Comorbidities associated with adult asthma: a population-based matched cohort study in Finland.

BACKGROUND: Asthma is a common chronic disease characterised by variable respiratory symptoms and airflow limitation, affecting roughly 4%-10% of the adult population. Adult asthma is associated with higher all-cause mortality compared to individuals without asthma. In this study, we investigate the comorbidities that may affect the management of asthma. METHODS: Total of 1648 adults with asthma and 3310 individuals without asthma aged 30-93 were matched with age, gender and area of residency, and followed from 1 January 1997 to 31 December 2013. Baseline information was collected with questionnaires 1997 and follow-up register data from the national discharge registry Finnish Institute for Health and Welfare. Data included diagnoses from outpatient care and day surgery of specialised health care, and data from inpatient care of specialised and primary health care. We included all main diagnoses that had at minimum 200 events and number of diagnoses based on their common appearance with adult asthma. RESULTS: The mean follow-up time varied between 14.2 and 15.1 years, and age at the time of enrolment was 53.9 years for subjects without asthma and 54.4 years for patients with asthma. Chronic obstructive pulmonary disease was 10 times more common among asthmatics. Risk of acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis and vocal cord dysfunction was fourfold and risk of pneumonia, and chronic rhinosinusitis was 2.5 times more common among asthmatics. Sleep apnoea, gastro-oesophageal reflux disease, diabetes, allergic rhinitis and dysfunctional breathing were twofold and cataract nearly twofold higher in the asthmatic group. Adult asthma was also significantly associated with musculoskeletal diseases, incontinence and bronchiectasis. CONCLUSIONS: The most common and most severe comorbidity of adult asthma in this study was chronic obstructive pulmonary disease. Other common comorbidities of adult asthma include acute rhinosinusitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, allergic rhinitis, dysfunctional breathing, diabetes, pneumonia, sleep apnoea and gastro-oesophageal reflux disease.

Psychiatric disorders and mortality due to external causes following diagnosis of endometriosis at a young age: a longitudinal register-based cohort study in Finland.

BACKGROUND: Endometriosis diagnosed in adults is associated with increased risk of various psychiatric disorders. However, little is known concerning psychiatric comorbidity and mortality due to external causes associated with endometriosis diagnosed at a young age. OBJECTIVE: This longitudinal cohort study aimed to investigate the link between surgical diagnosis of endometriosis at a young age and subsequent psychiatric disorders and mortality due to external causes. In addition, we compared the occurrence of the most common psychiatric disorders between different sites of surgically confirmed endometriosis (ovarian vs other) because of possible differences in pain manifestations. STUDY DESIGN: We conducted a retrospective register-based cohort study. Altogether 4532 women with surgically confirmed diagnosis of endometriosis before the age of 25 years from 1987 to 2012 were identified from the Finnish Hospital Discharge Register. They were matched with women without surgically diagnosed endometriosis for age and municipality on the index day (n=9014). Women were followed up from the index day until the end of 2019 for the outcomes of interest, which included 9 groups of psychiatric disorders (inpatient episodes since 1987, outpatient episodes since 1998) and death due to external causes, including deaths due to accidents, suicides, and violence (Finnish Register of Causes of Death). Cox proportional hazard models were applied to assess the crude and parity-adjusted hazard ratios and 95% confidence intervals. RESULTS: The cohort's median age was 22.9 years (interquartile range, 21.3-24.1) at the beginning and 42.5 years (36.7-48.3) after a median follow-up time of 20.0 years (14.5-25.7). We observed a higher hazard of depressive, anxiety, and bipolar disorders in women with endometriosis compared with the reference cohort, with depressive and anxiety disorders being the two most common psychiatric disorders. These differences appeared early and remained the same during the entire follow-up, irrespective of whether assessed from the data on inpatient episodes only or the data on both in- and outpatient episodes. The corresponding adjusted hazard ratios were 2.57 (95% confidence interval, 2.11-3.14) and 1.87 (1.65-2.12) for depressive disorders, 2.40 (1.81-3.17) and 2.09 (1.84-2.37) for anxiety disorders, and 1.71 (1.30-2.26) and 1.66 (1.28-2.15) for bipolar disorders, respectively. A higher hazard was observed for nonorganic sleeping disorders for the first 10 years only (3.83; 2.01-7.30) when assessed using the data on both in- and outpatient episodes. When based on inpatient records, a higher hazard for alcohol/drug dependence after 15 years of follow-up (2.07; 1.21-3.54) was observed. The difference in hazard for personality disorders tended to increase during follow-up (<10 years, 2.12 [1.28-3.52]; ≥10 years, 3.08 [1.44-6.57]). Depressive and anxiety disorders occurred more frequently in women with types of endometriosis other than ovarian endometriosis. No difference in deaths due to external causes was observed between the endometriosis and reference cohorts. CONCLUSION: Surgical diagnosis of endometriosis at a young age was associated with increased incidence of several psychiatric disorders. Moreover, within the endometriosis population, psychiatric comorbidity was more common in women with types of endometriosis other than ovarian endometriosis. We speculate that chronic pain is essential in the development of these psychiatric disorders, and that early and effective pain management is important in reducing the risk of psychiatric morbidity in young women. More research concerning the associations and management of endometriosis and associated psychiatric disorders is warranted.

