Prescribed Combination Therapy Research Articles

Evaluating and understanding combination therapy decision drivers for the treatment of overactive bladder in the United States.

ObjectiveTo understand factors guiding overactive bladder (OAB) therapy selection and experience with combination therapy (antimuscarinics and beta-3 agonists).MethodsCross-sectional surveys of OAB patients and OAB-treating physicians in the USA were conducted. Patients receiving monotherapy with antimuscarinics were categorized by OAB treatment history: monotherapy only; third-line procedures (e.g., onabotulinumtoxinA injections) and combination therapy; third-line therapy only; and combination therapy only. The patient survey assessed therapy choice drivers and barriers, treatment satisfaction and sociodemographic/clinical characteristics. The physician survey assessed drivers of and barriers to OAB treatment choices.ResultsOf 200 patients, 86.5% reported involvement in treatment decision-making; doctor’s recommendation was the most frequently considered factor (84.4%). Most patients (71%) were unaware of combination therapy. The primary reason why those patients aware of combination therapy had not used it (N = 43/200; 21%) was physician recommendation of other treatments (69.8%). For physicians (N = 50), the most frequently considered factors when prescribing OAB treatment were effectiveness (92.0%) and side effects (84.0%); 70% prescribed combination therapy, primarily for symptom severity (82.9%). The main reasons for not prescribing combination therapy were cost/insurance coverage (80%) and lack of information (53.3%).ConclusionsShared decision-making guided treatment decisions; the main considerations were treatment safety and efficacy.

Risk assessment tools for survival prognosis: An era of new surrogacy endpoints for clinical outcome measurement in pulmonary arterial hypertension clinical trials?

Developing a new medication in a rare disease indication like pulmonary arterial hypertension (PAH) is very challenging. This is especially true now that clinical trials often employ time to clinical worsening (TTCW) as an endpoint (thus requiring a relatively large and lengthy trial) and since patients are more frequently prescribed combination therapy. During the last few decades, several tools have been developed to predict mortality in PAH and have demonstrated generally good discrimination. The objective of this review article is to assess the available data on the different tools and methods described in the literature and identify potential candidates that could be used as surrogate endpoints in pivotal randomized clinical trials in future. Some of these tools have been validated in various registries and in post-hoc analyses of clinical trial data, but none have been assessed in a prospective clinical trial and we still lack the evidence necessary for endorsement by health authorities. In this review, we identify several promising options that warrant further investigation as potential surrogate endpoints in clinical trials to replace TTCW or 6-minute walk distance. Prospective inclusion of such tools in new clinical trials may help build a stronger surrogacy for prognosis of disease progression and mortality.

Drug Utilization Pattern of Anti-Diabetic Medication: A Prospective Observational Study

Background: Diabetes mellitus is a chronic disease and is responsible for the significant morbidity and mortality. It is critical to conduct a drug use research of anti-diabetic medications in order to encourage rational drug use in diabetes.
 Objective: The purpose of this study was to analyze the pattern of drug use of antidiabetic drugs, as well as the prevalence of diabetes and related risk factors throughout treatment period in our sample group.
 Materials & methods: This is a prospective observational research involving 200 secondary care hospital in-patients. During a 6-month period, the prescribing pattern was studied and assessed, and drug-related difficulties in subsequent patients were report.
 Results: Among 200 patients, 111 (55.46%) were male and 89 (44.5%) were female. Subject of age 65-80 (n=73) were observed to be more suspected. Hypertension 130 (61.32%) was the most common risk factors. In 200 cases, the most commonly used therapy was monotherapy in 89 subjects (44.5%) followed by combination therapy 55(27.5%). Insulin 192(54.5%) was most commonly used followed by oral drugs 160 (45.4%). The most usually prescribed monotherapy was metformin, followed by glimepiride, while the most commonly prescribed combination therapy were metformin+glimepiride.
 Conclusion: Prescribing pattern of drugs in diabetic patients concluded that optimized drug therapy led to minimal ensuing DRPs. A continuous observation and reporting of the prescribing practice of anti-diabetic drugs can help the physicians result in therapeutically effective treatment for the patients.
 Keywords: Antidiabetics, Drug utilization pattern, Drug related problem, Comorbidities, metformin

