The development and productivity of a measure for identifying low language abilities in children aged 24-36 months.

BACKGROUND: Accurate early identification of children with low language ability is important but existing measures generally have low sensitivity. This remains an area of concern for preventive and public health services. This study aimed to create and evaluate a measure of child language, communication and related risks which can be used by community health nurses to accurately identify children with low language aged 24-30 months. METHODS: The Early Language Identification Measure (ELIM) was developed and comprised five measurement sections, each measuring different aspects of development combined into a single measure. This was tested blind against a reference standard language measure, the Preschool Language Scale-5 (PLS-5), at the universal 24-30-month health visitor review in England. The threshold for likely low language was the tenth centile or below on the PLS-5. The aim was to ascertain the performance of the five individual sections in the scale, and consider the optimum combination of sections, for predicting low language ability. Specificity, sensitivity, and positive and negative predictive values were reported for each of the five sections of the ELIM alone and in conjunction with each other. The performance for children from monolingual English-speaking families and those who spoke languages other than English were also considered separately. RESULTS: Three hundred and seventy-six children were assessed on both the ELIM identification measure and the PLS-5 with 362 providing complete data. While each section of the ELIM predicted low language ability, the optimal combination for predicting language outcome was the parent reported vocabulary checklist coupled with the practitioner observation of the child's communication and related behaviours. This gave a sensitivity of 0·98 with a specificity of 0·63. CONCLUSIONS: A novel measure has been developed which accurately identifies children at risk of low language, allowing clinicians to target resources efficiently and intervene early.

ProNGF Expression and Targeting in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most lethal adult brain cancer. Temozolomide (TMZ), the standard chemotherapeutic drug used in GBM, has limited benefit and alternate therapies are needed to improve GBM treatment. Nerve growth factor (NGF) and its precursor proNGF are increasingly recognized as stimulators of human tumor progression. The expression and stimulatory effect of NGF on GBM cell growth has previously been reported, but the status of proNGF in GBM is unreported. In this study, we have investigated proNGF expression and biological activity in GBM. A clinical cohort of GBM (n = 72) and low-grade glioma (n = 20) was analyzed by immunohistochemistry for proNGF and digital quantification. ProNGF expression was significantly increased in GBM compared to low grade gliomas and proNGF was also detected in patient plasma samples. ProNGF was also detected in most GBM cell lines by Western blotting. Although anti-proNGF blocking antibodies inhibited cell growth in GBM cells with methylated MGMT gene promoter, targeting proNGF could not potentiate the efficacy of TMZ. In subcutaneous xenograft of human GBM cells, anti-proNGF antibodies slightly reduced tumor volume but had no impact on TMZ efficacy. In conclusion, this data reveals that proNGF is overexpressed in GBM and can stimulate cancer cell growth. The potential of proNGF as a clinical biomarker and therapeutic target warrants further investigations.

Differences in assistive technology installed for people with dementia living at home who have wandering and safety risks.

BACKGROUND: Assistive Technology for people with dementia living at home is not meeting their care needs. Reasons for this may be due to limited understanding of variation in multiple characteristics of people with dementia including their safety and wandering risks, and how these affect their assistive technology requirements. This study therefore aimed to explore the possibility of grouping people with dementia according to data describing multiple person characteristics. Then to investigate the relationships between these groupings and installed Assistive Technology interventions. METHODS: Partitioning Around Medoids cluster analysis was used to determine participant groupings based upon secondary data which described the person characteristics of 451 people with dementia with Assistive Technology needs. Relationships between installed Assistive Technology and participant groupings were then examined. RESULTS: Two robust clustering solutions were identified within the person characteristics data. Relationships between the clustering solutions and installed Assistive Technology data indicate the utility of this method for exploring the impact of multiple characteristics on Assistive technology installations. Living situation and caregiver support influence installation of assistive technology more strongly than level of risk or cognitive impairment. People with dementia living alone received different AT from those living with others. CONCLUSIONS: Results suggest that caregiver support and the living situation of the person with dementia influence the type and frequency of installed Assistive Technology. Reasons for this include the needs of the caregiver themselves, the caregiver view of the participants' needs, caregiver response to alerts, and the caregiver contribution to the assistive technology assessment and selection process. Selection processes should be refined to account for the needs and views of both caregivers and people with dementia. This will require additional assessor training, and the development of validated assessments for people with dementia who have additional impairments. Policies should support the development of services which provide a wider range of AT to facilitate interventions which are focused on the needs of the person with dementia.

