Clinical characteristics governing treatment adjustment in COPD patients: results from the Swiss COPD cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a widespread chronic disease characterised by irreversible airway obstruction [1]. Features of clinical practice and healthcare systems for COPD patients can vary widely, even within similar healthcare structures. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is considered the most reliable guidance for the management of COPD and aims to provide treating physicians with appropriate insight into the disease. COPD treatment adaptation typically mirrors the suggestions within the GOLD guidelines, depending on how the patient has been categorised. However, the present study posits that the reasons for adjusting COPD-related treatment are hugely varied. OBJECTIVES: The objective of this study was to assess the clinical symptoms that govern both pharmacological and non-pharmacological treatment changes in COPD patients. Using this insight, the study offers suggestions for optimising COPD management through the implementation of GOLD guidelines. METHODS: In this observational cohort study, 24 general practitioners screened 260 COPD patients for eligibility from 2015-2019. General practitioners were asked to collect general information from patients using a standardised questionnaire to document symptoms. During a follow-up visit, the patient's symptoms and changes in therapy were assessed and entered into a central electronic database. Sixty-five patients were removed from the analysis due to exclusion criteria, and 195 patients with at least one additional visit within one year of the baseline visit were included in the analysis. A change in therapy was defined as a change in either medication or non-medical treatment, such as pulmonary rehabilitation. Multivariable mixed models were used to identify associations between given symptoms and a step up in therapy, a step down, or a step up and a step down at the same time. RESULTS: For the 195 patients included in analyses, a treatment adjustment was made during 28% of visits. In 49% of these adjustments, the change in therapy was a step up, in 33% a step down and in 18% a step up (an increase) of certain treatment factors and a step down (a reduction) of other prescribed treatments at the same time. In the multivariable analysis, we found that the severity of disease was linked to the probability of therapy adjustment: patients in GOLD Group C were more likely to experience an increase in therapy compared to patients in GOLD Group A (odds ratio [OR] 3.43 [95% confidence interval {CI}: 1.02-11.55; p = 0.135]). In addition, compared to patients with mild obstruction, patients with severe (OR 4.24 [95% CI: 1.88-9.56]) to very severe (OR 5.48 [95% CI: 1.31-22.96]) obstruction were more likely to experience a therapy increase (p <0.0001). Patients with comorbidities were less likely to experience a treatment increase than those without (OR 0.42 [95% CI: 0.24-0.73; p = 0.002]). A therapy decrease was associated with both a unit increase in COPD Assessment Test (CAT) score (OR 1.07 [95% CI: 1.01-1.14; p = 0.014]) and having experienced an exacerbation (OR 2.66 [95% CI: 1.01-6.97; p = 0.047]). The combination of steps up as well as steps down in therapy was predicted by exacerbation (OR 8.93 [95% CI: 1.16-68.28; p = 0.035]) and very severe obstruction (OR 589 [95% CI: 2.72 - >999; p = 0.109]). CONCLUSIONS: This cohort study provides insight into the management of patients with COPD in a primary care setting. COPD Group C and airflow limitation GOLD 3-4 were both associated with an increase in COPD treatment. In patients with comorbidities, there were often no treatment changes. Exacerbations did not make therapy increases more probable. The presence of neither cough/sputum nor high CAT scores was associated with a step up in treatment.

Factors Affecting Best-Tolerated Dose of Pirfenidone in Patients with Fibrosing Interstitial Lung Disease.

The aim of the study was to examine the best-tolerated dose of pirfenidone, the adverse effects profile, and potential factors other than drug dose influencing the tolerability of pirfenidone in patients with fibrosing interstitial lung diseases (ILDs). We performed an observational retrospective study of 113 patients with IPF and other fibrosing ILDs treated with pirfenidone. Baseline liver function tests (LFTs) and dose escalation of pirfenidone were recorded for all patients. The best-tolerated dose was continued if the patient did not tolerate full dose (2400 mg) despite repeated dose escalation attempts. Potential risk factors such as age, height, weight, body mass index (BMI), body surface area (BSA), gender, smoking, and presence of comorbidities were analyzed between 3 groups of best-tolerated pirfenidone doses: 2400 mg/day vs. <2400 mg/day, 2400 mg/day vs. 1800 mg/day, and 2400 mg/day vs. 1200 mg/day. A total of 24 patients tolerated 2400 mg/day, and 89 patients tolerated <2400 mg/day (43 tolerated 1800 mg/day, 45 tolerated 1200 mg/day and 1 tolerated 600 mg/day). Patients who tolerated 2400 mg/day were taller and had a larger BSA as compared to those tolerating <2400 mg/day. Overall, males tolerated the drug better. Presence of comorbidities or smoking did not affect the tolerance of pirfenidone, except for the presence of cerebrovascular diseases. Various adverse effects did not have any significantly different frequencies between the compared groups. Moreover, 71.7% of patients experienced at least one side effect. 1200 mg/day was the best-tolerated dose in the majority of the patients. Male patients with a larger BSA and greater height showed better tolerability of pirfenidone overall.

Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. METHODS: COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. RESULTS: Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). CONCLUSION: Nomograms built from these models can assist clinicians in the decision-making process of COPD care.

Predictors of Length of Stay, Rehospitalization and Mortality in Community-Acquired Pneumonia Patients: A Retrospective Cohort Study.

BACKGROUND: Community-acquired pneumonia (CAP) represents one of the leading causes of hospitalization and has a substantial impact on the financial burden of healthcare. The aim of this study was to identify factors associated with the length of hospital stay (LOHS), rehospitalization and mortality of patients admitted for CAP. METHODS: A retrospective cohort study was conducted with patients presenting to a Swiss public hospital between January 2019 and December 2019. Zero-truncated negative binomial and multivariable logistic regression analyses were performed to assess risk factors. RESULTS: A total of 300 patients were analyzed (median 78 years, IQR [67.56, 85.50] and 53% males) with an average LOHS of 7 days (IQR [5.00, 9.00]). Of the 300 patients, 31.6% (97/300) were re-hospitalized within 6 months, 2.7% (8/300) died within 30 days and 11.7% (35/300) died within 1 year. The results showed that sex (IRR = 0.877, 95% CI = 0.776-0.992, p-value = 0.036), age (IRR = 1.007, 95% CI = 1.002-1.012, p-value = 0.003), qSOFA score (IRR = 1.143, 95% CI = 1.049-1.246, p-value = 0.002) and atypical pneumonia (IRR = 1.357, 95% CI = 1.012-1.819, p-value = 0.04) were predictive of LOHS. Diabetes (OR = 2.149, 95% CI = 1.104-4.172, p-value = 0.024), a higher qSOFA score (OR = 1.958, 95% CI = 1.295-3.002, p-value = 0.002) and rehabilitation after discharge (OR = 2.222, 95% CI = 1.017-4.855, p-value = 0.044) were associated with a higher chance of being re-hospitalized within 6 months, whereas mortality within 30 days and within one year were both associated with older age (OR = 1.248, 95% CI = 1.056-1.562, p-value = 0.026 and OR = 1.073, 95% CI = 1.025-1.132, p-value = 0.005, respectively) and the presence of a cancer diagnosis (OR = 32.671, 95% CI = 4.787-369.1, p-value = 0.001 and OR = 4.408, 95% CI = 1.680-11.43, p-value = 0.002, respectively). CONCLUSION: This study identified routinely available predictors for LOHS, rehospitalization and mortality in patients with CAP, which may further advance our understanding of CAP and thereby improve patient management, discharge planning and hospital costs.

Factors associated with one-year mortality after hospital discharge: A multicenter prospective cohort study.

OBJECTIVES: 1) To identify predictors of one-year mortality in hospitalized medical patients using factors available during their hospital stay. 2) To evaluate whether healthcare system use within 30 days of hospital discharge is associated with one-year mortality. STUDY DESIGN AND SETTING: This prospective, observational study included adult patients from four mid-sized hospital general internal medicine units. During index hospitalization, we retrieved patient characteristics, including demographic and socioeconomic indicators, diagnoses, and early simplified HOSPITAL scores from electronic health records and patient interviews. Data on healthcare system use was collected using telephone interviews 30 days after discharge. Survival status at one year was collected by telephone and from health records. We used a univariable analysis including variables available from the hospitalization and 30-day post-discharge periods. We then performed multivariable analyses with one model using index hospitalization data and one using 30-day post-discharge data. RESULTS: Of 934 patients, 123 (13.2%; 95% CI 11.0-15.4%) were readmitted or died within 30 days. Of 814 patients whose primary outcome was available, 108 died (13.3%) within one year. Using factors obtained during hospitalization, the early simplified HOSPITAL score (OR 1.50; 95% CI 1.31-1.71; P < 0.001) and not living at home (OR 4.0; 95% CI 1.8-8.3; P < 0.001) were predictors of one-year mortality. Using 30-day post-discharge predictors, hospital readmission was significantly associated with one-year mortality (OR 4.81; 95% CI 2.77-8.33; P < 0.001). SIGNIFICANCE: Factors predicting one-year mortality were a high early simplified HOSPITAL score, not living at home, and a 30-day unplanned readmission.

