Post-operative volumes following endoscopic surgery for non-functioning pituitary macroadenomas are predictive of further intervention, but not endocrine outcomes.

BACKGROUND: Transsphenoidal surgery (TSS) remains the treatment of choice for non-functioning pituitary macroadenomas (NFPMA). The value of measuring tumour volumes before and after surgery, and its influence on endocrine outcomes and further treatment of the residual or recurrent tumour are unknown. METHODS: Data from patients who underwent endoscopic TSS for a NFPMA (2009-2018) in a UK tertiary centre were analysed for pre- and post-operative endocrine and surgical outcomes. RESULTS: Of 173 patients with NFPMA, 159 (61% male) were treatment naïve. At presentation, 76.2% (77/101) had ≥1 pituitary axis deficit. Older age (p = 0.002) was an independent predictor for multiple hormonal deficiencies. Preoperative tumour volume did not correlate with degree of hypopituitarism. Postoperative tumour volume and extent of tumour resection were not predictive of new onset hypopituitarism. Hormonal recovery was observed in 16 patients (20.8%) with impaired pituitary function, with the greatest recovery in the hypothalamic-pituitary-adrenal axis (21.2%, 7/33). A larger residual tumour volume was predictive of adjuvant radiotherapy (3.40 vs. 1.24 cm3, p = 0.005) and likelihood for repeat surgery (5.40 vs. 1.67cm3, p = 0.004). CONCLUSION: Pre- and post-operative NFPMA volumes fail to predict the number of pituitary hormone deficits, however, greater post-operative residual volumes increase the likelihood of further intervention to control tumour growth.

Estimated glucose disposal rate as a candidate biomarker for thrombotic biomarkers in T1D: a pooled analysis.

PURPOSE: To determine the utility of estimated glucose disposal rate (eGDR) as a candidate biomarker for thrombotic biomarkers in patients with type 1 diabetes (T1D). METHODS: We reanalysed baseline pretreatment data in a subset of patients with T1D from two previous RCTs, consisting of a panel of thrombotic markers, including fibrinogen, tissue factor (TF) activity, and plasminogen-activator inhibitor (PAI)-1, and TNFα, and clinical factors (age, T1D duration, HbA1c, insulin requirements, BMI, blood pressure, and eGDR). We employed univariate linear regression models to investigate associations between clinical parameters and eGDR with thrombotic biomarkers. RESULTS: Thirty-two patients were included [mean ± SD age 31 ± 7 years, HbA1c of 58 ± 9 mmol/mol (7.5 ± 0.8%), eGDR 7.73 ± 2.61]. eGDR negatively associated with fibrinogen (P < 0.001), PAI-1 concentrations (P = 0.005), and TF activity (P = 0.020), but not TNFα levels (P = 0.881). We identified 2 clusters of patients displaying significantly different characteristics; 56% (n = 18) were categorised as 'higher-risk', eliciting significantly higher fibrinogen (+ 1514 ± 594 µg/mL; P < 0.001), TF activity (+ 59.23 ± 9.42 pmol/mL; P < 0.001), and PAI-1 (+ 8.48 ± 1.58 pmol/dL; P < 0.001), HbA1c concentrations (+ 14.20 ± 1.04 mmol/mol; P < 0.001), age (+ 7 ± 3 years; P < 0.001), duration of diabetes (15 ± 2 years; P < 0.001), BMI (+ 7.66 ± 2.61 kg/m2; P < 0.001), and lower mean eGDR (- 3.98 ± 1.07; P < 0.001). CONCLUSIONS: Compared to BMI and insulin requirements, classical surrogates of insulin resistance, eGDR is a suitable and superior thrombotic risk indicator in T1D. TRIAL REGISTRATION: ISRCTN4081115; registered 27 June 2017.

A kinetic and thermodynamic investigation into the removal of methyl orange from wastewater utilizing fly ash in different process configurations.

