Pharmacotherapy Monitoring Research Articles

Register-based study on prescription renewal without the prescriber meeting the patient.

Renewing prescriptions is important for the continuity of pharmacotherapy. However, renewing without the prescriber meeting the patient might lead to insufficient pharmacotherapy monitoring. This study investigated the prevalence of renewed prescriptions, prescriptions renewed without the prescriber meeting the patient and the factors associated with renewals made without meeting the patient. This register-based study employed data on electronic prescriptions and health care contacts from Finnish registers. Prescriptions were classified as renewed if there was a renewal request or a previous prescription for the same ATC code. Prescriptions were considered as being renewed without meeting the patient if there was no patient contact on the renewal date. Descriptive and logistic generalized estimating equation analyses were conducted. The random sample of prescriptions (10%) from the year 2019 amounted to 2 804 048. Of these, 41.9% were original, 35.4% were renewals without meeting the patient and 22.7% were renewed with meeting the patient. Characteristics such as male sex, age 35-54 years, prescription for cardiovascular system preparations and the prescription being renewed during the summer (June-August) were associated with renewals made without meeting the patient. Further research is needed on the implementation of pharmacotherapy monitoring in the case of renewals without the prescriber meeting the patient.

#2556 Therapeutic monitoring in patients with APRT deficiency using UPLC-MS/MS-based plasma assay

Abstract Background and Aims Adenine phosphoribosyltransferase (APRT) deficiency is a rare disorder of purine metabolism, characterized by urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to nephrolithiasis and chronic kidney disease (CKD). Treatment with xanthine oxidoreductase (XOR) inhibitor, allopurinol or febuxostat, reduces DHA excretion and slows or halts CKD progression. The aim of the study was to optimize and validate an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)-based assay for simultaneous quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in human plasma, for monitoring of pharmacotherapy in patients with APRT deficiency. Method The UPLC-MS/MS-based assay was optimized employing the chemometric approach design of experiments, using the software Modde Pro 13 (Sartorius, Umeå, Sweden). The assay was validated and used for absolute quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in plasma samples from both untreated and treated APRTd patients and healthy controls. Results Accuracy and precision were within ±15% for all analytes, and the analytes were stable in plasma for 12 months at −80°C. The median (range) concentration of DHA in plasma samples from six APRT deficiency patients was 204.0 (187.2–315.8) ng/mL when they were untreated and 69.2 (below the limit of quantification [BLQ]–131.6) ng/mL when treated with allopurinol (400 mg/day), and BLQ when febuxostat (80 mg/day) was the therapeutic agent. The median (range) plasma adenine concentration was 238.1 (218–502) ng/mL in the untreated patients, and 561.1 (418–2104) and 856.0 (726–1711) ng/mL in those on treatment with allopurinol and febuxostat, respectively. DHA was not detected in plasma samples from healthy controls. The median (range) plasma concentration of allopurinol, oxypurinol and febuxostat in patients receiving XOR inhibitor therapy was 1657 (BLQ-3266) ng/mL, 8102 (4778–34906) ng/mL and 109 (BLQ-1657) ng/mL, respectively. Conclusion The UPLC-MS/MS-based assay provides accurate and precise quantification of DHA, adenine, allopurinol, oxypurinol and febuxostat in human plasma. Measurement of plasma DHA is being implemented as a diagnostic test for APRT deficiency and the full assay for monitoring of XOR inhibitor treatment in patients with the disorder.

Factors influencing hospitalization or emergency department visits and mortality in type 2 diabetes following the onset of new cardiovascular diagnoses in a population-based study.