Basic principles of combination therapy: focus on drug-drug interaction

The article is devoted to the issue of drug interactions in the combination regimens. Today, when drug therapy is the first-line approach for patients with noncommunicable diseases, and the world population ageing leads to an increase in the number of patients with severe comorbidity and polypharmacy, the problem of drug-drug interaction is especially relevant. The article discusses the main types of drug interactions — pharmacokinetic (related to absorption, distribution, metabolism and excretion of drugs) and pharmacodynamic ones, leading to synergy or antagonism of the pharmacological effects. The consequences of drug interactions can be desirable and undesirable, while the latter are much more common. Attention should be directed precisely to preventing such interactions. Also, using data from special scales and lists (Beers criteria, STOPP/START criteria), the options for various adverse drugdrug interactions are briefly described. In addition, the article provides a number of Internet resources that allow assessing the drug interaction risk when prescribing combination therapy.

When is preservative-free therapy of glaucoma needed and advisable?

Purpose: to estimate the demand for preservative-free medical therapy of glaucoma in real clinical practice as part of the analysis of the compliance of specialized medical care of glaucoma patients and the approved clinical guidelines.Material and methods. Head non-staff ophthalmologists in 34 regions of Russia were surveyed to find out the share of patients with a newly diagnosed primary open-angle glaucoma; systemic contraindications; diseases of ocular surface tissues; using combination therapy if monotherapy proves ineffective. Also, we analyzed the current annual need for glaucoma treatment drugs in Russia and estimated the expected need for these drugs.Results. The survey showed that, on average, (1) 64.35 % of glaucoma patients are prescribed monotherapy; (2) in the presence of systemic contraindications, nonselective beta-blockers are avoided in 85 % of cases; (3) ca. 53 % of glaucoma patients require preservative-free therapy; (4) almost 61 % of patients for whom monotherapy proved ineffective are prescribed combination therapy. As shown by calculated annual and projected demand for antiglaucomatous drugs in 2020, the leading position is taken by timolol (43.96 %), followed by dorzolamide (38.04 %), and tafluprost (11.93 %). Diseases of the ocular surface in glaucoma patients with glaucoma averaged 52.6 % in the surveyed regions.Conclusion. The actual demand for preservative-free therapy in clinical practice in the analyzed regions is higher than the annual and predicted need as it is required by about 54% of all patients with glaucoma. Further epidemiological, pharmacological and economic studies of ocular surface disease incidence in patients with glaucoma and of the demand for preservative-free therapy are required in order to solve the issue of drug supply in regions of Russia.

Prescription pattern of anti-hypertensive drugs in Chitwan Medical College Hospital

Background and Objectives: Hypertension is a crucial health issue globally. Cardiovascular and kidney disease is one of the results of hypertension which remarkably confer to overall mortality. Thus, the aim of this study is to investigate the prescribing pattern of anti-hypertensive drugs to hypertensive patients and also to establish the current trend of prescribing pattern of anti-hypertensive drugs at Chitwan Medical College (CMC).
 Material and Methods: A descriptive cross-sectional study was conducted among 290 patients to assess the prescribing pattern of anti-hypertensive drugs from hypertensive patients visiting medicine OPD of CMC during study period and fulfilling the inclusion criteria. A standard proforma was used to collect information about patient’s socio-demographic details and anti-hypertensive drugs used for them. Data was collected, compiled and analyzed by using Statistical Package of Social Science (SPSS) version 16.
 Results: Out of 290 prescriptions, 201 (69.3%) patients received monotherapy while only 89 (30.7%) patients received combination therapy. In monotherapy, calcium channel blockers (CCBs) and Angiotensin receptor blockers (ARBs) were most commonly prescribed, while angiotensin receptor blockers (ARBs) + diuretics were the most commonly prescribed combination therapy.
 Conclusion: In the present study, it was found that CCBs and ARBs were the most commonly prescribed anti-hypertensive drug in monotherapy.

