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Sheep respiratory disease (SRD) is a multifactorial illness commonly affecting sheep. Mesomycoplasma (Mycoplasma) ovipneumoniae is one of the most important etiological agents of SRD and should be better understood, especially in countries where it was recently detected, such as Brazil. Also, the intensive use of quinolones in mycoplasmal infections increases the selective pressure for resistance to this drug class, and no data about antimicrobial resistance in Brazil is available. Therefore, this study aimed to perform a comparative genomic analysis of newly isolated Brazilian M. ovipneumoniae strains, identify point mutations in target genes that may be associated with antibiotic resistance, and perform a phylogenomic analysis of these strains with available genome representatives of M. ovipneumoniae. Glucose-fermenting fried egg-like colonies identified as M. ovipneumoniae were obtained after a culture of tracheobronchial lavage from infected sheep. The genomes were sequenced, de novo assembled and comparatively evaluated. Important putative virulence factors were detected in all isolates: the analysis of the average nucleotide homology of all these genes with the M. ovipneumoniae ATCC 29419 revealed associations between clpB, lgt, tuf, and dnaJ genes and geographic location. In addition, nucleotide substitutions in a few positions of the Quinolone-Resistant Determinant Region of the gyrA gene, including the Ser83Ala, were detected. The phylogenomic analysis showed that the Brazilian isolates belonged to two different clades corresponding to geographic location, and the isolates from São Paulo showed high similarity, which differs from isolates from Rio de Janeiro. This first genomic analysis of the Brazilian M. ovipneumoniae genomes demonstrates strain segregation according to location and health status, reinforcing the importance of continuous surveillance and diagnostics of this bacteria causing sheep respiratory disease in the Brazilian flocks.

Assuntos

DNA Girase , Genoma Bacteriano , Mycoplasma ovipneumoniae , Filogenia , Doenças dos Ovinos , Brasil/epidemiologia , Animais , Ovinos , Doenças dos Ovinos/microbiologia , Doenças dos Ovinos/epidemiologia , DNA Girase/genética , Mycoplasma ovipneumoniae/genética , Mutação , Antibacterianos/farmacologia , Genômica , Fatores de Virulência/genética , Farmacorresistência Bacteriana/genética , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/veterinária , Pneumonia por Mycoplasma/epidemiologia

RESUMO

STUDY OBJECTIVES: Cannabis is a common sleep aid; however, the effects of its use prior to sleep are poorly understood. This study aims to determine the impact of nonmedical whole plant cannabis use 3 hours prior to sleep and measured cannabis metabolites on polysomnogram measures. METHODS: This is a cross-sectional study of 177 healthy adults who provided detailed cannabis use history, underwent a 1-night home sleep test and had measurement of 11 plasma and urinary cannabinoids, quantified using mass spectroscopy, the morning after the home sleep test. Multivariable models were used to assess the relationship between cannabis use proximal to sleep, which was defined as use 3 hours before sleep, and individual home sleep test measurements. Correlation between metabolite concentrations and polysomnogram measures were assessed. RESULTS: In adjusted models, cannabis use proximal to sleep was associated with increased wake after sleep onset (median 60.5 vs 45.8 minutes), rate ratio 1.59 (1.22, 2.05), and increased proportion of stage 1 sleep (median 15.2% vs 12.3%), effect estimate 0.16 (0.06, 0.25). Compared to nonusers, frequent cannabis users (> 20 days per month) also had increased wake after sleep onset and stage 1 sleep, in addition to increased rapid eye movement latency and decreased percent sleep efficiency. Δ9-tetrahydrocannabinol metabolites correlated with these home sleep test measures. CONCLUSIONS: Cannabis use proximal to sleep was associated with minimal changes in sleep architecture. Its use was not associated with measures of improved sleep including increased sleep time or efficiency and may be associated with poor quality sleep through increased wake onset and stage 1 sleep. CITATION: Althoff MD, Kinney GL, Aloia MS, Sempio C, Klawitter J, Bowler RP. The impact of cannabis use proximal to sleep and cannabinoid metabolites on sleep architecture. J Clin Sleep Med. 2024;20(10):1615-1625.

