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Patients with Down syndrome have significant specialized health care needs. Our objective was to understand the needs, satisfaction, and online habits of caregivers as they care for persons with Down syndrome. A mixed-method survey was distributed through REDCap from April 2022 to June 2022 in the United States; a Spanish-translated version was distributed through SurveyMonkey from August 2022 to March 2023 in Mexico. We received 290 completed responses from the United States and 58 from caregivers in Mexico. We found that current health care options are not meeting the needs of many individuals with DS in both the United States (39.7%) and Mexico (46.6%). Caregivers expressed frustrations with the inaccessibility and inapplicability of health care information. In particular, they often found the volume of information overwhelming, given their limited medical background. Additionally, health care recommendations were not customized and lacked practical recommendations. Most caregivers in both the United States (72.1%) and Mexico (82.8%) believe it is not easy to find answers to medical questions about their loved ones with DS. Online platforms with customized, specific health information related to DS could offer innovative solutions to these unmet needs for families and primary care providers.
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Cuidadores , Síndrome de Down , Humanos , Estados Unidos , Alfabetización , Atención a la Salud , Satisfacción PersonalRESUMEN
INTRODUCTION: Many surgeons require patients to quit smoking prior to elective surgeries to reduce the risk of postoperative complications. Our aim was to qualitatively evaluate the communication and care experiences of patients and clinicians involved in conversations about quitting smoking prior to elective orthopaedic surgery. METHODS: A qualitative interview study of rural-residing Veterans, primary care providers (PCPs), and Veterans Administration (VA) orthopaedic surgery staff and pharmacists, who care for rural Veterans. We performed a combination of deductive and inductive approaches to support conventional content analysis using a Patient-Centered Care framework. RESULTS: Patients appreciated a shared approach with their PCP on the plan and reasons for cessation. Despite not knowing if the motivation for elective surgeries served as a teachable moment to facilitate long-term abstinence, almost all clinicians believed it typically helped in the short-term. There was a lack of standardized workflow between primary care and surgery, especially when patients used care delivered outside of VA. CONCLUSIONS: While clinician-provided information about the reasons behind the requirement to quit smoking preoperatively was beneficial, patients appreciated the opportunity to collaborate with their care teams on developing a plan for cessation and abstinence. Other aspects of patient-centered care need to be leveraged, such as the therapeutic alliance or patient-as-person, to build trust and improve communication surrounding tobacco use treatment. System-level changes may need to be made to improve coordination and connection of clinicians within and across disciplines. IMPLICATIONS: This study included perspectives from patients, primary care teams, and surgical teams and found that, in addition to providing information, clinicians need to address other aspects of patient-centered care such as the therapeutic alliance and patient-as-person domains to promote patient engagement in tobacco use treatment. This, in turn, could enhance the potential of surgery as a teachable moment and patient success in quitting smoking.
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OBJECTIVE: This study aimed to compare the clinical endotracheal tube (ETT) depth after initial stabilization of infants with congenital diaphragmatic hernia (CDH) to weight and gestational age-based depth estimates. STUDY DESIGN: This retrospective analysis included 58 inborn infants with left-sided CDH. We compared a standard anatomic ETT depth calculated from initial chest radiographs and the clinical depth of the ETT after adjustments to predicted depths using weight and gestational age-based estimates. RESULTS: The standard anatomic depth was deeper than age (standard deviation 1.29 ± 1.15 cm, p < 0.001) and weight-based (standard deviation 0.59 ± 0.95 cm, p < 0.001) estimates. The clinical ETT depth was also deeper than age (standard deviation 1.01 ± 0.77 cm, p < 0.001) and weight-based (standard deviation 0.26 ± 0.50 cm, p < 0.001) estimates. CONCLUSION: Established strategies to predict ETT depth underestimate the ideal depth in infants with left-sided CDH. These data suggest utilizing caution during initial ETT placement based on standard depth estimates for patients with CDH. KEY POINTS: · CDH patients present unique stabilization challenges.. · Standard ETT depth estimates are too shallow.. · Resuscitation teams should cautiously choose ETT depth..