Exploring the needs of people with dementia living at home reported by people with dementia and informal caregivers: a systematic review and Meta-analysis.

OBJECTIVES: To provide prevalence estimates of needs of people with dementia living at home, and to determine sources of variation associated with needs for this population. METHOD: A systematic review and meta-analysis was performed searching CINAHL, MEDLINE, PsycINFO and ASSIA databases. Following quality checks, random effects meta-analysis produced prevalence estimates for needs reported by people with dementia and by their informal caregivers. Fixed effects models were undertaken to compare caregiver and person with dementia reported needs. Heterogeneity was explored through sensitivity analysis. The study protocol was registered with Prospero #CRD42017074119. RESULTS: Six retrieved studies published between 2005 and 2017 including 1011 people with dementia and 1188 caregivers were included in the analysis. All data were collected using Camberwell Assessment of Need for the Elderly. Prevalence estimates are provided for 24 needs reported by participants in The Netherlands, United Kingdom, Poland, Ireland, Germany, Norway, Portugal, Italy and Sweden. Most prevalent needs reported by people with dementia were Memory 0.713 [95% CI 0.627, 0.791]; Food 0.706 [95% CI 0.547, 0.842]; Household activities 0.677 [95% CI 0.613, 0.738]; and Money 0.566 [95% CI 0.416, 0.711]. Caregivers reported greater prevalence than people with dementia did for 22 of 24 needs, although the priority ranking of needs was similar. Exploration of heterogeneity revealed that people with young onset dementia were the major source of variation for 24 out of 48 analyses. CONCLUSION: Increased understanding of prevalence of needs of people with dementia and associated heterogeneity can assist in planning services to meet those needs.

The relationship between adult attachment and coping with brain tumour: the mediating role of social support.

OBJECTIVE: A primary brain tumour diagnosis is known to elicit higher distress than other forms of cancer and is related to high depressive symptomatology. Using a cross-sectional design, the present study explored how individuals cope with this diagnosis using an attachment theory framework. Attachment anxiety and attachment avoidance were hypothesised to be positively related to helplessness/hopelessness, anxious preoccupation, and cognitive avoidance; and negatively related to fighting spirit and fatalism coping. We proposed perceived social support to play a mediating role in those associations. METHODS: Four hundred and eighty participants diagnosed with primary brain tumours completed the Mini-Mental Adjustment to Cancer Scale (Mini-MAC), the Experiences in Close Relationships Questionnaire-Revised (ECR-R), and the modified Medical Outcomes Study-Social Support Scale (mMOS-SSS) online. RESULTS: Lower perceived social support mediated the positive associations between both higher attachment anxiety and avoidance and higher helpless/hopeless coping. Attachment anxiety was also positively associated with anxious preoccupation. This relationship was not mediated by perceived social support. Cognitive avoidance was unrelated to both attachment dimensions and social support. CONCLUSIONS: The findings highlight that the differences in coping repertoire are associated with social relatedness factors, specifically attachment security and its relationship to perceived social support. Implications of the findings are discussed.

Community-based participation of children with and without disabilities.

