martes, 22 de noviembre de 2011

Sopoerte avanzado de la vida

Guías 2011 del ACLS
Advanced Cardiac Life Support guidelines 2011.
Anantharaman V, Gunasegaran K.
Department of Emergency Medicine, Singapore General Hospital, Outram Road, Singapore 169608. anantharaman@sgh.com.sg
Singapore Med J. 2011 Aug;52(8):548-55; quiz 556.
Abstract
The main emphasis in the Advanced Cardiac Life Support (ACLS) guidelines are in the areas of good quality chest compressions, ensuring normoventilation, removal of atropine from the cardiac arrest algorithm, removal of the use of the endotracheal route for drug administration, and renewed focus on the care provided after return of spontaneous circulation. In addition, the need for monitoring of quality of the various care procedures is emphasised. While the various ACLS procedures are being carried out, there is a need to minimise interruptions to chest compressions for maintenance of coronary perfusion pressures. In addition, the resuscitation team needs to continually look out for reversible causes of the cardiac arrest.
http://smj.sma.org.sg/5208/5208ra4.pdf
 
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lunes, 21 de noviembre de 2011

avances en manejo de fibrilacion auricular

al parecer el uso de dranedarona disminuye el riesgo de stroke y hospitalacion. comparado con betabloqoeuadores. La warfarina no protege mas que aspirina de embolias provenientes de placas de aorta.
Cotrariamente a la aspirina que no protege cuando el resgo coronario no es alto las estatinas si. Previene stroke  e infarto en prevencion primaria cuando hay varios factores de riesgo.
El apixaban directo inhividor de la trombina redijo el riesgo de hemorragia y estroke hemorragico pero no redujo mas el riesgo de estroke. No necesitan laboratorio pero son mas caros y no tienen un farmaco que revierta su efecto en caso de hemorragia seria. Los inhibidores del factor Xa dabigatran  (PRADAXA) tambien ofrecen similar ventyaja-.
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jueves, 17 de noviembre de 2011

medicos que no respetan.

es simple y elemental mi estimado colega. Falta total de respeto. Usted cree que la gente podria confiar en alguien que no tiene el mas minimo sentido del respeto. El doctor Cuadros ya ha sido claro al respeto pero olimpicamente hacen  caso omiso.
 
DR. CUADROS

CON TODO RESPETO Y EL AGRADECIENTO ANTE UNA INICIATIVA LOABLE PARA LOS QUE VEMOS LO ACADEMICO COMO UNA NECESIDAD DE MEJORA.


1. NO ESTA BIEN QUE SE UTILICE UN GRUPO QUE SE REUNIO CON UNA FINALIDAD PARA INVOLUCRARLOS EN OTRA.
2. ESTA SEGUNDA ACTIVIDAD, LA GREMIAL NO ES QUE NO ESTEMOS DE ACUERDO, UNA VEZ MAS SOLICITO EN TODO CASO SE LES ABRA UNA PAGINA PARA QUE HAGAN SUS COMENTARIOS.
3. ME DA MUCHA LASTIMA VER QUE NO NOS ENTENDEMOS A PESAR DE HABLAR CASTELLANO. NO ES NECESARIO HUMILLARNOS Y MALTRATARNOS ENTRE NOSOTROS, ES NECESARIO RESPETAR EL PENSAR DE TODOS.
4. LA FALTA YA SE HA REPETIDO, NO ES SOLO POR LAS ELECCIONES DEL CMP. CUANDO LAS ELECCIONES  DE LA PRESIDENCIA TAMBIEN APARECIERON SITUACIONES MOLESTAS COMO ESTA.
5. SUGIERO A USTED COMO MODERADOR DE LA PAGINA SER EL FILTRO Y AQUELLOS COMENTARIOS PONERLOS EN OTRA PAGINA Y OFRECERLO A QUIENES QUIERAN HACERLO.
6. ASI MISMO RECORDAR QUE NO ES LEAL EL OFRECER APOYO SOLO A UNA LISTA, SE DEBE SER INCLUSIVOS, PLURALES, DEMOCRATICOS.  PERO NO SOLO NO LO HEMOS VISTO UNA VEZ SINO EN VARIAS OPORTUNIDADES, LO QUE DESDICE DE LA SERIEDAD DE LA MOTIVACION DE ESTOS COMENTARIOS.

