Comparative Investigation of pH-Dependent Availability of Pancreatic Enzyme Preparations In Vitro.

This study aimed to compare different pancreatic enzyme preparations (PEPs) available in Germany regarding particle geometry and size, and to evaluate enzyme activity under physiologically relevant conditions in vitro. Pancreatic endocrine insufficiency is characterized by deficiency of pancreatic enzymes resulting in maldigestion. It is orally treated by pancreatic enzyme replacement therapy. The formulations differ in their physical properties and enzyme release behavior, potentially resulting in inconsistent dosages and poor interchangeability of products. A total of 25 products were analyzed for particle size and number of particles per capsule. Enzyme activities of lipase, amylase, and protease were measured by digestion of olive oil emulsion, starch, and casein, respectively. To analyze enzyme release, gastric environments were simulated by incubating PEPs at pH 1, 4, or 5. Duodenal conditions were simulated by subsequent incubation at pH 6. Regarding physical properties and enzyme release kinetics, considerable differences between different PEPs were found. Furthermore, compared to the label claim, excess lipase activity was observed for most products, reaching up to 148%. These in vitro results suggest poor interchangeability of PEPs, potentially explained by physical and release characteristics. Physicians and patients should be aware of the potential gap between label claims and the real-life performance of different PEPs.

Activity and Participation, Bimanual Function, and Prosthesis Satisfaction are Strong Predictors of General Well-Being Among Upper Limb Prosthesis Users.

Objective: To determine the role of multiple factors on general well-being for upper limb prosthesis users. Design: Retrospective cross-sectional observational design. Setting: Prosthetic clinics across the United States. Participants: At the time of analysis, the database consisted of 250 patients with unilateral upper limb amputation seen between July 2016 and July 2021. Intervention: Not applicable. Main Outcomes Measures: Dependent variable: well-being (Prosthesis Evaluation Questionnaire- Well-Being). Independent variables included in analysis: activity and participation (Patient Reported Outcomes Measurement Information System [PROMIS] Ability to Participate in Social Roles and Activities), bimanual function (PROMIS-9 UE), prosthesis satisfaction (Trinity Amputation and Prosthesis Experience Scales-Revised; TAPES-R), PROMIS pain interference, age, gender, average daily hours worn, time since amputation, and amputation level. Results: A multivariate linear regression model using a forward enter method was applied. The model included 1 dependent variable (well-being) and 9 independent variables. Within the multiple linear regression model, the strongest predictors of well-being were activity and participation (ß=0.303, P<.0001), followed by prosthesis satisfaction (ß=0.257, P<.0001), pain interference (ß=-0.187, P=.001), and bimanual function (ß=0.182, P=.004). Age (ß=-0.036, P=.458), gender (ß=-0.051, P=.295), time since amputation (ß=0.031, P=.530), amputation level (ß=0.042, P=.385), and hours worn (ß=-0.025, P=.632) were not significant predictors of well-being. Conclusion: Reducing pain interference and improving clinical factors such as prosthesis satisfaction and bimanual function with their associated effects on activity and participation will positively affect the well-being of individuals living with upper limb amputation/congenital deficiency.

Integrating Telepsychiatry Into Rural Primary Care for Upstream Prevention: Feasibility Case Study of the Faith Net Program.

INTRODUCTION: For decades, there has been a deficit of mental health services in rural areas of the United States. Beyond that longstanding need, the COVID-19 pandemic has reportedly increased the prevalence of unmet mental health needs among adults. Presently, many non-critical but urgent mental health concerns are first identified in rural emergency departments. This report describes the results of a 6-month feasibility case study of a program to integrate telepsychiatric triage "upstream" from emergency departments in rural primary care. METHODS: At routine primary care encounters in a single midwestern rural county, patients at risk for moderate-severe or severe depression, expressing thoughts of self-harm, or otherwise presenting in a way that raised clinical concern for mental or behavioral health, were referred to on-site telepsychiatric triage. Patients whose triage indicated further concern were provided six psychiatric and/or social work encounters for stabilization and treatment. RESULTS: 68 patients were referred to telepsychiatric triage during the pilot study (.85% of the estimated adult population in the county). Of those, only two had a documented mental/behavioral health diagnosis prior to triage, but 46 were diagnosed with at least one psychiatric disorder during the program. CONCLUSIONS: This model of telepsychiatric triage was feasible in rural primary care and may support identification and mitigation of unmet mental health needs.

