Extrapulmonary tuberculosis as a cause of complex perianal fistula disease.

Extrapulmonary tuberculosis (TB) in the gastrointestinal tract is a rare, but yet an essential differential diagnosis to patients with complex fistula disease, since the initiation of immunosuppressive therapy for presumed Crohn's disease can lead to a fulminant course of TB. This case report presents a young Danish woman with a progressive complex fistula disease, where cause and treatment were uncovered by interprofessional collaboration between pulmonologists, gastroenterologists and surgeons including a screening test for TB as well as multiple biopsies from the anal fistula tissue.

Mortality and exacerbations associated with Stenotrophomonas maltophilia in chronic obstructive pulmonary disease. A regional cohort study of 22,689 outpatients.

OBJECTIVES: The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD. METHODS: An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression. RESULTS: Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1). CONCLUSIONS: A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment.

Long-term non-invasive ventilation for COPD patients following an exacerbation with acute hypercapnic respiratory failure: a randomized controlled trial.

Introduction: It remains unclear whether long-term non-invasive ventilation (LT-NIV) for patients with chronic obstructive pulmonary disease (COPD) improves survival and reduces admissions as results from randomized trials are inconsistent. We aim to determine whether LT-NIV initiated after an admission with acute hypercapnic respiratory failure (AHRF) can affect survival and admission rate in COPD patients. Methods: A randomized controlled open-label trial, allocating patients with COPD to LT-NIV or standard of care immediately after an admission with AHRF treated with acute NIV. LT-NIV was aimed to normalize PaCO2 using high-pressure NIV. Results: The study was discontinued before full sample size due to slow recruitment. 28 patients were randomized to LT-NIV and 27 patients to standard of care. 42% of patients had a history of ≥ 2 admissions with AHRF. Median IPAP was 24 cmH2O (IQR 20-28). The primary outcome, time to readmission with AHRF or death within 12 months, did not reach significance, hazard ratio 0.53 (95% CI 0.25-1.12) p = 0.097. In a competing risk analysis, adjusted for history of AHRF, the odds ratio for AHRF within 12 months was 0.30 (95% CI 0.11-0.87) p = 0.024. The LT-NIV group had less exacerbations (median 1 (0-1) vs 2 (1-4) p = 0.021) and readmissions with AHRF (median 0 (0-1) vs 1 (0-1) p = 0.016). Conclusion: The risk of the primary outcome, time to readmission with AHRF or death within 12 months was numerically smaller in the LT-NIV group, however, did not reach significance. Nevertheless, several secondary outcome analyses like risk of AHRF, number of episodes of AHRF and exacerbations were all significantly reduced in favour of high-pressure LT-NIV, especially in patients with frequent AHRF.

Inhalation devices and inhaled corticosteroids particle size influence on severe pneumonia in patients with chronic obstructive pulmonary disease: a nationwide cohort study.

BACKGROUND: Inhaled corticosteroids (ICSs) are associated with an increased risk of pneumonia among patients with chronic obstructive pulmonary disease (COPD). The introduction of extrafine particle ICS has aimed to improve the distribution of medicine in the airways by altering deposition within the lungs, potentially affecting efficacy and side effects. It remains unclear if extrafine particle ICS administration alters the risk of pneumonia compared with standard particle size ICS. METHODS: An observational cohort study including all Danish COPD outpatients receiving ICS from 2010 to 2017. The primary outcome was pneumonia hospitalisation in the different ICS particle dosing regimens. The primary analysis was an adjusted Cox proportional hazards model. For sensitivity analysis, a subgroup analysis of patients receiving spray devices was done. Further, we created a propensity score matched cohort, in which we matched for the same covariates as adjusted for in the main analysis. RESULTS: A total of 35 691 patients were included of whom 1471 received extrafine particle ICS. Among these patients, 4657 were hospitalised due to pneumonia. Patients with COPD receiving extrafine particle ICS had a lower risk of hospitalisation due to pneumonia compared with patients receiving standard particle size ICS in our primary analysis (HR 0.75; 95% CI 0.63 to 0.89; p=0.002), subgroup analysis (HR 0.54; 95% CI 0.45 to 0.65; p<0.0001) and the propensity-matched population (HR 0.72; 95% CI 0.60 to 0.87; p=0.0006). INTERPRETATION: The use of extrafine particle ICS administration was associated with a lower risk of pneumonia hospitalisation in patients with COPD compared with those who received standard size treatment.

Sedating antihistamine treatment with promethazine in patients with severe COPD with and without asthma: death and severe exacerbations in a nationwide register study.

Background: Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome. Methods: Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma. Results: In our registry of 56,523 patients with COPD, 5,661 collected promethazine (n = 3,723) or melatonin (n = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis.Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27-1.58, p < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32-1.77, p < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine (p = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94-2.38, p<0.0001). Conclusions: Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.

