Effects of Inpatient Occupational Rehabilitation vs. Outpatient Acceptance and Commitment Therapy on Sick Leave and Cost of Lost Production: 7-Year Follow-Up of a Randomized Controlled Trial.

OBJECTIVES: Previously, we reported that an inpatient multimodal occupational rehabilitation program (I-MORE) was more effective than outpatient Acceptance and Commitment Therapy (O-ACT) in reducing sickness absence and was cost-effective over a 24-month period. Here we present 7-years of follow-up on sick leave and the cost of lost production. METHODS: We randomized individuals aged 18-60, sick-listed due to musculoskeletal or mental health disorders to I-MORE (n = 82) or O-ACT (n = 79). I-MORE, lasting 3.5 weeks, integrated ACT, physical training, and work-related problem-solving. In contrast, O-ACT mainly offered six weekly 2.5 h group sessions of ACT. We measured outcomes using registry data for days on medical benefits and calculated costs of lost production. Our analysis included regression analyses to examine differences in sickness absence days, logistic general estimating equations for repeated events, and generalized linear models to assess differences in costs of lost production. RESULTS: Unadjusted regression analyses showed 80 fewer days of sickness absence in the 7-year follow-up for I-MORE compared to O-ACT (95% CI - 264 to 104), with an adjusted difference of 114 fewer days (95% CI - 298 to 71). The difference in costs of production loss in favour of I-MORE was 27,048 euros per participant (95% CI - 35,009 to 89,104). CONCLUSIONS: I-MORE outperformed O-ACT in reducing sickness absence and production loss costs during seven years of follow-up, but due to a limited sample size the results were unprecise. Considering the potential for substantial societal cost savings from reduced sick leave, there is a need for larger, long-term studies to evaluate return-to-work interventions.

Healthcare costs associated with overweight and obesity at an individual versus a population level - a HUNT study. / Helsetjenestekostnader ved overvekt og fedme på individnivå versus populasjonsnivå ­ en HUNT-studie.

BACKGROUND: The interpretation of research results is affected by how results are presented. We show the importance of presenting the association between body mass index (BMI) and healthcare costs from both the individual perspective and the population perspective. MATERIAL AND METHOD: Using measurements of height and weight from the Nord-Trøndelag Health Study (HUNT Study) linked to register data on specialist healthcare costs and demographics, we estimated the association between BMI and specialist healthcare costs by means of regression analyses. RESULTS: From an individual perspective, the association between BMI and specialist healthcare costs was strongest in people in obesity classes 2 and 3 (BMI ≥ 35 kg/m2). In contrast, from a population perspective, the association was strongest in the case of overweight (BMI ≥ 25 kg/m2) or obesity class 1 (BMI ≥ 30 kg/m2), as there are more people in this BMI range. INTERPRETATION: The study emphasises the importance of including the population perspective in research studies and policy decision-making processes. People with severe obesity have a high individual risk, but their use of health services has less significance for the overall costs of health care since they are fewer people in this group.

Effectiveness of 'motivational interviewing' on sick leave: a randomized controlled trial in a social insurance setting.

OBJECTIVE: This study aimed to evaluate the effectiveness of motivational interviewing (MI) - a counselling approach offered by caseworkers at the Norwegian Labor and Welfare Administration (NAV) - on return to work (RTW) for individuals sick-listed for ≥8 weeks due to any diagnoses. MI was compared to usual case management and an active control during 12 months of follow-up. METHODS: In a randomized clinical trial with three parallel arms, participants were randomized to MI (N=257), usual case management (N=266), or an active control group (N=252). MI consisted of two MI sessions while the active control involved two sessions without MI, both were offered in addition to usual case management. The primary outcome was number of sickness absence days based on registry data. Secondary outcomes included time to sustainable RTW, defined as four consecutive weeks without medical benefits. RESULTS: The median number of sickness absence days for the MI group was 73 days [interquartile range (IQR) 31-147], 76 days (35-134) for usual care, and 75 days (34-155) for active control. In total 89%, 88% and 86% of the participants, respectively, achieved sustainable RTW. The adjusted hazard ratio (HR) for time to sustainable RTW was 1.12 (95% CI 0.90-1.40) for MI compared to usual case management and HR 1.16 (95% CI 0.93-1.44) compared to the active control. CONCLUSIONS: This study did not provide evidence that MI offered by NAV caseworkers to sick-listed individuals was more effective on RTW than usual case management or an active control. Providing MI in this context could be challenging as only half of the MI group received the intervention.