Incidence of Type 1 Diabetes in Relation to Exposure to Rotavirus Infections in Pre- and Postvaccine Birth Cohorts in Finland.

OBJECTIVE: To explore the incidence of type 1 diabetes in children in relation to exposure to rotavirus infections. RESEARCH DESIGN AND METHODS: A nationwide register-based ecological study on the 1995-2015 birth cohorts in Finland compared those born before and after the national implementation of the rotavirus vaccine in 2009. RESULTS: When the prevaccine 2001-2005 birth cohorts were compared with the postvaccine birth cohorts, the number of children exposed to rotavirus infection by the age of 5 years decreased from 2,522 per 100,000 children (2.5%) to 171 per 100,000 children (0.2%), while the incidence of type 1 diabetes in those aged <5 years decreased from 71.5 to 54.4 per 100,000 person-years (incidence rate ratio 0.79, 95% CI 0.71-0.86). CONCLUSIONS: At the population level, a decrease in exposure to rotavirus infections was associated with a decrease in the incidence of type 1 diabetes in young children.

Risk of malignant disease in 1-year sepsis survivors, a registry-based nationwide follow-up study.

BACKGROUND: Cancer and sepsis share risk factors, and sepsis patients may have impaired immune response and increased morbidity long after intensive care. This study aimed to assess whether sepsis survivors are at increased risk for cancer. Our objective was to assess the incidence of new cancer in 1-year sepsis survivors and test the hypothesis that it is higher than that of the general population. METHODS: We obtained data on ICU admissions of adult patients from Swedish Intensive care registry (SICR) from 2005 to 2017. We included patients with an explicit ICD-10 code for sepsis for the primary ICU admission. We obtained data on cancer diagnoses (2001-2018), death (2005-2018) and emigration (2005-2018) from Cancer and Cause of death and National Patient Registry databases of the National Board of Health and Welfare; age and sex-specific cancer incidence rates in Sweden from NORDCAN registry from 2006 to 2018. One-year survivors formed the final cohort, that was followed for new cancer diagnoses until death, emigration, or end of 2018, whichever came first. The main outcome measure was standardized incidence rate ratio (SIR) to compare the incidence of cancer in 1-year sepsis survivors to that in the general population (NORDCAN). We also performed several sensitivity analyses. RESULTS: In a cohort of 18,550 1-year survivors, 75,427 person years accumulated during a median follow-up (FU) of 3.36 years (IQR 1.72-5.86), 6366 (34.3%) patients died, and 1625 (8.8%) patients were diagnosed with a new cancer after a median FU of 2.51 (IQR 1.09-4.48) years. The incidence ratio of any new cancer over the whole FU was 1.31 (95% CI 1.23-1.40) for men and 1.74 (95% CI 1.61-1.88) for women. The difference in incidence rates persisted in several sensitivity analyses. The SIRs were highest in cancers of gastrointestinal tract, genital organs, and skin. CONCLUSION AND RELEVANCE: Compared to general population, incidence of cancer is increased in 1-year sepsis survivors. Variation in the findings depending on follow-up time suggests that factors other than sepsis alone are involved. Surveillance for malignant disease may be warranted in sepsis survivors.

SARS-CoV-2 and type 1 diabetes in children in Finland: an observational study.

