Early genetic testing in pediatric epilepsy: Diagnostic and cost implications.

The identification of numerous genetically based epilepsies has resulted in the widespread use of genetic testing to inform epilepsy etiology. Our study aims to investigate whether a difference exists in the diagnostic evaluation and healthcare-related cost expenditures of pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis through multigene epilepsy panel (MEP) testing and comparing those who underwent early (EGT) versus late genetic testing (LGT). Testing was defined as early (less than 1 year), or late (more than 1 year), following clinical epilepsy diagnosis. A retrospective chart review of pediatric individuals (1-17 years) with epilepsy of unknown etiology who underwent multigene epilepsy panel (MEP) testing identified 28 of 226 (12%) individuals with a pathogenic epilepsy variant [EGT n = 8 (29%); LGT n = 20 (71%)]. The average time from clinical epilepsy diagnosis to genetic diagnosis was 0.25 years (EGT), compared with 7.1 years (LGT). The EGT cohort underwent fewer metabolic tests [EGT n = 0 (0%); LGT n = 16 (80%) (P < 0.01)] and invasive procedures [EGT n = 0 (0%); LGT n = 5 (25%) (P = 0.06)]. Clinical management changes implemented due to genetic diagnosis occurred in 10 (36%) patients [EGT n = 2 (25%); LGT n = 8 (40%) (P = 0.76)]. Early genetic testing with a MEP in pediatric patients with epilepsy of unknown etiology who receive a genetic diagnosis is associated with fewer non-diagnostic tests and invasive procedures and reduced estimated overall healthcare-related costs. PLAIN LANGUAGE SUMMARY: This study aims to investigate whether a difference exists in the diagnostic evaluation and cost expenditures of pediatric patients (1-17 years) with epilepsy of unknown cause who are ultimately diagnosed with a genetic cause of epilepsy through multigene epilepsy panel testing and comparing those who underwent early testing (less than 1 year) versus late testing (more than 1 year) after clinical epilepsy diagnosis. Of the 28 of 226 individuals with a confirmed genetic cause of epilepsy on multigene epilepsy panel testing, performing early testing was associated with fewer non-diagnostic tests, fewer invasive procedures and reduced estimated overall healthcare-related costs.

Assessment of the Diagnostic Yield of Combined Cardiomyopathy and Arrhythmia Genetic Testing.

Importance: Genetic testing can guide management of both cardiomyopathies and arrhythmias, but cost, yield, and uncertain results can be barriers to its use. It is unknown whether combined disease testing can improve diagnostic yield and clinical utility for patients with a suspected genetic cardiomyopathy or arrhythmia. Objective: To evaluate the diagnostic yield and clinical management implications of combined cardiomyopathy and arrhythmia genetic testing through a no-charge, sponsored program for patients with a suspected genetic cardiomyopathy or arrhythmia. Design, Setting, and Participants: This cohort study involved a retrospective review of DNA sequencing results for cardiomyopathy- and arrhythmia-associated genes. The study included 4782 patients with a suspected genetic cardiomyopathy or arrhythmia who were referred for genetic testing by 1203 clinicians; all patients participated in a no-charge, sponsored genetic testing program for cases of suspected genetic cardiomyopathy and arrhythmia at a single testing site from July 12, 2019, through July 9, 2020. Main Outcomes and Measures: Positive gene findings from combined cardiomyopathy and arrhythmia testing were compared with findings from smaller subtype-specific gene panels and clinician-provided diagnoses. Results: Among 4782 patients (mean [SD] age, 40.5 [21.3] years; 2551 male [53.3%]) who received genetic testing, 39 patients (0.8%) were Ashkenazi Jewish, 113 (2.4%) were Asian, 571 (11.9%) were Black or African American, 375 (7.8%) were Hispanic, 2866 (59.9%) were White, 240 (5.0%) were of multiple races and/or ethnicities, 138 (2.9%) were of other races and/or ethnicities, and 440 (9.2%) were of unknown race and/or ethnicity. A positive result (molecular diagnosis) was confirmed in 954 of 4782 patients (19.9%). Of those, 630 patients with positive results (66.0%) had the potential to inform clinical management associated with adverse clinical outcomes, increased arrhythmia risk, or targeted therapies. Combined cardiomyopathy and arrhythmia gene panel testing identified clinically relevant variants for 1 in 5 patients suspected of having a genetic cardiomyopathy or arrhythmia. If only patients with a high suspicion of genetic cardiomyopathy or arrhythmia had been tested, at least 137 positive results (14.4%) would have been missed. If testing had been restricted to panels associated with the clinician-provided diagnostic indications, 75 of 689 positive results (10.9%) would have been missed; 27 of 75 findings (36.0%) gained through combined testing involved a cardiomyopathy indication with an arrhythmia genetic finding or vice versa. Cascade testing of family members yielded 402 of 958 positive results (42.0%). Overall, 2446 of 4782 patients (51.2%) had only variants of uncertain significance. Patients referred for arrhythmogenic cardiomyopathy had the lowest rate of variants of uncertain significance (81 of 176 patients [46.0%]), and patients referred for catecholaminergic polymorphic ventricular tachycardia had the highest rate (48 of 76 patients [63.2%]). Conclusions and Relevance: In this study, comprehensive genetic testing for cardiomyopathies and arrhythmias revealed diagnoses that would have been missed by disease-specific testing. In addition, comprehensive testing provided diagnostic and prognostic information that could have potentially changed management and monitoring strategies for patients and their family members. These results suggest that this improved diagnostic yield may outweigh the burden of uncertain results.

