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1.
Heart Fail Rev ; 29(3): 631-662, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38411769

RESUMO

This review provides a comprehensive overview of heart failure with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF), including its definition, diagnosis, and epidemiology; clinical, humanistic, and economic burdens; current pharmacologic landscape in key pharmaceutical markets; and unmet needs to identify key knowledge gaps. We conducted a targeted literature review in electronic databases and prioritized articles with valuable insights into HFmrEF/HFpEF. Overall, 27 randomized controlled trials (RCTs), 66 real-world evidence studies, 18 clinical practice guidelines, and 25 additional publications were included. Although recent heart failure (HF) guidelines set left ventricular ejection fraction thresholds to differentiate categories, characterization and diagnosis criteria vary because of the incomplete disease understanding. Recent epidemiological data are limited and diverse. Approximately 50% of symptomatic HF patients have HFpEF, more common than HFmrEF. Prevalence varies with country because of differing definitions and study characteristics, making prevalence interpretation challenging. HFmrEF/HFpEF has considerable mortality risk, and the mortality rate varies with study and patient characteristics and treatments. HFmrEF/HFpEF is associated with considerable morbidity, poor patient outcomes, and common comorbidities. Patients require frequent hospitalizations; therefore, early intervention is crucial to prevent disease burden. Recent RCTs show promising results like risk reduction of composite cardiovascular death or HF hospitalization. Costs data are scarce, but the economic burden is increasing. Despite new drugs, unmet medical needs requiring new treatments remain. Thus, HFmrEF/HFpEF is a growing global healthcare concern. With improving yet incomplete understanding of this disease and its promising treatments, further research is required for better patient outcomes.


Assuntos
Insuficiência Cardíaca , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Volume Sistólico/fisiologia , Efeitos Psicossociais da Doença , Função Ventricular Esquerda/fisiologia
2.
Cephalalgia ; 42(14): 1543-1564, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36081276

RESUMO

BACKGROUND: This meta-analysis evaluated the real-world effectiveness of onabotulinumtoxinA (BOTOX®), the first preventive treatment FDA-approved specifically for chronic migraine in 2010. METHODS: We systematically reviewed onabotulinumtoxinA observational data in chronic migraine published between 1 January 2010 and 31 March 2021. Random-effects models evaluated available data for primary and secondary endpoints defined in onabotulinumtoxinA pivotal trials at approximately 24 weeks and 52 weeks. RESULTS: Of the 44 full-text eligible studies (29 prospective; 13 retrospective; 2 other), seven evaluated change from baseline (mean[confidence interval]) at ∼24 weeks and ∼52 weeks, respectively, for onabotulinumtoxinA in: number of headache days/month: (-10.64 [-12.31, -8.97]; -10.32 [-14.92, -5.73]); number of days of acute headache pain medication intake per month (-7.40 [-13.04, -1.77]; overlapping CIs at 52 weeks); total Headache Impact Test-6 score (-11.70 [-13.86, -9.54]); -11.80 [14.70, -8.90]); and Migraine-Specific Quality-of-Life v2.1 score (MSQ; 23.60 [CI: 21.56, 25.64]; 30.90 [CI: 28.29, 33.51]). At ∼24 weeks onabotulinumtoxinA showed total Migraine Disability Assessment score of 44.74 [28.50, 60.99] and ≥50% reduction in migraine days response rate of 46.57% [29.50%, 63.65%]. A sensitivity analysis at study-end suggested durability of onabotulinumtoxinA effectiveness on MSQ. CONCLUSION: The meta-analysis reflecting real-world practice broadly corroborated with evidence from pivotal and long-term open-label studies of onabotulinumtoxinA in chronic migraine preventive treatment.


Assuntos
Dor Aguda , Toxinas Botulínicas Tipo A , Transtornos de Enxaqueca , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento , Doença Crônica , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Cefaleia/tratamento farmacológico
3.
Artigo em Inglês | MEDLINE | ID: mdl-38804215

RESUMO

This systematic literature review aimed to assess the efficacy and tolerability of agomelatine versus approved medications for the treatment of generalized anxiety disorder (GAD) in adult patients. We selected randomized controlled trials on various medications used to treat GAD in adult patients. An existing systematic literature review (Kong et al., 2020) was used to identify relevant studies published before 2020. Outcomes of remission and discontinuation due to adverse events (AEs) were analyzed, following a random-effects network meta-analysis approach. Of 25 identified studies, 20 and 22 studies were included in the network meta-analysis for studying the remission and discontinuation (due to AEs) outcomes, respectively. A statistically significant difference in the remission rate was observed between agomelatine and pregabalin [odds ratio (OR), 2.22; 95% confidence interval (CI), 1.19-4.21]. For the other comparators, the results were nonsignificant; however, all the point estimates were in favor of agomelatine. Similarly, for discontinuation because of AEs, the point estimates leaned consistently toward agomelatine suggesting its higher tolerability. The probabilities of agomelatine having the highest remission rate and lowest discontinuation (due to AEs) rate were 67% and 68%, respectively. Based on its demonstrated effectiveness and tolerability, agomelatine can be considered as a drug of choice for the treatment of GAD.