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Canabinoides , Polissonografia , Sono , Humanos , Canabinoides/urina , Masculino , Feminino , Estudos Transversais , Adulto , Sono/efeitos dos fármacos , Sono/fisiologia , Cannabis/efeitos adversos , Pessoa de Meia-Idade , Uso da Maconha/sangue , Uso da Maconha/urina

RESUMO

INTRODUCTION: The purpose of this study is to utilize a representative national sample to investigate the factors associated with margin positivity after attempted surgical resection. Given the changes in surgical approaches to lung cancer for the last 10 years, margin positivity and outcomes between robotic, video assisted thoracoscopic surgery (VATS) and open surgical resections may vary. METHODS: This retrospective cohort study utilized the National Cancer Database. Patients with non-small-cell lung cancer, 18 or older and who had a surgical lung resection between 2010 and 2019 were included. Demographic data, along with patient-level clinical variables were extracted. Patient-level outcome variables including 30-day, 90-day mortality and readmission rates were analyzed. Univariable and multivariable logistic regression was utilized to assess factors associated with margin positivity. RESULTS: A total of 226,884 patients were identified. Of the total cohort, 9229 had positive margins (4.2%). Patients with positive margins had statistically significant increased 30-day, 90-day mortality, as well as increased readmission rate. Older age, male sex, patients undergoing an open resection, patients who underwent a wedge resection, higher clinical stage, larger tumor size, squamous and adenosquamous histologies, and higher Charlson-Deyo Comorbidity Index were all associated with having a positive margin after resection. CONCLUSION: In conclusion, there was no difference in margin positivity when comparing robotic and VATS resection, however, open resection had increased rates of margin positivity. Increasing tumor size, clinical stage, squamous and adenosquamous histologies, male sex, and patients undergoing a wedge resection were all associated with increased rates of margin positivity.

Assuntos

Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Margens de Excisão , Pneumonectomia , Humanos , Masculino , Feminino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Estudos Retrospectivos , Idoso , Pneumonectomia/métodos , Pneumonectomia/mortalidade , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cirurgia Torácica Vídeoassistida/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Readmissão do Paciente/estatística & dados numéricos

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OBJECTIVE: To evaluate whether transfusions in infants born preterm contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We conducted a multihospital, retrospective study seeking associations between red blood cell or platelet transfusions and BPD. We tabulated all transfusions administered from January 2018 through December 2022 to infants born ≤29 weeks or <1000 g until 36 weeks postmenstrual age and compared those with BPD grade. We performed a sensitivity analysis to assess the possibility of a causal relationship. We then determined whether each transfusion was compliant with restrictive guidelines, and we estimated effects fewer transfusions might have on future BPD incidence. RESULTS: Eighty-four infants did not develop BPD and 595 did; 352 developed grade 1 (mild), 193 grade 2 (moderate), and 50 grade 3 (severe). Transfusions were given at <36 weeks to 7% of those who did not develop BPD, 46% who did, and 98% who developed severe BPD. For every transfusion the odds of developing BPD increased by a factor of 2.27 (95% CI, 1.59-3.68; P < .001). Sensitivity analyses suggested that transfusions might contribute to BPD. Fifty-seven percent of red blood cell transfusions and 68% of platelet transfusions were noncompliant with new restrictive guidelines. Modeling predicted that complying with restrictive guidelines could reduce the transfusion rate by 20%-30% and the moderate to severe BPD rate by ∼4%-6%. CONCLUSIONS: Transfusions were associated with BPD incidence and severity. Lowering transfusion rates to comply with current restrictive guidelines might result in a small but meaningful reduction in BPD rates.

Assuntos

Displasia Broncopulmonar , Recém-Nascido , Lactente , Humanos , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/etiologia , Estudos Retrospectivos , Transfusão de Plaquetas/efeitos adversos , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos , Idade Gestacional

