Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice.

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox-Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs. METHODS: A multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed. RESULTS: Eighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1-70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent. CONCLUSION: This is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

Comparing the COVID-19 Responses in Cuba and the United States.

The purpose of this analytic essay is to contrast the COVID-19 responses in Cuba and the United States, and to understand the differences in outcomes between the 2 nations. With fundamental differences in health systems structure and organization, as well as in political philosophy and culture, it is not surprising that there are major differences in outcomes. The more coordinated, comprehensive response to COVID-19 in Cuba has resulted in significantly better outcomes compared with the United States. Through July 15, 2021, the US cumulative case rate is more than 4 times higher than Cuba's, while the death rate and excess death rate are both approximately 12 times higher in the United States. In addition to the large differences in cumulative case and death rates between United States and Cuba, the COVID-19 pandemic has unmasked serious underlying health inequities in the United States. The vaccine rollout presents its own set of challenges for both countries, and future studies can examine the comparative successes to identify effective strategies for distribution and administration. (Am J Public Health. 2021;111(12):2186-2193. https://doi.org/10.2105/AJPH.2021.306526).

Equity and the Cuban National Health System's response to COVID-19.

Cuba's National Health System has managed to guarantee an effective and equitable response to COVID-19. Universal and free health coverage, based on primary care, follows the principle of equity and the greatest resources are allocated to areas of the lowest socioeconomic stratum (where higher risk is concentrated), followed by those of medium and high strata, in that order. This allowed for similar mortality rates in the three strata, and Cuban national mortality rate was one of the lowest in the Region of the Americas. Before the first case was identified in Cuba, a Plan for Coronavirus Prevention and Control was elaborated with multisectoral participation, and when the first case was confirmed the Temporary National Working Group to Fight COVID-19 was created as an advisory body of the government. The actions to face the pandemic began with preventive measures in the community, continued in the isolation centers and ended again in the community with actions of surveillance and follow up of recovered patients. Following the principle of territoriality, molecular diagnosis laboratories were created in the provinces that did not have one. Free medical care and treatment; the preparation of a single national intersectoral government plan; the use of particular strategies for research, diagnosis and case tracing; and the implementation of a universal protocol for disease prevention and treatment of confirmed cases made it possible to control the disease with a health equity perspective.

El Sistema Nacional de Salud de Cuba ha logrado garantizar una respuesta eficaz y con equidad en el enfrentamiento a la COVID-19. La cobertura de salud universal y gratuita, basada en la atención primaria, sigue el principio de equidad, por lo que los mayores recursos se asignan a los territorios del estrato socioeconómico más bajo, que concentra mayores riesgos de salud, seguidos de los de estratos medio y alto, en ese orden. Esto permitió tener tasas de letalidad similares en los tres estratos, y a nivel nacional la de Cuba es una de las tasas más bajas de la Región de las Américas. Antes de identificar el primer caso en Cuba, se elaboró el Plan para la Prevención y Control del Coronavirus, con participación multisectorial, y al confirmarse el primer caso se creó el Grupo Temporal de Trabajo para Enfrentar la COVID-19 como órgano asesor del Gobierno. Las acciones de enfrentamiento a la pandemia comienzan en la comunidad con medidas preventivas, continúan en los centros de aislamiento y terminan nuevamente en la comunidad, con acciones de vigilancia y acompañamiento a los enfermos recuperados. Siguiendo el principio de territorialidad, se crearon laboratorios de diagnóstico molecular en las provincias que no lo tenían. La atención médica y los tratamientos gratuitos; la preparación de un plan de gobierno intersectorial nacional único; la utilización de estrategias particulares para la pesquisa, diagnóstico y rastreo de casos; y la implementación de un protocolo universal para la prevención de la enfermedad y el tratamiento de los casos confirmados permitieron el control de la enfermedad con una perspectiva de equidad en salud.

