D. M. Purdie

Bevacizumab Beyond First Progression Is Associated With Prolonged Overall Survival in Metastatic Colorectal Cancer: Results From a Large Observational Cohort Study (BRiTE)

PURPOSEnBevacizumab provides a survival benefit in first- and second-line metastatic colorectal cancer (mCRC). In a large, observational, bevacizumab treatment study (Bevacizumab Regimens: Investigation of Treatment Effects and Safety [BRiTE]) in patients who had mCRC, a longer-than-expected overall survival (OS) of 25.1 months was reported. The association between various pre- and post-treatment factors (including the use of bevacizumab beyond first progression [BBP]) and survival was examined.nnnPATIENTS AND METHODSnThe 1,445 of 1,953 previously untreated patients with mCRC who were enrolled in BRiTE and who experienced disease progression (PD) were classified into three groups: no post-PD treatment (n = 253), post-PD treatment without bevacizumab (no BBP; n = 531), and BBP (n = 642). Relevant baseline and on-study variables, including BBP, were analyzed with a Cox model with respect to their independent effect on survival beyond first PD.nnnRESULTSnMedian OS was 25.1 months (95% CI, 23.4 to 27.5 months), and median progression-free survival was 10.0 months in the overall BRiTE population. Baseline and postbaseline factors were well balanced between the BBP and no-BBP groups. Median OS rates were 12.6, 19.9, and 31.8 months in the no post-PD treatment, no-BBP, and BBP groups, respectively. In multivariate analyses, compared with no BBP, BBP was strongly and independently associated with improved survival (HR, 0.48; P < .001). Hypertension that required medication was the only bevacizumab-related safety event that occurred more frequently in the BBP group (24.6% v 19.2%).nnnCONCLUSIONnThese results from a large, prospective, observational study suggest that continued vascular endothelial growth factor inhibition with bevacizumab beyond initial PD could play an important role improving the overall success of therapy for patients who have mCRC.

Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life

Background and aim: Obesity is a risk factor for progression of fibrosis in chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C. The aim of this study was to investigate the longer term effect of weight loss on liver biochemistry, serum insulin levels, and quality of life in overweight patients with liver disease and the effect of subsequent weight maintenance or regain. Patients: Thirty one patients completed a 15 month diet and exercise intervention. Results: On completion of the intervention, 21 patients (68%) had achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body weight. Improvements in serum alanine aminotransferase (ALT) levels were correlated with the amount of weight loss (ru200a=u200a0.35, pu200a=u200a0.04). In patients who maintained weight loss, mean ALT levels at 15 months remained significantly lower than values at enrolment (pu200a=u200a0.004), while in regainers (nu200a=u200a10), mean ALT levels at 15 months were no different to values at enrolment (pu200a=u200a0.79). Improvements in fasting serum insulin levels were also correlated with weight loss (ru200a=u200a0.46, pu200a=u200a0.04), and subsequent weight maintenance sustained this improvement. Quality of life was significantly improved after weight loss. Weight maintainers sustained recommended levels of physical activity and had higher fasting insulin levels (pu200a=u200a0.03) at enrolment than weight regainers. Conclusion: In summary, these findings demonstrate that maintenance of weight loss and exercise in overweight patients with liver disease results in a sustained improvement in liver enzymes, serum insulin levels, and quality of life. Treatment of overweight patients should form an important component of the management of those with chronic liver disease.

