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Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBV-seronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. L.U.P.L. and B.J. have received an unrestricted grant from Roche Diagnostics. H.H. has provided consultancy services for Incyte, Pierre Fabre, and SERB Pharmaceuticals., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has been effective in improving several outcomes in people living with cystic fibrosis (pwCF). Although clinical guidance regarding maintenance therapies has not changed, staff reports indicate that individuals reduce some therapies. This study aimed to evaluate ETI's effect on utilization of routine therapies among pwCF in Denmark., Methods: We included all pwCF initiating ETI between 1 September 2020 and 31 October 2022. Utilization of routine therapies was analysed by drug class (e.g., gastrointestinal medications) and individual treatments (e.g., pancreatic enzymes) before and after ETI initiation using national registry data. Odds ratios (ORs) for prescription redemptions pre- and post-ETI were calculated to assess ETIs impact on the use of routine therapies., Results: The study population consisted of 351 individuals. Median age was 23 years (IQR 14-32) and mean ppFEV 1 was 76 (SD 22) at index. Two-year follow-up was available for 205 individuals. Two years post ETI initiation, the one-year prevalence was reduced for airway medications, (89.5 % to 75.1 %) and inhaled antibiotics (59.5 % to 42.9 %.). OR for redeeming a prescription two years post-ETI initiation (95 % CI) was reduced for four out of five drug classes: airway medications (OR: 0.24 [0.19; 0.29]), inhaled antibiotics (OR: 0.28 [0.2; 0.39]), oral antibiotics (OR: 0.49 [0.41; 0.58]), gastrointestinal medications (OR: 0.66 [0.57; 0.77])., Conclusion: Two years after ETI initiation, reductions in the use of several routine therapies were observed in a national cohort of pwCF, with the largest declines in airway medications and antibiotics. These findings highlight ETI's real-world impact beyond conventional clinical metrics., Competing Interests: Declaration of competing interest The research project was funded by Vertex Pharmaceuticals, with all funds directed to the investigators' affiliated institutions. The sponsor provided feedback on the manuscript prior to submission but did not influence the choice of study design, analysis, or interpretation of data. The final decisions regarding study methodology, data presentation, and manuscript content were made by the investigators., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The objectives were to determine the structure of training programmes and assessment of physicians training to become infectious disease (ID) specialists in Europe in early 2024 and to document the provision of specialists, trainees and training centres in each country., Methods: Delegates to the ID Section and Board of the European Union of Medical Specialists entered national data on a web-based survey tool in late 2023-early 2024. Results were compared with European Union of Medical Specialists recommendations on the structure and content of postgraduate training in ID in Europe (2018), and to results of a similar survey in early 2021., Results: Responses were received from all 35 countries; 27/35 (77%) recognize ID as an independent speciality and 7/35 (20%) as a subspeciality. Spain does not officially recognize the speciality. In Cyprus, Iceland, and Luxembourg, despite official recognition of the sub-/speciality, ID training must be completed abroad. Paediatric ID was recognized in 16/35 (46%) countries. The number of adult ID specialists varied from 78.8 per million inhabitants in Sweden to 0.6 in Germany. Only 7/31 (23%) national programmes provide the minimum recommended 6 months of training in medical microbiology. Assessment methods included logbooks/portfolios in 25/31 (81%), final examinations in 25/31 (81%) and workplace-based assessments in 21/31 (68%)., Discussion: There has been little change since 2021 in speciality status or in structure and content of training programmes across Europe. There have been large increases in training position numbers in several countries, possibly in response to COVID-19. Continued low compliance with the 2018 recommendations to increase exposure to medical microbiology during training highlights the slow pace of change. Logistic barriers to change and to harmonization across Europe remain and are discussed in the context of published concerns of trainees., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The Danish National Patient Registry (DNPR) serves as a valuable resource for scientific research. However, to ensure accurate results in cystic fibrosis (CF) studies that rely on DNPR data, a robust case-identification algorithm is essential. This study aimed to develop and validate algorithms for the reliable identification of CF patients