Risk of antidepressant initiation among users of cardiovascular agents and metformin. Findings from the Trøndelag Health Study (HUNT) and Norwegian Prescription Database (NorPD), Norway: Findings from the Trøndelag Health Study (HUNT) and Norwegian Prescription Database (NorPD), Norway.

Cardiovascular disease and diabetes are risk factors for depression, yet the relationship between the drug treatments for these diseases and the risk of antidepressant initiation remains unclear. This study aimed to examine possible associations between the use of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), beta-blockers (BB), calcium channel blockers (CCB), diuretics, or metformin and risk of antidepressant initiation. The Trøndelag Health Study (HUNT3), Norway, was linked to the Norwegian Prescription Database (NorPD). Participants with no prescriptions of cardiovascular agents, metformin, or antidepressants for at least 6 months before HUNT3 (baseline) were eligible and followed for 10 years. The exposure was the use of cardiovascular agents or metformin, defined as mono- or polytherapy from baseline to end of follow-up. The outcome was the initiation of antidepressant use, indicated by the first drug dispensation during the study period and expressed as hazard ratios (HRs) with 95% confidence intervals (CI). Among 20 227 adults aged 40-70 years at baseline, we observed different associations between cardiovascular agents or metformin and the risk of antidepressant initiation. ARBs or CCB monotherapy was associated with a lower risk of initiating antidepressant use (HR 0.70; 95%CI 0.56-0.88 and HR 0.81; 95%CI 0.61-1.06, respectively) compared to no use of any drugs included in the study (reference). Reduced risk of antidepressant initiation was among ASA or statin polytherapy users, whereas there was a small increased risk among participants on ASA monotherapy. In contrast, there was no statistical evidence of associations between ACEI, BB, diuretics, or metformin and increased or decreased risk of antidepressant initiation. Our mixed findings indicate the possibility that some cardiovascular agents may be associated with a reduced risk of initiating antidepressant use while others may not. However, bias due to the limitations of the study design is possible.

Impact of altering referral threshold from out-of-hours primary care to hospital on patient safety and further health service use: a cohort study.

OBJECTIVES: To estimate the impact of altering referral thresholds from out-of-hours services on older patients' further use of health services and risk of death. DESIGN: Cohort study using patient data from primary and specialised health services and demographic data from Statistics Norway and the Norwegian Cause of Death Registry. SETTING: Norway PARTICIPANTS: 491 653 patients aged 65 years and older contacting Norwegian out-of-hours services between 2008 and 2016. ANALYSIS: Multivariable adjusted and instrumental variable associations between referrals to hospital from out-of-hours services and further health services use and death for up to 6 months.Physicians' proportions of acute referrals of older, unknown patients from out-of-hours work were used as an instrumental variable ('physician referral preference') for their threshold of referral for such patients whose clinical presentations were less clear cut. RESULTS: For older patients, whose referrals could be attributed to their physicians' threshold for referral, mean length of stay in hospital increased 3.30 days (95% CI 3.13 to 3.27) within the first 10 days, compared with non-referred patients. Such referrals also increased 6 months use of outpatient specialist clinics and primary care physicians. Importantly, patients with referrals attributable to their physicians' threshold had a substantially reduced risk of death the first 10 days (HR 0.53, 95% CI 0.31 to 0.91), an effect sustaining through the 6-month follow-up period (HR 0.72, 95% CI 0.54 to 0.97). CONCLUSIONS: Out-of-hours patients whose referrals are affected by physician referral threshold contribute substantially to the use of health services. However, the referral seems protective by reducing the risk of death in the first 6 months after the referral. Thus, raising the threshold for referral to lower pressure on overcrowded emergency departments and hospitals should not be encouraged without ensuring the accuracy of the referral decisions, ideally through high-quality randomised controlled trial evidence.

