Long-term life satisfaction in ageing women with work disability due to mental and musculoskeletal disorders.

BACKGROUND: Mental disorders (MDs) and musculoskeletal disorders (MSDs) are the major causes of global disability and increase in prevalence with age. AIMS: To support healthy ageing, we studied how work disability due to MDs or MSDs is related to life satisfaction (LS) cross-sectionally and in 5- and 10-year follow-ups among ageing women. METHODS: In the population-based OSTPRE cohort (women aged 58-67 in 1999), data on lifetime permanent work disability pensions (DPs) due to 'MDs only' (n = 337), 'MSDs only' (n = 942) and 'MDs + MSDs' (n = 212) and 'no DP' (n = 6322) until 1999 was obtained from the Finnish national register. The OSTPRE postal enquiry included a four-item life satisfaction (LS) scale (range 4-20: satisfied 4-6, intermediate 7-11, dissatisfied 12-20) at 5-year intervals, in 1999-2004 (n = 6548) and in 1999-2009 (n = 5562). RESULTS: In 1999, the risks of belonging to the dissatisfied LS group (score 12-20) vs. the satisfied group (score 4-6) were higher in 'MDs only' (OR = 4.30; 95%CI 2.95-6.28), 'MSDs only' (OR = 2.69; 2.12-3.40) and 'MDs + MSDs' (OR = 2.72; 1.77-4.16) groups than in the 'no DP' group. In the follow-ups, these risks were OR5yr = 5.59 (3.54-8.84) and OR10yr = 4.94 (2.80-8.73) for 'MDs only', OR5yr = 3.36 (2.58-4.37) and OR10yr = 3.18 (2.40-4.21) for 'MSDs only', and OR5yr = 4.70 (2.75-8.05) and OR10yr = 6.84 (3.53-13.27) for 'MDs + MSDs' (all: p ≤ 0.001). Adjusting for baseline LS did not change the pattern (all p ≤ 0.001). CONCLUSION: Work disability due to MDs and MSDs undermines healthy ageing among women via life dissatisfaction.

Comorbidity of mental and musculoskeletal disorders in ageing women: A data linkage study using national registries.

BACKGROUND: Mental disorders (MDs) and musculoskeletal disorders (MSDs) are the main causes of disability. Yet, their comorbidity has not received the deserved attention. OBJECTIVE: To investigate the extent of the comorbidity between MDs and MSDs in ageing women using national registries on prescription medications and work disability pensions (DPs). METHODS: The study included 7,809 Finnish women, born during 1932-41, from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) cohort, established in 1989. Lifetime permanent DPs due to: 1) 'MDs only' (n = 359), 2) 'MSDs only' (n = 954), 3) 'MDs + MSDs' (n = 227), were recorded till 2003. The reference group was 'no DP' (n = 6,269). Data from the OSTPRE questionnaires was obtained in 1994. Use of medications was recorded in 1995 and 2003. The use of musculoskeletal or psychotropic medications by women having a DP or medication due to MD, or MSD diagnoses, respectively, was considered as an indicator of comorbidity. RESULTS: In 1995, all DP groups had used psychotropic and musculoskeletal medications more often than the referents. Use of musculoskeletal medications was associated with a higher use of psychotropic medications, and vice versa (OR=2.45; 95% CI 2.17-2.77), compared with non-use. The 'MSDs only' group was more likely to use psychotropic (OR=1.79; 95% CI 1.50-2.12), and the 'MDs only' group musculoskeletal medications (OR=1.38; 95% CI 1.09-1.74), compared with those without DPs. The proportions of medication users were similar in 1995 and 2003; however, the amounts used increased. CONCLUSIONS: There was strong evidence for comorbidity between MDs and MSDs in ageing women. Further research concerning their longitudinal relationships is warranted.

Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients.

