Prenatal and Postnatal Exposure to Antibiotics and the Risk of Type 1 Diabetes in Finnish Children: A Registry-based Study.

OBJECTIVE: To study whether prenatal and postnatal exposure to antibiotics is associated with the risk of type 1 diabetes in childhood. STUDY DESIGN: This case cohort study included 2869 children diagnosed with type 1 diabetes by the end of 2009 who were born between January 1, 1996, and December 31, 2008, in Finland and a reference cohort (n = 74 263) representing 10% of each birth cohort. Exposure to antibiotics was assessed in different time periods. The data were derived from Special Reimbursement Register, Drug Prescription Register, and Population Register and analyzed with weighted Cox proportional hazards regression models. RESULTS: Exposure to any antibiotics before or during pregnancy, in the neonatal ward, during the first year of life, or during the 2 first years of life, was not associated with the risk of type 1 diabetes in the offspring. Exposure to macrolides in the year preceding pregnancy (adjusted hazard ratio [HR], 1.17; 95% CI, 1.02-1.33) and to sulfonamides and trimethoprim during pregnancy (adjusted HR, 1.91; 95% CI, 1.07-3.41) was associated with an increased risk of type 1 diabetes in the offspring. Exposure to sulfonamides and trimethoprim during first 2 years of life was associated with a decreased risk of type 1 diabetes (adjusted HR, 0.84; 95% CI, 0.73-0.97). The number of antibiotic purchases among mothers or children was not associated with type 1 diabetes risk. CONCLUSIONS: Prenatal and postnatal exposure to antibiotics in general did not increase the risk of type 1 diabetes in the offspring. However, the type of antibiotic and timing of exposure may play a role in type 1 diabetes risk.

Pregnancies in patients with systemic lupus erythematosus during 2000-2018 in Finland: a case-control study.

OBJECTIVES: The aim was to investigate, how pregnancies proceed in patients with systemic lupus erythematosus (SLE) compared to their individually matched population controls. MATERIAL AND METHODS: Adult incident SLE patients were identified from the register of new special reimbursement decisions for SLE drugs in 2000-2014. For each patient, 1-3 randomly selected controls from the Population Register Centre were matched. Data regarding pregnancies were obtained from the Finnish Medical Birth Register, Care Register and Register of Congenital Malformations until 2018. The study utilized data from the Drug Purchase Register and educational information from Statistic Finland. RESULTS: A total of 163 deliveries for 103 mothers with SLE and 580 deliveries for 371 population controls were identified. The duration of pregnancies in SLE women was significantly shorter compared to controls (38.9 versus 39.6 weeks). There were more urgent Caesarean Sections. (15% versus 9%) and need for care at neonatal intensive care unit (NICU) (21% versus 11%) among deliveries in SLE mothers. No statistical difference was observed between SLE and control groups in the occurrence of preeclampsia or major congenital malformations. Gestational age was 2.5 weeks shorter when the mother experienced pre-eclampsia. Hydroxychloroquine was purchased by 30% of SLE mothers during pregnancy. CONCLUSION: The course of pregnancies in Finnish SLE patients seems to be quite moderate compared to controls, and no new safety issues were detected. The low utilization of hydroxychloroquine indicates that the benefits of the drug to pregnancy and disease course are not optimally recognized by specialists treating SLE mothers.

Risk Factors of Cancer in Pediatric-Onset Inflammatory Bowel Disease in Denmark and Finland.

OBJECTIVES: Pediatric-onset inflammatory bowel disease (pIBD) increases the risk of developing several different cancer forms. In this case-control study, we aimed to assess the impact of medical treatment and disease activity on the risk of developing disease-associated cancer (DAC) and treatment-associated cancer (TAC). METHODS: In a previous study, we identified 27 cases of DAC (colorectal cancer, small bowel cancer, and cholangiocarcinoma) and 28 TAC (lymphoma and skin cancer) in 6689 patients with pIBD in Denmark and Finland during the period 1992-2015. In this study, the patient charts were reviewed manually. Cancer-free patients from another population-based pIBD cohort were included as controls. We recorded data on phenotype, medical treatment, surgery, and relapses. Logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) to estimate the relative risk. RESULTS: We included 16 cases with DAC, 21 with TAC, and 331 controls. For DAC, lower frequencies of IBD-relapses were associated with an increased risk of cancer (OR 0.2 [95% CI: 0.04-0.8]). For TAC, we found an increased risk in patients receiving thiopurines at any point during the follow-up period (aOR: 11.7 [95% CI: 2.1-116.2]) and an association with proportion of follow-up time being exposed to thiopurines (aOR 5.6 [95% CI: 1.1-31.5]). CONCLUSIONS: In this nation-wide study, covering all pIBD patients from Denmark and Finland, we found that pIBD patients treated with thiopurines had an increased risk of TAC.

