Cardiovascular risk in chronic myeloid leukaemia: A multidisciplinary consensus on screening and management.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for chronic myeloid leukaemia (CML), but cardiovascular (CV) risk and exacerbation of underlying risk factors associated with TKIs have become widely debated. Real-world evidence reveals little application of CV risk factor screening or continued monitoring within UK CML management. This consensus paper presents practical recommendations to assist healthcare professionals in conducting CV screening/comorbidity management for patients receiving TKIs. METHODS: We conducted a multidisciplinary panel meeting and two iterative surveys involving 10 CML specialists: five haematologists, two cardio-oncologists, one vascular surgeon, one haemato-oncology pharmacist and one specialist nurse practitioner. RESULTS: The panel recommended that patients commencing second-/third-generation TKIs undergo formal CV risk assessment at baseline, with additional investigations and involvement of cardiologists/vascular surgeons for those with high CV risk. During treatment, patients should undergo CV monitoring, with the nature and frequency of testing dependent on TKI and baseline CV risk. For patients who develop CV adverse events, decision-making around TKI interruption, cessation or change should be multidisciplinary and balance CV and haematological risk. CONCLUSION: The panel anticipates these recommendations will support healthcare professionals in implementing CV risk screening and monitoring, broadly and consistently, and thereby help optimise TKI treatment for CML.

Child and adolescent psychiatry in the Far East: A 5-year follow up on the Consortium on Academic Child and Adolescent Psychiatry in the Far East (CACAP-FE) study.

AIM: Data pertaining to child and adolescent psychiatry (CAP) training systems are limited as extant research has mostly been derived from one-time data collection. This 5-year follow-up survey collects updated information on CAP training systems in the Far East, allowing for the tracking of system changes over the past 5 years. METHODS: Data were obtained from 18 countries, or functionally self-governing areas, in the Far East, 17 of which were also included in the original study. An online questionnaire was completed by leading CAP professionals in each country. Questions were expanded in the present study to capture the contents of CAP training. RESULTS: When compared to data from the original study, there has been progress in CAP training systems in the last 5 years. Specifically, there has been an increase in the number of countries with CAP training programs and national guidelines for the training. In addition, the number of CAP departments/divisions affiliated with academic institutions/universities has increased. Findings from 12 of 18 countries in the present study provide data on clinical contents. All informants of the present study reported the need for more child and adolescent psychiatrists and allied professionals. CONCLUSION: Despite progress in CAP training systems over the last 5 years, the need for more professionals in child and adolescent mental health care in all the relevant areas in this region have yet to be adequately addressed. Continued national efforts and international collaborations are imperative to developing and sustaining new CAP training systems while facilitating improvements in existing programs.

Design, Synthesis, and Evaluation of N- and C-Terminal Protein Bioconjugates as G Protein-Coupled Receptor Agonists.

A G protein-coupled receptor (GPCR) agonist protein, thaumatin, was site-specifically conjugated at the N- or C-terminus with a fluorophore for visualization of GPCR:agonist interactions. The N-terminus was specifically conjugated using a synthetic 2-pyridinecarboxyaldehyde reagent. The interaction profiles observed for N- and C-terminal conjugates were varied; N-terminal conjugates interacted very weakly with the GPCR of interest, whereas C-terminal conjugates bound to the receptor. These chemical biology tools allow interactions of therapeutic proteins:GPCR to be monitored and visualized. The methodology used for site-specific bioconjugation represents an advance in application of 2-pyridinecarboxyaldehydes for N-terminal specific bioconjugations.

Suicidal ideation among single, pregnant adolescents: The role of sexual and religious knowledge, attitudes and practices.

