Rules Of Good Clinical Practice Research Articles

An update of the literature about rehabilitation tools used in the treatment of COVID-19-related disabilities: a systematic review of literature.

The role of rehabilitation during and after the COVID-19 pandemia was influenced by the progressive acquisition of knowledge on the pathology with the adaptation of the rehabilitative instruments to the heterogeneous impairments of the patients. The aim of this systematic review is to describe the effects of the rehabilitation tools applied in the last three years in the different phases of the COVID-19 disease. A literature search of MEDLINE (PubMed), Scopus and Physiotherapy Evidence Database (PEDro) was conducted. 2994 participants were included in this systematic review: 1225 patients for acute-COVID, 1331 patients for post-COVID, 438 patients for long-COVID. Of the initial 907 hits only 45 randomized controlled trials were included. The Cochrane library assessment tool was used to evaluate the risk of bias. The trials selected studied the effects of respiratory rehabilitation alone or in association with exercises, tele-rehabilitation, endurance training, virtual reality, electrostimulations in different settings and phases of the infection with the evaluation of clinical, quality of life and impairment outcome measures. All the rehabilitations tool were used based on the experts' opinion and on the rules of good clinical practice, during and after the pandemic period. Despite the heterogeneity of the studies, the different outcome measures and the small sample sizes, pulmonary rehabilitation, tele-rehabilitation and low/moderate intensity aerobic and endurance exercises seemed to improve clinical and quality of life outcomes at short (8 weeks) and mean time (2 months) after treatments in all phases of the infection.

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.

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.

Sleep-Cognition Hypothesis In maritime Pilots, what is the effect of long-term work-related poor sleep on cognition and amyloid accumulation in healthy middle-aged maritime pilots: methodology of a case–control study

IntroductionEvidence indicates a bidirectional relationship between poor sleep and Alzheimer’s disease (AD). While AD may lead to disruption of normal sleep, poor sleep in itself may play a causal role...

Metabolic Profiles, Phenotypes Classification and Prediction of Clinical Outcomes in Colonic Polyps

Colonic polyps (CP), especially adenomatous polyps with high incidence and recurrence are risk factors for colorectal cancer (CRC). However, data regarding the effective diagnosis of different types of CP have been lacking. To characterize serum metabolomics in different types of colonic polyps, and evaluated the potential biomarkers as non-invasive diagnostic tool for CP. We characterized and identified metabolites in 286 HCs and 286 CP patients with no definite pathologic type to screen potential biomarkers, and further validated in 298 HCs, 413 tubular adenoma (TA) patients, 66 tubulovillous adenoma (TVA) patients, 32 hyperplastic polyps (HP) patients, and 94 inflammatory polyps (IP) patients. Metabolites of four pathological types of CP were evaluated and different potential biomarker panels were screened. A total of 85 differential metabolites were identified. The disturbed metabolic pathways were glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, ether lipid metabolism, and glycerolipid metabolism. The 5 panels of specific biomarkers exhibited strong diagnostic ability with AUC > 0.86, sensitivity > 70.0 %, specificity > 75%, and offered excellent predictive values for distinguishing HCs vs. CP, as well as TA, TVA, HP, and IP. Potential biomarker panels displayed high correlation with gastrointestinal diseases, which may be benefit for the diagnosis of CP. Trial Registration: Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02986308. Funding Statement: This work was supported by grants from the Key Program of Natural Science Foundation of State (Grant No. 81830110, 81430093, 81373930, 81673586, 81703685, 81302905, 81503386), TCM State Administration Subject of Public Welfare of (Grant No. 2015468004). Declaration of Interests: The authors state: None declared. Ethics Approval Statement: This study was approved by the institutional review Board of First Affiliated Hospital of Harbin Medical University (201624). The study was performed in accordance with the Helsinki Declaration and rules of good clinical Practice. All participants signed written informed consents after the study protocol was fully explained.