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OBJECTIVE: To examine the origin of cervical vestibular evoked myogenic potential (cVEMP) late waves (n34-p44) elicited with air-conducted click stimuli. DESIGN: Using a retrospective design, cVEMPs from normal volunteers were compared to those obtained from patients with vestibular and auditory pathologies. STUDY SAMPLE: (1) Normal volunteers (n = 56); (2) severe-to-profound sensorineural hearing loss (SNHL) with normal vestibular function (n = 21); (3) peripheral vestibular impairment with preserved hearing (n = 16); (4) total vestibulocochlear deficit (n = 23). RESULTS: All normal volunteers had ipsilateral-dominant early p13-n23 peaks. Late peaks were present bilaterally in 78%. The p13-n23 response was present in all patients with SNHL but normal vestibular function, and 43% had late waves. Statistical comparison of these patients to a subset of age-matched controls showed no significant difference in the frequencies, amplitudes or latencies of their ipsilateral early and late peaks. cVEMPs were absent in all patients with vestibular impairment. CONCLUSION: The presence of long-latency cVEMP waves was not dependent on the integrity of sensorineural hearing pathways, but instead correlated with intact vestibular function. This finding conflicts with the view that these late waves are cochlear in origin, and suggests that vestibular afferents may assume a more prominent role in their generation.
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PURPOSE: The purpose of this special communication is to provide practical, evidence-based recommendations and examples of inclusive and accessible teaching practices that can be effectively used in pediatric physical therapy (PT) education to: (1) ensure equity in education, (2) elevate all voices, and (3) facilitate anti-oppressive learning environments. SUMMARY OF KEY POINTS: Concrete action items and strategies addressing these 3 recommendations are provided at all levels of the ecological model framework. STATEMENT OF CONCLUSIONS AND RECOMMENDATIONS FOR CLINICAL PRACTICE: Pediatric PT clinical and academic educators must work proactively to ensure learning environments are inclusive of everyone. Pediatric PT educators need to take the time to self-reflect, change their behaviors, and use inclusive, accessible, and anti-oppressive education practices. This will create equitable learning opportunities to successfully meet the needs of our learners, children, and families with whom we engage regularly in our personal and professional lives.
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PURPOSE OF REVIEW: To most neurologists, assessing the patient with vertigo is an unpleasant and worrisome task. A structured history and focused examination can be complemented by carefully selected laboratory tests, to reach an early and accurate diagnosis. We provide evidence-based recommendations for vestibular test selection. RECENT FINDINGS: The video head impulse test (vHIT), cervical and ocular vestibular evoked myogenic potential (VEMP) and home-video nystagmography are four modern, noninvasive methods of assessing vestibular function, which are equally applicable in the hospital and office-practice. Collectively, they enable assessment of all five vestibular end-organs. The prevalence and patterns of test abnormalities are distinct for each vestibular disorder. We summarize typical abnormalities encountered in four common vestibular syndromes. SUMMARY: In the context of acute vestibular syndrome, an abnormal vHIT with low gain and large amplitude refixation saccades and an asymmetric oVEMP separates innocuous vestibular neuritis from stroke. In episodic spontaneous vertigo, high-velocity ictal nystagmus and asymmetric cVEMP help separate Ménière's disease from vestibular migraine. In chronic imbalance, all three tests help detect unilateral or bilateral vestibular loss as the root cause. Recurrent positional vertigo requires no laboratory test and can be diagnosed and treated at the bedside, guided by video nystagmography.
