Oral Combination Therapy Research Articles

Reversal of New Onset Type 1 Diabetes by Oral Salmonella-Based Combination Therapy and Mediated by Regulatory T-Cells in NOD Mice.

Autoimmune diseases such as type 1 diabetes (T1D) involve the loss of regulatory mechanisms resulting in increased tissue-specific cytotoxicity. The result is destruction of pancreatic insulin-producing β-cells and loss of glucose homeostasis. We are developing a novel oral vaccine using live attenuated Salmonella to deliver TGFβ, IL10, and the diabetic autoantigen preproinsulin combined with low-doses of anti-CD3 mAb. Here we show that oral administration of Salmonella-based anti-CD3 mAb combined therapy reverses new-onset T1D in non-obese diabetic (NOD) mice. The therapeutic effect of the combined therapy was associated with induction of immune suppressive CD4+CD25+Foxp3+ Treg and CD4+CD49b+LAG3+ Tr1 cells. In adoptive transfer experiments, adding or depleting Treg or Tr1 cells indicated that both are important for preventing diabetes in combined therapy-treated mice, but that Tr1 cells may have a more central role. Furthermore, induced Tr1 cells were found to be antigen-specific responding to peptide stimulation by secreting tolerance inducing IL10. These preclinical data demonstrate a role for Treg and Tr1 cells in combined therapy-mediated induction of tolerance in NOD mice. These results also demonstrate the potential of oral Salmonella-based combined therapy in the treatment of early T1D.

Prescribing patterns and compliance with World Health Organization recommendations for the management of severe malaria: a modified cohort event monitoring study in public health facilities in Ghana and Uganda

BackgroundInjectable artesunate (AS) is the World Health Organization (WHO) recommended medication for the treatment of severe malaria followed with an oral artemisinin-based combination therapy (ACT). There are few studies indicating how physicians prescribe injectable AS, injectable quinine (Q) or injectable artemether (AR) and ACT for severe malaria. This study was undertaken to evaluate prescription compliance to the WHO recommendation in 8 public health facilities in Ghana and Uganda. This was a modified cohort event monitoring study involving patients who were administered with injectable anti-malarial for treatment of presumed or confirmed severe malaria. Patients prescribed at least one dose of injectable artesunate, artemether or quinine qualified to enrol in the study. Patients were recruited at inpatient facilities and followed up in the hospital, by phone or at home. Following WHO recommendations, patients are to be prescribed 3 doses of injectable AS, Q or AR for at least 24 h followed with oral ACT. Compliance rate was estimated as the number of patient prescriptions that met the WHO recommendation for treatment of severe malaria divided by the total number of patients who completed the study by end of follow up. Log-binomial regression model was used to identify predictors for compliance. Based on the literature and limitations of available data from the patients’ record, the diagnosis results, age, gender, weight, and country were considered as potential predictors of prescriber adherence to the WHO recommendations.ResultsA total of 1191 patients completed the study, of which 93% were prescribed injectable AS, 3.1% (injectable AR or Q) with 32.5% prescribed follow-on oral ACT and 26% on concomitant antibiotics. 391 (32.8%) were in Ghana and 800 (67.2%) in Uganda. There were 582 (48.9%) women. The median age was 3.9 years (IQR = 2, 9) and median weight was 13 kg (IQR = 10, 20). Of the 1191 patients, 329 of the prescriptions complied with the WHO recommendation (compliance rate = 27.6%; 95% CI = [25.2, 30.2]). Diagnostic results (Adjusted prevalence ratio (aPR) = 4.56; 95% = [3.42, 6.08]; p < 0.0001) and weight (20 + kg vs < 10 kg: aPR = 0.65; 95% = [0.44, 0.96]; p = 0.015) were identified as factors independently associated with compliance.ConclusionInjectable AS is the most commonly prescribed medicine in the management of severe malaria in Ghana and Uganda. However, adherence to the WHO recommendation of at least 3 doses of injectable anti-malarial in 24 h followed by a full course of ACT is low, at less than 30%.

Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails.

