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1.
Lancet ; 401(10380): 939-949, 2023 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-36828001

RESUMEN

BACKGROUND: People living with HIV have accounted for 38-50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3). METHODS: A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive. FINDINGS: We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30-43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117-291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100-200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance. INTERPRETATION: A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death. FUNDING: None.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Mpox , Adulto , Masculino , Humanos , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Recuento de Linfocito CD4 , Carga Viral
2.
Clin Infect Dis ; 76(7): 1311-1314, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-36370091

RESUMEN

We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox.


Asunto(s)
Mpox , Humanos , Femenino , Orofaringe , Frotis Vaginal
3.
Emerg Infect Dis ; 29(8): 1682-1684, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37486318

RESUMEN

The Chembio DPP (Dual Path Platform) Syphilis Screen & Confirm kit (https://chembio.com) is a rapid serologic test that can be used to diagnose yaws. We evaluated its capacity to detect patients with ulcers that tested PCR positive for Treponema pallidum subsp. pertenue. DPP detected 84% of ulcers that were positive by PCR.


Asunto(s)
Úlcera Cutánea , Buba , Humanos , Treponema pallidum/genética , Úlcera/diagnóstico , Buba/diagnóstico , Úlcera Cutánea/diagnóstico , Pruebas Serológicas
4.
Lancet ; 400(10353): 661-669, 2022 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-35952705

RESUMEN

BACKGROUND: In May, 2022, several European countries reported autochthonous cases of monkeypox, which rapidly spread globally. Early reports suggest atypical presentations. We aimed to investigate clinical and virological characteristics of cases of human monkeypox in Spain. METHODS: This multicentre, prospective, observational cohort study was done in three sexual health clinics in Madrid and Barcelona, Spain. We enrolled all consecutive patients with laboratory-confirmed monkeypox from May 11 to June 29, 2022. Participants were offered lesion, anal, and oropharynx swabs for PCR testing. Participant data were collected by means of interviews conducted by dermatologists or specialists in sexually transmitted infections and were recorded using a standard case report form. Outcomes assessed in all participants with a confirmed diagnosis were demographics, smallpox vaccination, HIV status, exposure to someone with monkeypox, travel, mass gathering attendance, risk factors for sexually transmitted infections, sexual behaviour, signs and symptoms on first presentation, virological results at multiple body sites, co-infection with other sexually transmitted pathogens, and clinical outcomes 14 days after the initial presentation. Clinical outcomes were followed up until July 13, 2022. FINDINGS: 181 patients had a confirmed monkeypox diagnosis and were enrolled in the study. 166 (92%) identified as gay men, bisexual men, or other men who have sex with men (MSM) and 15 (8%) identified as heterosexual men or heterosexual women. Median age was 37·0 years (IQR 31·0-42·0). 32 (18%) patients reported previous smallpox vaccination, 72 (40%) were HIV-positive, eight (11%) had a CD4 cell count less than 500 cells per µL, and 31 (17%) were diagnosed with a concurrent sexually transmitted infection. Median incubation was 7·0 days (IQR 5·0-10·0). All participants presented with skin lesions; 141 (78%) participants had lesions in the anogenital region, and 78 (43%) in the oral and perioral region. 70 (39%) participants had complications requiring treatment: 45 (25%) had a proctitis, 19 (10%) had tonsillitis, 15 (8%) had penile oedema, six (3%) an abscess, and eight (4%) had an exanthem. Three (2%) patients required hospital admission. 178 (99%) of 180 swabs from skin lesions collected tested positive, as did 82 (70%) of 117 throat swabs. Viral load was higher in lesion swabs than in pharyngeal specimens (mean cycle threshold value 23 [SD 4] vs 32 [6], absolute difference 9 [95% CI 8-10]; p<0·0001). 108 (65%) of 166 MSM reported anal-receptive sex. MSM who engaged in anal-receptive sex presented with proctitis (41 [38%] of 108 vs four [7%] of 58, absolute difference 31% [95% CI 19-44]; p<0·0001) and systemic symptoms before the rash (67 [62%] vs 16 [28%], absolute difference 34% [28-62]; p<0·0001) more frequently than MSM who did not engage in anal-receptive sex. 18 (95%) of 19 participants with tonsillitis reported practising oral-receptive sex. The median time from onset of lesions to formation of a dry crust was 10 days (IQR 7-13). INTERPRETATION: In our cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak. FUNDING: None.


