Takeda (Sweden)

Abstract Aims/hypothesis Chronic stimulation of β 2 -adrenoceptors, opposite to acute treatment, was reported to reduce blood glucose levels, as well as to improve glucose and insulin tolerance in rodent models of diabetes by essentially unknown mechanisms. We recently described a novel pathway that mediates glucose uptake in skeletal muscle cells via stimulation of β 2 -adrenoceptors. In the current study we further explored the potential therapeutic relevance of β 2 -adrenoceptor stimulation to improve glucose homeostasis and the mechanisms responsible for the effect. Methods C57Bl/6N mice with diet-induced obesity were treated both acutely and for up to 42 days with a wide range of clenbuterol dosages and treatment durations. Glucose homeostasis was assessed by glucose tolerance test. We also measured in vivo glucose uptake in skeletal muscle, insulin sensitivity by insulin tolerance test, plasma insulin levels, hepatic lipids and glycogen. Results Consistent with previous findings, acute clenbuterol administration increased blood glucose and insulin levels. However, already after 4 days of treatment, beneficial effects of clenbuterol were manifested in glucose homeostasis (32% improvement of glucose tolerance after 4 days of treatment, p < 0.01) and these effects persisted up to 42 days of treatment. These favourable metabolic effects could be achieved with doses as low as 0.025 mg kg −1 day −1 (40 times lower than previously studied). Mechanistically, these effects were not due to increased insulin levels, but clenbuterol enhanced glucose uptake in skeletal muscle in vivo both acutely in lean mice (by 64%, p < 0.001) as well as during chronic treatment in diet-induced obese mice (by 74%, p < 0.001). Notably, prolonged treatment with low-dose clenbuterol improved whole-body insulin sensitivity (glucose disposal rate after insulin injection increased up to 1.38 ± 0.31%/min in comparison with 0.15 ± 0.36%/min in control mice, p < 0.05) and drastically reduced hepatic steatosis (by 40%, p < 0.01) and glycogen (by 23%, p < 0.05). Conclusions/interpretation Clenbuterol improved glucose tolerance after 4 days of treatment and these effects were maintained for up to 42 days. Effects were achieved with doses in a clinically relevant microgram range. Mechanistically, prolonged treatment with a low dose of clenbuterol improved glucose homeostasis in insulin resistant mice, most likely by stimulating glucose uptake in skeletal muscle and improving whole-body insulin sensitivity as well as by reducing hepatic lipids and glycogen. We conclude that selective β 2 -adrenergic agonists might be an attractive potential treatment for type 2 diabetes. This remains to be confirmed in humans.

BACKGROUND: Individuals with ADHD are at increased risk for poor occupational outcomes. Educational attainment and psychiatric comorbidity may be important contributing factors for these outcomes, but the role of these factors is not well characterized. This study aimed to investigate the associations between ADHD and occupational outcomes, and to examine the influence of educational attainment, comorbid developmental disorders and intellectual disability on these associations. METHODS: We linked the Swedish population graduating from compulsory school 1998-2008 (N = 1.2 millions) to population-wide register-based data on clinical psychiatric diagnoses and medications, objective annual measures of educational, and occupational outcomes. Individuals were followed for between 6 to 16 years after graduation. RESULTS: Individuals with ADHD had annually on average 17 percent lower income, ratio = 0.83 (95% CI 0.83-0.84), 12.19 (11.89-12.49) more days of unemployment, and a higher likelihood of receiving disability pension, odds-ratio = 19.0 (18.4-19.6), compared to controls. Comorbid diagnoses of intellectual disability and developmental disorder explained most of the association between ADHD and disability pension, while lifetime educational attainment partially explained associations between ADHD and all occupational outcomes. Analyses of occupational trajectories found that income was lower and unemployment elevated relative to controls with the same educational attainment. Higher educational attainment correlated with higher income similarly among individuals with ADHD and controls after accounting for individual background factors. CONCLUSIONS: The occupational burden associated with ADHD is substantial. Comorbid developmental disorders, intellectual disability and educational difficulties (e.g., failing grades) from childhood to adulthood are important factors to consider when designing interventions to improve occupational outcomes in individuals with ADHD.

