Objective
To evaluate the outcomes and complications of video‐assisted thoracoscopic (VATS) treatment of chylothorax in cats.
Study design
Multi‐institutional retrospective study.
Animals
Fifteen ...client‐owned cats.
Methods
The medical records of cats undergoing thoracoscopic thoracic duct ligation (TDL) for treatment of idiopathic chylothorax were reviewed. Cats undergoing additional procedures including thoracoscopic pericardectomy and/or laparoscopic cisterna chyli ablation (CCA)_were included. Follow up was obtained through communication with the referring veterinarian or owner.
Results
All cats underwent thoracoscopic TDL. Thirteen cats underwent simultaneous pericardectomy and two cats underwent laparoscopic CCA without pericardectomy. Conversion from a thoracoscopic to open approach was necessary in 2/15 (13%) of thoracic duct ligations and 1/11 (9%) of pericardectomies. The most common postoperative complication was persistent pleural effusion in five cats (33%). Four of 15 cats (27%) died or were euthanized prior to hospital discharge following surgery. Recurrence of effusion occurred in 1/7 (14%) of cats that sustained resolution of the effusion at the time of surgery with a median follow up of 8 months. The overall mortality attributed to chylothorax was 47%.
Conclusion
Thoracoscopic treatment of idiopathic chylothorax resulted in a low incidence of intraoperative complications or conversion in the study population; however, mortality related to feline idiopathic chylothorax remained high.
Clinical significance
While VATS treatment of idiopathic chylothorax is technically feasible, further consideration of the underlying pathology and current treatment algorithm is needed to improve outcomes as this remains a frustrating disease to treat in the feline population.
Reports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients' and caregivers' views on the clinical ...relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE).
First, we used focus groups including SMA patients and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment on the clinical relevance of possible changes of HFMSE scores over time. As functional data of individual patients were available, some of the questions were tailored according to their functional level on the HFMSE.
Part 1: Sixty-three individuals participated in the focus groups. This included 30 caregivers, 25 patients and 8 professionals who facilitated the discussion. The caregivers provided a comparison to activities of daily living for each of the HFMSE items. Part 2: One hundred and forty-nine caregivers agreed to complete the questionnaire: in response to a general question, 72% of the caregivers would consider taking part in a clinical trial if the treatment was expected to slow down deterioration, 88% if it would stop deterioration and 97% if the treatment was expected to produce an improvement. Caregivers were informed of the first three items that their child could not achieve on the HFMSE. In response 75% indicated a willingness to take part in a clinical trial if they could achieve at least one of these abilities, 89% if they could achieve two, and 100% if they could achieve more than 2.
Our findings support the use of the HFMSE as a key outcome measure in SMA clinical trials because the individual items and the detected changes have clear content validity and clinical meaningfulness for patients and their caregivers.
Mutations in GBA1, which encodes the lysosomal acid beta-glucosidase (GCase), cause GCase deficiency in Gaucher disease (GD) and is the most common genetic risk factor for Parkinson disease (PD). ...There are no effective treatments available for neuronopathic GD and PD that can stop or slow neurodegeneration. In this study, we evaluated a novel non-invasive cell transplantation therapy in a GD mouse model (9H/PS-NA) exhibiting alpha-synuclein aggregation, a key PD-relevant phenotype. A subclass of iPSC-derived neural progenitor cells (NPCs) expresses VLA4 which allows systemically-delivered NPCs to cross the blood-brain-barrier. We established VLA4+ mouse iPSC-derived NPCs harboring lentiviral-mediated overexpression of wild-type human GCase (hGCase). In-vitro, VLA4+ hGCase+ NPCs were expandable without loss of multipotency and secreted GCase which was taken up by lysosomes of adjacent Gba1-null cells. In-vivo efficacy was evaluated in 9H/PS-NA mice. VLA4+ hGCase+ NPCs were intravenously administered by weekly tail-vein injection and mice were analyzed at 14 weeks of age for effects on neuropathic and PD phenotypes. Injected cells engrafted throughout the brain, including thalamus, cortex, brainstem and midbrain, and differentiated into neural lineages. Human GCase protein was detected in the transplanted mouse brains with specific anti-human GCase antibody. Histological analyses of brain sections showed reduced neurodegeneration by Fluoro-Jade C staining in the regions of NPC migration. CNS inflammation, detected by anti-CD68 and anti-GFAP antibodies, was significantly decreased in the brain of transplanted mice. Compared to vehicle treated mice, VLA4+ hGCase+ NPC-transplanted mice showed ~50% reduction of α-synuclein aggregates in the substantia nigra. Together, these results demonstrate the efficacy of non-invasive delivery of iPSC-derived NPCs overexpressing hGCase in GD mouse model and establish the feasibility of combined cell and gene therapy for GBA1-associated PD. This approach provides a potential treatment for both rare and common neurological diseases.