O Sistema Nacional de Saúde de Cuba tem assegurado uma resposta eficaz e com equidade ao enfrentar a pandemia de COVID-19. A cobertura de saúde universal e gratuita baseada na atenção primária se pauta no princípio da equidade. Mais recursos são destinados às áreas de nível socioeconômico mais baixo que concentram risco de saúde maior e a seguir, nesta ordem, às áreas de nível socioeconômico médio e alto. Assim, a taxas de letalidade tem sido semelhante nos três níveis e a taxa nacional é uma das mais baixas da Região. Antes de o primeiro caso de COVID-19 ter sido detectado em Cuba, preparou-se o Plano para prevenção e controle do coronavírus com participação multissetorial. Quando o primeiro caso da doença foi confirmado, instituiu-se o Grupo de trabalho temporário para combater a COVID-19 como um órgão assessor do governo. As ações de combate à pandemia começam na comunidade com medidas preventivas, prosseguem nos centros de isolamento e retornam à comunidade com medidas de vigilância sanitária e o acompanhamento dos pacientes recuperados. E, seguindo o princípio de territorialidade, laboratórios de diagnóstico molecular foram instituídos nas províncias onde eles inexistiam. A atenção médica, o tratamento gratuito, a preparação de um plano de governo único intersetorial nacional, o emprego de estratégias próprias para pesquisa, diagnóstico e rastreio de casos e a implementação de um protocolo universal para prevenção da doença e tratamento dos casos confirmados possibilitaram controlar a doença de uma perspectiva de equidade em saúde.

Consensus statement for the management of generalized tonic-clonic seizures in Spain.

OBJECTIVE: To develop recommendations for the management of patients with primary or secondary generalized tonic-clonic seizures (GTCS) based on best evidence and experience. METHODS: The Delphi methodology was followed. A multidisciplinary panel of 10 experts was established, who defined the scope, users and preliminary recommendations. Systematic and narrative reviews of the current literature were performed to assess data on the risk of sudden unexpected death in epilepsy and the efficacy and safety of add-on therapy in patients with GTCS. Twenty-five definitive recommendations were generated which were then graded on a scale of 1 (totally disagree) to 10 (totally agree) by the experts and 45 neurologists. Consensus was reached if at least 70% of the participants applied a score of ≥7. Each recommendation was then assigned a level of evidence, a grade of agreement and a grade of recommendation. The entire process was supervised by an expert methodologist. RESULTS: Overall, 24 out of 25 recommendations achieved consensus. These included specific recommendations on diagnosis, evaluation and treatment. The recommendations also emphasized the importance of proper psychological evaluation and effective communication between patients and health professionals, and the importance of patient and family education and support. SIGNIFICANCE: The recommendations generated by this consensus can be used as a guide for the diagnosis and management of patients with GTCS.

[Equity and the Cuban National Health System's response to COVID-19Equidade e resposta do Sistema Nacional de Saúde de Cuba à pandemia de COVID-19]. / Equidad y respuesta del Sistema Nacional de Salud de Cuba ante la COVID-19.

Cuba's National Health System has managed to guarantee an effective and equitable response to COVID-19. Universal and free health coverage, based on primary care, follows the principle of equity, and the greatest resources are allocated to areas of the lowest socioeconomic stratum (which concentrates the higher health risks), followed by those of medium and high strata, in that order. This allowed for similar mortality rates in the three strata, and Cuban national mortality rate was one of the lowest in the Region of the Americas. Before the first case was identified in Cuba, a Plan for Coronavirus Prevention and Control was elaborated with multisectoral participation, and when the first case was confirmed the Temporary Working Group to Fight COVID-19 was created as an advisory body of the government. The actions to face the pandemic began with preventive measures in the community, continued in the isolation centers and ended again in the community with actions of surveillance and follow up of recovered patients. Following the principle of territoriality, laboratories of molecular diagnosis were created in the provinces that did not have it. Free medical care and treatment; the preparation of a single national intersectoral government plan; the use of particular strategies for research, diagnosis and case tracing; and the implementation of a universal protocol for disease prevention and treatment of confirmed cases allowed to control the disease with a perspective of equity in health.

