Peta Forder

Whole brain radiotherapy after local treatment of brain metastases in melanoma patients--a randomised phase III trial.

BackgroundCerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete.Methods/DesignThis trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function.DiscussionAccrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain metastases. The trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG-study 01-07), and the Trans Tasman Radiation Oncology Group (TROG) but international participation is encouraged. Twelve sites are open to date with 43 patients randomised as of the 31st March 2011. The target accrual is 200 patients.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000512426

A Randomized Controlled Trial of a Standardized Educational Intervention for Patients with Cancer Pain

CONTEXT Published literature has not defined the effectiveness of standardized educational tools that can be self-administered in the general oncology population with pain. OBJECTIVES We sought to determine if an educational intervention consisting of a video and/or booklet for adults with cancer pain could improve knowledge and attitudes about cancer pain management, pain levels, pain interference, anxiety, quality of life, and analgesic use. METHODS Eligible participants had advanced cancer, a pain score >/=2 of 10 in the last week, English proficiency, an estimated prognosis of more than one month, and were receiving outpatient cancer treatment at participating hospitals. Participants completed baseline assessments and then were randomly allocated to receive a booklet, a video, both, or neither, in addition to standard care. Outcome measures at two and four weeks included the Barriers Questionnaire (BQ), Brief Pain Inventory, Global Quality of Life Scale, and Hospital Anxiety and Depression Scale. Adequacy of analgesia and severity of pain were assessed with the Pain Management Index and a daily pain diary. RESULTS One hundred fifty-eight participants were recruited from 21 sites over 42 months. Baseline mean barriers scores were lower than reported in previous Australian studies at 1.33 (standard deviation: 0.92). Mean average pain and worst pain scores improved significantly in patients receiving both the video and booklet by 1.17 (standard error [SE]: 0.51, P=0.02) and 1.12 (SE: 0.57, P=0.05), respectively, on a 0-10 scale. The addiction subscale of the BQ score was improved by 0.44 (SE: 0.19) for participants receiving any part of the intervention (P=0.03). CONCLUSION Provision of a video and/or booklet for people with cancer pain was a feasible and effective adjunct to the management of cancer pain.

Delayed versus Immediate Cord Clamping in Preterm Infants

Background The preferred timing of umbilical‐cord clamping in preterm infants is unclear. Methods We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late‐onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention‐to‐treat basis, accounting for multiple births. Results Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed‐clamping group and 9.0% in the immediate‐clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. Conclusions Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088.)

Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer. A randomized clinical trial

Importance Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, −5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, −3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, −3.0% to 4.2%]; P = .76). Conclusions and Relevance Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516

Agreement between self-reported perinatal outcomes and administrative data in New South Wales, Australia

BackgroundMany epidemiological studies that focus on pregnancy rely on maternal self-report of perinatal outcomes. The aim of this study was to evaluate the agreement between self-reported perinatal outcomes (gestational hypertension with or without proteinuria, gestational diabetes, premature birth and low birth weight) in a longitudinal study and linked to administrative data (medical records).MethodsSelf-reported survey data from the Australian Longitudinal Study on Women’s Health was linked with the New South Wales Perinatal Data Collection. Agreement between the two sources was evaluated using percentage agreement and kappa statistics. Analyses were conducted at two levels by: i) the mother and ii) each individual child.ResultsWomen reliably self-report their perinatal outcomes (≥87 % agreement). Gestational hypertension with or without proteinuria had the lowest level of agreement. Mothers’ reports of perinatal outcomes were more reliable when evaluated by child. Restricting the analysis to complete and consistent reporting further strengthened the reliability of the child-specific data, increasing the agreement from >92 to >95 % for all outcomes.ConclusionsThe present study offers a high degree of confidence in the use of maternal self-reports of the perinatal outcomes gestational hypertension, gestational diabetes, preterm birth and low birth weight in epidemiological research, particularly when reported on a per child basis. Furthermore self-report offers a cost-effective and convenient method for gathering detailed maternal perinatal histories.

Prevalence correlates and impact of fecal incontinence among older women.

BACKGROUND: Fecal incontinence is a common problem that has been associated with anatomic, physiological, and medical conditions. There are very few data on the factors associated with fecal incontinence in elderly women. OBJECTIVES: We aimed to determine the factors associated with fecal incontinence via a population-based survey in a large cohort of elderly Australian women. DESIGN AND SETTING: Data from a large longitudinal population-based study of elderly Australian women aged 82 to 87 years were analyzed. PATIENTS: Participants were 5560 women (aged 82–87 years) who participated in the Australian Longitudinal Study on Women’s Health; 4815 women responded to questions relating to fecal incontinence. MAIN OUTCOME MEASURES: Fecal incontinence was defined as leakage of liquid and/or solid stool at least once per month over the past 12 months. Self-reported medical conditions and lifestyle factors as well as demographic factors were recorded. RESULTS: The prevalence of fecal incontinence was 10.4% (95% CI, 9.6–11.3) (n = 510). The prevalence was significantly higher among institutional- versus community-dwelling women (14.1% vs 9.7%; p = 0.0002). Univariately, lifestyle factors including fruit intake and fluid intake, along with a range of comorbidities, were associated. However, independent factors for fecal incontinence among community-dwelling women included diabetes mellitus (OR, 1.51; 95% CI, 1.14–2.01; p = 0.004), depression (OR, 1.84; 95% CI, 1.30–2.62; p = 0.001), urinary incontinence (OR, 2.29; 95% CI, 1.83–2.86; p < 0.0001), and osteoarthritis (OR, 0.73; 95% CI, 0.57–0.94; p = 0.013). Among institutional-dwelling women, however, we found urinary incontinence (OR, 4.43; 95% CI, 2.83–6.93; p < 0.0001) and poorer general health (OR, 0.98; 95% CI, 0.97–0.99; p = 0.003) to be independently associated. LIMITATIONS: This is a cross-sectional study, which prevents making conclusions about the cause and effect of observed correlations. CONCLUSIONS: The independent factors associated with fecal incontinence in this population do not appear readily modifiable, and many previously identified risk factors may not be important in the elderly women with fecal incontinence.

