Regional Ethics Committee Research Articles

Low-dose dobutamine in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (the DOBERMANN-D trial): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

BackgroundCardiogenic shock (CS) occurs in 5–10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development.MethodsThis investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h).The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24–48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed.DiscussionEarly inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up.Trial registrationThe Regional Ethics Committee: H-21045751. EudraCT: 2021–002028-19. ClinicalTrials.gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277–8523.

Role of ultra-processed foods in modulating the effect of Mediterranean diet on human and planet health—study protocol of the PROMENADE randomized controlled trial

BackgroundThe Mediterranean diet (MD), globally recognized for its sustainability and health benefits, traditionally emphasizes the consumption of plant-based foods in raw or minimally processed forms. However, shifting lifestyles, even in Mediterranean regions, have led to an increasing consumption of ultra-processed foods (UPF). Epidemiological evidence suggests that UPF consumption may be detrimental to human health, but there is only one clinical trial on this topic which is largely debated in the scientific community. This study aims to investigate the impact of the inclusion of UPF within a Mediterranean-based dietary pattern on cardiometabolic markers, gut microbiota, and other markers of human and planet health.MethodsFifty clinically healthy individuals showing overweight and presenting a low-to-moderate cardiovascular risk profile will be recruited for a 7-month randomized, open, cross-over dietary trial. Eligible participants will be randomly assigned to a 3-month high-UPF MD (intervention group) or a low-UPF MD (control group), with a 1-month wash-out period. Both intervention diets will have identical food group compositions, with the intervention group consuming 5 servings/day of selected UPF items, and the control group consuming raw/minimally processed items from the same food group. Blood, urine, and fecal samples, alongside food/lifestyle diaries, will be collected from each participant before and after the dietary interventions. The primary endpoint will be the change in plasma LDL-cholesterol levels from baseline. Additional markers include blood pressure, anthropometric parameters, chemical parameters, glucose and lipid-related metabolic markers, incretins, inflammatory and oxidative stress markers, fecal microbiota composition, and short-chain fatty acids. Finally, food waste production will be evaluated through specific validated food diaries. The study has been approved by the Ethical Committee of the University of Milan and the Tuscany Regional Ethics Committee of the Azienda Ospedaliera Universitaria (AOU) - Careggi, Florence.DiscussionResults from the PROMENADE study will improve knowledge about the impact of UPF consumption on human and planet health and will contribute to the scientific debate on this topic.Trial registrationClinicalTrials.gov NCT06314932. Registered on March 13, 2024.

Interdisciplinary CBT treatment for patients with odontophobia and dental anxiety related to psychological trauma experiences: a case series

BackgroundWhile cognitive-behavioural therapy (CBT) is a well-established treatment for odontophobia, research is sparse regarding its effect on patients with dental anxiety related to psychological trauma experiences. This study aimed to evaluate changes in symptoms and acceptability of interdisciplinary Torture, Abuse, and Dental Anxiety (TADA) team treatment for patients with odontophobia or dental anxiety. We also wanted to describe the sample’s oral health status. The TADA teams offer targeted anxiety treatment and adapted dental treatment using a CBT approach.MethodsThe study used a naturalistic, case series design and included 20 consecutively referred outpatients at a public TADA dental clinic. Pre- and post-treatment assessments included questionnaires related to the degree of dental anxiety, post-traumatic stress, generalized anxiety, and depression. Patients underwent a panoramic X-ray before treatment. Before dental restoration, patients underwent an oral health examination to determine the mucosal and plaque score (MPS) and the total number of decayed, missing, and filled teeth (DMFT). Patients were referred to dentist teams for further dental treatment and rehabilitation (phase 2) after completing CBT in the TADA team (Phase 1). Results from the dental treatment in phase 2 is not included in this study.ResultsAll patients completed the CBT treatment. There were significant improvements in symptoms of dental anxiety, post-traumatic stress, and depression and moderate changes in symptoms of generalized anxiety. Dental statuses were heterogeneous in terms of the severity and accumulated dental treatment needs. The TADA population represented the lower socioeconomic range; 15% of patients had higher education levels, and half received social security benefits. All patients were referred to and started adapted dental treatment (phase 2).ConclusionsTADA treatment approach appears acceptable and potentially beneficial for patients with odontophobia and dental anxiety related to psychological trauma experiences. The findings suggest that further research, including larger controlled studies, is warranted to validate these preliminary outcomes.Trial registrationThe study was approved by the regional ethical committee in Norway (REK-Midt: 488462) and by the Data Protection Board at Møre and Romsdal County Authority.

