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1.
Biomedicines ; 9(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34829737

RESUMO

In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as candidate biomarkers in human diseases as well. Different types of ncRNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in every step of pregnancy progression, although studies taking into consideration fetal sex as a central variable are still limited. To date, most of the available data have been obtained investigating sex-specific placental miRNA expression. Several studies revealed that miRNAs regulate the (patho)-physiological processes in a sexually dimorphic manner, ensuring normal fetal development, successful pregnancy, and susceptibility to diseases. Moreover, the observation that ncRNA profiles differ according to cells, tissues, and developmental stages of pregnancy, along with the complex interactions among different types of ncRNAs in regulating gene expression, strongly indicates that more studies are needed to understand the role of sex-specific ncRNA in pregnancy and associated disorders.

2.
J Clin Med ; 10(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34441993

RESUMO

This study explores which patient characteristics could affect the likelihood of starting low back pain (LBP) treatment with opioid analgesics vs. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in an Italian primary care setting. Through the computerized medical records of 65 General Practitioners, non-malignant LBP subjects who received the first pain intensity measurement and an NSAID or opioid prescription, during 2015-2016, were identified. Patients with an opioid prescription 1-year before the first pain intensity measurement were excluded. A multivariable logistic regression model was used to determine predictive factors of opioid prescribing. Results were reported as Odds Ratios (ORs) with a 95% confidence interval (CI), with p < 0.05 indicating statistical significance. A total of 505 individuals with LBP were included: of those, 72.7% received an NSAID prescription and 27.3% an opioid one (64% of subjects started with strong opioid). Compared to patients receiving an NSAID, those with opioid prescriptions were younger, reported the highest pain intensity (moderate pain OR = 2.42; 95% CI 1.48-3.96 and severe pain OR = 2.01; 95% CI 1.04-3.88) and were more likely to have asthma (OR 3.95; 95% CI 1.99-7.84). Despite clinical guidelines, a large proportion of LBP patients started with strong opioid therapy. Asthma, younger age and pain intensity were predictors of opioid prescribing when compared to NSAIDs for LBP treatment.

3.
JAMA Netw Open ; 4(6): e2113186, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34125221

RESUMO

Importance: Polypharmacy is a major health concern among older adults. While deprescribing may reduce inappropriate medicine use, its effect on clinical end points remains uncertain. Objective: To assess the clinical implications of discontinuing the use of statins while maintaining other drugs in a cohort of older patients receiving polypharmacy. Design, Setting, and Participants: This retrospective, population-based cohort study included the 29 047 residents in the Italian Lombardy region aged 65 years or older who were receiving uninterrupted treatment with statins, blood pressure-lowering, antidiabetic, and antiplatelet agents from October 1, 2013, until January 31, 2015, with follow-up through June 30, 2018. Data were collected using the health care utilization database of Lombardy region in Italy. Data analysis was conducted from March to November 2020. Exposures: Cohort members were followed up to identify those who discontinued statins. Among this group, those who maintained other therapies during the first 6 months after statin discontinuation were 1:1 propensity score matched with patients who discontinued neither statins nor other drugs. Main Outcome and Measures: The pairs of patients discontinuing and maintaining statins were followed up from the initial discontinuation until June 30, 2018, to estimate the hazard ratios (HRs) and 95% CIs for fatal and nonfatal outcomes associated with statin discontinuation. Results: The full cohort inclued 29 047 patients exposed to polypharmacy (mean [SD] age, 76.5 [6.5] years; 18 257 [62.9%] men). Of them, 5819 (20.0%) discontinued statins while maintaining other medications, and 4010 (68.9%) of them were matched with a comparator. In the discontinuing group, the mean (SD) age was 76.5 (6.4) years, 2405 (60.0%) were men, and 506 (12.6%) had Multisource Comorbidity Scores of 4 or 5. In the maintaining group, the mean (SD) age was 76.1 (6.3) years, 2474 (61.7%) were men, and 482 (12.0%) had multisource comorbidity scores of 4 or 5. Compared with the maintaining group, patients in the discontinuing group had increased risk of hospital admissions for heart failure (HR, 1.24; 95% CI, 1.07-1.43) and any cardiovascular outcome (HR, 1.14; 95% CI, 1.03-1.26), deaths from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.05-1.19). Conclusions and Relevance: In this study of patients receiving polypharmacy, discontinuing statins while maintaining other drug therapies was associated with an increase in the long-term risk of fatal and nonfatal cardiovascular outcomes.

