Characteristics of a cost-effective blood test for colorectal cancer screening.

BACKGROUND: Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing (FIT) or decennial colonoscopy. METHODS: We used the three CISNET-Colon models to compare scenarios of no screening, annual FIT, decennial colonoscopy, and a blood test meeting CMS coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (AAs, 10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years gained (QALYG) from screening and costs for an US average-risk 45-year-old cohort. RESULTS: Annual FIT yielded 125-163 QALYG per 1,000 at a cost of $3,811-5,384 per person, whereas colonoscopy yielded 132-177 QALYG at a cost of $5,375-7,031 per person. A blood test with 92% CRC sensitivity and 50% AA sensitivity yielded 117-162 QALYG if used every three years and 133-173 QALYG if used every year but would not be cost-effective if priced above $125 per test. If used every three years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALYG, at a cost of $8,559-9,413 per person. CONCLUSION: Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or FIT due to lower benefit. Blood tests need higher AA sensitivity (above 40%) and lower costs (below $125) to be cost-effective.

Emulator-Based Bayesian Calibration of the CISNET Colorectal Cancer Models.

PURPOSE: To calibrate Cancer Intervention and Surveillance Modeling Network (CISNET)'s SimCRC, MISCAN-Colon, and CRC-SPIN simulation models of the natural history colorectal cancer (CRC) with an emulator-based Bayesian algorithm and internally validate the model-predicted outcomes to calibration targets. METHODS: We used Latin hypercube sampling to sample up to 50,000 parameter sets for each CISNET-CRC model and generated the corresponding outputs. We trained multilayer perceptron artificial neural networks (ANNs) as emulators using the input and output samples for each CISNET-CRC model. We selected ANN structures with corresponding hyperparameters (i.e., number of hidden layers, nodes, activation functions, epochs, and optimizer) that minimize the predicted mean square error on the validation sample. We implemented the ANN emulators in a probabilistic programming language and calibrated the input parameters with Hamiltonian Monte Carlo-based algorithms to obtain the joint posterior distributions of the CISNET-CRC models' parameters. We internally validated each calibrated emulator by comparing the model-predicted posterior outputs against the calibration targets. RESULTS: The optimal ANN for SimCRC had 4 hidden layers and 360 hidden nodes, MISCAN-Colon had 4 hidden layers and 114 hidden nodes, and CRC-SPIN had 1 hidden layer and 140 hidden nodes. The total time for training and calibrating the emulators was 7.3, 4.0, and 0.66 h for SimCRC, MISCAN-Colon, and CRC-SPIN, respectively. The mean of the model-predicted outputs fell within the 95% confidence intervals of the calibration targets in 98 of 110 for SimCRC, 65 of 93 for MISCAN, and 31 of 41 targets for CRC-SPIN. CONCLUSIONS: Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis, such as the CISNET CRC models. In this work, we present a step-by-step guide to constructing emulators for calibrating 3 realistic CRC individual-level models using a Bayesian approach. HIGHLIGHTS: We use artificial neural networks (ANNs) to build emulators that surrogate complex individual-based models to reduce the computational burden in the Bayesian calibration process.ANNs showed good performance in emulating the CISNET-CRC microsimulation models, despite having many input parameters and outputs.Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis.This work aims to support health decision scientists who want to quantify the uncertainty of calibrated parameters of computationally intensive simulation models under a Bayesian framework.

Pedal Acceleration Time An Alternative Tool To Ankle-Brachial Index In Peripheral Arterial Disease.