On-demand phosphodiesterase type 5 inhibitor (PDE5i) monotherapy is a first-line treatment for erectile dysfunction (ED), but 30%-40% of patients exhibit little or no response. The success rate of alprostadil therapy is high in these patients, but this treatment requires painful intracavernosal injection. To systematically review the efficacy and safety of second-line oral pharmacologic combination therapies of ED when PDE5i monotherapy fails. PubMed and Embase were searched to identify reports providing quantitative data on the treatment of ED in patients failing PDE5i monotherapy. The measures of erectile function were the International Index of Erectile Function (IIEF) and the Erectile Function Domain (EFD). Chronic treatment with the PDE5i tadalafil alone or in combination with sildenafil on demand showed similar IIEF-5 score improvements. None of the 3 randomized controlled trials (RCTs) in patients who had failed PDE5i monotherapy found a superior effect on IIEF scores from the combination of androgen plus PDE5i compared with PDE5i monotherapy. Combination therapy with androgen supplementation and PDE5i appears safe. In 1 RCT, combination therapy with PDE5i and an α1-adrenoceptor antagonist was not superior to PDE5i monotherapy. Six other studies, each with a different combination of PDE5i and another drug (eg, metformin, folic acid, 5-alpha-reductase inhibitors), were identified, but further research is required to investigate their efficacy in treating ED. For ED, chronic treatment with low-dose PDE5i can be attempted when standard on-demand regimens fail. Combination therapy with androgen supplementation and a PDE5i appears to be safe. The combination of an α1-adrenoceptor antagonist and PDE5i shows no advantageous effect on ED compared with PDE5i monotherapy. The efficacy of combining PDE5i with metformin, folic acid, or 5-alpha-reductase inhibitors is uncertain and requires further research. There is an unmet need for oral treatment of ED in nonresponders to PDE5i treatment. Munk NE, Knudsen JS, Comerma-Steffensen S, etal. Systematic Review of Oral Combination Therapy for Erectile Dysfunction When Phosphodiesterase Type 5 Inhibitor Monotherapy Fails. Sex Med Rev 2019;7:430-441.

Improving Survival in Patients with Pulmonary Arterial Hypertension: Focus on Intravenous Epoprostenol.

Pulmonary arterial hypertension represents a devastating disease, causing progressive increase of pulmonary vascular resistance leading to right ventricular dysfunction and death. Therapeutic management has rapidly advanced in recent years due to improved understanding of pathophysiology and new drugs have been developed; however, survival remains poor. Oral agents as phosphodiesterase type V inhibitors, the soluble guanylyl cyclase stimulator riociguat, the prostacyclin receptor agonist selexipag and the endothelin receptor antagonists have each achieved evidence-based validation and are recommended for pulmonary arterial hypertension. Initial oral monotherapy or combination therapy is recommended for patients with low or intermediate risk according to each patient's risk stratification. Intravenous epoprostenol is a synthetic prostacyclin and the first drug approved for the disease. Although it represents the only treatment shown to reduce mortality, it is underused. Survival rates for patients treated with oral combination drug therapies are lower than those for patients treated with initial combination therapies including intravenous epoprostenol. This raises the interesting question of whether intermediate risk pulmonary arterial hypertension patients should be routinely introduced to therapies including intravenous epoprostenol rather than combination oral therapies.

A pharmacoeconomic analysis to compare cost-effectiveness of metformin plus teneligliptin with metformin plus glimepiride in patients of type-2 diabetes mellitus.

