Afasia primaria progresiva variante no fluente/agramática / Non-fluent/agrammatic variant of primary progressive aphasia

Introducción: Entre las enfermedades neurodegenerativas se encuentra un grupo de patologías que se caracterizan por un compromiso prominente del lenguaje, denominadas usualmente afasias primarias progresivas, las cuales se subdividen en 3 tipos: variante logopénica, variante semántica y variante no fluente o agramática. Presentación del caso: Paciente con cuadro clínico que inicia a los 65 años, con disminución en la interacción social. Un par de meses después, la esposa nota que el lenguaje del paciente se torna poco fluido, habla con palabras o frases cortas, no logra decir oraciones completas, además de presentar cambios en la entonación de las palabras y alteraciones del lenguaje escrito. El paciente manifiesta que su principal limitación en el momento es el no poder expresar lo que quiere decir, y por este motivo consulta. Discusión: En el caso de este paciente, se describe inicialmente un cambio en su personalidad que no compromete su funcionalidad, sin embargo, al poco tiempo se presenta compromiso del lenguaje como síntoma prominente y que genera mayor compromiso en su calidad de vida, con pruebas neuropsicológicas y hallazgos de neuroimagen que apoyan el diagnóstico de afasia primaria progresiva (APP) variante no fluente o agramatical, con síntomas comportamentales y motores asociados. Conclusión: Las APP son un grupo de trastornos neurocognitivos cuya característica primordial es el compromiso en el lenguaje, cada variante de APP tiene unas características clínicas y criterios diagnósticos específicos que se deben conocer para lograr sospechar el diagnóstico y hacer un abordaje apropiado en el paciente.

Introduction: In the group of neurodegenerative diseases, there is a group of pathologies that are characterized by a prominent compromise of language, normally called primary progressive aphasias, these are subdivided into 3 types: logopenic variant, semantic variant and non-fluent or agrammatic variant. Case presentation: Patient with a clinical picture that begins at age 65, with decreased social interaction, a couple of months later his wife notices that his language becomes not fluent, speaks in short words or phrases, cannot say complete sentences, in addition to changes in the intonation of words and alterations in written language, the patient states that his main limitation at the moment is not being able to express what he wants to say and for this reason they consult. Discussion: In the case of this patient, a change in his personality is initially described that does not compromise his functionality, however soon after a language involvement is presented as the main symptom and the one that generates a compromise in his quality of life, with neuropsychological tests and findings on neuroimaging that supports the diagnosis of primary progressive aphasia (PPA) non-fluent or agrammatical variant, with associated behavioral and motor symptoms. Conclusion: APPs are a group of neurocognitive disorders whose primary characteristic is language impairment. Each APP variant has specific clinical characteristics and diagnostic criteria that must be known in order to suspect the diagnosis and make an appropriate approach to the patient.

Ankle-Foot-Orthosis "Hermes" Compensates Pathological Ankle Stiffness of Chronic Stroke-A Proof of Concept.

Individuals with an upper motor neuron syndrome, e.g., stroke survivors, may have a pathological increase of passive ankle stiffness due to spasticity, that impairs ankle function and activities such as walking. To improve mobility, walking aids such as ankle-foot orthoses and orthopaedic shoes are prescribed. However, these walking aids generally limit the range of motion (ROM) of the foot and may therewith negatively influence activities that require a larger ROM. Here we present a new ankle-foot orthosis "Hermes", and its first experimental results from four hemiparetic chronic stroke patients. Hermes was designed to facilitate active ankle dorsiflexion by mechanically compensating the passive ankle stiffness using a negative-stiffness mechanism. Four levels of the Hermes' stiffness compensation (0%, 35%, 70% and 100%) were applied to evaluate active ROM in a robotic ankle manipulator and to test walking feasibility on an instrumented treadmill, in a single session. The robotic tests showed that Hermes successfully compensated the ankle joint stiffness in all four patients and improved the active dorsiflexion ROM in three patients. Three patients were able to walk with Hermes at one or more Hermes' stiffness compensation levels and without reducing their preferred walking speeds compared to those with their own walking aids. Despite a small sample size, the results show that Hermes holds great promise to support voluntary ankle function and to benefit walking and daily activities.

Optimal Blood Flow Restriction Occlusion Pressure for Shoulder Muscle Recruitment With Upper Extremity Exercise.