BACKGROUND: A better understanding of the trajectories and economic burden of psychiatric and somatic disorders (multimorbidity) in ADHD from childhood to adulthood is important for guiding more targeted areas for treatment of ADHD and prevention of multimorbidity, and for forecasting demands on the medical infrastructure. This study aimed to investigate patterns of healthcare utilization and costs of multimorbidity across young adulthood in individuals with a childhood ADHD diagnosis, and additionally in individuals who continue to have ADHD-related contact with health services (persisters) and those who do not (remitters). METHODS: We prospectively followed a cohort (N = 445,790) born 1987-1990 from the ages of 18 to 26 years. Data on healthcare utilization were obtained from the Swedish National Patient Register (inpatient and outpatient care) and the Prescribed Drug Register (medication prescriptions). RESULTS: Mean annual costs per capita from multimorbidity was €890 ($1,223) in individuals with a childhood ADHD diagnosis (persisters/remitters: €1,060[$1,456]/€609[$837]) and €304 ($418) in individuals without. Costs were largely driven by inpatient hospital admissions, mainly from drug abuse and injuries. Healthcare utilization and costs of psychiatric and somatic disorders at 18 years was significantly higher in individuals with childhood ADHD compared to those without. These group differences remained stable or increased across young adulthood for most outcomes and were generally larger in women than in men. ADHD remitters continued to show significantly greater healthcare utilization and costs compared to individuals without childhood ADHD, although their profiles were not as severe as ADHD persisters. CONCLUSIONS: Childhood ADHD has long-term associations with both psychiatric and somatic disorders. Findings demonstrate the individual and societal burden of ADHD in adulthood and highlight the importance of continued support from childhood-adolescent to adult health services and early prevention of multimorbidity. Findings also point to specific targets for intervention that may be effective, such as drug abuse and injuries.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality. We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities. METHODS: Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death. Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits. Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index. RESULTS: In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations. CONCLUSIONS: COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn’s disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn’s disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn’s disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn’s disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn’s disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn’s disease and ulcerative colitis patients ( p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Abstract Background Studies using self-reports indicate that individuals with ADHD are at increased risk for functional impairments in social and occupational settings, but evidence around real-life instability remains limited. It is furthermore unclear if these functional impairments in ADHD differ across sex and across the adult lifespan. Method A longitudinal observational cohort design of 3,448,440 individuals was used to study the associations between ADHD and residential moves, relational instability and job shifting using data from Swedish national registers. Data were stratified on sex and age (18–29 years, 30–39 years, and 40–52 years at start of follow up). Results 31,081 individuals (17,088 males; 13,993 females) in the total cohort had an ADHD-diagnosis. Individuals with ADHD had an increased incidence rate ratio (IRR) of residential moves (IRR 2.35 [95% CI, 2.32–2.37]), relational instability (IRR = 1.07 [95% CI, 1.06–1.08]) and job shifting (IRR = 1.03 [95% CI, 1.02–1.04]). These associations tended to increase with increasing age. The strongest associations were found in the oldest group (40–52 years at start of follow). Women with ADHD in all three age groups had a higher rate of relational instability compared to men with ADHD. Conclusion Both men and women with a diagnosis of ADHD present with an increased risk of real-life instability in different domains and this behavioral pattern was not limited to young adulthood but also existed well into older adulthood. It is therefore important to have a lifespan perspective on ADHD for individuals, relatives, and the health care sector.