Pregnant adolescents are a high-risk population for suicide. However, a knowledge gap still exists on how sexual and religious knowledge, attitudes and practices (KAP) influence suicidal ideation (SI) in teenage pregnancy. We aim to explore the interplay between psychiatric diagnoses, sociodemographic factors and KAP of sexual and religious issues as risk factors of SI among 114 pregnant Malaysian adolescents from 6 rehabilitation centers and a tertiary hospital. Single sexual partner was an independent predictor of SI, suggesting the role of less sexual experience as a risk factor for SI after controlling for major depression. Participants who were unsure versus those who agreed with the statement that most religions' viewed sex outside marriage as wrong had a lower risk of SI after controlling for major depression. Pregnant adolescents with a single sexual partner were significantly associated with current SI. Ambivalence towards religious prohibitions on premarital sex may protect against suicidal ideation.

Behavioral and emotional problems in a Kuala Lumpur children's home.

BACKGROUND: There is a dearth of studies on behavioral and emotional problems in residential care children in Malaysia. This study describes the behavioral and emotional problems in a sample of children in a government residential care home and compares them with their classmates living with their birth parents. METHODS: A comparative cross-sectional study was carried out where carers from both groups were asked to fill in the translated Bahasa Melayu version of the Child Behavior Check List. RESULTS: Forms for 53 residential care children and 61 classmates were completed. The residential care children had significantly higher scores on the rule-breaking (P < 0.001) and Diagnostic and Statistical Manual of Mental Disorders (DSM) conduct problem subscales (P < 0.001). Residential care children's age significantly correlated with DSM somatic problems (P = 0.03) and post-traumatic stress (P = 0.023). Duration of care was significantly positively correlated with rule-breaking (P = 0.008), DSM conduct problems (P = 0.018) and externalizing scores (P = 0.017). Abuse and neglect cases had higher anxiety and depression scores (P = 0.024). Number of reasons in care positively correlated with several subscales, including total behavioral problem score (P = 0.005). Logistic regression revealed the greater number of reasons for placement a child had was significantly associated with having externalizing scores in the clinical range (P = 0.016). However, after Bonferroni correction, only the initial findings regarding rule-breaking and DSM conduct problem scores remained significant. CONCLUSIONS: Challenges exist in managing residential care children in Malaysia, especially regarding externalizing behavior. More studies are required to describe the Malaysian scene.

Identifying and overcoming barriers to participation of minority populations in clinical trials: Lessons learned from the VanDAAM study.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time.

Functional outcomes after lateral crural J-flap repair of external nasal valve collapse.

OBJECTIVES: We evaluated the lateral crural J-flap technique in the surgical repair of external nasal valve collapse with standardized and validated outcome measurements. METHODS: Prospective data were gathered on consecutive cases, performed by a single surgeon between 2007 and 2010, of adult patients who underwent a lateral crural approach to repair of external nasal valve collapse. Data were collected on diagnosis, surgical outcomes, and complications. Outcome measures included the Nasal Obstructive Symptom Evaluation and the Rhinoplasty Outcome Evaluation. RESULTS: Fifteen patients were included in the study. Their follow-ups ranged from 9 to 13 months. All patients had statistically significant improvements in Nasal Obstructive Symptom Evaluation scores. There was no significant change in perceived nasal appearance after surgery as measured by the Rhinoplasty Outcome Evaluation. There were no surgical complications. CONCLUSIONS: The lateral crural J-flap approach to repair of external nasal valve collapse is a technically straightforward and relatively safe procedure. The efficacy is excellent at the 1-year follow-up examination.

A case of sexual abuse by a traditional faith healer: are there potential preventions?

Adolescent sexual abuse is not an uncommon phenomenon in Malaysia. It is a traumatic experience that complicates the psychosocial development of young people on the threshold of adulthood. This case report highlights the psychosocial sequelae of adolescent sexual abuse by a traditional healer and discusses management issues in the context of unique cultural and belief systems.

Implementation of problem-based learning in child and adolescent psychiatry: shared experiences of a special-interest study group.

