Antenatal care of women who use opioids: a qualitative study of practitioners' perceptions of strengths and challenges of current service provision in Scotland.

BACKGROUND: The increasing rise of women using opioids during pregnancy across the world has warranted concern over the access and quality of antenatal care received by this group. Scotland has particularly high levels of opioid use, and correspondingly, pregnancies involving women who use opioids. The purpose of this study was to investigate the different models of antenatal care for women using opioids during pregnancy in three Scottish Health Board Areas, and to explore multi-disciplinary practitioners' perceptions of the strengths and challenges of working with women who use opioids through these specialist services. METHODS: Thirteen semi-structured interviews were conducted with health and social care workers who had experience of providing antenatal and postnatal care to women who use drugs across three Scottish Health Board Areas: NHS Greater Glasgow and Clyde, NHS Lothian, and NHS Tayside. Framework Analysis was used to analyse interview data. The five stages of framework analysis were undertaken: familiarisation, identifying the thematic framework, indexing, charting, and mapping and interpretation. RESULTS: Each area had a specialist antenatal pathway for women who used substances. Pathways varied, with some consisting of specialist midwives, and others comprising a multidisciplinary team (e.g. midwife, mental health nurse, social workers, and an obstetrician). Referral criteria for the specialist service differed between health board areas. These specialised pathways presented several key strengths: continuity of care with one midwife and a strong patient-practitioner relationship; increased number of appointments, support and scans; and highly specialised healthcare professionals with experience of working with substance use. In spite of this, there were a number of limitations to these pathways: a lack of additional psychological support for the mother; some staff not having the skills to engage with the complexity of patients who use substances; and problems with patient engagement. CONCLUSIONS: Across the three areas, there appears to be high-quality multi-disciplinary antenatal services for women who use opioids during pregnancy. However, referral criteria vary and some services appear more comprehensive than others. Further research is needed into the perceptions of women who use opioids on facilitators and barriers to antenatal care, and provision in rural regions of Scotland.

Comparison of breast cancer HER-2 receptor testing with immunohistochemistry and in situ hybridization.

PURPOSE: Human epidermal growth factor receptor-2 (HER2) status can be tested with immunohistochemistry (IHC) and in situ hybridization (ISH). The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guidelines suggest initial HER2 testing using IHC and further testing IHC equivocal cases with ISH. However, many institutions perform both IHC and ISH on the same specimen. This study aims to analyze the concordance between HER2 IHC and ISH in order to evaluate the benefit of repeating HER2 testing on the same breast cancer specimens. METHOD: Patients diagnosed with invasive breast cancer through BreastScreen NSW Sydney West program between January 2018 and December 2020 were identified and their HER2 IHC and HER2 ISH results on core needle biopsy (CNB) and surgical excisions (SE) were retrospectively collected. Specimens with both IHC and ISH results were then analyzed for agreement and concordance using unweighted kappa values. Equivocal IHC (2+) cases were excluded from concordance analysis. RESULTS: Overall, there were 240 invasive breast cancer specimens (CNB and SE) with both IHC and ISH recorded. Concordance between HER2 IHC and ISH was 100% (95% CI: 96.2-100%; κ = 1.00 (P < 0.001)). Of the IHC equivocal cases (n = 146), 94.5% were ISH negative. CONCLUSION: There was perfect positive concordance and agreement between non-equivocal IHC and ISH results. This reinforces that IHC alone can be utilized reliably for testing HER2 status of non-equivocal cases consistent with the 2018 ASCO/CAP guidelines.

The association of immune response and colostral immunoglobulin G in Canadian and US Holstein-Friesian dairy cows.

