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Background: Epidemiological data on anticoagulation for venous thromboembolism (VTE) in prostate cancer are sparse. We aimed to investigate associations between anticoagulation duration and risks of VTE recurrence after treatment cessation and major on-treatment bleeding in men with prostate cancer in Sweden. Methods: Using nationwide prostate cancer registry and prescribing data, we followed 1413 men with VTE and an outpatient anticoagulant prescription following prostate cancer diagnosis. Men were followed to identify cases of recurrent VTE, and hospitalized major bleeding. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between anticoagulation duration (reference ≤3 months) and recurrent VTE using Cox regression. We estimated 1-year cumulative incidences of major bleedings from anticoagulation initiation.Results: The outpatient anticoagulation prescribed was parenteral (64%), direct oral anticoagulant (31%), and vitamin K antagonist (20%). Median duration of anticoagulation was 7 months. Adjusted HRs (95% CI) for off-treatment recurrent pulmonary embolism (PE) were 0.32 (0.09–1.15) for >3–6 months’ duration, 0.21 (0.06–0.69) for >6–9 months and 0.16 (0.05–0.55) for >9 months; corresponding HRs for deep vein thrombosis (DVT) were 0.67 (0.27–1.66), 0.80 (0.31–2.07), and 1.19 (0.47–3.02). One-year cumulative incidences of intracranial, gastrointestinal and urogenital bleeding were 0.9%, 1.7%, 3.0% during treatment, and 1.2%, 0.9%, 1.6% after treatment cessation.Conclusion: The greatest benefit in reducing recurrent VTE risk was with >9 months anticoagulation for PE and >3–6 months for DVT. Risks of major bleeding were low not being substantially different to the risks after treatment cessation.

BACKGROUND At the request of the European Medicines Agency, a Prescriber Guide and Patient Alert Card were developed to increase awareness and understanding about the initiation of rivaroxaban and potential bleeding risk associated with its use. This study evaluated physician and patient awareness and understanding of key safety messages in these educational materials in three waves. RESEARCH DESIGN AND METHODS Three cross-sectional surveys were administered to physicians and one survey was administered to patients (wave 1 only) with recent rivaroxaban experience in France, Germany, Spain, and the United Kingdom. RESULTS Patient and physician knowledge of key safety information in the educational materials was generally high. Patients' knowledge was high for questions related to bleeding risk (80% responded correctly), indication (96%), consulting their doctor (86%-91%), and informing other physicians they are taking rivaroxaban (95%). Physicians' knowledge was particularly high for questions related to bleeding risk (92%-94% across waves), populations at increased risk of serious side effects (76%-94%), contraindications (70%-92%), and invasive procedures (76%-82%). CONCLUSIONS Among patients and physicians, the highest levels of knowledge were on the most important risks, as expected. The Prescriber Guide and Patient Alert Card were found to be useful sources of information.

Over the past decades, there has been an increase in the incidence of asymptomatic hyperuricemia (AHU), which includes an increased level (>360 μmol/L) of uric acid (UA) in the blood serum of patients with no clinical manifestations of gout. AHU is reported in various rheumatic diseases, mainly in osteoarthritis, in which AHU is one of the manifestations of the metabolic syndrome. There is relationship between AHU and pulmonary hypertension in systemic sclerosis, arterial hypertension (AH) in men with seronegative rheumatoid arthritis, extensive cutaneous psoriasis and metabolic disorders in psoriatic arthritis. There are almost no data on AHU in ankylosing spondylitis (AS), which served objective for this work.Objective: to assess the association of AHU with AS duration and activity and the presence of comorbid diseases.Patients and methods. A retrospective analysis of 48 medical histories of patients with diagnosed AS, who were treated in V.A. Nasonova Research Institute of Rheumatology from 2015 to 2019 years, whose serum UA level was >360 μmol/L.Results and discussion. More than half of patients with AS and AHU were overweight, 21% were obese. AH was diagnosed in 43.7% of patients. Stage II–III chronic kidney disease was detected in 16.7% of patients, urolithiasis – in 18.8%. 4 (8.3%) patients had diabetes mellitus. The serum UA level in patients with AS was 422.0 ± 61.6 μmol/L. In patients with AS, an association between AHU and age, duration and disease activity was noted. There was no statistically significant rela- tionship between HG and blood glucose, cholesterol, creatinine levels, body mass index. Correlation analysis revealed a statistically significant relationship between the glomerular filtration rate (GFR) and the age of patients (r=-0.54, p0.05).Conclusion. In AS, an association between an increased level of UA in the blood serum and the duration and activity of the disease, and patient's age, was established.

Objective: to compare depression treatment efficacy with and without antidepressants (ADs) in men and women with bipolar affective disorder (BAD).Patients and methods. We enrolled 100 patients with BAD (F31.3–F31.5 according to ICD-10), including 50 women aged 33.0 [23.0; 50.2] years and 50 men aged 37.5 [29.5; 47.2] years using prospective and retrospective methods. Various antidepressants, normothymics, antipsychotics combinations were used to treat depression. We performed a comparative analysis of treatment efficacy with and without antidepressants in men and women subgroups. Clinical assessment at the baseline and the end of 1, 2, 4, 6-th week of therapy (or at discharge) included a specially developed clinical examination chart and the following psychometric scales: Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression – Severity of illness (CGI-S), Clinical Global Impression – Improvement (CGI-I).Results and discussion. Women tended to have a slower improvement in the condition compared to men. Maximum reduction in MADRS score and a CGI-I, CGI-S higher frequency of clinical improvement and remission was observed in men and women who did not receive antidepressants than patients who did not receive antidepressants. When BAD type was included in the analysis, in patients treated with antidepressants, transient symptoms of the opposite pole occurred in 24.7% of patients of both sexes with bipolar affective I disorder (BAD I) and in 16.8% with bipolar affective II disorder (BAD II). There were no significant gender differences in patients with BAD I, while women predominated in BAD II group (22.5% compared to 7.8% men). No significant treatment-emergent affective switch was observed with tricyclic antidepressants and selective serotonin and norepinephrine reuptake inhibitors in both groups (21; 16.7; 16.7% in men and 28; 21.8; 12.5% in women, respectively). The assessment of intermission revealed that women were significantly more likely to have shorter periods between phases (42% compared to 22% in men). In addition, women were significantly more likely to have shorter periods between phases (42% compared to 22% in men) when the intermission duration was included in the analysis. In some patients with severe depression and infective first-line therapy (anticonvulsants and atypical antipsychotics), antidepressants prescription can increase treatment effectiveness. However, several factors should be considered, such as BAD type and variant, depression severity, treatment-emergent affective switch in history, and gender.Conclusion. A decision about antidepressants' dosage and treatment duration requires a dynamic follow-up of the patient in order to discontinue the antidepressants as fast as possible and decrease the risk of treatment-emergent affective switch and shortening of remission period.

