Characteristics of Early Interventions for Pain and Function Following Lower Extremity Joint Replacement: Systematic Review.

Occupational therapy is beneficial among adults with chronic pain; however, occupational therapy interventions addressing earlier phases of pain have not been clearly explicated. This systematic review characterized acute and subacute interventions billable by occupational therapy after hip or knee replacement to improve pain and function. Seven articles met inclusion criteria. Six articles had a low risk of bias. Three intervention types were found: task-oriented exercise, water-based, and modalities. Only task-oriented interventions improved both pain and function one-year after surgery. There are long-term benefits to early task-oriented exercise. Further research is needed to contextualize occupational therapy's role in early pain interventions.

Evaluation of Horn Bud Wound Healing Following Cautery Disbudding of Dairy Calves With and Without the Use of Oxytetracycline Aerosol Spray.

Oxytetracycline is commonly applied as a topical agent to burn lesions post cautery disbudding of calves. Judicial use of antibiotics dictates that they should only be used where necessary to reduce the development of resistance in target bacteria. The objective of this study, therefore, was to evaluate the efficacy of topical oxytetracycline spray on wound healing post cautery disbudding of dairy calves over a 6-week period. Dairy calves were disbudded by veterinarians, technicians, or veterinary surgeons, using a standard cautery disbudding protocol. Oxytetracycline spray was randomly applied to the right or left horn bud of each animal (OXY), while the other horn bud received no antibiotic spray (NA). The outcomes measured were wound diameter (WD) and lesion score (LS), either normal healing (NH) or abnormal healing (AH). These assessments were conducted every 14 days following disbudding, until 42 days. A total of 360 animals completed the study. There was a difference in wound diameter and lesion score on day 14 post disbudding between the two groups. Cautery lesions sprayed with oxytetracycline (OXY) were 0.5 ± 0.15 mm smaller than NA lesions (P = 0.001), and there were fewer abnormal healing lesions for OXY compared to the NA (2.5 vs. 11%, respectively; P ≤ 0.001). There were no differences at day 28 and day 42 post disbudding, and on day 42, 34% of wounds had healed in both groups. In summary, the authors were unable to demonstrate a difference in healing between the groups using the described methods.

Factors influencing the detection of antibacterial-resistant Escherichia coli in faecal samples from individual cattle.

AIMS: To investigate whether on-farm antibacterial usage (ABU), environmental antibacterial-resistant (ABR) Escherichia coli prevalence, sampling and sample handling methodologies are associated with ABR E. coli positivity in individual faecal samples from dairy heifers. METHODS AND RESULTS: Three hundred and sixty-four heifers from 37 farms were sampled via rectal or faecal pat sampling. Samples were stored at -80°C for variable periods before microbiological analysis. Data analysis was done through a multilevel, multivariable logistic regression approach. Individual rectal samples had increased odds of positivity for amoxicillin-, cefalexin- and tetracycline-resistant E. coli. Sample storage for 6-12 months was associated with decreased odds of finding amoxicillin- and tetracycline-resistant E. coli. On-farm ABU had little influence, and environmental ABR E. coli prevalence had no significant influence on the odds of sample-level positivity for ABR E. coli. CONCLUSIONS: Sampling methodology and sample handling have a greater association than on-farm factors with the detection of ABR E. coli in individual faecal samples from dairy heifers. SIGNIFICANCE AND IMPACT OF THE STUDY: Sampling and storage methodologies should be considered carefully at the point of designing ABR surveillance studies in livestock and their environments and, where possible, these methodologies should be standardized between and within future studies.

Ceasing the use of the highest priority critically important antimicrobials does not adversely affect production, health or welfare parameters in dairy cows.

Due to scientific, public and political concern regarding antimicrobial resistance (AMR), several EU countries have already taken steps to reduce antimicrobial (AM) usage in production animal medicine, particularly that of the highest priority critically important AMs (HP-CIAs). While veterinarians are aware of issues surrounding AMR, potential barriers to change such as concerns of reduced animal health, welfare or production may inhibit progress towards more responsible AM prescribing. Farmers from seven dairy farms in South West England engaged in changing AM use through an active process of education and herd health planning meetings. Prescribing data were collected from veterinary sales records; production and health data were accessed via milk recording and farm-recorded data. This study demonstrates that cattle health and welfare-as measured by production parameters, fertility, udder health and mobility data and culling rates-can be maintained and even improved alongside a complete cessation in the use of HP-CIAs as well as an overall reduction of AM use on dairy farms. This study also identified a need to consider different metrics when analysing AM use data, including dose-based metrics as well as those of total quantities to allow better representation of the direction and magnitude of changes in AM use.