The removal of methyl orange using coal fly ash, which is a widely available low-cost adsorbent, has been investigated. Adsorption studies for dye removal were conducted using various configurations such as batch, column and heap adsorption at various temperatures and adsorbent dosages at neutral pH. The Langmuir, Freundlich and Tempkin isotherm models were used to describe the process. The Freundlich model best represented the adsorption. Kinetic studies show the adsorption followed pseudo-second-order kinetics. Thermodynamic studies show that the process is spontaneous, endothermic and random. Column configuration was found to be the most efficient with a dye removal percentage of 99.95%, followed by heap adsorption at 99.25% removal and lastly batch configuration with 96.68% removal. Economic analysis shows that column operation would be the most effective for practical implementation.

What proportion of patients with chronic noncancer pain are prescribed an opioid medicine? Systematic review and meta-regression of observational studies.

Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random-effects model. Meta-regression investigated study-level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate-quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0-21.0%, n = 15 studies, low-quality evidence), versus 8.5% (95% CI 7.2-9.9%, n = 15 studies, low-quality evidence)). Meta-regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time.

Compliance and persistence to oral bisphosphonate therapy following initiation within a secondary fracture prevention program: a randomised controlled trial of specialist vs. non-specialist management.

UNLABELLED: Following initiation of oral bisphosphonate therapy through a secondary fracture prevention program, 2-year treatment compliance and persistence remained high and were similar in patients randomised to follow-up by either the program or primary care physician. Thus, community-based and specialist management are equally effective in supporting compliance and persistence with anti-osteoporotic treatments. INTRODUCTION: The purpose of this study was to determine whether management by a secondary fracture prevention (SFP) program (aka "fracture liaison service") results in better compliance and persistence to oral bisphosphonate therapy than follow-up by the primary care physician, after initiation within an SFP program. METHODS: This prospective RCT included 102 patients with incident osteoporotic fractures referred to a SFP program in Sydney, Australia. Following oral bisphosphonate therapy initiation, patients were randomised to either 6-monthly follow-up with the SFP program (group A) or referral to their primary care physician with a single SFP program visit at 24 months (group B). Compliance and persistence to treatment were measured using pharmaceutical claims data. Predictors of compliance and persistence and associations between compliance and persistence, and changes in bone mineral density (BMD) or bone resorption marker, urinary deoxypyridinoline over 24 months were analysed. RESULTS: The median medication possession ratio at 24 months was 0.78 (IQR, 0.50-0.93) in group A and 0.79 (IQR, 0.48-0.96) in group B (p = 0.68). Persistence at 24 months was also similar in both groups (64 vs. 61%, respectively; p = 0.75). After adjusting for confounders, patients in group A were not more likely to be compliant (OR, 1.06; 95% CI, 0.46-2.47) or persistent (HR, 0.83; 95% CI, 0.27-1.67) than those randomised to group B. Time-based changes in BMD or bone turnover were not associated with compliance or persistence. CONCLUSION: Compliance and persistence to oral bisphosphonate therapy remain high amongst patients initiated within an SFP program, with community-based and SFP program management being equally effective in maintaining therapeutic compliance and persistence over 2 years. These results indicate that one of the main functions of an SFP program may be the initiation of therapy rather than continuous patient monitoring.

The role of comorbidities on the uptake of systemic treatment and 3-year survival in older cancer patients.

BACKGROUND: Older patients are notably absent from clinical trials. Thus, observational studies are the primary avenue for understanding the role of comorbidity in cancer care and survival. We examined the impact of comorbidity on systemic treatment initiation and 3-year survival in a cohort of older cancer patients. PATIENTS AND METHODS: Our cohort comprised 2753 Australian veterans aged ≥65 years with full health coverage and a cancer registry notification for colorectal (CRC), breast, prostate or non-small-cell lung cancer (NSCLC). We established comorbidities based on drugs prescribed in the 6 months prior to cancer diagnosis. RESULTS: Patients with higher comorbidity burden were more likely to receive systemic treatment for prostate cancer [adjusted odds ratio 1.21, 95% confidence interval (CI) 1.05-1.39] but less likely for NSCLC (0.63, 95% CI 0.45-0.86). After adjusting for receipt of treatment, increased comorbidity resulted in shorter survival for CRC [adjusted hazard ratio (aHR) 1.16, 95% CI 1.07-1.26] and breast cancer (aHR 1.23, 95% CI 1.02-1.48). However, we did not demonstrate significant improvements in 3-year survival for patients receiving systemic treatment. CONCLUSION: Comorbidity influences systemic treatment uptake and adversely affects survival, with impact dependent upon comorbidity and cancer type. Clinical trials should be undertaken in older patients to better understand the risks and benefits of cancer treatments.