Objective
We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim ...of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status.
Methods
HFMSE longitudinal changes were assessed using piecewise linear mixed‐effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12‐month assessments.
Results
A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = −1.15, p < 0.0001) and IIIB (β = −0.69, p = 0.002).
Interpretation
Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real‐world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109–1117
Considering the critical role that American Indian and Alaska Native (Native) men play in family and child health, there is an urgent need to collaborate with Native communities in developing ...interventions and policies to improve Native men's health status. This study aims to address a significant gap in research by designing and implementing a culturally grounded health promotion program to increase economic stability, promote positive parenting, and build healthy relationships among Native fathers. The Azhe'é Bidziil ("Strong Fathers") study protocol, developed in response to community advisory board feedback, illustrates a community-engaged approach to developing and implementing a fatherhood program in two Diné (Navajo) communities.
Azhe'é Bidziil was adapted from three evidence-based interventions developed in collaboration with Native communities. Intervention lessons were iteratively reviewed by a tribal working group to ensure that the content is culturally appropriate and relevant. A pre-post study will assess feasibility, acceptability, and satisfaction with the Azhe'é Bidziil intervention, as well as short-term impacts on positive parenting, economic stability, and healthy relationship outcomes. The intervention is composed of 12 weekly group sessions conducted with fathers (
= 750) that focus on developing knowledge and skills for positive father involvement, economic stability, and healthy relationships. Lesson content includes: honoring our roles as fathers, building healthy relationships, understanding the impact of historical trauma, goal-setting, and budgeting basics. Each of the 12 group lessons, consisting of 8-12 participants per group, last approximately 2 h. Eligible fathers or father figures are age ≥18 years, live within 50 miles of the participating Diné communities, and must be caregivers of at least one child ≤ 24 years. The outcomes for this study are acceptability, feasibility, and satisfaction with the intervention, as well as father involvement, quality of (co-) parenting communication, healthy relationships, fathers' engagement and communication with their children, protective factors (e.g., cultural connectedness and educational/career aspirations), and economic empowerment and stability. Participants will complete an outcome assessment at pre- and post-intervention (12 weeks later).
This study protocol presents one of the few evaluations of a fatherhood intervention to increase economic stability, promote positive parenting, and build healthy relationships among Native fathers in rural tribal communities. Such a study is sorely needed to address the health disparities perpetuated by social and Indigenous determinants of health that Native men experience today. If proven efficacious, this pre- post-study will inform a large scale randomized controlled trial to evaluate intervention impact, and if proven efficacious may be disseminated widely in tribal nations. Study findings may also deepen our understanding of peer mentoring, Native men's health status, involvement with their children, co-parenting relationships, family relationships, cultural connectedness, and economic status. The data collected may also inform strategies to ensure acceptability, feasibility, and satisfaction of an intervention designed specifically for Native fathers.
To determine whether pentoxifylline (PTX) slows the decline of muscle strength and function in ambulatory boys with Duchenne muscular dystrophy (DMD).
This was a multicenter, randomized, ...double-blinded, controlled trial comparing 12 months of daily treatment with PTX or placebo in corticosteroid-treated boys with DMD using a slow-release PTX formulation (~20 mg/kg/day). The primary outcome was the change in mean total quantitative muscle testing (QMT) score. Secondary outcomes included changes in QMT subscales, manual muscle strength, pulmonary function, and timed function tests. Outcomes were compared using Student t tests and a linear mixed-effects model. Adverse events (AEs) were compared using the Fisher exact test.
A total of 64 boys with DMD with a mean age of 9.9 ± 2.9 years were randomly assigned to PTX or placebo in 11 participating Cooperative International Neuromuscular Research Group centers. There was no significant difference between PTX and the placebo group in total QMT scores (p = 0.14) or in most of the secondary outcomes after a 12-month treatment. The use of PTX was associated with mild to moderate gastrointestinal or hematologic AEs.
The addition of PTX to corticosteroid-treated boys with DMD at a moderate to late ambulatory stage of disease did not improve or halt the deterioration of muscle strength and function over a 12-month study period.
This study provides Class I evidence that treatment with PTX does not prevent deterioration in muscle function or strength in corticosteroid-treated boys with DMD.
Little is known about the need and demand for integrated reproductive health and HIV services at the population level.
Descriptive data analysis of household surveys collected by the Integra ...Initiative.
