Prospective Open-label Observational Study Research Articles

Perfusion index as an early predictor of hypotension during advanced oncothoracic operations (pilot study)

Introduction. Current standards of intraoperative monitoring significantly reduce the response time to a decrease in blood pressure, but do not include methods for predicting changes in hemodynamics to avoid the effects of systemic hypoperfusion.The objective was to evaluate the usefulness of determining the perfusion index for predicting the development of hypotension and its earlier correction during advanced oncothoracic operations.Materials and methods. A prospective open-label observational study was conducted, which included 100 patients who underwent elective oncothoracic surgery. Standard monitoring was established, as well as continuous monitoring of the perfusion index. The perfusion index value was recorded immediately before induction. The patients were divided into 2 groups: in the 1st group (n = 37), patients experienced a decrease in blood pressure, requiring vasopressor support; in the 2nd group (n = 63), no vasopressor support was required.Results. A moderate linear relationship was revealed with a correlation coefficient (r) equal to (–0.68), p < 0.001, and a strong non-linear relationship with a coefficient (ρ) equal to (–0.95), p < 0.001. To identify the relationship model, polynomial regression analysis was performed. A prognostic formula for the use of vasopressors was calculated depending on the preoperative level of perfusion index. At the next stage, a classification tree for analyzing the data array was used. The entire d data array (n = 100) is randomly divided into training (n = 70) and test samples (n = 30). It was revealed that hypotension requiring vasopressor support occurred in patients whose initial perfusion index was ≤ 2.85. ROC analysis determined an AUC of 0.952 (95% CI: 0.888–1.016).Conclusion. A low PI value before induction of anesthesia during advanced oncothoracic operations can be used to monitor the functional activity of the autonomic nervous system and predict intraoperative hypotension. Patients with a baseline PI ≤ 2.85 have a higher risk of developing hypotension during advanced oncothoracic surgery compared with those with a baseline PI ≥ 2.85. The effectiveness of the method in patients with concomitant pathologies has not been tested.

Baseline monocyte count predicts symptom improvement during intravenous ketamine therapy in treatment-resistant depression: a single-arm open-label observational study.

Neuroinflammatory processes in depression are associated with treatment resistance to conventional antidepressants. Ketamine is an effective new therapeutic option for treatment-resistant depression (TRD). Its well-established immunomodulatory properties are hypothesized to mediate its antidepressant effect. In this context, higher levels of inflammation may predict a better treatment response. However, conclusive evidence for this hypothesis is lacking. We thus investigated whether standard peripheral inflammatory cell markers and C-reactive protein (CRP) levels could predict symptom improvement during intravenous ketamine therapy in TRD patients. 27 participants with TRD were treated with six weight-adjusted intravenous ketamine infusions (0.5 mg/kg bodyweight) over three weeks. Baseline assessments included CRP, absolute monocyte count (AMC), and absolute neutrophil count (ANC). Depression severity was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline (D1), after the first (D3) and before the last ketamine infusion (D18). Raters were blinded for the baseline laboratory assessments. 13 participants responded to ketamine treatment, and 8 participants partially responded. Baseline AMC showed a strong negative correlation with MADRS change at D3 (r=-0.57, p=0.002) and at D18 (r =-0.48, p=0.010), indicating that a high baseline AMC was associated with greater symptom improvement. A generalized linear model confirmed the association of baseline AMC with symptom improvement during ketamine treatment when additionally accounting for age, sex, and body mass index. Specifically, baseline AMC demonstrated predictive value to discriminate responders and partial responders from non-responders, but lacked discriminative ability between partial responders and responders. Baseline ANC correlated with the MADRS changes at D3 (r=-0.39, p=0.046), while CRP values did not correlate at all. Our prospective single-arm open-label observational study demonstrated that baseline AMC reliably predicted symptom improvement during intravenous ketamine treatment in TRD patients. AMC could therefore serve as a simple and easily accessible marker for symptom improvement during ketamine therapy in daily clinical practice. Future studies with larger sample sizes and a more detailed longitudinal assessment of AMC subtypes are needed to better understand the specific relationship between monocytes and the neuromodulatory effects of ketamine.

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.

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.

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.

