Open-label Uncontrolled Study Research Articles

Bosentan Does Not Affect Renal Resistive Index in Scleroderma/Systemic Sclerosis Patients

Introduction: If properly evaluated, chronic kidney disease can be found in up to 50% of patients with systemic sclerosis (SSc). The renal resistive index (RRI) is a marker of intrarenal vascular resistance and can predict SSc-associated vasculopathy. This study aimed to determine the impact of bosentan, a nonselective endothelin-1 receptor antagonist, on RRI and kidney function in SSc patients with recurrent digital ulcers. Methods: Twenty-one patients (age 57 ± 9 years, 19 females) were recruited in a 16-week prospective open-label uncontrolled study. Standardized procedures were used to measure general clinical and laboratory characteristics, systolic, diastolic, and mean arterial pressure (MAP), pulse pressure (PP), diastolic to systolic blood pressure (D/S) ratio, and urinary endothelin-1 levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate kidney function as an estimated glomerular filtration rate (eGFR). RRI was measured by Doppler ultrasound as the average of three samplings of intrarenal blood flow in different kidney regions of both kidneys. Patients with secondary causes of kidney disease or kidney diseases associated with albuminuria were excluded. Results: Bosentan treatment for 16 weeks did not change RRI (0.731 ± 0.049–0.730 ± 0.054, p = 0.925), but increased urine endothelin-1 to creatinine ratio (0.27 ± 0.15–0.49 ± 0.57 pg/mg, p = 0.032) and reduced MAP (123 ± 10–101 ± 11 mm Hg, p < 0.001), PP (76 ± 11–68 ± 10 mm Hg, p = 0.003), D/S ratio (0.563 ± 0.044–0.538 ± 0.031, p = 0.006), and eGFR (92 ± 20–84 ± 24 mL/min/1.73 m2, p = 0.003). Discussion/Conclusion: In conclusion, in patients with SSc complicated by digital ulcers and normal to mildly diminished kidney function, bosentan had no effect on intrarenal hemodynamics, but reduced blood pressure levels and kidney function.

Comparative assessment of modern parameters of glycemic control in children with type 1 diabetes after switching to fast-acting insulin aspart using Flash Glucose Monitoring in real clinical practice

BACKGROUND: Postprandial hyperglycaemia contributes significantly to the lack of glycaemic control in patients with type 1 diabetes mellitus (DM1). At least a quarter of patients forget to inject insulin before meals once a week, and more than 40% of them inject bolus insulin immediately before meals, which does not correspond to the pharmacokinetic effects of ultrashort insulins and determines the need to use insulins with better imitations of physiological insulin secretion.AIM: To assess the effect of fast acting insulin aspart (FIAsp) on the current parameters of glycaemic control in children with DM1 after switching from insulin Asp (iAsp) using continuous glucose monitoring.MATERIALS AND METHODS: A multicenter observational 12-week prospective open-label uncontrolled comparative study was initiated. A group of insufficiently controlled patients were identified (n = 48) including a group on multiple insulin injections therapy (MII) (insulin degludec and IAsp) and a group on continuous subcutaneous insulin infusion (CSII) of iAsp. Three 14-day flash glucose monitoring (FMG) were performed: before transferring patients to FiAsp and after 2 and 12 weeks of the transfer. Key endpoints: HbA1c after 2 and 12 weeks on FiAsp relative to baseline, analysis of 5 FMG target glucose ranges, presented as an ambulatory glycemic profile. Additional indicators: dynamics of insulin daily dose, frequency of glucose self- monitoring, the number of severe hypoglycemia, adverse events that occurred during treatment.RESULTS: 2 weeks after the transfer from IAsp to FIAsp, TIR increased in the entire group of patients: from 53% [44.3; 66.5] to 57% [47.4; 71.0] (p-value = 0.010) and TAR decreased from 38% [24.8; 50.2] to 30.5% [22.0; 45, 0] (p-value = 0.0124). Maintaining and increase time spent in the target glucose ranges during a 12-week observation period, in parallel with a significant decrease in hypoglycemic episodes &lt;3.9 mmol / L per week, on FIAsp therapy naturally leads to an improvement in diabetes control: a decrease in HbA1c from 8.15% up to 7.75% (p-value = 0.0224), more pronounced in the group of patients on CSII — from 7.9% to 7.5% (p-value = 0.028).CONCLUSION: Switching from IAsp to BDIAsp in routine clinical practice in the MII and CSII regimen in children and adolescents with type 1 diabetes allows achieving better glycemic control compared to the previous generation prandial insulin analog Iasp. The better diabetes control is associated with an increase or a trend towards an increase in TIR and a decrease or a trend towards a decrease in TAR and TBR, as well as a significant decrease in episodes of hypoglycemia.

Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study.

Background:An extrafine formulation triple therapy combination of beclomethasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) has been developed for the maintenance treatment of asthma and chronic obstructive pulmonary disease. This study used gamma scintigraphy to evaluate the intrapulmonary and extrapulmonary in vivo deposition of BDP/FF/GB, and the intrapulmonary regional distribution of the deposited formulation.Methods:This open-label uncontrolled nonrandomized single-dose study recruited 10 healthy volunteers and 9 patients with asthma. After a krypton-81m (81mKr) ventilation scan was conducted, subjects inhaled study drug (four inhalations of BDP/FF/GB 100/6/12.5 μg radiolabeled using technetium-99 m [99mTc]) through pressurized metered-dose inhaler, and a series of scintigraphic images were taken. The primary objective was to evaluate intrapulmonary drug deposition of BDP/FF/GB, determined as the percentage of nominal (i.e., metered) dose. Secondary endpoints included central/peripheral deposition ratio (C/P), and the standardized central/peripheral ratio (sC/P; 99mTc aerosol C/P/81mKr gas C/P).Results:All participants completed the study, with all scintigraphy procedures performed at one site. In patients with asthma, mean ± standard deviation intrapulmonary deposition was 25.50% ± 6.81%, not significantly different to that in healthy volunteers (22.74% ± 9.19%; p = 0.4715). Approximately half of the lung dose was deposited in the peripheral region of the lung (fraction deposited 0.52 ± 0.07 and 0.49 ± 0.06 in healthy volunteers and patients with asthma, respectively), resulting in C/P ratios of 0.94 ± 0.25 and 1.06 ± 0.25, respectively, with sC/P ratios of 1.80 ± 0.40 and 1.94 ± 0.38. Deposition patterns were similar in the two populations. BDP/FF/GB was well tolerated.Conclusions:This study confirmed that the extrafine particles delivered by BDP/FF/GB penetrate the peripheral areas of the lungs, with a similar proportion of particles deposited in the central and peripheral regions. Importantly, the deposition patterns were similar in healthy volunteers and patients with asthma, suggesting that disease characteristics are unlikely to impact drug deposition.Clinical Trial Registration number: NCT03795350.

The First-in-Human Clinical Trial of iPSC-Derived Platelets (iPLAT1): Autologous Transfusion to an Aplastic Anemia Patient with Alloimmune Platelet Transfusion Refractoriness

The First-in-Human Clinical Trial of iPSC-Derived Platelets (iPLAT1): Autologous Transfusion to an Aplastic Anemia Patient with Alloimmune Platelet Transfusion Refractoriness

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.

Nail Peeling with Glycolic Acid 50%: A Prospective Study of 20 Cases

Background: Surface abnormalities of the nail may be due to nail diseases or chemical abuse. So, every nail plate change does not require medical treatment. The aim of our study was to support the benefit of glycolic acid (GA) in both pathological conditions and dry, discolored nails due to cosmetics. Methods: A prospective single open label uncontrolled study is conducted in our department from January until April 2017. We divided our cases into 2 groups: G1 (consequences of cosmetics) and G2 (pathological conditions). In G1, we used 1–2 coat of GA 50% in 1–2 sitting at weekly intervals, but we needed multiple sittings (6–12 weeks) in G2 with 2–4 coats. Results: We have collected 20 cases: 12 in G1 and 8 in G2. In G1, 8 patients had good response. In G2, 6 had good response. Adverse effects were tolerable. Conclusion: Good response in G1 was also noted in the Indian report. The improvement in the chemotherapy side effect led us to widen the sample in order to have more credible results. GA 50% peels can offer aesthetically better looking nails. However, larger studies with a longer follow-up are required to validate the results.

