SMILE: a predictive model for Scoring the severity of relapses in MultIple scLErosis.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), relapse severity and residual disability are difficult to predict. Nevertheless, this information is crucial both for guiding relapse treatment strategies and for informing patients. OBJECTIVE: We, therefore, developed and validated a clinical-based model for predicting the risk of residual disability at 6 months post-relapse in MS. METHODS: We used the data of 186 patients with RRMS collected during the COPOUSEP multicentre trial. The outcome was an increase of ≥ 1 EDSS point 6 months post-relapse treatment. We used logistic regression with LASSO penalization to construct the model, and bootstrap cross-validation to internally validate it. The model was externally validated with an independent retrospective French single-centre cohort of 175 patients. RESULTS: The predictive factors contained in the model were age > 40 years, shorter disease duration, EDSS increase ≥ 1.5 points at time of relapse, EDSS = 0 before relapse, proprioceptive ataxia, and absence of subjective sensory disorders. Discriminative accuracy was acceptable in both the internal (AUC 0.82, 95% CI [0.73, 0.91]) and external (AUC 0.71, 95% CI [0.62, 0.80]) validations. CONCLUSION: The predictive model we developed should prove useful for adapting therapeutic strategy of relapse and follow-up to individual patients.

Pitfalls and challenges associated with phenoconversion in forensic toxcicology.

PURPOSE: In recent years, several publications have demonstrated the interest and the usefulness of pharmacogenetics in forensic toxicology. However, this approach remains namely focused on DNA-based phenotype, which may potentially lead to misinterpretation. Other determinants such as co-medication or physiological parameters may also impact the phenotype. This article aims to highlight the importance of considering such determinants in forensic toxicology, through the original case of a heroin-related fatality. METHOD: Ethanol concentration determination and toxicological screening were performed using gas chromatography with flame ionization detection, liquid chromatography with diode array detection and gas chromatography with mass spectrometry detection. CYP2C19 and CYP2D6 genotypes were determined by Taqman® real-time PCR analyses. RESULTS: Femoral blood analyses revealed the presence of ethanol, morphine, codeine, venlafaxine (VEN), O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV), paroxetine, and risperidone. 6-acetylmorphine was also identified in urine. VEN, paroxetine and risperidone were quantified at supra-therapeutic or toxic blood concentrations. NDV was not quantified. The metabolic ratio of VEN (ODV to VEN) was exceptionally low (about 0.7). Pharmacogenetics testing showed that the patient was heterozygous for the CYP2C19*2 loss-of-function allele, which predict an intermediate metabolism for CYP2C19. None of the deficient CYP2D6 alleles investigated were identified. Those results suggest an extensive CYP2D6-metabolism phenotype. CONCLUSION: A discrepancy was seen between the results of the genomic evaluation and the observed metabolic ratio of VEN. This tends to exclude a genetic origin and lead us to formulate other hypotheses, such as phenoconversion that may have been induced by drug interaction involving patients' regular medications. Phenoconversion is as a complex phenomenon that leads to genotype-phenotype mismatch without any genetic abnormality particularly described for cytochromes P450 2D6 and 2C19. Although transient, phenoconversion can have a significant impact on the analysis and interpretation of genotype-focused clinical outcomes correlation and in forensic toxicology conclusions.

Gunshot suicides caused by cane-gun and alarm garden gun cannon: Two cases report."

Obtaining a firearm is not always easy, which is why some firearms that are antique or whose use is not intended to kiss are modified for suicide purposes. The two cases report a suicide with an original historical firearm as the canegun, a walking stick which conceals a firearm and a suicide with a modified alarm cannon, which is a small cannon, which fires blanks to scare away garden animals. The aims of the study were to describe the scene, the corpse external examination and the autopsy to understand the death mechanism. We wish to highlight the importance of the forensic pathologist's fieldwork, especially in complex or atypical suicides.

The problem with medical research on tissue and organ samples taken in connection with forensic autopsies in France.

