Low-Intensity Cognitive Behavioral Therapy for Insomnia as the Entry of the Stepped-Care Model in the Community: A Randomized Controlled Trial.

Background/Objectives: Diverse low-intensity interventions are available as the entry points in the stepped-care model for insomnia. The study aims to compare a single-session cognitive behavioral therapy for insomnia (CBTI) workshop, self-help CBTI and sleep hygiene education (SHE) workshop among adults with insomnia in the community, in terms of insomnia severity, anxiety and depressive symptoms, the quality of life, treatment adherence and credibility.Participants: Two-hundred-and-ten Hong Kong adults with DSM-5 defined insomnia disorder for at least one month were recruited in the community.Methods: A three-arm-parallel, active-treatment-controlled and assessor-blinded randomized controlled trial was performed. Participants were block-randomized to the half-day CBTI workshop, self-help Internet-delivered CBTI and half-day SHE workshop groups evenly. Eight-week and 16-week post-baseline follow-ups were conducted. The primary outcome measure was the Insomnia Severity Index whereas the secondary measures included the Hospital Anxiety and Depression Scale, the Short-Form Six-Dimension Health Survey, treatment adherence and credibility.Results: All arms demonstrated a significant treatment effect on insomnia severity, anxiety and depressive symptoms and the quality of life. However, there was no difference between arms. Treatment adherence did not vary among the three groups, but treatment credibility of the self-help group dropped whereas that of the CBTI workshop group rose after interventions (p = .037).Conclusions: Despite the lack of between-group differences, self-help CBTI can be considered as the preferred entry point of the stepped-care model for insomnia. It demonstrates comparable efficacy and adherence rate to the workshop-based interventions, and is highly accessible and convenient with few resources required.

Establishment of a novel CYP3A4-transduced human hepatic sinusoidal endothelial cell model and its application in screening hepatotoxicity of pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) are extensively distributed in plants and are known to damage hepatic sinusoidal endothelial cells (HSECs) via metabolic activation mediated by hepatic cytochrome P450 enzymes (CYPs), particularly the CYP3A4 isozyme. Different PAs have distinct toxic potencies and their toxic effects on HSECs are difficult to be determined in cultured cells, because HSECs lack the key CYP3A4 isozyme for metabolic activation. This study aims to establish a novel, convenient and reliable CYP3A4-expressing HSEC model using human HSECs transduced with lentivirus carrying CYP3A4-ires-eGFP, for evaluating the hepatotoxicity of different PAs on their target HSECs. The developed CYP3A4-expressing HSEC (HSEC-CYP3A4) model was verified by the expression of GFP and CYP3A4 and by the ability to metabolize nifedipine, a classic CYP3A4 substrate. Treated with retrorsine, a representative toxic PA, HSEC-CYP3A4 cells showed significantly reduced cell viability, depletion of GSH, and increased formation of pyrrole-protein adducts. Furthermore, this newly developed cell model successfully discriminated the cytotoxic potency of different PAs evidenced by their IC40 values. In conclusion, the established HSEC-CYP3A4 cell model can be used as a rapid screening platform for assessing the relative potencies of individual PAs on their target HSECs and for investigating the mechanisms underlying PA-induced hepatic sinusoidal damage.

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells.

BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. OBJECTIVE: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aß)-induced microglial toxicity associated with the production of pro-inflammatory mediators. METHOD: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aß. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. RESULTS: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1ß, IL-6 and TNF-α in Aß-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aß-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1ß, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. CONCLUSIONS: These findings provided evidence that PS root extracts confer neuroprotection against Aß- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer's disease (AD).

Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aß)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aß)-induced microglia-mediated neurotoxicity. MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aß-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aß-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits. RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aß-induced secretion of pro-inflammatory cytokines (IL-1ß and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aß-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins. CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aß-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.

Factors predicting patient satisfaction in women with advanced breast cancer: a prospective study.

