Resumen Las infecciones por el virus de la varicela-zóster han aumentado globalmente, con complicaciones como neu ralgia postherpética y secuelas neurológicas. La vacuna recombinante contra el herpes zóster se propone como estrategia preventiva. Esta revisión sistemática evalúa su efectividad y seguridad en poblaciones sanas y de alto riesgo. Se realizó una revisión sistemática de ensayos controlados aleatorios que comparaban la efectividad y seguridad de la vacuna. La búsqueda se efectuó en Epistemonikos. Dos investigadores evaluaron indepen dientemente la elegibilidad de los estudios y se evaluó el riesgo de sesgo con la herramienta Cochrane Risk of Bias 2. Se realizó un metanálisis de resultados homogéneos y se evaluó la certeza de la evidencia mediante GRADE. Se adoptó un enfoque mínimamente contextualizado utilizando umbrales predeterminados. Se seleccionaron 9 ensayos controlados aleatorios. La vacuna demostró una reducción significativa en la incidencia de herpes zóster en poblaciones de alto riesgo (diferencia de riesgo de 140 menos por 1000) con alta certeza. Sin embargo, en poblaciones sanas, el efecto fue trivial (28 menos por 1000). No se observaron diferencias significativas en la incidencia de neuralgia postherpética en ninguna de las poblaciones. En cuanto a la seguridad, se registró un aumento de eventos adversos en ambas poblaciones, aunque no se presentaron diferencias en los eventos adversos graves. En poblaciones de alto riesgo, donde la incidencia de herpes zóster y sus complicaciones es más alta, la vacuna demostró eficacia en la reducción de la inciden cia de la enfermedad, aunque no en la de la neuralgia postherpética. Por otro lado, en población sana, el impac to de la vacuna fue trivial. Es crucial adoptar un enfoque individualizado e informado al recomendar esta vacuna.

Abstract Varicella-zoster virus infections have increased glob ally, with complications such as postherpetic neuralgia and neurological sequelae. The recombinant vaccine against herpes zoster is proposed as a preventive strat egy. This systematic review evaluates its effectiveness and safety in healthy and high-risk populations. A sys tematic review of randomized controlled trials com paring the effectiveness and safety of the vaccine was conducted. The search was carried out in Epistemonikos. Two researchers independently assessed the eligibility of the studies and the risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A meta-analysis of ho mogeneous results was conducted, and the certainty of the evidence was evaluated using GRADE. A minimally contextualized approach was adopted using predeter mined thresholds. Nine randomized controlled trials were selected. The vaccine demonstrated a significant reduction in the incidence of herpes zoster in high-risk populations (risk difference of 140 fewer per 1000) with high certainty. However, in healthy populations, the effect was trivial (28 fewer per 1000). No significant dif ferences were observed in postherpetic neuralgia in any of the populations analyzed. Adverse events increased in both populations, though no discrepancies in serious adverse events were noted. In high-risk populations, where the incidence of herpes zoster and its complica tions is higher, the vaccine demonstrated effectiveness in lowering the incidence of the disease, though not in that of postherpetic neuralgia. Conversely, in healthy populations, the impact of the vaccine was trivial. Indi vidualized and informed recommendations are crucial when considering this vaccine.

Resumen En Argentina, el virus del dengue ha experimentado un aumento en los últimos años. Este estudio se propone realizar una revisión sistemática para evaluar la efectividad y seguridad de la vacuna TAK-003 tetravalente contra el dengue en este contexto. Se llevó a cabo una revisión sistemática de ensayos clínicos controlados aleatorizados que comparaban la efectividad y seguridad de la vacuna con placebo en la población general. La búsqueda se efectuó en Epistemonikos y dos investigadores evaluaron los estudios de manera independiente. El riesgo de sesgo se evaluó con la herramienta Rob 2 de Cochrane. Se realizó un metaanálisis de los resultados y la certeza en la evidencia se evaluó mediante la metodología GRADE. Concluimos, con alta certeza de evidencia, que la vacuna tetravalente contra el dengue reduce las infecciones graves (RR 0.17, IC 95% 0.12 a 0.24) e infecciones por el virus del dengue (RR 0.40, IC 95% 0.36 a 0.45) en una población de ≤17 años. La vacuna podría no incrementar el riesgo de eventos adversos serios, aunque es importante destacar la baja certeza de evidencia (RR 1.04, IC 95%: 0.69-1.55). La aplicación de la vacuna tetravalente contra el dengue disminuye el riesgo de infecciones graves y no graves por el dengue en esa población. No obstante, existe baja certeza en la evidencia en relación a la seguridad de la vacuna. La decisión de la vacunación debe considerar la magnitud de los beneficios en función del riesgo de infección.

