Replicating an effective VA program to train and support family caregivers: a hybrid type III effectiveness-implementation design.

BACKGROUND: Caring for a growing aging population using existing long-term care resources while simultaneously supporting and educating family caregivers, is a public health challenge. We describe the application of the Replicating Effective Programs (REP) framework, developed by the Centers for Disease Control Prevention and used in public health program implementation, to scale up an evidence-based family caregiver training intervention in the Veterans Affairs (VA) healthcare system. METHODS: From 2018 to 2020, clinicians at eight VA medical centers received REP-guided implementation including facilitation, technical assistance, and implementation tools to deliver the training program. The project team used the REP framework to develop activities across four distinct phases - (1) pre-conditions, (2) pre-implementation, (3) implementation, and (4) maintenance and evolution - and systematically tracked implementation facilitators, barriers, and adaptations. RESULTS: Within the REP framework, results describe how each medical center adapted implementation approaches to fit local needs. We highlight examples of how sites balanced adaptations and intervention fidelity. CONCLUSIONS: The REP framework shows promise for national expansion of the caregiver training intervention, including to non-VA systems of care, because it allows sites to adapt while maintaining intervention fidelity. TRIAL REGISTRATION: NCT03474380 . Date registered: March 22, 2018.

The effect of timing of oral meloxicam administration on physiological responses in calves after cautery dehorning with local anesthesia.

Dehorning is a painful husbandry procedure that is commonly performed in dairy calves. Parenteral meloxicam combined with local anesthesia mitigates the physiological and behavioral effects of dehorning in calves. The purpose of this study was to determine the influence of timing of oral meloxicam administration on physiological responses in calves after dehorning. Thirty Holstein bull calves, 8 to 10 wk of age (28-70 kg), were randomly assigned to 1 of 3 treatment groups: placebo-treated control group (n=10), calves receiving meloxicam administered orally (1 mg/kg) in powdered milk replacer 12h before cautery dehorning (MEL-PRE; n=10), and calves receiving meloxicam administered as an oral bolus (1 mg/kg) at the time of dehorning (MEL-POST; n=10). Following cautery dehorning, blood samples were collected to measure cortisol, substance P (SP), haptoglobin, ex vivo prostaglandin E2 (PgE2) production after lipopolysaccharide stimulation and meloxicam concentrations. Maximum ocular temperature and mechanical nociceptive threshold (MNT) were also assessed. Data were analyzed using noncompartmental pharmacokinetic analysis and repeated measures ANOVA models. Mean peak meloxicam concentrations were 3.61±0 0.21 and 3.27±0.14 µg/mL with average elimination half-lives of 38.62±5.87 and 35.81±6.26 h for MEL-PRE and MEL-POST, respectively. Serum cortisol concentrations were lower in meloxicam-treated calves compared with control calves at 4 h postdehorning. Substance P concentrations were significantly higher in control calves compared with meloxicam-treated calves at 120 h after dehorning. Prostaglandin E2 concentrations were lower in meloxicam-treated calves compared with control calves. Mechanical nociceptive threshold was higher in control calves at 1h after dehorning, but meloxicam-treated calves tended to have a higher MNT at 6h after dehorning. No effect of timing of meloxicam administration on serum cortisol concentrations, SP concentrations, haptoglobin concentrations, maximum ocular temperature, or MNT was observed. However, PgE2 concentrations in MEL-PRE calves were similar to control calves after 12h postdehorning, whereas MEL-POST calves had lower PgE2 concentrations for 3 d postdehorning. These findings support that meloxicam reduced cortisol, SP, and PgE2 after dehorning, but only PgE2 production was significantly affected by the timing of meloxicam administration.

Effect of castration method on neurohormonal and electroencephalographic stress indicators in Holstein calves of different ages.

