RETRO-POPE: A Retrospective, Multicenter, Real-World Study of All-Cause Mortality in COPD.

Purpose: The Phenotypes of COPD in Central and Eastern Europe (POPE) study assessed the prevalence and clinical characteristics of four clinical COPD phenotypes, but not mortality. This retrospective analysis of the POPE study (RETRO-POPE) investigated the relationship between all-cause mortality and patient characteristics using two grouping methods: clinical phenotyping (as in POPE) and Burgel clustering, to better identify high-risk patients. Patients and Methods: The two largest POPE study patient cohorts (Czech Republic and Serbia) were categorized into one of four clinical phenotypes (acute exacerbators [with/without chronic bronchitis], non-exacerbators, asthma-COPD overlap), and one of five Burgel clusters based on comorbidities, lung function, age, body mass index (BMI) and dyspnea (very severe comorbid, very severe respiratory, moderate-to-severe respiratory, moderate-to-severe comorbid/obese, and mild respiratory). Patients were followed-up for approximately 7 years for survival status. Results: Overall, 801 of 1,003 screened patients had sufficient data for analysis. Of these, 440 patients (54.9%) were alive and 361 (45.1%) had died at the end of follow-up. Analysis of survival by clinical phenotype showed no significant differences between the phenotypes (P=0.211). However, Burgel clustering demonstrated significant differences in survival between clusters (P<0.001), with patients in the "very severe comorbid" and "very severe respiratory" clusters most likely to die. Overall survival was not significantly different between Serbia and the Czech Republic after adjustment for age, BMI, comorbidities and forced expiratory volume in 1 second (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65-0.99; P=0.036 [unadjusted]; HR 0.88, 95% CI 0.7-1.1; P=0.257 [adjusted]). The most common causes of death were respiratory-related (36.8%), followed by cardiovascular (25.2%) then neoplasm (15.2%). Conclusion: Patient clusters based on comorbidities, lung function, age, BMI and dyspnea were more likely to show differences in COPD mortality risk than phenotypes defined by exacerbation history and presence/absence of chronic bronchitis and/or asthmatic features.

COVID-19 vaccination acceptance, safety and side-effects in European patients with severe asthma.

Background: Vaccination is vital for achieving population immunity to severe acute respiratory syndrome coronavirus 2, but vaccination hesitancy presents a threat to achieving widespread immunity. Vaccine acceptance in chronic potentially immunosuppressed patients is largely unclear, especially in patients with asthma. The aim of this study was to investigate the vaccination experience in people with severe asthma. Methods: Questionnaires about vaccination beliefs (including the Vaccination Attitudes Examination (VAX) scale, a measure of vaccination hesitancy-related beliefs), vaccination side-effects, asthma control and overall safety perceptions following coronavirus disease 2019 (COVID-19) vaccination were sent to patients with severe asthma in 12 European countries between May and June 2021. Results: 660 participants returned completed questionnaires (87.4% response rate). Of these, 88% stated that they had been, or intended to be, vaccinated, 9.5% were undecided/hesitant and 3% had refused vaccination. Patients who hesitated or refused vaccination had more negative beliefs towards vaccination. Most patients reported mild (48.2%) or no side-effects (43.8%). Patients reporting severe side-effects (5.7%) had more negative beliefs. Most patients (88.8%) reported no change in asthma symptoms after vaccination, while 2.4% reported an improvement, 5.3% a slight deterioration and 1.2% a considerable deterioration. Almost all vaccinated (98%) patients would recommend vaccination to other severe asthma patients. Conclusions: Uptake of vaccination in patients with severe asthma in Europe was high, with a small minority refusing vaccination. Beliefs predicted vaccination behaviour and side-effects. Vaccination had little impact on asthma control. Our findings in people with severe asthma support the broad message that COVID-19 vaccination is safe and well tolerated.

Implementation of the Baveno Classification in Obstructive Sleep Apnea and Its Correlation with Symptoms of Anxiety and Depression.

