RESUMEN
Despite the empirical literature suggesting the benefits of providing patient support and psychotherapy, research examining patient satisfaction with psychological services integrated within inpatient psychiatric treatment settings remains scarce. A sample of 122 adults within a voluntary inpatient psychiatric unit, who were receiving psychological services completed a satisfaction questionnaire. Overall, participants reported high levels of satisfaction with psychological services and perceived them as helpful to their overall care. These results remained consistent when exploratorily examining satisfaction and helpfulness prior to and during the COVID-19 pandemic. These findings suggest the importance of integrating psychologists within inpatient psychiatric treatment settings. Future research may investigate the influence of psychological services on patient outcomes and how psychologists are perceived by other treatment team members.
Asunto(s)
COVID-19 , Pacientes Internos , Trastornos Mentales , Satisfacción del Paciente , Servicio de Psiquiatría en Hospital , Humanos , Masculino , Femenino , Adulto , Pacientes Internos/psicología , COVID-19/psicología , Persona de Mediana Edad , Trastornos Mentales/terapia , Trastornos Mentales/psicología , Encuestas y Cuestionarios , Psicoterapia/métodos , SARS-CoV-2 , Adulto Joven , Anciano , Servicios de Salud MentalRESUMEN
PURPOSE: To assess the safety and efficacy of AAV8-hCARp.hCNGB3 in participants with CNGB3-associated achromatopsia (ACHM). DESIGN: Prospective, phase 1/2 (NCT03001310), open-label, nonrandomized clinical trial. METHODS: The study enrolled 23 adults and children with CNGB3-associated ACHM. In the dose-escalation phase, adult participants were administered 1 of 3 AAV8-hCARp.hCNGB3 dose levels in the worse-seeing eye (up to 0.5 mL). After a maximum tolerated dose was established in adults, an expansion phase was conducted in children ≥3 years old. All participants received topical and oral corticosteroids. Safety and efficacy parameters, including treatment-related adverse events and visual acuity, retinal sensitivity, color vision, and light sensitivity, were assessed for 6 months. RESULTS: AAV8-hCARp.hCNGB3 (11 adults, 12 children) was safe and generally well tolerated. Intraocular inflammation occurred in 9 of 23 participants and was mainly mild or moderate in severity. Severe cases occurred primarily at the highest dose. Two events were considered serious and dose limiting. All intraocular inflammation resolved following topical and systemic steroids. There was no consistent pattern of change from baseline to week 24 for any efficacy assessment. However, favorable changes were observed for individual participants across several assessments, including color vision (nâ¯=â¯6/23), photoaversion (nâ¯=â¯11/20), and vision-related quality-of-life questionnaires (nâ¯=â¯21/23). CONCLUSIONS: AAV8-hCARp.hCNGB3 for CNGB3-associated ACHM demonstrated an acceptable safety and tolerability profile. Improvements in several efficacy parameters indicate that AAV8-hCARp.hCNGB3 gene therapy may provide benefit. These findings, with the development of additional sensitive and quantitative end points, support continued investigation.
Asunto(s)
Defectos de la Visión Cromática , Humanos , Adulto , Niño , Preescolar , Defectos de la Visión Cromática/genética , Defectos de la Visión Cromática/terapia , Estudios Prospectivos , Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética , Terapia Genética , InflamaciónRESUMEN
Calcium is ubiquitously present in all living cells and plays important regulatory roles in a wide variety of biological processes. In yeast, many effects of calcium are mediated via the action of calcineurin, a calcium/calmodulin-dependent protein phosphatase. Proper signaling of calcium and calcineurin is important in yeast, and the calcineurin pathway has emerged as a valuable target for developing novel antifungal drugs. Here, we report a role of YDL206W in calcium and calcineurin signaling in yeast. YDL206W is an uncharacterized gene in yeast, encoding a protein with two sodium/calcium exchange domains. Disrupting the YDL206W gene leads to a diminished level of calcium-induced activation of calcineurin and a reduced accumulation of cytosolic calcium. Consistent with a role of calcineurin in regulating pheromone and cell wall integrity signaling, the ydl206wΔ mutants display an enhanced growth arrest induced by pheromone treatment and poor growth at elevated temperature. Subcellular localization studies indicate that YDL206W is localized in endoplasmic reticulum and Golgi. Together, our results reveal YDL206W as a new regulator for calcineurin signaling in yeast and suggest a role of the endoplasmic reticulum and Golgi in regulating cytosolic calcium in yeast.
Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Transducción de Señal , Calcineurina/genética , Calcineurina/metabolismo , Calcio/metabolismo , Quitina/metabolismo , Regulación Fúngica de la Expresión Génica/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transducción de Señal/genéticaRESUMEN
Purpose: Blue cone monochromacy (BCM) is a rare inherited cone disorder in which both long- (L-) and middle- (M-) wavelength sensitive cone classes are either impaired or nonfunctional. Assessing genotype-phenotype relationships in BCM can improve our understanding of retinal development in the absence of functional L- and M-cones. Here we examined foveal cone structure in patients with genetically-confirmed BCM, using adaptive optics scanning light ophthalmoscopy (AOSLO). Methods: Twenty-three male patients (aged 6-75 years) with genetically-confirmed BCM were recruited for high-resolution imaging. Eight patients had a deletion of the locus control region (LCR), and 15 had a missense mutation-Cys203Arg-affecting the first two genes in the opsin gene array. Foveal cone structure was assessed using confocal and non-confocal split-detection AOSLO across a 300 × 300 µm area, centered on the location of peak cell density. Results: Only one of eight patients with LCR deletions and 10 of 15 patients with Cys203Arg mutations had analyzable images. Mean total cone density for Cys203Arg patients was 16,664 ± 11,513 cones/mm2 (n = 10), which is, on average, around 40% of normal. Waveguiding cone density was 2073 ± 963 cones/mm2 (n = 9), which was consistent with published histological estimates of S-cone density in the normal eye. The one patient with an LCR deletion had a total cone density of 10,246 cones/mm2 and waveguiding density of 1535 cones/mm2. Conclusions: Our results show that BCM patients with LCR deletions and Cys203Arg mutations have a population of non-waveguiding photoreceptors, although the spectral identity and level of function remain unknown.
Asunto(s)
Defectos de la Visión Cromática , Masculino , Humanos , Defectos de la Visión Cromática/diagnóstico , Defectos de la Visión Cromática/genética , Defectos de la Visión Cromática/patología , Fóvea Central/patología , Células Fotorreceptoras Retinianas Conos/patología , Oftalmoscopía/métodosRESUMEN
BACKGROUND: Clinical practice guidelines (CPGs) and health system policies to mitigate inappropriate opioid prescribing practices may have an extended impact on low-dose opioid (e.g., tramadol) and non-opioid (e.g., gabapentinoid) pain medication prescribing practices. OBJECTIVE: To evaluate changes in opioid, tramadol, and gabapentinoid prescribing rates from January 2016 to February 2020 within the Military Health System, including the degree to which prescribing rates changed after release of a US Defense Health Agency Procedural Instruction. METHODS: In this observational health services research study, opioid, tramadol, and gabapentin prescription dispense events of US Military Health System beneficiaries enrolled in care at military treatment facilities prior to US Defense Health Agency Procedural Instruction release (January 2016-May 2018) were used to forecast values from the post-intervention period (June 2018-February 2020). RESULTS: The median opioid and tramadol prescribing rates decreased from January 2016 to February 2020, aside from tramadol prescribing in Surgery Clinics, which increased. Gabapentinoid prescribing rate changes were mixed. In Bayesian time series models, the forecasted proportion of patients receiving each of the three medications, regardless of age group or clinic type, did not significantly vary from the actual prescribing rates in the post-intervention period. CONCLUSION: Overall, CPGs and policies targeting opioid prescribing practices may have provided the maximal impetus for providers to re-evaluate their prescribing practices, as the policy did not appear to change the slope in prescribing rates. However, it is unclear whether the policies mitigated the likelihood of plateaus in prescribing rates. Further work is needed to assess the degree to which providers simultaneously altered other non-opioid pain medication prescribing practices, self-management recommendations, and non-pharmacological therapy referrals.