Implementing a web-based oncology protocol system in Australia: evaluation of the first 3 years of operation.

BACKGROUND: EviQ is a web-based oncology protocol system launched across Australia in 2005 (http://www.eviq.org.au). We evaluated eviQ use at the point-of-care and determined the factors impacting on its uptake and routine use in the first three years of operation. METHODS: We conducted a suite of qualitative and quantitative studies with over 200 Australian oncology physicians, nurses and pharmacists working at treatment centres in diverse geographical locations. RESULTS: EviQ was part of routine care at many hospitals; however, the way in which it was used at the point-of-care varies according to clinician roles and hospital location. We identified a range of factors impacting on eviQ uptake and routine use. Infrastructure, such as availability of point-of-care computers, and formal policies endorsing eviQ are fundamental to increasing uptake. Furthermore, the level of clinical and computer experience of end-users, the attitudes and behaviour of clinicians, endorsement and promotion strategies, and level and type of eviQ education all need to be considered and managed to ensure that the system is being used to its full potential. CONCLUSION: Our findings show that the dissemination of web-based treatment protocols does not guarantee widespread use. Organisational, environmental and clinician-specific factors play a role in uptake and utilisation. The deployment of sufficient computer infrastructure, implementation of targeted training programmes and hospital policies and investment in marketing approaches are fundamental to uptake and continued use. This study highlights the value of ongoing monitoring and evaluation to ensure systems like eviQ achieve their primary purpose - reducing treatment variation and improving quality of care.

Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer.

BACKGROUND: Cardiotoxicity is a concern in patients on trastuzumab therapy, and cardiac function assessment is a recommended practice. In 2006, trastuzumab was publically subsidised for human epidermal growth factor receptor-2 early stage breast cancer with a requirement for cardiac testing prior to and during treatment. AIM: To investigate the spillover effects of this requirement on testing rates in metastatic patients treated with trastuzumab where no monitoring requirements are applied. METHODS: We examined cardiac testing (echocardiography or multiple-gated acquisition scan) in 3779 women with metastatic breast cancer receiving trastuzumab between December 2001 and February 2010 and used interrupted time-series analyses to estimate changes in testing rates. The main outcome measures were the proportion of eligible patients, by quarter, receiving a cardiac function test pretreatment and during trastuzumab therapy. RESULTS: Only 21% of women had a cardiac function test pretreatment, and 47% were tested at some point during the first year of trastuzumab therapy. The introduction of mandatory cardiac testing for early breast cancer was associated with an immediate 8% increase (95% confidence interval, 2-14%) in pretreatment cardiac testing and an immediate 7% increase (95% confidence interval, 4-10%) in testing during therapy in metastatic patients. Testing rates during therapy increased steadily from early 2005, coinciding with the release of interim results from several trastuzumab trials reporting cardiac-safety outcomes. CONCLUSION: The introduction of mandatory cardiac testing for early stage disease spilled over to the metastatic setting. While deviation from guidelines may be warranted in some cases, this study suggests underutilisation of cardiac testing among patients treated with trastuzumab in the metastatic setting.

Governance approval for multisite, non-interventional research: what can Harmonisation of Multi-Centre Ethical Review learn from the New South Wales experience?

BACKGROUND: In 2007, New South Wales Health mandated the separation of ethical and scientific review from research governance at all New South Wales public health sites based on their distinction in the National Health and Medical Research Council National Statement. This separation allowed for single-site ethical review of multicentre studies. AIMS: To investigate the time taken for governance approval of multicentre studies through the site-specific approval (SSA) process. METHODS: A retrospective audit of the SSA process for five non-interventional studies proposed by a university cancer research unit. RESULTS: The median total governance approval time for all submissions (n= 28) was 12 weeks (range 2.5-64); median time from starting the SSA to submission was 8 weeks (range 1-48) and median time for governance approval was 5 weeks (range 0.3-40). Approval times were shorter for public compared to private institutions. Reasons for delays in finalising submissions for approval were the absence of institutional governance officers, lack of clarity regarding signatories, the need to identify a principal investigator employed by the institution, and lack of recognition of ethical approval by private institutions. The need to develop legal agreements between the university and hospital was the main reason for lengthy delays in obtaining approval. CONCLUSIONS: The advantages of a harmonised single ethical review process were undermined by the coexistence of a fragmented, complex and lengthy governance approval process. This experience has implications for the success of the national Harmonisation of Multi-Centre Ethical Review (HoMER) model. A harmonised and fully supported national approach to research governance should be developed contemporaneously with HoMER.

