Search

Anne-Sophie Halkjær Christensen,1 Casper Roed,1 Peter H Andersen,2 Åse Bengård Andersen,3 Niels Obel1 1Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, 3Department of Infectious Diseases, Odense University Hospital, Odense, Denmark Background: Long-term mortality and causes of death in patients with pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) are poorly documented. In this study, long-term mortality and causes of death in PTB and EPTB patients were compared with the background population and it was investigated whether mortality was associated with family-related risk factors. Methods: A nationwide cohort study was conducted including: all adult Danes notified with PTB or EPTB from 1977 to 2008 and alive 1 year after diagnosis; a randomly selected comparison cohort matched on birth date and sex; adult siblings of PTB patients; and population controls. Data were extracted from national registries. All-cause and cause-specific mortality rate ratios were calculated for patients and siblings and compared with their respective control cohorts. A total of 8,291 patients (6,402 PTB and 1,889 EPTB), 24,873 population controls, 1,990 siblings of PTB patients and 11,679 siblings of PTB population controls were included. Results: Overall, the mortality rate ratio was 1.86 (95% confidence interval [CI] 1.77–1.96) for PTB patients and 1.24 (95% CI 1.12–1.37) for EPTB patients. Both patient cohorts had significantly increased risk of death due to infectious diseases and diabetes. Further, the PTB patients had increased mortality due to cancers (mainly respiratory and gastrointestinal tract), liver and respiratory system diseases, and alcohol and drug abuse. The PTB patients had increased mortality compared with their siblings (mortality rate ratio 3.55; 95% CI 2.57–4.91) as did the siblings of the PTB patients compared with the siblings of population controls (mortality rate ratio 2.16; 95% CI 1.62–2.87). Conclusion: We conclude that adult PTB patients have an almost two-fold increased long-term mortality whereas EPTB patients have a slightly increased long-term mortality compared with the background population. The increased long-term mortality in PTB patients stems from diseases associated with alcohol, tobacco, and drug abuse as well as immune suppression, and family-related factors. Keywords: pulmonary tuberculosis, extrapulmonary tuberculosis, mortality, causes of death, siblings, cohort study

A retrospective nationwide study including all culture-verified multidrug-resistant (MDR) tuberculosis (TB) cases was performed in Denmark. The aim was to examine the long-term treatment outcome of MDR-TB, to assess if MDR-TB transmission occurs, and to evaluate a rapid mutation analysis detecting rifampin and isoniazid resistance in this cohort. Clinical data were obtained from patient records. A restriction fragment length polymorphism genotype database of all TB cases was compared for identical strains indicating active transmission. Twenty-nine cases of MDR-TB were identified and the incidence was low at 0.5%. Acquired MDR-TB and active transmission was rare. Mutations in rifampin ( rpoB) and isoniazid ( katG, inhA) genes correctly determined resistance in 100% and 82% of all isolates tested, respectively. Initial treatment success was 89% for 27 MDR-TB patients with available outcome data. Initially 3 patients defaulted; no deaths were reported. Including successfully re-treated default patients and censoring patients who spent <2 y in the cohort, long-term treatment success was achieved for all 26 patients (mean follow-up 8.9 y). MDR-TB has a good prognosis in the high-income, low TB burden country of Denmark. Continued surveillance and rapid detection of resistance mutations directly in smear-positive patients may improve the standard of MDR-TB care. [ABSTRACT FROM AUTHOR]

A patient with polymyositis developed tuberculosis during immunosuppressive treatment. Tuberculin Skin Test and chest X-ray failed to demonstrate latent tuberculosis, whereas a blood sample that was tested with a modified QuantiFERON-TB-assay, using the recombinant ESAT-6 and CFP-10, was positive indicating that this patient was latently infected before immunosuppressive therapy. This case indicates the risk of progressing from latent to active tuberculosis given that the subject is RD1 responsive, and we believe that preventive anti-tuberculous treatment could have prevented this case of tuberculosis. We suggest that RD1 based tests are evaluated further in immunocompromised patients. [ABSTRACT FROM AUTHOR]

