Archive for Junho, 2013


In patients with acute ischemic stroke, even small reductions in the time to thrombolytic therapy are associated with improved outcomes, according to a study in JAMA.

 

Using a national stroke registry, U.S. researchers examined outcomes among some 58,000 patients, at nearly 1400 hospitals, who received intravenous tissue plasminogen activator (tPA) within 4.5 hours after symptom onset. They found that with each 15-minute decrease in time to tPA therapy, patients were significantly less likely to die in the hospital or experience intracranial hemorrhage (odds ratio for each, 0.96). In addition, each 15-minute reduction was significantly associated with a greater likelihood to walk independently at discharge (OR, 1.04) and to be discharged home (OR, 1.03).

“These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke,” the researchers conclude.

Time to Treatment With Intravenous Tissue Plasminogen Activator and Outcome From Acute Ischemic Stroke

Importance  Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain.

Objective  To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA.

Design, Setting, and Patients  Data were analyzed from 58 353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012.

Main Outcomes and Measures  Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination.

Results  Among the 58 353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45 029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19 491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22 541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P < .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P < .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P < .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P < .001).

Conclusions and Relevance  In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke.

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Em que consiste?

A ultrassonografia vascular cérvico-encefálica consiste na utilização dos ultra-sons para o estudo dos principais vasos responsáveis pela perfusão sanguínea cerebral. No estudo do doente com AVC é importante a avaliação a nível cervical dos eixos carotídeos e artérias vertebrais, e a nível intracraniano das artérias da base do crânio (cerebrais médias, anteriores e posteriores, oftálmicas, vertebrais no trajeto intracraniano e basilar); para o estudo destas últimas utilizam-se ‘janelas’ ósseas para a passagem dos ultra-sons – janelas orbitária, temporal e occipital.

Usa-se geralmente o termo eco-Doppler, dado ser possível por um lado a avaliação ecográfica da morfologia arterial, e por outro a avaliação da velocidade de fluxo através do efeito Doppler. É importante salientar que a nível transcraniano as técnicas atuais não permitem a caracterização das paredes arteriais, sendo o vaso ‘desenhado’ pelo seu fluxo através do Doppler codificado a cor; neste exame privilegia-se assim a análise velocimétrica. Portanto no fundo vamos encontrar neste exame um registro das velocidades de fluxo que indiretamente nos dão informação sobre as condições hemodinâmicas e os diversos tipos de patologia. 

Quais as suas vantagens e desvantagens?

Trata-se de uma técnica não invasiva, relativamente barata, se necessário pode ser efetuada à beira do leito, fornece informação em tempo real e pode ser repetido permitindo monitorização. Fornece não só a avaliação morfológica do vaso mas também o perfil hemodinâmico da circulação através da análise das velocidades de fluxo. Há utilidade em associar o estudo cervical e craniano, pois só assim se obtém uma noção mais global do estado circulatório cerebral.

Tem a desvantagem de depender do operador, que deverá ter a preparação teórica e prática adequadas à aquisição e interpretação dos dados no contexto do quadro clínico. Por outro lado não estuda toda a circulação cervical e cerebral, como faz a angiografia, que contudo tem outro tipo de problemas como o carácter invasivo e potenciais complicações. O doppler transcraniano tem a desvantagem de depender da qualidade da janela óssea, impedindo um exame conclusivo; os novos produtos de contraste ultrassonográficos tentam melhorar a aquisição de registos nestes casos.

Que informação pode fornecer o eco-Doppler carotídeo e vertebral cervical e qual a possível repercussão na orientação clínica?

    1. Dados sobre a morfologia da artéria – tortuosidades, diâmetro anormalmente pequeno (hipoplasia) ou grande (mega-artéria). As alterações da morfologia da artéria  excepcionalmente requerem reparação cirúrgica.