RESUMO

Objectives: Although sublobar resections have gained traction, wedge resections vary widely in quality. We seek to characterize the demographic and facility-level variables associated with high-quality wedge resections. Methods: The National Cancer Database was queried from 2010 to 2018. Patients with T1/T2 N0 M0 non-small cell lung cancer 2 cm or less who underwent wedge resection without neoadjuvant therapy were included. A wedge resection with no nodes sampled or with positive margins was categorized as a low-quality wedge. A wedge resection with 4 or more nodes sampled and negative margins was categorized as a high-quality wedge. Facility-specific variables were investigated via quartile analysis based on the overall volume and proportion of high-quality wedge or low-quality wedge resections performed. Results: A total of 21,742 patients met inclusion criteria, 6390 (29.4%) of whom received a high-quality wedge resection. Factors associated with high-quality wedge resection included treatment at an academic center (3005 [47.0%] vs low-quality wedge 6279 [40.9%]; P < .001). The 30- and 90-day survivals were similar, but patients who received a high-quality wedge resection had improved 5-year survival (4902 [76.7%] vs 10,548 [68.7%]; P < .001). Facilities in the top quartile by volume of high-quality wedge resections performed 69% (4409) of all high-quality wedge resections, and facilities in the top quartile for low-quality wedge resections performed 67.6% (10,378) of all low-quality wedge resections. A total of 113 facilities were in the top quartile by volume for both high-quality wedge and low-quality wedge resections. Conclusions: High-quality wedge resections are associated with improved 5-year survival when compared with low-quality wedge resections. By volume, high-quality wedge and low-quality wedge resections cluster to a minority of facilities, many of which overlap. There is discordance between best practice guidelines and current practice patterns that warrants additional study.

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OBJECTIVES: Non-small cell lung cancer (NSCLC) is frequently diagnosed during surgical resection. It remains unclear if lack of preoperative tissue diagnosis influences likelihood of receipt of guideline-concordant care or postoperative outcomes. METHODS: A retrospective cohort analysis was completed utilizing the National Cancer Database for patients undergoing lung resection with clinical stage 1 NSCLC from 2004 to 2018. Diagnosis during resection was defined as zero days between diagnosis and definitive lung resection. Patients receiving neoadjuvant therapy were excluded. Subgroup analyses were completed by resection type, including wedge resection. RESULTS: The cohort included 91,328 patients, 33,517 diagnosed during definitive resection and 57,811 diagnosed preoperatively. For patients diagnosed preoperatively, median time from diagnosis to surgery was 42 days (interquartile range 28-63 days). Patients diagnosed intraoperatively had smaller median tumor size (1.7 cm vs. 2.5 cm, P < .01) and were more likely to undergo wedge resection (10,668 [31.8%] vs. 7,617 [13.2%], P < .01). Intraoperative diagnosis resulted in lower likelihood of nodal sampling (27,356 [81.9%] vs. 53,183 [92.4%], P < .01) and nodal upstaging (2,482 [9.7%] vs. 7701 [15.5%], P < .01). Amongst patients with intraoperative diagnoses, those treated via wedge resection were less likely to undergo lymph node sampling (5,515 [52.0%] vs. 5,606 [61.1%], P < .01). Amongst patients with positive lymph nodes, patients diagnosed intraoperatively were less likely to receive adjuvant therapy (1,677 [5.0%] vs. 5,669 [9.8%], P < .01). CONCLUSIONS: Preoperative tissue diagnosis of NSCLC is associated with more frequent lymph node harvest, increased rates of upstaging and receipt of adjuvant therapy. Preoperative workup may contribute to increased rates of guideline-concordant lung cancer care.

Assuntos

Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Estudos Retrospectivos , Pneumonectomia/métodos , Estadiamento de Neoplasias , Linfonodos/patologia

RESUMO

Introduction: Field work with bats is an important contribution to many areas of research in environmental biology and ecology, as well as microbiology. Work with bats poses hazards such as bites and scratches, and the potential for exposure to infectious pathogens such as rabies virus. It also exposes researchers to many other potential hazards inherent to field work, such as environmental conditions, delayed emergency responses, or challenging work conditions. Methods: This article discusses the considerations for a thorough risk assessment process around field work with bats, pre- and post-occupational health considerations, and delves into specific considerations for areas related to biosafety concerns-training, personal protective equipment, safety consideration in field methods, decontamination, and waste. It also touches on related legal and ethical issues that sit outside the realm of biosafety, but which must be addressed during the planning process. Discussion: Although the focal point of this article is bat field work located in northern and central America, the principles and practices discussed here are applicable to bat work elsewhere, as well as to field work with other animal species, and should promote careful considerations of how to safely conduct field work to protect both researchers and animals.