De novo and recurrent metastatic breast cancer - A systematic review of population-level changes in survival since 1995.

BACKGROUND: Advances in breast cancer (BC) care have reduced mortality, but their impact on survival once diagnosed with metastasis is less well described. This systematic review aimed to describe population-level survival since 1995 for de novo metastatic BC (dnMBC) and recurrent MBC (rMBC). METHODS: We searched MEDLINE 01/01/1995-12/04/2021 to identify population-based cohort studies of MBC reporting overall (OS) or BC-specific survival (BCSS) over time. We appraised risk-of-bias and summarised survival descriptively for MBC diagnoses in 5-year periods from 1995 until 2014; and for age, hormone receptor and HER2 subgroups. FINDINGS: We identified 20 eligible studies (14 dnMBC, 1 rMBC, 5 combined). Potential sources of bias in these studies were confounding and shorter follow-up for the latest diagnosis period.For dnMBC, 13 of 14 studies reported improved OS or BCSS since 1995. In 2005-2009, the median OS was 26 months (range 24-30), a median gain of 6 months since 1995-1999 (range 0-9, 4 studies). Median 5-year OS was 23% in 2005-2009, a median gain of 7% since 1995-1999 (range -2 to 14%, 4 studies). For women ≥70 years, the median and 5-year OS was unchanged (1 study) with no to modest difference in relative survival (range: -1·9% (p = 0.71) to +2·1% (p = 0.045), 3 studies). For rMBC, one study reported no change in survival between 1998 and 2006 and 2007-2013 (median OS 23 months). For combined MBC, 76-89% had rMBC. Three of four studies observed no change in median OS after 2000. Of these, one study reported median OS improved for women ≤60 years (1995-1999 19·1; 2000-2004 22·3 months) but not >60 years (12·7, 11·6 months). INTERPRETATION: Population-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification. FUNDING: SL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21-001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).

The quality of web-based oncology guidelines and protocols: how do international sites stack up?

BACKGROUND: The Internet is a popular medium for disseminating information relevant to oncology practitioners. Despite the widespread use of web-based guidelines and protocols, the quality of these resources has not been evaluated. This study addresses this gap. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument was used to assess the quality of breast and sarcoma guidelines and protocols according to six independent domains. The oncology resources were selected from eight websites developed for healthcare settings in North America, the United Kingdom, Europe, and Australia. RESULTS: Mean quality scores across domains were highly variable for both guidelines (29-73%) and protocols (31-71%). Guidelines scored highly in terms of articulating their Scope and Purpose (72.6 ± 11.2%) but poorly with respect to Applicability in clinical practice (29.0 ± 17.3%). Protocols scored highly on Clarity of Presentation (70.6 ± 17.6%) but poorly in terms of the processes used to synthesise underlying evidence, develop, and update recommendations (30.8 ± 20.0%). CONCLUSION: Our evaluation provides a quick reference tool for clinicians about the strengths and limitations of oncology resources across several major websites. Further, it supports resource developers in terms of where to direct efforts to enhance guideline and protocol development processes or the communication of these processes to end-users.

The efficacy of HER2-targeted agents in metastatic breast cancer: a meta-analysis.

