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Hailey-Hailey disease (OMIM#169600) is an autosomal dominantly inherited genodermatosis characterized by erosions in the flexural areas of the body. Hailey-Hailey disease is caused by variants in ATP2C1, but for ~10% of the patients, no causative variant is found in the coding region of ATP2C1. We aimed to determine the genetic cause of Hailey-Hailey disease in a family without a variant in the coding areas of ATP2C1. By genome sequencing and analysis of all exon and intron sequences of ATP2C1, we identified the variant c.532-560 T>G (NM_014382.5) in intron 7 of ATP2C1. The variant is predicted by in silico tools to create a new deep intronic donor splice site. Segregation analysis detected the variant in the three affected family members. RNA sequencing confirmed that the variant creates a new deep intronic donor splice site that gives rise to an alternative exon. The identified deep-intronic variant in ATP2C1 is the likely cause of Hailey-Hailey disease. This is to our knowledge the first report of a deep-intronic variant as the cause of Hailey-Hailey disease, which shows that the analysis of the intronic sequences of ATP2C1 could increase the genetic diagnostic yield for Hailey-Hailey disease patients., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Although genetic variants in MYH7 are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric MYH7 -related DCM., Methods and Results: We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.54 [interquartile range, 0.01-10.8] years) with pathogenic/likely pathogenic variants in MYH7 diagnosed with DCM at pediatric age (<18 years) followed at 13 international centers. We also explored risk factors associated with a composite end point of end-stage heart failure defined as heart transplantation or heart failure-related death. Twenty-two patients (50%) were diagnosed at age <6 months, including 7 (16%) at birth. Left ventricular (LV) hypertrabeculation features were present in 15 (38%), particularly among patients with genetic variants in the head domain. After a median follow-up of 6.1 years (interquartile range, 1.9-13.4), 15 patients (36%) required a heart transplant (n=14) or died due to end-stage heart failure (n=1), 15 patients (36%) persisted with systolic dysfunction despite treatment, 12 (29%) had a significant increase in LV ejection fraction, and 2 were lost to follow-up. Overall, end-stage heart failure event rate was 25% at 5 years. New York Heart Association class III to IV (hazard ratio [HR], 7.67 [95% CI, 2.16-27.2]; P =0.002) and LV ejection fraction ≤35% (HR, 4.00 [95% CI, 1.11-14.4]; P =0.03) were the best predictors of bad prognosis., Conclusions: Pediatric MYH7 -related DCM is characterized by early onset, frequent LV hypertrabeculation, and poor prognosis. Advanced New York Heart Association class and low LV ejection fraction emerged as predictors of end-stage heart failure.

Marfan syndrome (MFS) is a complex connective tissue disorder characterized by considerable clinical variability. The diagnosis of MFS is based on the Ghent criteria, which require the presence of both clinical and genetic features. MFS is primarily caused by pathogenic alterations in FBN1, which encodes the fibrillin-1 protein. Fibrillin-1 comprises multiple domains rich in cysteine residues, with disulfide bonds formed between these residues. It has long been recognized that variants that alter or introduce cysteine residues damage protein function, leading to the development of MFS. In this study, we report a cysteine-introducing variant: FBN1 variant, c.6724C>T (p.[Arg2242Cys]). We have observed this variant in several individuals without MFS, challenging our previous understanding of the underlying mechanism of MFS. This finding emphasizes the importance of revisiting and reevaluating our current knowledge in light of new and unexpected observations. Moreover, our study highlights the significance of incorporating local and national data on allele frequencies, as well as employing multidisciplinary phenotyping approaches, in the classification of genetic variants. By considering a wide range of information, we can enhance the accuracy and reliability of variant classification, ultimately improving the diagnosis and management of individuals with genetic disorders like MFS., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Background: Many prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents., Methods: As part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs., Results: We included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N 2 O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N 2 O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs., Conclusion: We found low-quality evidence suggesting that both MF and N 2 O are safe and may have a role in the management of pain in the prehospital setting. There is low-quality evidence to support MF as a short-acting single analgesic or as a bridge to IV access and the administration of other analgesics. There may be occupational health issues regarding the prehospital use of N 2 O., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Aim: Renal excretion of excess HCO 3 - depends on renal cystic fibrosis transmembrane conductance regulator (CFTR) and is impaired in people with cystic fibrosis (pwCF). Urine HCO 3 - excretion following oral NaHCO 3 -loading may be a simple in vivo biomarker of CFTR function. In this study, we investigated changes in urine acid/base parameters following oral NaHCO 3 -loading to comprehensively assess the physiological response to the test and evaluate HCO 3 - as the primary test result., Methods: Urine acid/base parameters (titratable acid (TA), NH 4 + , net acid excretion (NAE) and pH) were measured in bio-banked urine samples from controls (n = 10) and pwCF (n = 50) who completed the challenged urine HCO 3 - test. The association between urine acid/base excretion parameters and clinical CF disease characteristics and CFTR modulator therapy-induced changes were assessed., Results: Before treatment, challenged urine acid/base excretion associated with important CF disease characteristics. TA excretion and NAE were lower in pwCF with residual function mutations, 7.9 and 16.6 mmol/3 h, respectively, and lower TA excretion and NAE associated with pancreatic sufficiency. A lower excretion of TA, NH 4 + , and NAE associated with a higher percentage of predicted FEV 1 (1.3%, 2.5% and 0.8% per mmol/3 h higher, respectively). Modulator treatment decreased TA excretion and NAE (-2.9 and -5.3 mmol/3 h, respectively)., Conclusion: Following acute NaHCO 3 -loading, increased base excretion is mirrored by decreased acid excretion. Urine HCO 3 - excretion sufficiently represents the additional urine acid/base parameters as test result. The observed changes in acid excretion support CFTR modulator-induced increase of CFTR-dependent type B intercalated cell HCO 3 - secretion and the use of the challenged urine HCO 3 - test as a possible CFTR-biomarker., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Aim: To analyse patterns of glucose-lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023., Materials and Methods: We examined time trends in the clinical profiles of people with T2D who initiated different glucose-lowering therapy classes for the first time. We furthermore investigated individual-level treatment trajectories following first-ever glucose-lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first-ever prescription for metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 inhibitors (SGLT-2is) or insulin, excluding those without HbA1c-confirmed T2D or probable type 1 diabetes., Results: We included 260 393 individuals initiating a new glucose-lowering therapy class from 2016 to 2023, during which there were 6- and 3-fold increases in initiators of GLP-1RAs and SGLT-2is, respectively. The median HbA1c level at treatment initiation with GLP-1RAs or SGLT-2is decreased, from 67-68 mmol/mol in 2016-2017 to 57-58 mmol/mol in 2022-2023. Among individuals who initiated metformin as first-line therapy, the proportion who started additional glucose-lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first-ever glucose-lowering therapy in 2020, 22% used SGLT-2is and 18% GLP-1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively., Conclusions: Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP-1RAs and SGLT-2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D)., Materials and Methods: We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication., Results: A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications., Conclusion: In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Intravenous therapies are essential for hospitalised patients. The rapid dissemination of portable ultrasound machines has eased ultrasound-guided intravenous access and facilitated increased use of long peripheral venous catheters (LPCs). This study aimed to evaluate the clinical performance and complications of LPCs., Methods: Retrospective, observational single-site study. Data from all consecutively inserted LPCs during a period of 18 months was evaluated. The primary endpoint was the all-cause incidence rate of catheter removal. Secondary endpoints included specific reasons for the catheter removal and the associations between predefined characteristics of the patients, the infusions and the catheters with catheter failure., Results: During the period, 751 PVCs were inserted in 457 patients. The reasons for catheter removal were recorded in 563 cases. The overall incidence rate of catheter removal was 95.8/1000 catheter days (95% CI 88.4-103.8). The median dwell time was 8 days (IQR 5-14), and the total dwell time was 6136 days. Catheter failure occurred in 283 (50.3%) cases, of which the most common cause was phlebitis (n = 101, 17.9%). In multivariable analyses, the use of the cephalic vein was significantly associated with both all-cause catheter failure (p < .001) and catheter failure due to phlebitis (p < .001). In multivariable analyses, vancomycin infusion was not significantly associated with all-cause catheter failure (HR 1.15 (0.55-2.42), p = .71) or catheter failure due to phlebitis (HR 1.49 (0.49-4.53), p = .49)., Conclusion: The overall incidence rate of catheter removal was 95.8/1000 catheter days, and the most common causes of catheter failure were phlebitis, infiltration and unintended catheter removal. The use of the cephalic vein was significantly associated with catheter failure in multivariable analyses. We did not find an association between vancomycin infusion and catheter failure in multivariable analyses., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Radiotherapy is routinely used for management of limited-stage follicular lymphoma (FL), yet half of patients ultimately relapse. We hypothesized that the presence of specific gene mutations may predict outcomes. We performed targeted sequencing of a 69-gene panel in 117 limited-stage FL patients treated with radiotherapy and identified recurrently mutated genes. CREBBP was most frequently mutated, and mutated CREBBP was associated with inferior progression-free survival, though not after false discovery rate adjustment. This association failed to validate in an independent cohort. We conclude that recurrent gene mutations do not predict outcomes in this setting. Alternative biomarkers may offer better prognostic insight., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Treatment with opioids is a mainstay in perioperative pain management. While the leading treatment paradigm has been procedure-specific pain management, efforts regarding personalized pain treatment are increasing. The OPI•AID project aims to develop personalized algorithms for perioperative pain management, taking demographic, surgical, and anaesthesiologic factors into account. We will undertake five parallel reviews to illuminate current evidence on different aspects of individual responses to perioperative opioid treatment., Methods: Inclusion of adult populations in English-written studies. Review-specific searches are developed for the following databases: CENTRAL, MEDLINE, Embase, clinicaltrials.gov, and clinicaltrial.eu. Two authors will independently screen citations, extract data, and assess the risks of bias in each review (QUIPS, PROBAST and RoB2, as relevant)., Conclusion: These reviews will evaluate various aspects of perioperative opioid treatment, including individualized treatment strategies, selection of specific opioids, and individual patient responses. These will guide future development of a personalized perioperative opioid treatment algorithm (OPI•AID) that will be validated and tested clinically against standard of care., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: To evaluate the five-year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR-screening programme., Methods: Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013-2018. According to the worse eye at first screening, DR was classified (levels 0-4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication., Results: At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five-year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63-1.89, and HR 2.04, 95% CI 1.73-2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10-1.47, and HR 2.80, 95% CI 2.23-3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05-1.36, and HR 1.98, 95% CI 1.53-2.57)., Conclusion: In a study of all patients with type 1 diabetes from the Danish DR-screening programme, we identified duration of diabetes, systemic disease and use of anti-hypertensive treatment as consistent risk markers for incident and progressive DR., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Inter-hospital transfer is necessary for the transport of patients to specialized treatment. Rotor-wing aircraft may be used in lieu of ambulances in time-critical conditions over long distances and when specialist team skills are called for. The purpose of the review is to assess the current scientific literature that describes the scenario to develop a national guideline for inter-hospital transfers using rotor-wing aircraft. The aim is to describe the patterns and challenges., Methods and Analysis: The authors will conduct a scoping review as per Joanna Briggs Institute guideline. The protocol for the scoping review will adhere to the Open Science Framework guideline for scoping reviews and we will report the findings of the scoping review as per PRISMA-ScR guideline. We have developed the search strategy with the help of a research librarian and will conduct search in relevant electronic databases and include gray literature as well, using the PRESS and PRISMA-S guidelines. Two authors will independently screen titles and abstracts for inclusion as per eligibility criteria and conflicts will be resolved by a third reviewer. Full text retrieval will be conducted accordingly. We will analyze the extracted data using validated statistical methods., Ethics and Dissemination: According to Danish law, scoping reviews are exempt from ethics committee approval. The findings of this scoping review will provide the scientific foundation for a national guideline on rotor-wing aircraft conveyed inter-hospital transfers in Denmark. Furthermore, we will publish the results of the scoping review in a relevant scientific journal., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Peripheral nerve blocks effectively alleviate postoperative pain. Animal studies and human research suggest that opioid tolerance may reduce the effectiveness of local analgesics. The reduced effectiveness has been observed in opioid-tolerant humans and animals undergoing spinal and infiltration anaesthesia with both lidocaine and bupivacaine. However, the impact on peripheral nerve blocks in humans has not been evaluated. This study aims to assess the onset time and duration of a radial nerve block in opioid-tolerant individuals compared to opioid-naive individuals. We hypothesise that peripheral nerve blocks may be less effective in producing sensory and motor blockades in opioid-tolerant individuals compared to their opioid-naive counterparts., Methods: Twenty opioid-tolerant individuals will be matched by sex and age with opioid-naïve counterparts. Participants will receive an ultrasound-guided radial nerve block. The primary outcome is the difference in the duration of sensory nerve blockade between the two groups. The secondary outcomes include the onset time of sensory blockade, onset time of motor blockade, and difference in duration of motor nerve blockade., Conclusion: This study will compare the effectiveness of a peripheral nerve block between opioid-tolerant and opioid-naïve individuals. Any found differences could support a specific postoperative protocol for opioid-tolerant individuals regarding the use of peripheral nerve blocks., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Postpartum psychotic- or mood disorders are psychiatric emergencies associated with risk of suicide and infanticide. Except from case reports, there are only few descriptions of its treatment. Therefore, we aimed to describe the treatment of women admitted with postpartum psychotic- or mood disorder in Denmark with emphasis on the use of electroconvulsive therapy (ECT)., Methods: We conducted a register-based cohort study of all women with incident postpartum psychotic- or mood disorder (no prior diagnoses of psychotic- or mood disorder or treatment with ECT) requiring admission in the period from 2011 to 2018. For these patients, we described the treatment and the 6-month readmission risk., Results: We identified 91 women with postpartum psychotic- or mood disorder with a median admission length of 27 days (interquartile range: 10-45). Of those, 19% received ECT with a median time from admission to first ECT of 10 days (interquartile range: 5-16). The median number of ECT sessions was eight (interquartile range: 7-12). In the 6 months following discharge, 90% of the women received some form of psychopharmacological treatment (62% antipsychotics, 56% antidepressants, 36% anxiolytics/sedatives, 19% lithium, and 9% mood stabilizing antiepileptics), and 31% were readmitted., Conclusion: Psychiatric admission for incident postpartum psychotic- or mood disorder is rare in Denmark. Among those admitted, ECT and psychopharmacological treatment is commonly used. The 6-month readmission risk is high, warranting close follow-up. The fact that there is no international consensus on the optimal treatment of postpartum psychotic- or mood disorder is problematic and calls for action., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: The "window of opportunity" for intensive care staff to deliver end-of-life (EOL) care lies in the timeframe from "documenting the diagnosis of dying" to death. Diagnosing the dying can be a challenging task in the ICU. We aimed to describe the trajectories for dying patients in Danish intensive care units (ICUs) and to examine whether physicians document that patients are dying in time to perform EOL care and, if so, when a window of opportunity for EOL care exists., Methods: From the Danish Intensive Care Database, we identified patients ≥18 years old admitted to Danish ICUs between January and December 2020 with an ICU stay of >96 h (four days) and who died during the ICU stay or within 7 days after ICU discharge. A chart review was performed on 250 consecutive patients admitted from January 1, 2020, to ICUs in the Central Denmark Region., Results: In most charts (223 [89%]), it was documented that the patient was dying. Of those patients who received mechanical ventilation, 171 (68%) died after abrupt discontinuation of mechanical ventilation, and 