BACKGROUND: Some epidemiological studies have suggested an increase in incidence of type 1 diabetes during the COVID-19 pandemic, however the mechanism(s) behind such an increase have yet to be identified. In this study we aimed to evaluate the possible role of the SARS-CoV-2 virus in the reported increase in the rate of type 1 diabetes. METHODS: In this observational cohort study using data from the Finnish Pediatric Diabetes Register (FPDR), we assessed the incidence of type 1 diabetes (number of children with newly diagnosed type 1 diabetes per 100 000 person-years during the pandemic and the reference period) during the first 18 months of the COVID-19 pandemic in children in Finland younger than 15 years old compared with a reference period which included three corresponding pre-pandemic periods also obtained from the FPDR. Children with confirmed monogenic diabetes were excluded. We also compared the phenotype and HLA genotype of the disease between these two cohorts, and analysed the proportion of newly diagnosed people with type 1 diabetes testing positive for SARS-CoV-2 antibodies. FINDINGS: 785 children and adolescents in Finland were diagnosed with type 1 diabetes from March 1, 2020, to Aug 31, 2021. In the reference period, which comprised three similar 18-month terms (from March 1, 2014, to Aug 31, 2015; March 1, 2016, to Aug 31, 2017; and March 1, 2018, to Aug 31, 2019) 2096 children and adolescents were diagnosed. The incidence of type 1 diabetes was 61·0 per 100 000 person-years (95% CI 56·8-65·4) among children younger than 15 years old during the pandemic, which was significantly higher than during the reference period (52·3 per 100 000 person-years; 50·1-54·6). The incidence rate ratio adjusted for age and sex for the COVID-19 pandemic was 1·16 (1·06-1·25; p=0·0006) when compared with the reference period. The children diagnosed during the COVID-19 pandemic had more often diabetic ketoacidosis (p<0·001), had a higher HbA1c (p<0·001), and tested more frequently positive for glutamic acid debarboxylase antibodies at diagnosis (p<0·001) than those diagnosed before the pandemic. There were no significant differences in the distribution of HLA genotypes between the two periods. Only five of those diagnosed during the pandemic (0·9%) of 583 tested positive for infection-induced SARS-CoV-2 antibodies. INTERPRETATION: Children and adolescents diagnosed with type 1 diabetes during the pandemic had a more severe disease at diagnosis. The observed increase in type 1 diabetes incidence during the first 18 months could be a consequence of lockdown and physical distancing rather than a direct effect of SARS-CoV-2 infection. FUNDING: Helsinki University Hospital Research Funds, EU Horizon 2020 (Versatile emerging infectious disease observatory project), Academy of Finland, Sigrid Jusélius Foundation, Jane & Aatos Erkko Foundation, and Medicinska understödsföreningen Liv och Hälsa. TRANSLATIONS: For the Finnish and Swedish translations of the abstract see Supplementary Materials section.

Finnish children carrying the high-risk HLA genotype have a 45-fold increased risk of type 1 diabetes compared to peers with neutral or protective genotypes.

The association between HLA genotypes and type 1 diabetes is well known. We set out to examine incidence rates and ratios of type 1 diabetes depending on the risk afflicted by HLA genotype. Children with the high-risk genotype have a 45-fold disease risk compared to peers with neutral or protective genotypes.

National register data are of value in studies on miscarriage-Validation of the healthcare register data in Finland.

