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The experience of the COVID-19 pandemic showed the importance of timely monitoring of admissions to the ICU admissions. The ability to promptly forecast the epidemic impact on the occupancy of beds in the ICU is a key issue for adequate management of the health care system.Despite this, most of the literature on predictive COVID-19 models in Italy has focused on predicting the number of infections, leaving trends in ordinary hospitalizations and ICU occupancies in the background.This work aims to present an ETS approach (Exponential Smoothing Time Series) time series forecasting tool for admissions to the ICU admissions based on ETS models. The results of the forecasting model are presented for the regions most affected by the epidemic, such as Veneto, Lombardy, Emilia-Romagna, and Piedmont.The mean absolute percentage errors (MAPE) between observed and predicted admissions to the ICU admissions remain lower than 11% for all considered geographical areas.In this epidemiological context, the proposed ETS forecasting model could be suitable to monitor, in a timely manner, the impact of COVID-19 disease on the health care system, not only during the early stages of the pandemic but also during the vaccination campaign, to quickly adapt possible preventive interventions.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , SARS-CoV-2 , Hospitalização , Unidades de Terapia Intensiva , Itália/epidemiologiaRESUMO
We report on the automatic alignment of a transmission electron microscope equipped with an orbital angular momentum sorter using a convolutional neural network. The neural network is able to control all relevant parameters of both the electron-optical setup of the microscope and the external voltage source of the sorter without input from the user. It can compensate for mechanical and optical misalignments of the sorter, in order to optimize its spectral resolution. The alignment is completed over a few frames and can be kept stable by making use of the fast fitting time of the neural network.
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The component of orbital angular momentum (OAM) in the propagation direction is one of the fundamental quantities of an electron wave function that describes its rotational symmetry and spatial chirality. Here, we demonstrate experimentally an electrostatic sorter that can be used to analyze the OAM states of electron beams in a transmission electron microscope. The device achieves postselection or sorting of OAM states after electron-material interactions, thereby allowing the study of new material properties such as the magnetic states of atoms. The required electron-optical configuration is achieved by using microelectromechanical systems technology and focused ion beam milling to control the electron phase electrostatically with a lateral resolution of 50 nm. An OAM resolution of 1.5â is realized in tests on controlled electron vortex beams, with the perspective of reaching an optimal OAM resolution of 1â in the near future.
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BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.
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COVID-19/mortalidade , Respiração Artificial , Síndrome do Desconforto Respiratório/mortalidade , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Intubação , Itália , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/virologia , Volume de Ventilação PulmonarAssuntos
Betacoronavirus , Redes Comunitárias/normas , Infecções por Coronavirus/epidemiologia , Surtos de Doenças/prevenção & controle , Número de Leitos em Hospital/normas , Unidades de Terapia Intensiva/normas , Pneumonia Viral/epidemiologia , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Humanos , Itália/epidemiologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , SARS-CoV-2RESUMO
BACKGROUND: Since 2010 Veneto region (North-Eastern Italy) planned a special integrated surveillance of summer fevers to promptly identify cases of West Nile Fever (WNF), dengue (DENV) and chikungunya (CHIKV). The objectives of this study were (i) To increase the detection rate of imported CHIKV and DENV cases in travellers from endemic areas and promptly identify potential autochthonous cases.(ii) To detect autochthonous cases of WNF, besides those of West Nile Neuroinvasive Disease (WNND) that were already included in a national surveillance. METHODS: Human surveillance: a traveler who had returned within the previous 15 days from endemic countries, with fever >38°C, absence of leucocytosis (leukocyte count <10,000 µL), and absence of other obvious causes of fever, after ruling out malaria, was considered a possible case of CHIKV or DENV. A possible autochthonous case of WNF was defined as a patient with fever >38°C for <7 days, no recent travel history and absence of other obvious causes of fever. Entomologic surveillance: for West Nile (WNV) it was carried out from May through November placing CDC-CO2 traps in five provinces of Veneto Region, while for DENV and CHIKV it was also performed around residences of viremic cases. RESULTS: Human surveillance: between 2010 and 2012, 234 patients with fever after travelling were screened, of which 27 (11,5%) were found infected (24 with DENV and 3 with CHIKV). No autochthonous case of DENV or CHIKV was detected. Autochthonous patients screened for WNF were 408, and 24 (5,9%) were confirmed cases. Entomologic surveillance: the WNV was found in 10, 2 and 11 pools of Culex pipiens from 2010 to 2012 respectively, in sites of Rovigo, Verona, Venezia and Treviso provinces). No infected Aedes albopictus with DENV or CHIKV was found. CONCLUSIONS: Veneto is the only Italian region reporting WNV human cases every year since 2008. WNV is likely to cause sporadic cases and unforeseeable outbreaks for decades. Including WNF in surveillance provides additional information and possibly an early alert system. Timely detection of DENV and CHIKV should prompt vector control measures to prevent local outbreaks.