Probiotic Lactobacillus plantarum may reduce cardiovascular risk: An experimental study.

BACKGROUNDReduction of cardiovascular risk (CVR) is based on the correction of risk factors, especially dyslipidemia. Due to the limiting factors of conventional lipid-lowering medications, the investigation of alternative approaches is necessary.METHODSThe present open, comparative, randomized, and parallel investigation was conducted on 77 patients. Participants were of both sexes, 40-74 years-of-age, and had dyslipidemia. The participants were divided into 2 groups; the treatment group (n = 41) received a combination of Lactobacillus plantarum and simvastatin 20 mg once a day, and the control group (n = 36) received simvastatin 20 mg once a day. The trial included 5 visits; screening on the first 2, and treatment on the next 3 (on weeks 4, 8, and 12). On visits 1, 3, 4, and 5, the lipid profile was evaluated and CVR was calculated using 5 tools.RESULTSThe combination treatment led to a more pronounced decrease in total cholesterol (TC) and low-density lipoproteins (LDL) after 8 weeks (P = 0.002 and 0.016, respectively), that persisted after 12 weeks (P < 0.001 and 0.002, respectively). Reduction in TC and LDL by ³ 20% was observed more predominantly in the treatment group. A significant reduction was observed in CVR in the treatment group according to the Prospective Cardiovascular Münster (ýPROCAM) score (P = 0.004). Reduction of CVR by ³ 20% was mostly observed as a result of prescribing combination therapy according to the Framingham Risk Score ý(70.7%; P = 0.003), 2013 ACC/AHA ASCVD Risk Calculator ý(51.2%; P = 0.035), PROCAM (65.9%; P < 0.001), and WHO CVD risk chart (56.1%; P = 0.012).CONCLUSIONAdditional supplementation with Lactobacillus plantarum was more effective in the reduction of TC, LDL, and CVR according to PROCAM and the attainment of treatment goals regarding lipid profile and CVR levels.

An audit of high-dose and combination antipsychotic prescribing across the general adult inpatient wards in Mersey Care NHS Foundation Trust

AimsTo review the number of prescriptions of regular high-dose antipsychotics and combination antipsychotic therapy across the eight general adult inpatient wards in Mersey Care NHS Foundation Trust and examine whether these prescriptions followed Trust recommendations for high-dose antipsychotic therapy (HDAT).BackgroundThe two main rationales behind prescribing HDAT are pharmacokinetics differ in individuals and so insufficient amounts of antipsychotic may reach the effect site at maximum dose in some patients and variations in the effect site between patients may mean higher doses are required to achieve therapeutic effect.MethodThe electronic prescription records for all patients on the eight general adult inpatient wards were scrutinised. 121 patients were prescribed antipsychotic medication. Any patients on a combination of regular antipsychotic medication or on HDAT were identified. Any patient on combination therapy or HDAT was studied to determine if Clozapine had been considered. The electronic notes of HDAT patients were analysed to ascertain whether tests recommended by Trust guidelines – BMI, blood pressure (B.P), pulse rate, ECG, FBC, U and Es, LFTs, serum prolactin, serum cholesterol and HbA1c level had been performed prior to initiation and following any dose increase.Result21 of 121 patients prescribed antipsychotic medication were on combination therapy. 11 were subject to HDAT. 8 of the 11 HDAT patients were on combination therapy. Clozapine was considered before initiating HDAT in 9 of the HDAT patients. Clozapine was considered in 13 of the 21 patients on combination antipsychotic therapy, but only two were initiated on Clozapine (combined with Olanzapine or Risperidone).100% of HDAT patients had an ECG prior to initiation of HDAT; only 36% had one after dose increases above BNF maximum. 100% of HDAT patients had their BMI measured before initiation. 91% had baseline B.P and heart rate checked. Of the recommended blood tests, 100% of HDAT patients had baseline FBC, U and Es, LFTs and serum cholesterol. Fewer patients had a baseline HbA1c level (91%) or serum prolactin (46%) measured.ConclusionPrevalence of HDAT across the general adult inpatient wards in the Trust was 9%, much lower than the 28% reported in the HDAT audit completed by the Prescribing Observatory for Mental Health in 2012. Patients within Mersey Care are more likely to be prescribed combination therapy than HDAT. Not every HDAT patient has been considered for Clozapine. There is a need to ensure Trust monitoring guidelines for HDAT patients are being strictly adhered to.

