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1.
BMJ Open Respir Res ; 8(1)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34362761

RESUMO

BACKGROUND: Correct inhaler use can be challenging in real life, with incorrect use resulting in poor symptom control. The aim of this study was to examine factors associated with poor inhaler technique and poor therapy adherence among patients with obstructive lung disease in community pharmacies. METHODS: A cross-sectional study was conducted in patients with obstructive lung diseases in nine Belgian community pharmacies. Logistic regression analyses identified factors associated with poor inhaler technique and poor therapy adherence (assessed by the Test of Adherence to Inhalers and the modified Medication Possession Ratio). RESULTS: Seventy obstructively impaired community patients (median age 64 y, 56% females) were included and the technique of 122 inhalers was assessed. Inhaler technique scored generally poor, with half of patients making critical errors in using at least one of their inhalers. In multivariable analysis, the use of multiple devices (adjusted OR, aOR 11.68; 95% CI 3.29 to 41.51) and a diagnosis of asthma-Chronic Obstructive Pulmonary Disease overlap (ACO; aOR 7.06; 95% CI 1.15 to 43.35), were associated with making critical errors in inhaler technique independent of quality of life. Non-adherence occurred in more than one-third of patients, and occurred in up to one half of the patients when also taking overuse into account. In multivariable analysis for therapy adherence, current smoking was associated with poor therapy adherence (aOR 0.15; 95% CI 0.02 to 0.96) independently of age and poor treatment knowledge. Therapy adherence was poor in patients with asthma compared with those with ACO. Current smokers and highly educated patients seemed to be at increased risk for inhaler overuse. CONCLUSIONS: Given the important role of a correct inhaler technique and therapy adherence in disease control, these findings emphasise the need for patient education and aiming uniformity in the inhaler device. TRIAL REGISTRATION NUMBER: B670201835229.

2.
Am J Ind Med ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34254700

RESUMO

BACKGROUND: Greater than average loss of one-second forced expiratory volume (FEV1 ) is a risk factor for asthma, chronic obstructive pulmonary disease (COPD), and asthma/COPD overlap syndrome in World Trade Center (WTC)-exposed firefighters. Inhaled corticosteroids and long-acting beta agonists (ICS/LABA) are used to treat obstructive airways disease but their impact on FEV1 -trajectory in this population is unknown. METHODS: The study population included WTC-exposed male firefighters who were treated with ICS/LABA for 2 years or longer (with initiation before 2015), had at least two FEV1 measurements before ICS/LABA initiation and two FEV1 measurements posttreatment between September 11, 2001 and September 10, 2019. Linear mixed-effects models were used to estimate FEV1 -slope pre- and post-treatment. RESULTS: During follow-up, 1023 WTC-exposed firefighters were treated with ICS/LABA for 2 years or longer. When comparing intervals 6 years before and 6 years after treatment, participants had an 18.7 ml/year (95% confidence interval [CI]: 11.3-26.1) improvement in FEV1 -slope after adjustment for baseline FEV1 , race, height, WTC exposure, weight change, blood eosinophil concentration, and smoking status. After stratification by median date of ICS/LABA initiation (January 14, 2010), earlier ICS/LABA-initiators had a 32.5 ml/year (95% CI: 19.5-45.5) improvement in slope but later ICS/LABA-initiators had a nonsignificant FEV1 -slope improvement (7.9 ml/year, 95% CI: -0.5 to 17.2). CONCLUSIONS: WTC-exposed firefighters treated with ICS/LABA had improved FEV1 slope after initiation, particularly among those who started earlier. Treatment was, however, not associated with FEV1 -slope improvement if started after the median initiation date (1/14/2010), likely because onset of disease began before treatment initiation. Research on alternative treatments is needed for patients with greater than average FEV1 -decline who have not responded to ICS/LABA.

