To Örebro University

INTRODUCTION: Irritable bowel syndrome (IBS) is a common condition that should be diagnosed using the Rome criteria and limited laboratory testing. The aim of this retrospective, medical record-based study was to evaluate the adherence of Swedish primary health care practitioners to diagnostic guidelines for IBS.

METHODS: Using the electronic patient register in primary care, we identified 1943 new IBS cases in patients aged 18-65 between January 2015 and December 2019 in Region Örebro County. A random sample of 400 patients was selected and their medical records were scrutinized to evaluate diagnostic methods.

RESULTS: Of the 309 eligible medical records, only 36.2% of patients met the Rome III or IV criteria. The criteria were explicitly documented in 4.9% of cases, and subclassification was noted in 5.5%. There were no significant differences in diagnostic practices between GPs and other physicians. Only 9.4% were diagnosed without laboratory testing, although 69.9% did not undergo all recommended tests according to local guidelines. Rectoscopy was performed in 14.2%, while 9.7% and 5.8% of patients were referred for colonoscopy or CT, respectively, with significantly higher referral rates in patients over 40 years. Men were more frequently referred for colonoscopy while other diagnostic procedures showed no significant sex differences.

CONCLUSIONS: Adherence to IBS diagnostic guidelines in Swedish primary care seems to be limited among both GPs and non-GPs. The documented use of Rome criteria is minimal, and guideline-compliant laboratory testing is insufficient. Increased awareness and structured implementation of IBS diagnostic criteria are warranted.

BACKGROUND: The majority of individuals in Sweden with type 2 diabetes have their sole health care provider in primary health care. Metformin treatment often causes gastrointestinal side-effects. Our aim was to construct and validate a questionnaire assessing gastrointestinal symptoms before and after starting metformin treatment for type 2 diabetes.

METHODS: In the Interaction Between Metformin and Microbiota (MEMO) study, 54 participants rated six gastrointestinal symptoms at baseline and after 2 months of metformin treatment in a questionnaire (measured change, i.e. the difference between assessments at these two time points), as well as direct assessment of perceived change in symptoms after 2 months in a separate validation questionnaire (reported change, i.e. how participants themselves have perceived the change between the same two time points). Spearman's ρ was calculated and reported with its 95% CI.

RESULTS: The agreement between reported and measured change of symptoms, measured as Spearman's ρ, was above 0.4 for 4 out of 6 symptoms (poor appetite 0.60 [95% CI 0.39-0.75], loose stool or diarrhea 0.58 [95% CI 0.37-0.74], flatulence 0.45 [95% CI 0.21-0.64], and abdominal pain 0.45 [95% CI 0.20-0.65]). The agreement was lower for nausea and vomiting, although these were numerically above 75% in agreement, likely due to few symptomatic participants overall.

CONCLUSION: For common side-effect symptoms associated with metformin treatment, our study shows that symptom change measured as the difference between assessments at two different time-points was in overall agreement, validating the usability of the constructed questionnaire for metformin side-effects.

BACKGROUND: The prevalence of obesity is a global health challenge, as obesity is associated with various comorbidities, reduced quality of life, and increased mortality. Providing effective treatment to improve health and quality of life for people with obesity is a major health care concern. Internet-delivered treatment (IDT) is an alternative treatment that increases patient accessibility and reachability; however, pilot testing is required before such interventions are evaluated in full-scale studies or implemented.

OBJECTIVE: This study aims to investigate the feasibility and user-friendliness of an IDT program for obesity (IDT-O); to evaluate body weight, dietary habits, physical activity, psychosocial functioning, and experiences of treatment in those who completed the 6-month treatment; and to investigate the dropouts' experiences of the treatment.

METHODS: A prospective 1-year observational approach, evaluated through a multimethod research design, was adopted. Inclusion criteria were age 18 years and older, BMI of ≥30 kg/m2, or BMI of 28-29.9 kg/m2 with obesity-related comorbidity. Participants were offered a 6-month therapist-assisted IDT-O program providing evidence-based obesity treatment, behavioral and lifestyle support, and strategies to address weight stigma. BMI, participants' dietary habits, self-reported physical activity, psychosocial functioning, experiences of treatment effects, and treatment satisfaction were measured before treatment and after 6 and 12 months. Dropouts were followed up through qualitative interviews.

