Open-label Observational Study Research Articles

Safinamide as adjunctive therapy to levodopa monotherapy for patients with Parkinson's disease with wearing-off: The Japanese observational J-SILVER study

BackgroundSafinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. MethodsThis multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. ResultsIn total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change −7.0 [p = 0.012], −2.4 [p = 0.007] and − 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. ConclusionSafinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. Study registrationUniversity Hospital Medical Information Network in Japan; study ID: UMIN000044341.

Local Excision for organ preservation in early REctal cancer with No Adjuvant treatment (LORENA Trial): prospective observational study protocol

IntroductionLocal resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME. Patients and methodAn international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI +/− endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy. DiscussionThe prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information.The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients.Trial registration number: NCT05927584.

Tumor microenvironment parameters as a predictor of the duration of clinical effectiveness of immunotargeted therapy in advanced or metastatic endometrial cancer: A pilot multicenter observational study

Background. The inclusion of lenvatinib in the immunotherapy regimen for patients with MSS/pMMR endometrial cancer (EC) is due to its ability to modulate the tumor microenvironment, which allows the use of pembrolizumab in low-immunogenic tumors. However, only 30 % of patients with advanced or metastatic EC have a clinical response when treated with pembrolizumab and lenvatinib. In this regard, there is an obvious need to identify biomarkers that allow accurate selection of candidates for this type of therapy.Aim. To determine the predictive value of subpopulations of lymphocytes and macrophages, their expression of PD-1, expression of estrogen receptors, as well as vessel density in immunotargeted therapy for advanced or metastatic EC.Materials and methods. An open-label non-randomized observational association study was performed, involving a total of 22 patients with advanced or metastatic MSS/pMMR EC treated with pembrolizumab and lenvatinib. Duration of clinical effectiveness was used as a parameter to stratify patients. Using TSA-associated multiplex immunofluorescence, the proportions of CD8+ T lymphocytes, CD20+ B lymphocytes, FoxP3+ T regulatory lymphocytes and CD163+macrophages in tumor samples before the start of immunotargeted therapy were analyzed.Results. Three microenvironmental parameters were found to be associated with duration of clinical efficacy: the proportion of CD20+ B cells, the proportion of FoxP3+ T regulatory lymphocytes, and the ratio of CD8+/CD20+ lymphocytes in the tumor microenvironment. However, the CD8+/CD20+ lymphocyte ratio had the greatest predictive value; a value below 3.219 was associated with long clinical efficacy in patients with advanced or metastatic EC.Conclusion. The ratio of cytotoxic and B-lymphocytes in the microenvironment is a reliable predictor marker of the duration of the period of clinical effectiveness of immunotargeting therapy in advanced or metastatic EC.

Open-label observational study of effectiveness and tolerability of ipidacrine in treatment of patients with diabetic polyneuropathy (DIAMANT study)

Diabetic polyneuropathy (DPN) is one of the most common complications of diabetes mellitus, leading to the development of flaccid paresis, neuropathic pain syndrome, sensitive ataxia, as well as trophic disorders in the distal parts of the lower extremities.The purpose of the randomized, open-label, comparative, prospective study was to evaluate the effectiveness and tolerability of ipidacrine in the complex treatment of patients with DPN.Materials and methods. Patients with DPN (n = 60) were randomized into 2 groups. Both groups received basic therapy (alpha-lipoic acid, B vitamins, gabapentin); in the treatment of patients of the main group (n = 30), in addition, ipidacrine was used (Ipidacrine-SZ, North Star Co., Russia). We have analyzed the intensity of pain syndrome (VAS-P), the average daily dosage of gabapentin, and the results of the neuropathic dysfunctional scale (modified version, NDSm), Pittsburgh Sleep Quality Index, PSQI), Global Rating of Change Scale (GROC), the results of electroneuromyography (ENMG). The total duration of the observation and treatment period was 2 months.Results. After 2 months of therapy in the main group of patients, compared with the control group, there was significantly more complete pain control (VAS-P: 3.0 ± 0.9 vs 3.6 ± 0.8), a decrease in the average daily dosage of gabapentin (390 vs 500 mg/day), reduction in the severity of clinical manifestations of polyneuropathic syndrome (NDSm: 4.4 ± 1.0 vs 4.9 ± 1.0 points) and improvement in sleep quality (PSQI: 6.8 ± 1.3 vs 7.9 ± 1.7). According to ENMG data, patients in the main group showed a significant improvement in the neurophysiological parameters of both motor and sensory fibers, which was significantly more pronounced compared to the control group. A significantly larger proportion of patients in the main group assessed the improvement from the therapy as ‘pronounced’ (GROC: 10/33.3 % vs 6/20.0 %).Conclusions. The use of ipidacrine in complex therapy of patients with DPN can significantly reduce the clinical manifestations of disease and improve the neurophysiological parameters of the peripheral nerves of the lower extremities. Ipidacrine can be considered as a basic drug for the treatment of patients with neurological complications of diabetes mellitus.

