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Background: HER2-positive, estrogen receptor-positive breast cancer (HER2+, ER+ BC) is a distinct disease subtype associated with inferior response to chemotherapy plus HER2-targeted therapy compared with HER2+, ER-negative BC. Bi-directional crosstalk leads to cooperation of the HER2 and ER pathways that may drive treatment resistance; thus, simultaneous co-targeting may optimize treatment impact and survival outcomes in patients with HER2+, ER+ BC. First-line (1L) treatment for patients with HER2+ metastatic BC (mBC) is pertuzumab, trastuzumab, and taxane chemotherapy. In clinical practice, dual HER2 blockade plus a fixed number of chemotherapy cycles are given as induction therapy to maximize tumor response, with subsequent HER2-targeted maintenance treatment given as a more tolerable regimen for long-term disease control. For patients whose tumors co-express ER, maintenance endocrine therapy (ET) can be added, but uptake varies due to lack of data from randomized clinical trials investigating the superiority of maintenance ET plus dual HER2 blockade versus dual HER2 blockade alone. Giredestrant, a novel oral selective ER antagonist and degrader, shows promising clinical activity and manageable safety across phase I-II trials of patients with ER+, HER2-negative BC, with therapeutic potential in those with HER2 co-expression., Methods: This phase III, randomized, open-label, two-arm study aims to recruit 812 patients with HER2+, ER+  locally advanced (LA)/mBC into the induction phase (fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] plus a taxane) to enable 730 patients to be randomized 1:1 to the maintenance phase (giredestrant plus PH FDC SC or PH FDC SC [plus optional ET]), stratified by disease site (visceral versus non-visceral), type of LA/metastatic presentation (de novo versus recurrent), best overall response to induction therapy (partial/complete response versus stable disease), and intent to give ET (yes versus no). The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include overall survival, objective response rate, clinical benefit rate, duration of response, safety, and patient-reported outcomes., Discussion: heredERA BC will address whether giredestrant plus dual HER2 blockade is superior to dual HER2 blockade alone, to inform the use of this combination in clinical practice for maintenance 1L treatment of patients with HER2+, ER+ LA/mBC., Trial Registration: ClinicalTrials.gov, NCT05296798; registered on March 25, 2022. Protocol version 3.0 (November 18, 2022)., Sponsor: F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124 4070, Basel, Switzerland., (© 2024. The Author(s).)