POR ULTIMO, NO ES NADA SERIO EL COGER COMO  CABALLO DE TROYA EL PADECER DE NUESTROS COLEGAS PARA TRATAR DE CONSEGUIR LOS MOTIVOS PARTICULARES DE DETERMINADOS Y CONOCIDOS PERSONAJES, DR. NO LO PERMITA.


CON TODO RESPETO

MUY AGRADECIDA

DRA. GARCIA.
CMP 24803

---------- Mensaje reenviado ----------
De: juana maria garcia espinoza <juanige8@yahoo.com>
Fecha: 17 de noviembre de 2011 10:44
Asunto: Re: [interno_residente_medico_PERU] A TODOS LOS MIEMBROS
Para: "interno_residente_medico_PERU@yahoogroups.com" <interno_residente_medico_PERU@yahoogroups.com>


 

DR. CUADROS

CON TODO RESPETO Y EL AGRADECIENTO ANTE UNA INICIATIVA LOABLE PARA LOS QUE VEMOS LO ACADEMICO COMO UNA NECESIDAD DE MEJORA.

1. NO ESTA BIEN QUE SE UTILICE UN GRUPO QUE SE REUNIO CON UNA FINALIDAD PARA INVOLUCRARLOS EN OTRA.
2. ESTA SEGUNDA ACTIVIDAD, LA GREMIAL NO ES QUE NO ESTEMOS DE ACUERDO, UNA VEZ MAS SOLICITO EN TODO CASO SE LES ABRA UNA PAGINA PARA QUE HAGAN SUS COMENTARIOS.
3. ME DA MUCHA LASTIMA VER QUE NO NOS ENTENDEMOS A PESAR DE HABLAR CASTELLANO. NO ES NECESARIO HUMILLARNOS Y MALTRATARNOS ENTRE NOSOTROS, ES NECESARIO RESPETAR EL PENSAR DE TODOS.
4. LA FALTA YA SE HA REPETIDO, NO ES SOLO POR LAS ELECCIONES DEL CMP. CUANDO LAS ELECCIONES  DE LA PRESIDENCIA TAMBIEN APARECIERON SITUACIONES MOLESTAS COMO ESTA.
5. SUGIERO A USTED COMO MODERADOR DE LA PAGINA SER EL FILTRO Y AQUELLOS COMENTARIOS PONERLOS EN OTRA PAGINA Y OFRECERLO A QUIENES QUIERAN HACERLO.
6. ASI MISMO RECORDAR QUE NO ES LEAL EL OFRECER APOYO SOLO A UNA LISTA, SE DEBE SER INCLUSIVOS, PLURALES, DEMOCRATICOS.  PERO NO SOLO NO LO HEMOS VISTO UNA VEZ SINO EN VARIAS OPORTUNIDADES, LO QUE DESDICE DE LA SERIEDAD DE LA MOTIVACION DE ESTOS COMENTARIOS.

POR ULTIMO, NO ES NADA SERIO EL COGER COMO  CABALLO DE TROYA EL PADECER DE NUESTROS COLEGAS PARA TRATAR DE CONSEGUIR LOS MOTIVOS PARTICULARES DE DETERMINADOS Y CONOCIDOS PERSONAJES, DR. NO LO PERMITA.