4.
J Mark Access Health Policy ; 11(1): 2262073, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808119

RESUMO

Background: Heart failure is a chronic disease linked with significant morbidity and mortality, and uncontrolled resting heart rate is a risk factor for adverse outcomes. This systematic literature review aimed to assess the efficacy, safety, and patient-reported outcomes (PROs) of ivabradine in patients with heart failure (HF) with reduced ejection fraction (HFrEF) in randomized controlled trials (RCTs) and observational studies. Methods: We searched electronic databases from their inception to July 2021 to include studies that reported on efficacy, safety, or PROs of ivabradine in patients with HFrEF. Results: Of 1947 records screened, 51 RCTs and 6 observational studies were identified. Ivabradine on top of background therapy demonstrated a significant reduction in composite outcomes including hospitalization for HF or cardiovascular death. In addition, observational studies suggested that ivabradine was associated with a significant reduction in mortality. Across all studies, ivabradine use on top of background therapy was associated with greater reductions in heart rate, improved EF, and improved health-related quality of life (QoL) and comparable risk of total adverse events compared to those treated with background therapy alone. Conclusions: Ivabradine on top of background therapy is beneficial for heart rate, hospitalization risk for HF, mortality, EF, and patients' QoL. Moreover, these benefits were achieved with no significant increase in the overall risk of total adverse events.

5.
J Nephrol ; 36(4): 1135-1167, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36422853

RESUMO

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria. OBJECTIVE: We conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients. RESULTS: A total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting. CONCLUSIONS: Despite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.


Assuntos
Doenças Cardiovasculares , Nefropatias Diabéticas , Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico
6.
Przegl Epidemiol ; 63(3): 437-42, 2009.
Artigo em Polonês | MEDLINE | ID: mdl-19899605

RESUMO

The objective of the study was analysis of the relationship between the quality of ambient air and icidence of lung cancer based on the results of measurements of selected indicator substances and epidemiological data from the localities/provinces in the Silesian Region. The levels of pyrene, benzoanthracene, benzopyrene and dibenzo(a,h)anthracene were analysed, as well as the concentrations of PM10 fractions sampled on glass fibre filters at sampling stations in 5 localities and 8 provinces in the Silesian Region. The classification of morbidity to lung cancer for the localities and provinces in the study was presented based on the data from the Regional Silesian Cancer Registry. In the group of males a relationship was observed between an increased morbidity to lung cancer and an increasing concentration of pyrene and PM10 respirable dust fraction in ambient air. The preliminary analyses confirmed the strong effect of the quality of ambient air on incidence of lung cancer in the Silesian Region.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental/estatística & dados numéricos , Neoplasias Pulmonares/epidemiologia , Adulto , Benzo(a)Antracenos/análise , Benzopirenos/análise , Causalidade , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Polônia/epidemiologia
7.
Adv Clin Exp Med ; 26(6): 939-945, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29068594

RESUMO

BACKGROUND: Exposure to lead (Pb) in environmental and occupational settings continues to be a serious public health problem and may pose an elevated risk of genetic damage. OBJECTIVES: The aim of this study was to assess the level of oxidative stress and DNA damage in subjects occupationally exposed to lead. MATERIAL AND METHODS: We studied a population of 78 male workers exposed to lead in a lead and zinc smelter and battery recycling plant and 38 men from a control group. Blood lead levels were detected by graphite furnace atomic absorption spectrophotometry and plasma lead levels by inductively coupled plasma-mass spectrometry. The following assays were performed to assess the DNA damage and oxidative stress: comet assay, determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation and total antioxidant status (TAS). RESULTS: The mean concentration of lead in the blood of the exposed group was 392 ± 103 µg/L and was significantly higher than in the control group (30.3 ± 29.4 µg/L, p < 0.0001). Oxidative DNA damages measured by comet assay showed no significant differences between populations. The concentration of 8-OHdG was about twice as high as in the control group. We found a significant positive correlation between the level of biomarkers of lead exposure [lead in blood, lead in plasma, zinc protoporphyrin (ZPP)] and urine concentration of 8-OHdG. The level of oxidative damage of DNA was positively correlated with the level of lipid peroxidation (TBARS) and negatively with total anti-oxidative status (TAS). CONCLUSIONS: Our study suggests that occupational exposure causes an increase in oxidative damage to DNA, even in subjects with relatively short length of service (average length of about 10 years). 8-OHdG concentration in the urine proved to be a sensitive and non-invasive marker of lead induced genotoxic damage.