Individuals with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD) which necessitates monitoring of risk factors and appropriate pharmacotherapy. This study aimed to identify factors predicting emergency department visits, hospitalizations, and mortality among T2D patients after being newly diagnosed with CVD. In a retrospective observational study conducted in Region Halland, individuals aged > 40 years with T2D diagnosed between 2011 and 2019, and a new diagnosis of CVD between 2016 and 2019, were followed for one year from the date of CVD diagnosis. The first encounter for CVD diagnosis was categorized as inpatient-, outpatient-, primary-, or emergency department care. Follow-up included laboratory tests, blood pressure, pharmacotherapies, and healthcare utilization. Hazard ratios (HR) in two Cox regression analyses determined relative risks for emergency visits/hospitalization and mortality, adjusting for age, sex, glucose regulation, lipid levels, kidney function, blood pressure, pharmacotherapy, and healthcare utilization. The study included a total of 1759 T2D individuals who received a new CVD diagnosis, with 67% diagnosed during inpatient care. The average hospitalization stay was 6.5 days, and primary care follow-up averaged 10.1 visits. Patients with CVD diagnosed in primary care had a HR 0.52 (confidence interval [CI] 0.35-0.77) for emergency department visits/hospitalization, but age had a HR 1.02 (CI 1.00-1.03). Pharmacotherapy with insulin, DPP4-inhibitors, aldosterone antagonists, and beta-blockers had a raised HR. Highest mortality risk was observed when CVD was diagnosed inpatient care, systolic blood pressure < 100mm Hg and elevated HbA1c. Age had a HR 1.05 (CI 1.03-1.08), eGFR < 30ml/min HR 1.46 (CI 1.01-2.11), and LDL-Cholesterol > 2,5h 1.46 (CI 1.01-2.11) and associated with increased mortality risk. Pharmacotherapy with metformin had a HR 0.41 (CI 0.28-0.62), statins a HR 0.39 (CI 0.27-0.57), and a primary care follow-up < 30 days a HR 0.53 (CI 0.37-0.77) and associated with lower mortality risk. T2D individuals who had a new diagnosis of CVD were predominantly diagnosed when hospitalized, while follow-up typically occurred in primary care. Identifying factors that predict risks of mortality and hospitalization should be a focus of follow-up care, underscoring the critical role of primary care in the effective management of T2D and CVD.

Financial dissatisfaction in people with psychotic disorders - A short report on its prevalence and correlates in a large naturalistic psychosis cohort

Psychotic disorders have a strong negative impact on multiple aspects of daily life, including people's financial situation. This exploratory study examines the level of financial dissatisfaction and its correlates in a large cohort of people with psychotic disorders. Data from the first assessments of people with psychotic disorders (n = 5271) who were included in the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS; 2006–2020), which is conducted in the northern Netherlands, were used. The Manchester Short Assessment of Quality of Life (MANSA) was used to measure financial dissatisfaction. In addition, sociodemographic and psychiatric characteristics, substance use and global and social functioning were assessed. One-fifth to one-third of people with psychotic disorders report financial dissatisfaction, fluctuating over the year in which they were assessed. These proportions are considerably higher than in the general population. Cannabis and other substance use were associated with higher levels of financial dissatisfaction (small to medium effect). The other significant associations showed (very) small effect sizes. Therefore, we conclude that financial dissatisfaction in people with psychotic disorders appears to be relatively independent of other demographic and psychiatric characteristics, and global and social functioning. These findings are an important first step for increasing knowledge on financial dissatisfaction among people with psychotic disorders. The findings can also contribute to raising awareness about the topic for healthcare professionals working in this field.

OP134 Mapping The Health Of The Nation Outcomes Scale To The EQ-5D Using The Pharmacotherapy Monitoring And Outcome Survey