CON TODO RESPETO

MUY AGRADECIDA

DRA. GARCIA.
CMP 24803
De: Máximo Cuadros <maximocuadros@yahoo.es>
Para: "interno_residente_medico_PERU@yahoogroups.com" <interno_residente_medico_PERU@yahoogroups.com>
Enviado: Jueves, noviembre 17, 2011 9:48 A.M.
Asunto: [interno_residente_medico_PERU] A TODOS LOS MIEMBROS [Archivo adjunto 1]

 
  1. EN TODOS LOS MENSAJES QUE UDS RECIBEN VIENE AL FINAL ESTOS LINK QUE A CONTINUACION MAS ABAJO LES RE-ENVIO Y USARLOS DE ACUERDO A LA DECISION QUE FINALMENTE HAN TOMADO CON RESPECTO AL GRUPO
  2. Y A PESAR QUE HE REITERADO QUE NO ES NECESARIO SALIRSE DEL GRUPO PARA NO PERDER LA PACIENCIA Y NUESTRA INTOLERANCIA ENTONCES LEAN ATENTAMENTE LO QUE CADA LINK LE ESTA DICIENDO Y TOMENN CADA UNO SU ELECCION FINAL
  3. Y SI INGRESO UN MENSAJE MOLESTO PARA SU CRITERIO (Y BUENO PARA EL RESTO)... ENTONCES CADA UNO ENFRENTEMOS ESE MENSAJE CON 2 O 3 MENSAJES CON EL CONTENIDO QUE UDS QUISIERA QUE HUBIERA TRAIDO
  4. EL QUE LES ESCRIBE ES EL MODERADOR Y VEO CON ASOMBRO QUE SOBRE EL TEMA de estos ultimos dias se ha escrito mas de 37 mensajes y TODOS sin excepcion se olvidadron de escribir sus aportes academicos que tanto defienden y no lo practican.... ver imagen
  5. Si estas siempre colocandote en la tribuna no te puedo obligar a escribir de la noche a la mañana con la facilidad que lo hace el resto... pero si te exijo que levantes la voz cuando se introduscan excecivos mensajes sobre un tema ya zanjado o se abuse de su condicion de miembro
  6. Si ya elijieron salirse del GRUPO solo les dire que no era necesario esa opcion ... y yo les puedo pasar a la mejor opcion si UDS me dan permiso que lo haga... ESTE GRUYPO OFRECE LITERATURA A DIARIO SIN LE CUESTE NI UN CENTAVO Y LOS QUE SEGUIMOS EN ESA LINEA DE COMPARTIR TAMPOCO EXIGIMOS NADA A CAMBIO..... PERO COMO SU MODERADOR SOLO LES PUEDO OFRECER DE MI PERSONA SEGUIR MANDANDO APORTES Y MAS APORTES Y CREO QUE EL RESTO QUE ME ACOMPAÑA EN ESA LINEA TAMBIEN LO HARA.... LOS MENSAJES MINORITARIOS QUE POR ESTA COYUNTURA LOS ESTA MOLESTANDO DURARAN HASTA EL 27 DE NOVIEMBRE Y OJALA QUE EL TRIUNFADOR DE ESTAS NUEVAS ELECCIONES INSTITUCIONALES DEL CMP NACIONAL Y REGIONAL QUE NOS COMPETE A LA MAYORIA DE MEDICOS PERUANOS QUE ESTAMOS EN ESTE GRUPO --- HAGAN DEL CMP UN NUEVO LIDER REORIENTADO HACIA LO QUE POR AÑOS NO HAN TOCADO
  7. Nuevamente gracias a los miembros por apoyarme en este buen grupo y para los que se van solo les digo que las puertas siempre estaran abiertas para su reingreso
  8. Con este mensaje espero haber asegurado que ya no ingresen mensajes pidiendo salir "porque no logran hacerlo" y principalmente espero que ya no le sigan dando a un duro a un tema que para mi ya quedo zanjado y punto final.... ya que 37 mensajes sobre lo mismo hace rato que harto a una mayoria
  9. l e e r    a t e n t a m e n t e    l o s    a l c a n c e s    d e    c a d a    L I N K    y    s o l o   e j e c u t a r l o s
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__._,_.___
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miércoles, 16 de noviembre de 2011

guias enfermedad arterial ´periferica

https://mail.google.com/mail/?ui=2&ik=14d8f0f8db&view=att&th=1339d4b0a3c428c9&attid=0.1&disp=safe&realattid=f_guy4pe200&zw