Background and Objectives: The Baveno classification represents a new approach to the assessment of the severity of OSA (Obstructive sleep apnea), which takes significant comorbidities into account: atrial fibrillation, arterial hypertension, heart failure, stroke, diabetes mellitus, and OSA symptoms expressed through the Epworth sleepiness scale (ESS). The authors believe that the Baveno classification facilitates a better stratification of patients with OSA and can be a good guide for deciding on the therapeutic approach and clinical monitoring of patients with OSA, compared to the AHI (apnea-hypopnea index) itself. The aim of this paper is to confirm the advantage of applying the Baveno classification to the evaluation of symptoms of anxiety and depression in the OSA patients compared to the application of the AHI as a single parameter. Materials and Methods: This research represents an observational retrospective study that was performed at the Pulmonology Clinic of the University Clinical Center in Kragujevac, Serbia. The study sample included 104 patients with diagnosed OSA. Patients were divided into four categories retrogradely according to the Baveno classification (A, B, C, and D). Statistical data processing was performed using the IBM SPSS Statistics version 25.0 program. Results: In our study, we proved that the Baveno classification is better at predicting the depressive disorder in OSA patients compared to the AHI itself, according to abnormal BDI-II (Beck Depression Inventory) score (value greater than ten) and HADS-D (Hospital anxiety and depression) scale (value greater than eight). The average AHI in the entire group of examined patients was 44.3 ± 19.8, while in category A the average AHI was 25.2 ± 10, in category B, 53.4 ± 20.6; in category C, 38.2 ± 18.5; and in category D, 48.1 ± 19.2. In the total sample, AHI did not correlate with the depressive episodes, but individually, the highest frequency of the depressive symptoms was precisely in the categories with the highest AHI (group D and B), where more than half of the subjects had an abnormal score. The frequency of the anxiety disorder (HADS-A) between the analyzed groups did not differ significantly, although the largest number of patients with significant anxiety were in category B, according to the Baveno classification. Conclusions: We proved that the Baveno classification is applicable in real life, and it is better at evaluating anxiety and depression using questionnaires and can identify new patients who need CPAP therapy, independently of other OSAS symptoms, primarily daytime sleepiness.

Transforming growth factor beta 1 (TGF-ß1) in COVID-19 patients: relation to platelets and association with the disease outcome.

Transforming growth factor beta (TGF-ß) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-ß1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-ß1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-ß1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-ß1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-ß1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-ß1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients.

Admission Predictors of Mortality in Hospitalized COVID-19 Patients-A Serbian Cohort Study.

Background: Early prediction of COVID-19 patients' mortality risk may be beneficial in adequate triage and risk assessment. Therefore, we aimed to single out the independent morality predictors of hospitalized COVID-19 patients among parameters available on hospital admission. Methods: An observational, retrospective−prospective cohort study was conducted on 703 consecutive COVID-19 patients hospitalized in the University Clinical Center Kragujevac between September and December 2021. Patients were followed during the hospitalization, and in-hospital mortality was observed as a primary end-point. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis, including complete blood cell count, inflammation biomarkers and other biochemistry, coagulation parameters, and cardiac biomarkers. Socio-demographic and medical history data were obtained using patients' medical records. Results: The overall prevalence of mortality was 28.4% (n = 199). After performing multiple regression analysis on 20 parameters, according to the initial univariate analysis, only four independent variables gave statistically significant contributions to the model: SaO2 < 88.5 % (aOR 3.075), IL-6 > 74.6 pg/mL (aOR 2.389), LDH > 804.5 U/L (aOR 2.069) and age > 69.5 years (aOR 1.786). The C-index of the predicted probability calculated using this multivariate logistic model was 0.740 (p < 0.001). Conclusions: Parameters available on hospital admission can be beneficial in predicting COVID-19 mortality.

DNA damage in peripheral blood lymphocytes of severely ill COVID-19 patients in relation to inflammatory markers and parameters of hemostasis.

