Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume & Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.

Effect of Shared Decision‐Making for Stroke Prevention on Treatment Adherence and Safety Outcomes in Patients With Atrial Fibrillation: A Randomized Clinical Trial

Background Guidelines promote shared decision‐making (SDM) for anticoagulation in patients with atrial fibrillation. We recently showed that adding a within‐encounter SDM tool to usual care (UC) increases patient involvement in decision‐making and clinician satisfaction, without affecting encounter length. We aimed to estimate the extent to which use of an SDM tool changed adherence to the decided care plan and clinical safety end points. Methods and Results We conducted a multicenter, encounter‐level, randomized trial assessing the efficacy of UC with versus without an SDM conversation tool for use during the clinical encounter (Anticoagulation Choice) in patients with nonvalvular atrial fibrillation considering starting or reviewing anticoagulation treatment. We conducted a chart and pharmacy review, blinded to randomization status, at 10 months after enrollment to assess primary adherence (proportion of patients who were prescribed an anticoagulant who filled their first prescription) and secondary adherence (estimated using the proportion of days for which treatment was supplied and filled for direct oral anticoagulant, and as time in therapeutic range for warfarin). We also noted any strokes, transient ischemic attacks, major bleeding, or deaths as safety end points. We enrolled 922 evaluable patient encounters (Anticoagulation Choice=463, and UC=459), of which 814 (88%) had pharmacy and clinical follow‐up. We found no differences between arms in either primary adherence (78% of patients in the SDM arm filled their first prescription versus 81% in UC arm) or secondary adherence to anticoagulation (percentage days covered of the direct oral anticoagulant was 74.1% in SDM versus 71.6% in UC; time in therapeutic range for warfarin was 66.6% in SDM versus 64.4% in UC). Safety outcomes, mostly bleeds, occurred in 13% of participants in the SDM arm and 14% in the UC arm. Conclusions In this large, randomized trial comparing UC with a tool to promote SDM against UC alone, we found no significant differences between arms in primary or secondary adherence to anticoagulation or in clinical safety outcomes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: clinicaltrials.gov. Identifier: NCT02905032.

Safety assessment of a new anti-tuberculosis drug in silico and with the participation of healthy volunteers

Relevance. In connection with the increase in the number of cases of multidrug-resistant tuberculosis (MDR-TB), the search for new anti-tuberculosis drugs (ATD) is necessary. The assessment of its effect on the human body outside the aspect of the therapeutic effect is one of the main directions in the development of anti-TB drugs.Aim. Evaluation of the possible toxicity of thiosonide, a new domestic anti-TB drug, combining a consistent study of this side of the drug using a bioinformatics approach and an analysis of the results of a clinical safety study.Methods. The bioinformatic assessment was carried out using web services and models to predict the toxicity of thiosonide. The safety assessment in relation to healthy volunteers was carried out as part of a clinical study according to the protocol: «An open-label study of the pharmacokinetics, safety and tolerability of the drug thiozonide, capsule 100 mg with a single dose of increasing doses by various groups of healthy volunteers.» (2013, Permit No. 187 to conduct a clinical trial dated March 22, 2013, issued by the Ministry of Health of the Russian Federation).Results. Potential unwanted targets were identified, the predicted activity value for which was greater than 7. The results obtained indicate the likelihood of the effect of thiosonide on these protein targets and, possibly, the ability of the latter to cause side effects associated with changes in the activity of these molecules. The cytotoxic and carcinogenic effect of thiosonide is not predicted. During a clinical study, the drug thiosonide showed good tolerance and safety, since the identified adverse events did not show a definite or reliable relationship with the study drug. The resolution of all adverse events was complete, and dose escalation did not affect the number, severity of AEs and association with the study drug.Conclusion. The safety analysis of thiosonide demonstrated its good tolerability both during in silico assessment and in a study with the participation of healthy volunteers.

