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OBJECTIVE: To investigate the association between oral contraceptive (OC) pill use and the risk of developing Multiple Sclerosis (MS), attempting to address the limitations present in previous studies which produced conflicting results. DESIGN: Population-based cohort study using data from the UK Biobank. SUBJECTS: The study included 181,058 women of white ethnicity born in England between 1937 and 1970, among which 1131 had an MS diagnosis. EXPOSURE: OC use, considering the self-reported age of initiation and discontinuation. The exposures of interest include: i) ever use, ii) current use, iii) duration of current use in years, and iv) age and year at initiation. MAIN OUTCOME MEASURES: MS diagnosis (ICD-10: G35) was used as outcome of interest, and the associations with the exposures of interest were investigated using marginal structural models with a time-to-event approach. To adjust for confounding, we included in the models several variables including MS polygenic risk score (MS-PRS), education level, parity, smoking, fertility problems, obesity, and mononucleosis. We further aimed to evaluate the influence of parity using a mediation analysis. RESULTS: The association of both ever and current OC use did not result in a statistically significant MS hazard increase (ever vs never users, HR=1.30 [95%CI:0.93,1.82, p=0.12]; current vs never users, HR=1.35 [95%CI:0.81,2.25, p=0.25]). However, we highlighted parity as an effect modifier for this association. In nulliparous women, ever and current use resulted in a significant two-fold and three-fold MS hazard increase (HR=2.08 [95%CI:1.04,4.17, p=0.04] and HR=3.15 [95%CI:1.43,6.92, p=0.004]). These associations were supported by significant MS hazard increases for a higher duration of current use and for an earlier age at initiation. We further highlighted genetic MS susceptibility as another effect modifier, as a stronger OC-MS hazard association was found in women with a low MS-PRS. CONCLUSION: Our findings highlighted how the association between OC use and MS vary based on individual characteristics such as parity and genetic MS susceptibility. Importantly, current use in nulliparous women was found to be associated with a three-fold increase in MS hazard. We acknowledge the need for cautious causal interpretation and further research to validate these findings across diverse populations and OC types.
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BACKGROUND: Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime. OBJECTIVE: We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort. METHODS: We used the UK Biobank data, considering the observation period from birth up to 31 December 2022. We considered genetic risk, using a multiple sclerosis polygenic risk score (MS-PRS), and various early life factors. Tobacco smoking and infectious mononucleosis diagnosis were also considered as time-varying variables along the follow-up. Using a Cox proportional hazards model, we examined the associations between these factors and MS diagnosis instantaneous risk. RESULTS: We analyzed 345,027 participants, of which 1669 had an MS diagnosis. Our analysis revealed age-dependent effects for sex (females vs males) and higher MS-PRS, with greater hazard ratios observed in young adults. CONCLUSION: The age-dependent effects suggest that retrospective studies could have underestimated sex and genetic variants' risk roles during younger ages. Therefore, we emphasize the importance of a time-to-event approach using longitudinal data to better characterize age-dependent risk effects.
