Quality-adjusted survival as an end point in breast cancer trials

Breast cancer treatment recommendations will often require an appraisal of likely benefits in relation to likely side-effects on survival and quality of life (QoL) endpoints, and possibly also an evaluation of the size of the anticipated net clinical benefit against financial costs. Quality-adjusted survival (QAS) analysis methods provide a formal approach for deriving an estimate of net clinical benefit to facilitate this appraisal process. QAS analysis methods have been applied in trials with breast cancer patients of adjuvant therapies as well as treatments for advanced/metastatic disease. QAS analyses based solely on trial data may fail to capture plausible longer-term benefits; thus methods to explore the possible outcomes of treatment beyond the limits of trial data have been developed. These modelling approaches can help researchers gain insights and identify future research priorities, but do not replace the need for long-term evidence from randomised trials.NHMR

Which lipid measurement should we monitor? An analysis of the LIPID study

OBJECTIVES: To evaluate the optimal lipid to measure in monitoring patients, we assessed three factors that influence the choice of monitoring tests: (1) clinical validity; (2) responsiveness to therapy changes and (3) the size of the long-term ‘signal-to-noise’ ratio. DESIGN: Longitudinal analyses of repeated lipid measurement over 5 years. SETTING: Subsidiary analysis of a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study—a clinical trial in Australia, New Zealand and Finland. PARTICIPANTS: 9014 patients aged 31–75 years with previous acute coronary syndromes. INTERVENTIONS: Patients were randomly assigned to 40 mg daily pravastatin or placebo. PRIMARY AND SECONDARY OUTCOME MEASURES: We used data on serial lipid measurements—at randomisation, 6 months and 12 months, and then annually to 5 years—of total cholesterol; low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and their ratios; triglycerides; and apolipoproteins A and B and their ratio and their ability to predict coronary events. RESULTS: All the lipid measures were statistically significantly associated with future coronary events, but the associations between each of the three ratio measures (total or LDL cholesterol to HDL cholesterol, and apolipoprotein B to apolipoprotein A1) and the time to a coronary event were better than those for any of the single lipid measures. The two cholesterol ratios also ranked highly for the long-term signal-to-noise ratios. However, LDL cholesterol and non-HDL cholesterol showed the most responsiveness to treatment change. CONCLUSIONS: Lipid monitoring is increasingly common, but current guidelines vary. No single measure was best on all three criteria. Total cholesterol did not rank highly on any single criterion. However, measurements based on cholesterol subfractions—non-HDL cholesterol (total cholesterol minus HDL cholesterol) and the two ratios—appeared superior to total cholesterol or any of the apolipoprotein options. Guidelines should consider using non-HDL cholesterol or a ratio measure for initial treatment decisions and subsequent monitoring

Chaucer and Bawdy

The reputation of a medieval poet is such that a successful dramatist of the 1960s could rely on the mere mention of his name to convey to the audience of the play the ideas of naughtiness and bawdy. Presumably the expansion of senior-secondary and tertiary education after World War II, the gradual relaxation of sexual mores, and the ready availability of a lively translation of the Canterbury Tales had all been factors that contributed to a popular dissemination of Chaucer's reputation for bawdiness. If that is so, it occurred in the absence of scholarly activity and interest in the topic. It is true that Chaucer shares with Shakespeare the singular honour of having a book devoted to his bawdy; yet that book was published as recently as 1972 and, modelling itself on Partridge's pioneering work on Shakespeare, takes the form of discursive glosses, apart from a brief, conceptually uncritical introduction. In general, before the later 1960s, while many medievalists privately took pleasure in Chaucer's treatment of sexual and excretory matters, they did not write upon this aspect of his work with the same unembarrassed candour that the poet himself had shown. Among general readers this aspect of Chaucer, and to an extent Chaucer's very name, was very often an occasion for sniggering