BACKGROUND/OBJECTIVE: Problem-based learning (PBL) represents a major development and change in educational practice that continues to have a large impact across subjects and disciplines worldwide. It would seem that child and adolescent psychiatry, because of its inherently integrative, bio-psycho-social nature and emphasis on teamwork and collaboration, would be a specialty learned optimally through PBL. Thus, there was a need to establish an international group where experiences in implementing PBL in child and adolescent psychiatry could be shared. This article reports on the first meeting and plans of the Problem-Based Learning in Child and Adolescent Psychiatry (CAP) Special Interest Study Group (SISG), held at the annual meeting of the American Academy of Child and Adolescent Psychiatry. METHODS: Through international collaboration and information-sharing, the SISG aims to promote knowledge among Child and Adolescent Psychiatrists on PBL, to explore evaluation methods of PBL in CAP, and to discuss development of PBL-based curricula. RESULTS: Problem-based learning (PBL) represents a major change in education that has had a large impact across disciplines worldwide. CONCLUSION: The core steps in PBL are the following: presentation of the initial problem; discussion of the problem, and development of learning objectives; independent learning focused on the objectives; and discussion, exploration of new ideas, and discovery of solutions in the reconvened group. Different from the traditional teacher's role, the PBL tutor is an active facilitator who guides learners to identify issues and ways to learn, rather than a "content expert" who provides facts.

Growing wealth and growing pains: child and adolescent psychiatry in Hong Kong, Malaysia and Singapore.

OBJECTIVE: Several Asian regions have undergone a dramatic transformation, some becoming very affluent. This paper aims to ascertain how countries that are becoming wealthy have dealt with child and adolescent mental health issues. METHOD: Population health status, child and adolescent mental health services, child psychiatry training, the number of child psychiatrists and related matters were examined in Hong Kong, Malaysia and Singapore. RESULTS: Hong Kong, Malaysia and Singapore are ethnically, religiously, socially and politically very different. In spite of considerable wealth and a growing recognition that mental health problems in the young are increasing, they face similar problems--lack of access to treatment due to a dearth of services and a lack of child psychiatrists (2.5, 0.5 and 2.8 per million people, respectively). CONCLUSIONS: Because the number of child psychiatrists is so small, their ability to provide services, advocate, train, maintain a professional identity, and deal with future crises is very limited. Other rapidly developing countries can learn from this experience and should take action early to prevent a similar outcome.

Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities.

The aim of this pilot study was to examine the relationship between clinical response, adverse effects, sertraline (SERT) plasma concentrations and the genetic polymorphism of the serotonin transporter gene-linked polymorphic region (5HTTLPR) in 2 ethnic patient groups. The study involved 45 patients in a clinical trial who received a fixed dose regimen of 50 mg SERT for one week, then a variable-dose regimen for a further 6 weeks for major depressive disorder. At weeks 1 and 6, the following assessments were completed: Hamilton Depression Rating Scale (HDRS), Clinical Global Impression (CGI), drug adverse reaction scale and measurement of plasma SERT levels. Genomic analysis for the long and short allele variants of the 5HTTLPR polymorphism was also carried out. Caucasian subjects had a higher rate of l/l genotype while Chinese subjects had higher frequencies of l/s and s/s genotypes. Comparison of the subjects with the 5HTTLPR s/s genotype and those with the l/l and l/s genotypes found no significant differences in the HDRS scores, CGI scores, response rates, adverse effects and SERT plasma concentrations at week 6.

Incidence and Risk Factors of Velopharyngeal Insufficiency Postadenotonsillectomy.

