Characteristics, comorbidities, and treatment practices of lichen planus in Northern Finland: A register-based study among 619 subjects.

Background and Aims: Lichen planus (LP) is a common itching skin disease where lesions appear on the skin and mucous membranes. However, the epidemiology of LP is not yet sufficiently understood. The aim of this study was to retrospectively map out the characteristics, comorbidities and treatments of patients diagnosed with LP. Methods: This is a retrospective hospital patient registry-based study performed between 2009 and 2021 in a secondary care hospital (Oulu University Hospital) in Northern Finland. All patients with recorded diagnosis of LP were included in the study. Characteristics, comorbidities, and treatments of LP patients were studied. Results: In total, 619 patients were verified from the hospital health records. The mean age of patients was 54.2 years and the majority were female (58.3%). Most of the patients had symptoms in more than two skin areas (mean 2.7 skin areas), lower limbs being the most common site (74.0%). A third of patients (34.7%) had oral LP lesions. Nearly fifth (19.4%) of the subjects had a history of previous LP. Of comorbidities found among LP subjects, obesity (22.5%), malignancies (19.4%), depression (12.8%), and thyroiditis (12.4%) were seen more often than in general Finnish population. The most used form of treatment was topical corticosteroids (97.6%), followed by phototherapy 26.8%. Systemic treatments such as prednisolone and methotrexate had been used in 7.6% and 1.1% of the patients, respectively. Conclusion: LP patients had a heightened risk for several comorbidities, which should be considered when managing patients with LP.

The association of body mass index with quality of life and working ability: a Finnish population-based study.

PURPOSE: The impact of obesity on quality of life (QoL) and working ability vary in different dimensions. This study investigated the association of obesity with QoL and working ability in Finnish adults. Comorbidities as associative factors were also characterised. METHODS: This cross-sectional study included 4956 randomly selected adults. QoL (EUROHIS-QOL 8 total score and individual components), perceived physical and psychological working ability, and sick leave days were analysed in different body mass index (BMI) groups. Regression models were used to study the role of comorbidities as associative factors. RESULTS: EUROHIS-QOL 8 total score was significantly lower in BMI group 25.0-29.9 kg/m2 (4.01; 95% confidence interval 3.97-4.05), BMI 30.0-34.9 kg/m2 (3.85; 3.79-3.91), BMI 35.0-39.9 kg/m2 (3.75; 3.66-3.85), and BMI ≥ 40.0 kg/m2 (3.73; 3.46-4.00) compared to individuals with normal (18.5-24.9 kg/m2) BMI (4.08; 4.04-4.12). Individuals with obesity (BMI ≥ 30.0 kg/m2) rated their QoL lower than individuals with normal BMI in seven of the eight EUROHIS-QOL 8 components. A lesser proportion of individuals (53-73%) with obesity rated their physical working ability as very or fairly good compared to individuals with normal BMI (90%, p values < 0.001). The psychological working ability was rated as very or fairly good by 71-75% of individuals with obesity compared to 85% of individuals with normal BMI (p = 0.008 and p = 0.001 in individuals with BMI 30.0-34.9 and BMI 35.0-39.9 kg/m2, respectively). CONCLUSIONS: Obesity was negatively associated with both physical and psychological components of QoL, even after accounting for obesity-related comorbidities. Obesity treatment can benefit from a holistic approach that considers these multifaceted associations.

Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study.

BACKGROUND: Obesity is associated with inflammation but the role of vitamin D in this process is not clear. OBJECTIVES: We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. METHODS: Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. RESULTS: In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. CONCLUSIONS: The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.

Vitamin D Status and Components of Metabolic Syndrome in Older Subjects from Northern Finland (Latitude 65°North).

