Objectives To describe the rates of pediatric antibiotic use across 6 countries on 3 continents. Study design Cross-national analysis of 7 pediatric cohorts in 6 countries (Germany, Italy, South ...Korea, Norway, Spain, and the US) was performed for 2008-2012. Antibiotic dispensings were identified and grouped into subclasses. We calculated the rates of antimicrobial prescriptions per person-year specific to each age group, comparing the rates across different countries. Results A total of 74 744 302 person-years from all participating centers were included in this analysis. Infants in South Korea had the highest rate of antimicrobial consumption, with 3.41 prescribed courses per child-year during the first 2 years of life. This compares with 1.6 in Lazio, Italy; 1.4 in Pedianet, Italy; 1.5 in Spain; 1.1 in the US; 1.0 in Germany; and 0.5 courses per child-year in Norway. Of antimicrobial prescriptions written in Norway, 64.8% were for first-line penicillins, compared with 38.2% in Germany, 31.8% in the US, 27.7% in Spain, 25.1% in the Italian Pedianet population, 9.8% in South Korea, and 8% in the Italian Lazio population. Conclusions We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents.
Use of azithromycin and risk of ventricular arrhythmia Trifirò, Gianluca, MD PhD; de Ridder, Maria, PhD; Oteri, Alessandro, PhD ...
Canadian Medical Association journal (CMAJ),
04/2017, Letnik:
189, Številka:
15
Journal Article
Recenzirano
Odprti dostop
ABSTRACT BACKGROUND There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the ...risk of ventricular arrhythmia. METHODS We conducted a nested case–control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997–2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders. RESULTS We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio OR 1.97, 95% confidence interval CI 1.35–2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48–1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis. INTERPRETATION Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.
Study Type – Prognosis (inception cohort) Level of Evidence 2b
OBJECTIVE
To evaluate serum sex steroid hormone concentrations and long‐term risk of subsequent lower urinary tract symptoms (LUTS) in a ...cohort of community‐dwelling older men.
SUBJECTS AND METHODS
Between 1984 and 1987, serum sex hormone concentrations were measured in participants in the Rancho Bernardo Study, a prospective, community‐based study. In 2006, the American Urological Association Symptom Index (AUA‐SI) was mailed to surviving male participants. Logistic regression was used to examine associations of baseline hormone concentrations with AUA‐SI.
RESULTS
Among 158 surviving men with complete data and no history of prostate cancer, the mean (sd) age at serum sex steroid assessment was 58 (6.6) years with a mean (sd) follow‐up of 20.3 (0.6) years. In age‐adjusted logistic regression, there was a significant inverse association of testosterone : dihydrotestosterone (DHT) with LUTS (P = 0.05). Also, men with higher concentrations of bioavailable testosterone had a 56% decreased risk of LUTS compared with those with hypogonadal concentrations, although the association was not statistically significant (odds ratios 0.44, 95% confidence interval 0.14–1.40) or distributed evenly among quartiles. There were no significant associations of total testosterone, oestradiol (E2), testosterone : E2, DHT, or dehydroepiandrosterone with LUTS or with any measured hormones and urinary bother.
CONCLUSIONS
In this cohort, men with higher mid‐life levels of testosterone : DHT and bioavailable testosterone had a decreased 20‐year risk of LUTS. These data support other studies reporting inverse associations of serum testosterone with LUTS. Clinical trials of testosterone therapy should include LUTS and clinical benign prostatic hyperplasia as outcomes.
Clinical decision-making for statin treatment in older patients with coronary artery disease (CAD) is under debate, particularly in community-dwelling frail patients at high risk of death. In this ...retrospective observational study on 2,597 community-dwelling patients aged ≥65 years with a previous hospitalization for CAD, we estimated mortality risk assessed with the Multidimensional Prognostic Index (MPI), based on the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA), used to determine accessibility to homecare services/nursing home admission in 2005 to 2013 in the Padua Health District, Veneto, Italy. Participants were categorized as having mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) baseline mortality risk, and propensity score–adjusted hazard ratios (HRs) of 3-year mortality rate were calculated according to statin treatment in these subgroups. Greater MPI-SVaMA scores were associated with lower rates of statin treatment and higher 3-year mortality rate (MPI-SVaMA-1 = 23.4%; MPI-SVaMA-2 = 39.1%; MPI-SVaMA-3 = 76.2%). After adjusting for propensity score quintiles, statin treatment was associated with lower 3-year mortality risk irrespective of MPI-SVaMA group (HRs 95% confidence intervals 0.45 0.37 to 0.55, 0.44 0.36 to 0.53, and 0.28 0.21 to 0.39 in MPI-SVaMA-1, -2, and -3 groups, respectively interaction test p = 0.202). Subgroup analyses showed that statin treatment was also beneficial irrespective of age (HRs 95% confidence intervals 0.38 0.27 to 0.53, 0.45 0.38 to 0.54, and 0.44 0.37 to 0.54 in 65 to 74, 75 to 84, and ≥85 year age groups, respectively interaction test p = 0.597). In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment, although the frailest patients were less likely to be treated with statins.
