Impact of ACE I gene insertion/deletion, A-240T polymorphisms and the renin-angiotensin-aldosterone system on COVID-19 disease.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to an enormous burden on patient morbidity and mortality. The renin-angiotensin-aldosterone system (RAAS) plays a significant role in various pulmonary diseases. Since SARS-CoV-2 utilizes the angiotensin-converting enzyme (ACE)2 receptor to exert its virulence and pathogenicity, the RAAS is of particular importance in COVID 19. METHODS: Our preliminary study investigates retrospectively the influence of selected ACE-polymorphisms (I/D location at intron 16 in the B-coding sequence (rs4646994) and A-240T (rs 4291) at the A-promoter) as well as ACE1 and ACE2 serum levels on disease severity and the inflammatory response in inpatients and outpatients with COVID-19. RESULTS: Our study included 96 outpatients and 88 inpatients (65.9% male, mean age 60 years) with COVID-19 from April to December 2020 in four locations in Germany. Of the hospitalized patients, 88.6% participants were moderately ill (n = 78, 64% male, median age 60 years), and 11.4% participants were severely ill or deceased (n = 10, 90% male, median age 71 years). We found no polymorphism-related difference in disease, in age distribution, time to hospitalization and time of hospitalization for the inpatient group. ACE1 serum levels were significantly increased in the DD compared to the II polymorphism and in the TT compared to the AA polymorphism. There was no significant difference in ACE 1 serum levels l between moderately ill and severely ill patients. However, participants requiring oxygen supplementation had significantly elevated ACE1 levels compared to participants not requiring oxygen, with no difference in ACE2 levels whereas females had significantly higher ACE2 levels. CONCLUSIONS: Although there were no differences in the distribution of ACE polymorphisms in disease severity, we found increased proinflammatory regulation of the RAAS in patients with oxygen demand and increased serum ACE2 levels in women, indicating a possible enhanced anti-inflammatory immune response. CLINICAL TRIAL REGISTRATION: PreBiSeCov: German Clinical Trials Register, DRKS-ID: DRKS00021591, Registered on 27th April 2020.

A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation.

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6-32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p = .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients.

Reversibility of Hypercapnia after an Acute Exacerbation of COPD.

BACKGROUND: After an episode of hypercapnic AECOPD, some patients show reversible, prolonged or persistent hypercapnic respiratory failure. However, at the time of patient discharge, it is uncertain whether patients will remain hypercapnic or may return to a physiologic gas status. METHODS: Data were retrospectively collected from COPD patients with an acute hypercapnic exacerbation (AECOPD). Out of 143 total COPD inpatients, complete data set was available for 82 patients in stable condition. According to the first available capillary or arterial pCO2, patients were divided into those with persistent hypercapnia (PHG) and those with reversible hypercapnia. RESULTS: In this study, 51% of patients with acute hypercapnic AECOPD and follow-up (FUP) visits developed normocapnia after a time period of several weeks. These patients were characterized by lower carbon dioxide partial pressure (PaCO2), HCO3-, and BE levels prior to the AECOPD event, at discharge and at FUP. pH was higher at discharge and FUP in this group. Greater disease severity and lower forced vital capacity were prominent in patients with PHG. Binary logistic regression revealed GOLD D and higher PaCO2 at discharge as predicting factors for PHG. CONCLUSIONS: A large percentage of patients has prolonged hypercapnia following acute hypercapnic COPD exacerbation. The risk profile of patients with irreversible hypercapnia should be carefully evaluated following AECOPD in order to choose selected patients for home-noninvasive ventilation.

Risk Assessment for Patients with Chronic Respiratory Conditions in the Context of the SARS-CoV-2 Pandemic Statement of the German Respiratory Society with the Support of the German Association of Chest Physicians.

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases.

Predictors of psychiatric comorbidity in cancer patients at the time of their discharge from the hospital.