Asunto(s)
Servicios de Salud Militares , Tramadol , Analgésicos Opioides/uso terapéutico , Teorema de Bayes , Prescripciones de Medicamentos , Humanos , Dolor/tratamiento farmacológico , Políticas , Pautas de la Práctica en Medicina , Tramadol/uso terapéuticoRESUMEN
The incidence of acetabular fractures in the geriatric population is growing, yet the optimal treatment algorithm remains a controversial topic among orthopaedic surgeons. This review highlights key studies published over the past 5 years on the outcomes of various treatment options for geriatric acetabular fractures. Topics include surgical timing, mortality and risk factors, nonoperative treatment, open reduction internal fixation, and acute total hip arthroplasty.
Asunto(s)
Acetábulo , Fracturas de Cadera , Acetábulo/cirugía , Anciano , Fijación Interna de Fracturas/efectos adversos , Fracturas de Cadera/epidemiología , Fracturas de Cadera/cirugía , Humanos , Reducción Abierta/efectos adversos , Resultado del TratamientoRESUMEN
The population of Hawai'i is uniquely connected to the Ocean and to open water sports. Shoulder injuries, particularly those to the rotator cuff, are among the most common injuries sustained to athletes participating in ocean sports such as surfing, paddling, and swimming. In addition, rotator cuff injuries increase in prevalence with advanced age. As a consequence, the number of patients in Hawai'i who present with an injury to the subscapularis tendon will continue to rise. However, limited research has been done to delineate the involvement of subscapularis injuries in this population. This article covers the anatomy and function of the subscapularis, the epidemiology and classification of tears in this tendon, and the management of tears. The anatomy section will cover innervation, vascular supply and insertional anatomy of the subscapularis tendon. The function of the subscapularis in regards to both stability and motion of the glenohumeral joint will be examined. The focus of the article will then shift to the tears of the subscapularis, starting with an in depth look at the epidemiology and classification of these tears. The article will then cover the different imaging modalities and their utility in regards to subscapularis tears. Finally, the operative and non-operative management and indications for each modality will be discussed in detail.
Asunto(s)
Lesiones del Manguito de los Rotadores , Articulación del Hombro , Traumatismos de los Tendones , Hawaii , Humanos , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/epidemiología , Lesiones del Manguito de los Rotadores/terapia , Traumatismos de los Tendones/cirugíaRESUMEN
Counseling patients regarding when to return to driving following a foot and ankle procedure can be difficult, and 6 to 9 weeks is often recommended based on brake reaction times quoted in the literature. However, patients are ultimately responsible for the decision to drive. We aimed to determine when patients actually return to driving following outpatient foot and ankle surgery, what influences their decision, and whether any adverse events were experienced. Thirty-seven patients who underwent a right-sided foot and ankle procedure by a single orthopedic surgeon in an outpatient surgery center between September 2016 and December 2017 were recruited retrospectively for this study. Seventeen patients met inclusion criteria and participated in a telephone survey that inquired about their experiences and attitudes regarding return to driving following right-sided foot or ankle surgery. Of the patients surveyed, 100% drove a motor vehicle as their primary mode of transportation. Ten patients (59%) recalled having a discussion with the surgeon regarding when to resume driving, of which only 4 (23.5%) returned to driving at the suggested time they remembered. One patient (6%) returned to driving 2 weeks sooner, and 1 patient (6%) returned to driving 4 weeks later than recommended. No patient reported experiencing a driving-related adverse event. This study suggests that despite surgeons' recommendations, patients are returning to driving sooner than traditionally recommended. The surgeon's advice regarding when to return to driving may not be as influential as a patient's own self-assessment of their readiness to operate a vehicle after outpatient foot and ankle surgery.