INTRODUCTION: Vitamin D deficiency has been linked to the increased risk of several chronic diseases, especially in people living in the Northern Latitudes. The aim of this study was to assess the vitamin D status in older subjects born in 1945 in Northern Finland (latitude 65°North), and to examine its associations to components of metabolic syndrome (MetS). METHODS: In this cross-sectional study, we invited 904 subjects born in 1945 from the Oulu region (Oulu45 cohort), out of an original cohort of 1332 subjects. In the cohort, plasma 25 hydroxyvitamin D (25OHD) levels were determined by an enzyme immunoassay of 263 men and 373 women, with a mean age baseline of 69±0.5 years old. We assessed the participants' usage of vitamin D supplements, as well as their lifestyle factors, using a questionnaire. RESULTS: Nearly 80% of the subjects had low vitamin D levels [either vitamin D deficient (<50 nmol/L) or insufficient (50 - 75 nmol/L)], and only 20% of the participants had sufficient vitamin D levels (>75 nmol/L) (based on the American Endocrine Society guidelines). The low vitamin D status was associated with a high prevalence of MetS; a significantly higher number of subjects with MetS (41%) had low vitamin D levels in comparison to the non-MetS subjects (38%) (p ≤ 0.05). The subjects under vitamin D supplementation had a significantly lower incidence of MetS (42.6% vs 57.4%) and its components in comparison to the non-supplemented subjects (p ≤ 0.05). CONCLUSIONS: Low vitamin D levels are a risk factor for MetS amongst other lifestyle factors, such as dietary habits and physical inactivity, among older subjects in the Northern Latitudes (65°North). Optimal supplementation of vitamin D, along with rich dietary sources of vitamin D, are highly recommended for older subjects as a means to positively affect, e.g., hypertension, insulin resistance, and obesity, as components of the MetS.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab - a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO).

OBJECTIVES: The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn's disease (CD) and ulcerative colitis (UC) patients. METHODS: This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation. RESULTS: A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=-5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =-0.5, p = .003) at month 6. CONCLUSIONS: Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

Potential determinants of vitamin D in Finnish adults: a cross-sectional study from the Northern Finland birth cohort 1966.

OBJECTIVE: Evidence from randomised controlled trials suggests that vitamin D may reduce multimorbidity, but very few studies have investigated specific determinants of vitamin D2 and D3 (two isoforms of 25-hydroxyvitamin D). The aim of the study was to investigate the determinants of vitamin D2 and D3 and to identify the risk factors associated with hypovitaminosis D. DESIGN: Cross-sectional study. SETTING: Northern Finland Birth Cohort 1966. PARTICIPANTS: 2374 male and 2384 female participants with data on serum 25(OH)D2 and 25(OH)D3 concentrations measured at 31 years of age (1997), together with comprehensive measures of daylight, anthropometric, social, lifestyle and contraceptive cofactors. METHODS: We assessed a wide range of potential determinants prior to a nationwide fortification programme introduced in Finland. The determinants of 25(OH)D2, 25(OH)D3 and 25(OH)D concentrations were analysed by linear regression and risk factors for being in lower tertile of 25(OH)D concentration by ordinal logistic regression. RESULTS: At the time of sampling, 72% of the participants were vitamin D sufficient (≥50 nmol/L). Low sunlight exposure period (vs high) was associated positively with 25(OH)D2 and negatively with 25(OH)D3 concentrations. Use of oral contraceptives (vs non-users) was associated with an increase of 0.17 nmol/L (95% CI 0.08 to 0.27) and 0.48 nmol/L (95% CI 0.41 to 0.56) in 25(OH)D2 and 25(OH)D3 concentrations. Sex, season, latitude, alcohol consumption and physical activity were the factors most strongly associated with 25(OH)D concentration. Risk factors for low vitamin D status were low sunlight exposure defined by time of sampling, residing in northern latitudes, obesity, higher waist circumference, low physical activity and unhealthy diet. CONCLUSIONS: We demonstrate some differential associations of environmental and lifestyle factors with 25(OH)D2 and 25(OH)D3 raising important questions related to personalised healthcare. Future strategies could implement lifestyle modification and supplementation to improve vitamin D2 and D3 status, accounting for seasonal, lifestyle, metabolic and endocrine status.

Transcranial bright light and symptoms of jet lag: a randomized, placebo-controlled trial.

