Evaluation of point-of-care multiplex polymerase chain reaction in guiding antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark: A multicentre randomised controlled trial.

BACKGROUND: Rapid and accurate detection of pathogens is needed in community-acquired pneumonia (CAP) to enable appropriate antibiotics and to slow the development of antibiotic resistance. We aimed to compare the effect of point-of-care (POC) polymerase chain reaction (PCR) detection of respiratory pathogens added to standard care with standard care only (SCO) on antibiotic prescriptions after acute hospital admission. METHODS AND FINDINGS: We performed a superiority, parallel-group, open-label, multicentre, randomised controlled trial (RCT) in 3 Danish medical emergency departments (EDs) from March 2021 to February 2022. Adults acutely admitted with suspected CAP during the daytime on weekdays were included and randomly assigned (1:1) to POC-PCR (The Biofire FilmArray Pneumonia Panel plus added to standard care) or SCO (routine culture and, if requested by the attending physician, target-specific PCR) analysis of respiratory samples. We randomly assigned 294 patients with successfully collected samples (tracheal secretion 78.4% or expectorated sputum 21.6%) to POC-PCR (n = 148, 50.4%) or SCO (146, 49.6%). Patients and investigators owning the data were blinded to the allocation and test results. Outcome adjudicators and clinical staff at the ED were not blinded to allocation and test results but were together with the statistician, blinded to data management and analysis. Laboratory staff performing standard care analyses was blinded to allocation. The study coordinator was not blinded. Intention-to-treat and per protocol analysis were performed using logistic regression with Huber-White clustered standard errors for the prescription of antibiotic treatment. Loss to follow-up comprises 3 patients in the POC-PCR (2%) and none in the SCO group. Intention-to-treat analysis showed no difference in the primary outcome of prescriptions of no or narrow-spectrum antibiotics at 4 h after admission for the POC-PCR (n = 91, 62.8%) odds ratio (OR) 1.13; (95% confidence interval (CI) [0.96, 1.34] p = 0.134) and SCO (n = 87, 59.6%). Secondary outcomes showed that prescriptions were significantly more targeted at 4-h OR 5.68; (95% CI [2.49, 12.94] p < 0.001) and 48-h OR 4.20; (95% CI [1.87, 9.40] p < 0.001) and more adequate at 48-h OR 2.11; (95% CI [1.23, 3.61] p = 0.006) and on day 5 in the POC-PCR group OR 1.40; (95% CI [1.18, 1.66] p < 0.001). There was no difference between the groups in relation to intensive care unit (ICU) admissions OR 0.54; (95% CI [0.10, 2.91] p = 0.475), readmission within 30 days OR 0.90; (95% CI [0.43, 1.86] p = 0.787), length of stay (LOS) IRR 0.82; (95% CI [0.63, 1.07] p = 0.164), 30 days mortality OR 1.24; (95% CI [0.32, 4.82] p = 0.749), and in-hospital mortality OR 0.98; (95% CI [0.19, 5.06] p = 0.986). CONCLUSIONS: In a setting with an already restrictive use of antibiotics, adding POC-PCR to the diagnostic setup did not increase the number of patients treated with narrow-spectrum or without antibiotics. POC-PCR may result in a more targeted and adequate use of antibiotics. A significant study limitation was the concurrent Coronavirus Disease 2019 (COVID-19) pandemic resulting in an unusually low transmission of respiratory virus. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04651712).

Associations between care home residents' characteristics and acute hospital admissions - a retrospective, register-based cross-sectional study.