Multicentre investigation on the effect of decompressive surgery on Balance and physical ActiviTy Levels amongst patients with lumbar Spinal stenosis (B-ATLAS): protocol for a prospective cohort study

IntroductionPatients with lumbar spinal stenosis may have poor balance, decreased physical function and problems maintaining physical activity levels due to radiculopathy. Decompressive surgery is often indicated if conservative management fails...

P-096 Seminal microbiome and its possible association with poor sperm quality

Abstract Study question Does seminal microbiome differ between men with good and poor sperm quality parameters? Summary answer Men with poor sperm quality values presented a higher microbial richness, while after rigorous contamination controlling no specific bacteria associated with sperm quality parameters. What is known already Infertility represents a major health concern affecting 1 in every 6 couples. Approximately 50% of infertility cases are attributed to male factor, where seminal quality is crucial. Recent studies have brought to light the role of the microbiome in sperm quality and function. Changes in microbial communities can impact reproductive functions, as these microorganisms may affect spermatozoa by releasing specific molecules or influencing direct adhesion. Since current evidence in the field is inconclusive, as the studies are performed on small sample sizes and lack proper positive and negative controls, there is a need for rigorous studies on bigger cohorts. Study design, size, duration This cross-sectional study included 115 men (age= 33.6±9.6 years; BMI= 25.0±3.5). Semen samples assessment was performed between March 2019 and July 2021 at the sperm biobank and University Hospital. The study was approved by the regional Ethics Committee. Participants/materials, setting, methods The study population was categorized into two seminal quality groups based on WHO reference values. Accordingly, 66 men presented good sperm quality while 49 poor sperm quality. Sperm concentration and progressive motility parameters were assessed in semen. Seminal microbiome was analyzed using 16 rRNA gene sequencing. For rigorous contamination controlling, negative controls together with in silico decontamination (MicroDecon package) were applied. Microbial diversity and composition were assessed including age and BMI as confounders. Main results and the role of chance After rigorous decontamination analysis including negative controls, 774 microorganisms were identified in the semen. Ninety-one bacteria were detected as contaminants. Next, a filter of 30% prevalence was applied to identify the core seminal microbiome, which resulted in a total of 36 bacterial genera in the semen in our cohort of men. Bacteria such as Actinomyces, Finegoldia, Campylobacter, Anaerococcus and Peptoniphilus were the the most prevalent among seminal samples. Men with poor sperm quality presented a richer seminal microbiome compared to good sperm quality group (α-diversity p-value=0.022), while β-diversity did not show a significant microbial dissimilarity between groups (R2=0.012, p-value&amp;gt;0.05). Differential abundance analysis on the core microbiome detected increased abundances of Veillonella (logFC=1.836), Gemella (logFC=1.612) and a member of Pasteurellaceae family (logFC=1.628) in men with lower sperm quality (all p-values&amp;lt;0.05). However, differences did not remain significant after multiple comparison correction (FDR p-values&amp;gt;0.05). Limitations, reasons for caution This study reported specific microbial alterations in men with poor sperm quality parameters, which should be investigated further considering different life-style factors such as smoking and diet. Wider implications of the findings With our rigorous study protocol, we see that although seminal microbiome could have some potential implications on seminal quality, the core microbiome does not seem to associate with seminal parameters. More research is needed, but it could be there has been previously overinterpretation of the microbiome associations with seminal parameters. Trial registration number not applicable

