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BACKGROUND: Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. METHODS: We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. RESULTS: We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. CONCLUSION: Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results. TRIAL REGISTRATION: PROSPERO (CRD42019128790).

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INTRODUCTION: Oral cancer has a 5-year survival rate of 50% because diagnosis is commonly performed at an advanced stage of the disease, so new diagnostic tools are needed. Nowadays, there is a vast number of publications suggesting the use of salivary biomarkers for oral cancer and potentially malignant disorders diagnosis, but their diagnostic accuracy is unclear. Thus, the goal of this systematic review is to evaluate the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. METHODS: This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will include primary studies assessing the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. Studies must report data about sensitivity and specificity; gold standard must be the histopathology diagnosis. We will search MEDLINE, EMBASE, the Cochrane Library, and gray literature. Two authors will independently select the studies and extract the data. The methodology quality of studies will be determined using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). EXPECTED RESULTS AND CONCLUSION: Our findings will provide information about the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders.

INTRODUCCIÓN: El cáncer oral tiene una tasa de supervivencia a los cinco años de 50%, debido a que frecuentemente su diagnóstico es realizado en estadios avanzados. Por lo tanto, son necesarias nuevas ayudas diagnósticas. Actualmente, existe un número significativo de publicaciones científicas sugiriendo el uso de biomarcadores salivales para el diagnóstico de cáncer oral. Sin embargo, son desconocidas las propiedades diagnósticas de estos biomarcadores. El objetivo de esta revisión sistemática es evaluar la evidencia sobre la precisión diagnóstica de biomarcadores salivales usados en la identificación de cáncer oral y desórdenes potencialmente malignos. MÉTODOS: Este protocolo es reportado en concordancia con el Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Se incluirán estudios evaluando la precisión diagnóstica de biomarcadores salivales para cáncer oral y desórdenes potencialmente malignos. Estos deberán reportar sensibilidad y especificidad, y utilizar como estándar de referencia un diagnóstico histopatológico. Se realizará una búsqueda en MEDLINE, EMBASE, Cochrane Library y literatura gris. Dos autores independientemente seleccionarán los estudios y extraerán los datos. La calidad metodológica de los estudios será determinada usando The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). RESULTADOS ESPERADOS Y CONCLUSIÓN: Los hallazgos de esta revisión sistemática proporcionarán información acerca de la precisión diagnóstica de los biomarcadores salivales para diagnóstico de cáncer oral y desórdenes potencialmente malignos.

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Objetivo: identificar la inclusión de la propuesta temática curricular de la Federación Latinoamericana de Obstetricia y Ginecología (FLASOG) sobre salud sexual y reproductiva en programas de pregrado (Medicina) y posgrado (Obstetricia y Ginecología) en un grupo de universidades e instituciones de educación superior de Latinoamérica y el Caribe. Método: estudio descriptivo de corte transversal en el cual se aplicó una encuesta a universidades de Latinoamérica y El Caribe durante el año 2017 para determinar si los contenidos de los programas con relación a salud sexual y reproductiva corresponden a la propuesta temática de la FLASOG, tanto en pregrado (Medicina) como en posgrado (Obstetricia y Ginecología). Resultados: todos los programas de pregrado evaluados incluyen dentro del currículo los siguientes temas: m étodos anticonceptivos, aborto y morbimortalidad materna y el 36,4 % contemplan salud sexual en la tercera edad. Todos los programas de posgrado evaluados estudian métodos anticonceptivos, anticoncepci ón en posparto y posaborto, morbimortalidad materna, aborto, y maternidad saludable. Solo el 55,6 % de ellos tienen temáticas relacionadas con interrupción voluntaria del embarazo y salud sexual en la tercera edad. Conclusiones: los programas evaluados cuentan con docentes dedicados a educación en salud sexual y reproductiva en sus programas, aunque en la mayoría de las instituciones (76,9 % ) no existe un proceso formal de evaluación y retroalimentación. Todas las universidades que respondieron la encuesta trabajan tres temas en sus contenidos curriculares de pregrado: aborto, anticoncepción y morbimortalidad materna, t ópicos que han sido considerados de alto impacto en la salud sexual y reproductiva de las mujeres. La interrupción voluntaria del embarazo se discute en dos de cada tres universidades que respondieron la encuesta. El tema de salud sexual en la tercera edad no se incluye en los programas.