4.
Pharmacoepidemiol Drug Saf ; 30(2): 210-219, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33190379

RESUMO

PURPOSE: To estimate the risk of kidney disease in high-potency statin users compared to those treated with low-potency statins without history of kidney disease at statin initiation, linking the Swedish national healthcare registers and laboratory data. METHODS: Incident users of statins, ≥40 years of age, with estimated Glomerular Filtration Rate (eGFR) >60 ml/min/1.73 m2 and no diagnosis of kidney disease at treatment initiation were identified between 2006 and 2007 and then followed for 2-years. The outcome was the incidence of kidney disease identified by the presence of the diagnostic code in the healthcare registers or eGFR <60 ml/min/1.73 m2 . We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjusted and propensity score (PS)-matched Cox proportional hazards models. RESULTS: A total of 27 385 patients were identified, 25.2% of which treated with a high-potency statin. During the follow-up, 68 (0.25%) patients were identified with a diagnosis of kidney disease from the registers. The number increased to 2498 (9.1%) when the criteria of eGFR <60 ml/min/1.73 m2 was added. The adjusted HR of kidney disease in high-potency statin users was 1.14 (95%CI 1.03-1.25) compared to low-potency users; the result was unchanged after the PS approach. CONCLUSIONS: Adding information from laboratory data to those from the national health registers, a slightly increased risk for kidney disease was found in high-potency statin users without pre-existing kidney disease at treatment initiation compared to those treated with low-potency statins.

5.
Life (Basel) ; 10(12)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33352991

RESUMO

Hepatitis C virus (HCV) infection remains a pressing public health issue. Our aim is to assess the linkage to care of patients with HCV diagnosis and to support the proactive case-finding of new HCV-infected patients in an Italian primary care setting. This was a retrospective cohort study of 44 general practitioners (GPs) who managed 63,955 inhabitants in the Campania region. Adults with already known HCV diagnosis or those with HCV high-risk profile at June 2019 were identified and reviewed by GPs to identify newly diagnosed of HCV and to assess the linkage to care and treatment for the HCV patients. Overall, 698 HCV patients were identified, 596 with already known HCV diagnosis and 102 identified by testing the high-risk group (2614 subjects). The 38.8% were already treated with direct-acting antivirals, 18.9% were referred to the specialist center and 42.3% were not sent to specialist care for treatment. Similar proportions were found for patients with an already known HCV diagnosis and those newly diagnosed. Given that the HCV infection is often silent, case-finding needs to be proactive and based on risk information. Our findings suggested that there needs to be greater outreach, awareness and education among GPs in order to enhance HCV testing, linkage to care and treatment.

6.
Sci Rep ; 10(1): 13988, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814794

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer death. Chemoresistance is a pivotal feature of cancer cells leading to treatment failure and ATP-binding cassette (ABC) transporters are responsible for the efflux of several molecules, including anticancer drugs. The Hedgehog-GLI (HH-GLI) pathway is a major signalling in CRC, however its role in chemoresistance has not been fully elucidated. Here we show that the HH-GLI pathway favours resistance to 5-fluorouracil and Oxaliplatin in CRC cells. We identified potential GLI1 binding sites in the promoter region of six ABC transporters, namely ABCA2, ABCB1, ABCB4, ABCB7, ABCC2 and ABCG1. Next, we investigated the binding of GLI1 using chromatin immunoprecipitation experiments and we demonstrate that GLI1 transcriptionally regulates the identified ABC transporters. We show that chemoresistant cells express high levels of GLI1 and of the ABC transporters and that GLI1 inhibition disrupts the transporters up-regulation. Moreover, we report that human CRC tumours express high levels of the ABCG1 transporter and that its expression correlates with worse patients' prognosis. This study identifies a new mechanism where HH-GLI signalling regulates CRC chemoresistance features. Our results indicate that the inhibition of Gli1 regulates the ABC transporters expression and therefore should be considered as a therapeutic option in chemoresistant patients.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias Colorretais/metabolismo , Proteínas Hedgehog/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/genética , Humanos , Estimativa de Kaplan-Meier , Oxaliplatina/farmacologia , Regiões Promotoras Genéticas/genética , Ligação Proteica , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteína GLI1 em Dedos de Zinco/genética
7.
BMC Rheumatol ; 4: 9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32072134