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Enfermedad de Meniere , Potenciales Vestibulares Miogénicos Evocados , Neuronitis Vestibular , Prueba de Impulso Cefálico , Humanos , Enfermedad de Meniere/diagnóstico , VértigoRESUMEN
INTRODUCTION: Patients with vestibular disorders sometimes report cognitive difficulties, but there is no consensus about the type or degree of cognitive complaint. We therefore investigated subjective cognitive dysfunction in a well-defined sample of neuro-otology patients and used demographic factors and scores from a measure of depression, anxiety, and stress to control for potential confounding factors. METHODS: We asked 126 neuro-otology clinic outpatients whether they experienced difficulties with thinking, memory, or concentration as a result of dizziness or vertigo. They and 42 nonvertiginous control subjects also completed the Neuropsychological Vertigo Inventory (NVI, which measures cognitive, emotional, vision, and motor complaints), the Everyday Memory Questionnaire (EMQ), and Depression, Anxiety, and Stress Scales (DASS). RESULTS: In the initial interview questions, 60% of patients reported experiencing cognitive difficulties. Cognitive questionnaire scores were positively correlated with the overall DASS score and to a lesser extent with age and gender. Therefore, we compared patients and controls on the NVI and EMQ, using these mood and demographic variables as covariates. Linear regression analyses revealed that patients scored significantly worse on the total NVI, NVI cognitive composite, and 3 individual NVI cognition subscales (Attention, Space Perception, and Time Perception), but not the EMQ. Patients also scored significantly worse on the NVI Emotion and Motor subscales. CONCLUSIONS: Patients with dizziness and vertigo reported high levels of cognitive dysfunction, affecting attention, perceptions of space and time. Although perceptions of cognitive dysfunction were correlated with emotional distress, they were significantly elevated in patients over and above the impact of depression, anxiety, or stress.
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Disfunción Cognitiva , Mareo , Ansiedad/complicaciones , Cognición , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/psicología , Mareo/complicaciones , Humanos , Vértigo/complicacionesRESUMEN
BACKGROUND: We characterise the history, vestibular tests, ictal and interictal nystagmus in vestibular migraine. METHOD: We present our observations on 101 adult-patients presenting to an outpatient facility with recurrent spontaneous and/or positional vertigo whose final diagnosis was vestibular migraine (n = 27) or probable vestibular migraine (n = 74). Ictal and interictal video-oculography, caloric and video head impulse tests, vestibular-evoked myogenic potentials and audiometry were performed. RESULTS: Common presenting symptoms were headache (81.2%), spinning vertigo (72.3%), Mal de Débarquement (58.4%), and motion sensitivity (30.7%). With fixation denied, ictal and interictal spontaneous nystagmus was observed in 71.3 and 14.9%, and purely positional nystagmus in 25.8 and 55.4%. Spontaneous ictal nystagmus was horizontal in 49.5%, and vertical in 21.8%. Ictal spontaneous and positional nystagmus velocities were 5.3 ± 9.0°/s (range 0.0-57.4), and 10.4 ± 5.8°/s (0.0-99.9). Interictal spontaneous and positional nystagmus velocities were <3°/s in 91.8 and 23.3%. Nystagmus velocities were significantly higher when ictal (p < 0.001/confidence interval: 2.908â6.733, p < 0.001/confidence interval: 5.308â10.085). Normal lateral video head impulse test gains were found in 97.8% (mean gain 0.95 ± 0.12) and symmetric caloric results in 84.2% (mean canal paresis 7.0 ± 23.3%). Air- and bone-conducted cervical-vestibular-evoked myogenic potential amplitudes were symmetric in 88.4 and 93.4% (mean corrected amplitude 1.6 ± 0.7, 1.6 ± 0.8) with mean asymmetry ratios of 13.0 and 9.0%. Air- and bone-conducted ocular-vestibular-evoked myogenic potentials were symmetric in 67.7 and 97.2% (mean amplitude 9.2 ± 6.4 and 20.3 ± 12.8 µV) with mean asymmetry ratios of 15.7 and 9.9%. Audiometry was age consistent and symmetric in 85.5%. CONCLUSION: Vestibular migraine is characterised by low velocity ictal spontaneous nystagmus, which can be horizontal, vertical, or torsional, and normal audiovestibular test results.
