Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Current State of Knowledge Regarding WHO High Priority Pathogens-Resistance Mechanisms and Proposed Solutions through Candidates Such as Essential Oils: A Systematic Review.

Combating antimicrobial resistance (AMR) is among the 10 global health issues identified by the World Health Organization (WHO) in 2021. While AMR is a naturally occurring process, the inappropriate use of antibiotics in different settings and legislative gaps has led to its rapid progression. As a result, AMR has grown into a serious global menace that impacts not only humans but also animals and, ultimately, the entire environment. Thus, effective prophylactic measures, as well as more potent and non-toxic antimicrobial agents, are pressingly needed. The antimicrobial activity of essential oils (EOs) is supported by consistent research in the field. Although EOs have been used for centuries, they are newcomers when it comes to managing infections in clinical settings; it is mainly because methodological settings are largely non-overlapping and there are insufficient data regarding EOs' in vivo activity and toxicity. This review considers the concept of AMR and its main determinants, the modality by which the issue has been globally addressed and the potential of EOs as alternative or auxiliary therapy. The focus is shifted towards the pathogenesis, mechanism of resistance and activity of several EOs against the six high priority pathogens listed by WHO in 2017, for which new therapeutic solutions are pressingly required.

Perindopril Induces TSP-1 Expression in Hypertensive Patients with Endothelial Dysfunction in Chronic Treatment.

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

Comparative Solid-State Stability of Perindopril Active Substance vs. Pharmaceutical Formulation.

This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG-thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine.

Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both genetic and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variants that can be transmitted from one generation to another can be a significant contributor to causing family or sporadic hereditary DCM. Genetic variants also play a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a large range of phenotypic expressions. It is crucial to select patients who are most probable to gain advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the relationships between genotype and phenotype, risk assessment, and personalized therapy for both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

Schizophrenia and Heart Health: Are Antipsychotics a Friend or Foe?

Schizophrenia is one of the most disabling of the psychiatric diseases. The Brief Psychiatric Rating Scale Extended (BRSE) is used to evaluate the severity of psychiatric symptoms. Long-acting injectable (LAI) antipsychotics are commonly used and are preferred over oral antipsychotic medications. A two-center-based cross-sectional study was performed on 130 patients diagnosed with schizophrenia or schizoaffective disorder based on the International Classification of Diseases 10 criteria. We studied the relation between the development of cardiovascular risk factors and the antipsychotic medication that was administered in these patients. Our study demonstrates strong links between several cardiovascular risk factors and the duration of psychosis; the duration of the LAI antipsychotic treatment; the duration between the onset of the disease and the start of LAI antipsychotic treatment; and the use of specific LAI antipsychotic medications.

Insulin Resistance in Long COVID-19 Syndrome.

Background: The COVID-19 pandemic has caused severe health issues worldwide and contributed to huge financial losses. Key comorbidities linked to an increased risk of severe COVID-19 and higher mortality rates include cardio-metabolic disorders such as type 1 and type 2 diabetes mellitus (T1DM and T2DM), atherosclerotic cardiovascular disease, chronic kidney disease, hypertension, heart failure, and obesity. The persistence of symptoms even after the acute phase is over is termed long COVID-19 syndrome. This study aimed to evaluate the relationship between long COVID-19 syndrome and the development of insulin resistance in previously non-diabetic patients. Methods: A prospective observational study was performed on 143 non-diabetic patients who had tested positive for SARS-CoV-2 infection by a PCR test and were hospitalized in our hospital between January 2020 and December 2022. The clinical and para-clinical data at 0, 4, and 12 months of hospital admission for post-COVID-19 infection follow-up was collected and labeled as t0, t4, and t12. Blood glucose, insulin, and C-peptide levels were measured at the beginning and further at 2, 5, 10, and 30 min after the intravenous arginine stimulation test. Similarly, BMI was calculated, and hs-CRP and ESR levels were noted. The results obtained were statistically analyzed. Results: More than one-third (30.7%) of the included patients developed long COVID-19 syndrome. It was found that 75% of patients with long COVID-19 hospitalized in our clinic developed diabetes within a year of acute infection with COVID-19; therefore, it can be said that the presence of long COVID-19 is a major risk for an altered metabolic status, which can cause diabetes. When comparing the glycemia levels (106 mg/dL) with the BMI at t0, t4, and t12 time intervals, the p-values were found to be 0.214, 0.042, and 0.058, respectively. Almost 62% of the patients having BMI > 30 kg/m2 were found to have an increase in blood glucose levels at 1 year. Similarly, insulin resistance was noted during this interval. A negative correlation of 0.40 for hsCRP and 0.38 for ESR was noted when compared with acute infection with COVID-19. Conclusions: The association between long COVID-19 and insulin resistance highlights the varied and widespread impacts of SARS-CoV-2 infection. Addressing the complexities of long COVID-19 requires a holistic strategy that encompasses both respiratory and metabolic considerations, which is crucial for enhancing the well-being of those enduring this persistent condition.