IntroductionIn clinical practice, health outcomes relevant for economic evaluations, such as health-related quality of life (i.e., utilities), are not always available. However, algorithms can be developed to map available outcome measures to utilities. In the Netherlands, the Health of the Nations Outcomes Scores (HoNOS) is a physician-reported, disease-specific outcome measure frequently used for patients with severe mental illness for which no mapping algorithms for utilities currently exist. The aim of this study was to develop an algorithm to map responses on the HoNOS to EQ-5D utilities for use in economic evaluations.MethodsA dataset was obtained from the Pharmacotherapy Monitoring and Outcome Survey cohort study containing data from patients with psychotic disorders. The dataset contains EQ-5D-3L domain and HoNOS scores, the age and sex of patients, and additional demographics. Correlation between the EQ-5D-3L and HoNOS was evaluated. To derive mapping functions, least absolute shrinkage and selection operator (LASSO) regression and random forest algorithms were applied with various predictor variables using a machine learning approach, whereby data were split into separate training and test sets. Cross-validation was then used to compare the performance of different models using R-squared and the root mean square error (RMSE).ResultsA total of 2,111 patients were included in the study. Spearman’s correlation coefficients indicated a weak to moderate negative correlation of -0.31. Based on model performance metrics, LASSO models outperformed random forest models on the training set, where the model including all individual HoNOS items and the age and sex of patients showed the best overall performance with an RMSE of 0.237 and an R-squared of 0.218. When applied to the test set, this resulted in an R-squared of 0.233 and a mean absolute error of 0.177.ConclusionsThe HoNOS can be mapped onto EQ-5D-3L utilities with moderate predictive accuracy. The reported mapping algorithm may be sufficient to predict overall population utility scores for use in health economic evaluations but lacks accuracy for individual patient predictions.

S-MARSA: A novel assay for quantifying biomarkers in Parkinson’s disease and schizophrenia pharmacotherapy monitoring

S-MARSA: A novel assay for quantifying biomarkers in Parkinson’s disease and schizophrenia pharmacotherapy monitoring

Implementation of pharmacotherapy monitoring: Experiences and views of medicine users

IntroductionIn long-term illnesses, monitoring is an essential part of successful pharmacotherapy. Medicine users' experiences on monitoring have not been widely studied even though they have an important role in the implementation of pharmacotherapy. ObjectivesThe aim of this study was to investigate the medicine users' experiences on the implementation of pharmacotherapy monitoring. The focus was on the instructions received regarding the frequency of follow-up visits in health care, the actual frequency of the visits, and the experienced sufficiency of monitoring. Furthermore, we aimed to identify the characteristics of respondents and pharmacotherapy that were associated with implementation of pharmacotherapy monitoring. MethodsWe conducted an online survey targeted at Finnish people ≥18 years who have requested a prescription renewal in MyKanta patient portal in October 2021. We used descriptive statistics and logistic regression in the analyses. Results1723 individuals completed the questionnaire. Of them, 97.9% (n = 1687) were using prescription medicines and were included in the study. Of the study population, 57.1% had received instructions regarding follow-up visits in health care related to pharmacotherapy monitoring, 70.3% had an annual follow-up visit, and 64.3% felt monitoring was sufficient with all their pharmacotherapies. Several respondents and pharmacotherapy related characteristics were associated with the implementation of pharmacotherapy monitoring. Having diabetes and a designated health care unit responsible for monitoring were associated with well-implemented monitoring, while unfamiliarity with the goals set for pharmacotherapy was strongly associated with poorly implemented monitoring. ConclusionsIn most cases, the medicine users experienced that the monitoring of pharmacotherapies was well-implemented. Having diabetes, a designated health care unit and familiarity with the goals set for pharmacotherapy were associated with well-implemented monitoring. These findings indicate that monitoring practices are well-implemented for diabetes. Furthermore, centralized monitoring in health care unit and understanding of goals set for pharmacotherapy would enhance individual's monitoring of pharmacotherapy.

The Pharmacy of the Future: Pharmacy Professionals' Perceptions and Contributions Regarding New Services in Community Pharmacies.

