Objective radiological disease control with Sandostatin monotherapy in metastatic neuroendocrine tumours

Conventional cytotoxic chemotherapy is not usually effective in neuroendocrine tumours (NET). Somatostatin analogues (SSA) such as octreotide (Sandostatin; octreotide LAR and lanreotide) are typically used to treat symptoms caused by NET, but not as the primary treatment aiming for an objective response. Recently, results from the PROMID (Placebo-controlled prospective Randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumours) trial were published showing that octreotide LAR significantly lengthens the time to tumour progression compared with a placebo in patients with functionally active and inactive metastatic midgut NET. We report a retrospective descriptive analysis of six patients, treated at two Australian institutions, who obtained an objective radiological tumour response on long acting SSA. In this retrospective series of NET, radiological responses were observed using single agent SSA, which was administered mainly for symptom management. This could be due to an antiproliferative and/or antiangiogenic activity of this agent in NET. A response can occur beyond 12 months, which might explain why the response rate is under reported in NET trials. Further investigation in prospective trials is warranted and the possibility for late responses might have implications for trial design.

Precision engineering of the chicken genome for disease control

The thesis examines the application of precision genome engineering technology to improve the disease resistance in chicken model.

A shared framework for the common mental disorders and Non-Communicable Disease: key considerations for disease prevention and control.

BACKGROUND: Historically, the focus of Non Communicable Disease (NCD) prevention and control has been cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), cancer and chronic respiratory diseases. Collectively, these account for more deaths than any other NCDs. Despite recent calls to include the common mental disorders (CMDs) of depression and anxiety under the NCD umbrella, prevention and control of these CMDs remain largely separate and independent. DISCUSSION: In order to address this gap, we apply a framework recently proposed by the Centers for Disease Control with three overarching objectives: (1) to obtain better scientific information through surveillance, epidemiology, and prevention research; (2) to disseminate this information to appropriate audiences through communication and education; and (3) to translate this information into action through programs, policies, and systems. We conclude that a shared framework of this type is warranted, but also identify opportunities within each objective to advance this agenda and consider the potential benefits of this approach that may exist beyond the health care system.

Use of phosphite as a control for Phytophthora cinnamomi in southeastern Victorian vegetation communities

One of the major aims of the research presented in this thesis was to assist managers of native vegetation communities in southeastern Australia in understanding the dynamics of P. cinnamomi with an important ecological species, Xanthorrhoea australis. It trialed the use of phosphite in large-scale field applications to establish the usefulness of this management option for the first time on Victorian flora. This thesis describes the process of disease development within mature X. Australia plants. For the first time it was shown that within X. australis plants, secondary disease symptoms are related to the percentage of stem that has been infested by the disease. It was evident that after initial invasion the pathogen moves via root xylem and throughout the plant within vascular to the stem, especially within the desmium. The research shows that the pathogen could not be isolated consistently even though it was considered to be responsible for disease symptoms. Trials of a control fungicide (Foli-R-fos 200) shows that protection occurs in many susceptible plants when 2 and 6g a.i./L phosphite is applied. Phytotoxicity occurred in native plants at Anglesea and within controlled environment trials when using ≥ 6g a.i./L. It will be shown that 2g a.i./L phosphite controls disease in sprayed plots within heathlands at Anglesea and a recently burnt coastal woodland community at Wilson’s Promontory. The proportion of healthy X. australis plants treated with phosphite was significantly higher than the proportion in control plots without phosphite. The research shows that phosphite was recovered from leaves of three species treated with Foli-R-fos 200 in the field. For the first time it has been shown that seed germination was reduced in two species when high concentrations of phosphite were applied. The first documentation of the effect that phosphite has on soil properties showed that nitrogen and oxidised organic carbon were the only parameters to alter significantly. This thesis provides answers to some important questions, answers that can now be used by managers in formulating better policies and actions at an operational level. There has been a dire need in Victoria to address many issues regarding P. cinnamomi and this thesis provides relevant and informative approaches to disease control, and a better understanding of the disease progress.

Multi-envelope HIV-1 vaccine devoid of SIV components controls disease in macaques challenged with heterologous pathogenic SHIV

A central obstacle to the design of a global HIV-1 vaccine is virus diversity. Pathogen diversity is not unique to HIV-1, and has been successfully conquered in other fields by the creation of vaccine cocktails. Here we describe the testing of an HIV-1 envelope cocktail vaccine. Six macaques received the vaccine, delivered by successive immunizations with recombinant DNA, recombinant vaccinia virus and recombinant envelope proteins. Following vaccination, animals developed a diversity of anti-envelope antibody binding and neutralizing activities toward proteins and viruses that were not represented by sequence in the vaccine. T-cells were also elicited, as measured by gamma-interferon production assays with envelope-derived peptide pools. Vaccinated and control animals were then challenged with the heterologous pathogenic SHIV, 89.6P. Vaccinated monkeys experienced significantly lower virus titers and better maintenance of CD4+ T-cells than unvaccinated controls. The B- and T-cell immune responses were far superior post-challenge in the vaccinated group. Four of six vaccinated animals and only one of six control animals survived a 44-week observation period post-challenge. The present report is the first to describe pathogenic SHIV disease control mediated by a heterologous HIV-1 vaccine, devoid of 89.6 or SIV derivatives.