Background: Umbilical lesions in pigs have a negative impact on animal welfare and productivity. It has been suggested that lifting young piglets by one hind leg may be a risk factor for developing omphalitis and umbilical hernia. However, the hypothesis that lifting piglets by one hind leg should stretch the umbilical wall and impede the healing of the umbilicus has not yet been investigated. The present study examined if piglets caught, lifted, and carried by one hind leg have an increased risk of developing lesions in the umbilicus and the hind legs compared to piglets caught, lifted, and carried with support under the abdomen., Materials and Methods: In a commercial indoor sow herd, 1901 piglets were randomly allocated into two groups on the day of birth. Piglets in Group 1 (986 piglets) were caught, lifted, and carried by one hind leg (either left or right, as the same leg was not necessarily used each time). Piglets in Group 2 (915 piglets), were caught, lifted, and carried with support under the abdomen. All piglets were lifted 8-10 times during the first 14 days of life as a part of routine management procedures. From each group, 50 female piglets, 14 days old, were randomly selected and euthanised for necropsy and histopathological evaluation., Results: The risk of having haemosiderophages in the umbilicus was 1.4 times higher in piglets caught, lifted, and carried by one hind leg compared to piglets caught, lifted, and carried with support under the abdomen (p = 0.01). No other variable differed significantly between the groups. Omphalitis was present in 68% and 58% of piglets in Groups 1 and 2, respectively. Moreover, umbilical herniation was present in 14% and 12% of piglets in Groups 1 and 2, respectively. Lesions were present in the hind legs of piglets in both groups and included synovial hyperplasia, neutrophilic granulocyte infiltration, oedema, and haemorrhage., Conclusion: Female piglets caught, lifted, and carried by one hind leg did not have an increased risk of umbilical hernia, omphalitis, or joint lesions compared to piglets caught, lifted, and carried with support under the abdomen., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Animal Ethics Institutional Review Board, University of Copenhagen. AEIRB no. 2023-02-PNH-002 A. A minor part of the study was presented at the 5th Cutting Edge Pathology Congress 2024 [36]. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Global migration has increased in recent decades due to war, conflict, persecutions, and natural disasters, but also secondary to increased opportunities related to work or study. Migrants' risk of tuberculosis (TB) differs by reasons for migration, socioeconomic status, mode of travel and TB risk in transit, TB incidence and healthcare provision in country of origin. Despite advances in TB care for migrants and new treatment strategies, decisions for the management of migrants at risk of TB often rely on expert opinions, rather than clinical evidence., Methods: A systematic literature search was conducted, studies were mapped to different recommendation groups and included studies were synthesized by meta-analysis where appropriate. Current evidence on diagnosis of active TB in migrants entering the European Union /European Economic Area (EU/EEA) &UK including the clinical presentation and diagnostic delay, treatment outcomes of drug susceptible TB, prevalence and treatment outcomes of multidrug/rifampicin-resistant (MDR/RR)-TB and TB/HIV co-infection was summarised. A consensus process was used based on the evidence., Results: We document a higher vulnerability of migrants for TB, including an increased risk of extrapulmonary TB, MDR/RR-TB, TB/HIV co-infection and worse TB treatment outcomes compared to host populations. Consensus recommendations include screening of migrants for TB/ latent TB infection (LTBI) according to country data; a minimal package for TB care in drug susceptible and MDR/RR-TB; implementation of migrant-sensitive strategies; free healthcare and preventive treatment for migrants with HIV co-infection., Conclusion: Dedicated care for TB prevention and treatment in migrant populations within the EU/EEA &UK is essential., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Surgical trauma causes immune impairment, but it is largely unknown whether surgery for cancer and benign diseases instigate comparable levels of immune inhibition. Here, we compared the impact of laparoscopic surgery on immunological biomarkers in patients with colorectal cancer (CRC) and ventral hernia (VH)., Methods: Natural Killer cell activity (NKA), leukocyte subsets, and soluble programmed death ligand 1 (sPD-L1) were measured in blood samples collected from CRC (n = 29) and VH (n = 9) patients preoperatively (PREOP) and on postoperative day (POD) 1, 3-6, 2 weeks and 3 months. NKA was evaluated by the NK Vue assay that uses the level of IFNγ as a surrogate marker of NKA. Normal NKA was defined as IFNγ > 250 pg/mL and low NKA was defined as IFNγ < 250 pg/mL., Results: The CRC cohort was classified into either PREOP LOW having preoperative low NKA or PREOP HIGH having preoperative normal NKA. The median NKA of the PREOP LOW subset was only in the normal range in the POD3 months sample, whereas median NKA of the PREOP HIGH subset and the VH cohort were only low in the POD1 sample. While PREOP LOW differed from VH in the PREOP-, POD1-, and POD3-6 samples (P =.0006, P = .0181, and P = .0021), NKA in PREOP HIGH and VH differed in the POD1 samples (P = .0226). There were no apparent differences in the distribution of leukocyte subsets in the perioperative period between the cohorts., Conclusion: CRC patients with preoperative normal NKA and VH patients showed the same pattern of recovery in NKA, while the CRC subset with preoperative low NKA seemed to experience prolonged NK cell impairment. As low NKA is associated with recurrence, preoperative level of NKA may identify patients who will benefit from immune-enhancing therapy in the perioperative period., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark., Method: Nationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance., Results: 433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3-4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9-1.2), possible disease 1.0 (95%CI 0.8-1.2), and isolation 1.7 (95%CI 1.4-1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR] = 2.1, 95%CI 1.9-2.3, p < 0.001), possible disease (IRR = 2.4, 95%CI 2.0-3.0, p < 0.001), and isolation (IRR = 4.6, 95%CI 3.9-5.4, p < 0.001) compared to Danish-born, but not of definite disease (IRR = 1.1, 95%CI 0.9-1.3, p = 0.562). IRs of migrants with positive NTM cultures did not increase over time (-0.8 %/year, p = 0.133)., Conclusions: Migrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for Mycobacterium tuberculosis. Microbiologically classified definite NTM disease is not substantially more common among migrants., Competing Interests: Declaration of competing interest VND and ABA participate on the advisory board for Nordicinfu Care Denmark, which distributes ARIKAYCE® (amikacin liposome inhalation suspension) for Insmed. The other 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Nontuberculous mycobacteria (NTM) are emerging as notable causative agents of opportunistic infections. To examine clinical significance, species distribution, and temporal trends of NTM in Denmark, we performed a nationwide register-based study of all unique persons with NTM isolated in the country during 1991-2022. We categorized patients as having definite disease, possible disease, or isolation by using a previously validated method. The incidence of pulmonary NTM increased throughout the study period, in contrast to earlier findings. Mycobacterium malmoense, M. kansasii, M. szulgai, and M. avium complex were the most clinically significant species based on microbiologic findings; M. avium dominated in incidence. This study shows the need for surveillance for an emerging infection that is not notifiable in most countries, provides evidence to support clinical decision-making, and highlights the importance of not considering NTM as a single entity.

Introduction: When older persons with dementia are admitted to hospital, they often feel disoriented and confused and their cognitive impairment may worsen, purely due to the sudden change in their environment. As such hospital design is recognised as an important aspect in the care and well-being of older persons with dementia. As the number of persons with dementia is increasing, the experience of admission to a hospital with, for example, single rooms is more relevant than ever., Aim and Methods: This scoping review aimed to identify, explore and conceptually map the literature reporting on what older people with dementia and their families experienced during admission to a hospital with single room accommodation. We followed the Joanna Briggs Institute recommendations for undertaking a scoping review. In addition, we used the Preferred Reporting Items for Systematic reviews (PRISMA-ScR) Checklist, which assisted the development and reporting of this scoping review., Results: We included 10 sources within a time frame of 23 years (1998-2021). The sources originate from Europe, Australia and Canada. We identified three conceptual maps: Safety and security, Privacy and dignity and Sensorial stimulation. Our review demonstrates that the themes of the three conceptual maps are experienced as mutually interdependent for the older persons with dementia and their families., Conclusion: We conclude that it is not merely the single room design that determines what the older persons with dementia and their families experience as important; the exposure to sensorial stimulation and the presence of well-trained staff taking a dignified patient-centred approach are also crucial for their experience of high-quality nursing care., (© 2024 The Author(s). International Journal of Older People Nursing published by John Wiley & Sons Ltd.)