RESUMO

OBJECTIVE: To differentiate diabetic ketoacidosis (DKA) from hyperglycemic ketosis due to cannabis hyperemesis syndrome (HK-CHS) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: Of 295 adults with type 1 diabetes who were seen with DKA-related ICD-10 codes, 68 patients with 172 DKA events meeting the inclusion criteria were analyzed. Cannabis use was defined as a positive urine test result for cannabis. Linear mixed models were used to define HK-CHS (pH ≥7.4 with bicarbonate ≥15 mmol/L [mEq/L]), and sensitivity and specificity were calculated using the receiver operating characteristic (ROC) curve. RESULTS: Cannabis users had significantly higher pH (7.42 ± 0.01 vs. 7.09 ± 0.02) and bicarbonate (19.2 ± 0.61 vs. 9.1 ± 0.71 mmol/L) (P < 0.0001) compared with nonusers. The area under the ROC curve for a positive cannabis urine test result predicting HK-CHS was 0.9892. CONCLUSIONS: In patients who present with DKA and higher pH, especially pH ≥7.4, cannabis use should be considered in the differential diagnosis.

Assuntos

Cannabis , Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Cetose , Adulto , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/complicações , Cetoacidose Diabética/diagnóstico , Humanos , Sensibilidade e Especificidade

RESUMO

OBJECTIVES: Globally congenital heart disease mortality is declining, yet the proportion of infant deaths attributable to heart disease rises in Colombia and other middle-sociodemographic countries. We aimed to assess the accessibility of paediatric cardiac surgery (PCS) to children <18 years of age in 2016 in the South American country of Colombia. METHODS: In Bogotá, Colombia, a multi-national team used cross-sectional and retrospective cohort study designs to adapt and evaluate 4 health system indicators at the national level: first, the population with timely geographic access to an institution providing PCS; second, the number of paediatric cardiac surgeons; third, this specialized procedure volume and its national distribution; and fourth, the 30-day perioperative mortality rate after PCS in Colombia. RESULTS: Geospatial mapping approximates 64% (n = 9 894 356) of the under-18 Colombian population lives within 2-h drivetime of an institution providing PCS. Twenty-eight cardiovascular surgeons report performing PCS, 82% (n = 23) with formal training. In 2016, 1281 PCS procedures were registered, 90% of whom were performed in 6 of the country's 32 departments. National non-risk-adjusted all-cause 30-day perioperative mortality rate after PCS was 2.73% (n = 35). CONCLUSIONS: Colombia's paediatric population had variable access to cardiac surgery in 2016, largely dependent upon geography. While the country may have the capacity to provide timely, high-quality care to those who need it, our study enables future comparative analyses to measure the impact of health system interventions facilitating healthcare equity for the underserved populations across Colombia and the Latin American region.

Assuntos

Procedimentos Cirúrgicos Cardíacos , Criança , Colômbia/epidemiologia , Estudos Transversais , Humanos , Estudos Retrospectivos , América do Sul

RESUMO

Small-scale fisheries are critically important for livelihoods around the world, particularly in tropical regions. However, climate variability and anthropogenic climate change may seriously impact small-scale fisheries by altering the abundance and distribution of target species. Social relationships between fishery users, such as fish traders, can determine how each individual responds and is affected by changes in fisheries. These informal cooperative and competitive relationships provide access, support, and incentives for fishing and affect the distribution of benefits. Yet, individuals' actions and impacts on individuals are often the primary focus of the economic analyses informing small-scale fisheries' formal management. This focus dismisses relevant social relationships. We argue that this leads to a disconnect between reality and its model representation used in formal management, which may reduce formal fisheries management's efficiency and efficacy and potentially trigger adverse consequences. Here, we examine this argument by comparing the predictions of a simple bioeconomic fishery model with those of a social-ecological model that incorporates the dynamics of cooperative relationships between fish traders. We illustrate model outcomes using an empirical case study in the Mexican Humboldt squid fishery. We find that (1) the social-ecological model with relationship dynamics substantially improves accuracy in predicting observed fishery variables to the simple bioeconomic model. (2) Income inequality outcomes are associated with changes in cooperative trade relationships. When environmental temperature is included in the model as a driver of species production dynamics, we find that climate-driven temperature variability drives a decline in catch that, in turn, reduce fishers' income. We observe an offset of this loss in income by including cooperative relationships between fish traders (oligopoly) in the model. These relationships break down following species distribution changes and result in an increase in prices fishers receive. Finally, (3) our social-ecological model simulations show that the current fishery development program, which seeks to increase fishers' income through an increase in domestic market demand, is supported by predictions from the simple bioeconomic model, may increase income inequality between fishers and traders. Our findings highlight the real and urgent need to re-think fisheries management models in the context of small-scale fisheries and climate change worldwide to encompass social relationship dynamics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s10113-021-01747-5).

