Ministry of Health

CONTEXT: The expression and release of tissue factor is a major trigger for the activation of coagulation in patients with sepsis. Tissue factor pathway inhibitor (TFPI) forms a complex with tissue factor and blood protease factors leading to inhibition of thrombin generation and fibrin formation. OBJECTIVES: To determine if administration of tifacogin (recombinant TFPI) provides mortality benefit in patients with severe sepsis and elevated international normalized ratio (INR) and to assess tifacogin safety in severe sepsis, including patients with low INR. DESIGN AND SETTING: A randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted from March 21, 2000, through September 27, 2001, in 245 hospitals in 17 countries in North America, Europe, and Israel. PATIENTS: The primary efficacy population consisted of 1754 patients (> or =18 years) with severe sepsis and a high INR (> or =1.2) randomly assigned to intravenous infusion of either tifacogin (0.025 mg/kg per hour for 96 hours, n = 880) or placebo (arginine citrate buffer, n = 874), and 201 patients with a low INR (<1.2) randomly assigned to receive the same dose of either tifacogin or placebo. MAIN OUTCOME MEASURE: All-cause 28-day mortality. RESULTS: Overall mortality at 28 days in the tifacogin-treated group (n = 880) vs the placebo group (n = 874) for high INR was 34.2% vs 33.9%, respectively (P =.88, Pearson chi2 test; P =.75, logistic regression model). None of the protocol-specified secondary end points differed between the tifacogin vs placebo groups. An analysis on the first 722 patients demonstrated a mortality rate of 38.9% for placebo vs 29.1% for tifacogin (P =.006, Pearson chi2 test). Tifacogin significantly attenuated prothrombin fragment 1.2 and thrombin:antithrombin complex levels (P<.001, 2-sample t test) in patients with high and low INR. Overall mortality was lower in the tifacogin response in patients with low INR (12%; n = 83) vs placebo (22.9%; n = 118) (P =.051, Pearson chi2 test; P =.03, logistic regression model). There was an increase in serious adverse events with bleeding in the tifacogin group in both cohorts (6.5% tifacogin and 4.8% placebo for high INR; 6.0% tifacogin and 3.3% placebo for low INR). CONCLUSIONS: Treatment with tifacogin had no effect on all-cause mortality in patients with severe sepsis and high INR. Tifacogin administration was associated with an increase in risk of bleeding, irrespective of baseline INR.

Many countries are seeking to improve health care delivery by reviewing the roles of health professionals, including nurses. Developing new and more advanced roles for nurses could improve access to care in the face of a limited or diminishing supply of doctors. It might also contain costs by delegating tasks away from more expensive doctors. This paper reviews the development of advanced practice nurses in 12 countries (Australia, Belgium, Canada, Cyprus, Czech Republic, Finland, France, Ireland, Japan, Poland, United Kingdom and United States), with a particular focus on their roles in primary care. It also reviews the evaluations of impacts on patient care and cost.

BACKGROUND: The beginning of the coronavirus disease (COVID-19) epidemic dates back to December 31, 2019, when the first cases were reported in the People's Republic of China. In the Czech Republic, the first three cases of infection with the novel coronavirus were confirmed on March 1, 2020. The joint effort of state authorities and researchers gave rise to a unique team, which combines methodical knowledge of real-world processes with the know-how needed for effective processing, analysis, and online visualization of data. OBJECTIVE: Due to an urgent need for a tool that presents important reports based on valid data sources, a team of government experts and researchers focused on the design and development of a web app intended to provide a regularly updated overview of COVID-19 epidemiology in the Czech Republic to the general population. METHODS: The cross-industry standard process for data mining model was chosen for the complex solution of analytical processing and visualization of data that provides validated information on the COVID-19 epidemic across the Czech Republic. Great emphasis was put on the understanding and a correct implementation of all six steps (business understanding, data understanding, data preparation, modelling, evaluation, and deployment) needed in the process, including the infrastructure of a nationwide information system; the methodological setting of communication channels between all involved stakeholders; and data collection, processing, analysis, validation, and visualization. RESULTS: The web-based overview of the current spread of COVID-19 in the Czech Republic has been developed as an online platform providing a set of outputs in the form of tables, graphs, and maps intended for the general public. On March 12, 2020, the first version of the web portal, containing fourteen overviews divided into five topical sections, was released. The web portal's primary objective is to publish a well-arranged visualization and clear explanation of basic information consisting of the overall numbers of performed tests, confirmed cases of COVID-19, COVID-19-related deaths, the daily and cumulative overviews of people with a positive COVID-19 case, performed tests, location and country of infection of people with a positive COVID-19 case, hospitalizations of patients with COVID-19, and distribution of personal protective equipment. CONCLUSIONS: The online interactive overview of the current spread of COVID-19 in the Czech Republic was launched on March 11, 2020, and has immediately become the primary communication channel employed by the health care sector to present the current situation regarding the COVID-19 epidemic. This complex reporting of the COVID-19 epidemic in the Czech Republic also shows an effective way to interconnect knowledge held by various specialists, such as regional and national methodology experts (who report positive cases of the disease on a daily basis), with knowledge held by developers of central registries, analysts, developers of web apps, and leaders in the health care sector.

OBJECTIVESpontaneous spondylodiscitis remains uncommon but is a serious complication of the vertebral column. Risk factors include diabetes, hemodialysis, intravenous drug abuse, and chronic steroid use, and pain is the most common presenting symptom. This study aims to review the literature and report on the incidence, management, and clinical outcome of spontaneous spondylodiscitis in 44 patients.METHODSThis is a prospective study including 44 patients with spontaneous spondylodiscitis managed in the neurosurgery department of Cairo University Hospitals during the period between January 2012 and October 2017. All patients had a full clinical assessment, laboratory tests, radiological studies in the form of MRI with and without contrast, and a postoperative follow-up of up to 12 months.RESULTSTwelve cases underwent conservative treatment in the form of complete bed rest, intravenous antibiotics, and a spinal brace. Ten cases underwent surgical intervention in the form of laminectomy, debridement, and open biopsy. Twenty-two cases underwent laminectomy and surgical stabilization with fusion. There were 15 cases of tuberculous spondylodiscitis, 6 cases of brucellosis, 6 cases of pyogenic infection, and 17 cases in which no organism could be detected.CONCLUSIONSOnce the primary diagnosis is confirmed, early and adequately prolonged antibiotic therapy is recommended for spontaneous spondylodiscitis. Some cases can be successfully treated with conservative treatment alone, whereas surgery may be needed in other cases such as severe destruction of endplates, spinal abscess formation, mechanical instability, neurological deficits, and severe pain that have failed to respond to conservative treatment.

Sentinel lymph node biopsy in patients with head and neck mucosal melanomas has not been performed so far. Therefore, this method as a staging tool was tested in a pilot study. In two consecutive patients, a lymphoscintigraphy, elective neck dissection with radio-guided sentinel lymph node identification, and resection of the primary were performed. The histopathological status of the sentinel lymph node was compared with the lymphadenectomy specimen and with the clinical course. Patient no. 1, in whom both the sentinel lymph node and the lymphadenectomy specimen were found to be free of tumour, is well and with no evidence of disease, the follow-up interval being 19 months. Patient no. 2, with the sentinel lymph node and remaining lymphatic basin being positive and negative, respectively, developed hematogenous dissemination 3 months after the primary treatment, and he was started on palliative chemotherapy. In mucosal melanoma, the prognostic significance of clinical nodal status is controversial, resulting in the lack of an official, applicable TNM classification and also of therapeutic guidelines. The presence of microscopic metastatic focus in the sentinel lymph node was associated with an early hematogenous dissemination. Therefore, sentinel lymph node biopsy, which represents a potentially efficient staging tool, warrants further investigation.

OBJECTIVE: To examine the extent to which peer drug use and sibling drug use predict alcohol abuse/dependence disorder status and the use of drugs other than alcohol among school-based youth in Mexico. METHODS: Data were collected on 1 203 middle and high school students in northern Mexico in May 1998. Participation was voluntary, and responses were confidential. Logistic regression analyses estimated the association that peer drug use and that sibling drug use had with alcohol abuse/dependence diagnosis and the lifetime use of drugs other than alcohol. RESULTS: Students who had siblings or peers who used alcohol and other drugs were more likely to meet the standard alcohol abuse/dependence criteria defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV), and were more likely to have used drugs other than alcohol. Controlling for potentially important confounders, we found that adolescents with the highest level of peer substance use were eight times as likely to meet alcohol abuse/dependence criteria and four times as likely to use other drugs. Youth who had siblings who used drugs were about twice as likely to meet alcohol abuse/dependence criteria and about 2.5 times as likely to use drugs other than alcohol when compared to youth with no sibling substance use. CONCLUSIONS: Consistent with extant findings among youth in the United States of America, peer and sibling substance use are major risk factors for substance use among school-based youth in Mexico. Students in Mexico may benefit from prevention strategies found to be effective among students in the United States.