O Sistema Nacional de Saúde de Cuba tem assegurado uma resposta eficaz e com equidade ao enfrentar a pandemia de COVID-19. A cobertura de saúde universal e gratuita baseada na atenção primária se pauta no princípio da equidade. Mais recursos são destinados às áreas de nível socioeconômico mais baixo que concentram risco de saúde maior e a seguir, nesta ordem, às áreas de nível socioeconômico médio e alto. Assim, a taxas de letalidade tem sido semelhante nos três níveis e a taxa nacional é uma das mais baixas da Região. Antes de o primeiro caso de COVID-19 ter sido detectado em Cuba, preparou-se o Plano para prevenção e controle do coronavírus com participação multissetorial. Quando o primeiro caso da doença foi confirmado, instituiu-se o Grupo de trabalho temporário para combater a COVID-19 como um órgão assessor do governo. As ações de combate à pandemia começam na comunidade com medidas preventivas, prosseguem nos centros de isolamento e retornam à comunidade com medidas de vigilância sanitária e o acompanhamento dos pacientes recuperados. E, seguindo o princípio de territorialidade, laboratórios de diagnóstico molecular foram instituídos nas províncias onde eles inexistiam. A atenção médica, o tratamento gratuito, a preparação de um plano de governo único intersetorial nacional, o emprego de estratégias próprias para pesquisa, diagnóstico e rastreio de casos e a implementação de um protocolo universal para prevenção da doença e tratamento dos casos confirmados possibilitaram controlar a doença de uma perspectiva de equidade em saúde.

MONOZEB: Long-term observational study of eslicarbazepine acetate monotherapy.

AIM: The aim of the study was to evaluate the effectiveness and tolerability of eslicarbazepine acetate (ESL) when used as monotherapy for 1 year or more in routine clinical use in patients with focal seizures in epilepsy clinics in Spain. METHODS: This is a retrospective, observational, noninterventional study. Eligible patients were aged ≥18 years, had focal seizures, and started on ESL ≥1 year before database closure. Primary endpoint was the following: proportion seizure-free for ≥6 months at 1 and 2 years. Secondary endpoints included retention on ESL monotherapy at 1 and 2 years, seizure frequency change, seizure worsening, and side effects. Other analyses included seizure freedom from baseline to 1 and 2 years and outcomes in special populations. RESULTS: Four hundred thirty-five patients were included (127 on first-line monotherapy and 308 converting to ESL monotherapy): median daily dose was 800 mg at all time points; 63.2% were seizure-free at 1 year, 65.1% at 2 years, and 50.3% for the entire follow-up. Mean duration of ESL monotherapy was 66.7 months; retention was 88.0% at 1 year and 81.9% at 2 years. Mean reduction in seizure frequency was 75.5% at last visit. Over the entire follow-up, seizure worsening was seen in 22 patients (5.1%), side effects in 28.0%, considered severe in 1.8%, and leading to discontinuation in 5.7%. Dizziness, hyponatremia (sodium <135 mEq/l), and somnolence were the most frequent side effects. Outcomes in special populations (patients aged ≥65 years and those with psychiatric history or learning difficulty) were consistent with the overall population. CONCLUSIONS: Patients with focal seizures taking ESL monotherapy had excellent retention, high seizure-free rates, and good tolerability up to 2 years.

Antiepileptic drug treatment of generalized tonic-clonic seizures: An evaluation of regulatory data and five criteria for drug selection.