3.
Sci Total Environ ; 789: 148043, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34323818

RESUMO

Wastewater-based epidemiology of SARS-CoV-2 could play a role in monitoring the spread of the virus in the population and controlling possible outbreaks. However, sensitive sample preparation and detection methods are necessary to detect trace levels of SARS-CoV-2 RNA in influent wastewater (IWW). Unlike predecessors, method optimization of a SARS-CoV-2 RNA concentration and detection procedure was performed with IWW samples with high viral SARS-CoV-2 RNA loads. This is of importance since the SARS-CoV-2 genome in IWW might have already been subject to in-sewer degradation into smaller genome fragments or might be present in a different form (e.g. cell debris, …). Centricon Plus-70 (100 kDa) centrifugal filter devices resulted in the lowest and most reproducible Ct-values for SARS-CoV-2 RNA. Lowering the molecular weight cut-off did not improve our limit of detection and quantification (approximately 100 copies/µL for all genes). Quantitative polymerase chain reaction (qPCR) was employed for the amplification of the N1, N2, N3 and E-gene fragments. This is one of the first studies to apply digital polymerase chain reaction (dPCR) for the detection of SARS-CoV-2 RNA in IWW. dPCR showed high variability at low concentration levels (100 copies/µL), indicating that variability in bioanalytical methods for wastewater-based epidemiology of SARS-CoV-2 might be substantial. dPCR results in IWW were in line with the results found with qPCR. On average, the N2-gene fragment showed high in-sample stability in IWW for 10 days of storage at 4 °C. Between-sample variability was substantial due to the low native concentrations in IWW. Additionally, the E-gene fragment proved to be less stable compared to the N2-gene fragment and showed higher variability. Freezing the IWW samples resulted in a 10-fold decay of loads of the N2- and E-gene fragment in IWW.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34312676

RESUMO

BACKGROUND: Macrolides are widely prescribed antibiotics for many different indications. However, there are concerns about adverse effects such as ototoxicity. OBJECTIVES: To investigate whether macrolide use is associated with tinnitus and hearing loss in the general population. METHODS: Cross-sectional (n = 4286) and longitudinal (n = 636) analyses were performed within the population-based Rotterdam Study. We investigated with multivariable logistic regression models the association between macrolides and tinnitus, and with multivariable linear regression models the association between macrolides and two different hearing thresholds (both ears, averaged over 0.25, 0.5, 1, 2, 4 and 8 kHz and 2, 4 and 8 kHz). Both regression models were adjusted for age, sex, systolic blood pressure, alcohol, smoking, BMI, diabetes, education level, estimated glomerular filtration rate and other ototoxic or tinnitus-generating drugs. Cumulative exposure to macrolides was categorized according to the number of dispensed DDDs and duration of action. RESULTS: In the fully adjusted model, ever use of macrolides was associated with a 25% higher likelihood of prevalent tinnitus (OR = 1.25; 95% CI 1.07-1.46). This association was more prominent in participants with a cumulative dose of more than 14 DDDs and among users of intermediate- or long-acting macrolides. Macrolide use in between both assessments was associated with more than a 2-fold increased risk on incident tinnitus. No general association between macrolides and hearing loss was observed. A borderline significant higher hearing threshold in very recent users (≤3 weeks) was found. CONCLUSIONS: Macrolide use was significantly associated with both prevalent and incident tinnitus. Macrolide-associated tinnitus was likely cumulative dose-dependent.