Linking the evidence: intermediate outcomes in medical test assessments

Objectives To review how health technology assessments (HTA) of medical tests incorporate intermediate outcomes in conclusions about the effectiveness of tests on improving health outcomes. Methods Systematic review of English-language test assessments in the HTA database from January 2005 to February 2010, supplemented by a search of the websites of International Network of Agencies for Health Technology Assessment (INAHTA) members. Results 149 HTAs from eight countries were assessed. Half evaluated tests for screening or diagnosis, a third for disease classification (including staging, prognosis, monitoring), and a fifth for multiple purposes. In 71 HTAs (48%) only diagnostic accuracy was reported, while in 17 (11%) evidence of health outcomes was reported in addition to accuracy. Intermediate outcomes, mainly the impact of test results on patient management, were considered in 61 HTAs (41%). Of these, 47 identified randomized trials or observational studies reporting intermediate outcomes. The validity of these intermediate outcomes as a surrogate for health outcomes was not consistently discussed; nor was the quality appraisal of this evidence. Clear conclusions about whether the test was effective were included in about 60% of HTAs. Conclusions Intermediate outcomes are frequently assessed in medical test HTAs, but interpretation of this evidence is inconsistently reported. We recommend that reviewers explain the rationale for using intermediate outcomes, identify the assumptions required to link intermediate outcomes and patient benefits and harms, and assess the quality of included studies

Localization of osteocalcin (BGP) during fish (Sparus aurata) development by in situ hybridization and immunohistochemistry: comparison between gene expression/protein distribution and skeletal mineralization

Osteocalcin (Bone Gla protein, BGP) is a small noncollagenous protein which is synthesized by osteoblasts and odontoblasts and is found exlusively in mineralized bony tissues. Although isolated for the first time in 1978, only recently has a function for this protein been suggested, specifically in controlling hydroxyapatite crystal growth. Appearance of osteocalcin could be linked to the presence of an hydroxyapatite-containing bony skeleton, since the protein was never found in cartilaginous fishes. Furthermore, within its primary sequence the amino acid residues known to be essential for its function are present in fish as well as in mammals, suggesting that function has been conserved over 400 million years of evolution. Taken totgether, these findings prompted us to study in detail the localization of osteocalcin gene expression in fish

Factores de riesgo vasculares prevalentes en la población adulta de La Rioja.

Hay evidencia que los factores de riesgo vasculares (FRV) contribuyen al ictus 3º causa de muerte. Los FRV modificables se asocian al 90 % de los ACV. La prevención y detección temprana pueden reducir esta probabilidad. Objetivo: Analizar la prevalencia de hipertensión (HTA) obesidad abdominal, diabetes, tabaquismo, alteraciones del pulso, dieta y sedentarismo en adultos de La Rioja, República Argentina. Material y Método: el estudio observacional descriptivo incluyó 853 adultos ( 40 a 90 años) 457 fueron mujeres. Resultados: HTA se encontró en el 46,26 % de mujeres, 57,07% de los hombres, media 54 años, DS+ -2,7 años en ambos sexos. Obesidad abdominal en la mujer: 76,15 % vs 55,30 % media a los 53 años, DS+- 2,8 años. Ambos FRV se asociaron en el 71 % de la muestra, mujeres 84,26 % vs 58,85 % y entre los 40 y 45 años el 100 % de hipertensas ostentó sobrepeso. Inversamente el 56,51 % de sujetos obesos asoció HTA: 52,30 % de mujeres vs 60,73 %. La diabetes prevaleció en 19,3 % de las mujeres y en 20,3 % de los hombres, media 53 y 54 años, DS+- 3,23. El tabaquismo estuvo presente en el 24,73 % de las mujeres vs 33,84 %. El pulso irregular se encontró en 4,92 % de la muestra, 5,69 % de mujeres vs 4,04%. Vida sedentaria refirió el 63 % del total. Consumo excesivo de carnes rojas 81,60 % Conclusiones: Los FRV son altamente prevalentes en nuestra población, deben ser abordados desde etapas tempranas de la vida con intervenciones específicas en el estilo de vida. Prevenir el riesgo vascular nos concierne a todos.Vascular risk factors prevalent in the dwellers of La Rioja.AbstractThere is evidence that vascular risk factors (VRF) contribute to stroke, 3rd cause of death . The modifiable VRF are associated to 90% of strokes. Prevention and early detection can reduce this probability. Objective: To analyze the prevalence of hypertension (HT) abdominal obesity, diabetes, smoking, abnormal pulse, diet and physical inactivity among adults in La Rioja, Republic Argentina. Material and Method: the descriptive observational study included 853 adults (age 40 to 90), 457 women. Results: HT was found in 46.26% of women, 57.07% of men, age mean 54, DS + - 2.7 years for both sexes. Abdominal obesity in women 76.15% vs 55.30% mean 53, DS + - 2.8. Both FRV were associated in 71% of the sample, women 84.26% vs 58.85%. Between 40 and 45 years, 100% of hypertensive women were overweight. Conversely 56.51% of subjects with obesity associated HT: 52.30 % women vs 60.73%. Diabetes was present in 19.3% of women vs 20.3% mean 53 and 54 years, SD + - 3.23. Smoking was present in 24.73% of women vs. 33.84%. The irregular pulse was found in 4.92% of total sample, 5.69% vs. 4.04% of women. Sedentary referred 63% both sex.Red meat excessive consumption the 81.60% Conclusions: FRV are highly prevalent in our population, must be addressed from early stages of life with specific interventions in lifestyle. Preventing vascular risk concerns us all.Keywords: Epidemiology; Vascular risk factor; Prevalence; Hypertension; Diabetes; Abdominal obesity