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Trastornos Migrañosos/diagnóstico , Nistagmo Patológico/diagnóstico , Vértigo , Adulto , Humanos , Nistagmo Fisiológico , Pruebas de Función VestibularRESUMEN
BACKGROUND: Closed incision negative pressure wound therapy (ciNPWT) may reduce surgical site complications following total joint arthroplasty. Although unlikely necessary for all patients, the criteria for utilizing ciNPWT in primary total knee arthroplasty (TKA) remain poorly defined. This study's purpose was to compare the incidence of incisional wound complications, non-incisional complications (ie, dressing reactions), reoperations, and periprosthetic joint infections (PJIs) among a group of high-risk primary TKA patients treated with ciNPWT vs an occlusive silver impregnated dressing. METHODS: One hundred thirty high-risk primary TKA patients treated with ciNPWT were 1:1 propensity matched and compared to a historical control group treated with an occlusive silver impregnated dressing. High-risk criteria included the following: active tobacco use, diabetes mellitus, body mass index >35 kg/m2, autoimmune disease, chronic kidney disease, Staphylococcus aureus nasal colonization, and non-aspirin anticoagulation. RESULTS: Age, gender, and risk factor profile were comparable between cohorts. The ciNPWT cohort had significantly fewer incisional wound complications (6.9% vs 16.2%; P = .031) and significantly more non-incisional complications (16.9% vs 1.5%; P < .001). No dressing reactions required clinical intervention. There were no differences in reoperations or periprosthetic joint infections (P = 1.000). In multivariate analysis, occlusive silver impregnated dressings (odds ratio 2.9, 95% confidence interval 1.3-6.8, P = .012) and non-aspirin anticoagulation (odds ratio 2.5, 95% confidence interval 1.1-5.6, P = .028) were associated with the development of incisional wound complications. CONCLUSION: Among high-risk patients undergoing primary TKA, ciNPWT decreased incisional wound complications when compared to occlusive silver impregnated dressings, particularly among those receiving non-aspirin anticoagulation. Although an increase in dressing reactions was observed, the clinical impact was minimal.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Terapia de Presión Negativa para Heridas , Artroplastia de Reemplazo de Rodilla/efectos adversos , Vendajes , Estudios de Cohortes , Humanos , Plata , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
Vertigo is a sensation of movement that results from disorders of the inner ear balance organs and their central connections, with aetiologies that are often benign and sometimes serious. An individual who develops vertigo can be effectively treated only after a correct diagnosis of the underlying vestibular disorder is reached. Recent advances in artificial intelligence promise novel strategies for the diagnosis and treatment of patients with this common symptom. Human analysts may experience difficulties manually extracting patterns from large clinical datasets. Machine learning techniques can be used to visualize, understand, and classify clinical data to create a computerized, faster, and more accurate evaluation of vertiginous disorders. Practitioners can also use them as a teaching tool to gain knowledge and valuable insights from medical data. This paper provides a review of the literatures from 1999 to 2021 using various feature extraction and machine learning techniques to diagnose vertigo disorders. This paper aims to provide a better understanding of the work done thus far and to provide future directions for research into the use of machine learning in vertigo diagnosis.
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Inteligencia Artificial , Mareo , Diagnóstico Diferencial , Mareo/diagnóstico , Humanos , Aprendizaje Automático , Vértigo/diagnósticoRESUMEN
BACKGROUND: Complicated grief (CG) is characterized by persistent, impairing grief after losing a loved one. Little is known about sleep disturbance in CG. Baseline prevalence of subjective sleep disturbance, impact of treatment on sleep, and impact of mid-treatment sleep on CG and quality of life outcomes were examined in adults with CG in secondary analyses of a clinical trial. METHODS: Patients with CG (n = 395, mean age =53.0; 78% female) were randomized to CGT+placebo, CGT+citalopram (CIT), CIT, or placebo. Subjective sleep disturbance was assessed by a grief-anchored sleep item (Pittsburgh Sleep Quality Index: PSQI-1) and a four-item sleep subscale of the Quick Inventory of Depressive Symptomatology (QIDS-4). Sleep disturbance was quantified as at least one QIDS-4 item with severity ≥2 or grief-related sleep disturbance ≥3 days a week for PSQI-1. Outcomes included the Inventory of Complicated Grief (ICG), Work and Social Adjustment Scale (WSAS), and Clinical Global Impressions Scale. RESULTS: Baseline sleep disturbance prevalence was 91% on the QIDS-4 and 46% for the grief-anchored PSQI-1. Baseline CG severity was significantly associated with sleep disturbance (QIDS-4: p = .015; PSQI-1: p = .001) after controlling for comorbid depression and PTSD. Sleep improved with treatment; those receiving CGT+CIT versus CIT evidenced better endpoint sleep (p = .027). Mid-treatment QIDS-4 significantly predicted improvement on outcome measures (all p < .01), though only WSAS remained significant after adjustment for mid-treatment ICG (p = .02). CONCLUSIONS: Greater CG severity is associated with poorer sleep beyond PTSD and depression comorbidity. Additional research including objective sleep measurement is needed to optimally elucidate and address sleep impairment associated with CG.