BACKGROUND: As blood flow restriction (BFR) utilization continues to rise, it is crucial to define optimal parameters for use. Currently unknown are the effects of occlusion level during BFR on muscle activity in the proximal shoulder. PURPOSE/HYPOTHESIS: The purpose of this study was to compare electromyographic amplitude (EMGa) of shoulder musculature during exercise using limb occlusion percentages (LOPs). The authors hypothesized that EMGa would increase concurrently with occlusion. STUDY DESIGN: Controlled laboratory study. METHODS: α Fifteen healthy adults were recruited and underwent 4 experimental sessions, performing 3 common rotator cuff exercises at low intensity (20% maximal strength) to failure in the following order: cable external rotation (ER), cable internal rotation (IR), and dumbbell scaption. Exercises were completed at a different occlusion pressure (0%, 25%, 50%, and 75% LOP- order randomized) applied at the proximal arm. EMGa was recorded from shoulder musculature proximal to the occlusion site and averaged across 5-repetition intervals and overall for the first 30 repetitions. An analysis of variance repeated on occlusion pressure followed by a Bonferroni post hoc test was used to compare EMGa, repetitions to fatigue, and ratings of discomfort (visual analog scale [VAS], 0-10) between occlusion pressures. The type 1 error was set at α = .05 for all analyses. RESULTS: Significant effects of the occlusion level on shoulder muscle EMGa were observed for all exercises (P < .05) with diminishing returns above 50% LOP (overall). For ER, elevations in EMGa were observed at ≥50% LOP for the anterior deltoid, middle deltoid, infraspinatus, and trapezius compared with 0% LOP (P < .05). For IR, elevations in EMGa were observed at ≥25% LOP for the anterior deltoid and trapezius compared with 0% LOP (P < .05). For the teres minor, a significant elevation in EMGa occurred at 75% LOP compared with 0%, 25%, and 50% LOP (P < .05). A decrease in EMGa was observed at ≥50% LOP compared with 0% LOP for the posterior deltoid (P < .05). For scaption, an increase in EMGa was observed at ≥25% LOP for the infraspinatus and teres minor muscles, at 75% LOP for the posterior deltoid, and at ≥50% LOP for the trapezius compared with 0% LOP (P < .05). Decreases in repetitions to failure relative to 0% LOP were observed at 75% LOP for ER (0%: 47 ± 5; 75%: 40 ± 2; P = .034), IR (0%: 82 ± 10; 75%: 64 ± 5; P = .017), and scaption (0%: 85 ± 9; 75%: 64 ± 6; P < .001). A significant linear increase in discomfort was observed for all exercises with increasing occlusion pressures (VAS: 0-10, 0% → 75% LOP; ER: 2.2 ± 0.4 → 7.2 ± 0.3; IR: 1.3 ± 0.2 → 6.1 ± 0.6; scaption: 1.3 ± 0.4 → 6.1 ± 0.4; P < .01). CONCLUSION: There are several differences in muscle activation about the shoulder based on exercise and occlusion when utilizing BFR. Increasing the percentage of limb occlusion leads to heightened EMGa with diminished returns past 50% LOP when considering muscle activation, discomfort, and achievable exercise volume. CLINICAL RELEVANCE: These findings may be used to refine upper extremity BFR guidelines.

The Allergenic Activity of Blo t 2, a Blomia tropicalis IgE-Binding Molecule.

Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a Blomia tropicalis allergen. Blo t 2 was produced as a recombinant protein in Escherichia coli. Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.

Eficacia y seguridad de la combinación de dosis fija montelukast-desloratadina 10 mg/5 mg cápsula en adultos mexicanos con rinitis alérgica persistente: Estudio controlado, aleatorizado, doble ciego y multicéntrico / Efficacy and safety of fixed-dose combination of montelukast-desloratadine 10 mg/5 mg capsule in Mexican adults with persistent allergic rhinitis: A double blind, randomized, controlled and multicenter study

