Responder analysis confirms results of a stroke transitional care trial but provides more interpretable results.

OBJECTIVES: Interpreting between-group differences in patient-reported outcome measures can be challenging. Responder analyses, which compare the proportions of patients who achieve a meaningful clinical change, represent a more interpretable approach. We conducted a secondary responder analysis of the Michigan Stroke Transitions Trial (MISTT). STUDY DESIGN AND SETTING: The MISTT randomized 265 patients with stroke to three treatment groups: usual care [UC], social work case management [SWCM], or social work case management plus access to a patient-oriented website [SWCM + website]. Two Patient-Reported Outcomes Measurement and Information System (PROMIS) Global-10 subscales (representing physical and mental health) and 5 additional patient-reported outcomes were collected at baseline and 90-days. Responder analyses were conducted using modified Poisson and linear regression using published minimal important differences. Multiple imputation was used to address missing data. RESULTS: For the PROMIS-10 global physical health subscale, responders were 80% more common in the SWCM + website group compared to the UC group (relative risk = 1.8, 95% confidence interval [CI]: 1.0, 3.1), with a number needed to treat of 7 (95% CI: 3, 112). No significant treatment effects were observed for the PROMIS-10 global mental health subscale. CONCLUSION: Results of this responder analysis were largely consistent with the original trial analysis but have the advantage of presenting treatment effects using more clinically interpretable number needed to treat metrics.

Effect of transitional care stroke case management interventions on caregiver outcomes: the MISTT randomized trial.

This study reports on outcomes for 169 caregivers enrolled in the Michigan Stroke Transitions Trial (MISTT), an RCT of social work case management for stroke patients returning home. A mixed-model approach examined the mean change from 7- to 90-days post-discharge with group-by-time interactions for differences between treatment groups. Caregivers reported few life changes or depressive symptoms from caregiving. There was no significant change over time or treatment effects. Negative aspects of stroke caregiving may take longer to develop. Focused caregiver assessment at discharge and a better understanding of how caregiving develops over time may improve the type and timing of support.

Changes in PHQ-9 depression scores in acute stroke patients shortly after returning home.

INTRODUCTION: Post-stroke depression is a disabling condition that occurs in approximately one-third of stroke survivors. There is limited information on changes in depressive symptoms shortly after stroke survivors return home. To identify factors associated with changes in post-stroke depressive symptoms during the early recovery period, we conducted a secondary analysis of patients enrolled in a clinical trial conducted during the transition period shortly after patients returned home (MISTT). METHODS: The Michigan Stroke Transitions Trial (MISTT) tested the efficacy of social worker case management and access to online information to improve patient-reported outcomes following an acute stroke. Patient Health Questionnaire-9 (PHQ-9) scores were collected via telephone interviews conducted at 7 and 90 days post-discharge; higher scores indicate more depressive symptoms. Generalized estimating equations were used to identify independent predictors of baseline PHQ-9 score at 7 days and of changes over time to 90 days. RESULTS: Of 265 patients, 193 and 185 completed the PHQ-9 survey at 7 and 90 days, respectively. The mean PHQ-9 score was 5.9 at 7 days and 5.1 at 90 days. Older age, being unmarried, and having moderate stroke severity (versus mild) were significantly associated with lower 7-day PHQ-9 scores (indicating fewer depressive symptoms). However, at 90 days, both unmarried patients and those with moderate or high stroke severity had significant increases in depressive symptoms over time. CONCLUSIONS: In stroke patients who recently returned home, both marital status and stroke severity were associated with depressive symptom scores; however, the relationships were complex. Being unmarried and having higher stroke severity was associated with fewer depressive symptoms at baseline, but both factors were associated with worsening depressive symptoms over time. Identifying risk factors for changes in depressive symptoms may help guide effective management strategies during the early recovery period.

Opening Pandora's Box: From Readmissions to Transitional Care Patient-Centered Outcome Measures.

