Search

Objective Examination of de-classified Monsanto documents from litigation in order to expose the impact of the company's efforts to influence the reporting of scientific studies related to the safety of the herbicide, glyphosate. Methods A set of 141 recently de-classified documents, made public during the course of pending toxic tort litigation, In Re Roundup Products Liability Litigation were examined. Results The documents reveal Monsanto-sponsored ghostwriting of articles published in toxicology journals and the lay media, interference in the peer review process, behind-the-scenes influence on retraction and the creation of a so-called academic website as a front for the defense of Monsanto products. Conclusion The use of third-party academics in the corporate defense of glyhphosate reveals that this practice extends beyond the corruption of medicine and persists in spite of efforts to enforce transparency in industry manipulation.

BACKGROUND: Point 7 of the Rome Declaration is aimed at improving data sharing and technological and knowledge transfer as instruments to implement health policies. OBJECTIVE: The objective of the current paper is to understand if the legal framework (especially at a transnational level) may actually help to achieve the objectives laid down by Principle 7 or if some interpretative or legislative actions will be necessary. METHODS: The paper analyses the legal sources at international and EU levels. RESULTS: The applicable rules are based on the idea that the information and material are forms of ‘property’ of the individuals or of the states (i.e., the sovereign). According to the traditional idea of property, the owner has a sort of absolute power over the res and is entitled to exclude others from any rights over the thing. The ‘property paradigm’ may be useful to protect some relevant interests, but it can also affect collective interests, such as those concerning health during the COVID-19 pandemic. CONCLUSIONS: In order to build a global system for the exchange of data and materials as provided for by Principle 7 of the Rome Declaration, a new legal approach should be elaborated which takes into consideration the international corpus of fundamental rights, including research freedom, the right to health and the principle of transnational ‘digital’ solidarity.

BACKGROUND: Real-world safety of bevacizumab in cancer patients is limited. OBJECTIVE: To review the adverse drug reactions (ADRs) due to bevacizumab in cancer patients, in published case reports. METHODS: PubMed was searched; case reports of patients with any type of cancer, administered with bevacizumab (monotherapy/combination) and reported ADRs were included. Causality of ADRs was presented as reported in individual papers. ADRs were classified using the information in the USFDA-approved prescribing information (PI) of bevacizumab as ‘Serious’, ‘Common’, and ‘Post-marketing surveillance’ ADRs; ADRs not mentioned in the bevacizumab PI were termed as ‘Non-label ADRs’. RESULTS: A total of 130 published papers comprising 154 cases from 22 different countries were included. Most papers (102/130; 78.46%) had moderate methodological quality. Age range of patients was 9-77 years. Off-label use of bevacizumab was found in 34/154 cases (22.08%). Ninety-six unique ADRs were found among 154 ADRs; most reported ADRs affected circulatory, digestive, and respiratory systems (33, 32, and 26 cases respectively). Most commonly reported ADRs were posterior leukoencephalopathy, fistulae, and gastrointestinal perforation (17, 17, and 16 cases respectively). Twenty-eight unique non-label ADRs (29.17%) were found. CONCLUSION: Bevacizumab is associated with more ADRs in the real world among cancer patients than those reported during clinical trials.

Best practice consent forms in company clinical trials detail the financial coverage for medical treatment of injuries. In trials undertaken for licensing purposes these arrangements can raise concerns. We detail three cases in which elements of the consent forms appear misleading and designed to elicit a consent to participation that might not be forthcoming if volunteers for these clinical trials were aware that what is outlined in principle is not likely to happen in practice. Beyond clinical trial participants, these consent forms have wider implications. Medical coverage of injuries sustained in a clinical trial is a nexus where business, scientific and ethical considerations meet. It is not clear that anyone to date has grappled with the issues posed. This paper uses three clinical trials to illustrate the problems to be addressed.

