Economic evaluation of oral ivermectin, alone or in combination with permethrin, versus permethrin, in the treatment of classic scabies in the Philippine Setting

Background and Objective@#Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies.@*Methods@#We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty.@*Results@#Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve.@*Conclusion@#Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.

Inefficacious drugs against covid-19: analysis of sales, tweets, and search engines / Medicamentos ineficazes contra covid-19: análise de vendas, tweets e mecanismos de busca

ABSTRACT OBJECTIVE Assess the correlation between the sales of two drugs with no proven efficacy against covid-19, ivermectin and chloroquine, and other relevant variables, such as Google® searches, number of tweets related to these drugs, number of cases and deaths resulting from covid-19. METHODS The methodology adopted in this study has four stages: data collection, data processing, exploratory data analysis, and correlation analysis. Spearman's method was used to obtain cross-correlations between each pair of variables. RESULTS The results show similar behaviors between variables. Peaks occurred in the same or near periods. The exploratory data analysis showed shortage of chloroquine in the period corresponding to the beginning of advertising for the application of these drugs against covid-19. Both drugs showed a high and statistically significant correlation with the other variables. Also, some of them showed a higher correlation with drug sales when we employed a one-month lag. In the case of chloroquine, this was observed for the number of deaths. In the case of ivermectin, this was observed for the number of tweets, cases, and deaths. CONCLUSIONS The results contribute to decision making in crisis management by governments, industries, and stores. In times of crisis, as observed during the covid-19 pandemic, some variables can help sales forecasting, especially Google® and tweets, which provide a real-time analysis of the situation. Monitoring social media platforms and search engines would allow the determination of drug use by the population and better prediction of potential peaks in the demand for these drugs.

RESUMO OBJETIVO Investigar a correlação entre as vendas de dois medicamentos sem eficácia comprovada no tratamento de covid-19, ivermectina e cloroquina, e outras variáveis relevantes: pesquisas no Google®, número de tweets relacionados aos medicamentos, casos e óbitos decorrentes da covid-19. MÉTODOS A metodologia adotada neste estudo se divide em quatro partes: coleta de dados; processamento dos dados; análise exploratória; e análise de correlação. Foi utilizado o método de Spearman para obter as correlações cruzadas entre cada par de variáveis. RESULTADOS Os resultados mostram similaridade entre os comportamentos das variáveis. Os picos ocorreram em períodos iguais ou próximos. A análise exploratória dos dados apontou que houve falta de cloroquina no período correspondente ao início das divulgações sobre a aplicação desses medicamentos para o tratamento da covid-19. Ambos os medicamentos apresentaram correlação alta e estatisticamente significativa com as demais variáveis analisadas. Também foi observado que algumas delas apresentaram maior correlação com as vendas de medicamentos quando assumiram defasagem temporal de um mês. No caso da cloroquina, isso ocorreu com a variável óbitos. No caso da ivermectina, ocorreu com as variáveis número de tweets, casos e óbitos. CONCLUSÕES Os resultados observados contribuem para a tomada de decisão durante a gestão de crises por parte de governo, indústrias e comércios. Em momentos de crises, como observado durante a pandemia, as variáveis mostraram que são capazes de auxiliar na previsão de vendas, em especial o Google® e os tweets, que proporcionam uma análise em tempo real da situação. Acompanhar as redes sociais e mecanismos de busca permitiria detecção de uso pela população e melhor previsão de potenciais picos de demanda desses medicamentos.

Eficácia da ivermectina e atazanavir no tempo de recuperação dos sintomas de covid-19: uma coorte prospectiva / Effectiveness of ivermectin and atazanavir on time to resolution from covid-19 symptoms: a prospective cohort / Eficacia de ivermectina y atazanavir en el tiempo hasta lá resolución de los síntomas de covid-19: una cohorte prospectiva

Objetivo: avaliar a eficácia da Ivermectina e do Atazanavir em comparação com placebo no tempo de resolução dos sintomas e no tempo de duração da doença por COVID-19. Método: estudo observacional, de coorte prospectivo, longitudinal, descritivo e analítico com pacientes sintomáticos ambulatoriais, acompanhados por 06 meses em duas Unidades Básicas de Saúde para atendimento de COVID-19 em Teresina- Piauí, Brasil, no período de novembro a abril de 2021 identificados por amostragem aleatória 1:1:1. Foram realizados exames Reverse transcription polymerase chain reaction (RT-PCR) para confirmação laboratorial da suspeita de infecção pelo novo coronavírus e avaliação sociodemográfica e clínica. Resultados: dos 87 pacientes randomizados, 62,1% (n=54) eram do sexo masculino, com média de idade de 35,1 anos, possuíam companheira (53,9%), baixa renda (50,6%), eutróficos (40,7%) e sem comorbidades de saúde (78,2%). Não houve diferença entre o tempo médio para resolução dos sintomas, que foi de 21 dias (IQR, 8-30) no grupo atazanavir, 30 dias (IQR, 5-90) no grupo ivermectina em comparação com 14 dias (IQR, 9-21) no grupo controle. No dia 180, houve resolução dos sintomas em 100% no grupo placebo, 93,9% no grupo atazanavir e 95% no grupo ivermectina. A duração mediana da doença foi de 08 dias em todos os braços do estudo. Conclusão: o tratamento com atazanavir (6 dias) e ivermectina (3 dias) não reduziu o tempo de resolução dos sintomas e nem o tempo de duração da doença entre os pacientes ambulatoriais com COVID-19 leve em comparação com o grupo placebo. Os resultados não suportam o uso de ivermectina e atazanavir para tratamento de COVID-19 leve a moderado.

Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piauí, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5- 90) in the ivermectin group compared with 14 days (IQR, 9- 21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.

Objetivo: evaluar la efectividad de Ivermectina y Atazanavir en comparación con placebo en el tiempo de resolución de los síntomas y duración de la enfermedad por COVID-19. Método: estudio de cohorte observacional, prospectivo, longitudinal, descriptivo y analítico con pacientes ambulatorios sintomáticos, seguidos durante 06 meses en dos Unidades Básicas de Salud para atención de COVID-19 en Teresina-Piauí, Brasil, de noviembre a abril de 2021 identificados por 1:1:1 muestreo aleatorio. Se realizaron pruebas de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) para confirmación de laboratorio de sospecha de infección por el nuevo coronavirus y evaluación sociodemográfica y clínica. Resultados: de los 87 pacientes aleatorizados, 62,1% (n=54) eran del sexo masculino, con una edad media de 35,1 años, tenían pareja (53,9%), bajos ingresos (50,6%), eutróficos (40,7%) y sin comorbilidades de salud (78,2%). No hubo diferencia entre la mediana de tiempo hasta la resolución de los síntomas, que fue de 21 días (RIC, 8-30) en el grupo de atazanavir, 30 días (RIC, 5- 90) en el grupo de ivermectina en comparación con 14 días (RIC, 9 - 21) en el grupo control. En el día 180, hubo una resolución de los síntomas del 100 % en el grupo de placebo, del 93,9 % en el grupo de atazanavir y del 95 % en el grupo de ivermectina. La mediana de duración de la enfermedad fue de 8 días en todos los brazos del estudio. Conclusión: El tratamiento con atazanavir (6 días) e ivermectina (3 días) no redujo el tiempo de resolución de los síntomas ni la duración de la enfermedad entre los pacientes ambulatorios con COVID-19 leve en comparación con el grupo placebo. Los resultados no respaldan el uso de ivermectina y atazanavir para el tratamiento de la COVID-19 de leve a moderada.

Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ivermectin is a US Food and Drug Administration (FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties. Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries, its potential therapeutic effect on pulmonary fibrosis (PF) has not been investigated. This study aimed to explore the ability of ivermectin (0.6 mg/kg) to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model. This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF. The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury, as manifested by the reduced infiltration of inflammatory cells, as well as decreased the inflammation and fibrosis scores. Intriguingly, ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-‍β1 (TGF-‍β1) and fibronectin protein expression, highlighting its anti-fibrotic activity. This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain (NOD)‍-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), with a subsequent decline in the interleukin‍-‍1β (IL‍-‍1β) level. In addition, ivermectin inhibited the expression of intracellular nuclear factor-‍κB (NF‍-‍κB) and hypoxia‑inducible factor‑1α (HIF‍-‍1α) proteins along with lowering the oxidative stress and apoptotic markers. Altogether, this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin. These beneficial effects were mediated, at least partly, via the downregulation of TGF-‍β1 and fibronectin, as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1α and NF-‍κB.

Uso de Ivermectina e Atazanavir no tratamento da Covid-19: uma revisão de escopo / Use of Ivermectin and Atazanavir in the treatment of Covid-19: a scoping review / Uso de Ivermectina y Atazanavir en el tratamiento de Covid-19: una revisión de alcance

Objetivo: Examinar e mapear as evidências científicas sobre a eficácia do uso de ivermectina e atazanavir no tratamento de COVID-19. Metodologia: Scoping Review, baseado nos procedimentos recomendados pelo Instituto Joanna Briggs. Estabeleceu-se a pergunta norteadora: "Quais são as evidências científicas sobre o uso de ivermectina e atazanavir no tratamento de pacientes com sintomas leves de COVID-19?". Foram realizadas buscas em seis bases de dados nacionais e internacionais, sobre trabalhos publicados até dezembro de 2022. Dos 357 estudos encontrados, 22 foram selecionados para leitura na íntegra, resultando em uma amostra final de 11 estudos analisados. Resultados: As 11 publicações analisadas foram publicadas de 2020 a 2022 durante período pandêmico, de âmbito nacional e internacional com delineamento de estudos experimentais, do tipo ensaio clínico com randomização. Apenas 03 estudos (25%) testaram o atazanavir como intervenção conjugada a outras drogas, não evidenciando melhorias significativas em relação ao seu uso. Já no tratamento com Ivermectina, dos oito (75%) estudos que a testaram, apenas três (37,5%) recomendaram seu uso e cinco (62,5%) não suportam seu uso para tratamento de COVID-19 leve. O tempo de resolução dos sintomas variou de 8 a 10 dias nos braços tratados com ivermectina e em média 07 dias no tratamento com atazanavir. Não se detectou eventos adversos graves relacionados ao uso das duas drogas. Conclusão: As evidências que recomendavam o uso de ivermectina datam do início do período pandêmico, 2020, mas posteriormente, com a realização de ensaios clínicos robustos e controlados, novas evidências não suportam o uso de ivermectina e atazanavir no tratamento de COVID-19 leve mostrando que não houve diferença no tempo de resolução dos sintomas, na taxa de mortalidade, taxa de internação na UTI e tempo de hospitalização.

Objective: To examine and map the scientific evidence on the effectiveness of using ivermectin and atazanavir in the treatment of COVID-19. Methodology: Scoping Review, based on the procedures recommended by the Joanna Briggs Institute. The guiding question was established, "What is the scientific evidence on the use of ivermectin and atazanavir in the treatment of patients with mild symptoms of COVID-19?" Searches were conducted in six national and international databases on papers published until December 2022. Of the 357 studies found, 22 were selected for reading in full, resulting in a final sample of 11 studies analyzed. Results: The 11 publications analyzed were published from 2020 to 2022 during pandemic period, of national and international scope with experimental study design, of clinical trial type with randomization. Only 03 studies (25%) tested atazanavir as a combined intervention with other drugs, showing no significant improvements in relation to its use. As for the treatment with Ivermectin, of the eight (75%) studies that tested it, only three (37.5%) recommended its use and five (62.5%) did not support its use for treating mild COVID-19. The time to symptom resolution ranged from 8 to 10 days in the ivermectin-treated arms and on average 07 days in the atazanavir treatment. No serious adverse events related to the use of the two drugs were detected. Conclusion: evidence recommending the use of ivermectin dates back to the beginning of the pandemic period, 2020, but subsequently, with robust controlled clinical trials, new evidence does not support the use of ivermectin and atazanavir in the treatment of mild COVID-19 showing that there was no difference in time to symptom resolution, mortality rate, ICU admission rate, and length of hospital stay.

Objetivo: Examinar y mapear la evidencia científica sobre la eficacia del uso de ivermectina y atazanavir en el tratamiento de COVID-19. Metodología: Scoping Review, basada en los procedimientos recomendados por el Instituto Joanna Briggs. La pregunta guía era: "¿Cuál es la evidencia científica sobre el uso de ivermectina y atazanavir en el tratamiento de pacientes con síntomas leves de COVID-19? Se realizaron búsquedas en seis bases de datos nacionales e internacionales, en artículos publicados hasta diciembre de 2022. De los 357 estudios encontrados, se seleccionaron 22 para su lectura completa, lo que dio lugar a una muestra final de 11 estudios analizados. Resultados: Las 11 publicaciones analizadas fueron publicadas entre 2020 y 2022 durante el periodo pandémico, de ámbito nacional e internacional con diseño de estudio experimental, de tipo ensayo clínico con aleatorización. Apenas 03 estudios (25%) probaron el atazanavir como intervención combinada con otras drogas, sin evidenciar mejoras significativas en relación con su uso. En cuanto al tratamiento con Ivermectina, de los ocho (75%) estudios que la probaron, sólo tres (37,5%) recomendaron su uso y cinco (62,5%) no apoyaron su uso para tratar la COVID-19 leve. El tiempo transcurrido hasta la resolución de los síntomas osciló entre 8 y 10 días en los brazos tratados con ivermectina y una media de 07 días en el tratamiento con atazanavir. No se detectaron acontecimientos adversos graves relacionados con el uso de los dos fármacos. Conclusión: las pruebas que recomiendan el uso de ivermectina se remontan al inicio del periodo pandémico, 2020, pero posteriormente, con ensayos clínicos controlados sólidos, las nuevas pruebas no apoyan el uso de ivermectina y atazanavir en el tratamiento de la COVID-19 leve, lo que demuestra que no hubo diferencias en el tiempo hasta la resolución de los síntomas, la tasa de mortalidad, la tasa de ingreso en la UCI y la duración de la estancia hospitalaria.