Evaluation of Regional and Institutional Research Ethics Committees’ Effectiveness in Iran: Results from a Study Using a Self-Assessment Tool

Evaluation of Regional and Institutional Research Ethics Committees’ Effectiveness in Iran: Results from a Study Using a Self-Assessment Tool

#2355 Eradication of Staphylococcus aureus carriage in patients undergoing peritoneal dialysis

Abstract Background and Aims Peritonitis is a common and serious complication of peritoneal dialysis (PD). A single episode of severe peritonitis or multiple peritonitis episodes frequently leads to diminished peritoneal ultrafiltration capacity, hospitalization, and a switch to hemodialysis. Prevention of infection is the mainstay for the reduction of peritonitis rate. According to the current guidelines, we use nasal antibiotic prophylaxis if patients are identified as nasal Staphylococcus aureus carriers on screening prior to PD beginning. Eradication of S. aureus Regular with nasal mupirocin reduces the rate of exit-site infections but has uncertain effects on the risk of peritonitis. The aim of this study was to evaluate the rate of S. aureus peritonitis in our cohort of patients receiving PD. Method A retrospective single-center study was conducted in a large Italian PD center. We reviewed all cases of bacterial peritonitis from 1999 to 2023. Demographic and clinical characteristics of the patients and microbiological features of the bacteria identified in cultures were extracted from electronic health record. From 2011, all patients were screened before surgery for Methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) with nares swabs. All patients with positive nasal colonization for MSSA and MRSA were treated with nasal mupirocin (nasal ointment twice daily for 5 consecutive days every 4 weeks) until eradication was confirmed by a nasal swab. According to our protocol, from 2011, screening for S. aureus carriage along peritoneal fluid culture was performed in all patients on PD with an episode of peritonitis to verify nasal colonization with S. aureus. The study was approved by the regional ethical committee of Emilia Romagna (507/2021/OSS/AOUMO SIRER ID 2845). Results Overall, 345 cases of peritonitis were reviewed in 214 patients who received peritoneal dialysis. In our center, the rate of peritonitis was 0.23 episodes/patient-year. After the introduction of nasal screening for S. aureus carriage, the episodes of S. aureus peritonitis decreased in frequency (0.0093 episodes/patient-year vs. 0.034 episodes/patient-year) and as absolute number (17.8% vs 3.6%; p = 0.001). No differences were observed in the rate of catheter removal in the two populations (p = 0.99). The age of 109 patients screened for S. aureus carriage was 64.1 ± 17 years. Males accounted for 58.9% and automated PD (APD) was chosen by 66% of the subjects. After an average period of 1.6 years from the start of PD, 7 patients experienced S. aureus peritonitis in the absence of exit-site or tunnel catheter infection. Nasal screening at the time of peritonitis showed that half of them were carriers of S. aureus and half were negative (one patient was not screened). Colonization from S. aureus was found in another 9 patients whose peritonitis was caused by a different type of bacteria (44% S. epidermidis, 33.3% Enterobacteriaceae, 11.1% Acinetobacter, and 11.1% culture-negative peritonitis). Conclusion Our data document that screening for S. aureus, along with other preventive measures, contributes to significantly reducing the rate of S. aureus peritonitis in patients screened and treated for S. aureus carriage at the time of PD start. Routine screening and the use of a mask during connection are required because recolonization occurs frequently in this population.

Informal care after hip fracture: prospective cohort.

