Effects of smoking on clinical treatment outcomes amongst patients with chronic inflammatory diseases initiating biologics: secondary analyses of the prospective BELIEVE cohort study.

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.

Impact of sex and socioeconomic status on the likelihood of surgery, hospitalization, and use of medications in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel diseases (IBDs) are associated with high healthcare utilization. This systematic review aimed to summarize what is known about the impact of sex, income, and education on the likelihood of bowel surgery, hospitalization, and use of corticosteroids and biologics among patients with IBD. METHODS: We used EMBASE, MEDLINE, CINAHL, and Web of Science to perform a systematic literature search. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis for the impact of sex on the likelihood of surgery and hospitalization. In addition, we performed subgroup analyses of the effect of IBD type (Crohn's disease or ulcerative colitis) and age. Finally, meta-regression was undertaken for the year of publication. RESULTS: In total, 67 studies were included, of which 23 studies were eligible for meta-analysis. In the main meta-analysis, male sex was associated with an increased likelihood of bowel surgery (HR 1.42 (95% CI 1.13;1.78), which was consistent with the subgroup analysis for UC only (HR 1.78, 95% CI 1.16; 2.72). Sex did not impact the likelihood of hospitalization (OR 1.05 (95% CI 0.86;1.30), although the subgroup analysis revealed an increased likelihood of hospitalization in CD patients (OR 1.42, 95% CI 1.28;1.58). In 9 of 10 studies, no significant sex-based differences in the use of biologics were reported, although in 6 of 6 studies, female patients had lower adherence to biologics. In 11 of 13 studies, no significant sex-based difference in the use of corticosteroids was reported. The evidence of the impact of income and education on healthcare utilization was sparse and pointed in different directions. The substantial heterogeneity between studies was explained, in part, by differences in IBD type and age. CONCLUSIONS: The results of this systematic review indicate that male patients with IBD are significantly more likely to have surgery than female patients with IBD but are not, overall, more likely to be hospitalized, whereas female patients appear to have statistically significantly lower adherence to biologics compared to male patients. Thus, clinicians should not underestimate the impact of sex on healthcare utilization. Evidence for income- and education-based differences remains sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022315788.

Analysis of traumatic event emergency department visits among care home residents aged 65 + years in Southern Jutland, Denmark: implications for comprehensive care and subsequent hospital admissions - a register-based cohort study.

BACKGROUND: Care home residents aged 65 + years frequently experience acute health issues, leading to emergency department visits. Falls and associated injuries are a common cause of these visits and falls in a geriatric population can be a symptom of an incipient acute illness such as infection. Conversely, the traumatic event can cause illnesses to arise due to consequences of the fall, e.g. delirium or constipation due to opioid use. We hypothesised that a traumatic event treat-and-release emergency department visit serves as an indicator for an upcoming acute hospital admission due to non-trauma-related conditions. METHODS: We studied emergency department visits for traumatic events among all care home residents aged 65+ (n = 2601) living in Southern Jutland, Denmark, from 2018 to 2019. Data from highly valid national registers were used to evaluate diagnoses, mortality, and admissions. Cox Regression was used to analyse the hazard of acute hospital admission following an emergency department treat-and-release visit. RESULTS: Most visits occurred on weekdays and during day shifts, and 72.0% were treated and released within 6 h. Contusions, open wounds, and femur fractures were the most common discharge diagnoses, accounting for 53.3% of all cases (n = 703). In-hospital mortality was 2.3%, and 30-day mortality was 10.4%. Among treat-and-release visits (n = 506), 25% resulted in a new hospital referral within 30 days, hereof 13% treat-and-release revisits (duration ≤ 6 h), and 12% hospital admissions (duration > 6 h). Over half (56%) of new hospital referrals were initiated within the first seven days of discharge. Almost three-fourths of subsequent admissions were caused by various diseases. The hazard ratio of acute hospital admissions was 2.20 (95% CI: 1.52-3.17) among residents with a recent traumatic event treat-and-release visit compared to residents with no recent traumatic event treat-and-release visit. CONCLUSION: Traumatic event treat-and-release visits among care home residents serve as an indicator for subsequent hospitalisations, highlighting the need for a more comprehensive evaluation, even for minor injuries. These findings have implications for improving care, continuity, and resource utilisation. TRIAL REGISTRATION: Not relevant.

Socioeconomic equality in initiation of biologic treatment in Danish patients with inflammatory bowel disease.