  • Aferição da espessura da parede arterial – o aumento da espessura do complexo íntima-média constitui um marcador de aterosclerose sistémica e correlaciona-se positivamente com os fatores de risco de aterosclerose; 

    1. Existência de placas ateroscleróticas, sendo importante para a sua caracterização referir a localização na artéria, a extensão longitudinal, a ecoestrutura (homo ou heterogênea, de predomínio hipo, iso ou hiperecogénico), o seu contorno (superfície regular, irregular ou ulcerada), a porcentagem de estenose – ou mesmo oclusão – do lúmen após avaliação em planos longitudinais e transversais, e a alteração do fluxo associada (ex.: aceleração, turbulência).
      A característica da placa com maior valor preditivo do risco de evento isquêmico cerebral ipsilateral é a sua porcentagem de estenose. No entanto o caráter hipoecogênico e a superfície ulcerada constituem fatores adicionais de aumento desse risco.
      A presença de placa aterosclerótica requer controle dos fatores de risco vascular e antiagregação plaquetária. Consoante as suas características e quadro clínico do doente poderá recomendar-se recanalização através de endarterectomia cirúrgica ou de angioplastia (tratamento endovascular). 
      Após estudos multicêntricos de larga escala (NASCET1,2, ECST3, ACAS4), nos quais os doentes com diferentes graus de estenose carotídea foram randomizados para tratamento conservador ou para endarterectomia, temos as 
      seguintes recomendações internacionais:

      Estenose sintomática – endarterectomia está recomendada para doentes com estenose 70-99% e deve apenas ser efetuada em centros com taxa de complicações peri-operatórias (AVC e morte) inferior a 6%. Está recomendado que a endarterecomia deve ser realizada assim que possível após o último evento isquémico, idealmente dentro de duas semanas. A endarterectomia pode estar indicada para alguns doentes com estenose de 50-69% se o risco peri-operatório for inferior a 3%, sendo mais benéfica em determinados subgrupos como os indivíduos do sexo masculino recentemente sintomáticos.
      Estenose assintomática – a endarterectomia carotídea pode estar indicada para alguns doentes com estenose de 60-99%. Apenas doentes com um risco operatório baixo (<3%) e expectativa de vida de pelo menos 5 anos poderão beneficiar da cirurgia.

  • Outras arteriopatias não ateroscleróticas, como dissecção, arterite/vasculite, displasia fibromuscular. É importante a detecção de dissecção na fase aguda pois recomenda-se anticoagulação, tentando assim impedir progressão. A sugestão de arterite/vasculite leva à procura de outros dados semiológicos e analíticos para confirmação de diagnóstico, seguido de eventual imunossupressão, ou tratamento de infecção associada.

  • Alterações hemodinâmicas refletindo indiretamente a existência de patologia a nível mais proximal (cardíaco, arco aórtico) ou distal (intracraniano). Alerta para a procura de lesões a esses níveis

Que informação pode fornecer o Doppler e o eco-Doppler transcraniano (DTC) e qual a possível repercussão na orientação clínica?

    1. Sinais de estenoses segmentares ou oclusão das artérias da base do crânio, de causa aterosclerótica ou vasculítica. Pode gerar, conforme os casos e a etiologia, tratamentos como fibrinólise, anticoagulação, antiagregação, imunossupressão, ou mesmo antibiótico se houver vasculite de causa infecciosa, para além de eventual angioplastia.

  • Existência e estado da colateralização intracraniana no contexto de lesão arterial cervical, através das artérias oftálmica,  comunicantes anterior ou posteriores. Fornece informação prognóstica e pode influenciar a orientação clínica sobre a lesão causal.

  • Pode sugerir cardioembolismo se uma oclusão de artéria intracraniana detectada na fase aguda desaparece espontaneamente nos primeiros dias, pois é comum assim acontecer com os êmbolos de origem cardíaca.

  • Sinais indiretos de oclusão de ramo da artéria cerebral média ou da vertebral.

  • Sinais indiretos de lesão mais distal, principalmente a nível da microcirculação em situações de hipertensão intracraniana associada ao AVC, permitindo a monitorização dessas alterações e resposta às terapêuticas; em casos fatais o DTC poderá levar ao reconhecimento de parada circulatória cerebral indicadora de morte cerebral.

  • Sinais de vasospasmo arterial, nomeadamente como complicação de hemorragia subaracnoideia. Para além da informação prognóstica, é muito importante o seu reconhecimento e monitorização para tratamento instituido, reduzindo o risco de isquemia tardia.

