'Joining the Dots: Linking Prenatal Drug Exposure to Childhood and Adolescence' - research protocol of a population cohort study.

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The Joining the Dots cohort study uses linked population data to understand the relationship between services, therapeutic interventions and outcomes of children with PDE. METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal social demographics or social determinants of health, and maternal physical and mental health comorbidities. Key outcome measures will include child mortality, academic standardised testing results, rehospitalisation and maternal survival. Data analysis will be conducted using Stata V.18.0. ETHICS AND DISSEMINATION: Approvals were obtained from the NSW Population and Health Services Research Ethics Committee (29 June 2020; 2019/ETH12716) and the Australian Capital Territory Health Human Research Ethics Committee (11 October 2021; 2021-1231, 2021-1232, 2021-1233); and the Aboriginal Health and Medical Research Council (5 July 2022; 1824/21), and all Australian educational sectors: Board of Studies (government schools), Australian Independent Schools and Catholic Education Commission (D2014/120797). Data were released to researchers in September 2022. Results will be presented in peer-reviewed academic journals and at international conferences. Collaborative efforts from similar datasets in other countries are welcome.

Trends and projections of cause-specific premature mortality in Australia to 2044: a statistical modelling study.

Background: Long-term projections of premature mortality (defined as deaths age <75 years) help to inform decisions about public health priorities. This study aimed to project premature mortality rates in Australia to 2044, and to estimate numbers of deaths and potential years of life lost (PYLL) due to premature mortality overall and for 59 causes. Methods: We examined the past trends in premature mortality rates using Australian mortality data by sex, 5-year age group and 5-year calendar period up to 2019. Cigarette smoking exposure data (1945-2019) were included to project lung cancer mortality. Age-period-cohort or generalised linear models were developed and validated for each cause to project premature mortality rates to 2044. Findings: Over the 25-year period from 1990-1994 to 2015-2019, there was a 44.4% decrease in the overall age-standardised premature mortality rate. This decline is expected to continue, from 162.4 deaths/100,000 population in 2015-2019 to 141.7/100,000 in 2040-2044 (12.7% decrease). Despite declining rates, total numbers of premature deaths are projected to increase by 22.8%, rising from 272,815 deaths in 2015-2019 to 334,894 deaths in 2040-2044. This is expected to result in 1.58 million premature deaths over the 25-year period 2020-2044, accounting for 24.5 million PYLL. Of the high-level cause categories, cancer is projected to remain the most common cause of premature death in Australia by 2044, followed by cardiovascular disease, external causes (including injury, poisoning, and suicide), and respiratory diseases. Interpretation: Despite continuously declining overall premature mortality rates, the total number of premature deaths in Australia is projected to remain substantial, and cancer will continue to be the leading cause. These projections can inform the targeting of public health efforts and can serve as benchmarks against which to measure the impact of future interventions. They emphasise the ongoing importance of accelerating the prevention, early detection, and treatment of key health conditions. Funding: No funding was provided for this study.

Fibrinogenolysis and fibrinolysis in vaccine-induced immune thrombocytopenia and thrombosis.

BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterized by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer, and hypofibrinogenemia. OBJECTIVES: To investigate abnormalities in fibrinolysis that contribute to the clinical features of VITT. METHODS: Plasma samples from 18 suspected VITT cases were tested for anti-PF4 by ELISA and characterized as meeting criteria for VITT (11/18) or deemed unlikely (7/18; non-VITT). Antigen levels of PAI-1, factor XIII (FXIII), plasmin-α2antiplasmin (PAP), and inflammatory markers were quantified. Plasmin generation was quantified by chromogenic substrate. Western blotting was performed with antibodies to fibrinogen, FXIII-A, and plasminogen. RESULTS: VITT patients 10/11 had scores indicative of overt disseminated intravascular coagulation, while 0/7 non-VITT patients met the criteria. VITT patients had significantly higher levels of inflammatory markers, IL-1ß, IL-6, IL-8, TNFα, and C-reactive protein. In VITT patients, both fibrinogen and FXIII levels were significantly lower, while PAP and tPA-mediated plasmin generation were higher compared to non-VITT patients. Evidence of fibrinogenolysis was observed in 9/11 VITT patients but not in non-VITT patients or healthy controls. Fibrinogen degradation products were apparent, with obvious cleavage of the fibrinogen α-chain. PAP complex was evident in those VITT patients with fibrinogenolysis, but not in non-VITT patients or healthy donors. CONCLUSION: VITT patients show evidence of overt disseminated intravascular coagulation and fibrinogenolysis, mediated by dysregulated plasmin generation, as evidenced by increased PAP and plasmin generation. These observations are consistent with the clinical presentation of both thrombosis and bleeding in VITT.