Assuntos
Dano ao DNA , Chumbo/efeitos adversos , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Estresse Oxidativo/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Ensaio Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Fontes de Energia Elétrica , Humanos , Descrição de Cargo , Chumbo/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Reciclagem , Fatores de Tempo , Urinálise , Soldagem , Adulto Jovem
8.
Environ Toxicol Pharmacol ; 39(3): 1091-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25899472

RESUMO

Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity. Two cohorts of children were examined for hearing [pure-tone audiometry (PTA), brain stem auditory evoked potentials (BAEP)], acoustic otoemission (transient emission evoked by a click) and blood-lead concentrations (B-Pb). The children were genotyped for polymorphisms in ALAD and VDR. The median B-Pbs were 55 and 36µg/L in the two cohorts (merged cohort 45µg/L). B-Pb was significantly associated with impaired hearing when tested with PTA (correlation coefficient rS=0.12; P<0.01), BAEP (rS=0.18; P<0.001) and otoemission (rS=-0.24; P<0.001). VDR significantly modified the lead-induced effects on PTA. Carriers of the VDR alleles BsmI B, VDR TaqI t and VDR FokI F showed greater toxic effects on PTA, compared to BsmI bb, VDR TaqI TT and VDR FokI ff carriers. No significant interaction was found for ALAD. Lead impairs hearing functions in the route from the cochlea to the brain stem at low-level exposure, and polymorphisms in VDR significantly modify these effects.


Assuntos
Perda Auditiva/fisiopatologia , Chumbo/sangue , Polimorfismo Genético , Sintase do Porfobilinogênio/genética , Receptores de Calcitriol/genética , Adolescente , Criança , Pré-Escolar , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/sangue , Perda Auditiva/etiologia , Perda Auditiva/genética , Testes Auditivos , Humanos , Chumbo/toxicidade , Masculino
9.
Pol Arch Med Wewn ; 125(3): 141-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25644227

RESUMO

INTRODUCTION: Prandial insulin is a key component in insulin treatment of type 1 diabetes mellitus (T1DM) and in many patients with type 2 diabetes mellitus (T2DM). The evidence-based data supporting the choice of an insulin preparation are still limited. OBJECTIVES: We performed a systematic review to summarize and update the evidence on relative efficacy and safety of insulin aspart (IAsp) and regular human insulin (RHI) in both types of diabetes. METHODS: Randomized controlled trials comparing IAsp with RHI in patients with either T1DM or T2DM and conducted until May 2013 were retrieved from a systematic search of MEDLINE, EMBASE, and Cochrane Library. RESULTS: Of 16 relevant trials, 11 involved patients with T1DM and 5--with T2DM. In the T1DM population, IAsp, when compared with RHI, provided a greater reduction in hemoglobin A1c (HbA1c) levels (weighted mean difference [WMD], -0.11%; 95% confidence interval [CI], -0.16 to -0.05; WMD, -1.2 mmol/mol; 95% CI, -1.7 to -0.5), and improved postprandial glucose levels following breakfast (WMD, -1.40 mmol/l; 95% CI, -1.72 to -1.07), lunch (WMD, -1.01 mmol/l; 95% CI, -1.61 to -0.41), and dinner (WMD, -0.89 mmol/l; 95% CI, -1.19 to -0.59). The risk of nocturnal hypoglycemia was lower in T1DM patients receiving IAsp (relative risk, 0.76; 95% CI, 0.64-0.91), while no difference was observed for severe hypoglycemia. In T2DM patients, IAsp led to a greater reduction in HbA1c levels (WMD, -0.22%; 95% CI, -0.39 to -0.05; -2.4 mmol/mol, -4.3 to -0.5) and postprandial blood glucose. The risk of overall hypoglycemia and severe adverse effects was comparable between the groups. CONCLUSIONS: IAsp provides better glycemic control when compared with RHI in patients with T1DM and T2DM. Fewer T1DM patients treated with IAsp experienced nocturnal hypoglycemia, while both interventions showed a comparable risk of severe hypoglycemic events in both types of diabetes.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Glicemia/metabolismo , Quimioterapia Combinada , Humanos , Insulina , Período Pós-Prandial/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Neurotoxicology ; 33(1): 37-43, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22101007

