Background Hip fractures cause extreme pain, primarily affecting the older and frail. The necessity of sufficient pain relief in combination with a lower tolerance for drugs makes the analgesic treatment of older patients difficult. A single dose of methadone might reduce postoperative pain and opioid consumption. However, the safety of using methadone for older and fragile patients is unknown. Aim Determine the maximal tolerable dose (MTD) of perioperative methadone in older hip fracture patients and assess the feasibility of this protocol for future clinical trials. Methods Hip fracture patients ≥60 years old were consecutively included at the hospital in the winter/spring of 2023. An adaptive algorithm allocated 0.10 mg/kg, 0.15 mg/kg, or 0.20 mg/kg of methadone to each patient, administered intravenously at the induction of anesthesia. The primary outcome was respiratory depression, which was monitored continuously. Occurrence required a dosage decrease, while absence allowed an increase. Registered Nurses at the orthopedic ward collected data using observation charts completed 6, 24, and 72 hours after surgery. Secondary outcomes include time spent in the post-anesthesia care unit (PACU), verbal rating pain score (VRS), opioid consumption, and nausea/vomiting. Results 30 patients completed the study. Nine received 0.10 mg/kg, and 21 received 0.15 mg/kg. Three patients experienced respiratory depression in PACU, all receiving 0.15 mg/kg methadone and undergoing general anesthesia. None of the spinal anesthesia patients or those receiving 0.10 mg/kg experienced respiratory depression. Conclusion Methadone is an effective analgesic for hip fracture surgery. The data suggests that the maximal tolerable dose of methadone in older hip fracture patients is 0.10 mg/kg. This study proves the feasibility of our trial setup and provides a foundation for future randomized controlled trials. Additionally, the findings suggest that the tolerability of methadone may vary depending on the type of anesthesia used, which merits further investigation.

Abstract Background Hip fractures are a source of severe pain among the elderly population and pose challenges due to limited analgesic tolerance. Perioperative methadone has shown promise in our pilot study suggesting a safe dose of 0.10 mg/kg, prompting further investigation into its benefits for elderly hip fracture patients. Methods This study employs a double-blinded randomized controlled trial to assess the analgesic effects of a single dose of methadone during hip fracture surgery. Patients aged ≥ 60 years are consecutively enrolled and randomized to receive either perioperative methadone (treatment group) or a saline solution (placebo group). A sample size of 130 patients is required for 88% statistical power. The medication is administered intravenously at anesthesia induction and monitored until discharge. A follow-up observation is conducted 3 months post-surgery. Discussion Primary outcome: Daily consumption of opioids within the first 3 days after surgery. Secondary outcomes include pain, mobility, nausea, vomiting, time to discharge, need for antidote, delirium, and constipation. The 3-month follow-up includes opioid use, pain, EQ-5D-5L scores, mobility, and persistent side effects. If statistically significant advantages are found in the treatment group, perioperative methadone could be considered as standard care for hip fracture patients, potentially enhancing their pain management. The study’s outcomes will provide insights into the feasibility and effectiveness of incorporating methadone into routine clinical practices for this patient group. Trial registration ClinicalTrials.gov ID: NCT06086171, submitted 4. October 2023. EU-CT: 2023–506252-24–00, UTN: U1111-1294–6125.

Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID.