PURPOSE: A cancer diagnosis can have a substantial impact on one's mental health. The present study investigated the prevalence and predictors of psychiatric comorbidities in cancer patients at the time of their discharge from the hospital. METHODS: Psychiatric comorbidities were assessed shortly before hospital discharge and half a year after hospitalization using a structured clinical interview (SCID), based on the diagnostic and statistical manual of mental disorders (DSM-IV). Frequencies at both time points were estimated using percentages and corresponding 95% confidence intervals. Predictors of mental disorders were identified using binary logistic regression models. RESULTS: At time of hospital discharge, 39 out of 334 patients (12%) were diagnosed with a psychiatric comorbidity, and 15 (7%) were diagnosed half a year later. Among the diagnoses, adjustment disorders (3%) were most frequent at the time of hospital release, while major depression (3%) was the most frequent 6 months later. Having a mental disorder was associated with unemployment (odds ratio (OR) 3.4, confidence interval (CI) 1.1-10.9, p = 0.04). There was no evidence that school education (OR 2.0, CI 0.4-9.0, p = 0.38), higher education (OR 0.7, CI 0.2-2.4, p = 0.60), income (OR 1.0, CI 1.0-1.0, p = 0.06), tumor stage (OR 1.1, CI 0.4-3.2, p = 0.85), type of disease (OR 0.6, CI 0.2-2.1, p = 0.47), pain (OR 1.0, CI 1.0-1.0, p = 0.15), fatigue (OR 1.0, CI 1.0-1.0, p = 0.77), or physical functioning (OR 1.0, CI 1.0-1.0, p = 0.54) were related to the presence of a psychiatric comorbidity. CONCLUSIONS: Unemployment was associated with at least a threefold increased risk of mental disorder, which highlights the need for special attention to be given to this subgroup of cancer patients.

Increased pulmonary serotonin transporter in patients with chronic obstructive pulmonary disease who developed pulmonary hypertension.

PURPOSE: Pulmonary hypertension (PH) is characterized by a progressive remodelling of the pulmonary vasculature resulting in right heart failure and eventually death. The serotonin transporter (SERT) may be involved in the pathogenesis of PH in patients with chronic-obstructive pulmonary disease (COPD). This study investigated for the first time the SERT in vivo availability in the lungs of patients with COPD and PH (COPD+PH). METHODS: SERT availability was assessed using SERT-selective [11C]DASB and positron emission tomography/computed tomography (PET/CT) with dynamic acquisition over 30 min in 4 groups of 5 participants each: COPD, COPD+PH, pulmonary arterial hypertension, and a healthy control (HC). Time activity curves were generated based on a volume of interest within the middle lobe. Tissue-to-blood concentration ratios after 25 to 30 min (TTBR25-30) served as receptor parameter for group comparison and were corrected for lung tissue attenuation. Participants underwent comprehensive pulmonary workup. Statistical analysis included group comparisons and correlation analysis. RESULTS: [11C]DASB uptake peak values did not differ among the cohorts after adjusting for lung tissue attenuation, suggesting equal radiotracer delivery. Both the COPD and COPD+PH cohort showed significantly lower TTBR25-30 values after correction for lung attenuation than HC. Attenuation corrected TTBR25-30 values were significantly higher in the COPD+PH cohort than those in the COPD cohort and higher in non-smokers than in smokers. They positively correlated with invasively measured severity of PH and inversely with airflow limitation and emphysema. Considering all COPD patients ± PH, they positively correlated with right heart strain (NT-proBNP). CONCLUSION: By applying [11C]DASB and PET/CT, semiquantitative measures of SERT availability are demonstrated in the lung vasculature of patients with COPD and/or PH. COPD patients who developed PH show increased pulmonary [11C]DASB uptake compared to COPD patients without PH indicating an implication of pulmonary SERT in the development of PH in COPD patients.

Returning to work in lung cancer survivors-a multi-center cross-sectional study in Germany.