Platelet-rich plasma in the treatment of alopecia

<p>Platelet rich plasma (PRP) is a promising treatment choice for patients with thinning hair. Despite excellent clinical safety and low cost, its clinical standing is still weak. The effectiveness of this method depends on its dosage, number of sessions, their intervals and technique of injection incorporated. PRP can produce particularly some phenomenal effects when applied in cosmetic dermatology. The therapeutic value of PRP is equivalent to stem cells and considered as one of the promising therapeutic agents in regenerative medicine. Harvesting of PRP plays a significant role, which is obtained from the patient's blood after centrifugation of the sample i.e., the platelet concentrates above the baseline which is the plasma fraction of the autologous blood. There are many applications of PRP in the medical field and has an incredibly significant role in dermatologic conditions e.g., tissue regeneration, wound healing, scar revision, skin rejuvenation and alopecia. In this review, we will be analyzing the authenticity of the use of PRP in the treatment of alopecia. PRP, in current scenario, is considered as a novel treatment modality. The efficacy of PRP therapy carries some deficiencies, which include lacking standard in preparation and concentration of platelets in PRP.</p><p><strong> </strong></p>

Priming With Red Blood Cells Allows Red Blood Cell Exchange for Sickle Cell Disease in Low-Weight Children

Red blood cell exchanges are frequently used to treat and prevent cerebrovascular complications in patients with sickle cell anemia (SCA). However, the low weight of young children represents serious concerns for this procedure. The Spectra Optia device can perform automatic priming using red blood cells (RBCs) (RCE/RBC-primed) which could allow RBC exchanges (RCE) to be performed in young children without hypovolemic complications, but this method requires evaluation. We prospectively analyzed the clinical safety of the RCE/RBC-primed procedure in 12 SCA low-weight children under either a chronic RCE program or emergency treatment over 65 sessions. We monitored grade 2 adverse events (AEs) such as a decrease in blood pressure, increase in heart rate, fainting sensation, or transfusion reactions and identified the critical times during the sessions in which AEs could occur. Post-apheresis hematocrit (Hct) and a fraction of cell remaining (FCR) values were compared to the expected values. We also compared the impact of automatic RCE (n = 7) vs. RCE/RBC-primed (n = 8) on blood viscosity and RBC rheology. A low incidence of complications was observed in the 65 RCE sessions with only seven episodes of transient grade 2 AEs. Post-apheresis Hct and FCR reached expected values with the RCE/RBC-primed method. Both the automatic and priming procedures improved RBC deformability and decreased the sickling tendency during deoxygenation. Blood rheological features improved in both RCE/RBC-primed and automatic RCE without priming conditions. The RCE/RBC-primed procedure provides blood rheological benefits, and is safe and efficient to treat, notably in young children with SCA in prophylactic programs or curatively when a SCA complication occurs.

CAR-NK Cells: From Natural Basis to Design for Kill

Chimeric antigen receptors (CARs) are fusion proteins with an extracellular antigen recognition domain and numerous intracellular signaling domains that have been genetically modified. CAR-engineered T lymphocyte-based therapies have shown great success against blood cancers; however, potential fatal toxicity, such as in cytokine release syndrome, and high costs are some shortcomings that limit the clinical application of CAR-engineered T lymphocytes and remain to overcome. Natural killer (NK) cells are the focal point of current immunological research owing to their receptors that prove to be promising immunotherapeutic candidates for treating cancer. However, to date, manipulation of NK cells to treat malignancies has been moderately successful. Recent progress in the biology of NK cell receptors has greatly transformed our understanding of how NK cells recognize and kill tumor and infected cells. CAR-NK cells may serve as an alternative candidate for retargeting cancer because of their unique recognition mechanisms, powerful cytotoxic effects especially on cancer cells in both CAR-dependent and CAR-independent manners and clinical safety. Moreover, NK cells can serve as an ‘off-the-shelf product’ because NK cells from allogeneic sources can also be used in immunotherapies owing to their reduced risk of alloreactivity. Although ongoing fundamental research is in the beginning stages, this review provides an overview of recent developments implemented to design CAR constructs to stimulate NK activation and manipulate NK receptors for improving the efficiency of immunotherapy against cancer, summarizes the preclinical and clinical advances of CAR-NK cells against both hematological malignancies and solid tumors and confronts current challenges and obstacles of their applications. In addition, this review provides insights into prospective novel approaches that further enhance the efficiency of CAR-NK therapies and highlights potential questions that require to be addressed in the future.