Background: The field of Advanced Practice Nursing (APN) has developed over the past six decades. However, the definition of roles and responsibilities of APN nurses seem to be contested due to both a lack of a clear definition of the concept and to institutional and cultural barriers that restrict the nurses' opportunities to practise to the full extent of their competencies., Aim: The objective of this scoping review was to identify, examine and conceptually map the available literature on APN nurses' core competencies for general health assessment in primary health care., Method: We performed a scoping review, following the methodological guidance for reporting as it is described by the Joanna Briggs Institute (JBI). Furthermore, the PRISMA-ScR statement and checklist for reporting scoping reviews were followed. Guiding the initial process for the search, we used the Population, Concept and Context mnemonic (PCC) to clarify the focus and context of the review., Results: We found three areas of core competencies on which APN nurse draw in performing general health assessments in primary health care: (1) 'Collaborative, leadership and management skills' (2) 'Person-centred nursing care skills' and (3) 'Academic and educational skills'. Furthermore, we found that the three areas are interrelated, because it is crucial that APN nurses draw on collaborative competencies related to leadership and management to meet the service users' needs and deliver high-quality and person-centred care., Conclusion: There is a need for a more specific investigation into how APN nurses' core competencies play a role during general health assessments of patients in primary care. We suggest an evaluation of what works for whom in what circumstances looking into the interrelation between competencies, skills and knowledge when an APN nurse performs a general health assessment in a primary healthcare setting., (© 2024 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

BackgroundDenmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB epidemiology over 147 years in Denmark.AimOur aim was to describe the TB disease burden in Denmark in relation to historical events, living conditions and health interventions during the past 147 years.MethodsWe performed a nationwide register-based ecological study including all persons with TB in Denmark from 1876 through 2022, correlating the TB incidence to social, economic and health indicators.ResultsIn Denmark, the overall TB incidence and mortality declined markedly over the past 147 years, only marginally influenced by specific TB interventions such as sanatoria, Bacillus Calmette-Guèrin (BCG) vaccination, mass screenings and antibiotics. Parallel to this decline, the country experienced improved living conditions, as illustrated by decreased infant mortality and increased life expectancy and wealth. In 1978, Denmark became a low-incidence country for TB with risk groups predominantly affected, and with a continuous change in demographics towards fewer Danish-born cases and relatively more migrant cases.ConclusionsThe decline over time in TB incidence and mortality in Denmark preceded specific TB interventions and can, first of all, be attributed to improved living conditions. TB has now become a rare disease in Denmark, predominantly occurring in particular risk groups. Future elimination of TB will require a combination of specific health interventions in these risk groups combined with a continued focus on improving socioeconomic status and living conditions.

Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The pathogenic inflammatory roots are still not well understood, and there is a lack of extensive biomarker studies to explain the disease debut and post-acute phase. This study aimed to deeply analyze the serum proteome and inflammatory response of PMR patients before and after glucocorticoid treatment. We included treatment-naïve PMR patients, collecting samples before and after 3 months of treatment. For comparison, disease-modifying antirheumatic drug (DMARD)-naïve RA patients were included and matched to healthy controls (CTL). The serum proteome was examined using label-free quantitative mass spectrometry, while inflammation levels were assessed using multiplex inflammatory cytokine and cell-free DNA assays. The serum proteomes of the four groups comprised acute phase reactants, coagulation factors, complement proteins, immunoglobulins, and apolipoproteins. Serum amyloid A (SAA1) was significantly reduced by active PMR treatment. Cell-free DNA levels in PMR and RA groups were significantly higher than in healthy controls due to acute inflammation. Complement factors had minimal changes post-treatment. The individual serum proteome in PMR patients showed over 100 abundantly variable proteins, emphasizing the systemic impact of PMR disease debut and the effect of treatment. Interleukin (IL)-6 and interferon-gamma (IFN-γ) were significantly impacted by glucocorticoid treatment. Our study defines the PMR serum proteome during glucocorticoid treatment and highlights the role of SAA1, IL-6, and IFN-γ in treatment responses. An involvement of PGLYRP2 in acute PMR could indicate a response to bacterial infection, highlighting its role in the acute phase of the immune response. The results suggest that PMR may be an aberrant response to a bacterial infection with an exacerbated IL-6 and acute phase inflammatory response and molecular attempts to limit the inflammation.

Background: Ventriculostomy-associated infection (VAI) is common after external ventricular drains (EVD) insertion but is difficult to diagnose in patients with acute brain injury. Previously, we proposed a set of criteria for ruling out VAI in traumatic brain injury. This study aimed to validate these criteria. For exploratory purposes, we sought to develop and validate a score for VAI risk assessment in patients with different types of severe acute brain injury., Methods: This retrospective cohort study included adults with acute brain injury who received an EVD and in whom CSF samples were taken over a period of 57 months. As standard non-coated bolt-connected EVDs were used. The predictive performance of biomarkers was analyzed as defined previously. A multivariable regression model was performed with five variables., Results: A total of 683 patients with acute brain injury underwent EVD placement and had 1272 CSF samples; 92 (13.5%) patients were categorized as culture-positive VAI, 130 (19%) as culture-negative VAI, and 461 (67.5%) as no VAI. A low CSF WBC/RBC ratio (< 0.037), high CSF/plasma glucose ratio (> 0.6), and low CSF protein (< 0.5g/L) showed a positive predictive value of 0.09 (95%CI, 0.05-0.13). In the multivariable logistic regression model, days to sample (OR 1.09; 95%CI, 1.03-1.16) and CSF WBC/RBC ratio (OR 34.86; 95%CI, 3.94-683.15) were found to predict VAI., Conclusion: In patients with acute brain injury and an EVD, our proposed combined cut-off for ruling out VAI performed satisfactorily. Days to sample and CSF WBC/RBC ratio were found independent predictors for VAI in the multivariable logistic regression model., (© 2024. The Author(s).)

