Advancement in the medicolegal requirement for testamentary capacity assessment in older adults: the dilemmas in Hong Kong.

Medical and legal professionals are increasingly involved in probate disputes in which the validity of a will due to a lack of testamentary capacity in older adults is frequently challenged. The legal test for testamentary capacity under common-law jurisdiction was established in the famous case of Banks v Goodfellow (1870). The High Court of Hong Kong recently issued new practice guidance for legal professionals on the preparation of a will for older adults. This paper discusses the dilemmas and competing issues among different parties on this medicolegal interface based on recent literature and local examples. We recommend a risk-based pragmatic framework for legal and medical professionals to minimise potential disputes in testamentary capacity assessment.

Pattern and determinants of burden in Chinese families of adults with obsessive-compulsive disorder.

The burden on caregivers of patients with obsessive-compulsive disorder (OCD) is an important yet under-researched area in the Chinese population. This study aimed to assess the pattern and determinants of burden reported by caregivers of adults with OCD in Hong Kong. Seventy-seven OCD patient-caregiver dyads were recruited from a psychiatric out-patient clinic. Adults were assessed with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Global Assessment of Functioning (GAF) scale. Caregivers were interviewed with the Chinese version of the Family Burden Interview Schedule. Ninety-nine percent of the caregivers experienced objective burden. Mothers of patients with OCD experienced the greatest caregiver subjective burden. Multivariate analysis showed that GAF explained 41.5% and 49.8% of the variance of objective and subjective burden respectively. The functional level of OCD adults was an important determinant of both the objective and subjective burden on caregivers.

The efficacy of oral appliances in the treatment of severe obstructive sleep apnea.

OBJECTIVES: The purpose of this study is to evaluate the efficacy of oral appliance (OA) treatment for subjects with severe obstructive sleep apnea (OSA) and to determine the dental parameters associated with treatment outcomes. STUDY DESIGN: This study uses a prospective longitudinal design. METHODS: Consecutive Chinese subjects with severe OSA who refused continuous positive airway pressure treatment were recruited. Their dental measurements were taken from lateral cephalometric radiographs. Polysomnograms with OA were repeated at 3 months and 1 year. Blood pressure was taken in the morning after sleep studies. RESULTS: Thirty-four subjects were evaluated at 3 months and 1 year according to the principle of intention-to-treat analysis. OA reduced AHI significantly in subjects with favorable responses, from 49.3 (37.4-67) to 12.5 (6.1-15.7), p < 0.001 at 3 months and from 47.5 (41.1-72.9) to 13.1 (6.0-14.0), p < 0.001 at 1 year. These OSA subjects had an increased overjet at baseline compared to those with unfavorable responses (p ≤ 0.05). Systolic blood pressure was significantly reduced in those hypertensive OSA subjects after 3 months and 1 year of treatment. CONCLUSIONS: OA reduces the severity of sleep apnea, and the effect is maintained at 1 year in subjects with retrognathism. OA appears to reduce systolic blood pressure in hypertensive OSA subjects at 3 months and 1 year.

A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies.

BACKGROUND: Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets. METHODS AND FINDINGS: In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5' CpG islands, are induced from undetectable levels by 5-aza-2'-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. CONCLUSIONS: By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention.

Validation of the Chinese Challenging Behaviour Scale: clinical correlates of challenging behaviours in nursing home residents with dementia.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are associated with considerable burden to patients with dementia and their caregivers. Formal caregivers in residential care settings face different challenges when delivering care. OBJECTIVE: This study aimed at assessing the clinical correlates of challenging BPSD using the Chinese version of the Challenging Behaviour Scale (CCBS) designed for residential care settings. METHODS: One hundred and twenty-five participants were recruited from three care-and-attention homes in Hong Kong. The CCBS was administered together with the Cantonese version of Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Disability Assessment for Dementia (DAD) and Neuropsychiatric Inventory (NPI) to explore the relationships between challenging behaviour and important clinical correlates. RESULTS: The CCBS had good internal consistency (alpha = 0.86), inter-rater (ICC = 0.79) and test-retest reliability (ICC = 0.98). A four-factor structure is demonstrated by factor analysis: hyperactivity behaviours, hypoactivity behaviours, verbally aggressive and aberrant behaviours. Challenging behaviours were associated with male gender, cognitive impairment, functional disability, neuropsychiatric symptoms, and higher caregiver's workload. CONCLUSIONS: The CCBS is a valid and reliable measure to assess BPSD in residential care settings in local Chinese community. It is useful in evaluating the challenges faced by formal caregivers during daily care of the dementia patients.