BACKGROUND: Measuring the effectiveness of transitional care interventions has historically relied on health care utilization as the primary outcome. Although the Care Transitions Measure was the first outcome measure specifically developed for transitional care, its applicability beyond the hospital-to-home transition is limited. There is a need for patient-centered outcome measures (PCOMs) to be developed for transitional care settings (ie, TC-PCOMs) to ensure that outcomes are both meaningful to patients and relevant to the particular care transition. The overall objective of this paper is to describe the opportunities and challenges of integrating TC-PCOMs into research and practice. METHODS AND RESULTS: This narrative review was conducted by members of the Patient-Centered Outcomes Research Institute (PCORI) Transitional Care Evidence to Action Network. We define TC-PCOMs as outcomes that matter to patients because they account for their individual experiences, concerns, preferences, needs, and values during the transition period. The cardinal features of TC-PCOMs should be that they are developed following direct input from patients and stakeholders and reflect their lived experience during the transition in question. Although few TC-PCOMs are currently available, existing patient-reported outcome measures could be adapted to become TC-PCOMs if they incorporated input from patients and stakeholders and are validated for the relevant care transition. CONCLUSION: Establishing validated TC-PCOMs is crucial for measuring the responsiveness of transitional care interventions and optimizing care that is meaningful to patients.

Presumed neuroprotective therapies prescribed by veterinary ophthalmologists for canine degenerative retinal and optic nerve diseases.

OBJECTIVE: To investigate veterinary ophthalmologists' use of presumed neuroprotective therapies for degenerative retinal and optic nerve diseases in dogs. PROCEDURES: An online survey was sent to 663 board-certified veterinary ophthalmologists who were Diplomates of the American College of Veterinary Ophthalmologists (ACVO), Asian College of Veterinary Ophthalmologists (AiCVO), Latin American College of Veterinary Ophthalmologists (Colegio Latinoamericano de Oftalmólogos Veterinarios, CLOVE), or European College of Veterinary Ophthalmologists (ECVO). The survey was created using Qualtrics® software and focused on the prescription of presumed neuroprotective treatments for canine glaucoma, sudden acquired retinal degeneration syndrome (SARDS), progressive retinal atrophy (PRA), and retinal detachment (RD). RESULTS: A total of 165 completed surveys were received, representing an overall response rate of 25%, which was comparable across the four specialty colleges. Of all respondents, 140/165 (85%) prescribed some form of presumed neuroprotective therapies at least once in the last five years: 114/165 (69%) for glaucoma, 51/165 (31%) for SARDS, 116/165 (70%) for PRA, and 50/165 (30%) for RD. The three most recommended neuroprotective reagents were the commercial Ocu-GLO™ Vision Supplement for animals, amlodipine, and human eye supplements. CONCLUSIONS: Despite lack of published clinical efficacy data, the majority of surveyed board-certified veterinary ophthalmologists previously prescribed a presumed neuroprotective therapy at least once in the last five years in dogs with degenerative retinal and optic nerve diseases.

Unmet Needs of US Acute Stroke Survivors Enrolled in a Transitional Care Intervention Trial.

BACKGROUND: Needs of patients that go unmet after a stroke can compromise the speed and extent of recovery. While unmet needs in long-term survivors has been studied, less is known about the unmet needs of acute stroke survivors. We examine unmet needs in the immediate postdischarge period among 160 participants in the (blinded for review) a transitional care intervention conducted in (blinded for review [1 US state]) during 2016 and 2017. METHODS: Bivariate and multivariate analyses using Poisson models were used to examine the relationship between total number of unmet needs and demographics, stroke type and severity, stroke effects, and stroke risk factors. RESULTS: The mean number of unmet needs was 4.55; number of unmet needs ranged from 2 to9; all participants had some unmet need. The most common unmet needs were stroke education (73.8%), financial (33.8%), and health-related (29.4%). In the final multivariate model income and education were inversely associated with number of unmet needs. As total number of stroke effects increased, so did number of unmet needs. Demographic variables (age, gender, and race), stroke risk factors, stroke type, and stroke severity were not statistically significantly associated with the number of unmet needs. CONCLUSIONS: These results identify that in the acute post discharge period stroke survivors have many unmet needs that range from physical to psychosocial. Targeting interventions to those with the potential for greater numbers of unmet needs might be a salient clinical approach to improving stroke recovery and rehabilitation.

Michigan Stroke Transitions Trial.

