In recent years, sleep-disordered breathing (SDB) has been recognized as a prevalent but under-diagnosed condition in adults and has prompted the need for new and better diagnostic and therapeutic options. To facilitate the development and availability of innovative, safe and effective SDB medical device technologies for patients in the United States, the US Food and Drug Administration collaborated with six SDB-related professional societies and a consumer advocacy organization to convene a public workshop focused on clinical investigations of SDB devices. Sleep medicine experts discussed appropriate definitions of terms used in the diagnosis and treatment of SDB, the use of home sleep testing versus polysomnography, clinical trial design issues in studying SDB devices, and current and future trends in digital health technologies for diagnosis and monitoring SDB. The panel’s breadth of clinical expertise and experience across medical specialties provided useful and important insights regarding clinical trial designs for SDB devices. Mann EA, Nandkumar S, Addy N, et al. Study design considerations for sleep-disordered breathing devices. J Clin Sleep Med. 2020;16(3):441–449.

Selection designs and futility designs offer investigators a way to screen potential therapies in early phase clinical research with fewer patients than would be required for a traditional phase 3 trial for each candidate. There are some avoidable-pitfalls when planning a futility study. The first is that if the sample size is too small, a rather awkward situation can arise. The last pitfall relates to the use of historical control data in the single-arm design. Selection procedures offer an attractive approach to the problem of screening potentially good treatments. There are many different procedures for general ranking and selection goals such as selection from among more than two treatments, selection of best subsets of treatments, and ranking treatments in order of efficacy. Although selection procedures efficiently achieve their goal of selecting best treatments, the desire to 'test something' with an accompanying statement of statistical significance seems irresistible.

*Centers for Disease Control and Prevention, Atlanta, Georgia; and †Food and Drug Administration, Bethesda, Maryland, U.S.A. Address correspondence and reprint requests to Jennita Reefhuis, Ph.D., National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Rd NE MS E-86, Atlanta, GA 30333, U.S.A.; E-mail: [email protected] The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the Food and Drug Administration.

Background. More than 11000 children in the United States with severe-to-profound hearing loss have cochlear implants. A 2002 investigation involving pediatric cochlear implant recipients identified meningitis episodes from January 1, 1997, through September 15, 2002. The incidence of pneumococcal meningitis in the cohort was 138.2 cases per 100000 person-years, >30 times higher than that for children in the general US population. Children with implants with positioners were at higher risk than children with other implant models. This higher risk of bacterial meningitis continued for up to 24 months after implantation. Objective. To evaluate additional reported cases to determine whether the increased rate of bacterial meningitis among children with cochlear implants extended beyond 24 months after implantation. Methods. Our study population consisted of the cohort of children identified through the 2002 investigation; it included 4265 children who received cochlear implants in the United States between January 1, 1997, and August 6, 2002, and who were <6 years of age at the time of implantation. We calculated updated incidence rates and incidence according to time since implantation. Results. We identified 12 new episodes of meningitis for 12 children. Eleven of the children had implants with positioners; 2 children died. Six episodes occurred >24 months after implantation. When cases identified in the 2002 and 2004 investigations were combined, the incidence rate of ≥24-months postimplantation bacterial meningitis among children with positioners was 450 cases per 100000 person-years, compared with no cases among children without positioners. Conclusions. Our updated findings support continued monitoring and prompt treatment of bacterial infections by health care providers and parents of children with cochlear implants. This vigilance remains important beyond 2 years after implantation, particularly among children with positioners. The vaccination recommendations for all children with implants, with and without positioners, and all potential recipients of implants continue to apply.

Emerging evidence indicates that medically recalcitrant sinusitis may be associated with a prolonged and excessive state of inflammation rather than a simple bacterial infection. Corticosteroids have been anecdotally reported to be helpful in treating patients with sinusitis; however, there are no scientific studies documenting the safety and efficacy of corticosteroid therapy in sinusitis. To resolve the controversy over whether corticosteroids promote or inhibit the resolution of sinusitis, we present a prospective study of 80 rabbits with surgically introduced pseudomonal sinusitis that were then treated in one of four arms: control, ceftazidime, methylprednisolone, and ceftazidime with methylprednisolone. Sinus cavities were then evaluated after 5, 14, 21, and 28 days of treatment both by histologic inflammation grading and bacterial quantification. Results showed a significant decrease in bacterial loads in both the antibiotic and antibiotic with steroid arms over control animals, although no difference was seen between the two. Histologic grading showed a similar trend, although statistical significance was not obtained. Overall, this study demonstrated no clear advantage of steroids in the treatment of sinus infections using this model. At the same point, no significant reduction in the effectiveness of antibiotic therapy was seen with concurrent steroid use. A number of limitations of the animal model are noted and the need for human studies in this area is discussed.