Commentary: raised c-troponin levels as a sign of myocardial injury after COVID-19 vaccination in healthy individuals are worrying.

BACKGROUND: Recently, Buergin et al. (Eur J Heart Fail 25(10):1871-1881, 2023 doi:10.1002/ejhf.2978) thoroughly measured a frequency of 2.8% elevated high-sensitivity cardiac troponin T levels, a sign of myocardial damage, after mRNA-1273 (Moderna) booster vaccinations. In their discussion, they claim that before vaccinations were available, the incidence and extent of myocardial damage associated with COVID-19 infection would have been much higher. We here scrutinize this claim based on empirical data. MAIN BODY: Burgin et al. have only cited papers in support of their claim which considered hospitalized COVID-19 patients. After extracting COVID-19 infection data from Germany and Switzerland and the expected frequency of elevated troponin levels after COVID-19 infection in both hospitalized and non-hospitalized individuals, we find that the extent of myocardial damage after vaccinating a considerable proportion of the general population is expected to be much higher than after natural infections. CONCLUSIONS: The claim that the extent of myocardial injury after COVID-19 infection would be higher than after vaccination is not supported by empirical evidence and therefore wrong. We conclude that cross-national systematic observational studies should be conducted that allow a more precise estimation of the risk-benefit ratio of COVID-19 mRNA vaccinations.

Quality of Life in Breast Cancer Patients Treated With Mistletoe Extracts: A Systematic Review and Meta-Analysis.

BACKGROUND: Breast cancer is the most common cancer type in women and quality of life an essential part of patients' well-being. Although the treatment with mistletoe extracts is covered by multiple cancer guidelines and reviews, it is uncertain whether mistletoe extracts can improve the quality of life in breast cancer patients. We therefore performed a systematic review and meta-analysis on this topic. METHODS: This systematic review included randomized clinical trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the quality of life in breast cancer patients treated with mistletoe extracts as add-on therapy to control groups treated conventionally. We searched previous systematic reviews and multiple databases until January 2023. We conducted a meta-analysis and assessed the risk of bias according to the Cochrane Handbook via RoB 2 and ROBINS-I and the certainty of evidence via GRADE, respectively. RESULTS: Nine RCTs and 7 NRSIs with 833 and 2831 participants, respectively, were included. The pre-post changes for the quality of life resulted in a pooled standardized mean difference for RCTs of SMD = 0.61 (95% CI 0.47-0.75; P < .0001) and for retrospective NRSIs of SMD = 0.46 (95% CI 0.10-0.82; P = .01). The risk of bias was low to high for the RCTs and serious for all NRSIs. The certainty of evidence was moderate for RCTs and very low for NRSIs. DISCUSSION: Our results indicate a clinically relevant, medium-sized effect of mistletoe extracts on the quality of life in breast cancer patients which may be based on the immunomodulating effects of mistletoe extracts during chemotherapy. The limitations of evidence include the risk of bias which is mainly caused by the difficulty of blinding. Further RCTs and real-world evidence need to confirm this result, especially in the setting of neoadjuvant chemotherapy and in breast cancer survivors.

Systematic reviews and meta-analyses in Homeopathy: Recommendations for summarising evidence from homeopathic intervention studies (Sum-HomIS recommendations).

BACKGROUND: Mainly due to the use of different inclusion criteria and quality assessments, systematic reviews (SRs) and meta-analyses (MAs) with homeopathic intervention studies (HOMIS) have shown inconsistent results. We aimed to build recommendations for "Summarizing evidence from Homeopathic Intervention Studies" (Sum-HomIS recommendations) in order to approach standardization. METHODS: Against the background of a framework-project to update the evidence from homeopathic intervention studies, we launched an expert panel on how to assess the quality of HOMIS and how to summarize evidence from HOMIS. The results of a literature review and the expert communications in advance of the panel as well as the consensus from the discussions are presented here. We added specific considerations for homeopathic veterinary research. RESULTS: On top of the general guidelines when planning a review we report five basic Sum-HomIS recommendations. These are: 1) A broad literature search including special archives and consideration of so-called grey-literature; 2) The inclusion of controlled observational studies alongside randomized controlled trials; 3) The choice of a clear clinical research question in the terms that, if possible, the review project includes studies with predominantly homogeneous populations, interventions, comparators and outcomes (PICOs); 4) The use of a global quality assessment including the assessment of external, model and internal validity; 5) A summary of evidence using the GRADE-approach if the body of evidence is sufficiently large and homogenous or a descriptive summary if it is not so. CONCLUSIONS: We present recommendations for designing, conducting, and reporting SRs and MAs with HOMIS.