Currently, in France, it is legally impossible to conduct scientific research on tissue and organ samples taken from forensic autopsies. In fact, the law schedules the destruction of such samples at the end of the judicial investigation, and the common law rules governing cadaver research cannot be applied to the forensic context. However, nothing seems in itself to stand in the way of such research since, despite their specific nature, these samples from forensic autopsies could be subject, following legislative amendments, to common law relating to medical research on samples taken from deceased persons. But an essential legislative amendment, firstly to allow the Biomedicine Agency to become authorized to issue a research permit and secondly, to change the research conditions in terms of the non-opposition of the deceased to said research. Such an amendment would be a true breakthrough because it would allow teams to continue to move forward calmly in research, and allow this research to be placed within a legal framework, which would promote international exchanges.

Bone-patch type secondary projectiles: A report on two shots fired at point-blank range using hollow point bullets.

The number of head wounds due to firearms remains low in France because these cases are primarily linked to suicide (or attempted suicide) and, to a lesser extent, to attacks or hunting accidents [1]. Characterized by the impact of a projectile, which in most cases is made of metal, at high levels of kinetic energy, such acts generally result in severe trans-cerebral lesions with significant levels of morbidity/mortality [2]. Seldom are cases reported in the literature that give a detailed study of intracranial foreign bodies made of bone in such situations [3]. Here we report on the case of two suicides resulting from a transcranial gunshot wounds caused by weapons and ammunition issued by the French police force. Each case helped distinguish a characteristic bone fragment, in the form of a "patch", equivalent in size to the caliber of the bullet.

DES daughters in France: experts' points of view on the various genital, uterine and obstetric pathologies, and in utero DES exposure.

BACKGROUND: Compensation of diethylstilbestrol exposure depends on the judicial system. In France, girls having been exposed to diethylstilbestrol are currently being compensated, and each exposure victim is being evaluated. Fifty-nine expert evaluations were studied to determine the causal relation between exposure to diethylstilbestrol and the pathologies attributable to diethylstilbestrol. METHODS: The following were taken into consideration: age at the first signs of the pathology; age of the sufferer at the time of evaluation; the pathologies grouped into five categories: fertility disorders - cancers - mishaps during pregnancy - psychosomatic complaints - pathologies of "3rd generation DES victims"; submission of proof of DES exposure; the degree of causality determined (direct, indirect, ruled out). RESULTS: 61% of the cases related to fertility disorders, 28.8% to cancer pathologies (clear-cell adenocarcinoma), 18.6% to mishaps during pregnancy, 8.5% to disorders resulting from preterm delivery, and 3.4% to psychosomatic disorders. Some cases involved a combination of two types of complaints. Indirect causality was determined in 47.1% of the cases involving primary sterility, in 66.7% involving secondary sterility, and in 5 out of 6 cases of total sterility. There is direct causality between in utero diethylstilbestrol exposure and vaginal or cervical clear cell adenocarcinoma. Causality is indirect in the case of disorders linked to prematurity in third generation victims. CONCLUSION: Causality was determined by the experts on the basis of scientific criteria which attribute the presenting pathologies to diethylstilbestrol exposure. When other risk factors come into play, or when exposure is indirect (third generation), this causality is diminished.

Tomodensitometric survey of the distance between thoracic and abdominal vital organs and the wall according to BMI, abdominal diameter and gender: proposition of an indicative chart for the forensic activities.