5.
J Alzheimers Dis ; 82(2): 621-630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057085

RESUMO

BACKGROUND: The etiology of dementia may partly be underpinned by impaired lung function via systemic inflammation and hypoxia. OBJECTIVE: To prospectively examine the association between chronic obstructive pulmonary disease (COPD) and subclinical impairments in lung function and the risk of dementia. METHODS: In the Rotterdam Study, we assessed the risk of incident dementia in participants with Preserved Ratio Impaired Spirometry (PRISm; FEV1/FVC≥0.7, FEV1 < 80% predicted) and in participants with COPD (FEV1/FVC < 0.7) compared to those with normal spirometry (controls; FEV1/FVC≥0.7, FEV1≥80% predicted). Hazard ratios (HRs) with 95% confidence intervals (CI) for dementia were adjusted for age, sex, education attainment, smoking status, systolic blood pressure, body mass index, triglycerides, comorbidities and Apolipoprotein E (APOE) genotype. RESULTS: Of 4,765 participants, 110 (2.3%) developed dementia after 3.3 years. Compared to controls, participants with PRISm, but not COPD, had an increased risk for all-type dementia (adjusted HRPRISm 2.70; 95% CI, 1.53-4.75; adjusted HRCOPD 1.03; 95% CI, 0.61-1.74). These findings were primarily driven by men and smokers. Similarly, participants with FVC% predicted values in the lowest quartile compared to those in the highest quartile were at increased risk of all-type dementia (adjusted HR 2.28; 95% CI, 1.31-3.98), as well as Alzheimer's disease (AD; adjusted HR 2.13; 95% CI, 1.13-4.02). CONCLUSION: Participants with PRISm or a low FVC% predicted lung function were at increased risk of dementia, compared to those with normal spirometry or a higher FVC% predicted, respectively. Further research is needed to elucidate whether this association is causal and how PRISm might contribute to dementia pathogenesis.

6.
Minerva Med ; 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33988014

RESUMO

INTRODUCTION: Novel treatments target eosinophilic inflammation in type 2 asthma. We aimed to evaluate and meta-analyze the efficacy of monoclonal antibodies to reduce exacerbation rate. EVIDENCE ACQUISITION: PubMed and Embase were searched for phase II and phase III randomized clinical trials with monoclonal antibodies targeting key mediators of type 2-associated asthma between 2019 and 2021 to update our previous meta-analysis covering studies published from 2005 to 2018. Five-hundred and sixty six publications have been identified, of which six recent trials (on top of 30 previously identified) involving mepolizumab, benralizumab, reslizumab and dupilumab met our inclusion criteria. As no head-to-head trials were retrieved from literature, we performed an arm-based network meta-analysis including a total of 19 RCTs to compare effects on exacerbation rate between the different treatments. EVIDENCE SYNTHESIS: Benralizumab significantly reduced the risk of exacerbations compared to the pooled placebo in our network meta-analysis (median effect difference: -0.520, 95% CI (-1.010- -0.048) ). No biologic showed superiority over the others in indirect comparisons. Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n=2564) to demonstrate significantly decreased exacerbation rates both in the overall population and in the subgroup analysis of IL-5 acting agents compared to placebo. CONCLUSIONS: Monoclonal antibodies have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials. No biological showed superiority over the others emphasizing the need for clearly defined endotypes indicating those patients who will optimally benefit for each treatment.

7.
Am J Physiol Lung Cell Mol Physiol ; 321(1): L130-L143, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33909500

RESUMO

Genome-wide association studies (GWASs) have identified regions associated with chronic obstructive pulmonary disease (COPD). GWASs of other diseases have shown an approximately 10-fold overrepresentation of nonsynonymous variants, despite limited exonic coverage on genotyping arrays. We hypothesized that a large-scale analysis of coding variants could discover novel genetic associations with COPD, including rare variants with large effect sizes. We performed a meta-analysis of exome arrays from 218,399 controls and 33,851 moderate-to-severe COPD cases. All exome-wide significant associations were present in regions previously identified by GWAS. We did not identify any novel rare coding variants with large effect sizes. Within GWAS regions on chromosomes 5q, 6p, and 15q, four coding variants were conditionally significant (P < 0.00015) when adjusting for lead GWAS single-nucleotide polymorphisms A common gasdermin B (GSDMB) splice variant (rs11078928) previously associated with a decreased risk for asthma was nominally associated with a decreased risk for COPD [minor allele frequency (MAF) = 0.46, P = 1.8e-4]. Two stop variants in coiled-coil α-helical rod protein 1 (CCHCR1), a gene involved in regulating cell proliferation, were associated with COPD (both P < 0.0001). The SERPINA1 Z allele was associated with a random-effects odds ratio of 1.43 for COPD (95% confidence interval = 1.17-1.74), though with marked heterogeneity across studies. Overall, COPD-associated exonic variants were identified in genes involved in DNA methylation, cell-matrix interactions, cell proliferation, and cell death. In conclusion, we performed the largest exome array meta-analysis of COPD to date and identified potential functional coding variants. Future studies are needed to identify rarer variants and further define the role of coding variants in COPD pathogenesis.