BACKGROUND: The prescription opioid epidemic in the United States (US) is well documented, and recent measures have reduced prescribing rates in that country. Evidence suggests opioid prescriptions have been rising recently in other countries too. OBJECTIVE: The current paper aimed to compare trends in opioid prescribing in England and the US. METHODS: Trends in rates of prescriptions per 100 members of the population were calculated for England and the US using publicly available government data on prescriptions and population statistics. RESULTS: Rates of prescribing are converging. At the peak of the US epidemic in 2012, there were 81.3 prescriptions per 100 people, but this had fallen to 43.3 by 2020. Prescribing peaked in England in 2016 at 43.2 prescriptions per 100 people, but has fallen only slightly, so that in 2020 there were 40.9 prescriptions per 100 people. CONCLUSION: The data indicate that levels of opioid prescribing in England are now similar to those in the US. They remain high in both countries, despite recent falls. This suggests the need for further measures to prevent over-prescribing and to support people who would benefit from withdrawing from these drugs.

BACKGROUND: Public access to data has been a major step in attempting to reduce bias in scientific literature. Data to verify efficacy outcomes are now more accessible; however, little has been done to ensure public access to harms data from RCTs, which are equally important in ascertaining possible misreporting and protecting safety. OBJECTIVE: The treatment for adolescents with depression study (TADS) has influenced most international practice guidelines for treating children and adolescents with depression, supporting first-line prescription of fluoxetine in combination with cognitive behavioural therapy (CBT). However, after over 30 publications by the TADS team, reporting on harms remains highly deficient and we aimed to redress this lack. METHODS: In undertaking a restoring invisible and abandoned trials (RIAT) reanalysis of TADS’ effectiveness and safety outcomes, we sought access to de-identified serious adverse events (SAE) data. RESULTS: This paper describes our unsuccessful efforts to obtain more detailed SAE data from TADS’ data custodians, highlighting several problematic blocks to comprehensive safety reporting. CONCLUSION: Comprehensive access to clinical trial data is necessary to ensure safe and fully informed guidelines for treating children and adolescents with depression.

BACKGROUND: The new type of virus (SARS-CoV-2 or COVID-19) from Coronaviridae family, discovered in 2019, caused a global pandemic with several massive lock-downs around the globe. Science and politicians became the center of world attention, receiving many questions without having clear answers. The hopes of many rested on vaccine development, which was done fast, facing novel challenges such as the massive production and distribution for several billions of people. OBJECTIVE: In this paper, the global reaction to the pandemic is reviewed along with some critical comments. METHOD: Different groups, including nations, took part in global lockdowns, while vaccine development was running in parallel without having enough capacity for some of the biggest medical demands in history. This review will bring together views from all interested groups in this pandemic crisis. RESULTS: The Western world waited too long (4 months), after the first case was confirmed in China, to introduce lock-down and safety measures. On the other side, vaccine development was done too fast to give clear long-term safety profiles of the medications developed. Due to the focus on development, it was overlooked that production and distribution of sterile products such as vaccines might have limitations globally. Usually when such limitations occur, power comes to the surface. Therefore, buyers who had power will get the vaccines they need first. However, we should recognize the economic impact that directly influenced healthcare funding. All of this will lead to post-crisis challenges, including depression, violence, suicide, migration, and many other social problems. CONCLUSIONS: The COVID-19 pandemic is a test for all of us, which many governments, industries and non-state actors are failing. It is a perfect “general probe” to detect some of the weaknesses of the current structure of global health. If politics and science do not work together to make a global production plan for vaccines and learn from this pandemic, then all of the lives lost were for nothing.

BACKGROUND: The health sector has long been affected by programs, actions, plans to digitize data and care processes with a view to better protecting individual health, as well as public health, resulting in a slow and uneven development of different and often incompatible national services. OBJECTIVE: This paper aims to explore the grounds behind the urgency of turning the digital priority into concrete actions, as acknowledged by political leaders in the Rome Declaration, by explaining the capacity of digital tools to enhance healthcare management and the current obstacles. METHODS: It considers the progressive extension of the EU institutions’ scope of action during the pandemic, the related supporting financial strategies launched and some examples of digital contact tracing systems. RESULTS: It emerged that the pandemic highlighted the inadequacy of purely national policies and the advantages of leveraging the digital health data processing for governance, surveillance and response to cross-border and global threats. CONCLUSIONS: Considering what emerged during the pandemic and the solemn commitment of the world’s major political leaders, the solution to the still existing technical and organizational interoperability issues will no longer be postponed.