Tempolenses with variable magnification for sonic representation of medical data. Application for cardiac signals.

The purpose of this study was to develop the tools and the methodology for a systematic analysis of usefulness of adding sonic representation of data, supplementary to visualization. This paper is mainly dedicated various temporal lenses, including the newly developed lenses with variable magnification, proposed as a tool for a better perception of short events combined with a compression of irrelevant intervals. Sonification procedures are also briefly presented. The programs were tested using various cardiac signals: ECG and heart rate HR both in humans and in rats (experimental data). The results, represented by the sound files, were uploaded in an accessible library, which contains both sonic and visual representation of the signals.

Sex-Related Differences in the Pharmacological Response in SARS-CoV-2 Infection, Dyslipidemia, and Diabetes Mellitus: A Narrative Review.

Pharmacological responses vary by sex in several illnesses. This narrative review summarizes sex variations in pharmaceutical response in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Infection with SARS-CoV-2 is more severe and deadly in men than women. This may be attributed to immunological responses, genetics, and hormones. Some research shows that men may respond better to genomic vaccinations and females to antiviral medications such as remdesivir (Moderna and Pfizer-BioNTech). In dyslipidemia, women tend to have greater HDL-C and lower LDL-C than men. Some studies show that females may need lower statin dosages than men to obtain equal LDL-C reductions. Ezetimibe co-administered with a statin significantly improved lipid profile indicators in men compared to women. Statins reduce dementia risk. Atorvastatin decreased dementia risk in males (adjusted HR 0.92, 95% CI 0.88-0.97), whereas lovastatin lowered dementia risk in women (HR 0.74, 95% CI 0.58-0.95). In diabetes mellitus, evidence suggests that females may have a higher risk of developing certain complications such as diabetic retinopathy and neuropathy, despite having lower rates of cardiovascular disease than males. This could be the result of differences in hormonal influences and genetic factors. Some research shows females may respond better to oral hypoglycemic medications such as metformin. In conclusion, sex-related differences in pharmacological response have been observed in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Further research is needed to better understand these differences and to develop personalized treatment strategies for males and females with these conditions.

Untangling the Professional Web: Understanding the Impact of Work-Related Factors on the Mental Health of Healthcare Professionals During the Late Stages of Covid-19 Pandemic.

Purpose: The COVID-19 pandemic has determined an extraordinary challenge to healthcare systems worldwide. The extraordinary circumstances, characterized by elevated stress levels, prolonged working hours, new medical procedures, media attention, and high population expectations, have created an extremely stressful situation for healthcare professionals. This period has offered a unique opportunity to examine the medical system and the responses of healthcare practitioners to stress. This research aimed to identify the work-related factors that significantly impact the mental health of healthcare professionals. Patients and Methods: Three mental health variables were assessed: anxiety, depression and stress. The work-related factors considered were professional degree, type of medical unit (COVID or non-COVID), the number of hours spent at work in a single shift, type of shifts, monthly on-call frequency, and number of COVID-19 treated patients per month. In the spring of 2022, three inventories and a demographic survey were distributed and completed online by 300 healthcare professionals from Timisoara's public hospitals in Romania. Results: Among the respondents, 47.7% reported mild symptoms of anxiety, 65.3% reported moderate levels of stress, and 33% of the participants reported mild symptoms of depression. The intensity of anxious, depressive, and stress symptoms varied significantly depending on the professional degree, number of on-calls per month, the type of medical unit where the participants worked, and the number of SARS CoV-2 patients treated in the previous month. Conclusion: Current data underlines the urgency of implementing effective strategies to reduce the stress and anxiety of medical practitioners who work with COVID-19 patients. Possible interventions encompass a variety of approaches, such as improving working conditions, reducing working hours where possible, increasing access to mental health services, and promoting team-building activities to enhance social support among colleagues. Digital mental health interventions, including online counseling and stress management programs, have also shown promise in these challenging times. Sustaining the mental health of medical practitioners is vital to support the continued provision of first-rate care to patients and to build a resilient healthcare workforce capable of navigating future health crises.