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Bancos de Espécimes Biológicos , Esclerose Múltipla , Humanos , Feminino , Masculino , Esclerose Múltipla/genética , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Reino Unido/epidemiologia , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Predisposição Genética para Doença , Idoso , Fatores Etários , Estudos Prospectivos , Fatores Sexuais , Mononucleose Infecciosa/diagnóstico , Mononucleose Infecciosa/genética , Mononucleose Infecciosa/epidemiologia , Fumar Tabaco/efeitos adversos , Fatores de Tempo , Biobanco do Reino UnidoRESUMO
BACKGROUND: Migrants, mainly undocumented and low-income refugees, are at high risk of hepatitis C virus (HCV) infection, but are a difficult-to-reach and to-treat population. The aim of the study was to evaluate the effectiveness of a test and treat model with direct-acting antiviral for HCV infection in these migrants coming from low-income and living in southern Italy. METHODS: A prospective, multicenter, collaborative study based on a four-phase-program (educational counseling, screening, linkage-to-care and treatment) was designed in southern Italy; the study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021. After educational counseling on infectious diseases that are transmitted through blood or sexually pseudonymized HCV screening was offered to all undocumented migrants and low-income refugees observed at one of the 1st level clinical centers. The HCV-RNA-positive subjects were referred to one of the 3rd level units of Infectious Diseases (ID) and treated with a 12-week course of sofosbuvir-velpatasvir and observed for 12 weeks after the end of direct antiviral agents (DAA) treatment. STATISTICAL ANALYSIS: For the descriptive analysis, the categorical variables were reported as absolute numbers and relative frequencies. Continuous variables were summarized as mean and standard deviation (SD) if normally distributed, or as a median and interquartile range (IQR) if not normally distributed. We used Pearson chi-square or Fisher's exact test for categorical variables and Student's t test or Mann-Whitney test for continuous variables. A P value < 0.05 was considered to be statistically significant. Analyses were performed with SPSS 21.0. RESULTS: Of the 3501migrants observed in the study period, 3417 (97.6%) agreed to be screened; 185 (4.7%) were anti-HCV-positive and, of these, 53 (28.6%) were HCV-RNA-positive. Of these 53 subjects, 48 (90.5%) were referred to an ID unit and started DAA treatment. The HCV-RNA-positive-subjects were older [median 36 years (IQR: 32-21) vs 27.19 (IQR: 30.5-19.25); P = 0.001], and less frequently males [35 (66.03 %) vs 119 (90.1%), P < 0 .0001] than seronegative participants. They more frequently came from Eastern Europe (70.8%) stayed longer in Italy [months of stay in Italy, mean ± SD: 51.02 ± 52.84 vs 25.7 ± 42.65, P = 0.001], and had more years of schooling [years of schooling, mean ± SD: 9.61±2.81 vs 7.10 ± 4, P = 0.0001]. HCV-RNA-positive-subjects less frequently reported piercing, tattoos and tribal scars as risk factors (23.6%). Of these 48 HCV RNA positive subjects who started DAA, 47 (97.9%) showed a sustained virological response and one dropped-out in follow-up after DAA treatment. No subject had any adverse event. CONCLUSIONS: This model of HCV screening and linkage to care seems effective to eliminate HCV infectionin a difficult-to-reach and to-treat population, such as undocumented migrants and low-income refugees. The participation of cultural mediators in the study made possible a better interaction between migrants and physicians, as is evident from the large number of subjects enrolled. Eliminating HCV among migrants will have a long-term positive impact from a public health and healthcare perspective by reducing the number of individuals who potentially develop HCV-related complications such as liver cirrhosis and hepatocellular carcinoma and reducing the circulation of HCV in the regions that host them which often, as in the case of Italy, are low endemic for HCV infection.
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Antivirais , Hepatite C , Migrantes , Humanos , Itália/epidemiologia , Antivirais/uso terapêutico , Estudos Prospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/virologia , Migrantes/estatística & dados numéricos , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Sofosbuvir/uso terapêutico , Adulto Jovem , Programas de Rastreamento , Refugiados , PobrezaRESUMO
Carbapenemase-producing Enterobacteriaceae (CPE) are an increasing threat to global public health. Treatment of CPE isolates, like New Delhi metallo-ß-lactamase (NDM), is limited and often necessitates combination therapies. The aim of this study was to evaluate the synergistic meropenem/fosfomycin combination against K.pneumoniae-producing NDM isolates. Fosfomycin/meropenem, fosfomycin/colistin and meropenem/colistin were tested alone and in combination, using e-test and time-kill assay against 20 clinical carbapenemase-producing K. pneumonia (CPKp NDM) isolates collected from September 2022 to December 2022. K. pneumoniae strains were resistant to meropenem, ceftazidime/avibactam and ceftolozano/tazobactam, 75% and 80% of isolates were susceptible for cefiderocol and for colistin respectively. Fosfomycin/meropenem combination was synergic in 95% (n=19) strains. Fosfomycin/colistin and colistin/meropenem combination showed only 10% synergistic combination strains. In 16 isolates (80%) indifference action for fosfomycin/colistin and colistin/meropenem was reported. For 0.8% of CpKP NDM isolates colistin/meropenem and fosfomycin/colistin combinations found to be antagonistic. In this study, time kill assay showed combination therapies action versus K.pneumoniae metallo-b-lactamase producing (NDM) strains and confirmed the synergistic action of fosfomycin/meropenem combination. In vitro synergy testing should be routinely performed in multidrug resistance infections and combo therapies can be used as a possible alternative in targeted patients with the goal of reducing overall antibiotic costs.
