant parent(s); (iii) Europe, excluding Norway; (iv) Africa; (v) Asia, including Turkey; and (vi) other countries. Trends and differences between groups were analyzed using Poisson regression analyses with adjustments for variables other studies have found to influence screening participation. Trends were assessed by including half-years as a continuous variable in the models and reported as prevalence ratios with 95% confidence intervals. RESULTS: Screening participation increased in all groups, but was not statistically significant among women from Africa in the adjusted model. The highest increase was among Norwegian women, with a 2.2% increase per year. Interaction tests showed significantly smaller increases in screening among women born in Europe (p interaction < 0.0001), Africa (p interaction < 0.0001), Asia (p interaction < 0.0001), and countries in the "Other" category (p interaction = 0.004). There was also a smaller increase among Norwegian-born women with one or more immigrant parent(s), but this was not significant (p interaction = 0.178). CONCLUSIONS: The gap in screening participation and the increasing differences in trends suggest that healthcare services do not reach all women in Norway to the same extent. One should attempt to improve this while working toward further increasing screening participation for all.

Evaluation of an interprofessional follow-up intervention among people with type 2 diabetes in primary care-A randomized controlled trial with embedded qualitative interviews.

With an ageing population and improved treatments people live longer with their chronic diseases, and primary care clinics face more costly and difficult-to-treat multimorbid patients. To meet these challenges, current guidelines for the management of type 2 diabetes suggest that an interprofessional team should collaborate to enhance the delivery of worthwhile self-management support interventions. In this study, we aimed to evaluate the effects of an empowerment-based interprofessional follow-up intervention in people with type 2 diabetes in primary care on patient-reported outcomes, biomarkers and weight, and to explore the experiences of patients attending the intervention. We invited patients during regular visits to their general practitioners. The 12-month intervention included 1) empowerment-based counselling; 2) a standardized medical report. The control group received consultations with physicians only. The primary outcome was the Patient Activation Measure, a patient-reported measure assessing individual knowledge, skills, and confidence integral to managing one's health and healthcare. After the trial we conducted qualitative interviews. We observed no difference in the primary outcome scores. On secondary outcomes we found a significant between-group intervention effect in favor of the intervention group, with mean differences in glycemic control after 12 months (B [95% CI] = -8.6 [-17.1, -0.1] mmol/l; p = 0.045), and significant within-group changes of weight (B [95% CI] = -1.8 kg [-3.3, -0.3]; p = 0.02) and waist circumference (B [95% CI] = -3.9 cm [-7.3, -0.6]; p = 0.02). The qualitative data showed that the intervention opened patients' eyes for reflections and greater awareness, but they needed time to take on actions. The patients emphasized that the intervention gave rise to other insights and a greater understanding of their health challenges. We suggest testing the intervention among patients with larger disease burden and a more expressed motivation for change.

Association Between Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease: A Drug-wide Association Study.

BACKGROUND AND OBJECTIVES: The incidence rate of Parkinson disease (PD) has been increasing rapidly during the past years. Yet, no treatments exist to prevent or slow the progression of the disease. Moreover, we are unable to detect early disease stages during which intervention with disease-modifying therapies is most likely to succeed. The objective of this study was to perform an agnostic drug-wide association study estimating the association between the use of any of the drugs prescribed in Norway and the subsequent risk of PD. METHODS: This registry-based cohort study use data from the entire Norwegian population between 2004 and 2019 linked to the Norwegian Prescription Registry, with more than 600 million individual prescriptions. Drug classes were screened according to Anatomical Therapeutic Chemical codes at level 2, corresponding to therapeutic subgroups. We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the associations between drug classes and PD risk. All p values were corrected for multiple testing using the false discovery rate. In addition, we conducted sensitivity analyses of exposure definition as well as time-lag and dose-response analyses. RESULTS: The study population comprised 3,223,672 individuals, 15,849 of whom developed PD during the follow-up. We identified 31 drug classes that were statistically significantly associated with PD risk in Norway during the follow-up. Drugs acting on the renin-angiotensin system (HR 0.92, 95% CI 0.89-0.95), corticosteroids for systemic use (0.88, 95% CI 0.84-0.93), and vaccines (0.89, 95% CI 0.82-0.96) were associated with a decreased risk of PD even up to 10 years before PD onset. Drug classes used to treat symptoms related to prodromal signs of PD, such as constipation, urological issues, and depression, were associated with an increased risk of subsequent diagnosis of PD with HRs of 1.6 (95% CI 1.49-1.73), 1.48 (1.42-1.53), and 1.94 (1.87-2.01), respectively. DISCUSSION: This drug-wide study identified 31 drug classes that were associated with the PD risk change. It reveals the links of renin-angiotensin system medications, vaccines, and corticosteroids with PD risk and suggests that monitoring drug usage using pharmacoepidemiology may allow identifying individuals with prodromal PD.