INTRODUCTION: Despite the high prevalence of miscarriages, they are not systematically registered and few epidemiological studies have been done. As Finnish health registries are comprehensive and widely used in research, we validated the Finnish register data concerning diagnostics and treatment of miscarriage, and treatment-related adverse events. MATERIAL AND METHODS: We conducted a validation study regarding miscarriage-related codes of diagnoses and surgical procedures in a Finnish National Hospital Discharge Registry (NHDR) by comparing the information from the NHDR with that of the hospital records. We selected a random sample of 4 months during 1998-2016 from three hospitals, comprising 687 women aged 15-49 experiencing a first miscarriage during follow-up. Women with diagnoses unrelated to miscarriage, or proven to be other than miscarriage, were excluded. The final sample consisted of 643 women with confirmed miscarriage, which was used for analyses regarding the diagnosis, treatment and adverse events of miscarriage treatment. RESULTS: The majority of miscarriages registered in the NHDR were confirmed by the hospital records (positive predictive value [PPV] = 93.6% [95% confidence interval [CI] 91.8%-95.4%]). Different types of miscarriage were also reliably identified; spontaneous abortion with PPV = 85.6% (95% CI 80.9%-89.2%), missed abortion with PPV = 92.7% (95% CI 88.8%-95.3%) and blighted ovum with PPV = 91.1% (95% CI 84.3%-95.1%). The PPV of surgical treatment (62.2% [95% CI 55.7%-68.3%]) was lower than the PPV of non-surgical treatment (93.3% [95% CI 90.5%-95.3%]). The diagnoses regarding adverse events of miscarriage treatment could be reliably identified. The PPV for clinical infections was 76.0% (95% CI 56.6%-88.5%) and for retained products of conception or/and vaginal bleeding 96.8% (95% CI 83.8%-99.4%). CONCLUSIONS: The coverage of the NHDR was good concerning identification of miscarriages, different types of miscarriages and non-surgical treatment. Nevertheless, there is a need for clearly defined procedural codes concerning to medical treatment of miscarriage. The register-based data are reliable and practicable for both clinical evaluation and research concerning miscarriage.

Association between arterial hypertension and liver outcomes using polygenic risk scores: a population-based study.

Arterial hypertension (HTA) is associated with liver disease, but causality remains unclear. We investigated whether genetic predisposition to HTA is associated with liver disease in the population, and if antihypertensive medication modifies this association. Participants of the Finnish health-examination surveys, FINRISK 1992-2012 and Health 2000 (n = 33,770), were linked with national electronic healthcare registers for liver-related outcomes (K70-K77, C22.0) and with the drug reimbursement registry for new initiation of antihypertensive medication during follow-up. Genetic predisposition to HTA was defined by polygenic risk scores (PRSs). During a median 12.9-year follow-up (409,268.9 person-years), 441 liver-related outcomes occurred. In the fully-adjusted Cox-regression models, both measured systolic blood pressure and clinically defined HTA were associated with liver-related outcomes. PRSs for systolic and diastolic blood pressure were significantly associated with liver-related outcomes (HR/SD 1.19, 95% CI 1.01-1.24, and 1.12, 95% CI 1.01-1.25, respectively). In the highest quintile of the systolic blood pressure PRS, new initiation of antihypertensive medication was associated with reduced rates of liver-related outcomes (HR 0.55, 95% CI 0.31-0.97). HTA and a genetic predisposition for HTA are associated with liver-related outcomes in the population. New initiation of antihypertensive medication attenuates this association in persons with high genetic risk for HTA.

Oral health associated with incident diabetes but not other chronic diseases: A register-based cohort study.

Introduction: Oral infectious diseases are common chronic oral diseases characterized by a chronic inflammatory condition. We investigated chronic oral diseases as potential risk factors for systemic chronic diseases, diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis, and Crohn's disease, as well as severe psychotic and other severe mental disorders. Methods: The cohort comprised 68,273 patients aged ≥ 29 years with at least one dental visit to the Helsinki City Health Services between 2001 and 2002. The cohort was linked to the data on death (Statistics Finland), cancer (Finnish Cancer Registry), and drug reimbursement (Finnish Social Insurance Institution) and followed until death or the end of 2013. The outcomes of interest were the incidences of chronic diseases measured starting with special refund medication, which means Social Insurance Institution partly or fully reimburses medication costs. Outcomes of interest were diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis and Crohn's disease, and severe mental disorders. Results: The mean follow-up time was 9.8 years. About 25% of the study population had periodontitis, 17% caries, over 70% apical periodontitis, and 9% <24 teeth at the start of follow-up. Diabetes was the only chronic systemic condition associated with oral health variables. Having 24 to 27 teeth was associated with a higher incidence rate ratio (IRR) (1.21, 95% confidence interval 1.09-1.33) compared to having 28 or more teeth; the IRR for having 23 or less was 1.40 (1.22-1.60). Having periodontitis (1.10, 1.01-1.20), caries (1.12, 1.01-1.23), or apical periodontitis (1.16, 1.04-1.30) is also associated with a higher risk of diabetes. Conclusion: Our epidemiological 10 years follow-up study suggests that the association exists between chronic oral diseases and diabetes, warranting close collaboration among patient's healthcare professionals.

Editor's Choice - Epidemiology, Diagnostics, and Outcomes of Acute Occlusive Arterial Mesenteric Ischaemia: A Population Based Study.

