Open Prospective Clinical Trial Research Articles

Features of the quality of life of first graders taking into account gender differences and cognitive abilities

The purpose of the study: To study the features of the quality of life of first-graders, taking into account gender differences and cognitive abilities. Design: An open prospective non-randomized comparative clinical trial. Materials and methods: 631 children were examined, students of the first grades of secondary schools without a specialized bias № 110, 83, 75, 67, 9 Rostov-on-Don using the international questionnaire PedsQL 4.0 – Pediatric Quality of Life Inventory. To assess the cognitive development of children, the D. Wexler scale was used with the determination of the intellectual coefficient. Results: First-graders with a high level of cognitive development have reduced indicators of physical and emotional functioning, as well as the overall quality of life score. Girls with a high intellectual coefficient, in comparison with boys, have lower physical, emotional, school functioning and higher indicators of social functioning. The indicators of quality of life in children with a high level of cognitive development do not reflect the same in children who do "excellent". Conclusion: The revealed features of the quality of life of first-graders with different levels of cognitive development require differentiated medical, psychological and pedagogical support of children in this age period and further study of their health.

Efficacy of intra lesional injection of 5-flourouracil on keloid scar: A prospective open clinical trial

Background and objectives: The management of keloids stayed unsatisfactory. Intralesional 5-fluorouracil has not been broadly and intensively studied as a monotherapy in the treatment of keloids worldwide. So, the aim of this study was to evaluate the efficacy and safety of intralesional injection of 5-flourouracil in patients with keloids. Methods: In this prospective clinical trial study, a total of 20 patients aged >18 years at Shahid Jabar Dermatological Teaching Center, Sulaimaniyah, Iraq, from January 2022 to August 2022 were enrolled. Patients were treated at 1-week interval with intralesional injection of 5-flurouracil (50 mg/mL) at maximum of 6 sessions. Average injection volume was 0.2 mL/cm2. All patients were followed up for 6 months. Results: Most of the patients were aged <50 years (90%) with no family history of keloid (75%). Additionally, 45% of patients had keloid in the trunk region with a size of ?10 cm2 (65%). Most patients (80%) had the disease for ?5 years that caused by inflammation (55%), especially skin type IV (65%). After 6 sessions of treatment, 70% of patients showed moderate improvement, while 30% of patients showed minimum improvement. The main adverse effects after 6 sessions of treatment were hyperpigmentation in 3 patients, bullae in 2 patients, and tissue sloughing only in 1 patient. A significant correlation was found between the patient’s response and age/keloid location. Moreover, mean Redness, Elevation, Hardness, Itching, and Tenderness score after treatment was significantly lower than before treatment (p<0.001). Conclusions: Our results concluded that 5-flurouracil is a safe and effective therapy for the treatment of keloids.

Evaluation of the effect of low-intensity rhythmic transcranial magnetic stimulation on motor and non-motor manifestations of Parkinson's disease

BACKGROUND: The use of repetitive transcranial magnetic stimulation as a method of non-drug therapy of Parkinson's disease has been actively studied over the past decades. The prevailing number of repetitive transcranial magnetic stimulation protocols in Parkinson's disease use a high intensity of stimulation (80120% of the value of the threshold of the evoked motor threshold from the muscles of the hand), while the choice of the stimulation intensity parameter was carried out empirically.
 AIM: to study the effectiveness of low-intensity unilateral repetitive transcranial magnetic stimulation on motor and non-motor symptoms of Parkinson's disease.
 MATERIAL AND METHODS:An open prospective non-randomized clinical trial included 37 patients with stage IIII Parkinson's disease according to HoehnYahr (1967), akinetic-rigid and mixed (akinetic-rigid-tremor) forms. All patients underwent repetitive transcranial magnetic stimulation according to the protocol: M1 stimulation zone, frequency 5 Hz, intensity 40% of the cortical motor threshold, on 6s, off 8s, total number of pulses per session 3000. The course of treatment is 10 procedures with 2 days (weekend) off.
 RESULTS: All patients completed the study in accordance with the protocol. When analyzing the results of the UPDRS scale (Unified Parkinson's disease rating scale), positive dynamics was noted in all parts of the questionnaire: part I ― from 2 (0; 3) to 0 (0; 1) points, p 0.05; part II ― from 9 (5.5; 12.5) to 4 (2; 6.5) points, p 0.05; part III ― with 11 (7; 14.5) to 6 (2; 7.5) points, p 0.05; part IV (Schwab and England scale) ― from 80% (70; 95) to 90% (85; 100), p 0.05. There was also a selective effect on non-motor symptoms.
 CONCLUSION: Low-intensity exposure (40% of the motor threshold) has a significant clinical effect on motor and non-motor symptoms of Parkinson's disease; stimulation of the primary motor cortex can have an antidepressant effect; repetitive transcranial magnetic stimulation has a selective effect on non-motor symptoms of Parkinson's disease: a predominant effect has been demonstrated with respect to olfactory, emotional, cognitive disorders, sleep disorders and hypersalivation; when assessing the dynamics of motor disorders, a more pronounced effect was noted with respect to rigidity, postural disorders, walking speed, and to a lesser extent, the effect on tremor was noted.