Sex-Related Differences in Pharmacological Response to CNS Drugs: A Narrative Review.

In the last decades, both animal and human studies have neglected female subjects with the aim of evading a theorized intricacy of feminine hormonal status. However, clinical experience proves that pharmacological response may vary between the two sexes since pathophysiological dissimilarities between men and women significantly influence the pharmacokinetics and pharmacodynamics of drugs. Sex-related differences in central nervous system (CNS) medication are particularly challenging to assess due to the complexity of disease manifestation, drugs' intricate mechanisms of action, and lack of trustworthy means of evaluating the clinical response to medication. Although many studies showed contrary results, it appears to be a general tendency towards a certain sex-related difference in each pharmacological class. Broadly, opioids seem to produce better analgesia in women especially when they are administered for a prolonged period of time. On the other hand, respiratory and gastrointestinal adverse drug reactions (ADRs) following morphine therapy are more prevalent among female patients. Regarding antidepressants, studies suggest that males might respond better to tricyclic antidepressants (TCAs), whereas females prefer selective serotonin reuptake inhibitors (SSRI), probably due to their tolerance to particular ADRs. In general, studies missed spotting any significant sex-related differences in the therapeutic effect of antiepileptic drugs (AED), but ADRs have sex variations in conjunction with sex hormones' metabolism. On the subject of antipsychotic therapy, women appear to have a superior response to this pharmacological class, although there are also studies claiming the opposite. However, it seems that reported sex-related differences regarding ADRs are steadier: women are more at risk of developing various side effects, such as metabolic dysfunctions, cardiovascular disorders, and hyperprolactinemia. Taking all of the above into account, it seems that response to CNS drugs might be occasionally influenced by sex as a biological variable. Nonetheless, although for each pharmacological class, studies generally converge to a certain pattern, opposite outcomes are standing in the way of a clear consensus. Hence, the fact that so many studies are yielding conflicting results emphasizes once again the need to address sex-related differences in pharmacological response to drugs.

Left Ventricular Remodeling and Heart Failure Predictors in Acute Myocardial Infarction Patients with Preserved Left Ventricular Ejection Fraction after Successful Percutaneous Intervention in Western Romania.

(1) Acute myocardial infarction (AMI) patients are at risk of left ventricular (LV) remodeling and heart failure (HF), even after successful revascularization by percutaneous coronary intervention (PCI). We wanted to assess the independent predictors of these outcomes in AMI patients. (2) Methods: The study enrolled patients with a LVEF ≥50% after a successful PCI for their first AMI. After 24 months, patients were separated into two groups based on whether their LVEF remained ≥50% (group I), or decreased to <50% (group II). (3) Outcomes: 26% of the patients experienced a decrease in LVEF below 50%, 41% showed LV remodeling, and 8% had experienced HF hospitalizations. HF hospitalizations were significantly more frequent in group II patients (p < 0.0001). The Killip class at admission >2, infarct-related longitudinal strain ≤−12.5%, and the presence of LV remodeling were identified as independent predictors of HF hospitalizations. (4) Conclusions: About 26% of AMI patients with normal LV function after a successful PCI developed HF. More sensitive techniques are required that allow for a more efficient risk-stratification and preventive therapy to reduce LV remodeling and HF in AMI patients with LVEF ≥50% after a successful PCI. The detection of abnormal ventricular deformation patterns after PCI by speckle-tracking echocardiography might be a valuable method in this approach.