63 (25%) died after gradual withdrawal. Patients whose mechanical ventilation was discontinued abruptly died after a median of 1 h (interquartile range [IQR]: 0-15) and 5 h (IQR: 2-15) after a diagnosis of dying was recorded. In contrast, patients with a gradual withdrawal died after a median of 108 h (IQR: 71-189) and 22 h (IQR: 5-67) after a diagnosis of dying was recorded., Conclusions: EOL care hinges on the ability to diagnose the dying. This study shows that there is a window of opportunity for EOL care, particularly for patients who are weaned from mechanical ventilation. This highlights the importance of intensifying efforts to address EOL care requirements for ICU patients and those discharged from ICUs who are not eligible for readmission., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Prenatal exposures to xenobiotics during the masculinization programming window are suggested to impact male fecundity later in life. Frequently used nitrosatable drugs, such as penicillins and beta2-agonists, contain amines or amides that may form teratogenic compounds in reaction with nitrite., Objectives: We explored whether maternal nitrosatable drug use during gestation was associated with biomarkers of male fecundity in adulthood; moreover, the potential modifiable effect of nitrate and vitamin intake was investigated., Method: We performed a cohort study in the Fetal Programming of Semen Quality cohort that includes semen characteristics, reproductive hormone concentrations, and measures of testis size on 1058 young adult sons in the Danish National Birth Cohort. Information on maternal use of nitrosatable drugs was obtained from questionnaires and interviews around gestational weeks 11 and 16. A multivariable negative binomial regression model was used to obtain relative differences in biomarkers of male fecundity for those whose mothers used nitrosatable drugs compared to those without such maternal use. In sub-analyses, the exposure was categorized according to nitrosatable drug type: secondary amine, tertiary amine, or amide. We investigated dose dependency by examining the number of weeks with intake and explored potential effect modification by low versus high maternal nitrate and vitamin intake from diet and nitrate concentration in drinking water. We added selection weights and imputed values of missing covariates to limit the risk of selection bias., Results: In total, 19.6% of the study population were born of mothers with an intake of nitrosatable drugs at least once during early pregnancy. Relative differences in biomarkers related to male fecundity between exposed and unexposed participants were negligible. Imputation of missing covariates did not fundamentally alter the results. Furthermore, no sensitive subpopulations were detected., Conclusions: The results suggest that maternal use of nitrosatable drugs does not have a harmful influence on the male fecundity of the offspring., (© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Purpose: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown., Methods: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group., Results: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population., Conclusion: This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Decisions about when to change antidepressant treatment are complex and benefit from accurate prediction of treatment outcome. Prognostic accuracy can be enhanced by incorporating repeated assessments of symptom severity collected during treatment. Participants (n = 714) from the Genome-Based Therapeutic Drugs for Depression study received escitalopram or nortriptyline over 12 weeks. Remission was defined as scoring ≤ 7 on the Hamilton Rating Scale. Predictors included demographic, clinical, and genetic variables (at 0 weeks) and measures of symptom severity (at 0, 2, 4, and 6 weeks). Longitudinal descriptors extracted with growth curves and topological data analysis were used to inform prediction of remission. Repeated assessments produced gradual and drug-specific improvements in predictive performance. By Week 4, models' discrimination in all samples reached levels that might usefully inform treatment decisions (area under the receiver operating curve (AUC) = 0.777 for nortriptyline; AUC = 0.807 for escitalopram; AUC = 0.794 for combined sample). Decisions around switching or modifying treatments for depression can be informed by repeated symptom assessments collected during treatment, but not until 4 weeks after the start of treatment., (© 2024 The Author(s). American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Background: Alpha-gal syndrome is a novel food allergy to the oligosaccharide galactose-α-1,3-galactose (alpha-gal) present in mammalian meat. Tick bites are considered an important route of sensitization to alpha-gal. Data on alpha-gal sensitization in the general population is scant. We utilized a unique data source of repeated population-based health examination studies to assess prevalence, time trends, risk factors, and characteristics of alpha-gal sensitization., Methods: Alpha-gal sensitization was assessed in >11.000 adults from four health examination studies of randomly invited residents in the Copenhagen region conducted in 1990-1991, 2011-2012, 2012-2015, and 2016-2017. Alpha-gal sensitization was defined as serum specific IgE (sIgE) to alpha-gal ≥0.1 kU A /L; ≥0.35 kU A /L; ≥0.7 kU A /L; ≥3.5 kU A /L. The population was characterized according to genetically determined ABO blood group, aeroallergen sensitization, and pets at home., Results: The prevalence of sIgE to alpha-gal ≥0.1 kUA/L was 1.3% in 1990-1991, 3.7% in 2012-2015 and 3.2% in 2016-2017. Of those sensitized to alpha-gal >97% reported to consume red meat at least once a week, even for sIgE to alpha-gal ≥3.5 kU A /L. Male sex, older age, aeroallergen sensitization, cat at home, and blood group A were associated with increased odds of alpha-gal sensitization. The known protective effect of blood group B was confirmed., Conclusion: In this general adult population, the prevalence of alpha-gal sensitization had doubled from 1990-1991 to 2016-2017. This could potentially be due to increased tick exposure and an increased atopic predisposition., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Non-Western immigrant patients (NWIPs) may be a vulnerable population when diagnosed and treated for acute myeloid leukaemia (AML). Here we report selected quality parameters related to diagnosis, treatment, and outcome of newly diagnosed AML among NWIPs (n = 119) and Danish-born patients (DBPs) (n = 