OBJECTIVE: The exact incidence and outcomes of acute occlusive arterial mesenteric ischaemia (AMI) are unclear as most studies include only patients diagnosed correctly while alive. The aim of this study was to assess the incidence, mortality, and diagnostics of AMI by also including patients diagnosed post-mortem. METHODS: This retrospective study comprised patients diagnosed with AMI either alive or post-mortem between 2006 and 2015 within a healthcare district serving 1.6 million inhabitants. Key exclusion criteria were venous or non-obstructive ischaemia. RESULTS: A total of 470 patients were included in the study of which 137 (29%) were diagnosed post-mortem. The most common misdiagnoses on those not diagnosed alive were unspecified infection (n = 19, 17%), gastrointestinal bleeding (n = 13, 11%), and ileus (n = 13, 11%). Of those diagnosed alive (n = 333), 187 (56%) underwent active surgical or endovascular treatment. During the 2006 - 2015 period, the overall incidence of AMI was 3.05 (95% CI 2.78 - 3.34)/100 000 person years and 26.66 (95% CI 24.07 - 29.45) for those aged 70 years or more. The mean autopsy rate during the study period was 29% for the overall population (32% during 2006 - 2010 and 25% during 2011 - 2015) and 18% for those aged 70 years or more. Overall, the 90-day mortality was 83% in all patients. The ninety day mortality decreased, being 87% during the first period (2006 - 2010) and 79% during the second period (2011 - 2015) (p = .029), while at the same time the proportion of patients diagnosed alive rose from 71% to 80% (p = .030) and the number of endovascular revascularisations rose from 1% to 5% (p = .022). CONCLUSION: A significant proportion of patients with AMI are not diagnosed alive, which is reflected in the mortality rates. Post-mortem examinations and autopsy rate data continue to be key factors in epidemiological studies on AMI.

Association of post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke.

OBJECTIVE: We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. PATIENTS AND METHODS: The Helsinki Young Stroke Registry (HYSR) includes patients aged 15-49 years with their first-ever IS occurring 1994-2007. From nationwide registers, we obtained data on prescriptions (1993-2011) and outcomes of interest (1994-2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. RESULTS: Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0-12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5-10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32-7.12). No association emerged between PSAD initiation and other outcomes. CONCLUSIONS: In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding.KEY MESSAGESInitiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term.Patients starting antidepressants after IS should be followed up more closely in case of recurrent events.Future studies are needed to verify the results and to further study the nature of this finding.

Surgically confirmed endometriosis in adolescents in Finland-A register-based cross-sectional cohort study.

INTRODUCTION: Increasing awareness of endometriosis in adolescents requires data on the nature of the disease and its management. Our objective was to investigate the subtypes of surgically confirmed endometriosis in adolescents (aged <20 years) and trends in the incidence rates and endometriosis-related procedures during the study period, 1987-2012. MATERIAL AND METHODS: In this register-based cohort study, we identified 526 adolescents receiving their initial surgical diagnosis of endometriosis between 1987 and 2012 from the Finnish Hospital Discharge Register. The age-specific incidence rate of surgically confirmed endometriosis was calculated by dividing the number of adolescents during specific periods by person-years. We calculated the relative differences in incidence rates between the periods using crude incidence ratios. RESULTS: Adolescents were divided into three age groups, <17, 17-18, and 19 years, which comprised 8.2% (43/526), 39.7% (209/526), and 52.1% (274/526) of the study cohort, respectively. Peritoneal endometriosis and ovarian endometriosis were the most common types (379/526 [72%] and 119/526 [23%], respectively). The incidence rate of surgically confirmed endometriosis per 100 000 person-years varied from 5.63 (95% confidence interval [CI] 4.24-7.33) to 11.42 (95% CI 9.64-13.44). The incidence rate in 2001-2005 was significantly higher and was 1.6- to 2.0-fold that of the periods 1987-1990 and 2006-2012, respectively. Comparing the periods in which International Classification of Diseases, Ninth Revision (ICD-9; 1987-1995) and Tenth Revision (ICD-10; 1996-2012) codes were used, the use of laparoscopy (78.2% vs 88.9%), day surgery (10.3% vs 31.6%), and procedures for ovarian (18.8% vs 34.1%) and deep (0.6% vs 10.8%) endometriosis increased. The types of endometriosis and procedures did not differ between the age groups. CONCLUSIONS: Peritoneal endometriosis was the most common type of endometriosis overall and by age group. During the 26-year period, the incidence rate of initial surgical diagnosis of endometriosis peaked in 2001-2005 and decreased thereafter. The proportion of procedures performed for ovarian and deep endometriosis increased, as did the use of laparoscopy and day surgery.

