Respiratory symptoms (COPD Assessment Test and modified Medical Research Council dyspnea scores) and GOLD-ABCD COPD classification: the LASSYC study

Chronic obstructive pulmonary disease; Symptoms; COPDEnfermedad pulmonar obstructiva crónica; Síntomas; EPOCMalaltia pulmonar obstructiva crònica; Símptomes; MPOCObjective To assess the frequency and severity of 24-hour respiratory symptoms according to COPD GOLD-ABCD classification (2017-version), the distribution of the patients with COPD into GOLD categories using mMRC (≥2) or CAT (≥10) scores, and agreement between these cut-off points. Methods In this cross-sectional study (LASSYC study), 24-hour day respiratory symptoms were assessed by the Evaluating Respiratory Symptoms in COPD (E-RS) questionnaire, Nighttime Symptoms of COPD Instrument (NiSCI), Early Morning Symptoms of COPD Instrument (EMSCI), CAT and mMRC scores. Results Among the 734 patients with COPD, 61% were male, age 69.6±8.7 years, FEV1% post-BD 49.1±17.5%, mMRC 1.8±1.0 and CAT 15.3±.8.1. By mMRC 33.7% were group-A, 29.2% group-B, 10.2% group-C and 26.9% group-D. By CAT 22.3% were group-A, 41% group-B, 4.8% group-C and 31.9% group-D. Using the mMRC the severity of E-RS, NiSCI and EMSCI scores increased from group A to D. Using the CAT, the groups B and D had the higher scores. Agreement between mMRC and CAT was 89.5% (Kappa statistics=75.7%). For mMRC score of 2, CAT score of ≥11 showed the maximum Youden’s index (1.34). For mMRC score of 1, CAT score of ≥9 and ≥10 showed the maximum Youden’s index (1.48). Conclusion GOLD COPD classification by CAT seems to better discriminate 24-hour symptoms. Results do not support the equivalent use of CAT≥10 and mMRC≥2 for assessing symptoms.This observational study was funded by AstraZeneca Latin America. The funder had no input into the study design, analysis, or interpretation of the results

Genomic epidemiology of third-generation cephalosporin-resistant Escherichia coli from Argentinian pig and dairy farms reveals animal-specific patterns of co-resistance and resistance mechanisms

Control measures are being introduced globally to reduce the prevalence of antibiotic resistance (ABR) in bacteria on farms. However, little is known about the current prevalence and molecular ecology of ABR in bacterial species with the potential to be key opportunistic human pathogens, such as Escherichia coli, on South American farms. Working with 30 dairy cattle farms and 40 pig farms across two provinces in central-eastern Argentina, we report a comprehensive genomic analysis of third-generation cephalosporin-resistant (3GC-R) E. coli, which were recovered from 34.8% (cattle) and 47.8% (pigs) of samples from fecally contaminated sites. Phylogenetic analysis revealed substantial diversity suggestive of long-term horizontal and vertical transmission of 3GC-R mechanisms. CTX-M-15 and CTX-M-2 were more often produced by isolates from dairy farms, while CTX-M-8 and CMY-2 and co-carriage of amoxicillin/clavulanate resistance and florfenicol resistance were more common in isolates from pig farms. This suggests different selective pressures for antibiotic use in these two animal types. We identified the β-lactamase gene blaROB, which has previously only been reported in the family Pasteurellaceae, in 3GC-R E. coli. blaROB was found alongside a novel florfenicol resistance gene, ydhC, also mobilized from a pig pathogen as part of a new composite transposon. As the first comprehensive genomic survey of 3GC-R E. coli in Argentina, these data set a baseline from which to measure the effects of interventions aimed at reducing on-farm ABR and provide an opportunity to investigate the zoonotic transmission of resistant bacteria in this region

Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America

The aim of the present study was to evaluate the association between history of tuberculosis and airflow obstruction.A population-based, multicentre study was carried out and included 5,571 subjects aged >= 40 yrs living in one of five Latin American metropolitan areas: São Paulo (Brazil); Montevideo (Uruguay); Mexico City (Mexico); Santiago (Chile); and Caracas (Venezuela). Subjects performed pre- and post-bronchodilator spirometry and were asked whether they had ever been diagnosed with tuberculosis by a physician.The overall prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity post-bronchodilator < 0.7) was 30.7% among those with a history of tuberculosis, compared with 13.9% among those without a history. Males with a medical history of tuberculosis were 4.1 times more likely to present airflow obstruction than those without such a diagnosis. This remained unchanged after adjustment for confounding by age, sex, schooling, ethnicity, smoking, exposure to dust and smoke, respiratory morbidity in childhood and current morbidity. Among females, the unadjusted and adjusted odds ratios were 2.3 and 1.7, respectively.In conclusion, history of tuberculosis is associated with airflow obstruction in Latin American middle-aged and older adults.Univ Fed Pelotas, BR-96020220 Pelotas, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilNatl Inst Resp Dis, Mexico City, DF, MexicoUniv Republica, Montevideo, UruguayCatholic Univ Chile, Santiago, ChileCent Univ Venezuela, Caracas, VenezuelaUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Topical Analgesia with Lidocaine Plus Diclofenac Decreases Pain in Benign Anorectal Surgery: Randomized, Double-blind, and Controlled Clinical Trial

Objective: The aim of this study is to evaluate the efficacy and safety of a topical formulation containing lidocaine plus diclofenac (CLIFE1) compared to CLIFE2 (lidocaine), to decrease pain in benign anorectal surgery (BARS) to date not evaluated. Background: More than 50% of patients undergoing BARS, especially hemorrhoidectomy, suffer from moderate and severe postoperative pain. This remains an unresolved problem that could be addressed with the new CLIFE1 topical treatment. Methods: A multicenter, randomized double-blind, active-controlled parallel-group superiority trial, was conducted in two Spanish hospitals. Patients undergoing BARS (hemorrhoids, anal fistula and anal fissure) were randomized at the end of surgery at a 1:1 ratio to receive first dose either CLIFE1 (n=60) or CLIFE2 (n=60) anorectal topical treatment, and after every 12 hours for the first three postoperative days and once a day from the fourth to sixth. The primary outcome was average of pain decrease after topical treatment, measured with visual analogue scale (VAS) by the patients themselves, the evening in the surgery day and four times daily for the first three postoperative days. Results: The results of 120 patients included out of 150 selected undergoing BARS show a decrease in pain after CLIFE1 topical treatment (7.47±13.2) greater than with CLIFE2 (4.38±6.75), difference -3.21 (95% CI) -5.75; -0.676; p=0.008), decreasing significantly postoperative pain (≥ 9 mm, VAS) in 35% of patients undergoing benign anorectal surgery, compared to 18.33 % treated with lidocaine. Conclusions: The CLIFE1 topical treatment shows better analgesic efficacy than CLIFE2 in BARS

Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation

Introduction Periodontitis is a complex pathology characterized by the loss of alveolar bone. The causes and the mechanisms that promote this bone resorption still remain unknown. The knowledge of the critical regulators involved in the alteration of alveolar bone homeostasis is of great importance for developing molecular therapies. Procaine is an anesthetic drug with demethylant properties, mainly used by dentists in oral surgeries. The inhibitor role of Wnt signaling of procaine was described in vitro in colon cancer cells. Methods In this work we evaluated the role of procaine (1 uM) in osteo/odontogenesis of rat bone marrow mesenchymal stem cells. Similarly, the mechanisms whereby procaine achieves these effects were also studied. Results Procaine administration led to a drastic decrease of calcium content, alkaline phosphatase activity, alizarin red staining and an increase in the expression of Matrix Gla Protein. With respect to osteo/odontogenic markers, procaine decreased early and mature osteo/odontogenic markers. In parallel, procaine inhibited canonical Wnt/β-catenin pathway, observing a loss of nuclear β-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3β and an increase of phosphorylated β-catenin. The combination of osteo/ odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3β, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3β and β-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed. PLO

In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation

The present study investigates the differential effect of two vitamin D receptor agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells calcification in vitro. Human vascular smooth muscle cells were incubated in a high phosphate (HP) medium alone or supplemented with either calcitriol 10−8M (HP + CTR) or paricalcitol 3·10−8 M (HP + PC). HP medium induced calcification, which was associated with the upregulation of mRNA expression of osteogenic factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and osteocalcin. In these cells, activation of Wnt/β-catenin signaling was evidenced by the translocation of β-catenin into the nucleus and the increase in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican. Addition of calcitriol to HP medium (HP + CTR) further increased calcification and also enhanced the expression of osteogenic factors together with a significant elevation of nuclear β-catenin levels and the expression of cyclin D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not only reduced calcification but also downregulated the expression of BMP2 and other osteoblastic phenotype markers as well as the levels of nuclear β-catenin and the expression of its target genes. The role of Wnt/β-catenin on phosphate- and calcitriol-induced calcification was further demonstrated by the inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1), a specific natural antagonist of the Wnt/β-catenin signaling pathway. In conclusion, the differential effect of calcitriol and paricalcitol on vascular calcification appears to be mediated by a distinct regulation of the BMP and Wnt/β-catenin signaling pathways

