Pulmonary infections with nontuberculous mycobacteria.

This review focuses on the treatment of nontuberculous pulmonary disease caused by Mycobacterium avium complex and M. abscessus. It covers treatment indications, antibiotic choice, resistance and side effects. Treatment of nontuberculous pulmonary disease is complex, lengthy, and fraught with side effects. Increased attention on this disease is needed in order to alleviate the severe consequences of this growing disease. Cooperation between pulmonologists and infectious disease specialists is needed to ensure uniform treatment, and to account for the heterogeneity seen in patients and mycobacteria alike.

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up.

BACKGROUND: The epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we determine the incidence and prevalence of NTM infections and focus on social risk factors. In addition, we describe people with pulmonary and extrapulmonary NTM. RESEARCH QUESTION: What are the incidence and prevalence of NTM, and what are the characteristics of the affected patients? STUDY DESIGN AND METHODS: This is a nationwide retrospective register-based cohort study in Denmark. Adult patients in the Danish national registers who received a diagnosis of NTM disease from 2000 to 2017 were classified as having either pulmonary or extrapulmonary NTM disease. RESULTS: We identified 1,146 adults with an NTM diagnosis. Of these, 661 patients had pulmonary NTM, of whom 50.4% were male, whereas 485 had extrapulmonary NTM, of whom 59.6% were male. The median age (interquartile range) was 66 (18) years and 57 (32) years, respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary NTM (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 increased from 0.4 to 3.5 for pulmonary NTM and from 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest among those who were 70 years of age or older (19.3 per 100,000). Compared with patients with pulmonary NTM, patients with extrapulmonary NTM were more likely to be employed and had a higher educational level. INTERPRETATION: The prevalence of NTM disease in Denmark increased between 2000 and 2017. Patients with pulmonary NTM and patients with extrapulmonary NTM represent two distinct groups that differ in age, sex, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in the elderly after exclusion of more common lung infections.

Acute Exercise Increases GDF15 and Unfolded Protein Response/Integrated Stress Response in Muscle in Type 2 diabetes.

CONTEXT: Regular exercise is a key prevention strategy for obesity and type 2 diabetes (T2D). Exerkines secreted in response to exercise or recovery may contribute to improved systemic metabolism. Conversely, an impaired exerkine response to exercise and recovery may contribute to cardiometabolic diseases. OBJECTIVE: We investigated if the exercise-induced regulation of the exerkine, growth/differentiation factor 15 (GDF15) and its putative upstream regulators of the unfolded protein response (UPR)/integrated stress response (ISR) is impaired in skeletal muscle in patients with T2D compared with weight-matched glucose-tolerant men. METHODS: Thirteen male patients with T2D and 14 age- and weight-matched overweight/obese glucose-tolerant men exercised at 70% of VO2max for 1-h. Blood and skeletal muscle biopsies were sampled before, immediately after, and 3-h into recovery. Serum and muscle transcript levels of GDF15 and key markers of UPR/ISR were determined. Additionally, protein/phosphorylation levels of key regulators in UPR/ISR were investigated. RESULTS: Acute exercise increased muscle gene expression and serum GDF15 levels in both groups. In recovery, muscle expression of GDF15 decreased toward baseline, whereas serum GDF15 remained elevated. In both groups, acute exercise increased the expression of UPR/ISR markers, including ATF4, CHOP, EIF2K3 (encoding PERK) and PPP1R15A (encoding GADD34), of which only CHOP remained elevated 3-h into recovery. Downstream molecules of the UPR/ISR including XBP1-U, XBP1-S, and EDEM1 were increased with exercise and 3-h into recovery in both groups. The phosphorylation levels of eIF2α-Ser51, a common marker of UPR and ISR, increased immediately after exercise in controls, but decreased 3-h into recovery in both groups. CONCLUSION: In conclusion, exercise-induced regulation of GDF15 and key markers of UPR/ISR are not compromised in patients with type 2 diabetes compared with weight-matched controls.