Background We describe preoperative computed tomography (CT)–guided injection of radiotracer technetium99m macroaggregates (99m Tc-MAA) in challenging small lung nodules, intraoperative localization, ...and resection. Methods Between November 2007 and February 2010, 44 patients with 47 lung nodules which were detected incidentally or at screening and that were18 F-fluorodeoxyglucose positron emission tomography (18 F FDG-PET) positive or increasing in size at subsequent CT scans were candidates for surgical biopsy. Inclusion criteria for preoperative percutaneous CT-guided (low-dose technique)99m Tc-MAA localization included having at least one of the following characteristics: nodule size less than 1 cm, subsolid morphology, or distance from the pleura greater than 1 cm. Results Mean nodule size was 11 mm (range, 5 to 24 mm); 24 nodules were nonsolid, 15 nodules were partially solid, and 8 nodules had a solid morphology. Mean distance from the pleura was 11 mm (range, 0 to 35 mm). Localization complications included 13 minor asymptomatic pneumothoraces, 9 parenchymal hemorrhage suffusions, 1 mild allergic reaction to contrast medium, and 2 patients with chest pain after the procedure. Nine patients had mild extravasation of radiotracer into the pleura. In 2 cases, there was an extravasation of a significant quantity of radiotracer into the pleural cavity. Thoracoscopic biopsy was performed in 30 cases, 2 cases were converted to thoracotomy, and 12 patients underwent intentional thoracotomy. Conclusions Asymptomatic subjects with suspicious nodules detected by screening or incidental CT are best candidates due to small lesion size and high percentage of nonsolid morphology, making thoracoscopic biopsy potentially difficult. Radiotracer localization is a safe, versatile, simple technique to help perform diagnosis with a minimally invasive approach in nonpalpable lung lesions.
Background Indeterminate noncalcified lung nodules are a frequent finding when low-dose computed tomography (LD-CT) is used for lung cancer screening. The best clinical management for such nodules ...remains uncertain. We present results using positron tomography scanning (CT-PET) to evaluate LD-CT–detected lung nodules during the first year of the Continuing Observation of Smoking Subjects (COSMOS) early detection trial for lung cancer. Methods A total of 5200 asymptomatic current or former smokers (≥20 pack-years) older than 50 years of age were enrolled in a single-institution screening trial using annual LD-CT. Growing nodules and those with a maximum diameter exceeding 8 mm were studied with CT-PET. Transthoracic needle biopsy was not a routine part of the protocol. Results During the first year of study, 157 subjects underwent CT-PET, 66 of whom underwent surgical biopsy. Of the 58 lung cancers found on surgical biopsy, 51 were positive (standard uptake value >2.0) and seven were negative for malignancy by CT-PET. Sensitivity was 88% overall, but 100% in the subgroup with solid nodules of 10 mm or more. Among the 8 patients with benign disease at surgical biopsy, CT-PET was positive in 6 and negative in 2. Conclusions CT-PET is a highly promising modality for identifying potentially malignant lesions in screening-detected lung nodules and appears particularly useful as an alternative, in the screening setting, to invasive procedures for the further investigation of uncertain nodules. Our findings also indicate that the standard uptake value threshold for positivity should be lowered for small nodules (<10 mm). Longer follow-up and larger prospective studies are necessary to confirm these preliminary findings.
Abstract Objective To develop and validate the Italian Health Search Morbidity (HSM) Index to adjust health care costs in general practice. Methods The study population comprised 1,076,311 patients ...registered in the Health Search CSD Longitudinal Patient Database between January 1, 2008, and December 31, 2010. We randomly selected 538,254 and 538,057 patients to form the development and validation cohorts, respectively. To ensure model convergence, 5% of the aforementioned cohorts were selected randomly to create development and validation samples. The outcome was the total direct health care costs covered by the national health system. Interaction between age and sex, chronic diseases, and acute diseases were entered in a multilevel generalized linear latent mixed model with random intercepts (province of residence and general practitioner) to identify determinants associated with increased or decreased costs. The estimated coefficients were linearly combined to create the HSM Index for individual patients. The score was applied to the validation sample, and measures of predictive accuracy, explained variance, and the observed/predicted ratio were computed to evaluate the model’s accuracy. Results The mean yearly cost was €414.57 per patient, and the HSM Index had a median value of 5.08 (25th–75th range 4.44–5.98). The HSM Index explained 50.17% of the variation in costs. Concerning calibration, in 80% of the population, the margin of error in the estimation of costs was around 10%. Conclusions The HSM Index is a reliable case-mix system that could be implemented in general practice for costs adjustment. This tool should ensure fairer scrutiny of resource use and allocation of budgets among general practitioners.
Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality in end-stage renal disease patients. It is not clear if this effect is related to the ...elevated ESAs dosage for targeting hemoglobin levels or underlying morbid conditions that lead to ESA resistance. We retrospectively evaluated from 2008 to death or December 2011, 28 consecutive incident hemodialysis patients. We identified 2 cohort of patients based on their mean annual ESAs dosage. The correlation between data was evaluated with the Spearman's rho test. Kaplan-Meier curves were generated to assess survival in subjects with high and low ESAs mean dose. Median ESAs dosage, used as a cutoff point between patients at high and low ESAs dose, was at 11.000 IU/week for epoetin alfa and beta, 55 mcg/week for darbopoietin, and 220 mcg/month for cera. Mean hemoglobin (Hb) level was 10.58 ± 0.13 g/dL. Of 28 patients, during follow-up, 6 (21,4%) died of all causes. High-dose ESA therapy was associated with increased all-cause mortality (P = .047). Moreover, there was a negative correlation between ESAs dose and Hb levels (rho = -0.825; P < .001). Higher ESAs dose for the treatment of anemia in incident hemodialysis patients was associated with higher mortality risk. ESAs and Hb serum levels were inversely correlated with mortality. Together, these findings suggest that ESAs dosage and Hb level may play a role through an independent manner or an interactive effect that adversely affects mortality.
In this work we build a stack of machine learning models aimed at composing a state-of-the-art credit rating and default prediction system, obtaining excellent out-of-sample performances. Our ...approach is an excursion through the most recent ML / AI concepts, starting from natural language processes (NLP) applied to economic sectors' (textual) descriptions using embedding and autoencoders (AE), going through the classification of defaultable firms on the base of a wide range of economic features using gradient boosting machines (GBM) and calibrating their probabilities paying due attention to the treatment of unbalanced samples. Finally we assign credit ratings through genetic algorithms (differential evolution, DE). Model interpretability is achieved by implementing recent techniques such as SHAP and LIME, which explain predictions locally in features' space.
Il tesoretto Αρκαλοχώρι–Αστρίτσι 1936 (IGCH 154). Il tesoretto IGCH 154, rinvenuto a Creta (località Astritsi), consta di emissioni argentee provenienti dalle città cretesi e da Cirene, Corinto e ...colonie, Argo, Tebe ed Egina. Sono state studiate solo le emissioni non–cretesi che ammontano a cinquantacinque monete d’argento a cui vanno aggiunti altri sei esemplari provenienti da Cirene. Questi ultimi ufficialmente appartengono ad un tesoretto rinvenuto nel 1935 a Hierapytna (IGCH 318), ma molto probabilmente fannoparte del nostro ripostiglio, e sono attualmente conservati insieme ad esso presso il Museo Numismatico di Atene.
Unitamente al catalogo numismatico si è fornito un breve commento relativo alle singole emissioni monetali, nel tentativo di contestualizzare le serie e di chiarirne la cronologia assoluta e relativa. Particolare attenzione è stata riservata alla monetazionecirenea nel tentativo di motivarne la presenza nell’isola di Creta, alla luce dei rapporti economici e commerciali testimoniatici dalle scarse fonti storiche. Per tali serie si èsostenuta una cronologia «bassa» (300/290–280 a.C.) e si è proposto di identificarne lo standard ponderale con la fase intermedia del peso tolemaico adottato dal 310 a.C., probabilmente in concomitanza con un cambiamento della ratio tra oro e argento.
I «pegasi» provengono sia da Corinto che dalle sue colonie (Anactorion, Amphilochian Argos, Thyrrheion) e presentano simboli e monogrammi differenti, ma cronologicamente appartengono tutti al V periodo Ravel (387–306 a.C.).Delle emissioni argive, scarsamente studiate, si è presentata la classificazione e si è proposta una cronologia molto ampia, dovendo necessariamente appartenere al periodo precedente l’ingresso della città nella Lega Achea.
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