Clinical Outcomes Associated with Bevacizumab-Containing Treatment of Metastatic Colorectal Cancer: The BRiTE Observational Cohort Study

BACKGROUNDnThe Bevacizumab Regimens Investigation of Treatment Effects (BRiTE) study is a prospective, observational cohort study designed to elucidate safety and effectiveness outcomes associated with bevacizumab combined with chemotherapy as used in clinical practice for first-line treatment of metastatic colorectal cancer (mCRC).nnnPATIENTS AND METHODSnBaseline characteristics, prespecified bevacizumab-related adverse events, and effectiveness data were collected from 1,953 mCRC patients who were receiving first-line treatment including bevacizumab at 248 U.S. sites.nnnRESULTSnAt database lock, the median follow-up was 20.1 months. At baseline, 46% of patients were aged >or=65 years and 49% had an Eastern Cooperative Oncology Group performance status score >or=1. Fluorouracil, leucovorin, and oxaliplatin was the most common first-line chemotherapy regimen (56%). Overall rates of bevacizumab-related adverse events in the BRiTE study, such as gastrointestinal perforation (1.9%), arterial thromboembolic events (2%), grade 3-4 bleeding (2.2%), and de novo hypertension requiring medication (22%), were consistent with those reported in randomized clinical trials (RCTs) of bevacizumab in first-line mCRC treatment. The median progression-free survival (PFS) and overall survival (OS) times were 9.9 (95% confidence interval [CI], 9.5-10.3) months and 22.9 (95% CI, 21.9-24.4) months, respectively.nnnCONCLUSIONnThe median PFS and OS durations and safety profile of bevacizumab in the BRiTE study were similar to those in RCTs of bevacizumab plus chemotherapy in first-line mCRC patients. The observations from the BRiTE study complement and expand upon RCT data, providing clinical information in a large cohort of bevacizumab-treated patients and subgroups such as the elderly.

Magnetic resonance imaging and spectroscopy for monitoring liver steatosis

To compare noninvasive MRI and magnetic resonance spectroscopy (MRS) methods with liver biopsy to quantify liver fat content.

Early menstrual characteristics associated with subsequent diagnosis of endometriosis

OBJECTIVEnThe aim of this study was to investigate the association between early menstrual characteristics, before symptom onset, and later diagnosis of endometriosis.nnnSTUDY DESIGNnThis was a case-control study of 268 Australian women with surgically confirmed moderate-to-severe endometriosis (cases) and 244 women without endometriosis (controls). Early menstrual cycle characteristics, before age at symptom onset, were analyzed.nnnRESULTSnMenarche after age 14 years was strongly and inversely associated with endometriosis (odds ratio, 0.3; 95% confidence interval, 0.1-0.6). A history of dysmenorrhea was associated with subsequent endometriosis (odds ratio, 2.6; 95% confidence interval, 1.1-6.2). Despite a suggestive trend, shorter menstrual cycle length was not associated with endometriosis. Duration of natural menstruation and heaviness of flow were not associated with subsequent risk of endometriosis; neither was the reported type of sanitary protection used nor history of sexual intercourse during menstruation.nnnCONCLUSIONnThere is a decreased risk of endometriosis with late age at menarche and an increased risk in women who report an early history of dysmenorrhea.

Ten-year outcomes following traumatic brain injury: A population-based cohort

Primary objective: To quantify the 10 year health service use (HSU) and mortality outcomes for people with a traumatic brain injury (TBI). Research design: A population-based matched cohort study using linked administrative data from Manitoba, Canada (Manitoba Injury Outcome Study). Methods and procedures: An inception cohort (1988–1991) of hospitalized cases with TBI aged 18–64 years (n= 1290) was identified and matched to a non-injured comparison group (n= 1290). Survival analysis, Negative binomial and Poisson regression were used to quantify associations between injury and HSU/mortality outcomes for 10 years following the TBI event. Main outcome and results: The majority of deaths (47.2%) occurred in the first 60 days following injury. Excluding the first 60 days, the adjusted 10 year mortality remained elevated (mortality rate ratio = 1.48, 95% CI = 1.02–2.15). After adjusting for demographic characteristics and pre-existing health status, the TBI cohort had more post-injury hospitalizations (rate ratio (RR) = 1.54, 95% CI = 1.39–1.71), greater cumulative lengths of stay (RR = 5.14, 95% CI = 3.29–8.02) and a greater post-injury physician claims rate (RR = 1.44, 95% CI = 1.35–1.53) than the non-injured cohort. Conclusions: People who sustain a TBI and survive the initial acute phase of care experience substantially increased long-term morbidity compared to the general population, regardless of the level of injury severity.