Informal payments for healthcare are widespread in sub-Saharan Africa. They are often regressive, potentially limiting access to quality healthcare, particularly for the most vulnerable, and can have catastrophic consequences for households. Yet there is little empirical research that uses theory-driven hypotheses to explore what influences informal payments and, especially, from health workers’ perspectives. Consequently, we have explored the characteristics of health workers and facilities influencing informal payments in Tanzania, examining two hypotheses: health workers with power and position in the system are more likely to receive informal payments, and transparency and accountability measures can be bypassed by those who can game the system. We conducted a cross-sectional survey of 432 health workers from 42 public health facilities (hospitals and health centres) in 12 district councils from Pwani and Dar es Salam regions in Tanzania. Our dependent variable was whether the health worker has ever asked for or been given informal payments or bribes, while explanatory variables were measured at the individual and facility level. Given the hierarchical structure of the data, we used a multilevel mixed-effect logistic regression to explore the determinants. Twenty-seven percent of 432 health workers ever engaged in informal payment. This was more common amongst younger (

It was found that for the period from X.2017 to III.2020 among patients admitted to a multidisciplinary hospital with acute poisoning with narcotic drugs (NV) and psychoactive substances (PAS), persons in whose biological environment GHB was detected ranged from 20,1 to 40,1%. The prevalence of acute poisoning of the studied class in male patients (86%) of working age (the average age was 34,2 ± 2,9 year) was proved. The patients used 1,4-butanediol (1,4-BD) as a toxicant (GHB) in 95% of cases. The dynamics of the incidence of acute GHB poisoning over a three-year period was uneven, with peaks of maximum values in August (Me = 168), March (Me = 90), and September (Me = 103) and low rates - in June (Me = 71) and total upward trend - y = 6,6573x = 343,23, R2 = 0,053. The severity of acute GHB poisoning at the time of admission on the PSS scale was 2,2 ± 0,57 points, PSSSP – 22,7 ± 2,17 points. Acute GHB poisoning was characterized by signs of toxic-hypoxic encephalopathy, clinically manifested in the form of depression of consciousness to the level of deep stunning - coma. The duration of inpatient treatment of patients was (1,76 ± 3,7, min = 1, max = 35) days, the period of stay in the intensive care unit (ICU) was 4,2 ± 0,4 hours. The increase in hospitalization (more than a day) was due to somatic complications of acute poisoning (nasocomial pneumonia, systemic rhabdomyolysis, acute renal failure) - in 14% of cases, severe withdrawal syndrome with delirious confusion - in 3,5% of cases. The post-intoxication period was characterized by moderate withdrawal symptoms – 13,7 ± 2,1 points, according to the CIWA-Ar scale. The delirious syndrome was characterized by a protracted course (9,5 ± 1,2 days), an atypical clinical picture, and metabolic disorders. The mortality rate due to acute GHB poisoning increased from 0,09 to 0,22%, in 2019 the cause of death was pronounced degenerative changes in internal organs and varying degrees of severity of microcirculation disorders.

The article justifies for the need to identify and to keep track, in practice, of different groups of risks inherent in educational institutions under current conditions of pandemic and post-pandemic transformation of education under the influence of modern world uncertainty. Transformation of education functions in the epoch of digital economy changes the content and types of risks concomitant to the activities carried out by schools. Schools belong to the most conservative types of organizations. However, the environment in which schools operate is constantly changing. An educational institution, as any enterprise, has to engage in the activity aimed at risk management. Manifestation of the risk is, on the one hand, fraught with threats and damage, on the other hand, with opportunities. Assessment of possible threats and risks allows timely projection of undesirable results, creation of a system for situational response to unforeseen circumstances and, in the final analysis, formulation of a strategy for development of the university which would allow achievement of modern high quality education, its fundamentality and conformity to important topical requirements of the personality, society and state. Causes of developing risks characteristic of educational institutions are disclosed. External and internal risks characteristic of educational institutions, sources generating them and the importance of managing them are analyzed. The analysis of risks made reveals multi-varied threats and opportunities in the external and internal envi-ronment of the institution and their ability to have a significant effect on educational, organizational and financial activities of the schools.

Viral infections, hepatitis B and C and herpesvirus-induced infections in particular, are widespread in the population. Recent years have seen the emergence of new viral infections that were previously endemic. Understanding the role of viruses in the pathogenesis of rheumatic diseases (RDs) is of great importance. First, they cause the clinical manifestations characteristic of many RDs (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, and Sjö gren's disease). The author discusses several possible mechanisms of the involvement of viruses in the development of autoimmune disorders: molecular mimicry; polyclonal B cell activation with overproduction of antibodies and immune complexes; T cell activation with cytokine overproduction. Secondly, viral infection can be reactivated during immunosuppressive therapy (also using biological agents), which is widely used to treat RDs. The review presents data on both the most common viruses (hepatitis B and C viruses, HIV, and human herpesviruses types 1–6) and more rare ones (chikungunya virus and polyomavirus) in the Russian population.

Currently, the problem of reactive arthritis (ReA) retains its importance due to the fairly high prevalence of the disease, primarily in Russia. Analysis of epidemiological data allows us to put forward a number of possible reasons explaining the different frequency of ReA in certain regions of the Russian Federation and in other countries. The lecture describes the clinical picture of the disease, as well as analyzes the significance of various laboratory techniques aimed at identifying the causative agent of ReA. The Russian diagnostic criteria for ReA are presented. The main approaches to the therapy of ReA are outlined with an emphasis on the use of antimicrobial drugs. The effectiveness and safety of drug immunocorrection (inducers of interferon, polyoxidonium, immunofan, etc.) in the treatment of urogenital chlamydia in patients with ReA have not been confirmed by data from randomized controlled trials.

Graham-Little-Piccardi-Lassueur syndrome (GLPLS) is a rare syndrome characterized by the triad of cicatricial alopecia of the scalp, non-cicatricial alopecia of the axilla and groin and follicular lichen planus eruptions on the trunk and extremities. GLPLS is considered to be a variant of lichen planopilaris. We report two cases that have fulfilled all of the criteria for GLPLS. The first case was a 71-year-old woman, admitted to the Department of Dermatology for pruritic perifollicullar erythema and scaling of the scalp, cicatricial scalp alopecia and hair loss of the axilla and pubic region for five months. Subsequently, follicular hyperkeratotic eruptions and hyperpigmented macules on the skin of the chest and abdomen appeared. The second case was a 48-year-old man with pruritic follicular papules on the face, trunk and extremities for four months. All of the laboratory examinations in both patients were within normal limits. No alternation in the general condition of the patients was observed. Histological examinations in both patients confirmed the diagnosis GLPLS. The patients were treated with systemic and local corticosteroid resulting in marked improvement of the skin lesions; however, cicatricial scalp alopecia showed no response to the treatment.