Management of childhood and adolescent latent tuberculous infection (LTBI) in Germany, Austria and Switzerland.

Majority of active tuberculosis (TB) cases in children in low-incidence countries are due to rapid progression of infection (latent TB infection (LTBI)) to disease. We aimed to assess common practice for managing paediatric LTBI in Austria, Germany and Switzerland prior to the publication of the first joint national guideline for paediatric TB in 2017. Online-based survey amongst pediatricians, practitioners and staff working in the public health sector between July and November 2017. Data analysis was conducted using IBM SPSS. A total of 191 individuals participated in the survey with 173 questionnaires included for final analysis. Twelve percent of respondents were from Austria, 60% from Germany and 28% from Switzerland. Proportion of children with LTBI and migrant background was estimated by the respondents to be >50% by 58%. Tuberculin skin test (TST) and interferon-γ-release-assay (IGRA), particularly Quantiferon-gold-test, were reported to be used in 86% and 88%, respectively. In children > 5 years with a positive TST or IGRA a chest x-ray was commonly reported to be performed (28%). Fifty-three percent reported to take a different diagnostic approach in children ≤ 5 years, mainly combining TST, IGRA and chest x-ray for initial testing (31%). Sixty-eight percent reported to prescribe isoniazid-monotherapy: for 9 (62%), or 6 months (6%), 31% reported to prescribe combination therapy of isoniazid and rifampicin. Dosing of isoniazid and rifampicin below current recommendations was reported by up to 22% of respondents. Blood-sampling before/during LTBI treatment was reported in >90% of respondents, performing a chest-X-ray at the end of treatment by 51%. This survey showed reported heterogeneity in the management of paediatric LTBI. Thus, regular and easily accessible educational activities and national up-to-date guidelines are key to ensure awareness and quality of care for children and adolescents with LTBI in low-incidence countries.

Сравнительный анализ эффективности раннего и отложенного начала комбинированной медикаментозной терапии ДГПЖ

Introduction Currently, -blockers (-AB) and 5-alpha-reductase inhibitors (I-5-AR) are recommended as the drugs of choice for the treatment of patients with benign prostatic hyperplasia (BPH). However, despite the clear advantages of combination therapy, at the initial stages of treatment, I-5-AR is either not prescribed at all, or added to therapy after a few months. The aim of our study is to study the effectiveness of early and various options for delayed combined drug therapy of patients with BPH using -AB and I-5-AR. Materials and methods The study included 90 patients with BPH, who were divided into three groups of 30 people. In group 1, monotherapy with drugs from the -AB group was performed for 6 months, after which they were transferred to treatment with a combined drug. In group 2, monotherapy was performed for three months, after which they were also transferred to treatment with a combined drug. And in group 3, patients were prescribed combination therapy from day 1. Results Early combination therapy with dutasteride was more effective than delayed Therapy for 6 months. There were no significant differences in the main parameters studied between patients who simultaneously started combination therapy and switched to it after 3 months, by the end of the 12th month of treatment. However, early therapy is a combined drug made it possible to achieve a more rapid effect in relation to LUTS. Conclusion Thus, the data obtained confirm the clinical recommendations regarding the expediency of early initiation of combined therapy with an -adrenoblocker and a 5-reductase inhibitor in patients with moderate and severe LUTS caused by BPH and the risk of disease progression. Postponing the transition to combination therapy for 6 months or more may lead to a decrease in the effectiveness of treatment of patients in this category.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PurposeThe standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists’ use of thyroid hormones in hypothyroid and euthyroid patients.MethodsAn e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES).ResultsOut of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another.ConclusionThe treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40618-021-01555-y.

