Desempeño de la definición de caso sospechoso de influenza antes y durante la pandemia por COVID-19 / Performance of the case definition of suspected influenza before and during the COVID-19 pandemic

Objetivos Este estudio tuvo como objetivo evaluar el desempeño, antes y durante la pandemia de la COVID-19, de la definición de caso de sospecha de influenza en la vigilancia comunitaria en México. Métodos Se llevó a cabo un análisis transversal de un estudio de cohorte y, con el fin de confirmar o descartar la infección por virus influenza, se analizaron los casos que cumplían con los criterios de caso sospechoso (n = 20.511) y con evidencia concluyente de laboratorio (reacción cuantitativa en cadena de la polimerasa en tiempo real). Resultados Se documentaron una alta sensibilidad y una discreta especificidad, que posteriormente disminuyó, así como su precisión diagnóstica, durante el brote de la COVID-19. Sin embargo, no se observaron diferencias en el área bajo la curva de características operativas del receptor entre los períodos analizados. Conclusión La definición de caso evaluada sigue siendo una alternativa rentable para identificar a los pacientes que pueden beneficiarse de los medicamentos antivirales específicos contra la influenza, incluso durante el brote mundial de COVID-19 (AU)

Objective This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. Methods A cross-sectional analysis of a cohort study was perfomed and cases that met the suspected case criteria (n = 20,511) and that had laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection, were analysed. Results A high sensitivity and modest specificity were documented, which later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics curve among the analysed periods. Conclusion The evaluated case definition remains to be a cost-effective alternative for identifying patients who may benefit from influenza-specific antiviral drugs, even during the global COVID-19 outbreak (AU)

Performance of the case definition of suspected influenza before and during the COVID-19 pandemic.

OBJECTIVE: This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. METHODS: A cross-sectional analysis of a cohort study was performed and cases that met the suspected case criteria (n = 20,511) and that had laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection were analysed. RESULTS: A high sensitivity and modest specificity were documented, which later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics curve among the analysed periods. CONCLUSIONS: The evaluated case definition remains to be a cost-effective alternative for identifying patients who may benefit from influenza-specific antiviral drugs, even during the global COVID-19 outbreak.

Survival in adult pneumonia inpatients fulfilling suspected COVID-19 criteria and baseline negative RT-qPCR.

OBJECTIVES: The objective of this study was to evaluate the survival experience of suspicion COVID-19 hospitalized patients with pneumonia and negative baseline reverse-transcription quantitative polymerase chain reaction (RT-qPCR) test results. STUDY DESIGN: We conducted a nationwide retrospective cohort study in Mexico. METHODS: Adult pneumonia inpatients fulfilling suspected COVID-19 criteria, and hospital entry from March to August 2020, were enrolled. The Kaplan-Meier method was to use to compare survival estimates among patients with negative RT-qPCR nasopharyngeal or oropharyngeal swabs and those with a baseline positive test. RESULTS: Data from 64,624 individuals fulfilling suspected COVID-19 criteria were analyzed and 1.6% of them had negative RT-qPCR tests. The overall mortality rate was higher among laboratory-positive patients (48.5% vs. 34.2%, P < 0.001) and, at any given threshold, the survival estimates were higher among RT-qPCR-negative pneumonia inpatients. CONCLUSIONS: The pathogenic mechanism of COVID-19 remains poorly understood and suspected cases with pneumonia and negative laboratory results represent a major challenge for healthcare systems. Our findings suggest that RT-qPCR-negative inpatients may have an improved disease prognosis, but the in-hospital mortality was still high among them. However, further research is needed to clarify the clinical and epidemiological implications of our results.

Predictors of severe symptomatic laboratory-confirmed SARS-CoV-2 reinfection.