As public concern for food animal welfare increases, a need to validate objective pain assessment tools exists in order to formulate animal welfare policies and facilitate regulatory approval of compounds to alleviate pain in livestock in the United States. The aims of this study were (1) to compare the physiological response to pain induced by surgical and nonsurgical (band) castration in calves and (2) to elucidate age-related differences in pain response of calves subjected to different castration methods. Seventy-six Holstein bull calves were blocked by age (≤8-wk and ≥6-mo-old) and randomly assigned to 1 of 4 treatment groups: control (n=20), castration by banding (n=18), cut-and-clamp surgical castration (n=20), and cut-and-pull surgical castration (n=18). Measurements included electroencephalogram, heart rate variability, infrared thermography, electrodermal activity, and concentrations of serum cortisol and plasma substance P before, during, and within 20min following castration. Electroencephalogram recordings showed desynchronization for all treatments, consistent with increased arousal; yet the magnitude of desynchronization was greatest for 6-mo-old calves castrated by cut-and-clamp. Additionally, older calves in the cut-and-pull group showed greater desynchronization than younger calves in the same group. Based on the heart rate variability analysis, 6-mo-old calves in the control or cut-and-pull castration groups showed greater sympathetic tone than younger calves in the same treatment groups. Overall, younger calves showed lower electrodermal activity than older calves. Regardless of treatment, concentrations of cortisol and plasma substance P were greater in 6-mo-old calves relative to their younger counterparts, indicating a more robust response to all treatments in older calves. In summary, neurohormonal and electroencephalographic stress responses of calves to castration were age-specific. Castration by cut-and-clamp showed the most pronounced stress response in 6-mo-old calves. These findings provide evidence that support welfare policies recommending castration at an early age and the use of analgesic compounds at the time of surgical castration especially in older calves. However, the potential long-term negative consequences of early untreated pain must be considered and warrant further investigation.

The pharmacokinetics and effects of meloxicam, gabapentin, and flunixin in postweaning dairy calves following dehorning with local anesthesia.

Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed-effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic-treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam-treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration.

Test of Gross Motor Development-3 (TGMD-3) with the Use of Visual Supports for Children with Autism Spectrum Disorder: Validity and Reliability.

The validity and reliability of the Test of Gross Motor Development-3 (TGMD-3) were measured, taking into consideration the preference for visual learning of children with autism spectrum disorder (ASD). The TGMD-3 was administered to 14 children with ASD (4-10 years) and 21 age-matched typically developing children under two conditions: TGMD-3 traditional protocol, and TGMD-3 visual support protocol. Excellent levels of internal consistency, test-retest, interrater and intrarater reliability were achieved for the TGMD-3 visual support protocol. TGMD-3 raw scores of children with ASD were significantly lower than typically developing peers, however, significantly improved using the TGMD-3 visual support protocol. This demonstrates that the TGMD-3 visual support protocol is a valid and reliable assessment of gross motor performance for children with ASD.

Topography of ganglion cells in human retina.

We quantified the spatial distribution of presumed ganglion cells and displaced amacrine cells in unstained whole mounts of six young normal human retinas whose photoreceptor distributions had previously been characterized. Cells with large somata compared to their nuclei were considered ganglion cells; cells with small somata relative to their nuclei were considered displaced amacrine cells. Within the central area, ganglion cell densities reach 32,000-38,000 cells/mm2 in a horizontally oriented elliptical ring 0.4-2.0 mm from the foveal center. In peripheral retina, densities in nasal retina exceed those at corresponding eccentricities in temporal retina by more than 300%; superior exceeds inferior by 60%. Displaced amacrine cells represented 3% of the total cells in central retina and nearly 80% in the far periphery. A twofold range in the total number of ganglion cells (0.7 to 1.5 million) was largely explained by a similar range in ganglion cell density in different eyes. Cone and ganglion cell number were not correlated, and the overall cone:ganglion cell ratio ranged from 2.9 to 7.5 in different eyes. Peripheral cones and ganglion cells have different topographies, thus suggesting meridianal differences in convergence onto individual ganglion cells. Low convergence of foveal cones onto individual ganglion cells is an important mechanism for preserving high resolution at later stages of neural processing. Our improved estimates for the density of central ganglion cells allowed us to ask whether there are enough ganglion cells for each cone at the foveal center to have a direct line to the brain. Our calculations indicate that 1) there are so many ganglion cells relative to cones that a ratio of only one ganglion cell per foveal cone would require fibers of Henle radiating toward rather than away from the foveal center; and 2) like the macaque, the human retina may have enough ganglion cells to transmit the information afforded by closely spaced foveal cones to both ON- and OFF-channels. Comparison of ganglion cell topography with the visual field representation in V1 reveals similarities consistent with the idea that cortical magnification is proportional to ganglion cell density throughout the visual field.