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Infecções por Alphavirus/epidemiologia , Culicidae/classificação , Dengue/epidemiologia , Monitoramento Epidemiológico , Insetos Vetores/virologia , Febre do Nilo Ocidental/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Alphavirus/virologia , Animais , Febre de Chikungunya , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Culicidae/virologia , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Feminino , Doenças dos Cavalos/epidemiologia , Cavalos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Viagem , Febre do Nilo Ocidental/veterinária , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/genética , Vírus do Nilo Ocidental/isolamento & purificação , Adulto JovemRESUMO
BACKGROUND: Despite early cardiopulmonary resuscitation (CPR) by bystanders and early advanced cardiac life support (ACLS) maneuvers, some patients present to the emergency department with persistent cardiac arrest caused by a coronary artery occlusion. Although emergency percutaneous intervention (PCI) has been shown to be effective in improving survival, transporting patients in cardiac arrest to the hospital is not considered to be effective, due to the poor quality of CPR in the ambulance. In the case reported here, a mechanical chest compression device was used while transporting the patient by helicopter emergency medical services (HEMS). CASE REPORT: A mechanical chest compression device was used to deliver chest compressions to a 53-year-old man in cardiac arrest. This device permitted the transfer of the patient by HEMS helicopter to the catheterization laboratory facility for a PCI. Return of spontaneous circulation was achieved 115 min after cardiac arrest and the patient survived without any neurological deficit. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The mechanical chest compression device has permitted safe and effective CPR during helicopter transportation. Although this is only a single case, it may present a new perspective for the treatment of prehospital cardiac arrest that is refractory to ACLS therapies.
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Resgate Aéreo , Reanimação Cardiopulmonar/métodos , Massagem Cardíaca/instrumentação , Parada Cardíaca Extra-Hospitalar/terapia , Intervenção Coronária Percutânea , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do TratamentoRESUMO
The following article presents the relevant and unprecedented bioethical and biolaw issues posed by the SARS-COV-2 pandemic and summarizes the initiatives adopted by the Italian Society of Anesthesia and Resuscitation (SIAARTI) as well as by the Veneto Region ICU Network. Since the initial phase of the pandemic, in March 2020, there has been a strong appeal from both SIAARTI and the Veneto Region ICU Network to consider "the appropriate intensive treatment." During the pandemic, the principle of proportionality must be applied, in compliance with the main principle in bioethics. This encompasses the concept of clinical appropriateness, based on the efficacy of the treatment in specific case and context, as well as the concept of ethical appropriateness, which refers to ethical and juridical principles of acceptance of health care. The "appropriate treatment" must never interfere with the withdrawal of patients, who are not eligible for intensive treatments since they would not benefit from them and who are eligible for ordinary treatments that must be maintained, and, where necessary, palliative treatments were initiated. On the other hand, it must not encroach on unreasonable obstinacy. At the end of 2020, the SIAARTI-SIMLA (Italian Society of Insurance and Legal Medicine) document provides healthcare professionals with a tool for responding appropriately to the emergency of the pandemic, in the event of an imbalance between healthcare demand and available resources. The document states that the ICU triage should be based on global evaluation of each patient, taking into account well-defined parameters and stresses that each person potentially eligible for intensive care should have a shared care planning (SCP) stipulated, and, when necessary, a proxy should be nominated. This has illustrated how the biolaw issues encountered by intensivists during the pandemic, such as those relating to consent and refusal to medical treatment, even when it is lifesaving, as well as requests for treatment of unproven clinical efficacy, were subject to appropriate guidelines and solutions through the application of Law 219/2017 (provisions for informed consent and advance directives treatment). Communication with family members and the management of sensitive personal data; the evaluation of "legal capacity" of comprehension and informed decision-making regarding the proposed treatment plan; and the need for emergency medical intervention in the absence of consent are all addressed in light of the relevant regulations and the particular conditions of social isolation induced by the pandemic. The collaborative ICUs network sustained by the Veneto Region has given great prominence to clinical bioethics issues, and as a result, multidisciplinary integration with the help of legal and juridical experts was developed. This has led to an increase in skills in the bioethical field, as well as providing a valuable lesson for the improvement of therapeutic relationships with critically ill patients and their families.
