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1.
Angew Chem Int Ed Engl ; 63(31): e202404823, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-38728623

ABSTRACT

The use of noncovalent interactions based on electrophilic halogen, chalcogen, pnictogen, or tetrel centers in organocatalysis has gained noticeable attention. Herein, we provide an overview on the most important developments in the last years with a clear focus on experimental studies and on catalysts which act via such non-transient interactions.

2.
Eur Respir J ; 61(2)2023 02.
Article in English | MEDLINE | ID: mdl-36396145

ABSTRACT

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.


Subject(s)
Lung Neoplasms , Lung , Humans , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Thorax , Societies, Medical
3.
J Water Health ; 21(12): 1772-1783, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38153711

ABSTRACT

The WHO recommends a risk management approach to ensure safe drinking-water and sanitation, so-called Water Safety Planning and Sanitation Safety Planning. However, applying these risk management approaches separately in small-scale drinking-water supply and sanitation systems might be challenging for rural communities with limited human, financial, and administrative resources. An integrated approach seems a better option. In this study, an integrated water and sanitation safety planning (iWSSP) approach was developed together with guidance and training material for the practical application of this novel approach. The integrated approach was piloted in three small systems in rural Serbia to identify benefits and suggestions for improvement which can be used for potential future scaling-up. Implementing iWSSP at the pilot sites contributed to a better understanding of both drinking-water supply and sanitation systems. It also resulted in increased awareness, knowledge, and understanding among staff of drinking-water supply and sanitation services. Key experts, including external facilitators, played a crucial role in the implementation of iWSSP. Future scaling-up of the integrated approach could be enabled if more guidance, easy-to-use training materials and templates become available which can be adapted and updated as needed.


Subject(s)
Rural Population , Water , Humans , Sanitation , Serbia , Risk Management
4.
Folia Biol (Praha) ; 69(2): 59-68, 2023.
Article in English | MEDLINE | ID: mdl-38063002

ABSTRACT

Lung cancer (LC) is the second most common malignancy and leading cause of cancer death. The potential "culprit" for local and systemic telomere shortening in LC patients is oxidative stress. We investigated the correlation between the peripheral blood leukocyte (PBL) telomere length (TL) and the presence/severity of LC and oxidative stress, and its usefulness as LC diagnostic marker. PBL TL was measured in 89 LC patients and 83 healthy subjects using the modified Cawthon RTq-PCR method. The relative PBL TL, found to be a potential diagnostic marker for LC with very good accuracy (P < 0.001), was significantly shorter in patients compared to the control group (CG) (P < 0.001). Significantly shorter telomeres were found in patients with LC TNM stage IV than in patients with stages I-III (P = 0.014), in patients without therapy compared to those on therapy (P = 0.008), and in patients with partial response and stable/progressive disease compared to those with complete response (P = 0.039). The total oxidant status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB) and C-reactive protein (CRP) were significantly higher in patients compared to CG (P < 0.001) and correlated negatively with TL in both patients and CG (P < 0.001). PCA showed a relation between PAB and TL, and between the EGFR status and TL. Oxidative stress and PBL telomere shortening are probably associated with LC development and progression.


Subject(s)
Lung Neoplasms , Telomere Shortening , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Principal Component Analysis , Leukocytes/metabolism , Oxidative Stress , Telomere
5.
Respir Res ; 23(1): 135, 2022 May 27.
Article in English | MEDLINE | ID: mdl-35624513

