Quality assurance assessment of a specialized perinatal mental health clinic.

BACKGROUND: Mood and anxiety issues are the main mental health complaints of women during pregnancy and the postpartum period. Services targeting such women can reduce perinatal complications related to psychiatric difficulties. This quality assurance project aimed to examine changes in mood and anxiety symptoms in pregnant and postpartum women referred to the Women's Health Concerns Clinic (WHCC), a specialized outpatient women's mental health program. METHODS: We extracted patient characteristics and service utilization from electronic medical records of women referred between 2015 and 2016. We also extracted admission and discharge scores on the Edinburgh Postnatal Depression Scale (EPDS) and the Generalized Anxiety Disorder-7 (GAD-7) scale. RESULTS: Most patients accessed the WHCC during pregnancy (54%), had a diagnosis of major depressive disorder (54.9%), were prescribed a change in their medication or dose (61.9%), and accessed psychotherapy for perinatal anxiety (30.1%). There was a significant decrease in EPDS scores between admission and discharge (t(214) = 11.57; p = .000; effect size d = .86), as well as in GAD-7 scores (t(51) = 3.63; p = .001; effect size d = .61). A secondary analysis showed that patients with more severe depression and anxiety symptoms demonstrated even greater effect sizes. CONCLUSIONS: Changes in EPDS and GAD-7 scores indicate that the WHCC is effective in reducing mood and anxiety symptoms associated with the perinatal period. This project highlights the importance of quality assurance methods in evaluating the effectiveness of clinical services targeting perinatal mental health, in order to inform policy and funding strategies.

Evaluating the endometabolic and bone health effects of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukaemia: a systematic review protocol.

INTRODUCTION: Chronic Myeloid Leukaemia (CML) constitutes 15% of new adult leukaemia cases as well as 2%-3% of leukaemia in children under 15% and 9% of leukaemias in adolescents 15-19 years of age annually. The introduction of Tyrosine Kinase Inhibitors (TKI) therapy has dramatically improved survival in these patients, yet the off-target effects of this treatment may have long-term health impacts on CML survivors. The risk of adverse health outcomes is especially important in children, where TKI exposure may occur during critical windows of growth and puberty, and patients require treatment for prolonged periods of time. The aim of this systematic review protocol is to report on the methods used to conduct a systematic review to investigate the endometabolic and bone health effects of TKI therapy in CML. METHODS AND ANALYSIS: Searches will be conducted in the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from inception on August 1st, 2019. Searches may be updated while performing the systematic review to ensure new evidence is included if applicable. Grey literature search will include ClinicalTrials.gov and ProQuest Dissertations and Theses A&I. We will perform a meta-analysis if there are at least two studies reporting similar populations, interventions, methods and tracking the same outcome measures. The studies should also have similar age and sex distributions. ETHICS AND DISSEMINATION: As this is a systematic review protocol, it does not include patient data; therefore, Research Ethics Board approval is not indicated. The systematic review will be published in a peer-reviewed journal and presented at international conferences. PROSPERO REGISTRATION NUMBER: CRD42018091175.

Harmonization of United States, European Union and Canadian First-in-Human Regulatory Requirements for Radiopharmaceuticals-Is This Possible?

In recent years, several new radiotracers and radionuclide therapies have been developed. There is a renaissance in nuclear medicine and molecular imaging today, for example, in terms of the ability to image and treat neuroendocrine and prostate malignancies. In order to be able to bring a new drug product from bench to bedside and assist patients, while also ensuring patient safety, stringent regulations must be met. However, differences in regulatory requirements, often based on jurisdictional politics rather than scientific evidence, can hinder global co-operation, increase expense, and slow progress. In an effort to rise above these differences, nuclear medicine advocacy organizations, regulators, and international agencies have begun to identify commonalities in the regulations to achieve harmonization. Indeed, a more streamlined approach to radiopharmaceutical drug development across jurisdictions could be achieved through establishing harmonized requirements for pre-clinical studies and manufacturing standards. This paper provides an educational overview of the regulatory and submission requirements governing investigational radiopharmaceuticals for first-in-human radiopharmaceuticals across the European and North American continents. It is hoped that through ongoing collaboration, regulatory reform and harmonization can become a reality and speed access to the most up-to-date evidence-based patient care for all.