Estudio exploratorio de eficacia de ivermectina combinada a α- PD-1 en cáncer colorrectal resistente a quimioinmunoterapia / EXPLORATORY EFFECTIVENESS STUDY OF IVERMECTIN COMBINED WITH α-PD-1 IN CHEMOTHERAPY RESISTANT COLORRECTAL CANCER

[RESUMEN]. Las terapias inmunológicas con inhibidores de checkpoints (ICIs) han revolucionado el abordaje del cáncer colorrectal (CCR), pero su efectividad se restringe a tumores inmunorreactivos con deficiencia en la reparación de errores tipo mismatch (dMMR). La ivermectina (IVM), un agente antiparasitario, se propone como posible estrategia terapéutica debido a su impacto en la muerte celular inmunogénica (MCI) y la reversión de resistencia a medicamentos. La investigación evaluó el efecto antineoplásico de IVM combinado con α-PD-1 empleando el modelo murino CT-26, una línea de CCR KRAS-mutada y competentes para MMR. El análisis bioinformático mediante la plataforma GEPIA2 empleandola base TCGA confirmó la expresión diferencial de blancos moleculares de IVM en tejido tumoral versus normal, siendo más alta en tumores con inestabilidad microsatelital baja (MSI-L)/microsatelital estable (MSS) que en inestabilidad microsatelital alta (MSI-H). En experimentos in vitro, CT-26 mostró alta sensibilidad a IVM (IC50: 11 µM, luego de exposición por 72 horas), alterando el metabolismo y aumentando la secreción de IL-6. El análisis proteómico identificó 17 proteínas sobreexpresadas y 8 inhibidas, relacionadas con evasión inmunológica y proliferación celular. En ratones BALB/c portadores de tumores CT-26, la terapia combinada de IVM y α-PD-1 redujo significativamente el crecimiento tumoral y la progresión metastásica. La preinmunización con células CT-26 tratadas con IVM disminuyó la incidencia y la progresión tumoral. IVM podría potenciar la respuesta a ICIs en tumores "fríos". Estos hallazgos sugieren que la combinación de IVM y α-PD-1 puede mejorar la inmunorreactividad y respuesta terapéutica en CCR.

[ABSTRACT]. Matrix Assisted Laser DesorptionIonization ­ Time of Flight ­ MassSpectrometry (MALDI-TOF-MS) has emerged as anoutstandingtechnique in thefieldofclinicalmicrobiology, with a simple methodology and deliveryof precise results in anexceptionally short timeframe. Thistechnology has garnered notable success in recentyears, establishing as a fundamental toolboth in thecharacterizationofmicroorganisms and translationalresearch.Thecombinationoftheinherentfeaturesofthistechniquewiththepotentialof machine learninganalysis has provento be ofgreatvalue in clinicalmicrobiology, particularly in theantibioticresistancefield. Itsapplication has acceleratedbacterial diagnosis and opened new perspectives in criticalareasof medicine, such sepsis and oncology. In Argentina, several research groups actively contributing to its expansión, applying MALDI-TOF-MS in the fight against infectious diseases, including the COVID-19 pandemic. Theseeffortspromiseto continue drivingresearch and clinical diagnosis in the country and worldwide.

Sexual motivation and performance in sexual naïve and experienced rats treated with ivermectin: an ultrasonic vocalization study / Motivação e desempenho sexual em ratos com e sem experiência sexual tratados com ivermectina: um estudo da vocalização ultrassônica

In mammals, ivermectin acts as a GABAA receptor agonist and stimulates GABA release. Previous studies showed that ivermectin (IVM) reduces sexual performance, impairing the latency to the first mount and intromission. These parameters are usually considered motivational parameters of sexual behavior. However, IVM increases GABAergic activity leading to motor incoordination. Thus, it is reasonable to propose that IVM affects sexual performance via motor incoordination pathways. The present study analyzed ultrasonic vocalization in rats to verify whether IVM impairs sexual behavior via motivational mechanisms or motor impairment. Because sexual experience attenuates the impairment of motor performance, rats with sexual experience were also studied. Sexually naive and experienced rats were administered a therapeutic IVM dose and saline. The rats were exposed to receptive females, and the latency to the first mount was evaluated, followed by the 50-kHz USV test. IVM treatment in naïve rats increased the latency to first to mount relative to Saline naïve rats, while no differences were observed between saline and experienced rats. In naïve-IVM rats, a reduced frequency and total calls and increased mean time of calls occur relative to SAL-naïve rats. Experienced IVM rats did not show differences in the frequency, mean, and maximal calls close to Saline experienced rats. However, an increase in the total calls and the dominant frequency of calls were observed in IVM-experienced rats compared to Saline experienced rats. A negative and positive correlation occurred between the latency to the first mount and USVs in groups with and without ivermectin exposure. Hence, we propose that ivermectin increased the sexual motivation of rats exposed to a female in estrous based in USVs despite an increased latency to the first mount that occurred. The increased latency to the first mount resulted from motor incoordination, as previously observed and proposed by our group.(AU)

Em mamíferos, a ivermectina (IVM) atua como agonista do receptor GABAA e estimula a liberação de GABA. Estudos anteriores mostraram que a IVM reduz o desempenho sexual, prejudicando a latência para a primeira monta e intromissão. Esses parâmetros são geralmente considerados parâmetros motivacionais do comportamento sexual. Por outro lado, a IVM aumenta a atividade GABAérgica levando à incoordenação motora. Assim, é possível que a IVM afete o desempenho sexual devido a um impedimento motor. O presente estudo analisou a vocalização ultrassônica em ratos para verificar se a IVM prejudica o comportamento sexual via mecanismos motivacionais ou comprometimento motor. Uma vez que a experiência sexual atenua o comprometimento do desempenho motor, também foram estudados ratos com experiência sexual. Ratos sexualmente inexperientes e experientes foram administrados com uma dose terapêutica de IVM ou solução salina IVM. Os ratos foram expostos a fêmeas receptivas e foi avaliada a latência para a primeira monta, seguida do teste de vocalização ultrassônica (USV) de 50 kHz. O tratamento com IVM em ratos inexperientes aumentou a latência para a primeira monta em relação a ratos inexperientes tratados com solução salina, enquanto não foram observadas diferenças entre ratos experientes tratados com IVM e solução salina. Em ratos inexperientes tratados com IVM ocorreu redução da frequência e total de USVs, bem como aumento do tempo médio de USVs em relação aos ratos sem experiência. Ratos experientes tratados com IVM não mostraram diferenças na frequência, média e máxima das USVs em relação aos ratos experientes tratados com solução salina; no entanto, observou-se aumento no total de USVs e na frequência dominante de USVS em ratos experientes tratados com IVM comparados aos experientes tratados com solução salina. Observou-se correlação negativa e positiva entre a latência para a primeira monta e USVs nos grupos sem e com experiência tratados com IVM, respectivamente. Assim, propomos que a IVM aumentou a motivação sexual de ratos expostos a uma fêmea em estro com base em USVs, apesar de apresentar aumento na latência para a primeira monta. O aumento da latência para a primeira monta foi atribuída à incoordenação motora, conforme observado anteriormente e proposto por nosso grupo.(AU)