Asunto(s)
Tobillo , Conducción de Automóvil , Tobillo/cirugía , Humanos , Pacientes Ambulatorios , Tiempo de Reacción , Estudios RetrospectivosRESUMEN
The co-occurrence of sleep disruption and schizophrenia-spectrum symptomology is common, with current research supporting the use of interventions, such as cognitive behavioral therapy for insomnia (CBTi), which include sleep hygiene education. Sleep hygiene refers to patterns of pre-sleep behaviors that can promote or impair sleep. These behaviors are easily identified and modifiable, potentially holding promise as targets of research and clinical practice. However, there is little research examining sleep hygiene in those at-risk for schizophrenia, measured through clusters of sub-clinical symptoms known as schizotypy. Given the likelihood poor sleep exacerbates negative emotions, thus serving as an etiologically relevant stressor, the study of sleep hygiene in at-risk populations appears warranted. Additionally, quality of life (QOL) has previously been shown to be negatively associated with sleep hygiene and schizophrenia-spectrum risk. As such, QOL domains were included to quantify the extent pre-sleep habits and dimensional schizotypy impact individuals' wellbeing. Data was collected from a non-clinical sample of 385 young adults (M = 20.83, SD = 3.61). As anticipated, higher schizotypy was correlated with poorer sleep hygiene and reduced QOL, although only negative schizotypy predicted QOL in the final regression model controlling for sex differences. Sex differences were present for all variables of interest except disorganized schizotypy. Post-hoc item-level analyses suggested that higher levels of schizotypy were correlated with emotional rumination prior to sleep, while increased negative schizotypy was associated with reduced QOL. Future research should further evaluate sleep hygiene as a potentially relevant risk variable in the development of schizophrenia-spectrum symptomology and associated decline in QOL.
Asunto(s)
Esquizofrenia , Trastorno de la Personalidad Esquizotípica , Trastornos del Inicio y del Mantenimiento del Sueño , Emociones , Femenino , Humanos , Masculino , Calidad de Vida/psicología , Esquizofrenia/diagnóstico , Trastorno de la Personalidad Esquizotípica/psicología , Higiene del Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Adulto JovenRESUMEN
Severe light sensitivity is a feature common to a range of ophthalmological and neurological diseases. In inherited retinal diseases (IRDs) particularly, this may be accompanied by significant visual disruption. These symptoms are extremely debilitating for affected individuals and have significant implications in terms of day-to-day activities. Underlying mechanisms remain to be fully elucidated. Currently, there are many assessments of photoaversion (PA), however, all have limitations, with quantitative measurement in particular needing further evaluation. To understand the complexities associated with photoaversion from different pathologies, qualitative and quantitative assessments of the light aversion response must be standardized. There is no treatment to date, and strategies to alleviate symptoms focus on light avoidance. With respect to IRDs, however, gene therapy is currently being investigated in clinical trials and promising and further treatments may be on the horizon. The better characterization of these symptoms is an important end point measure in IRD gene therapy trials.
Asunto(s)
Enfermedades de la Retina , Terapia Genética , Humanos , Fenotipo , Retina , Enfermedades de la Retina/genética , Enfermedades de la Retina/terapiaRESUMEN
Purpose: To investigate the long-term natural history of retinal function of achromatopsia (ACHM). Methods: Subjects with molecularly confirmed ACHM were recruited in a prospective cohort study of mesopic microperimetry. Coefficient of repeatability and intraclass correlation coefficient (ICC) of mean sensitivity (MS) were calculated. Best-corrected visual acuity (BCVA), bivariate contour ellipse area (BCEA), contrast sensitivity (CS), MS, total volume (VTOT), and central field volume (V5°) from volumetric and topographic analyses were acquired. Correlation of functional parameters with structural findings from optical coherence tomography (OCT) was performed. Results: Eighteen subjects were recruited. Mean follow-up was 7.2 years. The MS test-retest repeatability coefficient was 1.65 decibels (dB), and the ICC was 0.973 (95% confidence interval, 0.837-0.98). Mean MS was similar for right and left eyes (16.97dB and 17.14dB, respectively). A negative significant correlation between logMAR BCVA and the retinal sensitivity indices (MS, VTOT, V5°) was found. A significant negative correlation between logCS and MS, VTOT, and V5° was also observed. BCVA and BCEA improved during follow-up. Mean CS, MS, VTOT, and V5° at final follow-up were similar to baseline. MS was similar between CNGA3- and CNGB3-ACHM. Patients with and without the presence of a foveal ellipsoid zone on OCT had similar MS (16.64 dB and 17.17 dB, respectively). Conclusions: We demonstrate a highly reproducible assessment of MS. Retinal function including MS, volumetric indices, and CS are stable in ACHM. Improvement of fixation stability and small changes of BCVA over time may be part of the natural history of the disease.