Abstract In Argentina, the dengue virus has experienced an increase in recent years. This study aims to conduct a systematic review to assess the effectiveness and safety of the tetravalent dengue vaccine TAK-003 in this context. A systematic review of randomized controlled clinical trials comparing the effectiveness and safety of the vaccine with a placebo in the general population was conducted. The search was carried out on Epistemonikos, and two investigators independently evaluated the studies. Bias risk was assessed using Cochrane’s Rob 2 tool. A meta-analysis of the results was performed, and the certainty of evidence was evaluated using the GRADE methodology. We concluded, with high certainty of evidence, that the tetravalent dengue vaccine reduces severe infections (RR 0.17, 95% CI 0.12 to 0.24) and infections by the dengue virus (RR 0.40, 95% CI 0.36 to 0.45) in a population aged ≤17 years. The vaccine may not increase the risk of serious adverse events, although it is important to note the low certainty of evidence (RR 1.04, 95% CI: 0.69-1.55). The use of the tetravalent dengue vaccine decreases the risk of severe and non-severe dengue infections in this population. However, there is low certainty of evidence regarding the vaccine’s safety. The decision to vaccinate should consider the magnitude of benefits relative to the risk of infection.

Resumen En Argentina, el virus del dengue ha experimentado un aumento en los últimos años. Este estudio se propone realizar una revisión sistemática para evaluar la efec tividad y seguridad de la vacuna TAK-003 tetravalente contra el dengue en este contexto. Se llevó a cabo una revisión sistemática de ensayos clínicos controlados aleatorizados que comparaban la efectividad y seguridad de la vacuna con placebo en la población general. La búsqueda se efectuó en Episte monikos y dos investigadores evaluaron los estudios de manera independiente. El riesgo de sesgo se evaluó con la herramienta Rob 2 de Cochrane. Se realizó un metaa nálisis de los resultados y la certeza en la evidencia se evaluó mediante la metodología GRADE. Concluimos, con alta certeza de evidencia, que la vacuna tetravalente contra el dengue reduce las infec ciones graves (RR 0.17, IC 95% 0.12 a 0.24) e infecciones por el virus del dengue (RR 0.40, IC 95% 0.36 a 0.45) en una población de ≤17 años. La vacuna podría no incre mentar el riesgo de eventos adversos serios, aunque es importante destacar la baja certeza de evidencia (RR 1.04, IC 95%: 0.69-1.55). La aplicación de la vacuna tetravalente contra el dengue disminuye el riesgo de infecciones graves y no graves por el dengue en esa población. No obstante, existe baja certeza en la evidencia en relación a la se guridad de la vacuna. La decisión de la vacunación debe considerar la magnitud de los beneficios en función del riesgo de infección.

Abstract In Argentina, the dengue virus has experienced an increase in recent years. This study aims to conduct a systematic review to assess the effectiveness and safety of the tetravalent dengue vaccine TAK-003 in this context. A systematic review of randomized controlled clini cal trials comparing the effectiveness and safety of the vaccine with a placebo in the general population was conducted. The search was carried out on Epistemoni kos, and two investigators independently evaluated the studies. Bias risk was assessed using Cochrane’s Rob 2 tool. A meta-analysis of the results was performed, and the certainty of evidence was evaluated using the GRADE methodology. We concluded, with high certainty of evidence, that the tetravalent dengue vaccine reduces severe infections (RR 0.17, 95% CI 0.12 to 0.24) and infections by the den gue virus (RR 0.40, 95% CI 0.36 to 0.45) in a population aged ≤17 years. The vaccine may not increase the risk of serious adverse events, although it is important to note the low certainty of evidence (RR 1.04, 95% CI: 0.69-1.55). The use of the tetravalent dengue vaccine decreases the risk of severe and non-severe dengue infections in this population. However, there is low certainty of evidence regarding the vaccine’s safety. The decision to vaccinate should consider the magnitude of benefits relative to the risk of infection.

Abstract Clinicians, guideline developers, and policymakers sometimes neglect important criteria, give undue weight to criteria, and do not use the best available evidence to inform their judgments. Explicit and transparent systems for decision making can help to ensure that all important criteria are considered and that decisions are informed by the best available research evidence. The GRADE Working Group has developed Evidence to Decision (EtD) frameworks for the different type of recommendations or decisions. The purpose of EtD frameworks is to help people use evidence in a structured and transparent way to inform decisions in the context of clinical recommendations, coverage decisions, and health system or public health recommendations and decisions. EtD frameworks have a common structure that includes formulation of the question, an assessment of the evidence, and drawing conclusions, though there are some differences between frameworks for each type of decision. EtD frameworks inform users about the judgments that were made and the evidence supporting those judgments by making the basis for decisions transparent to target audiences. EtD frameworks also facilitate dissemination of recommendations and enable decision makers in other jurisdictions to adopt recommendations or decisions, or adapt them to their context. This article is a translation of the original article published inBritish Medical Journal. The EtD frameworks are currently used in the Clinical Practice Guideline Programme of the Spanish National Health System, co-ordinated by GuíaSalud.

Resumen Los médicos y quienes elaboran guías y políticas a veces pasan por alto criterios importantes, les dan un peso indebido o no usan la mejor evidencia disponible para informar sus juicios. Los sistemas explícitos y transparentes para la toma de decisiones pueden ayudar a garantizar que se consideren todos los criterios importantes, y que las decisiones estén basadas en la mejor evidencia disponible. El grupo de trabajo GRADE ha desarrollado marcos «de la evidencia a la decisión» (EtD) para los diferentes tipos de recomendaciones o decisiones. El objetivo de los marcos EtD es ayudar a los paneles a usar la evidencia de una manera estructurada y transparente para informar las decisiones respecto de las recomendaciones clínicas, decisiones de cobertura sanitaria y recomendaciones o decisiones sobre el sistema sanitario o sobre salud pública. Los marcos EtD tienen una estructura común: formulación de una pregunta, evaluación de la evidencia y conclusiones. No obstante, existen diferencias entre los marcos para cada tipo de decisión. Los marcos EtD informan a los usuarios sobre los juicios que se han hecho y la evidencia que los apoya dotando de transparencia la base para las decisiones de los que tienen que tomarlas. Los marcos EtD también facilitan la diseminación de las recomendaciones y permiten a los decisores de otros ámbitos adoptar recomendaciones o decisiones, o adaptarlas a su contexto. El siguiente artículo es una traducción del artículo original publicado enBritish Medical Journal. Los marcos EtD se utilizan actualmente en el marco del Programa de Guías de Práctica Clínica en el Sistema Nacional de Salud, coordinado por GuíaSalud.

Abstract Clinicians, guideline developers, and policymakers sometimes neglect important criteria, give undue weight to criteria, and do not use the best available evidence to inform their judgments. Explicit and transparent systems for decision making can help to ensure that all important criteria are considered and that decisions are informed by the best available research evidence. The GRADE Working Group has developed Evidence to Decision (EtD) frameworks for the different type of recommendations or decisions. The purpose of EtD frameworks is to help people use evidence in a structured and transparent way to inform decisions in the context of clinical recommendations, coverage decisions, and health system or public health recommendations and decisions. EtD frameworks have a common structure that includes formulation of the question, an assessment of the evidence, and drawing conclusions, though there are some differences between frameworks for each type of decision. EtD frameworks inform users about the judgments that were made and the evidence supporting those judgments by making the basis for decisions transparent to target audiences. EtD frameworks also facilitate dissemination of recommendations and enable decision makers in other jurisdictions to adopt recommendations or decisions, or adapt them to their context. This article is a translation of the original article published inBritish Medical Journal. The EtD frameworks are currently used in the Clinical Practice Guideline Programme of the Spanish National Health System, co-ordinated by GuíaSalud.

Resumen Los médicos y quienes elaboran guías y políticas a veces pasan por alto criterios importantes, les dan un peso indebido o no usan la mejor evidencia disponible para informar sus juicios. Los sistemas explícitos y transparentes para la toma de decisiones pueden ayudar a garantizar que se consideren todos los criterios importantes, y que las decisiones estén basadas en la mejor evidencia disponible. El grupo de trabajo GRADE ha desarrollado marcos «de la evidencia a la decisión» (EtD) para los diferentes tipos de recomendaciones o decisiones. El objetivo de los marcos EtD es ayudar a los paneles a usar la evidencia de una manera estructurada y transparente para informar las decisiones respecto de las recomendaciones clínicas, decisiones de cobertura sanitaria y recomendaciones o decisiones sobre el sistema sanitario o sobre salud pública. Los marcos EtD tienen una estructura común: formulación de una pregunta, evaluación de la evidencia y conclusiones. No obstante, existen diferencias entre los marcos para cada tipo de decisión. Los marcos EtD informan a los usuarios sobre los juicios que se han hecho y la evidencia que los apoya dotando de transparencia la base para las decisiones de los que tienen que tomarlas. Los marcos EtD también facilitan la diseminación de las recomendaciones y permiten a los decisores de otros ámbitos adoptar recomendaciones o decisiones, o adaptarlas a su contexto. El siguiente artículo es una traducción del artículo original publicado enBritish Medical Journal. Los marcos EtD se utilizan actualmente en el marco del Programa de Guías de Práctica Clínica en el Sistema Nacional de Salud, coordinado por GuíaSalud.