Malignancies among newly diagnosed systemic lupus erythematosus patients and their survival.

The objective of this study was to evaluate the incidence of malignancies among newly diagnosed systemic lupus erythematosus (SLE) patients compared to reference individuals. Another aim was to assess the survival of SLE patients with malignancy compared to references with malignancy. Finnish adult (>17 years) newly diagnosed SLE patients were identified by their drug reimbursement decisions made during 1.1.2000-31.12.2014 from the register of the Social Insurance Institution. For each case, three population controls were individually selected by age, sex and place of residence. Overall, 1006 SLE patients (women 84%), with a mean age of 45.5 years (SD 16 years) and 3005 population controls were linked to Finnish Cancer Registry, and the information about incident malignancies was retrieved from the day the special reimbursement decision for SLE medication was accepted (index day, ID) until 31.12.2018 or until death. The patients diagnosed with malignancy were followed up until 31.12.2019 considering survival. During the follow-up, 85 SLE patients (women 78%) and 192 controls (women 78%) had developed one or more malignancy after the ID. The incidence rate ratio for any malignancy was 1.41 (95% CI 1.08-1.85). The most common malignancy in SLE patients was non-Hodgkin lymphoma, with twelve cases. SLE patients with malignancy had a lower adjusted 15-year survival than controls with malignancy, 27.1% versus 52.4%, and the adjusted hazard ratio for death was 1.68 (95% CI 1.17-2.43). Our results confirm that SLE patients have a higher risk for overall malignancy. The results also suggest that SLE patients with malignancy have lower survival than their references with malignancy.

Usage of drugs for cardiovascular diseases is increased in systemic lupus erythematosus (SLE) patients already before diagnosis of SLE.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients are considered as a high-risk population for cardiovascular diseases (CVDs). To explore whether their risk is increased already in preclinical episodes of the disease, we have studied the usage of CVD drugs in incident SLE cases five years before diagnosis of SLE compared to the population controls. METHODS: Adult SLE incident patients (age ≥18 years) from 2004 through 2014 were identified from a nationwide register. The date of granted reimbursement for SLE medication was defined as the date of diagnosis (index day). For each patient, three population controls were matched for age, sex and residence on the index day. The patients and controls were linked to the drug purchase register. All purchases of CVD drugs (Anatomical Therapeutic Chemical (ATC) - codes of C01-C04, C07-C09) and separately C10 were recorded in half-year periods over five years before the index day. RESULTS: A total of 653 SLE patients (mean age 45.7±15.9 years, 83% females) and 1924 population controls were found. Over five years before the index day, the proportion of SLE patients with purchased CVD drugs (46.7%) was greater compared to the controls (28.5%) (p<0.001). The relative risk for purchases started to increase more steeply during the last half-year period before SLE diagnosis. There was no significant difference in lipid-modifying agents between groups. CONCLUSIONS: Our finding that among SLE patients the use of CVD drugs was more common compared to their control population suggests increased CVD risk already before the diagnosis of SLE.

Early Start of Anti-Dementia Medication Delays Transition to 24-Hour Care in Alzheimer's Disease Patients: A Finnish Nationwide Cohort Study.

BACKGROUND: Dementia is one of the strongest predictors of admission to a 24-hour care facility among older people, and 24-hour care is the major cost of Alzheimer's disease (AD). OBJECTIVE: The aim of this study was to evaluate the association of early start of anti-dementia medication and other predisposing factors with 2-year risk of transition to 24-hour care in the nationwide cohort of Finnish AD patients. METHODS: This was a retrospective, non-interventional study based on individual-level data from Finnish national health and social care registers. The incident cohort included 7,454 AD patients (ICD-10, G30) comprised of two subgroups: those living unassisted at home (n = 5,002), and those receiving professional home care (n = 2,452). The primary outcome was admission to a 24-hour care facility. Exploratory variables were early versus late anti-dementia medication start, sociodemographic variables, care intensity level, and comorbidities. RESULTS: Early anti-dementia medication reduced the risk of admission to 24-hour care both in patients living unassisted at home, with a hazard ratio (HR) of 0.58 (p < 0.001), and those receiving professional home care (HR, 0.84; p = 0.039). Being unmarried (HR, 1.69; p < 0.001), having an informal caregiver (HR, 1.69; p = 0.003), or having a diagnosis of additional neurological disorder (HR, 1.68; p = 0.006) or hip fracture (HR, 1.61; p = 0.004) were associated with higher risk of admission to 24-hour care in patients living unassisted at home. CONCLUSION: To support living at home, early start of anti-dementia medication should be a high priority in newly diagnosed AD patients.