Determinants and health outcomes of trajectories of social mobility in Australia.

Objectives: To investigate trajectories in socio-economic position (SEP) and the onset of a range of physical and mental health outcomes and commencement of treatment. Methods: The Household Income and Labour Dynamics Australia (HILDA) study, a nationally representative prospective cohort study over the period 2001 to 2020 was used to define trajectories of SEP. Trajectories of low, low-middle, upper-middle and high SEP and decreasing (low-middle to upper-middle SEP) or increasing (upper-middle to lower-middle SEP) SEP were identified using k-longitudinal means. Cox-regression was used to assess SEP trajectories and physical (arthritis or osteoporosis, any cancer, asthma, chronic bronchitis or emphysema, Type 1 diabetes, Type 2 diabetes, hypertension or high blood pressure, and coronary heart disease), and mental health (depression or anxiety) outcomes, and treatment commencement. Predictors of SEP trajectories were also investigated using multinomial logistic regression and random forests. Results: Decreasing SEP had a higher relative risk of new onset illness than increasing SEP for all health outcomes. Increasing SEP had relative risk estimates that were more consistent with upper-middle income groups and decreasing SEP had a relative risk consistent with lower-middle income groups. In contrast, there was no socio-economic gradient in treatment commencement for physical health outcomes, or depression or anxiety, with the exception of arthritis or osteoporosis. Conclusion: Decreasing SEP was associated with poor health outcomes, and increasing SEP with better health outcomes. A range of socio-demographic and psychosocial determinants of SEP trajectories were identified to inform policy responses that could modify trajectories of health inequalities in the Australian context.

Designing a clinical trial of non-steroidal anti-inflammatory drugs for cancer pain: a survey of UK palliative care physicians.

OBJECTIVES: Insufficient quality evidence exists to support or refute the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the management of cancer pain. We aimed to determine the most clinically pragmatic design of a future randominsed controlled trial (RCT), based on how NSAIDs are currently used and perceived efficacy. METHODS: An online survey was distributed to members of the Association for Palliative Medicine of Great Britain and Ireland examining NSAID use, indications and perceived efficacy, as well as duration of respondents' experience in palliative medicine. RESULTS: 23% of 968 members responded. A placebo-controlled trial of NSAIDs as a strong opioid adjunct in cancer-related bone pain was considered the most clinically pragmatic design. Concerning current practice, oral administration was the preferential route (79.4%), dosed regularly (79.5%). Selective cyclooxygenase-2 (COX-2) inhibitors and non-selective COX-2 inhibitors were considered similarly effective by 45% in cancer pain; ibuprofen being the first line oral NSAID of choice (42.6%). Treatment efficacy is generally determined within 1 week (94.3%). On a Likert scale, most physicians consider NSAIDs improve cancer pain either 'sometimes' (57.7%) or 'often' (40%). Years of specialist palliative care experience did not affect perception of efficacy (p=0.353). CONCLUSIONS: A randomised controlled trial of NSAIDs as opioid adjuncts for cancer-related bone pain would be the most pragmatic design supported by palliative care clinicians to benefit clinical practice.

Characteristics of suicide decedents with no federally funded mental health service contact in the 12 months before death in a population-based sample of Australians 45 years of age and over.

INTRODUCTION: More than half of suicide decedents have no contact with mental health services 12 months before death. It is uncertain if they have different characteristics than decedents who use mental health services. METHODS: A case-series design. Participants 45 years and older, who died by suicide (2006-2018). Comparisons were made between those who did and did not have contact with mental health services, using individually linked data from federal services in the Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS). RESULTS: Of 186 cases, 71% had no contact with mental health services. Physical health services were used equally by 75%. Psychiatric medication use was uncommon, except for antidepressants, 50% with mental health service contact and 20% with no contact. Older age, lower income, involuntarily unemployed, firearms as suicide method, greater physical disability, less functional impairment due to emotional problems and lesser proportions with mental illness, were associated with no contact with mental health services. CONCLUSIONS: For suicide prevention, middle-older aged adults may have less requirement for mental health intervention, and greater requirement for the development of complementary interventions focused on physical health and social issues, which are not necessarily best delivered by clinical mental health services.

Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain: A database analysis to determine recruitment feasibility for a clinical trial.

BACKGROUND: Insufficient evidence exists to support or refute use of NSAIDs for managing cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain as the most pragmatic design to benefit clinical practice. AIM: We aimed to determine patient numbers receiving palliative radiotherapy for cancer-induced bone pain, estimate the suitability of NSAID prescription and determine survival, guiding future trial feasibility. DESIGN: A retrospective observational database analysis was undertaken using 5 years of routinely collected regional radiotherapy and healthcare data, filtered to achieve a cohort with cancer-induced bone pain. Demographics and survival were linked to available serology and co-morbidity data. SETTING/PARTICIPANTS: Data was sourced from the regional Leeds Cancer Centre, a tertiary care setting. Patients who underwent palliative single fraction 8 gray (Gy) radiotherapy treatment for cancer-induced bone pain were included, totalling 2411 over 5 years. RESULTS: A mean of 478 patients received palliative radiotherapy for cancer-induced bone pain annually. Median age (IQR) was 70 (62-77); negatively skewed (-0.69). 65.3% died within 1 year of radiotherapy; 48.0% within 6 months. Age was not associated with survival on univariable analysis (HR 0.999 (95% CI 0.996-1.003)). Serology from 1063 patients (44.2%) were available; eGFR was ⩾60 mL/min/1.73 m2 in 83.0%. From available data (1352 pts; 51.6% of sample), 20.2% had a coded co-morbidity contra-indicating NSAIDs. Combining serology and co-morbidities, 68.5% could be considered for NSAID prescription. CONCLUSIONS: Patient numbers at a regional radiotherapy centre support the feasibility of trial recruitment. Available serology and co-morbidity data suggest two-thirds may be suitable for NSAID prescription.

Watch me grow integrated (WMG-I): protocol for a cluster randomised controlled trial of a web-based surveillance approach for developmental screening in primary care settings.

INTRODUCTION: The increasing prevalence of developmental disorders in early childhood poses a significant global health burden. Early detection of developmental problems is vital to ensure timely access to early intervention, and universal developmental surveillance is recommended best practice for identifying issues. Despite this, there is currently considerable variation in developmental surveillance and screening between Australian states and territories and low rates of developmental screening uptake by parents. This study aims to evaluate an innovative web-based developmental surveillance programme and a sustainable approach to referral and care pathways, linking primary care general practice (GP) services that fall under federal policy responsibility and state government-funded child health services. METHODS AND ANALYSIS: The proposed study describes a longitudinal cluster randomised controlled trial (c-RCT) comparing a 'Watch Me Grow Integrated' (WMG-I) approach for developmental screening, to Surveillance as Usual (SaU) in GPs. Forty practices will be recruited across New South Wales and Queensland, and randomly allocated into either the (1) WMG-I or (2) SaU group. A cohort of 2000 children will be recruited during their 18-month vaccination visit or opportunistic visit to GP. At the end of the c-RCT, a qualitative study using focus groups/interviews will evaluate parent and practitioner views of the WMG-I programme and inform national and state policy recommendations. ETHICS AND DISSEMINATION: The South Western Sydney Local Health District (2020/ETH01625), UNSW Sydney (2020/ETH01625) and University of Queensland (2021/HE000667) Human Research Ethics Committees independently reviewed and approved this study. Findings will be reported to the funding bodies, study institutes and partners; families and peer-reviewed conferences/publications. TRIAL REGISTRATION NUMBER: ANZCTR12621000680864.

Oxycodone for cancer-related pain.