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The best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV ("straight intubation"). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the "straight intubation" group and the "NIV" group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation.
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The orbital angular momentum (OAM) sorter is an electron optical device for the measurement of an electron's OAM. It is based on two phase elements, which are referred to as an "unwrapper" and a "corrector" and are located in Fourier conjugate planes. The simplest implementation of the sorter is based on electrostatic phase elements, such as a charged needle for the unwrapper and electrodes with alternating charges or potentials for the corrector. Here, we use a formal analogy between phase shifts introduced by charges and vertical currents to propose alternative designs for the sorter elements, which are based on phase shifts introduced by magnetic fields. We use this concept to provide a general guide for phase element design, which promises to provide improved reliability of phase control in electron optics.
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Canine atopic dermatitis (CAD) is a pruritic allergic skin disease associated with IgE-mediated hypersensitivity. IgE is detected using Serum Allergen-Specific IgE test (SAT) in order to identify allergens. The present study aims to identify the environmental allergens in atopic dogs living in Northern Italy using SAT. The screening SAT (sSAT), using a monoclonal antibody cocktail-based ELISA to identify indoor and outdoor allergens, was performed. In all positive samples, an anti-IgE monoclonal antibody ELISA test was performed to extend panel of allergens. Out of 117 selected dogs, 69 were included in the study; 71% were positive and 29% were negative to sSAT. Among the 49 positive sSAT, 53% were positive for both indoor and outdoor, 38.8% only for indoor, and 8.2% only for outdoor allergens. This is the first study on the frequency of allergens involved in CAD in Italy using SAT. IgE hypersensitivity in atopic dogs of Northern Italy is usually associated with indoor allergens, primarily house dust mites. Among the outdoor allergens, an important role was played by Rumex acetosa. Polysensitization also commonly occurs. Therefore, since the numerous factors affect the IgE positivity in CAD, specific panels for geographical areas should be considered and re-evaluated at time intervals.
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Sierra Leone is one of the least developed low-income countries (LICs), slowly recovering from the effects of a devastating civil war and an Ebola outbreak. The health care system is characterized by chronic shortage of skilled human resources, equipment, and essential medicines. The referral system is weak and vulnerable, with 75% of the country having insufficient access to essential health care. Consequently, Sierra Leone has the highest maternal and child mortality rates in the world. This manuscript describes the implementation of a National Emergency Medical Service (NEMS), a project aiming to create the first prehospital emergency medical system in the country. In 2017, a joint venture of Doctors with Africa (CUAMM), Veneto Region, and Research Center in Emergency and Disaster Medicine (CRIMEDIM) was developed to support the Ministry of Health and Sanitation (MOHS) in designing and managing the NEMS system, one of the very few structured, fully equipped, and free-of-charge prehospital service in the African continent. The NEMS design was the result of an in-depth research phase that included a preliminary assessment, literature review, and consultations with key stakeholders and managers of similar systems in other African countries. From May 27, 2019, after a timeframe of six months in which all the districts have been progressively trained and made operational, the NEMS became operative at national level. By the end of March 2020, the NEMS operation center (OC) and the 81 ambulances dispatched on the ground handled a total number of 36,814 emergency calls, 35,493 missions, and 31,036 referrals.