Governance failures undermine efforts to achieve universal health coverage and improve health in low- and middle-income countries by decreasing efficiency and equity. Punitive measures to improve governance are largely ineffective. Social accountability strategies are perceived to enhance transparency and accountability through bottom-up approaches, but their effectiveness has not been explored comprehensively in the health systems of low- and middle-income countries in south and Southeast Asia where these strategies have been promoted. We conducted a narrative literature review to explore innovative social accountability approaches in Bangladesh, Bhutan, India, Indonesia, the Maldives, Myanmar and Nepal spanning the period 2007–August 2017, searching PubMed, Scopus and Google Scholar. To augment this, we also performed additional PubMed and Google Scholar searches (September 2017–December 2019) to identify recent papers, resulting in 38 documents (24 peer-reviewed articles and 14 grey sources), which we reviewed. Findings were analysed using framework analysis and categorized into three major themes: transparency/governance (eight), accountability (11) and community participation (five) papers. The majority of the reviewed approaches were implemented in Bangladesh, India and Nepal. The interventions differed on context (geographical to social), range (boarder reform to specific approaches), actors (public to private) and levels (community-specific to system level). The initiatives were associated with a variety of positive outcomes (e.g. improved monitoring, resource mobilization, service provision plus as a bridge between the engaged community and the health system), yet the evidence is inconclusive as to the extent that these influence health outcomes and access to health care. The review shows that there is no common blueprint which makes accountability mechanisms viable and effective; the effectiveness of these initiatives depended largely on context, capacity, information, spectrum of actor involvement, independence from power agendas and leadership. Major challenges that undermined effective implementation include lack of capacity, poor commitment and design and insufficient community participation.

Introduction. The article presents the epidemiological analysis of the structure of acute poisonings with modern psychoactive substances.The aim of the study was to analyze the structure of acute poisonings with modern psychoactive substances among patients hospitalized in General hospitals for 2019 to improve preventive measures.Material and methods. There were used data obtained from the consolidated accounting documents of branches of the Centre for the treatment of acute poisoning. The aggregation of the material used numerical characteristics of the variables with the assessment of their accuracy and reliability, the significance of differences increased non-parametric Pearson criterion.Results. The prevalence in biological fluids in hospitalized patients of γ-hydroxybutyrate was 46.6% (1452), synthetic α-PVP - 20,2% (631), synthetic opioids (methadone) and 13.2% (413). In the overall structure of acute poisonings registered in 2019, the proportion of poisoning with modern drugs amounted to 22.2% (4442), the case-fatality rate is 0.3%, which proves its high epidemiological significance. In the course of studying the dynamic characteristics of the epidemiological process the main peaks of the detection of psychoactive substances among the total number of performed laboratory research were established to be noted in July (52%), August (60,8%) and November (54,3%) 2019 based on the analysis conclusions are made about the feasibility of improving the system of prevention of acute poisonings with modern psychoactive substances at the pre-hospital and hospital stages.

Background Corruption is widespread in Nigeria’s health sector but the reasons why it exists and persists are poorly understood and it is often seen as intractable. We describe a consensus building exercise in which we asked health workers and policy-makers to identify and prioritise feasible responses to corruption in the Nigerian health sector. Methods We employed three sequential activities. First, a narrative literature review identified which types of corruption are reported in the Nigerian health system. Second, we asked 21 frontline health workers to add to what was found in the review (based on their own experiences) and prioritise them, based on their significance and the feasibility of assessing them, by means of a consensus building exercise using a Nominal Group Technique (NGT). Third, we presented their assessments in a meeting of 25 policy-makers to offer their views on the practicality of implementing appropriatemeasures. Results Participants identified 49 corrupt practices from the literature review and their own experience as most important in the Nigerian health system. The NGT prioritised: absenteeism, procurement-related corruption, underthe-counter payments, health financing-related corruption, and employment-related corruption. This largely reflected findings from the literature review, except for the greater emphasis on employment-related corruption from the NGT. Absenteeism, Informal payments and employment-related corruption were seen as most feasible to tackle. Frontline workers and policy-makers agreed that tackling corrupt practices requires a range of approaches. Conclusion Corruption is recognized in Nigeria as widespread but often seems insurmountable. We show how a structured approach can achieve consensus among multiple stakeholders, a crucial first step in mobilizing action to address corruption.

Neurofibromatosis type I is an autosomal dominant genetic disorder with an incidence of about 1 in 3000 births. Apart from the typical skin involvement NF1 may affect multiple organs with ocular, neurological, skeletal and cardiovascular manifestations. We present a case of a 38-year-old man with multiple café-au-lait macules and hundreds of neurofibromas disseminated on the trunk and extremities dating from childhood. To establish the diagnosis and to exclude any complications we performed multiple examinations, including skin biopsy, laboratory investigations, ophthalmologic assessment, consultations with a neurologist, internist and orthopedist, etc. The treatment of cutaneous NF1 is mainly symptomatic. Surgical excision aims to achieve cosmetic results. Recently novel and perspective conservative therapies have been investigated. In order to ensure better outcome for the patients with NF1 long-term multi-disciplinary approach is advised.

According to statistics from the Ministry of Health of Russia, the incidence of reactive arthropathies varies significantly by region and year. In ICD-10, reactive arthropathies include reactive urogenic arthritis (M02.3), other reactive arthropathies (M02.8), and reactive arthropathies, unspecified (M02.9). Information on reactive arthritis (ReA) cannot be extracted from these data.Objective: to specify the number of patients with ReA among inpatients with reactive arthropathies.Patients and methods. A retrospective analysis of 224 case histories was made in the patients treated at the V.A. Nasonova Research Institute of Rheumatology Clinic in 2009–2018 and discharged with Codes M02.3, M02.8, and M02.9.Results and discussion. Nineteen out of the 224 patients were diagnosed with reactive urogenic arthritis (M02.3), 128 had reactive arthropathies (M02.8), and 77 had reactive arthropathies, unspecified (M02.9). All the 19 patients with this diagnosis met the criteria for reactive urogenic arthritis. Among the 128 patients with reactive arthropathies, 77 met the ReA criteria, 8 of them were found to have reactive urogenic arthritis, since the clinical picture had a triad consisting of arthritis, urogenic or enterocolitic infection, and conjunctivitis. Twenty-five out of the 77 patients discharged with Code M02.9 met the criteria for certain ReA and 6 did those for possible ReA. Thus, the diagnosis fitted the criteria for ReA in only half (56.7%) of the patients with reactive arthropathies.Conclusion. The performed investigation revealed that clinicians paid insufficient attention to the diagnosis of ReA and that statisticians did this to the coding of reactive arthropathies.

Background: Nigeria has a huge burden of corruption, with the health system especially vulnerable. The media can play a role in tackling it, by shaping the narrative around it. However, its influence depends on the extent and framing of its reporting on corruption. This paper reviews, for the first time, coverage of corruption in the health system in the Nigerian print media. Methods: The top 10, by circulation, newspapers in Nigeria were selected and searched using the LexisNexis database for articles covering corruption in the health sector over a 2-year period (2016–2018). Two newspapers are not included in the database and were searched manually. 135 articles were identified and subject to content and framing analyses. Results: The Punch newspaper had the highest number of publications focussed on corruption in the health sector. The National Health Insurance Scheme (NHIS) was the organization attracting most coverage, followed by the Federal Ministry of Health. Corruption in the health sector was predominantly framed as a political issue. Most coverage was episodic, focused on the details of the particular case, with much less thematic, delving into underlying causes. Corruption was most often attributed to a lack of accountability while enforcement was the most frequent solution proffered. Conclusion: This study highlights the potential role of media analyses in helping to understand how newspapers cover corruption in the health sector in Nigeria. It argues that the media has the potential to act as an agent of change for tackling corruption within the health sector.