Obstructive sleep apnea and the metabolic syndrome in community-based Chinese adults in Hong Kong.

OBJECTIVE: To investigate the relationship between obstructive sleep apnea (OSA) and the metabolic syndrome, an established cardiovascular risk factor, in middle-aged Chinese subjects. DESIGN: A prospective cross-sectional study from community-dwelling volunteers. SUBJECTS: Subjects of either sex between 30 and 60 years old were recruited from the staff in public institutions or visitors to community centers in Hong Kong. METHODS: Demographic and anthropomentric indices, blood pressure and metabolic profile (fasting blood glucose, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) were measured. Overnight polysomnographic studies were conducted. Presence of obstructive sleep apnea (OSA) was defined as apnea-hypopnea index (AHI)5. Metabolic syndrome was defined by the criteria of the National Cholesterol Education Panel, but using Asian cut-off values for abdominal obesity. RESULTS: A total of 255 subjects (150 men, 105 women) were studied. Subjects with OSA had five-fold risk of having metabolic syndrome. OSA was associated with the metabolic syndrome or its components, including waist circumference, diastolic blood pressure and fasting glucose, after adjusting for confounding variables. The independent determinants of OSA were age, gender, body mass index (BMI) and the metabolic syndrome. CONCLUSION: Among community-based middle-aged Chinese subjects, the metabolic syndrome was independent predictor of OSA.

Primary adenocarcinomas of the lung in nonsmokers show a distinct pattern of allelic imbalance.

Lung cancer development in nonsmokers, particularly in females, has long been observed,but the genetic pathways of oncogenesis are still unclear. The purpose of this study was to identify important targets of chromosomal alteration involved in non-tobacco-related adenocarcinomas of lung. In this study, loci of recurrent allelic imbalance (AI) were identified by microsatellite analysis, focusing on tumors with low frequencies of AI (FAL) relative to the mean level. We reasoned that studying such tumors would facilitate the identification of essential genetic changes needed for the malignant phenotype, which could be masked by genomic instability and widespread nonspecific alterations, especially in tumors showing high FAL. Forty-two adenocarcinomas from nonsmokers (NT-ADs) were analyzed by a broad spectrum of 84 markers covering all nonacrocentric chromosomal arms. Using the mean AI frequency (40%) as the threshold, loci in 7q31, 8p23.2, 10p14-p15, 13q12.3, 16q24, 17p13.1-p13.3, 17q22, 19q13.3, and Xq11.2-q12 showed recurrent AI in the low-FAL tumors, which suggested that essential targets of carcinogenesis may be present. To analyze whether loci, frequently altered in NT-ADs, were uniquely involved in these tumors, 43 loci were also studied in 29 adenocarcinomas from smokers. 2q, 6p, 10p, 13q, 16q, 17q, 19p, 19q, 20p, and 20q showed frequent aberrations in NT-ADs, whereas 1q, 2p, 3p, 3q, 7q, 8p, 9p, 9q, 10q, 11q, 13q, 14q, TP53, 17p, 18q, and 21q were commonly altered in both of the tumor groups. Further comparison of their low-FAL tumors showed that AI involving 16q24, 17q22, and 19q13.3 were significantly associated with NT-ADs; whereas those involving 7q31, 8p23.2, 10p14-p15, 13q12.3, and 17p13.1-p13.3 were observed in both. The findings suggest that oncogenesis in the lung of smokers and nonsmokers involve overlapping yet distinct genetic pathways, whereas the recurrent loci of alteration in NT-ADs may provide a basis for the further mapping of critical molecular targets in these pathways.