Mortality in SLE patients compared with population controls in Finland in years 2000-2015.

OBJECTIVE: To estimate the risk of mortality in the Finnish incident SLE cohort in a 16-year period compared with the general population. METHODS: Adults with new-onset SLE between 1 January 2000 and 31 December 2014 identified from the national drug reimbursement register and their individually matched controls from the Population Register Centre were followed up until death or 31 December 2015. Data on deaths were retrieved from the national causes of death register. Comorbidities and education were obtained by linkage to the other national registries. RESULTS: A total of 1006 patients with incident SLE and 3005 population controls were found (mean follow-up 8.6 years). Of these, 98 SLE patients subsequently died. Their 5 -, 10-, and 15-year survival rates were 95.0% (95% CI: 93.3, 96.2), 88.8% (86.2, 91.0), and 82.1% (77.6, 85.8), respectively. Crude hazard ratio (HR) was 1.61 (95% CI: 1.26, 2.06), adjusted for education level was almost the same 1.61 (95% CI: 1.26, 2.05). After adjustment for comorbidities and education at baseline, the difference in mortality disappeared: HR 1.14 (95% CI: 0.88, 1.48). The leading causes of death were cardiovascular diseases (CVDs) (33%), malignancies (27%) and neurological diseases (10%). Subhazard ratio for CVD deaths was 1.28 (95% CI: 0.85, 1.93), adjusted for comorbidities and education 0.88 (95% CI: 0.56, 1.39). CONCLUSIONS: These results suggest that the increased mortality in SLE patients is highly associated with comorbidities present at diagnosis. This underlines the importance to screen and treat comorbidities and disease actively without delays.

Cow's milk allergy in infancy and later development of type 1 diabetes-nationwide case-cohort study.

BAKGROUND: It is suggested that early intake of cow's milk could be a risk factor for type 1 diabetes (T1DM). Further, the different immunological background, gives a suggestion of an inverse relationship for the occurrence of these diseases. The aim of this study was to explore the association between cow's milk allergy (CMA) and the risk of T1DM in a register-based case-cohort study. METHODS: Data were obtained from Finnish nationwide health registers. The study included all children born in Finland between January 01, 1986 and December 31, 2008 and diagnosed with T1DM before the age of 16 years (n = 7754). A 10% random sample from each birth year cohort was selected as a reference cohort (n = 137,798). T1DM, CMA, and asthma were defined based on valid special reimbursements for the costs of drugs/special formulas needed in the treatment of the diseases. Child's sex, birth decade, asthma, maternal diabetes and asthma, smoking during pregnancy, and previous deliveries were considered as confounding factors. Time-dependent, weighted Cox regression was applied for statistical analyses. RESULTS: Children with CMA had an increased risk of developing T1DM in fully adjusted model (HR = 1.17; 95% CI 1.02-1.34), but the association was no longer observed when including the use of special infant formulas in the definition of CMA in the sensitivity analysis (HR = 1.11; 95% CI 0.92-1.32). CMA was associated with an increased risk of T1DM in children without asthma (HR = 1.27; 95%CI 1.10-1.47), but not in children with asthma (HR = 0.80; 95% CI 0.92-1.27). CONCLUSION: Children with CMA may have an increased risk of T1DM.

Multimorbidity among incident Finnish systemic lupus erythematosus patients during 2000-2017.