4689). No adjusted differences were observed for time-to-diagnosis, time-to-treatment, treatment allocation, rates of complete remission, early death, allogeneic stem cell transplantation, and overall survival between NWIPs and DBPs. Among patients allocated for intensive chemotherapy, NWIPs were less likely to participate in clinical trials. The findings highlight equitable AML care but underscore the need to enhance NWIP participation in clinical trials., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c)., Methods: We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before., Results: In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication., Conclusion: This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: More than 50% of patients with hand eczema (HE) are colonized with Staphylococcus aureus. Comprehensive knowledge of the skin microbiome and its changes in patients with HE may provide insights into future potential therapeutical targets., Objective: To describe the skin microbiome in patients with moderate-to-severe chronic HE and assess its changes following treatment with topical corticosteroids (TCS)., Methods: Bacterial samples were collected from lesional and nonlesional skin before and after 2 weeks of TCS treatment using ESwabs and analysed by 16S rRNA and tuf gene sequencing. Clinically, the disease severity was assessed by the Hand Eczema Severity Index (HECSI)., Results: A cohort of 31 patients with HE were included and followed up. Compared to nonlesional skin, lesional skin differed in overall bacterial community composition (p = 0.02), displayed higher relative abundance of Staphylococcus, in particular S. aureus (p = 0.01) and lower abundance of Micrococcus (p = 0.02). As disease severity improved with treatment, these microbial characteristics on lesional skin shifted towards that of nonlesional skin on the hands., Conclusion: The bacterial skin microbiome was altered in lesions of HE and partly driven by S. aureus colonization, however, shifted towards nonlesional skin following treatment. Our results emphasize the future possibilities for anti-S. aureus treatment strategies., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram., Aims: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice., Method: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication., Results: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events., Conclusions: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Prone position ventilation (PPV) is recommended for patients with COVID-19 induced severe Adult Respiratory Distress Syndrome (ARDS) and is used for patients supported with V-V ECMO as well. The purpose of this study was to describe the use of PPV in these patients focusing on physiological effects with the hypothesis that PPV could reduce oxygen need and improve dynamic compliance., Methods: This study was a nationwide retrospective analysis of all COVID-19 patients in Denmark from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. Data on the number of patients treated with PPV, number of PPV sessions, timing, the time spent in prone position, pulmonary physiological response types with analysis of variables affecting the response are reported., Results: Out of 68 patients 44 were treated with 220 PPV sessions and a positive clinical response was observed in 80% of patients but only in 45% of sessions. On a single session level, increased compliance was observed in 38% and increased oxygenation in only 15% of 220 sessions, with within-patient heterogeneity. Higher dynamic compliance at the beginning of a PPV session was associated with a lower delta change in dynamic compliance during PPV. The response to a PPV session could not be predicted by the response in the prior session. Dynamic compliance did not change during the ECMO course., Conclusion: Eighty percent of patients responded positively during a PPV session, but this was not associated with overall pulmonary improvement. On a single patient level, responses were heterogenous and only 45% of sessions resulted in clinical improvement. Response in dynamic compliance was associated with starting values of compliance., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Access to the neuraxial space, including lumbar punctures and neuraxial anaesthesia, is an everyday procedure in clinical practice. Traditionally these procedures rely on manual palpation technique, but ultrasound is a useful tool when patients prove challenging. Presently, there is a lack of evidence-based guidelines for technical skills acquisition, both with and without ultrasound, and likewise, competency assessment approaches vary globally. Accordingly, we aim to assess the current evidence regarding learning and assessment in neuraxial access ± ultrasound, for future educational recommendations., Methods: This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic and Meta-Analysis (PRISMA) statement, together with the PRISMA Extension for Scoping Reviews. A systematic search strategy will be based on a PICO approach, focusing on physicians, medical students, or nurses being exposed to education, training, or assessment in procedural neuraxial access ± ultrasound. No comparators are obligated, but outcomes should be assessable using the Kirkpatrick four levels of training evaluation. The search will be performed in Cochrane Library, Embase, Medline, Scopus, PubMed, and CINAHL. Independently, two authors will screen the studies and conflicts will be resolved by a third author. Relevant predefined data will be extracted and analysed using a descriptive approach. The quality of the studies will be assessed using the Medical Education Research Study Quality Instrument., Discussion: This scoping review will contribute by presenting gathered evidence of an overview of the different approaches to achieving education and training of technical skills in neuraxial access, and how skills are tested, which could guide research and future recommendations for skills development and assessment., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Nasotracheal intubation is associated with a risk of epistaxis. Several drugs, including cocaine and xylometazoline may be used as decongestants prior to nasotracheal intubation to prevent this. We hypothesized that xylometazoline would prevent epistaxis more effectively than cocaine, demonstrated by a lower proportion of patients with bleeding after nasotracheal intubation., Methods: We conducted a single-center, outcome assessor and analyst-blinded, clinical randomized controlled trial following approval from