Use of reproductive health services among women using long- or short-acting contraceptive methods - a register-based cohort study from Finland.

BACKGROUND: Long-acting reversible contraceptives (LARCs) have superior contraceptive efficacy compared to short-acting reversible contraceptives (SARCs) and choosing LARCs over SARC methods reduces the need for abortion care. However, little is known how initiating these methods associates with the subsequent overall need of reproductive health services including family planning services, and visits for gynecological reasons in primary and specialized care. METHODS: We followed altogether 5839 non-sterilized women aged 15-44 years initiating free-of-charge LARC methods (n = 1689), initiating or switching SARC methods (n = 1524), or continuing with the same SARC method (n = 2626) at primary care family planning clinics in the City of Vantaa, Finland, 2013-2014 for 2 years using Finnish national health registers. We assessed the use of reproductive health services, namely attending public primary or specialized health care for gynecological reasons or attending the family planning clinics by applying unadjusted and adjusted negative binomial regression models on visit counts. RESULTS: A total of 11,290 visits accumulated during the two-year follow-up: 7260 (64.3%) at family planning clinics, 3385 (30.0%) for gynecological reasons in primary, and 645 (5.7%) in specialized health care. Altogether 3804 (52.4%) visits at the family planning clinics were for routine checkup, and 3456 (47.6%) for other reasons. Women initiating LARC methods used reproductive health services for reasons other than routine checkups similarly as women initiating or switching SARC methods (adjusted incidence rate ratio 0.93, 95% CI 0.82-1.05), while women continuing with SARC methods used the services less frequently (0.65, 0.59-0.72). Women initiating free-of-charge LARC and those continuing with the same SARC method used services less for abortion care than women initiating or switching SARC (adjusted incidence rate ratios 0.05, 95% CI 0.03-0.08 and 0.16, 95% CI 0.11-0.24, respectively). CONCLUSIONS: While women initiating LARC methods have lower need for abortion care compared to women initiating SARC methods, women initiating both LARC and SARC methods have similar overall need for reproductive health services. In contrast, women continuing with their SARC method need reproductive health services less than women initiating LARC or a new SARC method. These service needs should be acknowledged when planning and organizing family planning services, and when promoting long-acting reversible contraception.

Metabolomics profile of 5649 users and nonusers of hormonal intrauterine devices in Finland.

BACKGROUND: Use of hormonal intrauterine devices has grown during the last decades. Although hormonal intrauterine devices act mostly via local effects on the uterus, measurable concentrations of levonorgestrel are absorbed into the systemic circulation. The possible metabolic changes and large-scale biomarker profiles associated with hormonal intrauterine devices have not yet been studied in detail. OBJECTIVE: To examine through the metabolomics approach the metabolic profile of patients using hormonal intrauterine devices and how this metabolic profile is affected by duration and discontinuation of use. STUDY DESIGN: The study consisted of cross-sectional analyses of 5 population-based surveys (FINRISK and FinHealth studies), spanning from 1997 to 2017. All fertile-aged participants (18-49 years) in the surveys with available information on hormonal contraceptive use and metabolomics data (n=5649) were included in the study. Altogether, 211 metabolic measures of users of hormonal intrauterine devices (n=1006) were compared with those of nonusers of hormonal contraception (n=4643) via multivariable linear regression models. To allow comparison across multiple measures, association magnitudes were reported in standard deviation units of difference in biomarker concentration compared with the reference group. RESULTS: After adjustment for covariates, levels of 141 metabolites differed in current users of hormonal intrauterine devices compared with nonusers of hormonal contraception (median difference in biomarker concentration, 0.09 standard deviation): lower levels of particle concentration of larger lipoprotein subclasses, triglycerides, cholesterol and derivatives, apolipoproteins A and B, fatty acids, glycoprotein acetyls, and aromatic amino acids. The metabolic pattern of hormonal intrauterine device use did not change according to duration of use. When comparing previous users and never-users of hormonal intrauterine devices, no significant metabolic differences were observed. CONCLUSION: The use of hormonal intrauterine devices was associated with several moderate metabolic changes previously associated with reduced arterial cardiometabolic risk. The metabolic effects were independent of duration of use of the hormonal intrauterine devices. Moreover, the metabolic profiles were similar after discontinuation of hormonal intrauterine device use and in never-users.