Objetivo: El objetivo del presente estudio fue evaluar la eficacia y seguridad de la combinación de dosis fija montelukast/desloratadina 10mg/5mg cápsula versus la combinación de montelukast/loratadina 10 mg/10 mg tableta en adultos con diagnóstico de rinitis alérgica persistente. Material y métodos: El presente fue un estudio clínico aleatorizado, controlado, doble ciego, prospectivo, longitudinal, multicéntrico, con brazos paralelos. Sujetos con diag nóstico de rinitis alérgica persistente que cumplieran criterios de elegibilidad y firmaran consentimiento informado fueron enrolados para recibir uno de los dos tratamientos cada 24 horas vía oral durante 6 semanas. La eficacia se estableció mediante la evaluación clínica a través de escalas clínicas validadas en idioma español, siendo la variable primaria de eficacia la diferencia de puntuación del cuestionario SNOT-20 al final del tratamiento, mientras que la frecuencia y características de los eventos adversos fue considerada la variable de seguridad. Resultados: Se aleatorizaron 86 pacientes, 74 de ellos fueron analizados por protocolo. Los cuestionarios sobre síntomas de la enfermedad e indicadores de calidad de vida con ambos tratamientos mostraron que más del 90% de los pacientes no presentaron síntomas o solo fueron leves al final del estudio, por lo que ambos tratamientos me joraron significativamente (p < 0.05) la sintomatología de la enfermedad. Los eventos adversos presentados fueron leves a moderados. Conclusiones: El presente estudio demostró que la eficacia de montelukast/deslora tadina 10mg/5mg no es inferior al medicamento comparador. Por tanto, el tratamiento de prueba representa una alternativa eficaz y segura para el tratamiento de segunda línea de la rinitis alérgica persistente en pacientes que las monoterapias o primeras líneas de tratamiento no ofrecen mejoría clínicamente relevante.

Objective: The objective of the present study was to evaluate the efficacy and safety of the fixed dose combination of montelukast/desloratadine 10 mg/5 mg capsule versus the combination of montelukast/loratadine 10 mg/10 mg tablet in adults diagnosed with persistent allergic rhinitis. Materials and methods: The present study was a multicenter, controlled, prospective, longitudinal, randomized, double-blind clinical trial with parallel arms. Patients diagnosed with persistent allergic rhinitis who met eligibility criteria and signed informed consent were enrolled in the study to receive one of the two treatments every 24 hours orally for 6 weeks. Efficacy was established by clinical evaluation through clinical scales vali dated in Spanish, being the primary efficacy variable the difference in the score of the SNOT-20 (Sino-Nasal Outcome Test) questionnaire at the end of treatment; and the frequency and characteristics of adverse events were considered the safety variable. Results: 86 patients were randomized, 74 of which were analyzed per protocol. Ques tionnaires about the symptoms of the disease and quality of life indicators with both treatments showed that more than 90% of patients had mild symptoms or no symptoms at all at the end of the study. So, both treatments significantly improved (p < 0.05) the symptoms of the disease. Adverse events were mild to moderate. Conclusions: The present study showed that the efficacy of montelukast/desloratadine 10 mg/5 mg is not inferior to the comparator. Therefore, the study treatment represents an effective and safe alternative for the second-line treatment of persistent allergic rhinitis in patients in whom monotherapies or first-line treatments don't offer clinically relevant improvement.

Uso y resultados del astegolimab en el manejo del asma severa: ¿qué se conoce?

El asma es una enfermedad inflamatoria crónica de las vías respiratorias que acarrea elevados costos en salud, afecta sustancialmente la calidad de vida y, dependiendo de ciertos factores de riesgo asociados, disminuye la capacidad funcional de quien lo padece. Para el 2019, el asma afectó a 262 millones de personas (4,3 % de la población mundial) y causó 461 000 muertes. Se estima que habrá 100 millones de personas adicionales con asma para el año 2025. El asma severa es un fenotipo resistente a corticoides que ocasiona mayor número de exacerbaciones, afecta sustancialmente la calidad de vida y capacidad funcional del afectado. Su manejo inicialmente se encamina a suprimir los síntomas, y este ha ido evolucionando hasta la comprensión, aún no completa, de los sistemas intrínsecos de su generación, con lo cual se han estudiado nuevas formas de incidir en su manejo, mediante la modulación de la respuesta inmune y la cascada inflamatoria, con la generación de medicamentos biológicos. A raíz del estudio e identificación de endotipos y fenotipos variados, se han diseñado este tipo de medicamentos, con distintos mecanismos de acción, que han demostrado una utilidad sólida en los últimos años. No obstante, existe evidencia de que se ha encontrado resistencia incluso a estos medicamentos, por lo que ha sido necesario seguir investigando nuevas dianas terapéuticas. El astegolimab es un novedoso anticuerpo monoclonal Ig G2 humano que bloquea la señalización de IL-33 al dirigirse a ST2, su receptor, por consiguiente, controla la respuesta inflamatoria en el asma severa. Actualmente, se encuentra en realización de ensayo clínico fase 2b, aunque experimentaciones previas han encontrado resultados positivos y significativos respecto a la inmunomodulación, función pulmonar, sintomatología y calidad de vida. En la actualidad, casi no existe literatura que haya analizado el potencial del astegolimab en el asma grave, y están disponibles prácticamente solo los ensayos que lo han evaluado y algunas revisiones que han compartido su farmacocinética y farmacodinamia. Sobre la base de lo anterior, el objetivo de esta revisión consiste en sintetizar evidencia relacionada con los resultados del uso del astegolimab en asma severa, discutiendo aspectos epidemiológicos y fisiopatológicos que resalten la necesidad del desarrollo de un fármaco seguro, eficaz y eficiente.