Lifelong memory responses perpetuate humoral TH2 immunity and anaphylaxis in food allergy.

BACKGROUND: A number of food allergies (eg, fish, shellfish, and nuts) are lifelong, without any disease-transforming therapies, and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although persistent IgE titers have been attributed conventionally to long-lived IgE+ plasma cells (PCs), this has not been directly and comprehensively tested. OBJECTIVE: We sought to evaluate mechanisms underlying persistent IgE and allergic responses to food allergens. METHODS: We used a model of peanut allergy and anaphylaxis, various knockout mice, adoptive transfer experiments, and in vitro assays to identify mechanisms underlying persistent IgE humoral immunity over almost the entire lifespan of the mouse (18-20 months). RESULTS: Contrary to conventional paradigms, our data show that clinically relevant lifelong IgE titers are not sustained by long-lived IgE+ PCs. Instead, lifelong reactivity is conferred by allergen-specific long-lived memory B cells that replenish the IgE+ PC compartment. B-cell reactivation requires allergen re-exposure and IL-4 production by CD4 T cells. We define the half-lives of antigen-specific germinal centers (23.3 days), IgE+ and IgG1+ PCs (60 and 234.4 days, respectively), and clinically relevant cell-bound IgE (67.3 days). CONCLUSIONS: These findings can explain lifelong food allergies observed in human subjects as the consequence of allergen exposures that recurrently activate memory B cells and identify these as a therapeutic target with disease-transforming potential.

Retropupillary Fixation of Iris-Claw Intraocular Lens for Aphakic Eyes in Children.

PURPOSE: To report outcome, complications and safety of retropupillary fixated iris-claw intraocular lenses in a pediatric population. DESIGN: Retrospective study. PATIENTS AND METHODS: Ten consecutive pediatric patients (15 eyes) underwent placement of retropupillary fixated iris-claw intraocular lenses between October 2007 and July 2013 at the Department of Ophthalmology, Medical University Graz and General Hospital Klagenfurt, Austria. Postoperative visual acuity and complications were analyzed. RESULTS: Median final best-corrected visual acuity improved by 0.12 logMAR from preoperative baseline. Mean postoperative spherical equivalent was -0.05 ± 1.76 D. No serious complications were observed intra- or postoperatively during the entire follow-up period of up to 40 months. One patient experienced a haptic disenclavation with IOL subluxation immediately after a car accident. CONCLUSION: Our study demonstrates that iris-claw intraocular lens implantation behind the iris is safe in children with lack of capsular support and yields excellent visual outcome with low complication rate.

New synthetic prosthesis for peripheral nerve injuries: an experimental pilot study.

INTRODUCTION: Even the most modern technology has failed to induce satisfactory functional regeneration of traumatically severed peripheral nerves. Delayed neural regeneration and in consequence, slower neural conduction seriously limit muscle function in the area supplied by the injured nerve. This study aimed to compare a new nerve coaptation system involving an innovative prosthesis with the classical clinical method of sutured nerve coaptation. Besides the time and degree of nerve regeneration, the influence of electrostimulation was also tested. METHODS: The sciatic nerve was severed in 14 female Göttingen minipigs with an average weight of 40.4 kg. The animals were randomized into 2 groups: One group received the new prosthesis and the other underwent microsurgical coaptation. In each group, according to the randomization a part of the animals received postoperative electrostimulation. Postoperative monitoring and the stimulation schedule covered a period of 9 months, during which axonal budding was evaluated monthly. RESULTS: The data from the pilot study indicate that results with the nerve prosthesis were comparable with those of conventional coaptation. CONCLUSION: The results indicate that implantation of the nerve prosthesis allows for good and effective neural regeneration. This new and simple treatment option for peripheral nerve injuries can be performed in any hospital with surgical facilities as it does not involve the demanding microsurgical suture technique that can only be performed in specialized centers.