Evaluation of metrics for benchmarking antimicrobial use in the UK dairy industry.

The issue of antimicrobial resistance is of global concern across human and animal health. In 2016, the UK government committed to new targets for reducing antimicrobial use (AMU) in livestock. Although a number of metrics for quantifying AMU are defined in the literature, all give slightly different interpretations. This paper evaluates a selection of metrics for AMU in the dairy industry: total mg, total mg/kg, daily dose and daily course metrics. Although the focus is on their application to the dairy industry, the metrics and issues discussed are relevant across livestock sectors. In order to be used widely, a metric should be understandable and relevant to the veterinarians and farmers who are prescribing and using antimicrobials. This means that clear methods, assumptions (and possible biases), standardised values and exceptions should be published for all metrics. Particularly relevant are assumptions around the number and weight of cattle at risk of treatment and definitions of dose rates and course lengths; incorrect assumptions can mean metrics over-represent or under-represent AMU. The authors recommend that the UK dairy industry work towards the UK-specific metrics using the UK-specific medicine dose and course regimens as well as cattle weights in order to monitor trends nationally.

Antimicrobial use in food-producing animals: a rapid evidence assessment of stakeholder practices and beliefs.

Food-producing animals throughout the world are likely to be exposed to antimicrobial (AM) treatment. The crossover in AM use between human and veterinary medicine raises concerns that antimicrobial resistance (AMR) may spread from food-producing animals to humans, driving the need for further understanding of how AMs are used in livestock practice as well as stakeholder beliefs relating to their use. A rapid evidence assessment (REA) was used to collate research on AM use published in peer-reviewed journals between 2000 and 2016. Forty-eight papers were identified and reviewed. The summary of findings highlights a number of issues regarding current knowledge of the use of AMs in food-producing animals and explores the attitudes of interested parties regarding the reduction of AM use in livestock. Variation between and within countries, production types and individual farms demonstrates the complexity of the challenge involved in monitoring and regulating AM use in animal agriculture. Many factors that could influence the prevalence of AMR in livestock are of concern across all sections of the livestock industry. This REA highlights the potential role of farmers and veterinarians and of other advisors, public pressure and legislation to influence change in the use of AMs in livestock.

Does inclusion of glutamine in oral rehydration solutions improve recovery from mild to moderate diarrhoea in preweaned calves?

Critically Appraised Topics (CATs) are a standardised, succinct summary of research evidence organised around a clinical question, and a form of evidence synthesis used in the practice of evidence-based medicine (EBM) and evidence-based veterinary medicine (EBVM). Access to CATs enables clinicians to incorporate evidence from the scientific literature into clinical practice and they have been used to teach EBVM at the University of Bristol's School of Veterinary Sciences since 2011. Veterinary Record is including CATs from Bristol university in its Clinical Decision Making section. The first of these, along with an explanation of how they can be used, was published in VR, January 30, 2016, vol 178, pp 118-119.

The Wound Trend Scale: A Retrospective Review of Utility and Predictive Value in the Assessment and Documentation of Lower Leg Ulcers.