Percutaneous bone adhesive application for Jones fracture “at-risk” of nonunion or delayed union: a hypothesis

BackgroundBone adhesives have been on the forefront of orthopedic surgery research for decades due to the potential benefit they may have in fracture management. Current publications and research being conducted on bone adhesive could be applied to our current hypothesis for the benefit of a novel minimally invasive treatment option for a select cohort of fractures, Jones fractures. The select fracture’s gold standard of treatment would be nonoperative, but with risk of complications including nonunion and delayed union.Presentation of hypothesisWe hypothesize that percutaneous application of bone adhesive will provide an additional treatment option for fracture patterns that do not require operative fixation, but would benefit from additional stability. The primary outcome measures would be (1) duration of time required for bony consolidation (defined as 3 of 4 bridging cortices) and (2) duration of absenteeism (inability to work), and pain levels within the first week after the procedure. Secondary outcome measures would be the incidence of nonunion or delayed union. We hypothesize that the select bone adhesive would accelerate bony consolidation, decrease absenteeism, decrease pain levels within the first week after procedure, and decrease the incidence of delayed union and/or nonunion.Testing of hypothesisWe propose a prospective multicenter, randomized, and open label trial clinical trial to test the bone adhesive via percutaneous injection into acute non-displaced or minimally displaced Jones fractures.Implications of hypothesisBone adhesives are a new frontier in treatment of fractures, currently in laboratory and animal testing phases. The appropriate bone adhesive formula has not been approved for clinical trial use, but the implications of the bone adhesive may go beyond decreased complications and ease of stabilizing a select cohort of closed fractures. With the injectable compound illustrated (Fig. 1), the adhesive could be applied percutaneously in hopes of achieving improved outcomes compared to non-operative treatment. The overall goal of the clinical trial is to provide patients a safe treatment option for improved bone union rates of nonoperative fractures compared to the current gold standard management of the same fracture with earlier pain control, early bony consolidation and lower risk of delayed union/nonunion. The ideal patient population for use of a percutaneous bone adhesive in future studies would be for those with multiple medical comorbidities for whom surgical risks outweigh the benefits, in addition to patients at high risk for nonunion based on fracture pattern or systemic biology.

Appetite-inducing effect and safety evaluation of Habb-e-Hilteet in patients with Ḍu‘f al-Ishtihā (anorexia): An open prospective clinical trial

Objectives: Anorexia is one among the most prevalent conditions triggering malnutrition, drastic weight loss and serious health issues in people especially older adults. Habb-e-Hilteet is commonly prescribed Unani pharmacopoeial formulation for anorexia. However, no scientific data is available as to its safety and efficacy. The current study assessed the appetite-inducing effect and safety of Habb-e-Hilteet in Ḍu‘f al-Ishtihā (anorexia) patients.
 Methods: An open prospective clinical trial was carried out in 95 clinically diagnosed anorexia patients of either gender (19-65 yrs old). The study was approved by Institutional ethic committee and conducted in accordance with the GCP guidelines. Habb-e-Hilteet, 1 pill (500mg) was administered orally in patients twice daily for 14 days. The safety of the formulation was assessed by important pathological and biochemical indices and monitoring adverse events. The efficacy was assessed on the basis of improvement in the Simplified Nutritional Appetite Questionnaire (SNAQ) score.
 Results: Out of 95 patients recruited, 78 completed the trial and 17 patients lost to follow-up. The mean age of patients was 29.8 yrs, with the majority (59.0%) being female. Overall therapeutic response was found to be 96%. A significant (P<0.05) increase in the mean SNAQ score was observed after 7 and 14 days of treatment when compared to baseline. No significant difference before and after treatment was observed in pathological and biochemical indices. No adverse events were reported during the entire study period.
 Conclusion: The study results indicate that Habb-e-Hilteet could be a viable treatment option for anorexia with no safety concerns.
 Keywords: Ḍu‘f al-Ishtihā; Buṭlān al-Shahwa; Anorexia; Habb-e-Hilteet; Unani pharmacopoeal formulation.