OBJECTIVE: The aim of the study was to evaluate factors predicting severe symptomatic laboratory-confirmed (via Reverse transcription polymerase chain reaction, RT-PCR polymerase chain reaction) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. STUDY DESIGN: This is a nationwide retrospective cohort study that was conducted in Mexico. METHODS: Data from 258 reinfection cases (at least 28 days between both episodes onset) were analyzed. We used risk ratios (RRs) and 95% confidence intervals (CIs) to evaluate predictors of severe (dyspnea requiring hospital admission) secondary SARS-CoV-2 infection. RESULTS: The risk of severe disease was 14.7%, and the observed overall fatality rate was 4.3%. Patients with more serious primary disease were more likely to develop severe symptoms (39.5% vs. 5.5%, P < 0.001) during reinfection. In multiple analysis, factors associated with an increased risk of severe symptomatic SARS-CoV-2 reinfection were increasing age (RRper year = 1.007, 95% CI = 1.003-1.010), comorbidities (namely, obesity [RR = 1.12, 95% CI = 1.01-1.24], asthma [RR = 1.26, 95% CI = 1.06-1.50], type 2 diabetes mellitus [RR = 1.22, 95% CI = 1.07-1.38]), and previous severe laboratory-confirmed coronavirus disease 2019 (RR = 1.20, 95% CI = 1.03-1.39). CONCLUSIONS: To the best of our knowledge, this is the first study evaluating disease outcomes in a large set of laboratory-positive cases of symptomatic SARS-CoV-2 reinfection, and factors associated with illness severity were characterized. Our results may contribute to the current knowledge of SARS-CoV-2 pathogenicity and to identify populations at increased risk of a poorer outcome after reinfection.

Survival in adult inpatients with COVID-19.

BACKGROUND: The mortality of the coronavirus disease 2019 (COVID-19) pandemic is high, and data regarding its prognosis are scarce. We aimed to assess the survival experience and determining factors in adult inpatients with laboratory-confirmed COVID-19. METHODS: We conducted a nationwide and retrospective cohort study. Data from 66,123 individuals were analyzed using the Kaplan-Meier method, and a multivariate Cox proportional hazard regression model was fitted. RESULTS: The 7-day survival was 72.2% and went to 47.6%, 35.0%, and 23.9% on days 15, 21, and 30 of hospital stay, respectively. In the multiple analysis, factors associated with an increased risk of dying were male gender, age, pneumonia at hospital admission, immunosuppression, and personal history of chronic non-communicable diseases. Reduced risk of a fatal outcome was observed among patients with asthma history. CONCLUSIONS: To the best of our knowledge, this is the largest study analyzing the survival probability in a large subset of Latin-American adults with COVID-19, in whom the disease burden has been high. Our results contribute to achieving a better understanding of disease evolution.

[Performance of the case definition of suspected influenza before and during the COVID-19 pandemic]. / Desempeño de la definición de caso sospechoso de influenza antes y durante la pandemia por COVID-19.

OBJECTIVE: This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. METHODS: A cross-sectional analysis of a cohort study was perfomed and cases that met the suspected case criteria (n = 20,511) and that had laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection, were analysed. RESULTS: A high sensitivity and modest specificity were documented, which later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the area under the receiver operating characteristics curve among the analysed periods. CONCLUSION: The evaluated case definition remains to be a cost-effective alternative for identifying patients who may benefit from influenza-specific antiviral drugs, even during the global COVID-19 outbreak.

Predictors of laboratory-positive COVID-19 in children and teenagers.

OBJECTIVE: The aim of the study was to identify factors predicting laboratory-positive coronavirus disease 2019 (COVID-19) in pediatric patients with acute respiratory symptoms. STUDY DESIGN: We conducted a cross-sectional analysis of a prospective cohort study. METHODS: Data from 1849 individuals were analyzed. COVID-19 was confirmed (reverse transcription-quantitative polymerase chain reaction) in 15.9% of patients, and factors predicting a positive test result were evaluated through prevalence odds ratios and 95% confidence intervals. RESULTS: Increasing age, personal history of obesity, and household contact with a case were found to be associated, in the multiple regression model, with increased odds of a positive test result. Young patients residing in areas with higher population sizes, as well as those with severe respiratory symptoms, were less likely to be laboratory confirmed. CONCLUSIONS: Early identification and isolation of children and teenagers with suggestive symptoms of COVID-19 is important to limit viral spread. We identified several factors predicting the laboratory test result. Our findings are relevant from a public health policy perspective, particularly after the restart of in-person academic activities.

Measuring HIV vaccine efficacy.