Asthma is a chronic inflammatory disease of the respiratory tract which causes high health costs, substantially affects the quality of life and, depending on certain associated risk factors, reduces the functional capacity of the sufferer. By 2019, asthma affected 262 million people (4.3 % of the world's population) and caused 461,000 deaths. It is estimated that there will be an additional 100 million people with asthma by 2025. Severe asthma is a phenotype resistant to corticosteroids which causes a greater number of exacerbations and substantially affects the quality of life and functional capacity of the affected person. Its management was initially aimed at suppressing the symptoms and then evolved to understand, although not completely, the intrinsic systems of its generation. Thus, new ways of influencing its management have been studied by modulating the immune response and the inflammatory cascade with the generation of biological drugs. As a result of the study and identification of various endotypes and phenotypes, drugs with different mechanisms of action have been designed and have demonstrated to be considerably useful in recent years. However, there is evidence that resistance even to these drugs has occurred, being necessary to continue researching new therapeutic targets. Astegolimab is a novel human IgG2 monoclonal antibody that blocks IL-33 signaling by targeting ST2, its receptor, thus controlling the inflammatory response in severe asthma. A phase 2b clinical trial is currently undergoing, although previous results have found positive and significant results regarding immunomodulation, pulmonary function, symptomatology and quality of life. At present, there is almost no literature that has analyzed the potential of astegolimab in severe asthma, and practically only trials that have evaluated it and some reviews that have shared its pharmacokinetics and pharmacodynamics are available. Based on the above, the aim of this review is to synthesize evidence related to the results of the use of astegolimab in severe asthma and discuss epidemiological and pathophysiological aspects that highlight the need for the development of a safe, effective and efficient drug.

Lessons learned from a peer-supported diabetes education program in two dissimilar Mayan communities.

Background: A steady rise in type 2 diabetes (T2D) in Mexico over the last 30 years has led to 11.5 million Mexicans being affected by this condition. There is an urgent need to develop interventions to prevent complications of T2D. Diabetes self-management education is the cornerstone of promoting self-care. Among all educational strategies, peer support has shown to be an effective method to encourage ongoing self-management. However, customization of interventions for distinct communities is imperative, as failure to do so can hinder the intervention's effectiveness. Methods: We implemented a two-year prospective randomized controlled community-based trial in Conkal, a Mayan community from Yucatan, Mexico. The intervention consisted of receiving either a culturally sensitive peer support on top of a diabetes self-management education group (PLG); or a diabetes self-management education group only (EOG; control group). The primary outcome was changes in glycated hemoglobin, while secondary outcomes encompassed changes in systolic and diastolic blood pressure, body mass index, and diabetes self-care practices. Data collection was performed at baseline and every four months during the study period. Discussion: Our experiences have highlighted the significance of peer-leader support in cultivating diabetes self-care skills, particularly within smaller, underserved communities characterized by strong social and cultural ties. However, when applied in larger or suburban settings, selecting peer leaders should be meticulous, considering sectorization within specific neighborhoods to foster a sense of belonging and familiarity among natural community clusters. In larger settlemnts, factors such as transportation challenges, time limitations, caregiving obligations, limited venue access, and changes in session locations can drive program discontinuation. Additionally, individuals with lower educational attainment are more susceptible to abandonment. Notably, those with lower education, uncontrolled diabetes, and extended diabetes duration exhibit a greater potential for improving glycemic control than their counterparts. Clinical registration: https://www.isrctn.com/ISRCTN96897082.

Diseño de un protocolo con validez ecológica para la detección temprana de riesgo neurológico en población pediátrica de la primera infancia / Design of a protocol with ecological validity for the early detection of neurological risk in the pediatric population of early childhood

