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Dimanche 19 mai 2013 7 19 /05 /Mai /2013 22:02
Antibiotics could cure 40% of chronic back pain patients
Scientists hail medical breakthrough by which half a million UK sufferers could avoid major surgery and take antibiotics instead

guardian.co.uk, Tuesday 7 May 2013

Scientists in Denmark found that 20% to 40% of chronic lower back pain was caused by bacterial infections. Photograph: Alamy
Up to 40% of patients with chronic back pain could be cured with a course of antibiotics rather than surgery, in a medical breakthrough that one spinal surgeon says is worthy of a Nobel prize.

Surgeons in the UK and elsewhere are reviewing how they treat patients with chronic back pain after scientists discovered that many of the worst cases were due to bacterial infections.

The shock finding means that scores of patients with unrelenting lower back pain will no longer face major operations but can instead be cured with courses of antibiotics costing around £114.

One of the UK's most eminent spinal surgeons said the discovery was the greatest he had witnessed in his professional life, and that its impact on medicine was worthy of a Nobel prize.

"This is vast. We are talking about probably half of all spinal surgery for back pain being replaced by taking antibiotics," said Peter Hamlyn, a consultant neurological and spinal surgeon at University College London hospital.

Hamlyn recently operated on rugby player Tom Croft, who was called up for the British and Irish Lions summer tour last month after missing most of the season with a broken neck.

Specialists who deal with back pain have long known that infections are sometimes to blame, but these cases were thought to be exceptional. That thinking has been overturned by scientists at the University of Southern Denmark who found that 20% to 40% of chronic lower back pain was caused by bacterial infections.

In Britain today, around 4 million people can expect to suffer from chronic lower back pain at some point in their lives. The latest work suggests that more than half a million of them would benefit from antibiotics.

"This will not help people with normal back pain, those with acute, or sub-acute pain – only those with chronic lower back pain," Dr Hanne Albert, of the Danish research team, told the Guardian. "These are people who live a life on the edge because they are so handicapped with pain. We are returning them to a form of normality they would never have expected."

Claus Manniche, a senior researcher in the group, said the discovery was the culmination of 10 years of hard work. "It's been tough. There have been ups and downs. This is one those questions that a lot of our colleagues did not understand at the beginning. To find bacteria really confronts all we have thought up to this date as back pain researchers," he said.

The Danish team describe their work in two papers published in the European Spine Journal. In the first report, they explain how bacterial infections inside slipped discs can cause painful inflammation and tiny fractures in the surrounding vertebrae.

Working with doctors in Birmingham, the Danish team examined tissue removed from patients for signs of infection. Nearly half tested positive, and of these, more than 80% carried bugs called Propionibacterium acnes.

The microbes are better known for causing acne. They lurk around hair roots and in the crevices in our teeth, but can get into the bloodstream during tooth brushing. Normally they cause no harm, but the situation may change when a person suffers a slipped disc. To heal the damage, the body grows small blood vessels into the disc. Rather than helping, though, they ferry bacteria inside, where they grow and cause serious inflammation and damage to neighbouring vertebrae that shows up on an MRI scan.

In the second paper, the scientists proved they could cure chronic back pain with a 100-day course of antibiotics. In a randomised trial, the drugs reduced pain in 80% of patients who had suffered for more than six months and had signs of damaged vertebra under MRI scans.

Albert stressed that antibiotics would not work for all back pain. Over-use of the drugs could lead to more antibiotic-resistant bacteria, which are already a major problem in hospitals. But she also warned that many patients will be having ineffective surgery instead of antibiotics that could alleviate their pain.

"We have to spread the word to the public, and to educate the clinicians, so the right people get the right treatment, and in five years' time are not having unnecessary surgery," she said.

Hamlyn said future research should aim to increase the number of patients that respond to antibiotics, and speed up the time it takes them to feel an improvement, perhaps by using more targeted drugs.

