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.

Assessment of a taping method combined with manual therapy as a treatment of non-specific chronic low back pain - a randomized controlled trial.

BACKGROUND: Chronic low back pain is the most frequent medical problem and the condition with the most years lived with disability in Western countries. The objective of this study was to assess a new treatment, Medi-Taping, which aims at reducing complaints by treating pelvic obliquity with a combination of manual treatment of trigger points and kinesio taping in a pragmatic RCT with pilot character. METHODS: One hundred ten patients were randomized at two study centers either to Medi-Taping or to a standard treatment consisting of patient education and physiotherapy as control. Treatment duration was 3 weeks. Measures were taken at baseline, end of treatment and at follow-up after 2 months. Main outcome criteria were low back pain measured with VAS, the Chronic Pain Grade Scale (CPGS) and the Oswestry Low Back Pain Disability Questionnaire (ODQ). RESULTS: Patients of both groups benefited from the treatment by medium to large effect sizes. All effects were pointing towards the intended direction. While Medi-Taping showed slightly better improvement rates, there were no significant differences for the primary endpoints between groups at the end of treatment (VAS: mean difference in change 0.38, 95-CI [- 0.45; 1.21] p = 0.10; ODQ 2.35 [- 0.77; 5.48] p = 0.14; CPGS - 0.19 [- 0.46; 0.08] p = 0.64) and at follow-up. Health-related quality of life was significantly higher (p = .004) in patients receiving Medi-Taping compared to controls. CONCLUSIONS: Medi-Taping, a purported way of correcting pelvic obliquity and chronic tension resulting from it, is a treatment modality similar in effectiveness to complex physiotherapy and patient education. TRIAL REGISTRATION: This trial was registered retrospectively on July 24th, 2019 as Number DRKS00017051 in the German Register of Clinical Trials (Deutsches Register Klinischer Studien). URL of trial registry record: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017051 .

Recommendations for Designing, Conducting and Reporting Observational Studies in Homeopathy.

BACKGROUND: Randomized placebo-controlled trials are considered to be the gold standard in clinical research and have the highest importance in the hierarchical system of evidence-based medicine. However, from the viewpoint of decision makers, due to lower external validity, practical results of efficacy research are often not in line with the huge investments made over decades. METHOD: We conducted a narrative review. With a special focus on homeopathy, we give an overview on cohort, comparative cohort, case-control and cross-sectional study designs and explain guidelines and tools that help to improve the quality of observational studies, such as the STROBE Statement, RECORD, GRACE and ENCePP Guide. RESULTS: Within the conventional medical research field, two types of arguments have been employed in favor of observational studies. First, observational studies allow for a more generalizable and robust estimation of effects in clinical practice, and if cohorts are large enough, there is no over-estimation of effect sizes, as is often feared. We argue that observational research is needed to balance the current over-emphasis on internal validity at the expense of external validity. Thus, observational research can be considered an important research tool to describe "real-world" care settings and can assist with the design and inform the results of randomised controlled trails. CONCLUSIONS: We present recommendations for designing, conducting and reporting observational studies in homeopathy and provide recommendations to complement the STROBE Statement for homeopathic observational studies.

Application of Bayesian evidence synthesis to modelling the effect of ketogenic therapy on survival of high grade glioma patients.

