Impact of TNF inhibitor medication on working ability in axial spondyloarthritis: an observational national registry-based cohort study.

Objective: The aim was to investigate the effect of TNF inhibitor (TNFi) initiation on working ability and health-care resource utilization among axial SpA patients in a real-life setting. Methods: Patients with a clinical diagnosis of non-radiographic (nr-axSpA) or radiographic axial SpA initiating their first TNFi were identified from the National Register for Antirheumatic and Biologic Treatment in Finland. Sickness absences, including sick leave and disability pension, in- and outpatient days and rehabilitation rates, 1 year before and after initiating the medication were retrieved from national registries. Factors affecting result variables were studied using multivariate regression analysis. Results: Overall, 787 patients were identified. Rates of work disability days per year were 55.6 the year before treatment onset and 55.2 the year after, with significant differences between patient subgroups. The rate of sick leave decreased after starting TNFi treatment. However, the rate of disability pension continued to rise. Patients with a diagnosis of nr-axSpA experienced a decrease in overall work disability and, especially, fewer sick leaves. No sex differences were detected. Conclusion: TNFi interrupts the increase in work disabled days evident during the year before its initiation. However, the overall work disability remains high. Treating patients earlier in the nr-axSpA phase, regardless of sex, appears important in maintaining the ability to work.

Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial.

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.

Metabolic Syndrome, Disease Activity, and Adipokines in Patients With Newly Diagnosed Inflammatory Joint Diseases.

OBJECTIVE: To investigate metabolic syndrome (MetS), disease activity, and adipokine levels among patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA) at the time of diagnosis and after 1 year of follow-up. METHODS: Patients with inflammatory joint diseases participating in the Northern Savo 2010 population-based longitudinal epidemiological study were evaluated for components of MetS (by National Cholesterol Education Program's Adult Treatment Panel III) and clinical parameters of disease activity. The adipokines adiponectin, adipsin, resistin, and leptin were measured at baseline and after 1 year of treatment with disease-modifying antirheumatic drugs. RESULTS: Among 176 patients, MetS was detected in 42% of RA, 36% of SpA, and 51% of UA patients. Metabolic syndrome was associated with higher disease activity as measured by patient global assessment in RA and UA patients and increased pain in RA patients. Leptin levels were increased in patients with MetS, showing a linearly increasing trend with the number of components of MetS in SpA and UA, but not in RA. In RA patients, decrease in disease activity correlated with decrease in leptin levels. Resistin did not associate with MetS, but a decrease in resistin correlated with decrease in disease activity in RA and UA. In SpA, increased adiponectin level correlated with relief in disease activity, but not with MetS. CONCLUSIONS: Metabolic syndrome was common in patients with newly diagnosed arthritides and associated with higher disease activity and increased leptin levels. Resistin responded to treatment of arthritis in RA and UA, leptin in RA, and adiponectin in SpA.

Association of rheumatoid arthritis disease activity and antibodies to periodontal bacteria with serum lipoprotein profile in drug naive patients.

Objective: We investigated lipid concentrations, particle sizes and antibodies binding to periodontal bacteria Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and to malondialdehyde-acetaldehyde (MAA) modified low-density lipoprotein in immunoglobulin (Ig) class A, G and M among patients with newly diagnosed rheumatoid arthritis (RA) in a population-based cohort.Methods: Concentrations and sizes of lipoprotein particles analysed by proton nuclear magnetic resonance spectroscopy and antibody levels to MAA modified low-density lipoprotein were studied at baseline and after one-year of follow-up. Serum Ig A and G class antibodies to periodontal bacteria were determined at baseline.Results: Sixty-three patients were divided into tertiles according to disease activity by disease activity score with 28 joint count and erythrocyte sedimentation rate (ESR) (<3.9, 3.9-4.7, >4.7). Small low-density lipoprotein concentration was lowest in the tertile with the highest disease activity. In high-density lipoprotein, the concentrations of total, medium and small particles decreased with disease activity. The particle size in low-density lipoprotein associated with disease activity and the presence of antibodies to P. gingivalis. Ig G and M antibodies to MAA modified low-density lipoprotein correlated with disease activity. Inflammation associated changes faded by one year.Conclusions: Drug naive RA patients had proatherogenic changes in lipid profiles, but they were reversible, when inflammation diminished.Key messagesPatients with drug naive rheumatoid arthritis showed proatherogenic lipid profiles.Reversible changes in lipid profiles can be achieved as response to inflammation suppression.Active therapy aimed at remission is essential in all patients with rheumatoid arthritis.

