Luotettava lääketiede koronaviruksen kourissa

Lääkehype uhkaa pyyhkäistä loput remdesiviiritutkimukset mennessään ja jättää maailman ikuisesti epätietoiseksi lääkkeen tehosta

Koronan lääkehoito kehittyy, mutta kysymyksiä jää

publishedVersio

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 × 10$^{−9}$) and high $\Delta$EE (EE during the clamp − EE in the fasting state) (r = 0.602, P = 2.5 × 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-1$\beta$, 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] 1$\alpha$ 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

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.Peer reviewe

Variant near ADAMTS9 Known to Associate with Type 2 Diabetes Is Related to Insulin Resistance in Offspring of Type 2 Diabetes Patients—EUGENE2 Study

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.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.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

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

Key PointsQuestionWhat is the association of decision aids vs usual care with shared decision-making in men deciding whether to undergo prostate cancer screening? FindingsThis systematic review and meta-analysis of 19 randomized clinical trials comparing decision aids for prostate cancer screening (12781 men) found that decision aids are probably associated with a small reduction in decisional conflict and are possibly associated with an increase in knowledge. Decision aids are possibly not associated with whether physicians and patients discuss prostate cancer screening and are possibly not associated with actual screening decisions. MeaningRandomized clinical trials have failed to provide compelling evidence for the use of decision aids for men contemplating prostate cancer screening that have, up to now, undergone rigorous testing to determine their outcome. ImportanceUS guidelines recommend that physicians engage in shared decision-making with men considering prostate cancer screening. ObjectiveTo estimate the association of decision aids with decisional outcomes in prostate cancer screening. Data SourcesMEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL were searched from inception through June 19, 2018. Study SelectionRandomized trials comparing decision aids for prostate cancer screening with usual care. Data Extraction and SynthesisIndependent 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 MeasuresKnowledge, decisional conflict, screening discussion, and screening choice. ResultsOf 19 eligible trials (12781 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; I-2=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; I-2=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; I-2=60%; low quality) or with men's decision to undergo prostate cancer screening (risk ratio, 0.95; 95% CI, 0.88-1.03; I-2=36%; low quality). Conclusions and RelevanceThe 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. This systematic review and meta-analysis of 19 randomized clinical trials estimates the association of decision aids with decisional outcomes in prostate cancer screening.Peer reviewe

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.publishedVersionPeer reviewe

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.Peer reviewe