BACKGROUND: Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease. METHODS: Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 359 COVID-19 negative serum samples with an additional 81 DBSs. The assay was further validated in 226 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 426 COVID-19 negative clinical samples. RESULTS: A sensitivity and specificity of 98.6% (95% CI, 92.6-100.0), 98.3% (95% CI, 96.4-99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%). CONCLUSIONS: The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

Whole blood interleukin-2 release test to detect and characterize rare circulating gluten-specific T cell responses in coeliac disease.

Whole blood cytokine release assays (CRA) assessing cellular immunity to gluten could simplify the diagnosis and monitoring of coeliac disease (CD). We aimed to determine the effectiveness of electrochemiluminescence CRA to detect responses to immunodominant gliadin peptides. HLA-DQ2·5+ CD adults (cohort 1, n = 6; cohort 2, n = 12) and unaffected controls (cohort 3, n = 9) were enrolled. Cohort 1 had 3-day gluten challenge (GC). Blood was collected at baseline, and for cohort 1 also at 3 h, 6 h and 6 days after commencing 3-day GC. Gliadin peptide-stimulated proliferation, interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and 14- and 3-plex electrochemiluminescence CRA were performed. Poisson distribution analysis was used to estimate responding cell frequencies. In cohort 1, interleukin (IL)-2 dominated the gliadin peptide-stimulated cytokine release profile in whole blood. GC caused systemic IL-2 release acutely and increased gliadin peptide-stimulated IFN-γ ELISPOT and whole blood CRA responses. Whole blood CRA after GC was dominated by IL-2, but also included IFN-γ, C-X-C motif chemokine ligand 10/IFN-γ-induced protein 10 (CXCL10/IP-10), CXCL9/monokine induced by IFN-γ (MIG), IL-10, chemokine (C-C motif) ligand 3/macrophage inflammatory protein 1-alpha (CCL3/MIP-1α), TNF-α and IL-8/CXCL8. In cohorts 2 and 3, gliadin peptide-stimulated whole blood IL-2 release was 100% specific and 92% sensitive for CD patients on a gluten-free diet; the estimated frequency of cells in CD blood secreting IL-2 to α-gliadin peptide was 0·5 to 11 per ml. Whole blood IL-2 release successfully mapped human leucocyte antigen (HLA)-DQ2·5-restricted epitopes in an α-gliadin peptide library using CD blood before and after GC. Whole blood IL-2 release assay using electrochemiluminescence is a sensitive test for rare gliadin-specific T cells in CD, and could aid in monitoring and diagnosis. Larger studies and validation with tetramer-based assays are warranted.

Repurposing a fracture risk calculator (FRAX) as a screening tool for women at risk for sarcopenia.

Osteoporosis and sarcopenia share risk profiles, so we tested a fracture risk assessment tool (FRAX) as a screening tool for sarcopenia. FRAX probabilities without bone mineral density predicted sarcopenia with high sensitivity and reasonable specificity. There is potential to use this FRAX as a screening tool for sarcopenia. PURPOSE: There is a need for simple screening tools for sarcopenia. As osteoporosis and sarcopenia share risk profiles, we tested the performance of a fracture risk assessment tool for discriminating individuals at risk for sarcopenia. METHODS: In this longitudinal study, FRAX (Australia) probabilities were calculated for 354 women (ages 40-90 years) in the Geelong Osteoporosis Study. Sarcopenia was assessed a decade later using DXA-derived low appendicular lean mass (Lunar; ALM/height2 < 5.5 kg/m2) and low handgrip strength (Jamar; HGS < 16 kg), according to EWGSOP2. We determined FRAX probabilities (%) for hip fracture (HF-FRAX) and major osteoporotic fracture (MOF-FRAX), with and without BMD. Area under the receiver operator characteristic (AUROC) curves quantified the performance of FRAX for predicting sarcopenia. RESULTS: Baseline median (IQR) values for HF-FRAX without BMD were 0.4 (0.1-1.3) and for MOF-FRAX without BMD, 2.4 (1.2-5.2); comparable figures for HF-FRAX with BMD were 0.2 (0.0-0.7) and for MOF-FRAX with BMD, 2.1 (1.1-4.4). At follow-up, sarcopenia was identified for 11 (3.1%) women. When FRAX was calculated without BMD, the AUROC was 0.90 for HF-FRAX and 0.88 for MOF-FRAX. Optimal thresholds were 0.9 for HF-FRAX (sensitivity 90.9%, specificity 62.4%) and 5.3 for MOF-FRAX (sensitivity 81.8%, specificity 71.7%). Calculating FRAX with BMD did not improve the predictive performance of FRAX for sarcopenia. CONCLUSION: Here we provide preliminary evidence to suggest that FRAX probabilities without BMD might predict sarcopenia with high sensitivity and reasonable specificity. Given that FRAX clinical risk factors are identified without equipment, there is potential to use this or a modified version of the FRAX tool to screen for individuals at risk of sarcopenia.