An Up-to-Date Article Regarding Particularities of Drug Treatment in Patients with Chronic Heart Failure.

Since the prevalence of heart failure (HF) increases with age, HF is now one of the most common reasons for the hospitalization of elderly people. Although the treatment strategies and overall outcomes of HF patients have improved over time, hospitalization and mortality rates remain elevated, especially in developed countries where populations are aging. Therefore, this paper is intended to be a valuable multidisciplinary source of information for both doctors (cardiologists and general physicians) and pharmacists in order to decrease the morbidity and mortality of heart failure patients. We address several aspects regarding pharmacological treatment (including new approaches in HF treatment strategies [sacubitril/valsartan combination and sodium glucose co-transporter-2 inhibitors]), as well as the particularities of patients (age-induced changes and sex differences) and treatment (pharmacokinetic and pharmacodynamic changes in drugs; cardiorenal syndrome). The article also highlights several drugs and food supplements that may worsen the prognosis of HF patients and discusses some potential drug-drug interactions, their consequences and recommendations for health care providers, as well as the risks of adverse drug reactions and treatment discontinuation, as an interdisciplinary approach to treatment is essential for HF patients.

Prescription Habits Related to Chronic Pathologies of Elderly People in Primary Care in the Western Part of Romania: Current Practices, International Recommendations, and Future Perspectives Regarding the Overuse and Misuse of Medicines.

The European Commission's 2019 report regarding the state of health profiles highlighted the fact that Romania is among the countries with the lowest life expectancy in the European Union. Therefore, the objectives of the present study were to assess the current prescription habits of general physicians in Romania related to medicines taken by the elderly population for chronic conditions in both urban and rural setting and to discuss/compare these practices with the current international recommendations for the elderly (American-Beers 2019 criteria and European-STOPP/START v.2, 2015 criteria). A total of 2790 electronic prescriptions for chronic pathologies collected from 18 community pharmacies in the western part of Romania (urban and rural zones) were included. All medicines had been prescribed by general physicians. We identified the following situations of medicine overuse: 15% of the analyzed prescriptions involved the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for >2 weeks, 12% involved the use of a proton-pump inhibitor (PPI) for >8 weeks, theophylline was the bronchodilator used as a monotherapy in 3.17% of chronic obstructive pulmonary disease cases, and zopiclone was the hypnotic drug of choice for 2.31% of cases. Regarding the misuse of medicines, 2.33% of analyzed prescriptions contained an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) for patients with renal failure in addition to vitamin K antagonists (AVKs) and NSAIDs in 0.43% of cases. Prescriptions for COX2 NSAIDs for periods longer than 2 weeks for patients with cardiovascular disorders accounted for 1.33% of prescriptions, and trihexyphenidyl was used as a monotherapy for patients with Parkinson's disease in 0.18% of cases. From the included medical prescriptions, 32.40% (the major percent of 2383 prescriptions) had two potentially inappropriate medications (PIMs). Rural zones were found to be risk factor for PIMs. Decreasing the chronic prescription of NSAIDs and PPIs, discontinuing the use of hypnotic drugs, and avoiding potentially harmful drug-drug associations will have long term beneficial effects for Romanian elderly patients.

Impairment of the cardiac ejection fraction by blocking dopamine D2 receptors induced by long-acting injectable antipsychotic treatment.

INTRODUCTION: Atypical antipsychotics have numerous benefits compared to conventional ones in respect to the possible adverse effects. However, like the other ones, they may induce direct cardiovascular alterations, probably through the apoptotic effect of dopamine receptor D2 (DRD2) blockade. The main objective of the study was to assess the cardiac ejection fraction (EF) using transthoracic speckle tracking echocardiography (TSTE) in patients treated with long-acting injectable (LAI) atypical antipsychotics. PATIENTS, MATERIALS AND METHODS: This cross-sectional study was conducted on 123 patients with schizophrenia or schizoaffective disorder divided in four samples according to their treatment: Aripiprazole, Olanzapine, Paliperidone and Risperidone. We analyzed socio-demographic data, the intensity of psychiatric symptoms, the duration of psychosis and of LAI treatment, and the cardiac EF measured with TSTE. RESULTS: We found no statistically significant differences between the four antipsychotics regarding the values of the EF. Nevertheless, we observed a trend indicating that patients treated with an antipsychotic associated with a lower affinity for the DRD2, such as Olanzapine, have higher EF values than patients treated with antipsychotics with a stronger binding to the DRD2, such as Paliperidone and Risperidone. Patients receiving Aripiprazole, which has the strongest affinity for the DRD2 from all four antipsychotics but is also a partial DRD2 agonist, display higher EF values than those on Paliperidone and Risperidone. CONCLUSIONS: Antipsychotics with a lower affinity for the DRD2 or a partial agonism for it may be associated with higher EF. Cardiac monitoring should be performed periodically in patients on LAI antipsychotic therapy.