Diagnostic Workup and Outcome in Patients with Profound Hyponatremia.

Hyponatremia is the most common electrolyte disorder. A proper diagnosis is important for its successful management, especially in profound hyponatremia. The European hyponatremia guidelines point at sodium and osmolality measurement in plasma and urine, and the clinical evaluation of volume status as the minimum diagnostic workup for the diagnosis of hyponatremia. We aimed to determine compliance with guidelines and to investigate possible associations with patient outcomes. In this retrospective study, we analysed the management of 263 patients hospitalised with profound hyponatremia at a Swiss teaching hospital between October 2019 and March 2021. We compared patients with a complete minimum diagnostic workup (D-Group) to patients without (N-Group). A minimum diagnostic workup was performed in 65.5% of patients and 13.7% did not receive any treatment for hyponatremia or an underlying cause. The twelve-month survival did not show statistically significant differences between the groups (HR 1.1, 95%-CI: 0.58-2.12, p-value 0.680). The chance of receiving treatment for hyponatremia was higher in the D-group vs. N-Group (91.9% vs. 75.8%, p-value < 0.001). A multivariate analysis showed significantly better survival for treated patients compared to not treated (HR 0.37, 95%-CI: 0.17-0.78, p-value 0.009). More efforts should be made to ensure treatment of profound hyponatremia in hospitalised patients.

Pre-treatment comorbidities, C-reactive protein and eosinophil count, and immune-related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities.

BACKGROUND: The development of immune-related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre-treatment parameters on outcome in a large, real-life patient cohort. METHODS: We performed a single-centre, retrospective, observational study including patients who received CPIs from 2011 to 2018 and followed until 2021. The primary outcome was overall survival, and the secondary outcome was the development of irAEs. RESULTS: In total, 229 patients with different tumour entities (41% non-small cell lung cancer [NSCLC], 29% melanoma) received a total of 282 CPI treatment courses (ipilimumab, nivolumab, pembrolizumab or atezolizumab). Thirty-four percent of patients developed irAEs (of these 17% had CTCAE Grade ≥3). Factors independently associated with mortality were pre-treatment CRP ≥10 mg/L (hazard ratio [HR] 2.064, p = 0.0003), comorbidity measured by Charlson comorbidity index (HR 1.149, p = 0.014) and irAEs (HR 0.644, p = 0.036) (age-adjusted, n = 216). Baseline eosinophil count ≤0.2 × 109 /L was a further independent predictor of mortality (age-, CRP-, CCI- and irAE-adjusted HR = 2.252, p = 0.002, n = 166). Anti-CTLA-4 use (p < 0.001), and pre-treatment CRP <10 mg/L were independently associated with irAE occurrence (p = 0.037). CONCLUSIONS: We found an independent association between irAE occurrence and improved overall survival in a real-life cohort spanning multiple tumour entities and treatment regimens. Pre-treatment comorbidities, CRP and eosinophil count represent potential markers for predicting treatment response.

Risk factors for hospital outcomes in pulmonary embolism: A retrospective cohort study.

Background: Pulmonary embolism (PE) is not only a life-threatening disease but also a public health issue with significant economic burden. The aim of the study was to identify factors-including the role of primary care-that predict length of hospital stay (LOHS), mortality and re-hospitalization within 6 months of patients admitted for PE. Method: A retrospective cohort study was conducted with patients presenting to a Swiss public hospital with PE diagnosed at the hospital between November 2018 and October 2020. Multivariable logistic and zero-truncated negative binomial regression analyses were performed to assess risk factors for mortality, re-hospitalization and LOHS. Primary care variables encompassed whether patients were sent by their general practitioner (GP) to the emergency department and whether a GP follow-up assessment after discharge was recommended. Further analyzed variables were pulmonary embolism severity index (PESI) score, laboratory values, comorbidities, and medical history. Results: A total of 248 patients were analyzed (median 73 years and 51.6% females). On average patients were hospitalized for 5 days (IQR 3-8). Altogether, 5.6% of these patients died in hospital, and 1.6% died within 30 days (all-cause mortality), 21.8% were re-hospitalized within 6 months. In addition to high PESI scores, we detected that, patients with an elevated serum troponin, as well as with diabetes had a significantly longer hospital stay. Significant risk factors for mortality were elevated NT-proBNP and PESI scores. Further, high PESI score and LOHS were associated with re-hospitalization within 6 months. PE patients who were sent to the emergency department by their GPs did not show improved outcomes. Follow-up with GPs did not have a significant effect on re-hospitalization. Conclusion: Defining the factors that are associated with LOHS in patients with PE has clinical implications and may help clinicians to allocate adequate resources in the management of these patients. Serum troponin and diabetes in addition to PESI score might be of prognostic use for LOHS. In this single-center cohort study, PESI score was not only a valid predictive tool for mortality but also for long-term outcomes such as re-hospitalization within 6 months.