Serum cytokines elevated during gluten-mediated cytokine release in coeliac disease.

Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum interleukin (IL)-2 after gluten support a central role for T cell activation in the clinical reactions to gluten in coeliac disease. The aim of this study was to establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions. Sera were analyzed from coeliac disease patients on a gluten free-diet (n = 25) and from a parallel cohort of healthy volunteers (n = 25) who underwent an unmasked gluten challenge. Sera were collected at baseline and 2, 4 and 6 h after consuming 10 g vital wheat gluten flour; 187 cytokines were assessed. Confirmatory analyses were performed by high-sensitivity electrochemiluminescence immunoassay. Cytokine elevations were correlated with symptoms. Cytokine release following gluten challenge in coeliac disease patients included significant elevations of IL-2, chemokine (C-C motif) ligand 20 (CCL20), IL-6, chemokine (C-X-C motif) ligand (CXCL)9, CXCL8, interferon (IFN)-γ, IL-10, IL-22, IL-17A, tumour necrosis factor (TNF)-α, CCL2 and amphiregulin. IL-2 and IL-17A were earliest to rise. Peak levels of cytokines were generally at 4 h. IL-2 increased most (median 57-fold), then CCL20 (median 10-fold). Cytokine changes were strongly correlated with one another, and the most severely symptomatic patients had the highest elevations. Early elevations of IL-2, IL-17A, IL-22 and IFN-γ after gluten in patients with coeliac disease implicates rapidly activated T cells as their probable source. Cytokine release after gluten could aid in monitoring experimental treatments and support diagnosis.

Evaluation of Polysaccharide Typhim Vi Antibody Response as a predictor of Humoral Immunodeficiency in Haematological Malignancies.

An increasing healthcare challenge in the management of haematological malignancy (HM) is secondary immunodeficiency. From January 2019, the EMA included the evaluation of specific antibody (Ab) responses to better select patients for immunoglobulin replacement therapy (IgRT). We evaluated Ab responses to pneumococcal and Salmonella typhi pure polysaccharide immunization in a cohort of 42 HM patients and 24 healthy-controls. Pre-post specific Ab concentrations were measured by ELISA at 4 weeks. Globally, significantly lower Typhim Vi (TV) seroprevalence (9%) compared to 23-valent pneumococcal polysaccharide vaccine (PPV) (76%) (p <0.001) was observed. TV non responders (88%) were higher than PPV non responders (62%) (p <0.0001) and correlated better to infectious history. By ROC analysis, pre-post 5-fold TV increase was the best cut-off to discriminate HM with recurrent infections and controls (sensitivity 91%, specificity 100%). Despite the small sample cohort, our results suggest that specific anti-S typhi Ab response is a useful complementary assay in the diagnosis and management decision of SID to HM.

Inorganic particulate matter modulates non-typeable Haemophilus influenzae growth: a link between chronic bacterial infection and geogenic particles.