Therapeutics and COVID-19: living guideline - 16 September 2022

The WHO Therapeutics and COVID-19: living guideline contains the Organization's most up-to-date recommendations for the use of therapeutics in the treatment of COVID-19. The latest version of this living guideline is available in pdf format (via the 'Download' button) and via an online platform, and is updated regularly as new evidence emerges. This twelfth version of the WHO living guideline now contains 19 recommendations. This latest update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers and Janus kinase (JAK) inhibitors in patients with severe or critical COVID-19, and modifies previous recommendations for the neutralizing monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe COVID-19.

Infección pulmonar por Strongyloides stercoralis en paciente inmunocomprometido. Reporte de caso / Pulmonary infection caused by Strongyloides stercoralis in an immunocompromised patient. Case report

El Strongyloides stercoralis es un nemátodo intestinal capaz de completar su ciclo de vida dentro del huésped humano. Se presenta el caso clínico de una mujer de 57 años con residencia en la zona amazónica por 10 años, la que presenta antecedentes patológicos personales de hiperten-sión arterial, osteoporosis y diabetes mellitus tipo 2, lo que la cataloga como inmunocomprome-tida. Esta asiste a servicios de emergencia con cuadro agudo característico de infección de vías urinarias, recibe tratamiento en la unidad de cuidados intensivos por shock séptico de origen urinario versus pulmonar. La prueba de laboratorio clínico mediante muestra tomada a través de broncoaspiración arroja la existencia de larvas activas de Strongyloides stercoralis. La paciente mejoró sus condiciones de salud luego de un mes de evolución, respondiendo satisfactoriamente a la antibioticoterapia con carbapenémicos y el antiparasitario ivermectina. Los pacientes con factores de riesgo subyacentes tienen alta probabilidad a este tipo de infección agravada. La estrongiloidásis grave tiene una alta tasa de mortalidad, por lo que un diagnóstico temprano es indispensable para mejorar el pronóstico.

Strongyloides stercoralis is an intestinal nematode capable of completing its life cycle within the human host. The clinical case of a 57-year-old woman who has lived in the Amazon region for 10 years is presented. She has a personal pathological history of arterial hypertension, osteopo-rosis, and type 2 diabetes mellitus, which classifies her as immunocompromised. She attends emergency services with acute symptoms characteristic of urinary tract infection, receives treat-ment in the intensive care unit for septic shock of urinary versus pulmonary origin. The clinical laboratory test using a sample taken through bronchial aspiration shows the existence of active larvae of Strongyloides stercoralis. The patient's health conditions improved after a month of evolution, responding satisfactorily to antibiotic therapy with carbapenems and the antiparasitic ivermectin. Patients with underlying risk factors are at high risk for this type of aggravated infection. Severe strongyloidiasis has a high mortality rate, so early diagnosis is essential to improve prognosis

Miasis en pacientes con cáncer en el Instituto Nacional de Cancerología entre 2008 y 2018: Serie de Casos / Myiasis in cancer patients receiving medical care at a reference center in Bogotá, Colombia: 2008-2018. A case series

Resumen Introducción: La miasis puede ser considerada una enfermedad desatendida; corresponde a la infestación de larvas de dípteros en piel, heridas o cavidades naturales. La literatura para pacientes oncológicos con infestación es limitada para Colombia. Métodos: Se realizó una serie de casos de miasis en pacientes atendidos en el Instituto Nacional de Cancerología de 2008 a 2018; se obtuvieron datos de las historias clínicas con el fin de caracterizar variables sociodemográficas, oncológicas y tratamiento recibido. Resultados: Se encontraron 32 registros: 27 cumplieron con los criterios de inclusión, mediana de edad 69 años, 74% fueron hombres, 48% procedían de área rural, 33,3% de áreas con alturas superiores a 2000 msnm, 70% presentaban cáncer de cabeza y cuello, seguidos por cáncer de mama 14%; 40% ECOG 2-3; 77% visualizaron larvas antes de consultar; ningún paciente presentó sepsis al momento de consultar, 29% presentaban secreción en zona infestada, 85% recibieron ivermectina y curaciones por parte de enfermería; 70% recibió antibióticos sistémicos, y 60% otros tratamientos además de la remoción mecánica e ivermectina, la mediana de leucocitos al ingreso fue de 10280 y de eosinófilos 110. Conclusión: Ésta es la primera serie de casos informada de miasis en pacientes oncológicos para América. Es más frecuente en pacientes con neoplasias en áreas expuestas, aunque se puede presentar en zonas no expuestas; la infestación por larvas tiende a no ser purulenta. Se deben hacer estudios sobre el uso de ivermectina, otros antibióticos y las implicaciones pronósticas de esta patología en los pacientes con cáncer avanzado.

Abstract Introduction: Myiasis can be considered a neglected disease; it corresponds to the infestation of dipteran larvae in skin, wounds, or natural cavities. Literature for oncological patients with this infestation is limited for Colombia. Methods: A case series of myiasis was carried out in patients treated at the National Cancer Institute of Colombia from 2008 to 2018. Data were obtained from medical records in order to characterize sociodemographic and oncological variables and the treatment received. Results: Thirty-two records were found, 27 of them met the inclusion criteria. Median age was 69 years, 74% were men, 48% came from rural areas, 33.3% from areas with altitudes greater than 2,000 meters above sea level, 70% had head and neck cancer, followed by breast cancer in 14%; 40% had ECOG 2-3, and 77% visualized larvae before consulting. No patient presented with sepsis at the time of consultation, 29% presented with discharge in the infested area, 85% received ivermectin and treatment by the nursing staff; 70% received systemic antibiotics, and 60% other treatments in addition to mechanical removal and ivermectin. Median of leukocytes at admission was 10,280, while median of eosinophils was 110. Conclusion: This is the first reported case series of myiasis in cancer patients for Latin America. It is more common in patients with neoplasms in exposed areas, although it can occur in unexposed areas too. Larval infestation tends not to be purulent. Further studies are needed on the use of ivermectin, other antibiotics, and the prognostic implications of this pathology in patients with advanced cancer.