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Aflicción , Pesar , Trastornos del Sueño-Vigilia/fisiopatología , Citalopram/uso terapéutico , Comorbilidad , Depresión/complicaciones , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Sueño/efectos de los fármacos , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/psicología , Resultado del TratamientoRESUMEN
In normal humans, tapping the forehead produces a neck muscle reflex that is used clinically to test vestibular function, the cervical vestibular evoked myogenic potential (cVEMP). As stretch receptors can also be activated by skull taps, we investigated the origin of the early and late peaks of the bone-conducted cVEMP. In twelve normal participants, we differentially stimulated the vestibular and neck stretch receptors by applying vibration to the forehead (activating both vestibular and stretch receptors) and to the sternum (activating mainly stretch receptors). Patients with bilateral vestibulopathy (BVP; n = 26) and unilateral vestibular loss (uVL; n = 17) were also investigated for comparison. Comparison of peaks in normal subjects suggested that the early peaks were vestibular-dependent, while the later peaks had mixed vestibular and stretch input. The late peaks were present but small (1.1 amplitude ratio) in patients with BVP and absent VEMPs, confirming that they do not strictly depend on vestibular function, and largest in age-matched controls (1.5 amplitude ratio, p = 0.049), suggesting that there is an additional vestibular reflex at this latency (approx. 30 ms). Patients with uVL had larger late peaks on the affected than the normal side (1.4 vs 1.0 amplitude ratio, p = 0.034). The results suggest that the early responses in SCM to skull vibration in humans are vestibular-dependent, while there is a late stretch reflex bilaterally and a late vestibular reflex in the contralateral muscle.
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Conducción Ósea/fisiología , Reflejo de Enderezamiento/fisiología , Reflejo de Estiramiento/fisiología , Enfermedades Vestibulares/fisiopatología , Potenciales Vestibulares Miogénicos Evocados/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculos del Cuello , Cráneo , Vibración , Adulto JovenRESUMEN
Controlling the surface composition of shaped bimetallic nanoparticles could offer precise tunability of geometric and electronic surface structure for new nanocatalysts. To achieve this goal, a platform for studying the intermixing process in a shaped nanoparticle was designed, using multilayered Pd-Ni-Pt core-shell nanocubes as precursors. Under mild conditions, the intermixing between Ni and Pt could be tuned by changing layer thickness and number, triggering intermixing while preserving nanoparticle shape. Intermixing of the two metals is monitored using transmission electron microscopy. The surface structure evolution is characterized using electrochemical methanol oxidation. DFT calculations suggest that the low-temperature mixing is enhanced by shorter diffusion lengths and strain introduced by the layered structure. The platform and insights presented are an advance toward the realization of shape-controlled multimetallic nanoparticles tailored to each potential application.
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Four vestibular presentations caused by six different disorders constitute most of the neuro-otology cases seen in clinical practice. 'Acute vestibular syndrome' refers to a first-ever attack of acute, spontaneous, isolated vertigo and there are two common causes: vestibular neuritis / labyrinthitis and cerebellar infarction. Recurrent positional vertigo is most often caused by benign paroxysmal positional vertigo and less commonly is central in origin. Recurrent spontaneous vertigo has two common causes: Ménière's disease and vestibular migraine. Lastly, chronic vestibular insufficiency (imbalance) results from bilateral, or severe unilateral, peripheral vestibular impairment. These six disorders can often be diagnosed on the basis of history, examination, audiometry, and in some cases, basic vestibular function testing. Here we show that most common neuro-otological problems can be readily managed by general neurologists.
