Efficacy and Safety of “Three Chinese Patent Medicines and Three TCM Prescriptions” for COVID-19: A Systematic Review and Network Meta-Analysis

Objective. To systematically evaluate the efficacy, safety, and precision of TMTP for COVID-19. Methods. Randomized controlled trials and retrospective studies were searched in 11 electronic databases. This network meta-analysis included trials using TMTP to treat patients with COVID-19. The traditional pairwise meta-analysis was done by using Stata 15, and Bayesian network meta-analysis was done with WinBUGS. Results. 18 trials were included with 2036 participants and 7 drugs. The results showed that LHQW had the most significant effects on improving expectoration, shortness of breath, sore throat, nausea, emesis, inappetence, muscle soreness, and headache, and it could produce the least adverse reactions. XBJ was the best drug for fever, fatigue, and diarrhea, which showed great advantages in lowering WBC levels. XFBD was the most effective drug for cough and chest distress, which had the least exacerbation rate. JHQG was the most effective for rhinobyon and rhinorrhea, while QFPD was the best drug in decreasing CRP levels. Conclusion. This study was the first most large-scale and comprehensive research of TMTP for COVID-19. The results showed that LHQW had good efficacy without obvious adverse reactions. Therefore, we believe that it should be firstly recommended for COVID-19 treatment. In addition, XBJ is recommended for patients with a severe fever, fatigue, and diarrhea, and JHQG is recommended for patients with obvious rhinobyon and rhinorrhea; then, XFBD is recommended for patients with cough and chest tightness as the main manifestation. Our findings will help experts develop new COVID-19 treatment guidelines to better guide clinical medication for protecting the health of COVID-19 patients.

A Network Meta-Analysis of the Clinical Efficacy and Safety of Commonly Used Chinese Patent Medicines in the Auxiliary Treatment of Poststroke Depression

Background. Poststroke depression (PSD) is a serious complication of clinical cerebrovascular disease. Patients not only have depression-related emotional symptoms but also have physical symptoms, such as autonomic dysfunction. At the same time, patients with varying degrees of depression will delay the neurological function of stroke patients. The recovery time of cognitive function and limb function will increase the risk of accidental death and even aggravate the mortality of cerebrovascular disease. Through combining data analysis and related literature, seven types of Chinese patent medicines (CPMs) widely used in the clinical treatment of PSD have been screened out. These herbs exhibit some clinical comparability under the conditions that the syndrome type and dosage form are relatively uniform. Therefore, in this study, the network meta-analysis method was used to evaluate the safety and efficacy of the seven CPMs screened out, and the probability ranking was performed to screen the best clinical auxiliary treatment plan of CPM. Methods. We searched the Chinese databases, including CNKI, WANFANG, and VIP, as well as the English databases, including the Cochrane Library, EMBASE, and PubMed, from inception to May 31, 2020, to identify randomized controlled trials (RCTs) on seven kinds of CPMs that were the subjects of the clinical research. The bias risk and quality of the included studies were analyzed with the Cochrane Handbook (version 5.1), ADDIS, and R software, and the results were compared in a network meta-analysis (NMA). Results. In terms of clinical effectiveness, the seven kinds of CPMs all improved clinical curative effects, with Jieyu Anshen capsule adjuvant treatment having the most significant effect [odds ratio (OR) = 5.00, 95% CI (1.72–9.48)]. Wuling capsule AT can effectively reduce the score index of scale factors for the HAMD score, NIHSS score, and TESS score [mean difference (MD) = −3.95, 95% CI (−4.88–3.00); OR = −3.25, 95% CI (−5.46)–1.05); OR = 0.22, 95% CI (0.05–0.79), resp.]. Conclusion. The mechanisms of seven CPMs in the adjuvant treatment of PSD have advantages. In terms of safety and efficacy, the CPMs had better clinical adjuvant treatment performance. Although this study concluded that the Jieyu Anshen capsule is the preferred drug for clinical treatment, a clear conclusion still needs to be verified in a high-quality randomized controlled study. In clinical practice, accurate selection and application can be carried out according to the specific characteristics of patients.