The objective of the study was to examine the risk of other morbidities among patients with systemic lupus erythematosus (SLE). A total of 1006 adult new-onset SLE patients were identified during 1.1.2000- 31.12.2014 from the register of Social Insurance Institution. For each case three general population controls matched according to age, sex and place of residence at the index day were sampled from the population register. Both groups were followed up from the index date until the end of 2017 or until death. The national register on specialized care was explored to gather broadly their 12 organ-specific morbidities, which were found among 91.2% of SLE patients and 66.7% of comparators. The rate ratio (RR) was elevated in almost all disease groups. Musculoskeletal, cardiovascular and genitourinary conditions were the most common comorbidities with RRs of 1.82 (1.68 to 1.97), 1.91 (1.76 to 2.08) and 1.91 (1.73 to 2.09), respectively. Men with SLE had a significantly higher risk for diseases of the genitourinary system and endocrine, nutritional and metabolic diseases compared to women with SLE. The risk of concurrent morbidities is essential to note in the care of SLE patients.

Overall and Cause-Specific Mortality in Adult Celiac Disease and Dermatitis Herpetiformis Diagnosed in the 21st Century.

INTRODUCTION: We assessed whether celiac disease-associated mortality is increased in Finland among patients diagnosed in the 21st century, given recent improvements in diagnostic and treatment facilities. METHODS: Biopsy-proven patients with celiac disease (Marsh III) and dermatitis herpetiformis aged 20-79 years (median 50 years) diagnosed 2005-2014 (n = 12,803) were identified from the national dietary grant registry. Dates and causes of death were obtained from Statistics Finland. Overall mortality and causes of death were compared with reference individuals (n = 38,384) matched for age, sex, and area of residence (at the time of celiac disease diagnosis) selected from the Population Information System. RESULTS: During a mean follow-up of 7.7 years (SD ±3.0 years), 884 (6.9%) and 2,613 (6.8%) deaths occurred among the celiac cohort and reference group, respectively. Overall mortality (hazard ratio [HR] 1.01, 95% confidence intervals [CIs] 0.94-1.09), mortality from all malignancies (HR 1.11, 95% CI 0.96-1.27), gastrointestinal tract malignancies (HR 1.21, 95% CI 0.56-1.71), or cardiovascular diseases (HR 0.91, 95% CI 0.77-1.07) were not increased among patients with celiac disease. Overall, mortality from lymphoproliferative diseases (HR 2.36, 95% CI 1.65-3.39) and nonmalignant digestive diseases (HR 2.19, 95% CI 1.40-3.43) was increased, but HRs decreased after the exclusion of the first 2 years of follow-up (HR 1.71, 95% CI 1.10-2.66 and HR 1.75, 95% CI 1.01-3.05, respectively). DISCUSSION: The overall mortality in adult celiac disease diagnosed 2005-2014 was not increased. Mortality from lymphoproliferative diseases was increased but lower than previously reported.

First-year drug therapy of new-onset rheumatoid and undifferentiated arthritis: a nationwide register-based study.

BACKGROUND: In this retrospective cohort study, we evaluated the drug therapies used for early rheumatoid (RA) and undifferentiated (UA) arthritis patients. METHODS: From a nationwide register maintained by the Social Insurance Institution, information on sex, date of birth, and date of special medicine reimbursement decision for all new Finnish RA and UA patients between 2011 and 14 were collected, and their DMARD (Disease Modifying Antirheumatic Drug) purchases during the first year after the diagnosis were analyzed. RESULTS: A total of 7338 patients with early RA (67.3% female, 68.1% seropositive) and 2433 with early UA (67.8% female) were identified. DMARDs were initiated during the first month after the diagnosis to 92.0% of the patients with seropositive RA, 90.3% with seronegative RA and to 87.7% with UA (p < 0.001). Respectively, 72.1, 63.4, and 42.9% of the patients (p < 0.001) purchased methotrexate; 49.8, 35.9, and 16.0% (p < 0.001) as part of a DMARD combination during the first month. By the end of the first year after the diagnosis, self-injected biologics were purchased by 2.6, 5.3 and 3.1% (p < 0.001) of them. Only 1.4, 2.6 and 3.0% (p < 0.001) of the patients were not receiving any DMARDs. During the first year, 83.4% of the seropositive RA patients had purchased methotrexate, 50.4% sulfasalazine, 72.1% hydroxychloroquine, and 72.6% prednisolone. CONCLUSIONS: Currently, combination therapy including methotrexate is a common treatment strategy for early seropositive RA in Finland. Despite an easy access to biologics, these drugs are seldom needed during the first year after diagnosis.