Aim: Knowledge about the prevalence of sexual and gender-based harassment is hampered by disagreements about definitions and measurement methods. The two most common measurement methods are the self-labelling (a single question about exposure to sexual harassment) and the behavioural list method (an inventory of sexually harassing behaviours). The aim of this paper was to compare the self-labelling and the behavioural list methods for measuring sexual harassment and assess the association with depressive symptoms., Methods: The study is based on a convenience sample of 1686 individuals employed in 29 workplaces in Denmark. Survey data were collected from November 2020 until June 2021 and there were 1000 participants with full data on key variables. We used a linear mixed-effects model to examine the relationship between sexual harassment and depressive symptoms., Results: In total, 2.5% self-labelled as being sexually harassed, while 19.0% reported exposure to at least one type of sexual and gender-based harassment using the behavioural list method. Both groups reported higher levels of depressive symptoms compared with non-exposed employees. The most common types of behaviours were: that someone spoke derogatorily about women/men (11.6%); being belittled because of one's gender or sexuality (4.7%); and unwanted comments about one's body, clothes or lifestyle (4.5%)., Conclusions: The behavioural list method yielded a higher prevalence of sexual and gender-based harassment compared with the self-labelling method. Self-labelling and reporting at least one type of sexual and gender-based harassment was associated with depressive symptoms., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The combined single-breath measurement of the diffusing capacity of carbon monoxide (DL,CO) and nitric oxide (DL,NO) is a useful technique to measure pulmonary alveolar-capillary reserve in both healthy and patient populations. The measurement provides an estimate of the participant's ability to recruit and distend pulmonary capillaries. The method has recently been reported to exhibit a high test-retest reliability in healthy volunteers during exercise of light to moderate intensity. Of note, this technique permits up to 12 repeated maneuvers and only requires a single breath with a relatively short breath-hold time of 5 s. Representative data are provided showing the gradual changes in DL,NO and DL,CO from rest to exercise at increasing intensities of up to 60% of maximal workload. The measurement of diffusing capacity and evaluation of alveolar-capillary reserve is a useful tool to evaluate the lung's ability to respond to exercise both in the healthy population as well as in patient populations such as those with chronic lung disease.

Intersectoral collaboration (IC) plays a significant role in the delivery of diabetes care and treatment of patients with type 2 diabetes (DM2), as the treatment and care of these patients take place in both primary care and specialist settings. The collaboration involves a large number of actors from primary and secondary healthcare sectors, who are expected to fulfil various roles when they engage in IC. We explored the actors' roles by applying the framework of positioning theory with the aim of revealing seemingly embedded understandings of such roles. The empirical data consisted of individual and focus group interviews. Our results indicate that naturalised understandings of the roles of actors interact with the way in which health professionals, patients, managers and relatives strive to develop IC that aims to help and guide patients who live with DM2., (© 2023 John Wiley & Sons Ltd.)

Nowadays, it is common that newly built hospitals are designed with single-room accommodation, unlike in the past, where shared accommodation was the favoured standard. Despite this change in hospital design, very little is known about how single-room accommodation affects nurses' work environment and nursing care. This study evaluates how the single-room design affects nurses and nursing care in the single-room hospital design. Nurses working in the single-room design predominantly work alone with little opportunity for peer training, interaction and reflection. In addition, the single-room design affects the nurses' work environment due to changes in sensory stimulation and increased walking distances. Furthermore, a change in the discourse, namely, regarding the single room as the patient's home, makes the nurses react to queries, demands and tasks in a new way. Overall, the new hospital design forces the nurses into a more reactive role and affect their way of providing nursing care. Despite this, the nurses find single-room accommodation beneficial for the patients and their nursing care., (© 2023 The Authors. Nursing Inquiry published by John Wiley & Sons Ltd.)