RESULTS: A total of 20 participants (17 females and 3 male; mean age 44.2, SD 16.4 years) started the IDT-O program, and 35% (7/20) completed all 12 modules. Ten (8 females) out of 13 dropouts were interviewed. Both quantitative and qualitative findings showed that participants were generally satisfied with the content and design of the intervention. Those who completed the IDT-O lost some weight (mean 2.0%, 95% CI -1.09 to 5.13), reported improved dietary habits (effect size [ES] 0.25, 95% CI -0.51 to 1.00), increased physical activity (ES 0.93, 95% CI -0.08 to 1.87), and improved psychosocial functioning (distress: ES 0.43, 95% CI 0.-0.37 to 1.19; avoidance: ES 0.67, 95% CI -0.18 to 1.48), 6 months after completing the treatment. The qualitative analysis of the interviews revealed "The programme was OK, but it does not suit everyone" as the main theme. The main themes were based on the 3 subthemes: "It wasn't for me," "There were good things," and "There are things to improve."

CONCLUSIONS: The findings indicate that the IDT-O holds potential as a treatment for people with obesity, although one limitation is that only 35% (7/20) of the participants completed the pilot program. Improvements in lifestyle habits and psychosocial functioning were observed in those who completed the IDT-O, but these findings are preliminary and need to be confirmed in a more comprehensive study. The issue of nonadherence underscores the importance of both thoroughly assessing patients before treatment and further development of IDT-O programs.

AIMS: Low-energy diet (LED) plus cognitive-behavioural therapy (CBT) produces substantial short-term weight loss in obesity, but long-term maintenance remains difficult. We evaluated whether adding intragastric balloon (IGB) treatment to group-based CBT improves weight maintenance after initial weight loss using LED.

MATERIALS AND METHODS: In this open-label randomized controlled trial, adults aged 30-65 years with BMI 32.5-45 kg/m2 underwent a 6-month run-in period combining LED and group-based CBT and were subsequently randomized to CBT and 1-year IGB or CBT alone. The primary endpoint was weight change in percent between randomization (6 months from enrollment) and 18 months (from enrollment), compared to total body weight (TBW) at enrollment. Secondary outcomes included the proportion of participants achieving weight loss thresholds, metabolic parameters and health-related quality of life (HRQoL).

RESULTS: Of 126 enrolled (mean 43.7 years; BMI 38.0 kg/m2), 107 were randomized 6 months after enrollment (IGB n = 51; CBT n = 56) and lost -18.7% (SE: 0.64) of TBW. At 18 months, the mean weight change from randomization was 5.2% with IGB versus 10.1% with CBT (p < 0.001). A significantly greater proportion of IGB recipients achieved ≥ 5% (84.3% vs. 63.6%; p = 0.021) and ≥ 10% (70.6% vs. 45.5%; p = 0.013) weight loss after 18 months, compared to the CBT group. Improvements in metabolic parameters and HRQoL showed no between-group differences.

CONCLUSIONS: As an adjunct to group-based CBT and after LED-induced weight loss, IGB treatment provided a modest advantage in weight maintenance for up to 18 months, although safety concerns remain and long-term studies are warranted.

AIMS: Metformin has hitherto not been proven superior to other type 2 diabetes (T2D) medications for the prevention of organ complications. The aim of this study is to report baseline data and blinded interim analyses in the register-based randomised clinical trial (RRCT) SMARTEST, which compares metformin and the SGLT2 inhibitor dapagliflozin in early T2D. We also present learnings from the novel decentralised methodology of this first RRCT in diabetes care.

MATERIALS AND METHODS: Participants with T2D since <4 years and without major cardiovascular or renal disease were included at 36 centres across Sweden between 2019 and 2023 at on-site visits or via remote inclusion using digital informed consent. Participants were randomised 1:1 to open-label dapagliflozin 10 mg/day or metformin at an individualised dose, and they are followed for 2-6 years, with blinding of researchers to endpoints per treatment arm. The composite primary endpoint is time to first event of: myocardial infarction, stroke, heart failure (MACE), appearance or progression of microvascular complications or all-cause death. These events are collected from the Swedish National Diabetes Register and the National Patient Register using automated extraction.

