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1.
Mol Microbiol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619026

RESUMO

MucR belongs to a large protein family whose members regulate the expression of virulence and symbiosis genes in α-proteobacteria species. This protein and its homologs were initially studied as classical transcriptional regulators mostly involved in repression of target genes by binding their promoters. Very recent studies have led to the classification of MucR as a new type of Histone-like Nucleoid Structuring (H-NS) protein. Thus this review is an effort to put together a complete and unifying story demonstrating how genetic and biochemical findings on MucR suggested that this protein is not a classical transcriptional regulator, but functions as a novel type of H-NS-like protein, which binds AT-rich regions of genomic DNA and regulates gene expression.

2.
Int J Mol Sci ; 24(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37834166

RESUMO

Proteins of the MucR/Ros family play a crucial role in bacterial infection or symbiosis with eukaryotic hosts. MucR from Sinorhizobium meliloti plays a regulatory role in establishing symbiosis with the host plant, both dependent and independent of Quorum Sensing. Here, we report the first characterization of MucR isolated from Sinorhizobium meliloti by mass spectrometry and demonstrate that this protein forms higher-order oligomers in its native condition of expression by SEC-MALS. We show that MucR purified from Sinorhizobium meliloti can bind DNA and recognize the region upstream of the ndvA gene in EMSA, revealing that this gene is a direct target of MucR. Although MucR DNA binding activity was already described, a detailed characterization of Sinorhizobium meliloti DNA targets has never been reported. We, thus, analyze sequences recognized by MucR in the rem gene promoter, showing that this protein recognizes AT-rich sequences and does not require a consensus sequence to bind DNA. Furthermore, we investigate the dependence of MucR DNA binding on the length of DNA targets. Taken together, our studies establish MucR from Sinorhizobium meliloti as a member of a new family of Histone-like Nucleoid Structuring (H-NS) proteins, thus explaining the multifaceted role of this protein in many species of alpha-proteobacteria.


Assuntos
Proteínas Repressoras , Sinorhizobium meliloti , Proteínas Repressoras/genética , Sinorhizobium meliloti/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Transcrição/metabolismo , DNA/genética , DNA/metabolismo , Simbiose , Regulação Bacteriana da Expressão Gênica
3.
Molecules ; 28(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37630276

RESUMO

Glioblastoma, the most dangerous and aggressive type of CNS tumor, appears resistant to many chemotherapy drugs. In the patient-derived glioma cell lines NULU and ZAR, which exhibit drug-resistant phenotypes, we investigated the effect of combined AE (Aloe-emodin) and TMZ (temozolomide) and found a significant additive inhibitory effect on cell growth and a promising cytotoxic effect on both cell lines compared to treatment with single agents. We also examined the effect of combined AE and TMZ treatment on the drug-resistance protein MGMT. The results suggest that using AE combined with traditional drugs restores drug resistance in both primary resistant cell lines (NULU and ZAR). Furthermore, migration assays and scratch tests showed that the combined use of AE and TMZ can slow down the colony formation and migration of glioblastoma cells. These convincing results suggest that AE could be a natural adjuvant agent to potentiate the effects of traditional drugs (TMZ) and overcome drug resistance in glioblastoma cells.


Assuntos
Aloe , Emodina , Glioblastoma , Humanos , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Linhagem Celular
4.
Int J Mol Sci ; 21(23)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255744

RESUMO

The transcription factor CCCTC-binding factor (CTCF) modulates pleiotropic functions mostly related to gene expression regulation. The role of CTCF in large scale genome organization is also well established. A unifying model to explain relationships among many CTCF-mediated activities involves direct or indirect interactions with numerous protein cofactors recruited to specific binding sites. The co-association of CTCF with other architectural proteins such as cohesin, chromodomain helicases, and BRG1, further supports the interplay between master regulators of mammalian genome folding. Here, we report a comprehensive LC-MS/MS mapping of the components of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex co-associated with CTCF including subunits belonging to the core, signature, and ATPase modules. We further show that the localization patterns of representative SWI/SNF members significantly overlap with CTCF sites on transcriptionally active chromatin regions. Moreover, we provide evidence of a direct binding of the BRK-BRG1 domain to the zinc finger motifs 4-8 of CTCF, thus, suggesting that these domains mediate the interaction of CTCF with the SWI/SNF complex. These findings provide an updated view of the cooperative nature between CTCF and the SWI/SNF ATP-dependent chromatin remodeling complexes, an important step for understanding how these architectural proteins collaborate to shape the genome.