PURPOSE: To investigate the work situation of lung cancer survivors and to identify the factors associated with their returning to work. METHODS: Descriptive analysis and logistic regression were used to evaluate study population characteristics and independent factors of subsequently returning to work. To analyze time to return to work, Cox regression was used. RESULTS: The study sample included 232 lung cancer survivors of working age from 717 enrolled participants in the multi-center cross-sectional LARIS (Quality of Life and Psychosocial Rehabilitation in Lung Cancer Survivors) study. About 67% of the survivors were not employed during the survey. More than 51% of the survivors who were employed before their illness did not return to their work. The survivors who had returned to their careers were younger, associated with higher household income, lower fatigue score, and stable relationship and vocational training. Patients who received social service counseling showed a higher chance of regaining their career. CONCLUSIONS: Lung cancer survivors were found to be associated with a high risk of unemployment and very low professional reintegration after interruption due to illness. More comprehensive studies are needed to support lung cancer survivors and targeting of patients in need of special attention in rehabilitation that would benefit from the findings in the present study.

[S1 Guideline Post-COVID/Long-COVID]. / S1-Leitlinie Post-COVID/Long-COVID.

The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.

Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis: long-term results of the INSIGHTS-IPF registry.

OBJECTIVE: There is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions. METHODS: We analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy. RESULTS: Among the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity (D LCO) were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and D LCO was slow and did not differ significantly between patients with or without antifibrotic therapy. CONCLUSIONS: Survival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and D LCO.

A randomized trial of everolimus-based quadruple therapy vs standard triple therapy early after lung transplantation.

Calcineurin inhibitor (CNI) therapy after lung transplantation increases risk of kidney failure. Early everolimus-based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open-label, 12-month multicenter trial was conducted at 8 German sites. Patients 3-18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate (eGFR). In the quadruple low CNI regimen, patients received everolimus (target trough level 3-5 ng/mL) with reduced CNI (tacrolimus 3-5 ng/mL or cyclosporine 25-75 ng/mL) and a cell cycle inhibitor plus prednisone. In the standard triple CNI regimen, patients received tacrolimus (target trough level >5 ng/mL) or cyclosporine (>100 ng/mL) and a cell cycle inhibitor plus prednisone. Of the 180 patients screened, 130 were randomized: 67 in the quadruple low CNI group and 63 in the standard triple CNI group. The primary endpoint (eGFR after 12 months) demonstrated superiority of the quadruple low CNI regimen: 64.5 mL/min vs 54.6 mL/min for the standard triple group (least squares mean, analysis of covariance; P < .001). Key efficacy parameters (biopsy-proven acute rejection, chronic lung allograft dysfunction, and death) and safety endpoints were similar between both groups. Quadruple low CNI immunosuppression early after lung transplantation was demonstrated to be efficacious and safe. Clinical trials registry: ClinicalTrials.gov NCT01404325.

Use of psychosocial services by lung cancer survivors in Germany : Results of a German multicenter study (LARIS).

PURPOSE: Little is known about the use of psychosocial services in lung cancer survivors and patients who have survived the diagnosis for at least one year. We investigated the frequency of use, stratified by radiation therapy received, its associated factors, and the reasons for non-use of those services. METHODS: We performed a multicenter (n = 6 hospitals) cross-sectional study using data from medical records, patient reported questionnaires, and computer-assisted telephone interviews. Odds ratios (OR) for factors potentially associated with the use of any type of psychosocial services were calculated using multivariable logistic regression. RESULTS: We included 604 lung cancer patients/survivors. Of them, 60% (69% of those who had received radiotherapy) had used some kind of psychological and/or social service in the past (47% psychological, 42% social); 39% had used inpatient care, 24% outpatient care (cancer counselling center, general counselling center, psychological counselling by family doctor, psychotherapy, patient support group, pastoral work). Of those who visited a rehabilitation clinic, 66% received psychosocial care there. Factors associated with using psychosocial services in general were female gender (OR 1.96, 95% CI 1.32-2.93), poor emotional functioning (per unit decrease: OR 0.99, 95% CI 0.98-0.996), and younger age (per year decrease: OR 0.95, 95% CI 0.93-0.97). CONCLUSIONS/IMPLICATIONS: The high proportion of psychosocial care users among lung cancer survivors in Germany indicates that patients are interested in using it and that an unmet need exists. The creation of a broad spectrum of easily accessible services with high quality is important to enable and facilitate use.