Calcium dependence of differentiation of GABA immunoreactivity in spinal neurons.

The developmental regulation of neurotransmitter synthesis has been extensively studied and appears in many cases to depend on electrical activity. The central nervous system of the Xenopus embryo and young larva is an attractive subject for such studies, since action potentials first elicited from Xenopus spinal neurons at the time of closure of the neural tube are long in duration and calcium-dependent. Moreover, cells exhibit spontaneous elevations of intracellular calcium during this early period as a consequence of calcium influx through voltage-dependent channels, which induces calcium release from intracellular stores. Since the early differentiation of Xenopus spinal neurons in dissociated cell culture parallels development in vivo, we have examined the maturation of gamma-aminobutyric acid (GABA) immunoreactivity in cultured neurons and explored its dependence on spontaneous calcium influx at early stages of development. We find that specific GABA immunoreactivity develops in spinal neurons in dissociated cell culture with the same time course previously defined in vivo. Additionally, this process requires calcium influx that occurs spontaneously through voltage-dependent channels. The appearance of GABA immunoreactivity is blocked by transcriptional inhibitors. The early appearance of GABA raises the possibility that it may play additional roles at early stages of development.

Distribution and morphology of human cone photoreceptors stained with anti-blue opsin.

Primate cones maximally sensitive to short wavelength light (blue cones) have been previously identified by using indirect methods. We stained 7 wholemounted human retinas obtained from 6 female donors, using an affinity purified antibody to a 19 amino acid peptide sequence at the N-terminus of blue opsin (Lerea et al., '89: Neuron 3:367-376), standard PAP immunocytochemistry, and controls. Cones were counted where all outer segments could be traced to inner segments and were measured where cells were well aligned vertically. We find that: (1) 7% of cones within 4 mm of the foveal center are labeled by antiblue opsin; (2) compared to neighboring red/green cones, blue cone inner segments are 10% taller, have a larger cross-sectional diameter near the junction with the outer segment, and a smaller diameter near the external limiting membrane, resulting in a more cylindrical shape, (3) foveal blue cones are sparse, irregularly spaced, and missing in a zone about 100 microns (0.35 degrees) in diameter near the site of peak cone density, (4) the highest densities of blue cones (greater than 2,000 cells/mm2) are found in a ring at 0.1-0.3 mm eccentricity, and (5) the shortest distances between neighboring cones are between blue and red/green cones, and the blue and red/green mosaics are statistically independent. These findings are consistent with psychophysical reports of foveal tritanopia and maximum sensitivity to blue light at 1 degree eccentricity. Blue cone spacing may limit resolution of the blue channel out to 20-30 degrees eccentricity. The blue and red/green mosaics appear to be formed by separate processes.

Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina.

