Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Insurance-Based Disparities in Outcomes and ECMO Utilization for Hospitalized COVID-19 Patients.

BACKGROUND: The objective of this study was to examine insurance-based disparities in mortality, non-home discharges, and ECMO utilization in patients hospitalized with COVID-19. METHODS: Using a national database of U.S. academic medical centers and their affiliated hospitals, the risk-adjusted association between mortality, non-home discharge, and ECMO utilization and (1) the type of insurance coverage (private insurance, Medicare, dual enrollment in Medicare and Medicaid, and no insurance) and (2) the weekly hospital COVID-19 burden (0-5.0%; 5.1-10%, 10.1-20%, 20.1-30%, 30.1%-) was evaluated. Modelling was expanded to include an interaction between payer status and the weekly hospital COVID-19 burden to examine whether the lack of private insurance was associated with increases in disparities as the COVID-19 burden increased. RESULTS: Among 760,846 patients hospitalized with COVID-19, 214,992 had private insurance, 318,624 had Medicare, 96,192 were dually enrolled in Medicare and Medicaid, 107,548 had Medicaid, and 23,560 had no insurance. Overall, 76,250 died, 211,702 had non-home discharges, 75,703 were mechanically ventilated, and 2,642 underwent ECMO. The adjusted odds of death were higher in patients with Medicare (aOR 1.28; [95% CI: 1.21, 1.35]; P<0.0005), dually enrolled (aOR, 1.39; [1.30, 1.50]; P<0.0005), Medicaid (aOR, 1.28; [1.20, 1.36]; P<0.0005), and no insurance (aOR, 1.43; [1.26, 1.62]; P<0.0005) compared to patients with private insurance. Patients with Medicare (aOR, 0.47; [CI: 0.39, 0.58]; P <0.0005), dually enrolled (aOR, 0.32; [0.24, 0.43]; P<0.0005), Medicaid (aOR, 0.70; [ 0.62, 0.79]; P<0.0005), and no insurance (aOR, 0.40; [0.29, 0.56]; P<0.001] were less likely to be placed on ECMO than patients with private insurance. Mortality, non-home discharges, and ECMO utilization did not change significantly more in patients with private insurance compared to patients without private insurance as the COVID-19 burden increased. CONCLUSION: Among patients with COVID-19, insurance-based disparities in mortality, non-home discharges, and ECMO utilization were substantial, but these disparities did not increase as the hospital COVID-19 burden increased.

Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2.

BACKGROUND: The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). METHODS: To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups-a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). RESULTS: The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. CONCLUSION: In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.

The Use of Virtual Reality to Reduce Pain and Anxiety in Surgical Procedures of the Oral Cavity: A Scoping Review.

PURPOSE: Virtual reality (VR) is considered a nonpharmacological intervention to manage pain and anxiety for different procedures. We aimed to review the literature about the role of VR in reducing pain and anxiety in surgical procedures performed in the oral cavity. METHODS: A literature review was conducted using Medline and Embase with no restrictions on language or publication date. Our inclusion criteria were articles related to the use of VR to manage perioperative pain and anxiety on procedures in the oral cavity. RESULTS: Twenty-seven articles met the inclusion criteria. The number of publications increased significantly from 2 studies between 2000-2010 to 25 between 2011 and 2021. Of the 27 included studies, 22 (81.4%) studied patients undergoing dental procedures, and 5 (18.5%) in oral and maxillofacial surgery (OMS). There was heterogeneity in the VR software used in the different studies. Thirteen studies (41.9%) evaluated self or observational assessments of pain and anxiety. Pain alone was evaluated in 9 studies (29%) and anxiety alone in 8 studies (25.8%). Also, 6 studies (19.3%) evaluated physiological parameters such as heart rate and respiratory rate as objective measures of pain and anxiety. In oral surgery studies, VR was effective at reducing acute pain, fear, and anxiety levels. CONCLUSIONS: There is a paucity of research in OMS compared to dentistry. Given that this specialty involves highly stimulating and anxiety-provoking procedures, OMS could benefit from VR intervention for improved patient care.