Assuntos
Fator de Ligação a CCCTC/genética , Montagem e Desmontagem da Cromatina/genética , Proteínas Cromossômicas não Histona/genética , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Dedos de Zinco/genética , Adenosina Trifosfatases/genética , Sítios de Ligação/genética , Proteínas de Ciclo Celular/genética , Regulação da Expressão Gênica/genética , Genoma Humano/genética , Humanos , Complexos Multiproteicos/genética , Mapas de Interação de Proteínas/genética , Espectrometria de Massas em Tandem , Coesinas
5.
J Drugs Dermatol ; 15(6): 772-4, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27272089

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful, inflammatory disorder of hair follicles and manifests with several cutaneous findings, including double comedones, papules, cysts, nodules, draining abscesses, and sinus tracts. It is associated with tremendous morbidity and decreased quality of life. Treatment of HS is challenging. Recently, there have been mixed reports regarding the efficacy of anakinra, an interleukin 1 receptor antagonist, in the management of HS.
CASE: A 55-year-old African American male with a several year history of severe HS, recalcitrant to multiple prior treatments, was treated with a 12 week course of anakinra 100 mg subcutaneously daily. After 3 months of therapy, minimal change was observed, and the patient strongly preferred to cease therapy due to lack of improvement and pain associated with daily injections.
CONCLUSION: Our case of severe HS proved refractory to anakinra. Tolerance of this therapy may be a limiting factor for some patients due to necessity for daily injections.

J Drugs Dermatol. 2016;15(6):772-774.


Assuntos
Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Índice de Gravidade de Doença , Esquema de Medicação , Seguimentos , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Falha de Tratamento
6.
Dermatol Online J ; 21(11)2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26632937

RESUMO

Endometriosis is the presence of ectopic endometrial tissue outside the uterus and cutaneous endometriosis is a rare manifestation of this disease that may be found at the sites of surgical scars as a result of iatrogenic implantation. Herein we present a case of scar endometriosis in a 35-year-old woman. The scar was sustained following a remote caesarean section.


Assuntos
Cesárea/efeitos adversos , Cicatriz/patologia , Endometriose/patologia , Dermatopatias/patologia , Tela Subcutânea/patologia , Adulto , Endometriose/cirurgia , Feminino , Humanos , Gravidez , Dermatopatias/cirurgia , Tela Subcutânea/cirurgia
7.
Clin Chem Lab Med ; 52(10): 1457-64, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24803610

RESUMO

BACKGROUND: With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients' risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea. METHODS: We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed. RESULTS: A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum-minimum): 31 (0-905) versus 8 (0-13) pmol/L. Median copeptin value at admission was 42 (0-905) pmol/L in acute heart failure patients and 20 (0-887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001). CONCLUSIONS: In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.


Assuntos
Dispneia/sangue , Dispneia/diagnóstico , Glicopeptídeos/sangue , Admissão do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Idoso , Dispneia/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Determinação de Ponto Final , Feminino , Humanos , Masculino , Readmissão do Paciente , Prognóstico
8.
Am J Emerg Med ; 32(4): 334-41, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24559907

RESUMO

INTRODUCTION: Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency department patients with dyspnea. METHODS: To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF). RESULTS: Five hundred one patients were enrolled. Procalcitonin and MR-proADM values at admission and at 72 hours were significantly (P < .001) predictive for 30-day mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72 hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM baseline and 72 hours values showed a significant (P < .0001) predictive ability: baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF, group biomarkers predicted rehospitalization and mortality at 90 days, whereas in AHF + NO AHF group, they predict mortality at 30 and 90 days. CONCLUSIONS: In patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk stratification and management. Combined use of biomarkers is able to predict in the total cohort both rehospitalization and death at 30 and 90 days.