Asunto(s)
Infecciones por VIH , Mpox , Proctitis , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Viruela , Tonsilitis , Adulto , Femenino , Homosexualidad Masculina , Humanos , Masculino , Monkeypox virus , Estudios Prospectivos , Conducta Sexual , España
5.
Brief Bioinform ; 22(2): 1848-1859, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-32313939

RESUMEN

The fast accumulation of biological data calls for their integration, analysis and exploitation through more systematic approaches. The generation of novel, relevant hypotheses from this enormous quantity of data remains challenging. Logical models have long been used to answer a variety of questions regarding the dynamical behaviours of regulatory networks. As the number of published logical models increases, there is a pressing need for systematic model annotation, referencing and curation in community-supported and standardised formats. This article summarises the key topics and future directions of a meeting entitled 'Annotation and curation of computational models in biology', organised as part of the 2019 [BC]2 conference. The purpose of the meeting was to develop and drive forward a plan towards the standardised annotation of logical models, review and connect various ongoing projects of experts from different communities involved in the modelling and annotation of molecular biological entities, interactions, pathways and models. This article defines a roadmap towards the annotation and curation of logical models, including milestones for best practices and minimum standard requirements.


Asunto(s)
Biología Computacional/métodos , Modelos Biológicos , Guías de Práctica Clínica como Asunto , Reproducibilidad de los Resultados
6.
J Am Acad Dermatol ; 88(5): 1066-1073, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36641010

RESUMEN

BACKGROUND: In the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. OBJECTIVE: The objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. METHODS: The American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals. RESULTS: From August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases. LIMITATIONS: Registry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity. DISCUSSION: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.


Asunto(s)
COVID-19 , Mpox , Enfermedades de la Piel , Humanos , Cicatriz , COVID-19/epidemiología , Brotes de Enfermedades , Vesícula , Progresión de la Enfermedad
7.
Bioinformatics ; 36(24): 5712-5718, 2021 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-32637990

RESUMEN

MOTIVATION: A large variety of molecular interactions occurs between biomolecular components in cells. When a molecular interaction results in a regulatory effect, exerted by one component onto a downstream component, a so-called 'causal interaction' takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g. gene regulation) need to be described with a careful appreciation of the underlying molecular reactions. A proper description of this information enables archiving, sharing and reuse by humans and for automated computational processing. Various representations of causal relationships between biological components are currently used in a variety of resources. RESULTS: Here, we propose a checklist that accommodates current representations, called the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while fostering uniformity and interoperability of the data across resources. AVAILABILITY AND IMPLEMENTATION: The checklist together with examples is accessible at https://github.com/MI2CAST/MI2CAST. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Programas Informáticos , Causalidad , Humanos
8.
J Am Acad Dermatol ; 87(6): 1278-1280, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36075281

RESUMEN

The World Health Organization declared the global monkeypox outbreak a public health emergency of international concern in July 2022. In response, the American Academy of Dermatology and International League of Dermatological Societies expanded the existing COVID-19 Dermatology Registry to become the "AAD/ILDS Dermatology COVID-19, Monkeypox, and Emerging Infections Registry." The goal of the registry is to rapidly collate cases of monkeypox and other emerging infections and enable prompt dissemination of findings to front-line healthcare workers and other members of the medical community. The registry is now accepting reports of monkeypox cases and cutaneous reactions to monkeypox/smallpox vaccines. The success of this collaborative effort will depend on active case entry by the global dermatology community.


Asunto(s)
COVID-19 , Dermatología , Mpox , Estados Unidos/epidemiología , Humanos , COVID-19/epidemiología , Sociedades Médicas , Sistema de Registros
9.
Dermatol Ther ; 33(6): e14170, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32779280

RESUMEN

A previous study has defined the maculopapular subtype of manifestations of COVID-19. The objective of our study was to describe and classify maculopapular eruptions associated with COVI-19. We carried out a subanalysis of the maculopapular cases found in the previous cross-sectional study. Using a consensus, we defined seven clinical patterns. We described patient demographics, the therapy received by the patient and the characteristics of each pattern. Consensus lead to the description of seven major maculopapular patterns: morbilliform (45.5%), other maculopapular (20.0%), purpuric (14.2%), erythema multiforme-like (9.7%), pytiriasis rosea-like (5.7%), erythema elevatum diutinum-like (2.3%), and perifollicular (2.3%). In most cases, maculopapular eruptions were coincident (61.9%) or subsequent (34.1%) to the onset of other COVID-19 manifestations. The most frequent were cough (76%), dyspnea (72%), fever (88%), and astenia (62%). Hospital admission due to pneumonia was frequent (61%). Drug intake was frequent (78%). Laboratory alterations associated with maculo-papular eruptions were high C-reactive protein, high D-Dimer, lymphopenia, high ferritin, high LDH, and high IL-6. The main limitation of our study was the impossibility to define the cause-effect relationship of each pattern. In conclusion, we provide a description of the cutaneous maculopapular manifestations associated with COVID-19. The cutaneous manifestations of COVID-19 are wide-ranging and can mimic other dermatoses.


