Rules Of Good Clinical Practice Research Articles

Changes in heart rate variability and subclinical heart failure with preserved left ventricular ejection fraction in workers of the main professions at the coal industry

Introduction. The high prevalence of diseases of the circulatory system necessitates their detection and prevention at an early stage, especially in regions with high industrial potential. The occurrence of subclinical heart failure depends on a cascade of processes that are already occurring in the body and may eventually manifest themselves in clinically pronounced diseases. One of the possible mechanisms of its development is a violation of the balance of the autonomic nervous system with a violation of adaptive capabilities to the labour process, characterized by severe physical overloads among miners. The study aims to evaluate changes in heart rate variability in workers of the main professions at the coal industry with signs of heart failure with a preserved left ventricular ejection fraction. Materials and methods. The study included 78 employees of the main professions at the coal industry. Specialists performed ultrasound examination of the heart according to generally accepted methods with the study of longitudinal deformation of the myocardium. The concentration of NT-proBNP in the blood serum was determined by solid-phase enzyme immunoassay. The authors also conducted an analysis of heart rate variability, determined temporal, spectral and linear parameters. Results. Specialists revealed a decrease in longitudinal myocardial deformation in 38.5% of the examined patients, signs of diastolic dysfunction in 41%; in these groups, a tendency to increase the concentration of NT-proBNP was revealed. In the examined miners with heart failure with preserved ejection fraction, they revealed a significant decrease in the SDNN index and an increase in IC values. The increase in DFA and LF/HF indicators reflects a vegetative imbalance towards sympathetic activation observed in all surveyed miners. Limitations. This study is limited to a sample of employees of the main professions of the coal industry undergoing periodic medical examination at the Research Institute of Complex Problems of Hygiene and Occupational Diseases. Conclusion. The revealed relationship between indicators of heart failure and heart rate variability (SDNN, LF/HF, DFA and IC) in miners allows us to identify a group of people at greatest risk of adverse outcomes. Ethics. The study was conducted in compliance with the standards of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, established in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of Conducting medical Research with human participation as a subject" as amended in 2013 and the "Rules of Good Clinical Practice" approved by Order No. 200n of the Ministry of Health of the Russian Federation dated 04/01/2016. The subjects signed an informed consent to participate in the study.

On the effectiveness of virtual reality technology for relaxation of locomotive crew workers

Reducing the risks of occupational stress requires improving the methods of psychological support for employees of locomotive crews. Virtual reality technology offers restorative measures comparable to traditional techniques. The study aims to analyze the effectiveness of the impact of virtual reality technology on the basis of the analysis of the psycho-emotional state of employees of locomotive crews before and after rehabilitation measures; to evaluate the ratio of stress biomarkers before and after exposure to classical and technical techniques; to compare the effectiveness of psychological influence carried out by various methods. The scientists conducted a survey and diagnosis of the functional state of locomotive crew workers, followed by rehabilitation measures using various methods. The specialists performed a saliva analysis based on the concentration levels of cortisol and dehydroepiandrosterone. 120 people took part in the study, of which: 60 people according to the classical program and 60 people according to the virtual reality program, of which 15 people are at risk according to psychophysiological indicators. The session lasted 21 minutes. The average age of employees of locomotive crews participating in the study was 35.4 years. 88% of the subjects underwent functional state diagnostics and a full course of relaxation sessions in virtual reality. Of these, 73% have improved psychophysiological indicators: response accuracy, increased neuropsychiatric stability, and decreased anxiety levels. The authors noted calmness, improved mood and relief of muscle tension. 60% of the employees have completed a full course of rehabilitation measures using classical techniques. Of these, 70% have an improvement in their functional state according to certain parameters. There is a decrease in cortisol levels (unit of measurement — nanograms per milliliter) from 6.75 ng/ml to 6.28 ng/ml with a simultaneous increase in dehydroepiadrosterone levels (unit of measurement — micrograms per milliliter) from 0.53 mcg/100 ml to 1.77 mcg/100 ml, which corresponds to a decrease in the overall stress level. The analysis of the obtained results showed sufficient effectiveness of virtual methods comparable to classical approaches to relaxation. Immersive technologies more effectively activate natural compensatory mechanisms by expanding the individual regulatory capabilities of the nervous system. Scientists have identified areas for improving the latest methods of rehabilitation measures in order to correct the functional condition of locomotive crews. Limitations. The representativeness of the sample was ensured by the participation of 120 employees of locomotive crews in the study. The limitations are related to the gender homogeneity of the sample: only men are included, due to their professional status. Ethics. The study was performed in accordance with the rules of good clinical practice and the Helsinki Declaration of the World Medical Association, the conclusion of the ethics committee was not required.