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Mareo/diagnóstico , Mareo/etiología , Infarto Encefálico/complicaciones , Infarto Encefálico/diagnóstico , Enfermedades Cerebelosas/complicaciones , Enfermedades Cerebelosas/diagnóstico , Humanos , Enfermedad de Meniere/complicaciones , Enfermedad de Meniere/diagnóstico , Enfermedades Vestibulares/complicaciones , Enfermedades Vestibulares/diagnósticoRESUMEN
Owing to the progressive development of metal-organic-frameworks (MOFs) synthetic processes and considerable potential applications in last decade, integrating biomolecules into MOFs has recently gain considerable attention. Biomolecules, including lipids, oligopeptides, nucleic acids, and proteins have been readily incorporated into MOF systems via versatile formulation methods. The formed biomolecule-MOF hybrid structures have shown promising prospects in various fields, such as antitumor treatment, gene delivery, biomolecular sensing, and nanomotor device. By optimizing biomolecule integration methods while overcoming existing challenges, biomolecule-integrated MOF platforms are very promising to generate more practical applications.
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Estructuras Metalorgánicas , Técnicas Biosensibles , Sistemas de Liberación de MedicamentosRESUMEN
Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT: Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking.Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons.
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Corteza Cerebral/citología , Neuronas GABAérgicas/citología , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/fisiología , Interneuronas/citología , Proteínas del Tejido Nervioso/fisiología , Neurogénesis/fisiología , Proteínas Supresoras de Tumor/fisiología , Animales , Biomarcadores , Calbindina 2/análisis , Moléculas de Adhesión Celular Neuronal/análisis , Linaje de la Célula , Movimiento Celular , Corteza Cerebral/embriología , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/patología , Proteínas de la Matriz Extracelular/análisis , Neuronas GABAérgicas/metabolismo , Perfilación de la Expresión Génica , Interneuronas/clasificación , Interneuronas/metabolismo , Ratones , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/genética , Proteína Reelina , Serina Endopeptidasas/análisis , Proteínas Supresoras de Tumor/deficiencia , Péptido Intestinal Vasoactivo/análisisAsunto(s)
Enfermedades Autoinmunes/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Enfermedades del Laberinto/diagnóstico , Vértigo/diagnóstico , Anciano , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/terapia , Diagnóstico Diferencial , Movimientos Oculares/fisiología , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/terapia , Humanos , Enfermedades del Laberinto/complicaciones , Enfermedades del Laberinto/terapia , Masculino , Resultado del Tratamiento , Vértigo/etiología , Vértigo/terapiaRESUMEN
PURPOSE: To describe the process and assess outcomes for the first 2 years of newborn screening for severe combined immunodeficiency (SCID NBS) in New York State (NYS). METHODS: The NYS algorithm utilizes a first-tier molecular screen for TRECs (T-cell receptor excision circles), the absence of which is indicative of increased risk of immunodeficiency. RESULTS: During the first 2 years, 485,912 infants were screened for SCID. Repeat specimens were requested from 561 premature and 746 non-premature infants with low or borderline TRECs. A total of 531 infants were referred for diagnostic evaluation leading to identification of 10 infants with SCID and 87 with a clinically significant non-SCID abnormality based on flow cytometry or CBC results (positive predictive value 20.3 %). Nine infants were diagnosed with typical SCID and one with leaky SCID. SCID diagnoses included two patients with adenosine deaminase deficiency, three patients with typical and one with leaky IL2RG-related SCID, one patient with IL7Rα-related SCID, and three cases of typical SCID, etiology unknown. TRECs were undetectable in eight of the nine babies with typical SCID. Infants with other non-SCID conditions included 27 patients with a syndrome that included T-cell impairment, 18 of which had DiGeorge syndrome. Seventeen infants had T-cell impairment secondary to another clinically significant condition, and 13 were classified as 'other'. Among 30 infants classified as idiopathic T-cell lymphopenia, 11 have since resolved, and the remainder continues to be followed. One infant with undetectable TRECs had normal follow-up studies. Molecular studies revealed the presence of two changes in the infant's DNA. CONCLUSIONS: Overall, ten infants with SCID were identified during the first 2 years of screening in NYS, yielding an incidence of approximately 1 in 48,500 live births, which is consistent with the incidence observed by other states screening for SCID. The incidence of any clinically significant laboratory abnormality was approximately 1 in 5,000; both estimates are higher than estimates prior to the onset of newborn screening for SCID. Improvements to the NYS algorithm included the addition of a borderline category that reduced the proportion of infants referred for flow cytometric analysis, without decreasing sensitivity. We identified a large number of infants with abnormal TRECs and subsequent idiopathic T-cell lymphopenia. Long-term follow-up studies are needed to determine the prognosis and optimal treatment for this group of patients, some of whom may present with previously unrecognized, transient lymphopenia of infancy.