Bearing in the mind that a variety of agents can contribute to genome instability, including viral infections, the aim of this study was to analyze DNA damage in hospitalized COVID-19 patients and its relationship with certain laboratory parameters. The potential impact of applied therapy and chest X-rays on DNA damage was also estimated. The study population included 24 severely COVID-19 patients and 15 healthy control subjects. The level of DNA damage was measured as genetic damage index (GDI) by comet assay. The standard laboratory methods and certified enzymatic reagents for the appropriate autoanalyzers were performed for the determination of the biochemical and hematological parameters. COVID-19 patients had significantly higher level of DNA damage compared with control subjects. The absolute number of neutrophil leukocytes was statistically higher, while the absolute number of lymphocytes was statistically lower in COVID-19 patients than in healthy controls. The analysis of the relationship between DNA damage and laboratory parameters indicated that GDI was positively correlated with interleukin 6 (IL-6) concentration and negatively with platelet count in COVID-19 patients. The level of DNA damage was slightly higher in female patients, in whom it was demonstrated a positive correlation of GDI with C-reactive protein (CRP) and procalcitonin. Likewise, there was a negative relationship of GDI and platelet count, and positive relationship of GDI and activated partial thromboplastin time (aPTT) in female population. The applied therapy (antibiotics, corticosteroid, anticoagulant, and antiviral therapy) as well as chest X rays has been shown to have genotoxic potential. The level of DNA damage significantly corresponds to the inflammatory markers and parameters of hemostasis in COVID-19 patients. In conclusion, inflammation, smoking habit, applied therapy, and chest X rays contribute to a higher level of DNA damage in COVID-19 patients.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

Cytokine producing ability of peripheral blood cells from COVID-19 patients after unspecific in vitro stimulation.

OBJECTIVE AND DESIGN: Perturbations of peripheral T cell homeostasis and dysregulation of the immune response to SARS-CoV-2, especially in severely ill patients, were observed. The aim of this study was to analyze the cytokine producing ability of peripheral blood cells from severely ill COVID-19 patients upon non-specific in vitro stimulation with phytohemagglutinin (PHA). Possible associations of cytokine levels with patients' age and gender, glucocorticosteroid therapy, as well as the trend of the inflammatory process at the time of sampling (increased or decreased) were also analyzed. SUBJECTS AND METHODS: The study included 23 COVID-19 patients and 17 healthy control subjects. The concentrations of selected Th1/Th2/Th9/Th17/Th22 cytokines were determined using a multi-analyte flow assay kit. RESULTS: Our results showed that peripheral blood cells from severely ill COVID-19 patients had a much reduced ability to produce cytokines in comparison to healthy controls. When inflammation was raised, blood cells produced more IL-6 and IL-17, which led to increases of some Th17/Th1 and Th17/Th2 ratios, skewing towards the Th17 type of response. The methylprednisolone used in the treatment of patients with COVID-19 influences the production of several cytokines in dose dependent manner. CONCLUSION: Our results indicate that the stage of the inflammatory process at the time of sampling and the dose of the applied glucocorticosteroid therapy might influence cytokine producing ability upon non-specific stimulation of T cells in vitro.

Cardiopulmonary Exercise Test in the Detection of Unexplained Post-COVID-19 Dyspnea.

There is emerging evidence of prolonged recovery in survivors of coronavirus disease 2019 (COVID-19), even in those with mild COVID-19. In this paper, we report a case of a 39-year-old male with excessive body weight and a history of borderline values of arterial hypertension without therapy, who was mainly complaining of progressive dyspnea after being diagnosed with mild COVID-19. According to the recent guidelines on the holistic assessment and management of patients who had COVID-19, all preferred diagnostic procedures, including multidetector computed tomography (CT), CT pulmonary angiogram, and echocardiography, should be conducted. However, in our patient, no underlying cardiopulmonary disorder has been established. Therefore, considering all additional symptoms our patient had beyond dyspnea, our initial differential diagnosis included anxiety-related dysfunctional breathing. However, psychiatric evaluation revealed that our patient had only a mild anxiety level, which was unlikely to provoke somatic complaints. We decided to perform further investigations considering that cardiopulmonary exercise test (CPET) represents a reliable diagnostic tool for patients with unexplained dyspnea. Finally, the CPET elucidated the diastolic dysfunction of the left ventricle, which was the most probable cause of progressive dyspnea in our patient. We suggested that, based on uncontrolled cardiovascular risk factors our patient had, COVID-19 triggered a subclinical form of heart failure (HF) with preserved ejection fraction (HFpEF) to become clinically manifest. Recently, the new onset, exacerbation, or transition from subclinical to clinical HFpEF has been associated with COVID-19. Therefore, in addition to the present literature, our case should warn physicians on HFpEF among survivors of COVID-19.