Asunto(s)
Defectos de la Visión Cromática/fisiopatología , Fóvea Central/fisiopatología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Campos Visuales/fisiología , Adolescente , Adulto , Anciano , Niño , Femenino , Estudios de Seguimiento , Fóvea Central/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Adulto JovenRESUMEN
Purpose: To determine the extent of remnant cone structure within early foveal ellipsoid zone (EZ) lesions in macular telangiectasia type 2 longitudinally using both confocal and split detector adaptive optics scanning light ophthalmoscopy (AOSLO). Methods: Spectral domain optical coherence tomography (SDOCT), confocal and split detector AOSLO were acquired from seven patients (10 eyes) with small (early) EZ lesions on SDOCT secondary to macular telangiectasia type 2 at baseline, 6 months, and 12 months. The presence of cone structure on AOSLO in areas of EZ loss as well as cones at 1° eccentricity, and their change over time were quantified. Results: By split detector AOSLO, remnant cone structure was identified within and on the borders of all foveal EZ lesions. Within the extent of these lesions, cone spacing ranged from 4.97 to 9.95 µm at baseline, 5.30 to 6.10 µm at 6 months, and 4.99 to 7.12 µm at 12 months. Four eyes with significantly smaller EZ lesions showed evidence of recovery of EZ reflectivity on SDOCT B-scans. Remnant cone structure was identified in some areas where EZ reflectivity recovered at the following time point. Eyes that showed recovery of EZ reflectivity had a continuous external limiting membrane. Conclusions: Remnant cone structure can persist within small SDOCT-defined EZ lesions, which can wax and wane in appearance over time. AOSLO can help to inform the interpretation of SDOCT imaging. Translational Relevance: The absence of EZ in early macular telangiectasia type 2 and other retinal conditions needs careful interpretation because it does not always indicate an absence of underlying cone structure. The integrity of the external limiting membrane may better predict the presence of remnant cone structure and recovery of EZ reflectivity.
Asunto(s)
Fóvea Central , Humanos , Oftalmoscopía , Células Fotorreceptoras Retinianas Conos , Agudeza VisualRESUMEN
Purpose: To examine repeatability and reproducibility of foveal cone density measurements in patients with CNGA3- and CNGB3-associated achromatopsia (ACHM) using split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Methods: Thirty foveae from molecularly confirmed subjects with ACHM, half of whom harbored disease-causing variants in CNGA3 and half in CNGB3, underwent nonconfocal split-detection AOSLO imaging. Cone photoreceptors within the manually delineated rod-free zone were manually identified twice by two independent observers. The coordinates of the marked cones were used for quantifying foveal cone density. Cone density and difference maps were generated to compare cone topography between trials. Results: We observed excellent intraobserver repeatability in foveal cone density estimates, with intraclass correlation coefficients (ICCs) ranging from 0.963 to 0.991 for CNGA3 and CNGB3 subjects. Interobserver reproducibility was also excellent for both CNGA3 (ICC = 0.952; 95% confidence interval [CI], 0.903-1.0) and CNGB3 (ICC = 0.968; 95% CI, 0.935-1.0). However, Bland-Altman analysis revealed bias between observers. Conclusions: Foveal cone density can be measured using the described method with good repeatability and reproducibility both for CNGA3- and CNGB3-associated ACHM. Any degree of bias observed among the observers is of uncertain clinical significance but should be evaluated on a study-specific basis. Translational Relevance: This approach could be used to explore disease natural history, as well as to facilitate stratification of patients and monitor efficacy of interventions for ongoing and upcoming ACHM gene therapy trials.