Results of a clinical trial of the efficacy and safety of vildagliptin and metformin fixed combination in real clinical practice in Russia (MASTER study)

BACKGRAUND: The widespread prevalence of type 2 diabetes mellitus (T2DM), high mortality and disability of such patients are the reason for the constant active search for effective approaches to hypoglycemic therapy. Recent years have been marked by a change in the strategy for treatment initiation of T2DM. In clinical studies, evidence has been obtained about the benefits of prescribing combination therapy from the time of diagnosis. It seems important to study this treatment option also in real clinical practice.AIMS: To evaluate the effectiveness and safety of the initiation with Galvus Met® as compared with any other combination therapy approaches used in everyday clinical practice.MATERIALS AND METHODS: multicenter prospective observational study in 15 regions of Russia lasting 6 months. Patients were included in the study after the endocrinologist made a decision on the appointment of therapy. Of the men and women over 18 years of age with first diagnosed or previously untreated type 2 diabetes and a level of glycated hemoglobin &gt;7.5%, two groups were formed. The first group included patients who received vildagliptin + metformin (Galvus Met®) in a fixed dose of 50/1000 mg, n=729, the second — another double combination (with the exception of insulin and GLP-1), n=669. The primary endpoint was defined as the proportion of patients (%) who achieved the level of HbA1c &lt;7.0% without proven hypoglycemia at the end of the observation. The NHPQ questionnaire was used to assess the frequency of hypoglycemia.RESULTS: 1385 patients completed the study. For the other combination therapy group, metformin and sulfonylurea derivatives were most often selected (66.5%). In the Galvus Met® group, 68.7% of patients achieved an HbA1c level of &lt;7.0% without proven hypoglycemia, which is significantly better compared to the group of other combinations (40.7%, p &lt;0.001). Galvus Met® therapy contributed to a significantly greater decrease in HbA1c levels by the end of the study compared to other combinations (delta HbA1c -1.6 ± 0.8% versus -1.4 ± 0.9%, p &lt;0.001). In the same group, the average level of HbA1c reached 6.7 ± 0.6% by the end of the study versus 7.1 ± 0.8% in the comparison group, p &lt;0.001. In the Galvus Met® group, body weight decreased by 3.2 ± 3.9 kg, and in the comparison group by 1.3 ± 4.8 kg, p &lt;0.001. The frequency of hypoglycemia episodes in the Galvus Met® group by the end of the study was significantly lower than in the comparison group: 0.8 ± 0.7 episodes per person, versus 1.4 ± 0.8, p = 0.037. In the Galvus Met® group, there were significantly fewer adverse events (4.9% versus 17.7%, p &lt;0.001).CONCLUSIONS: In real clinical practice, Galvus Met® starting therapy has shown better efficacy and safety in terms of achieving glycemic control, HbA1c dynamics, effects on body weight, the frequency of hypoglycemic conditions compared with other combined oral hypoglycemic therapy.

Features of the therapy of non-alcoholic fatty liver disease in comorbid patients

The problem of modern medicine and modern society is a comorbid patient with metabolic disorders. Hypothetical portrait of such a patient: over 40 years old, overweight, arterial hypertension, coronary atherosclerosis, impaired carbohydrate and lipid metabolism, liver steatosis or steato-hepatitis, often with changes in the function of the musculoskeletal system. Rational pharmacotherapy of this patient is of fundamental importance. The article analyzes, from the point of view of polypotency, efficacy and safety, the main drugs used in Russia for treatment of non-alcoholic fatty liver disease in comorbid patients. Attention is paid to vitamin E, glycyrrhizin, ursodeoxycholic acid. Domestic and foreign studies of these drugs are analyzed, and the scope of their rational use is shown: reducing the risk of cardiovascular complications, a positive effect on the lipid spectrum, reducing the activity of serum transaminases and other hepatotropic effects. Their side effects are also considered, which should be taken into account when choosing the treatment of a comorbid patient. We have analyzed the efficacy and safety of new molecules that are in clinical trials and/or have not yet been registered in our country, e.g. obeticholic acid, cenicriviroc, tropifexor, etc. The ability of some molecules to act as biological enhancers is also highlighted, which is important to consider when prescribing combination therapy. Doctors are recommended to carefully consider and take into account all the features of a comorbid patient and choose for this category of patients safe drugs of hepatotropic action with simultaneous positive effect on the cardiovascular system. Among other things, it will avoid polypragmasy.