INTRODUCTION: Forensic doctors are frequently asked by magistrates when dealing principally with knife wounds, about the depth of the blade which may have penetrated the victim's body. Without the use of imaging, it is often difficult to respond to this question, even in an approximate way. Knowledge of the various distances between organs and the skin wall would allow an assessment to be made of the minimum blade length required to obtain the injuries observed. The objective of this study is thus to determine average distances between the vital organs of the thorax and abdomen, and the skin wall, taking into account the person's body mass index (BMI). MATERIALS AND METHODS: This is a prospective single-center study, carried out over a 2-month period at University Hospital in Angers. A sample of 200 people was studied. The inclusion criteria were as follows: all patients coming to the radiology department and the emergency department for an abdominal, thoracic or thoraco-abdominal scan with injection. The exclusion criteria included patients presenting a large lymphoma, a large abdominal or retroperitoneal tumor, a tumor in one of the organs targeted by our study and patients presenting ascites. The organs focused on were: the pericardium, pleura, aorta, liver, spleen, kidneys, abdominal aorta and femoral arteries. The shortest distance between the organ and the skin wall was noted. Median distances were calculated according to gender, abdominal diameter and BMI. RESULTS: We associated these values to propose an indicative chart which may be used by doctors in connection with their forensic activities. DISCUSSION: The problem of the depth of a wound is frequently exposed to the expert. Without a reliable tool, it is difficult to value and a personal interpretation is often done. Even if, in current days, tomodensitometry is frequently done in vivo or after death, measurement can be difficult because of the local conditions. We classified values according to the different factors of fat repartition (BMI, abdominal diameter, gender). These tables, collectively used, permit evaluation of the distance between wall and thoracic or abdominal vital organs. CONCLUSION: We suggest an indicative chart designed for forensic doctors in their professional life to help determine the minimum penetration length for a knife, which may wound a vital organ.

Fatal falls from bicycles: a case report.

Though rare occurrences, fatal falls from bicycles are generally linked to the absence of a protective helmet and/or a collision with another vehicle. The case presented here is exceptional due to its circumstances and the consequences of the accident: a fall with no obstacle at a low speed that brought about multiple traumas and the death of a cyclist wearing a protective helmet. Comparing this against a review of cyclist accidentology literature, this case is unique. The increased use of autopsy in terms of forensic accidentology is to be encouraged so as not to misunderstand the possibility of such lesion-based consequences following a simple fall from a bicycle.

Visceral surgeon and intraoperative cholangiography: Survey about French Wild West surgeons.

Cholecystectomy is one of the most common abdominal surgical procedures. No formal agreement has been reached about the routine practice of intraoperative cholangiography (IOC). The purpose of this survey was to describe the practices and the opinions of surgeons in western France. A survey was conducted among 300 visceral surgeons practicing in western France who were asked to respond to a questionnaire with objective and subjective items. One hundred forty-eight answers were interpretable. Among these 148 surgeons, 125 (83.4%) performed IOC routinely (IOCr group) and 23 (15.4%) selectively (IOCs group). Mean age of responding surgeons was 49.3 years. Groups IOCr and IOCs were not significantly different concerning surgical experience. Surgeons in both groups responded that IOC effectively screens for intraoperative bile duct injury. In our survey, routine practice of IOC was more common than reported by our English-speaking colleagues. The routine users responded that IOC can screen for intraoperative bile duct injury or choledocholithiasis. The selective users responded that IOC has its own morbidity. IOC is commonly performed in France during laparoscopic cholecystectomy. Although it may not be indispensable, it allows rapid screening for intraoperative bile duct injury. It also provides documented proof of good surgical practice in the event of a litigation claim after bile duct injury.

Recognition by French courts of compensation for post-vaccination multiple sclerosis: the consequences with regard to expert practice.

Over the past few years, despite scientific uncertainties, French courts have awarded compensation to sufferers of multiple sclerosis (MS) which occurred following vaccination against hepatitis B. These legal decisions have aroused fierce criticism in the medical world. Both a judgment given on 25 May 2004 by the Court of Cassation and a new publication in the journal Neurology have encouraged us to look once more at this controversial issue. French judges began compensating patients with MS at the end of the 1990s. One of the first judgments was given in 2001 by the Court of Appeal of Versailles when a pharmaceutical laboratory was held liable for the onset of MS following vaccination against hepatitis B. On appeal, the Court of Cassation overturned the judgment in September 2003, finding that the Court of Appeal judges had based their decision on a hypothetical causal link. However, the only reason why the Court of Appeal judgment was quashed was the contradictory evidence on which the judges had based their presumptions. Several of the judgments given since that date seem to confirm this hypothesis. On 25 May 2004, the 2nd civil law chamber recognized that MS which occurs following a vaccination against hepatitis B (a vaccination carried out for work-related purposes) could be considered as an accident at work, without questioning the possible causal link between the illness and the vaccine. This jurisprudence in the matter of hepatitis B vaccination shows the need for great care in expert practice. Effectively, when confronted with drug related imputability, the expert usually bases his reasoning on three points: the causal role of the generating factor, the chronology and other causes of damage. In terms of MS, all these factors are modified. More than ever, an expert must, in terms of imputability, be objective, prudent and clear in his conclusions.