In cattle, maternal immunoglobulins are transferred through colostrum to provide passive immunity to the neonatal calf once they are absorbed into circulation. Cows can be assessed for antibody- and cell-mediated immune responses (AMIR and CMIR, respectively), and through estimated breeding values (EBV) and genomic parent averages (GPA), cows can be classified as having high, average, or low immune response (IR). The objective of this study was to identify associations of colostral IgG concentrations with IR in dairy cows. High IR dairy cows identified by GPA or EBV were hypothesized to produce higher colostral IgG concentrations than cows with average or low IR. Colostrum was collected from Holstein dairy cows from 3 large commercial herds (n = 590) in the United States and 1 research herd at the Ontario Dairy Research Centre (n = 275) in Canada. For the US herds, IR GPA were available through genotyping. For the Canadian herd, IR EBV were available through phenotyping and pedigree information. Colostral IgG concentrations were measured by radial immunodiffusion and analyzed using general linear models in SAS. Based on a prediction equation, cows in US herds with a CMIR GPA of 1 would have colostral IgG concentrations 6.3 g/L higher on average than cows with a CMIR GPA of 0. High CMIR cows produced statistically greater colostral IgG concentrations (least squares mean ± standard error of the mean, 107.5 ± 7.7 g/L) than low CMIR cows (91.4 ± 7.1 g/L), with intermediate values for average CMIR cows (105.1 ± 5.6 g/L). No differences were found among AMIR categories in US cows. The Canadian herd showed a trend for cows with high CMIR EBV (continuous variable) to produce greater colostral IgG. No differences were observed among high, average, and low AMIR EBV classifications in Canadian cows. The findings suggest that selective breeding of Holstein cows to enhance CMIR could contribute to higher-quality colostrum in succeeding generations.

Risk factors for breast cancer-related lymphedema in patients undergoing 3 years of prospective surveillance with intervention.

BACKGROUND: To evaluate risk factors (treatment-related, comorbidities, and lifestyle) for breast cancer-related lymphedema (BCRL) within the context of a Prospective Surveillance and Early Intervention (PSEI) model of care for subclinical BCRL. METHODS: The parent randomized clinical trial assigned patients newly diagnosed with breast cancer to PSEI with either bioimpedance spectroscopy (BIS) or tape measurement (TM). Surgical, systemic and radiation treatments, comorbidities, and lifestyle factors were recorded. Detection of subclinical BCRL (change from baseline of either BIS L-Dex ≥6.5 or tape volume ≥ 5% and < 10%) triggered an intervention with compression therapy. Volume change from baseline ≥10% indicated progression to chronic lymphedema and need for complex decongestive physiotherapy. In this secondary analysis, multinomial logistic regressions including main and interaction effects of the study group and risk factors were used to test for factor associations with outcomes (no lymphedema, subclinical lymphedema, progression to chronic lymphedema after intervention, progression to chronic lymphedema without intervention). Post hoc tests of significant interaction effects were conducted using Bonferroni-corrected alphas of .008; otherwise, an alpha of .05 was used for statistical significance. RESULTS: The sample (n = 918; TM = 457; BIS = 461) was female with a median age of 58.4 years. Factors associated with BCRL risk included axillary lymph node dissection (ALND) (p < .001), taxane-based chemotherapy (p < .001), regional nodal irradiation (RNI) (p ≤ .001), body mass index >30 (p = .002), and rurality (p = .037). Mastectomy, age, hypertension, diabetes, seroma, smoking, and air travel were not associated with BCRL risk. CONCLUSIONS: Within the context of 3 years of PSEI for subclinical lymphedema, variables of ALND, taxane-based chemotherapy, RNI, body mass index >30, and rurality increased risk.

Concordance between core needle biopsy and surgical excision for breast cancer tumor grade and biomarkers.

PURPOSE: Histopathological biomarkers guide breast cancer management. Testing histopathological biomarkers on both core needle biopsy (CNB) and surgical excision (SE) in patients who are treated with upfront surgery is unnecessary and costly if there is high concordance between the two. This study investigated the concordance between CNB and SE for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), tumor grade and Ki-67. METHODS: Histopathological biomarker information were retrospectively collected from preoperative CNB and SE on patients diagnosed with breast cancer through the BreastScreen Sydney West program over a four-year period between January 2017 and December 2020. Data were then analyzed to calculate percentage of agreement and concordance using kappa values for ER, PR, HER2, tumor grade and Ki-67. RESULTS: A total of 504 cases of invasive breast cancers were analyzed. There was substantial level of concordance for ER 96.7% (κ = 0.687) and PR 93.2% (κ = 0.69). Concordance for HER2 negative (IHC 0, IHC 1 +) or positive (IHC 3 +) tumor on CNB was 100% (κ = 1.00). Grade and Ki-67 showed moderate level of concordance, 72.6% (κ = 0.545) and 70.5% (κ = 0.453), respectively. CONCLUSION: ER, PR and HER2 show high level of concordance. CNB is reliable in determining histopathological biomarkers for ER, PR positive and HER2 positive or negative tumors indicating that retesting these on SE may not be necessary.