Assessment of age-related features of the condition of heavy-duty truck drivers based on spectral analysis of EEG-ECG and stress tests during mass occupational examinations

The authors studied the physiological characteristics of drivers of heavy-duty coal mine vehicles based on spectral analysis of EEG-ECG and stress tests, which have prognostic value in professional activity. The study aims to assess the functional condition of heavy-duty truck drivers of different age groups based on a comprehensive spectral analysis of EEG-ECG under occupational examinations. During the survey, the authors have studied the spectral parameters of the EEG‒ECG in 300 male drivers aged 25 to 66 years. Specialists have performed EEG registration when placing electrodes in the 10–20 system. The EEG analysis was performed with a preliminary visual analysis followed by the removal of artifacts. The scientists assessed the level of representation of the main alpha rhythm and its spatial distribution. The ECG registration was in the first lead. The duration of EEG-ECG registration is about 15 minutes in a typical sequence of stress tests: baseline, rhythmic photostimulation, hyperventilation with recovery periods. The spectral analysis of the EEG‒ECG was performed automatically on a Neurotravel device (Italy). The authors found lower alpha and delta activity in the initial EEG spectra in older drivers aged 45–66 years, which contributed to the cumulative effect of stress load. Light stress stimulation significantly reduced alpha and delta activity and increased beta EEG activity in both groups, while in the older group the high-frequency range significantly exceeded the low-frequency range. Simultaneously with the changes in the EEG, stress photostimulation increased the energy of the ECG spectra in all frequency ranges. The authors established the appearance of additional stress indicators during light stimulation in older drivers based on the correlation of EEG‒ECG spectra (alpha/delta) and the absence of such changes in the group of young drivers aged 25–35 years. Moreover, the EEG–ECG correlation coefficients and their critical values increased in groups in increments of 6 years — from 35 to 65 years. Elderly drivers, based on neuro-cardiodynamic indicators, were in a state of chronic stress and the resulting risks to health and professional activity, and the identified physiological mechanisms of stress may be at the heart of ways to prevent it. Limitations. The study is limited to the assessment of EEG and ECG indicators in 300 heavy truck drivers. Ethics. The study was performed using non-invasive methods and approved by the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, Protocol No. 5, § 1 dated 12/26/2018, in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting medical research with human participation as a subject" as amended in 2013 and the "Rules of Good Clinical Practice" approved by by Order of the Ministry of Health of the Russian Federation No. 200n dated April 1, 2016. All the examined patients signed a voluntary informed consent to participate in the study.

Atherosclerotic vascular lesion in the coal industry workers of average and high fatal risk groups

Introduction. Experts do not take into account the presence of subclinical atherosclerosis when stratifying risk on the SCORE scale, however, it is the main substrate for the occurrence of cardiovascular disasters. Most primary cardiovascular events occur in low cardiovascular risk groups, which requires timely detection of atherosclerosis and preventive measures to preserve the working population's ability to work and reduce the economic burden of treatment of cardiovascular diseases. The study aims to research the incidence of atherosclerosis in workers of the main professions of the coal industry in the South of Kuzbass in groups of medium and high risk of fatal events on the SCORE scale. Materials and methods. We divided the subjects into two groups using the SCORE scale: high-risk (main) — from 5 to 9%, which included 60 people, and moderate-risk group — from 2 to 4% (comparison) — 70 employees. The average age of the first was 50.98±0.43 years, the comparison group was 49.96±0.35 years (p=0.070). The scientists examined the indicators of blood pressure, lipid, carbohydrate and purine metabolism, and performed an ultrasound examination of the main arteries. Results. The incidence of atherosclerotic plaques in at least one vascular basin was 80.0% in the main group and 78.6% in the comparison group, p=0.845. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The combination of thickening of the intima of vessels and the presence of atheromas tended to be more frequent in the main group — 83.6% compared with those in the comparison group — 70.1%, p=0.076 Limitations. The study is limited by the number of examined patients who underwent periodic medical examination at the Scientific Research Institute of Complex Problems of Hygiene and Occupational Diseases. Conclusion. The incidence of atherosclerosis among employees of coal enterprises turned out to be very high and did not statistically differ in the groups of medium and high fatal risk stratified on the SCORE scale, which requires more thorough screening and measures of enhanced angioprotective prevention, even in people with a low risk of fatal cardiovascular disasters. Ethics. All the subjects signed an informed consent to participate in the study, the Protocol of which corresponded to the requirements of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, executed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting medical research with human participation as a subject" as amended in 2013 and the "Rules of Good Clinical Practice" approved by the order Ministry of Health of the Russian Federation No. 200n dated April 1, 2016.