Some HIV vaccine candidates have a potential VE I (vaccine efficacy for infectiousness) type effect, which tends to reduce the viral load and may reduce infectiousness of an infected individual. In general, the efficacy of this kind of vaccine is very difficult to assess because it requires information on contacts of vaccinated infected individuals, and current methods to estimate VE I rely on the time elapsed between infections of an individual and his/her sexual partner, thus making infection of the sexual partner necessary to assess the efficacy. To avoid behavioural changes that may affect the estimates, HIV status is kept undisclosed to participants, which raises many ethical questions. Here we present a method that allows immediate notification of HIV status to both members of a couple, reducing the risk of infection when one of them has not been infected and allowing immediate medical treatment. The method allows for estimation of any VE I and VE S (vaccine efficacy for susceptibility) effect, and it is robust to the most common situations found in these type of studies, namely: differential risk of participants, staggered enrollment and small sample sizes.

Risk and protective factors associated with youth violence among secondary school students in a nationally representative sample in Puerto Rico

During the past decade, youth violence has received increasing attention as a major public health issue in Puerto Rico as well as in the United States. This study sought to identify risk and protective factors of youth violence in a representative sample of school adolescents in Puerto Rico. Risk and protective factors were grouped into five domains: individual, family, peer group, school and community. From a total of 2,385 participants, 10.7 reported at least one violent behavior and 3.4 reported two or more violent behaviors. In multiple regression analysis the risk factors identified were male gender, junior grade students, having a favorable attitude towards antisocial behavior, use of ecstasy, involvement with antisocial peers and reporting antisocial parents. Participation in family decisions was the only protective factor associated with violence. Findings from this study could have important implications for the development of preventive programs for the adolescent population in Puerto Rico

Risk and protective factors associated with youth violence among secondary school students in a nationally representative sample in Puerto Rico.

During the past decade, youth violence has received increasing attention as a major public health issue in Puerto Rico as well as in the United States. This study sought to identify risk and protective factors of youth violence in a representative sample of school adolescents in Puerto Rico. Risk and protective factors were grouped into five domains: individual, family, peer group, school and community. From a total of 2,385 participants, 10.7% reported at least one violent behavior and 3.4% reported two or more violent behaviors. In multiple regression analysis the risk factors identified were male gender, junior grade students, having a favorable attitude towards antisocial behavior, use of ecstasy, involvement with antisocial peers and reporting antisocial parents. Participation in family decisions was the only protective factor associated with violence. Findings from this study could have important implications for the development of preventive programs for the adolescent population in Puerto Rico.

[Factors that modify the larval indices of Aedes aegypti in Colima, Mexico]. / Factores que modifican los índices larvarios de Aedes aegypti en Colima, México.

OBJECTIVE: In order to investigate the variables that could have the greatest impact on larval indices of Aedes aegypti, the main vector of dengue, a descriptive, longitudinal study was carried out in the city of Colima, which is located in the Mexican Pacific coastal state of the same name. METHODS: A total of 187 dwellings were inspected to determine the house index (HI) and the number of positive containers per house (C+/H), during the rainy season and the dry season. The following were recorded as independent variables: the air temperature, the season, the use of ultra low volume (ULV) spraying of malathion, the Premise Condition Index (PCI), and the score on a survey of knowledge, attitudes, and practices (KAP). RESULTS: Both the multivariate logistic regression and the multivariate lineal regression showed a reduction of HI and C+/H due to the effect of the dry season. Paradoxically, the temperature seemed to have a negative correlation with the larval indices, and this effect was more pronounced during the dry season. The PCI showed the most significant correlation with HI and C+/H, independently of the other variables. The ULV sprayings showed a small negative effect on the indices, while the KAP score did not indicate any association at all. CONCLUSIONS: Some conclusions that can be drawn from this study are as follows: higher temperatures can reduce the larval indices during the dry season, the PCI can be an adequate estimator of the Ae. aegypti infestation rate, ULV spraying reduces the number of larval breeding sites, and the KAP score has little association with the larval indices.

A note on the distribution of the number of vaccinated infected under non-random mixing conditions.