EFFICACY AND SAFETY OF PHOTOTHERAPY IN TREATING PITYRIASIS LICHENOIDES CHRONICA IN PAEDIATRIC PATIENTS

Background- Pityriasis lichenoides is a benign disease that includes a continuous spectrum with two polar ends: pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC). It is a rare papulosquamous disorder of unknown etiology. Phototherapy (NBUVB) can be a safe and effective treatment for PLC in children. Objective- To assess the safety and efcacy of Phototherapy in children with PLC. Material and Methods- A prospective, single-center open-label uncontrolled study conducted at tertiary care hospital in Dermatology Outpatient department (OPD) between January 2018 to April 2019. A total of 12 patients were included in the study who were diagnosed as PLC. All the patients undergone phototherapy as a treatment modality. Result- Phototherapy was proved to be an efcient modality in treating PLC in children. Good response was seen in 58.3% of patients by the end of th 30 sitting. Conclusion- PLC is a chronic disease with remission and relapses. Narrow band UVB is an effective and safe modality of treatment for children.

Establishing the efficacy and safety of the novel use of common salt for the treatment of pyogenic granuloma

Recurrent bleeding episodes are often a cause of significant anxiety in patients with pyogenic granuloma (PG). The idea of using common salt for the treatment of PG arose from the need for a relatively safe and effective treatment because of the recurrent nature of the lesion. A prospective open-label uncontrolled study of 50 patients was conducted. All cases were treated with ordinary table salt from a commercially available package. White soft paraffin was first applied over the perilesional skin, then sufficient salt to cover the entire lesion was applied and the area was occluded with surgical adhesive tape. All patients were followed up for any complications or recurrence. Complete resolution of the lesion without any residual scar was seen in 100% of the cases, and 94% reported a decrease in the bleeding tendency of the lesion as an immediate response. The mean time to complete resolution was 14.77days. Recurrence was noted in one patient after 11months of resolution. Owing to the relative ease in application, lack of scarring and excellent response, we consider salt application to be an ideal treatment for PG lesions, especially in children and anxious patients reluctant to undergo any procedure.

Эффективность и переносимость специализированного продукта диетического лечебного питания при нарушениях обмена жирных кислот с длинной и очень длинной углеродной цепью у детей

Aim: to assess the efficacy and tolerability of a specialized dietary therapeutic product in long-chain and very long-chain fatty acid metabolism disorders in children. Patients and Methods: this open-label prospective uncontrolled study enrolled 5 children aged 35 ± 14 months who were diagnosed with longchain and very long-chain fatty acid metab-olism disorders. Diet therapy using the tested product (“Monogen”) was prescribed and corrected after the analysis of actual diet. Physical development and neurological status were evaluated, blood levels of specific acyl-carnitines (С16-ОН, С18-ОН, С18:1-ОН, С14:1, С14) were measured. Tolerability was assessed by the rate and severity of adverse events (including allergic reactions) and the changes in vital functions compared to baseline. Patient and doctor satisfaction was evaluated using a questionnaire. Results: children received the tested product throughout the study (30±2 days). The lev-els of acyl-carnitines were within normal ranges in all children. No dyspepsia, allergic reactions, somatic dysfunction, or neurological deviations were reported. Physical exam consistently fell in the range of normal for age. Parents and doctors were fully satisfied with the tested product (“Monogen”). Conclusions: “Monogen” is highly effective for therapeutic feeding of children with long-chain and very long-chain fatty acid metabolism disorders. KEYWORDS: long-chain fatty acid oxidation disorders, β-oxidation of fatty acids, long-chain acyl-coA dehydrogenase deficiency, biallelic mutation, therapeutic feeding. FOR CITATION: Semenova N.A., Shestopalova E.A., Kutsev S.I. Efficacy and tolerability of a specialized dietary therapeutic product in longchain and very long-chain fatty acid metabolism disorders in children. Russian Journal of Woman and Child Health. 2021;4(1):98–102. DOI: 10.32364/2618-8430-2021-4-1-98-102.

Response to combination of sofosbuvir and daclatasvir in chronic hepatitis C infection.