Chemical Zymogens and Transmembrane Activation of Transcription in Synthetic Cells.

In this work, synthetic cells equipped with an artificial signaling pathway that connects an extracellular trigger event to the activation of intracellular transcription are engineered. Learning from nature, this is done via an engineering of responsive enzymes, such that activation of enzymatic activity can be triggered by an external biochemical stimulus. Reversibly deactivated creatine kinase to achieve triggered production of adenosine triphosphate, and a reversibly deactivated nucleic acid polymerase for on-demand synthesis of RNA are engineered. An extracellular, enzyme-activated production of a diffusible zymogen activator is also designed. The key achievement of this work is that the importance of cellularity is illustrated whereby the separation of biochemical partners is essential to resolve their incompatibility, to enable transcription within the confines of a synthetic cell. The herein designed biochemical pathway and the engineered synthetic cells are arguably primitive compared to their natural counterpart. Nevertheless, the results present a significant step toward the design of synthetic cells with responsive behavior, en route from abiotic to life-like cell mimics.

Metal-Organic Framework Glass as a Functional Filler Enables Enhanced Performance of Solid-State Polymer Electrolytes for Lithium Metal Batteries.

Polymers are promising candidates as solid-state electrolytes due to their performance and processability, but fillers play a critical role in adjusting the polymer network structure and electrochemical, thermal, and mechanical properties. Most fillers studied so far are anisotropic, limiting the possibility of homogeneous ion transport. Here, applying metal-organic framework (MOF) glass as an isotropic functional filler, solid-state polyethylene oxide (PEO) electrolytes are prepared. Calorimetric and diffusion kinetics tests show that the MOF glass addition reduces the glass transition temperature of the polymer phase, improving the mobility of the polymer chains, and thereby facilitating lithium (Li) ion transport. By also incorporating the lithium salt and ionic liquid (IL), Li-Li symmetric cell tests of the PEO-lithium salt-MOF glass-IL electrolyte reveal low overpotential, indicating low interfacial impedance. Simulations show that the isotropic structure of the MOF glass facilitates the wettability of the IL by enhancing interfacial interactions, leading to a less confined IL structure that promotes Li-ion mobility. Finally, the obtained electrolyte is used to construct Li-lithium iron phosphate full batteries that feature high cycle stability and rate capability. This work therefore demonstrates how an isotropic functional filler can be used to enhance the electrochemical performance of solid-state polymer electrolytes.

Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial.

Background: The elderly population is expanding globally. This gives numerous challenges especially regarding hip fracture patients. In the US alone over 300.000 hip fracture patients are treated each year, and a large amount of those develop opoid addiction. Hip fractures require surgical intervention within 24 h and is associated with significant pain even at rest. Postoperative analgesic treatment need to be optimized to ensure adequate pain relief and to prevent subsequent opioid addiction. Previous studies have shown that methadone effectively decreases post-operative opioid consumption but the studies focused on younger patients undergoing elective surgery. This study focus on the use of methadone on the elderly, fragile patients undergoing acute surgery, by first determining the maximal tolerable dose.The hypothesis is the maximal tolerable doses of these hip-fracture patients lies between 0.10 mg/kg and 0.20 mg/kg. This trial aims to estimate the maximum tolerable dose of methadone when administered to elderly patients undergoing surgery for a hip fracture. Method: This project is an adaptive dose-finding trial. The continuous reassessment method will estimate the maximum tolerable dose of methadone. The primary outcome will be respiratory depression. The statistical analysis plan will be published a priori to the closure of patient recruitment and statistical analysis of database results. Conclusion: The results of this study will give valuable information about the maximally tolerated dose of methadone for postoperative pain relief for elderly patients with hip fractures and potential adverse events.This trial is registered on clinicaltrials.gov with trial registration: NCT05581901. Registered 17 October 2022, https://www.clinicaltrials.gov/ct2/show/NCT05581901?term=methadone&cond = hip&draw = 2&rank = 1.