BACKGROUND: Care home residents are frail, multi-morbid, and have an increased risk of experiencing acute hospitalisations and adverse events. This study contributes to the discussion on preventing acute admissions from care homes. We aim to describe the residents' health characteristics, survival after care home admission, contacts with the secondary health care system, patterns of admissions, and factors associated with acute hospital admissions. METHOD: Data on all care home residents aged 65 + years living in Southern Jutland in 2018-2019 (n = 2601) was enriched with data from highly valid Danish national health registries to obtain information on characteristics and hospitalisations. Characteristics of care home residents were assessed by sex and age group. Factors associated with acute admissions were analysed using Cox Regression. RESULTS: Most care home residents were women (65.6%). Male residents were younger at the time of care home admission (mean 80.6 vs. 83.7 years), had a higher prevalence of morbidities, and shorter survival after care home admission. The 1-year survival was 60.8% and 72.3% for males and females, respectively. Median survival was 17.9 months and 25.9 months for males and females, respectively. The mean rate of acute hospitalisations was 0.56 per resident-year. One in four (24.4%) care home residents were discharged from the hospital within 24 h. The same proportion was readmitted within 30 days of discharge (24.6%). Admission-related mortality was 10.9% in-hospital and 13.0% 30 days post-discharge. Male sex was associated with acute hospital admissions, as was a medical history of various cardiovascular diseases, cancer, chronic obstructive pulmonary disease, and osteoporosis. In contrast, a medical history of dementia was associated with fewer acute admissions. CONCLUSION: This study highlights some of the major characteristics of care home residents and their acute hospitalisations and contributes to the ongoing discussion on improving or preventing acute admissions from care homes. TRIAL REGISTRATION: Not relevant.

Robot-assisted versus laparoscopic short- and long-term outcomes in complete mesocolic excision for right-sided colonic cancer: a systematic review and meta-analysis.

BACKGROUND: Complete mesocolic excision (CME) surgery is increasingly implemented for the resection of right-sided colonic cancer, possibly resulting in improved 5-year overall and disease-free survival compared to non-CME surgery. However, it is not clear what surgical platform should be used. The aim of this study was to compare the following outcomes between robot-assisted and laparoscopic CME-surgery for right-sided colonic cancer: (i) short-term clinical outcomes, (ii) pathological specimen quality, and (iii) long-term oncological outcomes. METHODS: Medline, Embase, and Cochrane Database of Systematic Reviews were searched from inception until August 2021. Pooled proportions were calculated by applying the inverse variance method. Heterogeneity was explored by I-square and supplemented by sensitivity- and meta-regression analyses. The risk of bias was evaluated by either MINORS or Cochrane's risk-of-bias tool (RoB 2). RESULTS: Fifty-five studies with 5.357 patients (740 robot-assisted and 4617 laparoscopic) were included in the meta-analysis. Overall postoperative morbidity was 17% [95% CI (14-20%)] in the robot-assisted group and 13% [95%CI (12-13%)] in the laparoscopic group. Robot-assisted CME was associated with a shorter hospital stay, lower intraoperative blood loss, a higher amount of harvested lymph nodes, and better 3-year oerall and disease-free survival. MINORS and RoB2 indicated a serious risk of bias across studies included. CONCLUSIONS: This review which includes predominantly non-randomized studies suggests a possible advantage of the robot-assisted CME compared with a laparoscopic technique for several short-term outcomes.

Short-term outcomes in robot-assisted compared to laparoscopic colon cancer resections: a systematic review and meta-analysis.

BACKGROUND: Robot-assisted surgery is increasingly adopted in colorectal surgery. However, evidence for the implementation of robot-assisted surgery for colon cancer is sparse. This study aims to evaluate the short-term outcomes of robot-assisted colon surgery (RCS) for cancer compared to laparoscopic colon surgery (LCS). METHODS: Embase, MEDLINE, and Cochrane Library were searched between January 1, 2005 and October 2, 2020. Randomized clinical trials and observational studies were included. Non-original literature was excluded. Primary endpoints were anastomotic leakage rate, conversion to open surgery, operative time, and length of hospital stay. Secondary endpoints were surgical efficacy and postoperative morbidity. We evaluated risk of bias using RoB2 and ROBINS-I quality assessment tools. We performed a pooled analysis of primary and secondary endpoints. Heterogeneity was assessed by I2, and possible causes were explored by sensitivity- and meta-regression analyses. Publication bias was evaluated by Funnel plots and Eggers linear regression test. The level of evidence was assessed by GRADE. RESULTS: Twenty studies enrolling 13,799 patients (RCS 1740 (12.6%) and LCS 12,059 (87.4%) were included in the meta-analysis that demonstrated RCS was superior regarding: anastomotic leakage (odds ratio (OR) = 0.54, 95% CI [0.32, 0.94]), conversion (OR = 0.31, 95% CI [0.23, 0.41]), overall complication rate (OR = 0.85, 95% CI [0.73, 1.00]) and time to regular diet (MD = - 0.29, 95% CI [- 0.56, 0.02]). LCS proved to have a shortened operative time compared to RCS (MD = 42.99, 95% CI [28.37, 57.60]). Level of evidence was very low according to GRADE. CONCLUSION: RCS showed advantages in colonic cancer surgery regarding surgical efficacy and morbidity compared to LCS despite a predominant inclusion of non-RCT with serious risk of bias assessment and a very low level of evidence.

