'Value-based methodology for person-centred, integrated care supported by Information and Communication Technologies' (ValueCare) for older people in Europe: study protocol for a pre-post controlled trial.

BACKGROUND: Older people receive care from multiple providers which often results in a lack of coordination. The Information and Communication Technology (ICT) enabled value-based methodology for integrated care (ValueCare) project aims to develop and implement efficient outcome-based, integrated health and social care for older people with multimorbidity, and/or frailty, and/or mild to moderate cognitive impairment in seven sites (Athens, Greece; Coimbra, Portugal; Cork/Kerry, Ireland; Rijeka, Croatia; Rotterdam, the Netherlands; Treviso, Italy; and Valencia, Spain). We will evaluate the implementation and the outcomes of the ValueCare approach. This paper presents the study protocol of the ValueCare project; a protocol for a pre-post controlled study in seven large-scale sites in Europe over the period between 2021 and 2023. METHODS: A pre-post controlled study design including three time points (baseline, post-intervention after 12 months, and follow-up after 18 months) and two groups (intervention and control group) will be utilised. In each site, (net) 240 older people (120 in the intervention group and 120 in the control group), 50-70 informal caregivers (e.g. relatives, friends), and 30-40 health and social care practitioners will be invited to participate and provide informed consent. Self-reported outcomes will be measured in multiple domains; for older people: health, wellbeing, quality of life, lifestyle behaviour, and health and social care use; for informal caregivers and health and social care practitioners: wellbeing, perceived burden and (job) satisfaction. In addition, implementation outcomes will be measured in terms of acceptability, appropriateness, feasibility, fidelity, and costs. To evaluate differences in outcomes between the intervention and control group (multilevel) logistic and linear regression analyses will be used. Qualitative analysis will be performed on the focus group data. DISCUSSION: This study will provide new insights into the feasibility and effectiveness of a value-based methodology for integrated care supported by ICT for older people, their informal caregivers, and health and social care practitioners in seven different European settings. TRIAL REGISTRATION: ISRCTN registry number is 25089186 . Date of trial registration is 16/11/2021.

Plasma GDF-15 concentration is not elevated in open-angle glaucoma.

AIM: Recently, the level of growth differentiation factor 15 (GDF-15) in blood, was proposed as biomarker to detect mitochondrial dysfunction. In the current study, we evaluate this biomarker in open-angle glaucoma (OAG), as there is increasing evidence that mitochondrial dysfunction plays a role in the pathophysiology of this disease. METHODS: Plasma GDF-15 concentrations were measured with ELISA in 200 OAG patients and 61 age-matched controls (cataract without glaucoma). The OAG patient group consisted of high tension glaucoma (HTG; n = 162) and normal tension glaucoma (NTG; n = 38). Groups were compared using the Kruskal-Wallis nonparametric test with Dunn's multiple comparison post-hoc correction. GDF-15 concentration was corrected for confounders identified with forward linear regression models. RESULTS: Before correcting for confounders, median plasma GDF-15 levels was significantly lower in the combined OAG group (p = 0.04), but not when analysing HTG and NTG patients separately. Forward linear regression analysis showed that age, gender, smoking and systemic hypertension were significant confounders affecting GDF-15 levels. After correction for these confounders, GDF-15 levels in OAG patients were no longer significantly different from controls. Subgroup analysis of the glaucoma patients did not show a correlation between disease severity and plasma GDF-15, but did reveal that for NTG patients, intake of dietary supplements, which potentially improve mitochondrial function, correlated with lower plasma GDF-15. CONCLUSION: The present study suggests that plasma GDF-15 is not suited as biomarker of mitochondrial dysfunction in OAG patients.

Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES.

A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005-2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.-specifically in critical nutrients that support immune health-public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.

Micronutrient Inadequacy in Short Sleep: Analysis of the NHANES 2005-2016.

One third of U.S. adults report short sleep (<7 h), which has been linked to negative health outcomes. Inadequate intake of micronutrients across the U.S. adult population has been reported, and a relationship between sleep conditions and micronutrient intake is emerging. This cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES 2005-2016) (n = 26,211) showed that participants with short sleep duration had a lower usual intake (Food + Supplements) of calcium, magnesium, and vitamin D in all adults aged 19+ years, and vitamin K in adults aged 19-50 years, even after adjusting for covariates. In addition, participants reporting short sleep had a higher percentage of individuals with intake lower than the estimated average requirement (EAR) across multiple nutrients. Age and gender differences were observed in the prevalence of inadequate intake across multiple nutrients. Adults aged 51-99 years with short sleep duration had inadequate intake with respect to more nutrients. In females there was an association between short sleep and a higher prevalence of inadequate intake (Food + Spp) for calcium, magnesium, and vitamins A, C, D, E, and K (above adequate intake). Conversely, males reporting short sleep only had an inadequate intake of vitamin D. Overall, we demonstrate that short sleep is associated with increased nutrient inadequacy, emphasizing the possible need for dietary supplementation.

