Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease: A nationwide population-based cohort study from Sweden.

BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals. METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA. RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses. CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

Viable cartilage allograft outperforms existing treatments for focal knee cartilage defects.

PURPOSE: Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects. METHOD: In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results. RESULTS: The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm2 (mean = 4.58 cm2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8). CONCLUSION: VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options. LEVEL OF EVIDENCE: Level IV study.

Pharmacological treatment of asthma in Sweden from 2005 to 2015.

OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting ß2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment. METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression. RESULTS: Maintenance treatment with ICS together with long-acting ß2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use. CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

Diagnostic spirometry in COPD is increasing, a comparison of two Swedish cohorts.

Spirometry should be used to confirm a diagnosis of chronic obstructive pulmonary disease (COPD). This test is not always performed, leading to possible misdiagnosis. We investigated whether the proportion of patients with diagnostic spirometry has increased over time as well as factors associated with omitted or incorrectly interpreted spirometry. Data from medical reviews and a questionnaire from primary and secondary care patients with a doctors' diagnosis of COPD between 2004 and 2010 were collected. Data were compared with a COPD cohort diagnosed between 2000 and 2003. Among 703 patients with a first diagnosis of COPD between 2004 and 2010, 88% had a diagnostic spirometry, compared with 59% (p < 0.001) in the previous cohort. Factors associated with not having diagnostic spirometry were current smoking (OR 2.21; 95% CI 1.36-3.60), low educational level (OR 1.81; 1.09-3.02) and management in primary care (OR 2.28; 1.02-5.14). The correct interpretation of spirometry results increased (75% vs 82%; p = 0.010). Among patients with a repeated spirometry, 94% had a persistent FEV1/FVC or FEV1/VC ratio <0.70.

Caregiving and changes in health-related behaviour.

Potential health risks for informal caregivers have been hypothesised to be partly related to adverse changes in health-related behaviour, but evidence is limited. We examined whether smoking, drinking, eating, physical activity or leisure pursuits change in relation to co-resident or out-of-home caregiving (for someone outside the household), and if associations differ by sex, educational attainment, and welfare state typology. We conducted a longitudinal study using six waves of the Survey of Health, Ageing and Retirement in Europe, collecting data repeatedly from 2004 to 2017 for adults aged 50 years and older living in 17 European countries (57,962 individuals). To control for measured and unmeasured within-individual time-invariant confounders, we used fixed effects logistic models to analyse the repeated measures of caregiving, behaviour and covariates and estimated odds ratios (OR) with 95% confidence intervals (95%CI). Among male participants, unhealthy eating increased while smoking decreased [ORs 1.26 (95%CI 1.01-1.58) and 0.53 (0.36-0.78), respectively] in survey waves in which they provided co-resident care, compared with the waves that they did not. Among female participants, there was little change in behaviour between waves with and without co-resident caregiving. When providing out-of-home care, lacks of physical activity and leisure pursuits declined. But in the same time, drinking increased both men and women, and especially among individuals with lower educational attainment and residing in non-Nordic countries. To conclude, overall, increased drinking when providing out-of-home care was most consistent, especially among individuals with lower educational attainment and residing in non-Nordic countries. Otherwise, the associations varied by the type of care, behaviour and population subgroups. These findings indicated that not all caregivers are susceptible to behavioural changes, and that not all behaviour may be involved similarly in linking caregiving to health risks. This opens possibilities to target specific behaviour and groups to prevent adverse changes in health behaviour in caregivers.

Previous pre-eclampsia, gestational diabetes mellitus and the risk of cardiovascular disease: A nested case-control study in Sweden.