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura.

Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.

High number of hypoglycaemic episodes identified by CGM among home-dwelling older people with diabetes: an observational study in Norway.

BACKGROUND: A scoping review from 2021 identified a lack of studies on the incidence, prevention and management of hypoglycaemia in home-dwelling older people with diabetes. The aim of this study was to investigate the frequency and duration of hypoglycaemic episodes measured by continuous glucose monitoring (CGM) in older people with diabetes who received home care and who were treated with glucose-lowering medications, and to compare the frequency and duration of hypoglycaemic episodes between subgroups of the study population according to demographic and clinical variables. METHODS: This was an observational study investigating the occurrence of hypoglycaemia in people with diabetes aged ≥ 65 years. Data were collected using blinded continuous glucose monitoring (CGM, iPro2) for 5 consecutive days. Frequency and duration of hypoglycaemic episodes were assessed using a sensor glucose cut-off value of 3.9 mmol/L. A blood sample for measurement of HbA1c and creatinine-based eGFR (CKD-EPI) was obtained during the monitoring period. Demographic and clinical data were collected from electronic patient records. RESULTS: Fifty-six individuals were enrolled (median age 82 years and 52% were men). Of the 36 participants who were treated with insulin, 33% had at least one hypoglycaemic episode during the five-day period. Among 18 participants who neither used insulin nor sulfonylurea, but other glucose-lowering medications, 44% had at least one hypoglycaemicepisode. Of those with hypoglycaemic episodes, 86% lived alone. The median duration of the hypoglycaemia was 1 h and 25 min, ranging from 15 min to 8 h and 50 min. CONCLUSION: This study identified an unacceptably high number of unknown hypoglycaemic episodes among older home-dwelling people with diabetes receiving home care, even among those not using insulin or sulfonylurea. The study provides essential knowledge that can serve as a foundation to improve the treatment and care for this vulnerable patient group. The routines for glucose monitoring and other prevention tasks need to be considered more comprehensively, also, among those treated with glucose-lowering medications other than insulin.

Patient activation in adults attending appointments in general practice: a cross-sectional study.

BACKGROUND: Patient activation refers to patients' knowledge, confidence, skills, ability, beliefs, and willingness to manage their health and healthcare. Patient activation is an essential component of self-management and identifying patient activation levels will identify people at risk for health decline at an earlier stage. We aimed to explore patient activation in among adults attending general practice by (1) investigating differences in patient activation according to characteristics and markers of health-related behaviour; (2) examining the associations of quality of life and satisfaction with health with patient activation; and (3) comparing patient activation between persons with or without type 2 diabetes (T2D) and with or without elevated T2D risk. METHODS: We performed a cross-sectional study and recruited 1,173 adult patients from four Norwegian general practices between May to December 2019. The participants completed a questionnaire containing sociodemographic and clinical variables, the Patient Activation Measure (PAM-13), the quality of life and satisfaction with health items from the WHO Quality of Life-BREF, three questions about exercise (regularity, intensity and exercise time), the Finnish Diabetes Risk Score (FINDRISC) and Body Mass Index. We tested differences between groups and associations using Chi-squared tests, Fisher's exact tests, t-tests, one-way ANOVAs and Spearman's rho tests. RESULTS: The sample's mean PAM-13 score was 69.8 (0-100) (SD 14.8). In the total population, we found that participants reporting higher patient activation scores also reported more favourable health-related behaviours (exercise and healthy eating). We found positive correlations between the PAM-13 scores and, respectively, the quality of life score and the satisfaction with health score. We found no differences in patient activation between people with or without T2D and those with or without elevated T2D risk. CONCLUSIONS: We found that higher patient activation was associated with favourable health-related behaviours, a better quality of life and better satisfaction with health among adults attending four general practices in Norway. Assessing patient activation has the potential to help general practitioners identify patients who might benefit from closer follow-up in advance of negative health outcomes.

High-dose folic acid and cancer risk; unjustified concerns by von Wrede and colleagues regarding our paper.