Hepatopancreatobiliary surgery in a Mexican social security hospital during the COVID-19 pandemic.

INTRODUCTION: Data on hepatopancreatobiliary (HPB) surgery and COVID-19 are scarce. The objective of the study was to determine the outcomes HPB procedures during the COVID-19 pandemic and compare results to the previous year. METHODS: IRB approved study of HPB procedures (April, 2020-November, 2020). Primary endpoints: Thirty-day surgical morbidity/mortality, including COVID-19 infection. Secondary endpoints: Comparison between 2019 and 2020 procedures. RESULTS: Twenty-five patients were included. In 2020, HPB procedures decreased 31.6%. About 60% developed complications (Clavien-Dindo Grade III, 20%). Three patients developed post-operative COVID-19 infection (two deaths: 66% COVID-19 mortality). When compared to the previous year, there were more emergency cases, ventilator-assisted patients (p < 0.05) and pre-operative acute renal failure (p = 0.06). Clavien-Dindo complication grades were higher in 2020. Thirty-day mortality was also higher (16% vs. 5.6%). CONCLUSION: HPB surgical activity was negatively influenced by COVID-19 on 30-day morbidity/mortality. HPB patients who developed post-operative COVID-19 infection had a complicated course with significant mortality.

OBJETIVO: Los datos sobre cirugía hepatopancreatobiliar (HPB) y COVID-19 son escasos. El objetivo del estudio fue determinar los resultados de procedimientos de HPB durante la pandemia COVID-19 y comparar resultados con el año anterior. MATERIAL-MÉTODOS: Estudio de procedimientos HPB aprobado por el IRB (04/2020-11/2020). Criterios de valoración principales: morbilidad/mortalidad quirúrgica a los 30 días, incluida la infección por COVID-19. Criterios de valoración secundarios: comparación entre los procedimientos de 2019 y 2020. RESULTADOS: Se incluyeron 25 pacientes. En 2020, los procedimientos de HPB disminuyeron 31.6%. El 60% desarrolló complicaciones (grado III de Clavien-Dindo, 20%). 3 pacientes desarrollaron infección posoperatoria por COVID-19, (2 muertes: 66% de mortalidad por COVID-19). En comparación con el año anterior, hubo más casos de emergencia, pacientes asistidos por ventilador (p < 0.05) e insuficiencia renal aguda preoperatoria (p = 0.06). Los grados de complicación de Clavien-Dindo fueron más altos en 2020. La mortalidad a 30 días también fue más alta (16% frente a 5.6%). CONCLUSIÓN: La actividad quirúrgica de HPB fue influenciada negativamente por COVID-19 en la morbilidad/mortalidad a 30 días. Los pacientes con HPB que desarrollaron infección posoperatoria por COVID-19 tuvieron un curso complicado con una mortalidad significativa.

Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.

BACKGROUND: Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted. METHODS: An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated. RESULTS: Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN) or strong (DSP) evidence. Seven genes (14%; ACTC1, ACTN2, JPH2, NEXN, TNNI3, TPM1, VCL) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence. CONCLUSIONS: In the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.