The Impact of Reimbursement Practices on the Pharmaceutical Market for Off-Patent Medicines in Slovakia

Background: The aim of this study was to investigate the impact of selected legislative initiatives and their implementation for off-patent medicinal products in Slovakia compared with the rest of the Visegrád Group (V4 countries).Methods: We analyzed the development of applications for the reimbursement of generic and biosimilar drugs. Particular emphasis was placed on a) the availability and penetration of biosimilars from 2006 to 2020 in Slovakia, b) a comparative analysis of biosimilars in V4 countries based on the national reimbursement lists of medicinal products for August 2021. Data relating to the sales of generic and biosimilar medicines in Czechia, Hungary, Poland, and Slovakia were based on the IQVIA MIDAS MAT July 2021.Results: The number of applications for the reimbursement of generic drugs decreased from 296 in 2016 to 165 in 2020. In financial terms, the sales of generic medicines in Slovakia increased from 21.7% in 2015 to 22.3% in 2020. Over the same period, the sales of generic drugs in Poland fell from 40.4% in 2015 to 35.0% in 2020, from 26.2 to 22.1% in Hungary, and from 29.6 to 20.4% in Czechia. When considering the 66 biosimilars registered by the European Medicines Agency 38 drugs (58%) were available on the Slovak market as of August 1, 2021; this compared to 32 drugs (48%) in Poland, 38 drugs (58%) in Hungary, and 40 drugs (61%) in Czechia. In financial terms, the sales of biosimilars in Slovakia increased from 0.94% in 2015 to 2.00% in 2020. Over the same period, the sales of biosimilars in Poland increased from 0.59% in 2015 to 1.29% in 2020, from 0.72 to 2.23% in Hungary, and from 0.76 to 2.15% in Czechia.Conclusion: To intensify the use of generic and biosimilar medicines, we suggest the comprehensive re-evaluation of combinations of the three-threshold entry, the amount of mandatory price reductions, and external reference pricing requirements (as the average of the three lowest prices among the official prices of a medicinal product in other Member States) for generic and biosimilar drugs. We also suggest cancellation of the exception from the fixed co-payment of the insured.

Cheers! Selling Health and Happiness: Advertising Alcohol in New Zealand, c.1900-1945.

<p>Abstract At the turn of the 20th century New Zealand’s newspapers were filled with advertising material offering information on a wide variety of products. Among these advertisements were those for alcohol, a commodity which the advertisements claimed to have multiple benefits, including those of a restorative and curative nature. This thesis will examine how two product groups, alcoholic beverages claiming medicinal value, and patent medicines containing alcohol, were advertised in selected New Zealand newspapers and magazines during the years 1900-1945. The advertising of these two groups was, in many ways, similar. Both used evocative text and images, with the images changing from drawn illustrations to photographs, and both targeted groups, linking these to specific drinks. For example, tonic wine advertising was aimed at women suffering from psychological distress, while beer and spirit advertisements targeted men and sporting codes, and patent medicine advertisements were designed to attract mothers and those suffering from respiratory illnesses. While both alcohol and patent medicines were subject to legislation this was not always effective. The Quackery Act 1908, which should have impacted on both alcohol and patent medicine advertising had no effect on either group. Patent medicine advertisers however, responded to the Physical Welfare Recreation Act 1937, and the Social Welfare Act 1938 with images of active, healthy children. The Medical Advertisements Act 1942 impacted immediately on alcohol advertising. but was not as successful with patent medicines. Both groups had significant changes affecting their advertising. For example, patent medicine advertising was dramatically altered by the discovery of vitamins. This, to a large extent, moved the impetus of many of these advertisements from illness to health. Two factors influenced alcohol advertising: the first being Prohibition Referenda which saw the emergence of advertising focused on placing alcohol in the household medicine chest. This highlighted the use of alcohol as a commodity commonly used in the home for medical and other emergencies and these advertisements informed readers of what could be lost if prohibition were passed. The second, and most significant change came about with the Medical Advertisements Act 1942 when any mention of cure or relief became unlawful.</p>

Cheers! Selling Health and Happiness: Advertising Alcohol in New Zealand, c.1900-1945.

<p>Abstract At the turn of the 20th century New Zealand’s newspapers were filled with advertising material offering information on a wide variety of products. Among these advertisements were those for alcohol, a commodity which the advertisements claimed to have multiple benefits, including those of a restorative and curative nature. This thesis will examine how two product groups, alcoholic beverages claiming medicinal value, and patent medicines containing alcohol, were advertised in selected New Zealand newspapers and magazines during the years 1900-1945. The advertising of these two groups was, in many ways, similar. Both used evocative text and images, with the images changing from drawn illustrations to photographs, and both targeted groups, linking these to specific drinks. For example, tonic wine advertising was aimed at women suffering from psychological distress, while beer and spirit advertisements targeted men and sporting codes, and patent medicine advertisements were designed to attract mothers and those suffering from respiratory illnesses. While both alcohol and patent medicines were subject to legislation this was not always effective. The Quackery Act 1908, which should have impacted on both alcohol and patent medicine advertising had no effect on either group. Patent medicine advertisers however, responded to the Physical Welfare Recreation Act 1937, and the Social Welfare Act 1938 with images of active, healthy children. The Medical Advertisements Act 1942 impacted immediately on alcohol advertising. but was not as successful with patent medicines. Both groups had significant changes affecting their advertising. For example, patent medicine advertising was dramatically altered by the discovery of vitamins. This, to a large extent, moved the impetus of many of these advertisements from illness to health. Two factors influenced alcohol advertising: the first being Prohibition Referenda which saw the emergence of advertising focused on placing alcohol in the household medicine chest. This highlighted the use of alcohol as a commodity commonly used in the home for medical and other emergencies and these advertisements informed readers of what could be lost if prohibition were passed. The second, and most significant change came about with the Medical Advertisements Act 1942 when any mention of cure or relief became unlawful.</p>