Individual clinicians and organizations making health care decisions should not only consider the magnitude of the benefits and harms of different courses of action (interventions), but also the confidence we can have in those estimates. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach offers a systematic and transparent way to summarize the evidence, to rate the confidence we can have in the effects of the interventions and to move from evidence to recommendations. The GRADE approach has been adopted by several organizations worldwide, including the World Health Organization and the Cochrane Collaboration. In Chile, this approach has already been used by guidelines produced by the Chilean Ministry of Health. In this paper we describe the core concepts of the GRADE approach to rate the quality of the evidence and to grade the strength of recommendations. As clinicians, being familiar with such concepts may be helpful to make decisions informed by the best available evidence.

Odds Ratio (OR) is an effect measure frequently used to communicate results of health research. Mathematically, OR is the quotient between two odds, being odds an alternative way to express possibility of occurrence of an outcome or presence of an exposition. From a methodological perspective, OR can be calculated from prospective, retrospective and cross-sectional designs, and under certain conditions it can replace the Relative Risk. Based on a series of questions and examples, this article explains theoretical and methodological grounds underlying the concept of OR, in order to facilitate its interpretation for clinicians and researchers.

Odds Ratio (OR) es una medida de efecto comúnmente utilizada para comunicar los resultados de una investigación en salud. Matemáticamente un OR corresponde a un cociente entre dos odds, siendo un odds una forma alternativa de expresar la posibilidad de ocurrencia de un evento de interés o de presencia de una exposición. Desde un punto de vista metodológico, los OR pueden ser calculados en diseños prospectivos, retrospectivos y transversales, y bajo ciertas condiciones pueden reemplazar al Riesgo Relativo. En base a una serie de preguntas y ejemplos, el presente artículo explica los fundamentos matemáticos y metodológicos subyacentes al concepto de OR, con el objetivo de facilitar su interpretación a clínicos e investigadores.

BACKGROUND Hot flushes are common in women with a history of breast cancer. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects. The efficacy of non-hormonal therapies is still uncertain. OBJECTIVE To assess the efficacy of non-hormonal therapies in reducing hot flushes in women with a history of breast cancer. METHODS Search methods: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL (The Cochrane Library), Medline, Embase, Lilacs, CINAHL, PsycINFO (August 2008) and WHO ICTRP Search Portal. We handsearched reference lists of reviews and included articles, reviewed conference proceedings and contacted experts. Selection criteria: Randomized controlled trials (RCTs) comparing non-hormonal therapies with placebo or no therapy for reducing hot flushes in women with a history of breast cancer. Data collection and analysis: Two authors independently selected potentially relevant studies, decided upon their inclusion and extracted data on participant characteristics, interventions, outcomes and the risk of bias of included studies. MAIN RESULTS Sixteen RCTs met our inclusion criteria. We included six studies on selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation therapy and homeopathy, and one each on vitamin E, magnetic devices and acupuncture. The risk of bias of most studies was rated as low or moderate. Data on continuous outcomes were presented inconsistently among studies, which precluded the possibility of pooling the results. Three pharmacological treatments (SSRIs and SNRIs, clonidine and gabapentin) reduced the number and severity of hot flushes. One study assessing vitamin E did not show any beneficial effect. One of two studies on relaxation therapy showed a significant benefit. None of the other non-pharmacological therapies had a significant benefit. Side-effects were inconsistently reported. AUTHORS' CONCLUSIONS Clonidine, SSRIs and SNRIs, gabapentin and relaxation therapy showed a mild to moderate effect on reducing hot flushes in women with a history of breast cancer.

Background: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA and Australia. Objectives: To assess the effects of antibiotics for children with AOM. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2008, issue 2) which contains the Acute Respiratory Infections (ARI) Group's Specialized Register; MEDLINE (1966 to June week 4 2008); OLDMEDLINE (1958 to 1965); EMBASE (January 1990 to July 2008); and Current Contents (1966 to July 2008). Selection criteria: Randomised controlled trials comparing 1) antimicrobial drugs with placebo 2) immediate antibiotic treatment with observational treatment approaches in children with AOM. Data collection and analysis: Three review authors independently assessed trial quality and extracted data. Main results: We found 10 trials (2928 children) from high income countries with low risk of bias. Pain was not reduced by antibiotics at24 hours, but was at two to seven days, (relative risk (RR) 0.72; 95% confidence interval 0.62 to 0.83). However four trials (1271 children) comparing antibiotics prescribed immediately rather than initial observation found no difference at three to seven days. Antibiotics did not reduce tympanometry, perforation or recurrence. The only case of mastoiditis was in an antibiotic treated child. Vomiting, diarrhoea or rash was higher in children taking antibiotics (RR 1.37; 95% CI 1.09 to 1.76). Individual patient data meta-analysis of a subset of the included trials found antibiotics to be most beneficial in children: aged less than two; with bilateral AOM and with both AOM and otorrhoea. Authors' conclusions: Antibiotics slightly reduce the number of children with acute middle ear infection experiencing pain after a few days. However, most (78%) settle spontaneously in this time, meaning 16 children must be treated to prevent one suffering ear pain. This benefit must be weighed against the possible harms: 1 in 24 children experience symptoms caused by antibiotics. Antibiotics are most useful in children under two years of age, with bilateral AOM, and with both AOM and discharging ears. For most other children with mild disease, an expectant observational approach seems justified. We have no data on populations with higher risks of complications.

A special Committee on Internal Medicine and Public Health was established by Sociedad Médica de Santiago (Chilean Society of Internal Medicine) in April 2007 with the duty to write a Consensus Paper on the interaction between both branches of medical profession. The main objective was to find the common grounds on which to construct a positive approach to regain space for Internal Medicine, based on prevalent epidemiológica! features related to adult health issues. The authors describe the reasons to explain the gap between clinical medicine and population health and identify the nature and evolution of chronic diseases as the point of encounter between both. With Chilean health surveys data, they state that chronic diseases explain the high proportion of burden of disease, mortality and disability, and stress that by the year 2025 one in every five inhabitants will be over 65years of age, with ageing as another main problem for the health care sector. Population with multiple risks and multimorbidity is the most important challenge for the Chilean Health Care System. A new model of care is needed to tackle this scenario with new skills regarding psychosocial determinants of health. The leading role of internists and ideally geriatricians, will be crucial in this process and will help the implementation of sound population based interventions. Both individual and community level interventions will help to improve quality of life of Chilean families.

Context: The clinical validity of using computed tomography (CT) to diagnose peripheral pulmonary embolism is uncertain. Insufficient sensitivity for peripheral pulmonary embolism is considered the principal limitation of CT. Objective: To review studies that used a CT-based approach to rule out a diagnosis of pulmonary embolism. Data sources: The medical literature databases of PubMed, MEDLINE, EMBASE, CRISP, metaRegister of Controlled Trials, and Cochrane were searched for articles published in the English language from January 1990 to May 2004. Study selection: We included studies that used contrast-enhanced chest CT to rule out the diagnosis of acute pulmonary embolism, had a minimum follow-up of 3 months, and had study populations of more than 30 patients. Data extraction: Two reviewers independently abstracted patient demographics, frequency of venous thromboembolic events (VTEs), CT modality (single-slice CT, multidetector-row CT, or electron-beam CT), false-negative results, and deaths attributable to pulmonary embolism. To calculate the overall negative likelihood ratio (NLR) of a VTE after a negative or inconclusive chest CT scan for pulmonary embolism, we included VTEs that were objectively confirmed by an additional imaging test despite a negative or inconclusive CT scan and objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months. Data synthesis: Fifteen studies met the inclusion criteria and contained a total of 3500 patients who were evaluated from October 1994 through April 2002. The overall NLR of a VTE after a negative chest CT scan for pulmonary embolism was 0.07 (95% confidence interval [CI], 0.05-0.11); and the negative predictive value (NPV) was 99.1% (95% CI, 98.7%-99.5%). The NLR of a VTE after a negative single-slice spiral CT scan for pulmonary embolism was 0.08 (95% CI, 0.05-0.13); and after a negative multidetector-row CT scan, 0.15 (95% CI, 0.05-0.43). There was no difference in risk of VTEs based on CT modality used (relative risk, 1.66; 95% CI, 0.47-5.94; P = .50). The overall NLR of mortality attributable to pulmonary embolism was 0.01 (95% CI, 0.01-0.02) and the overall NPV was 99.4% (95% CI, 98.7%-99.9%). Conclusion: The clinical validity of using a CT scan to rule out pulmonary embolism is similar to that reported for conventional pulmonary angiography