Wound assessment is essential to manage wound care. The Wound Trend Scale (WTS) is a paper-and-pen instrument comprised of 14 parameters designed to guide assessment of findings relevant to lower leg ulcer management and includes an infection screen and cues for physician consultation. To determine its clinical utility, predictive value, and reliability, data were retrospectively analyzed from a random sampling of medical records of patients seen at a Foot and Leg Clinic between January 1, 2007 and December 31, 2008. Patients had 1 leg or foot ulcer, 3 consecutive assessments scheduled according to wound status (twice weekly if at high risk for nonhealing or amputation, weekly for moderate risk, or 1 to 2 months if stable), known outcomes, and a maximum treatment period of 3 months. Patient demographics included ulcer etiology, comorbid conditions (diabetes, neuropathy, peripheral arterial disease), and wound outcomes (closed, infection, amputation and surgery). Predictive values, inter- and intrarater reliability (assessed among the authors and 5 additional nurses with expertise using the study instrument), and the impact of WTS education on the wound assessment process were determined using 5 representative cases. Parameters were compared using the t-test. Seventy (70) patient records were examined and subdivided by ulcer site: foot (below ankle, 37) and leg (ankle and above, 33). Of the 13 etiologies, the foot group had 4 and the leg group 10; the foot group had more diabetes (92%), neuropathy (76%), and peripheral arterial disease (95%) than the leg group (52%, 5%, and 70%, respectively). Ulcer duration before referral averaged 16.42 (range 4-144) months. Wound outcomes included closed (57), infection (21), amputation (13), and surgery (3). Healing predictive values were sensitivity (99%), specificity (87%), and positive and negative predictive values and test efficiency (all 96%). Inter- and intrarater reliability were .85 (range .16-.96) and .86 (range .50-1.00), respectively. On admission, leg ulcers had larger surface area (P <0.05), more edema (P <0.01), more granulation (P <0.05), and higher total WTS scores (P <0.05) than foot ulcers, which had more infections (P <0.05). Foot ulcers at the third assessment had decreased tissue depth (P <0.05), increased epithelial tissue (P <0.01), and lower total WTS score (P <0.05). Significant third assessment parameters for leg ulcers were reduced depth (P <0.001), less necrotic tissue (P <0.001), less exudate (P <0.01), improved periwound condition (P <0.05), reduced edema (P <0.001), and increased epithelialization (P <0.01). After exposure to the WTS experience, the number of parameters assessed increased from 2.6 (registered nurses) and 1.5 (student nurses) to both using 15 (P <0.001). Nurses complied 100% with physician consultation for cued risks. Patient outcomes were 81% closure, and 70% had physician consultation for the risks identified. WTS predictive performance was excellent and improved nursing assessment practices. Future research to identify parameter criteria validity is warranted.

A Retrospective Quality Improvement Study Comparing Use Versus Nonuse of a Padded Heel Dressing to Offload Heel Ulcers of Different Etiologies.

Offloading heel ulcers is a challenging task because strategies deemed to be most optimal from a medical perspective may be unacceptable to patients. Observed adverse dressing events and problems with offloading devices led to a pilot study and subsequent change in practice at the authors' Foot and Leg Ulcer Clinic. Starting in 2004, patients requiring offloading received a nonremovable padded heel dressing (PHD) that was changed twice a week by the visiting nurse. A retrospective quality improvement review was conducted to compare outcomes, nursing visits, and nursing visit costs for 40 consecutive patients with heel ulcers treated at this clinic with a nonremovable PHD (n = 20) or without a PHD (n = 20) between January 20, 2001 and December 31, 2006. Patient demographic data, relevant comorbidities, wound depth, weeks of care, adverse events, and treatment-related narrative comments were abstracted from patient records. Relevant comorbidities were similar in both groups. The PHD group was younger (average age of 74.6 [range 35-91] years) compared to PHD nonuse group (average age 79.5 [range 25-95] years; P less than 0.04). The PHD group required fewer total weeks of care compared to the nonuse group (368 versus 527 weeks, respectively; P less than 0.001), and average duration of clinic treatment in the PHD group was 18.40 (range 5-51) weeks versus 40.54 (range 6-88) weeks in the nonuse group. The PHD group had fewer total nursing visits (736 versus 1,581, P less than 0.001); the average number of nursing visits for the PHD was 36.80 (range 10-102) compared to 121.61 (range 18-264) for the nonuse group. Nursing visit costs were lower for PHD users ($114,080 versus $245,055, P less than 0.001), and the cost-efficiency ratio was less than one third (1:3.3) of PHD nonuse for the average heel ulcer. All 20 patients in the PHD use group had wound closure compared with the PHD nonuse group, in which 13 out of 20 wounds closed, 3 amputations were performed, and 4 patients were lost to review (P less than 0.000). No adverse events were reported in the records of the PHD use group; the PHD nonuse group reported periwound maceration, skin stripping, pressure injury, and sensitivity. Patient and nurse feedback identified pain relief, improved mobility, easy technique, low cost, and reduced workload as benefits of PHD. The results of this quality improvement review warrant a prospective clinical study to examine the efficacy, effectiveness, and cost-effectiveness of PHD for the care of patients with heel ulcers.

Immunological visibility: posttranscriptional regulation of human NKG2D ligands by the EGF receptor pathway.

Human cytolytic T lymphocytes and natural killer cells can limit tumor growth and are being increasingly harnessed for tumor immunotherapy. One way cytolytic lymphocytes recognize tumor cells is by engagement of their activating receptor, NKG2D, by stress antigens of the MICA/B and ULBP families. This study shows that surface up-regulation of NKG2D ligands by human epithelial cells in response to ultraviolet irradiation, osmotic shock, oxidative stress, and growth factor provision is attributable to activation of the epidermal growth factor receptor (EGFR). EGFR activation causes intracellular relocalization of AUF1 proteins that ordinarily destabilize NKG2D ligand mRNAs by targeting an AU-rich element conserved within the 3' ends of most human, but not murine, NKG2D ligand genes. Consistent with these findings, NKG2D ligand expression by primary human carcinomas positively correlated with EGFR expression, which is commonly hyperactivated in such tumors, and was reduced by clinical EGFR inhibitors. Therefore, stress-induced activation of EGFR not only regulates cell growth but also concomitantly regulates the cells' immunological visibility. Thus, therapeutics designed to limit cancer cell growth should also be considered in terms of their impact on immunosurveillance.

A pilot study assessing the incidence and clinical significance of circulating tumor cells in esophagogastric cancers.

BACKGROUND: Circulating tumor cells (CTCs) have been found to be of clinical utility in predicting response to treatment and prognosis in several malignancies. Less is known of the prevalence and clinical relevance of CTCs in esophagogastric adenocarcinoma, with the available data arising from heterogeneous patient populations using varied detection methods. PATIENTS AND METHODS: A pilot study was undertaken to assess the prevalence of CTCs in patients with advanced esophageal or gastric adenocarcinoma. Patients were eligible if they had advanced disease and either had received no prior therapy or had progressed after prior chemotherapy. Blood samples for CTC analysis were obtained at baseline and during the course of treatment. The CellSearch immunomagnetic CTC detection platform was used. RESULTS: Twenty-two patients with metastatic esophageal or gastric adenocarcinoma were enrolled. Eighteen received first-line EOX (epirubicin/oxaliplatin/capecitabine) chemotherapy (± panitumumab) and had baseline samples suitable for CTC analysis. At baseline, ≥ 2 CTCs were detected in 8 patients (44%). Overall tumor response rate was 60% in patients with < 2 CTCs and 37.5% in patients with ≥ 2 CTCs. Median progression-free and overall survival were 6.1 and 10.5 months and 5.2 and 6.1 months in the groups of patients with < 2 CTCs and ≥ 2 CTCs, respectively. The study was prematurely discontinued, owing to the withdrawal of commercial support. CONCLUSION: The incidence of CTCs in locally advanced or metastatic esophagogastric cancer may be clinically relevant. Investigation of the potential clinical utility of CTCs is warranted in a larger cohort of patients with esophagogastric cancer.

MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.

Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial.

PURPOSE: Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment in advanced esophagogastric cancer. Panitumumab (P) is a fully human, immunoglobulin G2 monoclonal antibody targeting epidermal growth factor receptor. Randomized Trial of EOC +/- Panitumumab for Advanced and Locally Advanced Esophagogastric Cancer (REAL-3) will evaluate whether the addition of P to EOC improves survival in patients with advanced esophagogastric adenocarcinoma and undifferentiated carcinoma. PATIENTS AND METHODS: The original design of REAL-3 added P 9 mg/kg to the standard dose of EOC (dose level [DL] + 1). Due to toxicity, a dose de-escalation was made to EOC + P DL-1 (epirubicin 50 mg/m(2), oxaliplatin130 mg/m(2), capecitabine 1,000 mg/m(2)/d + P 9 mg/kg every 3 weeks). After additional toxicity was observed, the study was amended to include two additional EOC + P dose levels. Using a 3 + 3 design, dose-limiting toxicities (DLTs) were assessed weekly during cycle 1. Patients were randomly assigned 1:1 to EOC +/- P. RESULTS: Between July 2008 and October 2009, 29 patients were randomly selected for standard-dose EOC (n = 13) or EOC + P (n = 16). Five patients were treated at DL + 1, with grade 3 diarrhea in four of five patients by cycle 4. At DL-1, one patient had grade 3 diarrhea and grade 5 infection. Three patients were treated at DL-3, and then six were treated at DL-2, without DLTs. CONCLUSION: The recommended dose for EOC + P is epirubicin 50 mg/m(2), oxaliplatin 100 mg/m(2), capecitabine 1,000 mg/m(2)/d, and P 9 mg/kg every 3 weeks. This dose has been selected for the ongoing phase II/III REAL-3 study.