Review - Expert Opinion on Antibiotics and Antibiotic Resistance in Dermatology.

Antibiotic resistance has become a serious, severe problem worldwide. This issue does not only relate to the use of systemic antibiotics but to topical ones as well, like systemic therapies and local treatment of skin and mucosal infections. Antiseptics, an alternative to the topical treatment with antibiotics of wounds and some inflammatory dermatological conditions, tend to be microbicidal and have a broader spectrum of antimicrobial activity than antibiotics. Among these, polyhexanide (PHMB) allows for the control of the infection while avoiding the development of resistance. Recommendations on the rules of good clinical practice for the management of small wounds, burns and post-traumatic ulcerative wounds, impetigo or folliculitis in the initial stages, and acne. Literature review on the principal topical therapies for small wounds, injuries, impetigo, folliculitis, and acne and a proposal of innovative, highly-tolerated treatments. Given the abuse of topical antibiotics in dermatology, for the treatment of small wounds, injuries, localized folliculitis, impetigo, and acne, the use of alternative topical treatments like polyhexanide and Rigenase® is recommended.

The possibilities and advantages of conducting multicenter clinical trials on the basis of outpatient clinics in Moscow

The article presents the special role of the outpatient unit (urban polyclinics) in the system of urban medical organizations, which has significant development potential in the field of clinical research. This activity became possible due to the systematic work on equipping outpatient clinics with the most modern diagnostic equipment, the availability of specialists trained in the organization and conduct of clinical trials according to the international rules of good clinical practice. A special value lies in the fact that the polyclinic network has an extensive database that includes millions of patients and provides the opportunity to perform the highest level of medical expertise and research.

Quelle réponse apporter à un refus obstiné de soins lors de l’accouchement ?

Our team was confronted with a situation of stubborn refusal of care, including the indication of a cesarean section for an adult patient able to express her wishes. This refusal was formulated during pregnancy follow-up, during the discussion of the birth plan and during delivery, the patient having accepted the indication of a possible emergency cesarean section under general anesthesia only in the occurrence of severe fetal heart rate abnormalities. The impasse forced caregivers to violate the rules of good clinical practice, which indicated the performance of a cesarean section, and to wait for a complication to arise in order to be able to act, taking the risk of intervening too late. This situation has led to direct risks to the health of the mother and the unborn child, without putting the life of either of them in imminent danger. Finally, the time devoted to this patient in a tense organization was to the detriment of the care of other patients.

Risk factors for the development of heart failure with a preserved left ventricular ejection fraction in workers of the main professions of the coal industry

Introduction. In the coal industry, 78.7% of employees work in places with harmful working conditions, which play a leading role in the development of not only professional, but also industrial diseases, the leading of which are diseases of the cardiovascular system. The identification of preclinical systolic dysfunction of the left ventricle and the assessment of the role of traditional and professionally determined risk factors for the development of systolic dysfunction of the left ventricle in workers of the main professions of the coal industry is of scientific interest.
 The study aims to assess the risk factors for the development of heart failure with a preserved left ventricular ejection fraction in workers of the main professions of the coal industry.
 Materials and methods. The study included 101 employees of the main professions of the coal industry and 80 employees of the paramilitary mine rescue unit. The subjects had no somatic pathology, which could lead to structural and functional changes of the heart. The scientists performed echocardiographic and ultrasound examinations of the main arteries according to standard methods and assessed the generally accepted risk factors for the development of cardiovascular pathology (smoking, abdominal obesity, body mass index, total cholesterol, triglycerides, high and low density lipoprotein cholesterol, glycated hemoglobin).
 Results. The researchers revealed systolic dysfunction of the left ventricle significantly in miners more often in the form of a decrease in longitudinal deformation (27.7% of miners versus 7.6% of paramilitary rescuers, p=0.0005), while its average value is also significantly lower in miners and has a value below the established norm (–17.2±0.044 and –19.3±0.03, p=0.0005). The authors found no significant differences in the frequency of commonly accepted risk factors: abdominal obesity, smoking, atherosclerosis of the main arteries, dyslipidemia and the level of glycated hemoglobin in miners and workers of the mine rescue unit, as well as in miners, depending on the index of longitudinal deformation of the left ventricle.
 Conclusion. The obtained results indicate the need for a prenosological diagnosis of systolic dysfunction of the left ventricle, studying it in dynamics and simultaneously expanding the search for risk factors, which will allow early prevention of this complication in workers in harmful working conditions.
 Ethics. The study was conducted in compliance with the standards of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, established in accordance with the Helsinki Declaration of the World Association "Ethical Principles of Scientific Medical Research with Human Participation" as amended in 2013 and the "Rules of Good Clinical Practice" approved by Order of the Ministry of Health of the Russian Federation dated 01.04.2016 No. 200n. The subjects signed an informed consent to participate in the study.

Working conditions, medical support and morbidity of stress-related neurotic disorders among Russian Railways employees

Introduction. Shift work, as the main stress factor, leads to the development of desynchronosis and other neurotic diseases. The production necessity with such a work schedule requires increased provision of mental health specialists.
 The study aims to analyze the long-term dynamics of morbidity of employees of JSC "Russian Railways" with neurotic diseases associated with stress and somatoform disorders, depending on the intensity of work, availability of specialists responsible for psychoprophylactic work.
 Materials and methods. Scientists investigated the working conditions and their influence on the functional state of employees of JSC "Russian Railways". The authors have carried out a retrospective analysis of information from the Unified Medical Information and Analytical System from 2012–2021 for JSC "Russian Railways" and the Ministry of Health of Russian Federation. The analysis of morbidity in mental pathology included nosological units assigned by ICD-10 to F40–F48.
 Results. Work in the system of JSC "Russian Railways" is associated with the impact of a complex of unfavorable production factors, the key of which are psycho-emotional stress and shift work schedule — work in night shifts. Railway transport workers face various stressful factors on a daily basis, such as: desynchronosis due to shift work schedules, waiting for an emergency situation with a "system call", "broken" schedules, and related difficulties. The psychogenic factor, which is an etiological factor in the occurrence of neurotic disorders, constantly affects railway transport workers. Based on the analyzed data, it can be assumed that professionally conditioned factors of the working environment contribute to the formation of occupational stress and the formation of neurotic disorders among this category of workers. There is a connection with the growth of neurotic diseases and the annual trend of declining positions of psychologists and psychotherapists in the system of JSC "Russian Railways". There was a significant increase in the incidence of railway transport workers (p=0.043) and a decrease in specialists associated with the prevention of neuropsychiatric diseases for ten years (p=0.0001).
 Limitations. Limitations are presented in the form of a small sample of employees of JSC "Russian Railways", insufficient depth of study of materials of foreign literature on the issue under study.
 Conclusions. Neurotic disorders in persons who are under dispensary supervision in the system of JSC "Russian Railways" have a pronounced, statistically significant growth trend. There is a significant decrease in the number of medical specialists engaged in the diagnosis, treatment and prevention of psychogenic diseases of workers. Based on the results of the study, we have revealed a link between the growth of neurotic diseases of railway transport workers and the annual decline trend of psychologists and psychotherapists in JSC "Russian Railways".
 Ethics. This study was carried out in accordance with the rules of good clinical practice and the Helsinki Declaration and did not require the conclusion of the ethics committee.

Standards of Good Clinical Practice (GCP)

In the Eurasian Economic Union, the unified rules of Good Clinical Practice (GCP) came into force on May 6, 2017. These rules relate primarily to the circulation of medicines, and, along with good manufacturing practice (GMP) and good laboratory practice (GLP), are fundamental in matters of standardizing the quality of medical care for the population. The scope of these rules covers clinical trials of medicines, where the “subject” is an individual, and affects the ethical and moral aspects of conducting such trials [4]. Compliance with these rules is necessary when conducting clinical trials, the data of which are planned to be submitted to the authorized bodies of the Member States of the Eurasian Economic Union (EAEU).

Mortality of Russian Railways employees from cardio-vascular diseases during the COVID-19 pandemic

Introduction. Diseases of cardiovascular system are the leading causes of morbidity and mortality among the able-bodied population. There have been no studies of the impact of the COVID-19 epidemic on cardiovascular mortality in Russian Railways. The study aims to analyze the mortality of Russian Railways employees from diseases of the circulatory system during the COVID-19 pandemic with the working-age population of the Russian Federation. Materials and methods. The study was carried out on the basis of data obtained during the COVID-19 pandemic (2019-2021). Information on the mortality of employees of JSC "Russian Railways" is formed on the basis of the data of the CHUZ of JSC "Russian Railways". Information about the natural movement of the working-age population was formed on the basis of data from the Unified State Register of Civil Status Records. Results. During the pandemic, the mortality rate in JSC "Russian Railways" was 2.2 times lower compared to the working-age population of the country. Excess mortality by road polygons was different. The maximum mortality rate (3.4 per 1000 employees) was among employees of enterprises of central subordination, the minimum (2.1) was on the Northern Railway. 82.5% of deaths occurred in men, while the mortality rate among men is 2 times higher compared to women. The main cause of death of workers were diseases of the circulatory system (BSC) - 28.7%. The mortality rate from BSK in JSC "Russian Railways" was 0.656, which is 2.9 times lower than for the working-age population of Russia. Conclusion. The study showed that under the conditions of a new coronavirus infection, the mortality rate from circulatory system diseases in Russian Railways employees is lower than in working-age population of Russia. Ethics. We have carried out this study in accordance with the rules of good clinical practice and the Helsinki Declaration. The study did not require the conclusion of the Ethics committee.

Lesson of the Week: In the Nick of Time!

Management of diabetes lends itself very well to several classical rules of good clinical practice, an elaboration of which is out of the scope of this short story. However, a couple of these are noteworthy. “Diagnosis should precede treatment as much as possible except for measures of resuscitation” applies to diabetes as to all other conditions. In diabetes, diagnosis and classification are the same. Hence, a serious attempt to classify diabetes at the time of diagnosis or as soon as possible after that is mandatory.[1] In particular, when the patient's characteristics are atypical, or events do not follow the expected course, making assumptions under these circumstances can be very dangerous.[2] In this vignette, an unusual case of diabetes in a young woman is presented and discussed with an analysis of lessons to be learned. The present case report exemplifies several themes of “not expecting the expected,” “not making unfounded assumptions,” and “ignoring several alert signals.”

A comparative analysis of content requirements for clinical trials protocols in international regulatory documents

Aim to review the international regulatory documents on the requirements for the content of the protocol as the main document of a clinical trial.
 Material and methods. The ICH GCP, the EU Directive 536/2014, the Order 200n, the Rules of Good Clinical Practice of the EAEU and the FDA documents were reviewed. The analysis followed the 46 points of section 6 of ICH GCP E6 (R2).
 Results. As a result, 40 of the 46 points, considering the protocols content requirements, in all analyzed documents were similar. The essential differences were found in the Directive EU 236/2014. Firstly, the 6 points of the requirements were lacking; secondly, it contained points that were not reflected in any of the other 4 documents.
 Conclusion. The Directive EU 236/2016 obliges the protocol developers to employ a more detailed and qualitative approach to the protocol creation and prescribes to provide a more detailed description of certain measures and information about drugs. The Directive EU 236/2016 is not interchangeable with the 4 regulatory documents mentioned above. Sponsors need to more carefully analyze the possibility of conducting clinical trials in the Russian Federation according to the protocols developed in the EU, paying attention to the additional points of the local requirements.