The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry.

BACKGROUND: Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry. METHODS: Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George's Respiratory Questionnaire (SGRQ) were used. RESULTS: Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DLCO% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p < 0.001) and higher UCSD-SOBQ scores and lower EQ-5D VAS and WHO-5 scores. An absolute decline in FVC% predicted of > 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DLCO % predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DLCO. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p < 0.001). All QoL scores across the follow-up period were significantly worse in hospitalised patients compared to non-hospitalised patients, with the worst scores reported in those hospitalised for acute exacerbations. CONCLUSIONS: QoL assessments in the INSIGHTS-IPF registry demonstrate a close relationship between QoL and clinically meaningful changes in lung function, comorbidities, disease duration and clinical course of IPF, including hospitalisation and mortality.

High amplitude stretching of ATII cells and fibroblasts results in profibrotic effects.

Background: Inappropriate mechanical forces act on alveolar epithelial cells during mechanical ventilation e.g. in ARDS and possibly in patients with pulmonary fibrosis. These forces can cause lung injury and may contribute to the development or aggravation of pulmonary fibrosis. Aim of the study: We investigated the hypothesis that high amplitude mechanical stretching of alveolar type II (ATII) cells and lung fibroblasts promotes profibrotic processes. Material and Methods: ATII cells and fibroblasts were stretched on elastic membranes using a pattern of higher amplitudes ("unphysiological"). The production of profibrotic cytokines and extra cellular matrix (ECM) proteins were investigated in supernatants. In addition, we determined the expression of relevant microRNAs (miRNA) and the process of epithelial-mesenchymal transition (EMT) in ATII cells. Results: Unphysiological stretch of ATII cells led to increased release of TGF-ß1 into supernatants. We also found elevated protein levels of collagen I and IV in supernatants of stretched cells. By contrast, stretching of fibroblasts changed neither the expression of fibrosis-modulating factors nor ECM-proteins. However, fibroblasts significantly withstood stretch-induced cell injury and seemed to have a survival benefit. Further, stretched ATII cells exhibited a higher expression of miRNAs (miR-15b, miR-25, let-7d) relevant to EMT. The process of EMT, which is characterized by an increase of vimentin and a decrease of cytokeratin expression, was significantly accelerated due to stretching of ATII cells. Conclusion: These data provide evidence that unphysiological mechanical stretching of lung cells induced several profibrotic effects and accelerated EMT, which may have critical implications in terms of development or aggravation of pulmonary fibrosis in the clinical context.

The association of socioeconomic status with quality of life in cancer patients over a 6-month period using individual growth models.

PURPOSE: Studies examining longitudinal associations between socioeconomic factors and quality of life (QoL) in cancer patients are rare. This study investigates changes in QoL over a 6-month period. METHODS: Four hundred forty-two cancer patients (mean age 64, SD = 11, 70% male) completed standardized questionnaires at the beginning (t1) and end (t2) of their hospital stay and 3 (t3) and 6 months (t4) thereafter. QoL was assessed with the EORTC QLQ-C30 core questionnaire. Mixed effect models were employed to analyze individual changes in QoL in relation to socioeconomic status (education, income, job status) over the four timepoints. Age, sex, cohabitation, disease and treatment factors, and comorbidity were included as covariates in the models. RESULTS: Income was a predictive factor for QoL. Patients with a low income had 8.8 percentage points (PP) lower physical, 4.9 PP lower emotional, and 11.4 PP lower role functioning. They also had 6.6 PP lower global QoL. Lower social functioning (6.2 PP) was found in patients with higher education or university degrees compared with those who were less educated or had not undergone an apprenticeship. Income also influenced trajectories of role functioning. There was no evidence that primary or secondary education and job type were related to QoL. CONCLUSIONS: The fact that income is negatively associated with many aspects of quality of life should be considered during and after treatment with a focus on patients with special needs.

Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis.

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.

Effectiveness of nasal highflow in hypercapnic COPD patients is flow and leakage dependent.

BACKGROUND: Nasal Highflow (NHF) delivers a humidified and heated airflow via nasal prongs. Current data provide evidence for efficacy of NHF in patients with hypoxemic respiratory failure. Preliminary data suggest that NHF may decrease hypercapnia in hypercapnic respiratory failure. The aim of this study was to evaluate the mechanism of NHF mediated PCO2 reduction in patients with chronic obstructive pulmonary disease (COPD). METHODS: In 36 hypercapnic COPD patients (PCO2 > 45 mmHg), hypercapnia was evaluated by capillary gas sampling 1 h after NHF breathing under four conditions A to D with different flow rates and different degrees of leakage (A = 20 L/min, low leakage, two prongs, both inside; B = 40 L/min, low leakage, two prongs, both inside; C = 40 L/min, high leakage, two prongs, one outside and open; D = 40 L/min, high leakage, two prongs, one outside and closed). Under identical conditions, mean airway pressure was measured in the hypopharynx of 10 COPD patients. RESULTS: Hypercapnia significantly decreased in all patients. In patients with capillary PCO2 > 55 mmHg (n = 26), PCO2 additionally decreased significantly by increased leakage and/or flow rate in comparison to lower leakage/ flow rate conditions (A = 94.2 ± 8.2%; B = 93.5 ± 4.4%; C = 90.5 ± 7.2%; D = 86.8 ± 3.8%). The highest mean airway pressure was observed in patients breathing under condition B (2.3 ± 1.6 mbar; p < 0.05). CONCLUSIONS: This study demonstrates effective PCO2 reduction with NHF therapy in stable hypercapnic COPD patients. This effect does not correlate with an increase in mean airway pressure but with increased leakage and airflow, indicating airway wash out and reduction of functional dead space as important mechanisms of NHF therapy. These results may be useful when considering NHF treatment in hypercapnic COPD patients. TRIAL REGISTRATION: Clinical Trials: NCT02504814; First posted July 22, 2015.

Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study.

BACKGROUND: Data are scarce regarding real-world health care resource use (HCRU) for non-small cell lung cancer (NSCLC). An understanding of current clinical practices and HCRU is needed to provide a benchmark for rapidly evolving NSCLC management recommendations and therapeutic options. The objective of this study was to describe real-world HCRU for patients with advanced NSCLC. METHODS: This multinational, retrospective chart review study was conducted at academic and community oncology sites in Italy, Spain, Germany, Australia, Japan, South Korea, Taiwan, and Brazil. Deidentified data were drawn from medical records of 1440 adults (≥18 years old) who initiated systemic therapy (2011 to mid-2013) for a new, confirmed diagnosis of advanced or metastatic (stage IIIB or IV) NSCLC. We summarized HCRU associated with first and subsequent lines of systemic therapy for advanced/metastatic NSCLC. RESULTS: The proportion of patients who were hospitalized at least once varied by country from 24% in Italy to 81% in Japan during first-line therapy and from 22% in Italy to 84% in Japan during second-line therapy; overall hospitalization frequency was 2.5-11.1 per 100 patient-weeks, depending on country. Emergency visit frequency also varied among countries (overall from 0.3-5.9 per 100 patient-weeks), increasing consistently from first- through third-line therapy in each country. The outpatient setting was the most common setting of resource use. Most patients in the study had multiple outpatient visits in association with each line of therapy (overall from 21.1 to 59.0 outpatient visits per 100 patient-weeks, depending on country). The use of health care resources showed no regular pattern associated with results of tests for activating mutations of the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. CONCLUSIONS: HCRU varied across countries. These findings suggest differing approaches to the clinical management of advanced NSCLC among the eight countries. Comparative findings and an understanding of country-specific clinical practices can help to identify areas of need and guide future resource allocation for patients with advanced NSCLC. Further studies evaluating the costs associated with resource use are warranted.