BACKGROUND: A generalized tonic-clonic seizure (GTCS) is the most severe form of common epileptic seizure and carries the greatest risk of harm. The aim of this review is to provide an evidence-based guide for the selection of antiepileptic drugs (AEDs) for patients with GTCSs. Eight AEDs are approved in Europe and the USA for the treatment of both primarily GTCSs (PGTCSs) and secondarily GTCSs (SGTCSs) and are considered in this paper. METHODS: Each AED is evaluated using five criteria: (1) efficacy, by seizure type (a: PGTCSs and b: SGTCSs); (2) adverse effects; (3) interactions; (4) adherence and dosing; and (5) mechanism of action (MOA). To ensure the inclusions of robust data, only efficacy data accepted by regulatory authorities were considered, and data related to adverse effects, interactions, adherence, and MOA were all extracted from UK Summaries of Product Characteristics (SPCs). RESULTS: (1a) There is class 1 evidence of the efficacy of only four AEDs in controlling PGTCSs (lamotrigine, levetiracetam, perampanel, and topiramate). (1b) There is no class 1 evidence of the efficacy of any AED in SGTCSs although some evidence from pooled/subgroup analyses or meta-analyses supports the use of the four AEDs (levetiracetam, perampanel, topiramate, and with less robust data for lamotrigine). (2) AEDs are associated with different, but to some extent overlapping, common adverse effect profiles but have differing idiosyncratic adverse effects. (3) Pharmacokinetic interactions are seen with most, but not all, AEDs and are most common with carbamazepine and phenytoin. (4) Good adherence is important for seizure control and is influenced by frequency of dosing, among other factors. (5) Mechanism of action is also a consideration in rationalising AED selection when switching or combining AEDs. CONCLUSION: Ultimately, the choice of AED depends on all these factors but particularly on efficacy and adverse effects. Different patients will weigh the various factors differently, and the role of the treating physician is to provide accurate information to allow patients to make informed choices.

[Transformations in the health system in Cuba and current strategies for its consolidation and sustainabilityTransformações no sistema de saúde em Cuba e estratégias atuais para sua consolidação e sustentabilidade]. / Transformaciones en el sistema de salud en Cuba y estrategias actuales para su consolidación y sostenibilidad.

In Cuba, universal access and health coverage rest on three key principles: health as a human right, equity and solidarity. Although many of the Cuban health indicators are among the best in the Region of the Americas, in 2011 it was decided to reorganize health services, in line with the process of updating the Cuban economic and social model that occurred in all sectors. For this purpose, an action-research project was designed, including a situation diagnosis, implementation of changes and evaluation of the results, in several stages. As a result, human resources were rationalized with a reduction of more than 150 000 posts not directly linked to patient care, management structures were reduced in 57 municipalities, 46 polyclinics were compacted, the Family Physician and Nurse Program was optimized with 20 specialties for the community care, teaching was reorganized, and the international medical cooperation programs were revisited. These changes have contributed to improving the sustaina-bility of the National Health System and its performance: increase in the number of consultations at the primary level (19.3%) and oral care visits (56.6%), reduction in the number of visits to emergency rooms (16.1%), increase in the number of patients surgically treated (12.1%), increase in the number of research projects (300%) and increase in the number of medical students (55.7%), among others. In Cuba, transformations in health is an ongoing project.

Em Cuba, o acesso universal e a cobertura de saúde dependem de três princípios fundamentais: a saúde como direito humano, equidade e solidariedade. Embora muitos dos indicadores de saúde cubanos estejam entre os melhores da Região das Americas, em 2011 foi decidido reorganizar os serviços de saúde, de acordo com o processo de atualização do modelo econômico e social cubano ocorrido em todos os setores do país. Para o efeito, foi elaborado um projeto de pesquisa-ação, que incluiu o diagnóstico da situação, a implementação das mudanças e a avaliação dos resultados, em várias etapas. Como resultado, os recursos humanos foram racionalizados com uma redução de mais de 150 000 postos não diretamente ligados ao atendimento ao paciente, as estruturas de manejo foram reduzidas em 57 municípios, 46 policlínicas foram compactadas, o Programa Médico e Enfermeiro da Familia foi otimizado com a projeção para a comunidade de 20 especialidades, o ensino foi reorganizado, e os programas internacionais de cooperação médica foram reordenados. Essas mudanças contribuíram para melhorar a sustentabilidade do Sistema Nacional de Saúde e seu desempenho: aumento do número de consultas no nível primário (19,3%) e odontologia (56,6%), redução do número de consultas na emergência (16,1%), aumento do número de pacientes tratados cirurgicamente (12,1%), aumento do número de projetos de pesquisa (300%) e crescimento do número de estudantes de medicina (55,7%), entre outros. O projeto de transformação em saúde realizado em Cuba continua.