OBJECTIVES: To evaluate the incidence and risk factors of velopharyngeal insufficiency (VPI) postadenoidectomy, posttonsillectomy, and postadenotonsillectomy. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary care center (2007-2014). SUBJECTS AND METHODS: Retrospective review of patients who underwent adenoidectomies, tonsillectomies, or adenotonsillectomies by 1 pediatric otolaryngologist. Patient's age, sex, type of surgery, indication for surgery, medical syndromes, tonsil grade, adenoid size, and pre- and postoperative nasal air emissions were obtained. RESULTS: The VPI risk at 3 weeks postoperatively was 13.6% (95% CI: 9.0%, 18.2%) for adenotonsillectomies, 3.2% (95% CI: 1.2%, 7.6%) for adenoidectomies, and 2.2% (95% CI: 2.1%, 6.5%) for tonsillectomies. There was a significantly higher risk of VPI with combined procedures in comparison with adenoidectomies (P = .02) or tonsillectomies alone (P = .03). There was no significant difference in risk of VPI between adenoidectomies and tonsillectomies (P = .78); between surgical indication groups (sleep-disordered breathing vs other; P = .15); or in terms of sex (P = .80), age (P = .11), tonsil grade (P = .96), or adenoid size (P = .15). There was no qualitative difference in postoperative nasal air emissions between patients with and without medical syndromes. CONCLUSION: Our data are consistent with the literature that most VPI after adenotonsillectomy is temporary in nature and resolves by 5 months postoperatively. Combined procedures were shown to have a significantly higher risk of VPI. Our rates of VPI were much higher than that previously cited and may be indicative of subclinical cases of VPI, which were accounted for due to this study's unique methodology.

The aesthetic unit principle of facial aging.

IMPORTANCE: In youth, facial aesthetic units flow together without perceptible division. The face appears as a single dynamic structure with a smooth contour and very little if any shadowing between different anatomical regions. As one ages, facial aesthetic units slowly become distinct. This process may be a consequence of differences in skin thickness, composition of subcutaneous tissue, contour of the facial skeleton, and location of facial ligaments. Although the impact of aesthetic unit separation is clinically apparent, its fundamental role in perceived facial aging has not yet been defined empirically. OBJECTIVES: To evaluate and define the effect of aesthetic unit separation on facial aging and to empirically validate the rationale for the blending of aesthetic units as a principle for facial rejuvenation. DESIGN, SETTING, AND PARTICIPANTS: We prepared the photographs of 7 women for experimental evaluation of the presence or absence of facial aesthetic unit separation. Photographic stimuli were then presented to 24 naive observers in a blinded paired comparison. For each stimulus pair, observers were asked to select the facial photograph that they considered to be more youthful in appearance. Each stimulus was compared with all others. MAIN OUTCOMES AND MEASURES: We calculated a preference score for the total number of times any photograph was chosen to be more youthful compared with all others. Paired t tests were used to compare the preference scores between the facial stimuli with and without aesthetic unit separation. RESULTS: We generated 4032 responses for analysis. Photographs without facial aesthetic unit separation were consistently judged to be more youthful than their aged original or modified counterparts, with mean preference scores of 0.66 and 0.33, respectively (P ≤ .047). When we selected the paired stimulus that directly compared one photograph with aesthetic unit separation with another with blended aesthetic units (2015 pairs), observers indicated that the photograph with the blended aesthetic unit was younger 95% of the time. Within-rater reliability was found to be very good (r = 0.88). CONCLUSIONS AND RELEVANCE: Our data support the hypothesis that facial aesthetic unit separation influences perceived facial youthfulness among photographs of women. The presence of facial aesthetic unit separation results in a less youthful appearance. Based on these empirical data, the concept of facial aesthetic unit separation appears to play a significant role in perceived facial aging. LEVEL OF EVIDENCE: NA.

Lack of association of a single-nucleotide polymorphism of the mu-opioid receptor gene with anxiety-related traits: results from a cross-sectional study of adults and a longitudinal study of children.