The use of information and communication technologies (ICTs) has revolutionized the provision of health services, often referred to as eHealth, benefiting community pharmacies that can offer new services in innovative formats, namely through telepharmacy. This study aimed to explore the perceptions of pharmacy professionals (i.e., pharmacists and pharmacy technicians) on the provision of new services. The study consisted of administering an online questionnaire to pharmacy professionals nationwide. The questionnaire was developed by the research team, based on focus group methodology, from which an inductive analysis led to the categories that made up the dimensions of the survey. Participants were 95 pharmacy professionals with a mean age of 33.69 years old (SD = 10.75). Almost 79% were women. The results show overall receptivity to the development of new services in community pharmacies. Suggestions for the development of the new services, conditions necessary for their implementation, potential obstacles, and strategies to promote adherence to the new services, among others, are identified. The knowledge thus acquired will help community pharmacies to develop innovative solutions in counselling, pharmacotherapy monitoring, and pharmacovigilance, for example, of herb/dietary supplement-drug adverse reactions and interactions. Based on this information, new services can become more accessible, namely through the use of ICTs.

Review of adult gender transition medications: mechanisms, efficacy measures, and pharmacogenomic considerations.

Gender dysphoria is the imparity between a person's experienced gender and their birth-assigned gender. Gender transition is the process of adapting a person's sexual characteristics to match their experienced gender. The number of adults receiving sex hormone therapy for gender dysphoria is increasingly and these pharmacotherapies are increasing being prescribed in a general practice setting. The role of hormone therapy is to reverse or reduce physical sexual characteristics of the birth-assigned gender and enhance and build characteristics aligning to the expressed gender and these therapies apply to both transgender and gender nonconforming patients. Recognizing the options and interpreting the effects of gender transition therapies are fundamental to the discussion and treatment of gender dysphoria. This review summarizes pharmacodynamics, comparative dosing, adverse effects, monitoring, and potential pharmacogenetic influence of current pharmacotherapy. These include the use of 17-beta-estradiol, spironolactone, testosterone, GnRH agonists as well as adjunctive phosphodiesterase-5 inhibitors. The article also addresses gaps within the published literature including optimal routes of administration for individual patients, risks of malignancy and dosing reductions as transgender patients age.

PREVALENCE OF POTENTIAL DRUG-DRUG INTERACTIONS AMONG PROLANIS TYPE 2 DIABETES PATIENT WITH HYPERTENTION IN PRIMARY HEALTH CARE: CROSS SECTIONAL STUDY

Potential drug–drug interactions (pDDIs) are important factors resulting in adverse drug reactions or therapeutic failure. Therefore, pDDIs need to be identified to prevent the related risk and improve drug safety. The objective of this study was to assess the prevalence of pDDIs among Prolanis type 2 diabetes patients with hypertension. Additionally, this study aims to categorize and rate the identified pDDIs according to mechanism, severity and level of significance. This cross-sectional study was conducted at Kramat Jati District primary health care. Patient medical records from January to June 2018, were analysed using Drug Interaction Facts and Stockley’s Drug Interaction for pDDIs with a total 138 patients identified. pDDIs were detected in 35 patients (25.4%), with a total 57 interactions. They were clinically relevant with major (42.1%) in severity and refer to level one of significance (42.1%). The interaction type was unknown (64.9%), pharmacodynamic (64.9%) and pharmacokinetic (12.2%) respectively. The most common interaction was amlodipine-simvastatin in 19 cases (33.3%). Prolanis type 2 diabetes patients with hypertension were at risk to pDDIs, particularly to major pDDIs. Screening of prescriptions and medical records for pDDIs also monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.

Satisfaction with social connectedness as a predictor for positive and negative symptoms of psychosis: A PHAMOUS study