Does the Severity of Obstructive Sleep Apnea Have an Independent Impact on Systemic Inflammation?

Background and Objectives: This paper aims to show whether obstructive sleep apnea (OSA) severity increases the level of systemic inflammation markers regardless of body mass index (BMI) and body composition. Materials and Methods: In total, 128 patients with OSA were included in the study. Examinees were divided into two groups: one with mild OSA (apnea-hypopnea index (AHI) < 15) and one with moderate and severe OSA (AHI ≥ 15). Nutritional status was assessed using body mass index, body composition by dual X-ray absorptiometry. Systemic inflammation was assessed on the basis of plasma concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and serum level of C-reactive protein (CRP). Results: We found elevated mean values of the evaluated systemic inflammation markers (CRP, TNF-α, IL-6) in a group with AHI ≥ 15, although there was no statistical significance. Our research found a significant positive correlation with BMI (r = 0.633, p < 0.001), as well as with body fat percentage (r = 0.450, p = 0.024) and serum CRP values. Significant correlation was found between the plasma IL-6 concentration and body fat percentage (FM%) (r = 0.579, p = 0.003) and lean body mass (r = -0.501, p = 0.013). Multivariate regression analysis did not show any independent predictor (parameters of OSA, nutritional status, body composition) of the systemic inflammation markers. Conclusions: Neither one tested parameter (nutritional status and body composition) of the severity of OSA was identified as an independent prognostic factor for the severity of systemic inflammation in patients with OSA.

Characteristics of COPD Phenotypes in Serbia.

BACKGROUND: Establishing a regional/national/international registry of patients suffering from chronic obstructive pulmonary disease (COPD) is essential for both research and healthcare, because it enables collection of comprehensive real-life data from a large number of individuals. OBJECTIVE: The aim of this study was to describe characteristics of COPD patients from the Serbian patient registry, and to investigate actual differences of those characteristics among the COPD phenotypes. METHODS: The Serbian registry of patients with COPD was established in 2018 at University of Kragujevac, Faculty of Medical Sciences, based on an online platform. Entry in the Registry was allowed for patients who were diagnosed with COPD according to the following criteria: symptoms of dyspnea, chronic cough or sputum production, history of risk factors for COPD and any degree of persistent airflow limitation diagnosed at spirometry. RESULTS: In the Serbian COPD registry B and D GOLD group were dominant, while among the COPD phenotypes, the most prevalent were non-exacerbators (49.4%) and then frequent exacerbators without chronic bronchitis (29.6%). The frequent exacerbator with chronic bronchitis phenotype was associated with low levels of bronchopulmonary function and absolute predominance of GOLD D group. Anxiety, depression, insomnia, hypertension and chronic heart failure were the most prevalent in the frequent exacerbator with chronic bronchitis phenotype; patients with this phenotype were also treated more frequently than other patients with a triple combination of the most effective inhaled anti-obstructive drugs: long-acting muscarinic antagonists, long-acting beta 2 agonists and corticosteroids. CONCLUSION: In conclusion, the data from the Serbian registry are in line with those from other national registries, showing that frequent exacerbators with chronic bronchitis have worse bronchopulmonary function, more severe signs and symptoms, and more comorbidities (especially anxiety and depression) than other phenotypes. Other studies also confirmed worse quality of life and worse prognosis of the AE-CB phenotype, stressing importance of both preventive and appropriate therapeutic measures against chronic bronchitis.

Influence of inhaler technique on asthma and COPD control: a multicenter experience.