SEIR models in the light of Critical Realism - A critique of exaggerated claims about the effectiveness of Covid 19 vaccinations.

In a recent modeling study Watson et al. (Lancet Infect Dis 2022;3099:1-10) claim that Covid-19 vaccinations have helped to prevent roughly 14-20 million deaths in 2021. This conclusion is based on an epidemiological susceptible-exposed-infectious-recovered (SEIR) model trained on partially simulated data and yielding a reproduction number distribution which was then applied to a counterfactual scenario in which the efficacy of vaccinations was removed. Drawing on the meta-theory of Critical Realism, we point out several caveats of this model and caution against believing in its predictions. We argue that the absence of vaccinations would have significantly changed the causal tendencies of the system being modelled, yielding a different reproduction number than obtained from training the model on actually observed data. Furthermore, the model omits many important causal factors. Therefore this model, similar to many previous SEIR models, has oversimplified the complex interplay between biomedical, social and cultural dimensions of health and should not be used to guide public health policy. In order to predict the future in epidemic situations more accurately, continuously optimized dynamic causal models which can include the not directly tangible, yet real causal mechanisms affecting public health appear to be a promising alternative to SEIR-type models.

Bioenergy Treatment for Improving Well-Being: A Meta-Analysis.

BACKGROUND: Bioenergy treatment devices for self-treatment with the aim to improve well-being are widely available, have become popular, and are used by a rather large number of persons. Yet, a systematic analysis of the assumed effect of these devices has not yet been conducted. We meta-analyzed eight very similar studies of the Healy device to assess the joint effect size. METHOD: Eight studies with similar designs, some active controlled and some wait-list controlled, testing the Healy bioenergy device, were meta-analyzed. They were conducted by the producer of the device for quality assurance and further development of the application. An additional literature search revealed no additional, independent studies. RESULT: The overall effect size across studies, combining all active arms and averaging outcome measures, is Hedge's g = 0.757 (random effects model, I2 = 85.8; z = 6.57; p < 0.0001). The stronger active intervention against control yields a heterogeneous g = 0.825 (random effects, I2 = 82.5; z = 7.77; p < 0.0001). Active treatments against each other result in a significant g = 0.29 (fixed effects, I2 = 0.0; z = 8.34; p < 0.0001). DISCUSSION: The highest effect sizes are produced by a measure of coherence, followed by the WHO5 well-being questionnaire, the Perceived Stress Scale, with the Measure Your Own Medical Outcome Profile, resulting in the smallest effect size. Heterogeneity can be partially explained by the type of control, with active control producing smaller and wait-list control producing larger outcomes. Another source of heterogeneity is the sequencing of studies. Effect sizes grew for three studies, which were similar, and then fell and remained very similar for the rest of the studies. A limitation of this analysis is the fact that all studies were conducted by the R and D Department of the producer of the device. CONCLUSION: In this meta-analysis, the Healy device showed considerable effects, improving general well-being in healthy individuals. Nonetheless, an independent confirmation of these findings would be desirable. Moreover, the potential mechanisms of effect of the bioenergy device remain unclear, and further studies addressing this research question are warranted.

Bibliography of Homeopathic Intervention Studies (HOMIS) in Human Diseases.