Introducción. El desarrollo del ser humano está determinado por factores biológicos, ambientales y contextuales que determinan la adquisición de habilidades neurológicas, y que bajo situaciones patológicas aumentan el riesgo de alteraciones en el neurodesarrollo desde etapas tempranas. Objetivo. Diseñar un protocolo con validez ecológica para la detección temprana de riesgo neurológico en la primera infancia por parte de equipos interdisciplinarios de rehabilitación. Métodos. Se realizó un estudio mixto, retrospectivo, transversal y descriptivo con un diseño exploratorio secuencial (DESPLOX). En la fase cualitativa se conformaron dos grupos focales: uno con padres (n=8) y otro con profesionales (n=6), de los cuales se obtuvieron las categorías del protocolo. En la fase cuantitativa se revisaron sistemáticamente artículos científicos (n=30) para la construcción de las orientaciones de acción. Finalmente, el protocolo se validó mediante un panel de expertos empleando el coeficiente de V de Aiken. Resultados. En la fase cualitativa emergieron cuatro categorías: 1) detección temprana, 2) contextos del desarrollo, 3) plan de intervención y 4) calidad y humanización en la atención. En la fase cuantitativa se seleccionaron las orientaciones de acción ubicadas en los Q2 y Q3. Posteriormente se evidenció una validación del protocolo igual a X ̅ =0,98. Conclusiones. Un protocolo de neurorrehabilitación válido ecológicamente se caracteriza por reconocer las percepciones, vivencias y experiencias de familiares y profesionales; recoger evidencia científica confiable; aportar orientaciones y recomendaciones sistémicas para la atención de niñas y niños, y contener criterios de validación de contenido.

Introduction. The human being's development is determined by biological, environmental, and contextual factors that determine the acquisition of neurological skills and that, under pathological situations, increase the risk of alterations in neurodevelopment from early stages. Objective. Design a protocol with ecological validity for the early detection of neurological risk in early childhood by interdisciplinary rehabilitation teams. Methods. A mixed, retrospective, cross-sectional, and descriptive study was performed with Exploratory Sequential Designs (DEXPLOS). In the qualitative phase, two focus groups were formed: one with parents (n=8) and another with professionals (n=6), from which the protocol categories were obtained. In the quantitative phase, scientific articles (n=30) were systematically reviewed to construct the action guidelines. Finally, the protocol was validated by a panel of experts using Aiken's V coefficient. Results. In the qualitative phase, four categories emerged: 1) early detection, 2) development contexts, 3) intervention plan, and 4) quality and humanization of care. In the quantitative phase, the action orientations located in Q2 and Q2 were selected. Subsequently, a validation of the protocol equal to X ̅=0.98 was evidenced. Conclusions. An ecologically valid neuro-rehabilitation protocol is characterized by recognizing the perceptions, expe-riences, and experiences of relatives and professionals; collecting reliable scientific evidence; providing systemic guide-lines and recommendations for the care of girls and boys, and containing content validation criteria.

Myopathic dysphagia caused by thyrotoxicosis: a case report and review of the literature.

Summary: Myopathy caused by thyrotoxicosis is not uncommon. Skeletal muscles are commonly involved, but dysphagia is a rare manifestation of thyrotoxicosis. We aim to raise awareness of dysphagia caused by hyperthyroidism and review similar cases in the literature. We present a case of severe dysphagia caused by hyperthyroidism. We also summarize similar case reports in the literature. Our patient is a 77-year-old man who presented with thyrotoxicosis related to Graves' disease (GD), dysphagia to both liquid and solid food, and weight loss. Further investigations revealed severe esophageal dysphagia and a high risk for aspiration. He required the placement of a G-tube for feeding. After 8 weeks of methimazole treatment, his thyroid function normalized and his dysphagia improved significantly, leading to the removal of the feeding G-tube. We summarize 19 case reports published in the literature of hyperthyroidism leading to dysphagia. Patients with thyrotoxicosis and dysphagia are at higher risk for aspiration pneumonia and thyroid storm. Based on previous case reports, on average, approximately 3 weeks of treatment with anti-thyroidal drugs and beta-blockers is needed before patients can eat normally. We report a case of dysphagia associated with GD, which is rare and needs prompt recognition to restore euthyroid status. Dysphagia generally resolved with normalization of thyroid function. Learning points: Myopathy caused by thyrotoxicosis is not uncommon. Skeletal muscles are commonly involved, but dysphagia is a rare manifestation of thyrotoxicosis. Dysphagia due to hyperthyroidism resolves with normalization of thyroid function. Early recognition of dysphagia related to hyperthyroidism and early initiation of therapy may help reverse the dysphagia and prevent complications.

Consonant Age of Acquisition Reveals Nonlinear Effects in Nonword Repetition Performance.

