Investigation of mutation spectrum amongst patients with familial primary cardiomyopathy using targeted NGS in Indian population.

Genetic cardiomyopathies (CM) are disorders that affect morphology and function of cardiac muscle. Significant number of genes have been implicated in causing the phenotype. It is one of the leading genetic causes of death in young. We performed a study to understand the genetic variants in primary cardiomyopathies in an Indian cohort. Study comprised of 22 probands (13 with family history) representing hypertrophic (n = 10), dilated (n = 7), restrictive (n = 2) and arrhythmogenic ventricular(n = 3) cardiomyopathies. Genomic DNA was target captured with a panel of 46 genes and libraries sequenced on Illumina platform. Analysis identified, reported pathogenic as well as novel pathogenic (n = 6) variants in 16 probands. Of the 10 HCM patients, candidate variants were identified in nine of them involving sarcomere genes (62%, MYBPC3, MYH6, MYH7, MYL3, TTN), Z-disc (10%, ACTN2, LDB3, NEXN,), desmosome (10%, DSG2, DSP, PKP2) cytoskeletal (4%, DTNA) and ion channel (10% RYR2). In four DCM patients, variants were identified in genes NEXN, LMNA and TTN. Three arrhythmogenic right ventricular cardiomyopathy (ARVD) patients carried mutations in desmosome genes. Rare TTN variants were identified in multiple patients. Targeted capture and sequencing resulted in identification of candidate variants in about 70% of the samples which will help in management of disease in affected individual as well as in screening and early diagnosis in asymptomatic family members. Amongst the analysed cases, 22% were inconclusive without any significant variant identified. Study illustrates the utility of next-generation multi-gene panel as a cost-effective genetic testing to screen all forms of primary cardiomyopathies.

Psychometric assessment of the Bahasa Malaysia version of the Older Americans Resources and Services-Instrumental Activities of Daily Living (OARS-IADL).

OBJECTIVE: This study aimed to determine the psychometric properties of the Bahasa Malaysia (BM) version of the Older Americans Resources and Services-Instrumental Activities of Daily Living (OARS-IADL) questionnaire among older persons in Malaysia. METHODS: The English version of OARS-IADL was translated to BM. The psychometric properties of the BM version of OARS-IADL were tested among older persons attending a health-care facility. RESULTS: Two hundred and seventy-one older persons participated in the study. The mean age of participants was 67.7 ± 6.1 years. Internal consistency of the items was good (Cronbach's alpha, >0.7). Exploratory factor analysis revealed a single dimension with item factor loadings of >0.5. Confirmatory factor analysis results confirmed a single-factor model (AVE > 50%, CR > 0.7 and CR > AVE). CONCLUSION: The BM version of the OARS-IADL questionnaire is a valid and reliable instrument that can be used to assess the IADL among older persons in Malaysia.

Predictors of Quality of Life among Older People with Mild Cognitive Impairment Attending Urban Primary Care Clinics.

OBJECTIVES: To study the prevalence of Mild Cognitive Impairment (MCI) among older people attending primary care clinics and its predictors of QOL. METHODS: A cross-sectional study was conducted at two primary care clinics in Kuala Lumpur, Malaysia, recruiting 271 participants by utilizing the universal sampling method. Every patient who attended both the clinics during the study period and met the inclusion and exclusion criteria were approached and briefed about the study. Patients who gave consent were recruited as study participants. Information on sociodemographic, medical condition, and lifestyle behaviors were obtained. The Montreal Cognitive Assessment (MoCA) was used to screen for MCI at a score < 23. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire was used to evaluate QOL. RESULTS: Prevalence of MCI was 27.3%. Lower QOL scores were found in the physical (67.3 ± 1.4), psychological (67.3 ± 1.4), social (66.9 ± 1.6) and environmental (71.3 ± 1.3) domains among participants with MCI. Among them, predictors of QOL were depression in the physical domain, age and stroke in the psychological domain, presence of other types of disorders in the social domain and diabetes and stroke in the environmental domain. CONCLUSIONS: MCI was prevalent among study participants and were associated with poorer QOL in all domains of QOL. A better understanding of predictors of QOL in older people with MCI is deemed important. CLINICAL IMPLICATION: Routine cognitive screening at primary care clinics will facilitate early recognition of MCI and facilitates referral to memory clinics for further assessment and treatment.