Background: Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast cancer patients. Recently, neoadjuvant delivery of the programmed cell death protein-1 inhibitor pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was approved for patients with high-risk, early-stage TNBC, but this treatment regimen has not been evaluated in head-to-head trials with other neoadjuvant treatment regimens. Therefore, the objective of this study was to estimate the relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab versus other neoadjuvant treatments for early-stage TNBC through a systematic review and network meta-analysis (NMA)., Methods: EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts, and clinical trial registries were searched for randomized controlled trials evaluating neoadjuvant treatments for early-stage TNBC. NMA was performed to estimate relative treatment effects among evaluated interventions., Results: Five trials met the inclusion criteria and were included in the NMA. The relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab was favorable to paclitaxel followed by anthracycline + cyclophosphamide in terms of pathologic complete response (pCR), event-free survival (EFS), and overall survival; paclitaxel + carboplatin followed by anthracycline + cyclophosphamide in terms of pCR and EFS; paclitaxel + bevacizumab followed by anthracycline + cyclophosphamide + bevacizumab in terms of pCR; and paclitaxel + carboplatin + veliparib followed by anthracycline + cyclophosphamide in terms of EFS., Conclusions: Neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab confers benefits in response and survival outcomes versus alternative neoadjuvant treatments for early-stage TNBC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: A subset of triple-negative breast cancers (TNBCs) have homologous recombination deficiency with upregulation of compensatory DNA repair pathways. PIKTOR, a combination of TAK-228 (TORC1/2 inhibitor) and TAK-117 (PI3Kα inhibitor), is hypothesized to increase genomic instability and increase DNA damage repair (DDR) deficiency, leading to increased sensitivity to DNA-damaging chemotherapy and to immune checkpoint blockade inhibitors., Methods: 10 metastatic TNBC patients received 4 mg TAK-228 and 200 mg TAK-117 (PIKTOR) orally each day for 3 days followed by 4 days off, weekly, until disease progression (PD), followed by intravenous cisplatin 75 mg/m 2 plus nab paclitaxel 220 mg/m 2 every 3 weeks for up to 6 cycles. Patients received subsequent treatment with pembrolizumab and/or chemotherapy. Primary endpoints were objective response rate with cisplatin/nab paclitaxel and safety. Biopsies of a metastatic lesion were collected prior to and at PD on PIKTOR. Whole exome and RNA-sequencing and reverse phase protein arrays (RPPA) were used to phenotype tumors pre- and post-PIKTOR for alterations in DDR, proliferation, and immune response., Results: With cisplatin/nab paclitaxel (cis/nab pac) therapy post PIKTOR, 3 patients had clinical benefit (1 partial response (PR) and 2 stable disease (SD) ≥ 6 months) and continued to have durable benefit in progression-free survival with pembrolizumab post-cis/nab pac for 1.2, 2, and 3.6 years. Their post-PIKTOR metastatic tissue displayed decreased mismatch repair (MMR), increased tumor mutation burden, and significantly lower levels of 53BP1, DAG Lipase β, GCN2, AKT Ser473, and PKCzeta Thr410/403 compared to pre-PIKTOR tumor tissue., Conclusions: Priming patients' chemotherapy-pretreated metastatic TNBC with PIKTOR led to very prolonged response/disease control with subsequent cis/nab pac, followed by pembrolizumab, in 3 of 10 treated patients. Our multi-omics approach revealed a higher number of genomic alterations, reductions in MMR, and alterations in immune and stress response pathways post-PIKTOR in patients who had durable responses., Trial Registration: This clinical trial was registered on June 21, 2017, at ClinicalTrials.gov using identifier NCT03193853., (© 2023. The Author(s).)

Background: About 50% of women experience lumbopelvic pain (LBPP) during their pregnancy. LBPP has negative repercussions on sleep, social and sexual life, physical and work capacity, and psychological health and contributes to physical inactivity. The benefits of LBPP prevention or treatment in pregnant women through specific exercises should therefore be further investigated. This study protocol has been designed to establish the feasibility of implementing motor control exercise program with pregnant women presenting with a history of LBPP., Methods/design: Forty pregnant women with a history of LBPP will be recruited and randomly allocated to a control (20 participants) or intervention (20 participants) group. The control group will receive standard prenatal care, including basic information on what to do when suffering from LBPP. The intervention group will participate in three 40-min exercise sessions per week from < 20 weeks until 34-36 weeks of gestation: one supervised group session via the Zoom platform (once a month, this session will take place at the Université du Québec à Trois-Rivières) and two unsupervised sessions at home. A motor control exercise program will be developed to target strengthening of the lumbo-pelvic-hip core muscles and improve spinal and pelvic stabilization. Participants of this group will also receive standard prenatal care. Women of the control group will receive after 6 weeks postpartum an exercise program designed to reduce LBPP they may have developed during pregnancy and that may persist after delivery. Primary outcomes will be participants' recruitment, retention and adherence rates, safety, and acceptability of the intervention. Secondary outcomes will include LBPP incidence, frequency, and intensity, as well as self-reported functional disability, physical activity levels, fear avoidance behavior, anxiety, and depression., Discussion: This study will inform the feasibility of conducting a full-scale randomized controlled study to test the effectiveness of a motor control exercise program on the prevention and treatment of LBPP in women with a history of LBPP. Adequate prevention and treatment of pregnant women with a history of LBPP should help limit the recurrences of LBPP or the aggravation of its intensity during pregnancy., Trial Registration: US National Institutes of Health Clinical Trials registry NCT04253717 April 27, 2021., (© 2022. The Author(s).)