Background:With the available evidence of early combined oral drug therapies being more effective in lowering blood glucose levels than maximal doses of a single drug, many clinicians are taking the aggressive approach of adding a sulfonylurea or a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin as the initial therapy in type 2 diabetes mellitus (T2DM). Pharmacotherapy for a chronic disease like diabetes has substantial economic implications for patients especially in a developing country like India. So it is important to scientifically evaluate the cost-effectiveness of these commonly practiced combination therapies in the management of T2DM.Materials and Methods:This was a prospective observational randomized comparative study conducted over 8 weeks on patients of T2DM who were prescribed either of the two therapies of metformin (500 mg) plus glimepiride (1 mg) or metformin (500 mg) plus teneligliptin (20 mg). Cost-effectiveness analysis was done by calculating the expense incurred on 0.1% reduction in HbA1 c and 1 mg/dl reduction in fasting plasma glucose (FPG)/post-prandial plasma glucose (PPG) levels after 8 weeks and compared for both the groups. The same was also evaluated for differences in BMI levels.Results:The cost-effectiveness for per unit reduction in HbA1c and FPG was significant in metformin plus glimepiride group as compared to the metformin plus teneligliptin group though it was comparable for both the groups for per unit PPG reduction. There was no significant change in BMI levels between the groups.Conclusion:Compared to metformin plus teneligliptin, metformin plus glimepiride is a significantly cost-effective therapy when used as an initial combination therapy in patients of T2DM in lowering HbA1c and FPG.

Using the Pharmaceutical Collection Database to identify patient adherence to oral hypoglycaemic medicines.

INTRODUCTION Poor adherence to oral hypoglycaemic medicines is a key contributor to therapy failure and sub-optimal glycaemic control among people with type 2 diabetes. It is unclear how commonly non-adherence to oral hypoglycaemics occurs in the general population. This information is essential to design and implement local adherence strategies. AIM This study aimed to determine levels of sub-optimal adherence and identify patient groups who may need additional adherence support. METHODS The dispensing data of 340,283 patients from one District Health Board was obtained from the Pharmaceutical Collection Database for the period 2008-15. Of these, 12,405 patients received oral hypoglycaemic therapy during the study period. The proportion of days covered (PDC) was calculated for patients with complete data and a PDC value of ≥80% was used to indicate sufficient adherence. Patient demographics (gender, ethnicity, age, socioeconomic status) and therapy type (mono- or combination) were described. RESULTS Overall, 54.5% of the patients were found to have a PDC of <80% and so were considered non-adherent. Non-adherence was significantly higher in patients receiving combination oral hypoglycaemic therapy than monotherapy; in male patients; in New Zealand Māori patients; and in patients with higher socioeconomic deprivation. DISCUSSION In the study region, non-adherence to oral hypoglycaemic medicines was significant and widespread. Identification of such patients is important so that strategies to enhance adherence can be implemented. Prescribers need to be encouraged to optimise monotherapy before the addition of another oral hypoglycaemic, and adherence support services should be offered not only to older patients.

A 4-Day Incubation Period of Plasmodium falciparum Infection in a Nonimmune Patient in Ghana: A Case Report.

Plasmodium falciparum can cause severe infection and has the shortest incubation period compared with all the other Plasmodium species. Incubation periods of 9–14 days for the immune and 6–14 days for the nonimmune have been reported for P. falciparum. However, an incubation period of less than 5 days has not been reported, as of yet. This report presents a case of a 23-year-old nonimmune female who presented with signs and symptoms 4 days after being bitten by mosquitoes while visiting Ghana. The patient was successfully treated with a 1-day course of parenteral artesunate, followed by a 3-day course of oral artemisinin combination therapy.

Effect of systemic enzyme therapy on clinical manifestations of inflammation in gonarthrosis