INTRODUCTION: European Society of Endocrinology (ESE) guidelines provide goals for hypoparathyroidism management but do not define characteristics of chronic hypoparathyroidism that is not adequately controlled. Three European country-specific Delphi panels were conducted to gain consensus on these characteristics. METHODS: Delphi panels were conducted in the UK, Sweden, and Portugal using similar methodology. At each round, panellists considered patients with chronic hypoparathyroidism whose disease is not adequately controlled on conventional therapy according to a matrix of four presentations of patients with chronic hypoparathyroidism: normal biochemical levels/well (group 1), abnormal biochemical levels/well (group 2), normal biochemical levels/unwell (group 3), and abnormal biochemical levels/unwell (group 4), with wellness defined by the patient's persistent symptoms, comorbidities, and complications. For groups 2-4, panellists rated characteristics in five categories (patient characteristics, family history, comorbidities, biochemistry, and symptoms/impact on quality of life [QoL]) with respect to defining a patient as having chronic hypoparathyroidism that was not adequately controlled on conventional therapy. Consensus was achieved when more than 80% of respondents agreed. RESULTS: Among the three countries, panellists agreed that characteristics within four of the five categories (patient characteristics, comorbidities, biochemistry, and symptoms/impact on QoL) were important for defining inadequate control. Characteristics deemed important in groups 2-4 included a history of compliance problems and chronic kidney disease stages 4 and 5. In groups 2 and 4, the biochemical parameters deemed important were serum calcium, urinary calcium, and serum creatinine. In groups 3 and 4, tingling or numbness in the hands/feet and face was the only symptom deemed important in all three countries. CONCLUSION: Delphi panels conducted in three European countries provided national consensus on key parameters of patient characteristics, biochemistry, comorbidities, and symptoms/impact on QoL that define not adequately controlled chronic hypoparathyroidism. These characteristics should be tested more widely for their applicability in clinical practice. FUNDING: Shire International GmbH, Zug, Switzerland, a member of the Takeda group of companies.

OBJECTIVE: To evaluate treatment patterns for ADHD in Sweden. METHOD: Observational retrospective study of patients with ADHD from the Swedish National Patient Register and Prescribed Drug Register, 2018 to 2021. Cross-sectional analyses included incidence, prevalence, and psychiatric comorbidities. Longitudinal analyses (newly diagnosed patients) included medication, treatment lines, duration, time-to-treatment initiation, and switching. RESULTS: Of 243,790 patients, 84.5% received an ADHD medication. Psychiatric comorbidities were common, particularly autism among children, and depression in adults. Most frequent first-/second-line treatments were methylphenidate (MPH; 81.6%) and lisdexamfetamine dimesylate (LDX; 46.0%), respectively. In the second-line, LDX was most frequently prescribed (46.0%), followed by MPH (34.9%), then atomoxetine (7.7%). Median treatment duration was longest for LDX (10.4 months), followed by amphetamine (9.1 months). CONCLUSION: This nationwide registry study provides real-life insights into the current epidemiology of ADHD and the changing treatment landscape for patients in Sweden.

BACKGROUND: Despite the increasing use of biologics in patients with inflammatory bowel disease (IBD), real-world data about outcomes in the era of biologics remain inconclusive. AIMS: To investigate trends in surgeries, hospitalisations and medication use in patients with IBD in a multinational, population-based cohort METHODS: We included 42,894 patients with ulcerative colitis (UC) and 24,864 with Crohn's disease (CD) who were diagnosed between 2010 and 2017 in Denmark, Norway and Sweden. We extracted data about surgeries, hospitalisations and medications from national registries and compared across countries and diagnosis years. RESULTS: Between 2010 and 2017, 2-year surgery rates were 4-7% in UC and 10-15% in CD and were stable over time. Two-year hospitalisation rates increased in Denmark (UC: 20% to 35%; CD: 27% to 32%) but were stable in Norway and Sweden (fluctuating between 33% and 37% in UC, and 46% and 52% in CD). Two-year rates of biologic use increased in both UC (7% to 16% in Denmark, 8% to 18% in Norway) and CD (22% to 26% in Denmark; 21% to 35% in Norway). Two-year rates of immunomodulator use increased in Norway (from 14% to 23% in UC; 37% to 45% in CD) and Sweden (from 41% to 52% in CD), but were stable in Denmark (between 17% and 21% in UC; 39% to 46% in CD). CONCLUSION: Between 2010 and 2017, surgery rates among Scandinavian patients with IBD remained stable, with no clear changes in hospitalisation rates despite the increasing use of immunomodulators and biologics.