Web search activity data accurately predict population chronic disease risk in the USA

BACKGROUND: The WHO framework for non-communicable disease (NCD) describes risks and outcomes comprising the majority of the global burden of disease. These factors are complex and interact at biological, behavioural, environmental and policy levels presenting challenges for population monitoring and intervention evaluation. This paper explores the utility of machine learning methods applied to population-level web search activity behaviour as a proxy for chronic disease risk factors. METHODS: Web activity output for each element of the WHO's Causes of NCD framework was used as a basis for identifying relevant web search activity from 2004 to 2013 for the USA. Multiple linear regression models with regularisation were used to generate predictive algorithms, mapping web search activity to Centers for Disease Control and Prevention (CDC) measured risk factor/disease prevalence. Predictions for subsequent target years not included in the model derivation were tested against CDC data from population surveys using Pearson correlation and Spearman's r. RESULTS: For 2011 and 2012, predicted prevalence was very strongly correlated with measured risk data ranging from fruits and vegetables consumed (r=0.81; 95% CI 0.68 to 0.89) to alcohol consumption (r=0.96; 95% CI 0.93 to 0.98). Mean difference between predicted and measured differences by State ranged from 0.03 to 2.16. Spearman's r for state-wise predicted versus measured prevalence varied from 0.82 to 0.93. CONCLUSIONS: The high predictive validity of web search activity for NCD risk has potential to provide real-time information on population risk during policy implementation and other population-level NCD prevention efforts.

Mortality rates, prevalence of malnutrition, and prevalence of lost pregnancies among the drought-ravaged population of Tete province Mozambique

Background: Tete Province, Mozambique has experienced chronic food insecurity and a dramatic fall in livestock numbers due to the cyclic problems characterized by the floods in 2000 and severe droughts in 2002 and 2003. The Province has been a beneficiary of emergency relief programs, which have assisted >22% of the population. However, these programs were not based on sound epidemiological data, and they have not established baseline data against which to assess the impact of the programs. Objective: The objective of this study was to document mortality rates, causes of death, the prevalence of malnutrition, and the prevalence of lost pregnancies after 2.5 years of humanitarian response to the crisis. Methods: A two-stage, 30-cluster household survey was conducted in the Cahora Bassa and Changara districts from 22 October to 08 November 2004. A total of 838 households were surveyed, with a population size of 4,688 people. Results: Anthropometric data were collected among children 6-59 months of age. In addition, crude mortality rates (CMRs), under five mortality rates (U5MRs), causes of deaths, and prevalence of lost pregnancies were determined among the sample population. The prevalence of malnutrition was 8.0% (95% confidence interval (CI)=6.2-9.8%) for acute malnutrition, 26.9% (95% CI=24.0-29.9%) for being underweight, and 37.0% (95% CI=33.8-40.2%) for chronic malnutrition. Boys were more likely to be underweight than were girls (odds ratio (OR)=1.34; 95% CI=1.00, 1.82; p<0.05) after controlling for age, household size, and food aid beneficiary status. Similarly, children 30-59 months of age were significantly less likely to suffer from acute malnutrition (OR=0.45; 95% CI=0.26, 0.79; p<0.01) and less likely to be underweight (OR=0.37; 95% CI=0.27, 0.51; p<0.01) than children 6-29 months of age, after adjusting for the other, aforementioned factors. The proportion of lost pregnancies was estimated at 7.7% (95% CI=4.5-11.0%). A total of 215 deaths were reported during the year preceding the survey. Thirty-nine (18.1%) children <5 years of age died. The CMR was 1.23/10 000/day (95% CI=1.08-1.38), and an U5MR was 1.03/10 000/day (95% CI=0.71-1.35). Diarrheal diseases, malaria, tuberculosis, and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) accounted for more than two-thirds of all deaths. Conclusions: The observed CMR in Tete Province, Mozambique is three times higher than the baseline rate for sub-Saharan Africa and 1.4 times higher than the CMR cut-off point used to define excess mortality in emergencies. The current humanitarian response in Tete Province would benefit from an improved alignment of food aid programming in conjunction with diarrheal disease control, HIV/AIDS, and malaria prevention and treatment programs. The impact of the food programs would be improved if mutually acceptable food aid programme objectives, verifiable indicators relevant to each objective, and beneficiary targets and selection criteria are developed. Periodic re-assessments and evaluations of the impact of the program and evidenced-based decision-making urgently are needed to avert a chronic dependency on food aid.