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Tamizaje Neonatal , Inmunodeficiencia Combinada Grave/diagnóstico , Algoritmos , Femenino , Pruebas Genéticas/métodos , Humanos , Inmunofenotipificación/métodos , Recién Nacido , Masculino , Tamizaje Neonatal/métodos , New York , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Inmunodeficiencia Combinada Grave/etiología , Inmunodeficiencia Combinada Grave/terapiaRESUMEN
PCA3 is a prostate-specific non-coding RNA, with utility as a urine-based early detection biomarker. Here, we report the evaluation of tissue PCA3 expression by RNA in situ hybridization in a cohort of 41 mapped prostatectomy specimens. We compared tissue PCA3 expression with tissue level ERG expression and matched pre-prostatectomy urine PCA3 and TMPRSS2-ERG levels. Across 136 slides containing 138 foci of prostate cancer, PCA3 was expressed in 55% of cancer foci and 71% of high-grade prostatic intraepithelial neoplasia foci. Overall, the specificity of tissue PCA3 was >90% for prostate cancer and high-grade prostatic intraepithelial neoplasia combined. Tissue PCA3 cancer expression was not significantly associated with urine PCA3 expression. PCA3 and ERG positivity in cancer foci was positively associated (P<0.01). We report the first comprehensive assessment of PCA3 expression in prostatectomy specimens, and find limited correlation between tissue PCA3 and matched urine in prostate cancer.
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Antígenos de Neoplasias/genética , Biomarcadores de Tumor/genética , Hibridación in Situ/métodos , Proteínas de Fusión Oncogénica/genética , Neoplasia Intraepitelial Prostática/genética , Neoplasias de la Próstata/genética , ARN no Traducido/genética , Antígenos de Neoplasias/orina , Biomarcadores de Tumor/orina , Detección Precoz del Cáncer , Reordenamiento Génico , Humanos , Inmunohistoquímica , Masculino , Proteínas de Fusión Oncogénica/orina , Valor Predictivo de las Pruebas , Prostatectomía , Neoplasia Intraepitelial Prostática/patología , Neoplasia Intraepitelial Prostática/cirugía , Neoplasia Intraepitelial Prostática/orina , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/orina , ARN no Traducido/orinaRESUMEN
BACKGROUND: Vestibular migraine (VM) and Menière's disease (MD) are two common causes of recurrent spontaneous vertigo. Using history, video-nystagmography and audiovestibular tests, we developed machine learning models to separate these two disorders. METHODS: We recruited patients with VM or MD from a neurology outpatient facility. One hundred features from six "feature subsets": history, acute video-nystagmography and four laboratory tests (video head impulse test, vestibular-evoked myogenic potentials, caloric testing and audiogram) were used. We applied ten machine learning algorithms to develop classification models. Modelling was performed using three "tiers" of data availability to simulate three clinical settings. "Tier 1" used all available data to simulate the neuro-otology clinic, "Tier 2" used only history, audiogram and caloric test data, representing the general neurology clinic, and "Tier 3" used history alone as occurs in primary care. Model performance was evaluated using tenfold cross-validation. RESULTS: Data from 160 patients with VM and 114 with MD were used for model development. All models effectively separated the two disorders for all three tiers, with accuracies of 85.77-97.81%. The best performing algorithms (AdaBoost and Random Forest) yielded accuracies of 97.81% (95% CI 95.24-99.60), 94.53% (91.09-99.52%) and 92.34% (92.28-96.76%) for tiers 1, 2 and 3. The best feature subset combination was history, acute video-nystagmography, video head impulse test and caloric testing, and the best single feature subset was history. CONCLUSIONS: Machine learning models can accurately differentiate between VM and MD and are promising tools to assist diagnosis by medical practitioners with diverse levels of expertise and resources.