BACKGROUND: Psychiatric and somatic problems in young adulthood have been found to be main drivers of costs in individuals with childhood ADHD. However, knowledge of the patterns of healthcare utilization and costs of comorbidities in middle-aged adults with newly diagnosed ADHD is very limited. METHOD: We studied individuals born 1966-1978 (from the Swedish Total Population Register) with newly diagnosed ADHD between the ages of 30-45 years and individuals without ADHD matched on birthdate, birth county, and sex. Healthcare utilization and expenditure for psychiatric and somatic disorders were obtained over four years (two years pre- and post-initial ADHD diagnosis). RESULTS: Middle-aged adults with newly diagnosed ADHD showed higher levels of healthcare utilization and costs (outpatient, inpatient, medications) for psychiatric and somatic comorbidities relative to adults without ADHD, both before and after the initial diagnosis. Females showed greater average group differences across the study period for medication prescriptions than males. Total incremental annual costs per capita were €2478.76 in adults with ADHD relative to those without, and costs were mainly driven by inpatient care. Psychiatric outpatient visits were statistically significantly higher the year before the ADHD diagnosis compared with two years before and after the diagnosis. CONCLUSION: This study demonstrates the substantial burden of psychiatric and somatic comorbidities in middle-aged adults newly diagnosed with ADHD. Psychiatric outpatient visits peaked in the year leading up to the ADHD diagnosis. Findings further suggested that females with ADHD may seek more treatment for comorbidities than males, which may reflect a general female tendency.

OBJECTIVE: To evaluate cost-effectiveness of brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma who have received autologous stem cell transplantation, from a Scottish healthcare payer perspective. METHODS: A Microsoft Excel-based partitioned survival model comprising three health states (progression-free survival [PFS], post-progression survival, and death) was developed. Relevant comparators were chemotherapy with or without radiotherapy (C/R) and C/R with intent to allogeneic hematopoietic stem cell transplantation (alloSCT). Data were obtained from the pivotal phase II single-arm trial in 102 patients (SG035-0003; NCT00848926), a systematic literature review and clinical expert opinions (where empirical evidence was unavailable). PFS and overall survival for brentuximab vedotin were estimated using 5-year follow-up data from SG035-0003, and extrapolated using event rates observed for comparator treatments from published survival data. Resource use included drug acquisition and administration; alloSCT; treatment of adverse events; and long-term follow-up. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty. RESULTS: In the base case, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin was £38,769 per quality-adjusted life year (QALY) vs C/R, whereas C/R with intent to alloSCT was dominated by brentuximab vedotin. ICERs for brentuximab vedotin generated by the deterministic sensitivity analysis ranged between £32,000-£54,000 per QALY. Including productivity benefits reduced the ICER to £28,881 per QALY. LIMITATIONS: Limitations include lack of comparative data from this single arm study and the heterogeneous population. Inconsistent baseline characteristic reporting across studies prevented complete assessment of heterogeneity and the extent of potential bias in clinical and cost-effectiveness estimates. CONCLUSIONS: Although the base case ICER is above the threshold usually applied in Scotland, it is relatively low compared with other orphan drugs, and lower than the ICER generated using a previous data cut of SG035-0003 that informed a positive recommendation from the Scottish Medicines Consortium, under its decision-making framework for assessment of ultra-orphan medicines.

BACKGROUND: Gaucher disease (GD) is a rare inherited multiorgan disorder, yet a diagnosis can be significantly delayed due to a broad spectrum of symptoms and lack of disease awareness. Recently, the prototype of a GD point-scoring system (PSS) was established by the Gaucher Earlier Diagnosis Consensus (GED-C) initiative, and more recently, validated in Gaucher patients in UK. In our study, the original GED-C PSS was tested in Finnish GD patients. Furthermore, the feasibility of point scoring large electronic health record (EHR) data set by data mining to identify potential undiagnosed GD cases was evaluated. METHODS: This biobank study was conducted in collaboration with two Finnish biobanks. Five previously diagnosed Finnish GD patients and ~ 170,000 adult biobank subjects were included in the study. The original PSS was locally adjusted due to data availability issues and applied to the Finnish EHR data representing special health care recordings. RESULTS: mutations. One patient was a compound heterozygote with a novel variant, potentially pathogenic mutation. Finnish EHR data allowed the retrospective assessment of 27-30 of the 32 original GED-C signs/co-variables. Total point scores of GD patients were high but variable, 6-18.5 points per patient (based on the available data on 28-29 signs/co-variables per patient). All GD patients had been recorded with anaemia while only three patients had a record of splenomegaly. 0.72% of biobank subjects were assigned at least 6 points but none of these potential "GD suspects" had a point score as high as 18.5. Splenomegaly had been recorded for 0.25% of biobank subjects and was associated with variable point score distribution and co-occurring ICD-10 diagnoses. DISCUSSION: This study provides an indicative GED-C PSS score range for confirmed GD patients, also representing potential mild cases, and demonstrates the feasibility of scoring Finnish EHR data by data mining in order to screen for undiagnosed GD patients. Further prioritisation of the "GD suspects" with more developed algorithms and data-mining approaches is needed. FUNDING: This study was funded by Shire (now part of Takeda).