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Enterobacteriáceas Resistentes a Carbapenêmicos , Fosfomicina , Humanos , Meropeném/farmacologia , Fosfomicina/farmacologia , Colistina/farmacologia , Klebsiella pneumoniaeRESUMO
BACKGROUND: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections. METHODS: We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A. baumannii (CRAB) infections treated with cefiderocol, from June 12021 to October 30 2022. Primary endpoint was 30-day mortality, secondary end-points the clinical and microbiological response at 7 days and at the end of treatment. Furthermore, we compared the clinical and microbiological outcomes among patients who received cefiderocol in monotherapy or in combination. RESULTS: Thirty-eight patients with forty episodes of infection were included [mean age 65 years (SD+16.3), 75% males, 90% with hospital-acquired infections and 70% showing sepsis or septic shock]. The most common infections included unknown source or catheter-related bacteremia (45%) and pneumonia (40%). We observed at 7 days and at the end of therapy a rate of microbiological failure of 20% and 10%, respectively, and of clinical failure of 47.5% and 32.5%, respectively; the 30-day mortality rate was 47.5%. At multivariate analysis clinical failure at 7 days of treatment was the only independent predictor of 30-day mortality. Comparing monotherapy (used in 72.5%) vs. combination therapy (used in 27.5%), no differences were observed in mortality (51.7 vs 45.5%) and clinical (41.4 vs 63.7%) or microbiological failure (24.1 vs 9.1%). CONCLUSIONS: The findings of this study reinforce the effectiveness of cefiderocol in CRAB infections, also as monotherapy. However, prospective multicenter studies with larger sample sizes and a control group treated with standard of care are needed to identify the best treatment for CRAB infections.
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Infecções por Acinetobacter , Acinetobacter baumannii , Masculino , Humanos , Idoso , Feminino , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , CefiderocolRESUMO
To characterize viral hepatitis co-infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low-income refugees consecutively evaluated for a clinical consultation at one of the five first-level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) and anti-HIV; the HBsAg-positive were screened also for anti-delta. Of the 2923 subjects enrolled, 257 (8%) were HBsAg-positive alone (Control group B), 85 (2.9%) only anti-HCV-positive (Control group C), 16 (0.5%) HBsAg/anti-HCV-positive (Case group BC), and 8 (0.2%) HBsAg/anti-HDV-positive (Case group BD). Moreover, 57 (1.9%) subjects were anti-HIV-positive. HBV-DNA positivity was found less frequently in the 16 subjects in Case group BC (43%) and in the 8 in Case group BD (12.5%) than in the 257 in Control group B (76%; p = 0.03 and 0.0000, respectively). Similarly, HCV-RNA positivity was more frequent in Case group BC than in Control group C (75% vs. 44.7% p = 0.02). The subjects in Group BC had a lower prevalence of asymptomatic liver disease (12.5%) than Control group B (62.2%, p = 0.0001) and Control group C (62.3%, p = 0.0002). Conversely, liver cirrhosis was more frequently identified in Case group BC (25%) than in Control groups B and C (3.11% and 2.35%, p = 0.0000 and 0.0004, respectively). The present study contributes to the characterization of hepatitis virus co-infections in the immigrant population.
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Coinfecção , Emigrantes e Imigrantes , Hepatite B , Humanos , Antígenos de Superfície da Hepatite B , Hepatite B/epidemiologia , Estudos Prospectivos , Coinfecção/epidemiologia , Hepacivirus/genética , Itália/epidemiologia , Vírus da Hepatite B/genéticaRESUMO
BACKGROUND: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). METHODS: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-ß-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. RESULTS: Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. CONCLUSIONS: In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.