Platelets are formed elements of blood. Upon activation, they externalize phosphatidylserine, thus accelerating membrane-dependent reactions of blood coagulation. Activated platelets form two subpopulations, only one of which expresses phosphatidylserine. This study aimed to identify signalling pathways responsible for this segregation. Gel-filtered platelets, intact or loaded with calcium-sensitive dyes, were activated and labelled with annexin V and antibodies, followed by flow cytometric analysis. Calcium Green and Fura Red dyes were compared, and only the latter was able to detect calcium level differences in the platelet subpopulations. Phosphatidylserine-positive platelets produced by thrombin had stably high intracellular calcium level; addition of convulxin increased and stabilized calcium level in the phosphatidylserine-negative subpopulation. PAR1 agonist SFLLRN also induced calcium rise and subpopulation formation, but the resulting platelets were not coated with alpha-granule proteins. Adenylatecyclase activator forskolin inhibited phosphatidylserine-positive platelets formation several-fold, while its inhibitor SQ22536 had no effect. This suggests that adenylatecyclase inactivation is necessary, but not rate-limiting, for subpopulation segregation. Inhibition of mitogen-activated protein kinase kinase (U0126) and glycoprotein IIb-IIIa (Monafram(®)) was without effect, whereas inhibitors of phosphatidylinositol 3-kinase (wortmannin) and Src tyrosine kinase (PP2) decreased the procoagulant subpopulation threefold. These data identify the principal signalling pathways controlling platelet heterogeneity.

During the onset of the COVID-19 pandemic, the COVIDiSTRESS Consortium launched an open-access global survey to understand and improve individuals' experiences related to the crisis. A year later, we extended this line of research by launching a new survey to address the dynamic landscape of the pandemic. This survey was released with the goal of addressing diversity, equity, and inclusion by working with over 150 researchers across the globe who collected data in 48 languages and dialects across 137 countries. The resulting cleaned dataset described here includes 15,740 of over 20,000 responses. The dataset allows cross-cultural study of psychological wellbeing and behaviours a year into the pandemic. It includes measures of stress, resilience, vaccine attitudes, trust in government and scientists, compliance, and information acquisition and misperceptions regarding COVID-19. Open-access raw and cleaned datasets with computed scores are available. Just as our initial COVIDiSTRESS dataset has facilitated government policy decisions regarding health crises, this dataset can be used by researchers and policy makers to inform research, decisions, and policy.

Background New high‐performance liquid chromatography ( HPLC ) method was developed for the determination of vitamin K 1 and two forms of vitamin K 2 ( MK ‐4 and MK ‐7) in human serum, and the levels of vitamin K were determined in 350 samples of postmenopausal women. Methods Vitamin K was determined by HPLC with fluorescence detection after postcolumn zinc reduction. The detection was performed at 246 nm (excitation) and 430 nm (emission). The internal standard and 2 mL of ethanol were added to 500 μL of serum. The mixture was extracted with 4 mL of hexane, and solid phase extraction was then used. Results The HLPC method was fully validated. The intra‐ and interday accuracy and precision were evaluated on two QC samples by multiple analysis, and CV were less than 10%. The limit of quantification for MK ‐4 was found at 0.04 ng/mL, for K 1 0.03 ng/mL, and for MK ‐7 0.03 ng/mL. The mean recoveries of the corresponding compounds were 98%‐110%. Serum levels of MK ‐4, K 1 , and MK ‐7 in postmenopausal women with osteoporosis were 0.890 ± 0.291 ng/mL, 0.433 ± 0.394 ng/mL, and 1.002 ± 1.020 ng/mL, respectively (mean ± SD ). Serum levels of MK ‐4, K 1 , and MK ‐7 in postmenopausal women without osteoporosis were 0.825 ± 0.266 ng/mL, 0.493 ± 0.399 ng/mL, and 1.186 ± 1.076 ng/mL, respectively (mean ± SD). Conclusion New HPLC method for the determination of vitamins K 1 , MK ‐4, and MK ‐7 in serum was evaluated and validated. This method is highly specific and sensitive with the low limit of quantification.

Ageing is accompanied by deterioration in physical condition and a number of physiological processes and thus a higher risk of a range of diseases and disorders. In particular, we focused on the changes associated with aging, especially the role of small molecules, their role in physiological and pathophysiological processes and potential treatment options. Our previously published results and data from other authors lead to the conclusion that these unwanted changes are mainly linked to the hypothalamic-pituitary-adrenal axis can be slowed down, stopped, or in some cases even reversed by an appropriate treatment, but especially by a life-management adjustment.

For more than 30 years up to 2006, the incidence of human listeriosis in the Czech Republic has been low, ranging between 0.1 and 0.2 cases per 100 000 population per year. In 2006, however, the incidence of human listeriosis was about 0.7.

An updated Council of the EU recommendation on cancer screening was adopted in December 2022 during the Czech EU presidency. The recommendation included prostate cancer as a suitable target disease for organised screening, and invited countries to proceed with piloting and further research. To support further discussions and actions to promote early detection of prostate cancer, an international conference in November 2022 (Prostaforum 2022) resulted in a joint declaration. Here we describe the EU policy background, summarise the preparation of the declaration and the key underlying evidence and expert recommendations, and report the text of the declaration. The declaration summarises the striking inequalities in prostate cancer burden in Europe and calls on all stakeholders to consider and support concrete steps for advancement of organised early detection of prostate cancer. Our aim is to request endorsement of the text and potential initiation of practical actions by all stakeholders to support the aims of the declaration. Patient summary: Prostate cancer is among the most frequent cancers and is one of the most common causes of cancer death among men. The European Union has recommended new pilot programmes for prostate cancer screening. The Prostaforum 2022 declaration invites all stakeholders to support this new recommendation with specific steps.

The foundations of the modern era of the treatment of proximal femur fractures were laid by Cooper who in 1819 published the first therapeutically oriented classification of these fractures. During the following 100 years the clinical diagnostics were further developed; five classifications of proximal femur fractures were formulated including the terminology used until now (peritrochanteric, intertrochanteric), and surgical treatment was started. The first attempt at internal fixation of the proximal femur in the 1850s was by Langenbeck. His patient died of sepsis. The first successful internal fixation of proximal femur fractures was done in 1875 by König. At the beginning of the twentieth century the method of surgical treatment for proximal femur fractures was improved by Lambotte, Delbet, and Putti. However, the time was not ready yet for this method of treatment. Only technologic progress (stainless steel, new technology), the additional development of anesthesia and asepsis, improvement of xray apparatus, and introduction of the traction table created the prerequisites for successful gradation of Smith-Petersen's method from 1925 to 1931, and which a few years later was used worldwide.

BACKGROUND: Implementation of clinical health promotion (CHP) aiming at better health gain is slow despite its effect. CHP focuses on potentially modifiable lifestyle risks such as smoking, alcohol, diet, and physical inactivity. An operational program was created to improve implementation. It included patients, staff, and the organization, and it combined existing standards, indicators, documentation models, a performance recognition process, and a fast-track implementation model. The aim of this study was to evaluate if the operational program improved implementation of CHP in clinical hospital departments, as measured by health status of patients and staff, frequency of CHP service delivery, and standards compliance. METHODS: Forty-eight hospital departments were recruited via open call and stratified by country. Departments were assigned to the operational program (intervention) or usual routine (control group). Data for analyses included 36 of these departments and their 5285 patients (median 147 per department; range 29-201), 2529 staff members (70; 10-393), 1750 medical records (50; 50-50), and standards compliance assessments. Follow-up was measured after 1 year. The outcomes were health status, service delivery, and standards compliance. RESULTS: No health differences between groups were found, but the intervention group had higher identification of lifestyle risk (81% versus 60%, p < 0.01), related information/short intervention and intensive intervention (54% versus 39%, p < 0.01 and 43% versus 25%, p < 0.01, respectively), and standards compliance (95% versus 80%, p = 0.02). CONCLUSIONS: The operational program improved implementation by way of lifestyle risk identification, CHP service delivery, and standards compliance. The unknown health effects, the bias, and the limitations should be considered in implementation efforts and further studies. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01563575. Registered 27 March 2012. https://clinicaltrials.gov/ct2/show/NCT01563575.

OBJECTIVES: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC). METHODS: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates. RESULTS: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84). CONCLUSIONS: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary.

Background: The aim of the nationwide prospective seroconversion (PROSECO) study was to investigate the dynamics of anti-SARS-CoV-2 IgG antibodies in the Czech population. Here we report on baseline prevalence from that study. Methods: The study included the first 30,054 persons who provided a blood sample between October 2020 and March 2021. Seroprevalence was compared between calendar periods, previous RT-PCR results and other factors. Results: The data show a large increase in seropositivity over time, from 28% in October/November 2020 to 43% in December 2020/January 2021 to 51% in February/March 2021. These trends were consistent with government data on cumulative viral antigenic prevalence in the population captured by PCR testing - although the seroprevalence rates established in this study were considerably higher. There were only minor differences in seropositivity between sexes, age groups and BMI categories, and results were similar between test providing laboratories. Seropositivity was substantially higher among persons with history of symptoms (76% vs. 34%). At least one third of all seropositive participants had no history of symptoms, and 28% of participants with antibodies against SARS-CoV-2 never underwent PCR testing. Conclusions: Our data confirm the rapidly increasing prevalence in the Czech population during the rising pandemic wave prior to the beginning of vaccination. The difference between our results on seroprevalence and PCR testing suggests that antibody response provides a better marker of past infection than the routine testing program.