Relative weight at ages 10 and 16 years and risk of endometriosis: A case-control analysis

BACKGROUNDnAlthough previous epidemiological studies have shown that women with endometriosis are more likely to be thinner and underweight, it is currently not clear whether this is a true characteristic of women who develop endometriosis or a consequence of their disease and its symptoms. The aim of this study was to investigate the relationship between endometriosis and relative weight in childhood and adolescence, prior to diagnosis.nnnMETHODSnThis case-control study included 268 Australian women with surgically confirmed moderate to severe endometriosis (cases) and 244 women without endometriosis (controls). Relative weight at ages 10 and 16 years, as recalled and classified (underweight, average weight and overweight) separately by the women themselves and their mothers, was analyzed.nnnRESULTSnWomen who reported being overweight at 10 years had an increased risk of endometriosis (OR 2.8; 95% CI 1.1-7.5). Mothers reports and concordant responses among mother-daughter pairs were consistent with this association. There was no clear evidence of an association between relative weight at 16 years and risk of endometriosis.nnnCONCLUSIONSnThese data suggest that being overweight during late childhood is associated with the development of endometriosis; however, the results warrant confirmation in larger study populations.

Recognition of Genetic Factors Influencing the Progression of Hepatitis C

Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. Hepatic fibrosis may develop in subjects with chronic HCV infection, culminating in cirrhosis and an increased risk of hepatocellular carcinoma. The rate of development of fibrosis varies substantially between individuals; while it is influenced by a number of demographic and environmental factors, these account for only a small proportion of the variability.There are no clinical markers or tests that predict the rate of fibrosis progression in an individual subject. Thus, there has been increasing interest in the influence of host genetic factors on the rate of disease progression, and whether a genetic signature can be developed to reliably identify individuals at risk of severe disease. Numerous case-control, candidate gene, allele-association studies have examined the relationship between host single nucleotide polymorphisms or other genetic mutations and fibrosis in patients with chronic HCV infection. However, these studies have generally been irreproducible and disappointing. As seen with genetic studies for other diseases, small study cohorts and poor study design have contributed to limited meaningful findings. The successful determination of genetic signatures for fibrosis progression in chronic HCV will require multicenter collaborations using genome-wide association studies, with large, phenotypically well-defined sample sets. While these studies will require a significant financial commitment, a successful outcome offers the potential for personalized therapy and better patient management.

Long term health outcomes after injury in working age adults: a systematic review

Background: Estimating the contribution of non-fatal injury outcomes remains a considerable challenge and is one of the most difficult components of burden of disease analysis. The aim of this systematic review was to quantify the effect of being injured compared with not being injured on morbidity and health service use (HSU) in working age adults. Methods: Studies were selected that were population based, had long term health outcomes measured, included a non-injured comparison group, and related to working age adults. Meta-analysis was not attempted because of the heterogeneity between studies. Results: Nine studies met the inclusion criteria. In general, studies found an overall positive association between injury and increased HSU, exceeding that of the general population, which in some studies persisted for up to 50 years after injury. Disease outcome studies after injury were less consistent, with null findings reported. Conclusion: Because of the limited injury types studied and heterogeneity between study outcome measures and follow up, there is insufficient published evidence on which to calculate population estimates of long term morbidity, where injury is a component cause. However, the review does suggest injured people have an increased risk of long term HSU that is not accounted for in current methods of quantifying injury burden.

Population health and clinical data linkage: The importance of a population registry

Objective: The Australian National Collaborative Research Infrastructure Strategy supports development of a national research capability in population health and clinical data linkage. This paper illustrates the importance of incorporating a population registry within such a system using an example provided by the Manitoba Injury Outcome Study (MIOS) that quantified the long‐term burden of mortality attributable to injury in working‐age adults.