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Carbapenêmicos , Sepse , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Prospectivos , Bactérias Gram-Negativas , Sepse/tratamento farmacológico , Itália/epidemiologiaRESUMO
Bacterial co-infection in COVID-19 patients significantly contributes to the worsening of the prognosis based on morbidity and mortality. Information on the co-infection profile in such patients could help to optimize treatment. The purpose of this study was to describe bacterial co-infections associated with microbiological, clinical, and laboratory data to reduce or avoid a secondary infection. A retrospective cohort study was conducted at Sant'Anna and San Sebastiano Hospital from January 2020 to December 2021. Bacterial co-infection was detected in 14.3% of the COVID-19-positive patients. The laboratory findings on admission showed significant alterations in the median D-dimer, C-reactive protein, interleukin-6, and lactate dehydrogenase values compared to normal values. All inflammatory markers were significantly elevated. The most common pathogens isolated from blood cultures were E. faecalis and S. aureus. Instead, the high prevalence of respiratory tract infections in the COVID-19 patients was caused by P. aeruginosa (41%). In our study, 220 (82.4%) of the COVID-19 patients received antimicrobial treatment. Aminoglycosides and ß-lactams/ß-lactamase inhibitors showed the highest resistance rates. Our results showed that older age, underlying conditions, and abnormal laboratory parameters can be risk factors for co-infection in COVID-19 patients. The antibiotic susceptibility profile of bacterial pathogen infection provides evidence on the importance, for the clinicians, to rationalize and individualize antibiotic usage.
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BACKGROUND: Since few data are available in the literature on the prevalence of anti-Delta-positive subjects in immigrant populations, the aim of the present study was to evaluate the demographic and virological characteristics of HDV infection in a large cohort of immigrants living in southern Italy. METHODS: Between January 2012 and February 2020 all immigrants attending one of the 5 first- level centers were enrolled and screened for HBsAg, the HBsAg-positive for anti-Delta and if positive, for HDV-RNA and HDV genotype. RESULTS: Of the 3521 immigrants observed in the study period, 3417 (97.0%) agreed to be screened; they were mainly males (61%), with a median age of 27 years (IQR 8-74) and came prevalently (58%) from sub-Saharan Africa. Of the 3417 patients enrolled, 319 (9%) subjects were HBsAg-positive, and of those, 8 (2.5%) were anti-Delta-positive. No difference in the demographic and epidemiological characteristics was observed between the anti-Delta-negative vs -positive. Of the 8 anti-Delta-positive subjects, only one was HDV-RNA-positive (viral load: 7050 IU/mL), genotype 1, with clinical signs of cirrhosis. CONCLUSIONS: the present study showed a prevalence of HDV of 2.5% in a large cohort of asymptomatic immigrants, suggesting the need for screening campaigns for viral infections including delta hepatitis in this population.