Background: Lumbar spinal stenosis (LSS) and peripheral arterial disease (PAD) are two distinct conditions characterized by similar symptoms including leg pain and walking limitations due to claudication. Differentiation between both origins can be difficult and characteristics such as symptom manifestations, time to relief in rest position and pain localization should be considered when determining diagnosis and the treatment plan. The objectives of this study were to compare changes in walking time to symptom change during treadmill tests and self-reported outcomes measures related to claudication, kinesophobia and global health between individuals with LSS, PAD and non-specific low back pain (nLBP)., Method: Fifty-five patients (23 with LSS, 14 with PAD and 18 with nLBP) were recruited from May 2018 to March 2020 to complete a treadmill walking test involving two 5-min walking tasks (Upright and Forward Leaning Trunk (FLT) Walking tasks). The speed was set at 1.9 km/h (1.2 mph), and each task was followed by a 5-min rest period. Walking time to symptom change and Total walking time were recorded during each walking task. Patients were asked to complete four questionnaires related to the impact of claudication, walking impairment, kinesiophobia and global health. One-way ANOVAs were performed to compare walking time difference from the Upright to the FLT walking tasks and to compare questionnaires results between groups., Results: One-way ANOVAs showed a significant difference between groups regarding difference in Walking time to symptom change between both tasks (F = 4.12, p = 0.022). The LSS group improved its Walking time to symptom change from the Upright to the FLT walking tasks more than the PAD (p = 0.34) and the nLBP group (p = 0.12). The nLBP group was less impacted by claudication and less impaired during walking compared to the LSS and PAD groups (ps < 0.001). The nLBP group also had less kinesiophobia than the LSS one (p < 0.001), but was similar to the PAD group. The global health rating was not statistically different between groups (p = 0.118)., Conclusion: The test was able to distinguish neurogenic from vascular or nLBP related claudication. However, further studies are needed to validate this new treadmill walking test., Trial Registration: clinicaltrials.gov ( NCT04058171 ), Registered August 15, 2019 -Registered during recruitment., (© 2021. The Author(s).)

Background: Eribulin mesylate is a nontaxane microtubule dynamics inhibitor approved for second-line (European Union) or third-line (United States) treatment of metastatic breast cancer. Two phase 2 single trials, evaluating first-line eribulin as monotherapy (Study 206; NCT01268150) or in combination with trastuzumab (Study 208; NCT01269346) in locally recurrent or metastatic breast cancer, demonstrated objective response rates of 28.6 and 71.2%, respectively. Median progression-free survival was 6.8 and 11.6 months, respectively. Tolerability profiles were similar to those from previous studies. This secondary analysis was conducted to assess health-related quality of life (HRQoL) in both phase 2 trials., Methods: Patients received eribulin mesylate 1.4 mg/m 2 intravenously on days 1 and 8 of each 21-day cycle. Patients in Study 208 also received intravenous trastuzumab on day 1 of each cycle (8 mg/kg in cycle 1, then 6 mg/kg). HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life (QLQ-C30) assessment tool and the Quality-of-Life Questionnaire for Breast Cancer (QLQ-BR23) at baseline and cycles 2, 4, and 6. Results for clinically meaningful changes were based on previously published minimum important differences., Results: Of the 108 patients (56 in Study 206 and 52 in Study 208) treated, 57 and 87%, respectively, completed 6 cycles. Completion rates for both questionnaires were 94 and 98%, respectively, at cycle 6. Most patients had stable/improved HRQoL scores with some exceptions; for example, more patients experienced a worsening in cognitive functioning and systemic therapy side effects than experienced improvement. Mean QLQ-C30 symptom scores correlated with corresponding adverse event rates for nausea/vomiting, dyspnea, appetite loss, constipation, and diarrhea in Study 206 and for fatigue, nausea/vomiting, pain, dyspnea, insomnia, constipation, and diarrhea in Study 208., Conclusions: First-line eribulin ± trastuzumab therapy did not lead to deterioration of overall HRQoL in most patients, with more than 60% of patients having stable/improved global health status/quality-of-life scores. Eribulin has been demonstrated to be comparable with other chemotherapy agents with an acceptable safety profile. Therefore, further evaluation is warranted to determine whether eribulin ± trastuzumab therapy may be a potential option for first-line treatment in some patients with metastatic breast cancer who were recently treated in the neoadjuvant setting., Trial Registration: NCT01268150 (December 29, 2010), NCT01269346 (January 4, 2011).