Objective: to identify if Latin American and Caribbean higher education institutions include in their curriculum the sexual and reproductive health topics proposed by the Latin American Federation of Obstetrics and Gynecology (FLASOG for its acronym in Spanish) in undergraduate and graduate programs. Methods: descriptive, cross sectional study developed in the year 2017. A survey was sent to universities in Latin America and the Caribbean to evaluate if the sexual and reproductive health contents in the curriculum of undergraduate (medicine) and graduate schools (obstetrics and gynecology) correspond to the ones proposed by FLASOG. Results: 100 % of assessed undergraduate programs include the following topics in their curriculum: birth control methods, abortion, maternal morbidity and mortality, and 36.4 % include sexual health in the elderly. 100 % of graduate programs evaluated include: birth control methods, maternal morbidity and mortality, abortion, and healthy maternity, and 55.6 % include legal pregnancy termination and sexual health in the elderly. Conclusions: All the higher education programs evaluated have faculty for sexual and reproductive health, but most institutions (76 .9 % ) do not have a formal process for evaluation and feedback. All the universities include in their undergraduate programs the following topics: abortion, birth control methods and maternal morbidity and mortality, all of which have been considered of high impact in sexual and reproductive health of women. However, topics such as legal termination of pregnancy are only included in two out of three universities evaluated, and sexual health in the elderly is rarely included in the curriculum.

Objetivo: identificar a inclusão da proposta temática da Federação Latino-Americana de Obstetrícia e Ginecologia (FLASOG) em saúde sexual e reprodutiva nos programas de graduação (Medicina) e pós-graduação (Obstetrícia e Ginecologia) em um grupo de universidades e instituições de ensino superior da América Latina e do Caribe. Método: estudo descritivo transversal. Foi aplicado um questionário em programas de cursos de graduação e pós-graduação de universidades da América Latina e do Caribe em 2017, para determinar se o conteúdo dos programas relacionados à saúde sexual e reprodutiva correspondem à proposta temática da FLASOG no nível de graduação (Medicina) e de pós-graduação (Obstetrícia e Ginecologia). Resultados: todos os programas de graduação avaliados incluíram os seguintes tópicos no currículo: métodos contraceptivos, aborto e morbimortalidade materna; ainda, 36,4% dos programas abrangem temas relacionados à saúde sexual nos idosos. Todos os programas de pós-graduação avaliados estudam métodos contraceptivos, contracepção no pós-parto e pós-aborto, morbimortalidade materna, aborto e maternidade saudável. Apenas 55,6% desses programas têm tópicos relacionados à interrupção voluntária da gravidez e sobre a saúde sexual em idosos. Conclusões: os programas avaliados têm professores enfocados na educação da saúde sexual e reprodutiva, embora na maioria das instituições (76,9%) não exista um processo formal de avaliação e feedback. Todas as universidades que responderam à pesquisa trabalham com três tópicos em seu conteúdo curricular de graduação: aborto, contracepção e morbimortalidade materna, considerados de alto impacto na saúde sexual e reprodutiva das mulheres. A interrupção voluntária da gravidez é discutida em uma proporção de duas em cada três universidades que responderam ao questionário. A saúde sexual em idosos não está incluída nos programas

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BACKGROUND: Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps. METHODS: We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios. RESULTS: A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores. CONCLUSIONS: Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