Healthcare law in France: towards healthcare emancipation for minors.

In France, since 1974 the rights of minors have been gaining ground. The first provisions to this end concerned medical acts in relation to the minor's sexuality (contraceptives and pregnancy termination). The law dated March 4, 2002, relating to patients' rights, gave more scope to this movement, by widening minors' rights so that they could demand confidentiality with regard to their parents. The minor's exercising of these rights can pose a lot of problems. In French law, parental authority is the main representation of the minor. The medical doctor treating a minor must obtain parental authorization. However, the public healthcare code provides that the doctor can override parental wishes during some situations (emergency; parents refuse). But these situations are exceptional. Since 2002, the legislator has gone further, by allowing the doctor to grant requests for care by the minor without parental authorization. However, parental authority remains the normal framework for the protection of a minor. The doctor will have to judge the reasoning and motives of a minor requesting confidentiality regarding their parents in order to decide whether he should grant or refuse care in such conditions.

Contribution of the study of acetabulum for the estimation of adult subjects.

INTRODUCTION: The study of the posterior part of the pelvis is of interest in forensic anthropology since it is an anatomical region that is very often preserved. The Lovejoy technique, using the auricular surface has brought about many studies and attracted many authors, among them Buckberry and Chamberlain utilized the criteria described by Lovejoy and developed new methods. By using this research as a starting point, we have described acetabular criteria. The goal of this study was to test these criteria and to link them to auricular surface reading criteria, as described by Buckberry and Chamberlain. METHOD: The study concerned 52 pelvises of known age and sex. We studied the age correlation of various criteria read at the acetabulum level and that of the auricular surface. We then went on to draw up scores and established a correlation of these scores with age. Intra- and inter-observer variability was also studied. We used the SPSS software package for statistical analyses. DISCUSSION: We were able to isolate four acetabular criteria and four auricular surface criteria which have a correlation with age. Establishing these scores (sum of criteria) allows a better age-based correlation to be obtained. Establishing an overall score, including acetabular criteria and auricular surface criteria, allows a good level of correlation to be obtained with age, with low intra- and inter-observer variability. CONCLUSION: The study of acetabulum is of interest for the age estimation of adult subjects. The joint study of the acetabulum and the auricular surface allows a higher correlation with actual age to be obtained. This study must be broadened to include a wider sample so as to allow fine-tuning of a method.

[More on compensation of the handicapped child]. / Loi "anti-Perruche": suite et... suite.

By adopting a heading enTITREd "solidarity towards handicapped people" within the French law dated March 4, 2002 on health reform, the government hoped to put an end to the controversy that ensued after the so-called "Perruche" ruling. Since then, several rulings have been given by administrative jurisdictions and it seems that debate in this area is far from over. The first point developed concerns issues raised about the concept of 'characterized malpractice' introduced under this law, the only type of malpractice that may render a doctor liable. A ruling by the Council of State on February 19, 2003 and two decisions by the Administrative Appeal Courts dated February 19 and April 20, 2004 gave an answer. Recent decisions, namely a ruling by the Council of State dated February 9, 2005, seem to confirm this impression. Characterized malpractice that can render a doctor liable is not gross neglect but rather neglect that is simple, certain and cannot be contested. However, due to its intensity and its proof, this type of neglect is more than just ordinary negligence. The second point discussed is the limitation of parents' compensable hardship attributable to medical malpractice. The law dated March 4, 2002 limited this compensation "solely to parents' hardship" to the exclusion of expenses incurred as a result of the child's handicap. National solidarity, which was intended to absorb this expense, is taking some time to become apparent. The legal decisions given since 2002 have thus brought about a certain level of unease both in public opinion and the legal profession. In June 2003, the Parisian Court of Appeal gave a surprising but apt ruling that may nevertheless bring certain concerns to the surface. To our knowledge, the Council of State has yet to issue an opinion on this subject. Doctors' liability in terms of the birth of child born with a congenital handicap is still a possibility.