the local research ethics committee and the national medicine agency. Written informed consent was obtained from all patients. Patients scheduled for surgery under general anesthesia with nasotracheal intubation were randomized to receive either 2 mL 4% cocaine or 2 mL 0.05% xylometazoline prior to nasotracheal intubation. Immediately following intubation, epistaxis was evaluated by the blinded intubating anesthetist on a four-point scale. We measured heart rate and blood pressure the first 5 min after drug administration. Adverse events were followed up after 24 h., Results: A total of 53 patients received cocaine and 49 patients received xylometazoline. Bleeding occurred in 32 patients receiving cocaine (60.4%) and in 34 patients receiving xylometazoline (69.4%) (p = .41, Fisher's exact test) with a difference of 9.0% (95% CI: -9.4% to 27%). There was no statistically significant difference between groups regarding the heart rate or blood pressure. No adverse cardiac events were recorded in either group., Conclusion: We found no statistically significant difference between cocaine and xylometazoline in preventing epistaxis after nasotracheal intubation, and the choice of vasoconstrictor should be based on other considerations, such as pricing, availability and medicolegal issues., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Cocaine may be applied to decongest the nasal mucosa before nasotracheal intubation, but patients risk a criminal offence if cocaine is detected when patients drive a car shortly after surgery. We aimed to evaluate whether benzoylecgonine levels in saliva exceeded the cut-off point 24 h after administration in patients undergoing nasotracheal intubation and whether cocaine would be detectable above the Danish legal fixed limit in blood samples 1 and 24 h after surgery., Methods: We conducted a prospective study following approval from the local research ethics committee and the national medicine agency. Written informed consent was obtained from all patients. We included patients scheduled for surgery under general anaesthesia with nasotracheal intubation. They received 80 mg cocaine as a nasal spray 5 min before induction and nasotracheal intubation. The primary outcome was a dichotomous assessment of benzoylecgonine levels in saliva samples measured 24 h after administration of nasal cocaine with a cut-off limit of 200 ng/mL. Secondary outcomes were dichotomous assessments of cocaine in whole blood samples measured 1 and 24 h after administration of nasal cocaine with a cut-off limit of 0.01 mg/kg., Results: Overall, 70 patients had valid saliva samples and 75 had valid blood samples 24 h after cocaine administration. Benzoylecgonine in saliva was traceable above the cut-off in 9/70 patients (13%; CI 95% : 6% to 23%), and cocaine in blood was detected above the cut-off in 2/75 patients (3%; CI 95% : 0.3% to 9%)., Conclusion: We found benzoylecgonine traceable in saliva in 13% of patients and cocaine traceable in blood in 3% of patients 24 h after administration of 80 mg nasal cocaine. Patients should be informed when receiving cocaine and advised not to drive for at least 24 h., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Patient characteristics and platelet responses at romiplostim initiation according to the duration of immune thrombocytopenia (ITP) are poorly understood. Amongst romiplostim-exposed adults with ITP lasting ≥6 months during 2009-2018 in Denmark, Sweden, and Norway, we examined characteristics at romiplostim initiation, romiplostim dosage, and durable platelet response (≥75% of measurements ≥50 × 10 9 /L at 14-24 weeks) for subcohorts with newly diagnosed (duration <3 months), persistent (3-12 months), or chronic (>12 months) ITP initiating romiplostim. The 285 romiplostim initiators comprised 81 (28%) with newly diagnosed, 47 (16%) with persistent, and 157 (55%) with chronic ITP. More patients with newly diagnosed ITP than longer ITP duration, had low comorbidity levels, two or more prior ITP therapies, and previous bleeding requiring hospitalisation. The median romiplostim doses were similar across subcohorts. During treatment, median platelet counts were similar across subcohorts (75-76 × 10 9 /L), and the durable platelet response was 64.6%, 52.9%, and 52.7% for newly diagnosed, persistent, and chronic ITP, respectively. After treatment cessation, the median platelet count was 138 × 10 9 /L, 68 × 10 9 /L, and 71 × 10 9 /L, respectively. In conclusion, newly diagnosed patients, compared with romiplostim initiators with longer disease duration, had more severe ITP, higher frequency of durable platelet response, and higher median platelet count after cessation., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Over the past decade, ultrasound utilization has increased within anesthesia and intensive care medicine, enhancing patient safety and diagnostic accuracy. However, the frequency of ultrasound usage and operator training in the Nordic countries remain unclear. This project aims to perform a survey on ultrasound availability, daily clinical use, and how ultrasound skills are trained and assessed, among anesthesiologists., Methods: This online cross-sectional survey will include anesthesiologists from the Nordic countries. The survey will adhere to the CROSS checklist. Survey items will be developed based on a formative model with a conceptual model, consisting of three main parts, including demographics, ultrasound machines and use, and skills development and assessment. The clinical relevance of items will be secured by including anesthesiologists of various levels of experience in the development of the survey. Furthermore, experienced researchers in medical education will participate in the development, contributing with relevant medical educational perspectives. Data will be summarized using a non-parametric descriptive approach. A chi-squared test will examine relevant relationships between certain answers., Results: Results will be published in a peer-reviewed journal and presented at relevant scientific conferences and meetings., Conclusion: This study may find a high availability of ultrasound machines and frequent use in the clinical departments. Despite this expected daily use of ultrasound, missing standardized structured skills acquisition and assessment could be uncovered. The results of this study may contribute to mapping various aspects of clinical ultrasound and skills development for further use in research., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Objective: To investigate how reproductive history was associated