Modeling the Mechanical Parameters of Glaucoma.

Glaucoma is a major eye disease characterized by a progressive loss of retinal ganglion cells (RGCs). Biomechanical forces as a result of hydrostatic pressure and strain play a role in this disease. Decreasing intraocular pressure is the only available therapy so far, but is not always effective and does not prevent blindness in many cases. There is a need for drugs that protect RGCs from dying in glaucoma; to develop these, we need valid glaucoma and drug screening models. Since in vivo models are unsuitable for screening purposes, we focus on in vitro and ex vivo models in this review. Many groups have studied pressure and strain model systems to mimic glaucoma, to investigate the molecular and cellular events leading to mechanically induced RGC death. Therefore, the focus of this review is on the different mechanical model systems used to mimic the biomechanical forces in glaucoma. Most models use either cell or tissue strain, or fluid- or gas-controlled hydrostatic pressure application and apply it to the relevant cell types such as trabecular meshwork cells, optic nerve head astrocytes, and RGCs, but also to entire eyes. New model systems are warranted to study concepts and test experimental compounds for the development of new drugs to protect vision in glaucoma patients. Impact Statement The outcome of currently developed models to investigate mechanically induced retinal ganglion cell death by applying different mechanical strains varies widely. This suggests that a robust glaucoma model has not been developed yet. However, a comprehensive overview of current developments is not available. In this review, we have therefore assessed what has been done before and summarized the available knowledge in the field, which can be used to develop improved models for glaucoma research.

The Challenge of Integrating Care in Dual Diagnosis; Anti-NMDA-Receptor Encephalitis; Presentation And Outcome In 3 Cases Referred For Complex Specialist Rehabilitation Services.

The successful implementation of an integrated care pathway (ICP) for any given condition is a challenge. Even more challenging is successful ICP implementation for individuals who have multiple co-morbidities. This is further compounded when there are dual mental health and physical disabilities that require integrated working across multiple disciplines, specialties, institutions and organisations. Anti-NMDA-Receptor encephalitis (aNMDARe) is a relatively new diagnostic entity with patients typically presenting with significant psychiatric symptoms followed by progressive neurological deterioration. In this case series, we describe 3 cases of females with aNMDARe who were referred for complex specialist rehabilitation (CSR) to The National Rehabilitation Hospital. CSR is the total active care of patients with a disabling condition, and their families, by a multi-professional team who have undergone recognised specialist training in rehabilitation, led /supported by a consultant trained and accredited in rehabilitation medicine (RM). These services provide for patients with highly complex rehabilitation needs that are beyond the scope of local services. In these cases, referral to CSR resulted in the construction of a bespoke integrated care pathway (ICP) that transcended the barriers between primary, secondary and tertiary care and across the boundaries of physical and mental health. A care pathway is a complex intervention for the mutual decision-making and organisation of care processes Rehabilitation services acted as the coordinator of services in these cases to ensure implementation of the care plan and to ensure successful transitions of care and supported local specialist and general teams in the management of these complex cases.

Monitoring neovascularization in aggressive posterior retinopathy of prematurity using optical coherence tomography angiography.

We describe the use of optical coherence tomography angiography (OCTA) in detecting and monitoring regression of the neovascular complex (NVC) in a case of aggressive posterior retinopathy of prematurity (AP-ROP). A premature Asian Indian girl with AP-ROP underwent laser photoablation at 26 days of life. Persistent NVC at the posterior border of the lasered retinal bed was detected clinically. On en face spectral domain optical coherence tomography (SD-OCT) and OCTA, the NVC appeared as an arborizing vascular net in the superficial capillary plexus. The deep capillary plexus and outer retinal layers showed corresponding flow outlines that suggested deeper extensions of the lesion. Supplemental laser treatment of the NVC was performed. Ten days later repeat en face SD-OCT and OCTA of the identical retinal location revealed that the vascular tortuosity and dilatation had reduced and that the flow lesions in the deeper layers were undetectable. Our findings in this case suggest that the NVC in AP-ROP extends beyond the superficial retina.