BACKGROUND: The right to fully enjoy the highest possible state of health is certainly nothing new in the agenda of the world’s governments, and yet today it becomes a top priority not just in the restructuring of the health care system, but also in the promotion of multi-sector policies aimed at fostering and safeguarding the potential of every individual to achieve what could be defined, in general terms, as “common good”. OBJECTIVE: The current paper aimed at singling out the most useful strategies to promoting and achieving a healthy, more resilient and fairer society. METHODS : Starting from principles 1 and 14 of the Declaration of Rome, the aim was to analyse and develop the concepts of resilience and health, questioning their possible future variations against the background of the current health emergency and the increasingly radical widespread use of new technologies as universally-applied and cross-sectional tools for human progress. RESULTS: The “health for all” objective can only be achieved if we act on three key aspects: 1. Adding life to years; 2. Adding life to life; 3. Adding years to life. CONCLUSIONS: Each individual should raise their health awareness as a key resource to leading a fulfilling existence and to developing the required qualities to fully tap into health possibilities – whether integral or residual – to tackle life.

BACKGROUND: The COVID-19 pandemic represented a global earthquake that made the review of health policies aimed at strengthening common governance necessary. OBJECTIVE: The paper analyses the reasons for which the One Health approach has become fundamental in the control of pandemic phenomena, by arguing the necessity to place it at the basis not only of health policies but also of intersectoral policies. METHODS: The documents of the world organizations published before and after the pandemic were analyzed and studied in order to unpack the close relationship between new lifestyles and the increase of health risks. RESULTS: It emerged that the One Health approach is a paradigm that has been advanced for more than 30 years, but due to the inadequacy of local and world health policies, this approach was never translated into concrete actions to protect health, feeding problems at the cause of the COVID-19 pandemic. CONCLUSIONS: Having ascertained that the adoption of a One Health approach can no longer be postponed, this must be insisted on several interconnected sectors that establish the new concept of healthcare which, in addition to being interdisciplinary, necessarily takes on a global perspective.

Just once in a while, in the field of medical and pharmaceutical law, one encounters a case that can rightly be considered pivotal – a legal proceeding that stands out from the rest not merely by virtue of its inherent drama, but because it marked (or could well have marked) a turning point in the way in which society viewed rights and wrongs in the field. The case in which Mrs Ilo Grundberg brought proceedings against the Upjohn pharmaceutical company in 1989 for marketing a supposedly dangerous drug was one such event. It was not the first of its type, and many analogous cases in the field of pharmaceuticals were to be brought in its wake, continuing down to the present day, but after twenty years the Grundberg case merits reanalysis. Something of the events that preceded it became known at the time [9] but various writers who have sought to provide such a retrospective view [1, 4, 7, 11] have found themselves partly impeded by the secrecy surrounding certain of the events. There have been incidental revelations, notably in an industry news-sheet [2], but the story as a whole has remained untold. For Grundberg v. Upjohn never went before the United States District Court for the District of Utah. In the course of protracted depositions of a number of witnesses, the rights and wrongs of the matter had become so clear that the defendant company agreed to meet the staggering costs of an out-of-court settlement; one of the conditions of that settlement was that all the papers held by witnesses should be returned and all relevant papers should be sealed. Can one, as of 2010 and in the public interest, not dig a little deeper into the events of that time? Mrs Grundberg died in Las Vegas some years after the settlement, the Upjohn Company was absorbed into another concern and even today the files – if they still exist at all – remain sealed. But the notes and recollections of one who was closely involved in the case may provide sufficient to bring closure to the dramatic events of a generation ago and to provide some lessons for the present day.