Mental Load and Fatigue Assessment Instruments: A Systematic Review.

Mental load and fatigue are important causes of performance decreases and accidents in different activities. However, a robust systematic review, detailing the instruments used to quantify them, is currently lacking. The purpose of this study was to summarize and classify by derivations the validated instruments used to quantify mental load and fatigue. The most representative electronic databases in the scope of this review, PubMed, WOS, Scopus, SPORTDiscus, and PsycINFO (until September 2020) were searched for studies that included instruments to analyze mental load and fatigue. The quality of the selected studies was scored using a quality assessment checklist. A total of 40 papers were included. Most of the papers used subjective scales (75%) to quantify mental load and fatigue, with a small presence of behavioral (n = 5) and objective techniques (n = 5). Less is known about the analysis of mental load and fatigue using a combination of derivations. Despite the high cost and complexity of objective techniques, research that applies these measures is important for further analysis of brain processes in mental load and fatigue. The design of a battery of tests that include the three types of derivations also seems necessary.

A population-based mercury exposure assessment near an artisanal and small-scale gold mining site in the Peruvian Amazon.

Human exposure to mercury is a leading public health problem. Artisanal and small-scale gold mining (ASGM) is a major source of global mercury emissions. Although occupational mercury exposure to miners (via mercury vapor inhalation) is known, chronic mercury exposure to nearby residents that are not miners (via mercury-contaminated fish consumption) is poorly characterized. We conducted a population-based mercury exposure assessment in 23 communities (19 rural, 4 urban) around the Amarakaeri Communal Reserve, which is bordered on the east by heavy ASGM activity. We measured total mercury in hair (N = 2083) and blood (N = 476) from March-June 2015 and performed follow-up measurements (N = 723 hair and N = 290 blood) from February-April 2016. Mercury exposure risk was highest in communities classified as indigenous, or native, regardless of proximity to mining activity. Residence in a native community (vs. non-native) was associated with mercury levels 1.9 times higher in hair (median native 3.5 ppm vs. median non-native 1.4 ppm total mercury) and 1.6 times higher in blood (median native 7.4 ng/mL vs median non-native 3.2 ng/mL total mercury). Unexpectedly, proximity to mining was not associated with exposure risk. These findings challenge common assumptions about mercury exposure patterns and emphasize the importance of population-representative studies to identify high risk sub-populations.

Stroke care during the COVID-19 outbreak in Spain: the experience of Spanish stroke units.

BACKGROUND AND PURPOSE: Spain has been heavily affected by COVID-19. Reallocation of resources for managing the outbreak might have caused a disruption in stroke care. This study analyses the impact on stroke care of reorganising the healthcare system in response to the first COVID-19 outbreak peak in Spain and the strategies adopted by Spanish stroke units to deal with this impact. MATERIALS AND METHODS: We obtained data from a structured survey sent to the responsible of stroke units across the country. We recorded the number of strokes, stroke code activations, intravenous thrombolysis treatments and mechanical thrombectomies during February and March 2019 and 2020. We also collected information on the impact on workflow metrics and on the availability of specialised neurological care and rehabilitation treatments, the characteristics of stroke care for patients with SARS-CoV-2 infection and the impact on human resources. We compared the activity data between 2019 and 2020 and the information on activity and impact on stroke care between regions classified according to the disease incidence rate. RESULTS: Fifty-seven (75%) of all stroke units in Spain responded to the survey. There was an overall reduction in admissions for all stroke types during the outbreak's peak and in the number of stroke code activations and intravenous thrombolysis treatments, results that were independent of the COVID-19 incidence rate. Participants reported a delay in workflow metrics and a reduction of admissions to stroke units, outpatient clinics and rehabilitation therapies. Specific pathways and protocols for managing stroke patients with SARS-CoV-2 infection have been established. CONCLUSION: The COVID-19 outbreak has jeopardised all phases of stroke care. As a consequence, some patients with stroke did not receive adequate treatment.

Agroindustrial composts to reduce the use of peat and fungicides in the cultivation of muskmelon seedlings.