OBJECTIVE: Pre-eclampsia and gestational diabetes mellitus (GDM) are two common pregnancy complications that affect birth outcomes and are associated with a long-term risk of cardiovascular disease (CVD). The aims of this study were to investigate if the pre-eclampsia association with CVD is independent of GDM and modified by body mass index (BMI) or GDM. DESIGN: Case-control study. SETTING: Sweden. POPULATION: Cases were women with a first CVD event between 1991 and 2008 and a previous pregnancy who were matched with controls without CVD (1:5) by year of birth, age and region of birth. METHODS: Conditional logistic regression was used to evaluate the associations of GDM, pre-eclampsia and maternal BMI with CVD adjusted for potential confounders and effect modifications with interaction tests. MAIN OUTCOME MEASURES: CVD. RESULTS: There were 2639 cases and 13 310 controls with complete data. Pre-eclampsia and GDM were independent risk factors for CVD (adjusted odds ratio [aOR] 2.59, 95% CI 2.12-3.17 and aOR 1.47, 95% CI 1.04-2.09, respectively). After stratifying by maternal BMI, the adjusted association of pre-eclampsia with CVD did not differ notably between BMI groups: normal weight (aOR 2.65, 95% CI 1.90-3.69), overweight (aOR 2.67, 95% CI 1.52-4.68) and obesity (aOR 3.03, 95% CI 0.74-12.4). Similar findings were seen when stratifying on GDM/non-GDM. CONCLUSIONS: Pre-eclampsia and GDM are independent risk factors for later CVD and having both during pregnancy is a major risk factor for later CVD. The association between pre-eclampsia and CVD is not modified by BMI. Effective CVD preventive programs for high-risk women are urgently needed in order to improve women's long-term health.

Comorbid Heart Disease in Patients with COPD is Associated with Increased Hospitalization and Mortality - A 15-Year Follow-Up.

Purpose: The aim of this study was to examine the association of comorbid heart disease, defined as chronic heart failure or ischemic heart disease, on all-cause and cause-specific hospitalization and mortality in patients with COPD over a period of nearly 15 years. Materials and Methods: The cohort study included patients with COPD from primary and secondary care in 2005 with data from questionnaires and medical record reviews. The Swedish Board of Health and Welfare provided hospitalization and mortality data from 2005 through 2019. Cox regression analyses, adjusted for sex, age, educational level, smoking status, BMI, exacerbations, dyspnea score and comorbid diabetes or hypertension, assessed the association of comorbid heart disease with all-cause and cause-specific time to first hospitalization and death. Linear regression analyses, adjusted for the same variables, assessed this association with hospitalization days per year for those patients that had been hospitalized. Results: Of the 1071 patients, 262 (25%) had heart disease at baseline. Cox regression analysis showed a higher risk of hospitalization for patients with heart disease for all-cause (HR (95% CI) 1.55; 1.32-1.82), cardiovascular (2.14; 1.70-2.70) and other causes (1.27; 1.06-1.52). Patients with heart disease also had an increased risk of all-cause (1.77; 1.48-2.12), cardiovascular (3.40; 2.41-4.78) and other (1.50; 1.09-2.06) mortality. Heart disease was significantly associated with more hospitalization days per year of all-cause (regression coefficient 0.37; 95% CI 0.15-0.59), cardiovascular (0.57; 0.27-0.86) and other (0.37; 0.12-0.62) causes. No significant associations were found between heart disease and respiratory causes of hospitalization and death. Conclusion: Comorbid heart disease in patients with COPD is associated with an increased risk for all-cause hospitalization and mortality, mainly due to an increase of hospitalization and death of cardiovascular and other causes, but not because of respiratory disease. This finding advocates the need of a strong clinical focus on primary and secondary prevention of cardiovascular disease in patients with COPD.

Association of 5α-Reductase Inhibitors With Dementia, Depression, and Suicide.