Personalized targeted therapy of moderate and severe atopic asthma in Russia

Introduction. Taking into account the prevalence of asthma and especially severe atopic asthma which requires carefully selected and expensive therapy, the appearance of the domestic biosimilar omalizumab among biological therapy drugs makes the choice of treatment for this category more affordable. The article presents the results of an observational open prospective clinical trial of the omalizumab biosimilar in severe athopic asthma patients.The purposeof this study was to evaluate the efficacy and safety of the domestic production biosimilar in the real clinical practice.Materials and methods. The study involved 10 adult patients aged 19 to 55 years with a diagnosis of moderate to severe uncontrolled persistent asthma treated with mediun to high dose ICS and second&more controller (ACQ-5 ≥ 1,5, FEV1 < 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources. Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of breath and SABA using. An asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p >< 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment. Conclusions. Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety>< 80% of the predicted normal value). For 26 weeks all patients received the omalizumab. The evaluation of the efficacy was provided taking into account asthma symptoms improvement the results of ACQ-5, FEV1, PEF, asthma exacerbations and the use of health resources.Results. According to the results of data analysis due to omalizumab all patients demonstrated reducing daily asthma symptoms, nocturnal awakening and night time symptom, shortness of breath and SABA using. An asthma control improvement was observed after 1 month treatment (Δ ACQ-5 1.6 [1.2; 2.4], p = 0.0002 compared to the baseline data) with a continued tendency to further increase during 6 months of the study. A statistically significant increase in FEV1 was noted (initially, FEV1 56.7% [51.25; 61.8] of the predicted; after 1 month, FEV1 67.5% [63.45; 70.6] of the predicted, p = 0.00003; after 6 months, FEV1 80.6% [80.55; 84.05] of the predicted, p < 0.001). Omalizumab biosimilar used allowed to reduce the background asthma therapy. No asthma exacerbation was registered due to 26 weeks omalizumab treatment.Conclusions.Based on the results of the study, it was shown that the administration of the omalizumab biosimilar to patients with severe atopic asthma improves control over the symptoms, lung function and reduces the amount of asthma exacerbations, and has a good safety.

The effect of sulphate-sulphide mineral baths on blood glucose level in patients with knee osteoarthritis

Background/Aim: Type 2 diabetes is a common comorbidity in patients with knee osteoarthritis. Bearing in mind that obesity and insulin resistance are risk factors for the development of knee osteoarthritis, physical therapy and balneotherapy containing hydrogen sulphide (H2S) has a positive effect on the functional and metabolic status of these patients. This work was aimed to investigate the effect of sulphate-sulphide-rich mineral baths containing H2S on the level of serum glucose in patients with knee osteoarthritis. Methods: An open prospective randomised clinical trial included patients suffering from stage I and II of the knee osteoarthritis. Patients were divided into two groups of 40 subjects each: control group and experimental group. All subjects underwent inpatient physical treatment consisting of kinesitherapy and transcutaneous electrical nerve stimulation (TENS) 6 days a week. Patients from experimental group, in addition to all the mentioned treatments, also took sulphate-sulphide mineral water baths once a day for 30 minutes for 7 days, unlike the patients from control group who took tap water baths, according to the same schedule. The level of serum glucose was monitored in all patients on admission, after discharge and 6 months after the treatment. The Student t-test was used for statistical data processing and p < 0.05 was considered as statistically significant. Results: Study included 80 patients of both sexes, with an average age of 67.00 ± 5.75 years. All patients had elevated serum glucose values on admission. The initial levels of glycaemia in the control and experimental groups were not significantly different (6.99 ± 1.95 and 7.88 ± 1.90 mmol/L, respectively). At discharge, patients who performed balneotherapy had a statistically significant decrease in serum glucose values compared to patients from the control group (by 1.84 vs 0.26 mmol/L, p < 0.001). This effect did not persist six months after the end of the treatment (p > 0.05). Conclusion: The application of balneotherapy with sulphate-sulphide mineral baths containing H2S as a potent gas transmitter significantly reduces serum glucose levels in patients with knee osteoarthritis.

ЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ МОРОКТОКОГА АЛЬФА В ОТКРЫТОМ МНОГОЦЕНТРОВОМ ПРОСПЕКТИВНОМ КЛИНИЧЕСКОМ ИССЛЕДОВАНИИ У ДЕТЕЙ ОТ 2 ДО 6 ЛЕТ С ТЯЖЕЛОЙ ФОРМОЙ ГЕМОФИЛИИ A

The purpose of the study was to assess the efficacy, safety and pharmacokinetics of the moroctocog alfa (Octofactor) in children aged 2-6 with haemophilia A. Materials and methods of research : six patients between 2 and 6 years of age (average age 4.3±0.8 years) were included in the open multicenter prospective clinical trial. The efficacy of the drug was assessed against the background of the introduction of 30±10 IU/kg every 2–3 days, the safety was assessed by the frequency and causality of adverse reactions. Results: 7 post-traumatic bleeding was registered. The average prophylactic dose of the drug is 37.84±7.13 IU/kg. The dose of the drug for stopping bleeding was 1000 IU. 2 adverse events have been reported that are not related to moroсtocog alfa. Conclusion: the obtained data indicate the efficacy and safety of moroсtocog alfa in the study group of patients.