Introduction: Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes., Methods: We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961., Results: Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5)., Conclusion: Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress., Competing Interests: Declaration of Competing Interest CL reports support for the present manuscript (e.g., funding and medical writing) from DZIF (German Center of Infection Research); consulting fees from a consultation service to Insmed, a company that produced liposomal amikacin as an inhalative suspension for the treatment of non-tuberculous mycobacteria pulmonary disease (outside of the scope of this work); speakers' honoraria from Insmed, Gilead, and Janssen (all outside of the scope of this work); is a member of the data safety board of trials from Médecins Sans Frontières (outside of the scope of this work); is supported by the German Center for Infection Research (DZIF); and acknowledges funding from the European Commission (anTBiotic EU-H2020 733079, ClicTB EDCTP2 RIA2017T-2030, stool4TB EDCTP2 RIAD2018–2511, and UNITE4TB EU-IMI 101007873). ABA and VND are members of the advisory board for Nordicinfu Care Denmark who distributes ARIKAYCE® (amikacin liposome inhalation suspension) for Insmed (outside of the scope of this work). All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The aim of this study was to explore how a single-room hospital design influenced student nurses' learning and competence development in clinical practice compared with shared-room accommodation, refining the programme theory: The student nurses' conditions for learning in single-room hospital design are associated with the values of the patient room as the patient's home during hospitalisation., Background: It is evident that a hospital design with single-room accommodation influences several parameters for both the patients and staff. Furthermore, studies have shown that the physical as well as the psychological learning environment affects the learning outcome for student nurses. A premise for learning and education is that the physical learning space must promote person-centred and collaborative learning in order for the students to achieve their competence development goals., Design: The study was conducted as a realistic evaluation that compares second and fifth-semester undergraduate nurses' learning and competence development in clinical practice in shared accommodation (a pre-study) to single-room accommodation (a post-study)., Methods: In the data generation, we drew on an ethnographically inspired participant observation method. We gathered data during the period 2019-2021, covering the time before and approximately one year after relocation to all single-room accommodation. We undertook 120 h of participant observation for the pre-study and 146 h of participant observation for the post-study., Conclusion: We conclude that the learning environment in a single-room accommodation setting promotes task-oriented practices where the patient is often a mediator of activities related to nursing care. The learning environment in single-room accommodation places increased demands on the students' ability to reflect on verbal instructions on nursing activities whenever the chance for reflection presents itself. We also conclude that in a single-room accommodation setting, stakeholders must focus on conscious planning and follow-up on the student nurses' learning and educational activities which must support the students' competence development. Hence, summing up to a refined programme theory developed through the realistic evaluation process: The student nurse's conditions for learning in a single-room hospital design are associated with increased demands on the student's ability to reach out for professional reflection when the chance presents itself. This is because the value of the patient room as the patient's home during hospitalisation promotes a task-solving approach to nursing with the patient and the patient's relatives as instructors., 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: To assess outcome of a one-time human papillomavirus (HPV)-screening in 2017 of Danish women aged 70+., Material and Methods: Women born 1947 or before were personally invited to have a cell-sample collected by their general practitioner. Screening- and follow-up samples were analyzed in hospital laboratories in the five Danish regions and registered centrally. Follow-up procedures varied slightly across regions. Cervical intraepithelial neoplasia 2 (CIN2) was recommended treatment threshold. Data were retrieved from the Danish Quality Database for Cervical Cancer Screening. We calculated CIN2+ and CIN3+ detection rates per 1000 screened women, and number of biopsies and conizations per detected CIN2+ case. We tabulated annual number of incident cervical cancer cases in Denmark for the years 2009-2020., Results: In total, 359 763 women were invited of whom 108 585 (30% of invited) were screened; 4479 (4.1% of screened, and 4.3% of screened 70-74 years) tested HPV-positive; of whom 2419 (54% of HPV-positive) were recommended follow-up with colposcopy, biopsy and cervical sampling, and 2060 with cell-sample follow-up. In total, 2888 women had histology; of whom 1237 cone specimen and 1651 biopsy only. Out of 1000 screened women 11 (95% confidence interval [CI]: 11-12) had conization. In total, 579 women had CIN2+; 209 CIN2, 314 CIN3, and 56 cancer. Out of 1000 screened women five (95% CI: 5-6) had CIN2+. Detection rate of CIN2+ was highest in regions where conization was used as part of first-line follow-up. In 2009-2016, number of incident cervical cancers in women aged 70+ in Denmark fluctuated around 64; in 2017 it reached 83 cases; and by 2021 the number had decreased to 50., Conclusions: The prevalence of high-risk HPV of 4.3% in women aged 70-74 is in agreement with data from Australia, and the detection of five CIN+2 cases per 1000 screened women is in agreement with data for 65-69 year old women in Norway. Data are thus starting to accumulate on primary HPV-screening of elderly women. The screening resulted in a prevalence peak in incident cervical cancers, and it will therefore take some years before the cancer preventive effect of the screening can be evaluated., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Diabetic foot ulcer (DFU) is a common, complex and severe complication of diabetes that is associated with severely decreased health-related quality of life. Treatment of DFUs calls for a multi-sectoral approach, incorporating interdisciplinary care pathways. Telemedicine (TM) may be used as a communication tool between caregivers across healthcare sectors to obligate the need for close follow-up, including early intervention in preventing the recurrence of DFU. The objective of this review was to identify, examine and conceptually map the available literature on patients' experiences and views regarding the use of TM solutions among patients with DFUs. We identified the Population, Concept and Context to pinpoint the focus of this review, word the research question and title as well as facilitate the literature search strategy. The literature examined stems from 13 sources. We imposed no restrictions on the methodological approach of the included studies, neither on the format. During the review process, four main maps emerged: "A whole human not merely a hole in a human," "Less of a burden on the family, the community and the environment," "Competences and continuity of care are essential for high-quality care" and "The quality and modality of the technology." Further investigation from both the patients' and the multi-sectoral caregivers' perspective is needed, focusing on whatever modifications of the TM intervention may fit the DFU care pathway better., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Objectives: This study aimed to analyze mortality, risk factors, and causes of death among people with tuberculosis (TB)., Methods: This is a population-based cohort study with patients with TB ≥18 years notified from 1990 to 2018 in Denmark, compared with sex- and age-matched controls. Mortality was assessed in Kaplan-Meier models and risk factors for death were estimated in Cox proportional hazards models., Results: Overall mortality was twofold higher among people with TB compared with controls up to 15 years after TB diagnosis (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 2.06-2.29, P <0.0001). Danes with TB were three times more likely to die than migrants (adjusted HR: 3.13, 95% CI: 2.84-3.45, P <0.0001). Risk factors for death included living alone, being unemployed, having low income, and comorbidities such as mental illness with substance abuse, lung diseases, hepatitis, and HIV. TB was the most common cause of death (21%), followed by chronic obstructive pulmonary disease (7%), lung cancer (6%), alcoholic liver disease (5%), and mental illness with substance abuse (4%)., Conclusion: People with TB had substantially inferior survival up to 15 years after TB diagnosis, in particular, socially disadvantaged Danes with TB with specific comorbidities. This may reflect unmet needs for enhanced treatment of other medical/social conditions during TB treatment., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n = 20) and saline (CON, n = 18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 ( p = 2.07 * 10 -9 ), 28 ( p = 0.04), and 35 ( p = 0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e., 1 week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusion, early postnatal administration of FFT, showed positive clinical effects in post-weaning pigs, albeit with subtle effects on the gut mucosa and microbiome. Prophylactic treatment with FFT may offer a means to reduce morbidity, yet larger studies are required to document effect size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Larsen, Andersen, Sato, Brunse and Thymann.)