Importance: In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for benign prostatic hyperplasia and androgenic alopecia. Numerous studies and reports have indicated associations of 5-ARIs with depression and suicide. However, most of these studies had methodological shortcomings, and very little is known about the potential association of 5-ARIs with dementia. Objective: To investigate the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide. Design, Setting, and Participants: This Swedish register-based cohort study included 2 236 876 men aged 50 to 90 years between July 1, 2005, and December 31, 2018. Statistical analyses were performed from September 15, 2021, to May 25, 2022. Main Outcomes and Measures: A diagnosis of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide. Exposures: A recorded prescription in the Swedish national prescription register of finasteride or dutasteride and duration of use. Results: Of 2 236 876 men (median age at the start of follow-up, 55 years [IQR, 50-65 years] and at treatment initiation, 73 years [IQR, 66-80 years]), 70 645 (3.2%) started finasteride treatment, and 8774 (0.4%) started dutasteride treatment. Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22 [95% CI, 1.17-1.28]; dutasteride: HR, 1.10 [95% CI, 1.01-1.20]), Alzheimer disease (finasteride: HR, 1.20 [95% CI, 1.10-1.31]; dutasteride: HR, 1.28 [95% CI, 1.09-1.50]), vascular dementia (finasteride: HR, 1.44 [95% CI, 1.30-1.58]; dutasteride: HR, 1.31 [95% CI, 1.08-1.59]), and depression (finasteride: HR, 1.61 [95% CI, 1.48-1.75]; dutasteride: HR, 1.68 [95% CI, 1.43-1.96]). However, the magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over 4 years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride. In contrast, 5-ARIs were not associated with suicide (finasteride: HR, 1.22 [95% CI, 0.99-1.49]; dutasteride: HR, 0.98 [95% CI, 0.62-1.54]). Conclusions and Relevance: This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement. Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.

Beta-blocker use and urothelial bladder cancer survival: a Swedish register-based cohort study.

BACKGROUND: Recent observational studies linked ß-adrenergic receptor blocker use with improved survival in patients with several cancer types, but there is no information on the potential effects of ß-blockers in patients with bladder cancer. Literature from pre-clinical studies is also limited, but urothelial cancer can exhibit significant overexpression of ß-adrenergic receptors relative to normal urothelial tissue, suggesting that urothelial cancer may benefit from ß-blockade therapy. We thus aimed to explore the possible association between ß-blocker use and bladder cancer-specific mortality (BCSM) among patients with urothelial bladder cancer. MATERIAL AND METHODS: Patients diagnosed during 2006-2014 and identified from the Swedish Cancer Register (n = 16,669) were followed until 31 December 2015. Cox regression was used to evaluate the association of ß-blockers dispensed within 90 days prior to cancer diagnosis with BCSM (primary outcome) and all-cause mortality, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and surgical procedures. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. RESULTS: Overall, ß-blocker use was associated with lower BCSM [HR 0.88 (95%CI 0.81-0.96)]. Especially use of nonselective ß-blockers showed a clear inverse association in comparison with both nonuse [0.66 (0.50-0.86)] and use of other antihypertensive medications [0.72 (0.54-0.95)]. The inverse association was most pronounced among patients with locally advanced/metastatic disease: [0.35 (0.18-0.68)]. A lower-magnitude inverse association was observed for selective ß-blocker use [0.91 (0.83-0.99)]. Largely similar inverse associations were observed for hydrophilic [0.82 (0.70-0.95)] and lipophilic [0.91 (0.83-1.00)] ß-blocker use. CONCLUSION: ß-blocker use, particularly of the nonselective type, was associated with lower BCSM, especially in patients with locally advanced/metastatic urothelial bladder cancer.

Biomarkers, Clinical Course, and Individual Needs in COPD Patients in Primary Care: The Study Protocol of the Stockholm COPD Inflammation Cohort (SCOPIC).