Assuntos
Adrenomedulina/sangue , Calcitonina/sangue , Dispneia/sangue , Dispneia/mortalidade , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Pneumopatias/sangue , Pneumopatias/mortalidade , Precursores de Proteínas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Serviço Hospitalar de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Itália/epidemiologia , Masculino , Admissão do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco
9.
Toxins (Basel) ; 16(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38535801

RESUMO

Ribosome inactivating proteins (RIPs) are specific N-ß-glycosylases that are well-characterized in plants. Their enzymatic action is to damage ribosomes, thereby blocking protein translation. Recently, several research groups have been working on the screening for these toxins in edible plants to facilitate the use of RIPs as biotechnological tools and biopesticides and to overcome public prejudice. Here, four novel monomeric (type 1) RIPs have been isolated from the seeds of Atriplex hortensis L. var. rubra, which is commonly known as edible red mountain spinach. These enzymes, named hortensins 1, 2, 4, and 5, are able to release the ß-fragment and, like many other RIPs, adenines from salmon sperm DNA, thus, acting as polynucleotide:adenosine glycosidases. Structurally, hortensins have a different molecular weight and are purified with different yields (hortensin 1, ~29.5 kDa, 0.28 mg per 100 g; hortensin 2, ~29 kDa, 0.29 mg per 100 g; hortensin 4, ~28.5 kDa, 0.71 mg per 100 g; and hortensin 5, ~30 kDa, 0.65 mg per 100 g); only hortensins 2 and 4 are glycosylated. Furthermore, the major isoforms (hortensins 4 and 5) are cytotoxic toward human continuous glioblastoma U87MG cell line. In addition, the morphological change in U87MG cells in the presence of these toxins is indicative of cell death triggered by the apoptotic pathway, as revealed by nuclear DNA fragmentation (TUNEL assay).


Assuntos
Atriplex , Proteínas Inativadoras de Ribossomos Tipo 1 , Sementes , Humanos , Glioblastoma , Ribossomos , Proteínas de Plantas , Linhagem Celular Tumoral
10.
Drugs Aging ; 38(11): 1025-1037, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632551

RESUMO

BACKGROUND: Older patients are at increased risk of drug-drug interactions (DDIs) due to polypharmacy. Cardiovascular and central nervous system (CNS) drugs are commonly implicated in serious DDIs. OBJECTIVES: This study aimed to determine the prevalence and factors associated with potential 'severe' cardiovascular and CNS DDIs among older (≥ 70 years) community-dwellers. METHODS: This was a prospective cohort study using linked data from a national pharmacy claims database and waves 1 and 2 of The Irish LongituDinal study on Ageing (TILDA). 'Severe' cardiovascular and CNS DDIs were identified using the British National Formulary 77 and Stockley's Drug Interactions. The prevalence of 'severe' DDIs (any DDI vs. none) was calculated. Logistic regression was used to examine the association between sociodemographic, functional ability, and medication-related factors and the risk of DDI exposure between waves 1 and 2. RESULTS: A total of 1466 patients were included [mean age (standard deviation) = 78 (5.5) years; female n = 795, 54.2%]. In total, 332 community-dwellers aged ≥ 70 years [22.65%, 95% confidence interval (CI) 20.58-24.86] were potentially exposed to at least one 'severe' cardiovascular or CNS DDI, with more than half (54.82%) of this cohort dispensed the same DDI for a prolonged time (≥ 3 consecutive claims). Aspirin-warfarin was the most frequently dispensed (co-prescribed) DDI (n = 34, 10.24%, 95% CI 7.39-14.00), followed by atorvastatin-clarithromycin (n = 19, 5.72%, 95% CI 3.64-8.81). Polypharmacy [≥ 10 vs. < 5 drugs, odds ratio (OR) 13.40, 95% CI 8.22-21.85] and depression (depressed vs. not, OR 2.12, 95% CI 1.34-3.34) were significantly associated with these DDIs, after multivariable adjustment. CONCLUSION: 'Severe' cardiovascular and CNS DDIs are prevalent in older community-dwellers in Ireland, and those with polypharmacy and depression are at a significantly increased risk.