  • Detecção de alterações hemodinâmicas sugestivas de anastomoses artério-venosas, nomeadamente no contexto de hemorragia cerebral provocada por rotura de malformação vascular. Levantando a suspeita impõe-se realização de arteriografia para confirmação.

  • Monitorização dos efeitos de terapêuticas como fibrinolíticos para recanalização arterial, imunossupressão no tratamento de vasculites, terapêutica antiedematosa para controlo da hipertensão intracraniana, expansores plasmáticos e nimodipina no vasospasmo, embolização de malformação, etc.

  • Avaliação do estado de autorregulação e vasorreatividade cerebrais, geralmente para informação sobre a gravidade de patologia associada.

  • Diagnóstico de comunicações anormais intracardíacas como a patência do foramen oval, através da monitorização de sinais microembólicos na circulação cerebral após bolus endovenoso de contraste que não seja transpulmonar (ex. soro fisiológico agitado com pequena quantidade de ar), concomitantemente a manobra de Valsalva.

  • Monitorização de sinais microembólicos em doentes com patologia cardíaca ou carotídea para avaliação do seu potencial embolígênico, podendo influenciar a decisão terapêutica.

  1. Monitorização da circulação cerebral durante cirurgia carotídea ou cardíaca para fornecimento de informações ao cirurgião e assim minimizar o risco de infarto per-operatório.

Para além de toda a  informação que, como referido, a neurossonologia pode fornecer na fase aguda do AVC, é útil no seguimento do doente  para controle de estenoses e de eventual recanalização de dissecções, afora monitorização de velocidades na anemia falciforme

SAN FRANCISCO — The greater the overuse of smartphones, the greater the risk for severe psychopathologies in adolescents, new research suggests.

The study of nearly 200 adolescents in Korea showed that those who were very high users of smartphones had significantly more problematic behaviors, including somatic symptoms, attentional deficits, and aggression, than did those who were low users.

In addition, the investigators note that the effects of smartphone overuse were similar to those of Internet overuse. Internet use gaming disorder has been included in Section 3 of the just-released fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the section of the manual reserved for conditions considered worthy of further research.

“Regardless of addictive patterns, our results showed that the more addicted that youth were, the more severe their psychopathologies were,” study investigator Jonghun Lee, MD, PhD, professor of psychiatry at the Catholic University of Daegu School of Medicine in South Korea, told reporters attending a press briefing here at the the American Psychiatric Association’s (APA’s) 2013 Annual Meeting.

“The number of adolescents addicted to smartphone use will increase because the popularization of smartphones is an inevitable social trend. And the younger they are, the more vulnerable they are,” said Dr. Lee.

Therefore, he said, clinicians should try to screen for smartphone addiction, as well as for Internet or computer addiction, in their adolescent patients.

However, “there is no standardized scale for defining this, so we need to develop it. It’s important to identify youth who are at risk to prevent their addiction,” Dr. Lee told Medscape Medical News.

Press conference moderator Jeffrey Borenstein, MD, chair of the Council on Communications for the APA, added that “this raises an important opportunity” for clinicians to help their patients.

“The majority of people who have psychiatric illnesses — depression, for example — don’t get treatment. I think a part of the puzzle is educating the public, but it’s also improved screening,” said Dr. Borenstein.

Dramatic Increase in Cell Phone Use

According to a report released by the Pew Research Center last March, 37% of teens in the United States had smartphones in 2012 — up significantly from 23% in 2011. In addition, 95% of all teens use the Internet.

Dr. Lee reported that smartphone use in children and adolescents between the ages of 5 and 19 years in Korea increased dramatically from 7.5% in 2009 to 67% in 2012.

 
Dr. Jonghun Lee

“There are a wide range of smartphone functions, including Internet use, online gaming, digital cameras, and GPS [Global Positioning System] navigation. And you can use these functions anywhere and at any time. But these various convenient functions are contributing factors to excessive use,” he said.

He added that according to the Seoul Metropolitan Office of Education, 6.5% of Korean adolescents have reported that they are affected by excessive use of smartphones.