8.
Clin Cardiol ; 44(5): 599-608, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33769583

RESUMO

Although obesity is associated with the development and progression of atrial fibrillation (AF), an obesity paradox may be present, illustrated by seemingly protective effects of obesity on AF-related outcomes. Body mass index (BMI) has an impact on outcomes in AF patients using oral anticoagulants. After searching Medline and Embase, meta-analysis of results of four randomized and five observational studies demonstrated significantly lower risks of stroke or systemic embolism (RR 0.80, 95%CI [0.73-0.87]; RR 0.63, 95%CI [0.57-0.70]; and RR 0.42, 95%CI [0.31-0.57], respectively) and all-cause mortality (RR 0.73, 95%CI [0.64-0.83]; RR 0.61, 95%CI [0.52-0.71]; and RR 0.56, 95%CI [0.47-0.66], respectively) in overweight, obese and morbidly obese anticoagulated AF patients (BMI 25 to <30, ≥30 and ≥40 kg/m2 , respectively) compared to normal BMI anticoagulated AF patients (BMI 18.5 to <25 kg/m2 ). In contrast, thromboembolic (RR 1.92, 95%CI [1.28-2.90]) and mortality (RR 3.57, 95%CI [2.50-5.11]) risks were significantly increased in underweight anticoagulated AF patients (BMI <18.5 kg/m2 ). In overweight and obese anticoagulated AF patients, the risks of major bleeding (RR 0.86, 95%CI [0.76-0.99]; and RR 0.88, 95%CI [0.79-0.98], respectively) and intracranial bleeding (RR 0.75, 95%CI [0.58-0.97]; and RR 0.57, 95%CI [0.40-0.80], respectively) were also significantly lower compared to normal BMI patients, while similar risks were observed in underweight and morbidly obese patients. This meta-analysis demonstrated lower thromboembolic and mortality risks with increasing BMI. However, as this paradox was driven by results from randomized studies, while observational studies rendered more conflicting results, these seemingly protective effects should still be interpreted with caution.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33428092

RESUMO

PURPOSE: Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed. METHODS AND RESULTS: After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m2, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96] and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00] and RR 0.74, 95%CI [0.57-0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73-1.15] and RR 1.17, 95%CI [0.83-1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42-1.10]), were observed for NOAC- versus VKA-treated patients. CONCLUSION: The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m2) and on differences between NOACs in these patients.

10.
Clin Exp Allergy ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33428814

RESUMO

BACKGROUND: Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses. OBJECTIVE: We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is affected by ICS treatment. METHODS: We investigated the pharmacogenetic effect of 10 single nucleotide polymorphisms (SNPs) selected from the literature, including SNPs previously associated with response to ICS (assessed by change in lung function or exacerbations) and novel asthma risk alleles involved in inflammatory pathways, within all adults with asthma from the Dutch population-based Rotterdam study with replication in the American GERA cohort. The interaction effects of the SNPs with ICS on the incidence of asthma exacerbations were assessed using hurdle models adjusting for age, sex, BMI, smoking and treatment step according to the GINA guidelines. Haplotype analyses were also conducted for the SNPs located on the same chromosome. RESULTS: rs242941 (CRHR1) homozygotes for the minor allele (A) showed a significant, replicated increased risk for frequent exacerbations (RR = 6.11, P < 0.005). In contrast, rs1134481 T allele within TBXT (chromosome 6, member of a family associated with embryonic lung development) showed better response with ICS. rs37973 G allele (GLCCI1) showed a significantly poorer response on ICS within the discovery cohort, which was also significant but in the opposite direction in the replication cohort. CONCLUSION: rs242941 in CRHR1 was associated with poor ICS response. Conversely, TBXT variants were associated with improved ICS response. These associations may reveal specific endotypes, potentially allowing prediction of exacerbation risk and ICS response.