BACKGROUND: To test whether access to home-based social worker-led case management (SWCM) program or SWCM program combined with a website providing stroke-related information improves patient-reported outcomes in patients with stroke, relative to usual care. METHODS AND RESULTS: The MISTT (Michigan Stroke Transitions Trial), an open (unblinded) 3-group parallel-design clinical trial, randomized 265 acute patients with stroke to 3 treatment groups: Usual Care (group-1), SWCM (group-2), and SWCM+MISTT website (group-3). Patients were discharged directly home or returned home within 4 weeks of discharge to a rehabilitation facility. The SWCM program provided in-home and phone-based case management services. The website provided patient-orientated information covering stroke education, prevention, recovery, and community resources. Both interventions were provided for up to 90 days. Outcomes data were collected by telephone at 7 and 90 days. Primary patient-reported outcomes included Patient-Reported Outcomes Measurement Information System Global-10 Quality-of-Life (Physical and Mental Health subscales) and the Patient Activation Measure. Treatment efficacy was determined by comparing the change in mean response (90 days minus 7 days) between the 3 treatment groups using a group-by-time interaction. Subjects were aged 66 years on average, 49% were female, 21% nonwhite, and 86% had ischemic stroke. There were statistically significant changes in Patient-Reported Outcomes Measurement Information System Physical Health ( P=0.003) and Patient Activation Measure ( P=0.042), but not Patient-Reported Outcomes Measurement Information System Mental Health ( P=0.56). The mean change in Patient-Reported Outcomes Measurement Information System Physical Health scores for group-3 (SWCM+MISTT Website) was significantly higher than both group-2 (SWCM; difference, +2.4; 95% CI, 0.46-4.34; P=0.02) and group-1 (usual care; difference, +3.4; 95% CI, 1.41-5.33; P<0.001). The mean change in Patient Activation Measure scores for group-3 was significantly higher than group-2 (+6.7; 95% CI, 1.26-12.08; P=0.02) and marginally higher than group-1 (+5.0; 95% CI, -0.47 to 10.52; P=0.07). CONCLUSIONS: An intervention that combined SWCM with access to online stroke-related information produced greater gains in patient-reported physical health and activation compared with usual care or case management alone. There was no intervention effect on mental health. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02653170.

Congenital laryngeal paralysis in Alaskan Huskies: 25 cases (2009-2014).

OBJECTIVE To characterize congenital laryngeal paralysis (CLP) in Alaskan Huskies. DESIGN Prospective case series. ANIMALS 25 Alaskan Huskies with CLP. PROCEDURES Data were collected for each dog regarding signalment; history; results of physical, orthopedic, neurologic, and laryngeal examinations; esophagraphic findings; treatments; histologic findings; and outcomes. RESULTS Severely affected dogs were profoundly dyspneic at birth or collapsed after brief exercise; less affected dogs reportedly tired easily or overheated with minimal exercise. Mean age at initial onset of clinical signs was 6.4 months. Blue eyes, white facial markings, and oral mucosal tags or tissue bands were noted in 23 (92%), 19 (76%), and 13 (52%) dogs. Neurologic examination revealed signs of mononeuropathy of the recurrent laryngeal nerve but not of polyneuropathy. Histologic examination revealed neurogenic atrophy of the cricoarytenoideus dorsalis muscle but no polyneuropathy. Eight (32%) dogs underwent unilateral cricoarytenoid lateralization, resulting in substantial clinical improvement, including ability to compete in sled dog races. Without surgery, 4 (16%) dogs died of asphyxiation, 10 (40%) had spontaneous improvement of clinical signs (but insufficient improvement to race), and 3 (12%) remained affected. Results of pedigree analysis suggested an autosomal recessive mode of CLP inheritance, with variable penetrance. CONCLUSIONS AND CLINICAL RELEVANCE CLP in the evaluated Alaskan Huskies involved mononeuropathy of the recurrent laryngeal nerves, without polyneuropathy. Most affected dogs had blue eyes, white facial markings, and oral mucosal tags or tissue bands. Given the apparent genetic component to CLP in this breed, we recommend that dogs with these features be prevented from breeding.

ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.

BACKGROUND: Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. METHODS: ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. RESULTS: ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. CONCLUSIONS: This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of concept for ATR-101 as a novel agent for the treatment of endocrine disorders like Cushing's syndrome in humans.

Improving stroke transitions: Development and implementation of a social work case management intervention.

Strokes impact over 800,000 people every year. Stroke care typically begins with inpatient care and then continues across an array of healthcare settings. These transitions are difficult for patients and caregivers, with psychosocial needs going unmet. Our team developed a case management intervention for acute stroke patients and their caregivers aimed at improving stroke transitions. The intervention focusses on four aspects of a successful care transition: support, preparedness, identifying and addressing unmet needs, and stroke education. This paper describes the development and implementation of this program, and is an example of the synergy created between neuroscience and clinical practice.

Improving transitions in acute stroke patients discharged to home: the Michigan stroke transitions trial (MISTT) protocol.

