Health-related quality of life (HRQoL), though rarely considered as a primary endpoint in clinical trials, may be the single outcome reflective of patient priorities when living with a health condition. HRQoL is a multi-dimensional concept that reflects the degree to which a health condition interferes with participation in and fulfillment of important life areas. HRQoL is intended to capture the composite degree of physical, physiologic, psychological, and social impairment resulting from symptom burden, patient-perceived disease severity, and treatment side effects. Diminished HRQoL expectedly correlates to worsening disability and death; but interventions addressing HRQoL are linked to increased survival. Sarcoidosis, being a multi-organ system disease, is associated with a diffuse array of manifestations resulting in multiple symptoms, complications, and medication-related side effects that are linked to reduced HRQoL. Diminished HRQoL in sarcoidosis is related to decreased physical function, pain, significant loss of income, absence from work, and strain on personal relationships. Symptom distress can result clearly from a sarcoidosis manifestation (e.g., ocular pain, breathlessness, cough) but may also be non-specific, such as pain or fatigue. More complex, a single non-specific symptom, e.g., fatigue may be directly sarcoidosis-derived (e.g., inflammatory state, neurologic, hormonal, cardiopulmonary), medication-related (e.g., anemia, sleeplessness, weight gain, sub-clinical infection), or an indirect complication (e.g., sleep apnea, physical deconditioning, depression). Identifying and distinguishing underlying causes of impaired HRQoL provides opportunity for treatment strategies that can greatly impact a patient’s function, well-being, and disease outcomes. Herein, we present a reference manual that describes the current state of knowledge in sarcoidosis-related HRQoL and distinguish between diverse causes of symptom distress and other influences on sarcoidosis-related HRQoL. We provide tools to assess, investigate, and diagnose compromised HRQoL and its influencers. Strategies to address modifiable HRQoL factors through palliation of symptoms and methods to improve the sarcoidosis health profile are outlined; as well as a proposed research agenda in sarcoidosis-related HRQoL.

BackgroundAutism spectrum disorder (ASD) currently affects nearly 1 in 160 children worldwide. In over two-thirds of evaluations, no validated diagnostics are used and gold standard diagnostic tools are used in less than 5% of evaluations. Currently, the diagnosis of ASD requires lengthy and expensive tests, in addition to clinical confirmation. Therefore, fast, cheap, portable, and easy-to-administer screening instruments for ASD are required. Several studies have shown that children with ASD have a lower preference for social scenes compared with children without ASD. Based on this, eye-tracking and measurement of gaze preference for social scenes has been used as a screening tool for ASD. Currently available eye-tracking software requires intensive calibration, training, or holding of the head to prevent interference with gaze recognition limiting its use in children with ASD.MethodsIn this study, we designed a simple eye-tracking algorithm that does not require calibration or head holding, as a platform for future validation of a cost-effective ASD potential screening instrument. This system operates on a portable and inexpensive tablet to measure gaze preference of children for social compared to abstract scenes. A child watches a one-minute stimulus video composed of a social scene projected on the left side and an abstract scene projected on the right side of the tablet’s screen. We designed five stimulus videos by changing the social/abstract scenes. Every child observed all the five videos in random order. We developed an eye-tracking algorithm that calculates the child’s gaze preference for the social and abstract scenes, estimated as the percentage of the accumulated time that the child observes the left or right side of the screen, respectively. Twenty-three children without a prior history of ASD and 8 children with a clinical diagnosis of ASD were evaluated. The recorded video of the child´s eye movement was analyzed both manually by an observer and automatically by our algorithm.ResultsThis study demonstrates that the algorithm correctly differentiates visual preference for either the left or right side of the screen (social or abstract scenes), identifies distractions, and maintains high accuracy compared to the manual classification. The error of the algorithm was 1.52%, when compared to the gold standard of manual observation.DiscussionThis tablet-based gaze preference/eye-tracking algorithm can estimate gaze preference in both children with ASD and without ASD to a high degree of accuracy, without the need for calibration, training, or restraint of the children. This system can be utilized in low-resource settings as a portable and cost-effective potential screening tool for ASD.

Background-Sex is a well-recognized risk factor for sudden cardiac death (SCD). Sex differences in electrophysiological (EP) substrate of SCD are known. However, it remains unknown whether sex can modify an association of EP substrate with SCD. Methods-Participants from the Atherosclerosis Risk in Communities study with analyzableECGs (n=14,725; age, 54.2±5.8 yrs; 55% female, 74% white) were included. EP substrate was characterized by traditional 12-lead ECG (heart rate, QRS, QTc, Cornell voltage), spatial ventricular gradient (SVG) and sum absolute QRST integral (SAI QRST) metrics. Two competing outcomes were adjudicated SCD and nonSCD. Cox proportional hazards and Fine-Gray competing risk models were constructed. Relative hazard ration (RHR) and relative subhazard ratio (RSHR) with 95% confidence interval for SCD and nonSCD risk for women relative to men was calculated. Model 1 was adjusted for prevalent cardiovascular disease (CVD) and risk factors. Time-updated model 2 was in addition adjusted for incident non-fatal CVD events.Results-Over a median follow-up of 24.4 years, there were 530 SCDs (incidence 1.72 (1.58-1.88)/1000 person-years). Women experienced a greater than men risk of SCD associated with QRS duration (RHR 1.24(1.07-1.44); P=0.004) and QTc (RSHR 1.15(1.02-1.30); P=0.025), which was explained by incident CVD. Furthermore, Cornell voltage (RHR 1.18(1.06-1.32); P=0.003), SAI QRST (RHR 1.16(1.04-1.30); P=0.007), area SVG magnitude (RHR 1.24(1.05-1.45); P=0.009), and peak SVG magnitude (RHR 1.22(1.04-1.44); P=0.018) were associated with higher risk of SCD in women than in men, independently from incident CVD.Conclusions-Sex modifies an association of EP substrate with SCD. In women, global EP substrate is associated with up to 27% greater competing risk of SCD than in men. Development of sex-specific risk scores of SCD is necessary.

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