Australian Aboriginal populations have unacceptably high rates of bronchiectasis. This disease burden is associated with high rates of detection of pathogenic bacteria, particularly non-typeable Haemophilus influenzae (NTHi). While there is evidence to suggest that exposure to inorganic particulate matter (PM) is associated with worse respiratory infections, no studies have considered the direct effect of this PM on bacterial growth. Nine clinical isolates of pathogenic NTHi were used for this study. Isolates were exposed to two common iron oxides, haematite (Fe2O3) or magnetite (Fe3O4), or quartz (SiO2), as the main constituents of environmental inorganic PM. NTHi isolates were exposed to PM with varying levels of heme to identify whether the response to PM was altered by iron availability. The maximal rate of growth and maximum supported growth were assessed. We observed that inorganic PM was able to modify the maximal growth of selected NTHi isolates. Magnetite and quartz were able to increase maximal growth, while haematite could both increase and suppress the maximal growth. However, these effects varied depending on iron availability and on the bacterial isolate. Our data suggest that inorganic PM may directly alter the growth of pathogenic NTHi. This observation may partly explain the link between exposure to high levels of crustal PM and chronic bacterial infection in Australian Aboriginals.

The Inflammatory Effect of Iron Oxide and Silica Particles on Lung Epithelial Cells.

PURPOSE: Our understanding of the respiratory health consequences of geogenic (earth-derived) particulate matter (PM) is limited. Recent in vivo evidence suggests that the concentration of iron is associated with the magnitude of the respiratory response to geogenic PM. We investigated the inflammatory and cytotoxic potential of silica and iron oxide particles alone, and in combination, on lung epithelial cells. METHODS: Bronchial epithelial cells (BEAS-2B) were exposed to silica (quartz, cristobalite) and/or iron oxide (hematite, magnetite) particles. Cytotoxicity and cytokine production (IL-6, IL-8, IL-1ß and TNF-α) were assessed by LDH assay and ELISA, respectively. In subsequent experiments, the cytotoxic and inflammatory potential of the particles was assessed using alveolar epithelial cells (A549). RESULTS: After 24 h of exposure, iron oxide did not cause significant cytotoxicity or production of cytokines, nor did it augment the response of silica in the BEAS2-B cells. In contrast, while the silica response was not augmented in the A549 cells by the addition of iron oxide, iron oxide particles alone were sufficient to induce IL-8 production in these cells. There was no response detected for any of the outcomes at the 4 h time point, nor was there any evidence of IL-1ß or TNF-α production. CONCLUSIONS: While previous studies have suggested that iron may augment silica-induced inflammation, we saw no evidence of this in human epithelial cells. We found that alveolar epithelial cells produce pro-inflammatory cytokines in response to iron oxide particles, suggesting that previous in vivo observations are due to the alveolar response to these particles.

Differences in all-cause hospitalisation by ethnic group: a data linkage cohort study of 4.62 million people in Scotland, 2001-2013.

OBJECTIVES: Immigration into Europe has raised contrasting concerns about increased pressure on health services and equitable provision of health care to immigrants or ethnic minorities. Our objective was to find out if there were important differences in hospital use between the main ethnic groups in Scotland. STUDY DESIGN: A census-based data linkage cohort study. METHODS: We anonymously linked Scotland's Census 2001 records for 4.62 million people, including their ethnic group, to National Health Service general hospitalisation records for 2001-2013. We used Poisson regression to calculate hospitalisation rate ratios (RRs) in 14 ethnic groups, presented as percentages of the White Scottish reference group (RR = 100), for males and females separately. We adjusted for age and socio-economic status and compared those born in the United Kingdom or the Republic of Ireland (UK/RoI) with elsewhere. We calculated mean lengths of hospital stay. RESULTS: 9.79 million hospital admissions were analysed. Compared with the White Scottish, unadjusted RRs for both males and females in most groups were about 50-90, e.g. Chinese males 49 (95% confidence interval [CI] = 45-53) and Indian females 76 (95% CI 71-81). The exceptions were White Irish, males 120 (95% CI 117-124) and females 115 (95% CI 112-119) and Caribbean females, 103 (95% CI 85-126). Adjusting for age increased the RRs for most groups towards or above the reference. Socio-economic status had little effect. In many groups, those born outside the UK/RoI had lower admission rates. Unadjusted mean lengths of stay were substantially lower in most ethnic minorities. CONCLUSIONS: Use of hospital beds in Scotland by most ethnic minorities was lower than by the White Scottish majority, largely explained by their younger average age. Other countries should use similar methods to assess their own experience.