---------- Mensaje reenviado ----------
De: Claudio Mori gonzales <clagui57@gmail.com>
Fecha: 13 de noviembre de 2011 09:18
Asunto: guias enfermedad arterial ´perifericva
Para: clagui57@gmail.com



Publicado por en No hay comentarios:

martes, 1 de noviembre de 2011

drugs son seguras para ADHD

Original Article

ADHD Drugs and Serious Cardiovascular Events in Children and Young Adults

William O. Cooper, M.D., M.P.H., Laurel A. Habel, Ph.D., Colin M. Sox, M.D., K. Arnold Chan, M.D., Sc.D., Patrick G. Arbogast, Ph.D., T. Craig Cheetham, Pharm.D., Katherine T. Murray, M.D., Virginia P. Quinn, Ph.D., M.P.H., C. Michael Stein, M.B., Ch.B., S. Todd Callahan, M.D., M.P.H., Bruce H. Fireman, M.A., Frank A. Fish, M.D., Howard S. Kirshner, M.D., Anne O'Duffy, M.D., Frederick A. Connell, M.D., M.P.H., and Wayne A. Ray, Ph.D.

November 1, 2011 (10.1056/NEJMoa1110212)

Comments open through November 8, 2011

Abstract
Article
References
Comments

Medications that are used to treat attention deficit–hyperactivity disorder (ADHD) are prescribed for more than 2.7 million children in the United States each year1 and have been considered to be relatively safe.2-5 However, reports of adverse events from Canada and the United States that have included cases of sudden death, myocardial infarction, and stroke in conjunction with the use of these drugs have raised concern about their safety.6,7 Although case reports from adverse-event reporting systems can be an important source for identifying medication safety signals, they cannot reliably quantify risk. Thus, there is a compelling need to obtain better safety data for these drugs. We used data from four large, geographically and demographically diverse U.S. health plans to conduct a retrospective cohort study of the use of ADHD drugs and the risk of serious cardiovascular events in children and young adults, with review of medical records to validate study end points. The study was conducted in parallel with a study of ADHD drug use and serious cardiovascular events in adults between the ages of 25 and 64 years.

Methods

Data Sources

We obtained study data from computerized health records of four health plans that together annually covered 22.4 million persons during the study period: Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California (Northern and Southern regions), and OptumInsight Epidemiology (national private insurance health-plan data). We augmented health-plan data with linkage to state death certificates and the National Death Index. Health-plan data included enrollment records, outpatient and inpatient claims, and records of filled prescriptions (including the dispensing date, drug name, dose, quantity, and duration of supply), which have been shown to be good measures of medication use.8-11 The initiation of the study differed according to site on the basis of the earliest availability of the site's computerized data (ranging from 1986 to 2002). Follow-up concluded for all sites at the end of 2005. Each site prepared standardized files from health-plan data and used computer programs from the lead site (Vanderbilt University) to define study variables and create files in which identifiers of patients had been removed. These files were sent to the lead site for analyses.

Study Population

To assemble the cohort, we identified patients who met the following criteria: use of an ADHD drug (methylphenidate, dexmethylphenidate, dextroamphetamines, amphetamine salts, atomoxetine, or pemoline) during the study period; an age of 2 to 24 years on the first day of qualifying use; continuous enrollment with drug benefits for 365 days preceding the first day of qualifying use (allowing for short administrative gaps in enrollment); and the absence of possibly life-threatening serious illness (Section 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). Because patients with congenital heart disease may be vulnerable to the effects of ADHD medications, such patients were included in the study. Exclusion criteria included a hospital discharge during the preceding 365 days with a primary diagnosis of acute myocardial infarction or stroke. The last day of study follow-up was the last day of the study or the date on which the patient no longer met study criteria. A given patient was allowed to reenter the cohort as long as all the cohort eligibility requirements were met.