BACKGROUND: Rapid travel over multiple time zones usually results in transient de-synchronization between environmental time and the biological clock of the individual. Common symptoms are increased daytime sleepiness, reduced sleep duration and quality, and performance impairments. Exposure to ocular bright light is known to alleviate jet lag symptoms and facilitate adaptation to a new time zone. Recently, transcranial bright light (TBL) via the ear canals has been shown to have antidepressant, anxiolytic, and psychomotor performance-enhancing effects. In this case we studied whether intermittent TBL exposure can alleviate jet lag symptoms in a randomized, double-blind, placebo-controlled study. METHODS: Intermittent light exposures (4 × 12 min; day 0: 08:00, 10:00, 12:00, 14:00; days 1-6: 10:00, 12:00, 14:00, 16:00) were administered during the 7-d post-travel period after an eastward transatlantic flight. The symptoms of jet lag were measured by the Visual Analog Scale (VAS), the Karolinska Sleepiness Scale (KSS), and the Profile of Mood States (POMS). RESULTS: We found a significant reduction of overall jet lag symptoms (VAS), subjective sleepiness (KSS), and the fatigue, inertia, and forgetfulness subscales of the POMS when comparing the active TBL treatment group (N = 30) to the placebo group (N = 25). For example, the normalized values of VAS in the TBL, but not the placebo, group returned to pre-travel levels by the final post-travel day (6.16 vs. 15.34). DISCUSSION: Results suggest a cumulative effect of TBL, as the effects emerged on post-travel days 3-4. Intermittent TBL seems to alleviate jet lag symptoms.

Transcranial bright light treatment via the ear canals in seasonal affective disorder: a randomized, double-blind dose-response study.

BACKGROUND: Bright light treatment is effective for seasonal affective disorder (SAD), although the mechanisms of action are still unknown. We investigated whether transcranial bright light via the ear canals has an antidepressant effect in the treatment of SAD. METHODS: During the four-week study period, 89 patients (67 females; 22 males, aged 22-65, mean ± SD age: 43.2 ± 10.9 years) suffering from SAD were randomized to receive a 12-min daily dose of photic energy of one of three intensities (1 lumen/0.72 mW/cm(2); 4 lumens/2.881 mW/cm(2); 9 lumens/6.482 mW/cm(2)) via the ear canals. The light was produced using light-emitting diodes. The severity of depressive symptoms was assessed with the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD), the Hamilton Anxiety Rating Scale (HAMA), and the Beck Depression Inventory (BDI). Cognitive performance was measured by the Trail Making Test (TMT). The within-group and between-group changes in these variables throughout the study were analysed with a repeated measures analysis of variance (ANOVA), whereas gender differences at baseline within the light groups were analysed using Student's t-tests. RESULTS: Patients in all three groups showed significant decreases in their BDI, HAMA, and SIGH-SAD scores. Response rates, i.e., an at least 50% decrease of symptoms as measured by the BDI, were 74%-79% in the three treatment groups. Corresponding variations for the SIGH-SAD and the HAMA were 35-45% and 47-62%, respectively. No intensity-based dose-response relationships in the improvement of anxiety and depressive symptoms or cognitive performance between treatment groups were observed. Approximately one in four patients experienced mild adverse effects, of which the most common were headache, insomnia, and nausea. CONCLUSIONS: These results suggests that transcranial bright light treatment may have antidepressant and anxiolytic effect in SAD patients, as both self- and psychiatrist-rated depressive and anxiety symptoms decreased in all treatment groups. These improvements are comparable to findings of earlier bright light studies that used conventional devices. The lack of dose response may be due to a saturation effect above a certain light intensity threshold. Further studies on the effects of transcranial bright light with an adequate placebo condition are needed. TRIAL REGISTRATION: NCT01293409, ClinicalTrials.gov.

Altered resting-state activity in seasonal affective disorder.

At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD.

Do depressive symptoms have an impact on the effectiveness of lifestyle counseling in prevention of type 2 diabetes? One-year follow-up of FIN-D2D.

AIM: To examine whether depressive symptoms are associated with the effectiveness of lifestyle counseling on cardio-metabolic risk profile and glucose homeostasis during one-year follow-up in individuals at high risk for type 2 diabetes (T2D). METHODS: A total of 10,149 individuals took part in the implementation project of the national diabetes prevention program (FIN-D2D) conducted in primary health care setting in Finland. At baseline, altogether 2798 non-diabetic individuals participated in the one-year follow-up, and 2275 of them had at least one group or individual counseling visit. RESULTS: 4.0% of the individuals (n=78) had depressive symptoms, while 96.0% (n=1889) were free of depressive symptoms at baseline. Individuals who had depressive symptoms had higher body mass index and waist circumference at baseline than individuals without depressive symptoms. In terms of changes in cardio-metabolic risk profile and glucose homeostasis the effectiveness of lifestyle counseling was parallel between individuals with and without depressive symptoms during the one-year follow-up. CONCLUSIONS: Effectiveness of lifestyle counseling did not differ between individuals with and without depressive symptoms. Individuals with depressive symptoms should not be excluded from lifestyle intervention programs.