Comparative Effectiveness of Imaging Modalities for the Diagnosis of Intestinal Obstruction in Neonates and Infants:: A Critically Appraised Topic.

RATIONALE AND OBJECTIVES: The purpose of this study was to critically appraise and compare the diagnostic performance of imaging modalities that are used for the diagnosis of upper and lower gastrointestinal (GI) tract obstruction in neonates and infants. METHODS: A focused clinical question was constructed and the literature was searched using the patient, intervention, comparison, outcome method comparing radiography, upper GI contrast study, and ultrasound in the detection of upper GI tract obstruction such as duodenal atresia and stenosis, jejunal and ileal atresia, and malrotation and volvulus. The same methods were used to compare radiography and contrast enema in the detection of lower GI tract obstruction such as meconium plug syndrome, meconium ileus, Hirschsprung disease, and imperforate anus. Retrieved articles were appraised and assigned a level of evidence based on the Oxford University Centre for Evidence-Based Medicine hierarchy of validity for diagnostic studies. RESULTS: There were no sensitivities/specificities available for the imaging diagnosis of duodenal atresia or stenosis, jejunal or ileal atresias, meconium plug, and meconium ileus or for the use of cross-table lateral radiography for the diagnosis of rectal pouch distance from skin in imperforate anus. The retrieved sensitivity for the detection of malrotation on upper GI contrast study is 96%, and the sensitivity for the diagnosis of midgut volvulus on upper GI contrast study is 79%. The retrieved sensitivity and specificity for the detection of malrotation with volvulus on ultrasound were 89% and 92%, respectively. The retrieved sensitivity and specificity for the detection of Hirschsprung disease on contrast enema were 70% and 83%, respectively. The retrieved sensitivity of invertogram for the diagnosis of rectal pouch distance from skin in imperforate anus is 27%. The retrieved sensitivities of perineal ultrasound and colostography for the diagnosis of rectal pouch distance from skin in imperforate anus were 86% and 100%, respectively. CONCLUSIONS: There is limited evidence for the imaging diagnosis of duodenal atresia and stenosis, jejunal and ileal atresias, meconium plug, meconium ileus, and imperforate anus, with recommended practice based mainly on low-quality evidence or expert opinion. The available evidence supports the use of upper GI contrast study for the diagnosis of malrotation and volvulus, with ultrasound as an adjunct to diagnosis. Contrast enema is useful in the investigation of suspected Hirschsprung disease, but a negative study does not outrule the condition. Colostography is the investigation of choice for the work-up of infants with complex anorectal malformations before definitive surgical repair.

Lutein and Factor D: two intriguing players in the field of age-related macular degeneration.

Age-related macular degeneration (AMD) is a progressive eye disease that impairs central vision among elderly populations in Western, industrialized countries. In this review we will focus on the role of factor D (FD) and lutein in AMD. FD is a rate-limiting enzyme of the alternative complement activation pathway that may play an important role in the development of AMD. Several independent studies have shown a significant increase in the level of a number of complement factors of the alternative pathway, including factor D in the blood of AMD patients as compared to healthy individuals, which suggests a systemic involvement in the pathogenesis of AMD. FD, also called adipsin, is mainly produced by adipose tissue. Besides playing a role in the activation of the alternative pathway, FD is also known to regulate the immune system. Of interest is our preliminary finding that lutein supplementation of early AMD cases was shown to lower the level of systemic FD. If confirmed, these findings provide further support for the application of anti-factor D intervention as a new approach to control the development of this disease.

Vitamin D and neonatal immune function.

Vitamin D deficiency is widespread in the neonatal and paediatric population of northern latitudes, particularly in children of African, Middle Eastern and Asian ethnicity. This is associated with diminished immune function and increases the risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies have also shown a link between vitamin D deficiency in children and a more severe course of illness with lower respiratory tract infection or Respiratory Syncitial Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is complex. It acts through the innate immune system by inducing antimicrobial peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D in neonatal and paediatric immunomodulation requires further study.

The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma.

PURPOSE: To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care. METHODS: Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses. RESULTS: The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a ß-blocker was €12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and €1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER €173,486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER €21,516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'. CONCLUSIONS: From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable.

The use of psychotherapeutic interventions by primary care GPs in Ireland in the treatment of their methadone patients: a grounded theory study.