Asunto(s)
Defectos de la Visión Cromática , Defectos de la Visión Cromática/diagnóstico , Canales Catiónicos Regulados por Nucleótidos Cíclicos , Fóvea Central/diagnóstico por imagen , Humanos , Reproducibilidad de los Resultados , Células Fotorreceptoras Retinianas ConosRESUMEN
Purpose: The purpose of this study was to report GNAT2-associated achromatopsia (GNAT2-ACHM) natural history, characterize photoreceptor mosaic, and determine a therapeutic window for potential intervention. Methods: Patients with GNAT2-ACHM were recruited from a single tertiary referral eye center (Moorfields Eye Hospital, London, UK). We performed longitudinal clinical evaluation and ophthalmic examination, and multimodal retinal imaging, including adaptive optics scanning light ophthalmoscopy, quantitative analysis of the cone mosaic, and outer nuclear layer (ONL) thickness, including cone densities evaluation in selected regions of interest and comparison with reported healthy controls. Results: All nine subjects (3 women) presented with nystagmus, decreased visual acuity (VA), light sensitivity, and highly variable color vision loss. One patient had normal color vision and better VA. Mean VA was 1.01 (±0.10) logarithms of the minimal angle of resolution (LogMAR) at baseline, and 1.04 (±0.10) LogMAR after a mean follow-up (range) of 7.6 years (1.7-12.8 years). Optical coherence tomography showed preservation of the foveal ellipsoid zone (EZ; n = 8; 88.9%), and EZ disruption (n = 1; 11.1%). Mean ONL thickness (range, ± SD) was 84.72 µm (28.57-113.33, ± 25.46 µm) and 86.47 µm (28.57-113.33, ± 24.65 µm) for right and left eyes, respectively. Mean cone densities (±SD) at 190 µm, 350 µm, and 500 µm from the foveal center, were 48.4 (±24.6), 37.8 (±14.7), and 30.7 (±9.9), ×103 cones/mm2, respectively. Mean cone densities were lower than these of unaffected individuals, but with an overlap. Conclusions: The cone mosaic in GNAT2-ACHM is relatively well preserved, potentially allowing for a wide therapeutic window for cone-directed interventions.
Asunto(s)
Defectos de la Visión Cromática/genética , Defectos de la Visión Cromática/patología , Subunidades gamma de la Proteína de Unión al GTP/genética , Células Fotorreceptoras Retinianas Conos/patología , Adolescente , Adulto , Niño , Pruebas de Percepción de Colores , Electrorretinografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Nistagmo Patológico/diagnóstico , Oftalmoscopía , Imagen Óptica , Linaje , Fenotipo , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Adulto JovenRESUMEN
PURPOSE: To determine the reliability and repeatability of quantitative evaluation of areas of decreased autofluorescence (DAF) from fundus autofluorescence (FAF) images and track disease progression in children with Stargardt disease (STGD1), and to investigate clinical and genotype correlations, disease symmetry, and intrafamilial variability. DESIGN: Prospective cohort study. METHODS: Children and adults with molecularly confirmed STGD1 (n = 90) underwent longitudinal FAF imaging with subsequent semiautomated measurement of the area of DAF and calculation of the annual rate of progression. The age of disease onset was recorded for all subjects, as well as the electroretinography (ERG) group at baseline (n = 86). Patients were grouped for analysis based on the age at baseline and age of onset, into children (n = 56), adults with childhood-onset STGD1 (n = 15), and adults with adult-onset (n = 19). Fifty FAF images were selected randomly and analyzed by 2 observers to evaluate repeatability and reproducibility. Differences between groups, interocular symmetry, genotype-phenotype correlations, and intrafamilial variability were also investigated both for baseline measurements as well as progression rates. We measured visual acuity, molecular genetics, ERG group, FAF metrics, and their correlations. RESULTS: The mean age of onset ± SD was 9.6 ± 3.4 years for childhood-onset (n = 71) and 28.3 ± 7.8 years for adult-onset STGD1 (n = 19). The intra- and interobserver reliability of DAF quantification was excellent (intraclass correlation coefficients 0.995 and 0.987, respectively). DAF area was symmetric between eyes and the mean rate of progression (SD) was 0.69 (0.72), 0.78 (0.48), and 0.40 (0.36) mm2/year for children, adults with childhood-onset, and adults with adult-onset disease, respectively. Patients belonging to a group 3 ERG phenotype (generalized cone and rod dysfunction) had a significantly greater progression rate. Limited intrafamilial variability was observed. CONCLUSIONS: This is the first large prospective study of FAF in a cohort of molecularly confirmed children with STGD1. DAF area quantification was highly reliable and may thereby serve as a robust structural endpoint. A high rate of progression was observed in childhood-onset disease, making this subtype of STGD1 ideally suited to be considered for prioritization in clinical trials.