BACKGROUND: Meta-analysis is a powerful tool to identify Evidence Based medical technologies (interventions) for use in every day practice. Meta-analysis uses statistical approaches to combine results from multiple studies in an effort to increase power (over individual studies), improve estimates of the size of the effect and/or to resolve uncertainty when reports disagree. Meta-analysis is a quantitative, formal study design used to systematically assess previous research studies to derive conclusions from this research. Meta-analysis may provide more precise estimate of the effect of treatment or risk factor for a disease, or other outcomes, than any individual study contributing to the pooled analysis.We have quite a substantial number of Russian medical publications, but not so many Meta-Analyses published in Russian. Russian publications are cited in English language papers not so often. A total of 90% of clinical studies included in published Meta-Analyses incorporate only English language papers. International studies or papers with Russian co-authors are published in English language. OBJECTIVE: The main question is: what is the problem with inclusion of Russian medical publications in Meta-Analysis? RESULTS: The main reasons for this are the following: 1) It is difficult to find Russian papers, difficult to work with them and to work with Russian journals:a. There are single Russian Biomedical Journals, which are translated into English and are included in databases (PubMed, Scopus and other), despite the fact that all of them have English language abstracts.b. The majority the meta-analyses authors use in their work different citation management software such as the Mendeley, Reference Manager, ProCite, EndNote, and others. These citation management systems allow scientists to organize their own literature databases with internet searches and have adds-on for the Office programs what makes process of literature citation very convenient. The Internet sites of the majority of International Journals have built-in tools for saving citations to reference manager software. The majority of articles in Russian journals cannot be captured by citation management systems: they do not have special coding of articles descriptors.c. Some journals still have PDF files of the whole journal issue without dividing it into articles and do not provide any descriptors, making manual time-consuming input of information the only possibility. Moreover the context search of the article content is unavailable for search engines.2) The quality of research. This problem has been discussed for more than twenty years already. Still we have too many publications of poor quality of study design and statistical analysis. With the exception of pharmacological clinical tails, designed and supervised by international Pharma industry, many interventional studies, conducted in Russia, have methodological flaws inferring a high risk of bias:a. Absence of adequate control,b. No standard endpoints, duration of therapy and follow up,c. Absence of randomization and blinding,d. Low power of studies: sample sizes are calculated (if calculated at all) in such a way, that the main goal is to have as small sample size as possible. Very often statisticians have to solve the problem how to substantiate a small number of subjects, that sponsor could afford, instead of calculating the needed sample size to reach enough power.e. No standards of statistical analysis.f. Russian journals do not have standards for description and presentation of study results, in particular, results of statistical analysis (a reader even cannot see what is presented: standard deviation (SD) or standard error of the mean (SEM).We have a long standing experience in analysis of methodological and statistical quality of Russian biomedical publications and have found up to 80% publications with statistical and methodological errors and high risk of bias.In our practice, we had tried to perform two Meta-analyses for two local pharmaceutical products for prevention of stroke recurrence. For the first product, we did not found even two single Russian language studies suitable for the analysis (incomparable populations, different designs, endpoints, doses etc.). For the second product, only four studies had comparable populations and standard internationally approved scales for effectiveness analysis. However, the combinations of scales, the length of treatment and follow up differed widely, so that we could combine the results of only 2 or 3 studies for each end point. CONCLUSIONS: Russian researchers have to follow internationally recognised standards in study design, selection of endpoint, timelines and therapy regimens, data analysis and presentation of results. Russian journals need to develop consolidate rules for authors of clinical trials and epidemiological research of result reporting close to international standards. In this case the international Network EQUATOR (Enhancing the QUAlity and Transparency Of health Research http://www.equator-network.org/) is one to be taken into account. In addition, Russian Journals have to improve their online information for better interaction with search engines and citation managers. Language: en

The world is currently in the throes of the COVID-19 pandemic which has halted the tourism sector and created an unprecedented global economic crisis. This paper will outline economics pertaining to COVID-19 lockdown, recovery and the inevitable competition that will occur between countries for tourists who will be scarcer and therefore more valuable. Countries are competing with a variety of incentives in order to lure visitors. However, persistent first waves that extend into July will put off tourists, further reducing tourism revenues and accelerate job losses and bankruptcies in affected countries. The example of Sweden's response to COVID-19 in this regard will be described. Countries that have COVID-19 relatively under control but experience second waves will also manifest negative tourism effects. Governments and public health must act in unison so as to exit lockdown as speedily and as safely as feasible, with COVID-19 rises that are as low and brief as possible in order to better compete in the tourism sector with other countries. Websites are already online comparing not only safety for travellers vis-à-vis COVID-19 but also the incentives offered by different countries in their attempts to woo tourists in this difficult market.