BACKGROUND: Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated Cochrane review previously published in 2017. OBJECTIVES: To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2021. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions. SELECTION CRITERIA: We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference. DATA COLLECTION AND ANALYSIS: Two review authors independently sifted the search, extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and pain relief and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall certainty of the evidence using GRADE. MAIN RESULTS: For this update, we identified 19 new studies (1836 participants) for inclusion. In total, we included 42 studies which enrolled/randomised 4485 participants, with 3945 of these analysed for efficacy and 4176 for safety. The studies examined a number of different drug comparisons. Controlled-release (CR; typically taken every 12 hours) oxycodone versus immediate-release (IR; taken every 4-6 hours) oxycodone Pooled analysis of three of the four studies comparing CR oxycodone to IR oxycodone suggest that there is little to no difference between CR and IR oxycodone in pain intensity (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.1 to 0.34; n = 319; very low-certainty evidence). The evidence is very uncertain about the effect on adverse events, including constipation (RR 0.71, 95% CI 0.45 to 1.13), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), nausea (RR 0.85, 95% CI 0.56 to 1.28), and vomiting (RR 0.66, 95% CI 0.38 to 1.15) (very low-certainty evidence). There were no data available for quality of life or participant preference, however, three studies suggested that treatment acceptability may be similar between groups (low-certainty evidence). CR oxycodone versus CR morphine The majority of the 24 studies comparing CR oxycodone to CR morphine reported either pain intensity (continuous variable), pain relief (dichotomous variable), or both. Pooled analysis indicated that pain intensity may be lower (better) after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; n = 882 in 7 studies; low-certainty evidence). This SMD is equivalent to a difference of 0.27 points on the Brief Pain Inventory scale (0-10 numerical rating scale), which is not clinically significant. Pooled analyses also suggested that there may be little to no difference in the proportion of participants achieving complete or significant pain relief (RR 1.02, 95% CI 0.95 to 1.10; n = 1249 in 13 studies; low-certainty evidence). The RR for constipation (RR 0.75, 95% CI 0.66 to 0.86) may be lower after treatment with CR oxycodone than after CR morphine. Pooled analyses showed that, for most of the adverse events, the CIs were wide, including no effect as well as potential benefit and harm: drowsiness/somnolence (RR 0.88, 95% CI 0.74 to 1.05), nausea (RR 0.93, 95% CI 0.77 to 1.12), and vomiting (RR 0.81, 95% CI 0.63 to 1.04) (low or very low-certainty evidence). No data were available for quality of life. The evidence is very uncertain about the treatment effects on treatment acceptability and participant preference. Other comparisons The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability. The certainty of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes. AUTHORS' CONCLUSIONS: The conclusions have not changed since the previous version of this review (in 2017). We found low-certainty evidence that there may be little to no difference in pain intensity, pain relief and adverse events between oxycodone and other strong opioids including morphine, commonly considered the gold standard strong opioid. Although we identified a benefit for pain relief in favour of CR morphine over CR oxycodone, this was not clinically significant and did not persist following sensitivity analysis and so we do not consider this important. However, we found that constipation and hallucinations occurred less often with CR oxycodone than with CR morphine; but the certainty of this evidence was either very low or the finding did not persist following sensitivity analysis, so these findings should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that, while the reliability of the evidence base is low, given the absence of important differences within this analysis, it seems unlikely that larger head-to-head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.

Practice review: Evidence-based and effective management of anaemia in palliative care patients.

BACKGROUND: Anaemia is a common sequela of advanced disease and is associated with significant symptom burden. No specific guidance exists for the investigation and management of anaemia in palliative care patients. AIM: We aim to offer a pragmatic overview of the approaches to investigate and manage anaemia in advanced disease, based on guidelines and evidence in disease specific patient groups, including cancer, heart failure and chronic kidney disease. DESIGN: Scoping review methodology was used to determine the strength of evidence supporting the investigation and management of anaemia in patients with advanced disease. DATA SOURCES: A search for guidelines was performed in 2020. National or international guidelines were examined if they described the investigation or management of anaemia in adult patients with health conditions seen by palliative care services written within the last 5 years in the English language. Searches of MEDLINE, the Cochrane library and WHO guidance were made in 2019 to identify key publications that provided additional primary data. RESULTS: Evidence supports patient-centred investigation of anaemia, results of which should guide targeted intervention. Blanket use of blood transfusion should be avoided, with evidence supporting a more restrictive approach to transfusion. Routine use of oral iron and erythropoetin stimulating agents (ESAs) are not recommended. Insufficient evidence exists to determine the effectiveness of IV iron in this patient group. CONCLUSION: We advocate early consideration and investigation of anaemia, guided by symptom burden and patient preferences. Correction of reversible causes should be the mainstay of treatment, with a restrictive approach to blood transfusion. Research is required to evaluate the efficacy of IV iron in these patients.