Risk of hematoma after hemithyroidectomy in an outpatient setting: a systematic review and meta-analysis.

PURPOSE: After thyroid surgery, the overriding concern is the risk of post-thyroid bleeding (PTB). This systematic review and meta-analysis aimed to assess the safety of hemithyroidectomy in an outpatient setting compared to an inpatient setting. The objectives were to (1) find the proportion of PTB in patients scheduled for outpatient hemithyroidectomy, (2) examine if outpatient hemithyroidectomy is clinically safe compared to an inpatient setting and (3) evaluate which selection criteria are most relevant for hemithyroidectomy in an outpatient setting. METHODS: A systematic review was conducted using the following databases: MEDLINE (Ovid), EMBASE (Ovid) and the Cochrane Library from inception until September 2021. We included studies reporting on PTB of patients after hemithyroidectomy in an outpatient setting. The risk of bias was assessed using the Newcastle-Ottawa tool. The results were synthesised using Bayesian meta-analysis. Certainty in evidence was assessed using the GRADE approach. RESULTS: This review included 11 cohort studies and 9 descriptive studies reporting solely on outpatients resulting in a total of 46,866 patients. PTB was experienced by 58 of the 9025 outpatients (0.6%) and 415 of the 37,841 inpatients (1.1%). There was no difference between the PTB rate of outpatients and inpatients (RR 0.715 CrI [0.396-1.243]). The certainty of the evidence was very low due to the high risk of bias. CONCLUSION: The risk of PTB in an outpatient setting is very low, and outpatient hemithyroidectomy should be considered clinically safe. The most relevant selection criteria to consider in outpatient hemithyroidectomy are (1) relevant comorbidities and (2) psycho/-social factors.

Sample size determination in method comparison and observer variability studies.

The comparison of two quantitative measuring devices is often performed with the Limits of Agreement proposed by Bland and Altman in their seminal Lancet paper back in 1986. Sample size considerations were rare for such agreement analyses in the past, but recently several proposals have been made depending on how agreement is to be assessed and the number of replicates to be used. We have summarized recent developments and recommendations in various situations including a distinction between method comparison and observer variability studies. These include current state-of-the-art analysis of and reporting guidelines for agreement studies. General recommendations close the paper.

Improved perioperative outcomes and reduced inflammatory stress response in malignant robot-assisted colorectal resections: a retrospective cohort study of 298 patients.

BACKGROUND: Robot-assisted surgery is increasingly implemented for the resection of colorectal cancer, although the scientific evidence for adopting this technique is still limited. This study's main objective was to compare short-term complication rates, oncological outcomes, and the inflammatory stress response after colorectal resection for cancer performed laparoscopic or robot-assisted. METHODS: We conducted a retrospective cohort study comparing the robot-assisted approach to laparoscopic surgery for elective malignant colorectal neoplasm. Certified colorectal and da Vinci ® robotic surgeons performed resections at a Danish tertiary colorectal high volume center from May 2017 to March 2019. We analyzed the two surgical groups using uni- and multivariate regression analyses to detect differences in intra- and postoperative clinical outcomes and the inflammatory stress response. RESULTS: Two hundred and ninety-eight patients were enrolled in the study. Significant differences favoring robot-assisted surgery was demonstrated for; length of hospital stay (4 days, interquartile range (4, 5) versus 5 days, interquartile range (4-7), p < 0.001), and intraoperative blood loss (50 mL, interquartile range (20-100) versus 100 mL, interquartile range (50-150), p < 0.001) compared to laparoscopic surgery. The inflammatory stress response was significantly higher after laparoscopic compared to robot-assisted surgery reflected by an increase in C-reactive protein concentration (exponentiated coefficient = 1.23, 95% confidence interval (1.06-1.46), p = 0.008). No differences between the two groups were found concerning mortality, microradical resection rate, conversion to open surgery, and surgical or medical short-term complication rates. CONCLUSION: Robot-assisted surgery is feasible and can be safely implemented for colorectal resections. The robot-assisted approach, when compared to laparoscopic surgery, was associated with improved intra- and postoperative outcomes. Extensive prospective studies are needed to determine the short- and long-term outcomes of robotic surgery for colorectal cancer.