Assuntos
Vida Independente , Polimedicação , Idoso , Estudos de Coortes , Interações Medicamentosas , Feminino , Humanos , Estudos Longitudinais , Masculino , Prevalência , Estudos Prospectivos
11.
Int J Biol Macromol ; 168: 67-76, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33301849

RESUMO

ZBTB2 is a protein belonging to the BTB/POZ zinc-finger family whose members typically contain a BTB/POZ domain at the N-terminus and several zinc-finger domains at the C-terminus. Studies have been carried out to disclose the role of ZBTB2 in cell proliferation, in human cancers and in regulating DNA methylation. Moreover, ZBTB2 has been also described as an ARF, p53 and p21 gene repressor as well as an activator of genes modulating pluripotency. In this scenario, ZBTB2 seems to play many functions likely associated with other proteins. Here we report a picture of the ZBTB2 protein partners in U87MG cell line, identified by high-resolution mass spectrometry (MS) that highlights the interplay between ZBTB2 and chromatin remodeling multiprotein complexes. In particular, our analysis reveals the presence, as ZBTB2 candidate interactors, of SMARCA5 and BAZ1B components of the chromatin remodeling complex WICH and PBRM1, a subunit of the SWI/SNF complex. Intriguingly, we identified all the subunits of the NuRD complex among the ZBTB2 interactors. By co-immunoprecipitation experiments and ChIP-seq analysis we definitely identify ZBTB2 as a new partner of the NuRD complex.


Assuntos
Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Adenosina Trifosfatases/metabolismo , Linhagem Celular Tumoral , Cromatina/genética , Proteínas Cromossômicas não Histona/metabolismo , DNA/genética , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Glioblastoma/metabolismo , Humanos , Imunoprecipitação/métodos , Espectrometria de Massas/métodos , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/fisiologia , Proteínas Nucleares/genética , Nucleossomos/genética , Ligação Proteica/genética , Proteínas Repressoras/fisiologia , Fatores de Transcrição/metabolismo , Dedos de Zinco/fisiologia
12.
Front Pharmacol ; 11: 418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536861

RESUMO

BACKGROUND: Studies have emphasized the importance of geographical factors and general practitioner (GP) characteristics in influencing drug prescriptions. OBJECTIVES: To: (i) ascertain the prevalence rate (PR) of use of drugs in six therapeutic categories used for chronic conditions; (ii) assess how geographical characteristics and GP characteristics may influence drug prescribing. METHODS: This study is part of the EDU.RE.DRUG Project, a national collaborative project founded by Italian Medicine Agency (AIFA). Cross-sectional analyses were undertaken employing the pharmacy-claim databases of four local health units (LHUs) located in two Italian regions: Lombardy and Campania. Six drug categories were evaluated: proton-pump inhibitors; antibiotics; respiratory-system drugs; statins; agents acting on the renin-angiotensin system; psychoanaleptic drugs. The PR was estimated according to drug categories at the LHU level. A linear multivariate regression analysis was undertaken to evaluate the association between the PR and geographical area, age and sex of GPs, number of patients, and percentage of patients aged >65 per GP. RESULTS: LHUs in Campania showed a PR that was significantly higher than that in Lombardy. Antibiotics showed the highest PR in all the LHUs assessed, ranging from 32.5% in Lecco (Lombardy) to 59.7% in Naples-2 (Campania). Multivariate linear regression analysis confirmed the association of the PR with geographical area for all drug categories. Being located in Campania increased the possibility of receiving a drug prescription from the categories considered, with estimates more marked for antibiotics, proton-pump-inhibitors, and respiratory-system drugs. CONCLUSIONS: This study provides information about the PR of medications used for treating common and costly conditions in Italy and highlighted a significant geographical variation. These insights could help to develop area-specific strategies to optimize prescribing behavior.

