Substandard and Falsified Medications: A Barrier to Global Health Equity Exemplified in Ecuador.

Medicines have been developed and have become globalized at a pace faster than traditional medical education can keep up. Physicians, pharmacists, nurses, and advanced practice providers learn the names and functions of these medications, but not how they are made and how they get to the bedside. The often economically driven intricacies behind these processes have a dramatic effect on patient care and outcomes. A staggering proportion of medications worldwide are reported to be substandard or falsified. This article explores one country's story of how medication gets to the bedside, describes how this process can go wrong, and outlines what providers can do to work toward the goal of equitable access to quality medications for all.

Management of Refractory Status Epilepticus: An International Cohort Study (MORSE CODe) Analysis of Patients Managed in the ICU.

BACKGROUND AND OBJECTIVES: Status epilepticus that continues after the initial benzodiazepine and a second anticonvulsant medication is known as refractory status epilepticus (RSE). Management is highly variable because adequately powered clinical trials are missing. We aimed to determine whether propofol and midazolam were equally effective in controlling RSE in the intensive care unit, focusing on management in resource-limited settings. METHODS: Patients with RSE treated with midazolam or propofol between January 2015 and December 2018 were retrospectively identified among 9 centers across 4 continents from upper-middle-income economies in Latin America and high-income economies in North America, Europe, and Asia. Demographics, Status Epilepticus Severity Score, etiology, treatment details, and discharge modified Rankin Scale (mRS) were collected. The primary outcome measure was good functional outcome defined as a mRS score of 0-2 at hospital discharge. RESULTS: Three hundred eighty-seven episodes of RSE (386 patients) were included, with 162 (42%) from upper-middle-income and 225 (58%) from high-income economies. Three hundred six (79%) had acute and 79 (21%) remote etiologies. Initial RSE management included midazolam in 266 (69%) and propofol in 121 episodes (31%). Seventy episodes (26%) that were initially treated with midazolam and 42 (35%) with propofol required the addition of a second anesthetic to treat RSE. Baseline characteristics and outcomes of patients treated with midazolam or propofol were similar. Breakthrough (odds ratio [OR] 1.6, 95% CI 1.3-2.0) and withdrawal seizures (OR 2.0, 95% CI 1.7-2.5) were associated with an increased number of days requiring continuous intravenous anticonvulsant medications (cIV-ACMs). Prolonged EEG monitoring was associated with fewer days of cIV-ACMs (1-24 hours OR 0.5, 95% CI 0.2-0.9, and >24 hours OR 0.7, 95% CI 0.5-1.0; reference EEG <1 hour). This association was seen in both, high-income and upper-middle-income economies, but was particularly prominent in high-income countries. One hundred ten patients (28%) were dead, and 80 (21%) had good functional outcomes at hospital discharge. DISCUSSION: Outcomes of patients with RSE managed in the intensive care unit with propofol or midazolam infusions are comparable. Prolonged EEG monitoring may allow physicians to decrease the duration of anesthetic infusions safely, but this will depend on the implementation of RSE management protocols. Goal-directed management approaches including EEG targets may hold promise for patients with RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III data that propofol and midazolam are equivalently efficacious for RSE.

Effect of High Altitude on the Survival of COVID-19 Patients in Intensive Care Unit: A Cohort Study.

Purpose: The effect of high altitude ( ≥ 1500 m) and its potential association with mortality by COVID-19 remains controversial. We assessed the effect of high altitude on the survival/discharge of COVID-19 patients requiring intensive care unit (ICU) admission for mechanical ventilation compared to individuals treated at sea level. Methods: A retrospective cohort multi-center study of consecutive adults patients with a positive RT-PCR test for COVID-19 who were mechanically ventilated between March and November 2020. Data were collected from two sea-level hospitals and four high-altitude hospitals in Ecuador. The primary outcome was ICU and hospital survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Results: Of the study population (n = 670), 35.2% were female with a mean age of 58.3 ± 12.6 years. On admission, high-altitude patients were more likely to be younger (57.2 vs. 60.5 years old), presented with less comorbidities such as hypertension (25.9% vs. 54.9% with p-value <.001) and diabetes mellitus (20.5% vs. 37.2% with p-value <.001), less probability of having a capillary refill time > 3 sec (13.7% vs. 30.1%, p-value <.001), and less severity-of-illness condition (APACHE II score, 17.5 ± 8.1 vs. 20 ± 8.2, p < .01). After adjusting for key confounders high altitude is associated with significant higher probabilities of ICU survival/discharge (HR: 1.74 [95% CI: 1.46-2.08]) and hospital survival/discharge (HR: 1.35 [95% CI: 1.18-1.55]) than patients treated at sea level. Conclusions: Patients treated at high altitude at any time point during the study period were 74% more likely to experience ICU survival/discharge and 35% more likely to experience hospital survival/discharge than to the sea-level group. Possible reasons for these findings are genetic and physiological adaptations due to exposure to chronic hypoxia.