Socioeconomic differences in use of public, occupational and private health care: A register-linkage study of a working-age population in Finland.

There is little knowledge on socioeconomic differences in use of health care organized by different care schemes and on exclusive and concurrent use of health care at different schemes in different socioeconomic groups. In Finland, public, occupational and private schemes offer parallel outpatient primary health care services. Each scheme mainly reaches different population groups because of differences in availability, costs and gatekeeping. This study aimed to analyse how the probability of using health care organized by the three schemes differed by socioeconomic status in a working-age population. Individual-level register-based data on use of public, occupational and private outpatient primary health care during 2013 as well as data on sociodemographic covariates were linked for the total population aged 25-64 of the city of Oulu, Finland. Data were analysed with descriptive methods and multinomial logistic regression models. Those in the study population most often used only occupational care or only public care, or did not use any of the studied health care schemes at all. The lower the socioeconomic status, the higher was the probability of not using care or using only public care. The higher the socioeconomic status, the higher was the probability of using occupational care-either only occupational care or occupational care in combination with private care. Education, occupational class and income were all associated with care use also when adjusted for sociodemographic covariates and chronic disease, but income proved to be the strongest predictor of the three. The results reflect the design of the Finnish health care system, with a strong occupational health care scheme for the employed population contributing to inequality in use of health care and potentially to health inequality between socioeconomic groups.

Perinatal factors and the risk of type 1 diabetes in childhood and adolescence-A register-based case-cohort study in Finland, years 1987 to 2009.

OBJECTIVES: Our aim was to clarify previously reported associations and to explore new ones between various maternal background and perinatal factors and the risk of type 1 diabetes in childhood. METHODS: We identified all children born 1 January 1987 to 31 December 2008 in Finland and diagnosed with type 1 diabetes by age 16 years or end of 2009 from the Special Reimbursement Register (n = 6862). A 10% random sample from each birth year cohort was selected as a reference cohort (n = 127 216). Information on perinatal factors was obtained from the Finnish Medical Birth Register. RESULTS: Maternal diabetes (hazard ratios [HR] = 6.43; 95% confidence interval [CI] 5.35, 7.73), maternal asthma (HR = 1.23; 95% CI 1.06, 1.43), child's high birth length for gestational age (HR = 1.35; 95% CI 1.22, 1.51 highest vs lowest quintile) and premature or early term birth (HR = 1.21; 95% CI 1.05, 1.39 gestational weeks 33-36 and HR = 1.17; 95% CI 1.09, 1.26 gestational weeks 37-38 vs gestational weeks 39-40) was associated with an increased risk of type 1 diabetes when adjusted for several potential confounders. Maternal smoking during pregnancy (HR = 0.72; 95% CI 0.66, 0.77), high number of previous live births (HR = 0.65; 95% CI 0.55, 0.76 ≥ 4 vs 0 live births), and the child being born small for gestational age (HR = 0.80; 95% CI 0.67, 0.96) was associated with a decreased risk of type 1 diabetes. CONCLUSIONS: Findings on maternal asthma and high birth length for gestational age increasing the risk of type 1 diabetes are novel and need to be confirmed. Our findings indicate that perinatal factors may play a role in the development of type 1 diabetes.

Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children: A Nationwide Case-Cohort Study.

Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995-2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled ß-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled ß-agonists might be at increased risk of type 1 diabetes.

Impact of Anti-Dementia Medication on the Risk of Death and Causes of Death in Alzheimer's Disease.

BACKGROUND: The Finnish population offers many advantages for evaluating the impact of anti-dementia medication on mortality in Alzheimer's disease (AD) due to broad range of individual-level data collected in national health and social care registries and the fact that Finland has one of the highest mortality rates for dementia globally. OBJECTIVE: The aim of this study was to investigate the association of anti-dementia medication with 2-year risk of death and all-cause mortality in patients with AD. METHODS: This was a retrospective, non-interventional registry study based on individual-level data using Finnish national health and social care registries. An incident cohort of 9,204 AD patients (first AD diagnosis in 2012) was formed from a population of 316,470 individuals ≥74 years of age. The main outcome measure was overall 2-year risk of death. Statistical modelling was used to assess mortality (Kaplan-Meier) and adjusted hazard ratios (HR) (Cox proportional hazard model). RESULTS: Early start of anti-dementia medication (treatment started ≤3 months from AD diagnosis) reduced significantly the risk of all-cause death compared to AD patients who had late medication initiation (defined as treatment started >3 months from AD diagnosis/no medication; HR, 0.51; 95% confidence interval (CI), 0.46-0.57). Dementia was the most common recorded cause of death in both groups. CONCLUSION: This study places importance on early diagnosis of AD and subsequent early initiation of drug treatment in decreasing 2-year risk of death.