“This has become a social issue, and they noted that it has negatively affected their studies,” said Dr. Lee. In addition, according to the Korean Youth Counseling and Welfare Institute, 41.3% of youth reported excessive gaming, 12% reported abnormal behavior after losing their smartphone, 9.3% reported conflicts with parents, and 9% reported using their smartphone to look at obscene material.

“These are highly predictive of addiction,” said Dr. Lee. “Our earlier study showed that using it in particular situations was also associated with smartphone addiction, such as using it when going to bed or in the bathroom.”

“Recently, we have also heard that smartphone overuse by youth is associated with depression, more exposure to obscene material, and even suicide.”

For the current study, the investigators enrolled 195 adolescents who were questioned using the 2010 Smart-phone Addiction Rating Scale (SARS) and the Young Internet Addiction Scale (YIAS). In addition, the Korea–Youth Self Report (K-YSR) was used to assess possible psychopathologies, including somatic symptoms, attention problems, and aggression.

Results showed that total problematic behavior scores on the K-YSR were significantly correlated with both the total SARS (P < .001) and YIAS (P < .001) scores.

In post hoc analyses, the participants were divided into 4 subgroups: low Internet/low smartphone (low-low) users, high Internet/high smartphone (high-high) users, low Internet/high smartphone (low-high) users, and high Internet/low smartphone (high-low) users.

The low-low group had significantly lower scores than the other 3 groups on total problematic behaviors and internalizing problems (P < .01 for all), and that group had significantly fewer externalizing problems than the high-high group (P < .01).

In addition, there was a significant difference among the groups on 7 other subscales of the K-YSR, including withdrawal (P < .05), somatic symptoms (P < .01), and thought problems (P < .01), as well as depression/anxiety, attention problems, delinquency, and aggression (all, P < .001).

The investigators add that the number of adolescents affected is likely to increase as smartphones become more and more popular.

Intervene When Necessary

“I would say that parents and clinicians should have concern if smartphones affect the functioning of the child, including at school and interacting socially with friends and family,” Dr. Borenstein told Medscape Medical News.

 
Dr. Jeffrey Borenstein

“If there really begins to be some effects in functioning, that’s when I would have a concern and want to look further into it.” He added that clinicians should also advise parents that they are responsible and in charge and that, although it might be difficult, they need to establish a set of rules for use.

“These will be a little different for each family. But certainly if the use of the Internet or smartphones is getting in the way of the functioning of the child, the parent needs to intervene,” he said.

He noted that “we’re really just beginning to study these issues” with regard to causal effects between Internet and smartphone addictions and subsequent psychopathologies.

“That’s why this study is such an important one. But it’s hard to tease out the chicken and the egg off it. So finding an association is useful. It says: ‘Okay, there’s something here to be concerned about. So let’s investigate it further,'” said Dr. Borenstein.

“Probably if we tease it out we’ll find that for some people, that association is a cause and effect, and for others…it may be that something else was going on that resulted in them being on the Internet. But more work needs to be done.”

The study authors and Dr. Borenstein did not disclose any relevant financial relationships.

The American Psychiatric Association’s 2013 Annual Meeting. Abstract NR6-41. Presented May 19, 2013.

Report of the Guideline Development Subcommittee of the American Academy of Neurology

Clinicians managing antithrombotic medications periprocedurally must weigh bleeding risks from drug continuation against thromboembolic risks from discontinuation. Stroke patients undergoing dental procedures should routinely continue aspirin (Level A). Stroke patients undergoing invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound–guided prostate biopsy, spinal/epidural procedures, and carpal tunnel surgery should probably continue aspirin (Level B). Some stroke patients undergoing vitreoretinal surgery, EMG, transbronchial lung biopsy, colonoscopic polypectomy, upper endoscopy and biopsy/sphincterotomy, and abdominal ultrasound–guided biopsies should possibly continue aspirin (Level C). Stroke patients requiring warfarin should routinely continue it when undergoing dental procedures (Level A) and probably continue it for dermatologic procedures (Level B). Some patients undergoing EMG, prostate procedures, inguinal herniorrhaphy, and endothermal ablation of the great saphenous vein should possibly continue warfarin (Level C). Whereas neurologists should counsel that warfarin probably does not increase clinically important bleeding with ocular anesthesia (Level B), other ophthalmologic studies lack the statistical precision to make recommendations (Level U). Neurologists should counsel that warfarin might increase bleeding with colonoscopic polypectomy (Level C). There is insufficient evidence to support or refute periprocedural heparin bridging therapy to reduce thromboembolic events in chronically anticoagulated patients (Level U). Neurologists should counsel that bridging therapy is probably associated with increased bleeding risks as compared with warfarin cessation (Level B). The risk difference as compared with continuing warfarin is unknown (Level U).