Imputing pre-diagnosis health behaviour in cancer registry data and investigating its relationship with oesophageal cancer survival time.

BACKGROUND: As oesophageal cancer has short survival, it is likely pre-diagnosis health behaviours will have carry-over effects on post-diagnosis survival times. Cancer registry data sets do not usually contain pre-diagnosis health behaviours and so need to be augmented with data from external health surveys. A new algorithm is introduced and tested to augment cancer registries with external data when one-to-one data linkage is not available. METHODS: The algorithm is to use external health survey data to impute pre-diagnosis health behaviour for cancer patients, estimate misclassification errors in these imputed values and then fit misclassification corrected Cox regression to quantify the association between pre-diagnosis health behaviour and post-diagnosis survival. Data from US cancer registries and a US national health survey are used in testing the algorithm. RESULTS: It is demonstrated that the algorithm works effectively on simulated smoking data when there is no age confounding. But age confounding does exist (risk of death increases with age and most health behaviours change with age) and interferes with the performance of the algorithm. The estimate of the hazard ratio (HR) of pre-diagnosis smoking was HR = 1.32 (95% CI 0.82,2.68) with HR = 1.93 (95% CI 1.08,7.07) in the squamous cell sub-group and pre-diagnosis physical activity was protective of survival with HR = 0.25 (95% CI 0.03, 0.81). But the method failed for less common behaviours (such as heavy drinking). CONCLUSIONS: Further improvements in the I2C2 algorithm will permit enrichment of cancer registry data through imputation of new variables with negligible risk to patient confidentiality, opening new research opportunities in cancer epidemiology.

Long-read-sequenced reference genomes of the seven major lineages of enterotoxigenic Escherichia coli (ETEC) circulating in modern time.

Enterotoxigenic Escherichia coli (ETEC) is an enteric pathogen responsible for the majority of diarrheal cases worldwide. ETEC infections are estimated to cause 80,000 deaths annually, with the highest rates of burden, ca 75 million cases per year, amongst children under 5 years of age in resource-poor countries. It is also the leading cause of diarrhoea in travellers. Previous large-scale sequencing studies have found seven major ETEC lineages currently in circulation worldwide. We used PacBio long-read sequencing combined with Illumina sequencing to create high-quality complete reference genomes for each of the major lineages with manually curated chromosomes and plasmids. We confirm that the major ETEC lineages all harbour conserved plasmids that have been associated with their respective background genomes for decades, suggesting that the plasmids and chromosomes of ETEC are both crucial for ETEC virulence and success as pathogens. The in-depth analysis of gene content, synteny and correct annotations of plasmids will elucidate other plasmids with and without virulence factors in related bacterial species. These reference genomes allow for fast and accurate comparison between different ETEC strains, and these data will form the foundation of ETEC genomics research for years to come.

Augmenting cancer registry data with health survey data with no cases in common: the relationship between pre-diagnosis health behaviour and post-diagnosis survival in oesophageal cancer.

BACKGROUND: For epidemiological research, cancer registry datasets often need to be augmented with additional data. Data linkage is not feasible when there are no cases in common between data sets. We present a novel approach to augmenting cancer registry data by imputing pre-diagnosis health behaviour and estimating its relationship with post-diagnosis survival time. METHODS: Six measures of pre-diagnosis health behaviours (focussing on tobacco smoking, 'at risk' alcohol consumption, overweight and exercise) were imputed for 28,000 cancer registry data records of US oesophageal cancers using cold deck imputation from an unrelated health behaviour dataset. Each data point was imputed twice. This calibration allowed us to estimate the misclassification rate. We applied statistical correction for the misclassification to estimate the relative risk of dying within 1 year of diagnosis for each of the imputed behaviour variables. Subgroup analyses were conducted for adenocarcinoma and squamous cell carcinoma separately. RESULTS: Simulated survival data confirmed that accurate estimates of true relative risks could be retrieved for health behaviours with greater than 5% prevalence, although confidence intervals were wide. Applied to real datasets, the estimated relative risks were largely consistent with current knowledge. For example, tobacco smoking status 5 years prior to diagnosis was associated with an increased age-adjusted risk of all cause death within 1 year of diagnosis for oesophageal squamous cell carcinoma (RR = 1.99 95% CI 1.24,3.12) but not oesophageal adenocarcinoma RR = 1.61, 95% CI 0.79,2.57). CONCLUSIONS: We have demonstrated a novel imputation-based algorithm for augmenting cancer registry data for epidemiological research which can be used when there are no cases in common between data sets. The algorithm allows investigation of research questions which could not be addressed through direct data linkage.