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis.

BACKGROUND: Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. METHODS: We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. RESULTS: From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). CONCLUSIONS: Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium.

Ultrasound treatment of cutaneous side-effects of infused apomorphine: a randomized controlled pilot study.

Apomorphine hydrochloride is a dopamine agonist used in the treatment of advanced Parkinson's disease. Its administration by subcutaneous infusions is associated with the development of nodules that may interfere with absorption of the drug. This pilot study assessed the effectiveness of ultrasound (US) in the treatment of these nodules. Twelve participants were randomly assigned to receive a course of real or sham US on an area judged unsuitable for infusion. Following treatment, no significant change was observed in measures of tissue hardness and tenderness. However, 5 of 6 participants receiving real US rated the treated area suitable for infusion compared with the 1 of 6 receiving sham US. Sonographic appearance improved in both groups, but more substantially in the real US group. Power calculations suggest a total sample size of 30 would be required to establish statistical significance. A full-scale study of the effectiveness of therapeutic US in the treatment of apomorphine nodules is warranted.

Apomorphine nodules in Parkinson's disease: best practice considerations.

Apomorphine hydrochloride infusion therapy is used by approximately 1000 people with advanced Parkinson's disease in the UK (Britannia Pharmaceuticals Ltd, 2008). Subcutaneous nodules that develop as a result of these infusions can cause discomfort and may impact on the effectiveness of the drug therapy. Community nursing teams have a key role in supporting patients on apomorphine; they may be responsible for administering the drug, or supporting and empowering the patient or their carer to administer the infusion. A recent randomized controlled pilot study by a research group at the University of Hertfordshire investigated the use of therapeutic ultrasound for the treatment of apomorphine nodules. A number of observations about apomorphine nodules and the technique used to site infusions were made which may help to promote safe and effective management of apomorphine therapy. This article is a collaboration between one of the researchers and a Parkinson's disease nurse specialist from the University College of London Hospitals NHS Foundation Trust. It draws on best practice observations from both research and clinical experience and puts them in context of published research. It summarizes best practice considerations for administering infusions, identifies the current treatment and management options that participants from the trial reported using on their nodules, emphasizes the need for standardized documentation and suggests a rating system that may be useful to document nodule severity.

Pink1 suppresses alpha-synuclein-induced phenotypes in a Drosophila model of Parkinson's disease.

Parkinson's disease (PD) is the most prevalent human neurodegenerative movement disorder and is characterized by a selective and progressive loss of the dopaminergic neurons. Mutations in the genes parkin and PTEN-induced putative kinase 1 (PINK1) result in autosomal recessive forms of PD. It has been suggested that parkin and Pink1 function in the same pathway in Drosophila, with Pink1 acting upstream of parkin. Previous work in our laboratory has shown the ability of parkin to rescue an alpha-synuclein-induced PD-like phenotype in Drosophila. To investigate the ability of Pink1 to protect against alpha-synuclein-induced toxicity, we have performed longevity, mobility, and histological studies to determine whether Drosophila Pink1 can rescue the alpha-synuclein phenotypes. We have found that overexpression of Pink1 results in the rescue of the alpha-synuclein-induced phenotype of premature loss of climbing ability, suppression of degeneration of the ommatidial array, and the suppression of alpha-synuclein-induced developmental defects in the Drosophila eye. These results mark the first demonstration of Pink1 counteracting PD phenotypes in a protein toxicity animal model, and they show that Pink1 is able to impart protection against potentially harmful proteins such as alpha-synuclein that would otherwise result in cellular stress.