Relative Age and Psychotropic Drug Use in Preterm and Term-Born Children and Young Adults.

BACKGROUND AND OBJECTIVES: Being among the youngest within a school class is linked to disadvantages in various educational and mental health domains. This study aimed to investigate whether preterm born infants are particularly vulnerable to relative age effects on mental health, not previously studied. METHODS: We used registry data on all Norwegians born between 1989 and 1998 to compare prescription status for psychostimulants, antidepressants, hypnotics, anxiolytics, and antipsychotics per year from age 10 to 23 years (2004-2016) between exposure groups with different time of birth in the year (relative age) and different gestational age (preterm versus term). RESULTS: Of 488 470 individuals, 29 657 (6,1%) were born preterm. For term born in November/December, the adjusted odds ratio (aORs) for psychostimulant prescription compared with peers born in January/February was 1.80 (95% confidence interval [CI], 1.69-1.91) at ages 10 to 14 years, and 1.17 (95% CI, 1.08-1.27) at ages 20 to 23 years. Within preterm born, the corresponding results were 1.39 (95% CI, 1.13-1.69) and 1.34 (95% CI, 1,00-1.78) at ages 10 through 14 and 20 through 23 years, respectively. CONCLUSIONS: Being relatively young within the school group was associated with increased psychostimulant prescription in the preterm as well as the term population. In contrast to term peers, the relative age effect for psychostimulant prescription seemed to persist to young adulthood for the preterm population. The results suggest that preterm individuals are vulnerable to long-term effects of relative immaturity and that they require careful consideration from both health care professionals and the school system.

How do busy hospital circumstances affect mortality and readmission within 60 days: A cohort study of 680 000 acute admissions in Norway.

OBJECTIVE: To study mortality and readmissions for older patients admitted during more and less busy hospital circumstances. DESIGN: Cohort study where we identified patients that were admitted to the same hospital, during the same month and day of the week. We estimated effects of inflow of acute patients and the number of concurrent acute inpatients. Mortality and readmissions were analysed using stratified Cox-regression. SETTING: All people 80 years and older acutely admitted to Norwegian hospitals between 2008 and 2016. MAIN OUTCOME MEASURES: Mortality and readmissions within 60 days from admission. RESULTS: Among 294 653 patients with 685 197 admissions, mean age was 86 years (standard deviation 5). Overall, 13% died within 60 days. An interquartile range difference in inflow of acute patients was associated with a hazard ratio (HR) of 0.99, 95% confidence interval (95% CI) 0.98 to 1.00). There was little evidence of differences in readmissions, but a 7% higher risk (HR 1.07, 95% CI 1.06 to 1.09) of being discharged outside ordinary daytime working hours. CONCLUSIONS: Older patients admitted during busier circumstances had similar mortality and readmissions to those admitted during less busy periods. Yet, they showed a higher risk of discharge outside daytime working hours. Despite limited effects of busyness on a hospital level, there could still be harmful effects of local situations.

High ward occupancy, bedspacing, and 60 day mortality for patients with myocardial infarction, stroke, and heart failure.

AIMS: To study the consequences of crowded wards among patients with cardiovascular disease. METHODS AND RESULTS: This is a cohort study among 201 801 patients with 258 807 admissions who were acutely admitted for myocardial infarction (N = 107 895), stroke (N = 87 336), or heart failure (N = 63 576) to any Norwegian hospital between 2008 and 2016. The ward admitting most patients with the given clinical condition was considered a patient's home ward. We compared patients with the same condition admitted when home ward occupancy was different, at the same hospital and during comparable time periods. Occupancy was standardized such that a one-unit difference corresponded to the interquartile range in occupancy in the given month. One interquartile increase in home ward occupancy was associated with 7% higher odds of admission to an alternate ward [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.09 to 1.11], and length of stay was shorter (-0.10 days, 95% CI -0.18 to -0.09). Patients with heart failure had 15% higher odds of admission to alternate wards (OR 1.15, 95% CI 1.08 to 1.23) and increased mortality [hazard ratio (HR) 1.08, 95% CI 1.03 to 1.15]. We found no apparent effect on mortality for patients with myocardial infarction (HR 0.99, 95% CI 0.94 to 1.05) or stroke (HR 1.00, 95% CI 0.96 to 1.05). CONCLUSIONS: Patients with heart failure had higher risk of admission to alternate wards when home ward occupancy was high. These patients may be negatively affected by full wards.