The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.

Introduction: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score. Methods: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%). Conclusion: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.

A genome guided evaluation of the Lab4 probiotic consortium.

Draft genome sequences of the Lab4 probiotic consortium were deposited in Genbank: Bifidobacterium animalis subsp lactis CUL34 (PRJNA482550), Bifidobacterium bifidum CUL20 (PRJNA559984), Lactobacillus acidophilus CUL60 (PRJNA482335), Lactobacillus acidophilus CUL21 (PRJNA482434). Probiogenomic analyses confirmed existing taxonomies and identified putative gene sequences that were functionally related to the performance of each organism during in vitro assessments of bile and acid tolerability, adherence to enterocytes and susceptibility to antibiotics. Genomic stability predictions identified no significant risk of gene acquisition of both antibiotic resistance and virulence genes. These observations were supported by acute phase and repeat dose tolerability studies in Wistar rats. High doses of Lab4 did not result in mortalities, clinical/histopathological abnormalities nor systemic toxicity. Increased faecal numbers of Lab4 in supplemented rats implied survival through the gastrointestinal tract and/or impact the intestinal microbiota composition. In summary, this study provides multifaceted support for probiotic functionality and the safety of the Lab4 consortium.

Realist analysis of whether emergency departments with primary care services generate 'provider-induced demand'.

BACKGROUND: It is not known whether emergency departments (EDs) with primary care services influence demand for non-urgent care ('provider-induced demand'). We proposed that distinct primary care services in EDs encourages primary care demand, whereas primary care integrated within EDs may be less likely to cause additional demand. We aimed to explore this and explain contexts (C), mechanisms (M) and outcomes (O) influencing demand. METHODS: We used realist evaluation methodology and observed ED service delivery. Twenty-four patients and 106 staff members (including Clinical Directors and General Practitioners) were interviewed at 13 EDs in England and Wales (240 hours of observations across 30 days). Field notes from observations and interviews were analysed by creating 'CMO' configurations to develop and refine theories relating to drivers of demand. RESULTS: EDs with distinct primary care services were perceived to attract demand for primary care because services were visible, known or enabled direct access to health care services. Other influencing factors included patients' experiences of accessing primary care, community care capacity, service design and population characteristics. CONCLUSIONS: Patient, local-system and wider-system factors can contribute to additional demand at EDs that include primary care services. Our findings can inform service providers and policymakers in developing strategies to limit the effect of potential influences on additional demand when demand exceeds capacity.

What is in? What is out? Updating the British Society for Cutaneous Allergy facial series.

BACKGROUND: Allergic contact dermatitis (ACD) to cosmetics is widely reported. To ensure we are accurately diagnosing ACD, patch test series should be continually reviewed to identify relevant and emerging allergens and highlight those that are outdated. The current British Society for Cutaneous Allergy (BSCA) facial series recommends 26 allergens and was last modified in 2012. OBJECTIVES: To review and update the BSCA facial series. METHODS: We retrospectively reviewed the results from 12 UK and Ireland patch test centres' facial series from January 2016 to December 2017. We recorded the number of allergens tested in each centre and the detection rate for each allergen. Using a 0·3% positive rate as the inclusion threshold, we established which allergens in the BSCA facial series had positive patch test rates < 0·3% and > 0·3%. Allergens not in the BSCA facial series that had a positive patch test rate > 0·3% were identified. RESULTS: Overall, 4224 patients were patch tested to the facial series. The number of allergens included in individual centres' facial series ranged from 24 to 66, with a total of 103 allergens tested across all centres. Twelve of the 26 allergens in the BSCA facial series had a positive patch test rate < 0·3% and 14 had a rate > 0·3%. Twenty-five allergens not recommended in the BSCA facial series had a positive patch test rate > 0·3%. CONCLUSIONS: This audit has highlighted the significant variation in practice that exists among patch test centres, despite a recommended facial series. The BSCA facial series has been updated and now contains 24 allergens. Fifteen allergens remain, 11 allergens have been dropped and nine new allergens have been added.