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Serviços Médicos de Emergência , Doença pelo Vírus Ebola , Criança , Atenção à Saúde , Surtos de Doenças , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Humanos , Serra Leoa/epidemiologiaRESUMO
INTRODUCTION: Sierra Leone, one of the countries with the highest maternal and perinatal mortality in the world, launched its first National Emergency Medical Service (NEMS) in 2018. We carried out a countrywide assessment to analyse NEMS operational times for obstetric emergencies in respect the access to timely essential surgery within 2 hours. Moreover, we evaluated the relationship between operational times and maternal and perinatal mortality. METHODS: We collected prehospital data of 6387 obstetric emergencies referrals from primary health units to hospital facilities between June 2019 and May 2020 and we estimated the proportion of referrals with a prehospital time (PT) within 2 hours. The association between PT and mortality was investigated using Poisson regression models for binary data. RESULTS: At the national level, the proportion of emergency obstetric referrals with a PT within 2 hours was 58.5% (95% CI 56.9% to 60.1%) during the rainy season and 61.4% (95% CI 59.5% to 63.2%) during the dry season. Results were substantially different between districts, with the capital city of Freetown reporting more than 90% of referrals within the benchmark and some rural districts less than 40%. Risk of maternal death at 60, 120 and 180 min of PT was 1.8%, 3.8% and 4.3%, respectively. Corresponding figures for perinatal mortality were 16%, 18% and 25%. CONCLUSION: NEMS operational times for obstetric emergencies in Sierra Leone vary greatly and referral transports in rural areas struggle to reach essential surgery within 2 hours. Maternal and perinatal risk of death increased concurrently with operational times, even beyond the 2-hour target, therefore, any reduction of the time to reach the hospital, may translate into improved patient outcomes.
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Ambulâncias , Serviços Médicos de Emergência , Feminino , Humanos , Gravidez , Encaminhamento e Consulta , População Rural , Serra Leoa/epidemiologiaRESUMO
We aim to evaluate whether the first National Emergency Medical Service (NEMS) improved access to hospital care for the people of Sierra Leone. We performed an interrupted time-series analysis to assess the effects of NEMS implementation on hospital admissions in 25 facilities. The analysis was also replicated separately for the area of Freetown and the rest of the country. The study population was stratified by the main Free Health Care Initiative (FHCI) categories of pregnant women, children under 5 years of age, and populations excluded from the FHCI. Finally, we calculated direct costs of the service. We report a 43% overall increase in hospital admissions immediately after NEMS inception (RR 1.43; 95% CI 1.2-1.61). Analyses stratified by FHCI categories showed a significant increase among pregnant women (RR 1.54; 95% CI 1.33-1.77) and among individuals excluded from the FHCI (RR 2.95; 95% CI 2.47-3.53). The observed effect was mainly due to the impact of NEMS on the rural districts. The estimated recurrent cost per ambulance ride and NEMS yearly cost per inhabitant were 124 and 0.45 USD, respectively. To our knowledge, this is the first nationwide study documenting the increase in access to healthcare services following the implementation of an ambulance-based medical service in a low-income country. Based on our results, NEMS was able to overcome the existing barriers of geographical accessibility and transport availability, especially in the rural areas of Sierra Leone.
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Serviços Médicos de Emergência , Acessibilidade aos Serviços de Saúde , Criança , Pré-Escolar , Feminino , Serviços de Saúde , Humanos , Gravidez , População Rural , Serra LeoaRESUMO
The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality.