Objective: To identify measures used within Denmark evaluating any type of intervention designed to facilitate patient involvement in healthcare., Design: Environmental scan employing rapid review methods., Data Sources: MEDLINE, PsycInfo and CINAHL were searched from 6-9 April 2021 from database inception up to the date of the search., Eligibility Criteria: Quantitative, observational and mixed methods studies with empirical data on outcomes used to assess any type of intervention aiming to increase patient involvement with their healthcare. Language limitations were Danish and English., Data Extraction and Synthesis: Two independent reviewers extracted data from 10% of the included studies and, due to their agreement, the data from the rest were extracted by first author. Data were analysed with reference to existing categories of measuring person-centred care; findings were synthesised using narrative summaries. Adapted Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines were used to guide reporting., Results: Among 3767 records, 43 studies met the inclusion criteria, including 74 different measures used to evaluate interventions aimed at increasing patient involvement within healthcare in Danish hospital and community settings. Generic measures assessed: patient engagement (n=3); supporting self-management (n=8); supporting shared decision-making (n=9); patient satisfaction and experiences of care (n=11); health-related patient-reported outcome (n=20)., Conclusions: Across Denmark, complex interventions designed to improve patient involvement with healthcare vary in their goals and content. Some targeting healthcare professionals, some patient health literacy and some service infrastructure. A plethora of measures assess the impact of these interventions on patient, professional and service delivery outcomes. Few measures assessed patient involvement directly, and it is unclear which proxy measures capture indicators of perceived involvement. Lack of conceptual clarity between intervention goals, the components of change and measures makes it difficult to see what types of intervention can best support change in services to ensure patients are more effectively involved in their healthcare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease., Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated., Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%)., Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation., Competing Interests: Declaration of competing interest CW is on an advisory board for Pfizer on COVID-19 treatments and was recently lecturing on future pandemics for pulmonology specialists for Novartis. All other authors have no competing interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The global vision is a world free of tuberculosis (TB). Even in resource-rich TB low-incidence settings, we need more focus on the role of social risk factors to end the TB epidemic., Methods: Nationwide, retrospective register-based, case-control study from 1990 to 2018, including all TB patients in Denmark ≥18 years old (n = 9581) matched 1:3 on sex and age with population controls. TB risk factors were assessed in logistic regression models and estimated by odds ratio (OR)., Results: All TB patients had considerably lower socio-economic status compared with controls (P < 0.0001). Among ethnic Danes, TB was mostly found among males, persons between 35 and 65 years, those living alone, those with low educational level, persons on social welfare benefits and those with low income. Conversely, for migrants, being younger, sex and living alone were less important, whereas having children was protective. In an adjusted multivariable regression model among Danes, key risk factors for TB were being on disability pension (OR = 2.7) and cash benefits (OR = 4.7). For migrants, fewer social risk factors increased TB risk, although low income and cash benefits did (OR = 3.1)., Conclusion: Even today in a resourceful setting, socio-economic status drives disparities in health. In our study, multifactorial social deprivation was highly associated with TB. Especially household structure, education, employment and income were important risk factors that should be addressed in the future to accelerate TB control and end the TB epidemic., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

We have investigated the function of human topoisomerase 1 (TOP1) in regulation of G-quadruplex (G4) formation in the Pu27 region of the MYC P1 promoter. Pu27 is among the best characterized G4 forming sequences in the human genome and it is well known that promoter activity is inhibited upon G4 formation in this region. We found that TOP1 downregulation stimulated transcription from a promoter with wildtype Pu27 but not if the G4 motif in Pu27 was interrupted by mutation(s). The effect was not specific to the MYC promoter and similar results were obtained for the G4 forming promoter element WT21. The other major DNA topoisomerases with relaxation activity, topoisomerases 2α and β, on the other hand, did not affect G4 dependent promoter activity. The cellular studies were supported by in vitro investigations demonstrating a high affinity of TOP1 for wildtype Pu27 but not for mutant sequences unable to form G4. Moreover, TOP1 was able to induce G4 formation in Pu27 inserted in double stranded plasmid DNA in vitro. This is the first time TOP1 has been demonstrated capable of inducing G4 formation in double stranded DNA and of influencing G4 formation in cells., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

BackgroundPregnancy increases the risk of tuberculosis (TB), however, data on TB epidemiology in pregnant women are limited.AimTo guide possible interventions, we analysed risk factors for TB in pregnant and post-partum women.MethodsWe conducted a nationwide retrospective register-based case-control study from January 1990 to December 2018 in Denmark. Cases were women diagnosed with TB during their pregnancy or in the post-partum period. We selected two control groups: pregnant or post-partum women without TB, and non-pregnant women with TB. Differences were assessed by chi-squared or Fisher's exact test. Risk factors for TB were identified through logistic regression and estimated by odds ratio (OR).ResultsWe identified 392 cases, including 286 pregnant and 106 post-partum women. Most were migrants (n = 366; 93%) with a shorter median time spent in Denmark (2.74 years; interquartile range (IQR): 1.52-4.64) than non-pregnant TB controls (3.98 years; IQR: 1.43-8.51). Cases less likely had a Charlson comorbidity index ≥ 2compared with non-pregnant TB controls (p < 0.0001), and had no increased risk of severe disease (p = 0.847). Migrants from other World Health Organization regions than Europe, especially Africa (OR: 187; 95%CI: 125-281) had persistently higher odds of TB.ConclusionsIn Denmark, the risk of TB in pregnant and post-partum women is increased in migrant women who have stayed in the country a median time of approximately 3 years. We recommend increased focus on TB risk during pregnancy and suggest evaluating targeted TB screening of selected at-risk pregnant women to promote early case finding and prevent TB among mothers and their newborn children.

Objective: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of β-cell dysfunction and insulin resistance on pre-diabetes and diabetes., Methods: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of β-cell dysfunction and insulin resistance which was categorised as follows: normal β-cell function and insulin sensitivity, isolated β-cell dysfunction, isolated insulin resistance, and combined β-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of β-cell dysfunction and insulin resistance with outcome measures., Results: β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated β-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined β-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance, respectively., Conclusions: β-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results., (© 2021 John Wiley & Sons Ltd.)

Background: We aimed to describe the use and findings of cranial computerized tomography (CT-head), spine and brain magnetic resonance imaging (MRI-spine/MRI-brain) in Lyme neuroborreliose (LNB)., Methods: Patients with LNB were identified using a nationwide, population-based prospective cohort of all adults treated for neuroinfections at departments of infectious diseases in Denmark from 2015 to 2019. Multivariate logistic regression analyses assessed associations between clinical characteristics and MRI-findings consistent with LNB., Results: We included 368 patients (272 definite LNB and 96 probable LNB), 280 scans were performed in 198 patients. Neuroimaging was associated with older age (59 vs. 57, p = 0.03), suspicion of other diseases (77% vs. 37%, p < 0.0001), no history of tick bites (58% vs. 43%, p = 0.01), physical/cognitive deficits prior to admission (15% vs 5%, p = 0.006), peripheral palsy (10% vs. 2%, p = 0.0008), encephalitis (8% vs. 1%, p = 0.0007) and cognitive impairment (8% vs. 2%, p = 0.03) compared with those without neuroimaging. Normal or incidental findings were common (93/98 CT-head and 154/182 MRI). 1/98 CT-head, 19/131 MRI-brain and 6/51 MRI-spine had findings consistent with LNB. Symptoms ≥45 days was associated with MRI-findings consistent with LNB (adjusted odds ratio (aOR) 4.2, 95%confidence interval 1.2-14.4, p = 0.02)., Conclusion: In this Danish cohort including 368 LNB-patients, use of neuroimaging was common and often performed in older comorbid patients without previous tick-bite intended to investigate alternative diagnoses. The results were in general without pathology and neuroimaging cannot exclude LNB or replace lumbar puncture. MRI is of value when investigating alternative neurological diseases and may support suspicion of LNB in cases with meningeal/leptomeningeal/neural enhancement., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The risk of active TB among solid organ transplant (SOT) recipients and patients initiating chronic dialysis in a country with low incidence of TB is not well elucidated., Methods: Patients aged >18 years who were transplanted with a solid organ or initiated chronic dialysis at Copenhagen University Hospital in the period 2004-2017 were followed from date of transplantation or initiation of dialysis. Data on demographics and outcomes were obtained from nationwide registries., Results: We included 1,989 SOT recipients and 1,305 patients initiating chronic dialysis, who were followed for a total of 9,785 and 4,196 person-years (PY), respectively. Only a minority of patients had been screened for latent TB prior to SOT or initiation of dialysis. The incidence rates (IRs)/100,000 PY of TB among patients from medium/high TB endemic areas were 358 (95% CI 115-1,110) and 1,266 (95% CI 681-2354) for SOT and dialysis patients, respectively, whereas IRs among patients of Danish origin were 11 (95% CI 2-81) and 31 (95% CI 4-218)., Conclusion: The incidence of TB among immunosuppressed immigrants from medium/high TB endemic countries was very high, while the risk of TB among patients from low-endemic countries was minimal., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Marie Helleberg et al.)