For each patient receiving an ADHD medication, we randomly selected up to two nonuser control subjects from health-plan members at the same site who were enrolled on the first day of qualifying use at the age of 2 to 24 years, who met continuous-enrollment requirements, and who did not have a serious illness. Nonusers were matched with users on the basis of calendar year, age, and sex and were allowed to have previous nonqualifying use of ADHD drugs before the first day of qualifying use. Follow-up for nonusers began on the first day of qualifying use for the matched users of ADHD drugs and ended on the nonuser's last day of study follow-up (Section 2 in the Supplementary Appendix). Follow-up time did not include the time during hospitalization and the 30 days after discharge because in-hospital deaths were not considered to be study end points and health-plan files did not include drugs dispensed in the hospital.

Use of Study Drugs

Every person-day during study follow-up was classified according to use of ADHD drugs (Section 2 in the Supplementary Appendix). Current use was defined as use during the period between the prescription start date and the end of the days of supply (including up to a 7-day carryover from previous prescriptions). Former use was defined as use during the period after current use through the end of study follow-up. Nonuse was defined as no prescribed use of ADHD drugs on the day being classified or any preceding days. Former users and nonusers could become current users of ADHD drugs during follow-up, and when this occurred, their user person-time was classified as described above.

Study End Points

The primary study end point was a serious cardiovascular event, which was defined as sudden cardiac death, myocardial infarction, or stroke. Sudden cardiac death was defined as a sudden, pulseless condition or collapse consistent with a ventricular tachyarrhythmia occurring in a community setting and including both fatal and resuscitated cardiac arrest (cases in which an arrest occurred in the community but the patient was successfully resuscitated).12-16 The diagnosis of acute myocardial infarction required hospitalization and met the international diagnostic criteria for myocardial infarction.17-19 Stroke was defined as an acute neurologic deficit of sudden onset that persisted for more than 24 hours, corresponded to a vascular territory, and was not explained by other causes (e.g., trauma, infection, vasculitis, or profound systemic hypotension).17,20,21

Potential end points were identified from claims and vital records and adjudicated through review of all pertinent medical records, including hospitalizations, reports of emergency medical services, autopsies, and death certificates (Section 3 in the Supplementary Appendix). Criteria for potential cases were intentionally broad to increase sensitivity because we anticipated that study end points would be rare and planned to review medical records for all potential cases. All events were adjudicated by two cardiologists (for sudden cardiac death and acute myocardial infarction) or two neurologists (for stroke). These adjudicators reviewed cases from all sites and were unaware of exposure status (Section 4 in the Supplementary Appendix). Disagreements among adjudicators (<5% of cases) were resolved by consensus with the study principal investigator.

Cases were excluded if the documentation suggested a cause other than a cardiovascular cause (e.g., motor-vehicle accident or drug overdose) or for sudden cardiac death, if clinically severe heart disease was present and sudden cardiac death was not unexpected (e.g., end-stage congestive heart failure). Congenital heart defects that had not been diagnosed until autopsy were noted but did not result in the exclusion of the potential case. In cases in which we were unable to obtain pertinent medical records or had insufficient information for adjudication (21% of cases), we determined the case status using a computer case definition, derived from cases with completed adjudication. The positive predictive value of the computerized case definition for serious cardiovascular events was 91% (Section 5 in the Supplementary Appendix).

Study Oversight

The study was approved by the institutional review board at each of the participating institutions and by the Food and Drug Administration (FDA) Research in Human Subjects Committee. In addition, permission was obtained from the data sources for each site. In all cases the need for informed consent was waived. The study was planned by the authors. Data were gathered from each site and analyzed by the study biostatistician, who vouches for the data and the analysis along with the first author.

Statistical Analysis

We calculated the hazard ratio for users of ADHD drugs, as compared with nonusers, using Cox regression models with robust sandwich variance estimators to account for the matched study design and for persons entering the cohort multiple times.22 The hazard ratio was adjusted for both baseline characteristics and changes in characteristics that occurred during follow-up. We calculated the adjusted incidence of end points by multiplying the incidence rate in the nonusers by the hazard ratio.

Because the number of covariates that reflected baseline cohort characteristics was large in comparison to the number of end points, we adjusted for these covariates by including a site-specific propensity score in the regression models. The propensity score was defined as the probability that the patient was currently receiving an ADHD drug on the first day of study follow-up, estimated for each site by means of logistic regression.23 The baseline variables in the propensity score included sociodemographic characteristics as well as information on medical care encounters consistent with psychiatric disorders, asthma and other respiratory illnesses, seizure and other neurologic disorders, unintentional injuries, cardiovascular diseases, and other diseases. For each site, we tested the adequacy of the propensity-score models by calculating the propensity-score adjusted means of baseline variables for users and nonusers of ADHD drugs; these values were similar (Section 6 in the Supplementary Appendix).

In our primary analysis, we adjusted for study site, propensity-score decile, and several time-dependent covariates (medical and psychiatric conditions, health care utilization, age, and calendar year) (Section 7 in the Supplementary Appendix). In order to test key study assumptions, we performed additional analyses that were stratified according to age group (2 to 17 years and 18 to 24 years) and that used alternative exposure groups, cohort inclusion criteria, and end-point exclusions. We performed all statistical analyses using SAS software, version 9.1 (SAS Institute).

Results

Study Population

The study cohort included 1,200,438 children and young adults. The mean age of cohort members at baseline was 11.1 years (mean range at the study sites, 8.7 to 12.0) (Table 1Table 1Study Cohorts, According to Site.). The mean length of follow-up for the cohort was 2.1 years (mean range at the study sites, 1.5 to 3.9) for a total follow-up of 2,579,104 person-years. The characteristics of current users and nonusers at baseline are shown in Table 2Table 2Characteristics of Cohort Members, According to the Use of ADHD Drugs at Baseline.. Generally, current users had more evidence of health care utilization of all types. In addition, they had greater prevalence of psychiatric illnesses and greater use of psychotropic medications. Current users were also more likely to have asthma, seizures, and congenital heart defects. For both current users and nonusers, alcohol and drug use, as determined from records of medical care encounters, were uncommon.

Study End Points

A total of 81 cohort members had a serious cardiovascular event, or 3.1 per 100,000 person-years, including 33 sudden cardiac deaths (1.3 per 100,000 person-years), 9 acute myocardial infarctions (0.3 per 100,000 person-years), and 39 strokes (1.5 per 100,000 person-years). Characteristics of the confirmed cases according to exposure to an ADHD drug are shown in Section 8 in the Supplementary Appendix. In the multivariate model, an older age, current use of an antipsychotic drug, a major psychiatric illness, a serious cardiovascular condition, and chronic illness were associated with an increased risk of serious cardiovascular events (Section 7 in the Supplementary Appendix).

There were 7 confirmed events among 373,667 person-years of follow-up for current users, 25 confirmed events among 607,475 person-years of follow-up for former users, and 49 confirmed events among 1,597,962 person-years of follow-up for nonusers. As compared with the nonusers, the adjusted rate of serious cardiovascular events did not differ significantly among current users of ADHD drugs (hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85) or among former users (hazard ratio, 1.03; 95% CI, 0.57 to 1.89) (Figure 1Figure 1Adjusted Rates of Serious Cardiovascular Events, According to the Use of ADHD Drugs.). When former users served as the reference group (in which the possible effect of unmeasured confounding was assessed), there was no increased risk of serious cardiovascular events among current users (hazard ratio, 0.70; 95% CI, 0.29 to 1.72) (Section 9 in the Supplementary Appendix). There was also no evidence of increased risk for the individual end points of sudden cardiac death, acute myocardial infarction, or stroke (Table 3Table 3Adjusted Hazard Ratios for Individual Cardiovascular End Points, According to the Use of ADHD Drugs.). We found no evidence of increased risk for methylphenidate (hazard ratio, 0.96; 95% CI, 0.31 to 2.97), the most frequently used ADHD drug (Section 10 in the Supplementary Appendix). Data were too sparse for other individual drugs to fit regression models.