The NHS spends £480m on spinal surgery each year, the majority of which is for back pain. A minor operation can fix a slipped disc, which happens when one of the soft cushions of tissue between the bones in the spine pops out and presses on nearby nerves. The surgeons simply cut off the protruding part of the disc. But patients who suffer pain all day and night can be offered major operations to fuse damaged vertebrae or have artificial discs implanted.

"It may be that we can save £250m from the NHS budget by doing away with unnecessary operations. The price of the antibiotic treatment is only £114. It is spectacularly different to surgery. I genuinely believe they deserve a Nobel prize," said Hamlyn. Other spinal surgeons have met Albert and are reviewing the procedures they offer for patients.



Brian Clegg discusses the deeply random nature of the universe. Plus, Hanne Albert on her discovery that antibiotics may alleviate a particular kind of lower back pain

Back pain: should I ask my doctor for a course of antibiotics?
Par Chronimed
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Dimanche 19 mai 2013 7 19 /05 /Mai /2013 21:58
Doctors are protesting new guidance for the diagnosis of some mental disorders, including autism, contained in the revised edition of a professional manual to be released in coming days.

The so-called “psychiatric bible,” whose first update in 19 years will be released at a medical meeting that opens in San Francisco on May 18, also influences the way patients are treated and reimbursed for mental disorders. A petition that raised concerns about the manual’s diagnostic categories and patient safety received more than 3,000 signatures from Paris to Montreal in recent months.

The Diagnostic and Statistical Manual of Mental Disorders is the standard used by mental-health professionals for diagnosing illness and for research. The newest edition is meant to incorporate the latest research findings and has collapsed several conditions, including Asperger’s syndrome and child disintegrative disorder, into a single autism diagnosis.

The new guideline “is really an example of psychiatric imperialism,” said Gordon Parker, Scientia Professor of psychiatry at Sydney-based University of New South Wales. It has “a flawed logic and a flawed model which leads to compromised research and also compromises management.”

Parker was speaking to reporters today with other Australian academics who commented on the changes. In March, a group of British mental-health professionals issued a petition against the changes, according to a release posted on the British Psychological Society’s website.

The manual known as DSM is the most widely used classification system globally, Michael Berk, professor of psychiatry at Melbourne’s Deakin University, said in an interview last year.

By Natasha Khan - May 15, 2013

To contact the reporter on this story: Natasha Khan in Hong Kong at nkhan51@bloomberg.net
To contact the editor responsible for this story: Jason Gale at j.gale@bloomberg.net
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Dimanche 19 mai 2013 7 19 /05 /Mai /2013 21:50
Les troubles du « spectre autistique » recouvrent toute une série de difficultés de communication, de difficultés sociales, de restrictions des centres d’intérêts et de comportements stéréotypés.

Ils incluent l'autisme vrai, le syndrome d'Asperger, l'autisme atypique et les troubles envahissants du développement non spécifiques. A côté des facteurs génétiques, de nombreux éléments environnementaux peuvent intervenir dans leur déclenchement ; parmi eux, est suspectée l'exposition prénatale au valproate, médicament utilisé dans le traitement de l'épilepsie et de divers troubles neuro- psychiatriques.

Une étude a été menée afin de préciser si l'exposition pré natale au valproate était vraiment responsable d'un risque accru d'autisme chez l'enfant.

Ce travail a tenu compte des autres facteurs connus pouvant majorer ce risque , également de la dose de valproate administrée, de la date d'exposition, d'une poly thérapie éventuelle, des malformations congénitales possiblement associées et des antécédents maternels d' épilepsie.

Tous les enfants nés au Danemark pendant 11 ans

Tous les enfants nés vivants au Danemark entre le 1er janvier 1996 et le 31 décembre 2006 ont été identifiés à l'aide du Système Danois d'Enregistrement Civil.

Le Registre National des Prescriptions a fourni, quant à lui, toutes les informations sur les prises médicamenteuses des futures mères (à l'exception des seuls traitements administrés en milieu hospitalier, non comptabilisés dans le registre).