Background: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania., Methods: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes., Results: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT., Conclusions: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Camptothecin (CPT) and its derivatives are currently used as second- or third-line treatment for patients with endocrine-resistant breast cancer (BC). These drugs convert nuclear enzyme DNA topoisomerase I (TOP1) to a cell poison with the potential to damage DNA by increasing the half-life of TOP1-DNA cleavage complexes (TOP1cc), ultimately resulting in cell death. In small and non-randomized trials for BC, researchers have observed extensive variation in CPT response rates, ranging from 14 to 64%. This variability may be due to the absence of reliable selective parameters for patient stratification. BC cell lines may serve as feasible models for generation of functional criteria that may be used to predict drug sensitivity for patient stratification and, thus, lead to more appropriate applications of CPT in clinical trials. However, no study published to date has included a comparison of multiple relevant parameters and CPT response across cell lines corresponding to specific BC subtypes., Method: We evaluated the levels and possible associations of seven parameters including the status of the TOP1 gene (i.e. amplification), TOP1 protein expression level, TOP1 activity and CPT susceptibility, activity of the tyrosyl-DNA phosphodiesterase 1 (TDP1), the cellular CPT response and the cellular growth rate across a representative panel of BC cell lines, which exemplifies three major BC subtypes: Luminal, HER2 and TNBC., Results: In all BC cell lines analyzed (without regard to subtype classification), we observed a significant overall correlation between growth rate and CPT response. In cell lines derived from Luminal and HER2 subtypes, we observed a correlation between TOP1 gene copy number, TOP1 activity, and CPT response, although the data were too limited for statistical analyses. In cell lines representing Luminal and TNBC subtypes, we observed a direct correlation between TOP1 protein abundancy and levels of enzymatic activity. In all three subtypes (Luminal, HER2, and TNBC), TOP1 exhibits approximately the same susceptibility to CPT. Of the three subtypes examined, the TNBC-like cell lines exhibited the highest CPT sensitivity and were characterized by the fastest growth rate. This indicates that breast tumors belonging to the TNBC subtype, may benefit from treatment with CPT derivatives., Conclusion: TOP1 activity is not a marker for CPT sensitivity in breast cancer.

Background: Nontuberculous mycobacteria belonging to the Mycobacterium avium complex are recognized as opportunistic pathogens to humans. Mycobacterium arosiense is one of the novel members of the Mycobacterium avium complex. The organism has only rarely been reported in human clinical cases and may be routinely misidentified., Case Presentation: An adult male with a history of a discus prolapse and sarcoidosis presented with high fever and a strong back pain with projection to the extremities. A Magnetic Resonance Imaging scan of columna revealed a tumor suspect process at thoracic vertebrae 11/12 with changes at the second lumbar vertebra, which was partly removed by laminectomy. Biopsy smears revealed acid-fast bacilli and turned out to be Mycobacterium tuberculosis complex PCR negative. The routine line probe assay INNO-LiPa v2 (INNOGENETICS NV, Gent), which differentiates 16 mycobacterial species indicated the presence of a not readily identifiable NTM species. Whereas, the GenoType Mycobacterium CM v2.0 (HAIN Lifescience GmbH) that routinely differentiates 14 clinically relevant mycobacteria revealed a Mycobacterium intracellulare species. However, additional diagnostic sequencing of the 16S rRNA gene confirmed the presence of a Mycobacterium arosiense species., Conclusions: This is the second unusual case of osteomyelitis with clinical significance ever to be reported, caused by Mycobacterium arosiense and complicated by an underlying sarcoidosis. Mycobacterium arosiense has rarely been reported clinically and the first description of the species was identified as the cause of osteomyelitis in a child with a hereditary partial interferon gamma deficiency. Symptoms attributed to sarcoidosis waned on Mycobacterium arosiense treatment and it is inconclusive whether the patient ever suffered from sarcoidosis. Mycobacterium arosiense was misidentified by the GenoType as Mycobacterium intracellulare and implicates that the diagnosis requires supplemental sequencing of the 16S rRNA gene.

Several studies describe intersectoral collaboration in Western healthcare as hampered by lack of coordination of care and treatment and incoherent patient pathways. We performed an ethnographic study following elderly patients from admission to an emergency unit (EMU) to discharge and further treatment and care at other facilities in the healthcare system. The aim was to explore how health professionals work together across sectors in the Danish healthcare system and how they create patient pathways for elderly patients (+65) with multiple chronic illnesses. Intersectoral collaboration was identified as distant relations between large numbers of health professionals, where communication was conveyed by electronic health record (EHR) formats which promoted information delivery that focused on patients' immediate symptoms. Other significant 'mediators' of communication were the telephone that seemed to resemble face-to-face communication and the patient who delivered information from one professional to another. We suggest that the communication among professionals at various facilities interacts with the format and functionalities of the EHRs, which typically fall short in delivery of information across sectors, because the often complex needs of patients with multimorbidity do not fit in with the available functionalities of the EHR., (© 2019 John Wiley & Sons Ltd.)