CDK4/6 inhibitors in the treatment of metastatic breast cancer. Choosing optimal therapy for estrogen-receptor-positive HER2-negative metastatic breast cancer: analysis of doctors’ preferences (“Prometheus”) in Russia – first results of the survey

The emergence of a new class of drugs – inhibitors of cyclin-dependent kinases 4/6 (CDK4/6) – has changed the paradigm of treatment of patients with luminal HER2 negative metastatic breast cancer. Their effectiveness is confirmed not only by randomized, but also observational studies on a wide heterogeneous population of patients from daily clinical practice; the use of these drugs in the 1 st line is significantly expanding in the world. On the territory of the Russian Federation, an observational study of Prometheus was carried out, the purpose of which was to assess the frequency of prescribing CDK4/6 inhibitors, as well as other types of treatment in 1–2 nd lines in real clinical practice in Russia, as well as factors and preferences of doctors influencing the choice of therapy. A survey of the target audience, whose answers can be considered reliable and reflecting today’s Russian clinical practice in the treatment of breast cancer, showed that, despite the fact that the overwhelming majority of doctors (78 %) believe that the maximum benefit from the appointment of CDK4/6 inhibitors is expected for the 1 st line therapy, in real clinical practice, only 35 % of doctors practice 1 st line prescription. In the 2nd line of therapy, CDK4/6 inhibitors are prescribed by 45 % of experts, in the 3 rd (or more) line – 20 %. According to the respondents, the main obstacle to the appointment of CDK4/6 inhibitors is the unresolved issues of the availability of therapy (44 %) and its cost (34 %). Among all the proposed clinical criteria, only the criterion “visceral metastases with impaired function of internal organs” influences the decision not to prescribe a combination of hormonal therapy and a CDK4/6 inhibitor in 1–2 nd lines of therapy. Criteria such as ECOG status, menopause status, tumor subtype preceding chemotherapy, timing of progression do not determine the choice when deciding not to prescribe combination therapy.

The use of L-thyroxine in the treatment of thyroid pathologies and problems of therapy control (literature review)

Background. Thyroid disease is one of the most common pathologies in the world, wich includs hypothyroidism, hyperthyroidism and thyroid cancer. At the present, there is an increase in their cases. The thyroid gland is an extremely important for the health of a person, thyroid hormones are necessary for the normal functioning of all tissues in the body.&#x0D; Purpose. To structure and summarize scientific findings on the role of thyroid hormones (T4, T3 and rT3) in the development of hypothyroidism, their effect on inhibiting the growth of cancer cells and the cytotoxic effects of these hormones on thyroid cells.&#x0D; Results and discussion. In spite of a careful study of thyroid function, the use of thyroid hormones and laboratory monitoring in the treatment of various thyroid pathologies remains debatable up to now. In particular, it concerns LT4 + LT3 combination and the role of reversible T3. This is due to a complex regulation system depending on many factors: hormonal homeostasis, nutritional factors, physiological conditions, etc., which together maintain appropriate thyroid functioning. LT4 monotherapy remains the standard method of replacement therapy, however, according to the ETA recommendations, it is possible for individual patients to prescribe combination therapy LT4 + LT3 as an experimental approach. The use of the rT3 test as a prognostic / diagnostic indicator for monitoring the therapy of patients receiving L-thyroxine therapy is discussed. The use of L-thyroxine as a thyrotropic suppressive therapy in the treatment of thyroid cancer requires careful dose adjustment depending on the health status of each patient, the risk of recurrence, which requires monitoring and dynamic reassessment. Long-term suppressive therapy of LT4 can affect metabolism, contributing to weight loss.&#x0D; Conclusions. Given the analysis of the literature, which covered 20 years, today L-T4 monotherapy is the standard therapy for patients with hypothyroidism. LT4 + LT3 combination therapy can be recommended in patients receiving L-T4 treatment with complaints characteristic of hypothyroidism despite normal TSH levels, with the exception of other chronic and concomitant autoimmune diseases that may be the cause.