INTRODUCTION: Ankle-Brachial Index (ABI) is a well-established diagnostic tool for evaluating peripheral arterial disease (PAD). Limitations in its application led to the development of alternative diagnostic methods, including Toe-Brachial Index (TBI) and Transcutaneous Pressure of Oxygen (TcPO2), yet these are not as widely available as ABI. Recently, Pedal Acceleration Time (PAT), has gained popularity as a new tool to assess PAD, requiring only an ultrasound. This study seeks to further establish the correlation between ABI and PAT, determining whether PAT can be a reliable alternative for diagnosing and assessing the severity of PAD. METHODS: ABI and PAT were measured in patients attending our consult with no history of vascular or endovascular surgery. Limbs with unmeasurable ABI were excluded. Patients were categorized into groups based on their PAD stage according to the Fontaine classification. Patient demographics, comorbidities and respective ABI and PAT were analysed. RESULTS: Sixty-nine patients (114 limbs) were included in the study. Mean age 68 ± 11.7 years, 78.3% male and 33.3% diabetic patients. Fifty-three claudicant limbs (46.5%) and 26 limbs (22.8%) with chronic limb threatening ischemia. Pearson correlation coefficient between ABI and PAT, showed a strong negative correlation (r= -0.78; p<0.01). Mean ABI and PAT for limbs in Fontaine stage I were 0.94 ± 0.17 and 82.0 ± 27.4 ms; Fontaine stage IIa 0.69 ± 0.21 and 141.3 ± 57.8 ms; Fontaine stage IIb 0.54 ± 0.14 and 173.4 ± 65.1 ms; Fontaine stage III 0.43 ± 0.15 and 216 ± 33.2 ms; Fontaine stage IV 0.49 ± 0.17 and 206.7 ± 78.1 ms, respectively. CONCLUSION: Our study suggests an inverse correlation between ABI and PAT, in accordance with the findings published in the literature, thus supporting the use of PAT as an easily reproducible and efficient alternative to ABI for evaluating the severity of PAD.

Myoclonus improvement after seizures in progressive myoclonic epilepsy type 7: a case report.

BACKGROUND: Progressive Myoclonic Epilepsy (PME) is a group of rare diseases that are difficult to differentiate from one another based on phenotypical characteristics. CASE REPORT: We report a case of PME type 7 due to a pathogenic variant in KCNC1 with myoclonus improvement after epileptic seizures. DISCUSSION: Myoclonus improvement after seizures may be a clue to the diagnosis of Progressive Myoclonic Epilepsy type 7.

Identifying high-risk neurological phenotypes in adult-onset classic monogenic autoinflammatory diseases: when should neurologists consider testing?

BACKGROUND: Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized. METHODS: We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes. RESULTS: From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization. CONCLUSION: Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.

Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With a Blood Test That Meets the Centers for Medicare & Medicaid Services Coverage Decision.

BACKGROUND & AIMS: A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. METHODS: Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. RESULTS: Without screening, the models predicted 77-88 CRC cases and 32-36 CRC deaths per 1000 individuals, costing $5.3-$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600-$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5-24 QALYG) and less costly (-$3.2 to -$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. CONCLUSION: Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening.

Determination of the volatile chemical profile of Momordica charantia (bitter melon) leaf and fruit by GC-MS.

The plant Momordica charantia (Cucurbitaceae), popularly known as bitter melon, snake fruit, Saint Vincent's herb, or little melon, is an African species that has developed in tropical and subtropical biomes in various parts of Brazil. The fruit is used in various traditional medicinal applications. The study aimed to identify the compounds of the essential oil of the leaves obtained by hydrodistillation and in the fruit through Solid-Phase Microextraction by headspace mode (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS). The analysis of mature fruits led to the identification of 18 compounds, compared to the hydrodistillation, in which 21 compounds were identified. Benzaldehyde, linalool, and ß-cyclocitral were identified in both methods. Linalool was the major compound in both processes. These findings highlight the importance of knowing the chemical composition of organic volatile compounds (VOCs), given the potential for medicinal applications and popular use of plants.

Lobar or sublobar resection of peripheral stage I non-small cell lung cancer.

PURPOSE OF REVIEW: We aim to highlight two recent clinical trials that have altered the approach of the management of stage I nonsmall cell lung cancer. RECENT FINDINGS: The JCOG 0802 and CALGB 140503 trials demonstrated that sublobar resection is noninferior to lobectomy for overall and disease-free survival in patients with stage I nonsmall cell lung cancer. SUMMARY: Since 1962, lobectomy has been deemed the gold standard treatment for operable lung cancer. However, two recent clinical trials have demonstrated that, for select patients, sublobar resection is oncologically noninferior; results, which are leading us into a new era for the surgical management of lung cancer. Notwithstanding the progress made by these studies and the opportunities that have been put forth, questions remain. This review aims at reviewing the results of both trials and to discuss future perspectives for the surgical treatment of lung cancer.

Coverage and determinants of childhood vaccination during the COVID-19 pandemic in Fortaleza, Northeastern Brazil: a longitudinal analysis.