Association of women leaders in the C-suite with hospital performance

BackgroundWomen comprise 50% of the healthcare workforce, but only about 25% of senior leadership positions in the USA. No studies to our knowledge have investigated the performance of hospitals led by women versus those led by men to evaluate the potential explanation that the inequity reflects appropriate selection due to skill or performance differences.MethodsWe conducted a descriptive analysis of the gender composition of hospital senior leadership (C-suite) teams and cross-sectional, regression-based analyses of the relationship between gender composition, hospital characteristics (eg, location, size, ownership), and financial, clinical, safety, patient experience and innovation performance metrics using 2018 data for US adult medical/surgical hospitals with >200 beds. C-suite positions examined included chief executive officer (CEO), chief financial officer (CFO) and chief operating officer (COO). Gender was obtained from hospital web pages and LinkedIn. Hospital characteristics and performance were obtained from American Hospital Directory, American Hospital Association Annual Hospital Survey, Healthcare Cost Report Information System and Hospital Consumer Assessment of Healthcare Providers and Systems surveys.ResultsOf the 526 hospitals studied, 22% had a woman CEO, 26% a woman CFO and 36% a woman COO. While 55% had at least one woman in the C-suite, only 15.6% had more than one. Of the 1362 individuals who held one of the three C-suite positions, 378 were women (27%). Hospital performance on 27 of 28 measures (p>0.05) was similar between women and men-led hospitals. Hospitals with a woman CEO performed significantly better than men-led hospitals on one financial metric, days in accounts receivable (p=0.04).ConclusionHospitals with women in the C-suite have comparable performance to those without, yet inequity in the gender distribution of leaders remains. Barriers to women’s advancement should be recognised and efforts made to rectify this inequity, rather than underusing an equally skilled pool of potential women leaders.

Two-Year Clinical Follow-Up Assessment of the Novel Cingular Surgical Bovine Pericardial Valve

Objectives: To evaluate the 2-year clinical safety and hemodynamic outcomes of the Cingular bovine pericardial bioprosthesis.Methods: A prospective, multicenter, single-arm trial was conducted in patients who required aortic or mitral valve replacement. From March 2016 to October 2017, 197 patients were implanted with the Cingular bovine pericardial valve at five sites in China. The clinical outcomes and hemodynamic performance were assessed through a 2-year follow-up. Clinical safety events were reviewed by an independent clinical events committee, and echocardiographic data were assessed by an independent core laboratory.Results: The mean age was 66.9 ± 4.9 years. The 2-year survival rate was 96.4%. A complete 2-year clinical follow-up was achieved in 189 of 190 survivors. No case of structural valve deterioration, major perivalvular leak, prosthetic valve endocarditis, or valve-related reoperation was seen. For the aortic valve, the mean pressure gradient observed was 12.5 ± 4.0 mm Hg, and the effective orifice area (EOA) was 2.0 ± 0.3 cm2. For the smaller size aortic valves, 19 mm and 21 mm, respective mean EOA values of 1.7 ± 0.2 cm2 and 1.8 ± 0.2 cm2 were found. The values for mean pressure gradient and mean EOA for mitral bioprostheses were 4.0 ± 1.4 mm Hg and 2.2 ± 0.3 cm2, respectively. There was no significant change between 1-year and 2-year hemodynamic performance.Conclusions: The Cingular bovine pericardial valve showed favorable clinical safety and hemodynamic outcomes over a 2-year follow-up. Further follow-up is required to validate the long-term durability.

Orally administered epeleuton inhibits SARS-CoV-2 viral load, replication and pathology in the Syrian Hamster model

Early treatment of patients with confirmed COVID-19 presenting mild symptoms can reduce the number that progress to more severe disease and require hospitalization. Considering the potential for the development of drug resistance to existing therapies and the emergence of new SARS-CoV-2 variants, there is a need for an expanded armamentarium of treatment options for COVID-19. Epeleuton is a novel orally administered second-generation n-3 fatty acid with potential direct antiviral and immunomodulatory actions, and a favourable clinical safety profile. In this study we show that epeleuton inhibits SARS-CoV-2 infectious viral load, replication and disease pathology in the lungs and upper airways in the Syrian hamster model of SARS-CoV-2 infection. These data support the potential utility of epeleuton in the early treatment and prevention of SARS-CoV-2 infection. Clinical trials are needed to evaluate the efficacy of epeleuton as an outpatient treatment and prevention of COVID-19.