Implementing a prospective surveillance and early intervention model of care for breast cancer-related lymphedema into clinical practice: application of the RE-AIM framework.

PURPOSE: Chronic lymphedema following breast cancer (BC) affects individuals physically, functionally, psychologically, and financially. Despite national guidelines and evidence-based research supporting a prospective surveillance and early intervention model of care (PSM), bridging the gap between research and clinical practice has been difficult. METHOD: As part of an international randomized controlled trial (RCT), Australian women with BC from four hospitals were recruited, monitored for lymphedema at regular intervals over a 3-year period, and were provided a compression garment if intervention was triggered. The reach, effectiveness, adoption, implementation and maintenance (RE-AIM) evaluation framework was used retrospectively to assess a PSM at the individual and organizational level for those who had completed at least 2-year follow-up (N = 219) in the RCT. RESULTS: The application of the RE-AIM framework retrospectively demonstrated an extensive reach to patients across public and private settings; the effectiveness of prospective surveillance and early intervention was achieved through low progression rates to clinical lymphedema (1.8%), and all hospital sites initially approached adopted the research study. Key implementation strategies necessary for effectiveness of this model of care included education to health professionals and patients, staff acceptability, and development of a referral and care pathway. Maintenance dimensions were evaluated both at the individual level with 92-100% adherence rates for all nonoptional study appointments over the 2-year period, and at the organizational-level, PSM was sustained after recruitment ceased for the research study. CONCLUSION: The PSM for lymphedema in BC can be successfully implemented using the RE-AIM framework applied retrospectively. The implementation of the PSM used in the RCT has assisted in changing clinical practices and improving the quality and effectiveness of the health care system.

Desmoplastic melanoma: a review of its pathology and clinical behaviour, and of management recommendations in published guidelines.

Desmoplastic melanomas are uncommon. Their behaviour differs from that of other melanoma subtypes; therefore, management guidelines for non-desmoplastic melanomas may not be applicable. This review sought to examine all available evidence relating to the behaviour and management of desmoplastic melanomas, based on review of all relevant English-language publications, and to critically assess the recommendations for their management in current published melanoma management guidelines. Compared with other melanoma subtypes, patients with 'pure' desmoplastic melanomas (where ≥90% of the invasive melanoma is of desmoplastic melanoma subtype) have much lower rates of sentinel node positivity and distant metastasis. Local recurrence rates are higher for desmoplastic melanomas, but resection margins wider than those recommended for non-desmoplastic melanomas have not been shown to be of benefit. Adjuvant radiotherapy reduces the risk of local recurrence when a satisfactory histological clearance (≥8 mm) cannot be achieved. Of 29 published melanoma management guidelines identified, only 11 specified management for desmoplastic melanomas, while seven simply stated that the feature should be reported. Desmoplastic melanoma is a unique melanoma subtype with biology that differs from that of other melanoma subtypes. It requires specific management strategies but few current guidelines address these.

SURPRISINGLY FEW WOMEN WITH SEVERE OSTEOPOROSIS BY BONE DENSITOMETRY UNDERGO WORKUP FOR SECONDARY CAUSES - A RETROSPECTIVE EVALUATION.

We describe clinical features of women with extremely low bone density, and investigate secondary causes of osteoporosis. Our hypothesis was that this population would be enriched in identifiable causes of osteoporosis. We performed a retrospective review of medical records of all women seen at our university over 4 years with T-score on bone densitometry at/below -4 at any site. Historical and fracture details were abstracted. We considered a thorough work up to include Vitamin D, PTH, CBC, chemistry panel, cortisol, transglutaminase, myeloma screen, tryptase and 24-hour urine calcium. Results: 137 women were identified with T-score at/below -4. Percent identified as Asian was 26% (higher than local prevalence of 8%). Average BMI was 21.6 kg/m2. Clearly identifiable causes of osteoporosis were noted in 57% (inflammatory disorder, glucocorticoid or antacid exposure, prolonged immobilization and alcoholism were most prevalent). Of the remainder, full work up was performed only in 8%. Endocrine consultation and white race predicted thoroughness of secondary work-up. Conclusion: Fragility fractures, leanness and Asian race were common in women with very low T-score. However, few new causes were identified. Underlying etiology was either immediately evident or inadequately studied, especially in minorities.