BACKGROUND: Environmental concerns about peat extraction in wetland ecosystems have increased. Therefore, there is an international effort to evaluate alternative organic substrates for the partial substitution of peat. The aim of this work was to use different composts (C1-C10) obtained from the fruit and vegetable processing industry (pepper, carrot, broccoli, orange, artichoke residues, sewage sludge (citric and pepper) and vineyard pruning wastes) to produce added-value composts as growing media with suppressive effect against Fusarium oxysporum f.sp. melonis (FOM) in muskmelon. RESULTS: Composts showed values of water-soluble carbon fractions and dehydrogenase activity that allowed them to be considered mature and stabilized. All compost treatments produced significantly (F = 7.382; P < 0.05) higher fresh shoot weight than peat, treatment T-C2 showing the highest values. Treatments T-C5, T-C7 and T-C8 showed percentages of disease incidence that were significantly (F = 16.052; P < 0.05) the lowest, relative to peat, followed by T-C6, T-C10, T-C1 and T-C9 with values below 50%. CONCLUSION: Composts produced are suitable components of mixed compost-peat growing media, providing a 50% substitution of peat. Furthermore, some of these composts also showed an added value as a suppressive organic medium against Fusarium wilt in muskmelon seedling, a fact probably related to high pH and pepper wastes and high content of pruning waste as initial raw materials. © 2016 Society of Chemical Industry.

Carga de salmonelosis y shigelosis en cuatro departamentos de Guatemala, 2010 / Burden of salmonellosis and shigellosis in four departments of Guatemala, 2010

Objetivo. Estimar la carga de enfermedad por Salmonella spp. y Shigella spp. en cuatro departamentos de Guatemala en 2010. Métodos. Estudio de carga de enfermedad basado en el análisis documental de las encuestas poblacionales publicadas, los archivos de laboratorio y los datos de vigilancia del Sistema de Información Gerencial de Salud (SIGSA) de cuatro departamentos de Guatemala: Huehuetenango, Jutiapa, Quetzaltenango y Santa Rosa, en 2010. La información se complementó con una encuesta a laboratorios. La carga de enfermedad se estimó según la metodología de los Centros para el Control y la Prevención de Enfermedades de los Estados Unidos de América, adaptada por la Organización Mundial de la Salud. Resultados. Se encontraron 72 casos de salmonelosis y 172 de shigelosis en los datos de vigilancia. Según las encuestas poblacionales, el porcentaje de la población que consulta los servicios de salud por diarrea es de 64,7% (IC95%: 60,6%–68,7%) en Quetzaltenango y 61,0% (IC95%: 56,0%–66,0%) en Santa Rosa. En los 115 laboratorios que respondieron la encuesta (tasa de respuesta: 72,8%) se recolectaron 6 051 muestras sospechadas para coprocultivo y 3 290 para hemocultivo, y se procesaron 39,4% y 100,0% de ellas, respectivamente. Se aislaron 85 cepas de Salmonella spp. y 113 de Shigella spp. Se estimó que por cada caso notificado de salmonelosis y shigelosis existen 40 casos no informados en Quetzaltenango; 55 en Huehuetenango; 345 en Santa Rosa; y 466 en Jutiapa. La carga de enfermedad estimada varió entre 5 y 2 230 casos por 100 000 habitantes para salmonelosis y entre 60 y 1 195 casos por 100 000 habitantes para shigelosis. Conclusiones. La salmonelosis y la shigelosis constituyen un importante problema de salud pública en los departamentos estudiados y en Guatemala. La carga de enfermedad por estos patógenos es mayor que la informada por el SIGSA.

Objective. Estimate the burden of disease from Salmonella spp. and Shigella spp. in four departments of Guatemala in 2010. Methods. Burden of disease study based on document analysis of published population surveys, laboratory files, and surveillance data from the Health Management Information System (SIGSA) in four departments of Guatemala: Huehuetenango, Jutiapa, Quetzaltenango, and Santa Rosa, in 2010. Information was supplemented by a laboratory survey. Burden of disease was estimated using methodology adapted by the World Health Organization from the United States Centers for Disease Control and Prevention. Results. Surveillance data yielded 72 salmonellosis and 172 shigellosis cases. According to population surveys, the percentage of the population that consults health services for diarrhea is 64.7% (95% CI: 60.6%–68.7%) in Quetzaltenango and 61.0% (95% CI: 56.0%–66.0%) in Santa Rosa. In the 115 laboratories that answered the survey (72.8% response rate), 6 051 suspected samples were collected for stool culture and 3 290 for hemoculture; 39.4% and 100.0% of them were processed, respectively. In all, 85 Salmonella spp. and 113 Shigella spp. strains were isolated. For each reported case of salmonellosis and shigellosis, it was estimated that 40 cases are not reported in Quetzaltenango, 55 in Huehuetenango, 345 in Santa Rosa, and 466 in Jutiapa. Estimated burden of disease ranged from 5 to 2 230 cases per 100 000 population for salmonellosis and from 60 to 1 195 cases per 100 000 population for shigellosis. Conclusions. Salmonellosis and shigellosis are a major public health problem in the departments studied and in Guatemala. Burden of disease from these pathogens is higher than that reported by SIGSA.