Hip fracture is very common and it has life-shattering consequences for older persons. After discharge the older persons need help with even basic everyday activities from formal and informal caregivers. In Scandinavia formal care are well-developed however the presence of informal caregivers likely reflect on the amount of formal care and wears on the informal caregivers. This study explore how often and how much informal care (IC) older persons receive after hip fracture. We contacted 244 community-dwelling older persons every two weeks the first twelve weeks after discharge after hip fracture and asked them if they received care from family and/or friends and how much. We used non-parametric statistics and level of significance was 95%. The proportion of older persons receiving IC was 90% and the median amount of IC was 32 hours (IQR 14-66). The number of older persons who received IC was highest the first four weeks after discharge and so was the amount of hours of IC. The older persons that were high-dependence on IC received a median of 66 (IQR 46-107) hours compared to the low-dependent of 11 hours (IQR 2-20). IC is very frequent, especially the first two to four weeks after discharge. The median IC was 32 hours from discharge to the 12-week follow-up. However, this figure tended to rise for persons with, among other, reduced functionality and those residing with a partner. With respect to local differences, the findings in this study are likely applicable to other Scandinavian countries. We strongly suggest that the variation in older person need for informal caregiver be given consideration in the prioritisation of resources. This prospective cohort study of informal care, was part of a cluster-randomised stepped-wedge clinical controlled trial. Written consent was obtained required by regional ethics committee S-20200070. Data was collected in accordance with the Danish Data Protection Agency (20-21854).

The ethics of research informed consent from the Kyrgyz perspective: A qualitative study.

To ensure informed consent is tailored to ethnic Asian communities, it is necessary to establish an ethical foundation that is relevant to the specific populations. We hypothesized that certain communitarian factors unique to traditional Kyrgyz culture may influence an individual's decision to participate in research. Guided by Seedhouse's (2005) Rational Field Theory, we conducted qualitative, in-depth interviews with cultural experts in Kyrgyzstan to identify the ethical foundations of decision-making for informed consent in Kyrgyz culture. The results indicate that Kyrgyz people have a distinctive decision-making style influenced by their nomadic culture and history, which values and prioritizes family integrity and reputation. These findings indicate that a multidimensional approach based on socio-cultural sensitivities is necessary to assess the appropriateness of consent procedures. We believe our results may have implications for revising the guidelines of local and regional research ethics committees in Kyrgyzstan and other Central Asian countries.

Association between the length of in vitro embryo culture, mode of ART, and the initial endogenous hCG rise in ongoing singleton pregnancies.

Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation? Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies. Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture. This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021. The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation. The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts). The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation. This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy. No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest. The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law.

Cost analysis for initiating an integrated package of essential non-communicable disease interventions (PEN-Plus) in Kondoa District Hospital, Tanzania: a time-driven activity-based costing (TDABC) study protocol

IntroductionNon-communicable diseases (NCDs) constitute approximately 74% of global mortality, with 77% of these deaths occurring in low-income and middle-income countries. Tanzania exemplifies this situation, as the percentage of total disability-adjusted...

Compassionate Communication and Advance Care Planning to improve End-of-life Care in Treatment of Haematological Disease ‘ACT’: Study Protocol for a Cluster-randomized trial

IntroductionTo support the implementation of advance care planning and serious illness conversations in haematology, a previously developed conversation intervention titled ‘Advance Consultations Concerning your Life and Treatment’ (ACT) was found...

Orthodontic Status and Association with Oral-Health-Related Quality of Life-A Study of 16-Year-Old Norwegians with a Cleft Lip and Palate.