PURPOSE: Because previous studies suggested degeneration and loss of photoreceptors in aged human retina, the spatial density of cones and rods subserving the central 43 degrees of vision as a function of age was determined. METHODS: Cones and rods were counted in 27 whole mounted retinas from donors aged 27 to 90 years with macroscopically normal fundi. Photoreceptor topography was analyzed with new graphic and statistical techniques. RESULTS: Changes in cone density throughout this age span showed no consistent relationship to age or retinal location, and the total number of foveal cones was remarkably stable. In contrast, rod density decreased by 30%, beginning inferior to the fovea in midlife and culminating in an annulus of deepest loss at 0.5 to 3 mm eccentricity by the ninth decade. Space vacated by dying rods was filled in by larger rod inner segments, resulting in a similar rod coverage at all ages. At the temporal equator, cone density declined by 23%, but rods were stable throughout adulthood. CONCLUSIONS: The stability of both rod coverage and rhodopsin content despite decreasing cell number suggests plasticity of the adult rod system and that age-related declines in scotopic sensitivity may be due to postreceptoral factors. There is no evidence for the massive loss of foveal cones required to explain even modest decrements in acuity, consistent with evidence that visual deficits at high photopic levels may be largely due to optical factors. Why the rods of central retina, which share a common support system and light exposure with the neighboring cones, are preferentially vulnerable to aging remains to be determined.

Review of negative Papanicolaou tests. Is the retrospective 5-year review necessary?

New federal regulations require review of all available negative gynecologic smears within the previous 5 years for each patient with a current high grade squamous intraepithelial lesion (HGSIL) or above. Two university hospitals retrospectively reviewed all patients who had HGSIL or above and who had prior negative smears. During 18 months, 35,807 Papanicolaou tests were reported, from which we identified 44 patients with 80 negative smears before presenting with HGSIL or above. These 80 negative smears were rescreened and, on review, there was agreement with the original diagnosis in 66 cases (82.5%). Fourteen (17.5%) smears were reclassified: 2 unsatisfactory, 6 atypical squamous/glandular cells of undetermined significance, 3 low grade SIL, and 3 HGSIL or above. Of the 12 cases satisfactory for reclassification, 9 (75%) occurred within 2 years before the HGSIL or above. Two cases of atypical squamous/glandular cells occurred within 4 years. One case of HGSIL occurred more than 4 years before, but a negative Pap smear had been reclassified within the year before the diagnosis of HGSIL. The authors conclude that a 2-year retrospective review, which identified 75% of our false-negative cases, is an effective and efficient quality control and assurance practice.

A radical demise. Toxins and trauma share common pathways in hair cell death.

The pathologic similarities noted after ototoxic and/or traumatic injury to the cochlea as well as the key features of the cochlea that make it susceptible to reactive oxygen species (ROS) damage are reviewed. Recent evidence linking ROS to cochlear damage associated with both ototoxins and/or trauma are presented. Mechanisms of generation of ROS in the cochlea and how these metabolites damage the cochlea and impair function are also reviewed. Finally, examples of novel therapeutic strategies to prevent and reverse hearing loss due to noise and/or ototoxins are presented to illustrate the clinical relevance of these new findings.

New testing approaches in transfusion medicine.

A revolution has occurred in the availability of molecular diagnostic technology in the last decade. We are just now beginning to bridge the gap between research and the availability of rapidly licensed clinical assays. Many of these new technologies will be useful in the general practice of transfusion medicine. Some of these techniques may be discarded as impractical. However, many of these methods should prove to be useful in clinical transfusion research and diagnosis.

Ocular surface flora in drowning victims.

Contaminated allograft donor tissue represents a potential source of infection unique to keratoplasty. We prospectively studied perilimbal cultures of drowning victims over 30 months to determine if the ocular surface flora of drowning victims was unique. Twenty-eight donor eyes were cultured from 14 drowning victims. Ninety-three percent of limbal cultures were positive for one or more organisms, compared to results of a previous study of surface contamination of donor globes in which 65% were found to be culture positive. Fifty-seven percent (16 of 28) of donor eyes grew at least one streptococcal species, while 46% (13 of 28) grew two or more streptococcal species. A previous study identified streptococcal species in 7.9% of perilimbal cultures from nondrowning donor eyes, which demonstrates the unique effect of drowning on the ocular flora. The incidence of gram-negative isolates was also markedly higher in drowning victims, compared to previous studies of donor globes. This prospective study has shown that the ocular surface flora of drowning victims harbors markedly increased numbers of streptococcal species as well as gram-negative organisms. These findings demand careful globe decontamination, and emphasize the need for appropriate antibiotic coverage in corneal storage media.