Physiotherapy rehabilitation for osteoporotic vertebral fracture-a randomised controlled trial and economic evaluation (PROVE trial).

The trial compared three physiotherapy approaches: manual or exercise therapy compared with a single session of physiotherapy education (SSPT) for people with osteoporotic vertebral fracture(s). At 1 year, there were no statistically significant differences between the groups meaning there is inadequate evidence to support manual or exercise therapy. INTRODUCTION: To evaluate the clinical and cost-effectiveness of different physiotherapy approaches for people with osteoporotic vertebral fracture(s) (OVF). METHODS: >Prospective, multicentre, adaptive, three-arm randomised controlled trial. Six hundred fifteen adults with back pain, osteoporosis, and at least 1 OVF participated. INTERVENTIONS: 7 individual physiotherapy sessions over 12 weeks focused on either manual therapy or home exercise compared with a single session of physiotherapy education (SSPT). The co-primary outcomes were quality of life and back muscle endurance measured by the QUALEFFO-41 and timed loaded standing (TLS) test at 12 months. RESULTS: At 12 months, there were no statistically significant differences between groups. Mean QUALEFFO-41: - 1.3 (exercise), - 0.15 (manual), and - 1.2 (SSPT), a mean difference of - 0.2 (95% CI, - 3.2 to 1.6) for exercise and 1.3 (95% CI, - 1.8 to 2.9) for manual therapy. Mean TLS: 9.8 s (exercise), 13.6 s (manual), and 4.2 s (SSPT), a mean increase of 5.8 s (95% CI, - 4.8 to 20.5) for exercise and 9.7 s (95% CI, 0.1 to 24.9) for manual therapy. Exercise provided more quality-adjusted life years than SSPT but was more expensive. At 4 months, significant changes above SSPT occurred in endurance and balance in manual therapy, and in endurance for those ≤ 70 years, in balance, mobility, and walking in exercise. CONCLUSIONS: Adherence was problematic. Benefits at 4 months did not persist and at 12 months, we found no significant differences between treatments. There is inadequate evidence a short physiotherapy intervention of either manual therapy or home exercise provides long-term benefits, but arguably short-term benefits are valuable. TRIAL REGISTRATION: ISRCTN 49117867.

Effect of the American College of Surgeons Oncology Group Z0011 trial on axillary management in breast cancer patients in the Australian setting.

The American College of Surgeons Oncology Group Z0011 Trial demonstrated that early breast cancer patients with positive axillary sentinel lymph nodes treated with breast-conserving surgery and breast radiotherapy had no additional oncologic benefit of proceeding to an axillary lymph node dissection (ALND). The extent to which practice has changed in Australia remains unclear. The aim of this study was to investigate the effect of the Z0011 trial on the management of positive axillary sentinel nodes at an Australian institutional level. We reviewed all breast cancer cases treated at the Sydney Adventist Hospital over a 10-year period from 1 January 2008 to 31 December 2017. Patients who fulfilled the Z0011 trial criteria were selected. These patients were divided into two groups according to the year of surgery, before and after 1 January 2011 when the Z0011 study was published. Clinicopathologic data and axillary surgical management were compared. Of the 237 patients fulfilling the Z0011 trial criteria, there were 73 patients before and 158 patients after 1 January 2011. In the earlier group the rate of proceeding to an ALND following a positive sentinel node was 78.1% compared to 43.7% in the latter group (P < 0.0001). There was a significant decline in the rate of ALND over this 10-year period (r = -0.79, P = 0.006). The Z0011 trial has influenced the surgical management of the axilla leading to a significant reduction in the rate of an ALND in patients fulfilling the Z0011 trial criteria at our institution.

Large-scale bleaching of corals on the Great Barrier Reef.