Health related quality of life in patients with idiopathic pulmonary fibrosis in clinical practice: insights-IPF registry.

BACKGROUND: The INSIGHTS-IPF registry provides one of the largest data sets of clinical data and self-reported patient related outcomes including health related quality of life (QoL) on patients with idiopathic pulmonary fibrosis (IPF). We aimed to describe associations of various QoL instruments between each other and with patient characteristics at baseline. METHODS: Six hundred twenty-three IPF patients with available QoL data (St George's Respiratory Questionnaire SGRQ, UCSD Shortness-of-Breath Questionnaire SoB, EuroQol visual analogue scale and index EQ-5D, Well-being Index WHO-5) were analysed. Mean age was 69.6 ± 8.7 years, 77% were males, mean disease duration 2.0 ± 3.3 years, FVC pred was 67.5 ± 17.8%, DLCO pred 35.6 ± 17%. RESULTS: Mean points were SGRQ total 48.3, UCSD SoB 47.8, EQ-5D VAS 66.8, and WHO-5 13.9. These instruments had a high or very high correlation (exception WHO-5 to EQ-5D VAS with moderate correlation). On bivariate analysis, QoL by SGRQ total was statistically significantly associated with clinical symptoms (NYHA; p < 0.001), number of comorbidities (p < 0.05), hospitalisation rate (p < 0.01) and disease severity (as measured by GAP score, CPI, FVC and 6-min walk test; p < 0.05 each). Multivariate analyses showed a significant association between QoL (by SGRQ total) and IPF duration, FVC, age, NYHA class and indication for long-term oxygen treatment. CONCLUSIONS: Overall, IPF patients under real-life conditions have lower QoL compared to those in clinical studies. There is a meaningful relationship between QoL and various patient characteristics. TRIAL REGISTRATION: The INSIGHTS-IPF registry is registered at Clinicaltrials.gov ( NCT01695408 ).

Effects of stepped psychooncological care on referral to psychosocial services and emotional well-being in cancer patients: A cluster-randomized phase III trial.

OBJECTIVE: Emotional distress in cancer patients often goes unnoticed in daily routine; therefore, distress screening is now recommended in many national guidelines. However, screening alone does not necessarily translate into better well-being. We examined whether stepped psychooncological care improves referral to consultation-liaison (CL) services and improves well-being. METHODS: In a cluster-randomized trial, wards were randomly allocated to stepped versus standard care. Stepped care comprised screening for distress, consultation between doctor and patient about the patient's need for CL services, and provision of CL service. Primary outcomes were referral to psychosocial services and emotional well-being half a year after baseline, measured with the Hospital Anxiety and Depression Scale. A secondary endpoint was uptake of outpatient health care. Analysis employed mixed-effects multivariate regression modeling. RESULTS: Thirteen wards were randomized; 1012 patients participated. With stepped care (N = 570; 7 wards), 22% of the patients were referred to CL services and 3% with standard care (N = 442; 6 wards; odds ratio [OR] 10.0; P < .001). Well-being 6 months after baseline was 9.5 after stepped care (N = 341) and 9.4 after standard care (N = 234, ß -0.3; P = .71). After stepped care, patients with psychiatric comorbidity went more often to psychotherapists (OR 4.0, P = .05) and to psychiatrists (OR 2.3, P = .12), whereas patients without comorbidity used psychiatrists less often (OR 0.4, P = .04) than in standard care. CONCLUSIONS: Stepped care resulted in better referral to CL services. The patients' emotional well-being was not improved, but uptake of outpatient psychiatric help was increased in patients with psychiatric comorbidity and decreased in patients without.