Therapeutic Potential of Combined Herbal Medicine and Electroacupuncture in Mild Cognitive Impairment Through Cytokine Modulation: An Observational Study.

We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action. This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively. The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], p < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas. Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.

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

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.

Very Early Discharge of LOw-Risk ST Elevation MI patients after successful primary percutaneous coronary intervention (VEDLOR-STEMI) study

Abstract Background Current European guidelines recommend discharging low-risk STEMI patients after successful primary PCI at 48-72 hours, based on meta-analysis and large observational studies. There is overall trend towards reducing hospital stay after the COVID-19 pandemic with the risk of cross-infection and to reduce the strain on bed capacity in hospitals. Purpose With this background, we decided to create a pathway to implement very early discharge (within 48 hours) of low-risk STEMI patients after successful primary PCI. The aim of this study is to assess the feasibility and safety of this approach in our centre. Methods This is a single arm, open label prospective observational study of patients undergoing primary PCI in a single high volume tertiary cardiac center. The inclusion criteria included patients ≤70 years with STEMI presenting within 12 hours of symptom onset, one or two vessel disease (&amp;gt;50% stenosis) who underwent successful primary PCI with TIMI 3 flow with LVEF of ≥45% after 24 hrs. Patients with persistent arrhythmia after PCI, recurrent ischemic symptoms, severe anaemia (Hb ≤7 g/dl), eGFR ≤ 45ml/min/1.73 m2 and cardiogenic shock were excluded. We created specific pathways to identify and implement the very early discharge protocol (within 48 hours) in these patients with regular telephone follow up (1st and 3rd post-discharge days) and direct clinic visit at 1 week and after 1 month. The primary outcome of the study was major adverse cardiovascular event at 1 week and 30 days after discharge. Secondary outcome included patient’s satisfaction on early discharge. Results From Mar 2021 to Dec 2022, 84 [mean age 55 ± 9 yrs, 16 (18.2%) females] out of 106 patients provided informed consent to be included in the study. Diabetes, Hypertension, Dyslipidemia, and smoking history were noted in 46 (52.2%), 39 (44.3%), 41 (46.5%) and 6 (6.8%) patients respectively. Mean LVEF was 50±5% after 24 hours of primary PCI. The procedural characteristics of the patients are provided in Table 1. Five patients (5.7%) had minor complictions post discharge; 2 had access site pain, one had giddiness due to hypotension, one had chest pain post discharge, and another had allergic reaction. All of them were managed without the need for re-admission. At one week follow up, except for 2 patients, all others (98%) were satisfied with this early discharge protocol. There was no major adverse cardiac event at 1 week and 30 days. Conclusion This single centre study shows that very early discharge (within 48 hrs) of low-risk STEMI patients after successful primary PCI is feasible and safe with appropriate discharge pathway and follow-up arrangements. Larger studies are needed to confirm this finding.

Proton Pump Inhibitor Deprescription Prospective Study in Patients Without Indication: Are There Differences in Proportion of Restarts According to Withdrawal Strategy?

Background: The increasing utilization of proton pump inhibitors (PPIs) in patients without clear medical indications has raised concerns regarding potential risks, highlighting the importance of deprescription. However, comparative analyses of withdrawal strategies (abrupt vs gradual) in this context remain scarce or of low quality. Aim: This study aimed to evaluate the success rate of deprescribing PPIs in hospitalized patients without a documented indication and compare the proportion of treatment restarts based on withdrawal strategy. Method: An uncontrolled, open-label prospective observational study was conducted on patients receiving PPI treatment during hospital admission between May 2017 and July 2018. Deprescription was recommended for patients without a clear indication. Follow-up continued until discharge, with monitoring for rebound symptoms. The percentage of restarts based on the withdrawal strategy was compared using the chi-square test. Results: A total of 402 patients were reviewed, among whom 27% lacked a medical indication (mean age > 60 years, polymedicated), while 70% were prescribed PPIs electronically. Deprescription was performed in 49% of patients, with 64% undergoing abrupt withdrawal. Rebound symptoms led to treatment restart in 15% of cases. However, the chi-square test revealed no significant differences in restart proportions between the abrupt and gradual withdrawal groups (P = 0.365). Conclusion: Deprescribing PPIs is deemed safe, particularly for polymedicated geriatric patients, as it leads to a low percentage of restarts regardless of the chosen withdrawal strategy. However, the high percentage of PPI prescription without a clear indication underlines the need for periodic reassessment to avoid unnecessary risks and overuse.

Clinical experience with the use of citicoline in mild cognitive impairment of vascular origin

Cardiovascular factors significantly increase the risk of vascular cognitive impairment (VCI). Currently, there are no specific treatments for VCI. A promising therapeutic strategy is the administration of citicoline, which has a neuroprotective effect.Objective: to evaluate the effect of treatment with citicoline (Noocil®) on cognitive function and quality of life (QoL)in patients with mild cognitive impairment (MCI) developed in a background of arterial hypertension and cerebral arteriosclerosis.Material and methods. An open-label prospective observational study enrolled 32 patients with neuroimaging-confirmed vascular cognitive impairment who received baseline therapy (antihypertensive, lipid-lowering, and antiplatelet therapy) and achieved target blood pressure and low-density lipoprotein cholesterol levels. All patients were assessed with a neuropsychological status assessment (MoCA-test). The efficacy of therapy was assessed by the Short Form-36 Quality of Life Questionnaire (SF-36).Results. The most common complaints of the patients were poor concentration, fatigue, forgetfulness, mood lability, sleep disturbances, more often in the form of early waking, and headaches. After 3 months of taking the drug Noocil®, all patients noted an increase in the ability to work, an improvement in concentration, memory and reproduction of the information received, both physical and mental indicators of QoL improved. The positive dynamics in terms of cognitive status (especially the functions of attention, short-term memory, several aspects of executive functions), QoL of patients, which was associated with the effect of Noocil® therapy, was accompanied by the absence of adverse events. A distinctive feature of domestic citicoline (Noocil®) is the presence of an original dosage form – a 240 ml bottle for oral administration, which improves adherence to long-term therapy.Conclusion. The efficacy, safety and good tolerability of Noocil® therapy in patients with predemental VCI was demonstrated.

Patient-specific virtual three-dimensional surgical navigation for gastric cancer surgery: A prospective study for preoperative planning and intraoperative guidance.

Abdominal computed tomography (CT) can accurately demonstrate organs and vascular structures around the stomach, and its potential role for image guidance is becoming increasingly established. However, solely using two-dimensional CT images to identify critical anatomical structures is undeniably challenging and not surgeon-friendly. To validate the feasibility of a patient-specific 3-D surgical navigation system for preoperative planning and intraoperative guidance during robotic gastric cancer surgery. A prospective single-arm open-label observational study was conducted. Thirty participants underwent robotic distal gastrectomy for gastric cancer using a virtual surgical navigation system that provides patient-specific 3-D anatomical information with a pneumoperitoneum model using preoperative CT-angiography. Turnaround time and the accuracy of detecting vascular anatomy with its variations were measured, and perioperative outcomes were compared with a control group after propensity-score matching during the same study period. Among 36 registered patients, 6 were excluded from the study. Patient-specific 3-D anatomy reconstruction was successfully implemented without any problems in all 30 patients using preoperative CT. All vessels encountered during gastric cancer surgery were successfully reconstructed, and all vascular origins and variations were identical to operative findings. The operative data and short-term outcomes between the experimental and control group were comparable. The experimental group showed shorter anesthesia time (218.6 min vs. 230.3 min; P=0.299), operative time (177.1 min vs. 193.9 min; P=0.137), and console time (129.3 min vs. 147.4 min; P=0.101) than the control group, although the differences were not statistically significant. Patient-specific 3-D surgical navigation system for robotic gastrectomy for gastric cancer is clinically feasible and applicable with an acceptable turnaround time. This system enables patient-specific preoperative planning and intraoperative navigation by visualizing all the anatomy required for gastrectomy in 3-D models without any error. Clinicaltrials.gov, identifier NCT05039333.

Nocturnal acid breakthrough and esophageal acidification during treatment with dexlansoprazole as compared to omeprazole in patients with gastroesophageal reflux disease.

Nocturnal acid breakthrough (NAB) may differ based on duration of proton pump inhibitor (PPI) action and Helicobacter pylori (H. pylori) infection; NAB may influence esophageal acidification (EA) and mucosal damage. Dexlansoprazole, a long-acting PPI, was not compared with omeprazole for NAB, gastric acid suppression, and EA in relation to H. pylori infection. In this prospective open-label comparative observational study, gastroesophageal reflux disease (GERD) patients were evaluated using 24-h dual-channel pH-impedance monitoring while on dexlansoprazole (60 mg, n = 39) and omeprazole (20 mg, n = 41) to study the degree of gastric acid suppression, esophageal acid exposure, and NAB (primary outcome measures). H. pylori was detected by rapid urease test and histology. NAB tended to be frequent with omeprazole than dexlansoprazole (33/41 [80.5%] vs. 23/39 [59%]; p = 0.06). Though nocturnal mean esophageal pH was comparable between the dexlansoprazole and omeprazole groups, its duration was less with the former (181.5 [15.2-334.2] vs. 283 [158-366] min, p = 0.03). NAB was as frequent in the H. pylori-infected than the non-infected group (11/19 [57.9%] vs. 45/61 [73.8%]; p = 0.1). The nocturnal gastric and esophageal pH in the H. pylori-infected group was higher than in the non-infected group (4.6 ± 1.7 vs. 4 ± 1.6, p = 0.157; 6.1 ± 0.6 vs. 5.8 ± 0.6, p = 0.128). Dexlansoprazole tended to increase 24-h and nocturnal mean gastric pH among H. pylori-infected more than omeprazole (5.9 ± 1.1 vs. 4.2 ± 1.7, p = 0.023; 5.7 ± 1.2 vs. 3.8 ± 1.5, p = 0.006). Dexlansoprazole is more effective than omeprazole in suppressing gastric acid secretion, resulting in lesser EA and NAB, particularly in the presence of H. pylori.

Оценка эффективности и безопасности интерферона α-2b в профилактике острых респираторных инфекций (в том числе COVID-19) у детей в Узбекистане

Objective. To study the preventive efficacy and safety of interferon α-2b (IFN-α2b) with antioxidants against acute respiratory viral infections (ARVI) among children in Uzbekistan during the COVID-19 pandemic. Patients and methods. An open-label prospective observational study included 300 first-grade pupils (age 6–7 years) from schools in Tashkent (Uzbekistan). Children were evenly divided into three groups: the first and second (study) groups from different schools received IFN-α2b (Viferon® gel for external and local use, 36,000 IU/g); the third group (control) did not receive the medication. The main criteria for assessing the effectiveness of prevention were the incidence of ARVI within 3 months after inclusion in the study, duration and severity of clinical symptoms of the disease, and the frequency of adverse events associated with the use of the study medication. Results. Observation after 30 to 90 days from the beginning of treatment showed a statistically significant increase in the proportion of ARVI cases in the control group compared to the study groups where Viferon® gel was used. The average duration of the febrile period in children with ARVI in the first group was the lowest and amounted to 3.1 ± 0.4 days, in the second group – 3.8 ± 0.5 days, in the third group – 5.4 ± 1.1 days (p1–3 = 0.002 and p2–3 = 0.003, Mann–Whitney U test with adjustment to multiple comparisons). Also, the duration of intoxication symptoms and catarrhal phenomena in children with ARVI in the groups receiving IFN-α2b was significantly shorter than in the control group. No cases of COVID-19 were registered in the study groups during the entire period of observation, while in the control group, markers of infection were detected in 30 children. There were no adverse events associated with the administration of IFN-α2b (Viferon® gel for external and local use 36,000 IU/g). Conclusion. In children who received IFN-α2b with antioxidants, a statistically significant decrease in ARVI episodes was found, as well as rapid relief of intoxication symptoms and catarrhal phenomena in the event of disease. The pronounced effectiveness and the absence of adverse events give reason to recommend the use of Viferon® gel for the prevention of acute respiratory viral infections, as well as COVID-19 in children. Key words: interferon α-2b, antioxidants, prevention of acute respiratory viral infections, children

No room for pain: A prospective study showing effective and nearly pain-free treatment of actinic keratosis with simulated daylight photodynamic therapy (SDL-PDT) using the IndoorLux® System in combination with BF-200 ALA (Ameluz®)

BackgroundPhotodynamic therapy (PDT) with natural daylight is effective and less painful than conventional PDT when treating actinic keratosis (AK), however its weather dependency is restrictive. This prospective open-label observational single-arm study examined efficacy and safety of simulated daylight (SDL)-PDT using the IndoorLux® system in combination with 5-aminolevulinic acid gel (BF-200 ALA). Methods12 patients with mild/moderate AK on the face or scalp received two SDL-PDTs. BF-200 ALA was applied prior to a 2 h illumination with the IndoorLux® System. Patients evaluated pain during and after SDL-PDT on visual analogue scales (VAS). Primary endpoint was lesion count reduction three months after the second SDL-PDT. Secondary endpoint was pain during and after illumination. ResultsMedian individual clearance rate was 83.75% (66.7–100.0%); 33.3% of the patients and 84.9% of the lesions were completely cleared. Median size of the remaining partially cleared lesions decreased by 42.9%. The first SDL-PDT was pain-free for 7 patients (58.3%, VAS=0). Median VAS during and after the first treatment was 0 (0.0–0.3). For the second SDL-PDT, median VAS was 0.1 (0.0–5.5, during) and 0 (0.0–4.5, after). Both SDL-PDTs were pain-free for 6 patients. ConclusionSDL-PDT was effective and nearly pain-free, emphasizing its advantages and potential for common practice.

СПЕЦИФИКА МОЛЕКУЛЫ МОРОКТОКОГА АЛЬФА: РЕЗУЛЬТАТЫ ПРОСПЕКТИВНОГО МНОГОЦЕНТРОВОГО НАБЛЮДАТЕЛЬНОГО ИССЛЕДОВАНИЯ ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ У ПОДРОСТКОВ С ГЕМОФИЛИЕЙ A

The main method of treatment for hemophilia A is replacement therapy with drugs of blood coagulation factors VIII (FVIII). The active use of biotechnological methods in the production of recombinant drugs contributes to the development and registration of new FVIII drugs. The results of clinical trials of drugs in children usually include a limited number of patients for a specific period of time. Post-marketing observational studies provide additional information on the results of using a new drug in patients in clinical practice. The objectives of the study were to collect and analyze data on the efficacy and safety of domestic recombinant FVIII with a deleted B-domain, moroctocog alfa (Octofactor, GENERIUM JSC) in the treatment of adolescents aged 12–18 years with hemophilia A in routine clinical practice. Materials and methods of research: a prospective multicenter open-label observational study of the results of using the Octofactor in adolescents with hemophilia A (№ OCF-HPA-N01) included 24 male patients with severe hemophilia A aged 12 to 18 years (mean age 14,8±1,7 years), who received moroctocog alfa in routine clinical practice. Enrollment in the study was carried out after the signing of the informed consent form by the parent of the minor patient and the minor patient aged 14 to 18 years, taking into account the results of the screening examination. The follow-up period was 52±4 weeks, which, presumably, was sufficient to achieve at least 100 days of moroctocog alfa administration. To assess the effectiveness, we analyzed the incidence of spontaneous bleeding that occurred within 48–72 h after drug administration; the severity of spontaneous bleeding against the background of prophylactic treatment with moroctocog alfa, the number of injections and the dose of the study drug for prophylactic treatment, as well as for treatment at the request of one episode of bleeding, taking into account its severity; the researcher's determination of the response to treatment of acute hemarthrosis according to the scale of the World Federation of Hemophilia (2020). To assess safety, the frequency and characteristics of adverse events (AEs) associated with drug administration were analyzed, including the frequency of formation of an inhibitor to FVIII. Results: during the study, 59 bleedings were recorded, of which 21 (36%) were spontaneous and 38 (64%) were post-traumatic. Among spontaneous bleeding episodes, 5 (24%) episodes occurred within 48–72 hours after administration of the study drug. Spontaneous bleeding within 48–72 hours after administration of Octofactor was absent against the background of prophylactic treatment in most patients (81%) and was observed rarely during the observation period (1–3 times) in the remaining 19% of patients. The median number of bleeding within 48–72 h after study drug administration was 1 episode over the follow-up period. The proportion of mild to moderate bleeding was 97 [88; 100]% among all types of bleeding and 100 [84; 100]% among spontaneous bleeding within 48–72 hours after administration of the Octofactor drug. The median of a single dose of Octofactor for preventive treatment was 2000 [1500; 2000] IU or 31,7 [25,6; 38,5] IU/kg, and with treatment on demand ‒ 2000 [2000; 3000] IU or 34,1 [28,8; 38,5] IU/kg per single injection. To stop the resulting bleeding required 1 [1; 2] introduction in a single dose of 3000 [2000; 4000] IU; the average dose was 4490 ÷ 4993 IU. When doctors subjectively assess the response to treatment of acute hemarthrosis on the scale of the World Federation of Hemophilia, an excellent response was noted in 9 (27%) episodes, good and moderate ‒ in 2 (6%) and 22 (67%) episodes, respectively. Lack of response to treatment of acute hemarthrosis with moroctocog alfa was not revealed in the study. During the study, 23 AEs were recorded in 13 (54%) patients not related to the study drug. Conclusion: thus, the obtained results of the study indicates the efficacy and safety of the Octofactor both the prophylactic treatment and treatment of on-demand bleedings in 12 to 18 year old patients with severe hemophilia A.

Evaluation of Serum Ferritin Levels in Children of South Punjab (Pakistan) having Beta-Thalassemia Major with Iron-Overload Treated with Deferasirox

Objective: To evaluated serum ferritin levels in children having beta-thalassemia major with iron-overload treated with deferasirox. Study Design: A prospective open-label observational study. Place and Duration of the Study: The Outpatient Department of Hematological Disorder, Thalassemia and Bone Marrow Transplantation Centre, and Department of Biochemistry, “Bahawal Victoria Hospital, Quaid e Azam Medical College”, Bahawalpur, Pakistan from February 2020 to January 2021. Material and Methods: Children aged 2 to 17 years with diagnosis of β-thalassemia major having chronic iron overload (serum ferritin &gt; 1000 ng/ml) and 2 or more blood transfusions per month were included. Demographic information like gender, age, and residential status, contact number along with assessment of hepatitis serology, HIV status, electrocardiogram and ophthalmic findings were noted on a pre-designed proforma specially designed for this study. Deferasirox was initiated in a dose of 20 mg/kg/day and was adjusted at 3-months interval. Serum ferritin levels were measured at baseline, 3-months, 6-months, 9-months and 12-months. Results: In a total of 40 children, there were 23 (57.5%) male. Overall, mean age was calculated to be 9.1+4.2 years. Residential status of 28 (70.0%) children was rural. Mothers of 27 (67.5%) children were illiterate. At baseline, mean serum ferritin level was noted to be 4137+2319 ng/ml. Significant reduction in mean serum ferritin levels during the course of this study was found with the use of deferasirox as mean serum ferritin levels reduced significantly from baseline to 3-months, 6-months, 9-months and at 12-months as 3637+2119 ng/ml, 4081+2050 ng/ml, 4346+2349 ng/ml, 3252+2464 ng/ml and 2188+1195 ng/ml respectively (p&lt;0.001). Conclusion: Deferasirox was found to be an effective iron chelation therapy among transfusion dependent thalassemia children with iron-overload. Keywords: serum ferritin, Thalassemia, iron-overload, deferasirox.

The structure of cervical diseases in women suffering from pelvic floor dysfunction

Background. The prevalence of pelvic floor dysfunction (PFD) is soaring steadily. The protrusion of the cervix beyond vaginal opening when exposed to environmental factors can lead to the development of dystrophic, sclerotic and neoplastic processes of the cervix, which are mediated by changes in the pH, biocenosis of the vagina and environmental factors.&#x0D; Aim. To study the pathogenesis of cervical diseases in patients with PFD.&#x0D; Materials and methods. The study design is an open-label prospective observational study. The study included 40 patients of reproductive age: 26 patients with cervical disease with PFD (PFD group), 14 patients without cervical disease and PFD made up the second group.&#x0D; Results. The patients included in the study were comparable in terms of age and body mass index. Pap smear analysis revealed that the average number of leukocytes is significantly higher in patients with PFD compared to patients in the group without PFD 5.5 (1.520.0) and 1.5 (1.56.5) respectively (p=0.040). In PFD group, a high prevalence of the following conditions was observed: cervical leukoplakia (15%), CIN1 (38.5%), CIN2 (8%), chronic cervicitis (38.5%). Onco-cytological test results reviewed where the high prevalence of parakeratosis and hyperkeratosis (15%), ASCUS (15%), LSIL (23%) and HSIL (8%) were also noteworthy. It was observed that human papillomavirus type 16 was predominant in PFD patient group.&#x0D; Conclusion. The data obtained indicates an increased risk of developing cervical diseases in patients with PFD.

ОСОБЕННОСТИ КОМПОЗИЦИОННОГО СОСТАВА ТЕЛА И ОСНОВНОГО ОБМЕНА У ПОДРОСТКОВ С МОРБИДНЫМ ОЖИРЕНИЕМ

Objective of the study: to compare the values of basal metabolic rate and body composition in children with morbid and non-morbid obesity. Materials and methods of research: 87 adolescents with constitutionally exogenous obesity (CEO) were included in a prospective open-label observational single-center selective non-randomized uncontrolled study. The participants were divided into 2 groups: 43 with morbid obesity – mean age 15,7 years [14,9; 16,9], 20 boys (46%) and 23 girls (54%) and 44 with non-morbid obesity – the control group, mean age 15,3 years [10,1; 15,6], 19 boys (43%) and 25 girls (57%). All children underwent an assessment of body composition and basal metabolic rate. Results: adolescents with morbid obesity showed a statistically significantly greater amount of adipose tissue (51,5% [48,3; 56,2] vs 39,5% [35,4; 42,8], p&lt;0,0001) and lean mass (65,8% [56,3; 72,3] vs 51,0% [45,2; 59,8], p&lt;0,0001) compared with the group of non-morbid obesity. When assessing the amount of skeletal muscles, an increase in its absolute values was demonstrated in adolescents with severe obesity compared to the control group. The percentage of skeletal muscle mass in lean mass with severe obesity was statistically significantly higher compared to the group of non-morbid obesity (50,4% [45,1; 53,6] vs 41,8% [40,8; 43,3], p&lt;0,0001). There was a statistically significant increase in basal metabolic rate in the group of morbid obesity compared with the group of non-morbid obesity (2489 [2313; 2802] and 1829 [1525; 2117] kcal/day, respectively, p&lt;0,0001). These differences between the study groups persisted after the introduction of lean mass correction. Conclusion: the development of morbid obesity in adolescents is accompanied by an increase in basal metabolism, an increase in the amount of fat and lean mass. The increase in lean mass occurs mainly due to an increase in skeletal muscle.

Newly approved IV acetaminophen in Canada: Switching from oral to IV acetaminophen. Is IV worth the price difference? A systematic review.

The use of intravenous acetaminophen leads to meaningful health cost increases for paediatric institutions. Therefore, strict criteria for intravenous acetaminophen administration are needed. To undertake a systematic review of available evidence comparing oral versus intravenous acetaminophen use in children. A systematic literature search was conducted on five databases. All prospective interventional studies comparing intravenous to oral acetaminophen in patients <18 years old were included. Data collection and analysis were done according to PRISMA guidelines. Among 6,417 retrieved abstracts, 29 full-text articles were assessed of which 3 were retained. (1) Pharmacokinetic: Oral bioavailability (72% with a high inter-individual variability) was reported in 47 stable patients in a paediatric intensive care unit. (2) Analgesia: In a double-blind randomized controlled trial of 45 children, no difference in analgesia was found between oral and intravenous administration after cleft palate repair. (3) Fever: In an open-label prospective observational study of 200 children, temperature decreased faster after intravenous than oral administration but was similar 4 hours later. Available data are insufficient to guide clinicians with a rational choice of route of administration. Oral bioavailability should be studied in paediatric populations outside the intensive care unit. Despite the widespread use of intravenous acetaminophen, there is little evidence to suggest that it improves analgesia compared to the oral formulation. Similarly, fever weans faster but whether this translates into any meaningful clinical outcome is unknown. The lack of data plus the significantly higher costs of intravenous acetaminophen should motivate further research.