AIM: To describe and compare the socio-demographic characteristics and community-based participation of children with and without disabilities. METHOD: This cross-sectional study reports data on 1073 children with disabilities (663 males, 410 females) and 11 122 children without disabilities (5617 males, 5505 females) aged 10 to 12 years from the fifth sweep of the Millennium Cohort Study. χ2 was used to explore differences between the two groups. Logistic regression models were used to assess the relationships between childhood disability (dependent variable) and socio-demographic characteristics. Logistic regression models were also used to examine the associations between childhood disability (dependent variable) and participation in community-based activities. RESULTS: Children with disabilities were more likely to be male, have psychosocial and behavioural problems, live in single-parent households, and have a parent with a longstanding illness. Patterns of community-based participation were similar between children with and without disabilities. However, the extent to which the two groups participated differed. Children with disabilities participated with lower frequency in unstructured physical activities (adjusted odds ratio [OR] 2.41; 95% confidence interval [CI]: 1.95-2.99), organized physical activities (adjusted OR 2.29; 95% CI: 1.83-2.86), religious gatherings (adjusted OR 2.08; 95% CI: 1.35-3.20), and getting together with friends (adjusted OR 3.31; 95% CI: 2.61-4.20). INTERPRETATION: Socio-demographic characteristics differed between children with and without disabilities. Children with disabilities had greater restriction in participation compared to peers without disabilities. Participation promoting interventions are required to support the participation of children with disabilities in social and physical activities. WHAT THIS PAPER ADDS: Patterns of community-based participation were similar between children with and without disabilities. Children with disabilities had lower frequency of participation in physical activities, religious gatherings, and getting together with friends.

Minimum accelerometer wear-time for reliable estimates of physical activity and sedentary behaviour of people receiving haemodialysis.

BACKGROUND: Low levels of physical activity are implicated in low life expectancies of people receiving maintenance haemodialysis. Accelerometers are increasingly being used to quantify activity behaviours of this population but guidance to quality-assure such data is lacking. The objective of this study was to provide data processing and reduction recommendations to ensure accelerometer-derived outcomes are sufficiently reliable for interpretative analysis. METHODS: Seventy people receiving maintenance haemodialysis (age 55.9 ± 15.7 years, 34% women, 23% diabetic) from a single outpatient renal unit volunteered for the study. Participants wore Actigraph GT3x and ActivPAL monitors during waking hours over seven days. Reliability of accelerometer output (normalised to wear-time) was assessed via intraclass correlation coefficient (ICC). The Spearman-Brown prophecy formula was subsequently applied to the ICCs to derive the minimum required accelerometer wear-time for each behavioural outcome. RESULTS: Monitor wear compliance was greater on dialysis compared to non-dialysis days (90% v 77%). Participants were significantly more active on non-dialysis days compared to dialysis days but there were no significant differences in estimated behaviours between days within the same condition. Average measure ICCs for all accelerometer outcomes were high (range 0.76-0.96). Computations indicated that habitual physical activity and sedentary behaviour could be estimated with a minimum reliability level of 0.80 from one dialysis day and two non-dialysis days, and at least eight hours monitor wear per day. Applying this rubric allowed 90% of participant data to be retained for further analysis. CONCLUSIONS: Regardless of accelerometer, one dialysis and two non-dialysis days data with a minimum of eight hours wear each day should enable habitual activity of people receiving maintenance haemodialysis to be characterised with acceptable reliability. These recommendations reconcile the tension between wear-time criteria stringency and retention of an adequately representative sample.

The relative importance of frailty, physical and cardiovascular function as exercise-modifiable predictors of falls in haemodialysis patients: a prospective cohort study.