Using estimated probability of pre-diagnosis behavior as a predictor of cancer survival time: an example in esophageal cancer.

BACKGROUND: Information on the associations between pre-diagnosis health behavior and post-diagnosis survival time in esophageal cancer could assist in planning health services but can be difficult to obtain using established study designs. We postulated that, with a large data set, using estimated probability for a behavior as a predictor of survival times could provide useful insight as to the impact of actual behavior. METHODS: Data from a national health survey and logistic regression were used to calculate the probability of selected health behaviors from participant's demographic characteristics for each esophageal cancer case within a large cancer registry data base. The associations between survival time and the probability of the health behaviors were investigated using Cox regression. RESULTS: Observed associations include: a 0.1 increase in the probability of smoking 1 year prior to diagnosis was detrimental to survival (Hazard Ratio (HR) 1.21, 95% CI 1.19,1.23); a 0.1 increase in the probability of hazardous alcohol consumption 10 years prior to diagnosis was associated with decreased survival in squamous cell cancer (HR 1.29, 95% CI 1.07, 1.56) but not adenocarcinoma (HR 1.08, 95% CI 0.94,1.25); a 0.1 increase in the probability of physical activity outside the workplace is protective (HR 0.83, 95% CI 0.81,0.84). CONCLUSIONS: We conclude that probability for health behavior estimated from demographic characteristics can provide an initial assessment of the association between pre-diagnosis health behavior and post-diagnosis health outcomes, allowing some sharing of information across otherwise unrelated data collections.

Perinatal Distress and Depression in Culturally and Linguistically Diverse (CALD) Australian Women: The Role of Psychosocial and Obstetric Factors.

Perinatal distress and depression can have significant impacts on both the mother and baby. The present study investigated psychosocial and obstetric factors associated with perinatal distress and depressive symptoms among culturally and linguistically diverse (CALD) Australian women in Sydney, New South Wales. The study used retrospectively linked maternal and child health data from two Local Health Districts in Australia (N = 25,407). Perinatal distress was measured using the Edinburgh Postnatal Depression Scale (EPDS, scores of 10-12) and depressive symptoms, with EPDS scores of 13 or more. Multivariate multinomial logistic regression models were used to investigate the association between psychosocial and obstetric factors with perinatal distress and depressive symptoms. The prevalence of perinatal distress and depressive symptoms among CALD Australian women was 10.1% for antenatal distress; 7.3% for antenatal depressive symptoms; 6.2% for postnatal distress and 3.7% for postnatal depressive symptoms. Antenatal distress and depressive symptoms were associated with a lack of partner support, intimate partner violence, maternal history of childhood abuse and being known to child protection services. Antenatal distress and depressive symptoms were strongly associated with postnatal distress and depressive symptoms. Higher socioeconomic status had a protective effect on antenatal and postnatal depressive symptoms. Our study suggests that current perinatal mental health screening and referral for clinical assessment is essential, and also supports a re-examination of perinatal mental health policy to ensure access to culturally responsive mental health care that meets patients' needs.

Tuberculosis disease burden and attributable risk factors in Nigeria, 1990-2016.