We report on the use of the faecal egg count reduction test to evaluate the performance of ivermectin in treating gastrointestinal nematode infections in first grazing season (FGS) calves on four dairy farms in Co. Kilkenny, Ireland. On each farm, FGS calves were injected subcutaneously with ivermectin in accordance with their live weight (day 0). Calves were individually faecal sampled on both day 0 and day 14. Faecal egg counts were determined using the Mini-FLOTAC technique. Composite faecal cultures for each farm were performed on each sampling occasion. The faecal egg count reductions (mode) ranged from 17.3-80.2% with the lower 95% confidence limit ranging from 3.1-72.3% on the four farms, respectively. Ivermectin-resistant nematodes were detected on all farms, with evidence of Ostertagia resistance on one farm. This study highlights the urgent need for Irish producers to reappraise their parasite control practices., Competing Interests: This study was outside the scope of the scientific animal protection legislation and therefore a HPRA project authorisation under scientific animal protection legislation was not required in order to conduct this study.The authors provide consent for publication of this material.The authors declare they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Lapatinib has clinical efficacy in the treatment of trastuzumab-refractory HER2-positive breast cancer. However, a significant proportion of patients develop progressive disease due to acquired resistance to the drug. Induction of apoptotic cell death is a key mechanism of action of lapatinib in HER2-positive breast cancer cells., Methods: We examined alterations in regulation of the intrinsic and extrinsic apoptosis pathways in cell line models of acquired lapatinib resistance both in vitro and in patient samples from the NCT01485926 clinical trial, and investigated potential strategies to exploit alterations in apoptosis signalling to overcome lapatinib resistance in HER2-positive breast cancer., Results: In this study, we examined two cell lines models of acquired lapatinib resistance (SKBR3-L and HCC1954-L) and showed that lapatinib does not induce apoptosis in these cells. We identified alterations in members of the BCL-2 family of proteins, in particular MCL-1 and BAX, which may play a role in resistance to lapatinib. We tested the therapeutic inhibitor obatoclax, which targets MCL-1. Both SKBR3-L and HCC1954-L cells showed greater sensitivity to obatoclax-induced apoptosis than parental cells. Interestingly, we also found that the development of acquired resistance to lapatinib resulted in acquired sensitivity to TRAIL in SKBR3-L cells. Sensitivity to TRAIL in the SKBR3-L cells was associated with reduced phosphorylation of AKT, increased expression of FOXO3a and decreased expression of c-FLIP. In SKBR3-L cells, TRAIL treatment caused activation of caspase 8, caspase 9 and caspase 3/7. In a second resistant model, HCC1954-L cells, p-AKT levels were not decreased and these cells did not show enhanced sensitivity to TRAIL. Furthermore, combining obatoclax with TRAIL improved response in SKBR3-L cells but not in HCC1954-L cells., Conclusions: Our findings highlight the possibility of targeting altered apoptotic signalling to overcome acquired lapatinib resistance, and identify potential novel treatment strategies, with potential biomarkers, for HER2-positive breast cancer that is resistant to HER2 targeted therapies.

Background: Triple-negative breast cancer is an aggressive disease with unmet clinical needs. In a phase III study of patients with metastatic triple-negative breast cancer, first-line gemcitabine/carboplatin resulted in a median progression-free survival of 4.6 months. nab-paclitaxel-based regimens (with gemcitabine or carboplatin±bevacizumab) also demonstrated efficacy and safety in first-line phase II trials of human epidermal growth factor receptor 2-negative metastatic breast cancer., Trial Design: In this international, multicenter, open-label, randomized phase II/III trial, the efficacy and safety of first-line nab-paclitaxel with gemcitabine or with carboplatin will be compared with gemcitabine/carboplatin (control arm) for metastatic triple-negative breast cancer., Methods: In the phase II portion, 240 patients with measurable metastatic triple-negative breast cancer and treatment-naive for metastatic disease will be randomized 1:1:1 (stratified by disease-free interval: ≤1 versus>1 year) to nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg×min/mL, all given on days 1 and 8 of a 21-day cycle. Investigator-assessed progression-free survival (primary endpoint), overall response rate, overall survival, and safety will be assessed. A ranking algorithm of five efficacy and safety parameters will be used to pick the "winner" of the nab-paclitaxel regimens. In the phase III portion, 550 patients will be randomized 1:1 (stratified by disease-free interval: ≤1 versus >1 year, and prior adjuvant/neoadjuvant taxane use) to the nab-paclitaxel combination arm selected from the phase II portion or to the control arm. Patients in phase II will not be part of the phase III population. The phase III primary endpoint is blinded, independently-assessed progression-free survival; secondary endpoints include blinded, independently-assessed overall response rate, overall survival, disease control rate, duration of response, and safety. Biomarker and circulating tumor-cell exploratory analyses and quality-of-life assessments will also be performed. A list of approving ethical bodies was provided in Additional file 1., Discussion: The tnAcity trial aims to identify a new standard cytotoxic chemotherapy regimen for first-line treatment of metastatic triple-negative breast cancer., Trial Registration: ClinicalTrials.gov: NCT01881230 . Date of registration: 17 June 2013.