RESUMO

PURPOSE: Belize has one of the highest cervical cancer burdens among Latin American and Caribbean countries, despite the implementation of national policies to increase access to prevention and treatment services. This study evaluates the policies, infrastructure, and workforce of the cervical cancer management system in Belize to inform capacity building efforts. METHODS: In 2018, health facility assessments were conducted across all six districts of Belize at the national pathology facility and 12 public facilities identified as critical to cervical cancer control. Human and infrastructure resource availability and existing policies related to cervical cancer screening and treatment services were assessed through a structured instrument. RESULTS: The public cervical cancer screening workforce in Belize consists of 75 primary care nurses and physicians-one per 1,076 screening-eligible women, with 44% conducting rural outreach. All districts have at least one screening facility, but 50% perform screening services only once per week. Colposcopy and loop electrical excision procedures are available in three and four districts, respectively; radical hysterectomy and chemotherapy are available in two districts; and radiation therapy is unavailable. Of essential pathology equipment, 38.5% were present and functional, 23% were present but nonfunctional, and 38.5% were unavailable. Additionally, 35% of supplies were unavailable at the time of assessment, and 75% were unavailable at least once in the 12 months before assessment. CONCLUSION: Public-sector cervical cancer management services differ among districts of Belize, with tertiary service availability concentrated in the largest district. Screening, outreach, and pathology are limited mostly by resource availability. This study characterizes the current capacity of services in Belize and pinpoints health system components for future investment and capacity-building efforts.

Assuntos

Neoplasias do Colo do Útero , Belize , Colposcopia , Atenção à Saúde , Detecção Precoce de Câncer , Feminino , Humanos , Gravidez , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle

RESUMO

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV1 to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV1 and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV1 and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Assuntos

Obstrução das Vias Respiratórias , Doença da Artéria Coronariana , Vasos Coronários/diagnóstico por imagem , Pulmão , Enfisema Pulmonar , Fumar/epidemiologia , Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/fisiopatologia , Remodelação das Vias Aéreas , Doenças Assintomáticas/epidemiologia , Variação Biológica da População , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pletismografia/métodos , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória/métodos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Estados Unidos/epidemiologia

RESUMO

OBJECTIVE: To review the most common mental health strategies aimed at alleviating and/or preventing mental health problems in individuals during the coronavirus disease 2019 (COVID-19) and other coronavirus pandemics. METHODS: We conducted a systematic review of the literature assessing three databases (PubMed, SCOPUS, and PsycINFO). A meta-analysis was performed with data from randomized controlled trials (RCTs). For non-RCT studies, a critical description of recommendations was performed. RESULTS: From a total of 2,825 articles, 125 were included. Of those, three RCTs were included in the meta-analysis. The meta-analysis revealed that the interventions promoted better overall mental health outcomes as compared to control groups (standardized mean difference [SMD] = 0.87 [95%CI 0.33-1.41], p < 0.001, I2 = 69.2%), but did not specifically improve anxiety (SMD = 0.98 [95%CI -0.17 to 2.13], p > 0.05; I2 = 36.8%). Concerning the systematic review, we found a large body of scientific literature proposing recommendations involving psychological/psychiatric interventions, self-care, education, governmental programs, and the use of technology and media. CONCLUSIONS: We found a large body of expert recommendations that may help health practitioners, institutional and governmental leaders, and the general population cope with mental health issues during a pandemic or a crisis period. However, most articles had a low level of evidence, stressing the need for more studies with better design (especially RCTs) investigating potential mental health interventions during COVID-19. PROSPERO REGISTRATION: CRD42020190212.

Assuntos

COVID-19 , Humanos , Saúde Mental , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2