Switch-associated adverse events: focus on olanzapine.

OBJECTIVES:: Switching between different antipsychotic therapies is a frequent occurrence in the management of patients with schizophrenia and other psychotic disorders. This paper provides a review of the principles of antipsychotic switching and discusses pharmacological principles underlying adverse events that occur while switching olanzapine to another antipsychotic medication. It offers suggestions for management of switch-associated adverse events in clinical settings. CONCLUSIONS:: Few publications explore olanzapine switch-related adverse events, the underlying pharmacological principles and appropriate switching strategies to minimise the risk of adverse events. There is still a need for further studies to verify existing knowledge and assist in the development of 'gold standard' guidelines that outline appropriate switching strategies and duration of the switching process to reduce and avoid adverse events.

Psychometric Properties of the Malay Version of the Dutch Eating Behaviour Questionnaire (DEBQ) in a Sample of Malaysian Adults Attending a Health Care Facility.

OBJECTIVE: This study aims to investigate the psychometric properties of the Malay version of the Dutch Eating Behaviour Questionnaire (DEBQ) among Malaysian adults. METHOD: The Malay version of the DEBQ instrument was administered to 398 outpatients (269 women and 129 men) at the University of Malaya Medical Centre (UMMC). Confirmatory Factor Analysis (CFA) was conducted to study the construct validity of the instrument. Composite reliability coefficient, Raykov's rho, was used to determine the internal consistency. RESULTS: The proposed three-factor structure for the DEBQ instrument was appropriate, although three items (Items 21, 14 and 27) showed problematic loadings with inappropriate model fit and were removed. The modified version had an appropriate model fit χ2/df = 2.129, TLI = 0.908, CFI = 0.918, RMSEA = 0.053 (90%CI = 0.048-0.058), close-fit P-value = 0.136 and satisfactory internal consistency of 0.914 for emotional eating scale, 0.819 for external eating scale and 0.856 for restrained eating scale. DISCUSSION: The Malay version of the DEBQ is a valid instrument to study eating behaviour traits among Malaysian adults. Further research is warranted to determine if Items 14 and 27 are appropriate for the Malaysian population.

The 2004 tsunami in Penang, Malaysia: early mental health intervention.

Disasters, natural or man-made, bring numerous health care challenges. In any crisis, mental health programs are a requirement during both the acute and postemergency phases. In the Asian tsunami on December 26, 2004, some of the northwestern coastal areas of Malaysia, particularly the island of Penang, were affected with devastating effects on the residents. Such disasters can predispose to mental health problems among the affected people. An early mental health intervention program was carried out in Balik Pulau, Penang, an area badly affected by the tsunami. The objective of the intervention program was to identify the victims, counsel them, make referrals if necessary, and provide help and resources to prevent the development of mental health problems. Penang residents identified as tsunami victims by the local health authorities were recruited. A group of health care workers, school teachers, village authorities, and volunteers were trained to carry out the crisis intervention program by health care workers experienced in crisis interventions. A total of 299 adults participated in the crisis intervention program, with follow-up assessments being made 4 to 6 weeks later. At the follow-up assessment, 1% of the victims had a problem and they were then referred for further medical assessment. This indicates that the intervention program in the first 2 weeks after the tsunami disaster with referrals to medical services may have helped stabilize the victims.

Delayed fathering and risk of mental disorders in adult offspring.

INTRODUCTION: Delayed parenting and child bearing at a very young age impose various risks to development of the offspring. OBJECTIVE: This study aims to investigate the association between disparities in parental age and increased risk factor for common mental disorders in the progenies during adulthood. METHODOLOGY: The Malaysian Mental Health Survey (MMHS) was analysed for this study. Respondents were asked to estimate the age of their parents at their birth. Presence of common mental disorders (CMD) was determined by referring to the diagnosis given by the Clinical Interview Schedule-Revised (CIS-R) instrument in the Programmed Questionnaire System (PROQSY) format. The association between parental age disparities and CMD was studied using logistic regression. RESULT: Fifty three percent (n=1972) of the MMHS respondents (N=3666) knew the age of both parents and were included in the study. Three percent (n=53) had significant disparity in parental age, or a difference of 11 years or more. Respondents born to parents with significant age disparity had a prevalence rate of 24% (95% CI=22.12-25.89) for CMD in comparison to 6% (95% CI=5.99-6.11) in their counterparts and 3.4 times higher risk for CMD, after adjusting for demographic factors, paternal age at birth and presence of family history of mental disorders. Amongst those born to older fathers aged 50 and above, the presence of disparity increased the rate for CMD to 42% (95% CI=39.82-44.18). DISCUSSION: Disparity in parental age was significantly associated with increased risk for CMD. Various psychosocial factors contributing to age disparity in both the father and the mother could predispose to stress and mental health problems.

