GLA: D Årsrapport 2017

Godt Liv med Artrose i Danmark (GLA:D®) er et nationalt initiativ fra Forskningsenheden for Muskuloskeletal Funktion og Fysioterapi ved Syddansk Universitet. GLA:D® repræsenter en evidensbaseret behandlingsindsats for patienter med knæ- og hofteartrose bestående af patientuddannelse og neuromuskulær træning og understøtter implementering af de nationale kliniske retningslinjer på området. GLA:D® tilbydes i hele landet. Ved udgangen af 2017 er 1.109 klinikere uddannet i GLA:D® og 383 enheder heraf 34 kommuner har haft patienter i forløb. Næsten 30.000 patienter har i løbet af de sidste 5 år deltaget i et GLA:D® -forløb. I GLA:D® Årsrapport 2017 kan du bl.a. få et overblik over de resultater patienterne har opnået i form af lavere smerte, lavere forbrug af smertestillende medicin, bedre funktion og bedre livskvalitet

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

Chronic opioid use before and after exercise therapy and patient education among patients with knee or hip osteoarthritis

Objective: To investigate changes in opioid use after supervised exercise therapy and patient education among knee or hip osteoarthritis patients with chronic opioid use. Method: In this cohort study, we linked data from the Good Life with osteoArthritis in Denmark register (GLA:D®; standardised treatment program for osteoarthritis; January 2013 to November 2018) with national health registries. Among 35,549 patients, 1,262 were classified as chronic opioid users based on amount and temporal distribution of dispensed opioids the year before the intervention. We investigated changes in opioid use, measured as mg oral morphine equivalents (OMEQs), from the year before the intervention to the year after using generalized estimating equations. Results: We found a 10% decrease in mg OMEQs from the year before to the year after the intervention (incidence rate ratio [IRR]: 0.90, 95% confidence interval [CI]: 0.86, 0.94). Additional analyses suggested this decrease to be mainly attributable to regulatory actions targeting opioid prescribing during the study period (IRR among patients participating in the intervention before: 0.98 [95% CI: 0.89, 1.07] vs after: 0.83 [0.74, 0.93] regulatory actions). In a random general population sample of matched chronic opioid users, a similar opioid use pattern was observed over time, further supporting the impact of regulatory actions on the opioid use in the study population. Conclusion: Among patients with knee or hip osteoarthritis and chronic opioid use, a standardised treatment program did not change opioid use when regulatory changes in opioid prescribing were taken into account

Response of noctilucent cloud brightness to daily solar variations

For the first time, long-term data sets of ground-based observations of noctilucent clouds (NLC) around the globe have been analyzed in order to investigate a response of NLC to solar UV irradiance variability on a day-to-day scale. NLC brightness has been considered versus variations of solar Lyman-alpha flux. We have found that day-to-day solar variability, whose effect is generally masked in the natural NLC variability, has a statistically significant effect when considering large statistics for more than ten years. Average increase in day-to-day solar Lyman-α flux results in average decrease in day-to-day NLC brightness that can be explained by robust physical mechanisms taking place in the summer mesosphere. Average time lags between variations of Lyman-α flux and NLC brightness are short (0–3 days), suggesting a dominant role of direct solar heating and of the dynamical mechanism compared to photodissociation of water vapor by solar Lyman-α flux. All found regularities are consistent between various ground-based NLC data sets collected at different locations around the globe and for various time intervals. Signatures of a 27-day periodicity seem to be present in the NLC brightness for individual summertime intervals; however, this oscillation cannot be unambiguously retrieved due to inevitable periods of tropospheric cloudiness

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.Wellcome Trust (068545/Z/02)This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365

Publisher Correction:Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals (Nature Genetics, (2020), 52, 12, (1314-1332), 10.1038/s41588-020-00713-x)

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets