Objectives
LevelMind@JC youth mental wellness hubs have been launched as a novel early intervention initiative to mitigate the inevitable youth mental health problems in Hong Kong in 2019. The ...present study investigated the perceptions and experiences of these hubs amonst three key stakeholders, namely hub youths, hub carers of youths and hub staff.
Method
An online survey assessing the perceptions and experiences of hubs on 6 major domains (e.g., youth‐friendly and nonstigmatizing characteristics) was administered to three stakeholders in December 2020. Seventy‐one hub youths (12–35 years old), 18 hub carers (30–64 years old) and 25 hub staff (24–59 years old) completed the survey.
Results
On a 5‐point Likert scale with higher ratings representing better outcomes, all three stakeholders reported above‐average ratings on their overall satisfaction of hub experiences (hub youths: mean = 4.4, SD = 0.6; hub carers: mean = 4, SD = 0.8; hub staff: mean = 3.8, SD = 0.6). In addition, hub youths and hub carers reported above‐average ratings on youth‐friendly and nonstigmatizing characteristics regarding hubs (mean >=4.2).
Conclusions
The present findings suggest that the key stakeholders are generally satisfied with and show support to the youth‐friendly, empowering and nonstigmatizing LevelMind @JC hubs. These findings along with the suggestions for hub improvement made by the stakeholders highlight the importance of taking cultural values into consideration whilst planning for mental services. More importantly, clinical implications are also highlighted which give insight for the development and implementation of a scalable, effective, and replicable early community intervention for psychiatric practise pertaining to youth mental health.
Background:
Self-discrepancy is associated with poorer mental health, yet its mechanism is understudied. A recent study found that resilience plays a moderating role in the relationship between ...self-discrepancy and depressive symptoms in adults. The current study investigated whether there were any similar relationships among young people aged 15 to 24 years.
Methods:
As part of the ongoing Hong Kong Epidemiological Study of Mental Health (HK-YES) project, the current study analysed data from 1,144 participants who provided complete data on ideal-actual selfdiscrepancy, psychiatric conditions, resilience level and recent stressful life events (SLEs).
Results:
Ideal-actual self-discrepancies were associated with increased depressive and anxiety symptoms, as well as odds of 12-month major depressive episodes (MDEs) and generalised anxiety disorder (GAD). All these associations became nonsignificant after adjusting for resilience. Separate models found resilience mediating rather than moderating the relationship. According to four-way decomposition, the pure indirect effect explained most of the total effects of self-discrepancy on mental health conditions. The mediation effects on symptom severity were recently revealed to be more prominent among individuals with substantial exposure to SLE.
Conclusions:
Resilience functions mainly as a mediator in the relationship between self-discrepancy and mental health conditions, and its effect is weakened by the exposure of SLEs. Important implications are discussed regarding the use of resilience-focused interventions and the consideration of recent adversity.
Up to 20% of patients with polycythemia vera have karyotypic abnormalities at the time of the initial diagnosis. However, the cytogenetic abnormalities in polycythemia vera have not been well ...characterized and their prognostic impact is largely unknown. In this study, we aimed to address these issues using a large cohort of polycythemia vera patients with cytogenetic information available. The study included 422 patients, 271 in polycythemic phase, 112 with post-polycythemic myelofibrosis, 11 in accelerated phase, and 28 in blast phase. Abnormal karyotypes were detected in 139 (33%) patients, ranging from 20% in those in the polycythemic phase to 90% among patients in accelerated/blast phase. Different phases harbored different abnormalities: isolated del(20q), +8 and +9 were the most common abnormalities in the polycythemic phase; del(20q) and +1q were the most common abnormalities in post-polycythemic myelofibrosis; and complex karyotypes were the most common karyotypes in accelerated and blast phases. Patients with an abnormal karyotype showed a higher frequency of disease progression, a shorter transformation-free survival and an inferior overall survival compared with patients with a normal karyotype in the same disease phase. Cytogenetics could be effectively stratified into three risk groups, low- (normal karyotype, sole +8, +9 and other single abnormality), intermediate- (sole del20q, +1q and other two abnormalities), and high-risk (complex karyotype) groups. We conclude that cytogenetic changes in polycythemia vera vary in different phases of disease, and carry different prognostic impacts.