Background: Degenerative lumbar spinal stenosis is a prevalent condition in adults over the age of 65 and often leads to deconditioning. Although the benefits of surgery outweigh those of conservative approaches, physical rehabilitation may be used to improve function and to minimize the risk of persistent dysfunction. This study protocol was designed to establish the feasibility of a full-scale randomized controlled trial and to assess the efficacy of an active preoperative intervention program on the improvement of clinical parameters and functional physical capacity in patients undergoing surgery for lumbar spinal stenosis., Methods/design: Forty patients will be recruited and randomly allocated to one of the 2 treatment arms: 6 weeks supervised preoperative rehabilitation program (experimental group) or hospital standard preoperative management (control group). The intervention group will be trained three times per week, with each session aiming to improve strength, muscular endurance, spinal stabilization and cardiovascular fitness. Intensity and complexity of exercises will be gradually increased throughout the sessions, depending on each participant's individual progress. Primary outcomes are level of low back disability and level of pain. Secondary outcomes include the use of pain medication, quality of life, patient's global impression of change, lumbar extensor muscles endurance, maximum voluntary contraction of lumbar flexor and extensor muscles, maximum voluntary contraction of knee extensors, active lumbar ranges of motion, walking abilities, and cardiovascular capacity. Both the primary and secondary outcomes will be measured at baseline, at the end of the training program (6 weeks after baseline evaluation for control participants), and at 6 weeks, 3 and 6 months postoperatively., Discussion: This study will inform the design of a future large-scale trial. Improvements of physical performances before undergoing lumbar surgery may limit functional limitations occurring after a surgical intervention. Results of this study will provide opportunity to efficiently improve spinal care and advance our knowledge of favorable preoperative strategies to optimize postoperative recovery., Trial Registration: US National Institutes of Health Clinical Trials registry NCT02258672 , 10 February 2014.

Background: With concerns over the development of anthelmintic resistance in cattle nematode populations, we must re-examine our approach to nematode control in cattle. Targeted selective treatments (TST), whereby individual animals are treated instead of entire groups, are being investigated as an alternative. The study objective was to determine if anthelmintic usage could be reduced using a TST-based approach to nematode control in spring-born suckler beef cattle over their first and second grazing seasons (SGS) without affecting performance. In the first grazing season (FGS), 99 calves with an initial mean (s.d.) calf age and live weight on day 0 (June 28(th) 2012) of 107 (23.1) days and 160 (32.5) kg, respectively, were used. The study commenced on day 0 when calves were randomised and allocated to one of two treatments; 1), standard treatment (control) and 2), TST. Control calves were treated subcutaneously with ivermectin on days 0, 41 and 82 in the FGS. All calves were treated with ivermectin on day 124 and housed on day 133. In the SGS, only heifer calves from the FGS were used and control heifers were treated with ivermectin on day 393. Animals were weighed, blood and faecal sampled every three weeks. The TST animals were treated with ivermectin if thresholds based on a combination of plasma pepsinogen concentrations, faecal egg count and/or the presence of Dictyocaulus viviparus larvae in faeces (FGS only) were reached., Results: No TST calves reached the treatment threshold criteria in the FGS. The FGS average daily live weight gain (ADG ± s.e.m.) for control and TST group calves was 0.89 ± 0.02 kg and 0.94 ± 0.02 kg day(-1), respectively (P = 0.17). In the SGS, all heifers were treated with ivermectin on day 431 due to clinical signs of respiratory disease. The ADG for control and TST heifers from turnout on day 321 to day 431 was 0.90 ± 0.04 and 0.80 ± 0.04 kg day(-1), respectively (P = 0.03)., Conclusions: Spring-born FGS suckler beef calves require minimal anthelmintic treatment to maintain performance. In contrast, clinical parasitic disease may develop in the SGS unless appropriate anthelmintic treatment is provided.