Recent work has shown significant sublexical effects of long-term memory in nonword repetition (NWR) using a dichotomous consonant age of acquisition (CAoA) variable (Moore, 2018; Moore, Fiez, and Tompkins, 2017). Performance consistently decreased when stimuli comprised consonants acquired later versus earlier in speech development. To address potential confounds related to stimulus design and linearity, the purpose of this study was to test whether performance decreases as the CAoA value of stimuli increases in various linguistic tasks using a continuous CAoA variable. Thirty-one college students completed NWR and other linguistic tasks in which the stimuli varied in average CAoA values. Data were analyzed using multilevel modeling. After accounting for phonotactic probability, CAoA was a statistically significant predictor of performance across the models reported. The relationship was more complex in some of the models in which CAoA showed a statistically significant nonlinear relationship with the outcome measure. Results from this study support previous work showing that CAoA affects performance on NWR and other linguistic tasks that vary in their memory, auditory perceptual, and articulatory demands. Importantly, this line of work was extended here by demonstrating that the CAoA effect is robust across novel stimulus sets and study designs, and may be more complex than previously understood when using a dichotomous CAoA variable. Quadratic results suggest that the CAoA variable has a differential effect on performance for low to moderate CAoA values, but for higher CAoA values the effect is similarly negative. The nonlinear relationship between CAoA and measures of speed and accuracy on some of the tasks warrants further study into the complex relationship between various predictive factors that contribute to language performance.

Quality Indicators for the Diagnosis and Management of Primary Hyperparathyroidism.

IMPORTANCE: Primary hyperparathyroidism (pHPT) is a common endocrine disorder with many diagnostic and treatment challenges. Despite high-quality guidelines, care is variable, and there is low adherence to evidence-based treatment pathways. OBJECTIVE: To develop quality indicators (QIs) to evaluate the diagnosis and treatment of pHPT that could measure, improve, and optimize quality of care and outcomes for patients with this disease. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study used a guideline-based approach to develop QIs that were ranked by a Canadian 9-member expert panel of 3 endocrinologists, 3 otolaryngologists, and 3 endocrine surgeons. Data were analyzed between September 2020 and May 2021. MAIN OUTCOMES AND MEASURES: Candidate indicators (CIs) were extracted from published primary hyperparathyroidism guidelines and summarized with supporting evidence. The 9-member expert panel rated each CI on the validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND-University of California, Los Angeles appropriateness methodology. All panelists were then asked to rank the top 5 QIs for primary, endocrine, and surgical care. RESULTS: Forty QIs were identified and evaluated by the expert panel. After 2 rounds of evaluations and discussion, a total of 18 QIs were selected as appropriate measures of high-quality care. The top 5 QIs for primary, endocrine, and surgical care were selected following panelist rankings. CONCLUSIONS AND RELEVANCE: This quality improvement study proposes 18 QIs for the diagnosis and management of pHPT. Furthermore, the top 5 QIs applicable to physicians commonly treating pHPT, including general physicians, internists, endocrinologists, otolaryngologists, and surgeons, are included. These QIs not only assess the quality of care to guide the process of improvement, but also can assess the implementation of evidence-based guideline recommendations. Using these indicators in clinical practice and health system registries can improve quality and cost-effectiveness of care for patients with pHPT.

Differential return on investment: Academic growth in mathematics and reading based on initial performance.

BACKGROUND: Students vary in their initial achievement when they enter school and their rate of academic growth as they move through school. These differences have implications for classroom instruction and educational policy. Although previous research has examined initial achievement and growth differences, a gap remains in understanding how initial level of achievement interacts with subsequent growth as children move through school. AIM: Using Vygotsky's zone of proximal development (ZPD) and return on investment as theoretical grounding, this registered report examined how students' initial academic performance relative to their school predicts their subsequent academic achievement. The stage 1 accepted registered report is available at https://osf.io/9zmak/. Specifically, we tracked the achievement of a cohort of students who started at or above their school's mean at the beginning of third grade and tested a range of hypotheses regarding their achievement and growth as well as which students showed the greatest gains from their time in school. SAMPLE: Using a large database of student academic achievement in the United States, this registered report included de-identified data from all students from fall 2014 to spring 2017 in grades three through five from the ten US states with the highest participation for the Northwest Evaluation Association's Measures of Academic Progress (MAP®) - a computer adaptive test of academic achievement in mathematics and reading. Because the MAP is taken at least twice per school year, up to six scores were included on mathematics and reading achievement for effective samples of approximately 220,000 students. METHOD: We built separate reading and mathematics three-level piecewise longitudinal hierarchical linear models (student repeated measures, nested within students, nested within schools) to model student growth from the beginning of third grade to the end of fifth grade (i.e., three academic years and two summers). RESULTS: For both mathematics and reading, average student achievement growth slowed as they progressed from third through fifth grade. From there, the findings diverged. In mathematics, student growth was mostly similar across achievement levels and grades from third through fifth. However, in reading, above-average students demonstrated slower growth than average students during the school year but faster growth during the summer. Also of note, at the beginning of third grade, the highest achieving students outscored average students in their school by more than 2 years in mathematics and 3 years in reading. CONCLUSIONS: Our results may be able to be explained via a ZPD model, which posits development only occurs when students are placed in appropriately challenging environments. In mathematics, the observed pattern of relatively consistent growth across achievement levels suggests average students were just as likely to be in their ZPD as higher achieving students. In reading, as initial achievement increased, student reading growth slowed, which suggests the higher the initial achievement, the less likely students were to be in their ZPD. If a goal of education is for students to learn new things, our results suggest existing school offerings in reading are not meeting that goal equitably for students across the performance spectrum. Differential growth patterns should be considered when designing learning experiences for students who enter with a wide range of prior mastery.