IntroductionSocial connectedness might positively influence the course of clinical symptoms in people with psychotic disorders.ObjectivesThis study examines satisfaction with social connectedness (SSC) as predictor of positive and negative symptoms in people with a psychotic disorder.MethodsData from the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS, 2014-2019) was used from patients diagnosed with a psychotic disorder (N=2109). Items about social connectedness of the Manchester short assessment of Quality of Life (ManSA) were used to measure SSC. Linear mixed models were used to estimate the association of SSC with the Positive and Negative Syndrome Scale (PANSS) after one and two years against α=0.01. Analyses were adjusted for symptoms, time since onset, gender and age. Additionally, fluctuation of positive and negative symptom scores over time was estimated.ResultsMean duration of illness of the sample was 18.8 years (SD 10.7) with &gt;65% showing only small variation in positive and negative symptoms over a two to five-year time period. After adjustment for covariates, SSC showed to be negatively associated with positive symptoms after one year (β=-0.47, p&lt;0.001, 95% CI=-0.70,-0.25) and two years (β =-0.59, p&lt;0.001, 95% CI = -0.88,-0.30), and for negative symptoms after one year (β=-0.52, p&lt;0.001, 95% CI = -0.77,-0.27). The prediction of negative symptoms was not significant at two years.Conclusions This research indicates that interventions on SSC might positively impact mental health for people with psychosis. SSC is a small and robust predictor of future levels of positive symptoms. Negative symptoms could be predicted by SSC at one year.DisclosureNo significant relationships.

Effect of Lifestyle Coaching or Enhanced Pharmacotherapy on Blood Pressure Control Among Black Adults With Persistent Uncontrolled Hypertension

Greater difficulty in controlling blood pressure (BP) and adverse lifestyle practices such as higher salt intake or less physical activity may account for some of the differences between BP control rates in Black vs White adults, thereby exposing Black adults to a higher risk of vascular events. To determine whether a lifestyle coaching intervention or an enhanced pharmacotherapy protocol is more effective than usual care in improving BP control rates in Black adults treated within an integrated health care delivery system. Shake, Rattle & Roll, a cluster randomized clinical trial, was conducted from June 5, 2013, to June 11, 2018, in a large integrated health care delivery system. Enrollment was completed during a 12-month period and interventions were implemented for 12 months. Follow-up lasted 48 months after enrollment. Panels of Black adult members of the health care delivery system with BP of at least 140/90 mm Hg from 98 adult primary care physicians were randomly assigned at the primary care physician level to usual care (UC group [n = 1129]), enhanced pharmacotherapy monitoring (EP group [n = 346]) of current BP management protocol, or diet and lifestyle coaching consisting of photographs, stories, and recipes, for example, that are appropriate for Black adults (LC group [n = 286]) focused on the Dietary Approaches to Stop Hypertension (DASH) diet. Data were analyzed from June 1, 2016, to March 25, 2022. The UC group received care per customary protocol. The EP group was contacted by a research nurse and/or a clinical pharmacist to discuss barriers to hypertension control, and drug therapy emphasized the use of thiazide diuretic intensification and addition of spironolactone as needed. The LC group received as many as 16 telephone sessions with a lifestyle coach and an emphasis on implementing reduction of sodium intake and the DASH diet. Intention-to-treat analysis of BP control rates at end of the 12-month intervention. Among the 1761 participants, the mean (SD) age was 61 (13) years, and 1214 (68.9%) were women. At the end of the 12-month intervention period, there was no significant difference in BP control rate among study groups (UC, 61.8% [95% CI, 58.8%-64.9%]; EP, 64.5% [95% CI, 59.0%-69.4%]; LC, 67.8% [95% CI, 62.1%-73.2%]; LC vs EP, P = .07). However, greater BP control was present in the LC group vs UC at 24 months (UC, 61.2% [95% CI, 57.3%-64.7%]; EP, 67.6% [95% CI, 61.9%-72.8%]; LC, 72.4% [95% CI, 66.9%-78.1%]; LC vs UC, P = .001), and 48 months (UC, 64.5% [95% CI, 61.6%-67.2%]; EP, 66.5% [95% CI, 61.3%-71.3%]; LC, 73.1% [95% CI, 67.6%-77.9%]; LC vs UC, P = .006) after enrollment. The contribution of BP medication adherence to explain group differences was inconclusive. In this cluster randomized clinical trial including Black adults with persistent uncontrolled hypertension, a 12-month LC intervention was more effective at controlling BP than UC at 24 and 48 months after enrollment. Further research is needed to explore the potential implementation of this intervention into clinical practice. ClinicalTrials.gov Identifier: NCT01892592.