The paper examines the cyclical and structural changes in world trade that affect its development and dynamics. It is determined that each of the stages of development of international trade is characterized by certain factors and development trends; features that reflect the level of internationalization of production and the role of international trade in the development of national economies; priority methods of regulating foreign trade by most countries. The study of the dynamics of world trade since 1800, taking into account its general upward trend, has identified a certain cycle of its development, which at different times was caused by changes in the structure of productive forces, development of new technologies, actions and factors of political and military nature. The fluctuations obtained as a result of the study have different durations and reach the lowest points of fall and the highest points of growth of world trade at different intervals. The most stable in terms of frequency and amplitude of fluctuations in world trade are the periods from mid-1850 to the First World War and 1950-1974. The most critical is the period 1915-1938, for which cyclical fluctuations in world exports are characterized by the highest amplitude. Also, statistical analysis of the data allows to determine the cyclical development of the world economy and its synchronicity with the cyclical fluctuations of world trade with the definition of certain cycles equal to 15-18 years. The current stage is characterized by a slowdown in world export growth. In 2009, the decline in economic activity was the largest among all global recessions. The data show that trade is not even keeping pace with world production growth, and over the past eleven years its average rate has been 2.2% (with the exception of strong surges in 2010-2011) against 3.07% of world GDP growth. The lack of trade dynamism in the last ten years is explained by the weakness of aggregate demand, especially in the euro area. The slowdown in world trade is also linked to the completion of the integration of China and Central and Eastern Europe into the world trading system. The third explanation is the increasing appeal of countries around the world to protectionist measures in international trade in order to stabilize national economies. Many countries have temporarily abandoned normal trade conditions and opted for a more restrained format of mutual trade with other countries. Determining the prospects for the development of the world economy and international trade, WTO experts provide a range of forecast forecasts for 2020 - from 5% to 11% and from 8% to 20.4%, respectively.

In modern conditions, ensuring economic security at various levels is a priority task for any state. One of the elements of the formation of the state economy is business entities. Thus, enterprises are forced to adapt to the conditions of political and socio-economic instability, to solve the most difficult problems and apply methods to prevent threats to their functioning. This article reveals the essence of the economic security of an enterprise, gives a definition of the company's transparency, and also highlights the risks and problems of a "transparent" company in the context of ensuring economic security. Based on the analysis, recommendations were developed on the use of modern information technology solutions for the presentation of integrated reporting of the organization while ensuring the information component of the economic security of the enterprise.

This book accumulates authors’ practical knowledge and experience in pig pathology. It contains a big volume of theoretical and illustrative material, collected during authors’ many years long pig dissecting practice on pig farms in Russia. Most of the diseases presented in the book are diseases of the modern livestock of Russian pig farms, studied by the authors in the last 10 years until 2021. There are more than 460 original photographs of pig organs with pathological changes due to different diseases and pathological conditions. Methodological material on pig necropsy is also presented, as well as differential diagnosis tables.

Simple Summary The increasing number of data supporting use of a personalized approach in cancer treatment, is changing the path of patient's management. In the same time, the availability of technologies should allow patients to receive the best test for the specific individual condition. This is theoretically true, when a specific test is designed for the specific disease condition, while it is difficult to implement in the setting of agnostic therapies. Financial sources availability related to the non homogeneous health systems working in the different countries do not allow for an immediate implementation of the technologies and test commercially available. Future perspectives for targeted oncology include tumor-agnostic drugs, which target a given mutation and could be used in treating cancers from multiple organ types. Therefore, the present paper is aimed to both underline a how much important is this new view and also to sensitize the international bodies that supervise health policies at the decision-making level, with the aim of harmonizing cancer treatment pathways in at least all European countries. Rapid and continuing advances in biomarker testing are not being matched by uptake in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions-notably BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, the implementation of genetic testing in clinical routine setting is still challenging. Development is impeded by country-related heterogeneity, data deficiencies, and lack of policy alignment on standards, approval-and the role of real-world evidence in the process-and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework-starting with an update to outdated recommendations. We show herein the main issues and proposals that emerged during the previous advisory boards organised by the European Alliance for Personalized Medicine which mainly focus on possible scenarios of harmonisation of both oncogenetic testing and management of cancer patients.

Background: Psoriasis is a chronic cutaneous T-cell mediated disease, which has been associated with many comorbidities, especially with metabolic disorders such as dyslipidemia, diabetes mellitus, obesity, and metabolic syndrome, many of which are themselves risk factors for other diseases. The goal of this study was to evaluate the presence of dyslipidemia and hyperglycemia in patients with psoriasis. Methods: We compared 48 inpatients with plaque psoriasis aged 29-79, hospitalized between March 2018 and February 2019, to 48 age- and gender-matched controls. We evaluated dyslipidemia and hyperglycemia using enzymatic methods as part of a standard blood test, or medication history indicative of ongoing treatment of dyslipidemia and/or hyperglycemia. Hypertension was evaluated by registering blood pressure greater than 140/90 mmHg or ongoing antihypertensive treatment. Smoking habits were also noted. Results: There were statistically significant differences between psoriasis patients and controls for elevated total cholesterol (p=0,028), elevated LDL (p=0,015), hypertriglyceridemia (p=0,006), and hyperglycemia (p=0,021). The two groups had statistically insignificant differences for lowered HDL (p=0,084), hypertension (p=1), and smoking (p=0,836). Conclusion: Hypertriglyceridemia, hyperglycemia, and elevated LDL cholesterol were more prevalent in the group containing psoriatic patients compared to the control group. This indicates that further investigation of metabolic abnormalities should be conducted in psoriatic patients which could greatly benefit from early treatment of the aforementioned underlying conditions.

The emergence of new synthetic narcotic drugs is noted all over the world. The situation causes significant difficulties for toxicologists, resuscitators, narcologists, and clinical laboratory diagnostics doctors due to the lack of available data on the clinical picture of poisoning by these compounds and laboratory diagnostic methods. In most cases, the clinical picture of drug intoxication or poisoning with new synthetic substances differs from the symptoms caused by previously known drugs, such as cocaine or opiates. Therefore, chemical toxicological research is one of the important aspects for establishing the fact of intoxication or poisoning.

The concept of the relief-frequency characteristic of laser scanners is introduced. The necessity of using the relief-frequency characteristic is substantiated with a description of the frequency properties of laser scanners. A procedure for experimental determination of the relief-frequency characteristic of laser scanners has been developed, and studies were carried out. It is shown that the relief-frequency characteristic makes it possible to estimate most precisely the error of the laser scanner and to determine the range of reproduced spatial frequencies when scanning a relief. The proposed procedure can be used to describe the metrological characteristic of laser scanners.

Nonsuicidal self-injuries (autotomy, self-inflicted destruction, self-mutilation) is a variant of autoaggression in a patient without the intent to take his/her own life. Patients with the consequences of self-injuries receive help from physicians of various specialties, who often cannot determine their motivation for autoaggressive actions, since it is associated with mental disorders. The paper presents data on phenomenology, some classifications and motivation of nonsuicidal self-injuries. Various mental disorders are noted to be the most common cause of autoaggressive behavior. The paper describes a clinical case of a female patient who has mutilated her face for a long time, hiding the cause of her autoaggressive action. A detailed clinical and psychopathological analysis of her medical history and mental status allowed for classifying hypochondriacal delirium within schizophrenia as a cause of self-mutilating actions. The motivation for this behavior was to fight against a pseudotumor, for which the patient suffered pain and prolonged suppurative processes on the skin of the face, without visiting physicians.