Comparative Evidence for Intrahepatic Cholestasis of Pregnancy Treatment With Traditional Chinese Medicine Therapy: A Network Meta-Analysis

Background: Intrahepatic cholestasis of pregnancy (ICP) seriously threatens the health of pregnant women and newborns. A various number of Chinese prescriptions and patent medicines combined with ursodeoxycholic acid (UDCA) are used for treating ICP in China. However, there are still many doubts in choosing the suitable therapeutic drugs for the treatment of ICP in clinical practice.Methods: Several electronic databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), Wanfang, and VIP, were comprehensively searched from the database inception to February 22, 2021. Randomized controlled trials (RCTs) reporting the use of UDCA only, Chinese prescriptions plus UDCA, and patent medicine plus UDCA for the treatment of ICP were collected according to their inclusion and exclusion criteria. Cochrane Reviewers’ Handbook version 5.2 was applied for the risk assessment of the included trials. STATA 16.0 software was used for network meta-analysis (NMA). The pruritus score and the serum levels of total bile acid (TBA), alanine aminotransferase (ALT), and aspartate transaminase (AST) in ICP patients served as the primary outcomes. Moreover, this study had been registered in PROSPERO (https://www.crd.york.ac.uk/PROSPERO/#joinuppage), and the registration number is CRD42020188831.Results: Thirty-eight RCTs comprising 3,841 patients meeting the inclusion criteria were included in the network meta-analysis. The NMA results showed that compared with UDCA used alone, Yinchenhao decoction (seven different Chinese prescriptions or patent medicines) plus UDCA dramatically alleviated the primary outcomes of ICP, including the pruritus score, as well as the serum levels of TBA, ALT, and AST. The NMA results showed that the optimal drug ratio for the treatment of ICP was different from the dosage ratio of traditional Yinchenhao decoction. Significantly, the intervention plan f (IP-f) group [the similar prescription of Yinchenhao decoction 2 (Artemisia capillaris Thunb &gt;15 g, Gardenia &gt;9 g, and Rhubarb &lt;5 g) + UDCA] was the best therapeutics among the eight therapies.Conclusion: Overall, the combined use of Chinese prescriptions or patent medicine with UDCA was generally better than UDCA used alone. The dose of IP-f might be a beneficial therapeutic method for the clinical medication of ICP.Clinical Trail Registration:https://www.crd.york.ac.uk/, identifier CRD42020188831.

Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines

Asarum (Xixin), which contains analogues of aristolochic acid (AA), is the only species of the genus Aristolochia included in the Chinese Pharmacopoeia 2020. However, the contents and nephrotoxic effects of AA analogs in Asarum (Xixin) and its formulations have not been clarified. An automatic, effective solid phase extraction process and UPLC-MS/MS method were established for the pretreatment and quantitative detection of AA analogues in commercially available traditional Chinese patent medicines. The cytotoxicity and DNA damage induced by five analogues of AA were evaluated by CCK8 using human kidney cells (HK-2) and comet assays. HPLC was used to detect the analogues of AA in Asarum heterotropoides F. Schmidt (Xixin). The results showed that the contents of AA I, AA II, and AA IIIa were below the detection limit, while AA IVa and AL I presented relatively high contents of Asarum heterotropoides F. Schmidt (Xixin), within the range of 66.50–121.03 μg/g and 19.73–43.75 μg/g, respectively. The levels of AA analogues were in the nanogram-per-gram level in the main traditional Chinese patent medicines. AA I and AL I exhibited relatively high cytotoxicity at 48 h in CCK8 assays, while AA II, AA IIIa, and AA IVa showed weak cytotoxicity even at 800–1,000 μM. AA I induced significant pathological alterations and direct DNA damage at 40 mg/kg and 20 mg/kg, respectively. No distinct nephrotoxicity or hepatotoxicity was observed in mice treated with AA II, AA IIIa, AA IVa, or AL I at 40 mg/kg in this study. Consumption of Asarum heterotropoides F. Schmidt (Xixin) with controlled doses and periods is relatively safe as the contents of AA analogues in Asarum heterotropoides F. Schmidt (Xixin) and its formulations were far below those causing acute toxicity in this study. But, the long-term toxicity of Asarum heterotropoides F. Schmidt (Xixin) still needs further study.