Pulmonary Mycobacterium abscessus infection treated in combination with inhaled tigecycline.

Pulmonary disease caused by Mycobacterium abscessus is difficult to treat, as there is currently no reliable evidence-based treatment. Treatment is long, complex and has many side effects. In this case, we report a patient with treatment-refractory pulmonary M abscessus disease, treated with inhaled tigecycline. Treatment with inhaled tigecycline lasted 15 months with comparably limited side effects. There were no positive mycobacterial cultures in the follow-up period of 2 years. Inhaled tigecycline is an option in the treatment of pulmonary M. abscessus when first-line treatment fails. Additional research should investigate this further.

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

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

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

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

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

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

Transmembrane signaling by a synthetic receptor in artificial cells.

Signal transduction across biological membranes is among the most important evolutionary achievements. Herein, for the design of artificial cells, we engineer fully synthetic receptors with the capacity of transmembrane signaling, using tools of chemistry. Our receptors exhibit similarity with their natural counterparts in having an exofacial ligand for signal capture, being membrane anchored, and featuring a releasable messenger molecule that performs enzyme activation as a downstream signaling event. The main difference from natural receptors is the mechanism of signal transduction, which is achieved using a self-immolative linker. The receptor scaffold is modular and can readily be re-designed to respond to diverse activation signals including biological or chemical stimuli. We demonstrate an artificial signaling cascade that achieves transmembrane enzyme activation, a hallmark of natural signaling receptors. Results of this work are relevant for engineering responsive artificial cells and interfacing them and/or biological counterparts in co-cultures.

Gram Stain and Culture of Sputum Samples Detect Only Few Pathogens in Community-Acquired Lower Respiratory Tract Infections: Secondary Analysis of a Randomized Controlled Trial.

Identification of the bacterial etiology of lower respiratory tract infections (LRTI) is crucial to ensure a narrow-spectrum, targeted antibiotic treatment. However, Gram stain and culture results are often difficult to interpret as they depend strongly on sputum sample quality. We aimed to investigate the diagnostic yield of Gram stain and culture from respiratory samples collected by tracheal suction and expiratory technique from adults admitted with suspected community-acquired LRTI (CA-LRTI). In this secondary analysis of a randomized controlled trial, 177 (62%) samples were collected by tracheal suction, and 108 (38%) by expiratory technique. We detected few pathogenic microorganisms, and regardless of sputum quality, there were no significant differences between the sample types. Common pathogens of CA-LRTI were identified by culture in 19 (7%) samples, with a significant difference between patients with or without prior antibiotic treatment (p = 0.007). The clinical value of sputum Gram stain and culture in CA-LRTI is therefore questionable, especially in patients treated with antibiotics.

Vaccine effectiveness of the pneumococcal polysaccharide and conjugated vaccines in elderly and high-risk populations in preventing invasive pneumococcal disease: a systematic search and meta-analysis.