History of Pregnancy Loss Increases the Risk of Mental Health Problems in Subsequent Pregnancies but Not in the Postpartum

While grief, emotional distress and other mental health conditions have been associated with pregnancy loss, less is known about the mental health impact of these events during subsequent pregnancies and births. This paper examined the impact of any type of pregnancy loss on mental health in a subsequent pregnancy and postpartum. Data were obtained from a sub-sample (N = 584) of the 1973-78 cohort of the Australian Longitudinal Study on Womens Health, a prospective cohort study that has been collecting data since 1996. Pregnancy loss was defined as miscarriage, termination due to medical reasons, ectopic pregnancy and stillbirth. Mental health outcomes included depression, anxiety, stress or distress, sadness or low mood, excessive worry, lack of enjoyment, and feelings of guilt. Demographic factors and mental health history were controlled for in the analysis. Women with a previous pregnancy loss were more likely to experience sadness or low mood (AOR = 1.75, 95% CI: 1.11 to 2.76, p = 0.0162), and excessive worry (AOR = 2.01, 95% CI: 1.24 to 3.24, p = 0.0043) during a subsequent pregnancy, but not during the postpartum phase following a subsequent birth. These results indicate that while women who have experienced a pregnancy loss are a more vulnerable population during a subsequent pregnancy, these deficits are not evident in the postpartum.

Predictors of antenatal alcohol use among Australian women: a prospective cohort study.

To identify predictors of antenatal alcohol consumption among women who usually consume alcohol.

Risky drinking patterns are being continued into pregnancy: a prospective cohort study

Background Risky patterns of alcohol use prior to pregnancy increase the risk of alcohol-exposed pregnancies and subsequent adverse outcomes. It is important to understand how consumption changes once women become pregnant. Objective The aim of this study was to describe the characteristics of women that partake in risky drinking patterns before pregnancy and to examine how these patterns change once they become pregnant. Methods A sample of 1577 women from the 1973–78 cohort of the Australian Longitudinal Study on Women’s Health were included if they first reported being pregnant in 2000, 2003, 2006, 2009 and reported risky drinking patterns prior to that pregnancy. Multinomial logistic regression was used to determine which risky drinking patterns were most likely to continue into pregnancy. Results When reporting risky drinking patterns prior to pregnancy only 6% of women reported weekly drinking only, whereas 46% reported binge drinking only and 48% reported both. Women in both binge categories were more likely to have experienced financial stress, not been partnered, smoked, used drugs, been nulliparous, experienced a violent relationship, and were less educated. Most women (46%) continued these risky drinking patterns into pregnancy, with 40% reducing these behaviors, and 14% completely ceasing alcohol consumption. Once pregnant, women who binged only prior to pregnancy were more likely to continue (55%) rather than reduce drinking (29%). Of the combined drinking group 61% continued to binge and 47% continued weekly drinking. Compared with the combined drinking group, binge only drinkers prior to pregnancy were less likely to reduce rather than continue their drinking once pregnant (OR = 0.37, 95% CI  =  0.29, 0.47). Conclusions Over a third of women continued risky drinking into pregnancy, especially binge drinking, suggesting a need to address alcohol consumption prior to pregnancy.

Associations between the use of metformin, sulphonylureas, or diet alone and cardiovascular outcomes in 6005 people with type 2 diabetes in the FIELD study

AIMS We aimed to determine the associations between metformin or sulphonylurea monotherapy at study entry into the FIELD diabetes trial and (1) metabolic risk factors, (2) risk of a first major cardiovascular (CVD) outcome, and (3) the effect of each therapy on the risk-modifying effect of fenofibrate. METHODS Patients receiving metformin or sulphonylureas without insulin therapy were compared for the relative risk of CVD outcomes, adjusted for differences in baseline characteristics likely to affect risk. RESULTS Metformin-treated patients were likely to be younger, female, or obese. Metformin was associated with higher levels of lipids (other than LDL-C) and homocysteine (P<0.001). Sulphonylurea-treated patients had a longer history of diabetes and more CVD and microvascular disease. Sulphonylurea treatment was associated with higher plasma creatinine and lower plasma HDL-C (P<0.001). The risks of all CVD outcomes were higher for those on sulphonylureas than diet alone, but were nonsignificant after adjustment for the duration and intensity of diabetes and severity of risk factors. Metformin and sulphonylureas did not significantly influence the benefits of fenofibrate on CVD outcomes. CONCLUSIONS Apparent differences in the risk of CVD outcomes associated with oral hypoglycemics therapy were largely abolished by adjustment for diabetes and CVD risk factors.