Asunto(s)
COVID-19/virología , SARS-CoV-2/patogenicidad , Enfermedades Cutáneas Virales/virología , Piel/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , COVID-19/complicaciones , COVID-19/diagnóstico , Estudios Transversales , Femenino , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , SARS-CoV-2/efectos de los fármacos , Piel/patología , Enfermedades Cutáneas Virales/diagnóstico , España , Adulto Joven , Tratamiento Farmacológico de COVID-19
11.
Actas Esp Psiquiatr ; 46(6): 217-25, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30552811

RESUMEN

INTRODUCTION: Despite the high prevalence of sexual dysfunction in patients with schizophrenia, its origins are still unclear. THE AIM OF THIS STUDY: to determine the prevalence and causal factors of sexual dysfunction in a group of outpatients with schizophrenia. METHODS: The study was designed to be cross-sectional and naturalistic, including outpatients with schizophrenia undergoing second generation antipsychotic monotherapy. Patients receiving antidepressants and/or mood stabilisers were excluded. The following data were recorded: sexual functionality, sociodemographic information, sexual history, psychotic and depressive psychopathology, metabolic syndrome and BMI. Psychotropic-Related Sexual Dysfunction Questionnaire (PR SexDQ-Salsex); Positive and Negative Syndrome Scale; Hamilton Depression Rating Scale; Plasma concentrations of prolactin, testosterone, estradiol, progesterone and the International Diabetes Federation diagnostic criteria for metabolic syndrome, were used to complete the study. RESULTS: Of the 57 patients included in the study, 80% exhibited sexual dysfunction, one-third of which suffered severe levels of dysfunction. However, only 30% of patients spontaneously reported this problem. Although there were significant differences in the prevalence of hyperprolactinemia and metabolic syndrome according to the antipsychotic received, multivariant regression analysis did not show a correlation between sexual dysfunction and prolactin, sexual hormones, type of antipsychotic received, psychotic psychopathology or metabolic syndrome. Sexual dysfunction was only associated with age, civil status and depressive psychopathology. CONCLUSIONS: There is a high prevalence of sexual dysfunction in the patients with schizophrenia who participated in the study, but it was only associated with higher age, being single or divorced or having depressive psychopathology; this suggests a multifactorial etiology for sexual dysfunction in schizophrenia.


Asunto(s)
Antipsicóticos/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Psicológicas/epidemiología , Disfunciones Sexuales Psicológicas/etiología , Adulto , Estudios Transversales , Femenino , Humanos , Hiperprolactinemia/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Esquizofrenia/sangre , Adulto Joven
13.
Annu Rev Physiol ; 73: 135-62, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21054169

RESUMEN

Synthetic chemicals currently used in a variety of industrial and agricultural applications are leading to widespread contamination of the environment. Even though the intended uses of pesticides, plasticizers, antimicrobials, and flame retardants are beneficial, effects on human health are a global concern. These so-called endocrine-disrupting chemicals (EDCs) can disrupt hormonal balance and result in developmental and reproductive abnormalities. New in vitro, in vivo, and epidemiological studies link human EDC exposure with obesity, metabolic syndrome, and type 2 diabetes. Here we review the main chemical compounds that may contribute to metabolic disruption. We then present their demonstrated or suggested mechanisms of action with respect to nuclear receptor signaling. Finally, we discuss the difficulties of fairly assessing the risks linked to EDC exposure, including developmental exposure, problems of high- and low-dose exposure, and the complexity of current chemical environments.