BACKGROUND: The successful management of asthma and chronic obstructive pulmonary disease (COPD) mostly depends on adherence to inhalation drug therapy, the usage of which is commonly associated with many difficulties in real life. Improvement of patients' adherence to inhalation technique could lead to a better outcome in the treatment of asthma and COPD. OBJECTIVE: The aim of this study was to assess the utility of inhalation technique in clinical and functional control of asthma and COPD during a 3-month follow-up. METHODS: A total of 312 patients with asthma or COPD who used dry powder Turbuhaler were enrolled in this observational study. During three visits (once a month), training in seven-step inhalation technique was given and it was practically demonstrated. Correctness of patients' usage of inhaler was assessed in three visits by scoring each of the seven steps during administration of inhaler dose. Assessment of disease control was done at each visit and evaluated as: fully controlled, partially controlled, or uncontrolled. Patients' subjective perception of the simplicity of inhalation technique, disease control, and quality of life were assessed by using specially designed questionnaires. RESULTS: Significant improvement in inhalation technique was achieved after the third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively; P<0.001). Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively; P<0.001) and from visit 2 to visit 3 (74.5% and 77%, respectively; P<0.001). Patients' subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 (P<0.001). CONCLUSION: Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment. Therefore, health care professionals should insist on educational programs aimed at improving patients' inhalation technique with different devices, resulting in better long-term disease control and improved quality of life.

Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity.

OBJECTIVE: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP), correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. METHODS: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI) and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65) scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. RESULTS: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively). The major cost drivers, in descending order, were the opportunity cost (lost productivity); diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. CONCLUSIONS: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays) in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe.

OBJETIVO: Avaliar os custos médicos diretos e indiretos de diagnóstico e tratamento para pacientes com pneumonia adquirida na comunidade (PAC), correlacionando-os com a gravidade da PAC ao diagnóstico e identificando os principais fatores de custo. MÉTODOS: Análise de custos prospectiva utilizando custo bottom-up. A gravidade clínica e o risco de mortalidade foram determinados através de pneumonia severity index (PSI) e a escala mentalConfusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65), respectivamente. A amostra foi composta por 95 pacientes hospitalizados devido a PAC recém-diagnosticada. A análise foi realizada em uma perspectiva social com um horizonte de tempo de um ano. RESULTADOS: Expressos em média ± desvio-padrão em euros, os custos médicos diretos e indiretos por paciente com PAC foram de 696 ± 531 e 410 ± 283, respectivamente, sendo, portanto, o custo total por paciente de 1.106 ± 657. O impacto orçamentário combinado deste grupo de pacientes em euros foi de 105.087 (66.109 e 38.979 nos custos diretos e indiretos, respectivamente). Os principais fatores de custo, em ordem descendente, foram custo de oportunidade (perda de produtividade); diagnóstico e tratamento de comorbidades; e administração de medicamentos, oxigênio e derivados do sangue. Os escores CURB-65 e PSI correlacionaram-se com os custos indiretos do tratamento da PAC. O escore PSI correlacionou-se positivamente com a frequência global no uso de serviços médicos. Nenhum dos escores mostrou uma relação clara com os custos diretos do tratamento da PAC. CONCLUSÕES: A gravidade clínica na admissão parece não se correlacionar com os custos do tratamento da PAC. Esses custos são principalmente causados por internações hospitalares desnecessárias (ou por internação desnecessariamente prolongada) em casos de pneumonia leve, assim como pela prescrição exagerada de antibióticos. As autoridades devem se esforçar para melhorar a adesão às diretrizes e promover práticas de prescrição custo-efetivas entre os médicos do sudeste da Europa.

Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity, / Pneumonia adquirida na comunidade: economia de cuidados médicos, em relação à gravidade clínica

Objective: To assess the direct and indirect costs of diagnosing and treating community-acquired pneumonia (CAP), correlating those costs with CAP severity at diagnosis and identifying the major cost drivers. Methods: This was a prospective cost analysis study using bottom-up costing. Clinical severity and mortality risk were assessed with the pneumonia severity index (PSI) and the mental Confusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65) scale, respectively. The sample comprised 95 inpatients hospitalized for newly diagnosed CAP. The analysis was run from a societal perspective with a time horizon of one year. Results: Expressed as mean ± standard deviation, in Euros, the direct and indirect medical costs per CAP patient were 696 ± 531 and 410 ± 283, respectively, the total per-patient cost therefore being 1,106 ± 657. The combined budget impact of our patient cohort, in Euros, was 105,087 (66,109 and 38,979 in direct and indirect costs, respectively). The major cost drivers, in descending order, were the opportunity cost (lost productivity); diagnosis and treatment of comorbidities; and administration of medications, oxygen, and blood derivatives. The CURB-65 and PSI scores both correlated with the indirect costs of CAP treatment. The PSI score correlated positively with the overall frequency of use of health care services. Neither score showed any clear relationship with the direct costs of CAP treatment. Conclusions: Clinical severity at admission appears to be unrelated to the costs of CAP treatment. This is mostly attributable to unwarranted hospital admission (or unnecessarily long hospital stays) in cases of mild pneumonia, as well as to over-prescription of antibiotics. Authorities should strive to improve adherence to guidelines and promote cost-effective prescribing practices among physicians in southeastern Europe. .

Objetivo: Avaliar os custos médicos diretos e indiretos de diagnóstico e tratamento para pacientes com pneumonia adquirida na comunidade (PAC), correlacionando-os com a gravidade da PAC ao diagnóstico e identificando os principais fatores de custo. Métodos: Análise de custos prospectiva utilizando custo bottom-up. A gravidade clínica e o risco de mortalidade foram determinados através de pneumonia severity index (PSI) e a escala mental C onfusion-Urea-Respiratory rate-Blood pressure-age ≥ 65 years (CURB-65), respectivamente. A amostra foi composta por 95 pacientes hospitalizados devido a PAC recém-diagnosticada. A análise foi realizada em uma perspectiva social com um horizonte de tempo de um ano. Resultados: Expressos em média ± desvio-padrão em euros, os custos médicos diretos e indiretos por paciente com PAC foram de 696 ± 531 e 410 ± 283, respectivamente, sendo, portanto, o custo total por paciente de 1.106 ± 657. O impacto orçamentário combinado deste grupo de pacientes em euros foi de 105.087 (66.109 e 38.979 nos custos diretos e indiretos, respectivamente). Os principais fatores de custo, em ordem descendente, foram custo de oportunidade (perda de produtividade); diagnóstico e tratamento de comorbidades; e administração de medicamentos, oxigênio e derivados do sangue. Os escores CURB-65 e PSI correlacionaram-se com os custos indiretos do tratamento da PAC. O escore PSI correlacionou-se positivamente com a frequência global no uso de serviços médicos. Nenhum dos escores mostrou uma relação clara com os custos diretos do tratamento da PAC. Conclusões: A gravidade clínica na admissão parece não se correlacionar com os custos do tratamento da PAC. Esses custos são principalmente causados por internações hospitalares desnecessárias (ou por internação desnecessariamente prolongada) em casos de pneumonia leve, assim como pela prescrição exagerada de antibióticos. As autoridades devem se esforçar para melhorar a adesão às diretrizes ...

Risk factors for brain metastases in surgically staged IIIA non-small cell lung cancer patients treated with surgery, radiotherapy and chemotherapy.