BACKGROUND: The addition of HER2-targeted agents to standard treatment has been shown to improve outcomes for HER2 positive metastatic breast cancer patients. We undertook a meta-analysis to evaluate the efficacy of HER2-targeted therapy in addition to standard treatment in metastatic breast cancer patients. PATIENTS AND METHODS: Eligible trials were randomised controlled trials (RCTs) comparing the addition of HER2 therapy to standard treatment (hormone or chemotherapy) reporting overall survival (OS), time to progression (TTP), progression-free survival (PFS) and/or response rates. RESULTS: Eight trials comprising 1848 patients were eligible for inclusion. HER2-targeted agents were trastuzumab and lapatinib and therapeutic partners were taxanes (4 RCTs), anthracyclines (1), capecitabine (2), anastrozole (1) and letrozole (1). The addition of HER2-targeted agents improved OS [hazard ratios (HR) 0.78; 95% confidence interval (CI) 0.67-0.91], TTP (HR 0.56; 95% CI 0.48-0.64), PFS (HR 0.63; 95% CI 0.53-0.74) and overall response rate (relative risk 1.67; 95% CI 1.46-1.90). CONCLUSIONS: Our meta-analysis confirms the benefit of adding HER2-targeted therapy to standard treatment in HER2 positive metastatic breast cancer. Compared with OS, TTP, PFS and ORR overestimate treatment benefit. Trials in our meta-analysis differed in terms of partner drug or HER2 agents, yet delivered comparable outcomes.

Serum relaxin levels affect the in vivo properties of some but not all tendons in normally menstruating young women.

Relaxin (hRLX) is a hormone reported to affect collagen synthesis. Its effects are also thought to be modulated by other sex hormones, including oestrogen, which has previously been found to be associated with alterations of in vivo tendon properties. There is thus a potential for hRLX to impact on collagen, which could result in tendon structural and mechanical properties being modified. The present study therefore aimed to determine any interaction between hRLX and tendon stiffness, in normally menstruating women (n = 12). Tendon properties were determined using a combination of dynamometry and B-mode ultrasound, whilst serum hRLX levels were established by ELISA. Serum hRLX level was seen to be negatively associated with patellar tendon stiffness (r = -0.56; P < 0.001), explaining 31% of the variance in this parameter. There was no association between hRLX and gastrocnemius tendon stiffness (P > 0.05), or with the cross-sectional area of either of the two tendons (P > 0.05). In young, normally menstruating women, hRLX appears to have a significant effect on the patellar but not the gastrocnemius tendon stiffness. Where it has an effect, this appears to be on the intrinsic properties rather than on the dimensions of said tendon. Future work to elucidate the physiological cause of this selectivity in the impact of relaxin will be key to mapping the impact of the endocrine system on the phenotype of tendinous tissue.

Influence of maternal lead ingestion on caries in rat pups.

Lead is one of the most toxic and pervasive pollutants in society, and although there has been some lowering of blood lead levels in recent years, the levels continue to be of concern for African Americans, central city residents, residents in the Northeast region of the United States, persons with low income, and those with low educational attainment. Notably, these are the persons and the region where the highest prevalence of dental caries is observed. Information relating lead toxicity to oral health is sparse, but the preponderance of epidemiological data shows a relation between lead in the environment and the prevalence of dental caries. Using our well-defined rat caries model we found that pre- and perinatal exposure to lead results in an almost 40% increase in the prevalence of caries and a decrease in stimulated parotid function of nearly 30%. Levels of lead in milk from lead-treated dams were approximately 10 times as high as the corresponding blood lead levels, suggesting that lead is being concentrated by mammary glands. These findings may help in part to explain the comparatively high levels of dental caries observed in the inner cities of the United States where exposure to lead is common. Environmental sources of lead include drinking water, lead-based paint and, to a lesser extent, automobile and industrial emissions. In humans lead is accumulated and stored in bones (half-life of approximately 62 years), and even maternal exposure to lead decades before pregnancy can subsequently result in exposure of the developing fetus to elevated levels of lead. Moreover, lead concentration in maternal blood has been shown to increase during pregnancy and lactation because of mobilization of stored lead from bone, and typically, lead is found in milk at a higher concentration than the level found in maternal plasma at the same time point.

Identifying incident cancer cases in dispensing claims: A validation study using Australia's Repatriation Pharmaceutical Benefits Scheme (PBS) data.