11.
Pharmacogenomics J ; 21(1): 78-84, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32848197

RESUMO

Over the past decade, pharmacogenetics (PGx) became an essential tool for personalized medicine although its clinical implementation is still limited. We aimed to assess the current level of knowledge, applications, and expectations of Flemish pharmacists and physicians towards PGx and determine the factors that influence healthcare professionals' knowledge of PGx, aiming to guide future implementation initiatives. A web-based cross-sectional survey was conducted from 8 March 2019 to 8 April 2019, targeting pharmacists, physicians, and trainees of both professions. Ten questions were used to assess the participants' knowledge about PGx. Multivariable linear regression was used to assess the association of profession, experience, practice setting, and prior education with the level of PGx knowledge. In total, 201 Flemish healthcare providers participated, including 100 pharmacists, 73 physicians, and 28 trainees. The majority (78%) of participants were unfamiliar with the basic principles of PGx and its application in clinical practice. The mean percentage of correct answers achieved for the knowledge assessment questions was 34%. Only 9% had counseled patients, while 8% assisted other healthcare professionals on PGx tests the past year. Participants' PGx knowledge was significantly affected by their profession, practice setting, and level of prior education independent of years of experience. These findings provide insight into factors affecting the knowledge of PGx and the current level of PGx implementation in Flemish clinical practice. This may form a basis for developing educational initiatives to enhance the clinical application of PGx in Flanders.

12.
Int J Cardiol ; 328: 97-103, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33279589

RESUMO

BACKGROUND: This study aimed to evaluate the prevalence of potential drug-drug interactions (DDIs) and the appropriateness of direct oral anticoagulant (DOAC) dosing according to both the Summary of Product Characteristics (SmPC) and the European Heart Rhythm Association (EHRA) Practical Guide in a 'real-world' sample of non-valvular atrial fibrillation (NVAF) patients. METHODS AND RESULTS: Data of a cross-sectional observational study in a primary care sample of 654 long-term DOAC users were used for this sub-analysis. A total of 262 potential DDIs were identified in 220 patients (33.6%). Pharmacodynamic DDIs were present in 163 patients (24.9%) and pharmacokinetic DDIs in 82 patients (12.5%). One-third of patients (33.8%) received reduced DOAC dose. According to the dosing recommendations in the SmPC, 81.7% of DOACs were dosed appropriately. According to the EHRA recommendations, 76.6% of DOACs were dosed appropriately. Dosing recommendations were consistent for 90.7% of patients, with both the SmPC and EHRA Practical Guide considering DOACs dosed appropriately in 74.5% of patients, overdosed in 7.8%, underdosed in 7.6% and contraindicated in 0.8%. However, for the remaining 9.3% dosing recommendations differed between SmPC and EHRA. CONCLUSIONS: This 'real-world' analysis of DOAC dosing demonstrated that in about one-third of NVAF patients potential DDIs were present. In 18.3% and 23.4% of patients, DOACs were dosed inappropriately according to the SmPC and EHRA Practical Guide respectively. In almost 10% of the study population dosing advice was inconsistent between both references. More research is needed to ensure appropriate DOAC dosing in this 'grey zone' population.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos Transversais , Rotulagem de Medicamentos , Humanos , Acidente Vascular Cerebral/tratamento farmacológico
13.
Eur Respir Rev ; 29(158)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33268439

RESUMO

The European Respiratory Society journals publish respiratory research and policy documents of the highest quality, offering a platform for the exchange and promotion of scientific knowledge. In this article, focusing on COPD, the third leading cause of death globally, we summarise novel research highlights focusing on the disease's underlying mechanisms, epidemiology and management, with the aim to inform and inspire respiratory clinicians and researchers.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33291671

RESUMO

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001-10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001-1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV1), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001-10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005-10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV1, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.