Self-certification versus physician certification of sick leave for reducing sickness absence and associated costs.

BACKGROUND: From the societal and employers' perspectives, sickness absence has a large economic impact. Internationally, there is variation in sickness certification practices. However, in most countries a physician's certificate of illness or reduced work ability is needed at some point of sickness absence. In many countries, there is a time period of varying length called the 'self-certification period' at the beginning of sickness absence. During that time a worker is not obliged to provide his or her employer a medical certificate and it is usually enough that the employee notifies his or her supervisor when taken ill. Self-certification can be introduced at organisational, regional, or national level. OBJECTIVES: To evaluate the effects of introducing, abolishing, or changing the period of self-certification of sickness absence on: the total or average duration (number of sickness absence days) of short-term sickness absence periods; the frequency of short-term sickness absence periods; the associated costs (of sickness absence and (occupational) health care); and social climate, supervisor involvement, and workload or presenteeism (see Figure 1). SEARCH METHODS: We conducted a systematic literature search to identify all potentially eligible published and unpublished studies. We adapted the search strategy developed for MEDLINE for use in the other electronic databases. We also searched for unpublished trials on ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). We used Google Scholar for exploratory searches. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), controlled before-after (CBA) studies, and interrupted time-series (ITS) studies for inclusion. We included studies carried out with individual employees or insured workers. We also included studies in which participants were addressed at the aggregate level of organisations, companies, municipalities, healthcare settings, or general populations. We included studies evaluating the effects of introducing, abolishing, or changing the period of self-certification of sickness absence. DATA COLLECTION AND ANALYSIS: We conducted a systematic literature search up to 14 June 2018. We calculated missing data from other data reported by the authors. We intended to perform a random-effects meta-analysis, but the studies were too different to enable meta-analysis. MAIN RESULTS: We screened 6091 records for inclusion. Five studies fulfilled our inclusion criteria: one is an RCT and four are CBA studies. One study from Sweden changed the period of self-certification in 1985 in two districts for all insured inhabitants. Three studies from Norway conducted between 2001 and 2014 changed the period of self-certification in municipalities for all or part of the workers. One study from 1969 introduced self-certification for all manual workers of an oil refinery in the UK.Longer compared to shorter self-certificationfor reducing sickness absence in workersOutcome: average duration of sickness absence periodsExtending the period of self-certification from one week to two weeks produced a higher mean duration of sickness absence periods: mean difference in change values between the intervention and control group (MDchange) was 0.67 days/period up to 29 days (95% confidence interval (95% CI) 0.55 to 0.79; 1 RCT; low-certainty evidence).The introduction of self-certification for a maximum of three days produced a lower mean duration of sickness absence up to three days (MDchange -0.32 days/period, 95% CI -0.39 to -0.25; 1 CBA study; very low-certainty evidence). The authors of a different study reported that prolonging self-certification from ≤ 3 days to ≤ 365 days did not lead to a change, but they did not provide numerical data (very low-certainty evidence). OUTCOME: number of sickness absence periods per workerExtending the period of self-certification from one week to two weeks resulted in no difference in the number of sickness absence periods in one RCT, but the authors did not report numerical data (low-certainty evidence).The introduction of self-certification for a maximum of three days produced a higher mean number of sickness absence periods lasting up to three days (MDchange 0.48 periods, 95% CI 0.33 to 0.63) in one CBA study (very low-certainty evidence).Extending the period of self-certification from three days to up to a year decreased the number of periods in one CBA study, but the authors did not report data (very low-certainty evidence). OUTCOME: average lost work time per 100 person-yearsExtending the period of self-certification from one week to two weeks resulted in an inferred increase in lost work time in one RCT (very low-certainty evidence).Extending the period of self-certification (introduction of self-certification for a maximum of three days (from zero to three days) and from three days to five days, respectively) resulted in more work time lost due to sickness absence periods lasting up to three days in two CBA studies that could not be pooled (MDchange 0.54 days/person-year, 95% CI 0.47 to 0.61; and MDchange 1.38 days/person-year, 95% CI 1.16 to 1.60; very low-certainty evidence).Extending the period of self-certification from three days up to 50 days led to 0.65 days less lost work time in one CBA study, based on absence periods lasting between four and 16 days. Extending the period of self-certification from three days up to 365 days resulted in less work time lost due to sickness absence periods longer than 16 days (MDchange -2.84 days, 95% CI -3.35 to -2.33; 1 CBA study; very low-certainty evidence). OUTCOME: costs of sickness absence and physician certificationOne RCT reported that the higher costs of sickness absence benefits incurred by extending the period of self-certification far outweighed the possible reduction in costs of fewer physician appointments by almost six to one (low-certainty evidence).In summary, we found very low-certainty evidence that introducing self-certification of sickness absence or prolonging the self-certification period has inconsistent effects on the mean number of sickness absence days, the number of sickness absence periods, and on lost work time due to sickness absence periods. AUTHORS' CONCLUSIONS: There is low- to very low-certainty evidence of inconsistent effects of changing the period of self-certification on the duration or frequency of short-term sickness absence periods or the amount of work time lost due to sickness absence. Because the evidence is of low or very low certainty, more and better studies are needed.