An Open Prospective Study on Whether Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) Offers a Better Outcome Than Conventional Intracytoplasmic Sperm Injection (ICSI).

ObjectiveTo differentiate the in vitro fertilization (IVF) outcomes between the two procedures, intracytoplasmic morphologically selected sperm injection (IMSI) and intracytoplasmic sperm injection (ICSI) in terms of relation to chemical pregnancy percentage, clinical pregnancy, live birth, miscarriage, and fertilization rates, respectively.Patients and methodsThis Open Prospective clinical trial was conducted during the period between Jan 2016 and Dec 2017 at one IVF unit. A total of 446 ICSI cycles and 79 IMSI cycles were conducted. Females were divided into four subgroups according to age.ResultsThe study involved 525 couples (446 first trial ICSI cycles) and (79 first trial IMSI cycles). ICSI was statistically better than the IMSI in relation to the chemical pregnancy, clinical pregnancy (CPR), live birth (LBR), and fertilization rates, respectively (p < 0.05). However, there were no statistically significant differences between the ICSI and IMSI in relation to the miscarriage rate. There were statistically significant differences favoring ICSI in all subgroups except 35-37, in relation to chemical pregnancy; and in the 38-40 and >40 subgroups in relation to CPR. There were no statistically significant differences in these subgroups regarding the live birth, miscarriage, or fertilization rates.ConclusionsThis study showed that IMSI is not superior to conventional ICSI at the first attempt. Based on the findings in this study, we would not advise couples to choose IMSI at their first treatment attempt.

Effect of Ḥijāma (wet cupping), Dalk (massage) and Bukhūr (medicated steam) in amelioration of Waja al-Zahr (non-specific low back pain)- an open prospective clinical trial.

Low back pain is the most widespread musculoskeletal ailment and a common cause of disability worldwide. Conventional medicine typically treats low back pain with a combination of physical therapy; activity modification and rest; pain-relieving and anti-inflammatory medications which are associated with huge socioeconomic implications and adverse drug reactions. In contrast Ḥijāma, Dalk and Bukhūr are ancient medical techniques recommended in the management of musculoskeletal disorders with little or no adverse effects. To evaluate the safety and effectiveness of Ḥijāma bi'l Shart (wet cupping), followed by Dalk (Massage) with Roghan Dafli and Bukhūr (medicated steam) with Tukhm Soya (Anethum graveolens Linn) in patients of Waja al-Zahr (Non-specific Low back pain). Patients of either gender in the age group of 18-50 years with low back pain persisting for four weeks or more as chief complaint were recruited in the trial. The study was GCP compliant. The duration of the protocol therapy carried out was 14days. Ninty two patients of NSLBP were screened, of which 34 who fulfilled the inclusion criteria and were willing to participate in the study were recruited. Three participants were lost to follow-ups due to personal reasons and 31 patients completed the trial during the study period. Overall therapeutic response observed in this study was 97% while 3% of the patients did not respond to intervention. The study findings imply that there is a credible evidence to ensure that the regimens intervened are safe and effective in ameliorating the symptoms of Waja al-Zahr.

Non-Adherence to Antihypertensive Guidelines in Patients with Asymptomatic Carotid Stenosis

ImportanceHypertension and carotid stenosis are both risk factors for stroke, but the presence of carotid stenosis might dampen enthusiasm for tight control of hypertension because of concerns for hypoperfusion. ObjectiveTo determine the extent to which there are opportunities to potentially improve pharmacotherapy for hypertension in patients known to have asymptomatic high-grade carotid stenosis. DesignWe examined anti-hypertensive medication prescription and adherence to evidence-based hypertension treatment guidelines in a cross-sectional analysis of baseline data of patients enrolled in a clinical trial. SettingThe Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) is a multicenter prospective randomized open blinded end-point clinical trial of intensive medical management with or without revascularization by endarterectomy or stenting for asymptomatic high-grade carotid stenosis. Participants1479 participants (38.6% female; mean age 69.8 years) from 132 clinical centers enrolled in the CREST-2 trial as of April 6, 2020 who were taking ≥1 antihypertensive drug at baseline. ExposuresPharmacotherapy for hypertension. Main outcomeAdherence to evidence-based guidelines for treating hypertension. ResultsOf 1458 participants with complete data, 26% were on one, 31% on 2, and 43% on ≥3 antihypertensive medications at trial entry. Thirty-two percent of participants were prescribed thiazide; 74%, angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB); 38%, calcium channel blocker (CCB); 56%, a beta blocker; 11%, loop diuretic; and 27%, other. Of those prescribed a single antihypertensive medication, the proportion prescribed thiazide was 5%; ACEI or ARB, 55%, and CCB, 11%. The prevalence of guideline-adherent regimens was 34% (95% CI, 31-36%). Conclusions and relevanceIn a diverse cohort with severe carotid disease and hypertension, non-adherence to hypertension guidelines was common. All preferred classes of antihypertensive drug were under-prescribed. Using staged iterative guideline-based care for hypertension, CREST-2 will characterize drug tolerance and stroke rates under these conditions. Trial registrationClinicalTrials.gov Number NCT02089217.

Mucoperiodontal lesions: improvement of prosthodontic treatment considering initial indicators of patients' oral health

To assess the need for prosthodontic treatment and to substantiate the features and perspectives for optimizing prosthodontic treatment in patients with mucoperiodontal manifestations of lichen planus (LP). For assessment of the need and identification of problematic aspects of prosthetic treatment 74 patients (48.3% of the primary sample of all patients with oral LP) with oral LP-associated mucoperiodontal lesions (MPL) participated in a multicenter open cohort prospective controlled clinical trial with elements of retrospective analysis. The prospective part of the study summarizes the results of prosthodontic treatment of 41 patients (8 men and 33 women aged 45-70 years) carried out using improved therapeutic and diagnostic algorithms applied to the specifics of the MPL forms and stages. The use of standard protocols of prosthodontic treatment without taking into account the status of oral mucosa in patients with oral LP was associated with the development of nonspecific (prosthetic stomatitis - 25.8%; contact-allergic stomatitis - 22.6%; focal hyperplasia - 16.1%; decubital ulcers - 12.9%, etc.) and oral LP-associated specific reactions (Kebner's symptom - 35.5%; transformation of the typical form into complicated ones - 22.6%; desquamative gingivitis and gingival lichenization - 19.4% each; gum recession - 16.5%) with the involvement of skin and mucous membranes of other localizations (6.5%) and the appearance of symptoms of carcinophobia/dentophobia (25.8%). Prosthetic treatment according to improved protocols for the management of patients with oral LP indicated a decrease in the frequency of nonspecific oral mucosal reactions (by 70.7%, p<0.001), single (4.8%) specific reactions, improvement of masticatory efficiency by 32.8-55.3% (p<0.01), harmonization of speech function, maintenance of a high level of hygiene of prostheses, a significant reduction in the time of adaptation to removable dentures and increased satisfaction with the results of treatment on the GRS scale (1.06±0.3 points after treatment; 3.8±0.5 points before treatment; p<0.001). The best dynamics of clinical and sociological indicators was noted in persons with prosthetic replacement structures based on implants.

2013-P: Lifestyle Intervention, Metformin, and Acarbose Treatments Differentially Impact Liver Fat Content, Serum Lipids, and Hormone Profiles in Obese Polycystic Ovary Syndrome Patients with Impaired Glucose Tolerance

Introduction: Polycystic ovary syndrome (PCOS) is often associated with obesity, insulin resistance, abnormal glucose tolerance, lipid metabolic disorders, and fatty liver. It remains unknown how current therapies impact these different components of PCOS. Objective: We aim to evaluate the effects of lifestyle intervention (low calorie diet, LCD), metformin and acarbose treatment on fat mass, insulin sensitivity, hormone profiles, liver fat content and lipids profile in obese PCOS patients with impaired glucose tolerance (IGT). Methods: In a 12-week, randomized, open tag prospective clinical trial, we recruited thirty obese PCOS patients, and randomly divided them into three groups: LCD, metformin, and acarbose group. Body weight, adipose tissue distribution, and serum sex hormone levels were measured before and after treatment. MRI was used to measure the liver fat content (LFC) and abdominal fat mass (AFM); Insulin sensitivity and beta-cell function were evaluated by OGTT and two-step hyperglycemic clamp; Serum free fatty acids (FFAs) were measured by GC-MS. Results: In all three groups, AFM and insulin secretion were significantly decreased as measured by MRI, OGTT and glucose clamp, respectively. LCD significantly improved the insulin sensitivity as determined by HOMA-IR, disposition index, and matsuda index. Metformin significantly improved hyperandrogenism. Interestingly, we found only acarbose significantly decreased triglyceride, FFAs, and LFC. Conclusion: All treatment modalities were effective in the treatment of PCOS women with obesity and IGT, only acarbose significantly decreased the triglyceride and FFAs, and ameliorated the LFC, suggesting that acarbose is an effective agent that could be used in PCOS patients with IGT and fatty liver. Disclosure S. Li: None. Y. Wang: None. J. Cai: None. W. Liu: None. H. Yin: None. T. Tao: None.

Lithotriptic effect of Safūf Hajar-al Yahūd in patients of Hasat-ul Kilya (Nephrolithiasis) – an open prospective clinical validation trial

Hasat-ul Kilya (Nephrolithiasis) is one of the most common chronic conditions and has been known to the mankind since antiquity. The incidence is increasing globally with geographic, racial and gender variation in its occurrence. Medical management of Nephrolithiasis still poses a considerable challenge for modern medical practice. Unani drugs possessing lithotriptic activity are not only cost effective but also have least side effects. Safūf Hajar-al Yahūd has been used since long for the treatment of Hasat-ul Kilya (Nephrolithiasis) but no documentary evidence based on scientific parameters as to its safety and efficacy are available. To validate the safety and efficacy of Safūf Hajar-al Yahūd in the treatment of Hasat-ul Kilya. An open prospective clinical trial was carried out on 107 subjects of renal calculi of 3-7mm diameter diagnosed by Ultrasonogram-KUB (USG-KUB). Subjects were evaluated by clinical history & examination, laboratory investigations followed by USG-KUB for confirmation. The safety was assessed by reporting of adverse events and by pathological and biochemical investigations. Assessment of efficacy was based on improvement observed in VAS score and expulsion/reduction of stone size as detected by USG-KUB. Substantial reduction (53%) in the size of calculi confirmed by USG-KUB and considerable lowering of VAS score (75%) were observed with the active intervention in majority of the cases. The trial has revealed that the Unani pharmacopoeal formulation Safūf Hajar-al Yahūd was well tolerated and has the therapeutic potential in the reduction and expulsion of renal calculi.

NEOADJUVANT AND ADJUVANT CHEMOHORMONAL THERAPY IN PATIENTS WITH HIGH-RISK AND VERY HIGH-RISK PROSTATE CANCER: OUR EXPERIENCE

Background. The approach to the management of prostate cancer with lymph node metastases has recently moved towards aggressive multimodal treatment with the use of the most rational combinations that are currently available.Objective: to assess the efficacy and tolerability of chemohormonal therapy (CHT) in patients with high-risk and very high-risk prostate cancer.Materials and methods. An open prospective clinical trial evaluating the efficacy and tolerability of neoadjuvant and adjuvant CHT in patients with high-risk and very high-risk prostate cancer was initiated in 2016 at the P.A. Herzen Moscow Oncology Research Institute. Patient recruitment is still ongoing.A total of 64 patients with high-risk and very high-risk prostate cancer (сT3N0–T3N+М0, prostate specific antigen (PSA) ≥20 ng/mL, and Gleason score of 8–10) were recruited since July 2016. All patients were examined prior to treatment initiation and after 3 and 6 courses of therapy. The examination included pelvic magnetic resonance imaging, ultrasound imaging of the abdominal cavity and retroperitoneal space, transrectal ultrasound imaging, and chest radiography or computed tomography. Serum PSA level was evaluated before each course of therapy. Bone scintigraphy was performed before treatment and after its completion. Study participants were divided into two groups. Group A included patients that initially underwent surgical treatment and then 6 courses of CHT no later than 6 weeks after surgery: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. Patients also received hormonal therapy with luteinizing hormone-releasing hormone analogue (aLHRH) given in depot injections every 28 days.Group B included patients that initially received 6 courses of CHT: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. After that, patients underwent radical prostatectomy with pelvic lymphadenectomy no later than 4 weeks after the completion of chemotherapy. Patients also received hormonal therapy with aLHRH given in depot injections every 28 days. The total treatment duration was 6 months.Results. The group of adjuvant CHT included 24 patients with high-risk prostate cancer (T3b–4N+М0 with at least 5 regional lymph node metastases detected by morphological examination of surgical specimens). All patients had Gleason score 8–10 tumors. Mean age of patients was 63.0 ± 7.7 years (range: 46–72 years). In total, all patients received 142 courses of CHT. By the time of publishing this article, 23 (96 %) of patients completed their treatment.The group of neoadjuvant CHT included 40 patients with very high-risk prostate cancer (T3b–4N+М0 with metastases to pelvic and retroperitoneal lymph nodes detected by instrumental examination). All patients had Gleason score 8–10 tumors. Mean age of patients was 61.0± 6.4 years (range: 43–69 years). In total, all patients received 236 courses of CHT. By the time of publishing this article, 36 (90 %) of patients completed their treatment. Thirty-five patients (87 %) underwent radical prostatectomy with extensive pelvic and paraaortic lymphadenectomy. Routine pathological examination demonstrated that all patients had signs of tumor destruction. Thirty-three participants (94 %) had grade II therapeutic pathomorphosis, whereas 2 patients (6 %) had grade III therapeutic pathomorphosis.Median PSA relapse-free survival (PSA-RFS) rate in the neoadjuvant CHT group was 10 months. Serum PSA of 0.1 ng/mL 1 month postoperatively correlated with longer RFS (р = 0.04). Biochemical relapse (PSA level &gt;0.2 ng/mL) was observed in 6 patients (15 %) from this group. Later these patients received hormonal therapy with aLHRH. Median PSA-RFS in the adjuvant CHT group was 11 months.The main adverse events in the two groups were hematological toxicity, observed in 24 patients (34.29 %), and gastrointestinal toxicity, observed in 9 patients (12.86 %) (diarrhea (n = 6) and stomatitis (n = 3)). Only grade I–II toxicity was registered so far. Two patients (3.1 %) had febrile neutropenia, which required cytostatic dose reduction by 20 %. Relatively good tolerability and acceptable quality of life allowed the vast majority of patients to be treated on an outpatient basis.Conclusion. So far, we can make only a preliminary conclusion that adjuvant and neoadjuvant CHT is a promising treatment strategy for high-risk and very high-risk prostate cancer.

Efficacy of Apamarga Kshara application and Sclerotherapy in the management of Arsha (1st and 2nd degree piles) - An open-labeled, randomized, controlled clinical trial.

Background:Anorectal disorders are progressively increasing in the society. Out of many of the causes, some important are sedentary lifestyle, irregular and inappropriate diet, prolonged sitting or standing, and certain psychological disturbances. The prime cause of anorectal disorders is the instability of Jatharagni (digestive system), which further leads to constipation.Aim and Objective:To compare the efficacy of Apamarga Kshara application (AKA) and sclerotherapy (SCL) in the management of Arsha (1st and 2nd degree piles).Materials and Methods:In this study, 50 patients of Arsha (1st and 2nd degree piles) were selected and randomly allocated into two groups. In group AKA (n = 25), Apamarga Tikshna Kshara (alkaline of Achyranthes aspera linn.) application was done and in group SCL (n = 25), SCL was done in 1st and 2nd degree piles. The study was open prospective interventional clinical trial. Patients were assessed for relief in signs and symptoms at weekly interval for a month and another 1 month as follow-up period.Results:Patients of group SCL took more time than the patients of group AKA to get reduction in size of pile mass. In group SCL, maximum relief in bleeding as well as discharge per rectum was reported. AKA provided better results in ceasing the bleeding per rectum as well as reducing prolapse piles, than SCL.Conclusion:The study concluded that AKA is a effective procedure of choice for the management of 1st and 2nd degree internal piles as compared to SCL.

A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis

Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE). To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm. Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group). Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission. Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed.

Safety and Efficiency of New Nonacog Alfa Drug in the Treatment of Bleeding Episodes in Patients with Severe and Moderate Hemophilia B

The efficiency and safety of a new Russian recombinant factor IX - FIX (nonacog alpha, Innonafactor®, GENERIUM) in prevention of bleeding episodes in patients with severe and moderate hemophilia B (part 1 of phase II-III clinical trial) were studied in a controlled randomized open prospective multicenter clinical trial in comparison with plasma derived FIX - Octanine® F (filtered) (Octapharmazeutika Produktionsges mbH, Austria). The main objective of this study was to test therapeutic equivalence and safety of nonacog alfa compared to Octanine F® in patients with severe and moderate hemophilia B. The safety and efficiency were studied in "on demand" treatment in 18 patients. According to randomization, patients were divided into 2 groups. Patients in the 1st group (n=9) received the nonacog alfa (Innonafactor) and patients of the 2nd group were given the Octanine F®. In the 1st group there were 6 patients with severe hemophilia B (activity of FIX was less than 1%) and 3 patients with moderate form of the disease (activity of FIX was 1-5%). In the 2nd group 4 patients had severe and 5 patients moderate hemophilia B. During the follow up period (13±1 week) 64 bleeding episodes were registered in patients of the 1st group; 51 of them (79.7%) were mild and 13 (20.3%) were moderate (Tab.1). In the 2nd group 70 bleeding episodes were recorded, of which 4 (5,7%) were mild, 65 (92,9%) were moderate and 1 (1.4%) was severe. The average number of bleeding episodes in patients of the 1st group (7,11±3,72) was slightly less than in patients of the 2nd group (7,78±5,22; p=0,93). The average total duration of bleeding, as well as the average duration of one bleeding episode were lower in patients of the 1st group (9,44±5,53 versus 13,78±15,39 days and 1,3±0,43 versus 1,65±1,38 days). The differences were statistically non-significant for both measures (p=0,86; p=0,93). The vast majority of bleedings were stopped with 1 - 2 doses of study drugs: 64 (100%) episodes in the 1st group and 67 (95,71%) episodes in the 2nd group (p=0,512). There were no difference in the average number of injections required to stop one bleeding episode 1,06±0,08 in the 1st group versus 1,39±0,89 in the second group (p=0,96).During follow up period patients of the 1st group required fewer doses of drug to stop bleeding (7,56±3,91) than patients of the 2nd group (11,56±11,2), but the differences were statistically not significant (p=0,859). The average amount of drug that stanched one episode of bleeding was less in the 1st group (3346,01±801,51 ME) than in the 2nd one (4264,38±2987,58 ME; p=0,93). The average number of drug to stop all episodes of bleeding in one patient in the 1st group was less (23222,22±11659,52 ME) than in the 2nd group (35722,22±34726,71 ME; p=0,929). The average value of the maximum assessment of the pain severity by a visual analogue scale during episodes of bleeding in patients of the 1st group (5,5±1,6 points) did not differ significantly from the same indicator in patients of the 2nd group (5,38±score 1,19; p=0,914). The safety assessment was performed in 18 patients. There is no any side effects, infection transmission, or de novo inhibitor incident. Thus, the study showed that nonacog alfa is effective to stop bleeding in patients with severe and moderate hemophilia B, the results are comparable with the results of the use of Octanine F. Nonacog alfa is safe, and its use not accompanied with toxic, thrombogenic, immunogenic and allergic reactions. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Bioavailability of Gentamicin and Vancomycin Released from an Antibiotic Containing Bone Cement in Patients Undergoing a Septic One-Stage Total Hip Arthroplasty (THA) Revision: A Monocentric Open Clinical Trial

The purpose of this clinical investigation was to evaluate the systemic bioavailability of antibiotics from bone cement after implantation. This was done by determining the concentrations of gentamicin and vancomycin in plasma and urine of patients receiving a novel bone cement during one-stage revision in periprosthetic hip infections. The local concentrations of both antibiotic agents in wound exudate as well as the efficacy and tolerability were assessed as a secondary objective. In a prospective open clinical trial, 20 patients (mean age 62.5 years) with an implanted hip prosthesis requiring revision due to periprosthetic infection were treated with this antibiotic loaded bone cement (ALBC) between 2009 and 2011. The concentrations of gentamicin and vancomycin in plasma, urine and wound exudate were determined with quantitative liquid chromatography analysis (LC-MS-MS). The mean postoperative maximum gentamicin plasma concentration at 5.85 hours was 209.65 ng/mL. For vancomycin, a mean postoperative maximum plasma concentration of 134.64 ng/mL was determined at 20.03 hours. Small amounts of both antibiotics were excreted via the urine within the first 10 days after surgery. No reinfection was observed at the end of the hospital stay or during the follow-up period up to 7 months post surgery. Slow absorption of both antibiotics after release from the cement resulted in plasma concentrations well below toxic levels and did not result in a critical systemic concentration potientially inducing bacterial resistance. The treatment with this novel bone cement was assessed as efficacious and was very well tolerated by all patients.

The effects of structured self-monitoring of blood glucose on therapeutic effectiveness and adherence in patients with type 2 diabetes mellitus initiating insulin treatment

Aim. To compare the efficiency of standard and structured approaches to self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes mellitus (T2DM) initiating insulin treatment. Materials and Methods. This open prospective randomized clinical trial included 51 T2DM patients who initiated insulin therapy in either outpatient or inpatient setting. Subjects were randomized in standard and structured SMBG groups, the structured group used an advanced Accu-Chek 360 View protocol. Evaluation included clinical examination and laboratory testing of HbA1c levels at the beginning of the treatment and after 3 months of the follow-up period. Results. 70% of the structured self-monitoring group and 32% of the control group achieved therapeutic goals (p=0.008). Higher adherence was associated with better glycemic control in both groups ? and vice versa. However, among patients with low adherence, 73% of advanced SMBG group managed to achieve therapeutic goals vs. 19% in the control group (p=0.005). In addition, patients in the structured monitoring group gained less weight as compared to the control (1.0?2.88 kg vs. 3.2?2.56 kg; p=0.005). Conclusion. Structured SMBG commenced at the initiation of insulin therapy improves glycemic control in a greater fraction of patients, especially in those with low adherence to treatment. Structured SMBG also partially alleviates weight gain as side effect of insulin treatment.