Evaluation methods for assessing cytotechnology students' screening skills.

The development of slide screening skills to achieve diagnostic accuracy is the goal of cytotechnology education. There is limited time in the typical cytotechnology training program in which to acquire the didactic knowledge as well as screening experience. It is easier to teach the morphologic criteria necessary to refine diagnostic skills, but more difficult to teach and acquire locator skills. A survey was conducted to document and assess methods of evaluating screening skills utilized by U.S. cytotechnology educational programs. Graduation requirements and grading methods related to slide screening volume and accuracy were provided by survey participants. Current methods are varied, but appear to be effective in assessing diagnostic accuracy and graduate competence. A considerable period of time is required for students to gain enough screening experience to perform at required levels of volume and accuracy.

Bronchoalveolar lavage in the diagnosis of disseminated lung tumors.

We report our experience with bronchoalveolar lavage (BAL) and its value in the diagnosis of malignant lung infiltrates. A total of 162 patients with biopsy- or autopsy-proven cancer had an analysis of BAL fluid performed. Cytologic examination showed malignant cells in 123 (76%) patients. The diagnostic accuracy varied depending on the neoplastic nature and growth pattern of the disease. BAL disclosed cancer cells in 93% of 44 bronchioloalveolar carcinomas. Carcinomatous lymphangitis due to metastatic cancer was diagnosed in 83% of 69 cases. Hematogenous metastases (with sharply circumscribed nodules on chest radiography) were diagnosed in 45% of 22 such cases. We recognized 67% of 15 non-Hodgkin's lymphomas and 3 of 9 cases of Hodgkin's disease with pulmonary involvement. Immunocytochemistry using monoclonal and/or polyclonal antibodies was of value in the identification and classification of cells in non-Hodgkin's lymphoma.

Bronchoalveolar lavage in liver transplant patients.

Because immunosuppression is required to control rejection, liver allograft recipients are susceptible to a variety of opportunistic pathogens. A total of 191 bronchoalveolar lavage (BAL) specimens from 89 patients (53 adults and 36 children) who underwent orthotopic liver transplantation was reviewed. One case each of cytomegalovirus (CMV), staphylococcal and Enterobacter pneumonia was diagnosed with the aid of pretransplant BAL. The pretransplant BAL in 62 patients showed rare yeasts in 24.2%; these probably represent oropharyngeal contaminants since the patients involved had no symptoms of Candida pneumonia. Among 54 patients who developed respiratory symptoms and underwent posttransplant BAL, 23 (42.6%) were infected with opportunistic pathogens, including Pneumocystis carinii (22.2%), CMV (22.2%) and herpes simplex virus (HSV) (7.4%). Frequently, infection with multiple organisms was present. Adults constituted 100% of the HSV-infected group, 69.2% of the CMV-infected group and 16.6% of the group infected with P carinii. The diagnosis of these infections was aided by a combination of cytology, microbial culture and in situ hybridization techniques. Although BAL permitted the diagnosis and treatment of opportunistic infections, high mortality (62.5%) occurred with CMV and HSV pneumonia. Further studies into methods that permit earlier diagnoses of these infections are necessary.

Competency assessment and proficiency testing.