BACKGROUND: For some stroke patients and caregivers, navigating the transition between hospital discharge and returning home is associated with substantial psychosocial and health-related challenges. Currently, no evidence-based standard of care exists that addresses the concerns of stroke patients and caregivers during the transition period. Objectives of the Michigan Stroke Transitions Trial (MISTT) are to test the impact of a social worker home-based case management program, as well as an online information and support resource, on patient and caregiver outcomes after returning home. METHODS: The Michigan Stroke Transitions Trial is a randomized, pragmatic, open (un-blinded), 3-group parallel designed superiority trial conducted in 3 Michigan hospitals. Eligible participants are adult acute stroke patients discharged home directly or within 4 weeks of being discharged to a rehabilitation facility. The patient's primary caregiver is also invited to participate. Patients are randomized on the day they return home using a randomized block design. Consented patients discharged to a rehabilitation facility who do not go home within 4 weeks are dropped from the study. The 2 study interventions begin within a week of returning home and conclude 3 months later. The 3-group design compares usual care to either a home-based social worker stroke case management (SWSCM) program, or a combination of the SWSCM program plus access to an online information and support resource (MISTT website). Outcomes data are collected at 7-days and 90-days by trained telephone interviewers. Primary patient outcomes include the PROMIS global 10 score (a generic Quality of Life scale), and the Patient Activation Measure (PAM). Caregiver outcomes include the Bakas Caregiving Outcomes Scale. Final analysis will be based on 214 randomized acute stroke patients. To accommodate subjects excluded due to prolonged rehabilitation stays, as well as those lost-to-follow-up, up to 315 patients will be consented. DISCUSSION: The MISTT study will determine if a home-based case management program designed around the needs and preferences of stroke patients and caregivers, alone or in combination with a patient-centered online information and support resource can improve stroke survivor and caregiver outcomes 3 months after returning home. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02653170 (Protocol ID: 135457). Registered April 9, 2015.

Effects of prophylactic incisional gastropexy on markers of gastric motility in dogs as determined by use of a novel wireless motility device.

OBJECTIVE To evaluate effects of laparoscopic-assisted incisional gastropexy (LAIG) on gastric motility in dogs by use of a wireless motility device (WMD). ANIMALS 10 healthy client-owned large or giant-breed dogs. PROCEDURES 10 dogs owned by clients interested in prophylactic LAIG were enrolled. To determine effects of LAIG on gastrointestinal motility in dogs during the nonfed state, each dog was evaluated by use of a noninvasive WMD before and > 4 weeks after LAIG. All dogs underwent LAIG, with or without concurrent elective gonadectomy. Data obtained before and after LAIG were analyzed by use of proprietary software to determine the gastric emptying time, small bowel transit time, large bowel transit time, whole bowel transit time, and motility index. RESULTS No changes in variables were detected between measurements obtained before and after prophylactic LAIG. CONCLUSIONS AND CLINICAL RELEVANCE In this study, prophylactic LAIG did not have an effect on gastrointestinal motility. The WMD was tolerated well by all dogs and appeared to be a safe and effective method for evaluating gastrointestinal motility in this population of dogs.

The Effect of Low-Level Laser Therapy on the Healing of Open Wounds in Dogs.

OBJECTIVE: To evaluate the effects of low-level laser therapy (LLLT) on acute, full-thickness wound healing in dogs. STUDY DESIGN: Randomized block (dog); historical control. ANIMALS: Adult male Beagles (n = 10). METHODS: Two 2 × 2 cm(2) wounds were surgically created bilaterally on the trunk of each dog. Each side was randomized to receive LLLT (laser, LAS) or standard-of-care management (control, CON), 3 times weekly for 32 days. The LLLT consisted of a dual diode laser (7.5 mW/diode) at 635 nm and total energy density of 1.125 J/cm(2). Wound planimetry was performed on the caudal wounds, from which percent contraction and percent epithelialization were calculated. Histologic features were evaluated at 7 time points from cranial wound biopsies. Experimental data were also compared to wounds from a historical female control cohort (historical control, HCON). RESULTS: There was no difference between LAS and CON wounds for all parameters, including histology. The HCON wounds had significantly greater contraction and epithelialization compared to LAS and CON wounds. The LAS and CON wounds had significantly less inflammation than HCON wounds early in wound healing, but inflammation was significantly greater in LAS and CON wounds by day 21. Fibroblast infiltration and collagen deposition were significantly less in LAS and CON wounds than HCON wounds. CONCLUSION: There are no apparent beneficial effects of LLLT on the healing of acute wounds in healthy dogs using this LLLT protocol. Gender may influence wound healing in intact dogs.