“Hepatogenic diabetes” is an old term and new meaning

Introduction. Today, non-alcoholic fatty liver disease (NAFLD) is increasingly associated with the presence or risk of developing type 2 diabetes (D2). The term “hepatogenic diabetes”, proposed to refer to SD2 in patients with cirrhosis of the liver (CP), has acquired a new meaning, since this combination is of growing interest. The authors analyzed the current literature and summarized data on the pathogenesis, risk factors, and possible therapy of NAFLD.Objective: to evaluate the effectiveness of L-ornithine-L-aspartate (HEPA-Merz, Merz Pharma GmbH &amp; Co) in combination with biguanides in the treatment of NAFLD patients in combination with D2.Materials and methods. The study included 30 patients aged 26 to 60 years with a verified diagnosis of NAFLD of varying degrees of activity in combination with D2. All patients were prescribed combination therapy with the drug HEPA-Merz (“Merz Pharma GmbH and Co”) at a dose of 3 grams 3 times a day in combination with biguanides. The examination was performed on the 1st, 28-th and 56-th days of treatment. In order to determine the effectiveness of therapy, we evaluated the dynamics of clinical symptoms (asthenovegetative, dyspeptic syndromes, pain syndrome in the ball system), biochemical parameters of liver function (changes in markers of cytolysis, cholestasis), lipidogram indicators, glucose levels, glycated hemoglobin, and ultrasound results of abdominal organs.Results. On day 56, asthenovegetative, dyspeptic and pain syndrome were stopped during therapy. Most patients showed a decrease in body weight from 3 to 5 kg. When evaluating changes in biochemical parameters on the 28-th day, the activity of ALT, AST, GGTP and glucose levels significantly decreased against the background of the therapy. On the 56th day of treatment, the activity of transaminases, bilirubin, GGTP and GFR in all patients were within the reference values.Conclusion. Understanding the multifactorial nature of NAFLD and the mechanisms of associated diseases, including D2, will allow us to assess the prognosis of the disease and prescribe adequate timely therapy. The effectiveness of the original ornithineaspartate (Merz Pharma GmbH &amp; Co.) is manifested by a decrease in the processes of cytolysis of hepatocytes, normalization of lipid and carbohydrate metabolism.

EP43 Biologic retention in psoriatic arthritis: a real world study

Abstract Background Biologics have led to a sea change in the management of psoriatic arthritis (PsA) with unprecedented improvement in the signs, symptoms and radiographic damage, resulting in improvement in functionality and quality of life. However longitudinal data for their retention and tolerability is sparse. Our objective was to evaluate real-world biologic therapy duration and reasons for discontinuing treatment. Methods We conducted a retrospective analysis of our PsA electronic register from 1994 up to and including April 2019 at our university teaching hospital. We had access to full patient records including details on co-morbidities, drugs and disease management. Results 335 patients were identified with PsA. 58% were female with mean age 46 yr (13-81). 113 (33.7%) patients had been treated with a biologic with 105 (93%) continuing at the time of analysis. 60 individuals were prescribed combination therapy with DMARDs. Mean age was 43.3 (13-81) with 56% women. The biologics sample was ethnically diverse including 80% White Caucasian patients, 17% Asian and others (3%). Significant co-morbidities included cardiovascular disease (18.6%) and diabetes (4.4%). Eight different biologics were in use with adalimumab being the most prescribed (67%). 35 (30.9%) patients had stopped biologics at some point with 76 episodes of cessation. 6% of our sample had discontinued two or more biologic treatments. The mean duration before biologic therapy was discontinued was 18.2 months (8 days to 9.5 years), which was almost twice as long as the average period before discontinuing a DMARD (9.9 months). Main reasons for stopping treatment included 23% each due to GI symptoms, neurological causes, cutaneous symptoms and other side effects. The remaining 8% reported fatigue as the reason for stopping therapy. Conclusion To our knowledge this is the first dedicated retrospective review of a large real world PsA cohort comparing drug survival and tolerability of biologics against DMARDs. Biologic therapies are well tolerated in psoriatic arthritis. There is no significant difference amongst various modes of action. Over a quarter of the patients discontinue the drug owing to intolerance with mean drug survival of 18 months. In contrast nearly two-thirds were intolerant of DMARDs and stopped within ten months. Thus both the rate and duration of biologic retention is significantly better than conventional DMARDs. This has significant economic impact as NICE guidelines require an adequate trial of two DMARDs for six months prior to advanced therapy. However, this approach is unlikely to be cost effective as the disease progresses whilst patients struggle with DMARDs prescription and thus delay biologics which are more likely to be tolerated and retained longer. Hence there is an urgent need to review NICE guidelines to allow earlier employment of biologics in the treatment paradigm with significant benefits to both patients and the health economy. Disclosures: I. Jawad: None. M.K. Nisar: None.