There is evidence from animal experiments that the mu- and delta-opioid receptors may play a role in anxiety and depression. It might therefore be expected that functional polymorphisms of these genes in humans are associated with anxiety and depression. We investigated a single-nucleotide polymorphism (Asn40Asp) of the mu-opioid receptor gene (OPRM1). This association was investigated in two samples: 1) a cross-sectional survey of 867 community-living adults aged 18-79 years who were assessed for anxiety and depression symptoms and related personality traits; and 2) a longitudinal study of childhood temperament in which 660 children were followed from infancy to the mid-teens and assessed for anxiety-related temperament and behavior problems. The data did not support a role for the Asn40Asp polymorphism in anxiety and depression, despite adequate statistical power to detect small effects.

Recognition and treatment of oncologic emergencies.

An oncologic emergency is a clinical condition resulting from a structural or metabolic change caused by cancer or its treatment that requires immediate medical intervention to prevent loss of life or quality of life. Five oncologic emergencies (septic shock, syndrome of inappropriate antidiuretic hormone, tumor lysis syndrome, disseminated intravascular coagulopathy, and spinal cord compression) are defined and described physiologically and clinically. Also, appropriate treatment of each oncologic emergency is discussed.

Young female survivors of sexual abuse in Malaysia and depression: what factors are associated with better outcome?

INTRODUCTION: Research in the field of child sexual abuse is lacking in Malaysia. The aims of this study are to identify the association between sociodemographic factors and depression among sexually abused females. METHODS: A cross-sectional study was conducted among 51 young sexually abused female attendees at the Suspected Child Abuse and Neglect (SCAN) clinic of Hospital Kuala Lumpur, a tertiary referral centre. Upon obtaining informed consent from participant and guardian, participants were screened for depression using the Strength and Difficulty Questionnaire (SDQ) and interviewed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS) for depressive disorders and K-SADS-PL (Present and Lifetime version) to diagnose depression. Sociodemographic data and details of the abuse were also obtained. RESULTS: Of the survivors, 33.3% were depressed. Univariate analysis showed significant association between legal guardianship, living environment and duration of abuse with depression, however, multivariate analyses later showed that the sole predictor for depression was living environment. Respondents who lived with others were 23-times more likely to be depressed as compared to those who lived with their parents. DISCUSSION: Depression is common among young survivors of sexual abuse. Those who lived with parents appeared to have a better outcome. Thus, further research to explore possible protective factors associated with living with parents is vital. This will help clinicians develop strategies to empower parents and families help these young survivors get back on track with their lives despite the abuse.

Physician, heal thyself: the paradox of anxiety amongst house officers and work in a teaching hospital.

INTRODUCTION: Anxiety among house officers may impair functioning and health care delivery. This study aimed to determine the association between anxiety among house officers at Universiti Kebangsaan Malaysia Medical Center, sociodemographic and work-related factors. METHODS: A cross-sectional study using the self-rated and validated Malay Depressive Anxiety and Stress Scale 21, the General Stressor Questionnaire and a sociodemographic questionnaire. RESULTS: Of the 89 house officers, 60.7% were anxious. Multivariate logistic analysis showed work-related challenges, performance pressure (odds ratio [OR] = 9.000, 95% confidence interval [CI] = 1.812-44.705), poor relationship with supervisors (OR = 5.212, 95% CI = 2.033-3.365), poor relationship with colleagues (OR = 4.642, 95% CI = 1.816-11.866), bureaucratic constraints (OR = 3.810, 95% CI = 1.541-9.415) and poor job prospects (OR = 3.745, 95% CI = 1.505-9.321) strongly associated with anxiety. Family-related stressors were less significant (OR = 1.800, 95% CI = 0.760-4.266) unless they were work related (work-family conflicts [OR = 8.253, 95% CI = 2.652-25.684]). DISCUSSION: Almost two-thirds of this cohort reported work-related anxiety symptoms. Administrators need to address these mental health needs early. The subsequent improvement in communication skills, conflict resolution and anxiety reduction will result in short- and long-term benefits towards the young doctors's mental health. The cascading impact on these individuals, thus empowered, will be good work-life balance, improved patient care and safety, a satisfying medical career whilst contributing maximally to the country's health care.