Despite a significant number of studies on various schemes of OA therapy, there are only some studies with the use of systemic enzyme therapy (ETS) in combination with NSAIDs and / or SYSADOA. The aim was to study the effect of different groups of drugs (NSAIDs, ETS, SYSADOA) on the clinical course of gonarthrosis, as well as to develop an algorithm for the choice of treatment tactics depending on the clinical and sonographic manifestations of this disease. Methods. The data of 46 patients with stage I and stage II OA of Kellgren-Lawrence were analyzed. Patients of the first group received combined oral therapy with chondroitin sulfate (HS) 500 mg 2 times a day and glucosamine sulfate (GS) 750 mg 2 times a day in combination with selective NSAIDs. The second group of patients received combined therapy of HS 500 mg 2 times a day with the GS 750 mg 2 times daily together with Phlogenzym (PL), 2 tablets 3 times a day. All patients included in the study were examined initially, after 8 and 12 weeks. Procedures included clinical (VAS, WOMAC) and instrumental methods with the use of ultrasound of joints to evaluate the pathology of soft tissues and detect synovitis.. Results. Comparing groups 1 (HS, GS and NSAIDs) and 2 (HS and GS together with PL) on the effect on the structural state of cartilage and the dynamics of the main ultrasonic manifestations of OA knee joint, it should be noted that the effectiveness of drugs HS and GS in combination with enzyme therapy was higher, because in this group of treatment of synovitis decreased, whereas in the group of HS and GS, together with NSAIDs, these parameters either increased or remained unchanged. Conclusions. The use of polyenzyme drugs significantly increases the effectiveness of complex therapy in patients with osteoarthritis of the knee joints. In patients with gonarthrosis treated with a combination of chondroitin sulfate, glucosamine sulfate and phlogenzym was observed a significant reduction in the severity of synovitis, as well as more frequent lower daily dose of the selective NSAID or their full cancellation, compared with a control group of patients treated with symptomatic drugs retardation in combination with NSAIDs. (For citation: Mazurov VI, Dorovskikh AG, Trofimov EA. Effect of systemic enzyme therapy on clinical manifestations of inflammation in gonarthrosis. Herald of North-Western State Medical University named after I.I. Mechnikov. 2018;10(2):107-112).

Phase I Study of First-in-Class Oral Triplet Therapy DTRM-555 in Relapsed/Refractory Lymphoma Patients through Fixed-Dose Combination and Synthetic Lethality

Phase I Study of First-in-Class Oral Triplet Therapy DTRM-555 in Relapsed/Refractory Lymphoma Patients through Fixed-Dose Combination and Synthetic Lethality

432. Hold That Buzz: Timely Malaria Medication Access in New Orleans, Louisiana

BackgroundMalaria is a global health concern. Given increasing global travel and migration, hospitals may struggle to meet immediate malaria treatment needs resulting in serious and potentially fatal outcomes. New Orleans is a mid-size city with a significant immigrant population, large tourism industry, major academic centers with international faculty and many international industries with a diversity of medical systems. Assessing malaria medication accessibility across various clinical settings would address major gaps in treatment capacity and efficacy.MethodsInpatient pharmacy directors and formularies at three New Orleans-area hospitals (an academic medical center, a large safety-net hospital and a community hospital) were queried about their first-line antimalarial agents in stock within the hospital pharmacy, time needed to obtain both IV and PO first-line antimalarial agents, and barriers to expanding the formulary (including cost, number of cases, side effects, and shelf life of medications). The queries were carried out using a medications order system survey.ResultsFirst-line IV medications could not be provided in <24 hours at any of hospitals surveyed; however, all provided a form of first-line antimalarial coverage for non-severe malaria. Two of the three hospitals provided oral artemisinin-based combination therapies (ACTs) on their hospital formulary available in <24 hours and all three provided ACTs on their outpatient formularies. All hospitals surveyed could obtain intravenous ACTs from the CDC within 24–48 hours. Barriers identified for availability of oral ACTs and other antimalarials included the number of cases seen (reported by all threehospitals) and cost of medication (reported by one hospital).ConclusionOral first-line malaria treatments including ACTs could be obtained in the surveyed hospitals within 24–48 hours and all hospitals could obtain IV ACTs from the CDC within 24–48 hours. The main barrier preventing hospitals from providing ACTs and other anti-malarial medications was infrequency of malaria cases; cost was a secondary concern. This information can be used in attempts to educate hospital systems about appropriate and timely malaria treatment, inform policy and procedures, and design systems to track malaria diagnosis and treatment.Disclosures All authors: No reported disclosures.