Efficacy and safety of eslicarbazepine acetate monotherapy for partial-onset seizures: Experience from a multicenter, observational study.

Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9-87years) enrolled in the study and were treated with ESL at either 400mg/day (3.4% patients), 800mg/day (61% patients), 1200mg/day (27.1% patients) or 1600mg/day (8.5% patients). At 3months, 82.0% (n=72) of patients achieved a ≥50% reduction in seizure frequency, compared to 79.7% (n=67) of patients at 6months and 83.0% (n=49) at 12months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n=27), 69.6% (n=29), and 72.7% (n=16) at 3, 6, and 12months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n=9), somnolence (n=3), mild hyponatremia (n=3), headache (n=1), hypertriglyceridemia (n=1), and allergic reaction (n=1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects.

Role of Citicoline in Patients With Mild Cognitive Impairment.

The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders. Citicoline is a pharmaceutical product constituted by the combination of 2 natural molecules (cytidine and choline) and is marketed as a food supplement. It has been proposed to provide neuroprotective effects through diverse mechanisms of action. Taking into account the available literature, citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin. Moreover, it provides beneficial effects on vascular, Alzheimer, and mixed dementias, stroke sequelae, intracerebral hemorrhages, traumatic brain injuries, and neurodegenerative diseases. Long-term treatment with citicoline has also been demonstrated to be well-tolerated and has not been associated with severe adverse events. Citicoline is a safe, well-tolerated, and promising agent with evidenced neuroprotective properties.

Immediate effects and duration of a short and single application of transcutaneous auricular vagus nerve stimulation on P300 event related potential.

Introduction: Transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique that stimulates the auricular branch of the vagus nerve. The modulation of the locus coeruleus-norepinephrine (LC-NE) network is one of the potential working mechanisms of this method. Our aims were 1-to investigate if short and single applications of taVNS can modulate the P300 cognitive event-related potential (ERP) as an indirect marker that reflects NE brain activation under control of the LC, and 2-to evaluate the duration of these changes. Methods: 20 healthy volunteers executed an auditory oddball paradigm to obtain P300 and reaction time (RT) values. Then a 7 min active or sham taVNS period was initiated and simultaneously a new P300 paradigm was performed. We successively repeated the paradigm on 4 occasions with different time intervals up to 56 min after the stimulation onset. Results: During active taVNS an immediate and significant effect of increasing the amplitude and reducing the latency of P300, as well as a shortening in the RT was observed. This effect was prolonged in time up to 28 min. The values then returned to pre-stimulation levels. Sham stimulation did not generate changes. Discussion: Our results, demonstrate differential facilitating effects in a concrete time window after taVNS. Literature about the modulatory effect of taVNS over P300 ERP shows a wide spread of results. There is not a standardized system for taVNS and currently the great heterogeneity of stimulation approaches concerning targets and parameters, make it difficult to obtain conclusions about this relationship. Our study was designed optimizing several stimulation settings, such as a customized earbud stimulator, enlarged stimulating surface, simultaneous stimulation over the cymba and cavum conchae, a Delayed Biphasic Pulse Burst and current controlled stimulation that adjusted the output voltage and guaranteed the administration of a preset electrical dose. Under our stimulation conditions, targeting vagal nerve fibers via taVNS modulates the P300 in healthy participants. The optimal settings of modulatory function of taVNS on P300, and their interdependency is insufficiently studied in the literature, but our data provides several easily optimizable parameters, that will produce more robust results in future.

A multivariate spatio-temporal model for the incidence of imported COVID-19 cases and COVID-19 deaths in Cuba.

To monitor the COVID-19 epidemic in Cuba, data on several epidemiological indicators have been collected on a daily basis for each municipality. Studying the spatio-temporal dynamics in these indicators, and how they behave similarly, can help us better understand how COVID-19 spread across Cuba. Therefore, spatio-temporal models can be used to analyze these indicators. Univariate spatio-temporal models have been thoroughly studied, but when interest lies in studying the association between multiple outcomes, a joint model that allows for association between the spatial and temporal patterns is necessary. The purpose of our study was to develop a multivariate spatio-temporal model to study the association between the weekly number of COVID-19 deaths and the weekly number of imported COVID-19 cases in Cuba during 2021. To allow for correlation between the spatial patterns, a multivariate conditional autoregressive prior (MCAR) was used. Correlation between the temporal patterns was taken into account by using two approaches; either a multivariate random walk prior was used or a multivariate conditional autoregressive prior (MCAR) was used. All models were fitted within a Bayesian framework.