Adding Sound to Medical Data.

Medical data can be represented in various forms. The most common is visualization, but recent work started to also add sonic representation - sonification. In this study we start with a theoretical background, then focus on medical applications. The discussion synthesizes the authors view about the present state of the domain and tries to foresee future potential developments in medicine. In conclusion we present a set of original recommendations for developing new applications with potential use in medicine and healthcare.

The Predictive Value of Endothelial Inflammatory Markers in the Onset of Schizophrenia.

PURPOSE: This study aimed to assess the serum levels of intracellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1), in the first psychotic episode schizophrenia (SZ) patients, before and after six months of antipsychotic treatment. PATIENTS AND METHODS: The study included 50 patients with a first hospitalization for SZ and 50 healthy control subjects that were patient-matched regarding age, gender, body mass index and smoking status. The evaluation included the presence of cardiovascular risk factors, measurements of systolic and diastolic blood pressure, body mass index, smoking status, ankle-brachial index, carotid intima-media thickness, and echocardiography. The Brief Psychiatric Rating Scale (BPRS) score was calculated for the patients. The plasma levels of fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, sICAM-1 and sVCAM-1 were determined at baseline in all subjects and after six months of antipsychotic treatment. Thirty patients (60%) were treated with olanzapine and 20 (40%) with risperidone. RESULTS: The average age of patients experiencing their first episode of SZ was 29.7±6.6 years, and 23 (46%) were men. The initial sICAM-1 levels of the patients were lower than those of the control group (P<0.0001), and increased after treatment (P=0.02), but remained lower than in the healthy controls (P=0.026). The initial levels of sVCAM-1 levels were higher in the patients (P<0.0001) and decreased after treatment (P<0.0001) to values that were similar to those of the control group (P=0.39). The only independent predictor of a baseline BPRS over 120 was the baseline sVCAM-1 level (P<0.0001). Antipsychotic treatment induced significant decreases in BPRS score (P<0.0001), in systolic (P=0.005) and diastolic (P<0.0001) blood pressure, in HDL-c (P=0.02), as well as significant increases in blood glucose (P<0.01) and LDL-c (P<0.001), with no differences between olanzapine and risperidone. CONCLUSION: In the patients experiencing an FEP of SZ, the levels of sICAM-1 were lower, while the levels of sVCAM-1 were higher than in the healthy control subjects. The antipsychotics used in the treatment of schizophrenia increased sICAM-1 and decreased sVCAM. The baseline level of sVCAM-1 was an independent predictor of a BPRS score >120 at baseline.

Potentially Inappropriate Prescriptions in Ambulatory Elderly Patients Living in Rural Areas of Romania Using STOPP/START (Version 2) Criteria.