Objectives: To determine efficacy of sofosbuvir and daclatasvir in the treatment of chronic hepatitis C infection. Study Design: Open label uncontrolled interventional study. Setting: Hepatitis Clinic, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan. Period: June to December 2018. Material &amp; Methods: Five hundred treatment naïve chronic hepatitis C patients including those with compensated cirrhosis were included in the study. They were given sofosbuvir 400 mg daily and daclatasvir 60 mg daily. Weight based ribavirin was added if patient has evidence of cirrhosis. Treatment duration was 12 weeks for non-cirrhotic and 24 weeks for cirrhotics. End of treatment response (ETR) was recorded. Results: Mean age of the included patients was 41±11.69 with range from 8 to 82 years, while 217 (43.4 %) patients were male and 283 (56.6 %) were female. Cirrhosis was present in 59 (11.8 %) patients; among these 35.6 % were in Child A and 64.4 % in early Child B. End of treatment response occurred in 491 (98.2 %) patients and there was no significant difference in ETR between male and female patients, and between cirrhotic and non-cirrhotic. Similarly, there was no significant difference in age between those having ETR and those having no ETR. Fatigue was experienced by 13.2 % and headache by 4.2 % patients. Conclusion: The combination of sofosbuvir and daclatasvir has high response rate in chronic hepatitis C patients of our population.

Sildenafil orodispersible film in the treatment of erectile dysfunction after radical prostatectomy: A single-centre open-label uncontrolled trial.

Phosphodiesterase-5 inhibitors are the first-line therapy for erectile dysfunction (ED) after radical prostatectomy (RP). This single-centre open-label uncontrolled study evaluated the efficacy and safety of the new sildenafil orodispersible film (ODF) in ED treatment after RP. Sildenafil 100mg ODF was administered twice a week for 3months to patients under 75years of age, with a Framingham cardiovascular risk score<20% and a pre-operative International Index of Erectile Function (IIEF)-5 score≥17, who had undergone open RP between 2016 and 2018. Erectile function was assessed pre-operatively, post-operatively and after treatment through the IIEF-5 score, the Sexual Encounter Profile Question (SEP-Q) 2 and SEP-Q3; adverse events (AE) were also investigated after 3months. A total of 65 patients with a median (25th-75th percentile) post-operative IIEF-5 score of 8 (7-9) were treated. Nine (13.8%) patients reported AE of mild/moderate grade and discontinued treatment. A significant IIEF-5 score median (25th-75th percentile) increase of 10 (0-12) was found after treatment in the other 56 patients (p<.001). Sildenafil 100mg ODF was effective in ED after RP in terms of improved IIEF-5 score and improved SEP-Q2 and SEP-Q3 in 67.9% of patients. It could represent a valid alternative for those patients with low compliance to tablet intake.

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study.

Background:Ketamine’s defining side effects are dissociation and increased blood pressure/heart rate. An oral formulation with delayed absorption could minimize these effects. We recently reported safety and tolerability data for an extended release ketamine tablet in healthy volunteers.Methods:To assess safety, tolerability, efficacy, and pharmacokinetics of an extended release oral ketamine tablet in patients with treatment-resistant depression/anxiety. This was a multiple dose open-label flexible dose uncontrolled study in seven patients with treatment-resistant depression/anxiety, who had all previously demonstrated mood improvement to subcutaneous ketamine. Assessments included ratings of anxiety, depression and dissociation, safety and tolerability, and blood samples for ketamine pharmacokinetics and brain-derived neurotrophic factor (BDNF) concentrations.Results:Improvements in anxiety and depression ratings occurred gradually over 96 h; all patients had >50% improvements in mood ratings. Ketamine was safe and well tolerated, with no changes in vital signs, and a single brief report of dissociation. Ketamine may induce its own metabolism, as the ratio of norketamine to ketamine increased out to 96 h. Serum BDNF concentrations did not change during the study.Conclusion:Ketamine’s safety/tolerability may be improved with an extended release oral formulation. Onset of mood improvement is slightly delayed compared with parenteral dosing. These data support the further development of extended release ketamine tablets for treatment of resistant depression and anxiety disorders.