Effects of GP characteristics on unplanned hospital admissions and patient safety. A 9-year follow-up of all Norwegian out-of-hours contacts.

BACKGROUND: There are substantial differences in hospital referrals between general practitioners (GPs); however, there is little research on the consequences for patient safety and further healthcare use. OBJECTIVE: To investigate associations between out-of-hours GP characteristics, unplanned hospital admissions, and patient safety. METHODS: This cohort study included all Norwegian out-of-hours services contacts from 2008 to 2016, linked to registry data on patient characteristics, healthcare use and death, and GP age, sex, specialist status, out-of-hours service experience, and prior admission proportion. We estimated the impact from GP characteristics on (i) immediate unplanned hospital admissions for "all conditions," (ii) immediate unplanned hospital admissions for "critical conditions," (iii) 30-day unplanned hospital admissions, (iv) 30-day hospital costs, and (v) 30-day risk of death. To limit confounding, we matched patients in groups by age, time, and location, with an assumption of random assignment of GPs to patients with this design. RESULTS: Patients under the care of older and male GPs had fewer immediate unplanned hospital admissions, but the effects on cumulative 30-day unplanned hospital admissions and costs were small. The GPs' prior admission proportion was strongly associated with both immediate and 30-day unplanned hospital admissions. Higher prior admission proportion was also associated with admitting more patients with critical conditions. There was little evidence of any associations between GP characteristics and 30-day risk of death. CONCLUSIONS: GPs' prior admission proportion was strongly associated with unplanned hospital admissions. We found little effects on 30-day mortality, but more restrictive referral practices may threaten patient safety through missing out on critical cases.

Referral for specialized health services is a key part of the general practitioner (GP) role. Differences in referrals between primary care physicians have been widely studied, as they represent a target for reducing the use of specialized health services. However, the potential consequences beyond the actual referral have received little attention. Studying associations between physician characteristics and clinical decisions are difficult because physicians often systematically see different patient populations with different morbidity. Previous findings showing large differences in clinical decisions regarding referrals and hospital admissions may suffer from confounding. With our carefully matched study design, we could assume that the assignment of physicians to patients was random. We found substantial differences in referrals associated with GP characteristics. Seeing older and male GPs and specialists in family medicine were associated with fewer immediate unplanned hospital admissions but did not substantially influence unplanned hospital costs within 30 days. However, GPs with a history of admitting many of their recent patients had a substantial higher tendency to admit their future patients and represented a higher use of health services and costs. These GPs also referred more critically ill patients, an essential aspect of patient safety. The differences in referrals had minor impact on the patients' 30-day risk of death.

Corrigendum: Cognitive behavioral therapy improves physical function and fatigue in mild and moderate chronic fatigue syndrome: A consecutive randomized controlled trial of standard and short interventions.

[This corrects the article DOI: 10.3389/fpsyt.2021.580924.].

The relationship between body mass index and income: Using genetic variants from HUNT as instrumental variables.