BACKGROUND: Rational use of medications and monitoring of prescriptions in elderly patients is important to decrease the number and duration of hospitalizations, emergency medical consultations, mortality, as well as medical costs. PURPOSE: To identify potentially inappropriate medications (PIMs) and potential prescription omissions (PPOs), and determine their prevalence based on the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) v2 criteria and Screening Tool to Alert doctors to Right Treatment (START) v2 criteria for patients aged >65 years. METHODS: This cross-sectional study was conducted in two rural counties in Romania based on electronic prescriptions for chronic conditions (EPCCs) issued from 30 days to 90 days by a specialist or general practitioner. Collected EPCCs were evaluated by an interdisciplinary team of specialists based on 26 STOPP v2 criteria and 10 START v2 criteria. RESULTS: PIM prevalence was 25.80% and PPO prevalence was 41.72% for 646 EPCCs. The mean age of patients was 75 years and the mean number of drugs per EPCC was four. The most frequently identified PIMs were treatment duration (6.65%), theophylline administration (5.72%), drug indication (4.64%), cyclo-oxygenase-2 non-steroidal anti-inflammatory drugs (1.39%), and zopiclone prescription (0.77%). Statins (24.76%), beta-blockers (8.04%), and beta-2 agonist/antimuscarinic bronchodilators (5.88%) were the most frequently identified PPOs. CONCLUSION: PPOs were more prevalent than PIMs for elderly populations living in the two rural counties in Romania we studied. Health practitioners (family physicians, specialists, and pharmacists) should focus on prophylactic and curative considerations when prescribing agents to decrease the morbidity and mortality of elderly rural Romanian patients.

Solid State Stability and Kinetics of Degradation for Candesartan-Pure Compound and Pharmaceutical Formulation.

The aim of this work was to assess the impact of an excipient in a pharmaceutical formulation containing candesartan cilexetil over the decomposition of the active pharmaceutical ingredient and to comparatively investigate the kinetics of degradation during thermolysis in an oxidative atmosphere under controlled thermal stress. To achieve this, the samples were chosen as follows: pure candesartan cilexetil and a commercial tablet of 32 mg strength. As a first investigational tool, Universal attenuated total reflection Fourier transform infrared (UATR-FTIR) spectroscopy was chosen in order to confirm the purity and identity of the samples, as well as to check if any interactions took place in the tablet between candesartan cilexetil and excipients under ambient conditions. Later on, samples were investigated by thermal analysis, and the elucidation of the decomposition mechanism was achieved solely after performing an in-depth kinetic study, namely the use of the modified non-parametric kinetics (NPK) method, since other kinetic methods (American Society for Testing and Materials-ASTM E698, Friedman and Flynn-Wall-Ozawa) led to inadvertencies. The NPK method suggested that candesartan cilexetil and the tablet were degraded by the contribution of two steps, the main being represented by chemical degradation and the secondary being a physical transformation. The excipients chosen in the formulation seemed to have a stabilizing effect on the decomposition of the candesartan cilexetil that was incorporated into the tablet, relative to pure active pharmaceutical ingredient (API), since the apparent activation energy for the decomposition of the tablet was 192.5 kJ/mol, in comparison to 154.5 kJ/mol for the pure API.

Cardiovascular anomalies and evolutionary risk factors in schizophrenia - multifactorial approach.

Schizophrenia is a functional psychosis with a multifactorial etiopathogeny involving genetic, endocrine and immunological risk factors. The main pathogenic hypothesis involves dopamine dysregulation, with hyperfunction in the limbic system and hypofunction in the prefrontal cortex. Normal dopamine activity is critical for cognitive and emotional processing, but also for autonomic and immune regulation. Co-morbidity between schizophrenia and cardiovascular anomalies is complex. Genetic factors influence the development of brain, cardiac and vascular structures, as well as the activity of enzymes involved in dopamine synaptic turnover. Autoimmunity triggered by infections or related to systemic diseases affects both brain and heart in a direct manner through autoantibodies and/or indirectly through microvascular injury. In most cases, the co-morbidity between schizophrenia and cardiac diseases is secondary to metabolic dysfunctions induced by psychotropic medication or psychosis itself. Because of their diverse pharmacodynamic profiles, antipsychotics differ in their propensity to facilitate the development of the metabolic syndrome. The distress associated with acute psychotic symptoms or a sedentary lifestyle due to negative symptoms may have a negative impact on the energetic metabolism or cardiac function. Conclusions: An interdisciplinary approach is required between neurosciences and cardiology not only at the research level, but also in the clinical practice. Cardiac co-morbidity in subjects with schizophrenia may critically affect the survival rates of these patients. Moreover, the nature of the cardiac co-morbidity may guide the clinician in better understanding and differentiating functional psychoses from organic ones. The multifactorial approach can identify cardiovascular risk factors based on clinical, biological and neuroimaging markers.