Asunto(s)
Diabetes Mellitus Tipo 2/inducido químicamente , Disruptores Endocrinos/toxicidad , Exposición a Riesgos Ambientales , Contaminantes Ambientales/toxicidad , Síndrome Metabólico/inducido químicamente , Obesidad/inducido químicamente , Animales , Disruptores Endocrinos/análisis , Disruptores Endocrinos/química , Contaminantes Ambientales/análisis , Contaminantes Ambientales/química , Femenino , Humanos , Masculino , Ratones , Ratas , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal/efectos de los fármacos
14.
Lancet Infect Dis ; 24(4): 404-416, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38211601

RESUMEN

BACKGROUND: Management of syphilis, a sexually transmitted infection (STI) with increasing incidence, is challenged by drug shortages, scarcity of randomised trial data, an absence of non-penicillin alternatives for pregnant women with penicillin allergy (other than desensitisation), extended parenteral administration for neurosyphilis and congenital syphilis, and macrolide resistance. Linezolid was shown to be active against Treponema pallidum, the causative agent of syphilis, in vitro and in the rabbit model. We aimed to assess the efficacy of linezolid for treating early syphilis in adults compared with the standard of care benzathine penicillin G (BPG). METHODS: We did a multicentre, open-label, non-inferiority, randomised controlled trial to assess the efficacy of linezolid for treating early syphilis compared with BPG. We recruited participants with serological or molecular confirmation of syphilis (either primary, secondary, or early latent) at one STI unit in a public hospital and two STI community clinics in Catalonia (Spain). Participants were randomly allocated in a 1:1 ratio using a computer-generated block randomisation list with six participants per block, to receive either oral linezolid (600 mg once per day for 5 days) or intramuscular BPG (single dose of 2·4 million international units) and were assessed for signs and symptoms (once per week until week 6 and at week 12, week 24, and week 48) and reagin titres of non-treponemal antibodies (week 12, week 24, and week 48). The primary endpoint was treatment response, assessed using a composite endpoint that included clinical response, serological response, and absence of relapse. Clinical response was assessed at 2 weeks for primary syphilis and at 6 weeks for secondary syphilis following treatment initiation. Serological cure was defined as a four-fold decline in rapid plasma reagin titre or seroreversion at any of the 12-week, 24-week, or 48-week timepoints. The absence of relapse was defined as the presence of different molecular sequence types of T pallidum in recurrent syphilis. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference in rates of treatment response was higher than -10%. The primary analysis was done in the per-protocol population. The trial is registered at ClinicalTrials.gov (NCT05069974) and was stopped for futility after interim analysis. FINDINGS: Between Oct 20, 2021, and Sept 15, 2022, 62 patients were assessed for eligibility, and 59 were randomly assigned to linezolid (n=29) or BPG (n=30). In the per-protocol population, after 48 weeks' follow-up, 19 (70%) of 27 participants (95% CI 49·8 to 86·2) in the linezolid group had responded to treatment and 28 (100%) of 28 participants (87·7 to 100·0) in the BPG group (treatment difference -29·6, 95% CI -50·5 to -8·8), which did not meet the non-inferiority criterion. The number of drug-related adverse events (all mild or moderate) was similar in both treatment groups (five [17%] of 29, 95% CI 5·8 to 35·8 in the linezolid group vs five [17%] of 30, 5·6 to 34·7, in the BPG group). No serious adverse events were reported during follow-up. INTERPRETATION: The efficacy of linezolid at a daily dose of 600 mg for 5 days did not meet the non-inferiority criteria compared with BPG and, as a result, this treatment regimen should not be used to treat patients with early syphilis. FUNDING: European Research Council and Fondo de Investigaciones Sanitarias.


Asunto(s)
Penicilina G Benzatina , Sífilis , Adulto , Humanos , Antibacterianos , Farmacorresistencia Bacteriana , Linezolid/uso terapéutico , Macrólidos/farmacología , Penicilina G Benzatina/uso terapéutico , Estudios Prospectivos , Reaginas , Recurrencia , España , Sífilis/tratamiento farmacológico , Resultado del Tratamiento
15.
P R Health Sci J ; 42(1): 70-76, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36941102

