External validation of a nomogram for outcome prediction in management of medium-sized (1-2 cm) kidney stones.

BACKGROUND: Stone nomogram by Micali et al., able topredict treatment failure of shock-wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PNL) in the management of single 1-2 cm renal stones, was developed on 2605 patients and showed a high predictive accuracy, with an area under ROC curve of 0.793 at internal validation. The aim of the present study is to externally validate the model to assess whether it displayed a satisfactory predictive performance if applied to different populations. METHODS: External validation was retrospectively performed on 3025 patients who underwent an active stone treatment from December 2010 to June 2021 in 26 centers from four countries (Italy, USA, Spain, Argentina). Collected variables included: age, gender, previous renal surgery, preoperative urine culture, hydronephrosis, stone side, site, density, skin-to-stone distance. Treatment failure was the defined outcome (residual fragments >4 mm at three months CT-scan). RESULTS: Model discrimination in external validation datasets showed an area under ROC curve of 0.66 (95% 0.59-0.68) with adequate calibration. The retrospective fashion of the study and the lack of generalizability of the tool towards populations from Asia, Africa or Oceania represent limitations of the current analysis. CONCLUSIONS: According to the current findings, Micali's nomogram can be used for treatment prediction after SWL, RIRS and PNL; however, a lower discrimination performance than the one at internal validation should be acknowledged, reflecting geographical, temporal and domain limitation of external validation studies. Further prospective evaluation is required to refine and improve the nomogram findings and to validate its clinical value.

Stochastic Petri net model describing the relationship between reported maternal and congenital syphilis cases in Brazil.

INTRODUCTION: Syphilis is a sexually transmitted disease (STD) caused by Treponema pallidum subspecies pallidum. In 2016, it was declared an epidemic in Brazil due to its high morbidity and mortality rates, mainly in cases of maternal syphilis (MS) and congenital syphilis (CS) with unfavorable outcomes. This paper aimed to mathematically describe the relationship between MS and CS cases reported in Brazil over the interval from 2010 to 2020, considering the likelihood of diagnosis and effective and timely maternal treatment during prenatal care, thus supporting the decision-making and coordination of syphilis response efforts. METHODS: The model used in this paper was based on stochastic Petri net (SPN) theory. Three different regressions, including linear, polynomial, and logistic regression, were used to obtain the weights of an SPN model. To validate the model, we ran 100 independent simulations for each probability of an untreated MS case leading to CS case (PUMLC) and performed a statistical t-test to reinforce the results reported herein. RESULTS: According to our analysis, the model for predicting congenital syphilis cases consistently achieved an average accuracy of 93% or more for all tested probabilities of an untreated MS case leading to CS case. CONCLUSIONS: The SPN approach proved to be suitable for explaining the Notifiable Diseases Information System (SINAN) dataset using the range of 75-95% for the probability of an untreated MS case leading to a CS case (PUMLC). In addition, the model's predictive power can help plan actions to fight against the disease.

GRPR antagonist protects from drug-induced liver injury by impairing neutrophil chemotaxis and motility.

Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXC chemokine receptor 2 (CXCR2) ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life-threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration, and mechanisms underlying this phenomenon. We found that acetaminophen-overdosed mice treated with GRPR antagonist had reduced DILI and neutrophil infiltration in the liver. Intravital imaging and cell tracking analysis revealed reduced neutrophil mobility within the liver. Surprisingly, GRPR antagonist inhibited CXCL2-induced migration in vivo, decreasing neutrophil activation through CD11b and CD62L modulation. Additionally, this compound decreased CXCL8-driven neutrophil chemotaxis in vitro independently of CXCR2 internalization, induced activation of MAPKs (p38 and ERK1/2) and downregulation of neutrophil adhesion molecules CD11b and CD66b. In silico analysis revealed direct binding of GRPR antagonist and CXCL8 to the same binding spot in CXCR2. These findings indicate a new potential use for GRPR antagonist for treatment of DILI through a mechanism involving adhesion molecule modulation and possible direct binding to CXCR2.

Pharmacy clerks' prescribing practices for STD patients in Porto Alegre, Brazil: missed opportunities for improving STD control.

STDs are a significant public health problem in Brazil. A primary control strategy is the immediate treatment of symptomatic individuals. When services are unavailable, STD patients seek care in alternative settings. Probably the most frequently used settings are commercial pharmacies, where pharmacy clerks provide treatment, although Brazilian law prohibits selling antibiotics without prescription. Our objective was to evaluate prescribing practices by pharmacy clerks for STDs. We performed a cross-sectional study. Trained medical students visited 62 pharmacies in the city of Porto Alegre during March 2002. These were randomly chosen from a list of 863 registered pharmacies. The students presented to the pharmacy complaining of dysuria and urethral discharge. After obtaining a prescription, or not, they asked for additional instructions to be followed. Immediately after leaving the premises, the instructions were anonymously recorded. Of the 62 pharmacies visited, a clerk in 56 (90.3%, 95% confidence interval [CI]: 80.1%-96.4%) provided a prescription. Most frequently prescribed drugs were ampicillin with probenecide (29/51.8%) and rosoxacin (11/19.6%). Ministry of Health-recommended treatment was not suggested by any of the clerks. Forty-six additional recommendations were given. The use of condoms was the most frequent additional advice (42/46). Prescribing by pharmacy clerks is very prevalent in Porto Alegre. This may represent a lost opportunity for more comprehensive prevention effort (counselling, partner management, and diagnosing other STDs). Additionally, the most frequently prescribed drugs are not recommended by international or national health authorities for treatment of STDs, and none of these drugs covers chlamydia. We conclude that pharmacy clerks are a potentially important source of STD treatment and control but that their practices are in need of vast improvement.