Characteristics of Asthma Exacerbations in Emergency Care in Switzerland-Demographics, Treatment, and Burden of Disease in Patients with Asthma Exacerbations Presenting to an Emergency Department in Switzerland (CARE-S).

Emergency care for asthma is provided by general practitioners, pulmonologists, and emergency departments (EDs). Although it is known that patients presenting to EDs with acute asthma exacerbations are a vulnerable population and that this mode of presentation is a risk marker for more severe complications, research on this population is scarce. We conducted a retrospective study on patients with asthma exacerbations who presented to the ED of the University Hospital Basel, Switzerland, during 2017-2020. Of the last 200 presentations, 100 were selected and analyzed to assess demographic information, the use of previous and ED-prescribed asthma medication, and clinical outcomes after a mean period of time of 18 months. Of these 100 asthma patients, 96 were self-presenters, and 43 had the second highest degree of acuity (emergency severity index 2). Global Initiative for Asthma (GINA) step 1 and step 3 were the most common among patients with known GINA levels, accounting for 22 and 18 patients, respectively. A total of 4 patients were undergoing treatment with oral corticosteroids at presentation, and 34 were at discharge. At presentation, 38 patients used the combination therapy of inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA), and 6 patients underwent ICS monotherapy. At discharge, 68 patients were prescribed with ICS/LABA. At entry to the ED, about one-third of patients did not use any asthma medication. In total, 10 patients were hospitalized. None of them needed invasive or non-invasive ventilation. A follow-up for the study was precluded by the majority of patients. This group of asthma patients seemed particularly vulnerable as their asthma medication at presentation was often not according to guidelines or even lacking, and almost all the patients had self-presented to the ED without any reference from a physician. The majority of patients did not give consent to the collection of any follow-up information. These medical shortcomings reflect an urgent medical need to improve care for patients at high risk of asthma exacerbations.

Predictors for Unplanned Readmissions within 18 Days after Hospital Discharge: a Retrospective Cohort Study.

Since the introduction of the reimbursement system based on diagnosis-related groups (DRG) in Swiss hospitals in 2012, most readmissions occurring within 18 days and appertaining to the same major diagnostic category (MDC) are merged and thus often reimbursed to a lesser extent. While readmissions reflect increased distress for patients and their relatives, the causes are mainly patient-related and difficult to influence. However, it may be possible to identify cases at higher risk for readmission. Therefore, the aim of this study was to find predictors for early readmissions in the same MDC, to identify high-risk index hospitalizations and possibly prevent unnecessary readmissions. The data of all patients admitted to the Clinic of Internal Medicine at the University Hospital of Basel, Switzerland, hospitalized for longer than 24 hours during the pre-DRG period between October 2009 and September 2010 were retrospectively collected. Data were examined for predictors of unplanned readmission within 18 days under the same MDC ('relevant readmission') by means of logistic regression. 7479 patients (median age 67.8 years, 56% male) were admitted to the Clinic of Internal Medicine, with 232 patients (3.1%) being readmitted at least once. Logistic regression revealed male sex (p =0.035) and a high number of prescribed drugs at discharge (p <0.005) as patient-related predictors. The MDCs respiratory system, cardiovascular system, and gastrointestinal/hepatobiliary system were identified as high-risk categories (each p <0.005). Age and length of index hospital stay added no significant explanatory value to the regression model. Unplanned readmissions under the same MDC within 18 days were infrequent and not related to patients' age or length of hospital stay. Overall, multimorbid patients, and hospitalizations regarding the cardiovascular, respiratory, or gastrointestinal system appear to be most at risk and should therefore be specifically targeted in the prevention of early readmissions.