BACKGROUND: The methadone protocol placed responsibility on general practitioners (GPs) for the methadone treatment of stabilised drug-addicted patients. The protocol emphasised a medico-pharmacological model with minor reference to psychotherapeutic treatment. AIM: This qualitative study investigated how primary care GPs in Ireland use psychotherapeutic interventions in the treatment of methadone patients. METHOD: A grounded theory methodology was used. FINDINGS: There is a wide variation in the beliefs and knowledge of methadone-prescribing GPs regarding the efficacy of psychotherapeutic interventions for patients on methadone maintenance. GPs do not formally integrate psychotherapeutic interventions into methadone patient treatment. Accessing psychotherapeutic services raises concerns for GPs in terms of availability, location and quality. Primary care GPs who offer methadone maintenance view opiate abuse as a health issue similar to other such issues within their community. They take a holistic view of their methadone patient and, without formal guidelines, develop individual approaches to the use of psychotherapeutic interventions. The absence of a framework for the use of psychotherapeutic interventions in primary care methadone treatment in Ireland militates against the development of a basis for improving practice.

Drug users talk about HIV testing: motivating and deterring factors.

Injection drug use plays a critical role in the spread of HIV/AIDS, with an estimated 19,000 drug users infected each year. Counselling and testing services can be an important gateway for engaging HIV-infected individuals into medical care and can positively influence the preventive behaviours of IDUs. This study seeks to document and understand the complexity and range of motivations and deterrents to HIV testing among IDUs. Participants were recruited using a convenience sampling method. Interviews consisted of a qualitative guide and a quantitative survey to collect HIV testing histories, sex and drug risk behaviours, and demographic information. Interview data was coded and content analyzed to identify emerging themes and clarify the processes that drug users employ in deciding whether or not to test. Sixty-six drug users were interviewed. The sample reported a median of four lifetime HIV tests. Participants described a range of motivating and deterring factors to HIV testing across personal, interpersonal and structural categories. Drug users' decision to test is influenced by a complex network of factors. Better understanding of these motivators and deterrents can help providers develop a more holistic approach to targeting this high-risk population for HIV prevention efforts.

A benzylisoquinoline alkaloid from Doryphora sassafras.

Chemical investigation of the Australian rainforest plant Doryphora sassafras has resulted in the isolation of a new natural product, 2-methyl-1-(p-methoxybenzyl)-6,7-methylenedioxyisoquinolinium chloride (1). The iodide salt of compound 1 has previously been synthesized but only partially characterized. This paper reports the full spectroscopic characterization of 1 by MS, IR, UV, and NMR data.

Sideroxylonal C, a new inhibitor of human plasminogen activator inhibitor type-1, from the flowers of Eucalyptus albens.

Sideroxylonal C (3), a new phloroglucinol dimer, was isolated from the flowers of Eucalyptus albens through bioassay-guided fractionation. The structure elucidation was based on 1D and 2D NMR experiments, MS analysis, and comparison with sideroxylonals A (1) and B (2). Sideroxylonal C inhibited human plasminogen activator inhibitor type-1 at 4.7 microM without any significant effect on human tissue plasminogen activator.

Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study.

Following reports of childhood acute myeloid leukemia (AML) showing that patients with t(9; 11)(p22; q23) have a better prognosis than those with translocations between 11q23 and other chromosomes, we compared response to therapy and survival of 24 adult de novo AML patients with t(9; 11) with those of 23 patients with other 11q23 translocations [t(11q23)]. Apart from a higher proportion of French-American-British (FAB) M5 subtype in the t(9; 11) group (83% v 43%, P = .006), the patients with t(9; 11) did not differ significantly from patients with t(11q23) in terms of their presenting clinical or hematologic features. Patients with t(9; 11) more frequently had an extra chromosome(s) 8 or 8q as secondary abnormalities (46% v 9%, P = .008). All patients received standard cytarabine and daunorubicin induction therapy, and most of them also received cytarabine-based intensification treatment. Two patients, both with t(9; 11), underwent bone marrow transplantation (BMT) in first complete remission (CR). Nineteen patients (79%) with t(9; 11) and 13 (57%) with t(11q23) achieved a CR (P = .13). The clinical outcome of patients with t(9; 11) was significantly better: the median CR duration was 10.7 versus 8.9 months (P = .02), median event-free survival was 6.2 versus 2.2 months (P = .009), and median survival was 13.2 versus 7.7 months (P = .009). All patients with t(11q23) have died, whereas seven (29%) patients with t(9; 11) remain alive in first CR. Seven of eight patients with t(9; 11) who received postremission regimens with cytarabine at a dose of 100 (four patients) or 400 mg/m2 (2 patients) or who did not receive postremission therapy (2 patients) have relapsed. In contrast, 7 (64%) of 11 patients who received intensive postremission chemotherapy with high-dose cytarabine (at a dose 3 g/m2) (5 patients), or underwent BMT (2 patients) remain in continuous CR. We conclude that the outcome of adults with de novo AML and t(9; 11) is more favorable than that of adults with other 11q23 translocations; this is especially true for t(9; 11) patients who receive intensive postremission therapy.