Sentinel-lymph-node-based management or routine axillary clearance? Three-year outcomes of the RACS Sentinel Node Biopsy versus Axillary Clearance (SNAC) 1 trial

Purpose We sought to determine whether the benefits of sentinel-node-based management (SNBM) over routine axillary clearance (RAC) at 1 year persisted to 3 years of follow-up. Methods 1088 women with clinically node negative breast cancer were randomly assigned to SNBM versus RAC. Upper limb volume, symptoms and function were assessed at 1, 6, 12, 24 and 36 months after surgery objectively with upper limb measurements by clinicians, and subjectively by patients’ using validated self-rating scales. Results Upper limb volume increased in both groups over the first 2 years and differed between the two groups all time points beyond 1 month (P<0.02), but then plateaued. Upper limb swelling was no worse in women who had axillary clearance as two-stage procedure than in women assigned RAC as a one-stage procedure. Upper limb volume had increased 15% or more in 6.0% at 6 months and 17.6% at 3 years in those assigned RAC versus 4.2% and 11.9% in those assigned SNBM. Reductions in upper limb movement were also greater with RAC than SNBM over 6 months, but improved and were similar in the two groups from 1 to 3 years. Subjective ratings of upper limb swelling, symptoms, dysfunction, and disability over 3 years were worse in the RAC group. Upper limb swelling at 3 years was rated severe by few women (1.1%), but moderate by 9.4% in the RAC group and 2.5% in the SNBM group (P<0.001). Conclusions The benefits of SNBM over RAC persist 3 years after surgery.Royal Australasian College of Surgeon

The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study

Background: Based on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial. Methods: Individual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure. Results: The addition of bevacizumab to capecitabine monotherapy cost approximately $192,156 (95$135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to$149,455 (95% CI, $100,356 to$245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95$106,703 to $233,225). Conclusions: Bevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial.Roche Products Pty Lt

The cost effectiveness of bevacizumab when added to capecitabine, with or without mitomycin-C, in first line treatment of metastatic colorectal cancer: results from the Australasian phase III MAX study

Background: Based on the clinical data, bevacizumab has been approved in Australia and globally for the treatment of advanced colorectal cancer. However, limited evidence exists for its cost-effectiveness. The purpose of this study was to evaluate the cost effectiveness of adding bevacizumab to capecitabine monotherapy in patients with metastatic colorectal cancer, using data from the prospective economic evaluation conducted alongside the MAX trial. Methods: Individual patient level data on resource use and progression free survival were prospectively collected in the phase III MAX trial. Resource use data were collected for the period between randomisation and disease progression, and unit costs were assigned from the perspective of the Australian health care funder. Effectiveness was measured in quality adjusted progression free survival years, with utility scores obtained from both the community valued EQ-5D questionnaire and the patient valued UBQ-C questionnaire. Progression free survival was used as a secondary effectiveness measure. Results: The addition of bevacizumab to capecitabine monotherapy cost approximately $192,156 (95$135,619 to $326,894) per quality adjusted progression free survival year gained when using publicly listed pharmaceutical prices and utility values from the EQ-5D questionnaire. This decreased to$149,455 (95% CI, $100,356 to$245,910) when values from the UBQ-C questionnaire were applied. The incremental cost per progression free survival year was $145,059 (95$106,703 to $233,225). Conclusions: Bevacizumab was not found to be cost effective at its listed price, based on results from the MAX trial.Roche Products Pty Lt