Cost-effectiveness of abatacept, tocilizumab and TNF-inhibitors compared with rituximab as second-line biologic drug in rheumatoid arthritis.

OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors. METHODS: A patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted. RESULTS: Drug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX. CONCLUSIONS: TNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option.

Decision Aids for Prostate Cancer Screening Choice: A Systematic Review and Meta-analysis.

IMPORTANCE: US guidelines recommend that physicians engage in shared decision-making with men considering prostate cancer screening. OBJECTIVE: To estimate the association of decision aids with decisional outcomes in prostate cancer screening. DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL were searched from inception through June 19, 2018. STUDY SELECTION: Randomized trials comparing decision aids for prostate cancer screening with usual care. DATA EXTRACTION AND SYNTHESIS: Independent duplicate assessment of eligibility and risk of bias, rating of quality of the decision aids, random-effects meta-analysis, and Grading of Recommendations, Assessment, Development and Evaluations rating of the quality of evidence. MAIN OUTCOMES AND MEASURES: Knowledge, decisional conflict, screening discussion, and screening choice. RESULTS: Of 19 eligible trials (12 781 men), 9 adequately concealed allocation and 8 blinded outcome assessment. Of 12 decision aids with available information, only 4 reported the likelihood of a true-negative test result, and 3 presented the likelihood of false-negative test results or the next step if the screening test result was negative. Decision aids are possibly associated with improvement in knowledge (risk ratio, 1.38; 95% CI, 1.09-1.73; I2 = 67%; risk difference, 12.1; low quality), are probably associated with a small decrease in decisional conflict (mean difference on a 100-point scale, -4.19; 95% CI, -7.06 to -1.33; I2 = 75%; moderate quality), and are possibly not associated with whether physicians and patients discuss prostate cancer screening (risk ratio, 1.12; 95% CI, 0.90-1.39; I2 = 60%; low quality) or with men's decision to undergo prostate cancer screening (risk ratio, 0.95; 95% CI, 0.88-1.03; I2 = 36%; low quality). CONCLUSIONS AND RELEVANCE: The results of this study provide moderate-quality evidence that decision aids compared with usual care are associated with a small decrease in decisional conflict and low-quality evidence that they are associated with an increase in knowledge but not with whether physicians and patients discussed prostate cancer screening or with screening choice. Results suggest that further progress in facilitating effective shared decision-making may require decision aids that not only provide education to patients but are specifically targeted to promote shared decision-making in the patient-physician encounter.

Public, health professional and legislator perspectives on the concept of psychiatric disease: a population-based survey.

OBJECTIVE: To assess which mental health-related states of being are perceived as diseases by psychiatrists, non-psychiatric physicians, nurses, parliament members and laypeople. DESIGN AND SETTING: A population-based, mailed survey in Finland. PARTICIPANTS: Respondents from a random sample of 3000 laypeople, 1500 physicians, 1500 nurses and all 200 members of the parliament (MPs) of Finland. PRIMARY OUTCOME MEASURES: Respondents' perspectives on 20 mental health-related states of being as diseases, measuring the extent of agreement with the claim: '[This state of being] is a disease'. RESULTS: Of the 6200 people approached, we received 3259 eligible responses (53%). Two conditions (schizophrenia and autism) were considered to be diseases by at least 75% and two states (grief and homosexuality) were considered not to be diseases by at least 75% in each group. A majority (at least 50% in each group) considered seven states as diseases (anorexia, attention deficit hyperactivity disorder, bulimia, depression, generalised anxiety disorder, panic disorder and personality disorder) and three not to be diseases (absence of sexual desire, premature ejaculation and transsexualism). In six states, there was a wide divergence of opinion (alcoholism, drug addiction, gambling addiction, insomnia, social anxiety disorder and work exhaustion). Psychiatrists were significantly more inclined to considering states of being as diseases relative to other groups, followed by non-psychiatric physicians, nurses, MPs and laypeople. CONCLUSIONS: Respondents agreed that some conditions, such as schizophrenia and autism, are diseases and other states, such as grief and homosexuality, are not; for others, there was considerable disagreement. Psychiatrists are more inclined to consider mental health-related states of being as diseases compared with other physicians, who, in turn, are more inclined than other constituencies. Understanding notions of disease may underlie important debates in public policy and practice in areas of mental health and behaviour, and have implications for resource allocation and stigma.

SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity.

OBJECTIVE: Sirtuin 1 (SIRT1) is implicated in the regulation of mitochondrial function, energy metabolism, and insulin sensitivity in rodents. No studies are available in humans to demonstrate that SIRT1 expression in insulin-sensitive tissues is associated with energy expenditure and insulin sensitivity. RESEARCH DESIGN AND METHODS: Energy expenditure (EE), insulin sensitivity, and SIRT1 mRNA adipose tissue expression (n = 81) were measured by indirect calorimetry, hyperinsulinemic-euglycemic clamp, and quantitative RT-PCR in 247 nondiabetic offspring of type 2 diabetic patients. RESULTS: High EE during the clamp (r = 0.375, P = 2.8 x 10(-9)) and high DeltaEE (EE during the clamp - EE in the fasting state) (r = 0.602, P = 2.5 x 10(-24)) were associated with high insulin sensitivity. Adipose tissue SIRT1 mRNA expression was significantly associated with EE (r = 0.289, P = 0.010) and with insulin sensitivity (r = 0.334, P = 0.002) during hyperinsulinemic-euglycemic clamp. Furthermore, SIRT1 mRNA expression correlated significantly with the expression of several genes regulating mitochondrial function and energy metabolism (e.g., peroxisome proliferator-activated receptor gamma coactivator-1beta, estrogen-related receptor alpha, nuclear respiratory factor-1, and mitochondrial transcription factor A), and with several genes of the respiratory chain (e.g., including NADH dehydrogenase [ubiquinone] 1alpha subcomplex 2, cytochrome c, cytochrome c oxidase subunit IV, and ATP synthase). CONCLUSIONS: Impaired stimulation of EE by insulin and low SIRT1 expression in insulin-sensitive tissues is likely to reflect impaired regulation of mitochondrial function associated with insulin resistance in humans.

Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients--EUGENE2 study.

BACKGROUND: A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity. METHODOLOGY/RESULTS: Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2(nd) phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits. CONCLUSION: The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.

Single nucleotide polymorphisms of the MCHR1 gene do not affect metabolism in humans.

Melanin concentrating hormone receptor-1 (MCHR1) is a centrally and peripherally expressed receptor that regulates energy expenditure and appetite. Single nucleotide polymorphisms (SNPs) of the MCHR1 gene have been previously associated with obesity, but the results are inconsistent among different populations. This study was performed to determine whether SNPs of MCHR1 affect glucose and energy metabolism. We screened six SNPs of MCHR1 in a cross-sectional study of 217 middle-age, non-diabetic Finnish subjects who were offspring of type 2 diabetic patients. Insulin secretion was evaluated by an intravenous glucose tolerance test and insulin sensitivity and energy metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry. SNPs of MCHR1 were not associated with BMI, waist circumference, subcutaneous or intra-abdominal fat area, glucose tolerance, first-phase insulin release, insulin sensitivity, or energy metabolism. One SNP, which was in >0.50 linkage disequilibrium with the other five SNPs, was also screened in 1455 unrelated Finnish middle-age subjects in a population-based study. No differences in BMI, waist circumference, or glucose or insulin levels in an oral glucose tolerance test among the genotypes were found. In conclusion, SNPs of MCHR1 did not have effects on metabolic variables in humans.