The clinical features of asthma exacerbations in early-onset and eosinophilic late-onset asthma may differ significantly.

Over 20 years ago, the concept of asthma control was created and appropriate measurement tools were developed and validated. Loss of asthma control can lead to an exacerbation. Years ago, the term "clinically significant asthma exacerbation" was introduced to define when a loss of control is severe enough to declare it an asthma exacerbation. This term is also used by health insurances to determine when an exacerbation is eligible for reimbursement of biologics in clinical practice, however, it sometimes becomes apparent that a clear separation between loss of "asthma control" and an exacerbation is not always possible. In this review, we attempt to justify why exacerbations in early allergic asthma and adult eosinophilic asthma can differ significantly and why this is important in clinical practice as well as when dealing with health insurers.

Which hospital workers do (not) want the jab? Behavioral correlates of COVID-19 vaccine willingness among employees of Swiss hospitals.

In many countries, the current vaccination rates are stagnating, to the extent that vaccine hesitancy-the delay or refusal to take recommended vaccinations-forms a major obstacle to ending the COVID-19 pandemic. This tendency is particularly concerning when observed among healthcare workers who are opinion leaders on medical matters for their patients and peers. Our study surveys 965 employees of two large Swiss hospitals and profiles vaccine-hesitant hospital employees using not only socio-demographic characteristics, but also a comprehensive set of standard behavioral preference measures: (i) Big-5 personality traits, (ii) risk-, time- and social preferences, and (iii) perceived prevailing social norms. Using multinomial probit models and linear probability models, we find that vaccine-hesitant hospital employees are less patient and less likely to perceive vaccination as the prevailing social norm-in addition to replicating previously published socio-demographic results. Our findings are robust to a range of model specifications, as well as individual and situational covariates. Our study thus offers actionable policy implications for tailoring public-health communications to vaccine-hesitant hospital employees.

ERS/ATS technical standard on interpretive strategies for routine lung function tests.

BACKGROUND: Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation. METHODS: This technical standards document was developed by an international joint Task Force, appointed by the ERS/ATS with multidisciplinary expertise in conducting and interpreting PFTs and developing international standards. A comprehensive literature review was conducted and published evidence was reviewed. RESULTS: Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments. CONCLUSIONS: Interpretation of PFTs must be complemented with clinical expertise and consideration of the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.

ERS statement: a core outcome set for clinical trials evaluating the management of COPD exacerbations.

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.

Wearing a mask-For yourself or for others? Behavioral correlates of mask wearing among COVID-19 frontline workers.

Human behavior can have effects on oneself and externalities on others. Mask wearing is such a behavior in the current pandemic. What motivates people to wear face masks in public when mask wearing is voluntary or not enforced? Which benefits should the policy makers rather emphasize in information campaigns-the reduced chances of getting the SARS-CoV-2 virus (benefits for oneself) or the reduced chances of transmitting the virus (benefits for others in the society)? In this paper, we link measured risk preferences and other-regarding preferences to mask wearing habits among 840 surveyed employees of two large Swiss hospitals. We find that the leading mask-wearing motivations change with age: While for older people, mask wearing habits are best explained by their self-regarding risk preferences, younger people are also motivated by other-regarding concerns. Our results are robust to different specifications including linear probability models, probit models and Lasso covariate selection models. Our findings thus allow drawing policy implications for effectively communicating public-health recommendations to frontline workers during the COVID-19 pandemic.

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.

Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction.

AIMS: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS AND RESULTS: This article reports the autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. CONCLUSIONS: This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.

Handgrip Strength Seems Not to Be Affected by COPD Disease Progression: A Longitudinal Cohort Study.