13.
Risk Manag Healthc Policy ; 13: 63-71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099490

RESUMO

PURPOSE: The purpose was to analyze drug prescription and antibiotic use by age and sex in Italy's Campania Region, and to estimate the distribution of prescription rates in children (≤14 years old), adults (between 15 and 65 years old), and older adults (≥65 years old) at a municipality level. METHODS: This was a retrospective analysis of pharmacy records in Campania (Southern Italy), in 2016. Difference in antibiotic prescriptions in different age groups was assessed by prevalence rates. Age-adjusted prevalence rates were categorized into quintiles and mapped by the patient's municipality of residence. Relationship between prevalence rates for the different age groups was estimated using the non-parametric Spearman rank correlation test. RESULTS: There were 2,738,118 were patients with at least one antibiotic prescription. Antibiotics prescription was higher in children aged <5 years and in the older adults aged >70 years. Prevalence rate distribution was different among municipalities in all age groups. A positive correlation between the rank distribution of prevalence rates at municipality level was identified for children and adults (rs=0.56; P<0.01), adults and the older adults (rs=0.79; P<0.01), and children and the older adults (rs=0.46; P<0.01). Among the studied age groups, the most prescribed antibiotic class was penicillin (except the older adults aged ≥85 years) ranging from 45% in children to 27.2% in the older adults. Fluoroquinolones were the least prescribed antibiotic class, ranging from 0.2% in children to 30.2% in the older adults. CONCLUSION: A considerably high use of antibiotic drugs has been detected in Campania Region, with values exceeding the regional and national average. Prescriptions at municipal level differ from one age group to another. Antibiotic use is often unjustified, and to decrease the number of prescriptions and improve their appropriateness, several measures at territorial level are recommended.

14.
Biomolecules ; 10(5)2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32438765

RESUMO

The protein MucR from Brucella abortus has been described as a transcriptional regulator of many virulence genes. It is a member of the Ros/MucR family comprising proteins that control the expression of genes important for the successful interaction of α-proteobacteria with their eukaryotic hosts. Despite clear evidence of the role of MucR in repressing virulence genes, no study has been carried out so far demonstrating the direct interaction of this protein with the promoter of its target gene babR encoding a LuxR-like regulator repressing virB genes. In this study, we show for the first time the ability of MucR to bind the promoter of babR in electrophoretic mobility shift assays demonstrating a direct role of MucR in repressing this gene. Furthermore, we demonstrate that MucR can bind the virB gene promoter. Analyses by RT-qPCR showed no significant differences in the expression level of virB genes in Brucella abortus CC092 lacking MucR compared to the wild-type Brucella abortus strain, indicating that MucR binding to the virB promoter has little impact on virB gene expression in B. abortus 2308. The MucR modality to bind the two promoters analyzed supports our previous hypothesis that this is a histone-like protein never found before in Brucella.


Assuntos
Proteínas de Bactérias/genética , Brucella abortus/genética , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Fatores de Virulência/genética , Proteínas de Bactérias/metabolismo , Brucella abortus/metabolismo , Regulação Bacteriana da Expressão Gênica , Ligação Proteica , Fatores de Transcrição/metabolismo , Fatores de Virulência/metabolismo
15.
Expert Rev Pharmacoecon Outcomes Res ; 19(4): 463-471, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30644761