A Case Series Study of Weekly or Fortnightly Transcranial Magnetic Stimulation (TMS) in Major Depressive Disorder.

Major depressive disorder (MDD) is frequently chronic and relapsing. The use of maintenance or continuation transcranial magnetic stimulation (TMS) has received clinical and some research support. To conduct a case series study to report the outcomes of once-weekly (OW) or once-fortnightly (OF) continuation TMS in a real-life setting. We offered OW or OF TMS sessions to patients with MDD in remission or partial remission/relapse. Ten patients received OW TMS and four received OF TMS, for 8 to 46 weeks. No patients in either group who were in remission or partial remission at baseline experienced a relapse. Improvements in HAMD6 and CGI-S scores were statistically significant or of borderline significance for the total sample and the OW group. This naturalistic, open-label observational study indicates that OW TMS is effective as maintenance therapy in MDD, while also offering some support for OF TMS maintenance in preventing relapse.

Feasibility and acceptability of remotely monitoring spirometry and pulse oximetry as part of interstitial lung disease clinical care: a single arm observational study

BackgroundRemote monitoring of patient-recorded spirometry and pulse oximetry offers an alternative approach to traditional hospital-based monitoring of interstitial lung disease (ILD). Remote spirometry has been observed to reasonably reflect clinic spirometry in participants with ILD but remote monitoring has not been widely incorporated into clinical practice. We assessed the feasibility of remotely monitoring patients within a clinical ILD service.MethodsProspective, single-arm, open-label observational multi-centre study (NCT04850521). Inclusion criteria included ILD diagnosis, age ≥ 18 years, FVC ≥ 50% predicted. 60 participants were asked to record a single spirometry and oximetry measurement at least once daily, monitored weekly by their local clinical team. Feasibility was defined as ≥ 68% of participants with ≥ 70% adherence to study measurements and recording measurements ≥ 3 times/week throughout.ResultsA total of 60 participants were included in the analysis. 42/60 (70%) were male; mean age 67.8 years (± 11.2); 34/60 (56.7%) had idiopathic pulmonary fibrosis (IPF), Median ILD-GAP score was 3 (IQR 1–4.75). Spirometry adherence was achieved for ≥ 70% of study days in 46/60 participants (77%) and pulse oximetry adherence in 50/60 participants (83%). Recording ≥ 3 times/week every week was provided for spirometry in 41/60 participants (68%) and pulse oximetry in 43/60 participants (72%). Mean difference between recent clinic and baseline home spirometry was 0.31 L (± 0.72). 85.7% (IQR 63.9–92.6%) home spirometry attempts/patient were acceptable or usable according to ERS/ATS spirometry criteria. Positive correlation was observed between ILD-GAP score and adherence to spirometry and oximetry (rho 0.24 and 0.38 respectively). Adherence of weekly monitoring by clinical teams was 80.95% (IQR 64.19–95.79). All participants who responded to an experience questionnaire (n = 33) found remote measurements easy to perform and 75% wished to continue monitoring their spirometry at the conclusion of the study.ConclusionFeasibility of remote monitoring within an ILD clinical service was demonstrated over 3 months for both daily home spirometry and pulse oximetry of patients. Remote monitoring may be more acceptable to participants who are older or have more advanced disease.Trial Registrationclinicaltrials.gov NCT04850521 registered 20th April 2021

Brodalumab for moderate-severe hidradenitis suppurativa: An open-label multicentric cohort study in real clinical practice.

The use of biological therapy is becoming increasingly common in patients with hidradenitis suppurativa (HS). Levels of serum TNF-alfa and IL17 support the role of an immune system dysregulation in the pathogenesis of HS. Brodalumab targets the receptor A of IL-17, thus having a promising role in the treatment of HS. A multicenter retrospective observational open-label study was conducted in two tertiary hospitals. Adults with moderate to severe HS under treatment with brodalumab 210 mg at week 0, 1, 2 and then every 2 weeks were included and assessed at weeks 0 and 16 which was the median follow-up time. Demographic and disease-related variables as well as response parameters (HiSCR and IHS4) and safety data were recorded and analysed. A total of 16 patients (75% males) were included in our study. 50% of patients presented an inflammatory phenotype and mean BMI was 28.37. HiSCR was achieved in 50% of patients and mean IHS4 decreased from 24.13 to 16.81 (p = 0.002). No differences were found between those who achieved HiSCR and those who did not. Grade 2 adverse events were reported in three patients with no fatal outcomes and treatment discontinuation was advised in four patients. Brodalumab seems to be effective and safe in patients with moderate to severe HS, even in those that did not respond to adalimumab, which, at the moment, is the only widely approved biologic for this indication. Thus, it stands as an interesting option for the treatment of HS.

Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor

Introduction. Natalizumab (NTZ) is a humanized monoclonal antibody (mAb) that selectively inhibits α4-integrin adhesion molecule located on the surface of lymphocytes and prevents their trafficking into the central nervous system (CNS).
 The aim of this study was to identify characteristics of lymphocyte population and subpopulation pattern in the peripheral blood (PB) of multiple sclerosis (MS) patients who discontinued NTZ due to an increased risk of developing developing progressive multifocal leukoencephalopathy.
 Materials and methods. We conducted an open-label prospective observational study in 26 MS patients. Of those, 6 patients had rapidly progressive MS, 10 patients discontinued NTZ and had confirmed relapses afterwards, and 10 patients received NTZ and had no relapses during the washout period. Ten apparently healthy individuals were used as controls. Cell-mediated immunity parameters were evaluated by flow cytometry using a panel of mAbs to differentiation antigens of PB lymphocytes.
 Results. Patients who discontinued NTZ had significantly decreased absolute lymphocyte counts in PB, decreased T-cytotoxic, NKT and B1 lymphocyte subpopulation levels, and decreased activated T-cell (CD3+HLA–DR+) levels, which may be related to their redistribution, passing through the blood-brain barrier, and trafficking into the central nervous system. CD20+ В-cell levels did not differ from normal. Additional immune predictors of MS relapses after NTZ discontinuation can include decreased absolute count of PB lymphocytes and decreased percentage of CD3+CD8+ T-cell, NKT-cell, and B1-cell (CD19+CD5+) subpopulations. Significantly increased levels of CD25+- and CD38+-activated B-cells compared with the normal levels in naïve patients and subjects without relapses after NTZ discontinuation may suggest a high activation potential of the circulating B-cell pool and, therefore, a high risk of MS relapses.
 Conclusions. The changes in the lymphocyte subpopulation pattern in the PB of MS patients after NTZ discontinuation may have a prognostic value for assessing the risk of relapses; they justified switching patients to anti-B-cell therapy.

Immunogenicity and Safety of Half-Dose Heterologous mRNA-1273 Booster Vaccination for Adults Primed with the CoronaVac® and ChAdOx1-S Vaccines for SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational study to evaluate the immunogenicity and safety of half-dose mRNA-1273 as a booster vaccine among adults aged >18 years who underwent a complete primary SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination regimen with CoronaVac® and ChAdOx1-S. Adverse events (AEs), seropositivity rate, seroconversion, geometric mean titer (GMT) of SARS-CoV-2 antibodies, neutralizing antibodies, and T cells (CD4+ and CD8+) specific for SARS-CoV-2 were analyzed. Two hundred subjects were included in the final analysis, with 100 subjects in each priming vaccine group. Most of the AEs were mild, with systemic manifestations occurring between 1 and 7 days following vaccination. A significant difference was observed in the GMT and seropositivity rate following booster dose administration between the two groups. CD8+/CD3+, IFN (interferon)-producing CD8+, and TNF (tumor necrosis factor)-producing CD8+ cells showed significant increases in both groups. The administration of the half-dose mRNA-1273 booster is safe and effective in increasing protection against SARS-CoV-2 infection.

Recomendaciones farmacéuticas de adecuación terapéutica en pacientes con esclerosis múltiple

ObjectiveTo determine the prevalence of PIMDINAC criteria and to implement pharmacological interventions in a population with multiple sclerosis over 55 years of age. MethodsRetrospective observational open-label study including patients with multiple sclerosis aged 55 years and older between December 2022 and February 2023. The main variable determined was the percentage of compliance with the PIMDINAC criteria. ResultsNinety-five patients were included, with the presence of PIMDINAC criteria detected in 67.4%. The most frequently detected criterion was non-adherence to concomitant treatment (84,4%), followed by drug–drug interactions (56.2%) and potentially inappropriate medication (25%). A total of 20 pharmaceutical interventions were performed in 17 patients (17.9%). Potentially inappropriate medication was responsible for 11 interventions, non-adherence for 7 and drug–drug interactions for 2. The 81.8% of interventions were accepted, resulting in the discontinuation of 15 inappropriately prescribed drugs. The prevalence of PIMDINAC criteria in this group of patients is high. The study revealed that PIMDINAC criteria were prevalent in 67.4% of the study population, with polypharmacy playing an important role, suggesting the potential for a multidisciplinary approach, through pharmaceutical interventions to address unnecessary or duplicate treatments.

Radiological Progression and Predictors of Radiological Progression in Early Rheumatoid Arthritis Treated with Conventional Synthetic Disease-modifying Agents

Aim: To study the clinical and serological predictors of radiological progression at one year in a cohort of Indian patients with early rheumatoid arthritis (RA). Methods: In this prospective open-label observational study, consecutive patients with early RA (<six months) were examined at baseline and at each visit (0, 3, 6, 9 and 12 months) for disease activity, DAS ESR 28 and European League Against Rheumatism response. Radiography of the hands and feet was performed at baseline and at one year of treatment, and radiologic progression was assessed using van der Heijde’s Sharp score. The prognostic factors were evaluated using a logistic regression model. Results: Fifty-one eligible patients were analysed for disease outcomes, whereas 43 were eligible for radiographic progression. The mean duration of RA was 3.4 ± 1.85 months. At baseline, 96% of the patients had moderate to high disease activity. The proportion of patients with erosions increased from 16.3% to 37.2% at one year, whereas that of patients with joint space narrowing (JSN) increased from 21% to 39.5%. At one year, the mean increase in total Sharp’s score was 1.67, while 32.5% of patients had radiological progression. Age of onset, presence of erosions, JSN, anticitrullinated protein antibody (ACPA) titre and tender joint counts at baseline were associated with radiographic progression at one year. However, in the multivariate analysis, none of the variables predicted radiographic damage. Only JSN was positively associated with progression at one year. Conclusion: Age at onset, presence of erosions, JSN, ACPA titre and tender joint counts at baseline were associated with radiographic progression at one year, but further studies are required to confirm these results.

Breaking the chains of lipoprotein lipase deficiency: A pediatric perspective on the efficacy and safety of Volanesorsen

RationaleLipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency. MethodsThe patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions. ResultsWhile the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life. ConclusionThis study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.

P1067 Pan-enteric mucosal inflammation in CD patients treated with vedolizumab assessed by capsule endoscopy– interim results of a prospective observational study

Abstract Background Mucosal healing (MH) is a paramount treatment goal in Crohn’s disease (CD). The vast majority of data pertains to MH in the colon and terminal ileum; nonetheless, proximal small-bowel involvement can be detected in up to 50% of CD patients assessed by capsule endoscopy (CE). Data regarding pan-enteric MH among patients with active CD who were treated with vedolizumab (VDZ) are lacking. We aimed to evaluate the efficacy of VDZ for achieving pan-enteric MH using pan-enteric CE. Methods This was a prospective open-label observational study. Patients with CD who have started on VDZ, were included. Patients underwent small-bowel patency-assessment using patency capsule (PC) and were followed by CE (PillCam Crohn’s, Medtronic, USA) before /within 40 days of treatment onset and after 14 and 52 weeks. In patients with exclusive small-bowel involvement, colonic preparation was not performed and colon was not assessed in subsequent CE. Accordingly, Lewis score (LS) and Pan-enteric Pillcam score (PS) were calculated, when available. The primary outcome was pan-enteric MH defined as LS<135 and LS<135 & PS<4 for CE confined to the SB/SB &colon, respectively. The main secondary outcomes were small-bowel MH (LS<135) and colonic-MH (colonic PS<4). Results 57 patients were recruited, 41 patients were enrolled (median age: 28 [23-45] years, male-44%) and 16 patients were excluded (6- retained PC, 1- technical reason, 2 -did not start VDZ, 7-withdrew consent). Of them, six patients (1- retained PC, 1- multiple strictures, 1- lost to follow-up, 3- clinical flare) and eight patients (4- discontinued VDZ, 2- capsule adverse events, 1- lost to follow-up, 1- clinical flare) were dropped-out before week 14 and week 52, respectively. Pan-enteric MH was observed in 7/39 (18%) patients at week 14, and in 7/30 (23%) patients at week 52 (two patients and 11 patients have not yet reached 14/52-week, respectively). We observed higher rates of both small-bowel MH and colonic-MH during follow-up compared to baseline (Figure 1), and it was consistent with significant improvement at week 14 in both LS (900 [225-900] vs. 450 [0-900], p<0.001) and PS (12 [2-18] vs. 6 [0-14], p=0.001) compared to baseline. Improvement was even more prominent at week 52 (LS- 0 [0-300] PS- 2 [2-6]). No cases of retained capsule were observed during follow-up. Conclusion VDZ induces MH in both the small-bowel and the colon among patients with CD, and this effect may persist up to 52 weeks of treatment.

Autovaccine-Based Immunotherapy: A Promising Approach for Male Recurrent Urinary Tract Infections.

Recurrent Urinary Tract Infections (UTIs) in men range from 0.9 to 2.4/1000 individuals in younger men to 7.7/1000 in those over 85, significantly impacting their quality of life. Preventive strategies include autovaccines, but limited evidence exists for males. A prospective monocentric, open-label observational study was conducted from August 2018 to August 2021, with follow-up until August 2023 including patients with recurrent UTIs treated with immunotherapy. We evaluated the incidence rate of UTIs per year, the incidence rate of episodes after two or three rounds of the autovaccine, and quality of life measured with the IPSS-QoL questionnaire. A total of 49 patients fulfilled inclusion criteria. The mean age was 72 years (±15), and the median 61. The evolution of UTIs number of episodes after the autovaccine rounds: -37.74% for the first round from 5.3 to 3.3; -33.33% for the second round from 3.3 to 2.2; -45.45% for the third round from 2.2 to 1.2. The mean IPSS score improved from 10.69 to 7.27 after the treatment (32%). The mean QoL subscore enhancement was from 4.22 to 1.92 (54%). With a mean follow-up of 3 years, only nine patients required retreatment. Autovaccine treatment significantly reduced the number of UTI episodes, with a cumulative effect observed after multiple rounds of treatment, demonstrating an enhancement in QoL and with sustained effectiveness and a low need for retreatment.

Growth and micronutrient status parameters of Nigerian preterm infants consuming preterm formula or breastmilk.

Moderate-to-late preterm infants (32-34 weeks GA) have increased risk of neonatal morbidities compared to term infants, however dedicated nutritional guidelines are lacking. Moderate-to-late preterm infants received a preterm formula (n = 17) or breastmilk (n = 24) from age 2-10 weeks in a non-randomized, open-label observational study. Anthropometric measurements were assessed bi-weekly. Blood concentrations of hemoglobin, ferritin, serum retinol, and 25-hydroxy-vitamin D (25OHD) were analyzed at age 2 and 10 weeks. Average growth per day was 14.7 g/kg BW/day in formula-fed and 12.8 g/kg BW/day in breastmilk-fed infants but not different from each other. Length and head circumference in both groups were in line with the median reference values of the Fenton growth chart. At 10 weeks of age, hemoglobin tended to be higher in the formula-fed group (10.2 g/dL vs. 9.6 g/dL, p = 0.053). 25OHD increased in formula- and breastmilk-fed infants from 73.8 to 180.9 nmol/L and from 70.7 to 97.6 nmol/L, respectively. Serum retinol only increased in the formula-fed group (0.63 to 1.02 µmol/L, p < 0.001). Breastfeeding resulted in adequate growth in moderate-late preterm infants but was limiting in some micronutrients. The preterm formula provided adequate micronutrients, but weight gain velocity was higher than the Fenton reference value. Unfortified breastmilk resulted in adequate growth in weight, length and head circumference in Nigerian moderate to late preterm infants during an study period of 8 weeks, but status of vitamin D, vitamin A and iron needs to be monitored. The high-energy formula, developed for very preterm infants, resulted in higher growth in body weight in moderate to late preterm infants than the median of the Fenton preterm growth chart. This study supports the necessity of dedicated nutritional guidelines, and regular monitoring of growth and nutritional status of moderate to late preterm infants.

An open-label prospective observational study to evaluate the efficacy and safety of alternate day versus daily dosing of atorvastatin in patients of dyslipidemia

Background: Hypercholesterolemia is a main driver of atherosclerosis. Cholesterol-containing lipoproteins induce endothelial dysfunction and macrophage activation. Foam cell formation results from the uptake of cholesterol-containing lipoproteins by macrophages, it is an essential step in the initiation and progression of atherosclerosis. Aims and Objectives: To evaluate the efficacy and safety of alternate day versus daily dosing of atorvastatin in patients with dyslipidemia. Materials and Methods: This open-label, prospective, observational study was conducted on dyslipidemic patients who came into the medicine Outpatient Department of Dhanalakshmi Srinivasan Medical College and Hospital, Tamil Nadu. Approval for the study was taken from the Institutional Ethical Committee. The duration of the study was 3 months. The efficacy of atorvastatin was checked by noting their blood lipid profile status. Results: Out of 100 patients included in the study 79 completed the study whereas 21 patients were lost in follow-up, 42 patients were analyzed in daily dose (Group A), and 37 patients in alternate dose (Group B) of atorvastatin (20 mg). There was no statistically significant difference based on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels both prior and post-treatment in both the groups. Adverse drug reactions (ADR) profile showed a statistically significant difference between both the groups after treatment by atorvastatin (P=0.0001), with more ADRs noted in a daily dosing group. Conclusion: The results of this study show that alternate dosing of atorvastatin was better tolerated than daily dosing hence physicians can consider choosing an alternate day therapy to reduce pill burden on patients.

Клинико-анамнестические факторы риска развития преэклампсии как осложнения гестационного сахарного диабета

Aim. To identify the clinical and anamnestic risk factors of preeclampsia (PE) in gestational diabetes mellitus (GDM). Design. Open-label observational prospective study. Materials and methods. The study enrolled 204 pregnant women with GDM, 70 of which had their pregnancy complicated with PE (study group) and 134 patients did not have PE (controls). In the study group, clinical and anamnestic risk factors were searched for by tracing data from primary medical records. The age of participants was 21 to 46 years old. Extragenital conditions were studied as possible risk factors of PE in GDM. Results. It has been established that GDM with PE was more likely to be associated with chronic arterial hypertension (CAH) (χ2 = 7.72, р = 0.006, odds ratio (OR) = 8.52, 95% confidence interval (CI): 1.76–41.29); a history of respiratory diseases — severe sore throat (χ2 = 6.2, р = 0.01, OR = 3.98, 95% CI: 1.40–11.27), chronic tonsillitis (χ2 = 12.84, р &lt; 0.001, OR = 4.81, 95% CI: 2.03–11.40), acute bronchitis (χ2 = 6.0, р = 0.02, OR = 7.33, 95% CI: 1.48–36.32) than GDM without PE. Conclusion. Clinical and anamnestic risk factors of PE in women with GDM are CAH, a history of respiratory diseases (acute bronchitis, severe sore throat, chronic tonsillitis). Keywords: gestational diabetes mellitus, preeclampsia, risk factors.

Динамика психоэмоционального и когнитивного статусов женщин репродуктивного возраста на фоне приема комбинированного орального контрацептива, содержащего эстетрол

Objective. To study the dynamics of change in psycho-emotional and cognitive indicators in reproductive-aged women receiving a combined oral contraceptive (COC) with estetrol/drospirenone. Patients and methods. A prospective open-label observational study included 64 patients aged 18 to 45 years who applied for contraception selection. According to the study protocol, all patients underwent general clinical examination at baseline, 3 and 6 months from the start of COC administration. The examination included calculation of body mass index (BMI) by Brey formula, measurement of blood pressure, transvaginal ultrasound, assessment of psycho-emotional state and cognitive function. Results. The data obtained in this study indicate a positive effect of COC containing estetrol/drospirenone on the psychoemotional state and cognitive function in patients, which is characterized by increased levels of physical activity regardless of age, decreased levels of anxiety and depression, greater satisfaction with sleep quantity and quality, improved cognitive function due to a positive effect mainly on mild cognitive disorders. Conclusion. Current data on the neuroprotective effect of estetrol in relation to the central nervous system require further study and comprehension. Key words: psycho-emotional state, cognitive disorders, combined oral contraceptive, estetrol, drospirenone

Efficacy of the Enteroadsorbent Silicol®gel in Adults with Irritable Bowel Syndrome Subtypes IBS-D or Mixed: Observational Open-Label Study

Background. Irritable bowel syndrome (IBS) is a common chronic gut-brain interaction disorder with limited effective treatment options. Intestinal adsorbents have a high adsorption capacity for gut irritants and may provide nonpharmacological alternatives. Objectives. This post marketing study is aimed at providing up-to-date evidence to support the safety and efficacy in normal use of an established medical device for IBS treatment. Methods. In this open-label, observational study, adults with IBS with predominant diarrhoea (IBS-D) or IBS with mixed bowel habits (IBS-M), according to Rome IV criteria, received 4 weeks of treatment with the enteroadsorbent Silicol®gel, a CE-certified, licenced, medical device containing colloidal silicic acid. Eligible participants were assessed at baseline (visit 1; in-clinic) and after 1 (visit 2; telephone), 2 (visit 3; telephone), and 4 (visit 4; in-clinic) weeks of treatment. The primary endpoint was the proportion of participants with an overall reduction in the IBS severity scoring system IBS SSS &gt; 50 , representing clinically meaningful improvement. Key secondary endpoints were a reduction in common IBS symptoms and improved quality of life (QoL). Results. Among the 67 treated participants (IBS-D: 37; IBS-M: 30), 65 completed the study. At visit 4, 83.6% (56/67) of participants achieved a reduction in IBS SSS &gt; 50 . The mean (standard deviation [SD]) IBS SSS was 323.4 (55.7) at visit 1 and 160.3 (90.3) at visit 4 (overall change: -163.1 (101.7); 95% confidence interval [CI] 138.3, 187.9, p &lt; 0.001 ). Compared with visit 1, significant reductions in the severity of all key IBS symptoms and overall improvement in QoL were observed at visit 4 ( p &lt; 0.001 ), with improvements observed from visits 1 and 2. Conclusions. In this open-label study of participants with IBS-D and IBS-M, Silicol®gel provided clinically significant improvement in IBS symptoms, demonstrating that enteroadsorbents may be clinically beneficial in this population.

Mechanical bowel preparation in elective colorectal surgery: a propensity score-matched analysis of the Italian colorectal anastomotic leakage (iCral) study group prospective cohorts.

Retrospective evaluation of the effects of mechanical bowel preparation (MBP) on data derived from two prospective open-label observational multicenter studies in Italy regarding elective colorectal surgery. MBP for elective colorectal surgery remains a controversial issue with contrasting recommendations in current guidelines. The Italian ColoRectal Anastomotic Leakage (iCral) study group, therefore, decided to estimate the effects of no MBP (treatment variable) versus MBP for elective colorectal surgery. A total of 8359 patients who underwent colorectal resection with anastomosis were enrolled in two consecutive prospective studies in 78 surgical centers in Italy from January 2019 to September 2021. A retrospective PSMA was performed on 5455 (65.3%) cases after the application of explicit exclusion criteria to eliminate confounders. The primary endpoints were anastomotic leakage (AL) and surgical site infections (SSI) rates; the secondary endpoints included SSI subgroups, overall and major morbidity, reoperation, and mortality rates. Overall length of postoperative hospital stay (LOS) was also considered. Two well-balanced groups of 1125 patients each were generated: group A (No MBP, true population of interest), and group B (MBP, control population), performing a PSMA considering 21 covariates. Group A vs. group B resulted significantly associated with a lower risk of AL [42 (3.5%) vs. 73 (6.0%) events; OR 0.57; 95% CI 0.38-0.84; p = 0.005]. No difference was recorded between the two groups for SSI [73 (6.0%) vs. 85 (7.0%) events; OR 0.88; 95% CI 0.63-1.22; p = 0.441]. Regarding the secondary endpoints, no MBP resulted significantly associated with a lower risk of reoperation and LOS > 6days. This study confirms that no MBP before elective colorectal surgery is significantly associated with a lower risk of AL, reoperation rate, and LOS < 6days when compared with MBP.