Ivermectin treatment response in two rural villages with a high prevalence of onchocerciasis and epilepsy, Mahenge Tanzania

Background: Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages. Objectives: We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE). Methods: Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment. Results: The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean micro filarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the micro filarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High micro filarial density at baseline was the only significant predictor associated with higher micro filarial density in the post-ivermectin skin snips. Conclusion: Our study reports a decrease in micro filarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge

Análisis de publicaciones y comentarios sobre la ivermectina en Facebook durante la pandemia del COVID-19 en Perú / Analysis of Facebook publications and comments about ivermectin during the COVID-19 pandemic in Peru

Los datos de acceso público en plataformas de redes sociales se pueden utilizar para identificar percepciones, actitudes y sentimientos en relación con la COVID-19; ello puede ser útil para formular políticas de estado y enfrentar adecuadamente la emergencia. El presente trabajo tuvo por objetivo analizar las publicaciones y percepciones de los usuarios a través de sus comentarios en Facebook sobre el fármaco ivermectina durante la pandemia de COVID-19 en Perú. Las publicaciones y sus comentarios fueron seleccionados mediante búsqueda manual, utilizando los términos: ivermectina e #ivermectina, en julio de 2020. Su interpretación se efectuó por análisis de contenido cualitativo convencional, con proceso inductivo y apoyado por literatura científica. Se encontraron 17 publicaciones realizadas entre el 18 de mayo y 7 de julio del 2020, clasificadas en 5 temáticas: rumores (58,8 por ciento), basadas en evidencia científica (11,8 por ciento), precaución (11,8 por ciento), producción del fármaco (11,8 por ciento) y confrontación (5,9 por ciento). El 70,0 por ciento de los rumores surgieron de páginas de medios de comunicación. Los comentarios se clasificaron, según percepciones de los usuarios hacia la ivermectina, en cuatro temas: ivermectina como cura efectiva (64,8 por ciento), solicitud de información (25,3 por ciento), en contra del consumo de ivermectina (6,3 por ciento) y otros tratamientos (3,6 por ciento). Más de la mitad de la información sobre ivermectina en Facebook aparece en rumores, en su mayoría originados por páginas de medios de comunicación. Entre los comentarios se destaca la percepción de los usuarios que la consideran cura efectiva contra la COVID-19(AU)

The purpose of the study was to analyze Facebook publications and perceptions of users, expressed in their comments, about the drug ivermectin during the COVID-19 pandemic in Peru. The publications and their comments were selected by manual search using the terms ivermectin and #ivermectin in July 2020. Interpretation of publications and their comments was performed by conventional qualitative content analysis with inductive processing and supported by scientific literature. A total 17 publications were retrieved from the period extending from 18 May to 7 July 2020. These were classified into five topics: rumors (58.8percent), based on scientific evidence (11.8percent), caution (11.8percent), production of the drug (11.8percent) and confrontation (5.9percent). Paradoxically, 70.0percent of the rumors were spread by mass media pages. Comments, on the other hand, were classified into four topics based on user perceptions: ivermectin as effective cure (64.8percent), request for information about ivermectin (25.3percent), against the use of ivermectin (6.3percent) and other treatments (3.6percent). As a conclusion, it was found that more than half of the information about ivermectin circulating in Facebook publications is classified as rumors, and most is spread by mass media pages. Analysis of the comments found that user perception considers ivermectin to be the effective cure against COVID-19(AU)

Acesso da população a medicamentos durante a pandemia do novo coronavírus / Access of the population to medicines during the pandemic of the new coronavirus / Acceso de la poblacióna medicamentos durante la pandemia del nuevo coronavirus

Introdução:Em 2020 a Organização Mundial da Saúde declarou a pandemia do novo coronavírus. Diante desse cenário vários estudos começaram a ser realizados em busca de uma terapia eficaz para o manejo clínico dos pacientes. A Cloroquina e a Hidroxicloroquina foram os primeiros medicamentos testados. A divulgação dos resultados iniciais fez aumentar a procura desses medicamentos em farmácias e drogarias. Objetivo:Avaliar o acesso da população a medicamentos na pandemia e o uso das "promessas terapêuticas":Cloroquina, Hidroxicloroquina e Ivermectina para prevenção e tratamento da COVID-19. Metodologia:Trata-se de um estudo descritivo exploratório de abordagem quantitativa, não probabilístico e por conveniência. A coleta de dados foi realizada online,via Google Formulários. Participaram 1.754 pessoas, resultando em 1.748 questionários válidos. A amostra foi distribuída em 3 grupos, de acordo com a pergunta de nº 11 do formulário de pesquisa: "Você já teve COVID-19?". Resultados:Dos 1.748 respondentes, 200 (11,4%) pertenciam ao grupo que "teve COVID-19", 1.041 (59,6%) ao grupo que não teve a doença, e 507 (29%) responderam não saber se foram infectados. No que diz respeito ao acesso a medicamentos na pandemia, 55,2% do total da amostra relatou não ter sido afetado, e 29% disseram ter tido o acesso afetado de alguma forma. Em relação ao uso das "promessas terapêuticas", 61% dos respondentes disse não ter feito uso com finalidade de prevenção, e sim para tratamento, já 52,6% da população do estudo disse que não fez uso de jeito nenhum, e 46,2% relatou que fez uso dos medicamentos mencionados para tratar a COVID-19. Conclusões:Constatou-se que a explosão na busca por medicamentos durante a pandemia não afetou o acesso da população. Além disso, a Cloroquina e a Hidroxicloroquina, não foram amplamente utilizadas para prevenção da doença (AU).

Introduction:In 2020the World Health Organization declared the new coronavirus pandemic. In view of this scenario, several studies began to be carried out in search of an effective therapy for the clinical management of patients. The release of initial results has increased demand for Chloroquine and Hydroxychloroquine in pharmacies and drugstores. Objective: To assess the population's access to medicines in the pandemic and the use of "therapeutic promises": Chloroquine, Hydroxychloroquine and Ivermectin for the prevention and treatment of COVID-19. Methodology:Exploratory descriptive study with a quantitative approach, non-probabilistic and for convenience. Data collection was performed online, via Google Forms. 1,754 people participated, resulting in 1,748 valid questionnaires. The sample was divided into 3 groups, according to question #11 of the survey form: "Have you ever had COVID-19?". Results:Of the 1,748 respondents, 200 (11.4%) belonged to the group that "had COVID-19", 1,041 (59.6%) to the group that did not have the disease, and 507 (29%) answered not knowing if they were infected. With regard to access to medicines in the pandemic, 55.2% of the total sample reported not being affected, and 29% said their access was affected in some way. Regarding the use of "therapeutic promises", 61% of respondents said they did not use it for prevention purposes, but for treatment, while 52.6% of the study population said they did not use it at all, and 46, 2% used the medications mentioned to treat COVID-19. Conclusions:It wasfound that the explosion in the search for medicines during the pandemic did not affect the population's access. Furthermore, Chloroquine and Hydroxychloroquine have not been widely used for disease prevention (AU).