A Human-Centered Machine-Learning Approach for Muscle-Tendon Junction Tracking in Ultrasound Images.

Biomechanical and clinical gait research observes muscles and tendons in limbs to study their functions and behaviour. Therefore, movements of distinct anatomical landmarks, such as muscle-tendon junctions, are frequently measured. We propose a reliable and time efficient machine-learning approach to track these junctions in ultrasound videos and support clinical biomechanists in gait analysis. In order to facilitate this process, a method based on deep-learning was introduced. We gathered an extensive dataset, covering 3 functional movements, 2 muscles, collected on 123 healthy and 38 impaired subjects with 3 different ultrasound systems, and providing a total of 66864 annotated ultrasound images in our network training. Furthermore, we used data collected across independent laboratories and curated by researchers with varying levels of experience. For the evaluation of our method a diverse test-set was selected that is independently verified by four specialists. We show that our model achieves similar performance scores to the four human specialists in identifying the muscle-tendon junction position. Our method provides time-efficient tracking of muscle-tendon junctions, with prediction times of up to 0.078 seconds per frame (approx. 100 times faster than manual labeling). All our codes, trained models and test-set were made publicly available and our model is provided as a free-to-use online service on https://deepmtj.org/.

Clinical Relevance of Shrimp Sensitization in Patients with Allergic Rhinitis: Anti-Der p 10 IgE as Predictor.

INTRODUCTION: Cross-reactivity between shrimp and house dust mite (HDM) proteins has been widely documented. In tropical region, shrimp (5-15%) and mite sensitization (80-95%) is prevalent in allergic patients. However, the clinical relevance of shrimp sensitization in patients with allergic rhinitis (AR) has been poorly studied. The aim of this study was to determine the prevalence and the clinical relevance shrimp IgE sensitization in AR patients sensitized to Dermatophagoides pteronyssinus. METHODS: The study was conducted in Medellin (Colombia). A cross-sectional study in patients with AR sensitized to HDM was performed in 3 steps: (i) assessment of IgE sensitization frequency to shrimp Penaeus azteca, Litopenaeus vannamei, and tropomyosin homologous allergens rDer p 10, rPen a 1, and rLit v 1, (ii) evaluation of the clinical relevance of shrimp sensitization using oral challenge test (OCT) and (iii) identification of possible risk factors for positive-OCT results. Ethical committee approval was obtained. RESULTS: From 443 patients with AR, 86 (19.4%) were sensitized to shrimp and 23 of them (26.7%) had shrimp allergy diagnosis. Thirty-six of the patients sensitized to shrimp (41.2%) reported not previously consumed this food and eleven of them had a positive-OCT (30.5%). There was not statistically significant difference in total IgE or sIgE (D. pteronyssinus, P. azteca, L. vannamei, rPen a 1, and rLit v 1) between OCT groups (positive vs. negative results). Anti-Der p 10 IgE was associated with risk for a positive-OCT in different multivariable scenarios. DISCUSSION/CONCLUSION: Our results suggest that in patients with HDM-associated AR and shrimp IgE sensitization is necessary to evaluate the clinical relevance of shrimp IgE even if the patient has never consumed shrimp because of cross-reactivity. Anti-Der p 10 could be a possible biomarker of clinical relevance to shrimp sensitization and could reduce the need for OCTs.

Radical Germylzincation of Aryl- and Alkyl-Substituted Internal Alkynes.

The stereoselective germylzincation of internal alkynes delivering trisubstituted vinylgermanes is achieved via a radical chain process involving Ph3GeH and Et2Zn with AIBN as the initiator. Excellent levels of regiocontrol are observed for nonsymmetric (aryl, alkyl)-substituted alkynes and for propargylic alcohols with aryl-, alkyl-, or silyl-substituted alkynes. The germylzincation reaction can be combined in one pot with the Cu(I)-mediated electrophilic substitution of the C(sp2)-Zn bond to obtain synthetically challenging tetrasubstituted vinylgermanes.