L'exposition maternelle était définie comme la prise d’anti-épileptiques durant la période allant de 30 jours avant la conception jusqu'à la date de l’accouchement. Ont été considérées non seulement l'exposition au valproate mais aussi aux autres anti-épileptiques les plus communément utilisés (carbamazépine, clonazépam, lamotrigine et oxacarbazépine).

Pour chacune de ces molécules, la consommation a été estimée en fonction de la dose définie par jour (DDD) , élevée quand elle dépassait 50 % de la DDD, basse quand elle se situait à moins de 50 %. Parallèlement, le Registre Central Danois de Psychiatrie a permis d'identifier les enfants chez qui avait été porté, durant cette période, un premier diagnostic de troubles du spectre autistique ainsi que les possibles antécédents psychiatriques parentaux.

Les enfants ont été suivis depuis leur naissance jusqu' au 31 décembre 2010, sauf en cas de survenue d'une première manifestation d'autisme, de décès ou d'émigration.

L'objet principal de l'étude était d’apprécier le risque (Hazard Ratio [HR]) de troubles du spectre autistique chez l'enfant en cas d’administration de valproate chez la mère durant la période de conception et la grossesse, après ajustement pour les facteurs potentiels de confusion tels que âge des parents lors de la conception, âge gestationnel, poids de naissance, sexe, parité, malformations congénitales associées, antécédents épileptiques et/ou psychiatriques des parents.

Les enfants exposés au valproate ont été comparés aux enfants non exposés, chez lesquels l’incidence de l'autisme a été aussi examinée.

Dans un second temps, des analyses de sensibilité se sont attachés à déterminer le risque relatif de troubles autistiques pour les enfants dont la mère avait pris du valproate durant la période critique vs ceux dont la mère avait arrêté d'en consommer, à étudier l'impact des posologies forte ou faible, des associations médicamenteuses à d'autres anti-épileptiques, enfin l'importance du rôle du sexe eu égard à la prévalence plus élevée de l'autisme chez les garçons.

Un risque de troubles du spectre autistique plus que doublé en cas d’exposition au valproate

Après diverses exclusions, la cohorte d'enfants nés entre 1996 et 2006 regroupait 655 615 sujets, dont 428 400 issus de mères différentes. Quatre pour cent (n = 26 418) étaient issus de naissances multiples. A la fin du suivi, l'âge des enfants était en moyenne de 8,85 ans (4- 14).

Durant cette période ont été diagnostiqués 5 437 cas de troubles du spectre autistique, dont 2 067 autismes infantiles vrais ; 2644 enfants avaient été exposés à des drogues anti-épileptiques durant la grossesse, dont 508 au valproate.

Avec 14 ans de suivi, le risque absolu (incidence cumulée) de troubles du spectre autistique a été établi à 1,53 % (intervalle de confiance à 95 % [IC] : 1,47-1,58) et celui d’autisme vrai à 0,48 % (IC : 0,46-0, 51). L'exposition spécifique au valproate durant la grossesse, observé chez 508 enfants, accroît très considérablement le risque absolu, qui passe respectivement à 4,42 % (IC : 2,59- 7,46) et 2,5 % (IC : 1,30- 4,81), soit un HR de 2,3 (IC : 1,7- 4,9) et 5,2 (IC : 2,7- 10,0).

En ne prenant en compte que les enfants nés de mère épileptique (n= 6 584), le risque est, en cas d'exposition au valproate (n = 432), de 4,15 % pour l'ensemble des troubles du spectre autistique et de 2,95 % pour l'autisme vrai, soit un HR ajusté respectivement à 1,7 et 2,9, vs un risque de 2,44 et 1,02 pour les 6 152 enfants de mère épileptique non exposés au valproate. Ce risque est particulièrement accru chez les enfants de la cohorte dont la mère avait pris du valproate durant le premier trimestre de sa grossesse (HR à 2,9 et 4,7).