Background: Real-world data on long-term outcomes of vedolizumab (VDZ) are scarce. Objective: To assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD). Design: A nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH). Methods: After re-consent, data of patients with Crohn’s disease (CD) ( n = 68) and ulcerative colitis (UC) ( n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey–Bradshaw Index ⩽4 in CD and partial Mayo score ⩽2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes. Results: VDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale ( p < 0.01 for each dimension; CD, n = 51; UC, n = 33) and the EuroQol 5-Dimensions, 5-levels index value ( p < 0.01; CD, n = 39; UC, n = 30). Median plasma-C-reactive protein concentrations (mg/L) decreased from 5 at baseline to 4 in CD ( p = 0.01, n = 53) and from 5 to 4 in UC ( p = 0.03, n = 34) at 156 weeks. Correspondingly, median faecal-calprotectin (µg/g) decreased from 641 to 114 in CD patients ( p < 0.01, n = 26) and from 387 to 37 in UC patients ( p = 0.02, n = 17). Conclusion: VDZ demonstrated high continuation rates and was associated with improvements in clinical outcomes, HRQoL measures and inflammatory markers at 2 and 3 years after treatment initiation in this prospective national SVEAH extension study. Registration: ENCePP registration number: EUPAS22735.

BACKGROUND: Real-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce. AIMS: To assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care. METHODS: Adult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP). RESULTS: Altogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (μg/g) decreased from 459 (185-1001) to 65 (26-227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152-1450) to 49 (20-275) in ulcerative colitis (n = 58; p < 0.001). CONCLUSION: Initiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ.

Abstract Background Biological therapy has been suggested to decrease surgery and hospitalisation risk in patients diagnosed with inflammatory bowel disease (IBD). During 2010 to 2016, the use of biologics in Denmark (DEN), Sweden (SWE) and Norway (NOR) increased dramatically and the time to first biologic treatment declined.1 However, the impact of increasing use of biologics on disease outcomes remains to be shown in real-life practice. In this nationwide study in three Nordic countries, we aimed to investigate trends in surgery and hospitalisation rates in IBD patients in the biological era.1 Høivik ML et al. Time to first treatment with biologic agents for Ulcerative Colitis and Crohn’s Disease across four Nordic countries: Results from the TRINordic study, Submitted to ECCO 2020. Methods A total number of 67 758 IBD patients (42 894 patients with ulcerative colitis (UC) and 24 864 Crohn’s disease (CD) diagnosed during the period from 2010 to 2017 in DEN, NOR and SWE were included using the National Patient Registries. Patients were required to have 1-year follow-up; results are limited to patients diagnosed between 2010 and 2016, inclusive. Using the unique personal identification number, individual-level information on surgery, hospitalisation and drug treatment were extracted from the National Patient Registries and the National Prescription Registries. Disease outcomes within two years after diagnosis were compared across annual cohorts. Results During 2010 to 2016, 2-year surgery rates in CD patients showed a non-significant decline from 11.9% in 2011 to 9.5% in 2016 in SWE while remaining stable in NOR and DEN (Figure 1). No temporal pattern in surgery risk was observed for UC. The proportion of CD patients being hospitalised within two years from diagnosis declined in SWE and NOR from 52.3% and 51.0% in 2011 to 47.3% and 38.5% in 2015 (p &amp;lt; 0.001), respectively, while hospitalisation in UC remained stable. In contrast, 2-year hospitalisation rates in DEN increased in CD from 27.0% in 2011 to 31.5% in 2016 (p = 0.045) and similarly in UC from 20.4 to 35.0% (p &amp;lt; 0.001), respectively (Figure 2). Conclusion No clear pattern was seen in two-year surgery and hospitalisation rates in IBD patients during 2010 to 2017 despite a concurrent increase in biological use in all countries. However, differences in treatment practices across countries might influence these findings. The impact of increased biological use on long-term outcomes in IBD remains to be shown.

