Conditions Of Routine Clinical Practice Research Articles

Caracterización clínica y terapéutica de la cardiopatía isquémica en España. Importancia de los programas de rehabilitación cardiaca

Introduction and objectivesThe objective of the study was to characterize the clinical and therapeutic profile of patients with ischemic cardiopathy (IC) in Spain in patients (group 1) at the time of hospital discharge after an acute coronary syndrome (ACS), (group 2) at the first post-discharge follow-up visit, and (group 3) after one year of the ACS. Patients and methodsObservational, multicenter, cross-sectional, nationwide, performed in conditions of routine clinical practice. ResultsA total of 1018 patients were included: 354 (34.8%) in the group 1, 326 (32.0%) in the 2, and 338 (33.2%) in the 3. Compared with group 3, a higher percentage of patients from group 1 were smokers (32.2% versus 10.9%), consumed alcohol (28.2% versus 19.5%), did not do any physical exercise (61.0% versus 38.2%) or followed a diet (57.1% versus 32.5%). Of patients in group 1, 65.4% were referred to a cardiac rehabilitation program (CRP). Of those in group 2, 53.1% had not a scheduled appointment to initiate a CRP. Regarding group 3, 58.3% did not receive the recommendation of doing a CRP. Absence of obesity and attendance to a CRP were variables associated with the control of cardiovascular risk factors. ConclusionsCurrently, less than 50% of patients with IC in Spain are remitted to a CRP despite being associated with an improved control of cardiovascular risk factors.

Abstracts from the ISSAID 2021 Periodic Congress

Abstracts from the ISSAID 2021 Periodic Congress

Control metabólico y pautas de tratamiento en pacientes con diabetes tipo 1 en Castilla-La Mancha, 10 años después. Estudio DIACAM1 2020

ObjectiveTo evaluate degree of metabolic control and treatment regimens in patients with type 1 diabetes mellitus (T1DM) enrolled in the DIACAM1 study, after 10 years of follow-up under routine clinical practice conditions. Patients and methodsA total of 1,465 patients enrolled in the DIACAM1 study, a multicentre, cross-sectional study conducted in Castilla-La Mancha in 2010, were analysed. Of these patients, 58 (4%) died during the 10-year follow-up period. Anthropometric, clinical, laboratory and treatment data were reviewed for 1,121 (76.5%) patients in active follow-up. ResultsMean glycosylated haemoglobin (HbA1c) levels were 7.66% lower than in 2010 (P<.001), 26% of patients achieved HbA1c levels <7%, 24.4% were obese, 51.7% had dyslipidaemia and 33.6% had hypertension. The following were found to be predictive factors for good glycaemic control (HbA1c<7%): good glycaemic control in 2010 (odds ratio [OR] 4.8); the use of intensified insulin regimens, including insulin pumps and glucose monitoring (OR: 2.8); no hyperlipidaemia (OR: 1.97); and higher levels of education (OR: 1.4). The recommended targets for lipid and blood pressure control were met by 76% of patients; 40% of the patients enrolled required drug treatment. ConclusionsGlycaemic control in patients with T1DM in Castilla-La Mancha improved after 10 years of follow-up. The use of intensified insulin regimens and technology applied to diabetes care appear to be determining factors in achieving this improvement. Despite the increase in the prevalence of cardiovascular risk factors, the majority of the patients achieved good lipid and blood pressure control.

The PARADIGHM (physicians advancing disease knowledge in hypoparathyroidism) registry for patients with chronic hypoparathyroidism: study protocol and interim baseline patient characteristics