Inguinal hernia repair is a frequently performed surgical procedure, with laparoscopic repair emerging as the preferred approach due to its lower complication rate and faster recovery compared to open repair. Mesh-based tension-free repair is the gold standard for both methods. In recent years, robotic hernia repair has been introduced as an alternative to laparoscopic repair, offering advantages such as decreased postoperative pain and improved ergonomics. This study aims to compare the short- and long-term outcomes, including the surgical stress response, postoperative complications, quality of life, and sexual function, between robotic-assisted transabdominal preperitoneal (rTAPP) and laparoscopic TAPP inguinal hernia repairs. This randomized controlled trial will involve 150 patients from the Surgical Department of the University Hospital of Southern Denmark, randomized to undergo either rTAPP or laparoscopic TAPP. Surgical stress will be quantified by measuring C-reactive protein (CRP) and cytokine levels. Secondary outcomes include complication rates, quality of life, sexual function, and operative times. Data analysis will adhere to the intention-to-treat principle and will be conducted once all patient data are collected, with outcomes assessed at various postoperative intervals. This study holds significance in evaluating the potential advantages of robotic-assisted surgery in the context of inguinal hernia repairs. It is hypothesized that rTAPP will result in a lower surgical stress response and potentially lower the risk of postoperative complications compared to conventional laparoscopic TAPP. The implications of this research could influence future surgical practices and guidelines, with a focus on patient recovery and healthcare costs. The findings of this study will contribute to the ongoing discourse surrounding the utilization of robotic systems in surgery, potentially advocating for their broader implementation if the benefits are substantiated. ClinicalTrials.gov NCT05839587. Retrospectively registered on 28 February 2023.

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: NCT03173144. This cohort study examines the impact of smoking on biologic therapy response in patients with chronic inflammatory diseases. Among 205 participants, smokers had lower treatment response rates compared to non-smokers, though the difference was not statistically significant. In rheumatoid arthritis patients, however, smokers exhibited impaired response rates.image

Background Repair of large incisional hernias is challenging, and the risks of postoperative complications have been associated with obesity, smoking, and diabetes. The present study was conducted to determine the impact of these risk factors on short and long-term outcomes following the repair with the peritoneal flap hernioplasty (PFH). Methods Three hundred twenty-seven patients undergoing PFH for incisional hernia repair were identified. Patient demographics and clinical data were recorded. Patients presenting signs of complications were assessed during a visit to the outpatient clinic. A multivariable regression analysis was performed to evaluate the association between BMI, smoking and diabetes, and postoperative complications. Results The study included 157 males (48.0%) and 170 females (52.0%). Median BMI was 30.9 kg/m(2). Diabetes was present in 13.8% of patients. 23.2% were active smokers. The recurrence rate was 2.4%. The odds ratios for postoperative complications were increased by 9% per BMI unit (P < 0.01), due predominantly to a rise in superficial wound infections (P < 0.01) and seroma production (P = 0.07). The adjusted odds ratio increased fourfold in patients with BMI > 40 kg/m(2) (P = 0.06). Conclusion Incisional hernia repair with the PFH technique is associated with a low risk of short and long-term complications. The risk is associated with obesity and significantly increased in patients with a BMI exceeding 40 kg/m(2), where a fourfold increase was observed predominantly due to seroma and superficial wound infections. The recurrence rate was 2.4% and was unaltered across BMI categories. No association was established between smoking, diabetes, and the risk of all-cause complications.

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. To explore the potential association of socioeconomic status and time to first biologic treatment in a population-based IBD cohort. 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. 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

Abstract 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.

Minimal invasive inguinal hernia repair is conducted using among others the laparoscopic transabdominal preperitoneal (TAPP) procedure or the extended totally extraperitoneal (eTEP) approach. Robotic-assisted TAPP (R-TAPP) has recently been introduced as an alternative to laparoscopic TAPP and TEP, and a growing number of robotic-assisted procedures are performed worldwide. The present study was conducted to determine the risk of chronic pain and recurrence associated with the two methods. Three hundred ninety-five patients were retrospectively included in the study and underwent either laparoscopic TAPP (n = 177) or R-TAPP (n = 218). Data on patient demographics, hernia characteristics, and postoperative outcomes were retrieved from medical records. Kaplan-Meier curves and Cox proportional hazards regression were used to assess hernia recurrence. Logistic regression was used to analyze secondary outcomes such as inpatient status, hematoma, and chronic pain. The Kaplan-Meier curves indicated a consistently higher cumulative incidence of recurrence in the TAPP group compared to the R-TAPP. Consistent with this finding, the Cox regression showed a higher risk of recurrence in patients undergoing TAPP, with a hazard ratio (HR) of 3.489 (95

BackgroundInflammatory 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.MethodsWe 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.ResultsIn 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.ConclusionsThe 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 registrationPROSPERO CRD42022315788.

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.

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.