Features of conducting ethical review of research on artificial intelligence systems on the basis of the research and practical clinical center for diagnostics and telemedicine technologies of the Moscow Health Care Department, Moscow, Russian Federation

Ethical issues occupy a special place when conducting clinical trials of medicines, where it is impossible to predict in advance and accurately the effectiveness and safety of a new drug on the human body. Currently, during clinical trial examination, attention is paid to patients quality of life, and issues of compliance with patients rights, as well as compliance with the rules of good clinical practice and current legislation. Thanks to technological development, the number medical studies and devices using, among other things, specialized medical technologies and software is increasing.
 Automation, development, improvement, and structuring of the processes involved cause an increase in the use of technical devices that use not only programs but also systems in their work. Artificial intelligence system software have a special place in medical science development.
 Artificial intelligence, which was the field of science fiction 5080 years ago, is now firmly embedded in our everyday life. By introducing artificial intelligences capabilities into medical software, using it as part of medical equipment, and developing medical devices with artificial intelligence systems, we get a product that requires careful study and further development, which includes a complex of works on conducting scientific research, and registration and maintenance of such systems and complexes. All work is regulated by legislation in the field of circulation of medical devices and requires a deep systematic and scientific approach, including involving ethics to monitor compliance with the rights and safety of study participants and their medical data.
 The Ethics Committee is an independent body that monitors compliance with the rights and requirements of legislation and conducts ethical and scientific examination of research documentation. Ethical issues when planning any research involving a person or his/her data should be discussed and considered in detail. The ethics committees should be contacted not only at the stage of approving research materials, but also when planning the design and developing research documentation and materials for patients, as well as regularly at all stages of the study.

Spinal manipulation therapy in low back pain : Why? When? Where? How?

Manipulation and mobilisation for low back pain are presented in an evidence-based manner with regard to mechanisms of action, indications, efficacy, cost-effectiveness ratio, user criteria and adverse effects. Terms such as non-specific or specific are replaced by the introduction of "entities" related to possible different low back pain forms. MM is effective for acute and chronic low back pain in terms of pain relief, recovery of function and relapse prevention. It is equally effective but less risky compared to other recommended therapies. MM can be used alone in acute cases and not only in the case of chronic low back pain where it is always and necessarily part of amultimodal therapy programme, especially in combination with activating measures. The users of MM should exclusively be physician specialists trained according to the criteria of the German Medical Association (Bundesärztekammer) with an additional competence in manual medicine or appropriately trained certified therapists. The application of MM follows all rules of Good Clinical Practice. Significant adverse effects of MM for low back pain are reported in the international literature with afrequency of 1per 50,000 to 1per 3.7million applications, i.e. MM for low back pain is practically risk-free and safe if performed according to the rules of the European Training Requirements of the UEMS.

Differential miRNA plasma profiles associated with the spontaneous loss of HIV‐1 control: miR‐199a‐3p and its potential role as a biomarker for quick screening of elite controllers

Differential miRNA plasma profiles associated with the spontaneous loss of HIV‐1 control: miR‐199a‐3p and its potential role as a biomarker for quick screening of elite controllers

Spanish and Portuguese Societies of Internal Medicine consensus guideline about best practice in end-of-life care

AimTo develop consensus recommendations about good clinical practice rules for caring end-of-life patients. MethodsA steering committee of 12 Spanish and Portuguese experts proposed 37 recommendations. A two rounds Delphi method was performed, with participation of 105 panelists including internists, other clinicians, nurses, patients, lawyers, bioethicians, health managers, politicians and journalists. We sent a questionnaire with 5 Likert-type answers for each recommendation. Strong consensus was defined when >95% answers were completely agree or >90% were agree or completely agree; and weak consensus when >90% answers were completely agree or >80% were agree or completely agree. ResultsThe panel addressed 7 specific areas for 37 recommendations spanning: identification of patients; knowledge of the disease, values and preferences of the patient; information; patient’s needs; support and care; palliative sedation, and after death care. ConclusionsThe panel formulated and provided the rationale for recommendations on good clinical practice rules for caring end-of-life patients.

Remission in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide (varitrinox) As the First Line in Colombia