Objectives: Homeopathy (HOM) is a therapeutic method, which is widely used by patients and medical professionals. The medical conditions as well as the homeopathic medical products investigated vary strongly. There is an extensive amount of research, and this necessitates a bibliography that comprehensively presents the entire body of clinical evidence grouped according to medical conditions. Design: Thirty-seven online sources as well as print libraries were searched for HOM and related terms in eight languages (1980 to March 2021). We included studies that compared a homeopathic medicine or intervention with a control regarding the therapeutic or preventive outcome of a disease (classified according to International Classification of Diseases-10). The data were extracted independently by two reviewers and analyzed descriptively. Results: A total of 636 investigations met the inclusion criteria, of which 541 had a therapeutic and 95 a preventive purpose. Seventy-three percent were randomized controlled trials (n = 463), whereas the rest were non-randomized studies (n = 173). The leading comparator was placebo (n = 400). The type of homeopathic intervention was classified as multi-constituent or complex (n = 272), classical or individualized (n = 176), routine or clinical (n = 161) and isopathic (n = 19), or various (n = 8). The potencies ranged from 1X (dilution of -10,000) to 10 M (100-10.000). The included studies explored the effect of HOM in 223 medical indications. We present the evidence in an online database. Conclusions: This bibliography maps the status quo of clinical research in HOM. The data will serve for future targeted reviews, which may focus on the most studied conditions and/or homeopathic medicines, clinical impact, and the risk of bias of the included studies.

Survival of Cancer Patients Treated with Non-Fermented Mistletoe Extract: A Systematic Review and Meta-Analysis.

BACKGROUND: Mistletoe extracts (ME) are used in integrative cancer care to improve quality of life and to prolong survival. ME are available from different producers and differ in pharmaceutical processing, such as fermentation. In contrast to fermented ME, the impact of unfermented extracts on the survival of cancer patients has not yet been assessed in a meta-analysis. METHODS: We searched the databases Embase, CENTRAL, Europe PMC, Clinicaltrials.gov, Opengrey and Google Scholar, and selected controlled studies on cancer patients treated with non-fermented ME. We included randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs). The risk of bias was assessed with Cochrane's ROB2 and ROBINS-I; a meta-analysis was conducted. RESULTS: Eleven RCTs and eight NRSIs met the inclusion criteria. The studies were heterogeneous and their ROB2 and ROBINS-I displayed a moderate and high risk of bias, respectively. For RCTs, the pooled effect estimate of non-fermented ME on survival was HR = 0.81 (95% CI 0.69-0.95, P = .01). Subgroup analyses as well as the NRSIs estimation support the robustness of the finding. When active comparators are added to the analysis, the effect estimates become non-significant. CONCLUSION: The results may indicate a positive impact of non-fermented ME on the overall survival of cancer patients. High quality RCTs are necessary to substantiate our results. PROSPERO REGISTRATION: CRD42021233177.

Is the Network of World Economic Forum Young Global Leaders Associated With COVID-19 Non-Pharmaceutical Intervention Severity?

Background TheWorld Economic Forum (WEF) has spawned a global network of elites called Young Global Leaders (YGLs) with significant influence on large corporations, politics, academia, and media. This article scrutinizes the idea that through this network, the WEF had a significant influence on the scale and scope of the non-pharmaceutical interventions (NPIs) implemented in response to the COVID-19 crisis. We tested for associations between the country-level distribution of YGLs and the intensity and duration of the implemented NPIs summarized by the Government Response Severity Index (GRSI). Materials and methods The number and category of YGLs per country was extracted from the WEF website. We also extracted the maximum and median GRSI values for three time periods: (i) the beginning of the first wave of the pandemic (March 1, 2020, to April 30, 2020), (ii) the height of the second wave in Europe (December 1, 2020, to January 31, 2021), and (iii) the approximate first year (March 1, 2020, to January 31, 2021). Being a precondition for causality, any association between the total or category-specific number of YGLs and the GRSI values in each time period was evaluated using Spearman's ρ correlation coefficients and polynomial regression, respectively. Results There was a highly significant positive correlation between the total number of YGLs in a country and the median (ρ = 0.36, p = 2.5×10-7) and maximum (ρ = 0.34, p = 1.6×10-6) GRSI during the second wave of the pandemic, but not during the first wave. The total number of YGLs was also a significant predictor of higher median GRSI during the second wave of the pandemic in the best-fitting (four-degree) polynomial regression model (p<0.01); additional significant and positive predictor in this model was a country's location within Europe or South America, respectively (p<0.01). Investigating an influence-weighted number of YGLs in business, politics, and civic society separately yielded no significant associations with NPI severity for any of the three time periods. Conclusions As there were significant correlations during the second, but not the first wave of the pandemic, we conclude that the WEF might not have been the origin of but rather an echo-chamber or amplifier for certain opinions and strategies that were formed and implemented during or before the first months of the COVID-19 crisis. Future qualitative studies may reveal putative causal mechanisms underlying our observed correlations.