RESUMO

Background: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are autoimmune disorders associated with an increased risk for depression, anxiety and sleeping problems. The objective of this study was to analyze use of antidepressants and benzodiazepine-related hypnotics (BRH) in Sweden before and after first time treatment with anti-TNF and non-biological systemic (NBS) treatments among patients with the above diagnoses, and to correlate such use with that of randomly selected population controls. Methods: Patients and dispensed drugs were identified in nationwide Swedish healthcare registers. Proportions of subjects filling prescriptions of antidepressants and BRH from 2 years before start of treatment (index-date), and 2 years after index date were assessed. Using the period -6 months to index-date as reference, prevalence rate ratios were computed for 6 months' intervals before and after index. For up to ten randomly selected population controls per patient, the same measures were calculated. Results: A total of 6256 patients started anti-TNF treatment, and 13,241 NBS treatment. The mean age at index was 52.0 for the anti-TNF group and 56.1 for NBS. Use of antidepressants and BRH was similar in both treatment groups (10.4-12.8%), significantly more common than in the controls (6.6 to 7.6%). For all patients, proportions filling prescriptions for antidepressants and BRH decreased directly or soon after the index; no such changes were seen in the controls, who all showed a slow but steady increase in use over time. Starters of anti-TNF treatment did not show clearer decreases in use of psychotropics than those initiating NBS. Conclusions: Decreased rates of dispensed psychotropic drugs after the time of anti-TNF and NBS treatment initiation were seen among patients with autoimmune disorders but not population controls. This may correspond to treatment effects of anti-TNF and NBS also on psychiatric symptoms among these patients.

8.
Recenti Prog Med ; 111(2): 108-115, 2020 02.
Artigo em Italiano | MEDLINE | ID: mdl-32089560

RESUMO

INTRODUCTION: Low back pain is one of the most frequent causes of consultation of the General Practitioner (GP). The purpose of the present study is to analyze the therapeutic management of low back pain, in relation to pain intensity, in the primary care setting and to assess its impact on the patient's quality of life. METHODS: From the computerized medical records of 65 GPs, all working in the Salerno province (South of Italy), data concerning non-cancer subjects affected by low back or sciatica pain, over 18 years, who consulted the GP in the period between February 1, 2015 and January 31, 2016, were extracted. Pain intensity and quality of life were reported using the 0-10 numeric rating scale (NRS) and the EQ-5D instruments, respectively. RESULTS: A total of 2555 subjects were identified: 28.7% reported mild pain (NRS 0-3), 55.6% moderate pain (NRS 4-6) and 15.7% severe pain (NRS 7-10). Only 35% of patients received a prescription for pain therapy (24.5% in mild pain; 34.1% in moderate pain and 57.1% in severe pain); non-steroidal anti-inflammatory drugs in monotherapy were the most prescribed therapeutic category regardless of pain intensity (61.1% in mild pain, 65.1% in moderate pain and 57.6% in severe pain, p=0.099), followed by strong opioids (17.2%, 15.3% and 24.5%, p=0.011). Overall, mean value for EQ-5D utility was 0.44 (0.61 in mild pain, 0.47 in moderate pain, 0.22 in severe pain). CONCLUSIONS: The results of this study highlight that low back pain is a highly debilitating condition, probably still under-treated or inadequately treated by the GP.