The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.

In an era which marks an exceptional phase of growth in science and technology, the acute disparities in access to healthcare still persist. So where on one hand scientific advancement in medicine aims at increasing life expectancy, on the other hand there are millions who are denied access to existing medicines. Patents on medicines also pose a significant barrier to access new drugs, especially in low and middle income countries which already suffer from poor health financing mechanisms. The patent laws were built on the assumption of incentivizing the innovators by rewarding them with the exclusive right to produce, sell or market the innovation. The basic premise for granting patents was based on the thought that it would increase investment in research and development promoting dynamic gains through newer innovations. However, evidence found to support this justification is meager. So in a situation where the drug gap still persists and we aim to achieve sustainable development goals by 2030, this paper attempts to focus on understanding how compulsory licensing has been used in selected cases to alleviate the major legal and political barriers to access medicines. The methodology comprises of cross-country comparison of patent framework and compulsory licensing cases. The sample selected for study includes both developed as well as developing countries. The aim is to evaluate the policy approaches used by selected countries to grant compulsory licenses and to identify the best practices for evidence-based policy making on international issues related to pharmaceutical patents. In each case, a driving factor has been the international extension of patent laws through trade agreements; first bilaterally (US-Canada) and subsequently internationally (1995 Uruguay round, under which low- and middle-income countries were granted a grace period until 2005 to comply).

This paper argues that health policies should transcend national boundaries yet should not reach the supranational level. Along with multinational global health efforts, such cross-national health policies are essential to leverage joint efforts by countries learning from their peers that experience similar health system challenges. In our analysis, we used World Bank Health, Nutrition, and Population (HNP) data from 1995 to 2014 for East Asia Pacific (EAP) countries to explore health system comparability across member nations. We applied a hierarchical cluster analysis using Ward's method and a squared Euclidean distance approach to classify 24 EAP countries into four relatively stable clusters based on their (dis)similarities over nine selected health expenditure and health system performance related indicators. One-way analysis of variance (ANOVA) was used to assess the discreteness of the formed clusters. Each cluster had unique characteristics based on the included indicators and health system performance of the member countries. We present transnational health policy recommendations for the EAP region based on both our use of robust methodology and the resulting comparative clusters.

BACKGROUND: Millions of people are treated with antidepressants like selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This clinical practice is based on short-term trials that have exaggerated the benefits and underestimated the harms. We also know too little about long-term harms. AIM: To assess harms of SSRIs and SNRIs that persist after end of drug intake. METHODS: Systematic review of placebo-controlled randomised trials of any length in patients with a psychiatric diagnosis and a follow-up of at least six months. Our primary outcomes were mortality, functional outcomes, quality of life and core psychiatric events. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and checked the references for eligible articles. One researcher extracted data and another checked the data extraction. RESULTS: Our searches returned 9,153 unique records. We included 22 papers for 12 trials on SSRIs. Median intervention and follow-up periods were 15 and 52 weeks, respectively. Median number of randomised participants was 51; only two trials had a drop-out rate below 20%. Outcome reporting was less thorough during follow-up than for the intervention period and only two trials maintained the blind during follow-up. All authors concluded that the drugs were not beneficial in the long term. All trials reported harms outcomes selectively or did not report any. Only two trials reported on any of our primary outcomes (school attendance and number of heavy drinking days). CONCLUSION: The randomised trials currently available cannot be used to investigate persistent harms of antidepressants.