To assess the association between clinical orthodontic indicators and oral-health-related quality of life, adjusted for socio-demographic factors, focusing on 16-year-old patients with cleft lip and/or palate (CL/P). One hundred and twenty-two patients with CL/P, representing cleft-lip (CL), cleft-palate (CP), unilateral/bilateral cleft-lip-palate (UCLP/BCLP), enrolled in the national CLP-Team, Bergen, Norway. A cross-sectional study by two orthodontists assessing the number of teeth, intermaxillary sagittal relation (ANB-angle), dental arch and occlusion of 16-year-old patients with CL/P. All completed a digital questionnaire including self-reported socio-demographic variables, OHIP-14 questionnaire and dental aesthetics. Cross-tabulations with Pearson's Chi-square test were used to identify associations between self-reported OHRQoL and socio-demographic and clinical indicators. Multiple variable analyses were conducted with binary logistic regression analysis using the odds ratio (OR) and 95% confidence interval (CI) to assess associations between OHRQoL and clinical indicators adjusted for socio-demographic variables. Ethical approval was granted by the regional ethics committee. Patients with UCLP and BCLP had poorer clinical indicators compared to patients with CL and CP (p < 0.05). A total of 80% of the patients had OHIP-14 > 0. The highest oral impact was reported for psychological domains and articulation and the least for functional domains. Respondents with BCLP and those with poor intermaxillary relationships (ANB < 0°) reported a high impact on OHRQoL (p < 0.05). No statistically significant associations between other clinical indicators and socio-demographic variables such as gender, educational aspiration, and place of residence were reported. The study revealed an association between severe cleft diagnosis, missing teeth, misaligned teeth, negative overjet, and poor OHRQoL, but a statistically significant association was found only between OHRQoL and poor intermaxillary sagittal relations (unfavorable profile). To improve OHRQoL among patients with clefts, there is a need for an individual follow-up and prioritization of oral healthcare.

Neuropilin-1 and placental growth factor as prognostic factors in metastatic breast cancer

BackgroundAngiogenesis is crucial for tumor development, progression, and metastasizing. The most important regulator of angiogenesis is the vascular endothelial growth factor (VEGF) family, which is involved in multiple pathways in tumor microenvironment. The objective of this study was to investigate the prognostic value of the VEGF family in patients treated for metastatic breast cancer. The emphasis was on neuropilin-1 (NRP-1) and placental growth factor (PlGF).Materials and methodsAn analysis of eight members of the VEGF family was performed using baseline plasma samples of 65 patients treated for metastatic HER2 negative breast cancer in a phase II first-line bevacizumab plus chemotherapy trial. The patients were divided into two groups, high or low, according to the median for each VEGF family member. Progression-free survival (PFS) and overall survival (OS) were determined for each VEGF family member.ResultsThe patients with low plasma levels of NRP-1 and PlGF had a longer OS than those with high plasma levels [multivariable adjusted hazard ratios (HRs) 2.54 (95% confidence interval (CI) 1.11–5.82, p = 0.02) and 3.11 (95% CI 1.30–7.47, p = 0.01), respectively]. The patients with low levels of both NRP-1 and PlGF had a remarkably long OS with HR of 6.24, (95% CI 1.97–19.76, p = 0.002). In addition, high baseline NRP-1 level was associated with a significantly shorter PFS [multivariable adjusted HR 2.90 (95% CI 1.02–8.28, p = 0.04)] than that in the low-level group, and a high baseline vascular endothelial growth factor receptor-2 level was associated with a longer PFS [multivariable adjusted HR 0.43 (95% CI 0.19–0.98, p = 0.04)].ConclusionEspecially NRP-1 and PlGF have prognostic potential in metastatic breast cancer patients treated with a bevacizumab-taxane combination. Patients with low plasma levels of NRP-1 or PlGF have longer OS than patients with high levels. Patients with both low NRP-1 and PlGF levels appear to have excellent long-term survival.Trial registrationClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008.

Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project) – study protocol

IntroductionThe European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation...

Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes (HISTORI): protocol describing a prospective, randomised, placebo controlled and double-blinded multicentre trial

IntroductionSubjects with schizophrenia have a 2–3 fold higher mortality rate than the general population and a reduced life expectancy of 10–20 years. Approximately one-third of this excess mortality has been...