BackgroundThe PARADIGHM registry of adult and pediatric patients with chronic hypoparathyroidism evaluates the long-term safety and effectiveness of treatment with recombinant human parathyroid hormone, rhPTH(1-84), and describes the clinical disease course under conditions of routine clinical practice. In this first report, we detail the registry protocol and describe the baseline characteristics of two adult patient cohorts from an interim database analysis. One cohort after study entry were prescribed rhPTH(1-84), and the other cohort received conventional therapy of calcium and active vitamin D.MethodsAn observational study of patients with chronic hypoparathyroidism in North America and Europe, collecting data for ≥10 years per patient. Main outcome measures were baseline patient demographics, clinical characteristics, medications, and disease outcome variables of symptoms, biochemical parameters, and health assessments. Baseline is the enrollment assessment for all variables except biochemical measurements in patients treated with rhPTH(1-84); those measurements were the most recent value before the first rhPTH(1-84) dose. Exclusion criteria applied to the analysis of specified outcomes included pediatric patients, patients who initiated rhPTH(1-84) prior to enrollment, and those who received rhPTH(1-34). Clinically implausible biochemical outlier data were excluded.ResultsAs of 30 June 2019, data of 737 patients were analyzed from 64 centers; 587 (80%) were women, mean ± SD age 49.1±16.45 years. At enrollment, symptoms reported for patients later prescribed rhPTH(1-84) (n=60) and those who received conventional therapy (n=571), respectively, included fatigue (51.7%, 40.1%), paresthesia (51.7%, 29.6%), muscle twitching (48.3%, 21.9%), and muscle cramping (41.7%, 33.8%). Mean serum total calcium, serum phosphate, creatinine, and estimated glomerular filtration rate were similar between cohorts. Health-related quality of life (HRQoL) 36-item Short Form Health Survey questionnaire scores for those later prescribed rhPTH(1-84) were generally lower than those for patients in the conventional therapy cohort.ConclusionsAt enrollment, based on symptoms and HRQoL, a greater percentage of patients subsequently prescribed rhPTH(1-84) appeared to have an increased burden of disease than those who received conventional therapy despite having normal biochemistry measurements. PARADIGHM will provide valuable real-world insights on the clinical course of hypoparathyroidism in patients treated with rhPTH(1-84) or conventional therapy in routine clinical practice.Trial registrationEUPAS16927, NCT01922440

The First Real-World Evidence Prospective Registry of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm Treated with Tagraxofusp, a CD123-Targeted Therapy, in Europe

The First Real-World Evidence Prospective Registry of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm Treated with Tagraxofusp, a CD123-Targeted Therapy, in Europe

Vaginal health, endometrial thickness and changes in bone markers in postmenopausal women after 6 months of treatment with ospemifene in real clinical practice

Objective To assess vaginal health, endometrial thickness, and changes in bone markers in postmenopausal women with vulvovaginal atrophy (VVA) treated with 60 mg/day of ospemifene under routine clinical practice. Methods The AYSEX study is a Spanish observational and prospective study performed in one center in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated continuously with ospemifene 60 mg/day for 12 months as an appropriate therapeutic option. This article refers to the 3- and 6-months analysis. Vaginal health was assessed by pH and using Vaginal Health Index (VHI) at baseline and 3 months later. Endometrial thickness, measured by vaginal ultrasonography, and bone resorption marker (CTx) were assessed at baseline and 6 months later. Results A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, pH improved from 6.1 to 4.5 (p < .0001), and VHI improved from 10 to 19 points (p < .0001). The percentage of patients with VVA according to VHI decreased from 100% to 5.2% (p < .0001). After 6 months, mean CTx levels decreased from 0.42 pg/ml at baseline to 0.37 pg/ml 6 months later (p = .0018), and mean endometrial thickness changed from 2.24 to 2.15 mm (p = .6066). Conclusions Up to date, this is the only prospective and observational study with ospemifene in routine clinical practice conditions and confirms the results previously reported from randomized controlled clinical trials, improving VVA, not increasing endometrial thickness, and decreasing CTx levels by exerting an anti-resorptive function.

Insulin Management of Patients with Inadequately Controlled Type 2 Diabetes Admitted to Hospital: Titration Patterns and Frequency of Hypoglycemia as Results of a Prospective Observational Study (Hospital Study)

IntroductionDespite the continuously growing number of therapeutic options for type 2 diabetes mellitus (T2DM) including insulins, a large percentage of patients fail to achieve HbA1c targets. Several real-world studies focused on patients with T2DM receiving insulin treatment in outpatient settings were conducted, but information about real-world in-hospital insulin management is lacking. The aim of this study was to describe the management of insulin therapy with a focus on basal-bolus and premixed insulin regimens in patients with T2DM under routine in-hospital medical practice in the Czech Republic.MethodsThis non-interventional prospective study was conducted from June 2014 to December 2017 in 22 centers in the Czech Republic under routine clinical practice conditions. Adult patients admitted to hospital with metabolically uncontrolled T2DM [HbA1c ≥ 60 mmol/mol; > 7.6% Diabetes Control and Complications Trial (DCCT)] and there treated with basal-bolus and premixed insulin regimens were documented during hospitalization.ResultsOverall, 369 patients with T2DM (54.7% male, mean age 64.44 ± 13.84 years, BMI 31.10 ± 6.00 kg/m2, duration of diabetes 8.11 ± 9.93 years, HbA1c 95.90 ± 24.38 mmol/mol, length of stay was 7.94 ± 4.53 days) were included. The percentage of glucose values under 10 mmol/l at time of randomization (the group with basal-bolus insulin regimen vs. the premix insulin regimen group) was 24.2% vs. 33.5% (p = 0.053), at time of first insulin dose adjustment it was 43.1% vs. 50.0% (p = 0.330), and 1 day before hospital discharge it was 61.7% vs. 61.4% (p = 0.107). A hypoglycemic event occurred in a total of 15 patients in the basal-bolus regimen group, and no hypoglycemic event occurred in the premixed insulin regimen group.ConclusionIn-hospital insulin management regarding basal-bolus and premixed insulin regimens is safe and in concordance with current international recommendations.

Ospemifene in clinical practice for vulvo-vaginal atrophy: results at 3 months of follow-up of use

Objective To assess the effect of ospemifene 60 mg/day in vulvovaginal atrophy (VVA) in postmenopausal women under conditions of routine clinical practice after 3 months of follow-up. Methods The AYSEX study is a Spanish observational, prospective, and unicentric study in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, sexual health, dryness, dyspareunia, quality of life, and satisfaction with treatment were assessed at baseline and after three months using validated scales. Results A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, vaginal health index increased and vaginal pH, dryness, and dyspareunia decreased significantly (p < .0001). A significant improvement was observed in sexual function and quality of life. Conclusions This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, and satisfaction with the treatment.

Results of the Expert Forum on the application of perampanel in routine clinical practice

In February 2020, in Moscow, Expert Forum was held on the issues of the application of perampanel in routine clinical practice. The main aim of the Forum was to discuss the tolerance and safety profile of perampanel in patients with epilepsy in different age and gender groups in the conditions of routine clinical practice. Leading experts in neurology and epileptology took part in the Forum, wherein the acute data on the efficiency and safety of perampanel and the management of potential risks were presented.

Community pharmacy: a crucial enabler in creating the effectiveness study environment in the Salford Lung Studies.

ObjectiveCreating an environment that supports conditions of routine clinical practice and enables an effectiveness trial design with a pre‐licensed medicine is extremely challenging. Here, we summarise our experiences and achievements with engaging and mobilising community pharmacies in and around Salford, United Kingdom, in the Phase III effectiveness Salford Lung Studies (SLS).MethodsThis article provides the authors’ personal experiences and viewpoints on community pharmacy involvement in the SLS.Key findingsMore than 130 community pharmacies were enabled, and >2500 pharmacy staff trained, for involvement in the SLS. Key to community pharmacy participation in the SLS was the formation of the SLS Pharmacy Steering Group (PSG), contributing to study oversight, and the development of a pharmacy standard operating procedure document, the major principle of which was to ensure minimum disruption to the normal medicine dispensing process while ensuring compliance with regulations, guidelines, good clinical practice and requirements for pharmacovigilance. The high level of commitment and collaboration of community pharmacy in the SLS demonstrated a willingness to work together and take on additional and novel roles beyond their everyday commercial functions for the benefit of patients, despite normally competing for prescription business.ConclusionsThe involvement and integration of community pharmacy as a key partner in the SLS was pivotal in securing the delivery of these world‐first clinical effectiveness studies. To our knowledge, this has not been previously achieved in a study of a pre‐licensed maintenance therapy for a common disease in primary care.

Control del paciente diabético en Atención Primaria: influencia de cartera de servicios y otros factores

ObjectiveTo study the effect of the type of follow-up according to Service Portfolio and other associated factors, in the reduction of HbA1c levels in people with a new diagnosis of type 2 diabetes and poor initial control. DesignAnalytical observational study of a cohort under routine clinical practice conditions. Location262 Primary Health Care Centres in Madrid. Participants1,838 individuals older than 18 years with a new diagnosis of type 2 DM and initial HbA1c levels ≥ 7%, or ≥ 8.5% if older than 75 years. InterventionsThe exposure variable was the type of follow-up according to Portfolio, categorised as minimum, medium, and optimal, according to the number of interventions performed and periodicity of type of therapeutic-pharmacological plan. Main measurementsA study was made of the comorbidity, therapeutic-pharmacological plan, diet - exercise advice and deprivation index. The main outcome was the difference between the final and initial HbA1c. ResultsAfter 2 years of follow-up there was a mean decrease in HbA1c by -1.7 percentage points (95% CI: -1.6;-1.8), which was 0.36 points higher in patients with optimal follow-up: -2.1 (95% CI: -1.7;-2.4). The factors associated with a decrease in HbA1c were the optimal follow-up -0.29 (95% CI: -0.5;-0.1), the medium follow-up -0.26 (95% CI: -0.5; -0.0), and the initial HbA1c value -0.9 (95% CI: -0.9; -0.9. The factors associated with the increase were insulin treatment and living in socially disadvantaged areas. ConclusionsGlycaemic control was improved in patients with a new diagnosis of diabetes in which optimal follow-up is performed as proposed in the Service Portfolio.

Effectiveness of a hydrophobic dressing for microorganisms' colonization of vascular ulcers: Protocol for a randomized controlled trial (CUCO-UV Study).

AimTo determine the effectiveness of a hydrophobic dressing (Cutimed Sorbact®) against a silver dressing (Aquacel® Ag Extra) in the level of colonization of chronic venous leg ulcers. The secondary endpoints are health‐related quality of life, level of pain, and time to complete healing.DesignOpen randomized controlled trial, with blinded endpoint.MethodsPatients with chronic venous leg ulcers with signs of critical colonization will be randomized in a concealed sequence using computer software to receive one of the alternative dressings. A total of 204 participants recruited in Primary Health Care and nursing homes will be necessary to assure statistical power. Measures will include sociodemographic variables, wound‐related variables (area, exudate, and time to healing), level of pain, adverse effects, and health‐related quality of life. Smear samples will be collected from the ulcers and will be subject to DNA‐typing technique through polymerase chain reaction to obtain the level of colony‐forming units. Measures will be collected at baseline, 4, 8, and 12 weeks.DiscussionElevated levels of microorganisms prevent wound healing and favour its chronification. The main target when colonization is present is to reduce the bacterial load to levels that promote immune system mobilization. Hydrophobic dressings prevent the formation of biofilm in the wound by means of physical effect, so that the possibility of antimicrobial resistance is significantly reduced.ImpactCurrent evidence about the effectiveness of dressings to minimize venous leg ulcers colonization is very limited. Previous studies have important methodological flaws. This study will permit to obtain the effectiveness of hydrophobic dressings against silver dressings with a robust design based on conditions of routine clinical practice in Primary Health Care and nursing homes.

Safety of a trastuzumab biosimilar, used under routine clinical practice conditions in adult HER2+ breast cancer patients in Morocco.

e13024 Background: Hertraz, the first trastuzumab biosimilar was approved in Morocco in 2017. Real world data on trastuzumab biosimilars are very limited or not available. HERLife is a prospective, non-interventional phase IV study program that investigated the experience of using Hertraz, a biosimilar for trastuzumab (Herceptin), under routine clinical practice conditions in Morocco. The primary aim of this study was to confirm the acceptable safety and tolerability of Hertraz. Methods: Ninety-nine patients with HER2-positive breast cancer treated with Hertraz were enrolled from 8 public and private sector hospitals and followed up for 12 months as part of this non-interventional study. Cardiac events (LVEF) and other unexpected or serious adverse events were monitored. The study arms consisted of patients with early breast cancer (Arm 1, n=70) and metastatic breast cancer (Arm 2, n=29) whose median age was 53 years in both groups. Results: Switching from Herceptin to Hertraz was observed in 45% of 29 MBC patients and 27% of 70 EBC patients. Switching was done at a median of 4th cycle. Pertuzumab was used in combination with Hertraz in 69% and 19% of patients in the metastatic and neoadjuvant settings, respectively. Two patients had a decline in LVEF. One patient treated with Hertraz alone and one patient treated with Hertraz and pertuzumab developed a decrease in LVEF requiring a three-week treatment discontinuation of Hertraz. Treatment of Hertraz was continued after 1 skipped cycle without occurrence of new side effects. No other trastuzumab related adverse events was observed. Four patients in the metastatic group and 2 patients in the early breast cancer arm had a relapse in the 12 months of clinical follow-up. Conclusions: The management of HER2+ breast cancer in Morocco follows the international recommendations. This is the first real world safety data of Hertraz from Morocco. The 12-month follow-up treatment with Hertraz showed an acceptable cardiac safety profile. In cases where there was a switch from Herceptin to Hertraz or Hertraz combined with pertuzumab, the safety profile was similar to that previously reported in other studies.

SAT-399 Baseline Characteristics from the Observational PARADIGHM Registry of Patients with Chronic Hypoparathyroidism

PARADIGHM is an actively recruiting, prospective, observational registry (NCT01922440/EUPAS16927). The primary objective is to evaluate the safety and effectiveness of recombinant human parathyroid hormone, rhPTH(1-84), treatment in patients with chronic hypoparathyroidism (HypoPT) under routine clinical care. The secondary objective is to characterize the clinical course of chronic HypoPT under conditions of routine clinical practice. At enrollment, registry inclusion criteria are patients having a HypoPT diagnosis >6 months and receiving conventional therapy (CT; eg, calcium supplements and active vitamin D), rhPTH(1-84) plus CT, or rhPTH(1-84). We present baseline characteristics of patients as of a June 30 2019 data cut. Baseline was defined as the value entered at the time of enrollment (Visit 1). Baseline symptom data exclude patients who initiated rhPTH(1-84) prior to enrollment (n=68) and are herein presented as two groups: those subsequently prescribed with rhPTH(1-84) after enrollment or those treated with CT. All data are summarized descriptively. Patient data from 64 centers in Europe and North America were analyzed. In the analysis population (n=737), 587 patients (79.6%) were female, 620 (84.1%) were white, and the mean (SD) age was 49.1 (16.45) years. The mean (SD) BMI was 19.3 (5.73) kg/m2 and 30.0 (7.72) kg/m2 in patients aged <18 (n=25) and ≥18 (n=587) years, respectively. The primary cause of HypoPT was thyroid surgery (n=547 [74.2%]; of these, 281 [60.0%] underwent surgery for thyroid cancer). Endocrinologists were the prescribing specialists for most patients (n=660 [89.6%]). Vitamin D and analogs were prescribed for 90.1% of patients (calcitriol, 74.2%, native vitamin D, 47.4%, alfacalcidol, 7.9%,), calcium for 81.0% (calcium carbonate, 57.9%, calcium citrate, 27.1%), and thyroid hormones for 71.2% (levothyroxine, 73.4%; liothyronine, 5.8%). Symptoms reported at enrollment for the rhPTH(1-84) (n=66) and the CT groups (n=603), respectively, included fatigue (53.0%, 39.3%), paresthesia (48.5%, 29.2%), muscle twitching (48.5%, 21.1%), muscle cramping (40.9%, 33.0%), headaches (33.3%, 17.6%), anxiety (28.8%, 20.1%), muscle pain (28.8%, 19.2%), tetany (28.8%, 12.1%), and brain fog (27.3%, 16.3%). The baseline data for the overall population appear to be representative of patients with chronic HypoPT. Baseline data suggest that at enrollment patients prescribed rhPTH(1-84) after enrollment appear to have an increased burden of disease than patients receiving CT based on symptoms. PARADIGHM will be a valuable resource of real-world longitudinal data for patients with chronic HypoPT.

Insulin/carbohydrates ratio during the first 6-month therapy with insulin degludec in a paediatric population with type 1 diabetes previously treated with insulin glargine. An observational longitudinal study.

BackgroundNo data exist about the changes induced by the transition from first‐generation long‐acting insulins to second‐generation long‐acting analogues in the paediatric population.ObjectiveTo assess changes in insulin/carbohydrate ratio (I:CHO) after the first 6 months of degludec therapy in a paediatric population with type 1 diabetes previously treated with glargine U100.SubjectsAll patients treated with degludec under routine clinical practice conditions were retrospectively analysed.MethodsNonprofit observational retrospective study. Changes during the follow‐up in mean CHO/I ratio were assessed using longitudinal linear models for repeated measures. Rate of hypoglycaemia, ketoacidosis and adverse events was evaluated.ResultsOverall, 51 children (mean age 13.8 ± 4.6 years; mean diabetes duration 5.8 ± 3.9 years) started therapy with degludec in the period between April 2017 and April 2018. I:CHO ratio before starting degludec therapy significantly differed among the three meals, being the lowest at breakfast and the highest at dinner. After introducing degludec, I:CHO ratio at lunch (−1.29 95% CI −2.02;−0.57) and at dinner (−3.08 95% CI −4.35;−1.8) significantly decreased, while it slightly increased at breakfast (+1.37 95% CI 0.47;2.28). No episodes of severe hypoglycaemia, ketoacidosis and adverse event were recorded during 6 months.ConclusionsOur data show that the use of degludec is associated with a significant change in the I:CHO ratio at the different meals compared to the previous glargine therapy. This could derive from the flat and prolonged pharmacokinetic profile of degludec. This has important clinical implications for daily insulin dose adjustments.

Clinical, histopathological, and radiological features of unilateral nasal mass in Saudi Arabia: A retrospective study

Context: Nonneoplastic and neoplastic lesions of the nasal cavity are common conditions in routine clinical practice among almost all age group of people. Aims: This study examines the clinicopathological and radiological profiles of the unilateral nasal mass in an Ear, Nose, and Throat (ENT) clinic of AlHada Armed Forces Hospital. Settings and Design: The study design involves an ENT clinic of AlHada Armed Forces Hospital, Taif, Saudi Arabia. Subjects and Methods: A retrospective examination of patients' records was done to investigate the clinicopathological and radiological profiles of unilateral nasal masses between 2016 and 2018. Statistical Analysis Used: Descriptive statistics included mean, standard deviation, frequencies, and percentages, and inferential statistics such as independent t-test and Chi-square were carried out using the Statistical Package for the Social Sciences software (Version 20.0 IBM SPSS Corp., Armonk, NY, USA). Results: Nasal polyps were the most common diagnosis seen in seven (35%) cases, and the most common symptom was nasal obstruction (N: 12; 60%). Histopathological examination revealed that inflammatory lesions were more common (N: 13; 65%) than that of nonneoplastic masses (N: 7; 35%). In two patients with nasal polyps (n = 7), the radiological diagnosis was not correlated with the histopathological findings. Conclusions: Most of our cases of unilateral nasal mass were inflammatory nasal polyps followed by allergic fungal sinusitis. Clinicians should use caution in relying on radiological findings, and all lesions should undergo a pathological examination.

Questioning the Safety of Calcidiol in Hemodialysis Patients

Background. Epidemiological studies have suggested a survival benefit for hemodialysis patients on paricalcitol or calcitriol, but nutritional vitamin D supplementation of patients already on vitamin D receptor (VDR) activators is controversial. Methods. This observational retrospective cohort study was conducted with prospectively collected data from all consecutive patients with chronic kidney disease (CKD) who underwent hemodialysis under routine clinical practice conditions for two years. Results. Of the 129 patients, 89 were treated with calcidiol, paricalcitol, and/or calcitriol. The patients with any vitamin D formulation had higher serum concentrations of 25-hydroxy vitamin D and fibroblast growth factor-23 and tended to have higher mortality rates (42% vs. 25%, p = 0.07). On subgroup analysis, any calcidiol treatment or calcidiol combined with paricalcitol associated with significantly higher mortality rates than no treatment (47% and 62.5%, p = 0.043 and 0.008, respectively). The association between calcidiol/paricalcitol treatment and elevated mortality remained significant after adjusting for age, sex, diabetes, C-reactive protein, and hemodialysis vintage. Any calcidiol and calcidiol/paricalcitol treatment exhibited a dose-response relationship with mortality (p for trend: 0.002 and 0.005, respectively). Conclusions. These data draw attention to the hitherto unexplored safety of calcidiol supplementation in patients on hemodialysis, especially in those already on vitamin D. Until clinical trials demonstrate the safety and efficacy of this approach, caution should be exercised when prescribing these patients ≥0.5 calcidiol mg/month.

Addition of Basal Insulin to Oral Antidiabetic Agents in Patients with Inadequately Controlled Type 2 Diabetes Leads to Improved HbA1c Levels: Metabolic Control, Frequency of Hypoglycemia, and Insulin Titration Analysis as Results of a Prospective Observational Study (BALI Study).

IntroductionDespite the continuously growing number of therapeutic options for patients with type 2 diabetes mellitus (T2DM), a large percentage of these individuals fail to achieve their glycated hemoglobin (HbA1c) target. The aim of this study was to determine the change in metabolic control in insulin-naïve T2DM patients inadequately controlled with oral antidiabetic drugs (OADs) at 6 months after initiating basal insulin treatment as add-on to existing OADs.MethodsThis was a non-interventional prospective study conducted from June 2013 to December 2014 in 137 centers in the Czech Republic under routine clinical practice conditions. Adult patients whose diabetes was uncontrolled on their current OAD treatment (HbA1c ≥ 53 mmol/mol; Diabetes Control and Complications Trial [DCCT]-HbA1c 7%) and whose physician had decided to initiate treatment on a basal insulin regimen were documented over a 6-month period beginning from the time of initiation of basal insulin treatment.ResultsOverall, 1426 T2DM patients were included in the study, of whom 53% were male. The mean age of the study population was 63.8 ± 10.1 years, mean body mass index was 31.5 ± 5.3 kg/m2, and mean duration of diabetes was 10.2 ± 5.3 years. At the 6-month follow-up, the target HbA1c level of 53 mmol/mol (DCCT < 7%) was achieved by 18% of patients. The mean HbA1c overall had decreased from 77.2 ± 15.1 mmol/mol (DCCT 9.21 ± 1.38%) at baseline to 63.2 ± 12.5 mmol/mol (DCCT 7.93 ± 1.14 %) at the 6-month follow-up. This difference was significant at p < 0.001. The largest mean reduction in HbA1c, i.e., 20.9 mmol/mol (DCCT 2.4 %) was observed in the group of patients with a baseline HbA1c of ≥ 9%. The mean daily basal insulin dose at 6 months was 18.8 ± 8.9 units. Symptomatic hypoglycemia was reported in 12.3% of patients, of those only one patient (0.1%) suffered from severe hypoglycemia.ConclusionThe addition of basal insulin to the therapeutic regimen of insulin-naïve T2DM on OAD treatment resulted in an improved metabolic control of diabetes after 6 months of treatment. However, most patients did not achieve their HbA1c target, probably also due to inadequate titration of basal insulin.FundingSanofi, Czech Republic.

Clinical Impact of 5Years of Liraglutide Treatment on Cardiovascular Risk Factors in Patients with Type 2 Diabetes Mellitus in a Real-Life Setting in Italy: An Observational Study.

IntroductionBased on existing data regarding the durability of liraglutide in type 2 diabetes, this study aimed to assess its long-term effectiveness at 5 years and its overall impact on cardiovascular (CV) risk.MethodsThis was a multicenter retrospective observational study. Liraglutide was used under routine clinical practice conditions. Changes from baseline to 60 months in HbA1c, fasting plasma glucose (FPG), body weight, blood pressure, and lipid profile were assessed. United Kingdom Prospective Diabetes Study (UKPDS) scores were calculated at baseline and after 60 months to assess changes in the estimated 5- and 10-year risk for fatal and nonfatal coronary heart disease (CHD) and fatal and nonfatal stroke.ResultsOverall, 103 patients (age 59.0 ± 7.9 years, diabetes duration 10.4 ± 6.8 years) were involved in the study. After 60 months, HbA1c levels were reduced by − 1.0 ± 1.2%, FPG levels by − 24.5 ± 43.4 mg/dl, body weight by − 5.3 ± 6.4 kg, systolic blood pressure by − 6.5 ± 18.5 mmHg, diastolic blood pressure by − 3.6 ± 11.8 mmHg, and total cholesterol by − 16.9 ± 37.4 mg/dl. The proportion of patients achieving HbA1c levels of < 7% increased from 12.7% to 39.8% (p = 0.02). Based on the UKPDS scores, statistically significant reductions in the 5- and 10-year risk of nonfatal CHD and fatal CHD were found, with no change in the 5- and 10-year risk of fatal and nonfatal stroke.ConclusionIn patients prolonging treatment with liraglutide for 5 years, the benefits in relation to metabolic control and CV risk factors are maintained. The UKPDS risk scores suggest that liraglutide is associated with a reduced CHD risk, but not with a reduced stroke risk.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0503-4) contains supplementary material, which is available to authorized users.

Liraglutide and cardiovascular outcomes in a real world type 2 diabetes cohort.

In the last years, due to new regulatory guidelines requiring a stringent documentation of cardiovascular (CV) safety of novel drugs for type 2 diabetes, cardiovascular outcomes safety trials (CVOTs) are requested. CVOTs increase the knowledge about the safety profile of the new drugs, but they have intrinsic limits that make difficult their transferability to clinical practice. For this reason, real world evidence is considered an important complement to experimental data. Among the glucagon-like peptide-1 receptor agonists, liraglutide in the LEADER CVOT demonstrated superiority in reducing the risk of major CV events (MACEs) vs. placebo. We conducted an observational, retrospective, longitudinal study based on 307 patients with T2DM treated with liraglutide under routine clinical practice conditions. Real world impact of liraglutide on metabolic control, CV risk factors, hypoglycemia and CV events was assessed. Improvements during 36 months were found in HbA1c (-1.0%; p < 0.0001), fasting blood glucose (-17.6 mg/dL; p < 0.0001), body weight (-3.2 kg; p < 0.0001), waist circumference (-1.45 cm; p = 0.004), systolic blood pressure (-10.41 mmHg; p < 0.0001), diastolic blood pressure (-3.69 mmHg; p < 0.0001), total cholesterol (-7.96 mg/dL; p =0.008) and triglycerides (-20.60 mg/dl; p = 0.01). No severe hypoglycemia occurred. Incidence of MACEs in this cohort was lower than in the LEADER study (2.59 vs. 3.4 events per 100 person-years), confirming CV safety of liraglutide even in the real world. On the other hand, a higher incidence of CV event in patients with established CV disease was documented (8.1 events per 100 person-years), in spite of the use of liraglutide. In conclusion, 36-month durability and CV safety of liraglutide were documented in a real world cohort of T2DM patients, with sustained benefits on a large array of CV risk factors.