Why do people consent to receiving SARS-CoV-2 vaccinations? A representative survey in Germany.

OBJECTIVE: To answer the question: Why do people consent to being vaccinated with novel vaccines against SARS-CoV-2? DESIGN: Representative survey. SETTING: Online panel. PARTICIPANTS: 1032 respondents of the general German population. METHOD: A representative survey among German citizens in November/December 2021 that resulted in 1032 complete responses on vaccination status, sociodemographic parameters and opinions about the COVID-19 situation. RESULTS: Almost 83% of the respondents were vaccinated. The major motivation was fear of medical consequences of an infection and the wish to lead a normal life again. The major motivation to be not vaccinated was the fear of side effects and scepticism about long-term effectiveness and safety. Sixteen per cent of vaccinated respondents reported some serious side effect, while more than 30% reported health improvements, mostly due to the relief of psychological stress and social reintegration. We also validated a 'Corona Orthodoxy Score-COS' consisting of seven items reflecting opinions on COVID-19. The scale is reliable (alpha=0.76) and unidimensional. The COS was a highly significant predictor of vaccination status and readiness to be vaccinated in a multivariable logistic regression model. Those who were vaccinated were more likely to live in smaller households (OR=0.82, p=0.024), had a higher income (OR=1.27, p<0.001), a higher COS score (OR 1.4, p<0.0001) and used less alternative media (OR=0.44, p=0.0024) and scientific publications (OR=0.42, p=0.011) as information sources. CONCLUSIONS: The major motives for being vaccinated are fear of medical symptoms and the wish to lead a normal life. Those not wanting to be vaccinated cite a lack of knowledge regarding long-term safety and side effects as reasons. This can likely only be overcome by careful and active long-term efficacy and safety monitoring.

Identifying factors associated with COVID-19 related deaths during the first wave of the pandemic in Europe.

Aim: To clarify the high variability in COVID-19-related deaths during the first wave of the pandemic, we conducted a modeling study using publicly available data. Materials and methods: We used 13 population- and country-specific variables to predict the number of population-standardized COVID-19-related deaths in 43 European countries using generalized linear models: the test-standardized number of SARS-CoV-2-cases, population density, life expectancy, severity of governmental responses, influenza-vaccination coverage in the elderly, vitamin D status, smoking and diabetes prevalence, cardiovascular disease death rate, number of hospital beds, gross domestic product, human development index and percentage of people older than 65 years. Results: We found that test-standardized number of SARS-CoV-2-cases and flu vaccination coverage in the elderly were the most important predictors, together with vitamin D status, gross domestic product, population density and government response severity explaining roughly two-thirds of the variation in COVID-19 related deaths. The latter variable was positively, but only weakly associated with the outcome, i.e., deaths were higher in countries with more severe government response. Higher flu vaccination coverage and low vitamin D status were associated with more COVID-19 related deaths. Most other predictors appeared to be negligible. Conclusion: Adequate vitamin D levels are important, while flu-vaccination in the elderly and stronger government response were putative aggravating factors of COVID-19 related deaths. These results may inform protection strategies against future infectious disease outbreaks.

Carbon dioxide rises beyond acceptable safety levels in children under nose and mouth covering: Results of an experimental measurement study in healthy children.

Nose and mouth covering (NMC) has been made compulsory for children in many countries during the Covid-19 pandemic. We wanted to determine the average CO2 levels in inhaled air with NMC in children between age 6 and 17. We used short term measurements under surgical masks and FFP2 masks according to European norm EN 149, compared to baseline in an experimental, intra-individually controlled study over 25 min. CO2 content was measured every 15 s using an automated dual-wavelength infrared CO2 measurement device (G100, Geotech, Leamington Spa, UK) over 25 min in a short-term experimental setting, with children seated. After baseline measurement children were provided with two types of commonly worn NMC: surgical masks and FFP2--masks in randomized sequence for 3 min each. We kept ambient CO2-levels below 1000 parts per million (ppm) through frequent ventilation. We measured breathing frequency and pulse as potential physiological moderator variables. Forty-five children, 25 boys, 20 girls, with a mean age of 10.7 years (standard deviation 2.6) were measured. We measured 13,100 ppm (SD 380) under surgical mask and 13,900 ppm (SD 370) under FFP2 mask in inhaled air. A linear model with age as a covariate showed a highly significant effect of the condition (p < 1*10-9). We measured 2,700 ppm (SD 100) CO2 at pre-baseline and 2,800 ppm (SD 100) at post-baseline, a non-significant small difference. Appropriate contrasts revealed that the change was due to the masks only and the difference between the two types of masks was small and not significant. Wearing of NMC (surgical masks or FFP2- -masks) raises CO2 content in inhaled air quickly to a very high level in healthy children in a seated resting position that might be hazardous to children's health.