Introducción:En 2020, la Organización Mundial de la Salud declaró la nueva pandemia de coronavirus. Ante este escenario, se comenzaron a realizar varios estudios en busca de una terapia eficaz para el manejo clínico de lospacientes. La publicación de los resultados iniciales ha aumentado la demanda de cloroquina e hidroxicloroquina en farmacias y droguerías. Objetivo:Evaluar el acceso de la población a medicamentos en la pandemia y el uso de "promesas terapéuticas": cloroquina, hidroxicloroquina e ivermectina para la prevención y tratamiento de COVID-19. Metodología:Se trata de un estudio descriptivo exploratorio con enfoque cuantitativo, no probabilístico y por conveniencia. La recopilación de datos se realizó en línea, a través de Google Forms. Participaron 1.754 personas, resultando 1.748 cuestionarios válidos. La muestra se dividió en 3 grupos, de acuerdo con la pregunta # 11 del formulario de la encuesta: "¿Alguna vez ha tenido COVID-19?". Resultados: De los 1.748 encuestados, 200 (11,4%) pertenecían al grupo que "tenía COVID-19", 1.041 (59,6%) al grupo que no tenía la enfermedad y 507 (29%) respondieron sin saber si estaban infectados. Con respecto al acceso a medicamentos en la pandemia, el 55,2% del total de la muestra informó no estar afectado y el 29% dijo que su acceso se vio afectado de alguna manera. Con respecto al uso de "promesas terapéuticas", el 61% de los encuestados dijo que no lo usaba con fines de prevención, sino de tratamiento, mientras que el 52,6% de la población del estudio dijo que no lo usaba en absoluto, y el 46,2% informó que utilizaron los medicamentos mencionados para tratar COVID-19. Conclusiones: Se encontró que la explosión en la búsqueda de medicamentos durante la pandemia no afectó el acceso de la población. Además, la cloroquina y la hidroxicloroquina no se han utilizado ampliamente para la prevención de enfermedades (AU).

Development and validation of analytical methods by HPLC for quality control of avermectins and milbemycins in bulk samples

This work aims to develop analytical methods using high-performance liquid chromatography with a diode array detector (HPLC-DAD) for analysis and quantification of avermectins (AVMs) and milbemycins (MBMs) in bulk samples. First, the methods were optimized and some parameters such as temperature, flow rate, injection volume and mobile phase with different proportions of solvents were evaluated. The best chromatographic conditions were obtained using the Phenomenex® C18 (150 × 4.60 mm, 5 µm) column at a temperature of 20 °C, flow rate of 1.2 mL min-1, injection volume of 20 µL, and detection at 250 nm. Acetonitrile: ultrapure water (87: 13, v/v) was used as mobile phase for moxidectin and eprinomectin, and acetonitrile: methanol: ultrapure water (53: 35: 12, v/v/v) for abamectin and ivermectin. Under these conditions satisfactory results were obtained, with appropriate limits of detection and quantification, acceptable linearity, precision, accuracy, and robustness. These methods satisfy the need for analytical methods for the multi-determination of MBMs and the B1a and B1b forms of AVMs by HPLC-DAD, which can be considered simple, effective, innovative and should aid in the development of the fiel

Sales of "COVID kit" drugs and adverse drug reactions reported by the Brazilian Health Regulatory Agency / Vendas de "kit-COVID" e reações adversas a esses medicamentos relatadas pela Agência Nacional de Vigilância Sanitária / Ventas de medicamentos del "kit-COVID" y reacciones adversas a los medicamentos notificadas por la Agencia Nacional de Vigilancia Sanitaria

Off-label use of azithromycin, hydroxychloroquine, and ivermectin (the "COVID kit") has been suggested for COVID-19 treatment in Brazil without clinical or scientific evidence of efficacy. These drugs have known adverse drug reactions (ADR). This study aimed to analyze if the sales of drugs in the "COVID kit" are correlated to the reported number of ADR after the COVID-19 pandemic began. Data was obtained from the Brazilian Health Regulatory Agency (Anvisa) website on reported sales and ADRs for azithromycin, hydroxychloroquine, and ivermectin for all Brazilian states. The period from March 2019 to February 2020 (before the pandemic) was compared to that from March 2020 to February 2021 (during the pandemic). Trend adjustment was performed for time series data and cross-correlation analysis to investigate correlation between sales and ADR within the same month (lag 0) and in the following months (lag 1 and lag 2). Spearman's correlation coefficient was used to assess the magnitude of the correlations. After the pandemic onset, sales of all investigated drugs increased significantly (69.75% for azithromycin, 10,856,481.39% for hydroxychloroquine, and 12,291,129.32% for ivermectin). ADR levels of all medications but azithromycin were zero before the pandemic, but increased after its onset. Cross-correlation analysis was significant in lag 1 for all drugs nationwide. Spearman's correlation was moderate for azithromycin and hydroxychloroquine but absent for ivermectin. Data must be interpreted cautiously since no active search for ADR was performed. Our results show that the increased and indiscriminate use of "COVID kit" during the pandemic correlates to an increased occurrence of ADRs.

No Brasil, o uso off label de azitromicina, hidroxicloroquina e ivermectina (o "kit-COVID") foi sugerido para tratar COVID-19 sem que tivéssemos evidências clínicas ou científicas de sua eficácia. Estas drogas têm causado reações adversas (RA) em quem as tomam. Este estudo almejou analisar se a venda dos medicamentos que compõem o "kit-COVID" correlaciona-se com o número relatado de RAs após o início da pandemia da COVID-19. Os dados sobre vendas e RA associados a azitromicina, hidroxicloroquina e ivermectina foram obtidos no site da Agência Nacional de Vigilância Sanitária (Anvisa) para todos os estados brasileiros. Comparamos o período entre março de 2019 e fevereiro de 2020 (antes da pandemia) ao de março de 2020 a fevereiro de 2021 (durante a pandemia). Ajustamos tendências para os dados de séries temporais e as análises de correlação cruzada para investigar a correlação entre vendas e RA em um mesmo mês (lag 0) e nos seguintes (lag 1 e 2). O coeficiente de correlação de Spearman foi utilizado para avaliar a magnitude das correlações. Após o início da pandemia, as vendas de todos os medicamentos investigados aumentaram significativamente (69,75% para azitromicina, 10.856.481,39% para hidroxicloroquina e 12.291.129,32% para ivermectina). Os níveis de RAs de todos os medicamentos (com exceção de azitromicina) eram zero antes da pandemia mas aumentaram após seu início. A análise de correlação cruzada foi significativa no lag 1 para todas as drogas em todo o país. A correlação de Spearman foi moderada para azitromicina e hidroxicloroquina, mas ausente para ivermectina. Os dados devem ser interpretados com cautela, uma vez que não realizamos uma busca ativa por RA. Nossos resultados mostram que o uso aumentado e indiscriminado do "kit-COVID" durante a pandemia se correlaciona com uma ocorrência aumentada de RAs.