RESUMO

Lead has negative effect on cognitive functions in children. However, individuals differ in susceptibility. One possible explanation is a genetic predisposition. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity, but information regarding the central nervous system is very limited. The aim of the study was to determine whether ALAD and VDR polymorphisms modify blood lead (B-Pb), and the association between B-Pb and cognitive function (IQ) in children. In 2007-2010 a cohort of 175 children (age 6-10years, mean 7.8) was recruited in Southern Poland, tested for IQ (Wechsler intelligence scale) and analyzed for B-Pb (range 9.0-221; mean 46.6µg/L), ALAD (RsaI, MspI) and VDR (FokI, BsmI, TaqI) polymorphisms. ALAD or VDR genotypes were not associated with B-Pb. B-Pb was non-significantly negatively associated with full scale IQ (r(S)=-0.11; P=0.14), and significantly with performance subscale results (r(S)=-0.19; P=0.01). The ALAD RsaI polymorphism modified the relationship between full scale IQ and B-Pb: RsaI T carriers had a steeper slope compared to CC homozygote carriers (ß coefficient -0.06 vs 0.32, respectively, P for interaction <0.001, adjusted for the child's age, mother's education and family income). This means that with increasing B-Pb with 1µg/L, T carriers demonstrate 0.06 score lower IQ. For the VDR BsmI, B carriers had a steeper slope than the bb homozygotes carriers (ß coefficient -0.08 vs 0.16, respectively, P for interaction=0.001), and similar effect was found for TaqI t carriers vs TT homozygotes (P for interaction=0.02). For ALAD MspI and VDR FokI there was no significant modification. The ALAD RsaI, VDR BsmI and TaqI polymorphisms modified the relationship between IQ and B-Pb. Hence, there is a fraction of the population, which is particularly sensitive to lead neurotoxicity.


Assuntos
Predisposição Genética para Doença , Inteligência , Intoxicação por Chumbo/fisiopatologia , Polimorfismo Genético , Sintase do Porfobilinogênio/genética , Receptores de Calcitriol/genética , Adolescente , Criança , Estudos de Coortes , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Humanos , Testes de Inteligência , Chumbo/sangue , Chumbo/farmacologia , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/metabolismo , Masculino , Análise Multivariada , Testes Neuropsicológicos , Polônia , Sintase do Porfobilinogênio/metabolismo , Receptores de Calcitriol/metabolismo , Estudos Retrospectivos
11.
Ann Agric Environ Med ; 17(2): 231-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21186764

RESUMO

Lead plays a significant role in modern industry. This metal is related to a broad range of physiological, biochemical and behavioural dysfunctions. The genotoxic effects of lead have been studied both in animals and humans in in vitro systems but results were contradictory. The aim of this study was to investigate the association between DNA damage and occupational exposure to lead in workers. The study population consisted of 62 employees of metalworks exposed to lead in the southern region of Poland. The control group consisted of 26 office workers with no history of occupational exposure to lead. The concentration of lead (PbB) and zincprotoporphyrin (ZPP) in blood samples were measured. The DNA damage was analyzed in blood lymphocytes using alkaline comet assay. The level of DNA damage was determined as the percentage of DNA in the tail, tail length and tail moment. The lead exposure indicators were significantly higher in lead exposed group: PbB about 8.5 times and ZPP 3.3 times. Also, the percentage of DNA in the tail (60.3 ± 14 vs. 37.1 ± 17.6), comet tail length (86.9 ± 15.49 vs. 73.8 ± 19.12) and TM (57.8 ± 17.82 vs. 33.2 ± 19.13) were significantly higher in the study group when compared with the controls; however, the difference between the subgroups was only 5-10%. Years of lead exposure positively correlated with all comet assay parameters (R = 0.21-0.41). Both mean and current PbB and ZPP were correlated with tail DNA % and TM (R = 0.32; R = 0.33; R = 0.24; R = 0.26 and R = 0.34; R = 0.33; R = 0.28 and R = 0.28, respectively). This study shows that occupational exposure to lead is associated with DNA damage and confirmed that comet assay is a rapid, sensitive method suitable for biomonitoring studies.


Assuntos
Dano ao DNA , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/genética , Chumbo/sangue , Exposição Ocupacional/efeitos adversos , Protoporfirinas/sangue , Adulto , Ensaio Cometa , Humanos , Masculino , Análise de Regressão
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