BACKGROUND: Ketogenic therapy in the form of ketogenic diets or calorie restriction has been proposed as a metabolic treatment of high grade glioma (HGG) brain tumors based on mechanistic reasoning obtained mainly from animal experiments. Given the paucity of clinical studies of this relatively new approach, our goal is to extrapolate evidence from the greater number of animal studies and synthesize it with the available human data in order to estimate the expected effects of ketogenic therapy on survival in HGG patients. At the same time we are using this analysis as an example for demonstrating how Bayesianism can be applied in the spirit of a circular view of evidence. RESULTS: A Bayesian hierarchical model was developed. Data from three human cohort studies and 17 animal experiments were included to estimate the effects of four ketogenic interventions (calorie restriction/ketogenic diets as monotherapy/combination therapy) on the restricted mean survival time ratio in humans using various assumptions for the relationships between humans, rats and mice. The impact of different biological assumptions about the relevance of animal data for humans as well as external information based on mechanistic reasoning or case studies was evaluated by specifying appropriate priors. We provide statistical and philosophical arguments for why our approach is an improvement over existing (frequentist) methods for evidence synthesis as it is able to utilize evidence from a variety of sources. Depending on the prior assumptions, a 30-70% restricted mean survival time prolongation in HGG patients was predicted by the models. The highest probability of a benefit (> 90%) for all four ketogenic interventions was obtained when adopting an enthusiastic prior based on previous case reports together with assuming synergism between ketogenic therapies with other forms of treatment. Combinations with other treatments were generally found more effective than ketogenic monotherapy. CONCLUSIONS: Combining evidence from both human and animal studies is statistically possible using a Bayesian approach. We found an overall survival-prolonging effect of ketogenic therapy in HGG patients. Our approach is best compatible with a circular instead of hierarchical view of evidence and easy to update once more data become available.

Are pupils' 'Programme for International Student Assessment (PISA)' scores associated with a nation's fish consumption?

AIMS: Omega-3 fatty acids are essential for neurodevelopment. Fish is a major source of these essential nutrients. We asked whether a nation's fish consumption is associated with its pupils' PISA scores as measures of school achievement, independent of economic status and breastfeeding. Method (Design and Setting): This was a regression analytic study based on published data. RESULTS: Data on fish consumption and PISA scores were available for 64 countries. A significant regression model explained 72% of the variance in PISA scores. Breastfeeding does not enter the model. After controlling for technical and/or economic development, a nation's fish consumption remains a significant predictor, explaining an additional 4% of the variance. DISCUSSION: This effect is likely due to the fact that fish, as the major source of omega-3 polyunsaturated fatty acids for a population, is important for the omega-3 supply to mothers and the early neurodevelopment of their children. CONCLUSIONS: Fish consumption, as a proxy for a population's omega-3 supply, is an independent predictor of pupils' school achievement, in addition to a nation's economic development.

Scientific proving of ultra high dilutions on humans.

BACKGROUND: Homeopathic drug provings or pathogenetic trials (HPTs) are the pillar of homeopathy. This review summarizes the authors' findings and interpretations derived from a series of homeopathic drug proving between 1994 and 2015. It gives an overview over a series of attempts to use modern scientific experimental methodology to answer the question, whether such HPTs produce symptoms in healthy volunteers that can be distinguished from placebo symptoms. METHODS: Various experimental models were used: repeated crossover trials with categorical data collection, and a single-case, randomised study. Final models use diligent qualitative data-collection in experienced volunteers. In those, raters decide whether symptoms are typical for a remedy delivered or not. The design is triple-blind and placebo-controlled. RESULT: While previous attempts were inconclusive, this new model allowed to separate placebo symptoms from verum symptoms repeatedly in a series of two definitive studies following promising pilot studies. Results were statistically significant. Also, some signs of the purported non-local signature of homeopathic effects were visible, and the consequences for future methodology is discussed. CONCLUSION: Provided some cautionary notes are taken into account, HPTs can be used to separate out true specific symptoms from placebo symptoms. By the same token this is a road to experimental proof that homeopathic remedies are not just placebos. However, this needs to be taken forward by independent groups.

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.

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.

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.

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.

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.

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.

The combined effects of healthy lifestyle behaviors on all cause mortality: a systematic review and meta-analysis.