Assuntos
Corticosteroides , Bombeiros , Lesão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Ataques Terroristas de 11 de Setembro , Administração por Inalação , Corticosteroides/uso terapêutico , Adulto , Estudos de Coortes , Quimioterapia Combinada , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Lesão Pulmonar/tratamento farmacológico , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
15.
Open Heart ; 7(2)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33361315

RESUMO

AIMS: Oral anticoagulants (OACs) are crucial for treating atrial fibrillation (AF) patients at high thromboembolic risk. However, in AF patients at intermediate thromboembolic risk with a single non-sex-related stroke risk factor (CHA2DS2-VASc score 1 in men, 2 in women), guidelines advise to consider starting anticoagulation, which may result in OAC non-initiation due to underestimation of the thromboembolic risk of a single stroke risk factor and overestimation of the OAC-related bleeding risk. A critical appraisal of the role of OACs and the benefit-risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in this patient subgroup are needed. METHODS AND RESULTS: This systematic review provides an overview of literature on the effectiveness and safety of OACs in AF patients with a single non-sex-related stroke risk factor after searching Medline and Embase. Differences between individual stroke risk factors regarding the ischaemic stroke risk in non-anticoagulated AF patients are identified in a meta-analysis, demonstrating the highest increased risk in patients aged 65-74 years old or with diabetes mellitus, followed by heart failure, hypertension and vascular disease. Furthermore, meta-analysis results favour NOACs over VKAs, given their equal effectiveness and superior safety in AF patients at intermediate thromboembolic risk (HR 0.93, 95% CI 0.65 to 1.34 for stroke or systemic embolism; HR 0.60, 95% CI 0.45 to 0.80 for major bleeding; HR 0.48, 95% CI 0.14 to 1.59 for intracranial bleeding; HR 0.58, 95% CI 0.47 to 0.71 for mortality). CONCLUSION: Our systematic review with meta-analysis favours the use of anticoagulation in AF patients with a single non-sex-related stroke risk factor, especially when age ≥65 years or diabetes mellitus is present, with a preference for NOACs over VKAs.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Medição de Risco/métodos , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Fibrilação Atrial/complicações , Saúde Global , Humanos , Incidência , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
16.
Front Pharmacol ; 11: 583311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013422

RESUMO

Background and Objective: Atrial fibrillation (AF), the most common cardiac arrhythmia, typically increases with age. Oral anticoagulants (OACs) are the cornerstone of treatment to reduce the associated risk for systemic thromboembolism. Four large randomized controlled trials (RCTs) have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are non-inferior to vitamin K antagonists (VKAs) in preventing stroke and systemic embolism, as well as regarding their risk for major bleeding. However, as vulnerable geriatric patients with AF were largely underrepresented in these trials, physicians are faced with the challenge of choosing the right anticoagulant for geriatric patients in real-life clinical practice. In this vulnerable patient group, NOACs tend to be underused or underdosed due to concerns of excessive fall-related intracranial bleeding, cognitive impairment, multiple drug-drug interactions, low body weight or impaired renal function. As life expectancy continues to rise worldwide, the number of geriatric patients substantially increases. Therefore, there is an urgent need for a critical appraisal of the added value of NOACs in geriatric patients with AF at high thromboembolic and bleeding risk. Methods and Results: This systematic review provides an overview of the literature on the impact of increased age (≥75 years), multimorbidity, polypharmacy, increased falling risk, frailty and dementia on the effectiveness and safety of NOACs as compared to VKAs, after searching the Medline database. Moreover, a meta-analysis on the impact of increased age ≥75 years old was performed after pooling results from 6 post hoc analyses of RCTs and 6 longitudinal observational cohort studies, highlighting the superior effectiveness (hazard ratio (HR) 0.83, 95% confidence interval (CI) [0.74-0.94] for stroke/SE; HR 0.77, 95%CI [0.65-0.92] for mortality) and non-inferior safety (HR 0.93, 95%CI [0.86-1.01] for major bleeding; HR 0.58, 95%CI [0.50-0.67] for intracranial bleeding; HR 1.17, 95%CI [0.99-1.38] for gastrointestinal bleeding) of NOACs versus VKAs in older AF patients. Conclusion: Across geriatric subgroups, apixaban was consistently associated with the most favourable benefit-risk profile and should therefore be preferred in geriatric patients with AF. However, research gaps on the impact of increased falling risk, frailty and baseline dementia were identified, requiring careful consideration while awaiting more results.