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Emigrantes e Imigrantes , Hepatite D , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Vírus Delta da Hepatite/genética , Hepatite D/epidemiologia , Hepatite D/diagnóstico , Estudos Prospectivos , Antígenos de Superfície da Hepatite B , Prevalência , Itália/epidemiologia , RNA , Vírus da Hepatite B/genéticaRESUMO
Data regarding early predictors of clinical deterioration in patients with infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still scarce. The aim of the study is to identify early symptoms or signs that may be associated with severe coronavirus disease 2019 (COVID-19). We conducted a multicentre prospective cohort study on a cohort of patients with COVID-19 in home isolation from March 2020 to April 2021. We assessed longitudinal clinical data (fever, dyspnea, need for hospitalization) through video calls at three specific time points: the beginning of symptoms or the day of the first positivity of the nasopharyngeal swab for SARS-CoV-2-RNA (t0 ), and 3 (t3 ) and 7 (t7 ) days after the onset of symptoms. We included 329 patients with COVID-19: 182 (55.3%) males, mean age 53.4 ± 17.4 years, median Charlson comorbidity index (CCI) of 1 (0-3). Of the 329 patients enrolled, 171 (51.98%) had a mild, 81 (24.6%) a moderate, and 77 (23.4%) a severe illness; 151 (45.9%) were hospitalized. Compared to patients with mild COVID-19, moderate and severe patients were older (p < 0.001) and had more comorbidities, especially hypertension (p < 0.001) and cardiovascular diseases (p = 0.01). At t3 and t7 , we found a significant higher rate of persisting fever (≥37°C) among patients with moderate (91.4% and 58.0% at t3 and t7 , respectively; p < 0.001) and severe outcome (75.3% and 63.6%, respectively; p < 0.001) compared to mild COVID-19 outcome (27.5% and 11.7%, respectively; p < 0.001). Factors independently associated with a more severe outcome were persisting fever at t3 and t7 , increasing age, and CCI above 2 points. Persisting fever at t3 and t7 seems to be related to a more severe COVID-19. This data may be useful to assess hospitalization criteria and optimize the use of resources in the outpatient setting.
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COVID-19 , Deterioração Clínica , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Febre/epidemiologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , SARS-CoV-2RESUMO
OBJECTIVES: To compare the clinical and microbiological outcomes of patients treated with beta-lactam monotherapy or combination therapy for Pseudomonas aeruginosa infections. DATA SOURCES: MEDLINE, Google Scholar and the Cochrane Library. STUDY ELIGIBILITY CRITERIA AND INTERVENTIONS: Experimental and observational studies published as full papers up to December 2020 that compared the efficacy of beta-lactams used as monotherapy or in combination with other active agents as empirical or targeted therapy for bloodstream infections or hospital-acquired pneumonia/ventilator-associated pneumonia due to P. aeruginosa were included in this meta-analysis. The outcomes evaluated were in-hospital mortality rate, 14-day- or 30-day-mortality rate, microbiological cure rate and clinical cure rate. RESULTS: Of 8363 citations screened, six randomized controlled trials, six prospective cohort studies and 21 retrospective cohort studies were included in the analysis, accounting for a total of 3861 subjects. Considering the 14 studies evaluating empirical therapy, no significant difference in mortality rate was observed between the two groups [relative risk (RR) 1.06, 95% confidence interval (CI) 0.86-1.30; P=0.6]. Similar findings were obtained among the 18 studies analysing targeted therapy (RR 1.04, 95% CI 0.83-1.31; P=0.708); however, grouping the studies by design, higher mortality was observed among patients receiving monotherapy in five prospective studies (RR 1.37, 95% CI 1.06-1.79; P=0.018). Finally, no difference was observed between groups in terms of microbiological cure and clinical cure. CONCLUSIONS: This meta-analysis demonstrated no difference in mortality rate, clinical cure rate and microbiological cure rate in patients treated with beta-lactam monotherapy or combination therapy for P. aeruginosa infections.
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Pneumonia Associada à Ventilação Mecânica , Infecções por Pseudomonas , Sepse , Antibacterianos , Quimioterapia Combinada , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Estudos Prospectivos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Estudos Retrospectivos , Sepse/tratamento farmacológico , Resultado do Tratamento , beta-Lactamas/uso terapêuticoRESUMO
The objectives of the present study were to provide a snapshot analysis of antibiotic appropriateness in two hospitals in Southern Italy in three specific areas, surgical, medical and intensive care, and to evaluate the risk factors associated with inappropriateness in antimicrobial prescriptions. We conducted a multicentre observational study in two hospitals in the Campania region. We collected data of all patients admitted on the day of evaluation to antibiotic therapy or prophylaxis through a case report form. The primary outcome was to assess the inappropriateness of antibiotic prescribing, related to the spectrum, dose, route of administration and duration of treatment-in particular, to assess whether there was a difference in the adequacy of the prescriptive practice in the medical, surgical and intensive sectors. Prescriptive inappropriateness was more frequently observed in surgical units (79.8% of the 104 antimicrobial prescriptions) than in medical units (53.8% of the 65 prescriptions, p = 0.0003) or in intensive care units (64.1% of the 39 prescriptions, p = 0.052). The reasons for the inappropriate antimicrobial prescriptions were similar in the three areas evaluated: antimicrobial unnecessary and antimicrobial not recommended were the most frequent reasons for inappropriateness. Not participating in an antimicrobial stewardship program (ASP) was identified as a factor associated with inappropriate antimicrobial prescriptions in medical and surgical units, but not in Intensive Care Units (ICUs). ASPs may enhance the appropriateness of antimicrobial prescriptions especially in medical and surgical units. In ICUs, specific programs able to limit empirical therapies and encourage the collection of microbiological samples may be useful to set up targeted therapies and to design antimicrobial protocols.