Systemic hormonal contraception and risk of venous thromboembolism.

INTRODUCTION: The increased risk of venous thromboembolism associated with the use of hormonal contraception is well recognized, but evidence regarding hormonal contraception containing natural estradiol is limited. This study aimed to assess the associations between the patterns of use of different systemic hormonal contraceptives and the risk of venous thromboembolism during 2017-2019. MATERIAL AND METHODS: All fertile-aged women (15-49 years) living in Finland in 2017 and using hormonal contraception in 2017 and their 1:1 age- and residence-matched controls not using hormonal contraception in 2017 (altogether 587 559 women) were selected from the Prescription Centre. All incident venous thromboembolism cases during 2018-2019 and their 4:1 age-matched controls were further analyzed in a prospective nested case-control design to assess the associations between the use (starting, stopping, continuous vs no use) of different hormonal contraception types and venous thromboembolism. RESULTS: Altogether, 1334 venous thromboembolism cases occurred during the follow-up period (incidence rate 1.14 per 1000 person-years, 95% confidence interval [CI] 1.08-1.20), with an incidence rate ratio of hormonal contraception vs no hormonal contraception use of 1.42 (95% CI 1.27-1.58). Compared with non-use, starting the use of gestodene and ethinylestradiol (adjusted odds ratio [aOR] 2.85; 95% CI 1.62-5.03), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 0.98-2.44), desogestrel and ethinylestradiol (aOR 1.97; 95% CI 0.99-3.92), and transdermal patch releasing norelgestromin and ethinylestradiol (aOR 5.10; 95% CI 1.12-23.16), as well as continuing the use of gestodene and ethinylestradiol (aOR 2.60; 95% CI 1.61-4.21), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 1.02-2.37), cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.66; 95% CI 1.06-2.61), and vaginal ring releasing etonogestrel and ethinylestradiol (aOR 3.27; 95% CI 1.95-5.48) were associated with venous thromboembolism risk. Regarding the type of estrogen, the highest risk was associated with current use (vs non use in the previous 180 days) of ethinylestradiol-containing preparations (aOR 2.20; 95% CI 1.82-2.65), followed by estradiol-containing preparations (aOR 1.39; 95% CI 1.04-1.87) with no risk for progestin-only hormonal contraception. Current use of estradiol-containing preparations was not associated with venous thromboembolism risk after exclusion of cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.05; 95% CI 0.66-1.66). CONCLUSIONS: An increased risk of venous thromboembolism is associated with ethinylestradiol-containing combined preparations. The use of estradiol-containing combined preparations confers only a slightly increased risk, possibly driven by cyproterone-containing combined oral contraceptives, whereas the use of progestin-only contraception is not associated with venous thromboembolism.

Development and validation of a model to predict incident chronic liver disease in the general population: The CLivD score.

BACKGROUND & AIMS: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify those at high future risk of severe liver disease. Our aim was to develop and validate a risk prediction model for incident chronic liver disease in the general population based on widely available factors. METHODS: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40-70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5,058) and Copenhagen City Heart Study (CCHS) (n = 3,049) cohorts. RESULTS: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist-hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally validated Wolbers' C-statistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion (<2%) of the population with >10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. CONCLUSIONS: Based on widely available risk factors, the Chronic Liver Disease (CLivD) score can be used to predict risk of future advanced liver disease in the general population. LAY SUMMARY: Liver disease often progresses silently without symptoms and thus the diagnosis is often delayed until severe complications occur and prognosis becomes poor. In order to identify individuals in the general population who have a high risk of developing severe liver disease in the future, we developed and validated a Chronic Liver Disease (CLivD) risk prediction score, based on age, sex, alcohol use, waist-hip ratio, diabetes, and smoking, with or without measurement of the liver enzyme gamma-glutamyltransferase. The CLivD score can be used as part of health counseling, and for planning further liver investigations and follow-up.