in the DNPR., Methods: Using the Danish Cystic Fibrosis Registry (DCFR) as a reference, accuracy measures including sensitivity and positive predictive value (PPV) for case-finding algorithms deployed in the DNPR were calculated. Algorithms were based on minimum number of hospital contacts with CF as the main diagnosis and minimum number of days between first and last contact., Results: An algorithm requiring a minimum of one hospital contact with CF as the main diagnosis yielded a sensitivity of 96.1 % (95 % CI: 94.2 %; 97.4 %) and a PPV of 84.9 % (82.0 %; 87.4 %). The highest-performing algorithm required minimum 2 hospital visits and a minimum of 182 days between the first and the last contact and yielded a sensitivity of 95.9 % (95 % CI: 94.1 %; 97.2 %), PPV of 91.0 % (95 % CI: 88.6 %; 93.0 %) and a cohort entry delay of 3.2 months at the 75th percentile (95th percentile: 38.7 months)., Conclusions: The DNPR captures individuals with CF with high sensitivity and is a valuable resource for CF-research. PPV was improved at a minimal cost of sensitivity by increasing requirements of minimum number of hospital contacts and days between first and last contact. Cohort entry delay increased with number of required hospital contacts., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population., Methods: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality., Results: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts., Conclusions: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life., Competing Interests: Declaration of competing interest The research project is funded by Vertex Pharmaceuticals. All funds were given to the institutions of the investigators. The research was performed in collaboration with the sponsor., (Copyright © 2024. Published by Elsevier B.V.)

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved the clinical status of individuals with cystic fibrosis (CF), however, whether ETI impacts glucose tolerance remains unknown. We aimed to study the change in glycated hemoglobin (HbA1c) and CF related diabetes (CFRD) status after initiation of ETI., Methods: We included individuals ≥12 years treated with ETI in Denmark in a longitudinal observational study. HbA1c was measured at baseline, 3, 6, 9 and 12 months after treatment initiation. Change in HbA1c was assessed in mixed models adjusted for age, sex, glucose tolerance and prior CFTR modulator treatment. In a sub-population with CFRD, we assessed the change in insulin usage, hypoglycemic events and the 30-day continuous glucose monitoring (CGM) parameters (i.e., average blood glucose, time below (≤3.9 mM) and above (>10.0 mM) normal range, and the variation in glucose) after 12 months of treatment., Results: Among 321 individuals with CF, HbA1c declined by 2.1 mmol/mol [95 % confidence interval (CI): -2.6; -1.5 mmol/mol] after 3 months and by 2.3 mmol/mol [95 %CI: -2.8; -1.9 mmol/mol] after 12 months of ETI treatment. The decline was independent of glucose tolerance status at baseline. In 26 individuals with CFRD at baseline, the mean decline in HbA1c was 3.6 mmol/mol [95 %CI: -6.9; -0.4 mmol/mol] after 12 months, but we did not observe any change in insulin usage, weekly number of hypoglycemic events or CGM parameters., Conclusion: In the Danish CF cohort, HbA1c declined over 12 months of ETI treatment, however, among a subset with CFRD, we observed no change in insulin usage and CGM glucose levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper TP, HVO, MS received speaking fees from Vertex. TP, HVO, BU, IHMM, MS were PI/Sub-investigators in trials by Vertex. TA holds stocks in Novo Nordisk. The remaining authors declared no conflicts., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Staphylococcal biofilm formation is a severe complication of medical implants, leading to high antibiotic tolerance and treatment failure. Ultra-dense poly(ethylene glycol) (udPEG) coating resists adsorption of proteins, polysaccharides and extracellular DNA. It is therefore uniquely resistant to attachment by Staphylococcus epidermidis, which remains loosely adhered to the surface. Our aim was to determine if S. epidermidis remains susceptible to antibiotics when adhering to udPEG, and if udPEG coatings can improve the treatment outcome for implant-associated infections. We tested the in vitro efficacy of vancomycin treatment on recently adhered S. epidermidis AUH4567 on udPEG, conventional PEG or titanium surfaces using live/dead staining and microscopy. udPEG was then applied to titanium implants and inserted subcutaneously in mice and inoculated with S. epidermidis to induce infection. Mice were given antibiotic prophylaxis or a short antibiotic treatment. One group was given immunosuppressive therapy. After five days, implants and surrounding tissue were harvested for CFU enumeration. Only few S. epidermidis cells adhered to udPEG compared to conventional PEG and uncoated titanium, and a much