ABSTRACT

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) frequently have multiple comorbidities, which may influence survival but go under-recognised in clinical practice. We therefore report comorbidity, antifibrotic treatment use and survival of patients with IPF observed in the multi-national EMPIRE registry. METHODS: For this prospective IPF cohort, demographics, comorbidities, survival and causes of death were analysed. Comorbidities were noted by the treating physician based on the patient's past medical history or as reported during follow-up. Comorbidities were defined as prevalent when noted at enrolment, or as incident when recorded during follow-up. Survival was analysed by Kaplan-Meier estimates, log-rank test, and Cox proportional hazards models. Hazard ratios (HR) were adjusted for gender, age, smoking status and FVC at enrolment. RESULTS: A population of 3,580 patients with IPF from 11 Central and Eastern European countries was followed every 6 months for up to 6 years. At enrolment, 91.3% of patients reported at least one comorbidity, whereas more than one-third (37.8%) reported four or more comorbidities. Five-year survival was 53.7% in patients with no prevalent comorbidities, whereas it was 48.4%, 47.0%, 43.8% and 41.1% in patients with 1, 2, 3 and ≥ 4 comorbidities, respectively. The presence of multiple comorbidities at enrolment was associated with significantly worse survival (log-rank test P = 0.007). Adjusted HRs indicate that risk of death was increased by 44% in patients with IPF reporting ≥ 4 comorbidities at baseline compared with no comorbidity (P = 0.021). The relationship between number of comorbidities and decreased survival was also seen in patients receiving antifibrotic treatment (63% of all patients; log-rank test P < 0.001). Comorbidity as cause of death was identified in at least 26.1% of deaths. CONCLUSIONS: The majority of patients with IPF demonstrate comorbidities, and many have comorbidity-related deaths. Increasing numbers of comorbidities are associated with worse survival; and this pattern is also present in patients receiving antifibrotic therapy.


Subject(s)
Idiopathic Pulmonary Fibrosis , Comorbidity , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/epidemiology , Idiopathic Pulmonary Fibrosis/therapy , Proportional Hazards Models , Prospective Studies , Registries
6.
J Water Health ; 20(1): 12-22, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35100151

ABSTRACT

Provision of safe water, sanitation, and hygiene (WASH) services in health care facilities is a priority at the global, national, and local levels. To inform improvements planning, conditions of WASH, waste management, and environmental cleaning were assessed in 81 facilities in the Autonomous Province of Vojvodina, Serbia, as part of a nationally representative survey in 2019. The survey included on-site checks, structured interviews, and drinking-water quality analysis. WHO/UNICEF indicators for WASH service levels and an advanced service level defined at the national level were applied. The results showed that all investigated facilities provided basic water services; 94% of facilities provided basic hygiene and waste management services; 58 and 2%, respectively, provided basic cleaning and sanitation services. Only 1% of investigated facilities met the basic level for all five WASH dimensions. Advanced service levels were only met for hygiene, waste management, and/or cleaning in 15-38% of facilities. In 33% of health care facilities, drinking-water quality was not in compliance with the national standards. The results revealed that there is a need for increased awareness and efforts to ensure basic provisions for sanitation, environmental cleaning, and drinking-water safety.


Subject(s)
Sanitation , Water Supply , Delivery of Health Care , Hygiene , Serbia , Yugoslavia
7.
Medicina (Kaunas) ; 58(10)2022 Oct 06.
Article in English | MEDLINE | ID: mdl-36295566

ABSTRACT

Background: Cisplatin-induced peripheral neuropathy is a common complication of cisplatin therapy, which develops in most patients with lung cancer. There are no effective preventive measures and once it occurs there is no effective therapy, except symptomatic. In this study, we aimed to assess the effect of transcutaneous electrical nerve stimulation (TENS) therapy on the pain intensity and the quality of life of patients with cisplatin-induced neuropathy. Material and Methods: A prospective cohort study was performed from 2013 to 2018, at the Clinical Center of Serbia. After the initial evaluation of 106 newly diagnosed patients with lung cancer, 68 patients did not have peripheral neuropathy. These 68 patients continued in the study and started the cisplatin chemotherapy. Forty of these patients developed cisplatin-induced neuropathy, which was manifested by neuropathic symptoms and proven by ENG examination. All patients with cisplatin-induced neuropathy were treated with TENS therapy. Their neuropathic pain and quality of life were evaluated using the following questionnaires at diagnosis, after cisplatin therapy and after four weeks of TENS use: DN4, VAS scale, EORTC QLQ-C30 and FACT-L. Results: Two thirds (68%) of the patients with cisplatin-induced neuropathy were male and the majority were smokers (70%). Adenocarcinoma was the most common (38%), followed by squamous (33%) and small-cell carcinoma (28%). The application of TENS therapy had a positive effect on reducing the neuropathic pain and increasing the quality of life for patients with painful cisplatin-induced neuropathy. The VAS and DN4 scores significantly decreased after TENS therapy, in comparison to its values after cisplatin therapy (p < 0.001). After TENS therapy, patients had significantly higher values in most of the domains of EORTC QLQ-C30 and FACT- L, in comparison with the values after cisplatin therapy (p < 0.001). Conclusion: The application of TENS therapy has a positive effect on reducing neuropathic pain and increasing the quality of life for patients with lung cancer and cisplatin-induced neuropathy.