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COVID-19/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Intubação Intratraqueal/métodos , Ventilação não Invasiva/métodos , Insuficiência Respiratória/terapia , Idoso , COVID-19/complicações , COVID-19/virologia , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Insuficiência Respiratória/etiologia , Fatores de Risco , SARS-CoV-2/fisiologiaRESUMO
BACKGROUND: Since the beginning of coronavirus disease 2019 (COVID-19), the development of predictive models has sparked relevant interest due to the initial lack of knowledge about diagnosis, treatment, and prognosis. The present study aimed at developing a model, through a machine learning approach, to predict intensive care unit (ICU) mortality in COVID-19 patients based on predefined clinical parameters. RESULTS: Observational multicenter cohort study. All COVID-19 adult patients admitted to 25 ICUs belonging to the VENETO ICU network (February 28th 2020-april 4th 2021) were enrolled. Patients admitted to the ICUs before 4th March 2021 were used for model training ("training set"), while patients admitted after the 5th of March 2021 were used for external validation ("test set 1"). A further group of patients ("test set 2"), admitted to the ICU of IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, was used for external validation. A SuperLearner machine learning algorithm was applied for model development, and both internal and external validation was performed. Clinical variables available for the model were (i) age, gender, sequential organ failure assessment score, Charlson Comorbidity Index score (not adjusted for age), Palliative Performance Score; (ii) need of invasive mechanical ventilation, non-invasive mechanical ventilation, O2 therapy, vasoactive agents, extracorporeal membrane oxygenation, continuous venous-venous hemofiltration, tracheostomy, re-intubation, prone position during ICU stay; and (iii) re-admission in ICU. One thousand two hundred ninety-three (80%) patients were included in the "training set", while 124 (8%) and 199 (12%) patients were included in the "test set 1" and "test set 2," respectively. Three different predictive models were developed. Each model included different sets of clinical variables. The three models showed similar predictive performances, with a training balanced accuracy that ranged between 0.72 and 0.90, while the cross-validation performance ranged from 0.75 to 0.85. Age was the leading predictor for all the considered models. CONCLUSIONS: Our study provides a useful and reliable tool, through a machine learning approach, for predicting ICU mortality in COVID-19 patients. In all the estimated models, age was the variable showing the most important impact on mortality.
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This report describes the main adaptive and transformative changes adopted by the brand-new National Emergency Medical Service (NEMS) to face the novel coronavirus disease 2019 (COVID-19) in Sierra Leone, including ambulance re-distribution, improvements in communication flow, implementation of ad-hoc procedures and trainings, and budget re-allocation. In a time-span of four months, 1,170 COVID-19 cases have been handled by the NEMS through a parallel referral system, while efforts have been made to manage the routine emergencies of the country, causing a substantial intensification of daily activities.
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COVID-19/epidemiologia , Controle de Doenças Transmissíveis/organização & administração , Serviços Médicos de Emergência/organização & administração , Programas Governamentais , Humanos , Pandemias , SARS-CoV-2 , Serra Leoa/epidemiologiaRESUMO
The purpose of cardiopulmonary resuscitation after sudden cardiac arrest is to restore minimal blood flow to provide oxygen to the brain and other vital organs. Chest compressions and external defibrillation are the first line for circulatory support. Although early defibrillation is the main factor influencing survival, cardiopulmonary resuscitation must be characterized by high-quality external chest compressions. Unfortunately, the performance of manual chest compressions decreases during time and in hostile conditions. For these reasons, mechanical devices for chest compression are able to support rescuers during cardiopulmonary resuscitation. Commonly used mechanical chest compression devices in Europe include LUCAS and Autopulse. Routine utilization of mechanical chest compression devices cannot be recommended because randomized controlled trials, such as LINC and PARAMEDIC for LUCAS and CIRC for Autopulse, have not demonstrated their superiority compared with manual chest compressions. The aim of this review is to analyze recent data regarding utilization of mechanical chest compression devices, and to clarify advantages and limitations.