PCV33 - THE RATE OF CARDIOVASCULAR EVENTS IN DIABETIC PATIENTS IN COLOMBIA

To estimate the rate at which acute coronary events present themselves in diabetic patients from a Colombian insurance company through big data analysis. Based on cluster technics and association rules applied over databases of service consumption from a health insurance company with distribution across the country, diabetic patients from a sole year and those who presented acute coronary events, for at least a year or until death, were singled out for the study. Acute coronary events were defined via diagnosis and validated through registered consumption. Patients were analyzed globally and set apart by stage of treatment: monotherapy, oral combination therapy or insulinized. From 131’604.958 records from approximately 2’300.000 different users, 7,639 patients were diagnosed with type 2 diabetes mellitus for 2015 at a mean age of 56.4, from whom 37% were identified with at least one separate chronic pathology. From the specified population, 85 presented cardiovascular events; equal to a rate of 1.1%. When analyzing specifically those patients under insulinization the rate corresponded to 1.35%. The risk ratio of presenting a coronary event for the diabetic population which did not present any other pathologies was 0.39. The event rate obtained is similar to that of a study performed in international populations such as the one published in Lancet Diabetes Endocrinology in 2014. When analyzing the variations by type of population, it is proven that acute coronary events present a major risk factor in those patients with other chronic pathologies and that those patients who are insulinized have a 2.4% higher rate of presenting cardiovascular events.

Targeted therapy of pulmonary arterial hypertension: Updated recommendations from the Cologne Consensus Conference 2018

In the summer of 2016, delegates from the German Respiratory Society, the German Society of Cardiology and the German Society of Pediatric Cardiology met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary arterial hypertension (PAH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines and included new evidence, where available. The treatment algorithm for PAH was modified based on the observation that there are now many patients diagnosed with IPAH who are at an advanced age and have significant cardiopulmonary comorbidities. For patients newly diagnosed with classic forms of PAH, i.e. younger patients without significant cardiopulmonary comorbidities, the consensus-based recommendation was to use initial combination therapy as the standard approach. The use of monotherapies was no longer considered appropriate in such patients. The choice of treatment strategies should be based on the risk assessment as proposed in the European guidelines. In patients presenting with a low or intermediate risk, oral combination therapy with endothelin receptor antagonists and phosphodiesterase-5 inhibitors or soluble guanylate cyclase stimulators, respectively, should be used. In high-risk patients, triple combination therapy including a subcutaneous or intravenous prostacyclin analogue should be considered. For patients who suffer from PAH and significant cardiopulmonary comorbidities, initial monotherapy is recommended and the use of combination therapies should be considered on an individual basis. The latter recommendations are based on the scarcity of evidence supporting the use of combination therapy and the higher risk of drug-related adverse events in such patients.

Perfil da prescrição de medicamentos para o diabetes mellitus tipo 2 de um município paulista

Objetivo: Analisar as prescrições de medicamentos para o diabetes mellitus tipo 2 (DM2) considerando as atuais recomendações clínicas, em Unidades de Saúde da Família de Ribeirão Preto, São Paulo.Materiais e Métodos: Trata-se de um estudo retrospectivo realizado por meio da análise de prontuários das pessoas com DM2 usuárias de medicamentos. O tamanho da amostra calculado foi de 150 participantes. Foram obtidos os dados sociodemográficos, clínicos, medicamentos prescritos e resultado do teste laboratorial de hemoglobina glicada.Resultados: A maioria dos indivíduos pertencia ao sexo feminino (61,3%) e a média de idade foi de 66,4 anos. O controle glicêmico apresentou-se inadequado em 75,3% dos participantes, com hemoglobina glicada média de 8,8%. A média de medicamentos prescritos para o tratamento do DM2 foi de 1,7. Nas pessoas com idade inferior a 60 anos predominou a prescrição de sulfonilureias. Dentre os idosos, predominou a prescrição de metformina, seguido pelas sulfonilureias e insulina, respectivamente. Observou-se associação entre o controle glicêmico inadequado e pessoas em uso de terapia oral combinada [OR=0,32 (IC95% 0,12; 0,80)] e insulinoterapia isolada ou em associação com antidiabético oral [OR=0,05 (IC95% 0,01; 0,18)]. Além disso, evidenciou-se associação entre o controle glicêmico inadequado e pessoas com dois [OR=0,3 (IC95% 0,13; 0,67)] ou três [OR=0,08 (IC95% 0,01; 0,70)] medicamentos prescritos.Conclusão: O controle glicêmico apresentou-se inadequado na maioria dos participantes. A monoterapia foi o tratamento mais frequente, embora, uma parcela considerável estudada usasse sulfonilureia em monoterapia, o que está em desacordo com as atuais diretrizes preconizadas para o tratamento do DM2.