Systemic inflammatory response in robot-assisted and laparoscopic surgery for colon cancer (SIRIRALS): study protocol of a randomized controlled trial.

BACKGROUND: Robot-assisted surgery is being increasingly adopted in treating colorectal cancer, and the transition from laparoscopic surgery to robot-assisted surgery is a trend. The evidence of the benefits of robot-assisted surgery is sparse. However, findings are associated with improved patient-related outcomes and overall morbidity rates compared to laparoscopic surgery. This induction is unclear, considering both surgical modalities are characterized as minimally invasive. This study aims to evaluate the systemic and peritoneal inflammatory stress response induced by robot-assisted surgery compared with laparoscopic surgery for elective colon cancer resections in a prospective, randomized controlled clinical trial. METHODS: This study is a single-centre randomized controlled superiority trial with 50 colon cancer participants. The primary endpoint is the level of systemic inflammatory response expressed as serum C-reactive protein (CRP) and interleukin 6 (IL-6) levels between postoperative days one and three. Secondary endpoints include (i) levels of systemic inflammation in serum expressed by a panel of inflammatory and pro-inflammatory cytokines measured during the first three postoperative days, (ii) postoperative surgical and medical complications (30 days) according to Clavien-Dindo classification and Comprehensive Complication Index, (iii) intraoperative blood loss, (iv) conversion rate to open surgery, (v) length of surgery, (vi) operative time, (vii) the number of harvested lymph nodes, and (viii) length of hospital stay. The exploratory endpoints are (i) levels of peritoneal inflammatory response in peritoneal fluid expressed by inflammatory and pro-inflammatory cytokines between postoperative day one and three, (ii) patient-reported health-related quality of recovery-15 (QoR-15), (iii) 30 days mortality rate, (iv) heart rate variability and (v) gene transcript (mRNA) analysis. DISCUSSION: To our knowledge, this is the first clinical randomized controlled trial to clarify the inflammatory stress response induced by robot-assisted or laparoscopic surgery for colon cancer resections. Trial registration This trial is registered at Clinicaltrials.gov (Identifier: NCT04687384) on December, 29, 2020, Regional committee on health research ethics, Region of Southern Denmark (N75709) and Data Protection Agency, Hospital Sønderjylland, University Hospital of Southern Denmark (N20/46179).

Colonization with multiresistant bacteria in acute hospital care: the association of prior antibiotic consumption as a risk factor.

BACKGROUND: Antibiotic resistance poses a worldwide threat and knowledge concerning risk factors for colonization with multiresistant bacteria (MRB) is limited. OBJECTIVES: To examine the impact of prior antibiotic consumption on MRB colonization, with focus on type of antibiotic and timeline between antibiotic prescription and MRB colonization. METHODS: A nationwide case-control study was conducted and adults visiting emergency departments were invited to participate. All patients were swabbed in the throat, nose and rectum, and analysed for colonization with ESBL-producing Enterobacteriaceae (ESBL-E), MRSA, carbapenemase-producing enterobacteria and VRE. Antibiotic history 2 years prior to enrolment was collected at an individual level through a national register. Multivariate analyses were performed to examine the association between antibiotic consumption and MRB status. A subgroup analysis of ESBL-E-colonized cases was made. RESULTS: We included 256 patients colonized with MRB and 4763 controls. In the 2 years prior to study inclusion, 77% of cases and 68% of controls had at least one antibiotic prescription (P = 0.002). We found a significant increase in risk of colonization with ESBL-E if penicillins (OR = 1.58-1.65) or fluoroquinolones (OR = 2.25-6.15) were prescribed. The analysis of all MRB-colonized patients showed similar results. An assessment of the timeline showed a significant increase in risk of colonization up to 2 years after exposure to penicillins, fluoroquinolones and macrolides. CONCLUSIONS: The prevalence of ESBL-E colonization was related to fluoroquinolone, macrolide and penicillin consumption for at least 2 years after antibiotic treatment.