Correction to "Cuban Abdala vaccine: Effectiveness in preventing severe disease and death from COVID-19 in Havana, Cuba; A cohort study" [The Lancet Regional Health - Americas 2022; 16: 100366] https://doi.org/10.1016/j.lana.2022.100366.

[This corrects the article DOI: 10.1016/j.lana.2022.100366.].

Use of the Ultrasound Technique as Compared to the Standard Technique for the Improvement of Venous Cannulation in Patients with Difficult Access.

(1) Objective. We aimed to demonstrate that the use of the ultrasound-guided technique facilitates peripheral venous cannulation as compared to the standard technique in patients with difficult access at emergency services. (2) Method. A case-control study, randomized research. Variables were collected from a population with non-palpable or not visible veins, classified into size risk groups for 6 months. In the comparative analysis, the patients were divided into two groups: the cases group was composed of patients to whom the peripheral venous cannulation was performed with the ultrasound-guided technique (UST), while the control was composed of patients with whom the standard technique (ST) was performed. The ultrasound LOGIQ P5 750VA from General Electric Healthcare, with an 11 mHz linear probe, was utilized, along with peripheral venous catheters model InsyteTM AutoguardTM with gauges of 14G to 26G. (3) Results. Seventy-two cases. The use of the ultrasound decreased the time (618.34s ST, 126s UST) and the number of punctures (2.92 ST, 1.23 UST); about 25% of the patients did not have complications with the UST, as compared to 8% with the ST. The use of the ultrasound decreased the pain experienced by 1.44 points in the visual analog scale, as compared to 0.11 points with the ST. The rate of success of the first try with the UST was 76%, as compared to 16% of the ST. The gauge of the catheter increased with the UST, with successful cannulations obtained with 20G (56%) and 18G (41%) gauges. (4) Conclusions. The use of ultrasound facilitates venous cannulation according to the variables of the study. The ultrasound visualization of the vessels is associated with the selection of the catheter gauge. There was no relation between the complications and the depth of the blood vessels.

Cuban Abdala vaccine: Effectiveness in preventing severe disease and death from COVID-19 in Havana, Cuba; A cohort study.

Background: COVID-19 vaccines have proven safe and efficacious in reducing severe illness and death. Cuban protein subunit vaccine Abdala has shown safety, tolerability and efficacy (92·3% [95% CI: 85·7‒95·8]) against SARS-CoV-2 in clinical trials. This study aimed to estimate Abdala's real-world vaccine effectiveness (VE). Methods: This retrospective cohort study in Havana analyzed Cuban Ministry of Public Health databases (May 12-August 31, 2021) to assess VE in preventing severe illness and death from COVID-19 (primary outcomes). Cox models accounting for time-varying vaccination status and adjusting by demographics were used to estimate hazard ratios. A subgroup analysis by age group and a sensitivity analysis including a subgroup of tested persons (qRT-PCR) were conducted. Daily cases and deaths were modelled accounting for different VE. Findings: The study included 1 355 638 persons (Mean age: 49·5 years [SD: 18·2]; 704 932 female [52·0%]; ethnicity data unavailable): 1 324 vaccinated (partially/fully) and 31 433 unvaccinated. Estimated VE against severe illness was 93·3% (95% CI: 92·1-94·3) in partially- vaccinated and 98·2% (95% CI: 97·9-98·5) in fully-vaccinated and against death was 94·1% (95% CI: 92·5-95·4) in partially-vaccinated and 98·7% (95% CI: 98·3-99·0) in fully-vaccinated. VE exceeded 92·0% in all age groups. Daily cases and deaths during the study period corresponded to a VE above 90%, as predicted by models. Interpretation: The Cuban Abdala protein subunit vaccine was highly effective in preventing severe illness and death from COVID-19 under real-life conditions. Funding: Cuban Ministry of Public Health. Genetic Engineering and Biotechnology Centre.

Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses.

BACKGROUND: Electrical auricular vagus nerve stimulation (taVNS) is an emerging therapy. Stimuli are transported to brainstem nuclei, whereby its multiple projections reach to many subcortical and cortical areas, thus allowing the neuromodulation of several systemic physiological processes. We aim to define the best auricular target for taVNS through vagus somatosensory evoked potential (VSEP) elicited stimulating different auricular areas with different electrode sizes. METHODS: Twenty-six subjects were enrolled. Three stimulation areas were studied: simultaneous cymba and cavum (CC), cymba (C) and earlobe (L); and two electrode sizes: extra-large (X) and small (S). We studied the effect of five combinations (CCX, CCS, CS, LX and LS) on VSEP´s latency and amplitude, and sensory and pain threshold (Pt) using a lineal mixed model regression analysis. We used CS combination, used in a commercial device, as reference model. RESULTS: Valid VSEP were obtained for CCX, CCS and CS but not in LX and LS. Both CCS and CCX tests showed significant amplitude increases. The same effect was observed in CCX using CCS as reference. Significant increases in Pt were found for CCX and LX. The same effect was observed in CCX using LX as reference. CONCLUSION: The results suggest that CC and C areas are active targets for taVNS but not for earlobe, as anatomical data support. Considering that amplitude reflects the synchronized electrical activity generated, we conclude the most effective topography is the simultaneous stimulation of cymba and concha. The use of X-sized electrodes increases the amplitudes and makes the stimulation more comfortable.

COVID-19 in Cuba: Assessing the National Response.

The COVID-19 pandemic exhibits different characteristics in each country, related to the extent of SARS-CoV-2 local transmission, as well as the speed and effectiveness of epidemic response implemented by authorities. This study presents a descriptive epidemiological analysis of the daily and cumulative incidence of confi rmed cases and deaths in Cuba from COVID-19 in the fi rst 110 days after fi rst-case confi rmation on March 11, 2020. During this period, 2340 cases (20.7 x 100,000 population) were confi rmed, of which 86 patients died (case fatality 3.67%; 52 men and 34 women). Mean age of the deceased was 73.6 years (with a minimum of 35 years and a maximum of 101), with the average age of men lower than that of women. More than 70% of all deceased had associated noncommunicable diseases. The incidence curve ascended for fi ve weeks and then descended steadily. The average number of confi rmed cases and deaths for the last week included (June 23-28, 2020) were 25 and 1 respectively; the curve always moved within the most favorable forecast zone of available mathematical models and the effective reproductive number fell below 1 after the fi fth week following the onset of the epidemic.

Variation in almotriptan effectiveness according to different prophylactic treatments.

OBJECTIVE: To evaluate the effect of different migraine prophylaxis medications on subject responsiveness to almotriptan. BACKGROUND: There is evidence supporting an increase of responsiveness of symptomatic medications for migraine attacks by some prophylactic treatments although this has not been probed. METHODS: A total of 345 patients (230 women, mean age 37.3) with episodic or chronic migraine were classified according to the prophylaxis they were taking in the following groups: (1) no prophylactic medication; (2) propranolol; (3) topiramate; (4) flunarizine. Decrease in Analogical Visual Scale and pain-free at 2 hours after almotriptan intake was assessed at 2 months. Side effects and discontinuation or treatment were also assessed. RESULTS: Headache severity was reduced 4.2 in control group, 5.3 in propranolol group, 4.1 in topiramate group, and 4.0 in flunarizine group, whereas pain-free status was achieved in 37.3%, 48.7%, 36.1%, and 38.1% respectively. These two parameters were statistically significative between propranolol and control groups. Side effects were similar in all groups. CONCLUSIONS: Our results displayed a higher efficacy of almotriptan in propranolol group and we hypothesized it may be due to a common mechanism of action at serotoninergic receptors.