Asunto(s)
Enfermedad de Stargardt/diagnóstico por imagen , Enfermedad de Stargardt/diagnóstico , Transportadoras de Casetes de Unión a ATP/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Progresión de la Enfermedad , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Biología Molecular , Imagen Óptica , Estudios Prospectivos , Reproducibilidad de los Resultados , Retina/fisiopatología , Enfermedad de Stargardt/genética , Enfermedad de Stargardt/fisiopatología , Agudeza Visual/fisiología , Adulto JovenRESUMEN
INTRODUCTION: Sleep disorders are common in patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Polysomnography (PSG) is the gold standard diagnostic tool but is not easily available in all jurisdictions. We aimed to evaluate various questionnaires and wrist actigraphy as screening tools for sleep disorders in the context of ESKD, by comparing results to unattended home PSG results. MATERIALS AND METHODS: Consecutive patients with advanced CKD or ESKD were recruited and assessed using a combination of self-reported instruments (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, International Restless Legs Questionnaire, Short Form 36), wrist actigraphy, and unattended home PSG. The utility of the questionnaires was summarized. Agreement between acti-graphy and PSG scores was assessed. RESULTS: There was a high prevalence of self-reported sleep disturbance among the 54 participants. The questionnaires had low positive and negative predictive values for their corresponding PSG-measured variables. There were no significant differences between paired PSG and actigraphy summary results for sleep efficiency and time spent awake after sleep onset (n = 27 paired comparisons). CONCLUSION: Commonly used screening questionnaires do not accurately predict sleep disorders in the context of advanced CKD or ESKD. Wrist actigraphy accurately identifies those with low sleep efficiency and long time spent awake after sleep onset, who are likely to have the highest diagnostic yield with PSG. Neither approach obviates the need for PSG for accurate diagnosis of sleep disorders in this population.
Asunto(s)
Actigrafía , Fallo Renal Crónico/complicaciones , Polisomnografía , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/diagnóstico , Encuestas y Cuestionarios , Adulto , Anciano , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Polisomnografía/métodos , Valor Predictivo de las Pruebas , SueñoRESUMEN
Purpose: To perform deep phenotyping of subjects with PDE6C achromatopsia and examine disease natural history. Methods: Eight subjects with disease-causing variants in PDE6C were assessed in detail, including clinical phenotype, best-corrected visual acuity, fundus autofluorescence, and optical coherence tomography. Six subjects also had confocal and nonconfocal adaptive optics scanning light ophthalmoscopy, axial length, international standard pattern and full-field electroretinography (ERG), short-wavelength flash (S-cone) ERGs, and color vision testing. Results: All subjects presented with early-onset nystagmus, decreased best-corrected visual acuity, light sensitivity, and severe color vision loss, and five of them had high myopia. We identified three novel disease-causing variants and provide phenotype data associated with nine variants for the first time. No subjects had foveal hypoplasia or residual ellipsoid zone (EZ) at the foveal center; one had an absent EZ, three had a hyporeflective zone, and four had outer retinal atrophy. The mean width of the central EZ lesion on optical coherence tomography at baseline was 1923 µm. The mean annual increase in EZ lesion size was 48.3 µm. Fundus autofluorescence revealed a central hypoautofluorescence with a surrounding ring of increased signal (n = 5). The mean hypoautofluorescent area at baseline was 3.33 mm2 and increased in size by a mean of 0.13 mm2/year. Nonconfocal adaptive optics scanning light ophthalmoscopy revealed residual foveal cones in only one of two cases. Full-field ERGs were consistent with severe generalized cone system dysfunction but with relative preservation of S-cone sensitivity. Conclusions: PDE6C retinopathy is a severe cone dysfunction syndrome often presenting as typical achromatopsia but without foveal hypoplasia. Myopia and slowly progressive maculopathy are common features. There are few (if any) residual foveal cones for intervention in older adults.