Background: To facilitate effective personalized medicine, primary health care needs better methods of assessing and monitoring chronic obstructive pulmonary disease (COPD). Aim: This cohort study aims to investigate how biomarkers relate to clinical characteristics and COPD patients' subjective needs over time. Methods: Patients (n=750) in different COPD severity according to the GOLD criteria and age- and sex-matched controls (n=750) will be recruited over a period of 5 years from 15 primary health care centers in Region Stockholm, Sweden, and followed for 10 years in the first instance. Data on patients' subjective needs will be collected via telephone/email, data on clinical/physiological variables (eg, symptoms, exacerbations, comorbidities, medications, smoking habits, lung function) from existing databases that are based on medical records, and data on biomarkers via repeated blood sampling. Quantitative and qualitative methods will be used. Initial results are expected after 2 years (feasibility test), and a larger body of evidence after 5 years. Discussion: The study is expected to provide definitive and clinically useful scientific evidence about how biomarkers relate to clinical variables and patients' subjective needs. This new evidence will facilitate accurate, and personalized COPD management by the use of valid biomarkers. It will provide useful tools for primary care professionals and may facilitate optimal self-management.

Association Between Inflammatory Bowel Disease and Spondyloarthritis: Findings from a Nationwide Study in Sweden.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] has been associated with spondyloarthritis [SpA], but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD with the general population, overall and by IBD subtype and age. METHODS: We used a nationwide register-based cohort study of 39 203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390 490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios [ORs] for a prior [prevalent] SpA diagnosis and conditional Cox regression to calculate hazard ratios [HRs] for a subsequent [incident] SpA diagnosis in IBD patients. RESULTS: IBD patients were more likely to have prevalent SpA at IBD diagnosis [2.5%] compared with reference individuals [0.7%] with an OR of 3.48 [95% CI: 3.23, 3.75]. They also more often received an incident diagnosis of SpA; during 23 341 934 person-years of follow-up in IBD patients, there were 1030 SpA events [5.0/1000 person-years] compared with 1524 SpA events in the reference group [0.72/1000 person-years], corresponding to an HR of 7.15 [95% CI: 6.60, 7.75]. In subgroup analyses, associations were most pronounced among patients with Crohn's disease ([OR = 5.20; 95% CI: 4.59, 5.89], and [HR = 10.55; 95% CI: 9.16, 12.15]) and paediatric onset IBD ([OR = 3.63; 95% CI: 2.35, 5.59] and [HR = 15.03; 95% CI: 11.01, 20.53]). CONCLUSIONS: IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared with the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity, across IBD subtypes and age groups, calls for targeted approaches to facilitate timely diagnosis and intervention.

Chronic hepatitis B virus infection and the risk of hepatocellular carcinoma by age and country of origin in people living in Sweden: A national register study.

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), and surveillance is recommended for patients without cirrhosis when risk exceeds an incidence rate (IR) of 0.2%. Populations in Asia and sub-Saharan Africa have been associated with HCC at younger ages, but the risk after immigration to Western countries should be investigated. The aim of this study was to study HCC by age and country of origin in people with chronic HBV infection in Sweden. Through national registers, residents with chronic HBV diagnosis (1990-2015) were identified with information on country of origin, immigration/emigration, death, coinfections, antiviral therapy, and HCC. Observation time started at HBV diagnosis, and IR and hazard ratios for HCC were calculated by sex, age, and region of origin. Among 16,410 individuals (47% women), the origin and observation time (person years) were as follows: Western Europe, 2316 (25,415); Eastern Europe, 2349 (26,237); Middle East/North Africa, 4402 (47,320); sub-Saharan Africa, 3677 (30,565); Asia, 3537 (35,358); and other, 129 (1277). There were 232 individuals with HCC (82% in men). The IR increased with age and exceeded 0.2% for Asian men from age group 40-49 years (IR, 0.63; 95% confidence interval, 0.39-1.00), for men of other origins from age group 50-59 years, and for women aged ≥60 years originating from Eastern Europe, Asia, and Middle East/North Africa. After exclusion of patients with cirrhosis or HBV treatment, the IR still exceeded 0.2% in Asian men aged 40-49 years. This study demonstrates that HBV-infected men of Asian origin should be recommended HCC surveillance at younger ages, but there is a need for further studies of HCC incidence in African-born men without cirrhosis living in the Western world.