Assuntos
Medicina Geral , Dor Lombar/terapia , Atenção Primária à Saúde , Idoso , Analgésicos Opioides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Estudos Transversais , Feminino , Humanos , Itália , Dor Lombar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença
9.
PLoS One ; 14(7): e0219396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291351

RESUMO

BACKGROUND & AIMS: Hepatitis C (HCV) is associated with several extrahepatic manifestations, and estimates of the hospitalization burden related to these comorbidities are still limited. The aim of this study is to quantify the hospitalization risk associated with comorbidities in an Italian cohort of HCV-infected patients and to assess which of these comorbidities are associated with high hospitalization resource utilization. METHODS: Individuals aged 18 years and older with HCV-infection were identified in the Abruzzo's and Campania's hospital discharge abstracts during 2011-2014 with 1-year follow-up. Cardio-and cerebrovascular disease, diabetes and renal disease were grouped as HCV-related comorbidities. Negative binomial models were used to compare the hospitalization risk in patients with and without each comorbidity. Logistic regression model was used to identify the characteristics of being in the top 20% of patients with the highest hospitalization costs (high-cost patients). RESULTS: 15,985 patients were included; 19.9% had a liver complication and 48.6% had one or more HCV-related comorbidities. During follow-up, 36.0% of patients underwent at least one hospitalization. Liver complications and the presence of two or more HCV-related comorbidities were the major predictors of hospitalization and highest inpatient costs. Among those, patients with cardiovascular disease had the highest risk of hospitalization (Incidence Rate Ratios = 1.42;95%CI:1.33-1.51) and the highest likelihood of becoming high-cost patients (Odd Ratio = 1.37;95%CI:1.20-1.57). CONCLUSION: Beyond advanced liver disease, HCV-related comorbidities (especially cardiovascular disease) are the strongest predictors of high hospitalization rates and costs. Our findings highlight the potential benefit that early identification and treatment of HCV might have on the reduction of hospitalization costs driven by extrahepatic conditions.


Assuntos
Doenças Cardiovasculares/epidemiologia , Comorbidade , Hepatite C/epidemiologia , Hepatopatias/epidemiologia , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/virologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/fisiopatologia , Transtornos Cerebrovasculares/virologia , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Feminino , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/fisiopatologia , Hepatite C/virologia , Custos Hospitalares , Hospitalização , Humanos , Pacientes Internados , Itália/epidemiologia , Fígado/patologia , Fígado/virologia , Hepatopatias/complicações , Hepatopatias/fisiopatologia , Hepatopatias/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/virologia
10.
Therap Adv Gastroenterol ; 11: 1756284818791502, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30159036

RESUMO

Background: Scarce data are available on the epidemiological trend of diverticulitis and its financial burden in Italy. The aim of this work was to explore a potential variation in the rate and costs of hospital admissions for uncomplicated and complicated diverticulitis over the last decade. Methods: We selected all hospitalizations for diverticulitis of residents in the Abruzzo Region, Italy between 2005 and 2015. Age-standardized hospitalization rates (HRs) per 100,000 inhabitants for overall, uncomplicated and complicated diverticulitis were calculated. A linear model on the log of the age-standardized rates was used to calculate annual percentage changes (APC). Costs were derived from the official DRG tariff. Results: From 2005 to 2015, the HR for acute diverticulitis increased from 38.9 to 45.2 per 100,000 inhabitants (APC + 1.9%). The HR for complicated diverticulitis increased from 5.9 to 13.3 (APC + 7.6%), whereas it remained stable for uncomplicated diverticulitis. The mean hospital cost was 1.8-times higher for complicated diverticulitis compared with that for uncomplicated disease and 3.5-times higher for patients with a surgery stay compared with that for patients with a medical stay. Conclusion: During the last decade, in the Abruzzo Region, the HRs for diverticulitis and their costs increased significantly, mainly due to disease complications. Further studies are needed to explore strategies to prevent complications and to realise cost-saving policies.