Brazil has seen a decrease in vaccination coverage since 2016. This study analyzes the immunization status of children born during the COVID-19 pandemic in Fortaleza, Northeastern Brazil. This is a longitudinal analysis that included vaccination data of 313 children aged 12 and 18 months. Vaccination cards were checked for dose application considering the schedule of immunization recommended by the Brazilian Ministry of Health. Factors associated with no retention of vaccination cards and incomplete immunization by 18 months were identified by Tobit regression analysis. About 73% of mothers presented their child's vaccination card. Non-availability of vaccination cards was associated with maternal age < 25 years and mothers with paid jobs. Only 33% and 45% of the children aged 12 and 18 months had all vaccines up to date, respectively. For 3-dose vaccines, the delay rate was around 10% for the first dose application, but 40% for the third dose. Despite delays, most children with available vaccine cards had coverage above 90% by 18 months of age. Adjusted factors associated with incomplete vaccination included living in a household with more than one child (p = 0.010) and monthly income of less than one minimum wage (p = 0.006). Therefore, delays in child vaccine application were high during the COVID-19 pandemic but a considerable uptake by 18 months of age was found. Poorer families with more than one child were particularly at risk of not fully immunizing their children and should be the target of public policies.

Lignocellulosic-biomolecules conjugated systems: green-engineered complexes modified by covalent linkers.

Lignocellulosic biomass represents an abundant and eco-friendly material widely explored in recent years. The main lignocellulosic fractions include cellulose, hemicellulose, and lignin. Nonetheless, the heterogeneity and complexity of these components pose challenges in achieving the desired properties. Conversely, their attractive functional groups can covalently link with other biomolecules, facilitating the creation and enhancement of material properties. Lignocellulosic molecules can form different linkages with other biomolecules through classic and modern methods. Bioconjugation has emerged as a suitable alternative to create new nuances, empowering the linkage between lignocellulosic materials and biomolecules through linkers. These conjugates (lignocellulosic-linkers-biomolecules) attract attention from stakeholders in medicine, chemistry, biology, and agriculture. The plural formations of these biocomplexes highlight the significance of these arrangements. Therefore, this review provides an overview of the progress of lignocellulosic-biomolecule complexes and discusses different types of covalent bioconjugated systems, considering the formation of linkers, applicability, toxicity, and future challenges.

Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia.

Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.

Temporal trends and spatial and spatiotemporal distribution of schistosomiasis mansoni in northeast Brazil between 2005 and 2016.

BACKGROUND: Schistosoma mansoni is a parasitic disease of great magnitude for Brazilian public health. We aimed to analyse the temporal trend and spatial and spatiotemporal distribution of positivity rates for schistosomiasis mansoni in northeast Brazil. METHODS: This is a descriptive study with an ecological approach, carried out between 2005 and 2016. We calculated the positivity rate for the disease and then performed a segmented trend analysis (Joinpoint). For spatial analysis, we smoothed the positivity rates using the local empirical Bayesian method. We checked for spatial autocorrelation using Moran's global and local. Subsequently, we performed Kulldorff's space time sweep analysis. RESULTS: In the period under review, 7 745 650 tests were performed in the northeast, of which 577 793 were positive for Schistosoma mansoni. In the historical series of positivities, it is noted that the highest rates were in Sergipe, Alagoas and Pernambuco. The states of Alagoas and Sergipe showed higher positivity in relation to the average positivity of the northeast and of Brazil. The spatial analysis maps identify clusters of high risk of schistosomiasis cases, mainly in coastal municipalities. There was also stability in positivity rates in some states and the maintenance of endemic areas. CONCLUSIONS: Thus effective public health policies are needed in health education in order to reduce schistosomiasis positivity and improve the health conditions of the northeastern population.

Peculiar aetiology for orbital apex syndrome: Wyburn-Mason syndrome as orbital apex lesion.

Background: Wyburn-Mason syndrome is a rare, non-hereditary congenital disease, belonging to the group of neurocutaneous syndromes with fewer than 100 cases reported since its first description in 1937. Case report: A young adult man was initially evaluated at the age of 2 years for proptosis and progressive visual impairment of the right eye, followed by impairment in ocular abduction, adduction and elevation as well as amaurosis. MRI revealed an expansive formation centred in the right orbit compromising conal spaces with distortion of eye muscles and optic nerve. The lesion extended through the superior orbital fissure into the right cavernous sinus and to the contralateral orbit. Despite embolisation, proptosis and oedema of the periorbital tissue continued to worsen. The combination of facial, ocular and intracranial vascular malformations and the exclusion of alternative aetiologies led to a diagnosis of cerebrofacial arteriovenous metameric syndrome (CAMS) 1 (Wyburn-Mason syndrome). Discussion: Important differential diagnoses are other CAMS, such as Sturge-Weber syndrome, as well as other conditions such as retinal cavernous haemangioma and vasoproliferative tumours. The optimal treatment regimen for severe cases of this syndrome is still unclear. Wyburn-Mason syndrome should be considered in patients presenting multiple arteriovenous malformations with orbital apex lesions.