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INTRODUCCIÓN: El cáncer oral tiene una tasa de supervivencia a los cinco años de 50%, debido a que frecuentemente su diagnóstico es realizado en estadios avanzados. Por lo tanto, son necesarias nuevas ayudas diagnósticas. Actualmente, existe un número significativo de publicaciones científicas sugiriendo el uso de biomarcadores salivales para el diagnóstico de cáncer oral. Sin embargo, son desconocidas las propiedades diagnósticas de estos biomarcadores. El objetivo de esta revisión sistemática es evaluar la evidencia sobre la precisión diagnóstica de biomarcadores salivales usados en la identificación de cáncer oral y desórdenes potencialmente malignos. MÉTODOS: Este protocolo es reportado en concordancia con el Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Se incluirán estudios evaluando la precisión diagnóstica de biomarcadores salivales para cáncer oral y desórdenes potencialmente malignos. Estos deberán reportar sensibilidad y especificidad, y utilizar como estándar de referencia un diagnóstico histopatológico. Se realizará una búsqueda en MEDLINE, EMBASE, Cochrane Library y literatura gris. Dos autores independientemente seleccionarán los estudios y extraerán los datos. La calidad metodológica de los estudios será determinada usando The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). RESULTADOS ESPERADOS Y CONCLUSIÓN: Los hallazgos de esta revisión sistemática proporcionarán información acerca de la precisión diagnóstica de los biomarcadores salivales para diagnóstico de cáncer oral y desórdenes potencialmente malignos.

INTRODUCTION: Oral cancer has a 5-year survival rate of 50% because diagnosis is commonly performed at an advanced stage of the disease, so new diagnostic tools are needed. Nowadays, there is a vast number of publications suggesting the use of salivary biomarkers for oral cancer and potentially malignant disorders diagnosis, but their diagnostic accuracy is unclear. Thus, the goal of this systematic review is to evaluate the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. METHODS: This protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will include primary studies assessing the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders. Studies must report data about sensitivity and specificity; gold standard must be the histopathology diagnosis. We will search MEDLINE, EMBASE, the Cochrane Library, and gray literature. Two authors will independently select the studies and extract the data. The methodology quality of studies will be determined using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). EXPECTED RESULTS AND CONCLUSION: Our findings will provide information about the diagnostic accuracy of salivary biomarkers for oral cancer and potentially malignant disorders.

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BACKGROUND: Leukocytes contained in the allogeneic packed red blood cell (PRBC) are the cause of certain adverse reactions associated with blood transfusion. Leukoreduction consists of eliminating leukocytes in all blood products below the established safety levels for any patient type. In this systematic review, we appraise the clinical effectiveness of allogeneic leukodepleted (LD) PRBC transfusion for preventing infections and death in patients undergoing major cardiovascular surgical procedures. METHODS: We searched randomized controlled trials (RCT), enrolling patients undergoing a major cardiovascular surgical procedure and transfused with LD-PRBC. Data were extracted, and risk of bias was assessed according to Cochrane guidelines. In addition, trial sequential analysis (TSA) was used to assess the need of conducting additional trials. Quality of the evidence was assessed using the GRADE approach. RESULTS: Seven studies met the eligibility criteria. Quality of the evidence was rated as moderate for both outcomes. The risk ratio for death from any cause comparing the LD-PRBC versus non-LD-PRBC group was 0.69 (CI 95% = 0.53 to 0.90; I 2 = 0%). The risk ratio for infection in the same comparison groups was 0.77 (CI 95% = 0.66 to 0.91; I 2 = 0%). TSA showed a conclusive result in this outcome. CONCLUSIONS: We found evidence that supports the routine use of leukodepletion in patients undergoing a major cardiovascular surgical procedure requiring PRBC transfusion to prevent death and infection. In the case of infection, the evidence should be considered sufficient and conclusive and hence indicated that further trials would not be required.