Endotracheal Tube Cuff Overinflation Leading to Hypoxic Cardiac Arrest: A Case Report and Review of the Literature.

Endotracheal tube cuff overinflation has been shown to produce airway obstruction and subsequent ventilatory and hemodynamic compromise. Although rare, this complication is reversible and its prompt identification is paramount. We describe a case of a 68-year-old woman undergoing microlaryngoscopy and vocal cord lesion biopsy, who developed ventilatory failure and cardiac arrest following endotracheal tube overinflation intraoperatively. The patient was successfully resuscitated and was able to be ventilated after endotracheal tube replacement. We present a literature review and evidence-based management insights for endotracheal tube obstruction due to cuff overinflation.

Mindfulness as an Antidote to Burnout for Nursing and Support Staff in an Oncological Intensive Care Unit: A Pilot Study.

We set out to implement a pilot mindfulness-based intervention (MBI) to alleviate burnout, stress, anxiety, and depression in nursing and support staff of an oncological intensive care unit. We created an 8-week personalized yoga therapy MBI for nurses and patient care technicians in an oncological intensive care unit. Validated self-report scale tools were used to measure burnout, stress, anxiety, and depression in the intervention and control groups (Institutional Quality Improvement Registry no. 296, 2018). Changes in scores from baseline to postintervention were evaluated between groups. Forty-five staff, 21 in the control group and 24 in the intervention group, participated. Both groups at baseline had low prevalence of stress, anxiety, and depression (13% vs 36.8%, P = .11; 21.7% vs 52.6%, P = .17; 17.4% vs 26.3%, P = .48; respectively). Low rates of high emotional exhaustion, depersonalization, and low professional efficacy were observed for both groups (41.7% vs 35.0%, P = .65; 20.8% vs 15%, P = .71; 58.3% vs 50.0%, P = .58, respectively). Post-MBI, prevalence of depression, anxiety, stress, emotional exhaustion, and depersonalization remained low and similar between both groups. Notwithstanding, professional efficacy scores significantly improved in a between-group comparison (0.063 vs -0.25; P = .0336). We observed that burnout, stress, anxiety, and depression were remarkably low in our study relative to the literature. Implementation of the MBI faced many obstacles and had low compliance during participation. This presumably influenced results and should be addressed prior to any future intervention. Despite this, professional efficacy improved significantly. TRIAL REGISTRATION: Approved by MD Anderson Cancer Center Quality Improvement Registry (no. 296, 2018).

Perioperative Management of Ehlers-Danlos Type III Syndrome Associated With Postural Orthostatic Tachycardia in Patients Undergoing General Anesthesia.

Ehlers-Danlos syndrome (EDS) is an autosomal dominant inherited disorder of connective tissue with common clinical features of skin hyperelasticity, joint hypermobility, and easy bruising. Postural orthostatic tachycardia syndrome (POTS) refers to more than three months of a sustained increase in heart rate of more than 30 beats per minute and symptoms of orthostatic intolerance within 10 minutes of assuming a standing position without associated hypotension. These medical conditions can be associated with each other, potentially creating significant perioperative challenges. This paper describes two cases of young women with POTS and EDS hypermobility type (III) who presented for surgery under general anesthesia. The anesthesiologist performed an extensive preoperative evaluation, provided adequate preoperative hydration, ensured careful positioning during anesthetic induction, and avoided neck hyperextension during intubation. Gentle emergence and extubation were practiced with vigilance towards complications of cervical subluxation and airway mucosal injury. Robust communication between postoperative caregivers was prioritized. All these considerations facilitated the achievement of good outcomes. Here, a literature review and subsequent flow diagram of the anesthetic management and perioperative considerations for these patients is purposed.

Venous Gas Embolism During Radical Robotic Prostatectomy: A Case Report and Evidence-Based Management Algorithm.

