In the mammalian auditory system, sensory cell loss resulting from aging, ototoxic drugs, infections, overstimulation and other causes is irreversible and leads to permanent sensorineural hearing loss. To restore hearing, it is necessary to generate new functional hair cells. One potential way to regenerate hair cells is to induce a phenotypic transdifferentiation of nonsensory cells that remain in the deaf cochlea. Here we report that Atoh1, a gene also known as Math1 encoding a basic helix-loop-helix transcription factor and key regulator of hair cell development, induces regeneration of hair cells and substantially improves hearing thresholds in the mature deaf inner ear after delivery to nonsensory cells through adenovectors. This is the first demonstration of cellular and functional repair in the organ of Corti of a mature deaf mammal. The data suggest a new therapeutic approach based on expressing crucial developmental genes for cellular and functional restoration in the damaged auditory epithelium and other sensory systems.

Spiral ganglion neurons often degenerate in the deaf ear, compromising the function of cochlear implants. Cochlear implant function can be improved by good preservation of the spiral ganglion neurons, which are the target of electrical stimulation by the implant. Brain derived neurotrophic factor (BDNF) has previously been shown to enhance spiral ganglion survival in experimentally deafened ears. Providing enhanced levels of BDNF in human ears may be accomplished by one of several different methods. The goal of these experiments was to test a modified design of the cochlear implant electrode that includes a coating of fibroblast cells transduced by a viral vector with a BDNF gene insert. To accomplish this type of ex vivo gene transfer, we transduced guinea pig fibroblasts with an adenovirus with a BDNF gene cassette insert, and determined that these cells secreted BDNF. We then attached BDNF-secreting cells to the cochlear implant electrode via an agarose gel, and implanted the electrode in the scala tympani. We determined that the BDNF expressing electrodes were able to preserve significantly more spiral ganglion neurons in the basal turns of the cochlea after 48 days of implantation when compared to control electrodes. This protective effect decreased in the higher cochlear turns. The data demonstrate the feasibility of combining cochlear implant therapy with ex vivo gene transfer for enhancing spiral ganglion neuron survival.

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Models addressing urgent clinical needs for older adults with multiple advanced chronic conditions are lacking. This observational study describes a Community Paramedicine (CP) model for treatment of acute medical conditions within an Advanced Illness Management (AIM) program, and compares its effect on emergency department (ED) use and subsequent hospitalization with that of traditional emergency medical services (EMS). Community paramedics were trained to evaluate and, with telemedicine-enhanced physician guidance, treat acute illnesses in individuals' homes. They were also able to transport to the ED if needed. The CP model was implemented between January 1, 2014, and April 30, 2015 in a suburban-urban AIM program. Participants included 1,602 individuals enrolled in the AIM program with high rates of dementia, decubitus ulcers, diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease. Participants had a median age of 83 and an average of five activity of daily living dependencies (range 0-6). During the study period, there were 664 CP responses and 1,091 traditional EMS transports to the ED among 773 individuals. Only 22% of CP responses required transport; 78% were evaluated and treated in the home. Individuals that community paramedics transported to the ED had higher rates of hospitalization (82.2%) than those using traditional EMS (68.9%) (P < .001). Post-CP surveys showed that all respondents felt the program was of high quality. Results support the potential benefits of CP and invite further evaluation of this innovative care model.

As the cost of care rises and fragmentation of health care increases, care transitions have become critical parts of the health care system. Physicians and other inpatient providers have the responsibility to communicate to subsequent providers, but such communication occurs far less than is optimal. Timely discharge summaries for the next-level provider, postdischarge phone calls to patients, and postdischarge follow-up appointments with primary-care physicians or inpatient providers may improve postdischarge health care utilization. Pharmacists may also reduce medication errors, adverse medication events, and even readmissions. The most promising data, however, come from studies of multidisciplinary approaches, some of which have shown large reductions in postdischarge utilization and costs. More study is needed to pinpoint the most cost-effective and efficient strategies to improve transitions from the inpatient setting to other settings.