With the emergence of coronavirus disease 2019 (COVID-19) in late December 2019, many clinical studies on a group of the pre-existing medications have been conducted to treat this disease. The purpose of this review was to compile the clinical evidences on the use of the pre-existing medications and potential therapeutic options for the management of COVID-19. We reviewed the literature to highlight the clinical studies on the use of these medications to be available as a scientific overview for further perspectives. Inadequate clinical evidences are available to be affirmed for the repurposing of old medications, and large scale clinical studies are needed to be carried out to further confirm the use of these agents. The clinical use of these medications should be well explained and follow the framework of Monitored Emergency use of Unregistered Interventions (MEURI) of World Health Organization (WHO).
The advent of immune checkpoint inhibitors such as anti-PD-1 antibodies had a striking impact on the treatment for advanced malignant melanoma. However, less than half of the patients benefited from those antibodies, and biomarkers that could sensitively differentiate responders from non-responders are urgently needed. Herein, we explored such biomarkers by retrospectively analyzing clinical data from patients with advanced malignant melanoma treated with nivolumab and pembrolizumab. We found that anti-PD-1 antibody was especially effective for those with metastasis only to soft tissues. Although no significant difference was found in the baseline value of relative neutrophil count (RNC), relative lymphocyte count (RLC), neutrophil to lymphocyte ratio (NLR), and relative eosinophil count (REC) between responders and non-responders, responders after anti-PD-1 therapy revealed the increase of lymphocytes and eosinophils and the decrease of neutrophils within the first 6 weeks of the treatment. We also calculated the change of RNC and RLC 3 weeks and 6 weeks after the initiation of the therapy and designated as NΔ3-LΔ3 and NΔ6-LΔ6 respectively. NΔ3-LΔ3 was significantly decreased in responders, which suggest that the neutrophil decrease and lymphocyte increase after as early as 3 weeks of anti-PD-1 therapy might be a useful clinical indicator. In addition, the difference of NΔ6-LΔ6 between responders and non-responders was even more robust. These data suggest that change of RNC, RLC, and REC together with the combination of NΔ3-LΔ3 and NΔ6-LΔ6 might be a useful tool for early and sensitive biomarkers for anti-PD-1 therapy.
The aim of this study is to investigate the potential neuroprotective effect of high-doses vitamins B1, B6 and B12 in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent visual loss after acute optic neuritis (AON). Sixteen patients (20 eyes) diagnosed with RRMS and visual permanent disability following AON were enrolled for the present open, pilot study. Each patient was treated with oral high-doses 300 mg of vitamin B1, 450 mg of vitamin B6 and 1,500 mcg of vitamin B12, as add-on treatment to concomitant disease-modifying therapies (DMTs) for consecutive 90 days. Outcome measures were to determine changes from baseline to month three in visual acuity (VA) and visual field (VF) testing, with correlations with clinical parameters. Logistical regression was performed to evaluate predictors of final VA. A statistically significant improvement was registered in visual acuity (p = 0.002) and foveal sensitivity threshold (FT) (p = 0.006) at follow-up compared to baseline. A similar trend was demonstrated for mean deviation (MD) (p < 0.0001), and pattern standard deviation (PSD) (p < 0.0001). Age at the time of inclusion was positively correlated with latency time (rho = 0.47, p = 0.03), while showing a negative correlation with visual acuity (rho = – 0.45, p = 0.04) and foveal sensitivity threshold (rho = – 0.6, p = 0.005) at follow up. A statistically significant correlation was demonstrated between foveal sensitivity threshold and visual acuity at baseline (rho = 0.79, p < 0.0001). In a linear regression model, the main predictor of visual acuity at follow up was the foveal sensitivity threshold (B = 1.39; p < 0.0001). Supplemental high-dose vitamins B1, B6 and B12 resulted as effective therapy to improve visual function parameters in MS-related visual persistent disability.
The aim of this randomized, single-blind, active-controlled pilot study was to investigate the clinical efficacy of oral supplementation with Verbascox®, a proprietary herbal extract capable of inhibiting human cyclooxygenase-2 (COX-2), in patients with mild-to-moderate osteoarthritis (OA) of the knee. Patients in the control group (n = 50) did not undergo any treatment (watchful waiting). Patients in the Verbascox® group (n = 50) received oral supplementation (800 mg/day) with the herbal extract for 2 weeks. The final study group consisted of patients (n = 50) who received celecoxib, a known pharmacological inhibitor of COX-2, 200 mg/day for 2 weeks. Examining physicians and laboratory personnel were blinded to group assignment, whereas patients were unblinded. All participants were evaluated using standard measures of pain relief and improvement in functional capacity at baseline, after 1 week, and at the end of the 2-week treatment course. Moreover, serum levels of substance P (SP), a member of the tachykinin family of neuropeptides involved in pain perception, were measured at the three time points. Both Verbascox® and celecoxib reduced pain, improved functional capacity, and lowered serum SP levels at 2 weeks compared with baseline, without significant inter-arm differences. Both Verbascox® and celecoxib showed a limited number of treatment-emergent adverse events. In summary, oral supplementation with Verbascox® (800 mg/day) in patients with mild-to-moderate OA of the knee is as effective and safe as a standard therapeutic dose of celecoxib in terms of pain relief and improvement in functional capacity after a 2-week treatment course.