Robotic-assisted radical prostatectomy (RARP) has gained rapid popularity in the last two decades after early reports of excellent survival rates, quick learning curves, and minimal invasion or tissue damage. Given the anatomical location of surgical prostatectomies and the utilization of intra-abdominal gas during laparoscopy, there is a risk of developing venous air embolism (VAE). We present a case of a 62-year-old male with hypothyroidism and benign prostatic hyperplasia who underwent robotic suprapubic prostatectomy under general anesthesia. One hour after incision the ETCO2 suddenly dropped (40 mmHg to 25 mmHg) as did the SpO2 (98% to 90%). There were no other vital sign changes, nor was there significant blood loss. The surgical team was notified, which prompted the surgeon to inform us that he had just been dissecting around the pelvic venous plexus. At this point, with the clinical suspicion of VAE, abdominal insufflation pressure was lowered, and inspired oxygen was increased to 100%. After 10 minutes, SpO2 and ETCO2 normalized. A debrief and literature review inspired us to develop a laparoscopic-specific VAE management algorithm, with attention to robotic-case management issues. To the best of our knowledge, this is a rare case report describing a clinical VAE during RARP.

Artificial hyperventilation normalizes haemodynamics and arterial oxygen content in hypoxic rats.

INTRODUCTION: Although humans are capable of enduring critically low levels of oxygen, many hypoxaemic patients die despite aggressive therapies. Mimicking the physiological hyperventilation necessary to survive extreme hypoxic conditions could minimize the derangements caused by acute hypoxic-hypoxia. The objective of this study was to measure the haemodynamic-biochemical response to artificially induced hyperventilation in hypoxic rats. MATERIAL AND METHODS: Twenty-four deeply anaesthetized and mechanically ventilated rats were allocated to 3 groups: control (n = 5, FiO2 = 1); hypoxic spontaneously hyperventilating (n = 10, FiO2 = 0.08); and hypoxic artificially induced hyperventilation (n = 9, targeting PaCO2 = 10 mm Hg, FiO2 = 0.08). We compared the spontaneously and artificially hyperventilating groups. P-values < 0.01 were considered statistically significant. Mean arterial pressure (MAP) and serum chemistry were measured for 180 minutes. RESULTS: The control group remained stable throughout the experiment. The hypoxic groups developed profound hypotension after the decrease in FiO2. However, the artificially induced hyperventilated rats recovered their MAP to levels higher than the spontaneously hyperventilating group (117.1 ± 17.2 vs. 68.1 ± 16.0, P = 0.0048). In regard to the biochemical derangements, even though the serum lactate and PaO2 were not different among the hypoxic groups, the artificially hyperventilated group achieved significantly higher SaO2 (94.3 ± 3.6 vs. 58.6 ± 9.6, P = 0.005), pH (7.87 ± 0.04 vs. 7.50 ± 0.13, P = 0.005), and CaO2 (17.7 ± 2.6 vs. 10.2 ± 1.3, P = 0.005) at 180 minutes. CONCLUSIONS: Artificially induced hyperventilation led to the correction of arterial oxygen content, severe serum chemistry, and haemodynamic derangements. These findings may represent a novel rescue manoeuvre and serve as a bridge to a permanent form of support, but should be further studied before being translated to the clinical setting.

Levels of Evidence Supporting the North American and European Perioperative Care Guidelines for Anesthesiologists between 2010 and 2020: A Systematic Review.

BACKGROUND: Although there are thousands of published recommendations in anesthesiology clinical practice guidelines, the extent to which these are supported by high levels of evidence is not known. This study hypothesized that most recommendations in clinical practice guidelines are supported by a low level of evidence. METHODS: A registered (Prospero CRD42020202932) systematic review was conducted of anesthesia evidence-based recommendations from the major North American and European anesthesiology societies between January 2010 and September 2020 in PubMed and EMBASE. The level of evidence A, B, or C and the strength of recommendation (strong or weak) for each recommendation was mapped using the American College of Cardiology/American Heart Association classification system or the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The outcome of interest was the proportion of recommendations supported by levels of evidence A, B, and C. Changes in the level of evidence over time were examined. Risk of bias was assessed using Appraisal of Guidelines for Research and Evaluation (AGREE) II. RESULTS: In total, 60 guidelines comprising 2,280 recommendations were reviewed. Level of evidence A supported 16% (363 of 2,280) of total recommendations and 19% (288 of 1,506) of strong recommendations. Level of evidence C supported 51% (1,160 of 2,280) of all recommendations and 50% (756 of 1,506) of strong recommendations. Of all the guidelines, 73% (44 of 60) had a low risk of bias. The proportion of recommendations supported by level of evidence A versus level of evidence C (relative risk ratio, 0.93; 95% CI, 0.18 to 4.74; P = 0.933) or level of evidence B versus level of evidence C (relative risk ratio, 1.63; 95% CI, 0.72 to 3.72; P = 0.243) did not increase in guidelines that were revised. Year of publication was also not associated with increases in the proportion of recommendations supported by level of evidence A (relative risk ratio, 1.07; 95% CI, 0.93 to 1.23; P = 0.340) or level of evidence B (relative risk ratio, 1.05; 95% CI, 0.96 to 1.15; P = 0.283) compared to level of evidence C. CONCLUSIONS: Half of the recommendations in anesthesiology clinical practice guidelines are based on a low level of evidence, and this did not change over time. These findings highlight the need for additional efforts to increase the quality of evidence used to guide decision-making in anesthesiology.

Pain management during the withholding and withdrawal of life support in critically ill patients at the end-of-life: a systematic review and meta-analysis.

PURPOSE: To review and summarize the most frequent medications and dosages used during withholding and withdrawal of life-prolonging measures in critically ill patients in the intensive care unit. METHODS: We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Virtual Health Library from inception through March 2019. We considered any study evaluating pharmaceutical interventions for pain management during the withholding or withdrawing of life support in adult critically ill patients at the end-of-life. Two independent investigators performed the screening and data extraction. We pooled data on utilization rate of analgesic and sedative drugs and summarized the dosing between the moment prior to withholding or withdrawal of life support and the moment before death. RESULTS: Thirteen studies met inclusion criteria. Studies were conducted in the United States (38%), Canada (31%), and the Netherlands (31%). Eleven studies were single-cohort and twelve had a Newcastle-Ottawa Scale score of less than 7. The mean age of the patients ranged from 59 to 71 years, 59-100% were mechanically ventilated, and 47-100% of the patients underwent life support withdrawal. The most commonly used opioid and sedative were morphine [utilization rate 60% (95% CI 48-71%)] and midazolam [utilization rate 28% (95% CI 23-32%)], respectively. Doses increased during the end-of-life process (pooled mean increase in the dose of morphine: 2.6 mg/h, 95% CI 1.2-4). CONCLUSIONS: Pain control is centered on opioids and adjunctive benzodiazepines, with dosages exceeding those recommended by guidelines. Despite consistency among guidelines, there is significant heterogeneity among practices in end-of-life care.

Critical Care Admission of an HIV Patient with Diabetic Ketoacidosis Secondary to Pembrolizumab.

BACKGROUND: Pembrolizumab is a checkpoint inhibitor that targets the programmed cell death-1 receptor (PD-1) and has shown to be effective against several malignancies, including lung cancer. However, life-threatening immune-related adverse events can result from these immunotherapy treatments. Case presentation. A 62-year-old man with HIV, metastatic adenocarcinoma of the lung, and no previous history of diabetes presented to the emergency department with new-onset nausea, vomiting, and generalized weakness. Glucose was 1191 mg/dl, hemoglobin A1c 11%, and potassium 6.9 mEq/L. He had metabolic acidosis with a lactate of 6.6 mmol/L and anion gap of 38 mEq/L, and ketones were detected on the urinalysis. Severe diabetic ketoacidosis was diagnosed, and the patient was admitted to the intensive care unit. Additional investigations showed low C-peptide and negative anti-glutamic acid decarboxylase antibody, anti-insulin antibody, and anti-islet-antigen 2Ab antibody. After ruling out other possible etiologies, pembrolizumab was considered to be the cause of the diabetes and ketoacidosis. CONCLUSIONS: Life-threatening adverse drug events associated with checkpoint inhibitors such as pembrolizumab are on the rise. We recommend to closely follow and monitor patients receiving these immunotherapies. This strategy could lead to early detection and prevention, as well as reduction of more serious life-threatening complications requiring intensive care.

Clinical Practice Guidelines and Consensus Statements About Pain Management in Critically Ill End-of-Life Patients: A Systematic Review.

OBJECTIVES: To identify and synthesize available recommendations from scientific societies and experts on pain management at the end-of-life in the ICU. DATA SOURCES: We conducted a systematic review of PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and Biblioteca Virtual en Salud from their inception until March 28, 2019. STUDY SELECTION: We included all clinical practice guidelines, consensus statements, and benchmarks for quality. DATA EXTRACTION: Study selection, methodological quality, and data extraction were performed independently by two investigators. A quality assessment was performed by four investigators using the Appraisal of Guidelines for Research and Evaluation II instrument. The recommendations were then synthesized and categorized. DATA SYNTHESIS: Ten publications were included. The Appraisal of Guidelines for Research and Evaluation II statement showed low scores in various quality domains, especially in the applicability and rigor of development. Most documents were in agreement on five topics: 1) using a quantitative tool for pain assessment; 2) administering narcotics for pain relief and benzodiazepines for anxiety relief; 3) against prescribing neuromuscular blockers during withdrawal of life support to assess pain; 4) endorsing the use of high doses of opioids and sedatives for pain control, regardless of the risk that they will hasten death; and 5) using quality indicators to improve pain management during end-of-life in the ICU. CONCLUSIONS: In spite of the lack of high-quality evidence, recommendations for pain management at the end-of-life in the ICU are homogeneous and are justified by ethical principles and agreement among experts. Considering the growing demand for the involvement of palliative care teams in the management of the dying patients in the ICU, there is a need to clearly define their early involvement and to further develop comprehensive evidence-based pain management strategies. Based on the study findings, we propose a management algorithm to improve the overall care of dying critically ill patients.

Economic impact of dengue fever in Latin America and the Caribbean: a systematic review

[ABSTRACT]. Objectives. To assess the economic impact of dengue in Latin America and the Caribbean using a systematic review that includes studies not previously considered by other reviews. Methods. Cochrane methodology was used to conduct a systematic review of the cost of dengue in Latin America. PubMed Central, EMBASE, and the Biblioteca Virtual en Salud— which includes scientific, peer-reviewed journals not indexed by other databases—were searched from inception through August 2016. All articles that reported cost of illness data for countries in Latin America were included. Included studies underwent a methodological appraisal using a seven-question instrument designed for cost of illness studies. Extracted data were direct and indirect costs for outpatient and hospitalized cases and total cost of the disease. Values were adjusted to 2015 US dollars using the consumer price index. Results. From a total of 848 initial references, 17 studies were included, mainly from Brazil, Colombia, Cuba, Mexico, and Puerto Rico; costs were available for 39 countries. The methodological appraisal showed that 70% of the studies met more than 70% of the evaluated items. The main economic impact of dengue was due to productivity costs. Average annual cost was more than US$ 3 billion. Direct costs represented over 70% of the total share for hospitalized cases. For outpatients, direct medical costs were low, but social costs were significant since indirect costs may account for up to 80% of the total cost. Conclusions. Dengue fever has a significant economic impact in Latin America. It is essential to develop new public health interventions, such as dengue vaccination, to decrease the propagation of the disease and its total cost.

[RESUMEN]. Objetivos. Evaluar las repercusiones económicas del dengue en América Latina y el Caribe mediante una revisión sistemática que abarcó estudios no considerados en otras revisiones anteriores. Métodos. Se usó la metodología de Cochrane para hacer una revisión sistemática del costo del dengue en América Latina. Se hizo una búsqueda en PubMed Central, EMBASE y la Biblioteca Virtual en Salud, que incluyen revistas científicas arbitradas no indizadas por otras bases de datos, desde su aparición hasta agosto del 2016. Se incluyeron todos los artículos que contenían datos sobre el costo de la enfermedad para los países de América Latina. Los estudios incluidos se sometieron a una evaluación metodológica para la cual se usó un instrumento de siete preguntas diseñado para los estudios sobre los costos de las enfermedades. Los datos extraídos fueron los costos directos e indirectos para los casos de pacientes ambulatorios y hospitalizados y el costo total de la enfermedad. Los valores se ajustaron a dólares de los Estados Unidos del 2015 con base en el índice de precios al consumidor. Resultados. De un total de 848 referencias iniciales, se incluyeron 17 estudios, principalmente de Brasil, Colombia, Cuba, México y Puerto Rico; se encontraron datos sobre los costos en 39 países. La evaluación metodológica indicó que 70% de los estudios reunían más de 70% de los puntos evaluados. La principal repercusión económica del dengue se debió a los costos por pérdida en la productividad. El costo anual promedio fue de más de USD 3.000 millones. Los costos directos representaron más de 70% del total para los casos de pacientes hospitalizados. En cuanto a los pacientes ambulatorios, los costos médicos directos fueron bajos, pero los costos sociales fueron considerables, ya que los costos indirectos pueden representar hasta 80% del costo total. Conclusiones. El dengue tiene importantes repercusiones económicas en América Latina. Es fundamental elaborar nuevas intervenciones en materia de salud pública, como la vacunación contra el dengue, para reducir la propagación de la enfermedad y su costo total.

[RESUMO]. Objetivos. Avaliar o impacto econômico da dengue na América Latina e o Caribe por meio de uma revisão sistemática que incluiu estudos não considerados anteriormente por outras revisões. Métodos. Utilizou-se a metodologia Cochrane para realizar uma revisão sistemática do custo da dengue na América Latina. Foi realizada uma busca dos bancos de dados PubMed Central, EMBASE e Biblioteca Virtual em Saúde— a qual inclui periódicos científicos com avaliação por pares não indexados por outros repositórios— desde sua criação até agosto de 2016. Todos os artigos que relataram dados de custo de doença para países da América Latina foram incluídos. Os estudos incluídos foram submetidos a uma avaliação metodológica usando um instrumento de sete perguntas desenvolvido para estudos de custo de doença. Os dados extraídos foram os custos diretos e indiretos para casos ambulatoriais e hospitalizados e o custo total da doença. Os valores foram ajustados para dólares de 2015, usando-se o índice de preços ao consumidor. Resultados. De 848 referências inicialmente identificadas, 17 estudos foram incluídos, principalmente do Brasil, Colômbia, Cuba, México e Porto Rico; dados sobre custos estavam disponíveis para 39 países. A avaliação metodológica demonstrou que 70% dos estudos apresentavam mais de 70% dos itens avaliados. O principal impacto econômico da dengue foi devido aos custos de produtividade. O custo médio anual foi superior a US$3 bilhões. Para casos que exigiram hospitalização, os custos diretos representaram mais de 70% do custo total. Para pacientes ambulatoriais, os custos médicos diretos foram baixos, mas os custos sociais foram significativos, pois os custos indiretos podem representar até 80% do custo total. Conclusões. A dengue tem impacto econômico considerável na América Latina. É essencial desenvolver novas intervenções de saúde pública, como a vacinação contra a dengue, para diminuir a propagação da doença e seu custo total.

Atezolizumab-related encephalitis in the intensive care unit: Case report and review of the literature.