Acute promyelocytic leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) in which a chromosomal translocation t (15; 17) (q22; q12) is generated by fusing produces a hybrid PML / RARα gene, generating an altered signal . The combination of transretinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of newly diagnosed standard risk patients with acute promyelocytic leukemia (APL) in several countries. The objective of the present study is to describe the frequency of remission in patients with acute promyelocytic leukemia who were administered as a first line Arsenic Trioxide (varitrinox) during the period from November 2017 to June 2020 in Colombian patients. Methods: Retrospective observational and descriptive study of 12 patients diagnosed with acute promyelocytic leukemia treated with ATO Arsenic trioxide (Varitrinox) as first line, the source of information was provided by the treating hematologists (medical records) by filling out the technical concept format. Active pharmacovigilance scientist in Colombia, this format keeps the identification information of the patient anonymized and the confidentiality of the data is guaranteed as well as compliance with the rules of good clinical practice. Results: Twelve patients with age range between 22 and 69 years with a median age of 34.0 were analyzed. It was found in the analysis that 100% had induction hematologic remission with a median of 45 days. 75% of patients received ATO + ATRA and were at low and intermediate risk, the remaining 25% received ATRA + ATO + Chemotherapy and were at high risk, and intermediate risk. 91.7% of molecular remission in consolidation was obtained and it was measured in cycle 3 by means of PCR (undetectable), 8.3% (n = 1) was positive 3% and is finishing consolidation. Regarding the most frequent adverse events, intravascular coagulation (n = 9), neutropenia (n = 6) and thrombocytopenia (n = 6) were observed. 75% of patients are disease-free, 16.7% are on maintenance (they received ATO + ATRA + Induction chemotherapy) and 8.3% are on consolidation. So far, none of the patients under study have died. Conclusions: Our results support the use of ATO (Varitrinox) in newly diagnosed APL patients (as first line), as a care strategy for low, intermediate and high risk patients. The role of ATRA-ATO is guaranteed in other studies where they manage patients of different risks. Key words: Arsenic trioxide, leukemia promyelocytic acute, leukemia myeloid acute, remission induction, tretinoin. Disclosures No relevant conflicts of interest to declare.

Guía de práctica clínica de consenso sobre buenas prácticas en los cuidados al final de la vida de las Sociedades Española y Portuguesa de Medicina Interna

AimTo develop consensus recommendations about good clinical practice rules for caring end-of-life patients. MethodsA steering committee of 12 Spanish and Portuguese experts proposed 37 recommendations. A two rounds Delphi method was performed, with participation of 105 panelists including internists, other clinicians, nurses, patients, lawyers, bioethicians, health managers, politicians and journalists. We sent a questionnaire with 5 Likert-type answers for each recommendation. Strong consensus was defined when > 95% answers were completely agree or > 90% were agree or completely agree; and weak consensus when > 90% answers were completely agree or > 80% were agree or completely agree. ResultsThe panel addressed 7 specific areas for 37 recommendations spanning: identification of patients; knowledge of the disease, values and preferences of the patient; information; patient's needs; support and care; palliative sedation, and after death care. ConclusionsThe panel formulated and provided the rationale for recommendations on good clinical practice rules for caring end-of-life patients.

Design and Rationale of a Scandinavian Multicenter Randomized Study Evaluating if Once-Daily Tacrolimus Versus Twice-Daily Cyclosporine Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation (ScanCLAD Study).

BackgroundA low level of evidence exists regarding the choice of calcineurin inhibitor (CNI) for immunosuppression after lung transplantation (LTx). Therefore, we designed a randomized clinical trial according to good clinical practice rules to compare tacrolimus with cyclosporine after LTx.MethodsThe ScanCLAD study is an investigator-initiated, pragmatic, controlled, randomized, open-label, multicenter study evaluating if an immunosuppressive protocol based on anti-thymocyte globulin (ATG) induction, once-daily tacrolimus dose, mycophenolate mofetil, and corticosteroid reduces the incidence of chronic lung allograft dysfunction (CLAD) after LTx, compared to a cyclosporine-based protocol with all other immunosuppressive and prophylactic drugs being identical between groups. All patients will be followed for 3 years to determine the main endpoint of CLAD. The study is designed for superiority, and power calculations show that 242 patients are needed. Also, the study is designed with more than 10 substudies addressing other important and unresolved issues in LTx. In addition, the ScanCLAD study enabled the synchronization of the treatment and follow-up protocols of the lung transplantation programs of all five Scandinavian lung transplantation centers.Planned OutcomesRecruitment started in 2016. At the end of April 2019, 227 patients were randomized. We anticipate the last patient to be randomized in autumn 2019, and thus the last patient visits will be in 2022. The ScanCLAD study is enrolling and investigates which CNI is to be preferred from a CLAD perspective after LTx.Trial Registry NumberScanCLAD trial registered at ClinicalTrials.gov before patient enrollment (NCT02936505). EUDRACT number 2015-004137-27.