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To evaluate the effect that an education-based Antimicrobial stewardship program (ASP) implemented in two hospitals in southern Italy had on the quality and appropriateness of antibiotic prescription. We conducted a multicenter observational study in two hospitals in the Campania region. Only some departments of both hospitals were already participating in the ASP. We collected data on all patients admitted on the day of evaluation in antibiotic therapy or prophylaxis through a case report form. The primary outcome was to investigate the difference in the appropriateness of the antibiotic prescriptive practice in the departments that had joined the ASP and in those that had not participated in the project (non-ASP). The total number of patients assessed was 486. Of these, 78 (16.05%) were in antibiotic prophylaxis and 130 (26.7%) in antibiotic therapy. The prescriptive appropriateness was better in the units that had joined ASP than in those that had not, with respectively 65.8% versus 22.7% (p < 0.01). Patients in the non-ASP units more frequently received unnecessary antibiotics (44.9% versus 0%, p = 0.03) and, as surgical prophylaxis, the use of antibiotics not recommended by the guidelines (44.2% versus 0%, p = 0.036). Multivariable analysis of the factors associated with prescriptive appropriateness identified ASP units (p = 0.02) and bloodstream or cardiovascular infections (p = 0.03) as independent predictors of better prescriptive appropriateness. The findings of the present study reinforce the importance of adopting an educational ASP to improve the quality of antimicrobial prescription in clinical practice.
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OBJECTIVES: A growing amount of evidence suggests that the rifampicin dosing currently recommended for tuberculosis treatment could be associated with inadequate exposure and unfavourable outcomes. We aimed to compare clinical and microbiological efficacy and safety outcomes of standard and higher rifampicin dosing. METHODS: Data sources were MEDLINE, Google Scholar and the Cochrane Library. This was a systematic review and meta-analysis that included experimental or observational studies comparing 8-week sputum culture conversion, treatment failure, or safety outcomes in naïve patients with pulmonary tuberculosis treated with standard (10 mg/kg) or higher doses of rifampicin. RESULTS: Of a total of 9683 citations screened, eight randomized controlled trials were included, accounting for 1897 subjects; the risk of bias was low in three studies, high in two and intermediate in three. At week 8 a higher proportion of patients in the high-dose group obtained a sputum culture conversion than those in the standard dose group (83.7% versus 80.6%, RR 1.06; 95%CI 1.01-1.12, p 0.028); this result was confirmed in the sub-analysis including patients treated with a rifampicin dose of ≥20 mg/kg, but not in those treated with 11-19 mg/kg. Events of treatment failure at end of treatment showed no significant difference between the two groups (RR 0.84; 95%CI 0.59-1.21, p 0.362). In the analysis evaluating safety outcome, the difference in the occurrence of a grade 3 or 4 liver toxicity or adverse drug reactions leading to discontinuation was not significant at the statistical analysis among the groups (7.2% versus 5.4%, RR 1.19; 95%CI 0.81-1.73, p 0.370, and 1.5% versus 0.6%, RR 2.31; 95%CI 0.65-8.21, p 0.195, respectively). No statistical heterogeneity among studies was observed for each outcome. CONCLUSIONS: High doses of rifampicin were associated with an increased rate of sputum culture conversion at 8 weeks of treatment, particularly in patients receiving ≥20 mg/kg.