The data supporting the use of "antidepressants" in children and adolescents is largely unavailable. Academic publications give a different picture as regards benefits and harms to publications from regulatory other sources. Despite disagreements about the data driving use of these medicines, in practice "antidepressants" may now be the most commonly used drugs by adolescent girls, and children's mental health services are attracting increasing attention.This paper reviews the difficulties surrounding the data. It outlines a case for benefits (as well as risks) that would require physicians to exert a greater degree of professional autonomy than service managers might wish.

Background: Pharmaceutical companies fund the vast majority of the clinical research that is undertaken on medica- tions but face a conflict of interest between producing good science and results that will enhance the sales of their products. Objectives: To document concrete examples of bias in clinical research induced by pharmaceutical industry sponsorship. Methods: This paper uses a thematic approach to documenting the extent of these biases in the following areas: research question/topic, choice of doses and comparator agents, control over trial design and changes in protocols, early termination of clinical trials, reporting to regulatory authorities, reinterpretation of data, restrictions on publication rights, use of fake journals, journal supplements and symposia, ghostwriting, publication and reporting of results and outcomes. Results: Bias in favour of industry is apparent in every one of the themes examined with the result that research funded by industry undermines confidence in medical knowledge. Conclusions: Bias induced by commercial concerns can be countered in one of two ways. The first is to erect a firewall between the money and the people doing the research and the data analysis. The other approach is to develop an entirely separate funding source that is independent of the pharmaceutical industry.

A second wave of blockbuster products will go off-patent between 2012-2016 in Europe and USA, triggering a rush for the approval of biosimilars or follow-on biologics. Biosimilars are approved through an abbreviated route which relies on a limited safety and efficacy data enabling biogeneric companies to develop these products at lower cost giving a price benefit to the payer. This advantage needs to be weighed against the potential risk that any variation could have with respect to safety and efficacy, especially from long-term use. The paper attempts to rationalize the current "risk" perceptions regarding biosimilars, which have been in existence over a decade in the Indian market. The differences from the Reference product are substantial yet their safety record over a long use warrants a more "realistic" rather than "speculative" assessment, keeping cost-to-benefit as an important criteria and identify ways of mitigating potential risk that are perceived for biosimilar products.

Drawing on the work of numerous psychiatrists and psychopharmacologists and my own observations, I describe how most common psychiatric drugs are not only toxic but can be chronically traumatic, which I define in some detail throughout this paper. In addition to observing this occurrence among numerous of my patients over the past 20 years, I surveyed 9 mental health clinicians who had taken antidepressant drugs long-term. Of these 9, 7 (77%) experienced bothersome toxic drug effects and 2 (22%) had become clearly worse than they were before they had started the drugs. Based on others' and my observations I describe the genesis of this worsened condition which I call the Drug Stress Trauma Syndrome. These drug effects can be and are often so detrimental to the quality of life among a distinct but significant minority of patients that they can no longer be considered trivial or unimportant. Instead, they are so disruptive to many patients' quality of life that their effect becomes traumatic, and are thereby agents of trauma. These observations and preliminary data may encourage others to look into this matter in more depth.

Health care quality and safety is a public policy issue. In the past, issues of quality of care have been largely delegated to the medical profession. Now, however, governments may wish to assume a more active role and will need to know what governance tools are likely to be effective. This paper reviews the evidence on effectiveness for seven processes for governing the physician sector: informing; guiding; educating; reporting; incentivizing; re-licensing; and punishing. There is good evidence for modest to moderate effectiveness of the first three approaches, scant evidence for the next two, and no empirical data on the final two.