RESUMO

OBJECTIVE: To quantify the risk that transcutaneous bilirubin (TcB) screening would fail to recommend phototherapy for a neonate who would have qualified for it if total serum bilirubin (TSB) screening were used. STUDY DESIGN: We conducted a quality improvement project where simultaneous TcB and TSB were obtained on neonates ≥35 weeks of gestation during birth hospitalizations in our hospital system. Using our Utah bilirubin management algorithm, we quantified the risk that TcB screening would fail to identify the need for a confirmatory TSB when TSB screening alone would have revealed that phototherapy was indicated. RESULTS: In 3 hospitals, we obtained 727 paired TcB/TSB measurements. Two instances utilized a blood gas radiometer for TSB, and 725 utilized the clinical laboratory-based TSB method. One of the 727 instances had a TcB indicating NO PHOTOTHERAPY, when the simultaneous TSB indicated PHOTOTHERAPY NEEDED. The TSB from that instance was 1 of the 2 from the blood gas radiometer. We estimate the risk of such an error occurring is 1.4 per 1000 TcB measurements (95% CI 0.03-7.6 per 1000). When only the laboratory TSB is used, we estimate the risk of such an error occurring to be 0 per 1000 TcB measurements (95% CI 0.0-5.1 per 1000). CONCLUSIONS: Using TcB for screening at the birth hospital can identify those qualifying for phototherapy, using the Utah guidelines, with 1 of 727 neonates with a blood gas bilirubin and none of 725 with a laboratory-based analysis misidentified as not needing phototherapy when by TSB they did.

Assuntos

Bilirrubina/sangue , Atenção à Saúde/normas , Recém-Nascido Prematuro/sangue , Icterícia Neonatal/sangue , Triagem Neonatal/métodos , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Icterícia Neonatal/diagnóstico , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos

RESUMO

BACKGROUND: Surgical, anaesthetic, and obstetric (SAO) health-care system strengthening is needed to address the emergency and essential surgical care that approximately 5 billion individuals lack globally. To our knowledge, a complete, non-modelled national situational analysis based on the Lancet Commission on Global Surgery surgical indicators has not been done. We aimed to undertake a complete situation analysis of SAO system preparedness, service delivery, and financial risk protection using the core surgical indicators proposed by the Commission in Colombia, an upper-middle-income country. METHODS: Data to inform the six core surgical system indicators were abstracted from the Colombian national health information system and the most recent national health survey done in 2007. Geographical access to a Bellwether hospital (defined as a hospital capable of providing essential and emergency surgery) within 2 h was assessed by determining 2 h drive time boundaries around Bellwether facilities and the population within and outside these boundaries. Physical 2 h access to a Bellwether was determined by the presence of a motor vehicle suitable for individual transportation. The Department Administrativo Nacional de Estadística population projection for 2016 and 2018 was used to calculate the SAO provider density. Total operative volume was calculated for 2016 and expressed nationally per 100 000 population. The total number of postoperative deaths that occurred within 30 days of a procedure was divided by the total operative volume to calculate the all-cause, non-risk-adjusted postoperative mortality. The proportion of the population subject to impoverishing costs was calculated by subtracting the baseline number of impoverished individuals from those who fell below the poverty line once out-of-pocket payments were accounted for. Individuals who incurred out-of-pocket payments that were more than 10% of their annual household income were considered to have experienced catastrophic expenditure. Using GIS mapping, SAO system preparedness, service delivery, and cost protection were also contextualised by socioeconomic status. FINDINGS: In 2016, at least 7·1 million people (15·1% of the population) in Colombia did not have geographical access to SAO services within a 2 h driving distance. SAO provider density falls short of the Commission's minimum target of 20 providers per 100 000 population, at an estimated density of 13·7 essential SAO health-care providers per 100 000 population in 2018. Lower socioeconomic status of a municipality, as indicated by proportion of people enrolled in the subsidised insurance regime, was associated with a smaller proportion of the population in the municipality being within 2 h of a Bellwether facility, and the most socioeconomically disadvantaged municipalities often had no SAO providers. Furthermore, Colombian providers appear to be working at or beyond capacity, doing 2690-3090 procedures per 100 000 population annually, but they have maintained a relatively low median postoperative mortality of 0·74% (IQR 0·48-0·84). Finally, out-of-pocket expenses for indirect health-care costs were a key barrier to accessing surgical care, prompting 3·1 million (6·4% of the population) individuals to become impoverished and 9·5 million (19·4% of the population) individuals to incur catastrophic expenditures in 2007. INTERPRETATION: We did a non-modelled, indicator-based situation analysis of the Colombian SAO system, finding that it has not yet met, but is working towards achieving, the targets set by the Lancet Commission on Global Surgery. The observed interdependence of these indicators and correlation with socioeconomic status are consistent with well recognised factors and outcomes of social, health, and health-care inequity. The internal consistency observed in Colombia's situation analysis validates the use of the indicators and has now informed development of an early national SAO plan in Colombia, to set a data-informed stage for implementation and evaluation of timely, safe, and affordable SAO health care, within the National Public Health Decennial Plan, which is due in 2022. FUNDING: Zoll Medical.