Population-Based Randomized Controlled Trial of a Stage-Targeted Physical Activity Intervention

BACKGROUND: Intervention trials with self-selected participants have shown that mailed stage-targeted print materials can increase participation in physical activity in the short term. We examined the effects of a mailed stage-targeted print intervention designed to promote physical activity, in a random sample of adults living in a regional city.

METHOD: Participants (n = 462, 40-60 years of age) were randomly allocated to an intervention (n = 227) or control group (n = 235). Measures included validated 2-week physical activity recall and stage of motivational readiness for physical activity. The intervention consisted of a single mailing of a letter and full-color stage-targeted booklets (specific to precontemplation, contemplation, preparation, and action/maintenance) 1 week postbaseline. Follow-up interviews were conducted at 2 and 6 months postbaseline.

RESULTS: After 2 months, participants in the intervention group were significantly more likely to meet the current American College of Sports Medicine/Centers for Disease Control and Prevention recommendation for sufficient physical activity than those in the control group (adjusted odds ratio [OR] = 2.40; 95% confidence interval [CI] = 1.44-3.99). After 6 months, intervention participants who reported receiving and reading the intervention materials were significantly more likely to be meeting the sufficient physical activity criterion compared with the control group (adjusted OR = 2.03; 95% CI = 1.16-3.56).

CONCLUSIONS: The stage-targeted print intervention was effective in promoting short-term increases in physical activity and was most effective for participants who recognized and used the materials. This low-cost, generalizable intervention has demonstrated potential as a practical population-based physical activity promotion strategy. Further research is required before widespread dissemination would be justified, as additional strategies may be required to ensure sustained change.

Stability of body mass index in Australian children: a prospective cohort study across the middle childhood years

Objective: To investigate the prevalence and incidence of overweight and obesity, the frequency of overweight resolution and the influence of parental adiposity during middle childhood.

Design: As part of a prospective cohort study, height and weight were measured in 1997 and 2000/2001. Children were classified as non-overweight, overweight or obese based on standard international definitions. Body mass index (BMI) was transformed into age- and gender-specific Z-scores employing the LMS method and 2000 growth chart data of the Centers for Disease Control and Prevention. Parents self-reported height and weight, and were classified as underweight, healthy weight, overweight or obese based on World Health Organization definitions.

Setting: Primary schools in Victoria, Australia.

Subjects: In total, 1438 children aged 5–10 years at baseline.

Results: The prevalence of overweight and obesity increased between baseline (15.0 and 4.3%, respectively) and follow-up (19.7 and 4.8%, respectively; P < 0.001 for increase in overweight and obesity combined). There were 140 incident cases of overweight (9.7% of the cohort) and 24 of obesity (1.7% of the cohort); only 3.8% of the cohort (19.8% of overweight/obese children) resolved to a healthy weight. The stability of child adiposity as measured by BMI category (84.8% remained in the same category) and BMI Z-score (r = 0.84; mean change = −0.05) was extremely high. Mean change in BMI Z-score decreased with age (linear trend β = 0.03, 95% confidence interval 0.01–0.05). The influence of parental adiposity largely disappeared when children's baseline BMI was adjusted for.

Conclusions: During middle childhood, the incidence of overweight/obesity exceeds the proportion of children resolving to non-overweight. However, for most children adiposity remains stable, and stability appears to increase with age. Prevention strategies targeting children in early childhood are required.

Routine replacement of short peripheral intravenous cannulae in children: evidence of an unnecessary practice

Short peripheral intravenous cannulae (pIVC) are prone to specific problems such as thrombophlebitis, infiltration and bacterial colonisation. This paper presents data from a study of 80 polyurethane pIVC in 59 children within a general paediatric population. There was no significant colonisation of any cannula by bacterial or fungal organisms. This study provides evidence that it is safe not to routinely replace pIVC in this population. It supports the Centers for Disease Control and Prevention (CDC) guidelines for intravenous cannula (IVC) management in children.

Pandemic containment and management

In a pandemic, nurses will be the first health care contact for the general public in most cases. This clinical update provides information about the influenza virtus and its modes of transmission. The update will describe the principles of containment and management that will be important to understand in the event of a pandemic occurring.

A boarding school outbreak of pertussis in adolescents : value of laboratory diagnostic methods

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P<0·001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.