In 2015-2016, record temperatures triggered a pan-tropical episode of coral bleaching. In the southern hemisphere summer of March-April 2016, we used aerial surveys to measure the level of bleaching on 1,156 individual reefs throughout the 2,300 km length of the Great Barrier Reef, the world's largest coral reef system. The accuracy of the aerial scores was ground-truthed with detailed underwater surveys of bleaching at 260 sites (104 reefs), allowing us to compare aerial and underwater bleaching data with satellite-derived temperatures and with associated model predictions of bleaching. The severity of bleaching on individual reefs in 2016 was tightly correlated with the level of local heat exposure: the southernmost region of the Great Barrier Reef escaped with only minor bleaching because summer temperatures there were close to average. Gradients in nutrients and turbidity from inshore to offshore across the Great Barrier Reef had minimal effect on the severity of bleaching. Similarly, bleaching was equally severe on reefs that are open or closed to fishing, once the level of satellite-derived heat exposure was accounted for. The level of post-bleaching mortality, measured underwater after 7-8 months, was tightly correlated with the aerial scores measured at the peak of bleaching. Similarly, reefs with a high aerial bleaching score also experienced major shifts in species composition due to extensive mortality of heat-sensitive species. Reefs with low bleaching scores did not change in composition, and some showed minor increases in coral cover. Two earlier mass bleaching events occurred on the Great Barrier Reef in 1998 and 2002, that were less severe than 2016. In 2016, <9% of scored reefs had no bleaching, compared to 42% in 2002 and 44% in 1998. Conversely, the proportion of reefs that were severely bleached (>60% of corals affected) was four times higher in 2016. The geographic footprint of each of the three events is distinctive, and matches satellite-derived sea surface temperature patterns. Our aerial surveys indicate that past exposure to bleaching in 1998 and 2002 did not lessen the severity of bleaching in 2016. This data set of aerial bleaching scores provides a historical baseline for comparison with future bleaching events. No copyright restrictions apply to the use of this data set other than citing this publication.

Is the timed loaded standing test a valid measure of back muscle endurance in people with vertebral osteoporosis?

Timed loaded standing (TLS) is a suggested measure of back muscle endurance for people with vertebral osteoporosis. Surface electromyography revealed back muscles work harder and fatigue during TLS. The test end-point and total time were associated with back fatigue. The findings help demonstrate the concurrent validity of the TLS test. INTRODUCTION: The TLS test is suggested as a measure of back muscle endurance for patients with vertebral osteoporosis. However, to date, no study has demonstrated that TLS does measure back extensor or erector spinae (ES) muscle endurance. We used surface electromyography (sEMG) to investigate the performance of the thoracic ES muscles during TLS. METHODS: Thirty-six people with vertebral osteoporosis with a mean age of 71.6 (range 45-86) years participated. sEMG recordings were made of the ES at T3 and T12 bilaterally during quiet standing (QS) and TLS. The relative (%) change in sEMG amplitude between conditions was compared. Fatigue was evaluated by analysing the change in median frequency (MF) of the sEMG signal during TLS, and the correlation between maximal TLS time and rate of MF decline was examined. RESULTS: Activity in the ES increased significantly during TLS at all electrode locations. During TLS, the MF declined at a mean rate of -24.2% per minute (95% C.I. -26.5 to -21.9%). The MF slope and test time were strongly correlated (r2 = 0.71), and at test end, the final MF dropped to an average 89% (95% C.I. 85 to 93%) of initial MF. Twenty-eight participants (78%) reported fatigue was the main reason for stopping, and for eight (22%), it was pain. CONCLUSIONS: This study demonstrates that TLS challenges the ES muscles in the thoracic region and results in ES fatigue. Endurance time and the point at which the TLS test ends are strongly related to ES fatigue.

Performance of single skin masonry walls subjected to hydraulic loading.