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal disease of low malignancy consisting of inflammatory cells inside a mesenchymal stroma comprising myofibroblasts. Biological behavior is variable, recurrence is uncommon, metastatic disease is rare. Treatment strategy is based on the status of low-grade malignant tumor. Radical surgery is considered to be the principal treatment modality, except if it requires a mutilating procedure. Only 6 cases of pediatric patients treated for IMT of the esophagus have been reported in English-language literature. Herein, a case of a 13-year-old boy with an IMT of the esophagus is presented.

OBJECTIVES: Electroconvulsive therapy (ECT) is effective in the treatment of severe psychiatric disorders. Electroconvulsive therapy is applied to almost 1 million patients every year around the world. The aim of this study was to monitor the use of ECT in psychiatric facilities for adults in the Czech Republic (CR) in 2014 and to describe the national practice. METHODS: A 14-item questionnaire was sent to all Czech inpatient psychiatric facilities that provide ECT, with the aim of getting a detailed picture of the use of ECT in the CR. The questionnaire assessed the technical background for using ECT in each center, along with indications for the treatment, the procedure, and the manner of documenting and monitoring adverse effects. The data obtained were supplemented with information about national legal and ethical regulations as well as historical background. RESULTS: Electroconvulsive therapy is used in 26 centers across the CR. More than 1000 patients were treated with ECT in 2014. All centers use instruments delivering brief pulse stimuli, monitoring electroencephalogram and electrocardiogram. All patients have to be indicated for this treatment, which is a decision the patient's psychiatrist makes. All patients have to sign an informed consent form, excluding a situation where the patient's life is endangered. Somatic state is assessed in all patients. Bitemporal electrode placement is the preferred option in all centers. CONCLUSIONS: This article covers detailed information about the use of ECT in the CR. The results will be used to harmonize national practice and reduce the stigma associated with this method in the CR.

OBJECTIVES: The objective of this study was to compare evidence requirements for health technology assessment of pharmaceuticals by national agencies across Europe responsible for reimbursement decisions focusing specifically on relative effectiveness assessment. METHODS: Evidence requirements from thirty-three European countries were requested and twenty-nine national agencies provided documents to review. Data were extracted from national documents (manufacturer's submission templates and associated guidance) into a purpose-made framework with categories covering information about the health condition, the technology, clinical effectiveness and safety. RESULTS: The level of detail in the required evidence varies considerably across countries. Some countries include specific questions while others request information under general headings. Some countries include all information in a single document, which may or may not include guidance on how to complete the template. Others have specific guidance documents or methods and process manuals that help with the completion of the submission templates. Despite differences in quantity and detail, the content of the evidence requirements is broadly similar. All countries ask for information on the health technology, target disease, and clinical effectiveness and safety. However, one country only requests clinical effectiveness information as part of cost-effectiveness analyses. We found twenty-six evidence requirements for which generic answers may apply across borders and nineteen in which countries requested nationally specific information. CONCLUSIONS: This work suggests that it would be possible to put together a minimum set of evidence requirements for HTA to support reimbursement decisions across Europe which could facilitate collaboration between jurisdictions.

The aging of human populations, including those in Europe, is an indisputable fact. The challenge for the future is not simply prolonging human life at any cost or by any means but rather extending self-sufficiency and quality of life. Even in the most advanced societies, the eternal questions remain. Who will take care of the older generations? Will adult children's own circumstances be sufficient to support family members as they age? For a range of complex reasons, including socioeconomic conditions, adult children are often unable or unwilling to assume responsibility for the care of older family members. For this reason, it is imperative that aging adults maintain their independence and self-care for as long as possible. Movement is an important part of self-sufficiency. Moreover, movement has been shown to improve patients' clinical status. At a time when the coronavirus pandemic is disrupting the world, older people are among the most vulnerable. Our paper explores current knowledge and offers insights into the significant benefits of movement for the elderly, including improved immunity. We discuss the biochemical processes of aging and the counteractive effects of exercise and endogenous substances, such as vitamin D.