Syphilis and AIDS : historical and social comparisons

Drawing on the literatures of history, sociology, epidemiology, and microbiology, this thesis compares syphillis with human immunodeficiency virus, with special reference to the social and historical factors likely to be relevant to the control or eradication of acquired imune dificiency syndrom (AIDS). The sudden appearance of a new disease causing suffering and death in a community, engenders apprehension and fear which is often manifested as hysteria against, and vilification of, those who have the disease. This fear is greatly increased should the disease be sexually-transmitted. Syphilis in a venereal form, occured in Europe toward the end of the 15th Century. Initially it was an acute, fulminating disease which rapidly spread through Europe and Asia. Attempts to control the disease have gone through periods of either partial successes or massive failures and have ended in frustration for the authorities. When the syndrome of acquired immune deficiency (AIDS) was first reported, it was seen in Western countries in homosexual men. However, as non-homosexual community members and children became infected, it became apparent to authorities that a pandemic was accurring. Within a few years, the disease was identified worldwide. Isolation of the virus (HIV-1), and development of test for detection of carriers, plus restoration of clean blood and blood-product supplies, have reassured the community to some extent. The history of syphilis shows that neither the epidemiological medical, nor the economic political approaches to disease control work, although there are positive aspects resulting from both. It is social responses that will offer the most hope in the long term for the control of AIDS and other sexually-transmitted diseases.

Reducing obesity in early childhood : results from romp & chomp, an Australian community-wide intervention program

Background: There is growing evidence that community-based interventions can reduce childhood obesity in older children.
Objective: We aimed to determine the effectiveness of the Romp & Chomp intervention in reducing obesity and promoting healthy eating and active play in children aged 0–5 y.
Design: Romp & Chomp was a community-wide, multisetting, multistrategy intervention conducted in Australia from 2004 to 2008. The intervention occurred in a large regional city (Geelong) with a target group of 12,000 children and focused on community capacity building and environmental (political, sociocultural, and physical) changes to increase healthy eating and active play in early-childhood care and educational settings. The evaluation was repeat cross-sectional with a quasiexperimental design and comparison sample. Main outcome measures were body mass index (BMI), standardized BMI (zBMI; according to the Centers for Disease Control and Prevention 2000 reference charts), and prevalence of overweight/obesity and obesity-related behaviors in children aged 2 and 3.5 y.
Results: After the intervention there was a significantly lower mean weight, BMI, and zBMI in the 3.5-y-old subsample and a significantly lower prevalence of overweight/obesity in both the 2- and 3.5-y-old subsamples (by 2.5 and 3.4 percentage points, respectively) than in the comparison sample (a difference of 0.7 percentage points; P < 0.05) compared with baseline values. Intervention child-behavioral data showed a significantly lower intake of packaged snacks (by 0.23 serving), fruit juice (0.52 serving), and cordial (0.43 serving) than that in the comparison sample (all P < 0.05).
Conclusion: A community-wide multisetting, multistrategy intervention in early-childhood settings can reduce childhood obesity and improve young children's diets. This trial was registered with the Australian Clinical Trials Registry at anzctr.org.au as ACTRN12607000374460.

The longitudinal influence of home and neighbourhood environments on children's body mass index and physical activity over 5 years : the CLAN study

Objective: To determine the independent contributions of family and neighbourhood environments to changes in youth physical activity and body mass index (BMI) z-score over 5 years.

Methods: In 2001, 2004 and 2006, 301 children (10–12 years at baseline) had their height and weight measured (BMI was converted to z-scores using Centers for Disease Control and Prevention reference charts; see http://www.cdc.gov/growthcharts) and moderate-to-vigorous physical activity (MVPA) assessed using accelerometers. In 2001, parents reported on the home environment (social support, role modelling, rules and restrictions, physical environment) and perceived neighbourhood environment (local traffic, road safety, sporting venues, public transport), and Geographic Information Systems were used to map features of the neighbourhood environment (destinations, road connectivity, traffic exposure). Generalized estimating equations were used to predict average BMI z-score and MVPA over time from baseline home and perceived and objective neighbourhood environment factors.

Results: Among boys, maternal education and heavy traffic were inversely associated, and sibling physical activity, maternal role modelling of MVPA and the presence of dead-end roads were positively associated with MVPA. Having unmarried parents, maternal MVPA role modelling and number of home sedentary items were positively associated with BMI z-score among boys. Among girls, having siblings, paternal MVPA role modelling, physical activity rules and parental physical activity co-participation were positively associated with MVPA. Having unmarried parents and maternal sedentary behaviour role modelling were positively associated, and number of sedentary behaviour rules and physical activity items were inversely associated with BMI z-score among girls.

Conclusion: The home environment seems more important than the neighbourhood environment in influencing children's physical activity and BMI z-score over 5 years. Physical activity and weight gain programmes among youth should focus on parental role modelling, rules around sedentary and active pursuits, and parental support for physical activity. Intervention studies to investigate these strategies are warranted.