RESULTS: A total of 2072 patients, mean age 61.2 years, 39% women, entered randomised treatment. Signs of nephropathy, retinopathy and foot-at-risk were found in 6.1%, 13.2%, and 5.7%, respectively. Hypertension was present in 64.4%, and dyslipidaemia in 57.1%. In blinded interim analyses at a mean follow-up time of 19.0 months, the preliminary event rate of the primary composite endpoint was 11.7/100 patient-years (py) in the whole study population, mainly driven by microvascular complications. In contrast, rates of cardiovascular events and all-cause death were 0.6 and 0.3/100 py, respectively.

CONCLUSIONS: This decentralised RRCT in newly onset T2D demonstrates a highly feasible option for large-scale trials in the primary care setting, enabling representative participant recruitment. Blinded interim analyses showed a low risk of MACE or death, but unexpectedly high rates of microvascular complications. Study completion is event-driven and is expected by January 2026. The study will challenge or reinforce the current metformin paradigm in early T2D. (EUDRA-CT number 2019-001046-17; EU number 2024-516228-33-00; ClinicalTrials.gov Identifier: NCT03982381).

Highlights

•  Internet-delivered obesity treatment can help change lifestyle habits

•  Expectations for weight loss were not met

•  Life circumstances made it difficult to commit to treatment

•  Internet-delivered treatment is not for everyone.

OBJECTIVE: To estimate the effect on healthcare resource use after introducing the World Health Organization diagnostic criteria (WHO-2013) for gestational diabetes mellitus (GDM) compared to former criteria in Sweden (SWE-GDM). DESIGN: A cost-analysis alongside the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) randomised controlled trial.

SETTING: Sweden, with risk-factor based screening for GDM. POPULATION: 47 080 pregnant women and their infants. METHODS: A register-based cost-analysis from a healthcare perspective alongside a stepped-wedge cluster RCT of switching from SWE-GDM to WHO-2013 criteria in 2018. Analyses were made on the population level and repeated in the subgroup affected by the intervention, that is, those with plasma glucose values between SWE-GDM and WHO-2013 criteria. Sensitivity analysis by bootstrapping was performed.

MAIN OUTCOME MEASURES: Estimated costs for obstetric surveillance (including GDM-management), delivery and neonatal healthcare until 28 days postpartum. RESULTS: On a population level, the WHO-2013 criteria were associated with increased costs of obstetric surveillance (adjusted mean [bootstrap confidence interval]) €94.0 [24.5-169.1], delivery care €20.4 [-33.5 to 75.4] and neonatal care €331.0 [75.1-589.0] per pregnancy, and in the affected subgroup €606.9 [377.7-872.4], €348.5 [126.0-542.0] and €129.3 [-559.0 to 980.9] respectively.

CONCLUSIONS: Implementation of the WHO-2013 criteria in Sweden was associated with increased costs for obstetric surveillance and delivery on a population level, driven by the affected subgroup. The increased costs for neonatal care were associated with large uncertainty. A detailed understanding of the changes in resource use can guide decisions to mitigate cost increases.

Our aim was to provide new data on the incidence, prevalence, and secular trend of type 2 diabetes (T2D) in Sweden, specifically early-onset T2D. We followed the Swedish population 2006 to 2021 and calculated age-standardized incidence (per 100 000) and prevalence (%) of T2D (overall) and early-onset T2D (age 23-39 years) stratified by sex, region of birth, and educational level. We projected the future prevalence of early-onset T2D by combining observed trends with population projections. From 2006 to 2021, the prevalence of T2D rose from 4.87% to 7.50%, and incidence from 477 [95% confidence interval (CI) 471-482] to 574 (CI 568-579). Early-onset T2D incidence increased from 54 to 107 (4.7% annual rise; CI 3.7%-5.7%) during this period. Incidence of early-onset T2D was higher in individuals born outside Europe (211, CI 195-226 vs 89, CI 84-93 in 2021) or low education (204, CI 185-223 vs 71, CI 65-77 in 2021), but a rise in incidence was seen irrespective of educational level, region of origin, and sex. If the incidence of early-onset T2D continues to increase at the same pace, its prevalence is projected to increase from 0.64% in 2021 to 3.2% in 2050. While T2D incidence rose marginally in Sweden 2006 to 2021, there was a significant rise in early-onset T2D, seen across different socioeconomic characteristics, with prevalence more than doubling and incidence nearly doubling. This development calls for targeted preventive efforts.