High-pressure NIV for acute hypercapnic respiratory failure in COPD: improved survival in a retrospective cohort study.

INTRODUCTION: Updated treatment guidelines for acute hypercapnic respiratory failure (AHRF) in chronic obstructive pulmonary disease (COPD) with non-invasive ventilation (NIV) in 2016 recommended a rapid increase in inspiratory positive airway pressure (IPAP) to 20 cm H2O with possible further increase for patients not responding. Previous guidelines from 2006 suggested a more conservative algorithm and maximum IPAP of 20 cm H2O. AIM: To determine whether updated guidelines recommending higher IPAP during NIV were related with improved outcome in patients with COPD admitted with AHRF, compared with NIV with lower IPAP. METHODS: A retrospective cohort study comparing patients with COPD admitted with AHRF requiring NIV in 2012-2013 and 2017-2018. RESULTS: 101 patients were included in the 2012-2013 cohort with low IPAP regime and 80 patients in the 2017-2018 cohort with high IPAP regime. Baseline characteristics, including age, forced expiratory volume in 1 s (FEV1), pH and PaCO2 at initiation of NIV, were comparable. Median IPAP in the 2012-2013 cohort was 12 cm H2O (IQR 10-14) and 20 cm H2O (IQR 18-24) in the 2017-2018 cohort (p<0.001). In-hospital mortality was 40.5% in the 2012-2013 cohort and 13.8% in the 2017-2018 cohort (p<0.001). The 30-days and 1-year mortality were significantly lower in the 2017-2018 cohort. With a Cox model 1 year survival analysis, adjusted for age, sex, FEV1 and pH at NIV initiation, the HR was 0.45 (95% CI 0.27 to 0.74, p=0.002). CONCLUSION: Short-term and long-term survival rates were substantially higher in the cohort treated with higher IPAP. Our data support the current strategy of rapid increase and higher pressure.

Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19: a randomised double-blinded placebo-controlled trial.

BACKGROUND: Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: Placebo-controlled double-blind randomised multicentre trial. Patients aged ≥18 years, admitted to hospital for ≤48 h (not intensive care) with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR test were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice-daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (DAOH14). RESULTS: After randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on 1 February 2021. 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median (interquartile range) 9.0 (3-11) DAOH14 versus 9.0 (7-10) DAOH14 in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for one patient in the intervention group versus two patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for nine patients in the intervention group versus six patients receiving placebo (p=0.57). CONCLUSIONS: The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.

[Alpha-1-antitrypsin deficiency].

The subject of this review is alpha-1-antitrypsin deficiency (A1AD), which is a rare hereditary disease with great impact in adults, especially smokers, quality of life and longevity. Early diagnosis is crucial for treatment outcome. The primary care physician should refer patients younger than 50-years-old with COPD or emphysema, familiar accumulation of A1AD or liver cirrhosis of unknown cause. Most important treatment is smoking cessation, pulmonary rehabilitation and inhaled medication according to current guidelines. Substitution treatment with alpha-1-antitrypsin is now an option after its approval by the Danish medical council in January 2020.

Systemic Corticosteroids and the Risk of Venous Thromboembolism in Patients with Severe COPD: A Nationwide Study of 30,473 Outpatients.

Due to frequent exacerbations, many patients with chronic obstructive pulmonary disease (COPD) are exposed to oral corticosteroids (OCS), which may be thrombogenic. We evaluated the risk of hospitalisation with venous thromboembolism (VTE) and death in patients with acute exacerbation of COPD (AECOPD) treated with long and short OCS regimens. In this nationwide cohort study of 30,473 COPD outpatients treated for AECOPD, we compared the risk of VTE hospitalisation and all-cause mortality within 6 months in OCS dose of >250 mg vs. ≤250 mg. A multivariable Cox proportional hazard regression was used to estimate the risk. The incidence of VTE hospitalisations was 0.23%. A long OCS treatment course was associated with an increased risk of VTE compared to a short course (hazard ratio (HR) 1.69, [95% confidence interval (CI) 1.05 to 2.72], p < 0.031). A higher risk of all-cause mortality was seen in the group of COPD patients treated with a long OCS course (HR 1.71, [95% CI 1.63 to 1.79], p < 0.0001). The risk of reported VTE hospitalisation was higher among AECOPD patients treated with long courses of OCS, but the absolute risk was low, suggesting under-reporting of the condition.

Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. TRIAL DESIGN: This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study. PARTICIPANTS: 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals. INCLUSION CRITERIA: • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily. INTERVENTION AND COMPARATOR: Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 MAIN OUTCOMES: • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") RANDOMISATION: The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No). BLINDING (MASKING): Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study requires 226 patients randomised 1:1 with 113 in each group. TRIAL STATUS: Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Supervised pulmonary tele-rehabilitation versus pulmonary rehabilitation in severe COPD: a randomised multicentre trial.

RATIONALE: Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD. Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported. Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR). OBJECTIVE: To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR. METHODS: In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly). Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks' follow-up from baseline. The primary analysis was based on the intention-to-treat principle. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised. The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: -6.6 to 24.9)) or at 22 weeks' follow-up (-5.3 metres (95% CI: -28.9 to 18.3)). More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01). CONCLUSION: PTR was not superior to conventional PR on the 6MWD and we found no differences between groups. As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design. Trial registration number ClinicalTrials.gov (NCT02667171), 28 January 2016.

Chest x-ray findings in tuberculosis patients identified by passive and active case finding: A retrospective study.

BACKGROUND: Chest x-ray is central in screening and diagnosis of tuberculosis. However, sputum culture remains gold standard for diagnosis. AIM: To establish the rate of normal chest x-rays in tuberculosis patients found by spot sputum culture screening, and compare them to a group identified through passive case finding. METHOD: Chest x-rays from 39 culture-positive patients, identified by spot sputum culture screening in Copenhagen from 2012 to 2014, were included in the study (spot sputum culture group(SSC)). 39 normal chest x-rays from persons screened by mobile x-ray, and 39 chest x-rays from tuberculosis-patients identified through passive case finding(PCF) were anonymised and randomised. Two respiratory physicians and two radiologists assessed the chest x-rays. RESULTS: The normal chest x-ray rate was higher in the non-tuberculosis control group (median = 32 (82.1%), range = 74.4% - 100%), compared to the SSC group (median = 7 (17.9%), range = 10.3% - 33.3%), and the PCF controls (median = 3(7.7%), range = 2.6% - 15.4%). In the SSC group 14 (35.9%) were categorized as normal by at least one study participant. CONCLUSION: A substantial minority of patients diagnosed with tuberculosis by spot sputum culture screening, and through passive case finding would not have been identified with chest x-ray alone, highlighting that a normal chest x-ray does not exclude pulmonary tuberculosis.

NIV for acute respiratory failure in COPD: high in-hospital mortality is determined by patient selection.

Introduction: Hospital mortality among chronic obstructive pulmonary disease (COPD) patients receiving NIV for acute respiratory failure has shown to be significantly higher in clinical settings than in the randomized trials (RCTs) which clinical guidelines are based on. This may be due to the quality of care of NIV or patient selection. In daily clinical practice, we include patients with terminal pulmonary disease with a do-not-intubate (DNI) or a do-not-resuscitate (DNR) order with a high mortality risk compared to highly selected patients in RCTs. The aim of this study was to determine the role of patient selection for in-hospital mortality among patients receiving NIV for acute respiratory failure of COPD. Methods: We conducted a retrospective study including all patients receiving acute NIV due to acute respiratory failure at the respiratory wards in 2012-2013 at two hospitals in Greater Copenhagen. Results: Overall in-hospital mortality rate was 30%. In patients with a DNI/DNR order, mortality was 59% and in patients with no limitations in treatment 2%. Patients who fulfilled the exclusion criteria of the RCT by Plant et al. had a mortality of 41% compared to 25% in the remaining population. Conclusions: High overall in-hospital mortality reflects that patient selection in clinical practice is very different from RCT. Quality of acute NIV treatment seems acceptable in clinical practice for patients with less severe COPD and no limitations in treatment. Higher mortality in patients with DNI/DNR order may be due to inefficient NIV treatment for these patients with more severe COPD.

A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations - The CORTICO steroid reduction in COPD (CORTICO-COP) study protocol.

BACKGROUND: The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects. Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome. METHODS: This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark. The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L. The primary endpoint is length of hospital stay within 14 days after recruitment. The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage. DISCUSSION: This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02857842 , 02-august-2016. Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016.

COPD: Mortality and Readmissions in Relation to Number of Admissions with Noninvasive Ventilation.

In severe COPD, patients having survived acute hypercapnic respiratory failure (AHRF) treated with noninvasive ventilation (NIV) have a high mortality and risk of readmissions. The aim was to analyze the prognosis for patients with COPD having survived AHRF and to assess whether previous admissions with NIV predict new ones.We conducted a retrospective follow-up analysis of 201 patients two years after NIV treatment of AHRF. Comparison of time-to-event in patients previously treated with NIV versus patients with no previous NIV treatment. We found a one-year mortality of 33.8% and high risks of: readmission (53.2%), any event (67.7%), and life-threatening events (49.8%). Patients with previous NIV treatments had an increased hazard ratio for life-threatening events: 1.60, p = 0.023 despite having lower in-hospital mortality than patients with no previous NIV treatment (18.9% vs. 33.1%, p = 0.043). We found that having survived one episode of AHRF considerably worsened the prognosis for the affected patients.The prognosis for patients having survived AHRF with NIV treatment is poor: the prognosis worsens with additional episodes of AHRF. Future research and treatment should focus on patients with repeated episodes of AHRF.