BACKGROUND: The present study (1) examined patient satisfaction with care over the first year following the diagnosis of advanced breast cancer and (2) tested if unmet health system and information needs, physical symptom distress, and psychological distress predicted patient satisfaction. METHODS: Prospective study of 213 Chinese women with advanced breast cancer assessed while awaiting or receiving initial chemotherapy (baseline), then again at 1.5-, 3-, 6-, and 12-months post-baseline. Health system and information unmet (HSI) needs, psychological distress, physical symptom distress, and patient satisfaction were assessed at baseline; patient satisfaction was reassessed at each follow-up assessment. Latent growth curve analysis assessed changes in patient satisfaction over the 12 months follow-up; hierarchical multiple regression analysis tested if baseline health system information needs, physical symptom distress, anxiety and depression predicted patient satisfaction at one-year post-baseline. RESULTS: The level of patient satisfaction was high and did not change significantly over time. Only HSI needs (ß = - 0.27, p < 0.005) significantly associated with baseline patient satisfaction. Patient satisfaction at one-year post-baseline was predicted by HSI needs (ß = - 0.26, p < 0.005), Anxiety (ß = 0.23, p < 0.05) and Depression (ß = - 0.28, p < 0.005), adjusting for the effect of baseline patient satisfaction (ß = 0.22, p < 0.005). CONCLUSIONS: Unmet health information needs and greater depressive symptoms at initial treatment phased predicted subsequent poorer patient satisfaction. This highlights a need to reinforce the importance of patient-centered care model in managing advanced breast cancer.

Profile of mood states and quality of life of Chinese postmastectomy women in Hong Kong: Integrating variable- and person-centered approaches.

Understanding the mood state and its relationship with quality of life (QOL) of mastectomy recipients can serve as baseline within which a sound rehabilitation program can be developed. This study therefore was conducted to facilitate a better understanding of participants' postmastectomy mood states, identify their potential predictors, identify clusters of mood profiles, and clarify between-cluster differences in terms of QOL. Hong Kong mastectomy patients completed the Profile of Mood States and Ferrans and Powers Quality of Life Index. We extended the complementary strengths of the application of both variable- and person-centered approaches to clarify relationships and to identify profiles of mood states in relation to QOL in a sample of 200 women who had undergone a mastectomy in Hong Kong. Simultaneous regression identified age and educational attainment as predictors of mood states, and cluster analysis identified three distinct mood profiles that are able to explain differences in various measures of QOL after mastectomy. Implications for future research and practice are discussed.

Goal adjustment influence on psychological well-being following advanced breast cancer diagnosis.

OBJECTIVE: A diagnosis of advanced breast cancer (ABC) challenges a woman's ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment. METHODS: One hundred ninety three out of 225 women with ABC were assessed while they were awaiting/receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Goal disengagement, goal reengagement, optimism, hope, and psychological adjustment (anxiety, depression, and positive affect) were assessed at baseline; psychological adjustment was reassessed at each follow-up. Latent growth curve modeling was used to examine the change of psychological adjustment and test the study objectives. RESULTS: High goal disengagement, low reengagement, and high optimism were associated with lower initial anxiety, while high goal disengagement and optimism predicted a slower rate of change in anxiety. High goal disengagement, reengagement, and optimism were associated with lower initial depression. High goal reengagement, optimism, and hope were associated with initial positive affect scores, while optimism predicted its rate of change. Optimism moderated the effect of goal disengagement on anxiety and depression, whereas hope moderated the effect of goal reengagement on positive affect. CONCLUSION: Goal disengagement and reengagement are two relatively independent processes influencing psychological well-being. These findings will help clinicians to tailor specific interventions to help women coping with the diagnosis of ABC.

Clinical oncology and palliative medicine as a combined specialty--a unique model in Hong Kong.

The importance of early integration of palliative care (PC) into oncology treatment is increasingly being recognized. However, there is no consensus on what is the optimal way of integration. This article describes a unique model in Hong Kong where clinical oncology and palliative medicine (PM) is integrated through the development of PM as a subspecialty under clinical oncology.

The evolution of supportive care needs trajectories in women with advanced breast cancer during the 12 months following diagnosis.