Informal payments are widespread in many healthcare systems and can impede access to healthcare and thwart progress to achieving universal health coverage, a major element of the health-related Sustainable Development Goals. Gender may be an important driver in determining who pays informally for care, but few studies have examined this, particularly in low- and middle-income countries. Our study aimed to examine gender disparities in paying informally for healthcare in Africa. We used Afrobarometer Round 7 survey data collected between September 2016 and August 2018 from 34 African countries. The final sample was composed of 44 715 adults. We used multiple logistic regression to evaluate associations between gender and paying informally to obtain healthcare. Our results show that 12% of women and 14% of men reported paying informally for healthcare. Men were more likely to pay informally for healthcare than women in African countries [odds ratio 1.22 (95% confidence interval 1.13–1.31)], irrespective of age, residential location, educational attainment, employment status, occupation and indicators of poverty. To make meaningful progress towards improving universal healthcare coverage in African countries, we must improve our understanding of the gendered aspects of informal payments in healthcare, which can act as both a barrier to accessing care and a determinant of poor health.

The rise of digital mobile communications has made possible novel research methods that can provide a better understanding of patients’ experience of non-communicable diseases. This study explores the opportunities and challenges in employing “digital diaries” via mobile phones to track the lived experiences of people with hypertension in the Philippines. Following in-depth interviews, 40 hypertensive adults were invited to submit digital diaries over 12 months. Mobile phones were found to be an efficient way of reaching participants, although it was difficult to collect in-depth narratives about their experiences using the medium beyond nominal responses about symptoms and treatment. Possible explanations include the asymptomatic nature of hypertension, which limited the participants’ experiences of the illness, as well as the platform itself, which our mostly-elderly, low-income participants may not be comfortable with. Despite these challenges, “digital diaries” hold potential for the study of other chronic conditions, provided that researchers engage in extensive co-production with participants to understand their preferences. Researchers also need more training in the use of these methods appropriately as part of a suite of methods for capturing the experience of people living with chronic illness.

Background and Aims Acute kidney injury (AKI) is amongst the most common in-hospital complications especially in old age. Epidemiological data on incidence rates (IR) of nosocomial AKI in individuals aged 70+ years, stratified by age, gender and pre-existing diseases are scarce because older adults are usually underrepresented in clinical research. Method We used data from the Berlin Initiative Study (BIS), a longitudinal, population-based cohort of adults aged ≥70 with biennial follow-up visits (including blood and urine tests) in combination with claims data from the AOK Nordost insurance fund to complement information on diagnoses and in-hospital procedures (based on ICD-10 and OPS coding). Nosocomial AKI was defined as documented in-hospital diagnosis (ICD-10: N17.xx) excluding cases with AKI as admission diagnosis. Incidence rates (IR) and 95% confidence intervals (CI) of the first nosocomial AKI were calculated with the number of incident cases during observation divided by the total person-years of follow-up, for AKI cases truncated at the first incidence of nosocomial AKI. IR are reported by age strata, sex and preexisting diseases (diabetes, arterial hypertension, atrial fibrillation, heart failure, angina pectoris, peripheral artery disease and impaired kidney function). Results In 2020 individuals (mean age 80.5 years; 52.6% women), 383 developed nosocomial AKI over the median [IQR] follow up time of 8.8 [5.9-9.3] years (Fig.1). The IR of nosocomial AKI was 26.8 (95%CI 24.1-29.6) per 1000 person years among all patients, with higher IR in men compared to women, and - when stratified by age - lowest IR in age category 70-75 versus the highest IR in age category of ≥ 90 years (Fig.1). IR per 1000 person years were higher in patients with diabetes mellitus (IR: 39.3 vs 22.7), arterial hypertension (IR: 31.1 vs 12.2), chronic heart failure (IR: 41.9 vs 22.3), angina pectoris (IR: 37.6 vs 25.7), peripheral artery disease (IR: 55.0 vs 25.1) and impaired kidney function (IR: 43.3 vs 12.4), respectively (Fig.2). Conclusion Nosocomial AKI is an in-hospital complication common in older adults with IRs rising continuously with age above the age of 70 years. IR of AKI are considerably higher in patients with cardiovascular comorbidities. A better understanding of the patient population at risk is of great clinical relevance when aiming to improve prevention strategies.

Objective: to analyze trends in the incidence and prevalence of major rheumatic diseases (RDs) among the adult population of Russia in 2013 to 2017.Material and methods. The trends in the incidence and prevalence of major RDs were analyzed among the adult population of Russia over 5 years (in 2013 to 2017) according to the statistical reports of the Ministry of Health of Russia, which are based on the data of accounting form No. 12 “Information on the number of diseases recorded in patients living in the region served by a health care facility”. The analysis was carried out in eight Federal Districts (FDs).Results and discussion. Over 5 years, there was a slight increase in the number of patients (by 21,677) with musculoskeletal diseases (MSDs) among the adult population of Russia and a small (0.64%) decrease in their prevalence. Noninflammatory osteoarticular diseases, such as osteopathy, chondropathy, deforming dorsopathies, and arthropathies (74%), were leading among MSDs. The incidence of osteoarthritis (OA) was highest: more than 4 million people, which is a quarter of all RDs. The increase in the number of patients with OA was observed annually, but was insignificant for 5 years – 190.400 people; the prevalence of OA increased by 3.7%. The largest number of patients with OA was registered in the Central (1.1 million) and Volga (0.9 million) FDs.The incidence of rheumatoid arthritis (RA) increased insignificantly in the Central, Northwestern, Southern, Ural, and Siberian FDs and decreased in the Volga and Far Eastern FDs. There was a substantial (21%) decrease in the prevalence of RA in the North Caucasian FD. There was a significant increase in both the incidence and prevalence of spondylopathy (SP) in almost all FDs, except for the Volga FD. In contrast, these indicators for reactive arthritis (ReA) had decreased in five FDs by 2017 and slightly increased in three FDs. These indicators fluctuated in almost all FDs for 5 years.The incidence and prevalence of psoriatic arthritis (PsA) showed a annual increase particular in the North Caucasian FD by 29%. The incidence of PsA slightly decreased only in the Siberian FD. The number of patients with systemic connective tissue diseases (SCTD) increased insignificantly in all FDs, with the exception of the North Caucasian FD, in which the prevalence of SCTD reduced dramatically (by 42%). The incidence of osteoporosis (OP) fluctuated during 5 years; by 2017, there had been its rise in five FDs, especially in the Northwestern FD. The prevalence of OP was found to increase significantly (by 33.5%) in the North Caucasian FD.Evaluation of the age composition of patients showed that OA and OP were more common in the older age group; and ReA; SP and SCTD were in the younger age one. There were no differences in the age composition of patients with RA.Conclusion. The analysis of the statistical incidence and prevalence rates of RDs in the adult population of Russia suggests that there is an increase in the number of patients with this pathology throughout the country.

Individual well-being and self-esteem related to appearance of patients with multiple seborrheic keratoses (MSK), as well asan original strategy for complete removal of all lesions with CO2 laser are discussed. Presented are examples from our dermatological practice illustrating negative psycho-social impact of multiple SK on individual well-being. Seborrheic keratosis is considered a widespread dermatosis, as well as a cosmetic issue for its presence creates an overall impression of prematurely aged, and a “shabby” looking skin. Individuals with multiple SK often suffer low self-esteem in terms of their appearance which may improve after the aesthetic CO2 laser complete elimination of MSK lesions.