A comparative study of 2 new phosphate binders (sevelamer and lanthanum carbonate) in routine clinical practice.

INTRODUCTION: Lack of adherence may influence the efficiency of phosphate binders. Our clinical hypothesis was that if lanthanum carbonate (LC) might offer some advantage over sevelamer (S), that that would be in those patients in whom serum phosphate (P) levels were not controlled by S or in those requiring high doses of it, presuming that therapeutic compliance with S could be inadequate. The aim of this study was to compare the cost-consequences of changing from S to LC. METHODS: This was a prospective comparative before-after interventional study. Fifty-one hemodialysis patients prescribed a large number of tablets of S (≥ 9 tablets/day) and/or had serum phosphorus (P) levels >5.5 mg/dL were changed from S to LC; 68 patients who did not meet those criteria served as controls. RESULTS: Mean daily number of total phosphate binder tablets was reduced after the introduction of LC (13.9 ± 5.5 at time 0 vs. 7.7 ± 4.6 at 12 months; p<0.001). LC was suspended in 14 patients (31.1%), due to a wish to return to the previous medication (S). Percentage compliance with the objectives recommended by the NFK-KDOQI guidelines improved after the change (patients with P <5.5 mg/dL: 46.9% at month 0 and 72.5% at month 12; p<0.01). The incremental cost of changing from S (month 0) to LC (month 12) was -107.8 monthly, considering only the costs of phosphate binders. LC reached the P objective at a lower cost (euro 582.2 vs. euro 1,038.5; -44%; p<0.01). CONCLUSIONS: A complete change from S to LC in these particular kinds of patients significantly decreased the cost of treatment while also improving the achievement of NFK-KDOQI guideline objectives for mineral metabolism.

Expanded newborn screening in Puerto Rico and the US Virgin Islands: education and barriers assessment.

PURPOSE: The implementation of the expanded newborn screening panel of 29 disorders recommended by the American College of Medical Genetics in Puerto Rico and United States Virgin Islands is still in development or in early stages. Efforts in the territories are complicated by educational and resource barriers that generate a wide gap between the islands and the US mainland. METHODS: To meet immediate educational needs, we conducted in-services for local newborn screening professionals. The efficacy of the educational intervention was measured by pre and posttest scores and a seminar evaluation. An assessment was obtained to document local newborn screening needs and barriers, with focus on human resources, intervention, language, social issues, education, and communication. RESULTS: Statistical significance was found (P value < or =0.05) between pre and posttest scores of the educational intervention. Needs and barriers associated with expanded newborn screening were also documented. CONCLUSION: Puerto Rico and United States Virgin Islands face different challenges in their implementation of expanded newborn screening. The data obtained in the present study serves as foundation for the development of public policy and long-term educational programs.

Situación de salud, evaluación técnico administrativa de la sub-región Lara / Health status, technical administrative evaluation of the health sub-region for Lara

El objetivo del presente trabajo consistió en diseñar un método para evaluar el funcionamiento administrativo de una Dirección Sub-Regional del MSAS a fin de llegar a un diagnóstico de la situación de salud, y elaborar un plan de trabajo destinado a introducir mejoras en el funcionamiento de dicha organización. El contenido fué estructurado en 4 capítulos, primero se reseñan las características generales de la sub-región y sus factores condicionantes, el segundo reseña el estado de salud de la población, natalidad, mortalidad el tercero se refiere a organización y funcionamiento de la dirección de salud y sus programas médicos asistenciales y el cuarto capítulo fué dedicado a un análisis estadístico del Hospital General Antonio María Pineda