Sociodemographic risk factors and correlates of dementia in older Malaysians.

OBJECTIVE: The rapid expansion of the aged population in Malaysia is expected to greatly increase the number of persons with dementia in the country. However, data on dementia prevalence at the national level is lacking, and little is known about the sociodemographic risk factors and correlates of dementia. This paper describes a nationwide study of dementia prevalence and its sociodemographic risk factors and health correlates among older Malaysians. METHODS: In the nationwide study, the Mental Health and Quality of Life of Older Malaysians, AGECAT-GMS was used to diagnose dementia in a nationally representative sample of 2,980 persons aged 60 and above. RESULTS: The prevalence rate of dementia was 14.3%. Higher dementia prevalences were found in oldest age (26.3%), women (19.7%), no formal education (24.1%), Bumiputeras (32.2%), unmarried (19.4%), unemployed (31.3%) and very poor on self-rated health (33.3%). Multivariate logistic regression analyses showed that older age, female gender, no formal education, ethnicity and very poor self-rated health were independent risk factors and correlates of dementia. CONCLUSIONS: Relatively higher prevalence rates of dementia in older Malaysians were accounted for by greater proportions without education, Malay and Bumiputera ethnicity, and other unknown factors which should be further investigated.

Factors contributing to utilization of health care services in Malaysia: a population-based study.

OBJECTIVE: This paper examines the factors contributing to the under utilisation of health care services in the Malaysian population. METHODOLOGY: Using data derived from Malaysian Mental Health Survey (MMHS) information on utilisation of four basic health services in the previous three months, namely contact with health care professionals, ward admissions, having diagnostic or laboratory tests done and being on any medications were obtained. RESULTS: A total of 2202 out of 3666 or 60% of the MMHS participants were included in this study. Thirty percent of the subjects (n = 664) had contacts with health care professionals. Those with health complications, disabilities and those aged 50 years and above utilised health services more significantly as compared to those who lacked health facilities near their homes, had little family support during illnesses and were from the Chinese ethnic group. CONCLUSION: Factors leading to the under utilisation of health care services need to be further studied and needs in certain groups in the population should be addressed. Healthcare providers must be prepared to fulfil these needs.

Paternal age and common mental disorders.

INTRODUCTION: There is evidence in the literature that there are associations between advancing paternal age and psychosis or more specifically schizophrenia, but not enough to support a strong link between advancing paternal age and common mental disorders. OBJECTIVE: This study aims to explain the association between paternal age at birth and common mental disorders in progeny during their adulthood. METHODOLOGY: This is a sub-study from a larger survey which was planned to study the epidemiology of mental disorders in Malaysia. Respondents who could remember the age of parents at birth were included in the study. The diagnosis of common mental disorders (CMD) was made using the CIS-R (Clinical Interview Schedule-Revised) instrument in the PROQSY (Programmed Questionnaire System) format. Association between paternal age at birth and CMD was studied using logistic regression, after controlling for age, gender, ethnicity and presence of family history of mental disorders. RESULTS: Respondents with paternal age at birth of 19 and below and 50 above and had higher rates of 10 and 25% for common mental disorders (chi(2)=7.007, P=0.072) with odds ratios of 2.89 (95% CI of OR = 1.1-7.6) and 4.28 (1.4-12.7). DISCUSSION: Progenies of fathers under 20 and over 50 had higher risk for mental disorders. Factors such as immaturity in sperm of teenage fathers, mutation in germ line of older fathers, environmental and psychosocial factors could have contributed to increased prevalence of common mental disorders in the progeny.

Test anxiety: state, trait and relationship with exam satisfaction.