Single nucleotide polymorphisms of the melanocortin-3 receptor gene are associated with substrate oxidation and first-phase insulin secretion in offspring of type 2 diabetic subjects.

CONTEXT: The melanocortin-3 receptor (MC3R) is a part of the melanocortin system that regulates appetite and energy metabolism. The Thr/Thr 6 and Val/Val81 [corrected] polymorphisms of the MC3R gene have been previously associated with high insulin levels and obesity in children. OBJECTIVE: The objective was to determine whether single nucleotide polymorphisms (SNPs) of MC3R are associated with glucose, lipid, and energy metabolism. DESIGN, SETTING, AND PARTICIPANTS: We screened the Lys/Thr6 and Ile/Val81 mutations and six noncoding SNPs of MC3R in a cross-sectional study of 216 middle-aged nondiabetic Finnish subjects who were offspring of type 2 diabetic patients. MAIN OUTCOME MEASURES: Insulin secretion was evaluated by an iv glucose tolerance test, and insulin sensitivity and energy metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry. RESULTS: Carriers of the Lys 6 and Ile 81 [corrected] alleles had significantly lower rates of lipid oxidation [0.85 +/- 0.38 vs. 1.00 +/- 0.43 mg/kg of lean body mass (LBM)/min; P = 0.022, adjusted for sex, body mass index, age, and family relationship] and higher rates of glucose oxidation in the fasting state (11.28 +/- 4.64 vs. 9.71 +/- 4.53 micromol/kg of LBM/min; P = 0.031) than subjects with the Thr/Thr 6 and Val/Val 81 [corrected] genotypes. They had lower rates of lipid oxidation during the hyperinsulinemic clamp (0.32 +/- 0.41 vs. 0.44 +/- 0.34 mg/kg of LBM/min; P = 0.021) and higher insulin levels in an iv glucose tolerance test (insulin under the curve during the first 10 min, 3220 +/- 1765 vs. 2454 +/- 1538 pmol/liter.min; P = 0.025) compared to subjects with the common genotypes. CONCLUSIONS: Our results suggest that SNPs of MC3R may regulate substrate oxidation and first-phase insulin secretion.

The Val103Ile polymorphism of melanocortin-4 receptor regulates energy expenditure and weight gain.

OBJECTIVE: The melanocortin-4 receptor (MC4R) regulates energy intake. On the basis of animal studies, it may also regulate energy expenditure. RESEARCH METHODS AND PROCEDURES: The effect of the Val103Ile polymorphism of the MC4R gene on energy metabolism was studied in 229 middle-aged nondiabetic subjects (Group 1, age 51.2 +/- 9.8 years, BMI 26.8 +/- 4.5 kg/m2) and on weight gain in 1013 elderly subjects (Group 2, age 69.9 +/- 2.9 years, BMI 27.4 +/- 4.1 kg/m2) during a 3.5-year follow-up study. In Group 1, insulin sensitivity, energy expenditure, and substrate oxidation were measured with the hyperinsulinemic euglycemic clamp combined with indirect calorimetry. RESULTS: In Group 1, the Val103Ile genotype was associated with high rates of energy expenditure (63.42 +/- 13.40 in eight subjects with the Val103Ile genotype vs. 59.86 +/- 7.33 J/kg per minute in 221 subjects with the Val103Val genotype, p = 0.007), high rates of glucose oxidation (8.90 +/- 6.15 vs. 6.07 +/- 4.38 micromol/kg per minute, p = 0.020), and low levels of free fatty acids (0.45 +/- 0.18 vs. 0.56 +/- 0.23 mM, p = 0.029) in the fasting state, and with high rates of glucose oxidation during the clamp (18.88 +/- 4.63 vs. 17.60 +/- 3.24 micromol/kg per minute, p = 0.031). In Group 2, the 103Ile allele was associated with an increase in weight gain during the follow-up (0.78 +/- 3.98 vs. -0.82 +/- 3.98 kg, p = 0.038). DISCUSSION: The Val103Ile polymorphism of the MC4R gene is associated with energy expenditure in humans. Furthermore, it may associate with glucose oxidation, free fatty acid levels, and weight gain.