Background: Although diabetes is more common in HIV patients, the direct link between HIV and diabetes is unknown. Glucose abnormalities should be assessed among antiretroviral treatment (ART)-naive patients to reduce confounding by ART. We assessed diabetes status, insulin function and association with inflammation among Ethiopian ART-naive HIV patients., Methods: Among HIV patients initiating ART, we used glycosylated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to define prediabetes and diabetes. Insulin during OGTT was determined to calculate insulin function, and C-reactive protein and α1-acid glycoprotein were used as same-day markers of inflammation., Results: Among 332 HIV patients, mean (SD) age was 32.9 (8.8) years, and 222 (66.9%) were women. None had known diabetes, but we found diabetes prevalence using OGTT and HbA1c to be 7.6 and 8.5%, respectively. C-reactive protein and α1-acid glycoprotein were positively associated with hyperglycemia and insulin deficiency, but not insulin resistance. We found poor correlation between traditional risk factors (age and anthropometry) and diabetes, but participants generally had low BMI and waist circumference., Conclusion: ART-naive Ethiopian HIV patients had a high prevalence of prediabetes and diabetes, with a poor agreement between HbA1c and OGTT. Diabetes was associated with inflammation, but not with adiposity and age. Diabetes was linked to insulin deficiency, rather than insulin resistance, which may represent a different entity than type 1 and 2 diabetes. This has implications for choice of drugs, when managing diabetes in African HIV patients.

Introduction: Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK)., Objectives: The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature., Methods: Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. The included studies were assessed for bias and clinical relevance. PK data were extracted to provide insight into the difference of FLD PK between HIV-positive and HIV-negative TB patients. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and its protocol was registered at PROSPERO (registration number CRD42017067250)., Results: Overall, 27 studies were eligible for inclusion. The available studies provide a heterogeneous dataset from which consistent results could not be obtained. In both HIV-positive and HIV-negative TB groups, rifampicin (13 of 15) and ethambutol (4 of 8) peak concentration (C max ) often did not achieve the minimum reference values. More than half of the studies (11 of 20) that included both HIV-positive and HIV-negative TB groups showed statistically significantly altered FLD area under the concentration-time curve and/or C max for at least one FLD., Conclusions: HIV infection may be one of several factors that reduce FLD exposure. We could not make general recommendations with respect to the role of dosing. There is a need for consistent and homogeneous studies to be conducted.

Background: Compromised cerebral energy metabolism is common in patients with bacterial meningitis. In this study, simultaneous measurements of cerebral oxygen tension and lactate/pyruvate ratio were compared to explore whether disturbed energy metabolism was usually caused by insufficient tissue oxygenation or compromised oxidative metabolism of pyruvate indicating mitochondrial dysfunction., Subject and Methods: Ten consecutive patients with severe streptococcus meningitis were included in this prospective cohort study. Intracranial pressure, brain tissue oxygen tension (PbtO 2 ), and energy metabolism (intracerebral microdialysis) were continuously monitored in nine patients. A cerebral lactate/pyruvate (LP) ratio <30 was considered indicating normal oxidative metabolism, LP ratio >30 simultaneously with pyruvate below lower normal level (70 µmol/L) was interpreted as biochemical indication of ischemia, and LP ratio >30 simultaneously with a normal or increased level of pyruvate was interpreted as mitochondrial dysfunction. The biochemical variables were compared with PbtO 2 simultaneously monitored within the same cerebral region., Results: In two cases, the LP ratio was normal during the whole study period and the simultaneously monitored PbtO 2 was 18 ± 6 mm Hg. In six cases, interpreted as mitochondrial dysfunction, the simultaneously monitored PbtO 2 was 20 ± 6 mm Hg and without correlation with the LP ratio. In one patient, exhibiting a pattern interpreted as ischemia, PbtO 2 decreased below 10 mm Hg and a correlation between LP and PbtO 2 was observed., Conclusion: This study demonstrated that compromised cerebral energy metabolism, evidenced by increased LP ratio, was common in patients with severe bacterial meningitis while not related to insufficient tissue oxygenation., (© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Elite endurance athletes possess a high capacity for whole-body maximal fat oxidation (MFO). The aim was to investigate the determinants of a high MFO in endurance athletes. The hypotheses were that augmented MFO in endurance athletes is related to concomitantly increments of skeletal muscle mitochondrial volume density (Mito VD ) and mitochondrial fatty acid oxidation (FAO p ), that is, quantitative mitochondrial adaptations as well as intrinsic FAO p per mitochondria, that is, qualitative adaptations. Eight competitive male cross-country skiers and eight untrained controls were compared in the study. A graded exercise test was performed to determine MFO, the intensity where MFO occurs (Fat Max ), and V ˙ O 2 Max . Skeletal muscle biopsies were obtained to determine Mito VD (electron microscopy), FAO p , and OXPHOS p (high-resolution respirometry). The following were higher (P < 0.05) in endurance athletes compared to controls: MFO (mean [95% confidence intervals]) (0.60 g/min [0.50-0.70] vs 0.32 [0.24-0.39]), Fat Max (46% V ˙ O 2 Max [44-47] vs 35 [34-37]), V ˙ O 2 Max (71 mL/min/kg [69-72] vs 48 [47-49]), Mito VD (7.8% [7.2-8.5] vs 6.0 [5.3-6.8]), FAO p (34 pmol/s/mg muscle ww [27-40] vs 21 [17-25]), and OXPHOS p (108 pmol/s/mg muscle ww [104-112] vs 69 [68-71]). Intrinsic FAO p (4.0 pmol/s/mg muscle w.w/Mito VD [2.7-5.3] vs 3.3 [2.7-3.9]) and OXPHOS p (14 pmol/s/mg muscle ww/Mito VD [13-15] vs 11 [10-13]) were, however, similar in the endurance athletes and untrained controls. MFO and Mito VD correlated (r 2  = 0.504, P < 0.05) in the endurance athletes. A strong correlation between Mito VD and MFO suggests that expansion of Mito VD might be rate-limiting for MFO in the endurance athletes. In contrast, intrinsic mitochondrial changes were not associated with augmented MFO., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)