The incidence of cancer and mortality in paediatric onset inflammatory bowel disease in Denmark and Finland during a 23-year period: a population-based study.

BACKGROUND: Recent studies report increased risks of both cancer and mortality in paediatric onset inflammatory bowel disease (pIBD) but the reproducibility of this is unknown. AIM: To estimate the risk of cancer and mortality in the Danish and Finnish pIBD population in a 23-year period compared to the general population. METHODS: The pIBD population was defined as individuals registered in the national patient registries with a diagnosis of Crohn's disease (CD), ulcerative colitis (UC) or IBD-unclassified before their 18th birthday from 1992 to 2014. This cohort was cross referenced with the national cancer and mortality registries identifying all pIBD patients who subsequently developed cancer and/ or died and followed up to the end of 2014. Risk estimates are presented as standardised incidence ratios calculated based on incidence figures from the populations. RESULTS: Six thousand six hundred and eight-nine patients with pIBD were identified (median age at follow-up 22.3 years; median follow-up: 9.6 years [interquartile range: 4.8-16.0]). Seventy-two subsequently developed cancer and 65 died. The standardised incidence ratio of cancer in general was 2.6 (95% CI: 1.8-3.7) and 2.5 (95% CI: 1.8-3.4) in CD and UC, respectively. The standardised mortality ratios were 2.2 (95% CI: 1.4-3.4) and 3.7 (95% CI: 2.7-5.0) in CD and UC, respectively. The leading causes for mortality were cancer, suicide and infections. CONCLUSIONS: We found an increased risk of cancer and mortality in pIBD. This underlines the importance of cancer surveillance programs and assessment of mental health in the standard of care in adolescent pIBD patients.

Early part-time sick leave results in considerable savings in social security costs at national level: an analysis based on a quasi-experiment in Finland.

Objectives We analyzed social security costs based on an earlier quasi-experiment that compared work participation between partial sickness beneficiaries and a matched group of full sickness beneficiaries. Methods Utilizing a population-based 70% representative sample, 1878 persons with part-time sick leave (intervention group) due to musculoskeletal diseases or mental disorders at an early stage of work disability and their propensity-score-matched controls with full-time sick leave were followed for two years. The outcome was the difference (absolute and relative) in social security costs between the intervention and control groups during follow-up. Costs of sickness absence, vocational rehabilitation, unemployment, and retirement days were calculated from national administrative registers. Results A cost reduction of €2395 per person per year [95% confidence interval (CI) -2890- -1899) was observed in the intervention compared with the control group. The cost ratio was 0.512 (95% CI 0.511-0.513). The largest savings were attributable to differences in the costs of retirement and vocational rehabilitation. The savings were higher for the second compared with the first follow-up year. Costs were saved across both genders and diagnostic groups, however, savings for women with musculoskeletal diseases were lowest. Conclusions Part-time instead of full-time sick leave, at the early stage of work disability due to musculoskeletal diseases or mental disorders, leads to considerable social security cost savings during two years, in correspondence with increased work participation and in addition to earlier reported health benefits. Part-time sick leave can be recommended from an economic perspective; however more consideration should be given to women with musculoskeletal diseases.