The road to biologics in patients with hidradenitis suppurativa: a nationwide drug utilization study

Background: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. Objectives: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. Methods: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. Results: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. Conclusions: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS

Maturation of the gut microbiome and risk of asthma in childhood

Colonization of commensal bacteria is thought to impact immune development, especially in the earliest years of life. Here, the authors show, by analyzing the development of the gut microbiome of 690 children, that microbial composition at the age of 1 year is associated with asthma diagnosed in the first 5 years of life

Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring

© 2016 Massachusetts Medical Society. Bisgaard, H., Stokholm, J., Chawes, B. L., Vissing, N. H., Bjarnadóttir, E., Schoos, A.-M. M., … Bønnelykke, K. (2016). Fish Oil–Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring. New England Journal of Medicine, 375(26), 2530–2539. https://doi.org/10.1056/NEJMoa1503734BACKGROUND Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. METHODS We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. RESULTS A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. CONCLUSIONS Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lund-beck Foundation and others; ClinicalTrials.gov number, NCT00798226.)Lundbeck Foundatio

The effect of postexercise carbohydrate and protein ingestion on bone metabolism

Purpose To investigate the effect of feeding carbohydrate and protein (CHO+PRO), immediately or 2 h after an exhaustive run, on the bone turnover response in endurance runners. Methods 10 men (age 28±5 y, height 1.74±0.05 m, body mass 69.7±6.3 kg) performed treadmill running at 75%VO2max, until exhaustion, on three occasions. Blood was collected before and immediately, 1, 2, 3, 4 and 24 h post-exercise, for measurement of β-CTX, P1NP, PTH, PO4, ACa and Ca2+. This was a randomised, counterbalanced, placebo-controlled, single-blinded, cross-over study. The three trials were; i) placebo (PLA), PLA solution was ingested immediately and 2 h post-exercise, ii) immediate feeding (IF), CHO+PRO (1.5 g.kgBM-1 dextrose and 0.5 g.kgBM-1 whey) were ingested immediately post-exercise and PLA 2 h post-exercise, and iii) delayed feeding (DF), PLA was ingested immediately post-exercise and CHO+PRO solution 2 h post-exercise. Data were analysed using repeated measures ANOVA and post-hoc Tukey’s HSD. Results At 1 and 2 h post-exercise, β-CTX concentrations were lower in the IF trial than the DF and PLA trials (P≤0.001). At 3 h post-exercise, β-CTX concentrations were higher in the PLA trial than the IF (P≤0.001) and DF trials (P=0.026). At 4 h post-exercise, β-CTX concentrations were lower in the DF trial than the IF (P=0.003) and PLA trials (P≤0.001). At 4 h post-exercise, P1NP was higher in the IF trial than in DF (P=0.026) and PLA trials (P=0.001). At 3 h post-exercise, PTH was higher in the IF trial than the DF trial (P≤0.001). Conclusions Following exhaustive running, immediate ingestion of CHO+PRO may be beneficial, as it decreases bone resorption marker concentrations and increases bone formation marker concentrations; creating a more positive bone turnover balance

The road to biologics in patients with hidradenitis suppurativa - a nationwide drug utilization study

Background Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). While biologic therapies are now available, the patient’s treatment journey leading to biologic therapy is unclear. Objectives To examine treatment patterns and duration of systemic treatment use in HS patients preceding biologic therapy. Methods We identified all HS patients receiving treatment with biologics in the Danish National Patient Registry from 2010 through 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995.The patients’ treatment journeys were graphically displayed through Sankey diagrams, and generated box-plots to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with standard deviations (SDs) or medians with interquartile ranges (IQRs) for continuous variables. Results A total of 225 HS patients were included. Patients had most frequently been treated with penicillin (n=214; 95.1%), dicloxacillin (n=194; 86.2%), tetracycline (n=145; 64.4%) and rifampicin/clindamycin (n=111; 49.3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4.0 (SD 1.3) different systemic therapies, across a mean of 16.9 (SD 11.3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15.3 (SD 5.1) years (8.2 [SD 5.9] years when excluding penicillin and dicloxacillin). Conclusion HS patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Three-Dimensional Neurophenotyping of Adult Zebrafish Behavior

The use of adult zebrafish (Danio rerio) in neurobehavioral research is rapidly expanding. The present large-scale study applied the newest video-tracking and data-mining technologies to further examine zebrafish anxiety-like phenotypes. Here, we generated temporal and spatial three-dimensional (3D) reconstructions of zebrafish locomotion, globally assessed behavioral profiles evoked by several anxiogenic and anxiolytic manipulations, mapped individual endpoints to 3D reconstructions, and performed cluster analysis to reconfirm behavioral correlates of high- and low-anxiety states. The application of 3D swim path reconstructions consolidates behavioral data (while increasing data density) and provides a novel way to examine and represent zebrafish behavior. It also enables rapid optimization of video tracking settings to improve quantification of automated parameters, and suggests that spatiotemporal organization of zebrafish swimming activity can be affected by various experimental manipulations in a manner predicted by their anxiolytic or anxiogenic nature. Our approach markedly enhances the power of zebrafish behavioral analyses, providing innovative framework for high-throughput 3D phenotyping of adult zebrafish behavior