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BACKGROUND: Hepatic encephalopathy is a common and devastating neuropsychiatric complication of acute liver failure or chronic liver disease. Ammonia content in the blood seems to play a role in the development of hepatic encephalopathy. Treatment for hepatic encephalopathy is complex. Acetyl-L-carnitine is a substance that may reduce ammonia toxicity. This review assessed the benefits and harms of acetyl-L-carnitine for patients with hepatic encephalopathy. OBJECTIVES: To assess the benefits and harms of acetyl-L-carnitine for patients with hepatic encephalopathy. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and Science Citation Index Expanded for randomised clinical trials. We sought additional randomised clinical trials from the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. We performed all electronic searches until 10 September 2018. We looked through the reference lists of retrieved publications and review articles, and we searched the FDA and EMA websites. SELECTION CRITERIA: We searched for randomised clinical trials in any setting, recruiting people with hepatic encephalopathy. Trials were eligible for inclusion if they compared acetyl-L-carnitine plus standard care (e.g. antibiotics, lactulose) versus placebo or no acetyl-L-carnitine plus standard care. We are well aware that by selecting randomised clinical trials, we placed greater focus on potential benefits than on potential harms. DATA COLLECTION AND ANALYSIS: We selected randomised clinical trials, assessed risk of bias in eight domains, and extracted data in a duplicate and independent fashion. We estimated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. We measured statistical heterogeneity using I² and D² statistics. We subjected our analyses to fixed-effect and random-effects model meta-analyses. We assessed bias risk domains to control systematic errors. We assessed overall quality of the data for each individual outcome by using the GRADE approach. MAIN RESULTS: We identified five randomised clinical trials involving 398 participants. All trials included only participants with cirrhosis as the underlying cause of hepatic encephalopathy. Trials included participants with covert or overt hepatic encephalopathy. All trials were conducted in Italy by a single team and assessed acetyl-L-carnitine compared with placebo. Oral intervention was the most frequent route of administration. All trials were at high risk of bias and were underpowered. None of the trials were sponsored by the pharmaceutical industry.None of the identified trials reported information on all-cause mortality, serious adverse events, or days of hospitalisation. Only one trial assessed quality of life using the Short Form (SF)-36 scale (67 participants; very low-quality evidence). The effects of acetyl-L-carnitine compared with placebo on general health at 90 days are uncertain (MD -6.20 points, 95% confidence interval (CI) -9.51 to -2.89). Results for additional domains of the SF-36 are also uncertain. One trial assessed fatigue using the Wessely and Powell test (121 participants; very low-quality evidence). The effects are uncertain in people with moderate-grade hepatic encephalopathy (mental fatigue: MD 0.40 points, 95% CI -0.21 to 1.01; physical fatigue: MD -0.20 points, 95% CI -0.92 to 0.52) and mild-grade hepatic encephalopathy (mental fatigue: -0.80 points, 95% CI -1.48 to -0.12; physical fatigue: 0.20 points, 95% CI -0.72 to 1.12). Meta-analysis showed a reduction in blood ammonium levels favouring acetyl-L-carnitine versus placebo (MD -13.06 mg/dL, 95% CI -17.24 to -8.99; 387 participants; 5 trials; very low-quality evidence). It is unclear whether acetyl-L-carnitine versus placebo increases the risk of non-serious adverse events (8/126 (6.34%) vs 3/120 (2.50%); RR 2.51, 95% CI 0.68 to 9.22; 2 trials; very low-quality evidence). Overall, adverse events data were poorly reported and harms may have been underestimated. AUTHORS' CONCLUSIONS: This Cochrane systematic review analysed a heterogeneous group of five trials at high risk of bias and with high risk of random errors conducted by only one research team. We assessed acetyl-L-carnitine versus placebo in participants with cirrhosis with covert or overt hepatic encephalopathy. Hence, we have no data on the drug for hepatic encephalopathy in acute liver failure. We found no information about all-cause mortality, serious adverse events, or days of hospitalisation. We found no clear differences in effect between acetyl-L-carnitine and placebo regarding quality of life, fatigue, and non-serious adverse events. Acetyl-L-carnitine reduces blood ammonium levels compared with placebo. We rated all evidence as of very low quality due to pitfalls in design and execution, inconsistency, small sample sizes, and very few events. The harms profile for acetyl-L-carnitine is presently unclear. Accordingly, we need further randomised clinical trials to assess acetyl-L-carnitine versus placebo conducted according to the SPIRIT statements and reported according to the CONSORT statements.