Subject(s)
Lung Neoplasms , Neuralgia , Transcutaneous Electric Nerve Stimulation , Humans , Male , Female , Cisplatin/adverse effects , Transcutaneous Electric Nerve Stimulation/adverse effects , Quality of Life , Prospective Studies , Lung Neoplasms/drug therapy
8.
Acta Clin Croat ; 60(1): 131-135, 2021 Mar.
Article in English | MEDLINE | ID: mdl-34588733

ABSTRACT

Approximately 5% to 15% of patients with systemic sarcoidosis develop neurological complications. However, the actual prevalence of subclinical disease may be higher. Symptoms are not specific, and may resemble those of other neurological diseases. Hydrocephalus occurs in 6% of patients with neurosarcoidosis. Acute hydrocephalus is extremely rare and when it occurs, it is usually difficult to diagnose, thus leading to possible complications. We present a patient who developed acute hydrocephalus due to neurosarcoidosis, for which he had to be operated on; soon after the operation, cranial infection developed that required definitive drainage system and ventriculoperitoneal shunt had to be implanted. In further complicated clinical course, after four years on corticosteroid therapy (corticosteroid dependent sarcoidosis), he had to be urgently operated on because of significant ventricular catheter adhesions, but several days after the operation he died in coma because of progressive brain edema not responding to treatment. As hydrocephalus due to neurosarcoidosis has high morbidity and mortality, early diagnosis and proper treatment are of utmost importance.


Subject(s)
Central Nervous System Diseases , Hydrocephalus , Sarcoidosis , Central Nervous System Diseases/complications , Central Nervous System Diseases/diagnosis , Humans , Hydrocephalus/diagnosis , Hydrocephalus/etiology , Male , Sarcoidosis/complications , Sarcoidosis/diagnosis , Skull
9.
Oncologist ; 25(3): e598-e601, 2020 03.
Article in English | MEDLINE | ID: mdl-32162818

ABSTRACT

BACKGROUND: Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries. MATERIAL AND METHODS: The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries. RESULTS: Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies-even for ALK inhibitors and checkpoint inhibitors in first-line-there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries. CONCLUSION: The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Pharmaceutical Preparations , Carcinoma, Non-Small-Cell Lung/drug therapy , Europe , Humans , Lung Neoplasms/drug therapy , Medical Oncology
10.
Respir Res ; 21(1): 11, 2020 Jan 08.
Article in English | MEDLINE | ID: mdl-31915023

ABSTRACT

BACKGROUND: Several registries of idiopathic pulmonary fibrosis (IPF) have been established to better understand its natural history, though their size and duration of follow-up are limited. Here, we describe the large European MultiPartner IPF Registry (EMPIRE) and validate predictors of long-term survival in IPF. METHODS: The multinational prospective EMPIRE registry enrolled IPF patients from 48 sites in 10 Central and Eastern European countries since 2014. Survival from IPF diagnosis until death was estimated, accounting for left-truncation. The Cox proportional hazards regression model was used to estimate adjusted hazard ratios (HR) of death for prognostic factors, using restricted cubic splines to fit continuous factors. RESULTS: The cohort included 1620 patients (mean age at diagnosis 67.6 years, 71% male, 63% smoking history), including 75% enrolled within 6 months of diagnosis. Median survival was 4.5 years, with 45% surviving 5 years post-diagnosis. Compared with GAP stage I, mortality was higher with GAP stages II (HR 2.9; 95% CI: 2.3-3.7) and III (HR 4.0; 95% CI: 2.8-5.7) while, with redefined cut-offs, the corresponding HRs were 2.7 (95% CI: 1.8-4.0) and 5.8 (95% CI: 4.0-8.3) respectively. Mortality was higher with concurrent pulmonary hypertension (HR 2.0; 95% CI: 1.5-2.9) and lung cancer (HR 2.6; 95% CI: 1.3-4.9). CONCLUSIONS: EMPIRE, one of the largest long-term registries of patients with IPF, provides a more accurate confirmation of prognostic factors and co-morbidities on longer term five-year mortality. It also suggests that some fine-tuning of the indices for mortality may provide a more accurate long-term prognostic profile for these patients.


