Summary Background Stillbirth rates in high-income countries have shown little or no improvement over the past two decades. Prevention strategies that target risk factors could be important in rate ...reduction. This systematic review and meta-analysis was done to identify priority areas for stillbirth prevention relevant to those countries. Methods Population-based studies addressing risk factors for stillbirth were identified through database searches. The factors most frequently reported were identified and selected according to whether they could potentially be reduced through lifestyle or medical intervention. The numbers attributable to modifiable risk factors were calculated from data relating to the five high-income countries with the highest numbers of stillbirths and where all the data required for analysis were available. Odds ratios were calculated for selected risk factors, from which population-attributable risk (PAR) values were calculated. Findings Of 6963 studies initially identified, 96 population-based studies were included. Maternal overweight and obesity (body-mass index >25 kg/m2 ) was the highest ranking modifiable risk factor, with PARs of 8–18% across the five countries and contributing to around 8000 stillbirths (≥22 weeks' gestation) annually across all high-income countries. Advanced maternal age (>35 years) and maternal smoking yielded PARs of 7–11% and 4–7%, respectively, and each year contribute to more than 4200 and 2800 stillbirths, respectively, across all high-income countries. In disadvantaged populations maternal smoking could contribute to 20% of stillbirths. Primiparity contributes to around 15% of stillbirths. Of the pregnancy disorders, small size for gestational age and abruption are the highest PARs (23% and 15%, respectively), which highlights the notable role of placental pathology in stillbirth. Pre-existing diabetes and hypertension remain important contributors to stillbirth in such countries. Interpretation The raising of awareness and implementation of effective interventions for modifiable risk factors, such as overweight, obesity, maternal age, and smoking, are priorities for stillbirth prevention in high-income countries. Funding The Stillbirth Foundation Australia, the Department of Health and Ageing, Canberra, Australia, and the Mater Foundation, Brisbane, Australia.
Surgery for epithelial ovarian cancer (EOC) may activate stress-inflammatory responses that stimulate tumor growth and increase metastatic growth. Animal and in vitro studies have shown that ...inhibition of the catecholamine-induced inflammatory response via beta-adrenergic receptor blockade has antitumor potential in EOC. However, observational studies have reported mixed results. We assessed whether beta-blocker (BB) use at the time of primary ovarian cancer surgery was associated with improved survival in a large population-based study.
Using linked administrative data, a population-based cohort of 3,844 Australian women age 50 years or older with a history of cardiovascular conditions who underwent surgery for EOC was followed for survival outcomes. The average treatment effect of selective BB (SBB) and nonselective BB (NSBB) supply at the time of surgery on survival was estimated from a causal inference perspective using covariate-balanced inverse probability of treatment weights with flexible parametric survival models that allowed for time-varying survival effects.
Around the time of surgery, 560 (14.5%) women were supplied a SBB and 67 (1.7%) were supplied a NSBB. At 2 years postsurgery, the survival proportion was 80% (95% CI, 68 to 88) for women dispensed NSBBs at surgery compared with 69% (95% CI, 67 to 70) for women not supplied NSBBs. The survival advantage appeared to extend to at least 8 years postsurgery. No association was observed for women dispensed a SBB around the time of surgery.
Perioperative supply of NSBBs appeared to confer a survival advantage for women age over 50 years with a history of cardiovascular conditions. Long-term clinical trials are required to confirm these findings.
Objective: To measure progress, over the past decade, in reducing the disadvantage in cancer death rates among people living in regional and remote areas of Australia.
Design: Analysis of routinely ...collected death certificate and corresponding population data from the Australian Bureau of Statistics.
Setting: Population‐based, Australia‐wide comparison of mortality rates in regional and remote areas compared with metropolitan areas from 1 January 2001 to 31 December 2010.
Main outcome measures: Absolute and relative excess of cancer deaths in regional and remote areas.
Results: The number of excess cancer deaths in regional and remote areas from 2001 to 2010 was 8878 (95% CI, 8187–9572). For men, the age‐standardised mortality ratios (comparing regional and remote areas with metropolitan areas) showed no evidence of improvement, from 1.08 in 1997–2000 to 1.11 in 2006–2010. For women, they increased from 1.01 in 1997–2000 to 1.07 in 2006–2010. The age‐standardised cancer death rate in regional and remote areas (annual percentage change APC, − 0.6%; 95% CI, − 0.8% to − 0.4%) is decreasing more slowly than in metropolitan areas (APC, − 1.1%; 95% CI, − 1.3% to − 1.0%).
Conclusions: The regional and remote disadvantage for cancer deaths has been recognised as a problem for more than two decades, yet we have made little progress. This is not surprising — we have not invested in research into solutions. The benefits of laboratory and clinical research to identify innovative cancer treatments will not be fully realised across the entire Australian population unless we also invest in health systems and policy research.
Aim It has been reported that rates of epilepsy and mortality are higher among the population with autism spectrum disorder (ASD) than in the general population. The aim of this systematic review is ...to provide comprehensive evidence for clinicians, carers, and people with ASD regarding these outcomes.
Method Studies were eligible for inclusion if the main focus of the study involved observation over a period of 12 months or more of an initially defined population (with appropriate diagnostic label). Studies were also required to have at least 30 participants in order to differentiate case series from cohort studies. The Cochrane Database of Systematic Reviews, the Database of Reviews of Effectiveness, MEDLINE, PsycINFO, EMBASE, and CINAHL were searched. The date of the last search was September 2010. The risk of bias of included studies was assessed and a meta‐analysis was undertaken.