Can transcranial brain-targeted bright light treatment via ear canals be effective in relieving symptoms in seasonal affective disorder? A pilot study.

Bright light therapy (BLT) is widely accepted as first-line treatment of seasonal affective disorder (SAD). However, the mechanism of action of BLT is still widely unknown. On the other hand, in mammals, light penetrates the skull bone and reaches the brain, and extra ocular transcranial phototransduction has physiological influences such as changed reproductive cycles and increased brain serotonin levels. Therefore, we challenged the existing conceptual framework that light therapy would only be mediated through the eyes. Consequently, we run a pilot study on the putative effect of transcranial bright light in the treatment of SAD. The light was produced using light-emitting diodes (LEDs), which were attached to earplugs. The amount of photic energy was 6.0-8.5 lumens in both ear canals, and the length of treatment was 8 or 12 min five times a week during a four-week study period. Subjects were recruited through advertisements in the city of Oulu, Finland (latitude 65°01'N) during 14 January 2009-03 February 2009. The final patient series consisted of 13 (aged 37.1 ± 7.2 years) physically healthy indoor workers suffering from SAD according to DSM-IV-TR criteria. Severity of depressive symptoms was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI)-21. Furthermore, severity of anxiety symptoms was measured by the 14-item Hamilton Anxiety Rating Scale (HAMA). The HAMD-17 mean sum score at screening was 23.1 ± 1.6. Ten out of 13 SAD patients (76.9%) achieved full remission (i.e., HAMD-17 sum score ≤ 7), and 92.3% (12/13) at least 50% reduction in HAMD-17 sum scores at "Week 4". By using a mixed regression model of repeated measures (AR-1) controlling for age, gender, and HAMD-17 mean sum score at screening, significant differences were found comparing the HAMD-17 mean sum scores of "Week 0" with the corresponding scores at the "Week 3" (t=-2.05, p=0.045) and "Week 4" visit (t=-2.77, p=0.008). Correspondingly, significant differences were found comparing the BDI-21 mean sum scores (15.2 ± 6.7) of "Week 0" with the corresponding scores at the "Week 3" (t=-2.37, p=0.021) and "Week 4" visit (t=-3.65, p<0.001). The HAMA mean sum score at screening was 20.5 ± 5.4. During the study period, 12 out of 13 (92.3%) patients achieved at least 50% reduction in their HAMA sum scores, and in 10 out of 13 patients (76.9%), the HAMA sum score was <7. In conclusion, it is hard to believe that our findings could be explained solely by placebo effect. Consequently, the basic assumptions underlying extraocular photoreception in humans deserve to be reconsidered. Given that a proper placebo treatment can be implemented via ear canals, further investigations with randomized placebo-controlled and/or dose-finding study designs regarding the extraocular transcranial bright light in the treatment of SAD are called for.

Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study.

OBJECTIVE: Based on clues from epidemiology and animal experiments, low vitamin D during early life has been proposed as a risk factor for schizophrenia. The aim of this study was to explore the association between the use of vitamin D supplements during the first year of life and risk of developing schizophrenia. METHOD: Subjects were drawn from the Northern Finland 1966 Birth Cohort (n=9,114). During the first year of life, data were collected about the frequency and dose of vitamin D supplementation. Our primary outcome measures were schizophrenia, psychotic disorders other than schizophrenia, and nonpsychotic disorders as diagnosed by age 31 years. Males and females were examined separately. RESULTS: In males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia (Risk ratio (RR)=0.08, 95% CI 0.01-0.95; RR=0.12, 95% CI 0.02-0.90, respectively) compared with no supplementation. In males, the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23, 95% CI 0.06-0.95) compared to those on lower doses. There were no significant associations between either the frequency or dose of vitamin D supplements and (a) schizophrenia in females, nor with (b) nonpsychotic disorder or psychotic disorders other than schizophrenia in either males or females. CONCLUSION: Vitamin D supplementation during the first year of life is associated with a reduced risk of schizophrenia in males. Preventing hypovitaminosis D during early life may reduce the incidence of schizophrenia.