Background: Calf output is a key element in determining the profitability of a suckler beef enterprise. Infectious agents such as Bovine Virus Diarrhoea (BVD) virus, colostrum management and parasitic challenge can all affect calf output. Prior to the national BVD eradication programme, there was little published information on either the prevalence or effect of BVD in Irish beef herds. There is little published information on colostrum management practices in Irish commercial beef herds and there have also been few studies published on the prevalence of liver fluke or rumen fluke infection in Irish beef herds. Sixteen farms participating in the Teagasc/Farmers Journal BETTER farm beef programme were used in this study. Fourteen herds were screened for the presence of BVD virus in 2010 using RT-PCR. In 13 herds, blood samples were collected from calves (2-14 days of age) in November 2011 - April 2012 to determine their passive immune status using the zinc sulphate turbidity (ZST) test, while in 12 herds, blood and faecal samples were taken in order to determine the level of exposure to gastrointestinal and hepatic helminths., Results: The overall prevalence of BVD virus-positive cattle was 0.98% (range 0 - 3% per herd, range 0.6 - 3.0% per positive herd). Eighteen of the 82 calves (22%) sampled had ZST values less than 20 units (herd mean range 17.0 - 38.5 units) indicating a failure of passive transfer. The overall animal-level (herd-level) prevalence of liver fluke and rumen fluke infection in these herds was 40.5% (100%) and 20.8% (75%), respectively., Conclusions: The potential costs associated with the presence of animals persistently infected with BVD virus through the increased use of antibiotics; the rate of failure of passive transfer of colostral immunoglobulins and the high prevalence of liver fluke infection in these herds highlight that some Irish suckler beef farms may not be realizing their economic potential due to a range of herd health issues. The use of farm-specific herd health plans should be further encouraged on Irish suckler beef farms.

Background: Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in approximately 20% of invasive breast cancer cases and is associated with a more aggressive disease course than HER2-negative breast cancer. HER2-targeted therapies have altered the natural history of HER2-positive breast cancer, a trend that will likely further improve with the recent approval of new agents. A prospective, observational cohort study was designed and initiated to provide real-world insights into current treatment patterns, long-term survival, and patients' experiences with initial and subsequent treatments for HER2-positive metastatic breast cancer (MBC)., Methods/design: The Systematic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs) is a US-based prospective observational cohort study enrolling patients ≥18 years of age with recently diagnosed HER2-positive MBC not previously treated with systemic therapy in the metastatic setting. The primary objective of the study is to identify treatment patterns and clinical outcomes in recently diagnosed patients in a variety of practice settings. Secondary objectives include comparative efficacy, safety, and patient-reported outcomes (PROs). Healthcare resource utilization is an exploratory end point. Tumor tissue and blood sample collection is optional.The SystHERs registry will enroll approximately 1000 patients over a 3-year period, after which the study will continue for ≥5 years, allowing for a maximum follow-up of 8 years. The treating physician will determine all care and the frequency of visits. PRO measures will be completed at study enrollment and every 90 days. Clinical data will be abstracted quarterly from patient records. The first patient was enrolled in June 2012, and preliminary descriptive data based on 25% to 30% of the final study population are expected at the end of 2013, and as of April 25, 2014, 386 patients are enrolled., Discussion: SystHERs is expected to provide in-depth data on demographic, clinicopathological, and treatment patterns and their associations with clinical outcomes, PROs, and healthcare resource utilization. Tumor tissue and DNA repositories will also be established for use in future translational research., Trial Registration Number: NCT01615068 (ClinicalTrials.gov identifier).