RESUMO

Background: Antihypertensive drugs play a crucial role in reducing cardiovascular morbidity and mortality. Variability in prescribing patterns constitutes a major challenge for current healthcare systems. This study aimed to compare patterns of use of antihypertensives in general practice in two southern European populations. Methods: Observational study. Data on antihypertensive drugs consumption in primary care setting (2016) were obtained from pharmacy refill records in Campania (Italy) and Aragon (Spain). Prescribing rates and the number of defined daily doses [DDD/1,000 inhabitants/day (DID)] were calculated, and the Drug Utilization 90% (DU90%) approach used to reveal differences in prescribing patterns in both regions. Results: Antihypertensive prescribing rates in Campania and Aragon were 250.8 (95%CI: 250.2-251.3) and 201.7 (95%CI: 200.9-202.5) users/1,000 inhabitants/year. Overall consumption was of 310.1 and 256.8 DID, respectively. Spanish users, especially women and the elderly, consumed a greater volume of diuretics. Conversely, other therapeutic subgroups were more consumed in Campania. However, the most prescribed subgroups accounted for comparable proportions of the total consumption in each region. Conclusions: Both prescribing rates and intensity of antihypertensive use were higher in Campania. Pharmacy refill records in cross-country comparisons allow to know the factors influencing variability in prescribing habits with a view to improving prescribing quality.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/normas , Espanha
16.
Clinicoecon Outcomes Res ; 10: 251-258, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29765241

RESUMO

PURPOSE: The aim of this study was to analyze the geographic variation in systemic antibiotic prescription at a regional level and to explore the influence of socioeconomic and sociodemographic variables. METHODS: This study was a retrospective analysis of reimbursement pharmacy records in the outpatient settings of Italy's Campania Region in 2016. Standardized antibiotic prescription rates were calculated at municipality and Local Health Unit (LHU) level. Antibiotic consumption was analyzed as defined daily doses (DDD)/1000 inhabitants per day (DID). Logistic regression was performed to evaluate the association between antibiotic prescription and sociodemographic and socioeconomic determinants at a municipality level. RESULTS: The average antibiotic prevalence rate was 46.8%. At LHU level, the age-adjusted prevalence rates ranged from 41.1% in Benevento to 51.0% in Naples2. Significant differences were found among municipalities, from 15.2% in Omignano (Salerno LHU [Sa-LHU]) to 61.9% in Moschiano (Avellino [Av-LHU]). The geographic distribution also showed significant differences in terms of antibiotic consumption, from 6.7 DID in Omignano to 41.6 in San Marcelino (Caserta [Ce-LHU]). Logistic regression showed that both municipality type and average annual income level were the main determinants of antibiotic prescription. Urban municipalities were more than eight times as likely to have antibiotic high prevalence rates compared to rural municipalities (adjusted odds ratio [OR]: 8.62; 95% confidence interval [CI]: 4.06-18.30, P<0.001). Low average annual income level municipalities were more than eight times as likely to have antibiotic high prevalence rates compared to high average annual income level municipalities (adjusted OR: 8.48; 95% CI: 3.45-20.81, P<0.001). CONCLUSION: We provide a snapshot of Campania's antibiotic consumption, evidencing the impact of both socioeconomic and sociodemographic factors on the prevalence of antibiotic prescription. The observed intraregional variability underlines the lack of shared therapeutic protocols and the need for careful monitoring. Our results can be useful for decision makers to plan educational interventions, thus optimizing health resources and improving rational drug use.

18.
Clinicoecon Outcomes Res ; 9: 741-748, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29238210

RESUMO

PURPOSE: The aim was to describe the current use of biological therapies among patients affected by psoriasis and to analyze a drug utilization profile in naïve patients in terms of switching and treatment costs in a Local Health Unit (LHU) of Southern Italy. METHODS: We conducted an observational retrospective cohort analysis using the health-related administrative databases of a LHU in Southern Italy covering a population of about one million inhabitants. All subjects with a main or secondary diagnosis of psoriasis who received at least one prescription of biological therapies between January 1, 2010 and December 31, 2014 were analyzed. Switching rate was evaluated in naïve patients within the first year of treatment. Drug cost was calculated for all drugs prescribed and comprised both costs for psoriasis drugs and costs for other treatments. RESULTS: About 20% of patients identified with a diagnosis of psoriasis were under treatment with biological drugs. Among 385 subjects treated with biological therapy, 51.2% were in treatment with etanercept and 33% with adalimumab. Among naïve patients, switching rate to a different biological drug, within the first year of treatment, was 7.3%. The per patient yearly drug cost was €10,536: 96.8% for psoriasis-related drugs and 3.2% for other pharmaceutical treatments. The annual average cost per patient switching from the initial treatment was €13,021, while for those who did not switch from the initial treatment, the annual average cost was €10,342, with a significant difference of about €2,680 per patient per year (p=0.002). CONCLUSION: Our data may be useful in exploring the dynamics that characterize the use of biological therapy within a specific context and to optimize the use of resources for a better management of the disease.