lower fraction of cells on udPEG survived antibiotic treatment in vitro. In vivo, the bacterial load on implants in mice receiving vancomycin treatment was significantly lower on udPEG-coated compared to uncoated implants, also in neutropenic mice. Our results suggest that the improved outcome results from the coating's anti-adhesive properties that leads to less biofilm and increased efficacy of antibiotic treatment. Thus, the combination of udPEG with antibiotics is a promising strategy to prevent acute implant-associated infections that arise due to perioperative contaminations., Statement of Significance: Infections of medical implants is an ever-present danger. Here, bacteria develop biofilms that cannot be eradicated with antibiotics. By using an ultra-dense polymer-brush coating (udPEG), bacterial attachment and the subsequent biofilm formation can be reduced, resulting in increased antibiotic susceptibility of bacteria surrounding the implant. udPEG combined with antibiotics proved to significantly reduce bacteria on implants inserted into mice, in our animal model. As the coating is not antibacterial per se, it does not induce antimicrobial resistance and its effect is independent of the bacterial species. Our results are encouraging for the prospect of preventing and treating implant-associated infections that arise due to perioperative contaminations., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to develop an audit tool with a built-in database using Research Electronic Data Capture (REDCap®) as part of an antimicrobial stewardship program at a regional hospital in the Central Denmark Region, and to analyse the need, if any, to involve more than one expert in the evaluation of cases of antimicrobial treatment, and the level of agreement among the experts. Patients treated with systemic antimicrobials in the period from 1 September 2015 to 31 August 2016 were included, in total 722 cases. Data were collected retrospectively and entered manually. The audit was based on seven flow charts regarding: (1) initiation of antimicrobial treatment (2) infection (3) prescription and administration of antimicrobials (4) discontinuation of antimicrobials (5) reassessment within 48 h after the first prescription of antimicrobials (6) microbiological sampling in the period between suspicion of infection and the first administration of antimicrobials (7) microbiological results. The audit was based on automatic calculations drawing on the entered data and on expert assessments. Initially, two experts completed the audit, and in the cases in which they disagreed, a third expert was consulted. In 31.9% of the cases, the two experts agreed on all elements of the audit. In 66.2%, the two experts reached agreement by discussing the cases. Finally, 1.9% of the cases were completed in cooperation with a third expert. The experts assessed 3406 flow charts of which they agreed on 75.8%. We succeeded in creating an audit tool with a built-in database that facilitates independent expert evaluation using REDCap. We found a large inter-observer difference that needs to be considered when constructing a project based on expert judgements. Our two experts agreed on most of the flow charts after discussion, whereas the third expert's intervention did not have any influence on the overall assessment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Nontuberculous mycobacteria (NTM) are an emerging threat to cystic fibrosis (CF) patients but their epidemiology is not well described., Methods: In this retrospective observational study we identified all Scandinavian CF patients with a positive NTM culture from airway secretions from 2000 to the end of 2012 and used national CF databases to describe microbiological and clinical characteristics., Results: During the 13-year period 157 (11%) CF patients were culture positive for NTM at least once. Mycobacterium abscessus complex (MABSC) (45%) and Mycobacterium avium complex (MAC) (32%) were the predominant species with geographical differences in distribution. Younger patients were more prone to MABSC (p<0.01). Despite treatment, less than one-third of MABSC patients with repeated positive cultures cleared their infection and a quarter had a lung transplant or died., Conclusion: NTM are significant CF pathogens and are becoming more prevalent in Scandinavia. MABSC and MAC appear to target distinct patient groups. Having multiple positive cultures despite treatment conveys a poor outcome., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Staphylococcus aureus is the most commonly isolated pathogen in respiratory tract secretions from young patients with cystic fibrosis (CF), and several treatment strategies are used to control the infection. However, it is not known whether intensified treatment with antimicrobial agents causes eradication of S. aureus clones. We retrospectively determined the impact of intravenous (IV) antimicrobial