Assuntos

Indicadores de Qualidade em Assistência à Saúde , Procedimentos Cirúrgicos Operatórios/normas , Colômbia , Humanos , Sociedades Médicas

RESUMO

BACKGROUND: Patients with HER2-positive breast cancer who have received two or more previous therapies for advanced disease have few effective treatment options. The monarcHER trial aimed to compare the efficacy of abemaciclib plus trastuzumab with or without fulvestrant with standard-of-care chemotherapy of physician's choice plus trastuzumab in women with advanced breast cancer. METHODS: This phase 2, three-group, open-label trial was done across 75 hospitals, clinics, and medical centres in 14 countries. Eligible patients were women aged 18 years or older, who had hormone receptor-positive, HER2-positive advanced breast cancer with unresectable, locally advanced, recurrent or metastatic disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and who had previously received at least two HER2-targeted therapies for advanced disease. Patients were randomly assigned 1:1:1 to the abemaciclib, trastuzumab, and fulvestrant (group A), abemaciclib and trastuzumab (group B), or standard-of-care chemotherapy and trastuzumab (group C). Oral abemaciclib 150 mg 12 hourly was administered on days 1-21 of a 21-day cycle, intravenous trastuzumab 8 mg/kg on cycle 1 day 1, followed by 6 mg/kg on day 1 of each subsequent 21-day cycle, and intramuscular fulvestrant 500 mg on days 1, 15, and 29 and once every 4 weeks thereafter. Standard-of-care chemotherapy was administered as specified by the product label. Randomisation was by a computer-generated random sequence by means of an interactive web-response system and stratified by number of previous systemic therapies for advanced breast cancer and measurable versus non-measurable disease. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, first testing group A versus group C and, if this result was significant, then group B versus group C. Safety was assessed in all patients who had received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT02675231) and is ongoing for long-term survival follow-up. FINDINGS: Between May 31, 2016, and Feb 28, 2018, 325 patients were screened, of whom 237 eligible patients were enrolled and randomly assigned to groups A (n=79), B (n=79), and C (n=79). Median follow-up was 19·0 months (IQR 14·7-25·1). The study met its primary endpoint, showing a significant difference at the prespecified two-sided α of 0·2 in median progression-free survival between group A (8·3 months, 95% CI 5·9-12·6) and group C (5·7 months, 5·4-7·0; HR 0·67 [95% CI 0·45-1·00]; p=0·051). No difference was observed between median progression-free survival in group B (5·7 months, 95% CI 4·2-7·2) and group C (HR 0·94 [0·64-1·38]; p=0·77). The most common grade 3-4 treatment-emergent adverse event in groups A, B, and C was neutropenia (21 [27%] of 78 patients, 17 [22%] of 77, and 19 [26%] of 72). The most common serious adverse events were: in group A, pyrexia (three [4%]), diarrhoea (two [3%]), urinary tract infection (two [3%]), and acute kidney injury (two [3%]); in group B, diarrhoea (two [3%]) and pneumonitis (two [3%]); and in group C, neutropenia (four [6%]) and pleural effusion (two [3%]). Two deaths were attributed to treatment: one due to pulmonary fibrosis in group B and one due to febrile neutropenia in group C. INTERPRETATION: The combination of abemaciclib, fulvestrant, and trastuzumab significantly improved progression-free survival versus standard-of-care chemotherapy plus trastuzumab while showing a tolerable safety profile. Our results suggest that a chemotherapy-free regimen might potentially be an alternative treatment option for patients with hormone receptor-positive, HER2-positive advanced breast cancer. FUNDING: Eli Lilly and Company.

Assuntos

Aminopiridinas/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Antagonistas do Receptor de Estrogênio/administração & dosagem , Fulvestranto/administração & dosagem , Receptor ErbB-2/antagonistas & inibidores , Receptores de Estrogênio/efeitos dos fármacos , Trastuzumab/administração & dosagem , Idoso , Aminopiridinas/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Argentina , Austrália , Benzimidazóis/efeitos adversos , Brasil , Neoplasias da Mama/enzimologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Progressão da Doença , Antagonistas do Receptor de Estrogênio/efeitos adversos , Europa (Continente) , Feminino , Fulvestranto/efeitos adversos , Humanos , Pessoa de Meia-Idade , América do Norte , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , República da Coreia , Transdução de Sinais , Fatores de Tempo , Trastuzumab/efeitos adversos