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BACKGROUND: Red blood cell (RBC) transfusions are essential in health care. The quality of recommendations included in clinical practice guidelines (CPG), regarding this intervention, has not been systematically evaluated. This paper systematically assessed CPGs for RBC-transfusion, to appraise their methodological quality, to explore changes in quality over time, and to assess the consistency of the hemoglobin threshold (HT) recommendations. METHODS: We searched for CPGs that included recommendations of RBC-transfusion in generic databases, compiler entities, registries, clearinghouses and guideline developers. Three reviewers extracted data on CPGs characteristics and HT recommendations, independently appraised the quality of the studies using AGREE II and resolved disagreements by consensus. RESULTS: We examined 16 CPGs. Mean scores (mean ± SD) were: scope and purpose (59.4% ± 19.8%), stakeholder involvement (43.2% ± 22.6%), rigor of development (50% ± 25%), clarity of presentation (74.4% ± 12.6%), applicability (19.4% ± 18.8%), and editorial independence (41% ± 30%). Seven CPGs recommended a restrictive strategy for RBC transfusion; four CPGs gave a guarded statement considering an HT of 7 g/dL, as safe to prescribe an RBC transfusion. Eight CPGs did not provide an HT stating that RBC transfusions should not be prescribed by HT alone. CONCLUSIONS: Only 3 out of the 16 evaluated CPGs were "recommended" by the independent evaluators. Four domains "stakeholder involvement," "rigor of development," applicability," and "editorial independence" had serious shortcomings. Recommendations about the use of an HT for RBC-transfusion were heterogeneous among guidelines. Greater efforts are needed to provide high-quality CPGs in the RBC-transfusion practice.

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Few Orthopaedics and Traumatology journals from Latin America and Spain are indexed in major databases; controlled clinical trials published in these journals cannot be exhaustively retrieved using electronic literature searches. We aimed to identify, describe and assess the quality of controlled clinical trials published in Orthopaedics and Traumatology journals from Latin America and Spain through handsearching and evidence mapping methods. We identified controlled clinical trials published in eligible Orthopaedics/Traumatology journals in Spanish until July 2017 by handsearching. Data were extracted for controlled clinical trials main characteristics and the Cochrane risk of bias tool was used to assess the controlled clinical trials methodological quality. In addition, we mapped the main findings of these trials. As a result, we assessed 5631 references in 29 eligible journals of which 57 were controlled clinical trials (1.0%). Controlled clinical trials were published between 1995 and 2017 at a rate of 2.5 per year. Journals from Spain and Mexico published around 63% of the controlled clinical trials identified. The median sample size of patients enrolled was 60 (range = 30-300 participants). About conditions assessed, 38.5% of controlled clinical trials assessed issues related to knee conditions, 15.7% about hip and 10.5% about trauma or spine. The risk of bias domains most affected was selective reporting bias and random sequence generation. In addition, only two and seven trials had low risk of bias in all items related to participant/personnel and outcome assessment blindings, respectively. More than 40% of studies did not report differences on benefits/harms between the interventions assessed. As a conclusion, the number of controlled clinical trials published in Orthopaedics/Traumatology journals from Latin America and Spain is low. These controlled clinical trials had important methodological shortcomings and were judged as unclear or high risk of bias. These trials are now available in CENTRAL for their potential inclusion in systematic reviews and other documents of synthesis.