The field of health policy and systems research (HPSR) has grown rapidly in the past decade. Examining recently aggregated data from the Global Symposia on Health Systems Research, a key global fora for HPSR convened by the largest international society—Health Systems Global (HSG)—provides opportunities to enhance existing research on HPSR capacity using novel analytical techniques. This addresses the demand not only to map the field but also to examine potential predictors of acceptance to, and participation at, these global conferences to inform future work and strategies in promoting HPSR. We examined data from the abstracts submitted for two Global Symposia on Health Systems Research in 2016 and 2018 by type of institution, countries, regional groupings and gender. After mapping hotspot areas for HPSR production, we then examined how the corresponding author’s characteristics were associated with being accepted to present at the Global Symposia. Our findings showed that submissions for the Global Symposia increased by 12% from 2016 to 2018. Submissions increased across all participant groups, in particular, the for-profit organizations and research/consultancy firms showing the highest increases, at 58% for both. We also found reduced submissions from high-income countries, whereas submissions from low- and middle-income countries (LMICs), Sub-Saharan Africa and Latin America, increased substantially revealing the inclusivity values of Symposium organizers. Submissions increased to a larger extent among women than men. Being a woman, coming from a high-income country and having multiple abstracts submitted were found to be significant predictors for an abstract to be accepted and presented in the Symposia. Findings provide critical baseline information on the extent of interest and engagement in a global forum of various institutions and researchers in HPSR that can be useful for setting future directions of HSG and other similar organizations to support the advancement of HPSR worldwide.

In a number of cases, systemic therapy for rheumatoid arthritis (RA), including disease-modifying anti-rheumatic drugs, biological agents, glucocorticoids (GCs), and nonsteroidal anti-inflammatory drugs, fails to completely suppress joint inflammatory changes in the patients. Therefore, local methods are widely used in the combination therapy of RA. Intra-articular injection of hyaluronic acid (HA) is a highly local treatment modality. HA can be used as initial therapy when it is necessary to achieve rapid clinical improvement, or at a later stage of the disease, in exacerbation of arthritis. However, in some patients the effect of intra-articular HA can be short-lasting, and a favorable result can be obtained with local radiotherapy. It is based on powerful irradiation of the inflamed synovium, which is provided by intra-articular injection of radioactive isotope colloids. In Russia, RA was successfully treated with colloidal Au-198, but its production was ceased in the 1990s, and agents for radioisotope synovectomy have been long unavailable. Tungsten-188/Rhenium-188generator has been recently designed in Russia, which allows Rhenium-188 to be obtained in clinics. Preclinical trials have shown that intra-articular injection ensures good fixation of the drug in the knee joint with its insignificant accumulation in the liver and other non-target organs and tissues. Introduction of this drug into routine clinical practice can markedly improve the efficiency of treatment in patients with chronic arthritis.

The susceptibility of the field populations of the house fly Musca domestica L. (Diptera:Muscidae) from a livestock farm of the Tyumen region, Russia, to six insecticides (deltamethrin, cypermethrin, thiamethoxam, permethrin, fipronil, chlorfenapyr) is reported. After a forced contact of adult flies of susceptible strains and first generation of field populations with the residues of insecticides at the bottom of glass cups, the median lethal dose of each insecticide was determined by probit analysis. According to the resistance ratio, the susceptibility of the evaluated field population to insecticides increased in the order: cypermethrin < deltamethrin < permethrin ≤ chlorfenapyr < thiamethoxam < fipronil.

This article analyses individual innovative behaviour of employees in domestic and foreignowned companies operating in Russia. The authors focus on personal and organisational factors affecting the three stages of innovative processes at the micro-level: generating, proposing and implementing new ideas. Empirical analysis is based on the survey of 623 white-collar employees and managers in 17 private-owned organisations in Russia. In both domestic- and foreign-owned companies skilled workers and those having higher status in organisations — men; supervisors; having two or more higher education degrees; assessing their professional competencies as high — are characterized by higher innovative activity at the fist and second stage. At the third stage of the innovative process, employees of foreign-owned companies tend to report higher effectiveness of their innovative suggestions. The authors conclude that the organisational environment of foreign-owned companies is generally more conducive to innovative activities compared to Russian domestic companies. Better innovative performance of foreign-owned companies can be explained by their managerial incentives for employees’ innovative behaviour. In particular, direct incentives of individual innovative activity such as financial rewards or career promotions are more common in foreign-owned companies. Managers of these companies are less authoritarian and tend to use participative techniques of decision making. Employees of foreign-owned companies are more focused in their innovative activities and concentrated on a narrower range of issues than that of domestic Russian organisations. The authors underline the importance of fostering an innovative-friendly organisational environment that would provide formal and informal, tangible and intangible rewards for employee innovative behaviour. These rewards should create a synergy among personal and organisational antecedents of employee innovative activities. Selection and hiring of intrinsically motivated personnel, creation of an organisational climate that is favorable for the free flow of ideas and access to information, as well as direct incentives for innovative activities, are seen as crucially important.

Despite an expanding literature on Ebola-response, few studies detail or reflect on the responses of diverse systems of care. Little is known about how, why or in what ways, strategies of ill-health management were enacted locally, how health-systems power, authority and hierarchy were perceived and contested, or how other social systems, institutions and relationships shaped the response. This paper presents an interdisciplinary analysis of local responses in two early affected districts in Sierra Leone. Drawing on anthropological theories of social ordering and assemblage, we present an analysis of contrasting infection chains in three extended case studies from Bo and Moyamba districts. In contrast to previous scholarship which has understood local actions as being reactive (supporting or obstructing) to a national Ebola response, we show that local arrangements lead and shape responses. Our cases show how multiple, entangled, dynamic and co-existing systems of care influence these responses. Some individuals and communities collaborated with health authorities on measures like reporting and quarantine, others actively opposed them, or played an intermediary role. Collectively, formal health systems actors, local authorities and ordinary citizens negotiated and enacted new arrangements. These arrangements involved compromise and sometimes power was reconfigured. They were also shaped by wider political and historical contexts and by availability or absence of formal healthcare resources. Our research shows the critical importance of understanding how institutions and people involved in healthcare enact diverse “systems of care” and thereby shape Ebola response. Most importantly, our work underlines the need for alignment between formal health-systems and wider social, cultural, political and economic forms of organisation at family and community levels to improve crisis-response and promote sustainable care. In particular, health systems responders need to identify and engage with key brokers – or arrangers – in frontline care systems, with whom mutually acceptable, and effective, reconfigurations of care can be achieved.