[Patients refusal to be treated, the problem of Jehovah's witnesses]. / Refus de soins du patient, le problème épineux des témoins de Jéhovah.

The principle of respecting the patient's wishes is an international medical principle, found in several texts. In France, it was recalled in the 1994 Civil Code concerning bioethical laws and has recently been included in the Public health Code (law concerning patient's rights dated March 4, 2002). According to these various texts, the patient's wishes must always be respected, even in life threatening cases, so long as the patient has been informed of the risk. The refusal by Jehovah's witnesses to receive blood transfusion is always a problem. When, in full consciousness, a patient refuses a blood transfusion that his life depends on, what should the physician do? In June 1998, the Paris Court of Appeal ruled on this case. The judges found that "the obligation of the physician to always respect the wishes of the patient.is limited by the other obligation of the physician (the basis of a physician's activity) which is to protect the health and life of that same patient". In October 2001, the State Council ruling on this particular case found that, given the critical conditions of this case and the absence of a therapeutic alternative, the physicians had not committed an error. But it was also clearly underlined that a physician must respect the wishes of the patient and that this obligation must not be superseded by the duty of saving a life, thus disputing the judges of the Court of Appeal. Two questions. Two emergency interim rulings confirmed the position of the judges: the non-respect of the patient's wishes is an infringement of individual freedom. It is only in extreme and clearly defined circumstances that the physician will not be punished for this offence. This raises two questions: can a physician treat a patient against his/her wishes? And what risks does the physician take when respecting the patient's wishes when his/her life is at stake?

Evaluation of a training program for the prevention of lower back pain among hospital employees.

An evaluation of a training program for the prevention of lower back pain (LBP) was conducted over a two-year period in the Regional Hospital of Le Mans, which is located in the west of France and employs 2400 staff. The training program was based on a multidisciplinary approach to worker training in the prevention of LBP and in ergonomic efforts in the workplace. Workers received theoretical training on LBP, patient handling and ergonomics, and on-the-job ergonomics instruction to help them to implement participative ergonomics in their working groups. A cohort of 136 employees attended classes on safe posture and patient handling, then received advice from instructors who observed them while they performed their typical workday tasks.

[General practitioners' practices and attitudes in regard to suicidal behavior]. / Pratiques et attentes des médecins généralistes à l'égard des conduites suicidaires.

As demonstrated at the recent Consensus Conference on the "suicidal crisis" held by the French Psychiatry Union and the National Agency for the Accreditation and the Evaluation of Care, suicide is recognised as a current public health problem. The general practitioner's role is situated on two levels: in a preliminary stage, the early identification of risk, and in a secondary stage, the provision of care at the time of a suicide attempt and then the provision of on-going follow-up care in partnership with other special services. The study aimed at evaluating general practitioners' practices when encountered with suicidal patients and assessing their management of suicidal behaviour, as well as difficulties met and their expectations. Responses to a questionnaire were received from 290 general practitioners in one regional department in France. The results revealed that two-thirds of the respondents considered the identification of suicidal tendencies as being difficult, in particular with regard to the detection of young people at risk. General hospitals are the most common structures where patients are referred to in the event of a suicide attempt, as a facility that is permanently open and capable of delivering ambulatory care. A majority of the general practitioners expressed the need for training which was focused on methods for the early identification of risk as well as the development of listening skills.

[The obligation of means and the obligation of results]. / L'obligation de moyen et l'obligation de résultat.