BACKGROUND: Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling. Therefore, we aimed to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in these patients. METHODS: Ninety-three prevalent CKD-5 patients on HD from three Renal Units were recruited for this prospective cohort study, which was conducted between October 2015 and August 2018. At baseline, frailty status was assessed using the Fried's frailty phenotype, while physical function was evaluated through timed up and go (TUG), five repetitions chair sit-to-stand (CSTS-5), objectively measured physical activity, and maximal voluntary isometric strength. Baroreflex and haemodynamic function at rest and in response to a 60° head-up tilt test (HUT-60°) were also assessed by means of the Task Force Monitor. The number of falls experienced was recorded once a month during 12 months of follow-up. RESULTS: In univariate negative binomial regression analysis, frailty (RR: 4.10, 95%CI: 1.60-10.51, p = 0.003) and other physical function determinants were associated with a higher number of falls. In multivariate analysis however, only worse baroreflex function (RR: 0.96, 95%CI: 0.94-0.99, p = 0.004), and orthostatic decrements of BP to HUT-60° (RR: 0.93, 95%CI: 0.87-0.99, p = 0.033) remained significantly associated with a greater number of falls. Eighty falls were recorded during the study period and the majority of them (41.3%) were precipitated by dizziness symptoms, as reported by participants. CONCLUSIONS: This prospective study indicates that cardiovascular mechanisms implicated in the short-term regulation of BP showed a greater relative importance than frailty in predicting falls in CKD-5 patients on HD. A high number of falls appeared to be mediated by a degree of cardiovascular dysregulation, as evidenced by the predominance of self-reported dizziness symptoms. TRIAL REGISTRATION: ClinicalTrials.gov (trial registration ID: NCT02392299; date of registration: March 18, 2015).

Ultrasonographic features of mesenteric cysticercosis in a domestic rabbit (Oryctolagus cuniculus).

A 5-year-old, 0.92-kg (2-lb), spayed female Dwarf Hotot rabbit was evaluated for a 1-day duration of lethargy and anorexia. Survey radiographs revealed evidence of gastrointestinal stasis. Abdominal ultrasonography characterized multiple small, round, anechoic structures embedded in the mesentery. These structures were thin walled with hyperechoic strands/septations. Most of the structures contained a well-defined, eccentric, hyperechoic nodule adherent to the intraluminal wall. Mesenteric cysticercosis was confirmed via exploratory laparotomy and histopathology. To the authors' knowledge, this is the first description of the ultrasonographic features of mesenteric cysticercosis in a domestic rabbit.

Family factors associated with participation of children with disabilities: a systematic review.

AIM: The aim of this review was to synthesize empirical evidence of family factors associated with participation of children with disabilities aged 5 to 12 years to inform the development of family-centred participation-fostering interventions. METHOD: A systematic search was performed for articles published in English between 2001 and 2017 in MEDLINE, PsycINFO, CINAHL, Scopus, and ASSIA following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Quality of evidence was appraised using the Research Triangle Institute Item Bank. Family factors associated with participation were identified and assessed using a multistage 'semi-quantitative' approach. RESULTS: Thirty studies were included in the review. Four non-modifiable 'status' factors consistently associated with participation were parental ethnicity, parental education, family type, and family socio-economic status. Six modifiable 'process' factors with consistent associations with participation were parental mental and physical health functioning, parental self-efficacy beliefs, parental support, parental time, family preferences, and activity orientation. INTERPRETATION: Rehabilitation professionals should direct their focus towards modifiable family factors as primary targets for family-centred interventions. Strategies that can improve families' access to information, counselling, and community support services are likely to support children's participation by empowering families and optimizing their health and well-being. WHAT THIS PAPER ADDS: Non-modifiable 'status' and modifiable 'process' factors are important in participation of children with disabilities. Disadvantaged family circumstances shaped by status factors are associated with reduced participation. Key process factors for intervention are parental mental and physical health and parental self-efficacy beliefs. Other important process factors for intervention are parental support and time, family preferences, and activity orientation.