Deep learning in spatiotemporal cardiac imaging: A review of methodologies and clinical usability.

The use of different cardiac imaging modalities such as MRI, CT or ultrasound enables the visualization and interpretation of altered morphological structures and function of the heart. In recent years, there has been an increasing interest in AI and deep learning that take into account spatial and temporal information in medical image analysis. In particular, deep learning tools using temporal information in image processing have not yet found their way into daily clinical practice, despite its presumed high diagnostic and prognostic value. This review aims to synthesize the most relevant deep learning methods and discuss their clinical usability in dynamic cardiac imaging using for example the complete spatiotemporal image information of the heart cycle. Selected articles were categorized according to the following indicators: clinical applications, quality of datasets, preprocessing and annotation, learning methods and training strategy, and test performance. Clinical usability was evaluated based on these criteria by classifying the selected papers into (i) clinical level, (ii) robust candidate and (iii) proof of concept applications. Interestingly, not a single one of the reviewed papers was classified as a "clinical level" study. Almost 39% of the articles achieved a "robust candidate" and as many as 61% a "proof of concept" status. In summary, deep learning in spatiotemporal cardiac imaging is still strongly research-oriented and its implementation in clinical application still requires considerable efforts. Challenges that need to be addressed are the quality of datasets together with clinical verification and validation of the performance achieved by the used method.

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome.

Objective: The main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population. Methods: Patients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome. Results: In total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease. Conclusion: We present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.

Peer Support Added to Diabetes Education Improves Metabolic Control and Quality of Life in Mayan Adults Living With Type 2 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Yucatán, located in the southern region of Mexico, is the state with the country's highest prevalence of uncontrolled diabetes. Because of its particular cultural and socioeconomic characteristics, the residents of Yucatán face unique health-care challenges. The objective of our study was to evaluate the effect of peer support added to a diabetes education program on glycemic control and diabetes-related quality of life when compared with a conventional diabetes education program in patients with type 2 diabetes in a Mayan community in Mexico. METHODS: In March 2015, a total of 58 participants with a previous diagnosis of type 2 diabetes who were recruited from community health centres in Komchén were randomly assigned in equal numbers to 1 of 2 groups: 1) a peer support and diabetes self-management education group (PSEG) or 2) a conventional diabetes self-management education-only group. The primary outcomes of interest were glycated hemoglobin (A1C) values and diabetes-related quality of life. The majority of subjects were bilingual (Mayan and Spanish speakers), female and middle aged, and had a low level of formal education and high baseline A1C (mean, 8.7%). RESULTS: Whereas both groups showed significant improvements from baseline to study end in absolute levels of A1C, the PSEG group had a more pronounced clinical improvement, but no statistical improvement, in A1C compared with the conventional diabetes self-management education-only group. PSEG participants exhibited statistically significant improvement in diabetes-related quality of life at 8 months. CONCLUSIONS: Our study demonstrates the benefits of peer-support education above and beyond the impact of diabetes self-management education on diabetes-related quality of life in an underserved Mayan community in Mexico.

Quality and Safety in Healthcare for Medical Students: Challenges and the Road Ahead.

Background: The development of skills, behaviors and attitudes regarding patient safety is of utmost importance for promoting safety culture for the next generation of health professionals. This study describes our experience of implementing a course on patient safety and quality improvement for fourth year medical students in Mexico during the COVID-19 outbreak. The course comprised essential knowledge based on the patient safety curriculum provided by the WHO. We also explored perceptions and attitudes of students regarding patient safety. Methods: Fourth year medical students completed a questionnaire regarding knowledge, skills, and attitudes on patient safety and quality improvement in medical care. The questionnaire was voluntarily answered online prior to and after the course. Results: In total, 213 students completed the questionnaires. Most students were able to understand medical error, recognize failure and the nature of causation, perform root-cause analysis, and appreciate the role of patient safety interventions. Conversely, a disapproving perspective prevailed among students concerning the preventability of medical errors, utility of reporting systems, just culture and infrastructure (p < 0.05). Conclusion: We found students had a positive perspective concerning learning quality in healthcare and patient safety during our course; nevertheless, their perception of the usefulness of reporting systems to prevent future adverse events and prevent medical errors is uncomplimentary. Medical education should promote error reporting and just culture to change the current perception of medical students.