Genetic Research: The Role of Citizens, Public Health and International Stakeholders

Background:Genetic research has become an indispensable instrument for medical research, and the subjects involved have both divergent and convergent interests.Objective:The possibility of having more detailed genetic information undoubtedly offers benefits for the health of the subject, but could also pose risks and make the subject vulnerable to discrimination.Methods:The scientific community has viewed very favorably the public health utility of family history, in which data from a family whose members suffer from chronic pathologies is collected and filed, in order to develop a sort of “stratification of family risk.”Even though in the last decade the scientific and juridical literature has contributed greatly to the topic of biobanks, the perplexities that continue to surround this theme give the idea that current ethical protocols on research are inadequate.Results:Researchers, citizens, International stakeholders, mass media, Public Health and Governments play a key role in genetic research. It is obvious that the methods used for genetic research do not present intrinsic risks; they are much less dangerous than other activities of diagnosis and research. Before authorizing a research project, it is important to reflect on the responsibility and transparency of the studies to be conducted, and on the impact they may have on the interests of public health.Conclusion:We believe that the highest priority need is to develop a common language on the theme, as is the case in the sphere of clinical experimentation where rules of good clinical practice, albeit at times conflicting, have led to uniform convergences in the scientific world on the points to be actuated.

MEDICO-LEGAL RESPONSIBILITY IN MANAGEMENT OF ACUTE AND CHRONIC PAIN IN OBSTETRIC.

SUMMARYMedico-legal responsibility in the management of acute or chronic pain in broad sense implies acting by the rules of good clinical practice and reducing the potential treatment side effects and complications that may entail health impairment and possible legal proceedings. Patients with acute or chronic obstetric or nonobstetric pain should be informed on the mode and method of treatment, possible side effects, and effects of drugs or procedures on fetal growth and development (informed consent). The principles of perinatal pharmacology and toxicology should be respected, choosing the mode of treatment associated with the lowest rate of side effects and a minimally invasive procedure (Accordingly, medico-legal responsibility is a professional and deontological category that should be fostered and implemented in line with professional guidelines and safety for both patients and medical staff.)