Several studies have estimated effects of body mass index (BMI) on labour market outcomes, and these studies have mixed findings. A significant challenge has been to adequately control for omitted variables, selection, reverse causality, and measurement error. We examine the impact of BMI on income using genetic variants as instrumental variables for BMI. Individual-level pre-tax income from tax records was merged with health survey data containing measured height and weight, and data on genetic variants. The analyses were stratified by sex and a variety of methods were used to explore the sensitivity and validity of the instrumental variable (IV) strategy. For females we found that BMI had a negative effect on the logarithm of income. The effect estimated from the IV models (-0.02) was larger than the effect estimated from naïve ordinary least squares regressions (-0.01). For males, the coefficients for the effect of BMI on income were imprecise, and both positive and negative coefficients were estimated depending on the estimation method. Our results suggest that females are susceptible to reduced income levels following increased BMI.

Cognitive Behavioral Therapy Improves Physical Function and Fatigue in Mild and Moderate Chronic Fatigue Syndrome: A Consecutive Randomized Controlled Trial of Standard and Short Interventions.

Objective: To study whether standard cognitive behavioral therapy (CBT) and a shorter, interpersonal oriented cognitive behavioral therapy (I-CBT) can improve physical function and fatigue in patients diagnosed with mild to moderate chronic fatigue syndrome (CFS) in a multidisciplinary fatigue clinic. Design: Consecutively 236 participants 18-62 years old meeting the Centre of Decease Control, CDC 1994 criteria, with a subsample also fulfilling the Canadian criteria for CFS, were randomly allocated to one of three groups. Two intervention groups received either 16 weeks of standard CBT or 8 weeks of I-CBT vs. a waiting-list control group (WLC). Primary outcome was the subscale Physical Function (PF) from SF-36 (0-100). Secondary outcome was amongst others fatigue measured by Chalder Fatigue Questionnaire (CFQ) (0-33). Outcomes were repeatedly measured up to 52 weeks from baseline. Results: The additional effect relative to baseline at post-intervention for SF-36 physical function was 14.2 (95% CI 7.9-20.4 p < 0.001) points higher for standard CBT and 6.8 (0.5-13.2 p = 0.036) points higher for I-CBT compared with the control group. The additional effect relative to baseline at post-intervention for fatigue was 5.9 (95% CI 0.5-10.5 p = 0.03) points lower for standard CBT compared with the control group but did not differ substantially for I-CBT 4.8 (95% CI -0.4 to 9.9 p = 0.07). The positive change in physical function persisted at 1-year follow-up for both treatment groups, and for standard CBT also in fatigue. The two intervention groups did not differ significantly in self-reported physical function and fatigue at the 1-year follow-up. No serious adverse reactions were recorded in any of the groups during the trial period. Interpretation: A 16-week standard, individual CBT intervention improves physical function and fatigue in CFS outpatients with mild to moderate disease. A shorter 8-week I-CBT program improves physical function. Both treatments are safe, and the effect persist 1 year after baseline. Clinical Trial registration: ClinicalTrials.gov, Identifier: NCT00920777, registered June 15, 2009. REK-project number: 4.2008.2586, registered April 2, 2008. Funding: The Liaison Committee for Education, Research and Innovation in Central Norway.

Association of Preterm Birth With Prescription of Psychotropic Drugs in Adolescence and Young Adulthood.