Lower limb fracture presentations at a regional hospital.

We found that lower limb fractures, which were largely the result of minimal trauma, had high levels of hospitalisation, length of stay and surgery. It is therefore important to prevent fractures at all sites to avoid the associated morbidity and mortality. PURPOSE: Hip fractures are a major cause of morbidity and mortality, particularly in older women. In comparison, less is known about the epidemiology and burden of other lower limb fractures. The study aimed to investigate the epidemiology and burden of these fractures. METHODS: Incident fractures of the hip, femur, tibia/fibula, ankle and foot in women (≥ 20 years) managed through the University Hospital Geelong, Australia, were ascertained from 1 Jan. 2014 to 31 Dec. 2014 from radiology reports. Age, cause of fracture, post-fracture hospitalisation, surgery, length of stay and discharge location were ascertained from medical records. RESULTS: We identified 585 fractures of the lower limb (209 hip, 42 femur, 41 tibia/fibula, 162 ankle, 131 foot). Most fractures were sustained by women aged ≥ 50 years. Fractures were largely a result of minimal trauma. Most women with hip or femur fractures were hospitalised; fewer were hospitalised for fractures at other sites. Surgery for fracture followed the same pattern as hospitalisations. Length of stay was the highest for hip and femur fractures and the lowest for foot fractures. Women with hip or femur fractures were discharged to rehabilitation more often than home. Fractures at other sites were most commonly discharged home. CONCLUSIONS: Fractures of the lower limb occurred frequently in older women. Hospitalisation and subsequent surgery were common in cases of hip and femur fractures. It is important for prevention strategies to target fractures at a range of skeletal sites to reduce costs, hospitalisations, loss of independence and reduced quality of life.

Prediction of 90 Day and Overall Survival after Chemoradiotherapy for Lung Cancer: Role of Performance Status and Body Composition.

AIMS: If appropriate patients are to be selected for lung cancer treatment, an understanding of who is most at risk of adverse outcomes after treatment is needed. The aim of the present study was to identify predictive factors for 30 and 90 day mortality after chemoradiotherapy (CRT), and factors that were prognostic for overall survival. MATERIALS AND METHODS: A retrospective cohort study of 194 patients with lung cancer who had undergone CRT in South East Scotland from 2008 to 2010 was undertaken. Gender, age, cancer characteristics, weight loss, body mass index (BMI), performance status (Eastern Cooperative Oncology Group; ECOG) and computed tomography-derived body composition variables were examined for prognostic significance using Cox's proportional hazards model and logistic regression. RESULTS: The median overall survival was 19 months (95% confidence interval 16.3, 21.7). Four of 194 patients died within 30 days of treatment completion, for which there were no independent predictive variables; 22/194 (11%) died within 90 days of treatment completion. BMI < 20 and ECOG performance status ≥2 were independent predictors of death within 90 days of treatment completion (P = 0.001 and P = 0.004, respectively). Patients with either BMI < 20 or ECOG performance status ≥ 2 had an odds ratio of death within 90 days of 5.97 (95% confidence interval 2.20, 16.19), rising to an odds ratio of 13.27 (1.70, 103.47) for patients with both BMI < 20 and ECOG performance status ≥ 2. Patients with low muscle attenuation had significantly reduced overall survival (P = 0.004); individuals with low muscle attenuation had a median survival of 15.2 months (95% confidence interval 12.7, 17.7) compared with 23.0 months (95% confidence interval 18.3, 27.8) for those with high muscle attenuation, equating to a hazard ratio of death of 1.62 (95% confidence interval 1.17, 2.23, P = 0.003). CONCLUSION: Poor performance status, low BMI and low muscle attenuation identify patients at increased risk of premature death after CRT. Risk factors for adverse outcomes should inform personalised discussions with patients about the potential harms as well as the intended benefits of treatment.