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BACKGROUND: Acute high altitude illness is defined as a group of cerebral and pulmonary syndromes that can occur during travel to high altitudes. It is more common above 2500 metres, but can be seen at lower elevations, especially in susceptible people. Acute high altitude illness includes a wide spectrum of syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude cerebral oedema' and 'high altitude pulmonary oedema'. There are several interventions available to treat this condition, both pharmacological and non-pharmacological; however, there is a great uncertainty regarding their benefits and harms. OBJECTIVES: To assess the clinical effectiveness, and safety of interventions (non-pharmacological and pharmacological), as monotherapy or in any combination, for treating acute high altitude illness. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science, CINAHL, Wanfang database and the World Health Organization International Clinical Trials Registry Platform for ongoing studies on 10 August 2017. We did not apply any language restriction. SELECTION CRITERIA: We included randomized controlled trials evaluating the effects of pharmacological and non-pharmacological interventions for individuals suffering from acute high altitude illness: acute mountain sickness, high altitude pulmonary oedema or high altitude cerebral oedema. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of study reports, the risk of bias for each and performed the data extraction. We resolved disagreements through discussion with a third author. We assessed the quality of evidence with GRADE. MAIN RESULTS: We included 13 studies enrolling a total of 468 participants. We identified two ongoing studies. All studies included adults, and two studies included both teenagers and adults. The 13 studies took place in high altitude areas, mostly in the European Alps. Twelve studies included participants with acute mountain sickness, and one study included participants with high altitude pulmonary oedema. Follow-up was usually less than one day. We downgraded the quality of the evidence in most cases due to risk of bias and imprecision. We report results for the main comparisons as follows.Non-pharmacological interventions (3 studies, 124 participants)All-cause mortality and complete relief of AMS symptoms were not reported in the three included trials. One study in 64 participants found that a simulated descent of 193 millibars versus 20 millibars may reduce the average of symptoms to 2.5 vs 3.1 units after 12 hours of treatment (clinical score ranged from 0 to 11 ‒ worse; reduction of 0.6 points on average with the intervention; low quality of evidence). In addition, no complications were found with use of hyperbaric chambers versus supplementary oxygen (one study; 29 participants; low-quality evidence).Pharmacological interventions (11 trials, 375 participants)All-cause mortality was not reported in the 11 included trials. One trial found a greater proportion of participants with complete relief of AMS symptoms after 12 and 16 hours when dexamethasone was administered in comparison with placebo (47.1% versus 0%, respectively; one study; 35 participants; low quality of evidence). Likewise, when acetazolamide was compared with placebo, the effects on symptom severity was uncertain (standardized mean difference (SMD) -1.15, 95% CI -2.56 to 0.27; 2 studies, 25 participants; low-quality evidence). One trial of dexamethasone in comparison with placebo in 35 participants found a reduction in symptom severity (difference on change in the AMS score: 3.7 units reported by authors; moderate quality of evidence). The effects from two additional trials comparing gabapentin with placebo and magnesium with placebo on symptom severity at the end of treatment were uncertain. For gabapentin versus placebo: mean visual analogue scale (VAS) score of 2.92 versus 4.75, respectively; 24 participants; low quality of evidence. For magnesium versus placebo: mean scores of 9 and 10.3 units, respectively; 25 participants; low quality of evidence). The trials did not find adverse events from either treatment (low quality of evidence). One trial comparing magnesium sulphate versus placebo found that flushing was a frequent event in the magnesium sulphate arm (percentage of flushing: 75% versus 7.7%, respectively; one study; 25 participants; low quality of evidence). AUTHORS' CONCLUSIONS: There is limited available evidence to determine the effects of non-pharmacological and pharmacological interventions in treating acute high altitude illness. Low-quality evidence suggests that dexamethasone and acetazolamide might reduce AMS score compared to placebo. However, the clinical benefits and harms related to these potential interventions remain unclear. Overall, the evidence is of limited practical significance in the clinical field. High-quality research in this field is needed, since most trials were poorly conducted and reported.

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