Effects of negative pressure wound therapy on healing of free full-thickness skin grafts in dogs.

OBJECTIVE: To compare healing of free, full-thickness, meshed skin grafts under negative pressure wound therapy (NPWT) with bolster dressings in dogs. STUDY DESIGN: Randomized, controlled experimental study, paired design. ANIMALS: Dogs (n = 5) METHODS: Full-thickness skin wounds (4 cm × 1.5 cm) were created bilaterally on the antebrachia of 5 dogs (n = 10). Excised skin was grafted to the contralateral limb. Grafts were randomized to NPWT or bolster dressings (control; CON). NPWT was applied continuously for 7 days. Grafts were evaluated on Days 2, 4, 7, 10, 14, and 17, biopsied on days 0, 4, 7, and 14, and had microbial culture on Day 7. Outcome variables were: time to first appearance of granulation tissue, percent graft necrosis, and percent open mesh. Significance was set at P < .05. Histologic findings, culture results, and graft appearance were reported. RESULTS: Granulation tissue appeared earlier in the NPWT grafts compared with CON grafts. Percent graft necrosis and remaining open mesh area were both greater in CON grafts compared with NPWT grafts at most time points. Histologic results showed no significant difference in all variables measured, and all cultures were negative. CONCLUSIONS: Variables of graft acceptance were superior when NPWT was used in the first week post-grafting. Fibroplasia was enhanced, open meshes closed more rapidly and less graft necrosis occurred with NPWT application. More preclinical studies are required to evaluate histologic differences.

Effects of a cross-linked hyaluronic acid based gel on the healing of open wounds in dogs.

OBJECTIVE: To compare effects of a cross-linked hyaluronic acid (HA) based gel (CMHA-S) to a standard wound management protocol on the healing of acute, full-thickness wounds in dogs. STUDY DESIGN: A prospective, controlled, experimental study. ANIMALS: Purpose-bred, adult, female beagles (n = 10). METHODS: Two 2 × 2 cm wounds were surgically created bilaterally on the trunk of each dog and each side randomized to treatment (CMHA-S) or control (CON) groups. Total and open wound areas were measured with digital image planimetry at 15 time points. From these data, percent contraction and percent epithelialization were calculated. Tissue biopsies were obtained at 6 time points and histologic features were scored. RESULTS: Total wound area was significantly larger and percent contraction was significantly less in CMHA-S compared to CON wounds at all data points between days 9 and 18. At day 25, and for the remainder of the study, CMHA-S wounds were smaller and contracted more than CON wounds, reaching significance at day 32. Percent epithelialization was significantly less in CMHA-S compared to CON wounds at all data points after day 11. Histologically, fibroblastic cellular infiltration was significantly higher in CMHA-S wounds at day 21. CONCLUSIONS: CMHA-S wounds healed more slowly than CON wounds. This HA-based gel is not indicated in acute, full-thickness skin wounds in dogs as administered in this study. However, treatment may be beneficial in the mid-to-late repair stage of healing, or if scar minimization is desired. Further studies to evaluate the effects of the CMHA-S gel on canine wounds are indicated.

Effects of negative pressure wound therapy on healing of open wounds in dogs.

OBJECTIVE: To compare the effect of negative pressure wound therapy (NPWT) with standard-of-care management on healing of acute open wounds in dogs. STUDY DESIGN: Prospective, controlled, experimental study. ANIMALS: Adult dogs (n=10). METHODS: Full-thickness 4 m × 2 m wounds were surgically created on each antebrachium and in each dog were randomized to receive either NPWT or standard wound dressings (CON) for 21 days. Dressing changes and wound evaluations were made at 8 time points. First appearance of granulation tissue, smoothness of granulation tissue, exuberance, percent epithelialization, and percent contraction were compared. Biopsies for histopathology were taken, and histologic scores determined, at 5 time points, and aerobic bacterial wound cultures performed at 2 time points. RESULTS: Granulation tissue appeared significantly earlier, and was smoother and less exuberant in NPWT wounds compared with CON wounds. Percent contraction in NPWT wounds was less than CON wounds after Day 7. Percent epithelialization in NPWT wounds was less than CON wounds on Days 11, 16, 18, and 21. Histologic scores for acute inflammation were higher in NPWT on Day 3, and lower on Day 7, than CON wounds. Bacterial load was higher in NPWT on Day 7. CONCLUSION: NPWT accelerated appearance of smooth, nonexuberant granulation tissue; however, prolonged use of NPWT impaired wound contraction and epithelialization.