FACTORES FAMILIARES ASOCIADOS CON LA PARTICIPACIÓN DE NIÑOS CON DISCAPACIDAD: UN ESTUDIO SISTEMÁTICO: OBJETIVO: El objetivo de esta revisión fue sintetizar la evidencia empírica de los factores familiares asociados con la participación de niños con discapacidad entre los 5 y 12 años para informar el desarrollo de intervenciones que fomentan la participación centrada en la familia METODO: Una búsqueda sistemática fue realizada en artículos publicados en ingles entre 2001 y 2017 en MEDLINE, PsycINFO, CINAHL, Scopus, y ASSIA de acuerdo con los items reportados preferentes para guías de Búsqueda Sistemática y Meta-Análisis. La calidad de la evidencia fue evaluada utilizando el Banco de Items del Research Triangle Institute (RTI). Fueron identificados los factores familiares asociados con la participación y evaluados utilizando un enfoque semicuantitativo de varias etapas. RESULTADOS: Fueron incluidos 30 estudios en esta revisión. Cuatro factores no modificables de ¨estado¨ asociados sistemáticamente con la participación fueron la etnia de los padres, el nivel de educación de los padres, el tipo de familia, y el estatus socioeconómico de las familias. Seis factores de ¨proceso ¨modificables con asociaciones consistentes con la participación fueron el funcionamiento de salud física y mental de los padres, creencia de autoeficacia de los padres, soporte parenteral, tiempo de los padres, preferencias familiares, y orientación a la actividad. INTERPRETACION: Los profesionales de la rehabilitación deben dirigir su foco hacia los factores modificables como objetivo primario para las intervenciones centradas en la familia. Estrategias que puedan mejorar el acceso de las familias a la información , asesoramiento, y servicios de apoyo comunitario que apoyen la participación de los niños y empoderar a las familias y optimizar su salud y bienestar.

FATORES FAMILIARES ASSOCIADOS COM PARTICIPAÇÃO EM CRIANÇAS COM INCAPACIDADES: UMA REVISÃO SISTEMÁTICA: OBJETIVO: O objetivo desta revisão foi sintetizar a evidência empírica de fatores familiares associados com participação de crianças com incapacidades de 5 a 12 anos para informar o desenvolvimento de intevenções centradas na família que promovam a participação. MÉTODO: Uma busca sistemática foi realizada por artigos publicados em ingles entre 2001 e 2007 na Medline, PsycINFO, CINAHL, Scopus, e ASSIA seguindo as diretrizes para Itens preferidos a serem reportados em revisões sistemáticas. A qualidade da evidência foi avaliada usando o Banco de Itens Do Institututo do Triângulo das Pesquisas (ITR). Fatores familiares associados à participação foram identificados e avaliados usando uma abordagem semi-quantitativa multi-estágios. RESULTADOS: Trinta estudos foram incluídos na revisão. Quatro fatores com estado "não-modificável" consistentemente associados com participação foram etnia parental, educação parental, tipo de família e situação sócio-econômica da família. Seis fatores de "processo" modificáveis com associações consistentes com participação foram saúde e funcionamento mental e físico dos pais, auto-eficácia parental, apoio parental, tempo parental, preferências familiares e orientacões para atividades. INTERPRETAÇÃO: Profissionais de reabilitação devem direcionar o foco para fatores familiares potencialmente modificáveis como alvos primários para intervenções centradas na família. Estratégias que podem melhorar o acesso da família a informação, aconselhamento e serviços de suporte na comunidade têm probabilidade de apoiar a participação da criança por empoderar famílias e otimizar sua saúde e bem estar.

Association of proximal elements of social disadvantage with children's language development at 2 years: an analysis of data from the Children in Focus (CiF) sample from the ALSPAC birth cohort.