Competency assessment is an ongoing, continuous process of monitoring individuals' abilities to perform their specific job functions. A variety of methods are useful in monitoring cytology competency, including rescreening studies, descriptive monitors (abnormality rates), discrepancy rates, workload patterns, competency-based educational programs and programs using unknown slide challenges. The goal of proficiency testing (PT) is to ascertain and assess the ability of individuals beyond the particular items or challenges presented. However, cytology PT faces many challenges for implementation as it cannot duplicate normal working conditions, and there is often no gold standard to define the truth. PT is just one measure of performance and should be considered in conjunction with other quality assessment monitors. There is no consensus on the value or validity of a large-scale regulatory PT program. Any regulatory PT program should be field tested prior to implementation, and the grading system should be scientifically defensible. Scoring of performance on PT should occur in a timely fashion, and there should be an opportunity for educational feedback. The ultimate aim of both competency assessment and PT is to positively affect laboratory procedures and improve the cervical cancer screening process.

Lower extremity preference during gross and fine motor skills performed in sitting and standing postures.

The evaluation of lower limb preference in physical therapy practice is critical in order for the clinician to assist patients with functional retraining tasks. No studies in the physical therapy literature present a systematic approach to determine the criteria needed to identify the preferred limb. This research was designed to present a series of tests for effectiveness in determining limb preference. The purpose of this study was to determine whether lower limb preference existed in a group of recreationally athletic women when performing either stability or dynamic skills with the lower extremities while sitting or standing. The relationship of such a preference to handedness was also determined. Forty female recreational athletes, 20 right-handed subjects and 20 left-handed subjects, who ranged in age from 21 to 35 years, participated in this study. Subjects performed three repetitions of the following tests in both sitting and standing: kick a ball, swing a leg over a box, pick up a marble with the toes, and trace a triangle with the toes. The subjects were also asked to stand on one leg. The order of performing the tests was randomized. The results indicated that right-handed subjects performed activities more consistently with one lower extremity when compared with left-handed subjects, regardless of posture (sitting or standing). The difference in limb choice between right- and left-handed subjects was significant for all activities (p < .05). The considerable sensitivity of foot and leg performance following neurological insult renders the assessment of foot and leg preference very important for purposes of clinical rehabilitation.

The role of sex and genotype on antiorthostatic suspension effects on the mouse peripheral skeleton.

Previous antiorthostatic suspension studies have used a single sex and strain of rat or mouse. Nonetheless, broadly similar effects of suspension on the two species indicates a generalized effect of suspension not attributed to specific genetic, behavioral, or sex-linked etiology. In order to directly test genetic and sex-linked factors, the effects of suspension on the appendicular bone of male and female BALB-CJ, C57BL-6J, and DBA-2J mice were compared. These genotypes were selected based on their widely different developmental and behavioral characteristics as well as on past research involving a heterogeneous strain derived from these strains. The effects of suspension on the geometric, mechanical, and material properties of the femora, humeri, and tibiae were determined. Among the bone types, the femora were most significantly affected by suspension. The effects of suspension were similar in nature in male and female mice aged 1.7 months. Strain-dependent suspension effects may be indicative of bone developmental differences in the strains at the age chosen.

Bronchoalveolar lavage in the diagnosis of low-grade, MALT type, B-cell lymphoma in the lung.

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type represents one of the most frequent primary lymphomas in the lung. This study demonstrates the value of bronchoalveolar lavage (BAL) in the diagnosis of this entity. Three patients with biopsy proven MALT lymphoma in the lung were submitted to bronchoscopy. BAL fluid analysis showed an increased cellularity and a striking lymphocytosis. Cytological features consistent with a low-grade malignant lymphoma were present in two cases (medium sized lymphoid cells with an evident lymphoplasmocytoid differentiation, and irregular nuclear borders). In all cases, flow cytometry analysis showed a high percentage of cells expressing a B phenotype (52, 40 and 28%, respectively). In two cases, there was a striking monotypic expression of surface light-chain immunoglobulin (Kappa/Lambda ratio = 38 and 0.04, respectively). Bronchoalveolar lavage appears to be a valuable procedure in the diagnosis of low-grade B-cell lymphoma of MALT type in the lung.