Zanechání kouření a riziko diabetes mellitus 2. typu

Risk of type 2 diabetes mellitus (T2DM) is higher in tobacco smokers compared to non-smokers. The risk declines after smoking cessation. However, ex-smokers are also more prone to the metabolic syndrome. The question thus is, whether ex-smokers could temporarily have a higher risk of T2DM than current smokers. The available studies on this topic are not in agreement in their conclusions, as most of them also primarily do not compare ex-smokers to current smokers, but to non-smokers. However, based on the available studies, it rather seems the risk of T2DM is temporarily higher after smoking cessation. The higher risk of T2DM seems to be enhanced by weight gain that typically occurs first years after smoking cessation without intervention. Therefore, smoking cessation in patients who are in an increased risk of T2DM should be accompanied by T2DM preventative measures (lifestyle modification, weight monitoring and recommendation of pharmacotherapy of tobacco addiction to lower the risk of weight gain) and more frequent checks of blood glucose level to ensure early T2DM detection.

Pharmaco-epidemiological analysis of approaches to the prescription of antibacterial drugs in the treatment of acute respiratory viral infections in children

The pharmacoepidemic analysis of 500 clinical charts of children aged 1 day to 15 years on the basis of 7 pediatric polyclinics is earned out. If the indications and quality of prescribing antibacterial drugs in acute respiratory viral infections are taken into account, their injustified use is established in 36,5% of the cases, the discrepancy between standard doses on a number of drugs is established in 3361,5% of the cases. This justifies the necessity of phamiacoepidemic monitoring of pharmacotherapy of patients with acute respiratory viral infections.

Satisfaction with social connectedness as a predictor for positive and negative symptoms of psychosis: A PHAMOUS study

PurposeThis study examines satisfaction with social connectedness (SSC) as predictor of positive and negative symptoms in people with a psychotic disorder. MethodsData from the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS) was used from patients assessed between 2014 and 2019, diagnosed with a psychotic disorder (N = 2109). Items about social connectedness of the Manchester short assessment of Quality of Life (ManSA) were used to measure SSC. Linear mixed models were used to estimate the association of SSC with the Positive and Negative Syndrome Scale (PANSS) after one and two years against α = 0.01. Analyses were adjusted for symptoms, time since onset, gender and age. Additionally, fluctuation of positive and negative symptom scores over time was estimated. ResultsThe mean duration of illness of the sample was 18.8 years (SD 10.7) with >65% showing only small variation in positive and negative symptoms over a two to five-year time period. After adjustment for covariates, SSC showed to be negatively associated with positive symptoms after one year (β = −0.47, p < 0.001, 95% CI = −0.70, −025) and two years (β = −0.59, p < 0.001, 95% CI = −0.88, −0.30), and for negative symptoms after one year (β = −0.52, p < 0.001, 95% CI = −0.77, −0.27). The prediction of negative symptoms was not significant at two years. ConclusionThis research indicates that interventions on SSC might positively impact mental health for people with psychosis. SSC is a small and robust predictor of future levels of positive symptoms. Negative symptoms could be predicted by SSC at one year.

Shaping of the evidence-based substitution conceptual framework of the original medicines to generic counterparts in Ukraine