Low health literacy and multiple medications in community-dwelling older adults: a population-based cohort study.

OBJECTIVES: Adequate health literacy is important for patients to manage chronic diseases and medications. We examined the association between health literacy and multiple medications in community-dwelling adults aged 50 years and older in England. DESIGN, SETTINGS AND PARTICIPANTS: We included 6368 community-dwelling people of median age 66 years from the English Longitudinal Study of Ageing. Health literacy was assessed at wave 5 (2010/11) with 4 questions concerning a medication label. Four correct answers were categorised as adequate health literacy, otherwise low. Data on medications were collected at wave 6 (2012/13). To examine the difference in the number of medications between low and adequate health literacy, we used zero-inflated negative binomial regression, estimating odds ratio (OR) for zero medication and incidence rate ratios (IRR) for the number of medications, with 95% CIs. Associations were adjusted for demographic, socioeconomic and health characteristics, smoking and cognitive function. We also stratified the analysis by sex, and age (50-64 and ≥65 years). To be comparable with preceding studies, multinomial regression was fitted using commonly used thresholds of polypharmacy (0 vs 1-4, 5-9, ≥10 medications). RESULTS: Although low health literacy was associated with a lower likelihood of being medication-free (OR=0.64, 95% CI: 0.45 to 0.91), health literacy was not associated with the number of medications among those at risk for medication (IRR=1.01, 95% CI: 0.96 to 1.05), and this finding did not differ among younger and older age groups or women. Among men, low health literacy showed a weak association (IRR=1.06, 95% CI: 0.99 to 1.14). Multinomial regression models showed graded risks of polypharmacy for low health literacy. CONCLUSIONS: Although there was no overall association between health literacy and the number of medications, this study does not support the assertion that low health literacy is associated with a notably higher number of medications in men.

Use of Antibiotics and Risk of Psychiatric Disorders in Newly Diagnosed Cancer Patients: A Population-Based Cohort Study in Sweden.

BACKGROUND: Antibiotic-induced dysbiosis is associated with an increased risk of depression and anxiety in the general population. A diagnosis of cancer is associated with an immediately and dramatically elevated risk of psychiatric disorders, but the potential influence of prediagnostic antibiotic-induced dysbiosis is unknown. METHODS: Based on a national cohort of cancer patients in Sweden, we included 309,419 patients who were diagnosed with a first primary malignancy between July 2006 and December 2013. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of first-onset psychosis, depression, anxiety, or stress-related disorders during the first year after cancer diagnosis for antibiotic use during the year before cancer diagnosis. RESULTS: Compared with no antibiotic use, use of antibiotics was associated with a higher rate of the aforementioned psychiatric disorders (HR, 1.23; 95% CI, 1.16-1.30) after adjustment for sociodemographic factors, comorbidity, potential indications for antibiotics, and cancer stage and type. The magnitude of the association was higher for broad-spectrum antibiotics (HR, 1.27; 95% CI, 1.18-1.37), higher doses (HR, 1.32; 95% CI, 1.22-1.44), more frequent use (HR, 1.33; 95% CI, 1.21-1.46), and recent use (HR, 1.26; 95% CI, 1.17-1.35). CONCLUSIONS: Use of antibiotics, especially of broad-spectrum type, of high dose and frequency, with recent use, was associated with an aggravated risk of psychiatric disorders, compared with no antibiotic use. IMPACT: A better understanding of the microbiota-gut-brain axis may open up a wide avenue for the prevention and treatment of psychiatric disorders in cancer patients.

Duration of the pushing phase of labor is inversely associated with expression of TNF, IL6, IGF1 and IGF2 in human placenta.