RESUMO

Type 1 conventional dendritic cells (cDC1s) are typically thought to be dysregulated secondarily to invasive cancer. Here, we report that cDC1 dysfunction instead develops in the earliest stages of preinvasive pancreatic intraepithelial neoplasia (PanIN) in the KrasLSL-G12D/+ Trp53LSL-R172H/+ Pdx1-Cre-driven (KPC) mouse model of pancreatic cancer. cDC1 dysfunction is systemic and progressive, driven by increased apoptosis, and results in suboptimal up-regulation of T cell-polarizing cytokines during cDC1 maturation. The underlying mechanism is linked to elevated IL-6 concomitant with neoplasia. Neutralization of IL-6 in vivo ameliorates cDC1 apoptosis, rescuing cDC1 abundance in tumor-bearing mice. CD8+ T cell response to vaccination is impaired as a result of cDC1 dysregulation. Yet, combination therapy with CD40 agonist and Flt3 ligand restores cDC1 abundance to normal levels, decreases cDC1 apoptosis, and repairs cDC1 maturation to drive superior control of tumor outgrowth. Our study therefore reveals the unexpectedly early and systemic onset of cDC1 dysregulation during pancreatic carcinogenesis and suggests therapeutically tractable strategies toward cDC1 repair.

Assuntos

Carcinogênese/imunologia , Células Dendríticas/imunologia , Neoplasias Experimentais/imunologia , Neoplasias Pancreáticas/imunologia , Idoso , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinogênese/genética , Carcinogênese/patologia , Células Dendríticas/patologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia

RESUMO

OBJECTIVE: We examined the frequency of diabetic ketoacidosis (DKA) in cannabis users compared with nonusers in the T1D Exchange clinic registry (T1DX). RESEARCH DESIGN AND METHODS: The association between cannabis use by total substance score for cannabis (TSC) and DKA in the past 12 months was examined using a logistic regression model adjusted for potential confounders among adults in the T1DX. RESULTS: Of 932 adults with type 1 diabetes, 61 had a TSC >4, which classified them as moderate cannabis users. Adjusting for sex, age at study visit, and HbA1c, cannabis use was associated with a twofold increase in risk for DKA among adults with type 1 diabetes (odds ratio 2.5 [95% CI 1.0-5.9]). CONCLUSIONS: Cannabis use was associated with an increased risk for DKA among adults in the T1DX. Providers should inform their patients of the potential risk of DKA with cannabis use.

Assuntos

Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/epidemiologia , Abuso de Maconha/epidemiologia , Fumar Maconha/epidemiologia , Adolescente , Adulto , Cannabis/efeitos adversos , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/etiologia , Feminino , Humanos , Masculino , Abuso de Maconha/complicações , Fumar Maconha/efeitos adversos , Sistema de Registros , Fatores de Risco , Adulto Jovem

RESUMO

Mexico is recognized as the center of origin and domestication of maize. Introduction of modern maize varieties (MVs) into Mexico raised concerns regarding the possible effects of gene flow from MVs into maize landraces (LRs) and their wild relatives (WRs), teosintes. However, after more than 60 y from the release of the first MVs, the impact of the sympatry with LRs and their WRs has not been explored with genetic data. In this work, we assessed changes in the genomes of 7 maize LRs and 2 WR subspecies from collections spanning over 70 y. We compared the genotypes obtained by genotyping by sequencing (GBS) for LRs and WRs before and after the adoption of MVs, and observed introgression from sympatric MVs into LRs and into the WR Zea mays ssp. mexicana sampled after the year 2000. We also found a decrease in the paired divergence index (FST ) between MV-LR and MV-WR over the same time frame. Moreover, we determined that LR genetic diversity increased after 2000, probably as a result of gene flow from MVs introduced in the 1990s. Our findings allowed us to identify ongoing changes in the domesticated and wild maize genetic pools, and concur with previous works that have evaluated short-term gene flow from MVs into LRs in other crops. Our approach represents a useful tool for tracking evolutionary change in wild and domesticated genetic resources, as well as for developing strategies for their conservation.

Assuntos

Fluxo Gênico/genética , Genoma de Planta/genética , Zea mays/genética , Produtos Agrícolas/genética , Domesticação , Pool Gênico , Variação Genética/genética , Genótipo , México , Simpatria/genética