PURPOSE: This longitudinal study examined if the evolution of supportive care needs differed over the first year following the diagnosis of advanced breast cancer and examined factors differentiating these trajectories. METHODS: Two hundred twenty-eight of 276 Chinese women with advanced breast cancer were assessed while they were awaiting or receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Supportive care needs (SCNS-34-Ch), psychological distress (Hospital Anxiety and Depression scale), symptom distress (MSAS-Ch), and patient satisfaction (PSEQ-9) were assessed at baseline; supportive care needs were reassessed at each follow-up assessment. Latent growth mixture modeling explored if trajectories differed within each of four need domains: health system, information, and patient support (HSIPS); psychological; physical daily living (PDL); and sexuality needs. Logistic regression identified factors predicting trajectory patterns. RESULTS: Two distinct trajectories were identified for HSIPS and sexuality need domains and three distinct trajectories for psychological and physical daily living need domains. Most women showed stable low levels of HSIPS (78.9 %), psychological (82.4 %), PDL (83.7 %), and sexuality (97.4 %) supportive care needs. One in five and one in eight women showed high initial supportive care needs in HSIPS and psychological and PDL domains, respectively. With the exception of sexuality needs, trajectory patterns were predicted by physical symptom distress. Women in the high-decline group reported greater physical symptom distress. CONCLUSIONS: Most Chinese women with advanced breast cancer showed low stable supportive care needs. Physical symptom distress predicted high supportive care needs. Interventions should focus on optimizing symptom assessment and management.

Supportive care needs in Hong Kong Chinese women confronting advanced breast cancer.

BACKGROUND: Women with advanced breast cancer (ABC) are living longer, so understanding their needs becomes important. This cross-sectional study investigated the type and extent of unmet supportive care needs in Hong Kong Chinese women with advanced breast cancer. METHODS: Face-to-face interviews were conducted among women with stage III or stage IV disease mostly awaiting chemotherapy (76%) to identify unmet needs using the Supportive Care Needs Survey Short Form, psychological morbidity using the Hospital Anxiety and Depression Scale, symptom distress using the Memorial Symptom Assessment Scale, and satisfaction with care using the Patient satisfaction questionnaire (PSQ-9). RESULTS: About 27-72% of 198/220 (90%) women (mean age = 53.4 ± 9.74 (standard deviation) years) identified needs from the health system, information, and patient support (HSIPS) domain as the top 15 most prevalent unmet needs. 'having one member of hospital staff with whom you can talk to about all aspect of your condition, treatment, and follow-up' was most cited by 72% of the patients, with remaining unmet needs addressing mostly desire for information. Unmet need strength did not differ between women with stage III and stage IV disease, whereas women with first time diagnosis reported greater health system and information unmet needs compared with women with recurrent disease. Stepwise multiple regression analyses revealed that symptom distress was consistently positively associated with all but sexuality need domains, whereas low satisfaction with care was associated with HSIPS (ß = 3.270, p < 0.001) and physical and daily living (ß = 2.810, p < 0.01) domains. DISCUSSIONS: Chinese women with ABC expressed need for continuity of care and improved information provision. High symptom distress was associated with lower levels of satisfaction with care. These unmet needs appear to reflect current care services shortcomings.

Over-expression of c-erbB-2 correlates with nuclear morphometry and prognosis in breast carcinoma in Asian women.

AIM: We aimed to investigate the immunohistochemical expression of c-erbB-2 in invasive breast carcinoma in Asian women and its correlations with clinicopathological parameters and nuclear morphometry. Patients were followed up for disease relapse and overall survival, and the data were reviewed in conjunction with c-erbB-2 over-expression. METHODS: Paraffin sections from 321 invasive breast cancers were immunohistochemically stained with anti-human c-erbB-2 antibody using the streptavidin-biotin technique. RESULTS: c-erbB-2 was over-expressed in 110 (34.3%) cases, with an inverse correlation with oestrogen receptor (ER) and progesterone receptor (PR) status (p=0.0001) and a positive correlation with histological grade (p=0.017). Nuclear morphometry in 96 cases revealed rounder nuclei in c-erbB-2 negative tumours (p=0.0322) when compared with c-erbB-2 positive tumours. Among c-erbB-2 positive cases, malignant cells of histological grade 3 tumours revealed larger nuclear area and perimeter than grade 1 and 2 cases (p=0.0095, p=0.03, respectively) while increasing tumour size correlated with greater nuclear perimeter (p=0.046). c-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (p=0.0166) and for subsets of node positive, histological grade 1 and 2, and ER positive tumours, and in women aged over 50 years (p=0.0047, p=0.0367, p=0.0092, p=0.0096, respectively). CONCLUSIONS: c-erbB-2 was independently prognostic when histological grade, nodal and ER status were considered. Our results show that c-erbB-2 over-expression correlates with poor histological grade and negative ER/PR status, and predicts poor overall survival in Asian women with breast cancer.