Few studies have examined attention-deficit/hyperactivity disorder (ADHD) symptoms in middle- and older-aged adults. We aim to examine the phenotypic expression of ADHD symptoms in these age groups.

This study comprised a random sample (N = 1,562) from the US Health and Retirement Study 2016, a representative US sample aged 50 years and over. ADHD symptoms were assessed based on the Adult ADHD Self-Report Scale.

In the primary analysis, 10 competing confirmatory factor analytic models of ADHD symptoms in middle- and older-aged adults were compared. The best-fitting model was hierarchical with a general ADHD factor at the apex and underneath symptom factors of inattention, hyperactivity, and impulsivity (ꭓ2 = 319.34, df = 91.71, P = 0.00, TLI = 0.98, CFI = 0.96, RMSEA = 0.04, 95% CI = 0.04–0.05). In complementary analyses, this model was a satisfactory fit to the data: (1) in individuals without a history of cognitive impairment or dementia, and when the general ADHD factor was specified to load on (2) cognitive function, (3) depressive symptoms (which showed adequate fit), and (4) ADHD polygenic scores, (5) in middle- and older-aged adults, and (6) when weighted to represent the US population.

These results imply a hierarchical representation of ADHD symptoms in middle- and older-aged adults consisting of a general factor at the apex with neurocognitive and genetic correlates and underneath symptom factors of inattention, hyperactivity, and impulsivity. Collectively, this model offers a novel framework to study the mechanisms of ADHD symptoms in middle- and older-aged adults and points to treatment targets.

Zuranolone is an investigational positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and a neuroactive steroid in clinical development as a once-daily, oral, 14-day treatment course for adults with major depressive disorder or postpartum depression (PPD). The randomized, double-blind, placebo-controlled SKYLARK Study (NCT04442503) demonstrated that zuranolone 50 mg significantly improved depressive symptoms (as assessed by 17-item Hamilton Rating Scale for Depression total score) at Day 15 (primary endpoint; p<0.001) and was generally well tolerated in adults with PPD.

In the SKYLARK Study, patients were randomized 1:1 to receive zuranolone 50 mg or placebo for 14 days. Safety and tolerability were assessed by the incidence and severity of treatment-emergent adverse events (TEAEs), rates of dose reduction and treatment discontinuation, as well as weight gain and sexual dysfunction.

The SKYLARK Study assessed safety data from 98 patients treated with zuranolone 50 mg and 98 patients treated with placebo. TEAEs were reported in 66.3% of zuranolone-treated patients and 53.1% of placebo-treated patients. In patients that experienced TEAEs, most reported mild (zuranolone, 50.8%; placebo, 75%) or moderate (zuranolone, 44.6%; placebo, 23.1%) events. The most common (≥5%) TEAEs were somnolence (26.5%), dizziness (13.3%), sedation (11.2%), headache (9.2%), diarrhea (6.1%), nausea (5.1%), urinary tract infection (5.1%), and COVID-19 (5.1%) with zuranolone, and headache (13.3%), dizziness (10.2%), nausea (6.1%), and somnolence (5.1%) with placebo. Dose reduction due to TEAEs was 16.3% in patients receiving zuranolone vs 1.0% in patients receiving placebo; the most common TEAEs (>1 patient) leading to zuranolone dose reduction were somnolence (7.1%), dizziness (6.1%), and sedation (3.1%). Treatment discontinuation due to TEAEs was 4.1% in patients receiving zuranolone vs 2.0% in patients receiving placebo; TEAEs leading to zuranolone discontinuation in >1 patient included somnolence (2.0%). Serious TEAEs were reported in 2.0% of zuranolone-treated and 0% of placebo-treated patients; these included upper abdominal pain (1.0%, [1/98]), peripheral edema (1.0%, [1/98]), perinatal depression (1.0%, [1/98]), and hypertension (1.0%, [1/98]). Per investigators, serious TEAEs were not related to zuranolone. No signals for weight gain or sexual dysfunction were identified.

In adults with PPD, zuranolone 50 mg was generally well tolerated. Most TEAEs were mild or moderate in severity. Dose reduction due to TEAEs mainly resulted from somnolence, dizziness, and sedation, while treatment discontinuation due to TEAEs was low. No signals for weight gain or sexual dysfunction were identified.

Sage Therapeutics, Inc., and Biogen Inc.

Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice.

An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized.

Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals.

Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.

To present our data evaluating the feasibility of simultaneous cochlear implantation with resection of acoustic neuroma.

This paper describes a case series of eight adult patients with a radiologically suspected acoustic neuroma, treated at a tertiary referral centre in Newcastle, Australia, between 2012 and 2015. Patients underwent cochlear implantation concurrently with removal of an acoustic neuroma. The approach was translabyrinthine, with facial nerve monitoring and electrically evoked auditory brainstem response testing. Standard post-implant rehabilitation was employed, with three and six months’ follow-up data collected. The main outcome measures were: hearing, subjective benefit of implant, operative complications and tumour recurrence.

Eight patients underwent simultaneous cochlear implantation with resection of acoustic neuroma over a 3-year period, and had 25–63 months’ follow up. There were no major complications. All patients except one gained usable hearing and were daily implant users.

Simultaneous cochlear implantation with resection of acoustic neuroma has been shown to be a safe treatment option, which will be applicable in a wide range of clinical scenarios as the indications for cochlear implantation continue to expand.