Why so GLUMM? Detecting depression clusters through graphing lifestyle-environs using machine-learning methods (GLUMM).

BACKGROUND: Key lifestyle-environ risk factors are operative for depression, but it is unclear how risk factors cluster. Machine-learning (ML) algorithms exist that learn, extract, identify and map underlying patterns to identify groupings of depressed individuals without constraints. The aim of this research was to use a large epidemiological study to identify and characterise depression clusters through "Graphing lifestyle-environs using machine-learning methods" (GLUMM). METHODS: Two ML algorithms were implemented: unsupervised Self-organised mapping (SOM) to create GLUMM clusters and a supervised boosted regression algorithm to describe clusters. Ninety-six "lifestyle-environ" variables were used from the National health and nutrition examination study (2009-2010). Multivariate logistic regression validated clusters and controlled for possible sociodemographic confounders. RESULTS: The SOM identified two GLUMM cluster solutions. These solutions contained one dominant depressed cluster (GLUMM5-1, GLUMM7-1). Equal proportions of members in each cluster rated as highly depressed (17%). Alcohol consumption and demographics validated clusters. Boosted regression identified GLUMM5-1 as more informative than GLUMM7-1. Members were more likely to: have problems sleeping; unhealthy eating; ≤2 years in their home; an old home; perceive themselves underweight; exposed to work fumes; experienced sex at ≤14 years; not perform moderate recreational activities. A positive relationship between GLUMM5-1 (OR: 7.50, P<0.001) and GLUMM7-1 (OR: 7.88, P<0.001) with depression was found, with significant interactions with those married/living with partner (P=0.001). CONCLUSION: Using ML based GLUMM to form ordered depressive clusters from multitudinous lifestyle-environ variables enabled a deeper exploration of the heterogeneous data to uncover better understandings into relationships between the complex mental health factors.

Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery.

BACKGROUND: Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. METHODS: In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces). RESULTS: Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222). CONCLUSION: High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/).

Intra-operative assessment of excised breast tumour margins using ClearEdge imaging device.

INTRODUCTION: Breast conserving surgery (BCS) aims to remove a breast cancer completely and obtain clear margins. Complete excision is essential to reduce the risk of local recurrence. The ClearEdge™ (CE) imaging device examines margins of excised breast tissue intra-operatively. The aim of this study was to investigate the potential of the device in detecting margin involvement in patients having BCS. METHODS: In Phase-1 58 patients underwent BCS and had 334 margins assessed by the device. In Phase-2 the device was used in 63 patients having BCS and 335 margins were assessed. Patients with margins considered close or involved by the CE device were re-excised. RESULTS: The margin assessment accuracies in Phase-1 and Phase-2 compared to permanent section pathology were very similar: sensitivity (84.3% and 87.3%), specificity (81.9% and 75.6%), positive predictive value (67.2% and 63.6%), and negative predictive value (92.2% and 92.4%). The false positive rate (18.1% and 24.4%) and false negative rate (15.7% and 12.7%) were low in both phases. In Phase-2 re-excision rate was 37%, but in the 54 where the CE device was used appropriately the re-excision rate was 17%. Had all surgeons interpreted all images appropriately and re-excised margins detected as abnormal by the device in Phase-2 then the re-excision rate would have been 7%. CONCLUSION: This study shows that the CE device has potential to reduce re-excision after BCS and further randomized studies of its value are warranted.

Anxiety disorders and falls among older adults.