Validation of suPAR turbidimetric assay on Cobas® (c502 and c702) and comparison to suPAR ELISA.

suPAR is a plasma marker of chronic inflammation, and an elevated suPAR is consistently associated with worse outcome in a variety of clinical conditions. Quantification of suPAR is useful for determining patient risk in triage, but there is no fast automatized method for quick determination of suPAR. We developed and validated a rapid latex particle-enhanced turbidimetric immunoassay for quantification of plasma suPAR on the c502 and the c702 Roche Cobas® 8000 measurment systems. The turbidimetric assay was validated against the suPARnostic® ELISA (ViroGates, Denmark). This validation demonstrates suPAR can be analysed by turbidimetry giving very similar results (<15% difference) compared to the ELISA method and the observed correlations (n = 103) were strong, r > 0.95. Roche Cobas® 8000 instruments demonstrated repeatability and repoducibility, CV % at 3.4-4.1 and 5.7-11.4, respectively. The estimated limit of detection was 1.30 µg/L and 1.31 µg/L for the Cobas® c502 and c702, respectively. Dilution tests showed linearity of suPAR from 1.8 to 26.5 µg/L. The acceptable concentrations of Bilirubin, Intralipid and Hemoglobin, were 350 µmol/L, 3.3 g/L and 1.4 g/L, respectively. suPAR can be quantified reproducibly within 10 min using a turbidimetry assay. This assay is faster than ELISA with similar results, making it suitable for clinical routine analysis.

Short-term outcomes and inflammatory stress response following laparoscopy or robotic-assisted transabdominal preperitoneal inguinal hernia repair (TAPP): study protocol for a prospective, randomized trial (ROLAIS).

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT05839587. Retrospectively registered on 28 February 2023.

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.

Increased Insulin Secretion and Glucose Effectiveness in Obese Patients with Type 2 Diabetes following Bariatric Surgery.

Background: ß-cell dysfunction and insulin resistance are the main mechanisms causing glucose intolerance in type 2 diabetes (T2D). Bariatric surgeries, i.e., sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), are procedures both known to induce weight loss, increase insulin action, and enhance ß-cell function, but hepatic insulin extraction and glucose effectiveness may also play a role. Methods: To determine the contribution of these regulators on glucose tolerance after bariatric surgery, an oral glucose tolerance test (OGTT) was performed before and 2 months after surgery in 9 RYGB and 7 SG subjects. Eight healthy subjects served as metabolic controls. Plasma glucose, insulin, C-peptide, GLP-1, and GIP were measured during each OGTT. Insulin sensitivity and secretion, glucose effectiveness, and glucose rate of appearance were determined via oral minimal models. Results: RYGB and SG resulted in similar weight reductions (13%, RYGB (p < 0.01); 14%, SG (p < 0.05)). Two months after surgery, insulin secretion (p < 0.05) and glucose effectiveness both improved equally in the two groups (11%, RYGB (p < 0.01); 8%, SG (p > 0.05)), whereas insulin sensitivity remained virtually unaltered. Bariatric surgery resulted in a comparable increase in the GLP-1 response during the OGTT, whereas GIP concentrations remained unaltered. Following surgery, oral glucose intake resulted in a comparable increase in hepatic insulin extraction, the response in both RYGB and SG patients significantly exceeding the response observed in the control subjects. Conclusions: These results demonstrate that the early improvement in glucose tolerance in obese T2D after RYGB and SG surgeries is attributable mainly to increased insulin secretion and glucose effectiveness, while insulin sensitivity seems to play only a minor role. This trial is registered with NCT02713555.

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.

Self-reported health and adverse outcomes among women living with symptoms of angina or unspecific chest pain but no diagnosis of obstructive coronary artery disease-findings from the DenHeart study.