19.
Ann Lab Med ; 37(2): 137-146, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28029000

RESUMO

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. METHODS: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. RESULTS: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P<0.0001). In all patients, the sST2 level at arrival showed higher independent predictive power than hs-cTnI (odds ratio [OR] 20.13, P<0.0001 and OR 2.61, P<0.0008, respectively). sST2 at ED arrival showed a greater prognostic value for cardiovascular events in STEMI (area under the curve [AUC] 0.80, P<0.001) than NSTEMI patients (AUC 0.72, P<0.05). Overall, 51% of the STEMI patients with an sST2 value>35 ng/mL at ED arrival died during the 30-day follow-up. CONCLUSIONS: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value >35 ng/mL at ED arrival showed the highest predictive power for short-term mortality.


Assuntos
Síndrome Coronariana Aguda/mortalidade , Proteína 1 Semelhante a Receptor de Interleucina-1/análise , Troponina I/análise , Síndrome Coronariana Aguda/diagnóstico , Idoso , Área Sob a Curva , Biomarcadores/análise , Dor no Peito , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Curva ROC
20.
Eur Heart J Acute Cardiovasc Care ; 6(4): 339-347, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27073131

RESUMO

OBJECTIVES: The objective of this study was to investigate the prognostic role of quantitative reduction of congestion during hospitalization assessed by Bioelectrical Impedance Vector Analysis (BIVA) serial evaluations in patients admitted for acute heart failure (AHF). BACKGROUND: AHF is a frequent reason for patients to be admitted. Exacerbation of chronic heart failure is linked with a progressive worsening of the disease with increased incidence of death. Fluid overload is the main mechanism underlying acute decompensation in these patients. BIVA is a validated technique able to quantify fluid overload. METHODS: a prospective, multicentre, observational study in AHF and no AHF patients in three Emergency Departments centres in Italy. Clinical data and BIVA evaluations were performed at admission (t0) and discharge (tdis). A follow-up phone call was carried out at 90 days. RESULTS: Three hundred and thirty-six patients were enrolled (221 AHF and 115 no AHF patients). We found that clinical signs showed the most powerful prognostic relevance. In particular the presence of rales and lower limb oedema at tdis were linked with events relapse at 90 days. At t0, congestion detected by BIVA was observed only in the AHF group, and significantly decreased at tdis. An increase of resistance variation (dR/H) >11 Ω/m during hospitalization was associated with survival. BIVA showed significant results in predicting total events, both at t0 (area under the curve (AUC) 0.56, p<0.04) and at tdis (AUC 0.57, p<0.03). When combined with clinical signs, BIVA showed a very good predictive value for cardiovascular events at 90 days (AUC 0.97, p<0.0001). CONCLUSIONS: In AHF patients, an accurate physical examination evaluating the presence of rales and lower limbs oedema remains the cornerstone in the management of patients with AHF. A congestion reduction, obtained as a consequence of therapies and detected through BIVA analysis, with an increase of dR/H >11 Ω/m during hospitalization seems to be associated with increased 90 day survival in patients admitted for AHF.


Assuntos
Impedância Elétrica , Insuficiência Cardíaca/diagnóstico , Hospitalização/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Prognóstico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Dispneia/diagnóstico , Edema Cardíaco/complicações , Edema Cardíaco/diagnóstico , Serviço Hospitalar de Emergência , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Itália/epidemiologia , Extremidade Inferior/patologia , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Sons Respiratórios/diagnóstico
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