BACKGROUND: Falls are common among older adults and can lead to serious injuries, including fractures. We aimed to determine associations between anxiety disorders and falls in older adults. METHODS: Participants were 487 men and 376 women aged ≥60 years enrolled in the Geelong Osteoporosis Study, Australia. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition (SCID-I/NP), lifetime history of anxiety disorders was determined. Falls were determined by self-report. In men, a falls-risk score (Elderly Falls Screening Test (EFST)) was also calculated. RESULTS: Among fallers, 24 of 299 (8.0%) had a lifetime history of anxiety disorder compared to 36 of 634 (5.7%) non-fallers (p=0.014). Examination of the association between anxiety and falls suggested differential relationships for men and women. In men, following adjustment for psychotropic medications, mobility and blood pressure, lifetime anxiety disorder was associated with falling (OR 2.96; 95%CI 1.07-8.21) and with EFST score (OR 3.46; 95%CI 1.13-10.6). In women, an association between lifetime anxiety disorder and falls was explained by psychotropic medication use, poor mobility and socioeconomic status. LIMITATIONS: Sub-group analyses involving types of anxiety and anxiety disorders over the past 12-months were not performed due to power limitations. CONCLUSION: Although anxiety disorders were independently associated with a 3-fold increase in likelihood of reported falls and high falls risk among men, an independent association was not detected among women. These results may aid in prevention of falls through specific interventions aimed at reducing anxiety, particularly in men.

Association between underestimation of tumour size by imaging and incomplete excision in breast-conserving surgery for breast cancer.

BACKGROUND: Completeness of excision is the most important factor influencing local recurrence after breast-conserving surgery (BCS). The aim of this case-control study was to determine factors influencing incomplete excision in patients undergoing BCS. METHODS: Women with invasive breast cancer treated by BCS between 1 June 2008 and 31 December 2009 were identified from a prospectively collected database in the Edinburgh Breast Unit. The maximum size of the tumour, measured microscopically, was compared with the size estimated before operation by mammography and ultrasound imaging. A multivariable analysis was performed to investigate factors associated with incomplete excision. RESULTS: The cohort comprised 311 women, of whom 193 (62·1 per cent) had a complete (CE group) and 118 (40·7 per cent) an incomplete (IE group) excision. Mammography underestimated tumour size in 75·0 per cent of the IE group compared with 40·7 per cent of the CE group (P < 0·001). Ultrasound imaging underestimated tumour size in 82·5 per cent of the IE group compared with 56·5 per cent of the CE group (P < 0·001). The risk of an incomplete excision was greater when mammography or ultrasonography underestimated pathological size: odds ratio (OR) 4·38 (95 per cent c.i. 2·59 to 7·41; P < 0·001) for mammography, and OR 3·64 (2·03 to 6·54; P < 0·001) for ultrasound imaging. For every 1-mm underestimation of size by mammography and ultrasonography, the relative odds of incomplete excision rose by 10 and 14 per cent respectively. CONCLUSION: Underestimation of tumour size by current imaging techniques is a major factor associated with incomplete excision in women undergoing BCS.

A study of margin width and local recurrence in breast conserving therapy for invasive breast cancer.

PURPOSE: Debate continues on what is an adequate margin width to define a clear margin and whether there is a need to excise pectoral fascia or remove skin in breast conserving surgery. This study set out to provide answers to these questions. PATIENTS AND METHODS: 1411 patients with invasive breast cancer were treated by breast conserving surgery and post-operative whole breast radiotherapy from January 2000 to December 2005. Distance from each margin to any in situ or invasive cancer was measured and recorded. If full thickness of breast tissue was removed no re excision of anterior and posterior margins was performed even if disease was <1 mm from a margin. Patients ≤50 years of age and those with anterior or posterior margins <1 mm to invasive cancer had a radiation boost. Median follow-up time was 6.4 years. RESULTS: Local in breast tumour relapse (IBTR) occurred in 50 patients. The overall actuarial IBTR rate at 5 years was 2.2%. There was no difference in IBTR when comparing patients with radial margins of 1-5 mm or 5-10 mm. Anterior and posterior margins <1 mm or with ink on tumour cells were not associated with an increase in IBTR. CONCLUSION: There is no justification for radial margins of greater than 1 mm. If the anterior or posterior margin is <1 mm and full thickness of breast tissue has been removed, then re excision of these margins is unnecessary if boost radiotherapy is delivered.