Women using antiseizure medication in pregnancy are often advised to use high doses of folic acid supplements (1mg to 5 mg) to reduce the risk of teratogenicity. Recently, we published a report showing an association between maternal prescription fill of high dose folic acid in relation to pregnancy and childhood cancer in the offspring. The report has sparked a debate about which dose of folic acid that should be recommended in pregnancy in women in need of antiseizure medication. In this Commentary, we explain our findings and the method used in our report, and answer recent questions that have emerged.

Prevalence of increased risk of type 2 diabetes in general practice: a cross-sectional study in Norway.

BACKGROUND: Type 2 diabetes (T2D) is a global public health problem, but the onset can be delayed or prevented with adequate intervention in individuals with increased risk. Therefore, a major challenge in general practice is to identify individuals at risk of diabetes. However, limited knowledge is available about the prevalence of high diabetes risk individuals in a primary care population. In a cohort of consecutive patients in general practice we examined the prevalence of known diabetes and estimated risk of diabetes using The Finnish Diabetes Risk Score (FINDRISC) calculator, by sociodemographic and clinical characteristics. METHODS: This study was a cross-sectional study conducted in four general practices in Western and Eastern Norway. A total of 1682 individuals, 20-80 years of age, were assessed for eligibility from May to December 2019. We excluded patients who actively declined participation (n = 112), were lost because of various organization challenges (n = 103) and patients who did not fulfil the inclusions criteria (n = 63). Diabetes prevalence and prevalence of individuals at risk of T2D with 95% confidence intervals (CI) were estimated for the total sample, by age group and for men and women separately. We tested for differences between groups using t-test for continuous variables and chi-square test (Pearson Chi-Square) for categorical variables. RESULTS: Of 1404 individuals, 132 reported known diabetes, yielding a prevalence of 9.9% (95% CI 8.4-11.6). Among participants without a known diagnosis of diabetes, the following estimates of elevated risk assessment scores were found: FINDRISC score ≥ 11 32.8% (95% CI 30.3-35.4) and FINDRISC ≥ 15 10.0% (95% CI 8.6-11.9). Comparable results were found between the sexes. CONCLUSIONS: Detection of unknown diabetes and individuals with increased risk, is of high public health relevance for early implementation of preventive measures aimed to reduce the risk of diabetes and its complications through lifestyle modification. A simple, non-expensive questionnaire, such as FINDRISC, may be valuable as an initial screening method in general practice to identify those in need for preventive measures.

Intensified follow-up of patients with type 1 diabetes and poor glycaemic control: a multicentre quality improvement collaborative based on data from the Norwegian Diabetes Register for Adults.

BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) and poor glycaemic control are at high risk of developing microvascular and macrovascular complications. The aim of this study was to determine if a quality improvement collaborative (QIC) initiated by the Norwegian Diabetes Register for adults (NDR-A) could reduce the proportion of patients with T1DM with poor glycaemic control (defined as glycated haemoglobin (HbA1c)≥75 mmol/mol) and reduce mean HbA1c at participating clinics compared with 14 control clinics. METHOD: Multicentre study with controlled before and after design. Representatives of 13 diabetes outpatient clinics (n=5145 patients with T1DM) in the intervention group attended four project meetings during an 18-month QIC. They were required to identify areas requiring improvement at their clinic and make action plans. Continuous feedback on HbA1c outcomes was provided by NDR-A during the project. In total 4084 patients with type 1 diabetes attended the control clinics. RESULTS: Between 2016 and 2019, the overall proportion of patients with T1DM and HbA1c≥75 mmol/mol in the intervention group were reduced from 19.3% to 14.1% (p<0.001). Corresponding proportions in the control group were reduced from 17.3% (2016) to 14.4% (2019) (p<0.001). Between 2016 and 2019, overall mean HbA1c decreased by 2.8 mmol/mol (p<0.001) at intervention clinics compared with 2.3 mmol/mol (p<0.001) at control clinics. After adjusting for the baseline differences in glycaemic control, there were no significant differences in the overall improvement in glycaemic control between intervention and control clinics. CONCLUSIONS: The registry linked QIC did not result in a significantly greater improvement in glycaemic control at intervention clinics compared with control clinics. However, there has been a sustained improvement in glycaemic control and importantly a significant reduction in the proportion of patients with poor glycaemic control at both intervention and control clinics during and after the QIC time frame. It is possible that some of this improvement may be due to a spillover effect from the QIC.

Prenatal Exposure to Antiseizure Medication and Incidence of Childhood- and Adolescence-Onset Psychiatric Disorders.

Importance: Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied. Objective: To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy. Design, Setting, and Participants: This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023. Exposures: Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth. Main Outcomes and Measures: The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported. Results: Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07). Conclusions and Relevance: Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.