11.
Clinicoecon Outcomes Res ; 10: 389-398, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30087571

RESUMO

Background: Due to the success of antiretroviral therapy, human immunodeficiency virus (HIV) infection has been transformed into a lifelong condition. In Italy, little is known about the impact of comorbidities (CMs) on the risk of hospitalization and related costs for people who live with HIV (PWLHIV). The objective of the study was to quantify the risk of hospitalization and costs associated with CMs in an Italian cohort of PWLHIV. Methods: The study population included subjects aged ≥18 years with HIV infection, identified in the Abruzzo's hospital discharge database among files stored from 2004 until 2013 and then followed up until December 2015. Patients' CMs (Charlson Comorbidity Index [CCI)] were extracted from International Classification of Diseases, Ninth Revision, Clinical Modification codes in the hospital discharge abstracts. Poisson regression was used to compare the incidence rate of hospital admissions in patients with and without each CM class. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were adjusted for age, sex and the other CMs. A generalized linear model under gamma distribution was used to estimate adjusted mean hospital costs. Costs were derived from official Italian Diagnosis-related group (DRG) based reimbursements. Results: Among 1,026 HIV patients identified (mean age 47 years), 30% had at least one CM and 14.5% underwent hospital admission during the follow-up period. The risk of acute hospitalization significantly increased among patients with hepatitis C virus (HCV) coinfection (adjusted IRR 1.98; 95% CI: 1.59-2.47), renal (adjusted IRR 2.27; 95% CI: 1.45-3.56), liver (adjusted IRR 2.21; 1.57-3.13) and chronic pulmonary CMs (adjusted IRR 2.31; 1.63-3.32). Adjusted mean hospital costs were €2,494 in patients without CMs and €4,422 and €9,734 in those with CCI=1 or CCI ≥2, respectively. Conclusion: The presence of renal, liver and chronic pulmonary CMs, as well as HCV coinfection doubled the risk of hospitalization in the PWLHIV cohort. A CCI ≥2 is associated with a fourfold increase in hospitalization costs. Our study provides new evidence that CMs in PWLHIV increase the risk of hospitalization and local health service facilities.

12.
PLoS Genet ; 14(2): e1007223, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29444071

RESUMO

Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double-strand break (DSB) formation that in budding yeast takes place in gene promoters and is promoted by histone H3K4 di/trimethylation. This histone modification is recognized by Spp1, a PHD finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me3 and interacts with a DSB protein, Mer2, to promote DSB formation close to gene promoters. How Set1 complex- and Mer2- related functions of Spp1 are connected is not clear. Here, combining genome-wide localization analyses, biochemical approaches and the use of separation of function mutants, we show that Spp1 is present within two distinct complexes in meiotic cells, the Set1 and the Mer2 complexes. Disrupting the Spp1-Set1 interaction mildly decreases H3K4me3 levels and does not affect meiotic recombination initiation. Conversely, the Spp1-Mer2 interaction is required for normal meiotic recombination initiation, but dispensable for Set1 complex-mediated histone H3K4 methylation. Finally, we provide evidence that Spp1 preserves normal H3K4me3 levels independently of the Set1 complex. We propose a model where Spp1 works in three ways to promote recombination initiation: first by depositing histone H3K4 methylation (Set1 complex), next by "reading" and protecting histone H3K4 methylation, and finally by making the link with the chromosome axis (Mer2-Spp1 complex). This work deciphers the precise roles of Spp1 in meiotic recombination and opens perspectives to study its functions in other organisms where H3K4me3 is also present at recombination hotspots.


Assuntos
Quebras de DNA de Cadeia Dupla , Proteínas de Ligação a DNA/fisiologia , Histona-Lisina N-Metiltransferase/metabolismo , Meiose , Complexos Multiproteicos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/fisiologia , Proteínas de Ligação a DNA/metabolismo , Histonas/metabolismo , Meiose/genética , Metilação , Organismos Geneticamente Modificados , Dedos de Zinco PHD , Processamento de Proteína Pós-Traducional , Saccharomyces cerevisiae
13.
Pharmacoepidemiol Drug Saf ; 26(6): 615-624, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28133890

RESUMO

PURPOSE: To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. METHODS: New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing. RESULTS: We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. CONCLUSIONS: In this collaborative European study, most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events. © 2017 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.


Assuntos
Bases de Dados Factuais/tendências , Rotulagem de Medicamentos/tendências , Uso de Medicamentos/tendências , Uso Off-Label , Inibidores da Agregação Plaquetária/uso terapêutico , Tetrazóis/uso terapêutico , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Cilostazol , Bases de Dados Factuais/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Uso Off-Label/estatística & dados numéricos , Espanha/epidemiologia , Suécia/epidemiologia , Reino Unido/epidemiologia
14.
Recenti Prog Med ; 107(5): 234-41, 2016 May.
Artigo em Italiano | MEDLINE | ID: mdl-27311123