AIMS: The objectives were to describe differences in self-reported health at discharge between women diagnosed with angina or unspecific chest pain and investigate the association between self-reported health and adverse outcomes within 3 years. METHODS AND RESULTS: Data from a national cohort study were used, including data from the DenHeart survey combined with 3 years of register-based follow-up. The population included two groups of women with symptoms of angina but no diagnosis of obstructive coronary artery disease at discharge (women with angina and women with unspecific chest pain). Self-reported health measured with validated instruments was combined with register-based follow-up on adverse outcomes (a composite of unplanned cardiac readmissions, revascularization, or all-cause mortality). Associations between self-reported health and time to first adverse outcomes were investigated with Cox proportional hazard models, reported as hazards ratios with 95% confidence intervals. In total, 1770 women completed the questionnaire (49%). Women with angina (n = 931) reported significantly worse self-reported health on several outcomes compared to women with unspecific chest pain (n = 839). Within the 3 years follow-up, women with angina were more often readmitted (29 vs. 23%, P = 0.011) and more underwent revascularization (10 vs. 1%, P < 0.001), whereas mortality rates were similar (4 vs. 4%, P = 0.750). Self-reported health (physical and mental) was associated with adverse outcomes between both groups (on most instruments). CONCLUSION: Women with angina reported significantly worse self-reported health on most instruments compared to women with unspecific chest pain. Adverse outcomes varied between groups, with women diagnosed with angina experiencing more events. REGISTRATION: ClinicalTrials.gov (NCT01926145).

Troponin Cut-Offs for Acute Myocardial Infarction in Patients with Impaired Renal Function-A Systematic Review and Meta-Analysis.

Identifying acute myocardial infarction in patients with renal disease is notoriously difficult, due to atypical presentation and chronically elevated troponin. The aim of this study was to identify a specific troponin T/troponin I cut-off value for diagnosis of acute myocardial infarction in patients with renal impairment via meta-analysis. Two investigators screened 2590 publications from MEDLINE, Embase, PubMed, Web of Science, and the Cochrane library. Only studies that investigated alternative cut-offs according to renal impairment were included. Fifteen articles fulfilled the inclusion criteria. Six studies were combined for meta-analysis. The manufacturer's upper reference level for troponin T is 14 ng/L. Based on the meta-analyses, cut-off values for troponin in patients with renal impairment with myocardial infarction was 42 ng/L for troponin I and 48 ng/L for troponin T. For patients on dialysis the troponin T cut-off is even higher at 239 ng/L. A troponin I cut-off value for dialysis patients could not be established due to lack of data. The 15 studies analyzed showed considerable diversity in study design, study population, and the definition of myocardial infarction. Further studies are needed to define a reliable troponin cut-off value for patients with kidney disease, especially in dialysis patients, and to allow necessary subanalysis.

Time to End-of-Life of Patients Starting Specialised Palliative Care in Denmark: A Descriptive Register-Based Cohort Study.

Increasing numbers of patients are being referred to specialised palliative care (SPC) which, in order to be beneficial, is recommended to last more than three months. This cohort study aimed to describe time to end-of-life after initiating SPC treatment and to explore potential regional variations. We used national register data from all Danish hospital SPC teams. We included patients who started SPC treatment from 2015-2018 to explore if time to end-of-life was longer than three months. Descriptive statistics were used to summarise the data and a generalised linear model was used to assess variations among the five Danish regions. A total of 27,724 patients were included, of whom 36.7% (95% CI 36.2-37.1%) had over three months to end-of-life. In the Capital Region of Denmark, 40.1% (95% CI 39.0-41.3%) had over three months to end-of-life versus 32.5% (95% CI 30.9-34.0%) in North Denmark Region. We conclude that most patients live for a shorter period of time than the recommended three months after initiating SPC treatment. This is neither optimal for patient care, nor the healthcare system. A geographical variation between regions was shown indicating different practices, patient groups or resources. These results warrant further investigation to promote optimal SPC treatment.

Clinical procedures used to diagnose inflammatory bowel disease: real-world evidence from a Danish nationwide population-based study.