Sexual abuse and substance abuse increase risk of suicidal behavior in Malaysian youth.

INTRODUCTION: The aim of this study was to determine the association between sexual abuse, substance abuse and socio-demographic factors with suicidal ideation (SI), plans (SP) and deliberate self-harm (DSH) and propose steps to prevent youth suicidal behavior. METHODS: This was a cross-sectional study of 6786 adolescents aged 17-18 years, selected randomly from all Malaysian adolescents to undergo compulsory youth camps located in Selangor, Malaysia (2008-2009). Participants were assessed using self-administered questionnaires developed to reflect the local cultural setting. However, only 4581 subjects were analyzed after excluding incomplete data. RESULTS: The rates of SI, SP and DSH were 7.6%, 3.2% and 6.3%, respectively. The multivariable-adjusted odds ratio showed that sexual abuse was associated with SI 1.99 (95% CI: 1.56-2.55), SP 1.57 (95% CI: 1.09-2.27) and DSH 2.26 (95% CI: 1.75-2.94); illicit drug use was associated with SI 4.05 (95% CI: 2.14-7.67), SP 2.62 (95% CI: 1.05-6.53) and DSH 2.06, (95% CI: 1.05-4.04); for alcohol use DSH was 1.34 (95% CI: 1.00-1.79). Being female was associated with all suicidal behaviors: SI 2.51 (95% CI: 1.91-3.30), SP 2.07 (95% CI: 1.39-3.08) and DSH 1.59 (95% CI: 1.19-2.11). DISCUSSION: Given the well-founded concern of increasing risk of suicidal behavior among youth, preventive efforts should adopt a more comprehensive approach in dealing with sexual abuse and substance abuse, and their sequelae, especially in girls.

High frequency of activating PIK3CA mutations in human papillomavirus-positive oropharyngeal cancer.

IMPORTANCE: Large-scale whole-exome sequencing studies of head and neck squamous cell carcinoma (HNSCC) have established that the disease is dominated by frequent mutations in tumor suppressor genes with rare activating mutations in oncogenes that would be easily targetable with molecular agents. There was evidence in these reports, however, that activating mutations in phosphoinositide 3-kinase catalytic subunit p110α (PIK3CA) were common in patients with human papillomavirus (HPV)-positive tumors. We set out to test this prediction in oropharyngeal patient samples from our institution. OBJECTIVE: To confirm whether activating mutations in PIK3CA are frequent in HPV-positive HNSCC because this mutated oncogene represents a potential therapeutic target. DESIGN, SETTING, AND PARTICIPANTS: A retrospective search of the London Health Sciences Centre pathology database was performed to identify oropharyngeal cancer samples. DNA from pretreatment primary site biopsy samples from 87 patients were tested for high-risk HPV types 16 and 18 by real-time polymerase chain reaction. MAIN OUTCOMES AND MEASURES: Samples were tested for activating mutations at the 3 mutational hot spots (codons 542, 545, and 1047) by polymerase chain reaction followed by Sanger sequencing using forward and reverse primers. RESULTS: Only 4 of 41 HPV-negative tumors (10%) demonstrated PIK3CA hot spot mutations, including 3 at codon 1047 and 1 at codon 542. Of 46 HPV-positive tumors, 13 (28%) demonstrated activating PIK3CA mutations, including 7 at codon 542, 5 at codon 545, and 1 at codon 1047. The difference in PIK3CA mutation frequency was significantly different between HPV-positive and HPV-negative cancers (P = .03). CONCLUSIONS AND RELEVANCE: Although there has been a suggestion that activating PIK3CA mutations are common in HPV-positive HNSCC, to our knowledge, this is the first study to clearly identify this phenomenon. Targeting PIK3CA with molecular agents in HPV-positive patients may be a mechanism to improve cure rates and decrease treatment toxic effects in this rapidly growing cohort of patients.