Prescriptions hors AMM supervisées de méthylphénidate dans le TDAH de l’adulte

ObjectiveOff-label prescription is a common practice in psychiatry, raising health and economic concerns. Collegial consultation could allow a framed prescription of treatments that are not authorized in specific indications. Attention Deficit Hyperactivity in adult populations (ADHD) is a striking example of a pathology where off-label prescription is frequent. First considered to be a childhood disorder, the awareness of this condition in adults is increasing, leading to the development of new clinical practices and treatments. However, the adult ADHD diagnosis and its management are still emerging in France despite a high prevalence. Treatment of adult ADHD relies on methylphenidate prescription, but the initiation of this drug is not authorized in adult populations. Methylphenidate is a central nervous system stimulant that is structurally close to amphetamine and acts as a norepinephrine and dopamine reuptake inhibitor. Due to these pharmacological properties, neuropsychiatric and cardiovascular side-effects could occur. Furthermore, its addictive potential has led France to classify it as a psychoactive drug, dispensed via secured prescription. The first prescription and the one-year follow-up are restricted to neurologists, paediatrics, psychiatrists and sleep disorders specialists at hospital. The objective of this article is to propose a multidisciplinary framework for the off-label prescription of methylphenidate in adult ADHD. MethodsThe Multidisciplinary Advice Consultation for Exceptional Addiction Treatments (Consultation d’Avis Multidisciplinaire de Traitements d’Exception en Addictologie CAMTEA) was first set up in Lille for the prescription of baclofen in alcohol dependence and was then extended to topiramate in binge eating disorder. This procedure has been adapted to the particularities of ADHD in adult populations, the differential diagnosis (bipolar disorder, depressive disorder, anxious disorder, personality disorder, substance use disorder) and the co-morbidities requiring a full psychiatric and neuropsychological assessment. Moreover, a particular attention has been paid to the monitoring of neuropsychiatric, cardiovascular and misuse risk because of the potential side-effects of methylphenidate. ResultsThe proposed prescription framework is structured into several specialized consultations. A first psychiatric evaluation aims to diagnose adult ADHD, using the French version of the Diagnostisch Interview Voor ADHD 2.0 questionnaire (DIVA 2.0), and to assess the quality of life impact with the Weiss Functional Inventory Rating Scale (WIFRS). It also searches for the presence of differential diagnosis or co-morbidities. The second appointment consists of a pharmacological evaluation that aims to search for contraindications and potential drug interaction. A neuropsychological evaluation based on standardized tests (Weschler Adulte Intelligence Scale [WAIS IV], Conner's Continuous Performance Test 3 [CPT] and the Minnesota Multiphasic Personnality Inventory [MMPI]) is also required to evaluate neurocognitive disabilities and personality features. Once the parameters of the different assessments have been collected, the synthesis is presented during a multidisciplinary meeting in order to assess the risk-benefit ratio for each patient. Several specialties are involved in this multidisciplinary meeting: psychiatry, addictology, general medicine, addictovigilance, pharmacovigilance and neuropsychology. One strategy among three possibilities can be decided: (1) contraindication to treatment with methylphenidate, (2) attention deficit disorder that does not require medication management, and (3) indication of treatment with methylphenidate with the choice of the pharmacological form (immediate or prolonged release). A biological check-up and an electrocardiogram are carried out systematically before any treatment. If the decision is made to initiate treatment, it is started at the lowest dosage and followed by a titration phase. A weekly follow-up is carried out during the titration phase in order to assess treatment efficacy and safety. After treatment stabilization, the general practitioner can carry out the renewal, and the patient will be reassessed within the framework of the multidisciplinary consultation every 3 months. ConclusionWhen an off-label prescription is being considered, it must comply with the basic rules of good clinical practice, and the benefit/risk ratio should be constantly reassessed. The proposed multidisciplinary framework, adapted to the characteristics of adult ADHD and the pharmacological properties of methylphenidate, appears to be an interesting strategy to meet the requirements of the good clinical practice. The complementary assessments carried out and the collegial framework allow enhancing the patient's follow-up and minimize the drug risk, particularly in the psychiatric, addictive and cardiovascular adverse events. Finally, this framework could also help the monitoring of other off-label treatments for ADHD, such as atomoxetine or guanfacine.

Transcorneal Electrical Stimulation for Patients With Retinitis Pigmentosa: A Prospective, Randomized, Sham-Controlled Follow-up Study Over 1 Year.

After promising results of an exploratory study, this study was designed to assess the safety and efficacy of transcorneal electrical stimulation (TES) over 1 year in patients with retinitis pigmentosa (RP). We included 52 RP patients in this prospective, randomized, partially-masked study which was done in accordance with rules of good clinical practice. Transcorneal electrical stimulation by Okustim was applied monocularly for 30 minutes per week for 52 consecutive weeks. Patients were assigned randomly to the groups: sham, 150%, or 200% of individual electrical phosphene threshold (EPT). Visual acuity (retroilluminated Snellen charts), visual field (VF; Octopus 900), electroretinography (ERG), rod and cone full-field stimulus threshold, EPTs and IOP were assessed. Primary outcome measures were VF area; secondary outcome measures were development of ERG parameters. The application of TES was tolerated well. Dry eye symptoms (31 of 52 patients) were registered as the main adverse event. Throughout the study period, the VF area showed only a trend for prevention of VF loss in the 200% group (P = 0.24). A significant improvement of light-adapted single flash b-wave was noted for the 200% (P < 0.0001) and 150% (P = 0.006) groups compared to the sham group. Tendencies of improved function were observed for scotopic b-wave amplitude for the 200% group (P = 0.097). Other examination methods did not reach statistical significance. The safety and acceptable tolerability of weekly TES self-administered by patients at home was confirmed over the course of 1 year. Objectively measured improvements in retinal function with ERG provide support for the potential benefits of TES for RP patients.