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Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Antituberculosos/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Rifampina/efeitos adversosRESUMO
Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy. Retrospective, multicenter, observational study. All patients with streptococcal IE admitted from 2016 to 2018 were enrolled. Mortality and incidence of acute kidney injury (AKI) were compared between Group A (standard of care, SoC) and Group B (daptomycin-based aminoglycoside-sparing combination therapy). Fifty-four patients were enrolled, 33 in Group A and 21 in Group B. Mortality was 2/33 (6%) in Group A and 0 in Group B (p = 0.681); AKI incidence was 8/33 (24%) in Group A and 0 in Group B (p = 0.04). Daptomycin-based aminoglycoside-sparing combination therapy appears to be promising for the treatment of streptococcal endocarditis because of similar efficacy compared with SoC and significantly reduced incidence of AKI.
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Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , beta-Lactamas/uso terapêutico , Adulto , Idoso , Aminoglicosídeos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Daptomicina/administração & dosagem , Daptomicina/efeitos adversos , Quimioterapia Combinada , Endocardite Bacteriana/mortalidade , Feminino , Gentamicinas/administração & dosagem , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/induzido quimicamente , Estudos Retrospectivos , Infecções Estreptocócicas/mortalidade , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversosRESUMO
People who use drugs are a key population in global HCV control. We evaluated the efficacy of an innovative model to eliminate HCV infection in a high-risk population of PWUD in a service for substance use disorder (SUD). Between January 2018 and December 2018, we conducted a prospective, interventional, before and after study, based on audits performed by Infectious Diseases physicians in a SUD facility in Piedimonte Matese, in southern Italy, to improve the knowledge about HCV infection; a shared protocol for screening and linkage to care of patients was implemented. The pre-intervention period was defined as January-December 2017 and the post-intervention period as January-December 2018. The subjects followed up at SUD facility in the pre-intervention and post-intervention periods were 318 and 275, respectively. Compared with the pre-intervention period, the number of anti-HCV-positive subjects tested for HCV RNA was higher in the post-intervention period (91% vs 27%, P < .0001), as was the number who started directly acting antivirals (DAAs). Of the 18 HCV RNA-positive subjects in the pre-intervention period, only 3 (16.6%) started DAA, a percentage decisively lower than that observed after the start of the programme, 63 (84%) of 75 subjects (P < .0001), and all obtained SVR. The data were similar for people who inject drugs (PWID) and non-PWID sub-populations. The use of our innovative model with close interaction between the Infectious Disease Unit and the SUD facility determined a significant increase in HCV RNA testing, linkage to care and the start of DAA in the PWUD population.
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Hepatite C , Preparações Farmacêuticas , Abuso de Substâncias por Via Intravenosa , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Humanos , Estudos Prospectivos , Abuso de Substâncias por Via Intravenosa/tratamento farmacológicoRESUMO
BACKGROUND: Aim of this study was to evaluate the prevalence of blood-borne chronic viral infections in immigrants living in southern Italy and identify factors associated to viral infections. METHODS: A prospective screening program was performed in seven clinical centers operating in Campania, Apulia and Calabria regions in southern Italy, in order to identify immigrants with HBV, HCV or HIV infections. RESULTS: Of 4,125 immigrants observed in the study period, 3,839 (93.0%) agreed to be screened: 381 (9.9%) resulted HBsAg-positive, 136 (3.5%) anti-HCV, 62 (1.6%) anti-HIV and 1,448 (37.7%) HBsAg-negative and anti-HBc-positive. Ongoing or previous HBV infection was observed more frequently in males (p = 0.02 and p < 0.001, respectively), whereas HIV infection in females (p = 0.01). Immigrants from western Africa showed a higher rate of HBsAg positivity (p < 0.0001), HBsAg negativity/anti-HBc positivity (p < 0.0001) and anti-HIV positivity (p = 0.004) compared with those from other geographical areas. At multivariate analysis, ongoing HBV infection was associated with male sex (OR 1.49, 95% CI: 1.04-2.14) and origin from western Africa (OR 4.67, 95% CI: 1.70-12.80) and eastern Europe (OR 3.44, 95% CI: 1.17-10.08). HCV infection showed the tendency to be more frequent among males (OR 1.84, 95% CI: 0.99-3.42). HIV infection was associated with an older age (OR 1.04, 95% CI: 1.01-1.06), origin from western Africa (OR 4.09, 95% CI: 1.26-13.29) and female sex (OR 2.38, 95% CI: 1.29-4,39; p = 0.006). CONCLUSIONS: The high prevalence of HBV, HCV and HIV infections in our large cohort of immigrants should definitively prompt Italian Healthcare Authorities to develop adequate cost-effective screening policies.
Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Infecções por HIV/epidemiologia , Hepatite B Crônica/epidemiologia , Hepatite C/epidemiologia , Feminino , HIV/isolamento & purificação , Hepacivirus/isolamento & purificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Itália/epidemiologia , Masculino , Programas de Rastreamento , Estudos Prospectivos , Estudos SoroepidemiológicosRESUMO
BACKGROUND: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs). METHODS: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate. RESULTS: Five hundred and twenty HCV-infected PWID treated with all-oral DAA-based regimens were enrolled; a total of 168 (32.3%) patients presented genotype 1a, 109 (21.0%) genotype 1b, and 174 (33.5%) genotype 3; a total 152 of the 520 subjects (29.2%) were cirrhotics; a total 118 (22.7%) and 373 (71.7%) were treated with DAA regimens of second and third generation, respectively; a total 169 (33.6%) patients were receiving an opioid agonist at the start of antiviral therapy. Only 11 subjects (2.1%) did not show an SVR12. A significant correlation was found between treatment with opioid substitution therapy (p < 0.001), Human Immunodeficiency Virus (HIV) coinfection (p = 0.002), and treatment with first- or second-generation regimens (p = 0.0015) and HCV failure. Upon multivariate analysis, treatment with a first- or second-generation DAA was the only factor independently associated with failure (OR 10.4, 95% CI: 1.43 to 76.1, p = 0.02). CONCLUSIONS: Treatment with DAAs led to a high SVR12 rate (97.9%) in a large cohort of HCV-infected PWID. The only predictor of viral failure found in our analysis was treatment with first- and second-generation DAA.
RESUMO
OBJECTIVE: To describe morphological changes associated with degeneration and regeneration of large fibers in the skin using a model of chronic compression of the median nerve. METHODS: We studied cutaneous innervation in 30 patients with chronic compression of the median nerve at the wrist. Before surgery, we assessed the symptom severity and performed neurography, quantitative sensory testing, and analysis of nerve morphology and morphometry in skin biopsies from the third digit fingertip. Fifteen patients repeated all tests 12 months after the surgery. Thirty age- and sex-matched healthy subjects were included in the study. RESULTS: Clinical and neurophysiological basal assessment showed a moderate involvement of the median nerve. Quantitative sensory testing showed abnormal findings. The density of intraepidermal nerve fibers and intrapapillary myelinated endings was reduced. Myelinated fibers showed caliber reduction and nodal elongation. Meissner corpuscles had normal density but were located deeper in the dermis and their capsule appeared partially empty. During follow-up, patients exhibited a positive clinical and neurophysiological outcome. Quantitative sensory testing improved. Intraepidermal nerve fibers and intrapapillary myelinated endings remained unchanged, but the caliber of intrapapillary myelinated endings was increased. The neural component of the Meissner corpuscle filled the capsule of the mechanoreceptors that remained deeper in the dermis. The position of vasoactive intestinal peptide-immunoreactive fibers was more superficial compared to the basal assessment and controls. INTERPRETATION: We recognized and quantified the pathological changes associated with nerve degeneration and regeneration in skin and proposed new parameters that may increase the diagnostic yield of skin biopsy in clinical practice. Ann Neurol 2020;87:456-465.