Property owners are facing increasing threats from flooding and in response are likely to turn to products designed to waterproof or 'seal' the outside of the building in an effort to prevent the ingress of flood water. However, very limited research has been conducted on the effect of this sealing action and the consequent hydraulic load acting upon the structure of the building. The theoretical safe application of waterproofing products has been suggested to be between 0.6 and 1 m (published guidance suggests 0.9 m), although the experimental evidence supporting these suggestions is either absent or limited in nature. This paper presents the findings of an experimental programme that has examined the effect of out-of-plane hydrostatic loading on masonry walls typical of domestic or commercial buildings. The study, conducted at 1/6th scale using a geotechnical centrifuge considers wall panels constructed from a variety of masonry units (autoclaved aerated concrete block, brick and brick-block) bound together with two different types of mortar. The wall panels were subject to an axial load representative of 1 storey of loading and were simply supported on all 4 sides. The load-out-of-plane deflection response of the panels was captured by a 3D digital image correlation system, and the water level at failure was compared to that predicted from previous research and the established yield line analysis method with encouraging results. When partial material and load factors were taken into consideration the results illustrated that a safe sealing height of 0.9 m, as quoted in the literature, would generally be inappropriate, whilst the safe sealing height of 0.6 m was not suitable for every case investigated. This supports the need for a suitable approach for the calculation of water levels at failure rather than the use of fixed values given in published literature.

Efficacy and safety of point-of-care ultrasound-guided intra-articular corticosteroid joint injections in patients with haemophilic arthropathy.

INTRODUCTION AND OBJECTIVES: Intra-articular corticosteroid injections are standard of care for managing joint pain secondary to osteoarthritis or rheumatoid arthritis but are rarely used in haemophilic arthropathy. We have introduced and evaluated the efficacy and safety of ultrasound-guided corticosteroid injections for pain relief in patients with haemophilic arthropathy. PATIENTS AND METHODS: Ultrasound-guided intra-articular injections performed on haemophilia patients at UCSD between March 2012 and January 2016 were analysed. Needle placement and injection (40 mg triamcinolone; 3-5 mL lidocaine) were performed with musculoskeletal ultrasound and Power Doppler. Analysis included patient demographics, joint-specific parameters such as tissue hypervascularity and effusions, pain relief, and procedure-associated complications. RESULTS: Forty-five injections (14 ankles, 13 elbows, 18 knees) were administered in 25 patients. Advanced arthropathy with hypervascularity and/or effusions was present in 91% and 61% of joints, respectively. Ninety-one per cent of injections resulted in pain relief which was significant in 84% (>30% reduction). Median pain score was reduced from 7 of 10 to 1 of 10 (P < 0.001), usually within 24 h. Median duration of pain relief was 8 weeks (range 1-16 weeks). Haemophilia B patients experienced longer periods of relief, and high Pettersson scores were associated with shorter duration of relief. There were no procedure-associated complications. Repeat ultrasound of eight joints within 4 weeks of injection demonstrated nearly complete resolution of hypervascularity. CONCLUSIONS: Point-of-care ultrasound enabled intra-articular corticosteroid injections that provided highly effective, safe, and relatively long-lasting pain relief in haemophilic arthropathy. This approach should be used to improve pain management in haemophilic arthropathy.

Prognostic factors for musculoskeletal injury identified through medical screening and training load monitoring in professional football (soccer): a systematic review.

OBJECTIVES: To identify prognostic factors and models for spinal and lower extremity injuries in adult professional/elite football players from medical screening and training load monitoring processes. METHODS: The MEDLINE, AMED, EMBASE, CINAHL Plus, SPORTDiscus electronic bibliographic databases and the Cochrane Database of Systematic Reviews were searched from inception to July 2016. Searches were limited to original research, published in peer reviewed journals of any language. The Quality in Prognostic Studies (QUIPS) tool was used for appraisal and the modified GRADE approach was used for synthesis. Prospective and retrospective cohort study designs of spinal and lower extremity injury incidence were found from populations of adult professional/elite football players, between 16 and 40 years. Non-football or mixed sports were excluded. RESULTS: 858 manuscripts were identified. Removing duplications left 551 studies, which were screened for eligibility by title and abstract. Of these, 531 studies were not eligible and were excluded. The full text of the remaining 20 studies were obtained; a further 10 studies were excluded. 10 studies were included for appraisal and analysis, for 3344 participants. CONCLUSIONS: Due to the paucity and heterogeneity of the literature, and shortcomings in methodology and reporting, the evidence is of very low or low quality and therefore cannot be deemed robust enough to suggest conclusive prognostic factors for all lower limb musculoskeletal injury outcomes identified. No studies were identified that examined spinal injury outcomes or prognostic models.

A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias.

BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). METHODS: We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months. RESULTS: Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event. CONCLUSIONS: Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .).