An Individualized Low-Intensity Walking Clinic Leads to Improvement in Frailty Characteristics in Older Veterans.

BACKGROUND: Sedentary lifestyle leads to worse health outcomes with aging, including frailty. Older adults can benefit from regular physical activity, but exercise promotion in the clinical setting is challenging. OBJECTIVES: The objective of this clinical demonstration project was to implement a Geriatric Walking Clinic for older adults and determine whether this clinical program can lead to improvements in characteristics of frailty. DESIGN: This was a clinical demonstration project/quality improvement project. SETTING: Outpatient geriatrics clinic at the South Texas Veterans Health Care System (STVHCS). PARTICIPANTS: Older Veterans, aged ≥60 years. INTERVENTION: A 6-week structured walking program, delivered by a registered nurse and geriatrician. Patients received a pedometer and a comprehensive safety evaluation at an initial face-to-face visit. They were subsequently followed with weekly phone calls and participated in a final face-to-face follow-up visit at 6 weeks. MEASUREMENTS: Grip strength (handheld dynamometer), gait speed (10-ft walk), Timed Up and Go (TUG), and body mass index (BMI) were assessed at baseline and follow-up. Frailty status for gait speed was assessed using Fried criteria. RESULTS: One hundred eighty five patients completed the program (mean age: 68.4 ±7 years, 88% male). Improvements from baseline to follow-up were observed in average steps/day, gait speed, TUG, and BMI. Improvement in gait speed (1.13 ±0.20 vs. 1.24 ± 0.23 meter/second, p<0.0001) resulted in reduced odds of meeting frailty criteria for slow gait at follow-up compared to the baseline examination (odds ratio = 0.31, 95% confidence interval: 0.13-0.72, p = 0.01). CONCLUSIONS: Our findings demonstrate that a short duration, low-intensity walking intervention improves gait speed and TUG. This new clinical model may be useful for the promotion of physical activity, and for the prevention or amelioration of frailty characteristics in older adults.

Diabetes mellitus: an independent predictor of duration of prostaglandin labor induction.

OBJECTIVE: The objective of this study is to analyze the association of diabetes mellitus with progress and outcomes of prostaglandin (PG) labor induction using a retrievable vaginal insert. STUDY DESIGN: This is a secondary analysis of data collected during the Misoprostol Vaginal Insert Trial (Miso-Obs-004), a multicenter, double-blind, randomized controlled trial of women undergoing induction of labor with PGs. The duration, characteristics and outcomes of labor were compared in women with and without diabetes. Multivariable regression analysis was performed on all outcomes of interest, adjusting for differences in baseline characteristics. RESULTS: There were 122 women with diabetes within the sample of 1275 women who delivered during their first admission. The time to reach active labor was significantly prolonged among women with diabetes compared with those without (22.0±13.0 vs 18.5±11.1, P=0.008) as was the time to delivery (30.2±15.0 vs 26.0±12.6, P=0.004). Fewer women with diabetes delivered within 36 h (adjusted odds ratio: 0.41, 95% confidence interval: 0.26 to 0.66, P=0.0003) and 48 h (adjusted odds ratio: 0.36, 95% confidence interval: 0.19 to 0.71, P=0.004). These relationships were significant after a multivariate regression analysis of baseline characteristics that adjusted for age, race, parity, body mass index, baseline modified Bishop Score, gestational age at induction and treatment group allocation. CONCLUSION: After PG labor induction, women with diabetes took longer to reach active labor and to deliver. We emphasize that this result comes from a secondary analysis and needs confirmation with additional studies.

Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008-2013.

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non-mammary and non-thyroidal soft tissue and visceral EOS in dogs. Thirty-three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0-458 days) versus median survival time of 13 days (range: 0-20 days)]. The use of surgery should be considered in the management of dogs with non-mammary and non-thyroidal soft tissue and visceral EOS.

Induction of labour with retrievable prostaglandin vaginal inserts: outcomes following retrieval due to an intrapartum adverse event.

OBJECTIVE: To assess adverse event (AE) resolution, delivery mode and neonatal outcomes after misoprostol or dinoprostone vaginal insert (MVI or DVI) retrieval due to AE during induction of labour (IOL). DESIGN: Randomised, double-blind trial, EXPEDITE. SETTING: Thirty five obstetric departments, USA. POPULATION: Consisted of 1358 pregnant women with modified Bishop score ≤4 eligible for pharmacological IOL. METHODS: Post hoc analysis. MAIN OUTCOME MEASURES: AEs prompting insert retrieval, times to AE resolution, delivery, delivery mode and neonatal intensive care unit (NICU) admissions. RESULTS: 77/678 (11.4%) and 27/680 (4.0%) women had MVI and DVI retrieved due to AE, respectively (P < 0.001). The most common AEs prompting retrieval were uterine tachysystole with fetal heart rate (FHR) involvement and category II/III FHR pattern. Time to AE resolution varied for both treatments depending on the type of AE. For uterine tachysystole with FHR involvement, median resolution times were 1 hour 34.5 minutes (n = 36) and 8.5 minutes (n = 8) for MVI and DVI, respectively. Caesarean delivery occurred in a high proportion of women with insert retrieved due to AE (MVI: 44/77 (57.1%); DVI: 19/27 (70.4%)); the majority of caesareans were performed at least several hours after insert retrieval. Median times from retrieval to any delivery were not increased for women with insert retrieved due to AE. NICU admissions were 8/77 (10.4%) and 1/27 (3.7%) for MVI and DVI, respectively (P = 0.440). CONCLUSIONS: AEs leading to insert retrieval were primarily uterine tachysystole with FHR involvement and category II/III FHR patterns. Insert retrieval due to an AE did not prolong time to delivery for either prostaglandin insert. TWEETABLE ABSTRACT: Induction with prostaglandin vaginal inserts: outcomes following retrieval due to intrapartum adverse event.

DOG1 is a sensitive and specific immunohistochemical marker for diagnosis of canine gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) and leiomyosarcomas are histologically similar primary neoplasms commonly occurring in the gastrointestinal tract of dogs and humans. Immunohistochemical staining (IHC) is needed to differentiate between these 2 entities and positive reactivity for KIT (cluster of differentiation [CD]117) is regarded as the gold standard for diagnosis of canine GIST. Studies estimate 5-10% of human GISTs stain negative or only weakly positive for KIT and have identified DOG1 (discovered on gastrointestinal stromal tumors protein 1) as a highly sensitive and specific marker for human GISTs. The purpose of this study was to evaluate immunoreactivity of a commercially available DOG1 antibody for use in diagnosis of canine GISTs. Fifty-five primary mesenchymal gastrointestinal tumors with histologic features consistent with GIST or leiomyosarcoma were evaluated via IHC for KIT, DOG1, and desmin. A subset of tumors was additionally evaluated for reactivity for smooth muscle actin (SMA). Thirty-three tumors (60%) were diagnosed as GIST based on positive immunoreactivity for KIT or DOG1 regardless of reactivity for desmin or SMA. Most GISTs (32/33, 97.0%) had similar staining for both KIT and DOG1. DOG1 expression was identified in 2 tumors (1 study tumor and 1 additional tumor) negative for KIT and desmin that had histologic features consistent with KIT-negative, platelet-derived growth factor receptor-alpha (PDGFRA)-mutant human GISTs. Our results suggest that DOG1 has improved specificity and sensitivity to that of KIT for differentiating between canine GISTs and leiomyosarcomas. Inclusion of both DOG1 and KIT IHC in diagnostic panels will improve the accuracy of canine GIST diagnosis.

Prognostic significance of histologic features in canine renal cell carcinomas: 70 nephrectomies.

The prognostic significance of histologic and clinical features was evaluated in a retrospective study of 70 dogs treated with nephrectomy for renal cell carcinoma. Dogs presenting with hematuria and cachexia had significantly decreased overall and tumor-specific survival. Mitotic index (MI), nuclear size, nuclear pleomorphism, tumor differentiation, invasiveness, Fuhrman nuclear grade, and clear cell morphology were significantly associated with survival times (overall and tumor specific) in univariate analyses. A multivariate Cox proportional hazards model was constructed using stepwise selection to evaluate potential histologic predictor variables. This multivariate analysis revealed MI, defined as the number of mitotic figures in ten 400× fields, as the sole independent prognostic variable. Median survival for dogs with an MI >30 was 187 days compared with 1184 days for dogs with an MI of <10. Dogs with an intermediate MI of 10 to 30 had a median survival of 452 days. Canine renal carcinomas were categorized into the following subtypes based on histologic features and histochemical and immunohistochemical staining: (1) clear cell, (2) chromophobe, (3) papillary, and (4) multilocular cystic renal cell carcinomas. Clear cell carcinoma was diagnosed in 6 of 70 (9%) canine tumors and was associated with a significantly decreased median survival time. Papillary carcinomas were identified in 15 of 70 tumors (21%), chromophobe in 6 of 70 (9%), and the multilocular cystic variant of canine renal cell carcinoma in 3 of 70 tumors (4%). These findings facilitate uniform categorization of canine renal cell carcinoma and provide veterinary pathologists with criteria to determine prognostic information.

Histologic characteristics and KIT staining patterns of equine cutaneous mast cell tumors.

Mast cell tumors are uncommon in horses and typically have a benign clinical course, but there are occasional reports of more aggressive behavior. The objective of this study was to review histologic features and KIT expression patterns of 72 previously diagnosed equine cutaneous mast cell tumors to determine if either is associated with clinical outcomes. Biopsy specimens were reviewed using histologic criteria derived from grading schemes, and KIT antibody expression patterns used in canine tumors and surveys were sent to referring veterinarians for follow-up clinical data. Arabians were overrepresented relative to the reference population. Most tumors were well differentiated with low mitotic rates (96%), and aberrant KIT staining patterns, as described in dogs, were uncommonly identified (12%). Associated clinical disease was uncommon and no tumors exhibited malignant behavior. Overall, KIT staining pattern and histologic features were not associated with poor clinical outcome or abnormal tumor behavior.

Clinical outcome in 20 cases of lingual hemangiosarcoma in dogs: 1996-2011.

With the exception of solar-induced dermal hemangiosarcoma (HSA), the biologic behaviour of canine HSA is characterised by rapid tumour growth, a high metastatic rate and short survival times. Outcome of dogs with HSA of the tongue has not been previously reported. The purpose of this study was to assess outcome and prognostic factors in dogs with lingual HSA. Clinical data was collected retrospectively and histopathology was reviewed for 20 dogs. Median progression free survival was 524 days and the median overall survival time was 553 days. All dogs had low or intermediate grade tumours; most tumours were small and located on the ventral surface of the tongue. Prognostic factors significantly associated with increased survival included small tumour size and absence of clinical signs of an oral mass at the time of diagnosis. Dogs with HSA confined to the tongue may have a better prognosis compared with HSA in other organs.

Roughness parameter selection for novel manufacturing processes.

This work proposes a method of roughness parameter (RP) selection for novel manufacturing processes or processes where little knowledge exists about which RPs are important. The method selects a single parameter to represent a group of highly correlated parameters. Single point incremental forming (SPIF) is used as the case study for the manufacturing process. This methodology was successful in reducing the number of RPs investigated from 18 to 8 in the case study.

Elution of antimicrobials from a cross-linked dextran gel: In vivo quantification.

REASONS FOR PERFORMING STUDY: Use of a novel, biodegradable, antimicrobial-impregnated gel provides an alternative method of local treatment of infections in horses. OBJECTIVES: To determine in vivo elution of antimicrobial medications from antimicrobial-impregnated cross-linked dextran gel and to evaluate the effect on wound healing when implanted subcutaneously in horses. METHODS: Amikacin-, vancomycin- or amikacin/clindamycin-impregnated gel was placed subcutaneously in 11 horses' necks, using 6 replicates with a 3 month washout between experiments. Capillary ultrafiltration probes for collection of interstitial fluid were placed 0 cm and 1.5 cm from the gel-filled incisions. Samples were collected at 0, 4, 8 and 12 h, and on Days 1-10. Blood was collected on Days 0, 1 and 7. Amikacin and vancomycin samples were analysed via fluorescence polarisation immunoassay, and clindamycin samples via high-performance liquid chromatography. Histology of biopsy samples was performed at the completion of the study. Differences in mean histomorphological scores between groups were assessed using Wilcoxon's signed ranks test. RESULTS: Maximum antimicrobial concentrations were detected at 4 h (amikacin), and 8 h (vancomycin, and amikacin and clindamycin from the combination gel). Mean ± s.d. peak concentrations for amikacin, vancomycin, amikacin (amikacin/clindamycin) and clindamycin were 6133 ± 1461, 7286 ± 2769, 3948 ± 317 and 985 ± 960, respectively. Median number of days for which antimicrobial concentration remained above minimum inhibitory concentration for target microorganisms at implantation was ≥10 days for vancomycin, 9 days (± 1) for amikacin and 8 days (± 1) for clindamycin. Mean plasma amikacin and vancomycin concentrations were lower than detectable limits; mean serum clindamycin concentrations were 0.52 µg/ml and 0.63 µg/ml at 24 h and 7 days, respectively. There were no significant differences in histomorphological scores between treatment and control incisions (P≥0.22). CONCLUSIONS AND POTENTIAL RELEVANCE: Cross-linked dextran gel is a safe, effective alternative local antimicrobial delivery method.

Foreign body reaction to a retained surgical sponge (gossypiboma) mimicking an implant associated sarcoma in a dog after a tibial plateau levelling osteotomy.

A dog was presented with the complaint of an acute onset left pelvic limb lameness three years after a right tibial plateau levelling osteotomy had been performed. Radiographs taken at the time of presentation showed signs that were consistent with a diagnosis of an implant associated sarcoma. At revision surgery, a retained surgical sponge was identified, leading to a diagnosis of a gossypiboma. This is the first reported case of a gossypiboma as a complication of a tibial plateau levelling osteotomy surgery.

Surface roughness enhances the osseointegration of titanium headposts in non-human primates.

It is well recognized that micrometer and nanometer sized surface features enhance the skeletal attachment of implants within bone. However, little is known regarding the integration of implants placed outside the bone but in contact with the surface. Loosening of chronic skull anchored headposts in non-human primate based experiments can be a factor. The purpose of this study was to evaluate the effect of a simple and easily applied surface texture on bone apposition to titanium implants fixed to the periosteal surface of the skull. Implants possessed either a polished surface or a textured surface created by grit-basting followed by acid etching. The percent of bone in contact with the implant surface (bone apposition) to three polished and three textured implants was evaluated in one adult female monkey after 14 weeks. Upon harvest, implants were processed for undecalcified histology and regions of bone apposition were quantified using backscatter electron microscopy and digital image analysis. The bone apposition to textured implants was 62±20% and to polished implants was 42±21%. The application of a peak-and-pit like texture to the surface of titanium implants significantly increased bone apposition to titanium implants placed on the periosteal surface of the skull. This study demonstrates that titanium headposts can easily be modified to improve osseointegration using equipment and supplies available to most neurophysiological laboratories. In addition, implant texturing may have utility in areas including skeletal trauma and reconstruction where devices are placed in contact with the bone surface.

Protection provided by a recombinant ALVAC(®)-WNV vaccine expressing the prM/E genes of a lineage 1 strain of WNV against a virulent challenge with a lineage 2 strain.

The emergence of lineage 2 strains of WNV in Europe as a cause of clinical disease and mortality in horses raised the question whether the existing WNV vaccines, all based on lineage 1 strains, protect against circulating lineage 2 strains of WNV. In the present paper we have determined the level of cross protection provided by the recombinant ALVAC(®)-WNV vaccine in a severe challenge model that produces clinical signs of WNV type 2 disease. Ten horses were vaccinated twice at 4 weeks interval with one dose of the ALVAC-WNV vaccine formulated at the minimum protective dose. A further 10 horses served as controls. Two weeks after the second vaccination, all horses were challenged intrathecally with a recent neurovirulent lineage 2 strain of WNV. The challenge produced viraemia in 10 out of 10 and encephalitis in 9 out of 10 control horses. Three horses had to be euthanized for humane reasons. In contrast, none of the vaccinated horses developed WNV disease and only 1 vaccinated horse became viraemic at a single time point at low titre. The prevalence of WNV disease and viraemia were significantly lower in the vaccinated horses than in the control horses (P<0.0001 for both). Based on these results, the ALVAC-WNV vaccine will provide veterinarians with an effective tool to control infections caused by lineage 1 and 2 strains of WNV.

Prognostic factors for cutaneous and subcutaneous soft tissue sarcomas in dogs.

Soft tissue sarcomas (STSs) develop from mesenchymal cells of soft tissues, and they commonly occur in the skin and subcutis of the dog. Although phenotypically diverse with frequently controversial histogenesis, STSs are considered as a group because they have similar features microscopically and clinically. Following resection, local recurrence rates are low in general but vary according to histologic grade and completeness of surgical margins. Complete margins predict nonrecurrence. Even most grade I STSs with "close" margins will not recur, but propensity for recurrence increases with grade. The frequency of metastasis has not been accurately estimated, but it is believed to be rare for grade I STSs and most likely to occur with grade III STSs. However, metastasis does not necessarily equate with poor survival. High mitotic index is prognostic for reduced survival time. Further research is needed to determine more precise estimates for recurrence rates and survival as related to completeness of surgical margins and to delineate potential differences in metastatic rate and median survival time between grades. Other potential indicators of prognosis that presently require further investigation include histologic type, tumor dimension, location, invasiveness, stage, markers of cellular proliferation, and cytogenetic profiles. Common issues limiting prognostic factor evaluation include biases from retrospective studies, small sample sizes, poor verification of metastasis, inconsistent STS classification and use of nomenclature, difficulties in differentiating STS phenotype, and diversity of the study population (stage of disease and treatment status).

Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsy specimens in veterinary surgical pathology.

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.

Small data set analysis in surface metrology: an investigation using a single point incremental forming case study.

A new method for applying statistical techniques with small data sets in surface metrology is demonstrated. This method allows for surfaces or surface-creation processes to be differentiated with as few as six measurement regions. A case study in surface roughness of single point incremental forming is used to demonstrate this method because previous work in this area has not provided quantitative statistical testing to support conclusions. The results from the case study indicate that surface roughness parameters Sz and relative length at scales less than 200 nm are greater when the roll marks on the surface are oriented perpendicular rather than parallel to the forming direction.

Feline intestinal sclerosing mast cell tumour: 50 cases (1997-2008).

This case series presents a unique and unreported variant of feline intestinal mast cell tumour recognized at the CSU Veterinary Diagnostic Laboratory. Fifty cases of feline intestinal mast cell tumours described as having a significant stromal component were reviewed. Neoplastic cells formed a trabecular pattern admixed with moderate to abundant dense stromal collagen (sclerosis). Neoplastic cells had poorly discernible intracytoplasmic granules which demonstrated metachromasia with special histochemical stains consistent with mast cell granules. Additionally, a subset of cases stained for mast cell-specific tryptase and c-kit demonstrated positive immunoreactivity. Eosinophilic infiltrates were moderate to marked in almost all cases. Lymph node and hepatic metastases were present in 66% of the cases. Treatment and clinical outcome was available in 25/50 cases. Twenty-three of these patients died or were euthanized within 2 months of initial diagnosis. This is the first case series to characterize a sclerosing variant of intestinal mast cell tumour in the cat which appears to have a high propensity for metastasis and a guarded prognosis.

On discovering relevant scales in surface roughness measurement--an evaluation of a band-pass method.

When characterizing surfaces and searching for correlations to functional properties, such as friction, finding the right scale of roughness for evaluation can improve correlations. However, in traditional roughness parameter analysis, a wide range of scales, or all scales of topography in the surface roughness measurements are evaluated together. In this study a multi-scale method using a series of band-pass filters is employed for finding scales of topography with strong correlations to friction.

Implementing evidence-based patient self-management programs in the Veterans Health Administration: perspectives on delivery system design considerations.

While many patient self-management (PSM) programs have been developed and evaluated for effectiveness, less effort has been devoted to translating and systematically delivering PSM in primary and specialty care. Therefore, the purpose of this paper is to review delivery system design considerations for implementing self-management programs in practice. As lessons are learned about implementing PSM programs in Veterans Health Administration (VHA), resource allocation by healthcare organization for formatting PSM programs, providing patient access, facilitating PSM, and incorporating support tools to foster PSM among its consumers can be refined and tailored. Redesigning the system to deliver and support PSM will be important as implementation researchers translate evidence based PSM practices into routine care and evaluate its impact on the health-related quality of life of veterans living with chronic disease.

Cognitive effects of memantine in postmenopausal women at risk of dementia: a pilot study.

BACKGROUND: To determine the effects of memantine on cognition in a normal population of postmenopausal women with putative risk factors for Alzheimer's disease (AD) using a built-in control for the genetic risk factor for AD (apoE-epsilon4 status). METHODS: A prospective, open-label, 6-month pilot medication trial with memantine and follow-up after discontinuance conducted at the Center for Neuroscience in Women's Health, Stanford University School of Medicine. Neuropsychological data were collected on 22 community-dwelling postmenopausal women (11 apoE-epsilon4 carriers and 11 apoE-epsilon4 non-carriers) with at least one putative risk factor for AD. RESULTS: ApoE-epsilon4 status was not a significant predictor of change in neuropsychological performance. Changes associated with memantine treatment for entire sample included significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal. A positive medication effect was noted with executive functions and possibly category fluency. Trend-level improvements were seen in motor dexterity of the non-dominant hand and maintained even after drug discontinuance. CONCLUSIONS: Treatment with memantine appeared to have differential effects on cognitive performance in a population of women with putative risk factors for AD. ApoE-epsilon4 carrier status did not account for observed changes in cognition.