Asunto(s)
Defectos de la Visión Cromática/genética , Visión de Colores/fisiología , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/genética , Proteínas del Ojo/genética , Agudeza Visual , Adolescente , Adulto , Niño , Defectos de la Visión Cromática/diagnóstico , Defectos de la Visión Cromática/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/metabolismo , Electrorretinografía , Proteínas del Ojo/metabolismo , Femenino , Estudios de Seguimiento , Predicción , Humanos , Masculino , Persona de Mediana Edad , Oftalmoscopía , Fenotipo , Tomografía de Coherencia Óptica/métodos , Adulto JovenRESUMEN
None: Sleep disorders are prevalent in patients with end-stage renal disease (ESRD). In those patients on nocturnal dialysis, it is important to perform objective sleep assessment during regular dialysis. We present the case of a man on continuous cycler peritoneal dialysis with disabling fatigue and moderate restless legs syndrome (RLS). Actigraphy demonstrated excessive nocturnal movement. Unattended home polysomnography, performed during his regular peritoneal dialysis, confirmed frequent nocturnal periodic limb movements with disturbed sleep. Treatment with low dose pramipexole led to improved RLS and marked improvement in his energy. Clinicians caring for patients with ESRD should have a low threshold for objective sleep assessment given that sleep disorders are common, disabling and eminently amenable to treatment.
Asunto(s)
Fallo Renal Crónico/complicaciones , Síndrome de Mioclonía Nocturna/diagnóstico , Actigrafía , Agonistas de Dopamina/uso terapéutico , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Síndrome de Mioclonía Nocturna/tratamiento farmacológico , Síndrome de Mioclonía Nocturna/etiología , Polisomnografía , Pramipexol/uso terapéutico , Diálisis Renal/efectos adversosRESUMEN
Purpose: Mutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM. Methods: Seven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM. Results: Foveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports. Conclusions: Our data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM.
Asunto(s)
Factor de Transcripción Activador 6/genética , Defectos de la Visión Cromática/genética , Fóvea Central/anomalías , Mutación , Células Fotorreceptoras Retinianas Conos/patología , Adolescente , Adulto , Niño , Defectos de la Visión Cromática/diagnóstico por imagen , Defectos de la Visión Cromática/patología , Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética , Electrorretinografía , Femenino , Fóvea Central/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Oftalmoscopía , Epitelio Pigmentado de la Retina/diagnóstico por imagen , Epitelio Pigmentado de la Retina/patología , Células Fotorreceptoras Retinianas Bastones/patología , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
Purpose: To investigate retinal structure in subjects with CNGA3-associated achromatopsia and evaluate disease symmetry and intrafamilial variability. Methods: Thirty-eight molecularly confirmed subjects underwent ocular examination, optical coherence tomography (OCT), and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans were used for evaluating foveal hypoplasia, grading foveal ellipsoid zone (EZ) disruption, and measuring outer nuclear layer (ONL) thickness. AOSLO images were used to quantify peak foveal cone density, intercell distance (ICD), and the coefficient of variation (CV) of ICD. Results: Mean (±SD) age was 25.9 (±13.1) years. Mean (± SD) best corrected visual acuity (BCVA) was 0.87 (±0.14) logarithm of the minimum angle of resolution. Examination with OCT showed variable disruption or loss of the EZ. Seven subjects were evaluated for disease symmetry, with peak foveal cone density, ICD, CV, ONL thickness, and BCVA not differing significantly between eyes. A cross-sectional evaluation of AOSLO imaging showed a mean (±SD) peak foveal cone density of 19,844 (±13,046) cones/mm2. There was a weak negative association between age and peak foveal cone density (r = -0.397, P = 0.102), as well as between EZ grade and age (P = 0.086). Conclusions: The remnant cone mosaics were irregular and variably disrupted, with significantly lower peak foveal cone density than unaffected individuals. Variability was also seen among subjects with identical mutations. Therefore, subjects should be considered on an individual basis for stratification in clinical trials. Interocular symmetry suggests that both eyes have comparable therapeutic potential and the fellow eye can serve as a valid control. Longitudinal studies are needed, to further examine the weak negative association between age and foveal cone structure observed here.