RESUMO

INTRODUCTION: Non-valvular atrial fibrillation (NVAF) is the most common cardiac arrhythmia and it is associated with a 5-fold increase in risk of ischemic stroke. Although clinical guidelines recommend antithrombotic therapy for stroke prevention in patients at moderate or high risk for stroke, little is known on the extent to which the increase of the risks influence the choice of the therapy. AIM: The aim of the study was to assess the level of adherence to the guidelines for the prevention of thromboembolic risk in patients with NVAF. METHODS: A population-based cohort study was conducted using administrative data from a local health authority in the Campania Region (~1,000,000 inhabitants). NVAF was defined as one or more claims for atrial fibrillation between July, 2013 and June, 2014 where none of the claims were associated with cardioversion or cardiac ablation during the identification period and there was no evidence of valve-related diagnoses or procedures. The cohort was classified according to the first drug dispensing during 6 months from the discharge date for atrial fibrillation. Patients were categorized in low ischemic stroke risk (LR, score = 0), moderate-risk (MR, score = 1), high-risk (HR, score≥2) according to the CHA2DS2-VASc score. Multivariable logistic regression was used to evaluate the associations between ischemic stroke risk with the choice of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) therapy. RESULTS: A total of 1963 patients were identified: 4.9% LR, 7.6% MR and 87.5% HR patients. Overall, 36.4% of patients were not treated (LR: 56.7%, MR: 55.0%, HR: 33.7%patients). The Vitamin K antagonists were prescribed to 17% of the patients (LR: 10.3%, MR: 12,1%, HR: 17,8%), NOAC to 12,7% (LR: 10,3%, MR: 8,1%, HR: 13,2%), low-dose aspirin to 17.5% (LR: 13,4%, MR: 15,4%, HR: 17,9%), other antiplatelet to 12,3% (LR: 7,2%, MR: 6,0%, HR: 13,2%). The ischemic stroke was not significantly associated with the choice of anticoagulant drug. CONCLUSIONS: High proportion of NVAF patients with CHA2DS2-VASc score of 2 or greater not received oral anticoagulant as recommended. In contrast with recent guidelines, aspirin was commonly prescribed even in HR patients. The stroke risk stratification did not influence the choice of anticoagulant drug.


Assuntos
Fibrilação Atrial , Anticoagulantes , Isquemia Encefálica , Estudos de Coortes , Fibrinolíticos , Humanos , Acidente Vascular Cerebral
15.
Eur J Clin Pharmacol ; 72(3): 349-57, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26671240

RESUMO

PURPOSE: Persistence to statins is low, in part due to lack of perception of cardiovascular (CV) risk. High values of low-density lipoprotein cholesterol (LDL-C) might increase the motivation for patients to be persistent. We investigated whether the baseline LDL-C value influences the discontinuation of statin treatment in patients with and without previous CV events. METHODS: A cohort study was performed using information from the Swedish national registers concerning dispensed drugs, hospital contacts, cause of death, and socioeconomic status, and linked with data from clinical laboratories. Incident statin users 20 years of age or older and starting treatment between 2006 and 2007 were identified and followed for 1 year. Baseline LDL-C level was defined as the last available laboratory test result during 6 months before the index statin dispensing. Cox regression was used to study discontinuation and estimate the effect on persistence of the baseline LDL-C value adjusting for sex, age, income, comorbidity, previous CV events, type of prescriber, and country of birth. Subgroup analyses stratifying by previous CV events and by diagnosis of diabetes among subjects without previous CV events were performed. RESULTS: A total of 29,389 patients were identified; 35.4% had a previous CV event. A high baseline LDL-C value was associated with a lower discontinuation rate (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.72-0.91) in patients without previous CV events. When stratifying further by diabetes diagnosis, the association was confirmed only in patients without diabetes. No association between LDL-C and persistence was found in patients with previous CV events. CONCLUSIONS: High levels of LDL-C were positively associated with statin persistence in newly treated diabetes patients without previous CV events.