A common situation in vaccine efficacy (VE) estimation is dealing with non-randomly mixing populations, which may subject vaccinated and unvaccinated individuals to a different infection pressure. These conditions may lead to a bias in VE estimates. The derivation of the statistical distribution of the number of vaccinated and infected out of a sample of n infections in a VE trial is essential to develop estimates and their properties. For randomly mixing populations, it has been shown recently that this follows a hypergeometric distribution for 'all/nothing' vaccines, whereas it is a non-central hypergeometric distribution for 'leaky' ones. Here it is shown that these distributions still hold under non-random mixing conditions, provided that mixing preferences and contact rates are independent of vaccination status. These conditions are met when vaccine and placebo are randomized.

Urn models and vaccine efficacy estimation.

We derive the distribution of the number of infections among unvaccinated and vaccinated individuals for model 1 (leaky) and model 2 (all/nothing) vaccines, assuming random mixing of a homogeneous population. For all/nothing vaccines, we show that the distribution of the number of infected vaccinated individuals conditioning on n observed infections follows a hypergeometric distribution, and the vaccine efficacy estimate (VE) can be derived from the usual estimate of the total population size in a capture-recapture sampling program. For leaky vaccines, we show that the number of vaccinated infected follows a distribution that was first derived by Wallenius. We found that the current point estimates of VE for each model perform very well, but the urn model construction presented here provides a strong framework for estimation and hypothesis testing on the parameters, and can be applied when the available data are a sample of the population. Since the method does not require an underlying transmission model, it can be applied to estimate the VE for non-contagious diseases.

A basic result on the integral for birth-death Markov processes.

In this paper a regenerative argument is used to derive an expression for the expectation of the integral under the stochastic path of a birth-death Markov process up to extinction time as well as for the expected time to extinction. Some applications to classical-birth-death processes are given.

NGF prevents changes in rat brain glutathione-related enzymes following transection of the septohippocampal pathway.

The activities of the enzymes glutathione reductase (GRD), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were studied in several rat brain areas following the aspirative transection of the septohippocampal pathway (fimbria fornix) and the administration of nerve growth factor (NGF) or cytochrome c. One group of animals remained untreated. This lesion resulted in a decreased hippocampal GRD and septal GST activities, as well as, in an increase in GPX activity from the frontal cortex, striatum, and septum. NGF prevented the lesion-induced changes in hippocampal GRD and septal GPX. These findings show that the insult resulting from the aspiration of the fimbria fornix bundle involves modifications in glutathione-related enzymes, and, therefore, in the antioxidant status of brain tissue. These changes in glutathione metabolism could be a consequence of the oxidative damage to GRD and GST proteins or represent a compensatory response of GPX to the oxidative threat The restoring effects of NGF on altered enzyme activities are possibly linked to its known neuroprotective action.

Threshold parameters and metapopulation persistence.

A method is presented to estimate the minimum viable metapopulation size based on the basic reproductive number R(0) and the expected time to extinction tau(E) for epidemiological models. We exemplify our approach with two simple deterministic metapopulation models of the patch occupancy type and then proceed to stochastic versions that permit the estimation of the minimum viable metapopulation size.

Effects of nerve growth factor on brain glutathione-related enzymes from aged rats.

Neurotrophins, like the nerve growth factor (NGF), trigger a variety of biological effects in their targets. Stimulating effects on antioxidant defenses have been postulated to underlie neurotrophic influence on neuron survival and maintenance. To test whether NGF is capable of inducing changes in glutathione-related enzymes in the aged cognitively impaired brain, glutathione reductase (GRD), glutathione S-transferase (GST) and total glutathione peroxidase (GPX) activities were measured in the striatum, septum, hippocampus and frontal cortex of four Sprague-Dawley rat groups: young (2 months old), aged (20 months old) untreated, aged cytochrome c-treated, and aged NGF-treated (icv delivery, 34 micrograms during 28 days). All the aged rats utilized in the study were memory impaired according to their performance in the Morris water maze test. These aged rats showed increases in the activities of septal and hippocampal GST, as well as, in the hippocampal, striatal and cortical GPX. These increases could be interpreted as compensatory responses to cope with the oxidative damage that has been accumulated by the aged brain. The increases in hippocampal and cortical GPX activity were attenuated by NGF treatment, whereas the neurotrophin induced an increase in GRD activity in the striatum of aged rats. These results point out GRD and GPX as possible targets of the neurotrophic effects.