agents on the suppression and eradication of S. aureus clones. One thousand and sixty-one S. aureus isolates cultured from 2526 samples from 130 CF patients during a 2-year study period were subjected to spa typing. Intervals between positive samples and the occurrence of clone replacements were calculated in relation to courses of IV antimicrobial agents. Of 65 patients chronically infected with S. aureus, 37 received 139 courses of IV antimicrobial agents with activity against S. aureus (mean duration, 15 days; range, 6-31 days). Administration of IV antibiotics increased the time to the next sample with growth of S. aureus: the mean interval between two positive samples was 68 days if IV treatment had been administered, in contrast to 49 days if no IV treatment had been administered (p 0.003). When S. aureus recurred in sputum after IV treatment, the isolate belonged to a different clone in 33 of 114 (29%) intervals, in comparison with 68 of 232 (29%) intervals where IV treatment had not been prescribed (OR 0.98, 95% CI 0.60-1.61). In conclusion, we show that 2 weeks of IV antimicrobial treatment can significantly suppress chronic staphylococcal infection in CF, but is not associated with the eradication of persistent bacterial clones., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: In this nationwide retrospective study, we analysed species distribution, antimicrobial susceptibility and time to next occurrence of Achromobacter in Danish cystic fibrosis (CF) patients from 2000 to 2011., Methods: Thirty-four primary isolates were identified to species level and subjected to antimicrobial susceptibility testing. Effectiveness of early antimicrobial treatment was assessed by a Kaplan-Meier estimation of time to recurrence., Results: Achromobacter xylosoxidans accounted for 13 (38%) of the isolates, and an unnamed species accounted for 11 (32%) of the isolates. Meropenem, piperacillin-tazobactam and trimethoprim-sulfamethoxazole were highly active against chemotherapy-naïve Achromobacter, while ceftazidime, colistin and tobramycin were judged adequate for inhalation therapy. Fifty-five percent of 25 patients treated with inhaled ceftazidime, colistin, or tobramycin remained free of Achromobacter three years after acquisition, in contrast to 17% of 22 patients who did not receive inhaled antibiotics (P<0.01)., Conclusions: Early treatment with inhaled antibiotics may prevent or postpone chronic infection with Achromobacter in CF patients., (Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: An increased incidence of Achromobacter xylosoxidans infections has been observed at the Cystic Fibrosis Centre at Aarhus University Hospital, as the proportion of patients colonised with A. xylosoxidans increased from 6 to 10% from 2005 to 2009., Methods: Pulsed field gel electrophoresis (PFGE) was used to type isolates of A. xylosoxidans., Results: Four patients infected for 2-7 years were part of a larger epidemic spread involving both Danish CF centres, while 11 patients carried strains with unique genotypes. Longitudinal analysis of isolates from ten patients with multiple preserved isolates showed that each patient persistently carried isolates of a single genotype. Following lung transplantation, two patients showed re-colonisation of the lung grafts with the pre-transplant A. xylosoxidans strain., Conclusions: A. xylosoxidans has been transmitted between patients from our clinic, but the recent increase in incidence is not caused by cross infections., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the outcome of highly active antiretroviral therapy (HAART) in HIV-infected patients initiating equivalent regimens within and outside a randomized controlled trial (RCT)., Study Design and Setting: The Danish Protease Inhibitor Study (DAPIS) was a national multicenter RCT comparing initial treatment with indinavir, ritonavir, or saquinavir/ritonavir during 96 weeks. From the Danish HIV Cohort Study we identified all patients initiating one of these protease-inhibitor-based HAART regimens: 425 patients within DAPIS and 677 outside the trial. We compared viral load, CD4 count response, and mortality., Results: At weeks 96 and 240, trial participants were more likely than nonparticipants to have undetectable viral load (adjusted odds ratio [adOR] 1.28 [95% CI=0.94-1.74] and 1.70 [95% CI=1.16-2.50]) and a CD4 increase > or =100 cells/microl (adOR 1.37 [95% CI=1.03-1.82] and 1.53 [95% CI=1.04-2.25]). For antiretroviral-experienced, but not for antiretroviral-naïve patients, trial participants had a lower risk of death (mortality rate ratio [MRR]=0.46 [95% CI=0.27-0.77]) than nonparticipants. This effect was moderated in adjusted analyses (MRR=0.60 [0.33-1.07])., Conclusions: Compared to nontrial patients, trial participants had better response to HAART. The differences were small defying the notion that results obtained in RCTs are unachievable in routine clinical practice.