Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with hearing loss in clinical practice.

BACKGROUND: Hearing loss (HL) is a prevalent sensorineural disorder, and is among the most etiologically heterogeneous disorders. With the advent of next-generation sequencing (NGS) technologies, hundreds of candidate genes can be analyzed simultaneously in a cost-effective manner. METHODS: Ninety-four patients from 87 families diagnosed with non-syndromic or syndromic HL were enrolled. A custom-designed HL panel and clinical exome sequencing (CES) were applied to explore molecular etiology in the cohort, and the efficacy of the two panels was examined. RESULTS: The etiologic diagnosis for HL has been identified for 36 out of 87 probands (41.4%), 28 with an autosomal recessive (AR) inheritance pattern and 8 with an autosomal dominant (AD) pattern. Candidate variants in 18 different genes were identified in the study cohort, 10 with AR inheritance pattern and 8 with AD pattern. Fourteen of the variants identified in the study were novel. CONCLUSIONS: The custom-designed HL panel covers almost all known HL-associated genes, and can be used as an effective clinical diagnostic platform; CES evaluates all exons related to clinical symptoms, and is also suitable for clinical diagnosis of HL. Next-generation sequencing facilitates genetic diagnosis and improves the management of patients with HL in the clinical practice.

Development of a community-based hearing loss prevention and control service model in Guangdong, China.

BACKGROUND: Hearing loss is a prevalent sensorineural disorder and a major public health issue in China. It is suggested that half of all cases of hearing loss can be prevented through public health measures. However, national strategies for hearing healthcare are not implemented well in Guangdong and some other regions in China. METHODS: To develop a community-based service model for the prevention and control of hearing loss in Guangdong, we integrated the model with multiple maternal and child healthcare models, and set up a series of clinical programs along with an optimum timeline for the preventive measures and intervention treatments to take place. A total of 36,090 families were enrolled in the study, including 358 high-risk families and 35,732 general-risk families. RESULTS: The study lasted for 6.5 years, and 30,769 children were born during that period. A total of 42 children were born with congenital deafness; 17 of them were born into families with advanced genetic risks for hearing loss, 9 were born with specific medical conditions, and 16 were born into general-risk families. About one third of them were diagnosed prenatally, others were diagnosed within 3 months of age, and 72% of them received interventions initiated before 6 months of age. 13 children presented with delayed hearing loss; 9 of them were diagnosed with delayed hereditary sensorineural deafness in neonatal period, and 4 were diagnosed within 3 months after onset. Timely interventions were provided to them, with appropriate referrals and follow-ups. Beside these, 80 families were identified with genetic susceptibility to aminoglycoside ototoxicity. Detailed medication guides were provided to prevent aminoglycoside-induced hearing loss. Moreover, through health education and risk reduction strategies, the prevalence of TORCH syndrome decreased from 10.7 to 5.2 per 10,000. Additionaly, the awareness rates of health knowledge about hearing healthcare significantly increased in the cohort. CONCLUSIONS: Adapting national strategies for local or district projects could be an important step in implementing hearing loss prevention measures, and developing community-based service models could be of importance in carrying them out.

Parent Cognitive Satisfaction and Demand Research of Neonatal Hearing Screening.

The primary aim of the present study was to investigate parent cognitive satisfaction and demand by using a valid and reliable questionnaire developed for this purpose (Parent Cognitive Satisfaction and Demand Questionnaire with Neonatal Hearing Screening Program, PCSDQ-NHSP). About 1000 parents whose children received hearing screening participated in this study. The satisfaction questionnaire was found to be a useful instrument for identifying service shortfalls, and the routine use of the PCSDQ-NHSP in other neonatal hearing screening programs is recommended. Overall, parents focused their attention to the neonatal hearing screening results and had high levels of expectations. They also longed for more information about relevant knowledge. Screening ability differed in different areas of Guangdong province where grass-roots hospitals had poor ability to perform this well. More preappointment information leaflets or brochures should be sent to parents. Regular training for neonatal hearing screening test is needed in primary hospitals. We can establish a neonatal hearing screening network to link as many hospitals as possible, and develop a standardized neonatal hearing screening system.

On the SVMpath singularity.

This paper proposes a novel ridge-adding-based approach for handling singularities that are frequently encountered in the powerful SVMpath algorithm. Unlike the existing method that performs linear programming as an additional step to track the optimality condition path in a multidimensional feasible space, our new approach provides a simpler and computationally more efficient implementation, which needs no extra time-consuming procedures other than introducing a random ridge term to each data point. Contrary to the existing ridge-adding method, which fails to avoid singularities as the ridge terms tend to zero, our novel approach, for any small random ridge terms, guarantees the existence of the inverse matrix by ensuring that only one index is added into or removed from the active set. The performance of the proposed algorithm, in terms of both computational complexity and the ability of singularity avoidance, is manifested by rigorous mathematical analyses as well as experimental results.

Cost-effectiveness analysis of neonatal hearing screening program in China: should universal screening be prioritized?

BACKGROUND: Neonatal hearing screening (NHS) has been routinely offered as a vital component of early childhood care in developed countries, whereas such a screening program is still at the pilot or preliminary stage as regards its nationwide implementation in developing countries. To provide significant evidence for health policy making in China, this study aims to determine the cost-effectiveness of NHS program implementation in case of eight provinces of China. METHODS: A cost-effectiveness model was conducted and all neonates annually born from 2007 to 2009 in eight provinces of China were simulated in this model. The model parameters were estimated from the established databases in the general hospitals or maternal and child health hospitals of these eight provinces, supplemented from the published literature. The model estimated changes in program implementation costs, disability-adjusted life years (DALYs), average cost-effectiveness ratio (ACER), and incremental cost-effectiveness ratio (ICER) for universal screening compared to targeted screening in eight provinces. RESULTS AND DISCUSSION: A multivariate sensitivity analysis was performed to determine uncertainty in health effect estimates and cost-effectiveness ratios using a probabilistic modeling technique. Targeted strategy trended to be cost-effective in Guangxi, Jiangxi, Henan, Guangdong, Zhejiang, Hebei, Shandong, and Beijing from the level of 9%, 9%, 8%, 4%, 3%, 7%, 5%, and 2%, respectively; while universal strategy trended to be cost-effective in those provinces from the level of 70%, 70%, 48%, 10%, 8%, 28%, 15%, 4%, respectively. This study showed although there was a huge disparity in the implementation of the NHS program in the surveyed provinces, both universal strategy and targeted strategy showed cost-effectiveness in those relatively developed provinces, while neither of the screening strategy showed cost-effectiveness in those relatively developing provinces. This study also showed that both strategies especially universal strategy achieve a good economic effect in the long term costs. CONCLUSIONS: Universal screening might be considered as the prioritized implementation goal especially in those relatively developed provinces of China as it provides the best health and economic effects, while targeted screening might be temporarily more realistic than universal screening in those relatively developing provinces of China.