Emulator-based Bayesian calibration of the CISNET colorectal cancer models.

Purpose: To calibrate Cancer Intervention and Surveillance Modeling Network (CISNET) 's SimCRC, MISCAN-Colon, and CRC-SPIN simulation models of the natural history colorectal cancer (CRC) with an emulator-based Bayesian algorithm and internally validate the model-predicted outcomes to calibration targets. Methods: We used Latin hypercube sampling to sample up to 50,000 parameter sets for each CISNET-CRC model and generated the corresponding outputs. We trained multilayer perceptron artificial neural networks (ANN) as emulators using the input and output samples for each CISNET-CRC model. We selected ANN structures with corresponding hyperparameters (i.e., number of hidden layers, nodes, activation functions, epochs, and optimizer) that minimize the predicted mean square error on the validation sample. We implemented the ANN emulators in a probabilistic programming language and calibrated the input parameters with Hamiltonian Monte Carlo-based algorithms to obtain the joint posterior distributions of the CISNET-CRC models' parameters. We internally validated each calibrated emulator by comparing the model-predicted posterior outputs against the calibration targets. Results: The optimal ANN for SimCRC had four hidden layers and 360 hidden nodes, MISCAN-Colon had 4 hidden layers and 114 hidden nodes, and CRC-SPIN had one hidden layer and 140 hidden nodes. The total time for training and calibrating the emulators was 7.3, 4.0, and 0.66 hours for SimCRC, MISCAN-Colon, and CRC-SPIN, respectively. The mean of the model-predicted outputs fell within the 95% confidence intervals of the calibration targets in 98 of 110 for SimCRC, 65 of 93 for MISCAN, and 31 of 41 targets for CRC-SPIN. Conclusions: Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis, like the CISNET CRC models. In this work, we present a step-by-step guide to constructing emulators for calibrating three realistic CRC individual-level models using a Bayesian approach.

Coverage and determinants of childhood vaccination during the COVID-19 pandemic in Fortaleza, Northeastern Brazil: a longitudinal analysis / Cobertura e determinantes da vacinação infantil durante a pandemia de COVID-19 em Fortaleza, Nordeste do Brasil: uma análise longitudinal / Cobertura y determinantes de la vacunación infantil durante la pandemia de COVID-19 en Fortaleza, Nordeste de Brasil: un análisis longitudinal

Abstract: Brazil has seen a decrease in vaccination coverage since 2016. This study analyzes the immunization status of children born during the COVID-19 pandemic in Fortaleza, Northeastern Brazil. This is a longitudinal analysis that included vaccination data of 313 children aged 12 and 18 months. Vaccination cards were checked for dose application considering the schedule of immunization recommended by the Brazilian Ministry of Health. Factors associated with no retention of vaccination cards and incomplete immunization by 18 months were identified by Tobit regression analysis. About 73% of mothers presented their child's vaccination card. Non-availability of vaccination cards was associated with maternal age < 25 years and mothers with paid jobs. Only 33% and 45% of the children aged 12 and 18 months had all vaccines up to date, respectively. For 3-dose vaccines, the delay rate was around 10% for the first dose application, but 40% for the third dose. Despite delays, most children with available vaccine cards had coverage above 90% by 18 months of age. Adjusted factors associated with incomplete vaccination included living in a household with more than one child (p = 0.010) and monthly income of less than one minimum wage (p = 0.006). Therefore, delays in child vaccine application were high during the COVID-19 pandemic but a considerable uptake by 18 months of age was found. Poorer families with more than one child were particularly at risk of not fully immunizing their children and should be the target of public policies.