Evaluation of the efficacy of injectable chondroitin sulfate for knee osteoarthritis in real clinical practice

Objective : to carry out a statistical analysis of clinical material obtained in an open-label observational study of the efficacy and safety of injectable chondroitin sulfate (ICS) in real clinical practice. Patients and methods . A total of 170patients with knee osteoarthritis (OA) (78.8% females; mean age, 60.5+8.3 years) who experienced severe pain and needed to regularly take non-steroidal antiinflammatory drugs (NSAIDs) were examined. All the patients received a cycle of therapy with ICS (25 intramuscular injections every other day). The treatment results were assessed by the changes of pain intensity at rest and during movement and general health status (a 100 mm visual analogue scale) at 2 months after therapy initiation. The dynamics of NSAID use, therapy tolerance, and patient assessment of treatment outcomes were also taken into account. Results and discussion . There were decreases in the median severity of pain at rest from 40.0 [20.0; 70.0] to 10.0 [0.0; 20.0] mm, in pain during movement from 65.0 [58.0; 80.0] to 20.0 [10.0; 30.0] mm, and in overall health status assessment from 60.0 [50.0; 70.0] to 20.0 [10.0; 40.0] mm (p &lt; 0.001). It might be possible to discontinue NSAIDs or to reduce their dose/frequency in 87.9% of patients. 83.3% of patients rated their treatment results as good and excellent. No serious adverse reactions were observed. Such a beneficial effect of therapy should be taken with some caution, since it has been obtained during an open-label uncontrolled observational study. Although the injection of this type of pharmacological agents is practically not used in Western countries; Russia has meaningful and generally positive experience with injectable slow-acting symptom-modifying drugs (SMDs), including CS. The advantages of this procedure are an enhanced bioavailability of SMDs, an accelerated onset of an analgesic effect, and higher patient adherence to therapy. Conclusion . The findings showed the good efficacy and tolerance of ICS in patients with knee OA in real clinical practice.

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) on Delay Discounting in Major Depressive Disorder: An Open-Label Uncontrolled Pilot Study.

Background: Delay discounting (DD) refers to the decrease of a present subjective value of a future reward as the delay of its delivery increases. Major depressive disorder (MDD), besides core emotional and physical symptoms, involves difficulties in reward processing. Depressed patients often display greater temporal discounting rates than healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique applied in several countries to adult patients with treatment resistant depression. Studies suggest that this technique can be used to modulate DD, but no trial has assessed its effects on depressed patients. Methods: In this open-label uncontrolled trial, 20 patients diagnosed with MDD and at least stage II treatment resistance criteria underwent 20 HF-rTMS sessions over the dorsolateral prefrontal cortex (dlPFC; 10 Hz, 110% MT, 20 min). Pre-post treatment DD rates were compared. Effects on impulsivity, personality factors, and depressive symptoms were also evaluated. Results: No significant effect of HF-rTMS over the left dlPFC on DD of depressed individuals was observed, although rates seemed to increase after sessions. However, treatment resulted in significant improvement on cognitive impulsivity and depressive symptoms, and was well-tolerated. Conclusion: Despite the limitations involved, this pilot study allows preliminary evaluation of HF-rTMS effects on DD in MDD, providing substrate for further research.

Bacillus Calmette-Guerin Immunotherapy for Recurrent Multiple Warts: An Open-Label Uncontrolled Study.

Background:Cutaneous warts present a therapeutic challenge because of recurrence and multiplicity and may become a frustrating condition for both patients and physicians. In the past few years, there has been an increase in intralesional immunotherapy for recurrent multiple warts not only because of its encouraging results in the treatment but also due to its ability to clear distant warts and preventing recurrence.Objective:The objective of this study was to evaluate the efficacy and safety of intralesional bacillus Calmette–Guerin (BCG) vaccine immunotherapy in the treatment of recurrent multiple warts.Materials and Methods:This study included 40 adult patients with multiple recurrent extragenital warts of different sizes, numbers, and duration, with or without distant warts. Patients were injected intralesionally with 0.1 ml BCG vaccine into the largest wart at a 3-week interval, directly without a pre-sensitization skin test, until complete clearance or for a maximum of three sessions. Follow-up was done every month for 3 months to detect any recurrence.Results:Out of the 40 patients enrolled in the study, 34 patients completed the treatment protocol of three injections and 3 months of follow-up and six patients discontinued for various reasons. Complete clearance of the lesions was achieved in 25 (73.53%) patients, partial clearance in 8 (23.53%) patients, and no response in 1 (2.94%) patient. Complete response was demonstrated in 75% of those presenting with distant warts. Therapy-related side effects were mild in the form of pain during injection, itching, erythema at the site of injection, and flu-like symptoms. None of the patients with complete response showed recurrence of lesions in a 3-month follow-up period.Conclusion:Intralesional BCG immunotherapy is a safe, effective, and promising treatment modality for recurrent multiple warts.