Subject(s)
Idiopathic Pulmonary Fibrosis/epidemiology , Registries , Aged , Comorbidity , Europe/epidemiology , Female , Follow-Up Studies , Humans , Male , Prospective Studies , Reproducibility of Results , Survival Rate/trends , Time Factors
11.
12.
Eur Respir J ; 52(6)2018 12.
Article in English | MEDLINE | ID: mdl-30361252

ABSTRACT

The European Respiratory Society (ERS) task force for harmonised standards for lung cancer registration and lung cancer services in Europe recognised the need to create a single dataset for use in pan-European data collection and a manual of standards for European lung cancer services.The multidisciplinary task force considered evidence from two different sources, reviewing existing national and international datasets alongside the results of a survey of clinical data collection on lung cancer in 35 European countries. A similar process was followed for the manual of lung cancer services, with the task force using existing guidelines and national or international recommendations for lung cancer services to develop a manual of standards for services in Europe.The task force developed essential and minimum datasets for lung cancer registration to enable all countries to collect the same essential data and some to collect data with greater detail. The task force also developed a manual specifying standards for lung cancer services in Europe.Despite the wide variation in the sociopolitical landscape across Europe, the ERS is determined to encourage the delivery of high-quality lung cancer care. Both the manual of lung cancer services and the minimum dataset for lung cancer registration will support this aspiration.


Subject(s)
Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Medical Oncology/standards , Advisory Committees , Data Collection , Denmark , Europe/epidemiology , Humans , Interdisciplinary Communication , International Cooperation , Lung Neoplasms/therapy , Medical Oncology/trends , Quality of Health Care , Registries , Societies, Medical , United Kingdom
13.
Eur Respir J ; 51(1)2018 01.
Article in English | MEDLINE | ID: mdl-29371378

ABSTRACT

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.


Subject(s)
Phenotype , Sarcoidosis/diagnosis , Sarcoidosis/physiopathology , Abdomen , Acute Disease , Adult , Aged , Europe , Eye/physiopathology , Eye Diseases/physiopathology , Female , Forced Expiratory Volume , Genotype , Humans , Joint Diseases/physiopathology , Lung/physiopathology , Lung Diseases/physiopathology , Lymph Nodes/physiopathology , Male , Middle Aged , Skin/physiopathology , Skin Diseases/physiopathology , Tertiary Healthcare , White People
14.
BMC Cancer ; 18(1): 1144, 2018 Nov 20.
Article in English | MEDLINE | ID: mdl-30458807

ABSTRACT

BACKGROUND: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. METHODS: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. RESULTS: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. CONCLUSION: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.


Subject(s)
Data Collection/statistics & numerical data , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Medical Oncology/statistics & numerical data , Data Collection/methods , Databases, Factual/statistics & numerical data , Europe , Humans , Medical Oncology/methods
15.
Small ; 13(30)2017 08.
Article in English | MEDLINE | ID: mdl-28605131

ABSTRACT

Nowadays a large variety of applications are based on solid nanoparticles dispersed in liquids-so called nanofluids. The interaction between the fluid and the nanoparticles plays a decisive role in the physical properties of the nanofluid. A novel approach based on the nonradiative energy transfer between two small luminescent nanocrystals (GdVO4 :Nd3+ and GdVO4 :Yb3+ ) dispersed in water is used in this work to investigate how temperature affects both the processes of interaction between nanoparticles and the effect of the fluid on the nanoparticles. From a systematic analysis of the effect of temperature on the GdVO4 :Nd3+ → GdVO4 :Yb3+ interparticle energy transfer, it can be concluded that a dramatic increase in the energy transfer efficiency occurs for temperatures above 45 °C. This change is properly explained by taking into account a crossover existing in diverse water properties that occurs at about this temperature. The obtained results allow elucidation on the molecular arrangement of water molecules below and above this crossover temperature. In addition, it is observed that an energy transfer process is produced as a result of interparticle collisions that induce irreversible ion exchange between the interacting nanoparticles.

