The virtuous epidemiologist.

This article addresses the scholarly gap in the ethics of epidemiology by exploring what virtue ethics, one of the oldest ethical traditions in moral philosophy, has to say about 'the virtuous epidemiologist'. It expounds comparatively the content and merits of a virtue ethics approach against more popular contemporary schools of thought such as consequentialism and deontology. Without necessarily dismissing the value of principles and standards, it presents a vision that a virtuous epidemiologist should cultivate wisdom in making prudential judgments in conditions of uncertainty; fortitude in dealing with powerful politicians and administrators which does not sacrifice truth; temperance and self-restraint in keeping one's ideological views from compromising one's scientific credibility; and justice in giving due weight to individual rights and the public interest when doing research and giving advice on public health interventions.

Use of palliative chemotherapy in patients aged 80 years and over with incurable cancer: experience at three Sydney cancer centres.

BACKGROUND: Octogenarians represent a growing population reviewed in medical oncology clinics, yet there is a paucity of data on how chemotherapy is tolerated in this age group. AIM: To describe the use of palliative first-line chemotherapy in patients 80 years and over and factors associated with its use. METHODS: We identified all new patients aged 80 years or older diagnosed with incurable advanced solid organ cancer and seen in one of three Sydney medical oncology outpatient clinics between January 2009 and December 2013. Patient, disease and treatment details were summarised and factors associated with chemotherapy use explored. RESULTS: Of 420 eligible patients, 100 (24%) started first-line chemotherapy. Younger age at diagnosis was the only factor associated with receiving chemotherapy (median 82.9 vs 84.1 years, P = 0.002). A total of 78% of patients had single-agent chemotherapy, and 41% received a full dose for the first cycle. During treatment, 54% experienced toxicity, necessitating dose reduction, delay or omission, and 32% were hospitalised. These events were associated with receipt of combination chemotherapy (OR 5.1; P = 0.04) and full-dose chemotherapy for cycle 1 (OR 3.5; P = 0.02). Radiological disease control was achieved in 60%. Chemotherapy was stopped because of progressive disease (48%), toxicity (37%) or completion of planned course (17%). CONCLUSION: A quarter of patients 80 years and older received first-line palliative chemotherapy. Despite most receiving a modified dose, one third were hospitalised during treatment. These findings highlight the need for careful clinical assessment and selection of older cancer patients for chemotherapy.

Variable Assessment in Latent Class Models.

The latent class model provides an important platform for jointly modeling mixed-mode data - i.e., discrete and continuous data with various parametric distributions. Multiple mixed-mode variables are used to cluster subjects into latent classes. While the mixed-mode latent class analysis is a powerful tool for statisticians, few studies are focused on assessing the contribution of mixed-mode variables in discriminating latent classes. Novel measures are derived for assessing both absolute and relative impacts of mixed-mode variables in latent class analysis. Specifically, the expected posterior gradient and the Kolmogorov variation of the posterior distribution, as well as related properties are studied. Numerical results are presented to illustrate the measures.

Multi-profile hidden Markov model for mood, dietary intake, and physical activity in an intervention study of childhood obesity.

Motivated by an application to childhood obesity data in a clinical trial, this paper describes a multi-profile hidden Markov model (HMM) that uses several temporal chains of measures respectively related to psychosocial attributes, dietary intake, and energy expenditure behaviors of adolescents in a school setting. Using these psychological and behavioral profiles, the model delineates health states from the longitudinal data set. Furthermore, a two-level regression model that takes into account the clustering effects of students within school is used to assess the effects of school-based and community-based interventions and other risk factors on the transition between health states over time. The results from our study suggest that female students tend to decrease their physical activities despite a high level of anxiety about weight. The finding is consistent across intervention and control arms.

Social skills and associated psychopathology in children with chromosome 22q11.2 deletion syndrome: implications for interventions.

BACKGROUND: Although distinctive neuropsychological impairments have been delineated in children with chromosome 22q11 deletion syndrome (22q11DS), social skills and social cognition remain less well-characterised. OBJECTIVE: To examine social skills and social cognition and their relationship with neuropsychological function/behaviour and psychiatric diagnoses in children with 22q11DS. METHODS: Sixty-six children with 22q11DS and 54 control participants underwent neuropsychological testing and were administered the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) for face and auditory emotion recognition, a measure of social cognition: their parents/guardians were administered the Social Skills Rating System (SSRS) - parent version, Child Behavior Checklist (CBCL) - parent version and the Computerised Diagnostic Interview Schedule for Children (C-DISC). RESULTS: The 22q11DS group exhibited significantly lower social skills total score and more problem social behaviours, lower neurocognitive functioning, higher rates of anxiety disorders and more internalising symptoms than the control group. Participants with 22q11DS also exhibited significant deficits in their ability to read facial expressions compared with the control group, but performed no differently than the control participants in the processing of emotions by tone of voice. Within the 22q11DS group, higher social competency was correlated with higher global assessment of functioning and parental socio-economic status. Social competency was worse in those with anxiety disorders, attention deficit hyperactivity disorder, more than two psychiatric diagnoses on the C-DISC and higher internalising symptoms. No significant correlations of SSRS scores were seen with IQ, executive functions, attention, or verbal learning and memory. No correlations were found between social cognition and social skill scores. CONCLUSION: Our results indicate that social skills in children with 22q11DS are associated with behaviour/emotional functioning and not with neurocognition. Thus, treating the behaviour or emotional problems such as attention deficit hyperactivity disorder and anxiety disorders may provide a pathway for improving social skills in these children.

Dysregulation of DGCR6 and DGCR6L: psychopathological outcomes in chromosome 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans. It is typified by highly variable symptoms, which might be explained by epigenetic regulation of genes in the interval. Using computational algorithms, our laboratory previously predicted that DiGeorge critical region 6 (DGCR6), which lies within the deletion interval, is imprinted in humans. Expression and epigenetic regulation of this gene have not, however, been examined in 22q11DS subjects. The purpose of this study was to determine if the expression levels of DGCR6 and its duplicate copy DGCR6L in 22q11DS subjects are associated with the parent-of-origin of the deletion and childhood psychopathologies. Our investigation showed no evidence of parent-of-origin-related differences in expression of both DGCR6 and DGCR6L. However, we found that the variability in DGCR6 expression was significantly greater in 22q11DS children than in age and gender-matched control individuals. Children with 22q11DS who had anxiety disorders had significantly lower DGCR6 expression, especially in subjects with the deletion on the maternal chromosome, despite the lack of imprinting. Our findings indicate that epigenetic mechanisms other than imprinting contribute to the dysregulation of these genes and the associated childhood psychopathologies observed in individuals with 22q11DS. Further studies are now needed to test the usefulness of DGCR6 and DGCR6L expression and alterations in the epigenome at these loci in predicting childhood anxiety and associated adult-onset pathologies in 22q11DS subjects.

Treatment of minor depression in older adults: a pilot study comparing sertraline and exercise.

The purpose of this study was to conduct a pilot clinical trial to test the feasibility and efficacy of an exercise program and anti-depressant treatment compared with usual care in improving the emotional and physical functioning of older adults with minor depression. Participants were 37 older adults with minor depression who were randomized to exercise, sertraline, or usual care; 32 participants completed the 16-week study. Outcomes included measures of both emotional (clinician and self-report) and physical (observed and self-report) functioning. There were trends for the superiority of the exercise and sertraline conditions over usual care in improving SF-36 mental health scores and clinician-rated depression scores. Individuals in the exercise condition showed greater improvements in physical functioning than individuals in the usual care condition. Both sertraline and exercise show promise as treatments for late-life minor depression. However, exercise has the added benefit of improving physical functioning as well.

Human papillomavirus and its prognostic significance in invasive carcinoma of the cervix in young patients.

Of 1,200 Chinese patients treated for carcinoma of the cervix between 1975 and 1984, those aged 40 years (n = 70) or less had a poorer prognosis. Of the latter group, 71% had disease classified as less than International Federation of Gynecology and Obstetrics (FIGO) stage Ib, and in 91% the disease was less than stage IIa; however, the 5-year survival of the 45 patients with verified invasive carcinoma was 75% compared with 82% for the overall group. The polymerase chain reaction (PCR) was used to test for the presence of human papilloma virus (HPV) types 16 and 18 within paraffin-embedded tissue from the primary tumors. HPV-16 DNA sequences were detected in 69% of the cases, HPV-18 DNA sequences in 44%, and in 31% both HPV-16 and -18 DNA could be identified. Of the cases of invasive carcinoma, 82% (37 of 45) contained DNA of HPV types 16 and/or 18. The effects of the presence or absence of HPV DNA on known prognostic factors was investigated. Although the influence of traditional factors, especially lymph node involvement, was confirmed, careful statistical analysis could not demonstrate a prognostic influence for HPV-16/18.

Prevalence of low and high risk human papillomavirus types in cervical cells from Hong Kong pregnant Chinese using filter in situ hybridization.

Filter in situ hybridization, using separate probes for human papillomavirus deoxyribonucleic acid types 6, 11, 16 and 18, was used to determine the prevailing HPV types amongst a group of pregnant Chinese women. This group had been previously identified using a mixture of probes for HPV types 6, 11, 16, 18, 31, 33, 35 (Virapap). Specimens from six of the eleven cases contained one HPV type (55%) while five were positive for two types (45%). The "low-risk" types (HBV6, 11) were identified as frequently as the "high-risk" types (HPV16, 18) in this study.