Asenapine in the management of impulsivity and aggressiveness in bipolar disorder and comorbid borderline personality disorder: an open-label uncontrolled study.

Borderline personality disorder (BPD) often co-occurres with bipolar disorder (BD). Impulsivity and aggressiveness represent core shared features and their pharmacological management is mainly based on mood stabilizers and antipsychotics, although scarce evidence is available for this context of comorbidity. The aim of the present study was to evaluate the role of Asenapine as an adjunctive drug for reducing aggressiveness and impulsivity in a sample of Italian BD type I outpatients with or without a comorbid BPD. This was an observational 12-week open-label uncontrolled clinical study carried out from April to October 2014 in two psychiatric clinics in Sicily. Each patient was treated with asenapine at two dose options, 5 mg (twice daily) or 10 mg (twice daily), and concomitant ongoing medications were not discontinued. We measured impulsivity using the Barratt Impulsiveness Scale (BIS) and aggressiveness using the Aggressive Questionnaire (AQ). For the analysis of our outcomes, patients were divided into two groups: with or without comorbid BPD. Adjunctive therapy was associated with a significant decrease of BIS and AQ overall scores in the entire bipolar sample. Yet, there was no significant difference in BIS and AQ reductions between subgroups. Using a regression model, we observed that concomitant BPD played a negative role on the Hostility subscale and overall AQ score variations; otherwise, borderline co-diagnosis was related positively to the reduction of physical aggression. According to our post-hoc analysis, global aggressiveness scores are less prone to decrease in patients with a dual diagnosis, whereas physical aggressiveness appears to be more responsive to the add-on therapy in patients with comorbidity.

Assessing the Psychedelic "After-Glow" in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities.

BackgroundAyahuasca is a plant tea containing the psychedelic 5-HT2A agonist N,N-dimethyltryptamine and harmala monoamine-oxidase inhibitors. Acute administration leads to neurophysiological modifications in brain regions of the default mode network, purportedly through a glutamatergic mechanism. Post-acutely, ayahuasca potentiates mindfulness capacities in volunteers and induces rapid and sustained antidepressant effects in treatment-resistant patients. However, the mechanisms underlying these fast and maintained effects are poorly understood. Here, we investigated in an open-label uncontrolled study in 16 healthy volunteers ayahuasca-induced post-acute neurometabolic and connectivity modifications and their association with mindfulness measures.MethodsUsing 1H-magnetic resonance spectroscopy and functional connectivity, we compared baseline and post-acute neurometabolites and seed-to-voxel connectivity in the posterior and anterior cingulate cortex after a single ayahuasca dose.ResultsMagnetic resonance spectroscopy showed post-acute reductions in glutamate+glutamine, creatine, and N-acetylaspartate+N-acetylaspartylglutamate in the posterior cingulate cortex. Connectivity was increased between the posterior cingulate cortex and the anterior cingulate cortex, and between the anterior cingulate cortex and limbic structures in the right medial temporal lobe. Glutamate+glutamine reductions correlated with increases in the “nonjudging” subscale of the Five Facets Mindfulness Questionnaire. Increased anterior cingulate cortex-medial temporal lobe connectivity correlated with increased scores on the self-compassion questionnaire. Post-acute neural changes predicted sustained elevations in nonjudging 2 months later.ConclusionsThese results support the involvement of glutamate neurotransmission in the effects of psychedelics in humans. They further suggest that neurometabolic changes in the posterior cingulate cortex, a key region within the default mode network, and increased connectivity between the anterior cingulate cortex and medial temporal lobe structures involved in emotion and memory potentially underlie the post-acute psychological effects of ayahuasca.

Open-label uncontrolled pilot study on antipsoriatic activity of Rosa hemisphaerica

Background and objective: Rosa hemisphearica (Rosaceae) is highly cultivated worldwide as an ornamental plant and medicinally have an antibacterial and antioxidant effect. This study aimed to investigate clinically and histopathologically the anti-inflammatory activity of Rosa hemisphearica in psoriasis and to correlate the anti-inflammatory activity with the active constituents in the plant by the phytochemical study. Methods: In this open-label uncontrolled pilot study, a topical preparation of R. hemisphearica stem extract was used by 20 patients suffering from psoriasis for three weeks. Three histopathological slides for each patient, one each week for three weeks was done for anti-inflammatory response evaluation. Subsequently, total phenolic content was measured followed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis for the identification of phenolic acid content in the stem. Results: By histopathological examination revealed that both Munro’s and Kogoj’s abscesses were gradually disappeared, the granular layer gradually restored to normal and the inflammatory cells gradually reduced in number prominently polymorph (neutrophils) and eventually histocytes disappeared. Total phenolic contents in R. hemisphearica stem extract were determined as 205.625 µg gallic acid equivalent each gm of the sample extract, TLC, and HPLC results showed the presence of rosmarinic acid in the stem extract. On quantitative HPLC analysis, the percentage of rosmarinic acid in the stem extract was 0.024 with a retention time (Rt) of 3.4 min. The proposed HPLC method was found to be linear, accurate and precise. Conclusion: The organic solvent extract of R. hemisphearica stem showed a significant reduction in an inflammatory cell among psoriatic patients under study. Rosmarinic acid was identified by TLC and HPLC as important phenolic acid constituents.

Author response: Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial.

We thank Drs. Zou and Liu for their comment on our article,1 and for alerting us to an interesting Chinese study.2 In the open-label uncontrolled study of 52 young children with TSC, 56% of participants showed a seizure response of 50% or more on treatment with sirolimus.2 This effect size is in line with, but larger than, the effect size in our study and that of Krueger et al.1,3 This may be due to the younger age of the participants, but is difficult to assess. Without a control group, further conclusions regarding effectiveness remain uncertain. The results of the EXIST-3 study recently showed a statistically significant effect of everolimus on seizure control in a large group of 366 patients with a response rate of up to 40% of participants (children under the age of 2 years were not included).4 From the combination of these studies, a positive effect pattern emerges of both rapalogs on intractable epilepsy, with an effect size that our study was too underpowered to detect. We agree that it is important to investigate which patients may benefit from these therapies and at what point of treatment therapies will be most beneficial.

A retrospective open-label uncontrolled study of Epoetin zeta on the treatment of chemotherapy-induced anemia in solid tumors.

This is a single-center uncontrolled retrospective study to evaluate the efficacy and safety of the biosimilar epoetin zeta after approval in chemotherapy-induced anemia (CIA). Patients screened were >18years old suffering from solid malignancies and CIA with Hg ≤10 or <11g/dl if symptomatic anemia. Patients had measurable disease by TNM and Eastern Cooperative Oncology Group (ECOG). Patients were treated for at least 12weeks and the primary endpoint was to determine the incidence of blood transfusions, and secondarily, the overall safety and efficacy defined as ≥1g/dl rise in Hb concentration or ≥40,000cells/μl rise in reticulocyte count. Quality of life was assessed with ECOG performance status (PS) and functional assessment of cancer therapy-anemia (FACT-An) score. 1287 patients with median Hb 9.3g/dl (range 8.3-10.6) were enrolled and included in the evaluation. Median age was 63years (range 33-78). 74% of patients were stage III/IV. Patients received epoetin zeta subcutaneously at fixed 40,000-IU once weekly. Blood transfusions were given in 178 patients (13.8%; 95% CI 11.9-15.6%). Appropriate response was observed in 79% patients by week 4, 87% by week 8, and 91% by week 12. A mean Hb increase of 2.5g/dl was observed by week 12 which correlated with an improvement in PS and Fact-An score. Thrombotic events occurred in 5.2% (95% CI 3.4-7.1%) of patients. Epoetin zeta is effective in palliation and treatment of CIA in patients with solid tumors. Overall, it is well tolerated and safe even in patients with increased disease burden.