Importance: Individuals born preterm have increased risk of mental health impairment compared with individuals born at term. The associations between preterm birth and attention-deficit/hyperactivity disorder and autism are well established; for depression, anxiety, psychotic and bipolar disorder, studies show divergent results. Objective: To compare the prescription of psychotropic drugs in adolescence and young adulthood between those born preterm and those born at term. Design, Setting, and Participants: This cohort study used registry data to identify all Norwegians born after 23 weeks of completed gestation between 1989 and 1998. Included individuals were those without registered birth defects, alive at age 10 years, and with available maternal data. Individuals were followed up from 2004 to 2016. Psychotropic drug prescriptions received from age 10 to 23 years were compared between preterm groups and peers born at term. Individuals were compared with their siblings to control for shared family confounding. Data analyses were performed from August 2018 through February 2020. Exposures: Gestational age at birth (GA) was categorized in 4 groups: extremely preterm (GA, 23 weeks and 0 days to 27 weeks and 6 days), very preterm (GA, 28 weeks and 0 days to 31 weeks and 6 days), moderately or late preterm (GA, 32 weeks and 0 days to 36 weeks and 6 days), and full term (GA, 37 weeks and 0 days to 44 weeks and 6 days). Main Outcomes and Measures: Prescriptions of psychotropic drugs (ie, prescriptions specifically of psychostimulants, antidepressants, anxiolytics, hypnotics or sedatives, or antipsychotics or prescriptions of any of these 5 drugs) among preterm groups were compared with prescriptions among peers born at term and among siblings. Results: Among 505 030 individuals (259 545 [51.4%] males; mean [SD] birth weight, 3533 [580] g), 762 individuals (0.2%) were extremely preterm, 2907 individuals (0.6%) were very preterm, 25 988 individuals (5.1%) were moderately or late preterm, and 475 373 individuals (94.1%) were full term. Individuals born preterm had increased risk of psychotropic drug prescription, with a dose-response association between GA and prescription. The extremely preterm group had higher rates of prescription for all drug types compared with peers born at term, with odds ratios from 1.7 (95% CI, 1.4-2.1) for antidepressants to 2.7 (95% CI, 2.1-3.4) for psychostimulants. The elevated odds of prescription of all types were less pronounced in the moderately to late preterm group, including odds ratios of 1.1 (95% CI, 1.0-1.1) for antidepressants and 1.2 (95% CI, 1.1-1.2) for psychostimulants. The increases in odds were smaller in the sibling comparison, and increases were not significant for several groups. For example, the OR for any prescription in the sibling analysis was 1.8 (95% CI, 1.2-2.8) in the very preterm group and 1.0 (95% CI, 0.9-1.1) in the moderately or late preterm group. Conclusions and Relevance: This cohort study found higher rates of prescription of psychotropic drugs throughout adolescence and young adulthood among individuals with all degrees of preterm birth compared with those born at term. These results provide further evidence for an increased risk of mental health impairment among individuals born preterm and suggest that this is not restricted to the most preterm groups.

High volumes of recent surgical admissions, time to surgery, and 60-day mortality.

AIMS: Few studies have investigated potential consequences of strained surgical resources. The aim of this cohort study was to assess whether a high proportion of concurrent acute surgical admissions, tying up hospital surgical capacity, may lead to delayed surgery and affect mortality for hip fracture patients. METHODS: This study investigated time to surgery and 60-day post-admission death of patients 70 years and older admitted for acute hip fracture surgery in Norway between 2008 and 2016. The proportion of hospital capacity being occupied by newly admitted surgical patients was used as the exposure. Hip fracture patients admitted during periods of high proportion of recent admissions were compared with hip fracture patients admitted at the same hospital during the same month, on similar weekdays, and times of the day with fewer admissions. RESULTS: Among 60,072 patients, mean age was 84.6 years (SD 6.8), 78% were females, and median time to surgery was 20 hours (IQR 11 to 29). Overall, 14% (8,464) were dead 60 days after admission. A high (75th percentile) proportion of recent surgical admission compared to a low (25th percentile) proportion resulted in 20% longer time to surgery (95% confidence interval (CI) 16 to 25) and 20% higher 60-day mortality (hazard ratio 1.2, 95% CI 1.1 to 1.4). CONCLUSION: A high volume of recently admitted acute surgical patients, indicating probable competition for surgical resources, was associated with delayed surgery and increased 60-day mortality. Cite this article: Bone Joint J 2021;103-B(2):264-270.

How does general practitioner discontinuity affect healthcare utilisation? An observational cohort study of 2.4 million Norwegians 2007-2017.