Several important decisions were made in 2000 concerning the proof of malpractice and the fundamental principles of medical responsibility. In order to guarantee indemnities for victims of medical accidents, the French courts have facilitated the implication of medical responsibility for medical accidents. The notion of a "virtual fault" was developed allowing the courts to retain the responsibility of the surgeon for instance for injury to the sublingual nerve during extraction of a wisdom tooth or for injury to the popliteal artery (March 23, 2000). These decisions not only facilitate the demonstration of malpractice but also modify the definition of responsibility, all physicians being required to use all available means. Likewise, although jurisprudence asserts that a safe result is mandatory in certain areas, the essential obligation is the absence of "fault" and not the result despite the disquieting arguments put forward by the Paris appeals court in its January 15, 1999 decree. The patient's right to a result was sustained only in well defined areas.

Nosocomial Candida albicans acquisition in a geriatric unit: epidemiology and evidence for person-to-person transmission.

This prospective study, which included 69 patients over a two-month period, was conducted to evaluate the incidence of community-acquired carriage and hospital-acquired yeasts in elderly patients hospitalized in a short stay care unit. Furthermore, possible person-to-person transmission was investigated by means of genotyping the Candida albicans isolates obtained from samples (throat swabs, urine and stools) systematically taken from the patients at different times during the hospitalization and from healthcare workers (throat swabs and handwashes) in the middle of the observation period. This study showed a high prevalence rate of 64% for community-acquired yeast carriage and a 40% incidence rate for hospital- acquired yeasts. Mycological analysis of the samples from the healthcare workers revealed eight of them to be colonized in the oral cavity. In addition, pulsed field gel electrophoresis and mitochondrial DNA analysis of the C. albicans isolates demonstrated person-to-person transmission. This study suggests that regular mycological sampling should be done as hospitalized elderly patients are frequently colonized by yeasts. Likewise, oropharyngeal swabs from healthcare workers may be helpful in this setting.

[Evaluation of nutritional status in hospitalized aged persons]. / Evaluation de l'état nutritionnel de la personne âgée hospitalisée.

The health status of older people strongly depends on their nutritional status. Hospitalisation is a factor that aggravates protein-energy malnutrition among older people. A descriptive study was completed among 71 subjects over 65 years old and hospitalised in a gerontological internal medicine service. The study used a nutritional evaluation scale called the Mini Nutritional Assessment (MNA). The study showed that 21% of subjects had an acceptable nutritional status, 49% were considered to be "at risk of undernourishment", and 31% were malnourished. A relationship was observed between the MNA score, the degree of autonomy (AGGIR grid), cognitive functions (Mini Mental State: MMS) and the existence of an anxious-depressive state. These elements should be taken into consideration to avoid the aggravation of the nutritional status of older people in the hospital, or to improve it. In addition, certain simple biological exams (albumin, pre-albumin, reactive protein) are necessary to assess the endogenous or exogenous aspect of undernourishment.

Evaluation of an educational low back pain prevention program for hospital employees.

OBJECTIVES: To evaluate the impact of an educational low back pain prevention program in a cohort of hospital employees. METHODS: A cohort of 136 nonclerical hospital employees attended classes on safe postures and patient handling, then received advice by educators who observed them while they performed their typical workday tasks. Each of the subjects in this intervention group was matched on age, sex, and job category with a control. Musculoskeletal complaints and changes in habits during work and recreational activities were evaluated before the intervention (or the corresponding date in the control group) and after two years. RESULTS: In the intervention group, 36% of subjects with low back pain at baseline were free of this symptom at follow-up, whereas only 26% were in the opposite situation. The proportion of subjects with low back pain episodes lasting longer than 30 days increased significantly from baseline to follow-up in the control group (from 30% to 49%) but not in the intervention group. The number of sick leaves longer than 30 days decreased significantly in the intervention group. Only 33% of the intervention group subjects felt the intervention had been helpful; this proportion varied across job categories. CONCLUSION: Our data suggest that differences in job categories should be taken into account when designing educational programs for preventing low back pain. They also indicate that back school programs may be more effective in subjects with a history of low back pain, whereas instruction on safe postures and patient handling may be the best approach in subjects who have not previously experienced low back pain. Observing and providing advice to employees while they are performing their usual duties may be an essential component of low back pain prevention.