INTRODUCTION/AIM: Lung cancer is a leading cause of mortality among patients with carcinomas. The aim of this study was to point out risk factors for brain metastases (BM) appearance in patients with IIIA (N2) stage of nonsmall cell lung cancer (NSCLC) treated with three-modal therapy. METHODS: We analyzed data obtained from 107 patients with IIIA (N2) stage of NSCLC treated surgically with neoadjuvant therapy. The frequency of brain metastases was examined regarding age, sex, histological type and the size of tumor, nodal status, the sequence of radiotherapy and chemotherapy application and the type of chemotherapy. RESULTS: Two and 3-year incidence rates of BM were 35% and 46%, respectively. Forty-six percent of the patients recurred in the brain as their first failure in the period of three years. Histologically, the patients with nonsquamous cell lung carcinoma had significantly higher frequency of metastases in the brain compared with the group of squamous cell lung carcinoma (46%:30%; p = 0.021). Examining treatment-related parameters, treatment with taxane-platinum containing regimens was associated with a lower risk of brain metastases, than platinum-etoposide chemotherapy regimens (31%:52%; p = 0.011). Preoperative radiotherapy, with or without postoperative treatment, showed lower rate of metastases in the brain compared with postoperative radiotherapy treatment only (33%:48%; p = 0.035). CONCLUSION: Brain metastases are often site of recurrence in patients with NSCLC (IIIA-N2). Autonomous risk factors for brain metastases in this group of patients are non-squamous NSCLC, N1-N2 nodal status, postoperative radiotherapy without preoperative radiotherapy.

[Exercise tolerance and dyspnea in patients with chronic obstructive pulmonary disease].

BACKGROUND/AIM: Peripheral muscle weakness and nutritional disorders, firstly loss of body weight, are common findings in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to analyse the impact of pulmonary function parameters, nutritional status and state of peripheral skeletal muscles on exercise tolerance and development of dyspnea in COPD patients. METHODS: Thirty COPD patients in stable state of disease were analyzed. Standard pulmonary function tests, including spirometry, body pletysmography, and measurements of diffusion capacity were performed. The 6-minute walking distance test (6MWD) was done in order to assess exercise tolerance. Level of dyspnea was measured with Borg scale. In all patients midthigh muscle cross-sectional area (MTCSA) was measured by computerized tomography scan. Nutritional status of patients was estimated according to body mass index (BMI). RESULTS: Statisticaly significant correlations were found between parameters of pulmonary function and exercise tolerance. Level of airflow limitation and lung hyperinflation had significant impact on development of dyspnea at rest and especially after exercise. Significant positive correlation was found between MTCSA and exercise tolerance. Patients with more severe airflow limitation, lung hyperinflation and reduced diffusion capacity had significantly lower MTCSA. CONCLUSION: Exercise tolerance in COPD patients depends on severity of bronchoobstruction, lung hyperinflation and MTCSA. Severity of bronchoobstruction and lung hyperinflation have significant impact on dyspnea level.

[The influence of oxygen therapy on the hypercapnia in patients with chronic obstructive pulmonary disease].

BACKGROUND/AIM: Oxygen therapy is a necessary therapeutic method in treatment of severe chronic respiratory failure (CRF), especially in phases of acute worsening. Risks which are to be taken into consideration during this therapy are: unpredictable increase of carbon dioxide in blood, carbonarcosis, respiratory acidosis and coma. The aim of this study was to show the influence of oxygen therapy on changes of arterial blood carbon dioxide partial pressure. METHODS: The study included 93 patients in 104 admittances to the hospital due to acute exacerbation of CFR. The majority of the patients (89.4%) had chronic obstructive pulmonary disease (COPD), while other causes of respiratory failure were less common. The effect of oxygenation was controlled through measurement of PaO2 and PaCO2 in arterial blood samples. To analyse the influence of oxygen therapy on levels of carbon dioxide, greatest values of change of PaO2 and PaCO2 values from these measurements, including corresponding PaO2 values from the same blood analysis were taken. RESULTS: The obtained results show that oxygen therapy led to the increase of PaO2 but also to the increase of PaCO2. The average increase of PaO2 for the whole group of patients was 2.42 kPa, and the average increase of PaCO2 was 1.69 kPa. There was no correlation between the initial values of PaO2 and PaCO2 and changes of PaCO2 during the oxygen therapy. Also, no correlation between the produced increase in PaO2 and change in PaCO2 during this therapy was found. CONCLUSION: Controlled oxygen therapy in patients with severe respiratory failure greately reduces the risk of unwanted increase of PaCO2, but does not exclude it completely. The initial values of PaO2 and PaCO2 are not reliable parameters which could predict the response to oxygen therapy.