Background
Psychotic disorders are associated with a high rate of relapse. In addition to medication non‐adherence, some psychosocial factors have been found to be predictive of relapse (e.g., poor ...premorbid adjustment, high expressed emotion and substance misuse). Impairments in cognitive functions including general memory functioning, set shifting, attention, processing speed and working memory have also been indicative of a subsequent psychotic episode. As clinical appointments do not always allow for timely or accurate detection of these early warning signs, the ReMind app is developed to explore potential relapse predictors and enhance the process of relapse monitoring.
Aim
The ReMind app aims (1) to assess whether verbal or visual working memory predicts psychotic relapse in 1 year and (2) to determine whether social factors such as stressful life events, level of expressed emotion and medication adherence also predict relapse in 1 year.
Methods
This is a one‐year prospective follow‐up study involving 176 remitted patients diagnosed with schizophrenia or non‐affective psychoses. Monthly relapse predictor assessments will be conducted via ReMind throughout the one‐year study duration. These assessments include neurocognitive tasks and psychosocial questionnaires.
Results
Recruitment began in August 2017 and is still ongoing. Preliminary user feedback suggested an overall positive experience with the app.
Conclusion
The ReMind app presents a step forward to the identification and sensitive detection of reliable psychosis relapse predictors. With its anticipated success, it may offer an alternative means of monitoring relapse for the Chinese‐speaking population in the future.
Background
Immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) combinations are a new standard of care for the initial treatment of metastatic renal cell carcinoma (mRCC). Their efficacy ...and toxicity beyond the first‐line setting remain poorly defined.
Methods
We retrospectively reviewed charts for 85 adults with mRCC of any histology receiving combination of ICI/TKI in any line of treatment at two academic centers as of 05/01/2020. We collected clinical, pathological, and treatment‐related variables. Outcomes including objective response rate (ORR), progression‐free survival (PFS), and toxicity were analyzed via descriptive statistics and the Kaplan–Meier method.
Results
Patients received pembrolizumab, nivolumab, avelumab, or nivolumab–ipilimumab, with concurrent use of sunitinib, axitinib, pazopanib, lenvatinib, or cabozantinib. Thirty‐three patients received first‐line ICI/TKI therapy, while 52 received ≥ second‐line ICI/TKI. The efficacy of ICI/TKI therapy decreased with increasing lines of treatment (ORR: 56.7%, 37.5%, 21.4%, and 21%; median PFS mPFS: 15.2, 14.2, 10.1, and 6.8 months, for first, second, third, and ≥ fourth line therapy, respectively). In the ≥ second‐line setting, ICI/TKI was most useful in patients who received ICI only, with an ORR of 50% and a mPFS of 9.1 months. Efficacy was limited in patients who received both TKI and ICI previously, with an ORR of 20% and a mPFS of 5.5 months. Overall, ≥ second‐line ICI/TKI was tolerable with 25 of 52 (52%) patients developing grade ≥3 adverse events.
Conclusions
ICI/TKI combination therapy is feasible and safe beyond the first‐line setting. Prior treatment history appears to impact efficacy but has a lesser effect on safety/tolerability.
ICI/TKI combination therapy is effective and safe beyond the first‐line setting. Prior treatment history appears to impact efficacy but has a lesser effect on safety/tolerability.
Background
Salvage nivolumab and ipilimumab after prior anti‐PD‐1/PD‐L1 therapy is frequently used off‐label for clear cell metastatic renal cell carcinoma (mRCC). However, limited data are available ...to guide such therapy. We performed a meta‐analysis to characterize further the safety and efficacy of salvage nivolumab and ipilimumab.