Most healthcare interventions tested in Cochrane Reviews are not effective according to high quality evidence: a systematic review and meta-analysis.

OBJECTIVE: To estimate the proportion of healthcare interventions tested within Cochrane Reviews that are effective according to high-quality evidence. METHODS: We selected a random sample of 2,428 (35%) of all Cochrane Reviews published between 1 January 2008 and 5 March 2021. We extracted data about interventions within these reviews that were compared with placebo, or no treatment, and whose outcome quality was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We calculated the proportion of interventions whose benefits were based on high-quality evidence (defined as having high quality GRADE rating for at least one primary outcome, statistically significant positive results, and being judged by review authors as effective. We also calculated the proportion of interventions that suggested harm. RESULTS: Of 1,567 eligible interventions, 87 (5.6%) had high-quality evidence supporting their benefits. Harms were measured for 577 (36.8%) interventions. There was statistically significant evidence for harm in 127 (8.1%) of these. Our dependence on the reliability of Cochrane author assessments (including their GRADE assessments) was the main potential limitation of our study. CONCLUSION: More than 9 in 10 healthcare interventions studied within recent Cochrane Reviews are not supported by high-quality evidence, and harms are under-reported.

Opinion of German Immunologists on SARS-CoV-2: Results of an Online Survey.

Background Little is known about the opinion of professional academic immunologists regarding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methodology In this study, we designed an online survey to determine the opinion of immunologically competent academics on SARS-CoV-2 compared with seasonal flu (the infection fatality rate, infectivity, the challenge to the health system, the importance of vaccine development, and the importance of the virulence of the virus and host factors), in addition to collecting demographic status variables and information sources used. Links to the survey were sent to all German-speaking immunologists, bacteriologists, virologists, and infectiologists in Germany, Austria, and Switzerland. Results A total of 91 full datasets were returned after three waves of requests. Approximately half of the respondents were male and half were more junior. Slightly more than half of the respondents said that the infection fatality rate and the infectivity were higher compared to flu, and 82% said that the challenge to the health system is higher. Overall, 52% found that the immune system is more important than the virus, and a majority (59%) supported the current practice of vaccination development by telescoping. A majority were of the view that conspiracy theories and non-pharmacological interventions pose a greater danger than the virus. Respondents who were more junior but well-published and mostly informed by public channels were more likely to support a mainstream view. Conclusions German-speaking immunological professionals hold widely diverging opinions regarding SARS-CoV-2. Over half of the surveyed professionals considered SARS-CoV-2 to be more dangerous and infective than the seasonal flu. However, the majority considered the health system to be under higher strain. Interestingly, more than half of them found host factors more important.

Retracted: The Safety of COVID-19 Vaccinations-We Should Rethink the Policy.

Background: COVID-19 vaccines have had expedited reviews without sufficient safety data. We wanted to compare risks and benefits. Method: We calculated the number needed to vaccinate (NNTV) from a large Israeli field study to prevent one death. We accessed the Adverse Drug Reactions (ADR) database of the European Medicines Agency and of the Dutch National Register (lareb.nl) to extract the number of cases reporting severe side effects and the number of cases with fatal side effects. Result: The NNTV is between 200-700 to prevent one case of COVID-19 for the mRNA vaccine marketed by Pfizer, while the NNTV to prevent one death is between 9000 and 50,000 (95% confidence interval), with 16,000 as a point estimate. The number of cases experiencing adverse reactions has been reported to be 700 per 100,000 vaccinations. Currently, we see 16 serious side effects per 100,000 vaccinations, and the number of fatal side effects is at 4.11/100,000 vaccinations. For three deaths prevented by vaccination we have to accept two inflicted by vaccination. Conclusions: This lack of clear benefit should cause governments to rethink their vaccination policy.