BACKGROUND: An association between social disadvantage and early language development is commonly reported in the literature, but less attention has been paid to the way that different aspects of social disadvantage affect both expressive and receptive language in the first 2 years of life. AIMS: To examine the contributions of gender, parental report of early language skills and proximal social variables (the amount of stimulation in the home, the resources available to the child and the attitudes/emotional status of the primary carer and the support available to him/her) controlling for distal social variables (family income and maternal education) to children's expressive and receptive language development at 2 years in a community ascertained population cohort. METHODS & PROCEDURES: Data from 1314 children in the Children in Focus (CiF) sample from the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. Multivariable regression models identified the contribution of proximal (what parents do with their children) measures of social disadvantage adjusting for more distal (e.g., family income and material wealth) measures as well as early language development at 15 months to the development of verbal comprehension, expressive vocabulary and expressive grammar (word combinations) at 2 years of age. OUTCOME & RESULTS: In the final multivariable models gender, earlier language and proximal social factors, co-varying for distal factors predicted 36% of the variance for expressive vocabulary, 22% for receptive language and 27% for word combinations at 2 years. Language development at 15 months remained a significant predictor of outcomes at 24 months. Environmental factors were associated with both expressive scales but the picture was rather more mixed for receptive language suggesting that there may be different mechanisms underlying the different processes. CONCLUSIONS & IMPLICATIONS: This study supports the argument that social advantage makes a strong contribution to children's language development in the early years. The results suggest that what parents/carers do with their children is critical even when structural aspects of social disadvantage such as family income and housing have been taken into consideration although this relationship varies for different aspects of language. This has the potential to inform the targeting of public health interventions focusing on early language and pre-literacy skills on the one hand and home learning environments on the other and, potentially, the two in combination.

Early Home Activities and Oral Language Skills in Middle Childhood: A Quantile Analysis.

Oral language development is a key outcome of elementary school, and it is important to identify factors that predict it most effectively. Commonly researchers use ordinary least squares regression with conclusions restricted to average performance conditional on relevant covariates. Quantile regression offers a more sophisticated alternative. Using data of 17,687 children from the United Kingdom's Millennium Cohort Study, we compared ordinary least squares and quantile models with language development (verbal similarities) at 11 years as the outcome. Gender had more of an effect at the top of the distribution, whereas poverty, early language, and reading to the child had a greater effect at the bottom. The picture for TV watching was more mixed. The results are discussed in terms of the provision of universal and targeted interventions.

Cardiopulmonary Bypass in the Setting of Waldenström's Macroglobulinemia.

Waldenström's Macroglobulinemia (WM) is a rare lymphoma caused by the overproduction of immunoglobulin M (IgM). The elevated level of IgM causes serum hyperviscosity, cold agglutinins, and cryoglobulinemia. Anemia is also present because of impaired production of erythrocytes. For these reasons, placing a patient with WM on cardiopulmonary bypass (CPB) requires careful preparation. In this case, the patient was a 73-year-old male with known Waldenström's disease who required coronary artery bypass graft surgery. This report details the perioperative considerations used for successful CPB on a Waldenström's patient. Critical to this case was the use of plasmapheresis before surgery. Temperature management and acid/base status were carefully controlled. A successful coronary revascularization surgery was performed. Many of the Wadenstrom's disease complications expected on CPB failed to materialize.

Contribution of spoken language and socio-economic background to adolescents' educational achievement at age 16 years.

BACKGROUND: Well-documented associations exist between socio-economic background and language ability in early childhood, and between educational attainment and language ability in children with clinically referred language impairment. However, very little research has looked at the associations between language ability, educational attainment and socio-economic background during adolescence, particularly in populations without language impairment. AIMS: To investigate: (1) whether adolescents with higher educational outcomes overall had higher language abilities; and (2) associations between adolescent language ability, socio-economic background and educational outcomes, specifically in relation to Mathematics, English Language and English Literature GCSE grade. METHOD & PROCEDURES: A total of 151 participants completed five standardized language assessments measuring vocabulary, comprehension of sentences and spoken paragraphs, and narrative skills and one nonverbal assessment when between 13 and 14 years old. These data were compared with the participants' educational achievement obtained upon leaving secondary education (16 years old). Univariate logistic regressions were employed to identify those language assessments and demographic factors that were associated with achieving a targeted A* -C grade in English Language, English Literature and Mathematics General Certificate of Secondary Education (GCSE) at 16 years. Further logistic regressions were then conducted to examine further the contribution of socio-economic background and spoken language skills in the multivariate models. RESULTS & OUTCOMES: Vocabulary, comprehension of sentences and spoken paragraphs, and mean length utterance in a narrative task along with socio-economic background contributed to whether participants achieved an A* -C grade in GCSE Mathematics and English Language and English Literature. Nonverbal ability contributed to English Language and Mathematics. The results of multivariate logistic regressions then found that vocabulary skills were particularly relevant to all three GCSE outcomes. Socio-economic background only remained important for English Language, once language assessment scores and demographic information were considered. CONCLUSIONS & IMPLICATIONS: Language ability, and in particular vocabulary, plays an important role for educational achievement. Results confirm a need for ongoing support for spoken language ability throughout secondary education and a potential role for speech and language therapy provision in the continuing drive to reduce the gap in educational attainment between groups from differing socio-economic backgrounds.