Hypertension, a major risk factor for non-communicable diseases, remains poorly controlled in many countries. In the Philippines, it is still one of the leading causes of preventable deaths despite the accessibility and availability of essential technologies and medicine to detect and treat hypertension. This paper characterizes the 'therapeutic itineraries' of people with hypertension from poor communities in rural and urban settings in the Philippines. We employ longitudinal qualitative methodology comprised of repeat interviews and digital diaries using mobile phones from 40 recruited participants in 12 months. Our findings demonstrate that therapeutic itineraries, rather than being organized according to categories that stem from the structure of the health system (i.e., diagnosis, treatment, follow-up, adherence), diverge from clinical pathways. Therapeutic itineraries begin at a stage we label as 'pre-diagnosis' (PD). Following this, itineraries diverge according to two possible entry points into the healthcare system: via incidental diagnosis (ID) whereby participants were diagnosed with hypertension without deliberately seeking care for hypertension-related symptoms and symptom-driven diagnosis (SD) whereby their diagnosis was obtained during a clinical encounter specifically prompted by hypertension-related symptoms. Participants whose itineraries follow the SD route typically oscillated between periods of regular and intermittent medical treatment, while participants who were diagnosed incidentally (ID) typically opted for self-care As we follow our participants' therapeutic itineraries, we explore the confluence of factors informing their care journey, namely, their conceptions of hypertension, their social relationships, as well the choices and trade-offs they make. We conclude with policy implications from our findings, chief of which is our proposition that models of care based on mere access and availability of clinical interventions fail to reflect the complexity of people's lay understanding and their lived experiences of hypertension and are thus ultimately unhelpful in improving its control.

The health sector consistently appears prominently in surveys of perceived corruption, with considerable evidence that this has serious adverse consequences for patients. Yet this issue is far from prominent in the international health policy discourse. We identify five reasons why the health policy community has been reluctant to talk about it. These are the problem of defining corruption, the fact that some corrupt practices are actually ways of making dysfunctional systems work, the serious challenges to researching corruption, concerns that a focus on corruption is a form of victim blaming that ignores larger issues, and a lack of evidence about what works to tackle it. We propose three things that can be done to address this situation. First, seek consensus on the scale and nature of corruption. Second, decide on priorities, taking account the importance of the particular problem and the feasibility of doing something about it. Third, take a holistic view, drawing on a wide range of disciplines.

Objective: to evaluate the efficiency of combination therapy with methotrexate (MTX) and hydroxychloroquine (HC) in rheumatoid arthritis (RA) in real clinical practice.Patients and methods. The investigation enrolled 430 patients with documented RA who had been followed up for 16 weeks by rheumatologists in different regions of the country. Individual schedules were filled out for the patients, by adding demographic, clinical, and laboratory parameters that made it possible to assess the activity of the disease and to estimate the level of glucose, cholesterol, and low-density lipoproteins (LDL). The results of the investigation were evaluated at the inclusion of patients in it and then at 8 and 16 weeks. Taking into account the insufficient previous effect of MTX, the treatment was enhanced by HC.Results and discussion. By the end of the investigation, the combination therapy with MTX + HC led to significant decreases in the number of swollen and tender joints, the duration of morning stiffness, the severity of pain, and the integrated DAS28 index. The therapy showed a positive effect on the levels of fasting glucose, cholesterol, and LDL. The quality of life improved in patients by Visit 3. The results obtained are in good agreement with the data by foreign and Russian investigators on the greater efficiency of combination therapy with MTX + HC than that of MTX monotherapy and on the pleiotropic (hypolipidemic and hypolipidemic) effect of HC.Conclusion. It is concluded that in Russian practice when monotherapy with MTX shows an insufficient effect or its high doses cannot be administered to enhance the efficacy of RA therapy, it is possible to use a combination of MTX + HC, especially in older patients with comorbidity (hyperglycemia and hypercholesterolemia).

Objective: to study the clinical features of depression in women compared with men. Patients and methods. 120 women aged 18-65 years with recurrent depressive disorder (RDD; ICI-10 F33) (a study group) and 67 men of the same age with RDD (a control group) were clinically examined using a specially designed schedule and the Montgomery-Asberg Depression Scale. Results. The clinical picture and the course of RDD have gender differences. The earlier onset of the disease in women with a large number of depressive attacks and lower quality remissions is due to the relationship and mutual influence of menstrual and reproductive function and depression. Such typical symptoms of endogenous depression, as slow thinking, anhedony, decreased sleep duration and early morning awakenings, as well as diurnal swings of mood with its deterioration in the morning, were characteristic for most women and men. The pattern of depression in women is more commonly characterized by anxiety; ideas of self-accusation; suicidal thoughts; avoidance of contacts with others; weakness; fatigue; decreased or increased appetite; sleep onset insomnia; lack of sleep feeling. That in men is more often marked by symptoms, such as melancholy; motor retardation; decreased motivation; somatic symptoms of depression (tachycardia, constipation); comorbid panic attacks; and concomitant diseases of the cardiovascular, respiratory and genitourinary systems. Men more frequently abuse alcohol and other psychoactive substances. Conclusion. The revealed features of depression in women and men will be able to more accurately diagnose and to prescribe adequate therapy.

Background: \ud Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy.\ud \ud Methods: \ud We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5–12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64).\ud \ud Findings: \ud 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0–94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96–1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of −0·040 (95% central range −0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years.\ud \ud Interpretation: \ud Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate.\ud \ud Funding: \ud National Institute for Health Research Health Technology Assessment Programme.

ObjectiveTo evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF).MethodsWe undertook a population-based cohort study with nested case–control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked registries from the Region of Southern Denmark (RSD). Patients with AF (76 882 UK, 41 526 RSD) were followed to identify incident IS cases during 2016–2018. Incident IS cases were matched by age and sex to controls. Adjusted ORs for OAC discontinuation (vs current OAC use) were calculated using logistic regression.ResultsWe identified 616 incident IS cases in the UK and 643 in the RSD. ORs for IS with any OAC discontinuation were 2.99 (95% CI 2.31 to 3.86, UK) and 2.30 (95% CI 1.79 to 2.95, RSD), for vitamin K antagonist discontinuation they were 2.38 (95% CI 1.72 to 3.30, UK) and 1.83 (95% CI 1.34 to 2.49, RSD), and for non-vitamin K antagonist oral anticoagulant discontinuation they were 4.59 (95% CI 2.97 to 7.08, UK) and 3.37 (95% CI 2.35 to 4.85, RSD). ORs were unaffected by time since discontinuation and duration of use. Annually, up to 987 IS cases in the UK and 132 in Denmark could be preventable if OAC therapy is not discontinued.ConclusionsOur results suggest that patients with AF who discontinue OAC therapy have a significant twofold to threefold higher risk of IS compared with those who continue therapy. Addressing OAC discontinuation could potentially result in a significant reduction in AF-attributed IS.

Many microbial producers of coenzyme B12 family cofactors together with their metabolically interdependent pathways are comprehensively studied and successfully used both in natural ecosystems dominated by auxotrophs, including bacteria and mammals, and in the safe industrial production of vitamin B12. Metabolic reconstruction for genomic and metagenomic data and functional genomics continue to mine the microbial and genetic resources for biosynthesis of the vital vitamin B12. Availability of metabolic engineering techniques and usage of affordable and renewable sources allowed improving bioprocess of vitamins, providing a positive impact on both economics and environment. The commercial production of vitamin B12 is mainly achieved through the use of the two major industrial strains, Propionobacterium shermanii and Pseudomonas denitrificans, that involves about 30 enzymatic steps in the biosynthesis of cobalamin and completely replaces chemical synthesis. However, there are still unresolved issues in cobalamin biosynthesis that need to be elucidated for future bioprocess improvements. In the present work, we review the current state of development and challenges for cobalamin (vitamin B12) biosynthesis, describing the major and novel prospective strains, and the studies of environmental factors and genetic tools effecting on the fermentation process are reported.