BACKGROUND: According to the World Health Organization, Nigeria is one of the countries with a high burden of tuberculosis (TB) worldwide. Improving the burden of TB among HIV-negative people would require comprehensive and up-to-date data to inform targeted policy actions in Nigeria. The study aimed to describe the incidence, prevalence, mortality, disability-adjusted life years (DALYs) and risk factors of tuberculosis in Nigeria between 1990 and 2016. METHODS: This study used the most recent data from the global burden of disease study 2016. TB deaths were estimated using the Cause of Death Ensemble model, while TB incidence, prevalence and DALYs, as well as years of life lost and years of life lived with disability were calculated in the DisMod-MR 2.1, a Bayesian meta-regression tool. Using a comparative risk assessment approach, TB burden attributable to risk factors was estimated in a spatial-temporal Gaussian Process Regression tool. RESULTS: In 2016, the prevalence of TB among HIV-negative people was 27% (95% uncertainty interval [95% UI] 23-31%) in Nigeria. TB incidence rate (new and relapse cases) was 158 per 100,000 people (95% UI; 128-193), while the total number of TB mortality was 39,933 deaths (95% UI; 30,488-55,039) in 2016. Between 2000 and 2016, the age-standardised prevalence and incidence rates of TB-HIV negative decreased by 20.0 and 87.6%, respectively. The age-standardised mortality rate also dropped by 191.6% over the same period. DALYs due to TB among HIV-negative Nigerians was high but varied across the age groups. Of the risk factors studied, alcohol use accounted for the highest number of TB deaths and DALYs, followed by diabetes and smoking in 2016. CONCLUSION: The study shows an improving trend in TB disease burden among HIV-negative individuals in Nigeria from 1990 to 2016. Despite this progress, this study suggests that additional efforts are still needed to ensure that Nigeria is not left behind in the current global strategy to end TB disease. Reducing TB disease burden in the country will require a multipronged approach that includes increased funding, health system strengthening and improved TB surveillance, as well as preventive efforts for alcohol use, smoking and diabetes.

Examination of Child and Adolescent Hospital Admission Rates in Queensland, Australia, 1995-2011: A Comparison of Coal Seam Gas, Coal Mining, and Rural Areas.

Objectives At present, coal seam gas (CSG) is the most common form of unconventional natural gas development occurring in Australia. Few studies have been conducted to explore the potential health impacts of CSG development on children and adolescents. This analysis presents age-specific hospitalisation rates for a child and adolescent cohort in three study areas in Queensland. Methods Three geographic areas were selected: a CSG area, a coal mining area, and a rural area with no mining activity. Changes in area-specific hospital admissions were investigated over the period 1995-2011 in a series of negative binomial regression analyses for 19 International Classification of Diseases (ICD) chapters, adjusting for sociodemographic factors. Results The strongest associations were found for respiratory diseases in 0-4 year olds (7% increase [95% CI 4%, 11%] and 6% increase [95% CI 2%, 10%] in the CSG area relative to the coal mining and rural areas, respectively) and 10-14 year olds (9% increase [95% CI 1%, 18%] and 11% increase [95% CI 1%, 21%] in the CSG area compared to the coal mining and rural areas, respectively). The largest effect size was for blood/immune diseases in 5-9 year olds in the CSG area (467% increase [95% CI 139%, 1244%]) compared to the rural area with no mining activity. Conclusions for Practice Higher rates of hospitalisation existed in the CSG area for certain ICD chapters and paediatric age groups, suggesting potential age-specific health impacts. This study provides insights on associations that should be explored further in terms of child and adolescent health.

CKS1 expression in melanocytic nevi and melanoma.

Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, 19 ± 20, and 30 ± 29, respectively. While cytoplasmic Cks1 was found in 41% of melanocytic nevi, 84% primary and 95% metastatic melanomas with mean labeling index of 18 ± 34, 35 ± 34, and 52 ± 34, accordingly. Histologic stepwise model of tumor progression, defined as progression from benign nevi to primary melanomas, to melanoma metastases, revealed a significant increase in nuclear and cytoplasmic Cks1 expression with tumor progression. Nuclear and cytoplasmic Cks1 expression correlated with the presence of ulceration, increased mitotic rate, Breslow depth, Clark level, tumor infiltrating lymphocytes and gender. However, other well-known prognostic factors (age, anatomic site, and regression) did not correlate with any type of Cks1 expression. Similarly, increasing nuclear expression of Cks1 significantly correlated with worse overall survival. Thus, Cks1 expression appears to play a role in the progression of melanoma, where high levels of expression are associated with poor outcome. Cytoplasmic expression of Cks1 might represent high turnover of protein via the ubiquination/proteosome pathway.