Household surveys were conducted among 18-49-year-olds in Kenya (N = 1752) and Swaziland (N = 779) in 2009. Data on fertility intentions, contraceptive use, sexual behaviours and HIV testing were used to determine unmet needs. Demand for integrated services was defined as wanting reproductive health services with HIV/sexually transmitted infection (STI) services within one visit.
At the population level, family planning needs (90%) were higher than HIV/STI prevention needs: 53% (women) and 75% (men). Fewer had unmet family planning needs through non-use of contraceptives: 17% (women) and 27% (men); versus unmet HIV/STI prevention needs through inconsistent condom use: 48 and 26% of women; 51 and 32% of men in Kenya and Swaziland, respectively. Dual need was higher for men: 64% (Kenya) and 73% (Swaziland) versus women (48%) with more unmet in Kenya (43%) compared to Swaziland (25%). Missed opportunities for integrated service provision were high among women: 49 and 57% with unmet family planning needs; and 55 and 32% with unmet HIV/STI prevention needs in Kenya and Swaziland, respectively, used services, but did not receive the needed service. Most men with unmet needs were non-service users. Approximately a quarter of women wanted and received integrated reproductive health-HIV/STI services in both countries.
Demand creation at the community level and provider-initiated integrated service provision are needed, using different strategies for men and women, to address substantial family planning and HIV/STI prevention needs.
Ensuring high quality care for persons with diabetes remains a challenge for healthcare systems globally with consistent evidence of suboptimal care and outcomes. There is increasing interest in ...quality improvement strategies to improve diabetes management as reflected by a growing number of systematic reviews. These reviews are of varying quality and dispersed across many sources. In this paper, we present an overview of systematic reviews evaluating the impact of interventions to improve the quality of diabetes care.
We searched for systematic reviews evaluating the effectiveness of any intervention intended to improve intermediate patient outcomes and process of care measures for patients with any type of diabetes. Two reviewers independently screened search results, appraised each systematic review using AMSTAR and extracted data from high quality reviews (AMSTAR score ≥ 5). Within reviews, we used vote counting by direction of effect to report the number of studies favouring an intervention for each outcome. We produced summaries of results for each intervention category.
We identified 125 reviews of varying methodological quality and summarised key findings from 50 high quality reviews. We categorised reviews by quality improvement intervention. Eight reviews were broad based (involving a variety of strategies). Other reviews considered: patient education and support (n = 21), telemedicine (n = 10), provider role changes (n = 7), and organisational changes (n = 4). Reviews reported intermediate patient outcomes (e.g. glycaemic control) (n = 49) and process of care outcomes (n = 9). There was evidence of considerable overlap of included studies between reviews.
There is consistent evidence from high quality systematic reviews that patient education and support, provider role changes, and telemedicine are associated with improvements in glycaemic and vascular risk factor control in patients. There is less evidence about the impact of quality improvement interventions on other key process measures such as screening patients for diabetic complications. This paper provides decision makers with a comprehensive overview of evidence from high quality systematic reviews about the effects of quality improvement interventions on improving diabetes care.
Patient or user engagement with health and social care interventions is receiving increased attention and interest within practice settings and research. An English evaluation of three reablement ...services wished to include a measure of user‐engagement so as to explore its association with outcomes. As no measure of reablement engagement existed, an existing measure designed for use with physical rehabilitation patients (the Hopkins Rehabilitation Engagement Rating Scale) was adapted and its psychometric properties were tested. The adapted version was completed by reablement staff at the time an individual (n = 129) was discharged from one of the three reablement services. Outcomes data (Barthel Index, Nottingham Extended Activities of Daily Living Scale, General Health Questionnaire‐12) collected by the evaluation study at baseline (that is, at entry into reablement), discharge and 6 months postdischarge was used for some psychometric testing. Internal consistency and construct, predictive and discriminant validity were investigated. The adapted scale measured a single construct and had good internal consistency. Tests of predictive and discriminant validity were positive. Findings from a separate, small‐scale (n = 31) test–retest study offer an early indication that this is acceptable. There was, however, evidence of a ceiling effect and we consider ways this may be ameliorated. The Hopkins Rehabilitation Engagement Rating Scale – Reablement Version offers a means by which user engagement in reablement can be measured using a staff‐completed instrument. The association between engagement and reablement outcomes, revealed when testing for predictive validity, supports the argument for greater attention and investment in research on user engagement in reablement. More broadly, researching engagement within the context of an intervention often delivered by multiple practitioners offers the opportunity to further understand this concept which, in the past, has particularly focused on interventions delivered by a single practitioner. In addition, future work should include developing a companion measure completed by service users.
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