OBJECTIVES: Patients may benefit from continuity of care by a personal physician general practitioner (GP), but there are few studies on consequences of a break in continuity of GP. Investigate how a sudden discontinuity of GP care affects their list patients' regular GP consultations, out-of-hours consultations and acute hospital admissions, including admissions for ambulatory care sensitive conditions (ACSC). DESIGN: Cohort study linking person-level national register data on use of health services and GP affiliation with data on GP activity and GP characteristics. SETTING: Primary care. PARTICIPANTS: 2 409 409 Norwegians assigned to the patient lists of 2560 regular GPs who, after 12 months of stable practice, had a sudden discontinuity of practice lasting two or more months between 2007 and 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: Monthly GP consultations, out-of-hours consultations, acute hospital admissions and ACSC admissions in periods during and 12 months after the discontinuity, compared with the 12-month period before the discontinuity using logistic regression models. RESULTS: All patient age groups had a 3%-5% decreased odds of monthly regular GP consultations during the discontinuity. Odds of monthly out-of-hours consultations increased 2%-6% during the discontinuity for all adult age groups. A 7%-9% increase in odds of ACSC admissions during the period 1-6 months after discontinuity was indicated in patients over the age of 65, but in general little or no change in acute hospital admissions was observed during or after the period of discontinuity. CONCLUSIONS: Modest changes in health service use were observed during and after a sudden discontinuity in practice among patients with a previously stable regular GP. Older patients seem sensitive to increased acute hospital admissions in the absence of their personal GP.

Separating the genetics of childhood and adult obesity: a validation study of genetic scores for body mass index in adolescence and adulthood in the HUNT Study.

From a life-course perspective, genetic and environmental factors driving childhood obesity may have a lasting influence on health later in life. However, how obesity trajectories vary throughout the life-course remains unknown. Recently, Richardson et al. created powerful early life and adult gene scores for body mass index (BMI) in a comprehensive attempt to separate childhood and adult obesity. The childhood score was derived using questionnaire-based data administered to adults aged 40-69 regarding their relative body size at age 10, making it prone to recall and misclassification bias. We therefore attempted to validate the childhood and adult scores using measured BMI data in adolescence and adulthood among 66 963 individuals from the HUNT Study in Norway from 1963 to 2019. The predictive performance of the childhood score was better in adolescence and early adulthood, whereas the predictive performance of the adult score was better in adulthood. In the age group 12-15.9 years, the variance explained by the childhood polygenic risk score (PRS) was 6.7% versus 2.4% for the adult PRS. In the age group 24-29.9 years, the variance explained by the adult PRS was 3.9% versus 3.6% for the childhood PRS. Our findings support that genetic factors driving BMI differ at young age and in adulthood. Within the framework of multivariable Mendelian randomization, the validated childhood gene score can now be used to determine the consequence of childhood obesity on later disease.

Does cognitive behavioural therapy or mindfulness-based therapy improve mental health and emotion regulation among men who perpetrate intimate partner violence? A randomised controlled trial.

BACKGROUND: Intimate partner violence constitutes a serious health problem worldwide. To date the evidence is sparse on whether intimate partner violence group interventions could improve mental health outcomes among perpetrators and their partners. OBJECTIVES: To compare the effectiveness of nurse-led cognitive-behavioural group therapy vs. mindfulness-based stress reduction group therapy in improving reported mental health outcomes and emotion regulation at 12 months' follow-up amongst perpetrators who voluntarily seek help for violence in intimate partnerships. DESIGN: A randomised controlled trial. PARTICIPANTS: A total of 125 persons at an outpatient service run by a University Hospital in Norway for men who perpetrate intimate partner violence were enroled in the study. METHODS: The participants were randomly assigned to cognitive-behavioural group therapy (intervention group, N = 67) or mindfulness-based stress reduction group therapy (comparator group, N = 58). The pre-defined outcomes were symptoms of anxiety and depression as reported by the Hopkins Symptom Checklist 25 and general emotion regulation as reported by Difficulties in Emotion Regulation Scale at 12 months' follow-up. RESULTS: A reduction of symptoms of anxiety and depression was reported, with no between-group differences (intervention group: coefficient: - 0.17, P = 0.009; comparator group: coefficient: - 0.13, P = 0.036). Both groups had a small but statistically significant reduction in the Difficulties in Emotion Regulation Scale scores at 12 months' follow-up (intervention group: coefficient: - 0.47, P = <0.001; comparator group: coefficient: - 0. 34, P = <0.001). CONCLUSION: Even though there was reduction in symptoms in both groups at 12 months' follow-up with no between-group differences, the total symptom scores remained high in both groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01653860.

Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway: A longitudinal population-based cohort (the HUNT Study).

BACKGROUND: Obesity has tripled worldwide since 1975 as environments are becoming more obesogenic. Our study investigates how changes in population weight and obesity over time are associated with genetic predisposition in the context of an obesogenic environment over 6 decades and examines the robustness of the findings using sibling design. METHODS AND FINDINGS: A total of 67,110 individuals aged 13-80 years in the Nord-Trøndelag region of Norway participated with repeated standardized body mass index (BMI) measurements from 1966 to 2019 and were genotyped in a longitudinal population-based health study, the Trøndelag Health Study (the HUNT Study). Genotyping required survival to and participation in the HUNT Study in the 1990s or 2000s. Linear mixed models with observations nested within individuals were used to model the association between a genome-wide polygenic score (GPS) for BMI and BMI, while generalized estimating equations were used for obesity (BMI ≥ 30 kg/m2) and severe obesity (BMI ≥ 35 kg/m2). The increase in the average BMI and prevalence of obesity was steeper among the genetically predisposed. Among 35-year-old men, the prevalence of obesity for the least predisposed tenth increased from 0.9% (95% confidence interval [CI] 0.6% to 1.2%) to 6.5% (95% CI 5.0% to 8.0%), while the most predisposed tenth increased from 14.2% (95% CI 12.6% to 15.7%) to 39.6% (95% CI 36.1% to 43.0%). Equivalently for women of the same age, the prevalence of obesity for the least predisposed tenth increased from 1.1% (95% CI 0.7% to1.5%) to 7.6% (95% CI 6.0% to 9.2%), while the most predisposed tenth increased from 15.4% (95% CI 13.7% to 17.2%) to 42.0% (95% CI 38.7% to 45.4%). Thus, for 35-year-old men and women, respectively, the absolute change in the prevalence of obesity from 1966 to 2019 was 19.8 percentage points (95% CI 16.2 to 23.5, p < 0.0001) and 20.0 percentage points (95% CI 16.4 to 23.7, p < 0.0001) greater for the most predisposed tenth compared with the least predisposed tenth, defined using the GPS for BMI. The corresponding absolute changes in the prevalence of severe obesity for men and women, respectively, were 8.5 percentage points (95% CI 6.3 to 10.7, p < 0.0001) and 12.6 percentage points (95% CI 9.6 to 15.6, p < 0.0001) greater for the most predisposed tenth. The greater increase in BMI in genetically predisposed individuals over time was apparent after adjustment for family-level confounding using a sibling design. Key limitations include a slightly lower survival to date of genetic testing for the older cohorts and that we apply a contemporary genetic score to past time periods. Future research should validate our findings using a polygenic risk score constructed from historical data. CONCLUSIONS: In the context of increasingly obesogenic changes in our environment over 6 decades, our findings reveal a growing inequality in the risk for obesity and severe obesity across GPS tenths. Our results suggest that while obesity is a partially heritable trait, it is still modifiable by environmental factors. While it may be possible to identify those most susceptible to environmental change, who thus have the most to gain from preventive measures, efforts to reverse the obesogenic environment will benefit the whole population and help resolve the obesity epidemic.

Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses.

Estimates from Mendelian randomization studies of unrelated individuals can be biased due to uncontrolled confounding from familial effects. Here we describe methods for within-family Mendelian randomization analyses and use simulation studies to show that family-based analyses can reduce such biases. We illustrate empirically how familial effects can affect estimates using data from 61,008 siblings from the Nord-Trøndelag Health Study and UK Biobank and replicated our findings using 222,368 siblings from 23andMe. Both Mendelian randomization estimates using unrelated individuals and within family methods reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while Mendelian randomization estimates from samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects were strongly attenuated in within-family Mendelian randomization analyses. Our findings indicate the necessity of controlling for population structure and familial effects in Mendelian randomization studies.