17.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043054

RESUMO

Background: Elevated blood eosinophils have been associated with lower lung function and are believed to be associated with accelerated lung function decline. Method: Blood eosinophils were measured in four cohorts: <45 years cohort within the Vlagtwedde-Vlaardingen (V&V) study, the Uppsala cohort of the European Community Respiratory Health Survey (ECRHS-Uppsala; <45 years), ≥45 years cohort within the V&V study, and the Rotterdam study (≥45 years). Blood eosinophils at baseline were classified as normal (<300 cells·µL-1) or elevated (≥300 cells·µL-1). Lung function was measured at baseline and follow-up with spirometry: forced expiratory volume in 1 s (FEV1), vital capacity (VC) and their ratio FEV1/VC. The association between blood eosinophils and lung function was tested cross-sectionally using linear regression and longitudinally using a mixed model, both adjusted for age, sex, height, pack-years smoking and smoking status. Stratified analyses were done for asthma. Results: Elevated blood eosinophils were associated with lower FEV1 (regression coefficient -147 mL (95% CI -188 to -105 mL)), VC (-120 mL (-165 to -75 mL)) and FEV1/VC (-1.3% (-1.9% to -0.6%)) at baseline in the two <45 years cohorts, and with lower FEV1 (-70 mL (-112 to -27 mL)) and FEV1/VC (-1.8% (-2.6% to -1.0%)) in the two ≥45 years cohorts. Elevated blood eosinophils were associated with an accelerated decline in FEV1 (-5.5 mL·year-1 (95% CI -10.5 to -0.5 mL·year-1)) and VC (-6.4 mL·year-1 (-11.26 to -1.5 mL·year-1)) compared to normal blood eosinophils in the younger asthmatic subjects in the longitudinal studies. Conclusion: Elevated blood eosinophils are associated with lower lung function in the general population and with an accelerated lung function decline among asthmatic individuals.

18.
World Allergy Organ J ; 13(7): 100441, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32774661

RESUMO

Background: Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers' specialty and experience. Methods: We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared. Results: Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05). Conclusions: Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice.

19.
BMC Pulm Med ; 20(1): 193, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677943

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis. METHODS: We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach. RESULTS: There were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16, P = 5.6 × 10- 4 in the discovery and OR = 1.30, P = 1.8 × 10- 6 in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52-2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94-1.20). CONCLUSIONS: Our study shows that circulating blood GlycA is a biomarker of early COPD pathology.


Assuntos
Glicoproteínas/sangue , Metabolômica/métodos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Glicoproteínas/química , Humanos , Modelos Logísticos , Pulmão/metabolismo , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Fatores de Risco , Taxa de Sobrevida
20.
Lancet Respir Med ; 8(7): 696-708, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649918

RESUMO

BACKGROUND: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. METHODS: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. FINDINGS: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. INTERPRETATION: A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth. FUNDING: US National Institutes of Health, Wellcome Trust.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fatores de Risco , Capacidade Vital
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