Atezolizumab is a monoclonal antibody that targets programmed death ligand-1. Treatments with this drug may cause immune-related adverse events by creating an exaggerated inflammatory response. The most common side effects are fatigue, rash, and gastrointestinal symptoms. Cases of central nervous system toxicity such as encephalitis and encephalopathy are uncommon. We present the case of a 53-year-old female with metastatic squamous cell carcinoma of the cervix who presented to the emergency room 13 days after receiving atezolizumab with altered mental status, headache, and meningeal signs. She was admitted to the intensive care unit. Infectious, anatomical, and neoplastic etiologies were ruled out. Auto-immune meningoencephalitis was diagnosed and treated with high-dose steroids. Within 10 days of the diagnosis, she had clinical, radiological, and laboratory improvement. Given the increasing use of novel immunotherapies and life-threatening side effects associated with them, healthcare providers in the intensive care unit should be aware of their diagnosis and management.

Economic impact of dengue fever in Latin America and the Caribbean: a systematic review.

OBJECTIVES: To assess the economic impact of dengue in Latin America and the Caribbean using a systematic review that includes studies not previously considered by other reviews. METHODS: Cochrane methodology was used to conduct a systematic review of the cost of dengue in Latin America. PubMed Central, EMBASE, and the Biblioteca Virtual en Salud-which includes scientific, peer-reviewed journals not indexed by other databases-were searched from inception through August 2016. All articles that reported cost of illness data for countries in Latin America were included. Included studies underwent a methodological appraisal using a seven-question instrument designed for cost of illness studies. Extracted data were direct and indirect costs for outpatient and hospitalized cases and total cost of the disease. Values were adjusted to 2015 US dollars using the consumer price index. RESULTS: From a total of 848 initial references, 17 studies were included, mainly from Brazil, Colombia, Cuba, Mexico, and Puerto Rico; costs were available for 39 countries. The methodological appraisal showed that 70% of the studies met more than 70% of the evaluated items. The main economic impact of dengue was due to productivity costs. Average annual cost was more than US$ 3 billion. Direct costs represented over 70% of the total share for hospitalized cases. For outpatients, direct medical costs were low, but social costs were significant since indirect costs may account for up to 80% of the total cost. CONCLUSIONS: Dengue fever has a significant economic impact in Latin America. It is essential to develop new public health interventions, such as dengue vaccination, to decrease the propagation of the disease and its total cost.

Economic impact of dengue fever in Latin America and the Caribbean: a systematic review / Repercusiones económicas del dengue en América Latina y el Caribe: una revisión sistemática / Impacto econômico da dengue na América Latina e Caribe: revisão sistemática

ABSTRACT Objectives To assess the economic impact of dengue in Latin America and the Caribbean using a systematic review that includes studies not previously considered by other reviews. Methods Cochrane methodology was used to conduct a systematic review of the cost of dengue in Latin America. PubMed Central, EMBASE, and the Biblioteca Virtual en Salud—which includes scientific, peer-reviewed journals not indexed by other databases—were searched from inception through August 2016. All articles that reported cost of illness data for countries in Latin America were included. Included studies underwent a methodological appraisal using a seven-question instrument designed for cost of illness studies. Extracted data were direct and indirect costs for outpatient and hospitalized cases and total cost of the disease. Values were adjusted to 2015 US dollars using the consumer price index. Results From a total of 848 initial references, 17 studies were included, mainly from Brazil, Colombia, Cuba, Mexico, and Puerto Rico; costs were available for 39 countries. The methodological appraisal showed that 70% of the studies met more than 70% of the evaluated items. The main economic impact of dengue was due to productivity costs. Average annual cost was more than US$ 3 billion. Direct costs represented over 70% of the total share for hospitalized cases. For outpatients, direct medical costs were low, but social costs were significant since indirect costs may account for up to 80% of the total cost. Conclusions Dengue fever has a significant economic impact in Latin America. It is essential to develop new public health interventions, such as dengue vaccination, to decrease the propagation of the disease and its total cost.