Fighting Against Stroke in Latin America: A Joint Effort of Medical Professional Societies and Governments.

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments.

Short exposure of Artemia salina to group-12 metals: Comparing hatchability, mortality, lipid peroxidation, and swimming speed.

The hatchability, mortality rate, lipid peroxide levels, and swimming speed of Artemia salina have been compared based on short exposures of ZnCl2, CdCl2, and HgCl2 in artificial seawater. The hatching tests were carried out for 12, 24, 36, and 48 h at 28 °C. Mortality rate and lipid peroxide (LPO) levels were determined after 24 h of exposure at 28 °C, in the dark, and on living larvae using the FOX method. The swimming speed was determined after 24 h using a microcomputer coupled to a digital camera, with simultaneous treatment of the recorded images every 25 s, at 25 °C, under red-light irradiation. Results showed that Zn caused a gradual inhibition of the hatching for concentrations <900 µmol L-1; however, Cd and Hg displayed almost complete inhibition for concentrations ≤100 µmol L-1. Also, the heavy metals caused a dose-dependent increase of mortality (LD50) in the following order: Zn = 3290 µmol L-1 < Cd = 2206 µmol L-1 < Hg = 15.6 µmol L-1. Furthermore, significant LPO levels were found for Cd (1500-2000 µmol L-1, p < 0.001) and Hg (5-20 µmol L-1, p < 0.001). Finally, the swimming speed values increased significantly, for Zn ≈ 2.5 mm s-1 (1500 µmol L-1, p < 0.001), Cd ≈ 3.5 mm s-1 (2000 µmol L-1, p < 0.05), and Hg ≈ 4.0 mm s-1 (15 µmol L-1, p < 0.05), after 24 h exposure. There is a clear dose-dependent toxicity, indicating that Zn, Cd and Hg can induce significant changes in hatchability, mortality, and ethological and biochemical parameters.

The Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Development of Case Report Forms for Global Use.

Since its original report in January 2020, the coronavirus disease 2019 (COVID-19) due to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly become one of the deadliest global pandemics. Early reports indicate possible neurological manifestations associated with COVID-19, with symptoms ranging from mild to severe, highly variable prevalence rates, and uncertainty regarding causal or coincidental occurrence of symptoms. As neurological involvement of any systemic disease is frequently associated with adverse effects on morbidity and mortality, obtaining accurate and consistent global data on the extent to which COVID-19 may impact the nervous system is urgently needed. To address this need, investigators from the Neurocritical Care Society launched the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID). The GCS-NeuroCOVID consortium rapidly implemented a Tier 1, pragmatic study to establish phenotypes and prevalence of neurological manifestations of COVID-19. A key component of this global collaboration is development and application of common data elements (CDEs) and definitions to facilitate rigorous and systematic data collection across resource settings. Integration of these elements is critical to reduce heterogeneity of data and allow for future high-quality meta-analyses. The GCS-NeuroCOVID consortium specifically designed these elements to be feasible for clinician investigators during a global pandemic when healthcare systems are likely overwhelmed and resources for research may be limited. Elements include pediatric components and translated versions to facilitate collaboration and data capture in Latin America, one of the epicenters of this global outbreak. In this manuscript, we share the specific data elements, definitions, and rationale for the adult and pediatric CDEs for Tier 1 of the GCS-NeuroCOVID consortium, as well as the translated versions adapted for use in Latin America. Global efforts are underway to further harmonize CDEs with other large consortia studying neurological and general aspects of COVID-19 infections. Ultimately, the GCS-NeuroCOVID consortium network provides a critical infrastructure to systematically capture data in current and future unanticipated disasters and disease outbreaks.

Neuroemergencies in South America: How to Fill in the Gaps?

South America is a subcontinent with 393 million inhabitants with widely distinct countries and diverse ethnicities, cultures, political and societal organizations. The epidemiological transition that accompanied the technological and demographic evolution is happening in South America and leading to a rise in the incidence of neurodegenerative and cardiovascular diseases that now coexist with the still high burden of infectious diseases. South America is also quite heterogeneous regarding the existence of systems of care for the various neurological emergencies, with some countries having well-organized systems for some diseases, while others have no plan of action for the care of patients with acute neurological symptoms. In this article, we discuss the existing systems of care in different countries of South America for the treatment of neurological emergencies, mainly stroke, status epilepticus, and traumatic brain injury. We also will address existing gaps between the current systems and recommendations from the literature to improve the management of such emergencies, as well as strategies on how to solve these disparities.

Priorities to reduce the burden of stroke in Latin American countries.

The large and increasing burden of stroke in Latin American countries, and the need to meet the UN and WHO requirements for reducing the burden from non-communicable disorders (including stroke), brought together stroke experts and representatives of the Ministries of Health of 13 Latin American countries for the 1st Latin American Stroke Ministerial meeting in Gramado, Brazil, to discuss the problem and identify ways of cooperating to reduce the burden of stroke in the region. Discussions were focused on the regional and country-specific activities associated with stroke prevention and treatment, including public stroke awareness, prevention strategies, delivery and organisation of care, clinical practice gaps, and unmet needs. The meeting culminated with the adoption of the special Gramado Declaration, signed by all Ministerial officials who attended the meeting. With agreed priorities for stroke prevention, treatment, and research, an opportunity now exists to translate this Declaration into an action plan to reduce the burden of stroke.

Angiographic Features of Intracranial Aneurysms in Ecuador.

BACKGROUND: Most of the literature describing morphological features of intracranial aneurysms (IAs) is from North-America, East-Asia, and Europe. There is limited data from South-America. We describe the epidemiologic and angiographic features of ruptured and unruptured IAs in a cohort of patients from Ecuador. METHODS: We conducted a retrospective analysis of prospectively acquired databases from 3 different tertiary hospitals over a 3-year period (2014-2017). In a per-patient basis, odd ratios (ORs) of ruptured presentation for each variable using a univariate logistic regression model were calculated. An aneurysm-based multivariate analysis was performed to calculate rupture ORs for each variable. RESULTS: Our sample included 557 patients with 761 IAs. Mean patient age was 52.2 years (range 18-82). Sixty-eight percent were women, and almost 90% presented with ruptured aneurysms and concomitant subarachnoid hemorrhage (SAH). Mean size of all the IAs was 6.4 mm ± 3.98 mm. Most IAs were located in anterior circulation (96.6%): 28.4% medial cerebral artery, 24.4% anterior cerebral artery or anterior communicating artery (ACOM), and 23.5% posterior communicating artery (PCOM). Only 6 basilar tip aneurysms (0.8%) were reported. In the adjusted analysis, aneurysms located in the ACOM (OR 1.89, 95% CI 1.29-2.78) and PCOM (OR 1.84, 95% CI 1.25-2.71), size larger than 5 mm (OR 2.84, 95% CI 2.04-3.93) and 7 mm (OR 2.28, 95% CI 1.64-3.19), and those with non-saccular morphology (OR 9.87, 95% CI 2.21-44.14) were significantly associated with ruptured presentation. CONCLUSIONS: The prevalence of posterior circulation IAs in Ecuador, particularly basilar tip aneurysms, is low when compared to previous reports from developed countries. In our sample, IAs greater than 5 mm (and ≥7 mm) in size, ACOM and PCOM locations, and IAs with nonsaccular morphologies (blister and fusiform) were significantly associated with SAH presentation.

Retardo En La Llegada De Pacientes Con Ictus Isquémico A Un Hospital Terciario De Ecuador / Delay In The Arrival Of Ischemic Stroke Patients At A Tertiary Hospital In Ecuador

Resumen Introducción: El tratamiento del ictus isquémico con trombolisis farmacológica en el entorno de una unidad de ictus se asocia a una mejor recuperación. El objetivo de este estudio es identificar variables que pudieran relacionarse con un retardo en la llegada al hospital. Métodos: Se realizó un estudio prospectivo, longitudinal, en los pacientes con diagnóstico de ictus isquémico que ingresaron en la Unidad de Ictus del Hospital de especialidades Eugenio Espejo de la ciudad de Quito, Ecuador, en el periodo comprendido entre noviembre de 2016 a julio de 2017. Se compararon los pacientes que fueron tratados con r-Tpa con los que llegaron después de las 4,5 horas. Resultados: Se estudiaron un total de 61 pacientes: 51 de ellos arribaron al hospital después de las 4,5 horas, y 10 (16,4 %) fueron sometidos a trombolisis en periodo de ventana terapéutica. Ninguna de las variables sociodemográficas y clínicas excepto el antecedente de fibrilación auricular se relacionó con el arribo precoz. En el grupo que recibió r-Tpa el porcentaje de pacientes que buscó atención médica en el hospital como primera opción fue significativamente mayor respecto a los que llegaron después del periodo de ventana (90 vs 49 %, p 0,0170). El mayor impacto de la remisión precoz y la trombolisis fue sobre la diferencia de puntaje entre la evaluación inicial y al alta en la escala del NIHSS. Conclusiones: Los resultados apuntan a que existe desconocimiento acerca del ictus y qué conducta asumir. El tratamiento con r-Tpa demuestra beneficios en nuestro medio.

Abstract Introduction: In an Stroke unit, the ischemic stroke treatment with a pharmacological thrombolysis is associated with a better recovery. The aim of this study is to identify the variables having a significant impact in the delay of the arrival of patients at a tertiary hospital. Methods: A prospective and longitudinal study was undertaken in patients with an ischemic stroke diagnosis, who were admitted to the Stroke Unit of Eugenio Espejo Hospital of Quito city in Ecuador in the time period from November 2016 to July 2017. Patients treated with r-Tpa were compared to those who arrived 4,5 hours later. Results: A total of 61 patients were analyzed: of those, 51 arrived 4,5 hours after first symptoms at the hospital, and 10 (16,4%) were thrombolysed in the period of therapeutic window. None of the social, demographic and clinical variables were related to the early arrival, except the history of an atrial fibrillation. In the group of patients who received r-Tpa, a significantly higher percent sought for medical care as a first option compared with those arriving after the 4,5 hours (90 vs 49%, p 0,0170). The greatest impact of the early referral and the thrombolysis concerned the difference of score between the initial medical evaluation and the hospital discharge in the NIHSS scale. Conclusions: The results of this study point out to the unawareness of the stroke and the behavior to follow. The r-Tpa treatment shows clear benefits to the patients in our environment.

Real-time Noninvasive Monitoring of Intracranial Fluid Shifts During Dialysis Using Volumetric Integral Phase-Shift Spectroscopy (VIPS): A Proof-of-Concept Study.

BACKGROUND: Cerebral edema, which is associated with increased intracranial fluid, is often a complication of many acute neurological conditions. There is currently no accepted method for real-time monitoring of intracranial fluid volume at the bedside. We evaluated a novel noninvasive technique called "Volumetric Integral Phase-shift Spectroscopy (VIPS)" for detecting intracranial fluid shifts during hemodialysis. METHODS: Subjects receiving scheduled hemodialysis for end-stage renal disease and without a history of major neurological conditions were enrolled. VIPS monitoring was performed during hemodialysis. Serum osmolarity, electrolytes, and cognitive function with mini-mental state examination (MMSE) were assessed. RESULTS: Twenty-one monitoring sessions from 14 subjects (4 women), mean group age 50 (SD 12.6), were analyzed. The serum osmolarity decreased by a mean of 6.4 mOsm/L (SD 6.6) from pre- to post-dialysis and correlated with an increase in the VIPS edema index (E-Dex) of 9.7% (SD 12.9) (Pearson's correlation r = 0.46, p = 0.037). Of the individual determinants of serum osmolarity, changes in serum sodium level correlated best with the VIPS edema index (Pearson's correlation, r = 0.46, p = 0.034). MMSE scores did not change from pre- to post-dialysis. CONCLUSIONS: We detected an increase in the VIPS edema index during hemodialysis that correlated with decreased serum osmolarity, mainly reflected by changes in serum sodium suggesting shifts in intracranial fluids.

Foramen oval permeable, un diagnóstico posible en manos del neurólogo. Descripción de caso / Patent Foramen Ovale, A Possible Diagnosis From The Neurologist. Case Report

Resumen Introducción: En pacientes con ictus isquémico criptogénico se ha descrito una alta prevalencia de alteraciones del septum auricular relacionadas con un riesgo aumentado de presentar recurrencia. Objetivo: Presentar la historia clínica de un paciente joven con antecedente de diabetes mellitus e ictus isquémico en el que no se demuestran alteraciones arteriales. A partir de la realización de un estudio de Doppler trasncraneal con test de burbujas se diagnostica un foramen oval permeable. Conclusión: En el paciente que describimos, la realización de un estudio de DTC como parte de la evaluación inicial ayudó a precisar la etiología. La demostración de un foramen ovale permeable tiene implicaciones en la prevención secundaria del ictus.

Abstract Introduction: A high prevalence of atrial septal defects is reported in patients with cryptogenic ischemic stroke, also related to an increase of the risk of recurrence. Objective: To report case of a young patient with a history of diabetes mellitus and ischemic stroke without arterial changes proven. A transcraneal Doppler study with a bubble test helped to diagnose a patent foramen ovale. Conclusion: As part of the initial evaluation of this patient, a TCD study has helped to clarify the stroke etiology. The demonstration of a patent foramen ovale has implications for the secondary prevention of stroke.

Clinical Validation of a Transcranial Doppler-Based Noninvasive Intracranial Pressure Meter: A Prospective Cross-Sectional Study.

BACKGROUND: Noninvasive intracranial pressure (ICP) measurement would represent a major advance for patients with neurological problems. The Vittamed ICP meter is an ultrasound-based device reported to have high agreement with lumbar puncture cerebrospinal fluid (CSF) pressure measurement. However, previous studies included mostly patients with normal levels of ICP. The purpose of our study was to perform an independent clinical validation study of a transcranial Doppler-based noninvasive ICP meter in patients anticipated to have a wide range of ICP. METHODS: In a prospective cross-sectional design, we simultaneously measured ICP with the Vittamed device and the invasive lumbar CSF pressure. The operator of each procedure was blinded to the result of the other method. Data were analyzed using Bland-Altman plots, Pearson correlation coefficients, and receiver operator characteristic curves. RESULTS: Twenty-four independent paired measurements of Vittamed and lumbar CSF pressure were obtained; with mean absolute difference between paired measures of 4.5 mmHg (standard deviation 3.1). The 95% limits of agreement were -10.5 to +11.0. The systematic bias (mean of paired differences) was negligible at 0.25 mmHg. The sensitivity, specificity, and area under the curve for ICP >20 mmHg were 0.73, 0.77, and 0.71, respectively. CONCLUSIONS: The Vittamed ICP meter had fair agreement with lumbar CSF pressure measurement. The wide limits of agreement would preclude using this version of the device as a stand-alone method for ICP determination, but may be useful if combined with other ICP screening methods. Ongoing improvements to the Vittamed hardware and software may lead to improvements in accuracy and clinical utility of this device.

Update in the management of acute ischemic stroke.

Acute ischemic stroke is the fourth leading cause of death and the leading cause of disability in the United States. Stroke is a medical emergency. The development of stroke systems of care has changed the way practitioners view and treat this devastating disease. Ample evidence has shown that patients presenting early and receiving intravenous thrombolytic therapy have the best chance for significant improvement in functional outcome, particularly if they are transported to specialized stroke centers. Early detection and management of medical and neurologic complications is key at preventing further brain damage in patients with acute ischemic stroke.