Global, behavioral and self ratings of interpersonal skills among adult children of alcoholic, divorced and control parents.

OBJECTIVE: The goal of this study is to evaluate interpersonal skills and the relationships among interpersonal skills in a nonclinical sample of adult children of alcoholic, divorced and control parents using a multimethod assessment strategy. METHOD: Subjects were prescreened to rule out parental psychopathology and maternal alcoholism. Subjects (N = 238, 50% male, 86% white) interacted with a same- or opposite-sex confederate in a series of videotaped roleplays, which were either unstructured or structured via discussion topics and acquaintance instructions. The videotapes were coded for (1) global or general impression ratings of subject and (2) four behavioral components of interpersonal skill: talk, gaze, smile and self-manipulation. Subjects also rated their own skills and anxiety during the roleplays. RESULTS: Male and female children of alcoholics were judged to be more anxious when interacting with an opposite-sex partner than with a same-sex partner. Children of divorce and controls were not influenced by the gender of their interaction partner. Children of alcoholics were also judged to be less socially skilled then children of divorce. There was some suggestion that children of alcoholics and divorce may not accurately perceive their own level of skill. CONCLUSIONS: The findings provide some support for interpersonal skills deficits among adult children of alcoholics, although the deficits were not pervasive or consistent across methods. Limitations of the findings and the overall study were discussed.

Extrapituitary expression of the rat V1b vasopressin receptor gene.

[Arg8]vasopressin (AVP) stimulates adrenocorticotropic hormone release from the anterior pituitary by acting on the V1b AVP receptor. This receptor can be distinguished from the vascular/hepatic V1a and renal V2 AVP receptors by its differential binding affinities for structural analogous of AVP. Recent studies have shown that the cloned V1a and V2 receptors are structurally related. We have isolated a clone encoding the V1b receptor from a rat pituitary cDNA library using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is a protein of 421 amino acids that has 37-50% identity with the V1a and V2 receptors. Homology is particularly high in the seven putative membrane-spanning domains of these guanine nucleotide-binding protein-coupled receptors. Expression of the recombinant receptor in mammalian cells shows the same binding specificity for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP-stimulated phosphotidylinositol hydrolysis and intracellular Ca2+ mobilization in Chinese hamster ovary or COS-7 cells expressing the cloned receptor suggest second messenger signaling through phospholipase C. RNA blot analysis, reverse transcription PCR, and in situ hybridization studies reveal that V1b receptor mRNA is expressed in the majority of pituitary corticotropes as well as in multiple brain regions and a number of peripheral tissues, including kidney, thymus, heart, lung, spleen, uterus, and breast. Thus, the V1b receptor must mediate some of the diverse biological effects of AVP in the pituitary as well as other organs.

Antiinflammatory activity of a Ghanaian antiarthritic herbal preparation: III.

alpha-Amyrin palmitate, present in a Ghanaian antiarthritic herbal preparation of Alstonia boonei, Elaies guineensis and Rauvolfia vomitoria, was synthesised and tested on complete Freund's adjuvant-induced arthritic rats. Administered orally at 56 mg/kg body weight (BW) daily for 8 days from days 11 to 18 post adjuvant (acute) or at 66 mg/kg BW every 48 h for 5 days from days 32 to 40 (chronic), the drug returned the increases in serum hyaluronate and blood granulocytes towards non-arthritic levels and corrected the moderate anaemia of adjuvant arthritis. Histological examinations of the proximal interphalangeal foot joints showed reduced synovial proliferation and invasion of joints and reduced leucocyte infiltration of bone marrow and periarticular tissue in treated rats. The results suggest that alpha-amyrin palmitate contributes to the previously shown antiarthritic effect of the herbal preparation.