with urinary incontinence in midlife., Design: A follow-up study., Setting: Denmark., Population: A total of 39 977 mothers who participated in the Maternal Follow up (2013-2014) in the Danish National Birth Cohort. National registries provided their reproductive history., Methods: How parity, mode of birth and obstetric tears associated with urinary incontinence were estimated with adjusted odds ratios (OR) and 95% CI using logistic regression., Main Outcome Measures: Self-reported urinary incontinence including subtypes stress, urge and mixed urinary incontinence., Results: At an average age of 44 years, the prevalence of any urinary incontinence was 32% (21% stress, 2% urge, and 8% mixed urinary incontinence). Women with two births more often had urinary incontinence than women with one birth (OR 1.20, 95% CI 1.10-1.31). Compared with women with only spontaneous births, a history of only caesarean sections was associated with much lower odds of urinary incontinence (OR 0.39, 95% CI 0.35-0.42) and a history of instrumental births with slightly lower odds (OR 0.92, 95% CI 0.86-0.98). Compared with no tear/first-degree tear as the largest tear, episiotomy was associated with less urinary incontinence (OR 0.91, 95% CI 0.86-0.97) whereas third/fourth-degree tears were associated with more (OR 1.14, 95% CI 1.04-1.25). Findings were mainly explained by similar associations with stress and mixed urinary incontinence., Conclusions: Vaginal birth was associated with a higher risk of long-term urinary incontinence, but our results indicate that this risk may be reduced by shortening the second stage of birth., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Although acne is associated with scarring, mental health comorbidities and bullying, little is known about its impact on socio-economic outcomes., Objectives: To examine the association between acne and educational, labour market and relationship outcomes., Methods: We conducted a nationwide registry-based cohort study in Denmark. We included birth cohorts from 1982 to 1988 and compared those with and without acne identified using hospital diagnosis codes and redeemed prescriptions. Our main educational outcome was educational attainment. The main labour market outcomes were earned income at age 30 and long-term unemployment at any time before age 30. The main relationship outcomes were single partnership and childlessness by age 30. Outcomes were assessed using Poisson regression for binary outcomes and linear regression for continuous outcomes, adjusted for sex, calendar year, mother's socio-economic position and hormonal contraception use., Results: Those with acne had a lower risk of not completing upper secondary education (relative risk (RR): 0.79; 95% confidence interval [CI]: 0.76-0.83) and higher education (RR: 0.90; 95% CI: 0.88-0.91), with absolute differences up to 4 percentage points. Persons with acne had slightly higher income (mean percentile difference: 2.6%, 95% CI: 2.2-2.9) and lower risk of long-term unemployment than those without acne (9.8% vs. 11.4%; RR: 0.90; 95% CI: 0.87-0.93). The prevalence of being single until age 30 was similar (19.7% vs. 20.1%; adjusted RR: 0.96; 95% CI: 0.94-0.98) but childlessness was slightly more prevalent (60.5% vs. 57.5%; adjusted RR: 1.03; 95% CI: 1.02-1.04). However, all associations were attenuated or lost in secondary analysis restricted to exposure-discordant siblings to address confounding from family-related factors., Conclusions: Acne during adolescence does not seem to affect long-term educational, labour market or relationship outcomes. However, there is a need for additional studies to validate the findings in untreated patients and different health and social systems., (© 2024 European Academy of Dermatology and Venereology.)

Background: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown., Study Design and Methods: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9 /L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality., Results: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9 /L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied., Conclusions: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR-screening programme and non-diabetes adults., Methods: In this registry-based matched case-cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age- and sex-matched by five non-diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models., Results: Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20-1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08-1.30) as compared to non-diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72-0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR-levels 1-4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow-up (HR 1.23; 95% CI, 1.02-1.49)., Conclusion: In a nationwide matched case-cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Rationale: Despite cardiac rehabilitation and medical treatment being integrated parts of the pathway of patients with cardiovascular disease, as well as the well-establish positive effect, cardiac rehabilitation remains underutilised. In recent years, cardiac rehabilitation has increasingly been moved from the hospitals to the community healthcare services. This transition may be challenging for patients with cardiovascular disease., Aim: To investigate reflections and perspectives of patients opting out of cardiac rehabilitation in community healthcare services to improve participation and adherence to cardiac rehabilitation in the future., Results: A total of eight patients opting out of cardiac rehabilitation participated in individual interviews. Opting out of cardiac rehabilitation is defined as never enroled or did not complete cardiac rehabilitation. The Interpretive Description methodology was used in the analysis where two themes and six subthemes were identified: (1) 'Structural and organisational factors' with three subthemes; Being a patient in the healthcare system, Enroling into CR when it is meaningful, and Getting back to work is vital, and (2) 'Patients' internal factors' with three subthemes; Feeling a desire to regain control, Seeing yourself as recovered, and Being aware of own needs. The analysis indicates that patients' decision to opt out of CR was multidimensional and based on a combination of factors., Conclusion: Ensuring that the healthcare professionals in the community have sufficient information regarding the patient and a clear communication plan between the healthcare professionals and the patient may reduce the transition causing confusion and frustrations for patients. Incorporating a vocational element in CR and ensuring that employers understand the importance of CR may hamper returning to work as a challenge to CR. Ensuring timely CR referral and enrolment and a transition coordinator may reduce the challenge of patients not viewing CR as meaningful. However, further studies are needed to fully understand how CR could become meaningful for patients opting out of CR., (© 2024 The Author(s). Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Background: Whether blood laboratory analyses differ in patients who later suffer in-hospital cardiac arrest (IHCA) compared to other hospitalised patients remains unknown. The aim of this study was to describe pre-arrest sampling frequencies, results, and trends in blood laboratory analyses in patients with IHCA compared to controls., Methods: This study was a matched case-control study using national registries in Denmark. Cases were defined as patients with IHCA from 2017 to 2021. Controls were defined as hospitalised patients and were matched on age, sex, and date and length of admission. Data on a total of 51 different blood laboratory analyses were obtained. The laboratory analyses of primary interest were lactate, sodium, potassium, and haemoglobin. The index time for cases was defined as the time of cardiac arrest, and a corresponding index time was defined for controls based on the time to cardiac arrest for their corresponding case. Blood sampling frequencies were reported for blood laboratory analyses obtained either within the last 24 h before the index time or between the time of hospital admission and the index time. Blood sampling results were reported for blood laboratory analyses obtained within the last 24 h before the index time., Results: A total of 9268 cases and 92,395 controls were included in this study. Cases underwent more frequent sampling of all blood laboratory analyses compared to controls. This higher sampling frequency was more pronounced for lactate compared to sodium, potassium, or haemoglobin. The last measured lactate was higher in cases (median [IQR]: 2.3 [1.3, 4.9]) compared to controls (median [IQR]: 1.3 [0.9, 2.0]). Differences in sodium, potassium, and haemoglobin were negligible. The proportion of abnormally elevated levels of lactate and potassium increased as time to cardiac arrest decreased; no such effect was seen in controls. No temporal trend was evident for sodium or haemoglobin., Conclusions: Patients with IHCA undergo more frequent blood sampling prior to IHCA and have higher levels of lactate compared to matched controls., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear., Methods: We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness., Results: Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis., Conclusions: Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels., (© 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Background: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low., Methods: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios., Conclusions: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Individual dietary recommendations change as loss of kidney function progresses. Adopting these recommendations in everyday life poses major challenges for patients. Individualising dietary counselling is crucial to easy accessibility., Aim: To investigate patients' needs with regard to a dietary app for patients with chronic kidney disease, patients', and health professionals' immediate responses to such a dietary app and suggestions for improvement and further development of a prototype., Design: A prototype of the dietary app has been developed and demonstrates how all information it provides can be tailored to the individual patient according to stage of disease, anthropometrics, and phosphate and potassium levels. A qualitative evaluation of the prototype was conducted using the Consolidated Criteria for Reporting Qualitative Research checklist for reporting., Approach: Seven individual interviews and four focus groups were analysed using interpretive description., Participants: Individual interviews with seven patients who have stage 4 or 5 chronic kidney disease and are not on dialysis, and four focus groups: one with participants from the individual interviews, one with six patients on haemodialysis, one with 13 kidney dieticians and one with seven health professionals., Findings: Both patients and healthcare professionals were positive about the app. Individualisation is necessary for the app to work in practice. The patients reported access to a diet diary and recipes as important elements., Conclusion: There is a need to improve the tools we use today to enhance patient adherence to dietary recommendations. The development of an app for individual dietary counselling could be a useful solution., (© 2023 The Authors. Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Purpose: To investigate circumpapillary retinal nerve fibre layer (RNFL) thickness, pupillary function and diameter after phacoemulsification and lens implantation alone or combined with endothelial keratoplasty (EK)., Methods: This study was a secondary analysis of data from a randomized, single-masked trial, that included 72 patients with Fuchs' endothelial dystrophy and cataract, equally allocated (1:1) to ultrathin Descemet's stripping automated endothelial keratoplasty or Descemet's membrane endothelial keratoplasty. The cataract extraction (CE) group included 40 patients undergoing cataract surgery only. All patients were treated with phacoemulsification and lens implantation., Results: RNFL thickness was significantly lower in the CE group than after EK for the global (p < 0.01), nasal (p = 0.04), and temporal sectors (p = 0.01) 12 months after surgery. RNFL thickness was comparable between patients treated with rebubbling and others (p ≥ 0.16 for all comparisons) after 12 months. The CE group and patients treated with EK demonstrated a comparable scotopic (p = 0.34) and photopic pupil diameter (p = 0.95) as well as a comparable maximum (p = 0.83) and average pupillary constriction velocity (p = 0.95) after 12 months. In contrast, patients treated with rebubbling had a significantly smaller scotopic pupil diameter (p = 0.04)., Conclusion: In this study, no evidence was found indicating a negative impact on the RNFL thickness after EK when compared to CE 12 months after surgery. Iris function and pupil diameter were comparable between the CE group and patients treated with EK after 12 months., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)