The aim. To develop conceptual framework of the strategy for a reasonable transition from original to generic medicines by complex implementation of proper bioequivalence studies and sufficient therapeutic drug monitoring management.&#x0D; Materials and methods. To conduct the study, we used the lists of medicines included in the state reimbursement program “Dostupny Liky” (Affordable Medicines), and materials of reports on medicines public procurement provided on the website of the Ministry of Health of Ukraine and the National Health Service of Ukraine, as well as information data on the results of studies of the quality and effectiveness of these drugs provided by the Rx-Index website. In the course of the study, the methods of logical analysis, SWOT analysis, and statistical evaluation of results, Kingdon’s Policy Streams Approach and the method of flowcharts construction were used. The concept of evidence-based medicine substitution formation in Ukraine was designed applying the Policy Streams Approach.&#x0D; Results. The analysis of public procurement programs for drugs for the period 2018–2020, as well as the analysis of drugs included in the new list under the “Dostupny Liky” (Affordable Medicines) program, carried out in the course of the study, showed that the level of evidence of data on assessing their effectiveness remains low. At the same time, more than 1.5 billion UAH (~ 50 mln USD) is spent annually on the purchase of such drugs and reimbursement of their cost, and the question of the optimal selection and monitoring of pharmacotherapy with these drugs remains open. A structural model has been developed, in which three basic levels are identified: provision of regulatory and financial components, executive and the level of implementation of the results. The SWOT-analysis of the strengths and weaknesses, as well as external opportunities and threats for the implementation of the conceptual framework made it possible to substantiate the advantages and reveal the possibilities of attracting clinical centers of universities and research institutions to the implementation of the concept. A framework for the interaction of a research center with health care institutions in the implementation of therapeutic drug monitoring was developed for low-income and low-middle income countries on the example of Ukraine. Distribution of responsibilities was proposed and the basic principles of interaction between performers of therapeutic drug monitoring were highlighted.&#x0D; Conclusions. Based on the results of the analysis of the evidence of the quality and effectiveness of drugs included in public procurement and in reimbursement programs, the key problems of organizing pharmaceutical provision of an appropriate level of quality for a number of chronic diseases requiring lifelong therapy were identified. The conceptual framework of evidence-based original medicines substitution to generic counterparts have been formed; and the ways of its implementation in the conditions of scarce financial resources on the example of Ukraine have been substantiated

Clinical, societal and personal recovery in schizophrenia spectrum disorders across time: states and annual transitions.

Recovery in schizophrenia is a complex process, involving clinical, societal and personal recovery. Until now, studies analysed these domains separately, without examining their mutual relations and changes over time. This study aimed to examine different states of recovery and transition rates between states. The Pharmacotherapy Monitoring and Outcome Survey (2006-2017) yearly assesses patients with schizophrenia in the Northern Netherlands. Data from 2327 patients with one up to 11 yearly measurements on clinical, societal and personal recovery were jointly analysed with a mixture latent Markov model (MLMM). The selected MLMM had four states that differed in degree and pattern of recovery outcomes. Patients in state 1 were least recovered on any domain (16% of measurements), and partly recovered in states 2 (25%; featured by negative symptoms) and 3 (21%; featured by positive symptoms). Patients in state 4 (38%) were most recovered, except for work, study and housekeeping. At the subsequent measurement, the probability of remaining in the same state was 77-89%, transitioning to a better state was 4-12% and transitioning to a worse state was 4-6%; no transitions occurred between states 1 and 4. Female gender, shorter illness duration and less schizophrenia were more prevalent in better states. Quite a high recovery rate was present among a substantial part of the measurements (38%, state 4), with a high probability (89%) of remaining in this state. Transition rates in the other states might increase to a more favourable state by focusing on adequate treatment of negative and positive symptoms and societal problems.

Advances in personalized medicine and noninvasive diagnostics in solid organ transplantation.

Personalized medicine has been a mainstay and in practice in transplant pharmacotherapy since the advent of the field. Decisions pertaining to the diagnosis, selection, and monitoring of transplant pharmacotherapy are aimed toward the individual, the allograft, and the overall immunologic needs of the patient. Recent advances in pharmacogenomics, noninvasive biomarkers, and artificial intelligence (AI) technologies have the promise of transforming the way we individualize treatment and monitor allograft function. Pharmacogenomic testing can provide clinicians with additional data that can minimize toxicity and maximize therapeutic dosing in high-risk patients, leading to more informed decisions that may decrease the risk of rejection and adverse outcomes related to immunosuppressive therapies. Development of noninvasive strategies to monitor allograft function may offer safer and more convenient methods to detect allograft injury. Cell free DNA and gene expression profiling offer the potential to serve as "liquid biopsies" minimizing the risk to patients and providing clinicians with useful molecular data that may help individualize immunosuppression and rejection treatment. Use of big data in transplant and novel AI platforms, such as the iBox, hold tremendous promise in providing clinicians a "glimpse into the future" thereby allowing for a more individualized approach to immunosuppressive therapy that may minimize future adverse outcomes. Advances in diagnostics, laboratory science, and AI have made the application of personalized medicine even more tailored for solid organ transplant recipients. In this perspective, we summarize the current and emerging tools available, literature supporting use, and the horizon for future personalization of transplantation.