RESUMEN

OBJECTIVE: Currently, in Puerto Rico, there is a paucity of data regarding emotional health and depression in health professionals, specifically regarding trainees such as medical students and nursing students. The study intended to shed light on the prevalence of depression symptoms among medical and nursing students at a school of medicine in Puerto Rico. METHODS: In the fall of 2019, a descriptive cross-sectional study that included nursing and medical students in their first, second, and third years was performed. A survey consisting of the Patient Health Questionnaire (PHQ-9) and sociodemographic questions were used for data collection. Logistic regression analyses were used to determine the association of PHQ-9 scores and the risk factors linked to depression symptoms. RESULTS: A total of 173 (83.2%) out of 208 enrolled students participated in the study. Of the participants, 75.7% were medical students and 24.3% were nursing students. Of the risk factors studied, feelings of regret and lack of sleep were associated with a higher frequency of depression symptoms in medical students. For the nursing student population, suffering from a chronic disease was associated with a higher frequency of depression symptoms. CONCLUSION: Due to the increased risk of depression in healthcare professionals, identifying risk factors that can be addressed through early changes in behavior, or in institutional policies, is important in terms of working to mitigate the risk of mental health problems in this vulnerable population.


Asunto(s)
Estudiantes de Medicina , Estudiantes de Enfermería , Humanos , Depresión/epidemiología , Estudios Transversales , Estudiantes de Enfermería/psicología , Prevalencia , Factores de Riesgo , Estudiantes de Medicina/psicología
16.
EClinicalMedicine ; 57: 101898, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36936402

RESUMEN

Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

17.
Lancet Infect Dis ; 23(4): 445-453, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36521505

RESUMEN

BACKGROUND: Monkeypox DNA has been detected in skin lesions, saliva, oropharynx, urine, semen, and stool of patients infected during the 2022 clade IIb outbreak; however, the viral dynamics within these compartments remain unknown. We aimed to characterise the viral load kinetics over time in various parts of the body. METHODS: This was an observational, prospective, multicentre study of outpatients diagnosed with monkeypox in two hospitals and two sexual health clinics in Spain between June 28, 2022, and Sept 22, 2022. Men and women aged over 18 years were eligible if they reported having symptom onset within the previous 10 days of presentation, and were ineligible if disease was severe enough to be admitted to hospital. Samples were collected from five body locations (skin lesions, oropharynx, rectum, semen or vagina, and a dried blood spot) at six time points up to 57 days after the screening visit. Samples were analysed by quantitative PCR and a subset by cell culture. The primary endpoint was time from symptom onset to viral DNA clearance. FINDINGS: Overall, 1663 samples were collected from 77 study participants. 75 (97%) participants were men, the median age was 35·0 years (IQR 29·0-46·0), and 39 (51%) participants were living with HIV. The median time from symptom onset to viral clearance was 25 days (95% CI 23-28) in the skin lesions, 16 days (13-19) in the oropharynx, 16 days (13-23) in the rectum, 13 days in semen (9-18), and 1 day in blood (0-5). The time from symptom onset to viral clearance for 90% of cases was 41 days (95% CI 34-47) in skin lesions and 39 days (27-56) in semen. The median viral load in skin lesions was 7·3 log10 copies per mL (IQR 6·5-8·2) at baseline, compared with 4·6 log10 copies per mL (2·9-5·8) in oropharyngeal samples, 5·0 log10 copies per mL (2·9-7·5) in rectal samples, 3·5 log10 copies per mL (2·9-4·7) in semen samples, and 4·0 log10 copies per mL (4·0-4·0) in blood specimens. Replication-competent viruses were isolated in samples with high DNA levels (>6·5 log10 copies per mL). INTERPRETATION: In immunocompetent patients with mild monkeypox disease, PCR data alone would suggest a contact isolation period of 3 to 6 weeks but, based on detection of replication-competent virus, this time could be reduced. Based on findings from this cohort of patients, semen testing and prolonged use of condoms after recovery from monkeypox might not be necessary. FUNDING: University Hospital Germans Trias i Pujol and the YoMeCorono. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.


Asunto(s)
Mpox , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Estudios Prospectivos , España/epidemiología , Semen , Saliva , Carga Viral
18.
Eur J Dermatol ; 32(6): 731-735, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36856392