The influence of social status on hepatic glucose metabolism in rainbow trout Oncorhynchus mykiss.

The effects of chronic social stress on hepatic glycogen metabolism were examined in rainbow trout Oncorhynchus mykiss by comparing hepatocyte glucose production, liver glycogen phosphorylase (GP) activity, and liver ß-adrenergic receptors in dominant, subordinate, control, fasted, and cortisol-treated fish. Hepatocyte glucose production in subordinate fish was approximately half that of dominant fish, reflecting hepatocyte glycogen stores in subordinate trout that were just 16% of those in dominant fish. Fasting and/or chronic elevation of cortisol likely contributed to these differences based on similarities among subordinate, fasted, and cortisol-treated fish. However, calculation of the "glycogen gap"--the difference between glycogen stores used and glucose produced--suggested an enhanced gluconeogenic potential in subordinate fish that was not present in fasted or cortisol-treated trout. Subordinate, fasted, and cortisol-treated trout also exhibited similar GP activities (both total activity and that of the active or a form), and these activities were in all cases significantly lower than those in control trout, perhaps reflecting an attempt to protect liver glycogen stores or a modified capacity to activate GP. Dominant trout exhibited the lowest GP activities (20%-24% of the values in control trout). Low GP activities, presumably in conjunction with incoming energy from feeding, allowed dominant fish to achieve the highest liver glycogen concentrations (double the value in control trout). Liver membrane ß-adrenoceptor numbers (assessed as the number of (3)H-CGP binding sites) were significantly lower in subordinate than in dominant trout, although this difference did not translate into attenuated adrenergic responsiveness in hepatocyte glucose production in vitro. Transcriptional regulation, likely as a result of fasting, was indicated by significantly lower ß(2)-adrenoceptor relative mRNA levels in subordinate and fasted trout. Collectively, the data indicate that social status shapes liver metabolism and in particular glycogen metabolism, favoring accumulation of glycogen reserves from incoming energy in dominant fish and reliance on onboard fuels in subordinate fish.

Evaluation of limbal and pars plana silicone oil removal in aphakic eyes.

PURPOSE: To compare limbal and pars plana silicone oil removal (SOR) in aphakic eyes and to evaluate the acute effect of silicone oil flow to the corneal endothelium. METHODS: Sixteen aphakic patients with silicone oil endotamponade requiring SOR were recruited for this prospective study and randomly scheduled for limbal or pars plana SOR. The central corneal thickness (CCT), visual acuity (VA) and intraocular pressure were measured preoperatively, on the first postoperative day and 4 months after surgery. Endothelial cell density (ECD) was measured preoperatively and at the end of follow-up. The in vitro study was performed on ten enucleated porcine eyes. Corneoscleral discs were prepared and fixed on artificial anterior chamber followed by 2.5-mm limbal incision and 5-ml silicone oil injection in six cases and 5 ml balanced salt solution (BSS) in four cases. RESULTS: The ECD decreased by 239.2 ± 86.7 (13.9%) and 86.7 ± 22.4 cells/mm(2) (5%) after limbal (n = 8) and pars plana SOR (n = 8), respectively (p < 0.001 for both). The difference between the groups was significant (p < 0.001). A significant increase in CCT and corresponding decrease in VA was noted on the first postoperative day using both procedures. At the end of follow-up, the CCT and VA were comparable to initial values. Postoperative hypotony (≤6 mmHg) was observed more frequently after limbal SOR. In the experiment, lamellar abrasions of corneal endothelium were observed after silicone oil injection, whereas no changes were observed after BSS injection. CONCLUSION: Limbal SOR causes more considerable damage to the corneal endothelium than the pars plana approach because of mechanical abrasion.

sirt1-null mice develop an autoimmune-like condition.

The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease.

SirT1 regulates energy metabolism and response to caloric restriction in mice.

The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.