The efficacy and safety of ethyl methyl hydroxypyridine succinate used as part of sequential therapy in patients with chronic cerebral ischemia

Objective: to investigate the efficacy and safety of Mexidol ® FORTE 250 in patients with chronic cerebral ischemia (CCI) in the presence of hypertension and atherosclerosis. Patients and methods. The investigation enrolled 20 patients aged 45 to 75 years with CCI in the presence of hypertension and atherosclerosis, who received intravenous Mexidol ® administered dropwise at a dose of 500 mg once a day for 14 days, followed by oral Mexidol ® FORTE 250 mg thrice a day for 60 days (a study group). A control group consisted of 14 patients with CCI in the presence of hypertension concurrent with atherosclerosis, who were prescribed combination therapy for CCI without using these drugs. The patients were examined before and at 14 and 60 days of treatment. The investigators studied subjective complaints, neurological symptoms, and the indicators of the Tinetti Performance-Oriented Mobility Assessment in Elderly Patients; the Montreal Cognitive Assessment (MoCA); the Hamilton Anxiety Rating Scale (HARS); asthenia rating scales (Multidimensional Fatigue Inventory, MFI-20); and the Clinical Global Impression (CGI) scale over time. Results and discussion. Therapy with Mexidol ® in patients with CCI in the presence of hypertension and atherosclerosis was found to be accompanied by positive changes in the asthenia rating scale MFI-20, cognitive functions assessed by MoCA, as well as Tinetti movement coordination. No significant differences in these indicators were noted in patients of the control group. Combination treatment for CCI with Mexidol ® and Mexidol ® FORTE 250 as a sequential therapy was twice more effective than that without using these drugs, as shown by the scales as a whole and it was up to 10 times greater for individual scale parameters. Conclusion. The study of Mexidol ® FORTE 250 as part of the sequential therapy, which was used according to the above regimen, indicates its clinical efficacy and safety in patients with CCI.

Improving Medication Adherence in Cardiovascular Disease Prevention: What's New?

Improving Medication Adherence in Cardiovascular Disease Prevention: What's New?

National Medical Research Center for Preventive Medicine, Moscow, Russia

Arterial hypertension is the leading cause of cardiovascular morbidity and mortality. According to Russian and international studies, prevalence of hypertension is approximately 40%. In the next years an increase in the number of patients can be expected. Hypertension is the main independent risk factor for coronary heart disease for all age groups. Modern antihypertensive drugs can provide good control of blood pressure and reduce the incidence of complications and mortality. By prescribing antihypertensive therapy, it is necessary to achieve the target level of blood pressure, for most patients ≤130/80 mm Hg. When prescribing combination therapy, preference should be given to fixed combinations. Approximately 10% of patients with hypertension have resistance to therapy. Such patients often need an extended diagnostic search to exclude pseudoresistance and secondary hypertension. One of the main causes of pseudoresistance is poor adherence to therapy. Patients with resistant hypertension have a higher risk of adverse outcomes compared with patients without this type of disease.