Results Twenty‐one studies were identified, 16 measuring the percentage of participants with epilepsy and five measuring mortality using a standardized mortality ratio. The pooled estimate for the percentage of participants with epilepsy was 1.8% (95% CI 0.4–9.4%) in studies in which the majority did not have an intellectual disability and the mean age was <12 years at follow‐up, and 23.7% (95% CI 17.5–30.5%) in studies in which the majority did have an intellectual disability and the mean age at follow‐up was more than 12 years. The pooled estimate for the standardized mortality ratio was 2.8 (95% CI 1.8–4.2).
Interpretation The prevalence of epilepsy is higher among the population with ASD than in the general population. People with ASD have a higher risk of mortality than the general population. This has important health promotion implications.
On September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high ...(MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%-48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit-risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review.
The 20-year survival rates are unknown for the majority of melanoma patients-those with thin melanomas. We determined 20-year survival rates of patients diagnosed with thin melanomas (≤ 1.00 mm) in ...the general population and also determined the main prognostic factors.
Available clinical and histologic data from the Queensland Cancer Registry were obtained for all patients diagnosed with a single thin invasive melanoma from 1982 to 2006 and matched against national death registration data. Melanoma-specific survival estimates to December 31, 2007, were assessed, and subgroup differences in prognosis were determined by fitting multivariate Cox proportional hazard models.
Among 26,736 people in the state of Queensland diagnosed with thin melanomas, the 20-year survival was 96%. The most influential determinants of prognosis were tumor thickness ≥ 0.75 mm (adjusted hazard ratio HR, 4.33; 95% CI, 2.8 to 6.8 compared with tumors < 0.25 mm) and patient age at diagnosis older than 65 years (HR, 2.8; 95% CI, 1.8 to 4.5) compared with age younger than 25 years. Acral lentiginous and nodular tumors, male sex, tumor site on the scalp or neck, or tumor invasion of the entire papillary dermis each independently increased the risk of dying from thin invasive melanoma.
The outlook for patients with thin invasive melanoma is positive, although continued clinical vigilance is warranted for patients with nodular melanoma and those with the thickest tumors.
Abstract
Background
There are few readily modifiable risk factors for epithelial ovarian cancer; preclinical studies suggest bisphosphonates could have chemopreventive actions. Our study aimed to ...assess the association between use of nitrogen-based bisphosphonate medicine and risk of epithelial ovarian cancer, overall and by histotype.
Methods
We conducted a case-control study nested within a large, linked administrative dataset including all Australian women enrolled for Medicare, Australia’s universal health insurance scheme, between July 2002 and December 2013. We included all women with epithelial ovarian cancer diagnosed at age 50 years and older between July 1, 2004, and December 31, 2013 (n = 9367) and randomly selected up to 5 controls per case, individually matched to cases by age, state of residence, area-level socioeconomic status, and remoteness of residence category (n = 46 830). We used prescription records to ascertain use of nitrogen-based bisphosphonates (ever use and duration of use), raloxifene, and other osteoporosis medicines (no nitrogen-based bisphosphonates, strontium and denosumab). We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression.
Results
Ever use of nitrogen-based bisphosphonates was associated with a reduced risk of epithelial ovarian cancer compared with no use (OR = 0.81, 95% CI = 0.75 to 0.88). There was a reduced risk of endometrioid (OR = 0.51, 95% CI = 0.33 to 0.79) and serous histotypes (OR = 0.84, 95% CI = 0.75 to 0.93) but no association with the mucinous or clear cell histotypes.
Conclusion
Use of nitrogen-based bisphosphonates was associated with a reduced risk of endometrioid and serous ovarian cancer. This suggests the potential for use for prevention, although validation of our findings is required.
Objective: To update our previous analysis of trends for prostate‐specific antigen (PSA) testing, prostate cancer incidence, radical prostatectomy and prostate cancer mortality to assess whether men ...in rural and regional areas of Australia now have more equitable access to prostate cancer services, and improved outcomes.
Design, setting and participants: Descriptive study using population‐based data for Australian men aged 50–79 years from 1982 to the 2008–09 financial year (depending on data availability for each outcome measure).
Main outcome measures: Age‐standardised rates per 100 000 men and 5‐year survival rates.
Results: Overall, rates of PSA screening and radical prostatectomy increased, accompanied by reductions in mortality and improvements in survival throughout Australia. Incidence rates were similar for men in urban and rural areas. However, in the last year of data collection, for men in rural areas compared with urban areas, rates of PSA screening (21 267/100 000 v 24 606/100 000; P < 0.01) and radical prostatectomy (182.2/100 000 v 239.2/100 000; P < 0.01) remained lower, mortality remained higher (56.9/100 000 v 45.8/100 000; P < 0.01), and survival outcomes continued to be poorer (5‐year relative survival, 87.7% v 91.4%; P < 0.01).
Conclusions: With some limitations, these ecological data demonstrate that the use of diagnostic and treatment services among men living in rural areas of Australia remains lower than among their urban counterparts, their survival and mortality outcomes are poorer, and these differentials are continuing. There is an urgent need to explore further the reasons for these differences and to implement changes so these inequalities can be reduced.
Response to Lehrer and Rheinstein Tuesley, Karen M; Webb, Penelope M; Protani, Melinda M ...
JNCI : Journal of the National Cancer Institute,
10/2022, Letnik:
114, Številka:
10
Journal Article
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