Assuntos
LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adulto , Idoso , Doenças Cardiovasculares/tratamento farmacológico , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Adulto Jovem
16.
Menopause ; 22(4): 369-76, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25335101

RESUMO

OBJECTIVE: This work aims to study the effects of hormone therapy (HT) on the risk of cardiovascular outcomes and all-cause mortality in women treated with statins. METHODS: We included women aged 40 to 74 years and living in Sweden who filled a first statin prescription between 2006 and 2007. Women were categorized as HT users or as nonusers. Information on dispensed drugs, comorbidity, cardiovascular outcomes, and all-cause mortality was obtained from national health registers. RESULTS: A total of 40,958 statin users--2,862 (7%) HT users and 38,096 nonusers--were followed for a mean of 4.0 years. In total, 70% of the women used statins as primary prevention. Among HT users, there were five cardiovascular deaths per 10,000 person-years. The corresponding rate among nonusers was 18, which yielded a hazard ratio of 0.38 (95% CI, 0.12-1.19). The all-cause mortality rates were 33 and 87, respectively, and the hazard ratio was 0.53 (95% CI, 0.34-0.81). There were no associations with cardiovascular events. A similar pattern was found for both primary and secondary prevention. CONCLUSIONS: HT is associated with a reduced risk of all-cause mortality in women treated with statins. Although confounding factors, such as lifestyle and disease severity, might have influenced the results, HT does not seem to be detrimental to statin-treated women.


Assuntos
Doença das Coronárias/mortalidade , Doença das Coronárias/prevenção & controle , Terapia de Reposição de Estrogênios , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Causas de Morte , Feminino , Humanos , Fatores de Risco
17.
Menopause ; 22(6): 633-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25405572

RESUMO

OBJECTIVE: This study aims to assess use of hormone therapy (HT) after cervical cancer treatment in women of premenopause age. METHODS: We identified 837 women aged 45 years or younger at diagnosis of cervical cancer in the Swedish Cancer Register from January 1, 2005 to September 30, 2009 with a minimal follow-up of 1.5 years. Information on cancer treatment (surgical operation, radiotherapy, and/or chemotherapy) was obtained through the National Patient Register. Use of HT was estimated through HT dispensing during follow-up as recorded in the Prescribed Drug Register. Percentage of recommended dose was assessed by frequency of HT dispensing at half-year intervals up to April 1, 2011 or a maximal age of 50 years. RESULTS: A total of 257 women (31%) received acute estrogen deprivation due to bilateral salpingo-oophorectomy and/or radiotherapy. Among these women, 171 (67%) of 257 had at least one dispensing of HT during the period 0.5 to 1 year after diagnosis, and 118 (46%) of 257 were dispensed 75% or more of the recommended dose. Proportion users decreased to 39% at 4.5 to 5 years after diagnosis (21% with ≥ 75% of the recommended dose). Women younger than 40 years had a higher prevalence of HT use at 0.5 to 1 year (79%), decreasing to 45% after 4.5 to 5 years. The results did not vary by cancer histology. CONCLUSIONS: Fewer than half of cervical cancer survivors with therapy-induced early menopause used HT at or close to the recommended dose, and the use decreased during follow-up. Increased awareness of the health benefits of HT for this patient group is needed among professionals and women.


Assuntos
Terapia de Reposição de Estrogênios/métodos , Estrogênios/administração & dosagem , Pré-Menopausa , Neoplasias do Colo do Útero/terapia , Saúde da Mulher , Adulto , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Fogachos/tratamento farmacológico , Humanos , Histerectomia/métodos , Pessoa de Meia-Idade , Radioterapia Adjuvante/métodos , Sistema de Registros , Suécia/epidemiologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia
18.
Eur J Clin Pharmacol ; 70(6): 701-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24604354