Il n’apparaît pas de différence notable selon que les posologies aient été supérieures à 750 mg/j ou plus basses. A contrario, le risque n’est pas notablement majoré par la prise des autres anti-épileptiques référencés dans ce travail.

Point important, l’excès de risque persiste même après exclusion des 25 619 enfants porteurs de malformations congénitales.

Que la mère soit épileptique ou non

Ainsi, cette large étude de cohorte, basée sur l'ensemble de la population danoise, montre-t-elle que les enfants nés de mère ayant consommé du valproate durant leur grossesse sont à haut risque de troubles du spectre autistique et d'autisme vrai.

Cette élévation du risque concerne aussi bien les enfants de mères épileptiques que ceux de mères indemnes de comitialité. Elle ne parait pas influencée par les posologies journalières forte ou faible.

Elle n'est pas retrouvée avec d'autres anti-épileptiques tels que la carbamazépine, le clonazépam, le lamotrigine ou l'oxacarbazépine en monothérapie. Elle persiste après exclusion des enfants porteurs de malformations congénitales.

Dans cette étude, le risque de biais de sélection a été très faible de par la durée du suivi et le faible pourcentage (< 3 %) d'enfants perdus de vue.

Il faut certes rappeler que les prescriptions purement hospitalières de valproate n’ont pas été prises en compte. De même, les registres utilisés n’ont pas permis de prendre en compte la survenue de crises épileptiques au cours des grossesses ni celles l’existence d’une intempérance éthylique ou d’une prise préventive de l'acide folique.

En conclusion, la prise maternelle de valproate durant une grossesse augmente notablement le risque d'autisme infantile, même après ajustement pour les autres facteurs tels qu’épilepsie ou pathologie psychiatrique parentale.

Cette notion doit être présente lors de l’appréciation du rapport bénéfices/risques, avant d'instituer un traitement par valproate chez une femme en âge de procréer.


Dr Pierre Margent Publié le 19/05/2013

Christensen J et coll. : Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism. JAMA. 2013; 309: 1696- 1703.