A new guideline has been made available from the American Academy of Neurology on the difficult issue of whether to stop antithrombotic medication during surgery or other medical procedures.

The guideline, published in the May 28 issue of Neurology, was developed by a team led by Melissa Armstrong, MD, University of Maryland School of Medicine, Baltimore.

“We cast a broad net to find any possible article on discontinuing antithrombotic medication before an interventional procedure,” Dr. Armstrong commented to Medscape Medical News. “Most of the research has been done in patients undergoing minor procedures such as dental and dermatological procedures. And I think we can say in most minor procedures you probably don’t need to stop aspirin. This may also be the case for warfarin, but we have fewer studies available so the recommendation must be more cautious with warfarin.”

In terms of major procedures, Dr. Armstrong noted that there is little evidence on either drug. “At present, most physicians would stop both agents. But our research suggests it may be safe to continue aspirin in most situations except hip surgery.”

The guideline itself lists all the procedures for which there are data on stopping or continuing aspirin or warfarin and gives recommendations with levels of evidence used to make those recommendations. There is little information on other agents because few studies have been conducted.

Dr. Armstrong commented: “We can’t assume the recommendations for aspirin can be extrapolated to other antiplatelet drugs, or those for warfarin can be applied to other anticoagulants. Each drug works differently.”

No Information on New Oral Anticoagulants

The guideline team couldn’t find any information on this issue with the new oral anticoagulants. “It is very important to do studies with these new drugs. They work differently to warfarin so we cannot assume they will require the same advice on stopping for procedures. They have a shorter half-life so it is possible that they can be used closer to surgery. But we need a lot more research on this,” Dr. Armstrong said.

This is the first time such guidelines have been issued by the American Academy of Neurology. Dr. Armstrong pointed out that similar guidelines have been developed by the American College of Chest Physicians (published in Chest in February 2012). “These were focused more on the cardiology perspective, whereas we focused on patients at risk of stroke, but the two guidelines generally came to broadly similar conclusions.”

She noted that no studies looked at both stroke and bleeding risk in patients continuing or stopping antithrombotics. “So we had to divide our findings into 2 parts: 1) stroke risk on stopping antithrombotic therapy, and 2) bleeding risk on continuing treatment. The clinician will have to apply both sets of findings to individual patients.”

The guideline team found an increased risk of bleeding with aspirin only in hip surgery (moderate evidence), and with warfarin in colonoscopy procedures (weak evidence). However, there was no information on warfarin in hip surgery but because it is thought to be a stronger antithrombotic than aspirin, the risk of bleeding is generally higher and it would not normally be used in this situation, Dr. Armstrong explained.

She added: “These studies are generally done by surgeons, and most surgeons would be reluctant to design a study which allowed warfarin to be used during any type of major surgery. The default mode is to stop warfarin during surgery in most circumstances.”

Balancing the Risk and Benefits

She explained that they are trying to weigh up the risk of 2 different events with quite different consequences.

“A stroke is an uncommon event but has devastating consequences, whereas a bleed is more common but generally has milder consequences. Surgeons are more concerned about bleeding risk during their procedure, and neurologists are more focused on preventing strokes, so we probably have different agendas. But it is important that we come together as a team to balance these requirements.”

Dr. Armstrong concluded, “This guideline tells us that aspirin appears safe to continue in a number of minor procedures. And we need more studies to look at aspirin in major procedures. For warfarin, we have less information, and we need more studies in minor procedures before thinking about major procedures.”

Neurology. 2013;80:2065-2069. Abstract