INTRODUCTION: Dispensing claims are used commonly as proxy measures in pharmacoepidemiological studies; however, their validity is often untested. OBJECTIVES: To assess the performance of a proxy for identifying cancer cases based on the dispensing of anticancer medicines and estimate the misclassification of cancer status and potential for bias researchers may encounter when using this proxy. METHODS: We conducted our validation study using Department of Veterans' Affairs (DVA) client data linked with the New South Wales (NSW) Cancer Registry and Repatriation Pharmaceutical Benefits Scheme data. We included DVA clients aged ≥65 years residing in NSW between July 2004 and December 2012. We matched clients with a cancer diagnosis to clients without a diagnosis based on demographic characteristics and available observation time. We used dispensing claims for anticancer medicines dispensed between July 2004 and December 2013 as a proxy to identify clients with cancer and calculated sensitivity, specificity, positive predictive values and negative predictive values compared with cancer registrations (gold standard), overall and by cancer site. We illustrated misclassification by the proxy in a cohort of people initiating opioid therapy. Using the proxy, we excluded people with cancer from the cohort, in an attempt to delineate people potentially using opioids for cancer rather than chronic non-cancer pain. RESULTS: We identified 15,679 new cancer diagnoses in 14,112 DVA clients from the cancer registry and 62,663 clients without a diagnosis. Sensitivity of the proxy based on dispensing claims was 30% for all cancers and around 20% for specific cancers (range: 10-67%). Specificity was above 90% for all cancers. The dispensing proxy correctly identified 26% of people with a cancer diagnosis who initiated opioid therapy and failed to identify 74% those with a cancer diagnosis; the proxy was most robust for clients with breast cancer where 61% were correctly identified by proxy. CONCLUSIONS: Using dispensing of anticancer medicines to identify people with a cancer diagnosis performed poorly. Excluding patients with evidence of anticancer medicine use from cohort studies may result removal of a disproportionate number of women with breast cancer. Researchers excluding or otherwise using anticancer medicine dispensing to identify people with cancer in pharmacoepidemiological studies should acknowledge the potential biases introduced to their findings. KEYWORDS: cancer, diagnosis, proxy, dispensing records, validation study.

Demographic, social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: Little is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. METHODS: Baseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04-1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24-2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08-1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08-2.64), and current (OR 3.42, 95% CI 1.81-6.47) or former (OR 1.95, 95% CI 1.33-2.86) smokers. CONCLUSION: The consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.

Health-related predictors of cancer registry-notified cancer of unknown primary site (CUP).

BACKGROUND: The relationship between comorbid disease and health service use and risk of cancer of unknown primary site (CUP) is uncertain. METHODS: A prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia. Baseline questionnaire data were linked to cancer registration, health service records 4-27 months prior to diagnosis, and mortality data. We compared individuals with incident registry-notified CUP (n = 327; 90% C80) to two sets of randomly selected controls (3:1): (i) incident metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In fully adjusted models incorporating sociodemographic and lifestyle factors, people with cancer registry-notified CUP were more likely to have fair compared with excellent self-rated overall health (OR 1.78, 95% CI 1.01-3.14) and less likely to self-report anxiety (OR 0.48, 95% CI 0.24-0.97) than those registered with metastatic cancer of known primary. Compared to general cohort population controls, people registered with CUP were more likely to have poor rather than excellent self-rated overall health (OR 6.22, 95% CI 1.35-28.6), less likely to self-report anxiety (OR 0.28, 95% CI 0.12-0.63), and more likely to have a history of diabetes (OR 1.89, 95% CI 1.15-3.10) or cancer (OR 1.62, 95% CI 1.03-2.57). Neither tertiary nor community-based health service use independently predicted CUP risk. CONCLUSION: Low self-rated health may be a flag for undiagnosed cancer, and an investigation of its clinical utility in primary care appears warranted.

Analysis of collagen fibre shape changes in breast cancer.

Second harmonic generation microscopy was performed on both normal and diseased breast tissue. Differences in the collagen fibre shape between normal, benign and malignant breast tissue were compared and quantified using elliptical Fourier analysis. Principal shape analysis of these coefficients provided an understanding of the key differences in collagen fibre shape between the three tissue types. A Gaussian model was also used to associate the shape of the fibre with the probability that it had been sampled from malignant breast tissue. These results provide quantitative evidence for the alteration of collagen fibre shape in both benign and malignant breast tissue.