BACKGROUND: Invasive pneumococcal disease (IPD) is a major cause of morbidity and mortality globally. However, the literature on the vaccine effectiveness (VE) of 23-valent polysaccharide vaccine (PPV23) and 13-valent conjugated vaccine (PCV13) against IPD in adults is sparse. The aim was to summarize the available evidence on the VE of the PPV23 and the PCV13 in elderly individuals against IPD and to investigate how age and comorbidities influence VE against IPD. METHODS: A systematic search was conducted in Medline and Embase in February 2021. We used combinations of terms related to PPV23, PCV13, elderly, high-risk populations, and IPD. Eligible articles published since 2010 were included. Two authors reviewed and extracted data. RESULTS: Eight studies met the inclusion criteria for PPV23. The meta-analysis showed a reduced OR for all-type IPD with the use of PPV23 vaccine compared with unvaccinated controls (OR 0.69; 95%CI 0.54, 0.88) and a reduced OR for vaccine-type IPD compared with non-vaccine type IPD (0.69; 95%CI 0.63, 0.76). VE against vaccine-type IPD ranged from 28% to 54.1% for individuals aged 65-79 and from 7.5% to 34% for those aged ≥80-85 years. Most studies found a lower VE of PPV23 in populations with comorbidities and in immunocompromised populations compared with the VE for individuals without comorbidities.One study met the inclusion criteria for PCV13. The vaccine efficacy of PCV13 against IPD in individuals aged ≥65 was 75.0% (95% CI, 41.4 to 90.8). CONCLUSION: The results from this review show a reduction of IPD in elderly and high-risk populations vaccinated with PPV23 and PCV13. The protective effect may be lower in elderly individuals aged >80 and in individuals with comorbidities. However, the literature is sparse; large-scale prospective studies are required to evaluate the VE of PPV23 and PCV13 vaccination in adults against IPD.

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

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

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

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

Expiratory Technique versus Tracheal Suction to Obtain Good-Quality Sputum from Patients with Suspected Lower Respiratory Tract Infection: A Randomized Controlled Trial.

Microbiological diagnostics of good-quality sputum samples are fundamental for infection control and targeted treatment of lower respiratory tract infections (LRTI). This study aims to compare the expiratory technique and tracheal suction on the quality of sputa from adults acutely hospitalized with suspected LRTI. We performed an open-label, randomized controlled trial. Patients were randomized to sputum sampling by tracheal suction (standard care) or the expiratory technique. The primary outcome was quality of sputum evaluated by microscopy and was analysed in the intention-to-treat population. The secondary outcomes were adverse events and patients experience. In total, 280 patients were assigned to tracheal suction (n = 141, 50.4%) or the expiratory technique (n = 139, 49.6%). Sputum samples were collected from 122 (86.5%) patients with tracheal suction and 67 (48.2%) patients with expiratory technique. Good-quality sputa were obtained more often with tracheal suction than with expiratory technique (odds ratio 1.83 [95% CI 1.05 to 3.19]; p = 0.035). There was no statistical difference in adverse events (IRR 1.21 [95% CI, 0.94 to 1.66]; p = 0.136), but patient experience was better in the expiratory technique group (p < 0.0001). In conclusion, tracheal suction should be considered a routine procedure in emergency departments for patients with suspected LRTI.

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

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

Impact of fibre and red/processed meat intake on treatment outcomes among patients with chronic inflammatory diseases initiating biological therapy: A prospective cohort study.

Background: Biologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies. Objective: To investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID. Methods: In this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14-16 weeks of treatment. Results: Of the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group (N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group (N = 129), but the difference was not statistically significant (OR: 1.48, 0.72-3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35-71.56). Conclusion: Habitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial. Trial registration: (clinicaltrials.gov), identifier [NCT03173144].

Strongyloides stercoralis hyperinfection syndrome with cerebral involvement.

Strongyloidiasis is a disease caused by the intestinal helminth Strongyloides stercoralis When the immune system of infected individuals is compromised, larvae may migrate from the gastrointestinal tract to other tissues, causing S. stercoralis hyperinfection syndrome, which has a reported mortality of 71%. In this case, we report a patient with S. stercoralis hyperinfection syndrome with central nervous system (CNS) involvement. An elderly South East Asian male tourist presented with pulmonary symptoms, fever and infiltrates on chest X-ray. He later developed symptoms of CNS infection. S. stercoralis larvae were found in a stool sample. Microbiological examination of cerebrospinal fluid revealed S. stercoralis-specific DNA. The patient was treated with oral and rectal ivermectin and albendazole. The condition was complicated by sepsis, bacteraemia and hypereosinophilia. Unfortunately, the patient eventually died from pulmonary oedema and insufficiency. This case highlights the global importance of Strongyloides CNS infection in endemic and non-endemic regions.

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

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