Geographical Inequality in Tobacco Control in China: Multilevel Evidence From 98†058 Participants.

Background: We investigated the spatial patterning and correlates of tobacco smoking, exposure to secondhand smoke, smoking in public places, workplace smoking prohibition, pro- and counter-tobacco advertisements in mainland China. Methods: Choropleth maps and multilevel models were used to assess geographical variation and correlates of the aforementioned outcome variables for 98 058 participants across 31 provinces of China in 2010. Results: Current tobacco smoking prevalence was higher in the central provinces for men and in the north eastern provinces and Tibet for women. Secondhand smoke was higher for both genders in Qinghai and Hunan provinces. Workplace tobacco restrictions was higher in the north and east, whereas smoking in public places was more common in the west, central, and far northeast. Protobacco advertising was observed in public places more often by men (18.5%) than women (13.1%). Men (35.5%) were also more likely to sight counter-tobacco advertising in public places than women (30.1%). Awareness of workplace tobacco restrictions was more common in affluent urban areas. Lower awareness of workplace tobacco restrictions was in less affluent urban and rural areas. Sightings of tobacco smoking in public places was highest in restaurants (80.4% for men, 75.0% for women) and also commonly reported in less affluent urban and rural areas. Exposure to secondhand smoke was lower among women (but not men) where workplace tobacco restrictions was more common and higher regardless of gender in areas where smoking in public places was more commonly observed. Conclusions: Geographical and gender-sensitive targeting of tobacco prevention and control initiatives are warranted. Implications: This study demonstrates spatial patterning of China's 300 million smokers across the country that are different for men and women. Many of the factors that influence tobacco use, such as pro- and counter-advertising, also vary geographically. Workplace smoking restrictions are more commonly reported among individuals with higher educational attainment, but this not does appear to translate into reduced exposure to secondhand smoke. There is a need to intervene in other contexts, especially in restaurants and on public transport. Geographically targeted and gender-sensitive policy is required to advance effective tobacco control and prevention of noncommunicable diseases across all of China.

The impact of antenatal care, iron-folic acid supplementation and tetanus toxoid vaccination during pregnancy on child mortality in Bangladesh.

BACKGROUND: Appropriate antenatal care (ANC) is an important preventive public health intervention to ensure women's and newborn health outcomes. The study aimed to investigate the impact of ANC, iron-folic acid (IFA) supplementation and tetanus toxoid (TT) vaccination during pregnancy on child mortality in Bangladesh. METHOD: A cross-sectional study of three datasets from the Bangladesh Demographic and Health Surveys for the years 2004, 2007 and 2011 were pooled and used for the analyses. A total weighted sample of 16,721 maternal responses (5,364 for 2004; 4,872 for 2007 and 6,485 for 2011) was used. Multivariate logistic models that adjusted for cluster and sampling weights were used to examine the impact of ANC, IFA supplementation and TT vaccination during pregnancy on the death of a child aged 0-28 days (neonatal), 1-11 months (post-neonatal) and 12-59 months (child). RESULTS: Multivariable analyses revealed that the odds of postnatal and under-5 mortality was lower in mothers who had ANC [Odds Ratio (OR) = 0.60, 95% confidence interval (95% CI): 0.43-0.85], IFA supplementation [OR = 0.66, 95% CI: (0.45-0.98)] and ≥2 TT vaccinations (OR = 0.43, 95% CI: 0.49-0.78) for post-natal mortality; and for under-5 mortality, any form of ANC (OR = 0.69, 95% CI: 0.51-0.93), IFA supplementation (OR = 0.67, 95% CI: 0.48-0.94) and ≥2 TT vaccinations (OR = 0.50, 95% CI: 0.36-0.69). When combined, TT vaccination with IFA supplementation, and TT vaccination without IFA supplementation were protective across all groups. CONCLUSION: The study found that ANC, IFA supplementation, and TT vaccination during pregnancy reduced the likelihood of child mortality in Bangladesh. The findings suggest that considerable gains in improving child survival could be achieved through ensuring universal coverage of ANC, promoting TT vaccination during pregnancy and IFA supplementation among pregnant women in Bangladesh.