Background: There have been few studies published internationally which document herd health management practices in suckler beef herds and no published Irish studies. The study objective was to document herd health status and management practices on sixteen Irish suckler beef herds over a two year period (2009-2010). The farms used in the study were part of the Teagasc BETTER farm beef programme. The mean (s.d.) herd size, stocking rate and farm size was 68 cows (27.6), 2.0 LU/ha (0.3) and 64.3 (21.6) adjusted hectares, respectively. Two questionnaires were designed; 1) a farmer questionnaire to collect information on farm background and current herd health control practices and 2) a veterinary questionnaire to collect information on the extent of animal health advice given by veterinarians to their clients and identification of any on-farm herd health issues., Results: Dystocia, calf pneumonia, and calf diarrhoea, in that order, were identified as the primary herd health issues in these Irish suckler beef herds. In addition, substantial deficiencies in biosecurity practices were also identified on these farms., Conclusions: The findings of this study may serve as the focus for future research in animal health management practices in Irish suckler beef herds.

Background: A single group prospective study. Disc prostheses are believed to contribute to the restoration of the segmental movement and the preservation of the adjacent segments. The study's main objective was to determine if changes in neuromuscular patterns assessed using the flexion-relaxation phenomenon (FRP) can be observed following disc replacement surgery., Methods: Fifteen subjects participated in this study; they were evaluated before and after lumbar disc replacement surgery. Both assessments included ten repetitions of a trunk flexion and extension movement (with and without a load), where the surface electromyography (EMG) and kinematic data were recorded., Results: Following the disc replacement procedure (17.3 weeks ± 8.4), participants reported a significant reduction in their ODI and FABQ - physical activity scores. Increases in pelvic flexion as well as in erector spinae (ES) muscle activity at L5 in the flexion phase were observed. Following the disc replacement surgery, ES activity at L2 decreased during the quiet standing position., Conclusion: The results of this study suggest that although improvements in disability scores and fear-avoidance related to physical activities scores were noted after a disc replacement surgery, the lumbar ROM was not modified. Nevertheless, a significant increase in the hip ROM during the flexion-extension task as well as an increase in ES muscle activity in flexion was observed following surgery. The VAS, FABQ I and ODQ scores were positively correlated with change in the muscular activities during the FRP.

Background: When conservative therapies for low back pain (LBP) are not effective, elective surgery may be proposed to these patients. Over the last 20 years, a new technology, disc replacement, has become increasingly popular because it is believed to maintain or restore the integrity of spinal movement and minimize the side-effects compared to fusion. Although disc replacement may relieve a patient from pain and related disability, soreness and stiffness of the lumbopelvic region seem to be common aftermaths of the surgery. This prospective case series was undertaken to identify and describe potential adverse events of lumbar spinal manipulation, a common therapy for low back pain, in a group of patients with symptoms after disc prostheses., Cases Presentation: Eight patients who underwent lumbar spine total disc replacement were referred by an orthopaedic surgeon for chiropractic treatments. These patients had 1 or 2 total lumbar disc replacements and were considered stable according to the surgical protocol but presented persistent, post-surgical, non-specific LBP or pelvic pain. They were treated with lumbar spine side posture manipulations only and received 8 to 10 chiropractic treatments based on the clinical evolution and the chiropractor's judgment. Outcome measures included benign, self-limiting, and serious adverse events after low back spinal manipulative therapy. The Oswestry Disability Index, a pain scale and the fear avoidance belief questionnaire were administered to respectively assess disability, pain and fear avoidance belief about work and physical activity. This prospective case series comprised 8 patients who all had at least 1 total disc replacement at the L4/L5 or L5/S1 level and described persistent post-surgical LBP interfering with their daily activities. Commonly-reported side-effects of a benign nature included increased pain and/or stiffness of short duration in nearly half of the chiropractic treatment period. No major or irreversible complication was noted., Conclusions: During the short treatment period, no major complication was encountered by the patients. Moreover, the benign side-effects reported after lumbar spine manipulation were similar in nature and duration to those frequently experienced by the general population.