OBJECTIVE: Gene expression in placenta differs between vaginal and cesarean deliveries, but the influence of the duration of labor on placental gene expression is incompletely known. Our aim was to investigate associations between duration of labor and expression of some genes involved in growth or inflammation in human placental tissue. METHODS: Placenta samples (n = 126) were collected after an uncomplicated, singleton pregnancy and term vaginal delivery at Örebro University Hospital, Sweden. Duration of labor was recorded by the midwife in the delivery room. The expression of the following genes was analyzed by RT-qPCR: tumor necrosis factor (TNF), interleukin-6 (IL6), C-X-C motif chemokine ligand 8, toll-like receptor (TLR) 2, TLR4, insulin receptor, insulin-like growth factor (IGF) 1, IGF2, leptin, hepatocyte growth factor (HGF) and HGF receptor (MET). Multivariable linear regression models were used for the evaluation of associations with labor duration adjusting for potential confounding factors. The Benjamini-Hoschberg method was used to correct for multiple testing. RESULTS: The expression of TNF, IL6, IGF1 and IGF2 was inversely associated with the duration of the pushing phase of labor (B coefficients (95% confidence interval) = -0.150 (-0.277 to -0.023), -0.159 (-0.289 to -0.029), -0.099 (-0.176 to -0.021), and -0.081 (-0.145 to -0.017), respectively). CONCLUSIONS: Longer duration of pushing is associated with downregulation of the expression of genes in placenta from vaginal deliveries. Future research on gene expression in labored placenta should take into account associations with labor duration and especially the pushing phase. Potential impact of these associations on the mother, the fetus and the new-born infant should also be explored.

Association of Infectious Mononucleosis in Childhood and Adolescence With Risk for a Subsequent Multiple Sclerosis Diagnosis Among Siblings.

Importance: Epstein-Barr virus and its acute manifestation, infectious mononucleosis (IM), are associated with an increased risk of multiple sclerosis (MS). Whether this association is confounded by susceptibility to infection is still debated. Objective: To assess whether hospital-diagnosed IM during childhood, adolescence, or young adulthood is associated with subsequent MS diagnosis independent of shared familial factors. Design, Setting, and Participants: This population-based cohort study used the Swedish Total Population Register to identify individuals born in Sweden from January 1, 1958, to December 31, 1994. Participants aged 20 years were followed up from January 1, 1978, to December 31, 2018, with a median follow-up of 15.38 (IQR, 8.68-23.55; range, 0.01-40.96) years. Data were analyzed from October 2020 to July 2021. Exposure: Hospital-diagnosed IM before 25 years of age. Main Outcomes and Measures: Diagnoses of MS from 20 years of age were identified. Risk of an MS diagnosis associated with IM in childhood (birth to 10 years of age), adolescence (11-19 years of age), and early adulthood (20-24 years of age [time-dependent variable]) were estimated using conventional and stratified (to address familial environmental or genetic confounding) Cox proportional hazards regression. Results: Of the 2 492 980 individuals (1 312 119 men [52.63%] and 1 180 861 women [47.37%]) included, 5867 (0.24%) had an MS diagnosis from 20 years of age (median age, 31.50 [IQR, 26.78-37.54] years). Infectious mononucleosis in childhood (hazard ratio [HR], 1.98; 95% CI, 1.21-3.23) and adolescence (HR, 3.00; 95% CI, 2.48-3.63) was associated with an increased risk of an MS diagnosis that remained significant after controlling for shared familial factors in stratified Cox proportional hazards regression (HRs, 2.87 [95% CI, 1.44-5.74] and 3.19 [95% CI, 2.29-4.46], respectively). Infectious mononucleosis in early adulthood was also associated with risk of a subsequent MS diagnosis (HR, 1.89; 95% CI, 1.18-3.05), but this risk was attenuated and was not significant after controlling for shared familial factors (HR, 1.51; 95% CI, 0.82-2.76). Conclusions and Relevance: These findings suggest that IM in childhood and particularly adolescence is a risk factor associated with a diagnosis of MS, independent of shared familial factors.

Using a Convolutional Neural Network to Predict Remission of Diabetes After Gastric Bypass Surgery: Machine Learning Study From the Scandinavian Obesity Surgery Register.

BACKGROUND: Prediction of diabetes remission is an important topic in the evaluation of patients with type 2 diabetes (T2D) before bariatric surgery. Several high-quality predictive indices are available, but artificial intelligence algorithms offer the potential for higher predictive capability. OBJECTIVE: This study aimed to construct and validate an artificial intelligence prediction model for diabetes remission after Roux-en-Y gastric bypass surgery. METHODS: Patients who underwent surgery from 2007 to 2017 were included in the study, with collection of individual data from the Scandinavian Obesity Surgery Registry (SOReg), the Swedish National Patients Register, the Swedish Prescribed Drugs Register, and Statistics Sweden. A 7-layer convolution neural network (CNN) model was developed using 80% (6446/8057) of patients randomly selected from SOReg and 20% (1611/8057) of patients for external testing. The predictive capability of the CNN model and currently used scores (DiaRem, Ad-DiaRem, DiaBetter, and individualized metabolic surgery) were compared. RESULTS: In total, 8057 patients with T2D were included in the study. At 2 years after surgery, 77.09% achieved pharmacological remission (n=6211), while 63.07% (4004/6348) achieved complete remission. The CNN model showed high accuracy for cessation of antidiabetic drugs and complete remission of T2D after gastric bypass surgery. The area under the receiver operating characteristic curve (AUC) for the CNN model for pharmacological remission was 0.85 (95% CI 0.83-0.86) during validation and 0.83 for the final test, which was 9%-12% better than the traditional predictive indices. The AUC for complete remission was 0.83 (95% CI 0.81-0.85) during validation and 0.82 for the final test, which was 9%-11% better than the traditional predictive indices. CONCLUSIONS: The CNN method had better predictive capability compared to traditional indices for diabetes remission. However, further validation is needed in other countries to evaluate its external generalizability.

Skeletal adverse events in childhood cancer survivors: An Adult Life after Childhood Cancer in Scandinavia cohort study.

The dynamic growth of the skeleton during childhood and adolescence renders it vulnerable to adverse effects of cancer treatment. The lifetime risk and patterns of skeletal morbidity have not been described in a population-based cohort of childhood cancer survivors. A cohort of 26 334 1-year cancer survivors diagnosed before 20 years of age was identified from the national cancer registries of Denmark, Finland, Iceland and Sweden as well as a cohort of 127 531 age- and sex-matched comparison subjects randomly selected from the national population registries in each country. The two cohorts were linked with data from the national hospital registries and the observed numbers of first-time hospital admissions for adverse skeletal outcomes among childhood cancer survivors were compared to the expected numbers derived from the comparison cohort. In total, 1987 childhood cancer survivors had at least one hospital admission with a skeletal adverse event as discharge diagnosis, yielding a rate ratio (RR) of 1.35 (95% confidence interval, 1.29-1.42). Among the survivors, we observed an increased risk for osteonecrosis with a RR of 25.9 (15.0-44.5), osteoporosis, RR 4.53 (3.28-6.27), fractures, RR 1.27 (1.20-1.34), osteochondropathies, RR 1.57 (1.28-1.92) and osteoarthrosis, RR 1.48 (1.28-1.72). The hospitalization risk for any skeletal adverse event was higher among survivors up to the age of 60 years, but the lifetime pattern was different for each type of skeletal adverse event. Understanding the different lifetime patterns and identification of high-risk groups is crucial for developing strategies to optimize skeletal health in childhood cancer survivors.

Predictors of drug survival: A cohort study comparing anti-tumour necrosis factor agents using the Swedish inflammatory bowel disease quality register.

BACKGROUND: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown. AIMS: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF. METHODS: Biologic-naïve patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). RESULTS: In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration ≥10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates. CONCLUSIONS: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs.