Delay in the diagnosis of head and neck cancer can result in significant excess morbidity and mortality. How the pandemic has affected patient presentation in Scotland is unknown.

This retrospective cohort study compared all presentations of head and neck cancer between June and October of 2019 with the same period following the peak of the pandemic in 2020 in West Scotland, a region populated by 2.5 million people.

A total of 528 patients met our inclusion criteria. Compared with 2019, patients in 2020 were more likely to present with a higher American Joint Committee on Cancer stage (odds ratio, 1.67 (95 per cent confidence interval = 1.20 to 2.31); p = 0.002), a longer preceding symptom duration (odds ratio, 2.03 (95 per cent confidence interval = 1.44 to 2.87; p < 0.001) and to have an emergency presentation (odds ratio, 2.53, (95 per cent confidence interval = 1.15 to 5.55; p = 0.017).

Patients are presenting later with more advanced head and neck cancer following the coronavirus disease 2019 pandemic.

Compare quetiapine+antidepressant (AD) with lithium+AD, and quetiapine monotherapy with lithium+AD in open, rater-blinded treatment.

Patients with treatment resistant depression (Thase et al 1997 stage 1 and 2) with severity of MADRS ≥25 received: quetiapine XR 300mg/day plus AD (SSRIs or venlafaxine) (n=229), lithium (monitored to between 0.6 to 1.0 meq/l) plus AD (n=221) or quetiapine XR alone (300mg/day) (n=225) for 6 weeks. Primary efficacy measure was change from baseline in MADRS total score. The pre-specified non-inferiority limit was 3 points on the MADRS.

Fewer patients discontinued on quetiapine+AD (15.2%) than lithium+AD (20.5%) and quetiapine monotherapy (21.5%). Quetiapine+AD and quetiapine monotherapy, were not inferior to lithium+AD in the primary (per protocol) analysis with a mean difference (97.5%CI) on the MADRS of -2.32 (-4.6 to -0.05) favouring add-on quetiapine and -0.97 (-3.24 to 1.31) favouring quetiapine monotherapy. This mandated superiority testing on the modified ITT population showing no significant difference at endpoint.

In a post hoc analysis discounting multiplicity, quetiapine+AD was significantly more effective than lithium+AD on the MADRS change from baseline, p=0.046. The advantage was observed at day 4 (p=0.007) and persisted throughout. Efficacy was supported by CGI-I (p=0.07). Quetiapine+AD showed a numerically greater advantage over lithium+AD in those with two failed treatments (Stage 2) rather than one (Stage 1).

Quetiapine+AD and quetiapine monotherapy, were non-inferior to lithium+AD in treatment resistant depression. There was an early significant and persistent efficacy advantage on MADRS for quetiapine augmentation compared with lithium augmentation of SSRI or venlafaxine treatment.

To evaluate once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy (50, 150 and 300mg/day) (acute and maintenance treatment) or adjunct treatment (150 and 300mg/day) in patients with MDD.

Eight (7 acute, 1 maintenance) placebo-controlled studies were analysed. Primary endpoints: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (acute); time from randomisation to depressed event (maintenance). Statistical analyses: ANCOVA for difference between quetiapine XR and placebo in LSM change in MADRS total score from randomisation to study end (LOCF; acute); hazard ratio (HR) for time to recurrence of a depressed event (maintenance).

Figure 1 shows treatment differences (95% CIs) for primary efficacy variable for the seven acute studies. Four monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00014) were significant in favour of quetiapine XR; Study D1448C00004 (monotherapy) was not. Studies D1448C00006 and D1448C00007 were significant in favour of adjunct quetiapine XR. Time from randomisation to depressed event (Study D1448C00005) significantly increased with quetiapine XR; HR (95% CI): 0.34(0.25, 0.46); p< 0.001; number of depressed events: 55, quetiapine XR; 132, placebo. Safety findings were consistent with the known tolerability profile of quetiapine.

Quetiapine XR consistently demonstrated antidepressant efficacy, with 6/7 acute studies positive in favour of quetiapine XR (monotherapy or adjunct). Quetiapine XR maintenance therapy significantly reduced risk of a depressed event, demonstrating relapse prevention. AstraZeneca funded

Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine.

We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N = 931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed.

Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p < 0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American.

Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.

To evaluate efficacy and tolerability of quetiapine XR monotherapy in patients with MDD.

Data were analysed from two 6-week, multicentre, double-blind, placebo-controlled studies (D1448C00001, D1448C00002), prospectively designed to be pooled. Outpatients received quetiapine XR 150mg/day (n=315), 300mg/day (n=323), placebo (n=330). Primary outcome: change at Week 6 in MADRS total scores. Other assessments: MADRS individual item scores, HAM-A total scores, MADRS response and remission; AE reporting.

Quetiapine XR 150mg/day and 300mg/day reduced MADRS total scores at Week 6 (-14.7 and -14.7; p< 0.001) versus placebo (-11.1); significant reductions were also seen at Week 1 (p< 0.001).

Subgroup analyses showed the therapeutic effect of quetiapine XR was neither limited to nor driven by factors such as gender, age or depression severity.

Quetiapine XR demonstrated consistent improvements in MADRS items: both doses significantly improved 8/10 items at Week 6 versus placebo. At Week 6, MADRS response (≥50% decrease in total score) was 52.7% (p< 0.001), 49.5% (p< 0.001) versus 33.0%; MADRS remission (total score ≤10) was 33.7% (p< 0.01), 34.7% (p< 0.01) versus 24.2% for quetiapine XR 150mg/day and 300mg/day and placebo, respectively. Quetiapine XR 150mg/day and 300mg/day improved HAM-A total scores versus placebo at Week 1 (-4.6 [p< 0.01], -4.7 [p< 0.01], -3.6) and Week 6 (-8.1 [p< 0.001], -7.9 [p< 0.001], -6.2). Common AEs (≥10%) were dry mouth, sedation, somnolence, dizziness, headache and nausea with quetiapine XR.

In patients with MDD, quetiapine XR monotherapy improved a broad range of depressive symptoms, with improvements seen from Week 1. Quetiapine XR was generally well tolerated.

Medication non-compliance is common in the treatment of depression, particularly in Asia.

1) To describe the frequency and factors associated with medication non-compliance. 2) To study the influence of non-compliance on treatment outcomes.

Nine hundred and nine in- and out-patients from Asia presenting with a new or first episode of major depressive disorder were enrolled in a 3-month prospective observational study. Clinical severity and quality of life were assessed, using Hamilton Depression Scale (HAMD-17), Clinical Global Impression Severity (CGI-S), and EuroQoL measures (EQ-5D and EQ-VAS). Medication compliance was also assessed by the investigator and patient. Linear and logistic multiple regression models were used to analyze the consequences of non-compliance.

The proportion of non-compliant patients as assessed by the investigator was 16%. Sociodemographic factors and clinical severity were not associated with compliance at baseline. Regression models showed that medication non-compliance was associated with worse depression severity (difference in HAMD-17 -3.98; 95% CI -5.10, -2.87) and overall clinical severity (CGI-S difference -0.46; 95%CI -0.68, -0.24) at three months. Medication non-compliance was also associated with lower quality of life at three months (EQ-VAS difference -7.47; 95%CI -11.13, - 3.82) and EQ-5D score difference -0.08; 95%CI -0.1, -0.04)). Compliant patients had higher odds of response (odds ratio (OR) 3.18; 95% CI 1.98, 5.10) and remission (OR 3.94; 95% CI 2.42, 6.43) compared with non-compliant patients.

Patients non-compliant with medication had worse 3-month outcomes in terms of depression severity, quality of life, and response and remission rates, compared with compliant patients.

The analysis of medication discontinuation may allow the comparison of the effectiveness of different medications and may help us understand treatment patterns in depression. Clinical guidelines recommend at least six months of antidepressant maintenance treatment for major depressive disorder (MDD).

To determine the duration of antidepressant treatment in Asian patients treated with antidepressants for a major depressive episode and to understand the reasons and factors associated with discontinuation.

Nine hundred and nine in- and out-patients from Asia, of which 569 started an antidepressant medication at the baseline visit, presenting with a new or first episode of MDD were enrolled in a 3-month prospective observational study. The Kaplan-Meier method and Cox models were used to estimate discontinuation rates and factors associated with discontinuation. Survival analysis with competing risks was used to analyze the influence of different reasons for discontinuation.

Of the 569 patients included in the study, 430 (75.6%) were evaluated at three months and analyzed. Of them, 242 (56%) discontinued the treatment during the three months follow-up and 188 maintained it. Of the overall sample, half of the patients discontinued the medication within 70 days. The most frequent reason for discontinuation was inadequate response (n=155, 64%), followed by adequate response (n=62, 26%). A relatively high proportion of patients with adequate response (30% at 130 days) discontinued the medication. Country and type of antidepressant were associated with medication discontinuation.

Medication discontinuation in Asian patients with depression is high, even for patients who respond adequately to treatment.

The aims of this study were to determine the presence of painful physical symptoms (PPS) and its impact on depression outcomes in different gender and age groups.

Three hundred in- and out-patients from China presenting with a new or first episode of major depressive disorder were enrolled in a 3- month prospective observational study from Asia (N=909). Hamilton Depression Scale (HAMD-17), Clinical Global Impression Severity (CGI-S), EuroQoL and the pain-related items of the Somatic Symptom Inventory were administered. Patients were classified into three age groups (<40, n=119; =40-<60, n=133; =60, n=48). Linear and logistic regression models were fitted to assess the relationship between PPS at baseline and outcomes.

Older patients had higher HAMD-17 severity at baseline. HAMD score was 25.9 (SD 6.1) in =60 vs. 22.5 (SD 5.0) in <40 and 24.8 (SD 5.2) in =40-<60. There were no statistically significant differences in the proportion of patients with PPS across gender and age groups. During follow-up, depression severity improved. There were no statistically significant differences in the degree of improvement by gender, but there were differences by age group. Mean change in HAMD was -16.4 (95%CI -17.7;-15.1) for those <40, -19.9 (95%CI -21.1;-18.7) in 40-60 and - 20.3 (95%CI -22.6;-17.9) in >60. PPS positive patients had worse clinical and quality of life outcomes across genders and age groups.

The presence of painful physical symptoms is associated with a lower improvement in depression outcomes and a lower quality of life in patients with major depression across different gender and age groups.

Major depressive disorder (MDD) is the second leading cause of disability in China.

To analyze functioning during the course of treating MDD in China, Taiwan and Hong Kong.

To study the influence of pain and clinical remission on functioning.

This was a post-hoc analysis of a 6-month, prospective, observational study (n = 909) with 422 patients enrolled from China (n = 205; 48.6%), Taiwan (n = 199; 47.2%) and Hong Kong (n = 18; 4.2%). Functioning was measured with the Sheehan Disability Scale (SDS), pain with the Somatic Symptom Inventory, and severity of depression with the Quick Inventory of Depressive Symptomatology-Self Report 16 (QIDS). Patients were classified as having no pain, persistent pain (pain at any visit) or remitted pain (pain only at baseline). A mixed model with repeated measures was fitted to analyze the relationship between pain and functioning.

At baseline, 40% of the patients had painful physical symptoms. Patients with pain had a higher QIDS and lower SDS (P < 0.05) at baseline. At 6 months, patients with persistent pain had lower functioning (P < 0.05). The regression model confirmed that clinical remission was associated with higher functioning at endpoint and that patients with persistent pain had lower functioning at endpoint when compared with the no pain group.

Patients presenting with pain symptoms had lower functioning at baseline. At 6 months, pain persistence was associated with significantly lower functioning as measured by the SDS. Clinical remission was associated with better functional outcomes. The course of pain was related to the likelihood of achieving remission.

The authors have not supplied their declaration of competing interest.

The completion of a laser safety course remains a core surgical curriculum requirement for otolaryngologists training in the UK. This project aimed to develop a comprehensive laser safety course utilising both technical and non-technical skills simulation.

Otolaryngology trainees and consultants from the West of Scotland Deanery attended a 1-day course comprising lectures, two high-fidelity simulation scenarios and a technical simulation of safe laser use in practice.

The course, and in particular the use of simulation training, received excellent feedback from otolaryngology trainees and consultants who participated. Both simulation scenarios were validated for future use in laser simulation.

The course has been recognised as a laser safety course sufficient for the otolaryngology Certificate of Completion of Training. To the authors’ knowledge, this article represents the first description of using in situ non-technical skills simulation training for teaching laser use in otolaryngology.