16.
BMC Pulm Med ; 17(1): 15, 2017 01 12.
Article in English | MEDLINE | ID: mdl-28081703

ABSTRACT

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. RESULTS: We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. CONCLUSIONS: Our results demonstrate that RNA sequencing of RNA obtained from archived FFPE lung tissues is feasible. The results obtained from FFPE tissue are highly comparable to FF tissues. The ability to perform RNA-Seq on archived FFPE IPF tissues should greatly enhance the availability of tissue biopsies for research in IPF.


Subject(s)
Gene Expression Profiling , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/pathology , Lung/pathology , RNA/analysis , Case-Control Studies , Child , Freezing , Gene Regulatory Networks , Humans , Matrix Metalloproteinase 7/genetics , Microarray Analysis , Paraffin Embedding , Sequence Analysis, RNA , United States , Wnt Signaling Pathway
17.
Am J Respir Crit Care Med ; 192(6): 727-36, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-26051272

ABSTRACT

RATIONALE: Genetic variation plays a significant role in the etiology of sarcoidosis. However, only a small fraction of its heritability has been explained so far. OBJECTIVES: To define further genetic risk loci for sarcoidosis, we used the Immunochip for a candidate gene association study of immune-associated loci. METHODS: Altogether the study population comprised over 19,000 individuals. In a two-stage design, 1,726 German sarcoidosis cases and 5,482 control subjects were genotyped for 128,705 single-nucleotide polymorphisms using the Illumina Immunochip for the screening step. The remaining 3,955 cases, 7,514 control subjects, and 684 parents of affected offspring were used for validation and replication of 44 candidate and two established risk single-nucleotide polymorphisms. MEASUREMENTS AND MAIN RESULTS: Four novel susceptibility loci were identified with genome-wide significance in the European case-control populations, located on chromosomes 12q24.12 (rs653178; ATXN2/SH2B3), 5q33.3 (rs4921492; IL12B), 4q24 (rs223498; MANBA/NFKB1), and 2q33.2 (rs6748088; FAM117B). We further defined three independent association signals in the HLA region with genome-wide significance, peaking in the BTNL2 promoter region (rs5007259), at HLA-B (rs4143332/HLA-B*0801) and at HLA-DPB1 (rs9277542), and found another novel independent signal near IL23R (rs12069782) on chromosome 1p31.3. CONCLUSIONS: Functional predictions and protein network analyses suggest a prominent role of the drug-targetable IL23/Th17 signaling pathway in the genetic etiology of sarcoidosis. Our findings reveal a substantial genetic overlap of sarcoidosis with diverse immune-mediated inflammatory disorders, which could be of relevance for the clinical application of modern therapeutics.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Sarcoidosis/genetics , Adult , Black or African American/genetics , Aged , Case-Control Studies , Europe , Female , Genetic Markers , Genotype , Humans , Male , Middle Aged , Sarcoidosis/ethnology , Sarcoidosis/immunology , White People/genetics
18.
Palliat Support Care ; 14(1): 60-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26033400

ABSTRACT

OBJECTIVE: Under conditions in which palliative care has not yet become part of clinical practice, the differences in palliative care needs between patients with cancer and other life-limiting diseases can yield knowledge that will be very valuable for future planning. The aim of our investigation was to compare health-related quality of life (HRQoL) for patients with end-stage chronic obstructive pulmonary disease (COPD) and those with non-small-cell lung cancer (NSCLC) in Belgrade, Serbia. We also evaluated the influence of demographic, socioeconomic, and clinical factors on HRQoL for both patient groups. METHOD: This cross-sectional study included 100 NSCLC patients (stages IIIb and IV) and 100 patients with stage IV COPD. Measures included the SF-36 questionnaire, the EORTC QLQ-C30, the St. George's Respiratory Questionnaire, and the Beck Depression Inventory (BDI). Associations of demographic, socioeconomic, and clinical factors with QoL were examined using linear regression analyses. RESULTS: The COPD group scored significantly lower compared to NSCLC patients in all SF-36 domains except for bodily pain. Additionally, a significantly higher level of depressive symptoms was observed in COPD patients. A worse physical QoL for COPD patients was independently associated with a longer duration of unemployment, a lack of wage earning, lower Karnofsky Performance Status (KPS) scores, and higher levels of depression. A worse mental QoL for COPD patients was related to a longer duration of disease, poorer KPS scores, and higher BDI scores. The independent variables significantly associated with worse physical and mental QoL of NSCLC patients were lower KPS and higher BDI scores. SIGNIFICANCE OF RESULTS: A worse QoL, a significantly higher level of depressive symptoms, and adverse socioeconomic status in the COPD group imposes the need for development of more intensive psychosocial and community support for COPD patients during implementation of palliative care.