Se ha sugerido el uso fuera de lo establecido de azitromicina, hidroxicloroquina e ivermectina (el "kit-COVID") para el tratamiento de la COVID-19 en Brasil sin evidencia clínica o científica de su eficacia. Estos medicamentos tienen reacciones adversas (RAM) conocidas. Este estudio pretendía analizar si las ventas de medicamentos del "kit-COVID" están correlacionadas con el número de reacciones adversas notificadas tras el inicio de la pandemia de COVID-19. Los datos se obtuvieron del sitio web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa) sobre las ventas y las RAM notificadas para la azitromicina, la hidroxicloroquina y la ivermectina para todos los estados brasileños. Se comparó el periodo de marzo de 2019 a febrero de 2020 (antes de la pandemia) con el de marzo de 2020 a febrero de 2021 (durante la pandemia). Se realizó un ajuste de tendencia para los datos de las series de tiempo y un análisis de correlación cruzada para investigar la correlación entre las ventas y la RAM dentro del mismo mes (lag 0) y en los meses siguientes (lag 1 y lag 2). Se utilizó el coeficiente de correlación de Spearman para evaluar la magnitud de las correlaciones. Tras el inicio de la pandemia, las ventas de todos los medicamentos investigados aumentaron significativamente (69,75% para la azitromicina, 10.856.481,39% para la hidroxicloroquina y 12.291.129,32% para la ivermectina). Los niveles de RAM de todos los medicamentos, excepto la azitromicina, eran nulos antes de la pandemia, pero aumentaron tras su inicio. El análisis de correlación cruzada fue significativo en el lag 1 para todos los medicamentos a nivel nacional. La correlación de Spearman fue moderada para la azitromicina y la hidroxicloroquina, pero no para la ivermectina. Los datos deben interpretarse con cautela, ya que no se realizó una búsqueda activa de RAM. Nuestros resultados muestran que el uso creciente e indiscriminado del "kit-COVID" durante la pandemia se correlaciona con una mayor aparición de las RAM.

Sarna costrosa: revisión sobre aspectos clínicos de una ectoparasitosis desatendida y de presentación infrecuente / Crusty scabies: review of the clinical aspects of a neglected and infrequent ectoparasitosis

En esta revisión de la literatura se describen aspectos epidemiológicos, fisiopatológicos, clínicos y terapéuticos sobre una presentación atípica y grave de escabiosis, la sarna costrosa o noruega. Esta presentación de escabiosis destaca por afectar principalmente a personas con condiciones de inmunodepresión o sociales que las hacen susceptibles de una alta carga parasitaria, además se asocia a un peor pronóstico y a riesgo de complicaciones. Desde el punto de vista terapéutico, sus estrategias difieren del manejo de la escabiosis clásica.(AU)

This literature review describes epidemiological, pathophysiological, clinical and therapeutic aspects of an atypical and severe presentation of scabies, Norwegian or crusty scabies. This presentation of scabies stands out because it mainly affects people with immunosuppressive or social conditions that make them susceptibleto a high parasite load, it is also associated with a worse prognosis and risk of complications. From a therapeutic point of view, their strategies differ from the management of classic scabies.(AU)

Factores asociados a letalidad por COVID-19 en un hospital de la región Cajamarca en Perú / Factors associated with COVID-19 lethality in a hospital in the Cajamarca region in Peru

RESUMEN Objetivo. Identificar las características clínicas y epidemiológicas relacionadas a la letalidad en pacientes hospitalizados por COVID-19 en el Hospital Simón Bolívar de Cajamarca, durante junio-agosto de 2020. Materiales y métodos. Cohorte retrospectiva, con información recolectada de historias clínicas y sistemas oficiales de vigilancia epidemiológica (NOTIWEB, SISCOVID y SINADEF), sobre pacientes hospitalizados con diagnóstico confirmado de COVID-19. Se recolectó información sobre factores sociodemográficos y clínicos, considerando como desenlace el egreso (fallece/sobrevive) y los días de hospitalización. Resultados. La tasa de letalidad intrahospitalaria fue 39,6%, encontrándose diferencias significativas entre el tiempo de hospitalización y la condición de egreso en las personas mayores de 60 años (p<0,001). La edad mayor de 60 años (HR: 2,87; IC95%: 1,76-4,68),) solicitud de cama UCI no atendida (HR: 3,49; IC95%: 2,02-6,05), saturación de oxígeno menor a 80% al ingreso (HR: 2,73; IC95%: 1,35-5,53) y el uso de ivermectina (HR: 1,68; IC95% 1,06-2,68) fueron factores asociados a letalidad. El modelo de Machine Learning (ML) elegido consideró que las variables con mayor importancia fueron la saturación de oxígeno, la edad mayor de 60 años, tiempo de hospitalización y tiempo de síntomas. Conclusión. Los factores que podrían incrementar la letalidad en pacientes hospitalizados por COVID-19 fueron la edad, saturación de oxígeno menor a 80%, uso de ivermectina en la terapéutica hospitalaria y la solicitud no atendida de camas UCI. Futuros estudios con una mejor representatividad podrían confirmar estas posibles relaciones a nivel regional o nacional.

ABSTRACT Objective. To identify the clinical and epidemiological characteristics related to lethality in patients hospitalized for COVID-19 at the Simón Bolívar Hospital in Cajamarca, during June-August 2020. Materials and Methods. This was a retrospective cohort, that used information collected from clinical records and official epidemiological surveillance systems (NOTIWEB, SISCOVID and SINADEF), on hospitalized patients with confirmed COVID-19 diagnosis. Information was collected on sociodemographic and clinical factors, considering discharge (death/survival) and days of hospitalization as outcomes. Results. The in-hospital fatality rate was 39.6%, and significant differences were found between hospitalization time and status at discharge in people over 60 years of age (p<0.001). Age older than 60 years (HR: 2.87; 95% CI: 1.76-4.68),) unattended ICU bed request (HR: 3.49; 95% CI: 2.02-6.05), oxygen saturation less than 80% at admission (HR: 2.73; 95% CI: 1.35-5.53) and the use of ivermectin (HR: 1.68; 95%CI 1.06-2.68) were factors associated with lethality. The chosen ML model considered that the most important variables were oxygen saturation, age over 60 years, time of hospitalization and time of the onset of symptoms. Conclusion. The factors that could increase lethality in patients hospitalized for COVID-19 were age, oxygen saturation less than 80%, use of ivermectin as part of hospital treatment and unattended request for ICU beds. Future studies with better representativeness could confirm these possible relationships at the regional or national level.

Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience

SUMMARY OBJECTIVE: Hydroxychloroquine and Ivermectin are advocated as potential treatments for coronavirus disease 2019 (COVID-19) despite the lack of supportive clinical evidence. In this study, outcomes associated with Hydroxychloroquine and/or Ivermectin were determined in a series of patients with confirmed COVID-19 from a single institution in Brazil. METHODS: Consecutive patients admitted between March and July 2020 were retrospectively analyzed and divided into four treatment categories: no treatment (Group 0), Ivermectin only (Group I), Hydroxychloroquine only (Group II), and Hydroxychloroquine and Ivermectin (Group III). Intensive care unit admission, mechanical ventilation, and death were compared between the Groups. RESULTS: A total of 230 patients were included, with the following treatment distribution: 35.2% (0), 9.1% (I), 48.3% (II), and 7.4% (III). Groups I, II, and III had the higher rates of Intensive care unit admission, mechanical ventilation, or death (0: 23.5% versus I: 38.1% versus II: 37.8% versus III: 70.6%, p=0.002), and the greatest mortality was found in Group III (0 versus III: 13.6% versus 35.3%, p=0.03). In the multivariate analysis, Hydroxychloroquine remained significantly associated with death (OR 3.3, 95%CI 1.1-9.6, p=0.03). CONCLUSION: In a series of consecutive hospitalized patients with COVID-19, Ivermectin was not associated with improved outcomes and Hydroxychloroquine may have resulted in a harmful effect.

Children hospitalized for myiasis in a reference center in Uruguay / Niños hospitalizados por miasis en un centro de referencia de Uruguay

Abstract Background: Myiasis is an emerging disease caused by tissue invasion of dipteran larvae. In Uruguay, Cochliomyia hominivorax and Dermatobia hominis are the most frequent species. This study aimed to describe the epidemiological and clinical characteristics and the follow-up of children < 15 years hospitalized for myiasis in a reference center in Uruguay between 2010 and 2019. Methods: We conducted a descriptive and retrospective study by reviewing medical records. We analyzed the following variables: age, sex, comorbidities, origin, the month at admission, clinical manifestations, other parasitoses, treatments, complications, and larva species identified. Results: We found 63 hospitalized children: median age of 7 years (1 month-14 years), 68% of females. We detected risk comorbidities for myiasis (33%), of which chronic malnutrition was the most frequent (n = 6); 84% were from the south of the country; 76% were hospitalized during the summer. Superficial and multiple cutaneous involvements were found in 86%: of the scalp 50, furunculoid type 51, secondary to C. hominivorax 98.4%, and to D. hominis in 1.6%. As treatments, larval extraction was detected in all of them, surgical in 22%. Asphyctic products for parasites were applied in 94%, ether in 49. Antimicrobials were prescribed in 95%; cephradine and ivermectin were the most frequent. About 51% presented infectious complications: impetigo was found in 29, cellulitis in 2, and abscess in 1. Conclusions: Myiasis predominantly affected healthy schoolchildren during the summer months and was frequently associated with ectoparasites. Superficial infestation of the furuncle-like scalp by C. hominivorax was the most frequent form. Infectious complications motivated hospitalizations.

Resumen Introducción: La miasis es una enfermedad emergente producida por la invasión tisular por larvas de dípteros. En Uruguay, Cochliomyia hominivorax y Dermatobia hominis son las especies más frecuentes. El objetivo de este estudio fue describir las características epidemiológicas y clínicas, y el seguimiento, de niños menores de 15 años hospitalizados por miasis en un centro de referencia del Uruguay entre 2010 y 2019. Métodos: Se llevó a cabo un estudio descriptivo y retrospectivo mediante la revisión de las historias clínicas. Se analizaron las siguientes variables: edad, sexo, comorbilidad, procedencia, mes al ingreso, cuadro clínico, otras parasitosis, tratamientos, complicaciones y especie de larva identificada. Resultados: Se encontraron 63 casos de niños hospitalizados, con una mediana de edad de 7 años (rango: 1 mes a 14 años) y el 68% de sexo femenino. Se identificó comorbilidad de riesgo para miasis (33%), siendo la desnutrición crónica la más frecuente (n = 6). El 84% eran procedentes del sur del país y el 76% fueron hospitalizados en los meses estivales. Se encontró afectación cutánea superficial y múltiple en el 86%: de cuero cabelludo en 50, de tipo forunculoide en 51, secundaria a C. hominivorax en el 98.4% y a D. hominis en el 1.6%. Se realizó extracción larvaria en todos los casos, que fue quirúrgica en el 22%. Se aplicaron productos asfícticos para parásitos en el 94%, con éter en 49 niños. Se prescribieron antimicrobianos en el 95%; los más usados fueron cefradina e ivermectina. El 51% presentaron complicaciones infecciosas: 29 impétigo, 2 celulitis y 1 absceso. Conclusiones: La miasis afectó predominantemente a escolares sanos y durante los meses estivales, y se encontró frecuentemente asociada con ectoparasitosis. La infestación superficial del cuero cabelludo de tipo forunculoide por C. hominivorax fue la forma más frecuente. Las complicaciones infecciosas motivaron las hospitalizaciones.

Mecanismos de acción de agentes propuestos para el tratamiento farmacológico específico de la infección por SARS-CoV-2 / Mechanisms of action of proposed agents for the specific pharmacological treatment of SARS-CoV-2 infection

Resumen Desde la notificación de la pandemia por SARS-CoV-2, agente patógeno responsable del COVID-19, muchos de los tratamientos dirigidos a su manejo han estado sometidos a estudios de manera constante, con el fin de comprobar su eficacia y seguridad. El conocimiento de su virología y etiopatogenia posibilitaría objetivar los pasos moleculares específicos que puedan ser blancos terapéuticos de variados fármacos actualmente disponibles. Esta experiencia proviene principalmente de las infecciones por SARS-CoV y MERS-CoV, con resultados variados 'in vitro' en el SARS-CoV-2, sin evidencia clínica que demuestre efectividad y seguridad de dichos tratamientos. A la fecha, no se ha podido concretar con claridad un esquema de tratamiento específico, debido a que la evidencia surgida ha puesto en jaque cada uno de los fármacos propuestos. Esto ha motivado a continuar en la búsqueda de una estrategia efectiva que permita manejar esta pandemia con la seguridad y eficacia necesaria para que el beneficio terapéutico esté por sobre los posibles efectos adversos que estos esquemas farmacológicos pudiesen presentar. La siguiente revisión pretende mostrar la evidencia disponible a la fecha, definiendo la actividad de cada fármaco en función de su mecanismo de acción.

Since the beginning of the pandemic by SARS-CoV-2, the pathogen responsible for COVID-19, many of the therapeutic options for its management have been under constant revision, in order to verify their safety and efficiency. Knowledge of the viral structure and pathogenesis make it possible to determine the molecular pathways that may be targeted with current available drugs. The experience with these drugs comes mainly from infections caused by SARS-CoV and MERS-CoV, in vitro studies with SARS-CoV-2 that yield variable results, and clinical experience that does not ensure effectiveness and safety of such drugs. To date, it has not been possible to elucidate a specific treatment scheme, because of the constant release of evidence that challenges the usefulness of the proposed drugs. This has motived us to continue seeking for an effective strategy that allows to manage this pandemic in a safe and efficient manner, so that therapeutic benefit surpasses the related adverse drug reactions that can occur. The following review aims to showcase the evidence available to date by defining the activity of each drug based on its mechanism of action.