Comparative efficacy and tolerability of pharmacological agents for management of mild to moderate ulcerative colitis: a systematic review and network meta-analyses

The majority of patients with ulcerative colitis have mildly to moderately active disease. To inform the management of patients with left-sided or extensive mildly to moderately active ulcerative colitis, we assessed the comparative efficacy and tolerability of different therapies. In this systematic review and network meta-analysis, we searched Epub, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science from inception to Dec 14, 2015, and updated on MEDLINE on March 1, 2018, for randomised controlled trials in adults (age ≥17 years) with left-sided or extensive mild to moderate ulcerative colitis. Studies were included if patients were treated with oral sulfasalazine, diazo-bonded 5-aminosalicylates (5-ASAs), mesalazine (low dose <2 g/day, standard dose 2-3 g/day, or high dose >3 g/day), controlled ileal-release budesonide, or budesonide multimatrix, alone or in combination with rectal 5-ASA therapy, and were compared with each other or placebo for induction or maintenance of clinical remission. The minimum duration of therapy was 4 weeks for trials of induction and 24 weeks for trials of maintenance therapy. We did pairwise and random-effects network meta-analysis using a frequentist approach, and calculated odds ratios (ORs) and 95% CIs; agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to appraise quality of evidence. We examined heterogeneity with the I2 statistic. Our search identified 1316 unique studies, from which 75 randomised trials with 12 215 patients were eligible for analysis. Based on 48 induction randomised trials (8020 participants) that met inclusion criteria, combined oral and rectal 5-ASAs (SUCRA 0·99) and high-dose mesalazine (>3 g/day; SUCRA 0·82) were ranked highest for induction of remission. Both interventions were superior to standard-dose mesalazine (2-3 g/day; failure to induce remission with combined oral and rectal 5-ASAs OR 0·41, 95% CI 0·22-0·77; high-dose mesalazine 0·78, 0·66-0·93) with moderate confidence in estimates. On the basis of 28 randomised trials (4218 participants) that met inclusion criteria, all interventions were superior to placebo for maintenance of remission; however, neither combined oral and rectal 5-ASAs nor high-dose mesalazine were superior to standard-dose mesalazine. In patients with mildly to moderately active left-sided or extensive ulcerative colitis, combined oral and topical mesalazine therapy and high-dose mesalazine are superior to standard-dose mesalazine for induction of remission, but not maintenance of remission. Standard-dose mesalazine might be preferred for maintenance in most patients. None.

Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle.

Cyclophilins are a family of peptidyl-prolyl isomerases that are implicated in a wide range of diseases including hepatitis C. Our aim was to discover through total synthesis an orally bioavailable, non-immunosuppressive cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus (HCV) activity that could serve as part of an all oral antiviral combination therapy. An initial lead 2 derived from the sanglifehrin A macrocycle was optimized using structure based design to produce a potent and orally bioavailable inhibitor 3. The macrocycle ring size was reduced by one atom, and an internal hydrogen bond drove improved permeability and drug-like properties. 3 demonstrates potent Cyp inhibition ( Kd = 5 nM), potent anti-HCV 2a activity (EC50 = 98 nM), and high oral bioavailability in rat (100%) and dog (55%). The synthetic accessibility and properties of 3 support its potential as an anti-HCV agent and for interrogating the role of Cyp inhibition in a variety of diseases.

Challenging perspectives: Prescribing hormone replacement in premature ovarian insufficiency

The incidence of premature ovarian insufficiency (POI) is increasing in the general population with, among other reasons, more women surviving cancer treatments or having risk-reducing prophylactic oophorectomy due to BRCA status. The ovary is a vital endocrine gland and lost hormones need replacing to maintain system-wide health until the average age of the menopause (51 years). The combined oral contraceptive or hormone replacement therapy are recognised treatment choices for POI, but choosing the individual prescription may seen daunting. Through simple risk–benefit assessment and understanding modes of action, the nurse prescriber can guide effective decision-making and support long-term compliance.

P6341Haemodynamic and exercise effects of different types of initial oral combination therapy in pulmonary arterial hypertension

P6341Haemodynamic and exercise effects of different types of initial oral combination therapy in pulmonary arterial hypertension

Sex hormones and venous thromboembolism - from contraception to hormone replacement therapy.

The use of sex hormones such as combined oral contraceptives (COC) or hormone replacement therapy (HRT) increases the risk for venous thromboembolism (VTE) considerably, especially in patients with an increased intrinsic risk for thromboembolic complications. Despite public and media attention and increasing scientific evidence, prescription patterns seem to be hard to change. It is well recognized that the patient's baseline risk is the most relevant factor in the absolute risk for developing VTE. The relative risk increase associated with sex hormones, depends on the type and dosage of hormones, the route of application (oral, vaginal, transdermal), and for COC, on the specific combination of oestrogen and gestagen components. Consequently, a careful decision for or against any specific type of hormone treatment needs to be based on an assessment of the patient's risk profile (disposition) as well as on the treatment-associated risks and benefits (exposition). This review discusses the most common sex hormone treatments in contraception and HRT, the relevance for VTE risk patients, and strategies to counsel patients with regard to hormone use according to their risk profiles. Keywords: Oral contraceptives, hormonal contraception, hormone replacement therapy, venous thromboembolism.

Complete response of Palbociclib in metastatic breast cancer patient: A case report

Palbociclib, an oral inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6), has been approved for metastatic breast cancer (mBC) treatment of hormone receptor (HR)-positive/ human epidermal growth factor receptor 2 (HER2)-negative. The study reported the efficacy of Palbociclib as a new oral drug in a patient with mBC. A 40-year-old female with stage 2 right BC change to stage 4 after about two years later referred to oncology clinic. Due to HR-positivity/HER2-negative, she has treated with Palbociclib 125 mg (per one day for twoweek and one-week intervals) with Letrozole. In new assessment and after 8 months of this oral combination therapy, the chest x-ray of lung showed the complete response. Treatment with Palbociclib plus Letrozole had a complete response in the mBC patient after the common chemotherapies and hormone monotherapy.

IDegAsp Improves Glycemic Control with Minimal Hypoglycemia—An Indian Real-World Study in T2D Subjects

Background: IDegAsp is the first insulin co-formulation constituting 70% insulin degludec and 30% insulin aspart. In contrast to conventional premix analogues, degludec component of IDegAsp lowers variability, fasting glucose with comparable glycemic control and fewer hypoglycemic events. Re-suspension errors inherent to premix analogues also does not occur with IDegAsp. In routine diabetes practice, patients have customised A1c goals depending on the associated comorbidities and risk factors. Aim: To assess the safety and efficacy of IDegAsp in Indian T2D subjects in a real-world setting. Methods: T2D initiated on IDegAsp and on regular follow-up were de-identified from EMR. Clinical outcomes and hypoglycemic events were captured. n= 152, age= 52.9±11.9y, diabetes duration= 11.5±13.8y, 78.57% males, treatment duration= 10.3±6.5mths. Results: 92% of the patients achieved customised A1c targets.Reduction from baseline: 0.91% in A1c(p=0.0004), 41.4 mg/dL in FBS(p&amp;lt;0.0001), 0.80 kg in body weight(p=0.0083).Five hypoglycemic episodes were reported (none severe). There were no reported episodes of nocturnal hypos. Conclusion: In this real-world study involving T2D subjects in India, IDegAsp improved HbA1c and FBS significantly,with less hypoglycemia and no weight gain. Some of these outcomes are contrary to those reported in clinical trials and could have resulted from the new combination oral therapies. Disclosure J. Kesavadev: Advisory Panel; Self; Novo Nordisk India Private Limited. Speaker's Bureau; Self; Novo Nordisk India Private Limited. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; MSD. Speaker's Bureau; Self; MSD. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. B.D. Saboo: None. A. Shankar: None. A. David: None. R. Warrier: None. G. Krishnan: None. L. Ramachandran: None. S. Jothydev: None.