[Short-term effects of septo-hippocampal pathway transsection and cerebrolysin effects on glutathione-related enzymes in the rat brain]. / Efectos a corto plazo de la transección de la vía septohipocampal y del cerebrolysin sobre enzimas del sistema del glutatión en el cerebro de ratas.

INTRODUCTION: The cholinergic neurones of the basal forebrain play an important part in cognitive activity and axotomy of these neurones leads to their retrograde atrophy. The nootropic drug, Cerebrolysin, can protect these neurones from neurodegeneration induced by axotomy. Oxidative damage to biomolecules often occurs in neurodegenerative processes. OBJECTIVE: To determine whether transection of the septohippocampal bundle (fimbria-fornix, FF) and administration of Cerebrolysin induce alterations in antioxidant mechanisms. MATERIAL AND METHODS: Four groups of rats were studied: Healthy, treated with physiological saline; healthy treated with Cerebrolysin (2.5 ml/kg daily for one week, intraperitoneally); FF-lesioned and pretreated with physiological saline, and with lesions and pretreated with Cerebrolysin. Twenty four hours after the lesion was produced, the activity of the enzymes glutathione S-transferase (GST), glutathione reductase (GRD) and glutathione peroxidase were measured in various cerebral areas. RESULTS: The lesion caused reduced activity of the three enzymes in the hippocampus, and also in the activity of striatal GRD. Pretreatment with Cerebrolysin did not modify the enzymes in FF-lesioned rats, but did reduce the activity of hippocampal GST in healthy rats. CONCLUSIONS: The results show the sensitivity of enzyme of the glutathione system to denervation of the hippocampus, together with a modest effect of Cerebrolysin in this experimental paradigm.

Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol B-17. Five-year observations concerning lobular carcinoma in situ.

BACKGROUND: Extant information reveals inconsistencies concerning the natural history, pathologic features, and treatment of lobular carcinoma in situ (LCIS) of the breast. It is uncertain whether these are related to the methods of study, diagnostic criteria employed, relative paucity of cases, or varying lengths of follow-up. METHODS: The cohort was comprised of 182 women with LCIS who were enrolled in National Surgical Adjuvant Breast Project (NSABP) Protocol B-17 but received no treatment other than lumpectomy. Nineteen pathologic features were assessed and related to ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR) at a mean time on study of 5 years. RESULTS: Thirteen IBTR and 4 CBTR, including 1 instance of bilateral recurrence, were observed. All IBTR occurred in the same quadrant as the index LCIS. All 4 (2.2%) IBTR that were invasive cancers were of the lobular type, as was 1 of the 2 (1.1%) CBTR that were invasive. The other was a mucinous carcinoma. Three (1.6%) IBTR were pure ductal carcinoma in situ (DCIS) and another was accompanied by LCIS. One instance of CBTR was also comprised of DCIS and LCIS. The remaining five IBTR and one CBTR were LCIS only. The only pathologic parameter found to be significantly predictive for invasive IBTR and DCIS was type 3 and, to a lesser extent, type 2 LCIS. Some heretofore unrecognized or little appreciated pathologic features of LCIS are noted. Ancillary histochemical findings strongly implicate the derivation of LCIS from ductal or secretory cells rather than "new cells" or myoepithelial elements. All examples tested were found to be c-erb B-2 negative, universally diploid with normoproliferative DNA content, and estrogen receptor and progesterone receptor positive. No other events related to the breast were encountered. CONCLUSIONS: The number of events observed in this large cohort of patients with LCIS is markedly less than that noted by others after a comparable period of follow-up. Possible reasons for this dichotomy, including differences in patient characteristics, diagnostic criteria, and status of resection margins, are discussed. Considerations are also offered to support the view that LCIS may exhibit precursor activity as well as represent a risk factor (the term marker is literally inaccurate). In this light, the designation LCIS rather than lobular neoplasia is preferred. These preliminary findings and historical information presented in this study fail to provide any reason to perform mastectomy on patients with LCIS.