BACKGROUND: Low socioeconomic status is associated with disadvantages in health outcomes and delivery of medical care in patients with Inflammatory Bowel Disease (IBD). Inequality in the utilisation of biologic treatment is largely unexplored. AIM: To explore the potential association of socioeconomic status and time to first biologic treatment in a population-based IBD cohort. METHODS: All 37,380 IBD incidences between 2000 and 2017 from the Danish National Patient Register were identified and linked to socioeconomic information including educational level, income and occupational status at diagnosis. Hazard ratios for receiving biologic treatment among socioeconomic groups were estimated using Cox proportional hazard regression. RESULTS: No difference in time between diagnosis and biologic treatment initiation was found comparing patients with upper secondary, vocational, or academic education to those with lower secondary education in patients with IBD. Patients with Crohn's disease in the two highest income quartiles received biologic treatment earlier (HR 1.16; 95% CI: 1.04; 1.30 & HR 1.15; 95% CI: 1.03; 1.30). An elevated treatment rate was found for persons with "other" occupational status (unspecified source of income) compared to employed persons in patients with ulcerative colitis (HR 1.36; 95% CI: 1.11; 1.66), but not in patients with Crohn's disease. CONCLUSION: This study revealed equal initiation of biologic treatment among patients with IBD across different educational background, income and occupational status. However, results are limited to a setting with free universal healthcare coverage and treatment needs should be considered and addressed in future research.

Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial.

Background: The elderly population is expanding globally. This gives numerous challenges especially regarding hip fracture patients. In the US alone over 300.000 hip fracture patients are treated each year, and a large amount of those develop opoid addiction. Hip fractures require surgical intervention within 24 h and is associated with significant pain even at rest. Postoperative analgesic treatment need to be optimized to ensure adequate pain relief and to prevent subsequent opioid addiction. Previous studies have shown that methadone effectively decreases post-operative opioid consumption but the studies focused on younger patients undergoing elective surgery. This study focus on the use of methadone on the elderly, fragile patients undergoing acute surgery, by first determining the maximal tolerable dose.The hypothesis is the maximal tolerable doses of these hip-fracture patients lies between 0.10 mg/kg and 0.20 mg/kg. This trial aims to estimate the maximum tolerable dose of methadone when administered to elderly patients undergoing surgery for a hip fracture. Method: This project is an adaptive dose-finding trial. The continuous reassessment method will estimate the maximum tolerable dose of methadone. The primary outcome will be respiratory depression. The statistical analysis plan will be published a priori to the closure of patient recruitment and statistical analysis of database results. Conclusion: The results of this study will give valuable information about the maximally tolerated dose of methadone for postoperative pain relief for elderly patients with hip fractures and potential adverse events.This trial is registered on clinicaltrials.gov with trial registration: NCT05581901. Registered 17 October 2022, https://www.clinicaltrials.gov/ct2/show/NCT05581901?term=methadone&cond = hip&draw = 2&rank = 1.

Rate and Risk Factors of Acute Myocardial Infarction after Debut of Chronic Kidney Disease-Results from the KidDiCo.

Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease, including acute myocardial infarction. However, whether this risk is only associated with severe kidney disease or is also related to mildly impaired kidney function is still under debate. The incidence rate and risk factors of incident acute myocardial infarction (AMI) in patients with CKD are sparse. Potential differences in risk factor profiles between CKD patients with incident AMI and CKD patients with a prior AMI have not been sufficiently investigated. Furthermore, important factors such as albuminuria and socio-economic factors are often not included. The primary aim of this study was to establish the incidence rate of AMI after CKD debut. Secondly, to evaluate the importance of different CKD stages and the risk of having an AMI. Finally, to identify individuals at risk for AMI after CKD debut adjusted for prevalent AMI. Based on data from the kidney disease cohort of Southern Denmark (KidDiCo), including 66,486 CKD patients, we established incidence rates and characteristics of incident AMI among patients within a 5-year follow-up period after CKD debut. A Cox regression was performed to compute the cause-specific hazard ratios for the different risk factors. The incidence rate for CKD stage G3−5 patients suffering acute myocardial infarction is 2.5 cases/1000 people/year. In patients without a previous myocardial infarction, the risk of suffering a myocardial infarction after CKD debut was only significant in CKD stage G4 (HR = 1.402; (95% CI: 1.08−1.81); p-value = 0.010) and stage G5 (HR = 1.491; (95% CI: 1.01−2.19); p-value = 0.042). This was not the case in patients who had suffered an acute myocardial infarction prior to their CKD debut. In this group, a previous myocardial infarction was the most critical risk factor for an additional myocardial infarction after CKD debut (HR = 2.615; (95% CI: 2.241−3.05); p-value < 0.001). Irrespective of a previous myocardial infarction, age, male sex, hypertension, and a low educational level were significant risk factors associated with an acute myocardial infarction after CKD debut. The incidence rate of AMI in patients with CKD stage G3−5 was 2.5 cases/1000 people/year. Risk factors associated with incident AMI in CKD stage G3−5 patients were CKD stage, age, and hypertension. Female sex and higher educational levels were associated with a lower risk for AMI. Prior AMI was the most significant risk factor in patients with and without previous AMI before fulfilling CKD stage G3−5 criteria. Only age, sex, and a medium-long educational level were significant risk factors in this group.