Background The relevance of the problem of colorectal cancer (CRC) is evident because of extremely high morbidity and mortality rates, associated with this disease. CRC is mostly diagnosed only at very advanced stages. The reduction of mortality can be achieved by the popularization of screening-methods for early identification of CRC and adenomatous polyps of the colon, which are proved to be precancerous condition. Fecal occult blood test is a well-known method of screening for CRC. The advantages of this method when compared, for example, with colonoscopy are its simplicity and cost-effectiveness.Two techniques are usually used for detection of occult blood in the stool: Hemoccult (Guaiac) test and immunochemical test for hemoglobin. There is no consensus among researchers regarding the validity of these tests for the diagnosis of colorectal cancer. For example, J.S. Mandel (1996) notes 60% sensitivity of Guaiac-test for the detection of the early forms of colorectal cancer, while O.I. Kit (2014) suggets that it is not higher than 30%. There are also various opinions about specificity of these two tests. Objective To review the literature on the validity of the fecal occult blood tests for the diagnosis of CRC. Methods We looked for articles (electronic versions) available for free in the full-text versions, published from June 1, 1990 to December 31, 2014 in Russian or English. The following databases were used for search: E-LIBRARY; Cochrane; MEDLINE; EMBASE; Google search. Only original research papers were analyzed. Literature reviews or systematic reviews were not taken for analyses. Selection criteria 1) use of Guaiac and/or immunochemical fecal occult blood test as screening-tests for the detection of colorectal cancer and/or colon polyps (1 cm or more in diameter) in people older than 45 years; 2) comparing of results with the results of colonoscopy (colonoscopy is counted by majority of the authors as a "gold standard" for the diagnosis of CRC and adenomatous polyps). Results Initial keyword search returned 803 000 results, of which 449 sources were selected. After reading the abstracts, 29 articles that met inclusion criteria were kept. 10 other articles were excluded after that because they did not contain enough data for extraction or did not contain a control group. At the final step 19 articles were used for meta-analysis.Forest plot and Rock curve, which were developed with inclusion of the data from all studies, showed heterogeneity of the data. Additional analyzes were performed in subgroups with different diagnoses and various tests.The sensitivity of the Guaiac test for the diagnosis of colorectal cancer varied from 0.13 to 1.00, and specificity - from 0.69 to 0.99. The sensitivity of the immunochemical test for the diagnosis of CRC ranged from 0.42 to 0.94 with specificity ranging from 0.40 to 1.00.The sensitivity of the Guaiac test for the diagnosis of the colon polyps was between 0.05 and 0.69, and its specificity - from 0.67 to 0.98. The sensitivity of the immunochemical test for the diagnosis of polyps was from 0.24 to 0.75, and its specificity - from 0.40 to 0.97.Bivariate analysis of the validity of Guaiac test and immunochemical method for the diagnosis of colorectal cancer showed better results for the immunochemical test compared to Guaiac test. The tests showed very similar results when used for the diagnosis of polyposis. Bivariate analysis, comparing the validity of tests for the diagnosis of colorectal cancer versus polyposis demonstrated better results for CRC.Multivariate analysis of the validity of the Guaiac and immunochemical tests for the diagnosis of colorectal cancer and polyps also showed better results for detection of colorectal cancer compared with the polyps for both tests. At the same time the highest validity for the diagnosis of CRC was demonstrated for immunochemical analysis. Conclusions 1. The sensitivity of the Guaiac test for occult blood in stool is lower than its specificity.2. Broad dispersion of the validity characteristics of the fecal occult blood tests was observed.3. The validity of tests for occult blood was higher when they were used for detection of colorectal cancer than of colon polyposis.4. The highest validity rate has been demonstrated for the immunochemical test when it was used for colon cancer screening.

Response to The Letter to the Editor by Alfred K¨orblein concerning “Atomic bomb testing and its effects on global male to female ratios at birth” by Victor Grech, International Journal of Risk and Safety in Medicine 27 (2015), 35-44. DOI 10.3233/JRS-150641., In the recently published paper, no direct claims were made since only relatively indirect global ambient radioactivity levels are available.However, available data from reputable sources clearly shows a global annual average population radiation exposure that peaked in 1962 and 1963 shortly after a spike in atomic bomb testing that pre-empted the Partial Test Ban Treaty of 1963. Ambient global radiation levels fell progressively thereafter. Korblein’s statement that WHO data only goes as far back as 1970 is incorrect. For most countries, data is available as far back as 1950, and this data has been used not only to review country level data, but also data at continental level., N/A