OBJECTIVE: Lifestyle factors are related to mortality. Although much is known about the impact of single factors, the current evidence about the combined effects of lifestyle behaviors on mortality has not yet been systematically compiled. METHOD: We searched Medline, Embase, Global Health, and Somed up to February 2012. Prospective studies were selected if they reported the combined effects of at least three of five lifestyle factors (obesity, alcohol consumption, smoking, diet, and physical activity). The mean effect sizes that certain numbers of combined lifestyle factors have on mortality were compared to the group with the least number of healthy lifestyle factors by meta-analysis. Sensitivity analyses were conducted to explore the robustness of the results. RESULTS: 21 studies (18 cohorts) met the inclusion criteria of which 15 were included in the meta-analysis that comprised 531,804 people with a mean follow-up of 13.24 years. The relative risks decreased proportionate to a higher number of healthy lifestyle factors for all cause mortality. A combination of at least four healthy lifestyle factors is associated with a reduction of the all cause mortality risk by 66% (95% confidence interval 58%-73%). CONCLUSION: Adherence to a healthy lifestyle is associated with a lower risk of mortality.

Copper and iron in Alzheimer's disease: a systematic review and its dietary implications.

Fe and Cu could represent dietary risk factors for Alzheimer's disease (AD), which has become a global health concern. To establish the relationship between diets high in Cu and Fe and cognitive decline or AD, we have conducted a systematic review of the literature (up to January 2011). We identified two meta-analyses, two systematic reviews, eleven placebo-controlled trials, five observational studies, forty-five case-control studies, thirty autopsy and five uncontrolled studies, and one case report. There were eleven interventional trials that tried to either supplement or deplete Fe and Cu, but none of them provided clear evidence of a beneficial effect on cognitive performance in patients with AD. The prospective studies revealed an association between a diet simultaneously high in SFA and Cu and cognitive decline. Case-control and autopsy studies showed elevated Fe levels in the brains of AD patients, whereas the evidence was less consistent for Cu. In most of the studies, Cu concentrations were unchanged in the cerebrospinal fluid and the brain but increased in the serum. In conclusion, the existing data suggest that diets excessive in Fe or Cu, together with a high intake of SFA, should be avoided in the elderly who are not at risk of anaemia. Basic studies and, building on this, clinical investigations are needed to further elucidate in which dietary patterns and in which patient groups an Fe- and Cu-rich diet might foster the risk of developing AD.

Zinc diet and Alzheimer's disease: a systematic review.

OBJECTIVES: This paper reviews evidence of an association between zinc (Zn) nutrition and Alzheimer's disease (AD) or age-associated cognitive decline. The involvement of zinc in the pathology of AD has been reported hundreds of times. It is, however, still a matter of debate whether the disease progression can be influenced by modifying zinc in the diet. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane central register of controlled trials, the Cochrane database of systematic reviews, and different publisher databases, and included studies that dealt with zinc in the diet and AD or cognitive decline in elderly subjects. RESULTS: Fifty-five studies met the inclusion criteria. Neither randomized-controlled trials nor observational studies provide conclusive evidence whether Zn in the diet is associated with cognitive decline or AD. Case-control and autopsy studies suggest decreased systemic and increased brain Zn levels, respectively. DISCUSSION: The current state of evidence does not allow conclusions to be drawn on whether supplementation of Zn is beneficial for the prevention or treatment of AD, although a subclinical deficiency appears common in the elderly and subjects with AD. Dietary studies with animals suggest that the impact of dietary Zn on cognitive performance depend on additional nutrients. Further studies are necessary to determine whether Zn deficiency is a risk factor for AD in general terms or under certain dietary circumstances only.

Subjective concepts of chronically ill patients using distant healing.

Distant healing procedures consist of benevolent intentions, often taking the form of prayers for a patient. Despite inconclusive evidence regarding distant healing, prayers are a widespread health-related technique. We studied subjective concepts of distant healing in 17 patients suffering from chronic fatigue syndrome and multiple chemical sensitivity who were given distant healing during a randomized controlled trial. We applied reconstructive interview analysis when analyzing the results. The overall theme was the tension between mainstream medicine and the immaterial healing procedure. Several components highlighted this tension: (a) patterns of legitimizing the use of distant healing, (b) distant healing and the social setting, (c) integrating distant healing into their belief system, and (d) reconstruction of effects by means of hindsight. The interviews showed that patients felt the need to legitimize having tried distant healing. They had to bear the full ambiguity of biomedicine being in competition with distant healing, though also experiencing distant healing as giving support.