Resumo: O Brasil registra uma diminuição na cobertura vacinal desde 2016. Este estudo analisa a situação vacinal de crianças nascidas durante a pandemia de COVID-19 em Fortaleza, Nordeste do Brasil. Uma análise longitudinal incluiu 313 crianças com informações aos 12 e 18 meses de idade. A aplicação das doses foram conferidas com base nos cartões de vacinação, considerando o calendário de imunização recomendado pelo Ministério da Saúde. Fatores associados à não retenção do cartão de vacinação e imunização incompleta aos 18 meses foram identificados por meio da regressão de Tobit. Cerca de 73% das mães apresentaram o cartão de vacinação do filho. A não apresentação do cartão de vacinação associou-se à idade materna < 25 anos e à participação materna em emprego remunerado. Apenas 33% e 45% das crianças tinham todas as vacinas em dia aos 12 meses e 18 meses, respectivamente. Para as vacinas com 3 doses, a taxa de atraso foi de cerca de 10% para a aplicação da 1ª dose, mas de 40% para a 3ª dose. Apesar dos atrasos, a maioria das crianças com cartão de vacinação disponível tinha cobertura acima de 90% até os 18 meses de idade. Os fatores ajustados associados à vacinação incompleta foram residir em domicílio com mais de um filho (p = 0,010) e renda mensal inferior a 1 salário mínimo (p = 0,006). Em conclusão, os atrasos na aplicação da vacina infantil foram altos durante a pandemia de COVID-19, mas houve uma adesão considerável até os 18 meses de idade. As famílias mais pobres, com mais de um filho, correm o risco de não imunizar totalmente seus filhos e devem ser alvo de políticas públicas.

Resumen: Brasil ha experimentado una disminución en la cobertura vacunal desde el 2016. Este estudio analiza la situación vacunal de los niños nacidos durante la pandemia de COVID-19 en Fortaleza, Nordeste de Brasil. Un análisis longitudinal incluyó a 313 niños con información a los 12 y 18 meses de edad. Se revisaron los carnés de vacunación para aplicar la dosis considerando el calendario de inmunización recomendado por el Ministerio de Salud. Los factores asociados con la no retención del carné de vacunación y la inmunización incompleta a los 18 meses se identificaron mediante la regresión de Tobit. Alrededor del 73% de las madres presentaron el carné de vacunación de sus hijos. La no disponibilidad del carné de vacunación se asoció con la edad materna < 25 años y la participación materna en actividad remunerada. Solo el 33% y el 45% de los niños estaban al día con todas sus vacunas a los 12 meses y 18 meses, respectivamente. Para las vacunas de 3 dosis, la tasa de retraso fue de alrededor del 10% para la 1ª dosis, pero del 40% para la 3ª dosis. A pesar de los retrasos, la mayoría de los niños con el carné de vacunación disponible tenía una cobertura superior al 90% hasta los 18 meses de edad. Los factores ajustados asociados con la vacunación incompleta fueron vivir en un hogar con más de un hijo (p = 0,010) e ingreso mensual inferior a 1 salario mínimo (p = 0,006). En definitiva, los retrasos en la administración de la vacuna infantil fueron altos durante la pandemia de COVID-19, pero hubo una adhesión considerable hasta los 18 meses de edad. Las familias más pobres, con más de un hijo, corren el riesgo de no inmunizar completamente a sus hijos y deberían ser objeto de políticas públicas.

Outside the Cage Subcostal RATS Lobectomy: Technical Aspects and Results of the First Series of a Novel Approach to Pulmonary Lobectomy.

OBJECTIVE: The goal of minimally invasive surgery is to reduce trauma to patients and improve their postoperative outcomes. In this context, the utilization of robot-assisted thoracic surgery (RATS) in the treatment of lung cancer has increased worldwide. The feasibility of single-incision major pulmonary resections by RATS was recently reported, with the objective of minimizing the surgical trauma of the traditional multiportal RATS approach. However, both techniques require intercostal incisions, potentially causing immediate and chronic pain resulting from intercostal nerve injury. To reduce postoperative pain resulting from intercostal approaches, we developed a nonintercostal, outside the thoracic cage (OTC) approach for RATS lobectomy, avoiding intercostal instrumentation. This report aims to describe the results of the first reported series of OTC subcostal RATS lobectomies. METHODS: Retrospective analysis of a series of the first consecutive patients operated on using the novel OTC subcostal RATS lobectomy technique. RESULTS: Between August and December 2022, a total of 10 consecutive cases were analyzed. The median age was 63 (55 to 84) years, the mean body mass index was 29 (24 to 45) kg/m2, and the median American Society of Anesthesiologists score was III (II to IV). No serious adverse events were observed, and there was no conversion of the surgical technique. The mean operative time was 132.6 (98 to 223) min. The median length of stay was 2 days. No pain-related complications, readmissions, or 30-day mortality were observed. CONCLUSIONS: This series demonstrates that OTC RATS lobectomy is feasible and safe. A phase I clinical trial is currently underway to prospectively assess the safety of the technique as well as its clinical relevance.