Skeletal muscle dysfunction, functional exercise capacity impairment and reduced physical activity are characteristic features in patients with chronic obstructive pulmonary disease (COPD). Assessments addressing muscle strength of the upper limb, such as measurement of handgrip strength (HGS), are rarely performed and reported. We aimed to analyze the course of HGS and possible predictors of changes in HGS over time in COPD. Yearly assessments of various disease markers were performed for a follow-up of up to seven years in a cohort of COPD patients to assess the longitudinal disease process. Data of 194 patients with at least one follow-up measurement were analyzed. HGS decreased significantly by B = -0.86 (95% CI -1.09/-0.62, p < 0.001) over time. The multivariate mixed effects model showed an independent association between greater annual declines in HGS and lower numbers of steps per day by B = 0.11 (95% CI 0.03/0.18, p = 0.006) and an enhanced change in COPD Assessment Test scores by B = -0.01 (95% CI -0.01/-0.00, p = 0.034). No evidence for an independent association between annual decline in HGS and FEV1% pred. by B = -0.01 (95% CI -0.03/0.01, p = 0.297) was shown. Patients who died during follow-up did not exhibit greater declines in HGS compared to survivors (p = 0.884). Although HGS significantly decreased over time, no pathophysiological link with COPD disease progression could be demonstrated. Previous cross-sectional associations between HGS and mortality could not be confirmed in this longitudinal setting. Our data suggests that repeated monitoring of HGS in clinical settings seems not to be helpful to predict COPD specific disease progression.

High Incidence of New-Onset Joint Pain in Patients on Fluoroquinolones as Antituberculous Treatment.

BACKGROUND: Joint pain is frequently observed in patients on antituberculous treatment, and pyrazinamide is known to be associated with joint pain in patients receiving antituberculous treatment. Fluoroquinolone-associated joint pain and tendon injury have been reported in long-term corticosteroid and transplant recipients, but data are lacking in patients with tuberculosis. OBJECTIVES: The objective of this study was to examine the incidence of joint pain manifested during administration of antituberculous therapy and their association with fluoroquinolones. METHODS: Patients diagnosed with tuberculosis attending the outpatient clinic over a period of 1 year were reviewed and divided into 3 groups: group A receiving pyrazinamide, group B receiving a fluoroquinolone, and group C receiving both pyrazinamide and a fluoroquinolone. Latency to onset of joint pain was noted in all 3 groups. Joint pain was initially managed with analgesics, and associated hyperuricemia was treated with allopurinol/febuxostat. Causative drugs were stopped in case of intolerable joint pain. RESULTS: 260 patients (47% females, aged 38 ± 18 years; mean ± SD) were included [group A (n = 140), group B (n = 81), and group C (n = 39)]. Overall, 76/260 (29%) patients developed joint pain: group A - 24/140 patients (17%), group B - 32/81 patients (40%), and group C - 20/39 patients (51%). The median latency to the onset of joint pain was 83 days (interquartile range, IQR 40-167): 55 days (IQR 32-66) in group A, 138 days (IQR 74-278) in group B, and 88 days (IQR 34-183) in group C. Hyperuricemia was present in 12/24 (50%) patients in group A and 11/20 (55%) patients in group C. Pyrazinamide was stopped in 7/140 (5%) patients in group A, fluoroquinolones in 6/81 (7%) patients in group B, and both pyrazinamide and fluoroquinolones were stopped in 5/39 (13%) patients in group C because of intolerable joint pain. Major joints affected were knees and ankles. CONCLUSION: There is a high incidence of joint pain in patients receiving antituberculous treatment, which is higher when fluoroquinolones or the pyrazinamide-fluoroquinolone combination are administered as compared to pyrazinamide alone.

No impact of exacerbation frequency and severity on the physical activity decline in COPD: a long-term observation.

INTRODUCTION: COPD exacerbations are associated with a concomitant profound reduction in daily physical activity (PA). Thereby, exacerbation frequency and severity may have an amplifying effect. Whether the reduced level of PA returns to the level prior to exacerbation or has a sustained negative impact on activity behavior over time is unclear. METHODS: The number of steps per day over 1 week, as a measure of daily PA, was assessed annually in a cohort of patients with COPD. Exacerbation frequency and severity were documented. Uni- and multivariate mixed effect models were used to investigate associations between change in number of steps per day (dependent variable) and exacerbations. Stratification by possible confounders was performed. RESULTS: One hundred and eighty one COPD patients (median [quartile] age 64 [59/69] years, 65% male, median [quartiles] FEV1 % pred. 46 [33/65]) suffered a total of 273 exacerbations during the observation period (median [quartiles] follow-up time of 2.1 [1.6/3.1] years). Neither the frequency nor the severity of exacerbations was significantly related to the overall decline in PA over time. Stratification by different possible confounders such as age, sex and disease severity did not yield a subgroup in which exacerbations enhance the decrease in PA over time. CONCLUSION: The drop in PA during the phase of an acute exacerbation seems not to be a lasting phenomenon leading to a fundamental change in activity behavior. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01527773.