RESUMEN Objetivos Evaluar las repercusiones económicas del dengue en América Latina y el Caribe mediante una revisión sistemática que abarcó estudios no considerados en otras revisiones anteriores. Métodos Se usó la metodología de Cochrane para hacer una revisión sistemática del costo del dengue en América Latina. Se hizo una búsqueda en PubMed Central, EMBASE y la Biblioteca Virtual en Salud, que incluyen revistas científicas arbitradas no indizadas por otras bases de datos, desde su aparición hasta agosto del 2016. Se incluyeron todos los artículos que contenían datos sobre el costo de la enfermedad para los países de América Latina. Los estudios incluidos se sometieron a una evaluación metodológica para la cual se usó un instrumento de siete preguntas diseñado para los estudios sobre los costos de las enfermedades. Los datos extraídos fueron los costos directos e indirectos para los casos de pacientes ambulatorios y hospitalizados y el costo total de la enfermedad. Los valores se ajustaron a dólares de los Estados Unidos del 2015 con base en el índice de precios al consumidor. Resultados De un total de 848 referencias iniciales, se incluyeron 17 estudios, principalmente de Brasil, Colombia, Cuba, México y Puerto Rico; se encontraron datos sobre los costos en 39 países. La evaluación metodológica indicó que 70% de los estudios reunían más de 70% de los puntos evaluados. La principal repercusión económica del dengue se debió a los costos por pérdida en la productividad. El costo anual promedio fue de más de USD 3.000 millones. Los costos directos representaron más de 70% del total para los casos de pacientes hospitalizados. En cuanto a los pacientes ambulatorios, los costos médicos directos fueron bajos, pero los costos sociales fueron considerables, ya que los costos indirectos pueden representar hasta 80% del costo total. Conclusiones El dengue tiene importantes repercusiones económicas en América Latina. Es fundamental elaborar nuevas intervenciones en materia de salud pública, como la vacunación contra el dengue, para reducir la propagación de la enfermedad y su costo total.

RESUMO Objetivos Avaliar o impacto econômico da dengue na América Latina e o Caribe por meio de uma revisão sistemática que incluiu estudos não considerados anteriormente por outras revisões. Métodos Utilizou-se a metodologia Cochrane para realizar uma revisão sistemática do custo da dengue na América Latina. Foi realizada uma busca dos bancos de dados PubMed Central, EMBASE e Biblioteca Virtual em Saúde— a qual inclui periódicos científicos com avaliação por pares não indexados por outros repositórios—desde sua criação até agosto de 2016. Todos os artigos que relataram dados de custo de doença para países da América Latina foram incluídos. Os estudos incluídos foram submetidos a uma avaliação metodológica usando um instrumento de sete perguntas desenvolvido para estudos de custo de doença. Os dados extraídos foram os custos diretos e indiretos para casos ambulatoriais e hospitalizados e o custo total da doença. Os valores foram ajustados para dólares de 2015, usando-se o índice de preços ao consumidor. Resultados De 848 referências inicialmente identificadas, 17 estudos foram incluídos, principalmente do Brasil, Colômbia, Cuba, México e Porto Rico; dados sobre custos estavam disponíveis para 39 países. A avaliação metodológica demonstrou que 70% dos estudos apresentavam mais de 70% dos itens avaliados. O principal impacto econômico da dengue foi devido aos custos de produtividade. O custo médio anual foi superior a US$3 bilhões. Para casos que exigiram hospitalização, os custos diretos representaram mais de 70% do custo total. Para pacientes ambulatoriais, os custos médicos diretos foram baixos, mas os custos sociais foram significativos, pois os custos indiretos podem representar até 80% do custo total. Conclusões A dengue tem impacto econômico considerável na América Latina. É essencial desenvolver novas intervenções de saúde pública, como a vacinação contra a dengue, para diminuir a propagação da doença e seu custo total.