Alternative Analyses

We performed several alternative analyses to test the robustness of study findings (Table 4Table 4Alternative Analyses with Adjusted Hazard Ratios for Serious Cardiovascular Events, According to the Use of ADHD Drugs., and Section 11 in the Supplementary Appendix). To assess for possible bias from the inclusion of persons who used ADHD drugs before the beginning of follow-up,10 we restricted current users of ADHD drugs only to new users (which was defined as no use of ADHD drugs during the 365 days preceding the first day of qualifying use). Findings were essentially identical to those of the primary analysis (hazard ratio, 0.73; 95% CI, 0.24 to 2.10). When we included seven patients who had been excluded from the primary analysis because they had evidence of severe underlying cardiac disease for which sudden cardiac death would not be unexpected, we found no increased risk for current users (hazard ratio, 0.71; 95% CI, 0.29 to 1.72). In analyses that included only children 2 to 17 years of age, we found no association between the use of ADHD drugs and serious cardiovascular events (hazard ratio, 0.98; 95% CI, 0.41 to 2.36). When children with evidence of serious psychiatric disease were excluded, we also found no significant association (hazard ratio, 0.66; 95% CI, 0.20 to 2.16).

We also performed analyses to test other key study assumptions. A site-specific analysis suggested a potential difference between Medicaid and non-Medicaid sites, although numbers were very small and we saw no evidence of significant heterogeneity in pooled analyses of rate differences between users and nonusers (Section 12 in the Supplementary Appendix). Another analysis expanded the definition of current use to include the 89 days after the end of current use to account for a possible misclassification in exposure related to the clinical use of ADHD drugs or for drugs that were discontinued after prodromal symptoms of an end point (e.g., headache preceding stroke). Finally, we performed an analysis in which time-dependent variables were fixed at baseline. The findings of these analyses were essentially identical to those reported here.

Discussion

Several regulatory and policy decisions resulted from the review of adverse-event reports of serious cardiovascular events associated with the use of ADHD drugs in Canada and the United States. In Canada, Health Canada removed and then reinstated marketing of extended-release mixed amphetamine salts.6,7 In the United States, three different FDA advisory committees considered the issue and recommended a black-box warning for stimulants, as well as a medication guide for patients.24 In a controversial policy statement, the American Heart Association stated that obtaining electrocardiograms in children who were initiating ADHD stimulant therapy was "reasonable,"25 a recommendation that was subsequently revised on the basis of input from several pediatric organizations.24 This led to concern and confusion among health care providers, patients, and families about the risks of these drugs.26 In this context, we studied the cardiovascular safety of ADHD drugs in more than 1.2 million children and young adults from four geographically diverse health plans with more than 2.5 million person-years of follow-up. The point estimate of the relative risk provided no evidence that the use of ADHD drugs increased the risk of serious cardiovascular events, although the upper limit of the 95% confidence interval was consistent with up to a doubling in the risk.

In the study population, which excluded children with possibly life-threatening illness, the incidence of serious cardiovascular events was 3.1 per 100,000 person-years, a finding that was consistent with other studies.27-30 The low number of events limited the statistical power of the study, particularly for individual end points and individual drugs, as well as for subgroups that might be particularly vulnerable to the effects of ADHD drugs. We also had limited information for longer durations of use.

Could the study findings be the result of confounding? The comparison between current users and nonusers at baseline indicated a greater incidence of medical and psychiatric coexisting conditions among current users. The analyses were adjusted for an extensive set of cardiovascular disease variables, which were included in site-specific propensity scores. Using this method, we could account for many important risk factors for cardiovascular disease. However, differences in factors that we were unable to measure, such as adherence to a drug regimen, differential prescribing of ADHD drugs to children at lower risk for a study outcome, or illicit use of medications resulting in misclassification, may have affected the results.31,32

We performed several alternative analyses to test the robustness of our findings. We used former users as the reference group, which could address many of the issues related to comparability between current users and nonusers. We performed an analysis restricted to new users to address bias that would be introduced from the inclusion of prevalent users in the cohort.10 Another analysis included patients who had been excluded from the primary analysis because of preexisting severe cardiac disease for which sudden cardiac death would not be unexpected. We also performed analyses stratified according to age. The findings from these additional analyses were essentially identical to our primary analysis.