Associations between use of psychotropic medications and use of hormonal contraception among girls and women aged 15-49 years in Finland: a nationwide, register-based, matched case-control study.

OBJECTIVES: The relationship between the use of contraception and of psychiatric medications is understudied. We examined whether the current and past use of psychotropic medications is associated with the use and type of hormonal contraception (HC). DESIGN: Nationwide register-based matched case-control study. SETTINGS: All fertile-aged (15-49 years) girls and women living in Finland in 2017; data from several national registers. PARTICIPANTS: 294 356 girls and women with a redeemed prescription of HC in 2017, and their same-sized control group of non-users (n=294 356) identified through the Prescription Centre. MAIN OUTCOME MEASURES: Associations between the use of psychotropic medications and the use of HC, and the type of HC tested in logistic regression models. RESULTS: Altogether 19.5% of the HC users, and 18% of the HC non-users received at least one prescription for a psychotropic medication in 2017. Among HC users, the proportions of occasional and regular users of psychotropic medications in 2013-2016 were 4.5% and 14.8%, while among HC non-users the respective figures were 4.3% and 14.6%, respectively. In multivariable logistic regression models both the use of psychotropic medications in 2017, and their occasional or regular use between 2013-2016 were associated with higher odds of HC use, although with small to very small effect sizes (ORs between 1.37 and 1.06 and 95% CIs 1.22 to 1.53, and 1.03 to 1.09, respectively). After adjustment for covariates, when fixed combinations of progestogens and oestrogens for systemic use was the reference category, women using almost any class of psychotropic medications had higher odds of using other types of HC. CONCLUSIONS: Fertile-aged girls and women with current and past use of psychotropic medications have higher odds of using HC, with a specific pattern in the type of contraceptives used. Further research is warranted to examine whether our observations indicate a reduction of unwanted pregnancies in women with psychiatric disorders.

Heterogeneity of Type 1 Diabetes at Diagnosis Supports Existence of Age-Related Endotypes.

OBJECTIVE: Previous findings suggest that there are age-related endotypes of type 1 diabetes with different underlying etiopathological mechanisms in those diagnosed at age <7 years compared with those diagnosed at age ≥13 years. We set out to explore whether variation in demographic, clinical, autoimmune, and genetic characteristics of children and adolescents with newly diagnosed type 1 diabetes support the existence of these proposed endotypes. RESEARCH DESIGN AND METHODS: We used data from the Finnish Pediatric Diabetes Register to analyze characteristics of 6,015 children and adolescents diagnosed with type 1 diabetes between 2003 and 2019. We described and compared demographic data, clinical characteristics at diagnosis, autoantibody profiles, and HLA class II-associated disease risk between three groups formed based on age at diagnosis: <7, 7-12, and ≥13 years. RESULTS: We found significant age-related differences in most of the characteristics analyzed. Children diagnosed at age <7 years were characterized by a higher prevalence of affected first-degree relatives, stronger HLA-conferred disease susceptibility, and higher number of autoantibodies at diagnosis, in particular a higher frequency of insulin autoantibodies, when compared with older children. Those diagnosed at age ≥13 years had a considerably higher male preponderance, higher frequency of glutamic acid decarboxylase autoantibodies, longer duration of symptoms before diagnosis, and more severe metabolic decompensation, reflected, for example, by a higher frequency of diabetic ketoacidosis. CONCLUSIONS: Our findings suggest that the heterogeneity of type 1 diabetes is associated with the underlying disease process and support the existence of distinct endotypes of type 1 diabetes related to age at diagnosis.

Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study.

OBJECTIVE: Data on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults. METHODS: Helsinki Young Stroke Registry includes patients aged 15-49 years with first-ever IS, 1994-2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1 year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate. RESULTS: We followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100 days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48-4.31) and during later follow-up among those with silent infarcts (2.04; 1.27-3.28), prior use of antidepressants (2.09; 1.26-3.46) and moderate versus mild stroke (2.06; 1.18-3.58). The relative difference in the hazard rate for moderate-severe limb paresis persisted both within the first 100 days (3.84, 2.12-6.97) and during later follow-up (4.54; 2.51-8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11-1.97) as well as lower (1.78; 1.25-2.54) and upper white-collar workers (2.00; 1.24-3.23) compared to blue-collar workers. CONCLUSION: One-fourth of young adults started PSADs within 1 year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up.