Psychiatric and general medical comorbidity

The observation that chronic disorders occur together frequently has become of increasing interest as it is now viewed as the norm and not the exception. Of concern is the increasing trend of comorbidity in younger populations especially in areas of socioeconomic deprivation and low income countries. There are reasons why comorbidity is of great importance not only in the context of diagnostic classification, aetiology and pathogenesis but also for models of health-care delivery, rationalisation of pharmacotherapy, patients’ self management and the complex simultaneous utilisation of health-care systems. There is a need, therefore, for a better understanding of the coexistence of various diseases in order to develop more effective and cost-effective interventions to improve health and social outcomes. Comorbidity in medicine is now viewed as one of the major challenges in the twenty-first century in terms of prevention and treatment. With comorbidity comes the increasing risk of mental health problems especially depression leading to potentially more complications and worse prognosis overall. It is already well established that those with severe mental illness suffer increased comorbid conditions and a reduced life expectancy due to predominantly comorbid cardiovascular problems. Fragmentation in the health-care system and the current single disease model only exacerbate the problem of effectively helping people experiencing comorbidities and especially comorbidities involving both mental and physical conditions. New ways of thinking are required to redesign healthcare systems for the development of effective early intervention and screening to treat coexisting conditions and enable clinicians to deliver more integrated person-centred care to improve health outcomes and quality of life for this population

Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management

BACKGROUND: Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism.METHODS: Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations.RESULTS: The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years.CONCLUSION: The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.</p

Clinical pharmacokinetics and pharmacodynamics of mycophenolate in patients with autoimmune disease

Mycophenolic acid (MPA), the active drug moiety of mycophenolate, is a potent immunosuppressant agent, which is increasingly being used in the treatment of patients with various autoimmune diseases. An understanding of the pharmacokinetics and pharmacodynamics of mycophenolate in this population should assist the clinician with rational dosage decisions. This review aims to provide an overview of the published literature on the clinical pharmacokinetics of mycophenolate in autoimmune disease and a briefer summary of current pharmacodynamic knowledge, and to identify areas of potential future research in this field. A literature search was conducted using PubMed and EMBASE databases as well as bibliographies of relevant articles and 'on-line early' pages of key journals. Twenty-six pharmacokinetic/pharmacodynamic studies of mycophenolate in people with autoimmune disease were identified and appraised. Twenty-two of these studies used non-compartmental analysis techniques and four used population modelling methods to estimate mycophenolate pharmacokinetic parameters. Seven studies linked mycophenolate exposure to treatment outcomes. Only four studies measured free (unbound) as well as total mycophenolate exposure and only two studies characterised MPA disposition following entericcoated mycophenolate sodium (EC-MPS) administration. Across all studies MPA displayed erratic and complex pharmacokinetics with substantial between-subject variability. Based on total drug measurement, the dose-normalised MPA area under the plasma concentration-time curve (AUC) from 0 to 12 h post-dose (AUC(12)) varied at least five-to ten-fold between subjects. Typical values for apparent oral clearance (CL/F) of MPA during nonlinear mixed-effects modelling ranged from 8.3 to 25.3 L/h. Patient renal function, serum albumin levels, sex, ethnicity, food intake, concurrent administration of interacting drugs such as antacids, metal-containing medications and proton pump inhibitors and polymorphisms in genes encoding uridine diphosphate glucuronosyltransferase were identified in some studies as having a significant influence on the pharmacokinetics of mycophenolate. Typical MPA CL/F values in autoimmune disease patients were generally slightly lower than values published previously in population pharmacokinetic studies involving renal allograft recipients, possibly because of usage of ciclosporin, poorer renal function or lower serum albumin levels in the renal transplant cohort. In a single crossover study involving ten subjects only, significantly higher MPA AUC(12) and maximum MPA concentration (C-max) and lower MPA CL/F were reported following EC-MPS administration compared to mycophenolate mofetil administration. MPA exposure correlated well with treatment efficacy in patients with autoimmune disease (response to treatment, active disease and disease markers); however the relationship between MPA exposure and adverse events (infectious episodes, haematological toxicity and gastrointestinal symptoms) was unclear. Further investigation is required in autoimmune diseases such as chronic plaque psoriasis and rheumatoid arthritis and following EC-MPS administration. The extent of within-subject variability in the pharmacokinetics of mycophenolate is largely unknown and potential covariate influences need to be confirmed in studies with large subject numbers. A relationship between MPA and MPA metabolite exposure and toxicity needs to be established

ПОЯСНЮВАЛЬНА ЗАПИСКА кваліфікаційної роботи бакалавра студента Варганова_Дмитра_Дмитровича напряму підготовки 124 Системний аналіз

Об’єкт дослідження – підприємство КПШНЗ «СДЮСШОР з кінного спорту» ДМР. Предмет дослідження – приготування кормів для годування тренованих і спортивних коней. Мета дослідження: оптимізація витрат підприємства шляхом удосконалення технологій виробництва і рецептів кормів для тренованих і спортивних коней, підвищення їх якості та зниження питомих витрат на виробництво. Методи дослідження: методи багатокритеріальної та нечіткої оптимізації Економічна ефективність: очікується позитивною завдяки розробці оптимальних кормових сумішей, які дозволяють отримувати більше користі для коней та знизити витрати на компоненти, це дозволяє збільшити прибуток підприємства.Кваліфікаційна робота ступеня бакалавр напряму підготовки 124 Системний аналіз, НТУ "Дніпровська політехніка", м. Дніпро, 2020 р. Практична цінність роботи полягає у розробці математичних моделей, які дозволяють визначити оптимальну суміш корму, котра буде відповідати необхідним умовам