Black-White disparities in colorectal cancer outcomes: a simulation study of screening benefit.

The US Black population has higher colorectal cancer (CRC) incidence rates and worse CRC survival than the US White population, as well as historically lower rates of CRC screening. The Surveillance, Epidemiology, and End Results incidence rate data in people diagnosed between the ages of 20 and 45 years, before routine CRC screening is recommended, were analyzed to estimate temporal changes in CRC risk in Black and White populations. There was a rapid rise in rectal and distal colon cancer incidence in the White population but not the Black population, and little change in proximal colon cancer incidence for both groups. In 2014-2018, CRC incidence per 100 000 was 17.5 (95% confidence interval [CI] = 15.3 to 19.9) among Black individuals aged 40-44 years and 16.6 (95% CI = 15.6 to 17.6) among White individuals aged 40-44 years; 42.3% of CRCs diagnosed in Black patients were proximal colon cancer, and 41.1% of CRCs diagnosed in White patients were rectal cancer. Analyses used a race-specific microsimulation model to project screening benefits, based on life-years gained and lifetime reduction in CRC incidence, assuming these Black-White differences in CRC risk and location. The projected benefits of screening (via either colonoscopy or fecal immunochemical testing) were greater in the Black population, suggesting that observed Black-White differences in CRC incidence are not driven by differences in risk. Projected screening benefits were sensitive to survival assumptions made for Black populations. Building racial disparities in survival into the model reduced projected screening benefits, which can bias policy decisions.

Higher Prevalence of Nonsense Pathogenic DMD Variants in a Single-Center Cohort from Brazil: A Genetic Profile Study That May Guide the Choice of Disease-Modifying Treatments.

Dystrophinopathies are muscle diseases caused by pathogenic variants in DMD, the largest gene described in humans, representing a spectrum of diseases ranging from asymptomatic creatine phosphokinase elevation to severe Duchenne muscular dystrophy (DMD). Several therapeutic strategies are currently in use or under development, each targeting different pathogenic variants. However, little is known about the genetic profiles of northeast Brazilian patients with dystrophinopathies. We describe the spectrum of pathogenic DMD variants in a single center in northeast Brazil. This is an observational, cross-sectional study carried out through molecular-genetic analysis of male patients diagnosed with dystrophinopathies using Multiplex Ligation-dependent Probe Amplification (MLPA) followed by Next-Generation Sequencing (NGS)-based strategies. A total of 94 male patients were evaluated. Deletions (43.6%) and duplications (10.6%) were the most recurring patterns of pathogenic variants. However, small variants were present in 47.1% of patients, most of them nonsense variants (27.6%). This is the largest South American single-center case series of dystrophinopathies to date. We found a higher frequency of treatment-amenable nonsense single-nucleotide variants than most previous studies. These findings may have implications for diagnostic strategies in less-known populations, as a higher frequency of nonsense variants may mean a higher possibility of treating patients with disease-modifying drugs.

Identifying Optimal Methods for Addressing Confounding Bias When Estimating the Effects of State-level Policies.

BACKGROUND: Policy evaluation studies that assess how state-level policies affect health-related outcomes are foundational to health and social policy research. The relative ability of newer analytic methods to address confounding, a key source of bias in observational studies, has not been closely examined. METHODS: We conducted a simulation study to examine how differing magnitudes of confounding affected the performance of 4 methods used for policy evaluations: (1) the two-way fixed effects difference-in-differences model; (2) a 1-period lagged autoregressive model; (3) augmented synthetic control method; and (4) the doubly robust difference-in-differences approach with multiple time periods from Callaway-Sant'Anna. We simulated our data to have staggered policy adoption and multiple confounding scenarios (i.e., varying the magnitude and nature of confounding relationships). RESULTS: Bias increased for each method: (1) as confounding magnitude increases; (2) when confounding is generated with respect to prior outcome trends (rather than levels), and (3) when confounding associations are nonlinear (rather than linear). The autoregressive model and augmented synthetic control method had notably lower root mean squared error than the two-way fixed effects and Callaway-Sant'Anna approaches for all scenarios; the exception is nonlinear confounding by prior trends, where Callaway-Sant'Anna excels. Coverage rates were unreasonably high for the augmented synthetic control method (e.g., 100%), reflecting large model-based standard errors and wide confidence intervals in practice. CONCLUSIONS: In our simulation study, no single method consistently outperformed the others, but a researcher's toolkit should include all methodologic options. Our simulations and associated R package can help researchers choose the most appropriate approach for their data.