Antidépresseur pendant la grossesse et risque d’autisme : le lien reste à explorer
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Samedi 18 mai 2013 6 18 /05 /Mai /2013 12:00
Rapid Improvement of Acute Schizophrenia Symptoms After Intravenous Sodium Nitroprusside A Randomized, Double-blind, Placebo-Controlled Trial Jaime E. C. Hallak, MD, PhD; Joao Paulo Maia-de-Oliveira, MD; Joao Abrao, MD, PhD; Paulo R. Evora, MD, PhD; Antonio W. Zuardi, MD, PhD; Jose A. S. Crippa, MD, PhD; Paulo Belmonte-de-Abreu, MD; Glen B. Baker, PhD, DSc; Serdar M. Dursun, MD, PhD, FRCPC JAMA Psychiatry. 2013;():1-9. doi:10.1001/jamapsychiatry.2013.1292. The treatment of schizophrenia remains a challenge, and the currently available antipsychotic drugs are slow acting and produce a number of adverse effects. Objective To examine the effectiveness and safety of a single intravenous administration of sodium nitroprusside (0.5 μg/kg/min for 4 hours) on the positive, negative, anxiety, and depressive symptoms in patients with schizophrenia. Design Single-center, randomized, double-blind, placebo-controlled trial performed from March 9, 2007, to March 12, 2009. Setting University teaching hospital in São Paulo, Brazil. Participants Twenty inpatients aged 19 to 40 years with a diagnosis of schizophrenia who were in the first 5 years of the disease who are taking antipsychotics. Intervention Sodium nitroprusside administration. Main Outcome Measures The 18-item Brief Psychiatric Rating Scale and the negative subscale of the Positive and Negative Syndrome Scale. Results After the infusion of sodium nitroprusside, a rapid (within 4 hours) improvement of symptoms was observed. The placebo and experimental groups had significant differences in the 18-item Brief Psychiatric Rating Scale total score and subscale scores, which persisted for 4 weeks after infusion. Conclusions The results clearly show a therapeutic effect of sodium nitroprusside. If this drug is approved for routine clinical use in patients with schizophrenia, this discovery will be an important advance in the pharmacologic treatment of this devastating disorder. Trial Registration clinicaltrials.gov Identifier: NCT01548612 http://archpsyc.jamanetwork.com/article.aspx?articleid=1686035
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Vendredi 17 mai 2013 5 17 /05 /Mai /2013 20:58
May 2013 Flu in Pregnancy May Quadruple Child’s Risk for Bipolar Disorder NIH-funded Study Adds to Evidence of Overlap with Schizophrenia Pregnant mothers’ exposure to the flu was associated with a nearly fourfold increased risk that their child would develop bipolar disorder in adulthood, in a study funded by the National Institutes of Health. The findings add to mounting evidence of possible shared underlying causes and illness processes with schizophrenia, which some studies have also linked to prenatal exposure to influenza. This colorized transmission electron micrograph shows H1N1 influenza virus particles. Surface proteins on the virus particles are shown in black. Source: NIAID “Prospective mothers should take common sense preventive measures, such as getting flu shots prior to and in the early stages of pregnancy and avoiding contact with people who are symptomatic,” said Alan Brown, M.D., M.P.H, of Columbia University and New York State Psychiatric Institute, a grantee of the NIH’s National Institute of Mental Health (NIMH). “In spite of public health recommendations, only a relatively small fraction of such women get immunized. The weight of evidence now suggests that benefits of the vaccine likely outweigh any possible risk to the mother or newborn.” Brown and colleagues reported their findings online May 8, 2013 in JAMA Psychiatry. Although there have been hints of a maternal influenza/bipolar disorder connection, the new study is the first to prospectively follow families in the same HMO, using physician-based diagnoses and structured standardized psychiatric measures. Access to unique Kaiser-Permanente, county and Child Health and Development Study databases made it possible to include more cases with detailed maternal flu exposure information than in previous studies. Among nearly a third of all children born in a northern California county during 1959-1966, researchers followed 92 who developed bipolar disorder, comparing rates of maternal flu diagnoses during pregnancy with 722 matched controls. The nearly fourfold increased risk implicated influenza infection at any time during pregnancy, but there was evidence suggesting slightly higher risk if the flu occurred during the second or third trimesters. Moreover, the researchers linked flu exposure to a nearly sixfold increase in a subtype of bipolar disorder with psychotic features. A previous study, by Brown and colleagues, in a related northern California sample, found a threefold increased risk for schizophrenia associated with maternal influenza during the first half of pregnancy. Autism has similarly been linked to first trimester maternal viral infections and to possibly related increases in inflammatory molecules. “Future research might investigate whether this same environmental risk factor might give rise to different disorders, depending on how the timing of the prenatal insult affects the developing fetal brain,” suggested Brown. Bipolar disorder shares with schizophrenia a number of other suspected causes and illness features, the researchers note. For example, both share onset of symptoms in early adulthood, susceptibility genes, run in the same families, affect nearly one percent of the population, show psychotic behaviors and respond to antipsychotic medications. Increasing evidence of such overlap between traditional diagnostic categories has led to the NIMH Research Domain Criteria (RDoC) project, which is laying the foundation for a new mental disorders classification system based on brain circuits and dimensional mechanisms that cut across traditional diagnostic categories. The research was also funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Reference Gestational Influenza and bipolar Disorder in Adult Offspring. Parboosing R, Bao Y, Shen L, Schaefer CA, Brown AS. JAMA Psychiatry, May 8, 2013. Grant Numbers 5 R01 MH073080 05 5 K02 MH065422 10 5 R01 MH069819 05 N01-HD-1-3334 N01-HD-6-3258 ### The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website. The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the NICHD website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website. http://www.nimh.nih.gov/news/science-news/2013/flu-in-pregnancy-may-quadruple-childs-risk-for-bipolar-disorder.shtml
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