Subject(s)
Carcinoma, Non-Small-Cell Lung/psychology , Pulmonary Disease, Chronic Obstructive/psychology , Quality of Life/psychology , Terminal Care/psychology , Aged , Cross-Sectional Studies , Female , Humans , Karnofsky Performance Status , Male , Middle Aged , Psychiatric Status Rating Scales , Serbia , Surveys and Questionnaires
19.
Eur Respir J ; 43(5): 1254-77, 2014 May.
Article in English | MEDLINE | ID: mdl-24659546

ABSTRACT

Lung cancer is the commonest cause of cancer-related death worldwide and poses a significant respiratory disease burden. Little is known about the provision of lung cancer care across Europe. The overall aim of the Task Force was to investigate current practice in lung cancer care across Europe. The Task Force undertook four projects: 1) a narrative literature search on quality management of lung cancer; 2) a survey of national and local infrastructure for lung cancer care in Europe; 3) a benchmarking project on the quality of (inter)national lung cancer guidelines in Europe; and 4) a feasibility study of prospective data collection in a pan-European setting. There is little peer-reviewed literature on quality management in lung cancer care. The survey revealed important differences in the infrastructure of lung cancer care in Europe. The European guidelines that were assessed displayed wide variation in content and scope, as well as methodological quality but at the same time there was relevant duplication. The feasibility study demonstrated that it is, in principle, feasible to collect prospective demographic and clinical data on patients with lung cancer. Legal obligations vary among countries. The European Initiative for Quality Management in Lung Cancer Care has provided the first comprehensive snapshot of lung cancer care in Europe.


Subject(s)
Lung Neoplasms/therapy , Quality of Health Care , Benchmarking , Data Collection , Europe , Healthcare Disparities , Humans , International Cooperation , Lung Neoplasms/diagnosis , Multivariate Analysis , Neoplasm Staging , Outcome Assessment, Health Care , Practice Guidelines as Topic , Referral and Consultation , Review Literature as Topic
20.
J Clin Med ; 13(8)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38673704

ABSTRACT

Background: Lumbar pain is a condition of discomfort in the lower back caused by numerous factors, lasting for short or longer periods of time. Healthcare professionals, regardless of the type of care they are engaged in, are at risk of lumbar pain. This is the first study that deals with the problem of lumbar syndrome in health workers in Montenegro. Methods: This cross-sectional study included full-time health workers employed in the Clinical Center of Montenegro who were involved in the treatment of COVID-19 patients during 2020 and 2021. The survey consisted of general questions for collecting socio-demographic and COVID-19 engagement data; the Modified Nordic questionnaire was used for the analysis of musculoskeletal symptoms, and the EQ-5D-questionnaire was used to measure the quality of life associated with health. Results: The one-year prevalence of lumbar pain was 68.1%. Factors associated with lumbar pain were as follows: a higher degree of physical inactivity (each subject with a higher degree of physical inactivity had a 24% higher chance of occurrence of lumbar pain); a higher degree of load and over-engagement during the COVID-19 pandemic (each subject with a higher degree of workload had a nearly 50% higher chance of occurrence of lumbar pain); duration of engagement during the COVID-19 pandemic (subjects engaged up to a month were 4 times more likely to develop lumbar pain, and subjects engaged for 1-3 months were 3.5 times more likely to develop lumbar pain compared to those who were not engaged in COVID-19 treatment). This study also confirms that lumbar syndrome affects the quality of life of health workers. Conclusions: Lumbar syndrome is highly prevalent among healthcare professionals in the Clinical Center of Montenegro, especially in the population of nurses, where evidence-based preventive measures are needed.

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