High blood pressure (BP) is a frequent cause for visits to primary healthcare centers (PHCCs) in Sweden. Guidelines on methods for BP measurements for diagnosis of hypertension have recently been updated. We aimed to study adherence to diagnostic guidelines in hypertension management and evaluate whether adherence to guidelines was related to organizational or sociodemographic characteristics. Interviews with representatives from 76 randomly selected PHCCs from eight regions in Sweden were conducted. PHCCs' use of 24-h ambulatory BP monitoring (ABPM), home BP monitoring (HBPM) and BP measurements in both arms for the diagnosis of hypertension were chosen as proxy markers for adherence to diagnostic guidelines. An adherence index was created as a composite score of these diagnostic methods. The proportion of PHCCs stating they "often use" ABPM and HBPM were 13.7% and 16.0%, respectively, and 57.3% stated they performed BP measurements in both arms. Two PHCCs did not use ABPM, HBPM or BP measurements in both arms to diagnose hypertension. None of the organizational or sociodemographic characteristics (number of listed patients, Care Need Index (CNI), geographical location, ownership, investigation primarily led by doctor/nurse, dedicated team management, special training for hypertension and local routines) were associated with the adherence index. This study shows that adherence to diagnostic guidelines vary largely between PHCCs. No organizational characteristic, not even team-based management, was associated with adherence to diagnostic guidelines. The variation raises questions about inequity healthcare and novel strategies that may be needed to improve PHCCs' adherence to diagnostic guidelines in hypertension management. Trial Registration: ClinicalTrials.gov identifier: 263351 [www.researchweb.org].

Background and aims: Metformin is one of the most common oral medications for type 2 diabetes (T2D) worldwide. Metformin treatment is associated with occurrence of gastrointestinal (GI) symptoms, which limit patient adherence to the treatment. Previously, female sex, age ≤ 65 years and BMI ≥ 25 kg/m² have been associated with GI adverse events. Furthermore, it has also been suggested that higher levels of HbA1c at baseline are associated with GI adverse events. The number of studies on the topic are limited, and thus our aim was to assess the association between phenotype and GI adverse events in people with newly diagnosed T2D.

Materials and methods: The study was a prospective cohort study, called the MEtformin adverse events mediated by gut MicrobiOta (MEMO)-study. The study was performed in four Swedish regions: Västerbotten, Östergötland, Örebro, and Västra Götaland. Participants with newly diagnosed (<1 year) T2D and without medication were included and completed three visits in four months: a baseline visit (Table 1) before metformin treatment was initiated, and two visits after two and four months of metformin treatment. At each visit, data on phenotypic characteristics and metabolic biomarkers were collected. GI symptoms (diarrhoea, nausea, abdominal pain, bloating and loss of appetite) were assessed by questionnaire, and cases were defined as progression in GI symptoms compared to baseline. Statistical analysis was conducted using generalized linear regression modelling.

Results: We included 168 participants, 54% were male, the mean age was 63.3 years (SD ± 9.0), and the mean BMI was 32.0 kg/m² (SD ± 5.0). Sixty-one participants (36%) developed GI side effects symptoms (cases) and 64% did not (controls) (Table 1). There was no association between age, sex, BMI and GI adverse events. Furthermore, we observed no association between baseline HbA1c, c-peptide or cholesterol and the development of GI adverse events. However, fasting plasma glucose levels measured prior to metformin treatment initiation were inversely associated with development of GI side effects (OR 0.89, p=0.041).

Conclusion: Our study did not corroborate previously reported association between phenotype and gastro-intestinal adverse events of metformin in newly diagnosed people with T2D.