Background Social innovation has been applied increasingly to achieve social goals, including improved healthcare delivery, despite a lack of conceptual clarity and consensus on its definition. Beyond its tangible artefacts to address societal and structural needs, social innovation can best be understood as innovation in social relations, in power dynamics and in governance transformations, and may include institutional and systems transformations. Methods A scoping review was conducted of empirical studies published in the past 10 years, to identify how social innovation in healthcare has been applied, the enablers and barriers affecting its operation, and gaps in the current literature. A number of disciplinary databases were searched between April and June 2020, including Academic Source Complete, CIHAHL, Business Source Complete Psych INFO, PubMed and Global Health. A 10-year publication time frame was selected and articles limited to English text. Studies for final inclusion was based on a pre-defined criteria. Results Of the 27 studies included in this review, the majority adopted a case research methodology. Half of these were from authors outside the health sector working in high-income countries (HIC). Social innovation was seen to provide creative solutions to address barriers associated with access and cost of care in both low- and middle-income countries and HIC settings in a variety of disease focus areas. Compared to studies in other disciplines, health researchers applied social innovation mainly from an instrumental and technocratic standpoint to foster greater patient and beneficiary participation in health programmes. No empirical evidence was presented on whether this process leads to empowerment, and social innovation was not presented as transformative. The studies provided practical insights on how implementing social innovation in health systems and practice can be enhanced. Conclusions Based on theoretical literature, social innovation has the potential to mobilise institutional and systems change, yet research in health has not yet fully explored this dimension. Thus far, social innovation has been applied to extend population and financial coverage, principles inherent in universal health coverage and central to SDG 3.8. However, limitations exist in conceptualising social innovation and applying its theoretical and multidisciplinary underpinnings in health research. Graphic abstract

IntroductionThe emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household transmission in the population spread of SARS-CoV-2, and of host immunity in limiting transmission, is poorly understood. This paper describes a protocol for a prospective observational study of a cohort of households in Liverpool City Region, UK, which addresses the transmission of SARS-CoV-2 between household members and how immunological response to the infection changes over time.Methods and analysisHouseholds in the Liverpool City Region, in which members have not previously tested positive for SARS-CoV-2 with a nucleic acid amplification test, are followed up for an initial period of 12 weeks. Participants are asked to provide weekly self-throat and nasal swabs and record their activity and presence of symptoms. Incidence of infection and household secondary attack rates of COVID-19 are measured. Transmission of SARS-CoV-2 will be investigated against a range of demographic and behavioural variables. Blood and faecal samples are collected at several time points to evaluate immune responses to SARS-CoV-2 infection and prevalence and risk factors for faecal shedding of SARS-CoV-2, respectively.Ethics and disseminationThe study has received approval from the National Health Service Research Ethics Committee; REC Reference: 20/HRA/2297, IRAS Number: 283 464. Results will be disseminated through scientific conferences and peer-reviewed open access publications. A report of the findings will also be shared with participants. The study will quantify the scale and determinants of household transmission of SARS-CoV-2. Additionally, immunological responses before and during the different stages of infection will be analysed, adding to the understanding of the range of immunological response by infection severity.

OBJECTIVES To compare the incidence of deep surgical site infections (SSI) and acute kidney injuries (AKI) in patients who did and did not receive topical antibiotics during the open treatment of fractures. DESIGN Retrospective comparative cohort. SETTING Level 1 trauma center. PATIENTS/PARTICIPANTS Three hundred ninety-six patients undergoing open fixation of fractures. INTERVENTION The topical antibiotic group included 78 (20%) patients. Vancomycin only was used in 28 (7%) patients with the median dose (interquartile range) of 1 g (1-2 g) and vancomycin/tobramycin was used in 48 (12%) patients with a median dose (interquartile range) of 2 g (1-2 g)/1.2 g (1.2-1.2 g). MAIN OUTCOME MEASUREMENTS Deep SSI requiring debridement and AKI (>50% increase in creatinine compared with preoperative level). RESULTS There was no detectable difference in SSI between the topical antibiotic and control groups (13% vs. 10%, odds ratio (OR) 1.3, 95% confidence interval (CI) 0.6 to 2.9). Variables associated with SSI on multivariate analysis included open fracture (OR 3.2, CI 1.5 to 6.5) and an American Society of Anesthesiologists classification of >2 (OR 2.7, CI 1.3 to 5.3). There was no detectable difference in AKI between the topical antibiotic and control groups (1 (2%) vs. 7 (5%); OR 0.3, CI 0.04 to 3). CONCLUSION There was no detectable difference, with wide confidence intervals, in SSI and AKI between the topical antibiotic and control groups. Further studies need to be conducted to evaluate the relationship between topical antibiotics and clinical outcomes in orthopaedic trauma surgery. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Reports suggest that renal decline is greater among patients with non-valvular atrial fibrillation (NVAF) treated chronically with warfarin vs. some non-vitamin K antagonist oral anticoagulants.Using primary care electronic health records from the United Kingdom we followed adults with NVAF and who started rivaroxaban (20 mg/day, N = 5338) or warfarin (N = 6314), excluding those with estimated glomerular filtration rate (eGFR)50 ml/min/1.73mWe found clear evidence that patients with NVAF, preserved renal function at baseline and treated with rivaroxaban had a markedly reduced risk and rate of renal decline compared with those treated with warfarin.

Determination of food authenticity is an important issue in quality control and food safety. In recent years, many serious diseases appeared related to foodstuffs, so providing the motivation for the scientific community to work more intensively in this area. Authenticity is a quality criterion for food and food ingredients and is required more and more worldwide, as a result of legislative protection for regional foods. Reviews of analytical methods for the determination of geographical origin of food and beverages have been published. However, organic components of a food crop production depend on various conditions (e.g. fertilization, history of the field, climatic conditions in the year of cultivation, geographic location and soil composition), so it is not always possible to determine the origin of a product by analysing the organic components. Additionally, methods based on elemental composition have been reviewed as have methods based on isotope ratios. Over the past decade, with the development of new advanced analytical techniques [e.g. thermal ionization MS (TIMS), inductively coupled plasma MS (ICP-MS) and dynamic reaction cell-ICPMS (DRC-ICPMS)], we can successfully retrieve elemental and isotopic compositions of any given food sample and determine the geographic origin successfully. The growing concern of the consumers stimulated scientific research and publications in recent years, including multi-element and isotope ratio methods of analysis in food authentication after statistical evaluation of the results. Several aspects will be described: (a) propose a new technique for evaluating spatially explicit trace element profile in various environmental samples (with organic and inorganic complex matrixes); (b) evaluate whether element composition of the environmental samples can be attributed to large-scale geographic trace element variation associated with underlying geology or fine-scale spatial differences related to foraging habitat; (c) determine whether element profiles along the individual species are autocorrelated (i.e. occurring in a predictable or random pattern); (d) prove spatially resolved multi-element information that could be used for identification of geographical origin of various environmental samples and foodstuffs.