Objective: To evaluate care transition and medication use in young adults with ADHD in Sweden. Method: Observational retrospective study of patients with ADHD from the Swedish National Patient Register, Prescribed Drug Register, and Cause of Death Register (2018–2020). Last contact with pediatric psychiatric care, first contact with adult psychiatric care, and medication use were described for ages 18 to 21 years, inclusive. Results: Of 19,233 patients who had dispensed ADHD treatment, 85.8% had received adult psychiatric care by 21 years of age. The proportion of patients on medication was highest at age 18 years (80.1%), decreasing to 36.1% by age 21 years. By 21 years, there were significantly more patients on versus off ADHD medication who had received healthcare for autism, been prescribed selective serotonin re-uptake inhibitors, and received adult psychiatric outpatient visits (all p &lt; .0001). Conclusion: This study demonstrates declining ADHD medication use during the pediatric-to-adult care transition for patients in Sweden.

Background Regular outcome monitoring is essential for effective attention deficit hyperactivity disorder (ADHD) treatment, yet routine care often limits long-term contacts to annual visits. Smartphone apps can complement current practice by offering low-threshold, long-term sustainable monitoring capabilities. However, special considerations apply for such measurement which should be anchored in stakeholder preferences. Methods This mixed-methods study engaged 13 experienced clinicians from Region Stockholm in iterative qualitative interviews to inform development of an instrument for app-based ADHD monitoring: the mHealth scale for Continuous ADHD Symptom Self-monitoring (mCASS). A subsequent survey, including the mCASS and addressing app-based monitoring preferences, was administered to 397 individuals with self-reported ADHD. Psychometric properties of the mCASS were explored through exploratory factor analysis and examinations of internal consistency. Concurrent validity was calculated between the mCASS and the Adult ADHD Self-Report Scale-V1.1 (ASRS-V1.1). Additional quantitative analyses included summary statistics and repeated-measures ANOVAs. Results Clinicians identified properties influencing willingness to use and adherence including content validity, clinical relevance, respondent burden, tone, wording and preferences for in-app results presentation. The final 12-item mCASS version demonstrated four factors covering everyday tasks, productivity, rest and recovery and interactions with others, explaining 47.4% of variance. Preliminary psychometric assessment indicated satisfactory concurrent validity ( r = .595) and internal consistency ( α = .826). Conclusions The mCASS, informed by clinician and patient experiences, appears to be valid for app-based assessment of ADHD symptoms. Furthermore, insights are presented regarding important considerations when developing mobile health (mHealth) instruments for ADHD individuals. These can be of value for future, similar endeavours.

Background: Narcolepsy impacts both patients and society, yet there is limited data on its socioeconomic consequences. Methods: This retrospective longitudinal cohort study used pseudonymized patient-level data from Swedish registers and included narcolepsy patients from January 2015–December 2019 and age–sex matched controls. All patients received an index date corresponding to their first narcolepsy diagnosis. Results: This study included 466 incident narcolepsy patients and 2330 matched controls. During the years studied, healthcare resource utilization was 2–5 times higher for incident narcolepsy patients compared to matched controls (p &lt; 0.0001). Modafinil, stimulants, and antidepressants were prescribed more often to incident narcolepsy patients (p &lt; 0.0001). Work productivity was significantly impacted, as incident narcolepsy patients took 7.0–10.5 more sick leave days than their matched controls (p &lt; 0.0001) and had an average of 14.8 net days of disability leave (associated with indirect costs of EUR 1630) versus only 5.8 days among matched controls (EUR 638) during the year of the index (p = 0.027). After controlling for age, sex, and the Charlson comorbidity index, the odds of disability leave were 3.3 times higher in incident narcolepsy patients. Conclusions: This study provides evidence of the magnitude of the substantial societal economic burden due to narcolepsy in Sweden, evidenced by higher healthcare resource utilization and indirect costs.