Nerve Growth Factor and Related Substances: A Brief History and an Introduction to the International NGF Meeting Series.

Nerve growth factor (NGF) is a protein whose importance to research and its elucidation of fundamental mechanisms in cell and neurobiology far outstrips its basic physiological roles. It was the first of a broad class of cell regulators, largely acting through autocrine and paracrine interactions which will be described herein. It was of similar significance in establishing the identity and unique roles of neurotrophic factors in the development and maintenance of the peripheral and central nervous systems. Finally, it contributed to many advances in the elaboration of cell surface receptor mechanisms and intracellular cell signaling. As such, it can be considered to be a "molecular Rosetta Stone". In this brief review, the highlights of these various studies are summarized, particularly as illustrated by their coverage in the 13 NGF international meetings that have been held since 1986.

EVALUATION OF TWO CANINE DISTEMPER VIRUS VACCINES IN CAPTIVE TIGERS (PANTHERA TIGRIS).

Canine distemper virus (CDV) has caused clinical disease and death in nondomestic felids in both captive settings and in the wild. Outbreaks resulting in high mortality rates in tigers (Panthera tigris) have prompted some zoos to vaccinate tigers for CDV. In this study, six tigers received a recombinant canarypox-vectored CDV vaccine (1 ml s.c.) and were revaccinated with 3 ml s.c. (mean) 39 days later. Blood collection for CDV antibody detection via serum neutralization was performed on (mean) days 0, 26, and 66 post-initial vaccination. No tigers had detectable antibodies at days 0 or 26, and only two tigers had low (16 and 32) antibody titers at day 66. Eight additional tigers received a live, attenuated CDV vaccine (1 ml s.c.) on day 0 and were revaccinated with 1 ml s.c. (mean) 171 days later. Blood collection for CDV antibody detection via serum neutralization was performed on (mean) days 0, 26, 171, and 196. Seven of eight tigers receiving the live, attenuated vaccine had no detectable titers prior to vaccination, but all animals had titers of >128 (range 128-1,024) at day 26. At 171 days, all tigers still had detectable titers (geometric mean 69.8, range 16-256), and at 196 days (2 wk post-revaccination) all but two showed an increase to >128 (range 32-512). To determine safety, an additional 41 tigers were vaccinated with 2 ml of a recombinant vaccine containing only CDV components, and an additional 38 tigers received 1 ml of the live, attenuated vaccine, administered either subcutaneously or intramuscularly; no serious adverse effects were noted. Although both vaccines appear safe, the live, attenuated vaccine produced a stronger and more consistent serologic response in tigers.

CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

Effect of exercise training on estimated GFR, vascular health, and cardiorespiratory fitness in patients with CKD: a pilot randomized controlled trial.