Drug-induced liver injury (DILI) due to anti-tubercular treatment (ATT) leads to increased morbidity and mortality in patients with tuberculosis (TB). The aim of this study was to find the impact of malnutrition on the development of DILI. This was a prospective cohort study (September 2017 to August 2019) in which all newly diagnosed in-patients with tuberculosis above the age of 18 years were included. Those patients with a body mass index (BMI) of < 18.5 kg/m2 were considered malnourished. The patients were monitored for the development of DILI. Liver function tests were done at the baseline (before initiation of ATT), on the third day and at discharge in all the patients. Chi-square tests and conditional multiple logistic analysis was performed to identify risk factors associated with DILI. Out of the 319 subjects who were enrolled, a total of 138 patents chose to follow up at our hospital. A total of 14 patients (10%) developed DILI. The median time to onset of DILI was found to be ten days. Extra-pulmonary TB, low BMI and high baseline liver enzyme levels had a significant association with the development of DILI (p < 0.05). Low serum albumin had increased odds ratio but wasn't statistically significant. Malnutrition is an important risk factor for TB-DILI.
COVID-19 pandemic has accounted for ~ 4.3 million confirmed cases and ~ 292,000 deaths (till 12th May, 2020) across the globe since its outbreak. Several anti-viral drugs such as RNA dependent RNA polymerase inhibitors (remdesivir, favipiravir, ribavirin), protease inhibitors (lopinavir, ritonavir) and drugs targeting endocytic pathway (hydroxychloroquine) are being evaluated for COVID-19 but standard therapeutics yet not available. Severe health deterioration in critically ill patients is characterized by pulmonary edema, severe respiratory distress, cytokine storm and septic shock. To combat cytokine storm, immune-therapy targeting IL-1, IL-2, IL-6 and TNFα are being evaluated and one of the promising immune-modulator is the mesenchymal stem cells (MSCs) that can surmount the severity of COVID-19 infections. Recent studies have shown that MSC-therapy significantly dampens the cytokine storm in critically ill COVID-19 patients. This communication endows with the insight of stem cell therapy and summarizes the recent studies on COVID-19 patients.
In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In "chronic inflammatory diseases", the overexpression of delayed rectifier K+-channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.
Healthcare group purchasing organizations (GPOs) are considered to play an integral role in the healthcare supply chain by keeping prices low and helping all members of the healthcare system achieve their objectives. China has been exploring GPOs in the field of drug procurement since 2015, and there are currently three GPO models in Shanghai, Shenzhen, and Guangzhou. Although the three models operate differently and they have each been examined, they have all achieved certain results and demonstrated the ability to control drug expenditures. In 2018, the National Healthcare Security Administration implemented a national centralized drug procurement policy, also known as the 4 + 7 procurement policy ("4+7 Policy"). This policy context has also led to changes in the strategy for development of GPOs in China. GPOs need to explore strategies that do not overlap with the scope of 4 + 7 procurement, and they need to develop dynamic and personalized procurement plans that are more in line with first-line clinical practices to have a synergistic effect in combination with the "4+7 Policy." In the future, GPOs will grow rapidly in China. The number of GPOs need to be increased to prevent monopolies, and GPOs need to expand their diversified value-added services to perform more tasks in terms of supply chain management and data analysis.
Coronavirus disease 2019 (COVID-19) broke out in 2019 and spread rapidly around the world, causing a global pandemic. Traditional Chinese medicine has a history of more than 2,000 years in the prevention and treatment of epidemics and plagues. In guidelines on fighting COVID-19, the National Health Commission (NHC) has recommended some traditional Chinese medicines (TCM), including Jinhua Qinggan granules, Lianhua Qingwen capsules, XueBijing injections, a Qingfei Paidu decoction, a Huashi Baidu decoction, and a Xuanfei Baidu decoction. Based on current results, TCM has displayed some efficacy in combating COVID-19. However, TCM faces many challenges in terms of being recognized around the world. Therefore, evidence-based research is crucial to the development of TCM.
Community-acquired pneumonia (CAP) is the third leading contributor to lost disability-adjusted life years worldwide, and this is especially true in the elderly population. In order to reduce the burden of disease, effective management of CAP is crucial to public health in terms of maintaining and promoting the health of the elderly and involves safe drug use, vaccinations, early treatment in the ICU, and health education. Since the long-term mortality of CAP is particularly high in the elderly, biomarkers and a predictive diagnostic model of CAP should be developed in future research.