Clinical trials may not appropriately reflect real-world clinical practice. Therefore, we aimed to assess the clinical effectiveness of vedolizumab in a real-world Crohn’s disease (CD) cohort. This is a prospective, observational, multi-centre cohort study. Eligible patients had active CD confirmed by The presence of ulcers at colonoscopy, contrast enhancement, bowel thickening, or combs sign at magnetic resonance imaging, C-reactive protein (CRP) >upper threshold, Hs-CRP >2.87 mg/l or f-Calprotectin >200 µg/g at initiation of vedolizumab therapy and had started treatment with vedolizumab from 1/6/2015. Exclusion criteria included concurrent participation in a clinical trial in which IBD treatment is dictated by a study protocol and contraindications to vedolizumab. All patients provided a written consent. Data on clinical characteristics, treatment, disease activity and the short health scale (SHS) were recorded at baseline and prospectively, using an electronic Case Record Form, integrated with the Swedish National Quality Registry for IBD (SWIBREG). Data on the patients who had completed the 52 week follow-up are presented. The primary outcome at week 52 was clinical remission, defined as a Harvey Bradshaw Index (HBI) <5. Continuous data are presented as median (interquartile range). Differences between baseline and week 52 were assessed by the Wilcoxon-signed rank test. In total, 169 CD patients had been included by 19/09/2017. Clinical characteristics of patients (n = 104) who had completed the 52 week study period are shown in Table 1; 95/104 (91%) patients had failed prior anti-TNF therapy. At week 52, 71/104 (68%) were still on treatment with vedolizumab and 45/104 (43%) had achieved clinical remission. Among the 71 patients who had continued vedolizumab treatment, a decrease in the median HBI [6 (3–10) vs. 3 (2–5.5); n = 68; p < 0.001], median CRP [4.0 (2.0–10) g/l vs. 3.0 (1.4–5.0) g/l; n = 67; p = 0.01] and median f-Calprotectin [561 (139.5–830) vs. 232.5 (77.5–464) µg/g; n = 36; p = 0.09] was observed from baseline to week 52. Consistently, quality of life improved, defined by a significant reduction of the overall SHS score (n = 68; p < 0.001). Vedolizumab treated patients represented a treatment-refractory group. Significant improvements in clinical- and inflammatory activity, as well as in quality of life, were observed in patients who continued treatment through to week 52. The study was financially supported by Takeda.

Clinical trials may not readily reflect clinical practice. We aimed to assess the clinical effectiveness of vedolizumab in a real-world cohort of patients with ulcerative colitis (UC). This is a prospective, observational, multi-centre cohort study. Eligible patients had active UC confirmed by a Mayo endoscopic subscore ≥2 at initiation of vedolizumab and had started treatment from 1/6/2015. Exclusion criteria included concurrent participation in a clinical trial in which UC treatment is dictated and contraindications to vedolizumab. All patients provided a written consent. Data on clinical characteristics, treatment patterns, disease activity and the short health scale (SHS) were recorded at baseline and prospectively, using an electronic Case Record Form, integrated with the Swedish National Quality Registry for IBD (SWIBREG). Data on the patients who had completed the 52-week follow-up are presented. The primary outcome at Week 52 was clinical remission, defined as a Mayo score ≤2, with no subscore >1. Continuous data are presented as median (interquartile range). Differences between baseline and Week 52 were assessed by the Wilcoxon-signed rank test. One hundred and thirty UC patients had been included by 19/09/2017. Clinical characteristics of patients (n = 60) who had completed the 52-week study period are shown in Table 1; 49 of 60 (81.7%) patients had failed prior anti-TNF therapy. At Week 52, 36 of 60 (60%) were still on treatment with vedolizumab, 26 of 60 (43%) had achieved clinical remission (pMayo score), and 16 of 60 (27%) were in clinical and endoscopic remission (full Mayo score). Notably, information on endoscopy at Week 52 was absent in 10 patients (17%). Among the 36 patients who had continued vedolizumab treatment, a decrease in the median pMayo score [4 (4–6) vs. 1 (0–2); n = 34; p < 0.001], median full Mayo score [7 (6–8.5) vs. 1.5 (0–2.5); n = 24; p < 0.001], median f-Calprotectin [646 (403–894) vs. 281 (68–382) µg/g; n = 17; p = 0.01] and median C-reactive protein [3.0 (2.0–8.0) g/l vs. 2.4 (1.0–5.0) g/l; n = 35; p = 0.12] was observed from baseline to Week 52. Consistently, quality of life improved, defined as a significant reduction of the overall SHS score (n = 35; p < 0.001). Vedolizumab treated patients with UC represented a treatment-refractory group. Long-term effectiveness of vedolizumab can be achieved, in terms of clinical- and inflammatory activity as well as in quality of life. The study was financially supported by Takeda.