This study aimed to quantitatively investigate airborne particle load in the operating room during endoscopic or microscopic epitympanectomy or mastoidectomy.

In the transcanal endoscopic ear surgery group, drilling was performed underwater. A particle counter was used to measure the particle load before, during and after drilling during transcanal endoscopic ear surgery or microscopic ear surgery. The device counted the numbers of airborne particles of 0.3, 0.5 or 1.0 μm in diameter.

The particle load during drilling was significantly higher in the microscopic ear surgery group (n = 5) than in the transcanal endoscopic ear surgery group (n = 11) for all particle sizes (p < 0.01). In the transcanal endoscopic ear surgery group, no significant differences among the particle load observed before, during and after drilling were seen for any of the particle sizes.

Bone dissection carries a lower risk of airborne infection if it is performed using the endoscopic underwater drilling technique.

Treatment resistant depression (TRD) is estimated to affect 10–30% of patients with major depressive disorder (Al‑Harbi et al. Patient Prefer Adherence 2012; 6 369–88). Esketamine nasal spray (NS), in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI), increases remission and response rates in patients with TRD compared with placebo plus SSRI/SNRI (Popova et al. Am J Psychiatry 2019; 176 428–38). ESCAPE-TRD (NCT04338321) is the first randomised clinical trial to compare esketamine NS to quetiapine extended-release (XR), an antipsychotic augmentation therapy for patients with TRD.

To explore the efficacy and safety of esketamine NS compared with quetiapine XR in TRD over 32 weeks (wks).

In the ESCAPE-TRD phase IIIb open-label, rater-blinded trial, patients were randomised 1:1 to esketamine NS (56/84 mg; twice per wk, weekly or every 2 wks) or quetiapine XR (150–300 mg daily) both in combination with an ongoing SSRI/SNRI. Remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score of ≤10) and response (≥50% improvement in MADRS total score from baseline or MADRS≤10) rates were analysed over time using last observation carried forward. MADRS change from baseline was analysed using Mixed Models for Repeated Measures (MMRM). The most common adverse events (AEs) leading to discontinuation are reported for patients who received ≥1 dose of study medication.

At baseline, 336 patients were randomised to esketamine NS and 340 to quetiapine XR. A significantly higher percentage of patients in the esketamine NS group achieved remission (at each visit from Wk6 [p=0.008] onward) and response (at each visit from Day 15 [p<0.001] onward) versus patients treated with quetiapine XR. Esketamine NS significantly improved MADRS score compared to quetiapine XR at each visit from Day 8 onwards, with an average difference over time in the least squares means total MADRS score change from baseline of -2.4 (Figure). The most common AEs leading to treatment discontinuation for esketamine NS were dizziness (n=2, 0.6%), dissociation (n=2, 0.6%) and vomiting (n=2, 0.6%), and for quetiapine XR were sedation (n=7, 2.1%), weight increased (n=6, 1.8%) and somnolence (n=5, 1.5%).

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Esketamine NS increased the percentage of patients achieving response and remission and improved MADRS total score over time compared with quetiapine XR. Rates of discontinuation arising from the most common AEs were generally lower with esketamine NS than quetiapine XR.

We thank participating patients and all who assisted with the study. This study was funded by Janssen; medical writing support was provided by Carolyn Walsh, PhD, Costello Medical, UK.

A. Reif Grant / Research support from: Medice, Consultant of: National Care Guidelines (NVL, S3) on major depression, bipolar disorder, ADHD and suicidal behaviour (aided in developing guidelines); board member of DGBS, DGPPN, ECNP and German Depression Foundation, Speakers bureau of: (and participated in advisory boards over the last 3 years) for Cyclerion, Janssen, Medice, SAGE/Biogen and Shire/Takeda; received speaker’s honoraria from Das Fortbildungskolleg; , A. E. Anıl Yağcıoğlu Grant / Research support from: Participated as an investigator for Janssen, Speakers bureau of: (and participated in advisory boards over the last 3 years) for Janssen and Abdi İbrahim Otsuka, A. Luts Speakers bureau of: (or participated in advisory boards for or participated as an investigator) for Janssen-Cilag, Asarina Pharma, Bristol Meyer Squibb, Dr August Wolff GmbH & Co, Eli Lilly, Lundbeck, Pfizer, Allergan, Sunovion and Regeneron., T. Messer Consultant of: National Care Guidelines (NVL, S3) on major depression (aided in developing guidelines), Speakers bureau of: (and participated in advisory boards) for Janssen-Cilag and Otsuka/Lundbeck, R. Nielsen Consultant of: Board member of DSAL and IGSLi, Speakers bureau of: (or participated in advisory boards, received research funds or participated as investigator over the last 3 years) for Boehringer Ingelheim, Compass Pharmaceuticals, Janssen-Cilag, Lundbeck, Otsuka, Sage and Teva Pharmaceuticals, J. Buyze Employee of: Janssen, T. Ito Employee of: Janssen, Y. Kambarov Employee of: Janssen, S. Mulhern Haughey Employee of: Janssen, B. Rive Employee of: Janssen, I. Usankova Employee of: Janssen, C. von Holt Employee of: Janssen, Y. Godinov Employee of: Janssen

For patients with depression, the likelihood of remission decreases with each subsequent treatment failure. Per European Medicines Agency guidance, treatment resistant depression (TRD) is defined as nonresponse to ≥2 consecutive treatments at adequate dosage and duration in the current depressive episode. In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) increased the probability of achieving remission and remaining relapsefree, compared with quetiapine extended release (QXR) in patients with TRD. Here, we report the efficacy of esketamine NS vs QXR in patient subgroups with 2 or ≥3 consecutive prior treatment failures (PTFs).

ESCAPETRD was a phase IIIb trial comparing the efficacy of esketamine NS with QXR in patients with TRD. Patients (N = 676) were randomised 1:1 to esketamine NS (n = 336; 56/84 mg; twice weekly, weekly, or every 2 weeks [wks]) or QXR (n = 340; 150–300 mg daily, both in combination with an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. Randomisation was stratified by age (18-64 years; 65–74 years) and PTFs (2; ≥3).

The primary endpoint of remission (Montgomery-Åsberg Depression Rating Scale total score ≤10) at Wk8 and the secondary endpoint of remaining relapse-free through Wk32 after remission at Wk8, were analysed in PTF patient subgroups and compared between study arms, with treatment discontinuation considered as a negative outcome. The effect on time to remission was assessed using hazard ratios (HR) from a Cox regression model.

Of the randomised patients, 415 (61.4%; esketamine NS: 204, QXR: 211) had experienced 2 PTFs and 261 (38.6%; esketamine NS: 132, QXR: 129) had experienced ≥3.

Of patients with 2 PTFs, 54/204 (26.5%) esketamine NS-treated patients and 46/211 (21.8%) Q-XR-treated patients achieved remission at Wk8 (p = 0.267). Of patients with ≥3 PTFs, 37/132 (28.0%) and 14/129 (10.9%) patients achieved remission at Wk8 in esketamine NS and Q-XR arms, respectively (p < 0.001). Of patients with 2 and ≥3 PTFs, 49/204 (24.0%) and 24/132 (18.2%) of esketamine NS-treated patients and 38/211 (18.0%) and 10/129 (7.8%) of Q-XR-treated patients achieved remission at Wk8 without relapse to Wk32 (p = 0.133 and p = 0.013), respectively.

Esketamine NS significantly improved time to remission, with a greater effect in the ≥3 PTF subgroup (2 PTFs: HR = 1.547 [95% confidence interval (CI) 1.210–1.976]; p < 0.001 vs ≥3 PTFs: HR = 2.066 [95% CI 1.469–2.907]; p < 0.001).

Esketamine NS demonstrated a significantly superior remission rate versus QXR at Wk8 in patients with ≥3 PTFs, and significantly shorter time to remission versus Q-XR in both subgroups.

Vertigo and dizziness are frequent symptoms in patients at out-patient services. An accurate diagnosis for vertigo or dizziness is essential for symptom relief; however, it is often challenging. This study aimed to identify differences in diagnoses between primary-care physicians and specialised neurotologists.

In total, 217 patients were enrolled. To compare diagnoses, data was collected from the reference letters of primary-care physicians, medical questionnaires completed by patients and medical records.

In total, 62.2 per cent and 29.5 per cent of the patients were referred by otorhinolaryngologists and internists, respectively. The cause of vertigo or dizziness and diagnosis was missing in 47.0 per cent of the reference letters. In addition, 67.3 per cent of the diagnoses by previous physicians differed from those reported by specialised neurotologists.

To ensure patient satisfaction and high quality of life, an accurate diagnosis for vertigo or dizziness is required; therefore, methods or materials to improve the diagnostic accuracy are needed.

Sleep restriction has adverse effects on performance and neurobehavioral function. However, the mechanism of impaired performance and neurobehavioral function has not been studied yet.

We examined the effect of insufficient sleep on cerebral blood flow and cognitive function in 8 healthy adults (mean age 22.4 years).

All participants were in bed for 8 h (sufficient sleep), and for < 4 h (insufficient sleep). The oxyhemoglobin (oxyHb) level by a word fluency task was measured with a near-infrared spectroscopy recorder on the morning following sufficient and insufficient sleep periods. Wisconsin card sorting test (WCST), continuous performance test (CPT) and N-back test were evaluated on the same days.

The peak oxyHb level was significantly lower in the left and right frontal lobes after insufficient sleep than after sufficient sleep (left: 0.25 ± 0.10 vs. 0.70 ± 0.29 mmol, P < 0.05; right: 0.23 ± 0.13 vs. 0.73 ± 0.22 mmol, P < 0.05). There was no significant difference in the number of words generated during the word fluency task between sufficient and insufficient sleep states. The percentage of correct responses on CPT after insufficient sleep was significantly lower than that after sufficient sleep (86.6 ± 10.2 vs. 96.0 ± 4.9%, P < 0.05). The reaction time of WCST was significantly longer after insufficient sleep than after sufficient sleep (76.6 ± 13.4 vs. 70.6 ± 16.2 sec, P < 0.05).

One night sleep restriction decreased the concentration changes of oxyHb in brain tissue, leading to impaired cognitive function.

Little is known about the economic benefits of cognitive remediation and supported employment (CR + SE). The present study aimed to investigate the cost-effectiveness of CR + SE compared with traditional vocational services (TVS).

Individuals with mental illness and low cognitive function were recruited at six sites in Japan. A total of 111 participants were randomly allocated to the CR + SE group or the TVS group. Clinical and vocational outcomes were assessed at baseline and 12-month follow-up. Service utilization data were collected monthly. The data on outcomes and costs were combined to examine cost-effectiveness.

The data were obtained from a total of 92 participants. The CR + SE group resulted in better vocational and clinical outcomes (employment rate, 62.2%; work tenures, 78.6 days; cognitive improvement, 0.5) than the TVS group (19.1%, 24.9 days and 0.2). There was no significant difference in mean total costs between the groups (CR + SE group: $9823, s.d. = $6372, TVS group: $11 063, s.d. = $11 263) with and without adjustment for covariates. However, mean cost for medical services in the CR + SE group was significantly lower than that in the TVS group after adjusting covariates (Β = −$3979, 95% confidence interval −$7816 to −$143, p = 0.042). Cost-effectiveness acceptability curves for vocational outcomes illustrated the high probabilities (approximately 70%) of the CR + SE group being more cost-effective than TVS when society is not willing to pay additional costs.

CR + SE appears to be a cost-effective option for people with mental illness who have low cognitive functioning when compared with TVS.

The mode of onset and the course of schizophrenia illness exhibit substantial individual variations. Previous studies have pointed out that the mode of onset affects the duration of untreated psychosis (DUP) and clinical outcomes, such as cognitive and social functioning. This study attempted to clarify the association between the DUP and clinical features, taking the different modes of onset into consideration, in a prospective longitudinal study examining patients with first-episode schizophrenia.

This study was conducted in six areas of Japan. Patients with first-episode schizophrenia were followed for over 18 months. Cognitive function, psychopathology, and social functioning were assessed at baseline and at 6, 12, and 18-month follow-up points.

We identified 168 patients and sufficient information was available to determine the DUP and the mode of onset for 156 patients (92.9%): 79 had an acute onset, and 77 had an insidious onset. The DUP was significantly associated with quality of life (QOL), social functioning, and cognitive function at most of the follow-up points in the insidious-onset group. The DUP and negative symptoms at baseline were significant predictors of cognitive function at the 18-month follow-up in the insidious-onset group.

The present results further support the hypothesis that the DUP affects QOL, social functioning, and cognitive function over the course of illness, especially in patients with an insidious onset. Effective strategies for detecting and caring for individuals with insidious onset early during the course of schizophrenia will be essential for achieving a full patient recovery.