Effects of power training in older patients with multiple sclerosis on neurodegeneration, neuromuscular function, and physical function. A study protocol for the “power training in older multiple sclerosis patients (PoTOMS) randomized control trial

IntroductionApproximately one-third of all persons with multiple sclerosis (pwMS) are older, i.e., having an age ≥60 years. Whilst ageing and MS separately elicit deteriorating effects on brain morphology, neuromuscular function, and physical function, the combination of ageing and MS may pose a particular challenge. To counteract such detrimental changes, power training (i.e., a type of resistance exercise focusing on moderate-to-high loading at maximal intended movement velocity) presents itself as a viable and highly effective solution. Power training is known to positively impact physical function, neuromuscular function, as well as brain morphology. Existing evidence is promising but limited to young and middle-aged pwMS, with the effects of power training remaining to be elucidated in older pwMS. MethodsThe presented ‘Power Training in Older MS patients (PoTOMS)’ trial is a national, multi-center, parallel-group, randomized controlled trial. The trial compares 24 weeks of usual care(n = 30) to 24 weeks of usual care and power training (n = 30). The primary outcome is whole brain atrophy rate. The secondary outcomes include changes in brain micro and macro structures, neuromuscular function, physical function, cognitive function, bone health, and patient-reported outcomes. Ethics and disseminationThe presented study is approved by The Regional Ethics Committee (reference number 1-10-72-222-20) and registered at the Danish Data Protection Agency (reference number 2016-051-000001). All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences independent of the results. The www.clinicaltrials.gov identifier is NCT04762342.

Adalimumab Persistence and Its Biosimilar in Inflammatory Bowel Disease: A Real-World Study.

Adalimumab biosimilar experience is still recent. Interchangeability differences could reduce persistence times. Our goal was to compare biosimilar persistence differences with a reference. A retrospective observational study was performed in three groups divided according to the adalimumab received. The primary outcome measure was persistence, represented with Kaplan-Meier analysis, and we secondarily evaluated security, efficacy, and biomarkers. We obtained approval from the regional ethical committee, and the study was conducted following the Helsinki Declaration as revised in 2013. Data from 104 patients were collected: 50 received the biosimilar, 29 received the reference, and 25 switched from the original to the biosimilar. After a follow-up of 12 months, the biosimilar's persistence was higher, without differences in mild adverse events per group. In contrast, there were differences in severe events, with the switched group's frequency being higher. Biomarkers were reduced at similar proportions in all groups, and 43% had a clinical response at week 20 without differences. Adalimumab biosimilars are a valuable option for IBD based on clinical equivalence that are less expensive than the original drug. Their use does not have a detrimental influence on disease, although there are a few nuances in terms of interchangeability. These results support increasing confidence in using biosimilars, thus promoting the better sustainability of health systems.

AI-related data ethics oversight in UK policing

Abstract This paper considers the question of how police-related AI projects and data projects in general are normatively assessed in the UK. After locating data ethics in relation to policing ethics, I shall consider the workings of perhaps the leading regional data ethics committee in the UK. I go on to consider the approach of another committee that might in the future provide national data ethics advice for the police. Finally, I summarize the normative ethics frameworks in use in the two committees and their heavy reliance on the concepts of necessity and proportionality. I suggest that these concepts may have to be supplemented by systematic thinking about varieties of harm and the way in which severe harm may generate obligations to prevent it, where prevention may be assisted by AI models.

COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study

ObjectiveDevelopmental dysplasia of the hip (DDH) is a congenital condition affecting 2–3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30 ​% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome. DesignWe used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01, R2≥ 0.8 and Hardy-Weinberg equilibrium (HWE) P-value ≥ 0.0001. Significance level was set at p ​< ​5 ​× ​10−8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee. ResultsAnalysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 (β ​= ​−0.43, SE ​= ​0.07, p ​= ​8.4 ​× ​10−9) and rs6577334 (β ​= ​−0.43, SE ​= ​0.08, p ​= ​8.9 ​× ​10−9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis. ConclusionsThis large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed.