Open-label Observational Study Research Articles

A Water-Free Omega-3 Fatty Acid Eye Drop Formulation for the Treatment of Evaporative Dry Eye Disease: A Prospective, Multicenter Noninterventional Study.

Purpose: NovaTears®+Omega-3 is a water-free eye drop solution with non-animal-derived omega-3 fatty acids. It allows to supplement omega-3 fatty acids directly in the tear film of patients with dry eye disease (DED). This post-market clinical follow-up (PMCF) study evaluated for the first time the effects on clinical signs and patient symptoms of DED, and safety and tolerability of NovaTears+Omega-3 (0.2%) eye drops, when used in accordance with its approved label. Methods: A prospective, multicenter, single-arm, uncontrolled, open-label observational cohort study was performed in patients suffering from symptoms of evaporative DED. Patients were treated 4 times daily bilaterally according to the instructions for use for 8 weeks, and standard of care clinical end points were assessed at baseline and follow-up. The trial was conducted at 2 investigational sites in Germany, Europe. Results: Thirty-six patients were included and 33 completed the study. NovaTears+Omega-3 (0.2%) showed clinically and statistically significant improvements in various clinical signs, such as total corneal staining, tear film break-up time, and Meibomian gland dysfunction (MGD) score, as well as in symptoms measured by Ocular Surface Disease Index (OSDI©) and visual analog scales over the 8-week treatment period with change from baseline P values all <0.0001. No worsening of any safety parameter (intraocular pressure, slit-lamp examination, visual acuity) was observed, and no adverse event was reported throughout the study. Conclusions: In this observational PMCF study, NovaTears+Omega-3 was safe and well tolerated. Treatment over an 8-week period resulted in significantly improved clinical signs and subjective symptoms in patients with evaporative dry eye. The study was registered at www.clinicaltrials.gov (NCT04521465).

Effectiveness of Topical 0.5% Ivermectin Shampoo in the Treatment of Pediculosis Capitis among School-going Female Children.

Background:Pediculosis is a common ectoparasitic infestation in children. There are different treatment modalities that have been used in the treatment of pediculosis capitis from time immemorial, each with their own shortcomings. Increasing emergence of resistance to permethrin has led to the lookout for newer alternatives.Aims and Objectives:The role of topical ivermectin in the management of pediculosis in people with culturally different hair grooming practices is analyzed in this study.Materials and Methods:This observational open-label clinical study was conducted in September–November 2019 in the schools that were under the rural health center at South India among school-going female children aged between 13 and 16 years of age and diagnosed with pediculosis.Results:This study demonstrated that a single application of ivermectin shampoo was able to kill head lice in 86.2% of the participants. In participants with persistent infection (13.8%), a repeat application killed the entire louse and 100% efficacy was demonstrated. Topical ivermectin is devoid of systemic side effects of oral ivermectin. Topical ivermectin has found to be more effective than contemporary recommended agents such as malathion and permethrin.

Effectiveness and tolerability of perampanel in сhildren and adolescents (own experience of Svt. Luka’s Institute of Child Neurology and Epilepsy)

Effectiveness and tolerability of perampanel in сhildren and adolescents (own experience of Svt. Luka’s Institute of Child Neurology and Epilepsy)

Epilepsy and COVID-19: is infection related to an increased risk of seizure recurrence?

Background. Over the two last years the novel coronavirus infection, COronaVIrus Disease 2019 (COVID-19), has become one of the urgent health and social problems. Reports on the SARS-CoV-2 neuroinvasiveness raise the question as to whether the infection could be related to an increased risk of seizure recurrence in patients with concomitant epilepsy and COVID-19.Objective: to study the seizure dynamics in patients with epilepsy recovered after COVID-19 by analyzing clinical observations.Material and methods. A single-center retrospective uncontrolled open-label observational study regarding an impact of COVID-19 on the course of epilepsy was performed. Patients with epilepsy recovered after COVID-19 were interviewed between January and February 2021 by using a questionnaire containing three sets of questions. The study included 13 patients suffering from COVID-19 along with epilepsy: 7 cases (54%) of genetic (idiopathic) generalised form, 6 cases (46%) of focal form. The mean age was 34.31±12.68 years.Results. Seizure remission prior to COVID-19 was noted in 10 patients (77%), with no seizure control found in 3 cases (23%) of focal epilepsy at the time of COVID-19. No seizure frequency rise was observed in any case. No recurrent seizures were detected. Electroencephalographic follow-up showed no exacerbated seizures compared to the pre-infection parameters. Monotherapy with anti-epileptic drugs was used in 61% of cases. Levetiracetam monotherapy was administered to 50% of patients, and as a part of a polytherapy regimen – to 100%.Conclusion. The research findings and literature data show that patients with epilepsy are not at greater risk than the general population. Young age, seizure remission, absence of somatic comorbidities, modern drug use with no interaction with antibiotics and antivirals for the coronavirus disease treatment can be considered as positive predictive value of the course of epilepsy with COVID-19. Further studies are required to be performed in a larger patient sample.

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

A prospective observational open-label study to evaluate the effect of telmisartan on glycosylated hemoglobin and fasting plasma glucose levels in hypertensive patients with impaired fasting glycaemia

A prospective observational open-label study to evaluate the effect of telmisartan on glycosylated hemoglobin and fasting plasma glucose levels in hypertensive patients with impaired fasting glycaemia

The Efficacy of Sequential Biologic Agents in Refractory Rheumatoid Arthritis after Failure of Initial DMARD and anti-Tumor Necrosis Factor Therapy

Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent had failed in this open-label observational study. These patients were all treated with a second biologic agent and 27 ultimately required treatment with a third. The response to the therapy and disease activity were assessed at 6 and 12 months after each switch. Results: The remission rates at 6 months were lower than previously reported and the initiation of a second biologic agent resulted in significant improvement at 12 months, including DAS remission in 36% of patients. The response in those receiving a third biologic was less pronounced, as might be expected in this relatively treatment-refractory population. In this group, only patients treated with tocilizumab had maintained remission at one year. Conclusion: Patients who do not respond to an anti-TNF agent often benefit from being switched to a second, or even third, biologic. Importantly, it may take longer than expected to fully assess the effectiveness of a second or third agent in patients with refractory disease.

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.

Optimization of blood pressure control, organ protection and metabolic disorders using a fixed-dose combination of lisinopril+amlodipine+rosuvastatin in hypertensive patients after COVID-19

Aim. To evaluate the potential of a fixed-dose combination of lisinopril+amlodipine+rosuvastatin (Equamer®) in achieving additional vascular protection in patients with hypertension and high pulse wave velocity (PWV) after severe and very severe coronavirus disease 2019 (COVID-19), complicated by bilateral multisegmental viral pneumonia, with the use of biological therapy, who had not previously received combination antihypertensive therapy.Material and methods. This 12-week open-label observational study included 30 patients with or without antihypertensive therapy. The patients underwent 24-hour blood pressure monitoring, applanation tonometry (determination of the augmentation index (AI) and central blood pressure (CBP)), PWV measurement, blood laboratory tests (lipid profile, fasting glucose, C-reactive protein, complete blood count, ferritin, fibrinogen, D-dimer, alanine aminotransferase, aspartate aminotransferase, creatinine, uric acid) before and after switch to a fixed-dose combination of lisinopril+amlodipine+rosuvastatin.Results. At baseline, the patients had an increase in office blood pressure (BP) up to 152,6/89,1 mm Hg. After prescribing a fixed-dose combination of lisinopril+amlodipine+rosuvastatin, there was a decrease in systolic blood pressure (SBP) by 15,8% and diastolic blood pressure (DBP) by 12,2%. According to 24-hour blood pressure monitoring, the decrease in SBP was 15%, DBP — by 9%, PWV — by 23,8%, AI — by 9%, CBP — by 12,4% (p&lt;0,05 for all compared to baseline values). Vascular age (VA) was initially increased to 41,9 years with a chronological age of 35,03 years. After the end of therapy, there was a significant decrease in VA to 36,5 years, low-density lipoproteins by 46,8%, triglycerides by 16,8% and an increase in high-density lipoproteins by 10,7% (p&lt;0,05 for all compared to baseline values). In addition, the levels of C-reactive protein, fibrinogen, D-dimer, glucose, and uric acid significantly decreased.Conclusion. The fixed-dosed combination of lisinopril+amlodipine+rosuvastatin provides better blood pressure control, improved vascular elasticity parameters (AI, PWV, CBP, decrease in VA), and also improves lipid and carbohydrate metabolism, reduces inflammation in patients with hypertension and hyperlipidemia after severe COVID-19.

Impact of fenfluramine on the expected SUDEP mortality rates in patients with Dravet syndrome

PurposeTo assess the impact of fenfluramine (FFA) on the expected mortality incidence, including sudden unexpected death in epilepsy (SUDEP), in persons with Dravet syndrome (DS). MethodsIn this pooled analysis, total time of exposure for persons with DS who were treated with FFA in phase 3 clinical trials, in United States and European Early Access Programs, and in two long-term open-label observational studies in Belgium was calculated. Literature was searched for reports of SUDEP mortality in DS, which were utilized as a comparison. Mortality rates were expressed per 1000 person-years. ResultsA total of 732 persons with DS were treated with FFA, representing a total of 1185.3 person-years of exposure. Three deaths occurred, all in the phase 3 program: one during placebo treatment (probable SUDEP) and two during treatment with FFA (one probable SUDEP and one definite SUDEP). The all-cause and SUDEP mortality rates during treatment with FFA was 1.7 per 1000 person-years (95% CI, 0.4 to 6.7), a value lower than the all-cause estimate of 15.8 per 1000 person-years (95% CI, 9.9 to 25.4) and SUDEP estimate of 9.3 (95% CI, 5.0 to 17.3) reported by Cooper et al. (Epilepsy Res 2016;128:43−7) for persons with DS receiving standard-of-care. ConclusionAll-cause and SUDEP mortality rates in DS patients treated with FFA were substantially lower than in literature reports. Further studies are warranted to confirm that FFA reduces SUDEP risk in DS patients and to better understand the potential mechanism(s) by which FFA lowers SUDEP risk.Clinical Trial Registration: NCT02926898, NCT02682927, NCT02826863, NCT02823145, NCT03780127.

Update of Neuromodulation in Chronic Migraine.

Purpose of ReviewNeuromodulation devices have become an attractive alternative to traditional pharmacotherapy for migraine, especially for patients intolerant to medication or who prefer non-pharmacological options. In the past decades, many studies demonstrated the efficacy of neuromodulation devices in patients with episodic migraine (EM). However, the benefit of these devices on chronic migraine (CM), which is typically more debilitating and refractory than EM, remains not well studied.Recent FindingsWe reviewed the literature within the last five years on using FDA-cleared and investigational devices for CM. There were eight randomized controlled trials and 15 open-label observational studies on ten neuromodulation devices.SummaryNeuromodulation is promising for use in CM, although efficacy varies among devices or individuals. Noninvasive devices are usually considered safe with minimal adverse events. However, stimulation protocol and methodology differ between studies. More well-designed studies adhering to the guideline may facilitate FDA clearance and better insurance coverage.

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.

Epilepsy and COVID-19: Is infection correlated to an increased risk of seizure recurrence?

The objective is to study the seizure dynamics in suffering COVID-19 patients with epilepsy, based on clinical observations and analysis of seizure progression. The study design was a single-centre retrospective uncontrolled open-label observational study of the impact of COVID-19 on the course of epilepsy. Suffering COVID-19 patients with epilepsy were interviewed between January and February 2021 using a questionnaire containing three sets of questions. The study included 13 suffering COVID-19 patients with epilepsy: genetic (idiopathic) generalised (7/13;54%), 6 cases of focal epilepsy (6/13;46%). 2 questionnaires have not been answered yet. The mean age was 34.31 + −12.68. Seizure remission prior to COVID-19 was noted in 10 patients (77%), there was no seizure control in 3 cases of focal epilepsy at the time of COVID-19 (23%). No seizure frequency increase was observed in any case. No recurrent seizures were detected. EEG follow-up showed no exacerbation of seizures compared to the pre-outbreak indicators. AED monotherapy was used in 61% of cases. Levetiracetam monotherapy administered to 50% of patients and LEV taken as a part of a polytherapy regimen - in 100%. The research findings and literature data show that patients with epilepsy are at no greater risk than the general population. Young age, seizure remission, absence of somatic comorbidities, modern drug use with no interaction among AEDs and antibiotics and antivirals for the coronavirus disease treatment can be considered as positive predictive value of the course of epilepsy with COVID-19. Further studies with a large sample sizes are needed.

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.

5-HT1A Partial Agonist Tandospirone for Behavioral and Psychological Symptoms in Oldest-old Patients with Dementia at a Special Elderly Nursing Home.

ObjectiveTo investigate the efficacy of tandospirone, an azapirone anxiolytic similar to buspirone that is used in Japan, for behavioral and psychological symptoms of dementia (BPSD), especially in oldest-old patients.MethodsThis was an open-label observational study involving residents with BPSD in a special elderly nursing home between August 2013 and August 2018. The severity of dementia was assessed using the Clinical Dementia Rating (CDR) scale; as the main outcomes, the severity of BPSD was assessed using the Clinical Global Impressions-Severity scale (CGI-S) and Neuropsychiatric Inventory-12 (NPI-12) at baseline and 4 weeks after the maintenance dose of tandospirone was reached. The administration of tandospirone started at 30 mg, divided into three doses per day. Two weeks later, if the efficacy was sufficient based on the clinical nursing record, that dose was continued; if the efficacy was insufficient, the daily dose was increased from 40 mg/day to a maximum dose of 60 mg/day.ResultsThirty-three participants (25 females [76%], mean age 87.1 ± 5.4 years) completed the study. Twenty-three participants (70%) were oldest-old (18 females [78%], mean age 89.9 ± 3.4 years). The mean CDR score was 2.9 ± 0.3 in all participants. Tandospirone treatment showed few or no obvious adverse effects and significantly improved CGI-S scores, as well as total scores and many subscale scores on the NPI-12, in both the sample at large and the oldest-old participants.ConclusionThis study demonstrated the efficacy and safety of tandospirone for BPSD in oldest-old participants.

Safety evaluation of oliceridine for the management of postoperative moderate-to-severe acute pain

ABSTRACT Introduction Opioids for managing postoperative pain are associated with side effects including opioid-induced respiratory depression (OIRD) and gastrointestinal complications. Opioids induce analgesia via G-protein signaling, while adverse effects are mediated by the β-arrestin pathway. Oliceridine is a biased ligand that preferentially activates G-protein signaling over β-arrestin, theoretically reducing adverse effects. Oliceridine has been approved by the Food and Drug Administration to treat acute pain severe enough to require intravenous opioid analgesics. Areas covered Preclinical and clinical trials demonstrate the analgesic efficacy of oliceridine. Available evidence suggests that oliceridine may have a lower risk of OIRD and gastrointestinal complications compared to conventional opioids. Expert opinion The analgesic efficacy of oliceridine has been evaluated in several clinical trials. However, safety data were obtained from an open-label observational study and studies assessing adverse effects as secondary outcomes, as post-hoc analyses, or from retrospective studies. These may be affected by gaps in detecting adverse events, heterogeneity in the original studies, and the limitations of retrospective studies. Prospective trials examining the safety of oliceridine versus conventional opioids are needed. Studies are also needed to assess the safety and efficacy of oliceridine in obstetric and pediatric populations, and in the context of multimodal analgesia and Enhanced Recovery after Surgery protocols

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.

Safety of ibogaine administration in detoxification of opioid-dependent individuals: a descriptive open-label observational study.

Background and aimsIbogaine is an indole alkaloid used in rituals of the African Bwiti tribe. It is also used in non‐medical settings to treat addiction. However, ibogaine has been linked to several deaths, mainly due to cardiac events called torsades des pointes preceded by QTc prolongation as well as other safety concerns. This study aimed to evaluate the cardiac, cerebellar and psychomimetic safety of ibogaine in patients with opioid use disorder.DesignA descriptive open‐label observational study.SettingDepartment of psychiatry in a university medical center, the Netherlands.ParticipantsPatients with opioid use disorder (n = 14) on opioid maintenance treatment with a lasting wish for abstinence, who failed to reach abstinence with standard care.Intervention and measurementsAfter conversion to morphine‐sulphate, a single dose of ibogaine‐HCl 10 mg/kg was administered and patients were monitored at regular intervals for at least 24 hours assessing QTc, blood pressure and heart rate, scale for the assessment and rating of ataxia (SARA) to assess cerebellar side effects and the delirium observation scale (DOS) to assess psychomimetic effects.FindingsThe maximum QTc (Fridericia) prolongation was on average 95ms (range 29‐146ms). Fifty percent of subjects reached a QTc of over 500ms during the observation period. In six out 14 subjects prolongation above 450ms lasted beyond 24 hours after ingestion of ibogaine. No torsades des pointes were observed. Severe transient ataxia with inability to walk without support was seen in all patients. Withdrawal and psychomimetic effects were mostly well‐tolerated and manageable (11/14 did not return to morphine within 24 hours, DOS scores remained below threshold).ConclusionsThis open‐label observational study found that ibogaine treatment of patients with opioid use disorder can induce a clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia.

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.

Intravenous Ketamine Infusions in Treatment-Resistant Bipolar Depression: An Open-Label Naturalistic Observational Study

PurposeBipolar disorder is a chronic and recurrent condition often associated with treatment resistance and suicidality. There is an unmet need for effective treatment in this group of patients. Ketamine has been demonstrated to have antidepressant and antisuicidal properties in unipolar depression. Most of the available studies concern unipolar depression. Here, we present the efficacy and safety of IV ketamine as an add-on treatment in patients with bipolar I and bipolar II depression.Patients and MethodsThirteen patients with treatment-resistant bipolar depression (TRBD) received eight IV infusions of 0.5 mg/kg ketamine twice a week over four weeks. This is an open-label naturalistic observational study. Ketamine is an add-on treatment. Depressive symptoms were measured with the Montgomery–Asberg Depression Rating Scale (MADRS), and manic symptoms were measured with the Young Mania Rating Scale (YMRS). Psychomimetic symptoms were assessed with the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS).ResultsThe rates of response and remission after the seventh infusion of ketamine were 61.5% and 46.2%, respectively. A significant antisuicidal effect was observed in responders at the 7th infusion. Suicidality was measured with item 10 on the MADRS scale. The average time to respond was between 21.1 and 23.2 days to remission. There was an increase in the CADSS scores during the treatment compared to baseline and follow-up, but no differences between responders and non-responders were observed. No affective switch was observed according to the YMRS scale scores. Ketamine treatment was associated with a transient increase in arterial blood pressure. No serious adverse events, however, were observed.ConclusionThis report presents the preliminary results of IV ketamine effectiveness and safety in treatment-resistant bipolar depression. The findings suggest that it is a feasible, safe and well-tolerated treatment option in this group of patients. There is a definite need for more studies in this field.