Chronic Neurological Disorders: Genetic and Epigenetic Markers for Monitoring of Pharmacotherapy.

Chronic neurological diseases are a major cause of mortality and morbidity in the world. With increasing life expectancy in the developing world, the incidence and prevalence of these diseases are predicted to rise even further. This has also contributed to an increase in disability-adjusted life years (DALYs) for noncommunicable diseases. Treatment for such diseases also poses a challenge with multiple genetic and epigenetic factors leading to a varied outcome. Personalization of treatment is one way that treatment outcome/prognosis of disease can be improved, and pharmacogenomics plays a significant role in this context. This article reviewed the evidence pertaining to the association of genetic and epigenetic markers with major neurological disorders like multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD), which are a major source of burden among neurological disorders. Types of studies included are peer-reviewed original research articles from the PubMed database (1999-2018). This study compiled data regarding specific genetic and epigenetic markers with a significant correlation between the clinical diagnosis of the disease and prognosis of therapy from 65 studies. In a single platform, this review highlights the clues to some vital questions, such as why interferon beta (IFN-β) therapy fails to improve symptoms in all MS patients? why cholinesterase inhibitors fail to improve cognitive impairment in a subset of people suffering from AD? or why some individuals on levodopa (L-DOPA) for PD suffer from side-effects ranging from dyskinesia to hallucination while others do not? This article summarizes the genetic and epigenetic factors that may either require monitoring or help in deciding future pharmacotherapy in a patient suffering from MS, AD, and PD. As the health care system develops and reaches newer heights, we expect more and more of these biomarkers to be used as pharmacotherapeutic outcome indicators.

Differential expression of genes related to calcineurin and mTOR signaling and regulatory miRNAs in peripheral blood from kidney recipients under tacrolimus-based therapy.

BackgroundGenetic and epigenetics factors have been implicated in drug response, graft function and rejection in solid organ transplantation. Differential expression of genes involved in calcineurin and mTOR signaling pathway and regulatory miRNAs was analyzed in the peripheral blood of kidney recipient cohort (n=36) under tacrolimus-based therapy.MethodsPPP3CA, PPP3CB, MTOR, FKBP1A, FKBP1B and FKBP5 mRNA expression and polymorphisms in PPP3CA and MTOR were analyzed by qPCR. Expression of miRNAs targeting PPP3CA (miR-30a, miR-145), PPP3CB (miR-10b), MTOR (miR-99a, miR-100), and FKBP1A (miR-103a) was measured by qPCR array.ResultsPPP3CA and MTOR mRNA levels were reduced in the first three months of treatment compared to pre-transplant (P<0.05). PPP3CB, FKBP1A, FKBP1B, and FKBP5 expression was not changed. In the 3rd month of treatment, the expression of miR-99a, which targets MTOR, increased compared to pre-transplant (P<0.05). PPP3CA c.249G>A (GG genotype) and MTOR c.2997C>T (TT genotype) were associated with reduced expression of PPP3CA mRNA and MTOR, respectively. FKBP1B mRNA levels were higher in patients with acute rejection (P=0.026).ConclusionsThe expression of PPP3CA, MTOR and miR-99a in the peripheral blood of renal recipients is influenced by tacrolimus-based therapy and by PPP3CA and MTOR variants. These molecules can be potential biomarkers for pharmacotherapy monitoring.