RESUMEN

Background: "Convive con el Sol" (Living with the sun) is an educational programme to promote education about sun exposure and healthy photoprotection habits among Spanish children. Objectives: This study evaluated the effects of the "Convive con el Sol" school-based sun protection programme on the sun safety habits, attitudes, knowledge, and practices in preschool and first-year primary school students. Materials & Methods: A quasi-experimental pilot study was established with a pre-test/post-test design and without a control group to evaluate the efficacy of the "Convive con el Sol" programme in children aged 3-8 years. Two questionnaires were used to evaluate the programme: the CHRESI questionnaire and the SolSano questionnaire. Results: Seven educational centres participated in the study. The number of completed baseline questionnaires was 351 for the CHRESI survey and 226 for the SolSano survey. After the intervention, the students improved their sun protection practices; fewer students went to the beach or swimming-pool at noon (9.8% vs 5.5%; p = 0.03), and more schoolchildren used cream with an SPF rating >15 (37.6% vs 76.2%; p <0.01) and repeatedly applied sunscreen if continuously exposed (67.4% vs 82.7%; p <0.01). Conclusion: Our findings show that the "Convive con el Sol" educational intervention improved photoprotection practices in children aged 3-8 years, but did not reduce the percentage of sunburned children. This pilot study serves as a starting point for designing educational interventions, targeting students, teachers, and families.


Asunto(s)
Estudiantes , Niño , Preescolar , Humanos , Escolaridad , Proyectos Piloto , Instituciones Académicas
19.
Database (Oxford) ; 20222022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35411389

RESUMEN

SwissBioPics (www.swissbiopics.org) is a freely available resource of interactive, high-resolution cell images designed for the visualization of subcellular location data. SwissBioPics provides images describing cell types from all kingdoms of life-from the specialized muscle, neuronal and epithelial cells of animals, to the rods, cocci, clubs and spirals of prokaryotes. All cell images in SwissBioPics are drawn in Scalable Vector Graphics (SVG), with each subcellular location tagged with a unique identifier from the controlled vocabulary of subcellular locations and organelles of UniProt (https://www.uniprot.org/locations/). Users can search and explore SwissBioPics cell images through our website, which provides a platform for users to learn more about how cells are organized. A web component allows developers to embed SwissBioPics images in their own websites, using the associated JavaScript and a styling template, and to highlight subcellular locations and organelles by simply providing the web component with the appropriate identifier(s) from the UniProt-controlled vocabulary or the 'Cellular Component' branch of the Gene Ontology (www.geneontology.org), as well as an organism identifier from the National Center for Biotechnology Information taxonomy (https://www.ncbi.nlm.nih.gov/taxonomy). The UniProt website now uses SwissBioPics to visualize the subcellular locations and organelles where proteins function. SwissBioPics is freely available for anyone to use under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. DATABASE URL: www.swissbiopics.org.


Asunto(s)
Proteínas , Vocabulario Controlado , Animales
20.
Transplant Proc ; 53(9): 2685-2687, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34629188

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has especially affected kidney transplant (KT) recipients, who are more vulnerable than the general population because of their immunosuppressive status and added comorbidities. The purpose of this study was to determine risk factors related to infection and mortality from COVID-19 in KT recipients. METHODS: The study included 113 stable KT recipients who had polymerase chain reaction-confirmed COVID-19 infection between March 2020 and February 2021, from a total of 2150 KT recipients. Outcomes related to patient survival were analyzed. RESULTS: The mean (standard deviation) age of the patients was 56 (14) years; 62% (n = 70) were men. The median time between KT and infection was 88 months (interquartile range, 39-155 months); 90% (n = 102) were on tacrolimus therapy and 81% (n = 92) on mycophenolate mofetil. The clinical presentation was pneumonia (n = 57; 51%), fever (n = 61; 54%), cough (n = 62; 55%), dyspnea (n = 43; 38%), lymphopenia (n = 57; 50%), and gastrointestinal symptoms (n = 28; 25%). A total of 21% (n = 24) required intubation and intensive care unit admission, and 27 patients (25%) were asymptomatic. A total of 9% (n = 10) received hydroxychloroquine therapy plus azithromycin, 11% (n = 12) tocilizumab, 3.7% (n = 4) lopinavir/ritonavir, 49% (n = 55) steroids, 0.9% (n = 1) remdesivir, and 9.3% (n = 11) convalescent plasma. Immunosuppression was reduced in all symptomatic patients. Nineteen patients (17%) died. Cox univariate analysis showed that the factors significantly associated with death were patient age, presence of pneumonia or lymphopenia, and elevated C-reactive protein on admission. CONCLUSIONS: Mortality in KT recipients with COVID-19 is very high, more than for the general population. Risk factors are patient age, presence of pneumonia or lymphopenia, and a higher C-reactive protein level at the time of diagnosis.


Asunto(s)
COVID-19 , Trasplante de Riñón , COVID-19/terapia , Humanos , Inmunización Pasiva , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Riesgo , SARS-CoV-2 , España/epidemiología , Receptores de Trasplantes , Sueroterapia para COVID-19
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