BACKGROUND: Exercise capacity, which is predictive of all-cause mortality and cardiovascular disease risk, is reduced significantly in patients with non-dialysis-dependent chronic kidney disease. This pilot study examined the effect of moderate-intensity exercise training on kidney function and indexes of cardiovascular risk in patients with progressive chronic kidney disease stages 3 to 4. STUDY DESIGN: Single-blind, randomized, controlled, parallel trial. SETTING & PARTICIPANTS: 20 patients (aged 18-80 years; 17 men) randomly assigned to rehabilitation (n=10) or usual care (n=10). Participants were included if they were 18 years or older and had evidence of rate of decline in creatinine-based estimated glomerular filtration rate (eGFRcr)≥2.9mL/min/1.73m(2) per year for 12 months preintervention. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. INTERVENTION: The rehabilitation group received resistance and aerobic training (3 days per week) for a 12-month period. The usual care group received standard care. OUTCOMES: Kidney function assessed by comparing mean rate of change in eGFRcr (mL/min/1.73m(2) per year) from a 12-month preintervention period against the 12-month intervention period. Pulse wave velocity (PWV), peak oxygen uptake (Vo2peak), and waist circumference assessed at 0, 6, and 12 months. MEASUREMENTS: eGFR assessed using creatinine, cystatin C (eGFRcys), and a combination of both values (eGFRcr-cys). RESULTS: 18 participants (rehabilitation, 8; usual care, 10) completed the study. A significant mean difference in rate of change in eGFRcr (+7.8±3.0 [95% CI, 1.1-13.5] mL/min/1.73m(2) per year; P=0.02) was observed between the rehabilitation and usual care groups, with the rehabilitation group demonstrating a slower decline. No significant between-group mean differences existed in absolute eGFRcr, eGFRcr-cys, or eGFRcys at 12 months of study intervention. Significant between-group mean differences existed in PWV (-2.30 [95% CI, -3.02 to -1.59] m/s), waist circumference (-7.1±12.8 [95% CI, -12.4 to -3.2] cm), and Vo2peak (5.7 [95% CI, 1.34-10.10] mL/kg/min). Change in eGFRcr was correlated inversely with PWV (r=-0.5; P=0.04) at 12 months. LIMITATIONS: Small sample size, inconsistency between primary and secondary measures of kidney function. CONCLUSIONS: The effect of a 1-year exercise intervention on progression of kidney disease is inconclusive. A larger study with longer follow-up may be necessary.

Aerobic or Resistance Training and Pulse Wave Velocity in Kidney Transplant Recipients: A 12-Week Pilot Randomized Controlled Trial (the Exercise in Renal Transplant [ExeRT] Trial).

BACKGROUND: Cardiovascular disease remains the leading cause of death in kidney transplant recipients. This pilot study examined the potential effect of aerobic training or resistance training on vascular health and indexes of cardiovascular risk in kidney transplant recipients. STUDY DESIGN: Single-blind, randomized, controlled, parallel trial. SETTING & PARTICIPANTS: 60 participants (mean age, 54 years; 34 men) were randomly assigned to aerobic training (n=20), resistance training (n=20), or usual care (n=20). Participants were included if they had a kidney transplant within 12 months prior to baseline assessment. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. INTERVENTION: Aerobic training and resistance training were delivered 3 days per week for a 12-week period. The usual-care group received standard care. OUTCOMES & MEASUREMENTS: Pulse wave velocity, peak oxygen uptake (Vo2peak), sit-to-stand 60, isometric quadriceps force, and inflammatory biomarkers were assessed at 0 and 12 weeks. RESULTS: The anticipated 60 participants were recruited within 12 months. 46 participants completed the study (aerobic training, n=13; resistance training, n=13; and usual care, n=20), resulting in a 23% attrition rate. Analyses of covariance, adjusted for baseline values, age, and dialysis vintage pretransplantation, revealed significant mean differences between aerobic training and usual care in pulse wave velocity of -2.2±0.4 (95% CI, -3.1 to -1.3) m/s (P<0.001) and between resistance training and usual care of -2.6±0.4 (95% CI, -3.4 to -1.7) m/s (P<0.001) at 12 weeks. Secondary analyses indicated significant improvements in Vo2peak in the aerobic training group and in Vo2peak, sit-to-stand 60, and isometric muscle force in the resistance training group compared with usual care at 12 weeks. There were no reported adverse events, cardiovascular events, or hospitalizations as a result of the intervention. LIMITATIONS: Pilot study, small sample size, no measure of endothelial function. CONCLUSIONS: Both aerobic training and resistance training interventions appear to be feasible and clinically beneficial in this patient population.