Test anxiety is defined as the reaction to stimuli that is associated with an individual's experience of testing or evaluating situations. This study aims to examine the fluctuation pattern of anxiety symptoms during a clinical examination and its relationship with underlying anxiety traits. Fourth year medical students of Penang Medical College undertaking the Ophthalmology clinical examination participated in this study. First phase of the survey, on anxiety symptoms was conducted immediately after the Ophthalmology clinical examination while the second phase, on pre-existing anxiety traits was conducted six weeks later with the aid of STAI instrument. Responses for both stages were combined and analyzed. Sixty-three of 122 students responded to both phases of the study, giving a response rate of 52%. All symptoms except trembling peaked 10 minutes before the exam begun showing a downward progression with no resurgence thereafter. Students with pre-existing anxiety traits had high anxiety scores 10 minutes into the examination and while with the examiners. Anticipatory anxiety is a source of concern and can effect performance and appropriate steps should be taken to help the students with this. A few other studies should be done to conclude.

The Clinical Interview Schedule-Revised (CIS-R)-Malay Version, Clinical Validation.

Use of instruments or questionnaires in different cultural settings without proper validation can result in inaccurate results. Issues like reliability, validity, feasibility and acceptability should be considered in the use of an instrument. The study aims to determine the usefulness of the CIS-R Malay version in detecting common mental health problems specifically to establish the validity. The CIS-R instrument (PROQSY* format) was translated through the back translation process into Malay. Inter rater reliability was established for raters who were medical students. Cases and controls for the study were psychiatric in patients, out patient and relatives or friends accompanying the patients to the clinic or visiting the inpatients. The Malay version of CIS-R was administered to all cases and controls. All cases and controls involved in the study were rated by psychiatrists for psychiatric morbidity using the SCID as a guideline. Specificity and sensitivity of the CIS-R to the assessment by the psychiatrist were determined. The Malay version of CIS-R showed 100% sensitivity and 96.15% specificity at a cut off score of 9. The CIS-R can be a useful instrument for clinical and research use in the Malaysian population for diagnosing common mental disorders like depression and anxiety.

Anxiety, depression and psychosocial stress in patients with cardiac events.

Stress tends to worsen the prognosis of patients with coronary heart disease. The aim of the study is to determine the relationship between stress related psychosocial factors like anxiety, depression and life events and temporally cardiac events specified as acute myocardial infarction and unstable angina 65 subjects with confirmed myocardial infarction or unstable angina were interviewed using 2 sets of questionnaire, the Hospital Anxiety and Depression Scale (HADS) and Life Changes Stress Test, a segment of the Rahe's Stress and Coping Inventory first at time of occurrence of their cardiac event and the second time was 6 months later. Anxiety, depression and life events scores were calculated for both and recurrence of cardiac event for the 6 month duration was also recorded. Patients who had significant levels of depression and or life events were ten times more likely to have recurrence of cardiac events as compared to those without risk for either of these psychological symptoms. Anxiety, depression and stress levels are significantly increased after the onset of ischemic heart disease and could be contributing or predisposing factors for the recurrence of cardiac events for these patients.

An open label study of the use of EEG biofeedback using beta training to reduce anxiety for patients with cardiac events.

OBJECTIVE: To establish the effectiveness of EEG biofeedback using beta training as a relaxation technique and ultimately reducing anxiety levels of patients with confirmed unstable angina or myocardial infarction. METHODOLOGY: Patients with confirmed unstable angina or myocardial infarction referred by cardiologists were recruited 2-3 days after their cardiac event from the cardiology wards. Their initial anxiety scores were determined using the Hospital Anxiety and Depression Scale. Those that returned for therapy underwent instrument feedback training using EEG every two weeks for a total of five sessions. EEG frequencies were measured for all sessions. Dropouts who did not participate in the program agreed to return 3 months later for the second psychological assessment. The study design was uncontrolled. RESULTS: Subjects had significantly lower anxiety scores at the second screening (p < 0.001), while the dropouts had significantly higher scores (p < 0.001). Beta training was effective in increasing sensory motor rhythm (SMR) waves but no significant effect was present for the alpha waves. CONCLUSIONS: The uncontrolled nature of the study limits firm conclusions. However, the significantly lowered anxiety scores for subjects and enhancing of SMR waves indicate the effectiveness of beta training as a promising approach to EEG biofeedback for anxiety reduction.