RESUMO

PURPOSE: Persistence to statins is low, presumably due to lack of perception of risk. Having a close relative suffering from cardiovascular disease (CVD) might increase persistence to statins. We investigated whether family history of CVD influences the discontinuation of statin treatment. METHODS: A population-based cohort study was performed. Swedish registers on dispensed drugs, hospitalization and cause of death were linked to the Multi-generation Register. Incident statin users 20-72 years of age were identified between 2006 and 2007 and followed until 30 June 2009. Family history of CVD was defined as the presence of relatives with a previous cardiovascular event. Cox regression was used to study discontinuation and estimate the effect of the family history of CVD, adjusting for gender, age, education, income, healthcare provider, prevention's type, birth's country and residence's county. Stratified analysis by type and severity of cardiovascular event was performed. RESULTS: A total of 86,002 patients were enrolled; 61.5 % had a family history of CVD. Discontinuation of statin therapy was not associated with family history of CVD (HR: 0.98; 95 % CI:0.96-1.01), except for patients with a family history of death from myocardial infarction (MI) (HR: 0.95 95 % CI:0.92-0.98). Young age, foreign background, low income, and statin for primary prevention and for secondary prevention when prescribed by a general practitioner were associated with higher risk of statin discontinuation. CONCLUSIONS: Having relatives suffering from CVD did not consistently influence the persistence to statin treatment. A family history of death from MI had a slight significant positive effect on statin persistence, though not clinically relevant.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Adulto , Idoso , Doenças Cardiovasculares/genética , Estudos de Coortes , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Farmacoepidemiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Medição de Risco , Suécia/epidemiologia , Adulto Jovem
19.
PLoS One ; 8(11): e79762, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24244557

RESUMO

BACKGROUND: Few studies are available evaluating the impact of rapid-acting insulin analogues on long-term diabetes outcomes. Our aim was to compare the use of rapid-acting insulin analogues versus human regular insulin in relation to the occurrence of diabetic complications in a cohort of diabetic patients through the analysis of administrative databases. METHODS: A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients free of macrovascular disease at baseline and treated either with human regular insulin or rapid-acting insulin analogues were followed for a maximum of 3 years. The incidence of diabetic complications was ascertained by hospital discharge claims. Hazard ratios (HRs) and 95% CIs of any diabetic complication and macrovascular, microvascular and metabolic complications were estimated separately using Cox proportional hazard models adjusted for patients' characteristics and anti-diabetic drug use. Propensity score matching was also used to adjust for significant difference in the baseline characteristics between the two treatment groups. RESULTS: A total of 2,286 patients were included: 914 receiving human regular insulin and 1,372 rapid-acting insulin analogues. During the follow-up, 286 (31.3%) incident events occurred in the human regular insulin group and 235 (17.1%) in the rapid-acting insulin analogue group. After propensity score-based matched-pair analyses, rapid-acting insulin analogues users had a HR of 0.73 (0.58-0.92) for any diabetes-related complication and HRs of 0.73 (0.55-0.93) and 0.55 (0.32-0.96) for macrovascular and metabolic complications respectively, as compared with human regular insulin users. No difference between the two groups was found for microvascular complications. CONCLUSIONS: Our findings suggest that the use of rapid-acting insulin analogues is associated with a lower risk of cardiovascular and metabolic complications compared with human regular insulin use.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Regular Humana/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
20.
Menopause ; 20(2): 146-51, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22929038

RESUMO

OBJECTIVE: This work aims to determine whether discontinuation of hormone therapy (HT) in perimenopausal and postmenopausal women is associated with an increased risk of initiating antidepressant therapy. METHODS: A population-based cohort study was conducted using data from the Swedish Prescribed Drug Register and the Total Population Register for the period July 2005 to June 2009. We included women aged 45 to 70 years who had used HT continuously for more than 6 months before July 2008. Women with previous use of antidepressants since July 2005 were excluded. We compared the incidence rates of initiating antidepressant therapy during HT and after withdrawal of HT. The women were followed from July 2008 until the first dispensing of antidepressants, restart of HT, migration, death, or end of the study period, whichever occurred first. Poisson regression analysis was used to estimate the incidence rate ratios adjusting for potential confounders (age, calendar time, duration of HT use, and number of HT prescriptions). RESULTS: Of the 101,911 women enrolled in the cohort, 39.8% discontinued HT during follow-up. Discontinuation of HT was associated with an increased risk of antidepressant use (incidence rate ratio, 1.24; 95% CI, 1.11-1.38). Women 65 years or older and women who had used HT for 3 years or more had the highest risk estimates, but effect modification by age and duration was not significant. CONCLUSIONS: We found a slightly increased risk in the use of antidepressant therapy after discontinuation of HT.


Assuntos
Antidepressivos/administração & dosagem , Terapia de Reposição de Estrogênios/efeitos adversos , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Perimenopausa , Pós-Menopausa , Sistema de Registros , Síndrome de Abstinência a Substâncias/psicologia , Suécia
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