Methods
We conducted a systematic review in accordance with PRISMA. Studies of salvage nivolumab and ipilimumab in patients with mRCC published in English before June 1, 2021 were included. We also included patients treated at the Ohio State University from 2012 to 2020 through a retrospective chart review. The included studies were further stratified into adaptive and standard groups based on their designs. We calculated objective response rate (ORR) and adverse events (AEs) via pooled data and quantitative synthesis using the Stata metaprop procedure. A conservative random effect model was used to combine values.
Results
A total of 7 studies and 310 patients were included. Salvage nivolumab and ipilimumab had an ORR of 14% (95% CI, 0.09–0.21) and median progression‐free survival ranged between 3.7 and 5.5 months. Four out of the seven studies were standard design, whereas the other three studies were adaptive. The ORR was numerically higher in the standard group compared with the adaptive group (21% and 9–10%, respectively). The responses to salvage nivolumab and ipilimumab did not correlate with the initial anti‐PD‐1/PD‐L1 responses (odds ratio = 1.45; p = 0.5). Grade ≥3 AEs occurred in 26% of the patients (95% CI, 0.19–0.33). There were no new safety signals observed in this study.
Conclusion
Salvage nivolumab and ipilimumab demonstrated moderate antitumor activity and a manageable safety profile in patients with mRCC who had prior anti‐PD‐1/PD‐L1 therapy.
Implication for Practice
Patients with metastatic renal cell carcinoma have limited treatment options after progressive disease on anti‐PD‐1/PD‐L1 therapy. The role of salvage nivolumab and ipilimumab in this patient population is poorly defined. The studies on this highly important and clinically relevant topic are limited by small sample sizes. The results from our meta‐analysis suggest that nivolumab and ipilimumab are feasible in the salvage setting with moderate efficacy and acceptable toxicity profile. The response rates differ with different treatment designs. This information will be beneficial to guide clinical decision‐making and accurately estimating toxicity.
The role of salvage nivolumab and ipilimumab after progressive disease on anti‐PD‐1/PD‐L1 therapy is poorly defined. The studies on this highly important and clinically relevant topic are limited by small sample sizes. The results from our meta‐analysis suggest that nivolumab and ipilimumab are feasible in the salvage setting with moderate efficacy and acceptable toxicity profile. The response rates differ with different treatment designs.
This study aims to investigate the feasibility of improving the prognosis stratification of the N staging system of Nasopharyngeal Carcinoma (NPC) from quantitative spatial characterizations of ...metastatic lymph node (LN) for NPC in a multi-institutional setting. A total of 194 and 284 NPC patients were included from two local hospitals as the discovery and validation cohort. Spatial relationships between LN and the surrounding organs were quantified by both distance and angle histograms, followed by principal component analysis. Independent prognostic factors were identified and combined with the N stage into a new prognostic index by univariate and multivariate Cox regressions on disease-free survival (DFS). The new three-class risk stratification based on the constructed prognostic index demonstrated superior cross-institutional performance in DFS. The hazard ratios of the high-risk to low-risk group were 9.07 (p < 0.001) and 4.02 (p < 0.001) on training and validation, respectively, compared with 5.19 (p < 0.001) and 1.82 (p = 0.171) of N3 to N1. Our spatial characterizations of lymph node tumor anatomy improved the existing N-stage in NPC prognosis. Our quantitative approach may facilitate the discovery of new anatomical characteristics to improve patient staging in other diseases.
A concise, enantioselective synthesis of the potent dual orexin inhibitor suvorexant (1) is reported. Key features of the synthesis include a mild copper-catalyzed amination, a highly chemoselective ...conjugate addition, and a tandem enantioselective transamination/seven-membered ring annulation. The synthesis requires inexpensive starting materials and only four linear steps for completion.
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