Prevalence of smoking and incidence of initiation in the Latin American adult population: the PLATINO study

Background: the PLATINO project was launched in 2002 in order to study the prevalence of chronic obstructive pulmonary disease (COPD) in Latin America. Because smoking is the main risk factor for COPD, detailed data on it were obtained. the aim of this paper was to evaluate the prevalence of smoking and incidence of initiation among middle-aged and older adults (40 years or older). Special emphasis was given to the association between smoking and schooling.Methods: PLATINO is a multicenter study comprising five cross-sectional population-based surveys of approximately 1,000 individuals per site in São Paulo (Brazil), Santiago (Chile), Mexico City (Mexico), Montevideo (Uruguay) and Caracas (Venezuela). the outcome variable was smoking status (never, former or current). Current smokers were those who reported to smoke within the previous 30 days. Former smokers were those who reported to quit smoking more than 30 days before the survey. Using information on year of birth and age of smoking onset and quitting, a retrospective cohort analysis was carried out. Smoking prevalence at each period was defined as the number of subjects who started to smoke during the period plus those who were already smokers at the beginning of the period, divided by the total number of subjects. Incidence of smoking initiation was calculated as the number of subjects who started to smoke during the period divided by the number of non-smokers at its beginning. the independent variables included were sex, age and schooling.Results: Non-response rates ranged from 11.1% to 26.8%. the prevalence of smoking ranged from 23.9% (95% CI 21.3; 26.6) in São Paulo to 38.5% (95% CI 35.7; 41.2) in Santiago. Males and middle-aged adults were more likely to smoke in all sites. After adjustment for age, schooling was not associated with smoking. Using retrospective cohort analysis, it was possible to detect that the highest prevalence of smoking is found between 20-29 years, while the highest incidence is found between 10-19 years. Age of smoking onset tended to decline over time among females.Conclusion: the prevalence of smoking varied considerably across sites, but was lower among countries with national anti-smoking campaigns.Univ Fed Pelotas, Pelotas, BrazilUniv Republica, Montevideo, UruguayInst Nacl Enfermedades Resp, Mexico City, DF, MexicoUniversidade Federal de São Paulo, São Paulo, BrazilPontificia Univ Catolica Chile, Santiago, ChileCent Univ Venezuela, Caracas, VenezuelaUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

The availability, cost, and affordability of essential medicines for asthma and COPD in low-income and middle-income countries: a systematic review.

Asthma and chronic obstructive pulmonary disease (COPD) cause a considerable burden of morbidity and mortality in low-income and middle-income countries (LMICs). Access to safe, effective, quality-assured, and affordable essential medicines is variable. We aimed to review the existing literature relating to the availability, cost, and affordability of WHO's essential medicines for asthma and COPD in LMICs. A systematic review of the literature was done by searching seven databases to identify research articles published between Jan 1, 2010, and June 30, 2022. Studies on named essential medicines for asthma and COPD in LMICs were included and review articles were excluded. Two authors (MS and HT) screened and extracted data independently, and assessed bias using Joanna Briggs Institute appraisal tools. The main outcome measures were availability (WHO target of 80%), cost (compared with median price ratio [MPR]), and affordability (number of days of work of the lowest paid government worker). The study was registered with PROSPERO, CRD42021281069. Of 4742 studies identified, 29 met the inclusion criteria providing data from 60 LMICs. All studies had a low risk of bias. Six of 58 countries met the 80% availability target for short-acting beta-agonists (SABAs), three of 48 countries for inhaled corticosteroids (ICSs), and zero of four for inhaled corticosteroid-long-acting beta-agonist (ICS-LABA) combination inhalers. Costs were reported by 12 studies: the range of MPRs was 1·1-351 for SABAs, 2·6-340 for ICSs, and 24 for ICS-LABAs in the single study reporting this. Affordability was calculated in ten studies: SABA inhalers typically cost around 1-4 days' wages, ICSs 2-7 days, and ICS-LABAs at least 6 days. The included studies showed heterogeneity. Essential medicines for treating asthma and COPD were largely unavailable and unaffordable in LMICs. This was particularly true for inhalers containing corticosteroids. WHO and Wellcome Trust