Long-term non-invasive ventilation reduces readmissions in COPD patients with two or more episodes of acute hypercapnic respiratory failure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients who have had an episode of acute hypercapnic respiratory failure (AHRF) have a large 1-year risk of death or readmission. Acute non-invasive ventilation (NIV) has been shown to be an effective treatment of AHRF; and long-term NIV (LTNIV) has been shown to be an effective treatment of chronic respiratory failure in stable hypercapnic COPD. We investigated the effects of LTNIV in a group of patients with severe, unstable COPD: frequent admissions and multiple previous episodes of AHRF treated with NIV. METHODS: We conducted a retrospective analysis of 20 COPD patients treated with LTNIV after two or more episodes of AHRF during 1 year. RESULTS: The mean number of AHRF episodes decreased from 2.44 in the year prior to LTNIV initiation to 0.44 in the year following (p<0.0001). The median number of admissions decreased from 5.19 to 1.88 (p=0.0092). Four patients (20%) died in 1 year. LTNIV tended to reduce arterial CO2. No changes were found in lung function. CONCLUSIONS: LTNIV seems effective in reducing recurrent AHRF and readmissions in a highly select group of patients with severe, unstable COPD and frequent AHRF.

Home Non Invasive Ventilation (NIV) treatment for COPD patients with a history of NIV-treated exacerbation; a randomized, controlled, multi-center study.

BACKGROUND: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory failure, long-term noninvasive ventilation is controversial in unstable patients with frequent exacerbations, complicated by acute hypercapnic respiratory failure. In an uncontrolled group of patients with previous episodes of acute hypercapnic respiratory failure, treated with noninvasive ventilation, we have been able to reduce mortality and the number of repeat respiratory failure and readmissions by continuing the acute noninvasive ventilatory therapy as a long-term therapy. METHODS: Multi-center open label randomized controlled trial of 150 patients having survived an admission with noninvasive ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period. The primary endpoint is time to death or repeat acute hypercapnic respiratory failure; secondary endpoints are one-year mortality, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases. DISCUSSION: Though previous studies of long-term noninvasive ventilation have shown conflicting results, we believe the treatment can reduce mortality and readmissions when applied in patients with previous need of acute ventilatory support, regardless of persistent hypercapnia. TRIAL REGISTRATION: clinicaltrials.org: NCT01513655 16-Jan-2012.

Self-reported quality of ADL task performance among patients with COPD exacerbations.

OBJECTIVE: Patients suffering from chronic obstructive pulmonary disease (COPD) experience problems in the performance of activities of daily living (ADL) tasks. The objective was to examine the self-reported quality of ADL task performance among COPD patients, and to investigate whether age, gender, and routine COPD characteristics correlate with the self-reported ADL ability. METHODS: Eighty patients admitted to hospital with COPD exacerbations participated. In a cross-sectional study, the patients' self-reported ADL ability was assessed using the ADL-Interview (ADL-I) instrument. Data concerning age, gender, and routine COPD characteristics were drawn from the patients' medical records. RESULTS: The patients reported being inefficient to markedly inefficient when performing ADL tasks within the personal hygiene, toileting, dressing, household, mobility, and transportation domains. While more than 90% of the participants reported increased effort and/or fatigue when performing the ADL tasks, up to 88% of the participants relied on help from others in the performance of general household chores like cooking and shopping. Self-reported ADL ability did not correlate with age, gender, or routine COPD characteristics. CONCLUSIONS: Decreased quality of ADL task performance seemed to be extremely common among COPD patients. Therefore, addressing the problems in individually tailored pulmonary rehabilitation programmes may be advantageous.

[Two imported cases of West Nile fever in Denmark]. / To importerede tilfaelde af "West Nile fever" i Danmark.

In the light of the current American epidemic, and since West Nile fever (WNF) has never previously been reported in Denmark, we describe two cases imported from Israel and Canada, respectively. WNF was diagnosed in a 46-year-old Danish tourist returning from Israel and a visiting 73-year-old Canadian citizen with Danish ancestry. The former manifested itself clinically as a mild flu-like illness, the latter as serious infection of the central nervous system. Thus, in addition to representing a rare case of West Nile encephalitis, it also constitutes one of the first reported cases of human infection of Canadian origin.