OBJECTIVE: Although clinical guidelines exist, the diagnostic work-up for diagnosing inflammatory bowel disease (IBD) is complex and varies in clinical practice. This study used real-life data to characterise the current diagnostic procedures used to establish IBD diagnoses in a Danish nationwide setting. DESIGN: Person-level data on patients diagnosed with IBD between 1 January 2014 and 30 June 2018 were linked between Danish health registers. Information on age, sex, registration of other gastrointestinal diseases, and diagnostic procedures (endoscopies, biopsies, and imaging) performed in relation to the first IBD hospital admission was analysed for the total study population and was stratified by IBD type, sex, and age. RESULTS: The majority of the 12 871 patients with IBD included underwent endoscopy (84%), had a biopsy taken (84%), and/or underwent imaging procedures (44%). In total, 7.5% of the population (6% for Crohn's disease and 8% for ulcerative colitis) were diagnosed with IBD despite not undergoing any of these diagnostic procedures. Patients with Crohn's disease underwent more procedures than patients with ulcerative colitis (94% vs 92%, p<0.001). Children underwent slightly fewer diagnostic procedures than adults (92% vs 93%, p=0.004). Slightly more men underwent at least one procedure than women (92% vs 94%, p<0.001). CONCLUSION: For 7.5% of patients with IBD, this study did not detect any registrations of the recommended diagnostic procedures for establishing an IBD diagnosis. Further research is needed to examine whether these findings are mainly explained by limitations of the register data or also indicate shortcomings of the general approach to IBD.

Chronic Inflammatory Diseases - Diabetes Mellitus, Rheumatoid Arthritis, Coeliac Disease, Crohn's Disease, and Ulcerative Colitis Among the Offspring of Affected Parents: A Danish Population-Based Registry Study.

BACKGROUND: Chronic inflammatory diseases (CIDs) may share aetiological factors across diseases. We used registry data to evaluate the risk of developing five common childhood CIDs dependent on the parents' disease status. METHODS: We performed a national population-based registry study by linking data from the national Danish health registers from January 1973 to March 2016 to evaluate any potential associations between parents' disease and development of CIDs among the offspring. Results were adjusted for parental age at birth, the decade of birth, gender of the child, and type of birth. A cohort of 2,699,449 liveborn children was established for investigating the primary outcome measures: diabetes mellitus (DM), rheumatoid arthritis (RA), coeliac disease, Crohn's disease (CD), and ulcerative colitis (UC) and all diseases combined (CID). RESULTS: Children with one CID affected parent (Hazard ratio (HR), 95% confidence interval (95% CI)=1.75 (1.72-1.79, p<0.001)), one multiple CID affected parent (HR=2.23 (2.11-2.34), p<0.001), and both parents affected (HR=3.10 (2.98-3.22), p<0.001) were at higher risk than children without CID affected parents. Children with DM, RA, and COE affected parents were at increased risk of three specific diseases (DM, RA and COE), whereas children with CD and UC affected parents were at increased risk of two specific diseases (CD and UC). CONCLUSION: Children with CID affected parents were at increased risk of the same CID as their parents as well as other specific CIDs dependent on the parents' CID. Future studies should address the aetiology underlying these findings to support the development of new strategies for prevention, treatment, and cure.

Evaluation of factors influencing tick bites and tick-borne infections: a longitudinal study.

BACKGROUND: Various tick-borne infections like borreliosis and rickettsiosis pose a health risk to humans in many parts of the world. We investigated seroprevalence of and seroconversion to Borrelia burgdorferi and Rickettsia spp. and relation to tick-bites, weather and clinical manifestations in Denmark. METHODS: Blood donors were enrolled at the Hospital of Southern Jutland in June-July with follow-up November-February of 2018 and 2019. Blood samples were collected, and a questionnaire regarding tick bites, potential exposures and symptoms was completed at each visit. Samples were tested for presence of IgM and IgG antibodies directed against B. burgdorferi and Rickettsia spp. using R. helvetica and R. felis as antigens. Data were examined for correlation between tick bites, serological results, potential exposures and symptoms. RESULTS: Two-hundred and fourteen (93 follow-ups) and 130 (38 follow-ups) blood donors were included in 2018 and 2019, respectively. The total borrelia seroconversion rate was 6.3% (CI 2.1-10.5), while the prevalence of IgM and IgG antibodies was 7.8% (CI 4.9-10.6) and 6.7% (CI 4-9.3), respectively. Seroconversion to Rickettsia spp. was detected in one participant. Tick bites and seroconversion were not significantly associated with the reported unspecific symptoms, but unspecific symptoms were common in the study population. There was no significant difference in number of tick bites or seroconversion/prevalence between seasons with highly alternating weather. CONCLUSIONS: Results suggest that weather conditions in an individual year have a limited impact. Anti-Borrelia-antibodies do not seem to persist in serum for several years. Rickettsiosis is of limited concern in Denmark.