Our findings that the use of ADHD drugs was not associated with an increased risk of serious cardiovascular events in children and young adults are consistent with the results of several reports33-36 that have appeared since the FDA safety review of adverse-event data for ADHD drugs,6,7 although our results differed from the findings of another report.37 Our study included nearly twice the person-time of the combined person-time in four recent cohort studies and included several provisions to ensure accurate case ascertainment, including a review of medical records and autopsies.

In conclusion, in our study involving children and young adults with 2.5 million person-years of follow-up, there were 3.1 serious cardiovascular events per 100,000 person-years. Although the point estimates of the relative risks for ADHD drugs did not indicate increased risk, the upper limit of the 95% confidence interval suggested that a doubling in the risk could not be ruled out. However, the absolute magnitude of any increased risk would be low.

Supported by contracts (HHSA290-2005-0042, to Vanderbilt University; and HHSA290-2005-0033, to Harvard Pilgrim Health Care Institute) from the Agency for Healthcare Research and Quality, Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions about Effectiveness program; and by contracts (223-2005-10100C, to Vanderbilt University; 223-2005-10012, to Kaiser Permanente Northern California; 223-2005-10006C, to OptumInsight Epidemiology; and 223-2005-10012C, to Harvard Pilgrim Health Care Institute) from the FDA.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article (10.1056/NEJMoa1110212) was published on November 1, 2011, at NEJM.org.

We thank the TennCare Bureau, Tennessee Department of Health, Washington State Health and Recovery Services Administration, Kaiser Permanente California (Northern and Southern regions), and OptumInsight Epidemiology for providing data needed to conduct the study; Patricia A. Gideon, Michelle DeRanieri, Leanne Balmer, Shannon D. Stratton, James R. Daugherty, Judith A. Dudley, Lynne Caples, Tracy Crowley, Ning Chen, and Eli Poe of Vanderbilt University School of Medicine; Sherry Quinn, Eva Ng, and Clorinda Hoffman of OptumInsight Epidemiology; Connie Uratsu and Ninah Achacoso of Kaiser Permanente Northern California; Chantal Avila and Yan Luo of Kaiser Permanente Southern California; and Li Zheng of the University of Washington.

Source Information

From the Divisions of General Pediatrics (W.O.C.), Adolescent Medicine (S.T.C.), and Pediatric Cardiology (F.A.F.), Department of Pediatrics; the Department of Biostatistics (P.G.A.); the Division of Pharmacoepidemiology, Department of Preventive Medicine (W.O.C., W.A.R.); the Divisions of Cardiology (K.T.M.), Rheumatology (C.M. Stein), and Clinical Pharmacology (K.T.M., C.M. Stein), Department of Medicine; and the Stroke Division, Department of Neurology (H.S.K., A.O.) — all at Vanderbilt University, Nashville; the Division of Research, Kaiser Permanente Northern California, Oakland (L.A.H., B.H.F.); the Department of Population Medicine, Harvard Pilgrim Health Care, Harvard Medical School, and the Department of Pediatrics, Boston University School of Medicine — all in Boston (C.M. Sox); OptumInsight Epidemiology, Waltham, MA (K.A.C.); Pharmacy Analytical Service (T.C.C.) and the Research and Evaluation Department (V.P.Q.), Kaiser Permanente Southern California, Pasadena; and the School of Public Health, University of Washington, Seattle (F.A.C.).

Address reprint requests to Dr. Cooper at Suite 313, Oxford House, 1313 21st Ave. S., Nashville, TN 37232-4313, or at .

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