[Association between the type of major duodenal papilla and difficult biliary cannulation in a private tertiary center]. / Asociación entre el tipo de papila duodenal mayor y canulación biliar difícil en centro terciario privado.

INTRODUCTION: Difficult cannulation in cases of endoscopic retrograde cholangiopancreatography (ERCP) could be associated with several factors, including: type of major papilla, however, there are limited data regarding this possible association. OBJECTIVES: To determine the association between the type of papilla and difficult biliary cannulation. MATERIALS AND METHODS: A retrospective cross-sectional analytical study was conducted in patients over 18 years old who underwent ERCP on papilla naive, from July 2019 to April 2021, in a private institution. Unsuccessful cannulations were excluded. The papilla was classified based on Haraldsson classification. The crude association and adjusted for possible confounders between the type of papilla and difficult cannulation was evaluated. Relative risks (RR) and 95% confidence intervals were calculated. RESULTS: 188 patients were included. The mean age was 55 years, 66% female. The most frequent indication was choledocholithiasis with 88.5%. The most frequent type of major duodenal papilla was type 1 (32%), followed by type 3 (27%), type 2 (25%) and type 4 (16%). Type 2, 3, 4 papillae showed a significant relationship with difficult cannulation compared to type 1 (p<0.001, p<0.001 and p=0.008 respectively). The indication other than choledocholithiasis also showed a significant relationship with difficult cannulation (p<0.001). In the adjusted analysis, the RR for difficult cannulation compared to type 1 papilla was: 2.51 (95% CI 1.23-5.94) for type 2 papilla, 3.72 (95% CI 1.79-7.71) for papilla type 3 and 3.41 (95% CI 1.54-7.71) for type 4. Theindication other than choledocholithiasis was also associated with a higher risk of difficult cannulation with a RR of 2.36 (95% CI 1.57-3.56). The fistulotomy type precut was used more frequently in the type 3 papilla (46%), while the use of cannula was more frequent in the type 4 papilla (29.6%). CONCLUSIONS: Papilla types 2, 3 and 4 are associated with a higher risk of difficult cannulation. This should be considered when performing ERCP in order to reduce the risk of complications.

Development of a clinical prediction rule for tuberculous meningitis in adults in Lima, Peru.

OBJECTIVES: Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic. METHODS: We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model, we developed a score-based CPR. We assessed its internal validity and diagnostic performance. RESULTS: Of 155 analysed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10-500 cells in CSF and adenosine deaminase ≥ 6 U/l in CSF. It classifies patients into high-, moderate- or low-score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high- or the low-score group, permitting prompt decision-making. In patients in the high-score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores, a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity. CONCLUSION: This CPR could support decision-making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact are necessary before application in other settings.

[Neoendocrine carcinoma of the esophagus: report of a case]. / Carcinoma neuroendocrino de esófago: reporte de caso.

Neuroendocrine carcinoma of esophagus represents less than 2% of cases of cancer of the esophagus. This presentation is extremely unusual, as this type of carcinoma typically presents with greater frequency in bronchopulmonary regions. The symptoms are usually associated with esophageal obstruction and include odynophagia, dysphagia and weight loss and are not usually associated with Carcinoid syndrome. The diagnosis requires one or more of the following positive immunohistochemical markers: Chromogranin A, synaptophysin or CD56 positive, as well as the presence of EMA and PANCK positive. We report the case of a male patient with diagnosis of neuroendocrine tumor of esophagus.

Performance of clinical prediction rules for diagnosis of pleural tuberculosis in a high-incidence setting.

OBJECTIVES: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. METHODS: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. RESULTS: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. CONCLUSION: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT.

Algorithm for the diagnosis of smear-negative pulmonary tuberculosis in high-incidence resource-constrained settings.

OBJECTIVES: Diagnosis of smear-negative pulmonary tuberculosis (SNPT) remains a challenge, particularly in resource-constrained settings. We evaluated a diagnostic algorithm that combines affordable laboratory tools and a clinical prediction rule (CPR). METHODS: We derived, based on published evidence, a diagnostic algorithm for SNPT. Sputum concentration constitutes its first step. In suspects with negative results, SNPT probability is classified with a CPR as low (excluded), high (confirmed) or intermediate. For intermediate patients, sputum Middlebrook 7H9 liquid culture is performed, and they are assessed after 2 weeks. If clinically deteriorated, with still negative liquid culture, bronchoscopy is offered. Otherwise, results of Middlebrook 7H9 culture are awaited. We prospectively evaluated this algorithm against a reference standard of solid and liquid cultures in two reference hospitals in Lima, Peru. RESULTS: 670 SNPT suspects were included from September 2005 to March 2008. The prevalence of SNPT was 27% according to the reference standard. The algorithm's overall accuracy was 0.94 (95% CI 0.91-0.95), its sensitivity was 0.88 (95% CI 0.82-0.92) and its specificity, 0.96 (95% CI 0.94-0.98). Sputum concentration, the CPR, Middlebrook 7H9 sputum culture and bronchoscopic samples defined a diagnosis of SNPT according to the algorithm in 57 (37%), 25 (16%), 63 (41%) and 8(5%) of patients, respectively. 65% of patients were diagnosed within 3 weeks. CONCLUSIONS: The algorithm was accurate for SNPT diagnosis. Sputum concentration, CPR and selective Middlebrook 7H9 culture are essential components.

Sleep quality and perinatal depression in pregnant women treated in a primary care centre in Lima, Peru.

OBJECTIVE: The aim is to evaluate the association between sleep quality and perinatal depression in pregnant women between the 12th week of gestation and the 36th week of gestation in a maternity and child centre in Lima. METHODS: Analytical cross-sectional study in pregnant women cared for in a primary care centre between August and December 2019. The data were collected through a self-administered survey. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The evaluation of perinatal depression was performed with the Edinburgh Postnatal Depression Scale (EPDS). For the multivariate analysis, Poisson regression with robust variances was used to calculate the crude and adjusted prevalence ratios and their respective confidence intervals. RESULTS: The sample was composed of 200 participants. The median [IQR] age was 26 [22-32] years, and 111 (55.5%) pregnancies were unplanned. 52% presented a poor quality of sleep and the risk of perinatal depression was 31.5%. Poor quality of sleep was associated with a significantly higher frequency of perinatal depression (aPR = 4.8 for those with poor quality of sleep warranting medical attention, and aPR = 6.6 for those with poor quality of sleep warranting medical attention and treatment). CONCLUSIONS: There is a possible association between poor sleep quality and perinatal depression in pregnant women between weeks 12 and 36 of gestation. Operational research should be promoted to assess whether interventions to improve sleep quality could have a positive impact on reducing perinatal depression.

Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection.

The IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for Mycobacterium tuberculosis infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed. We conducted longitudinal studies to identify a combination of antigen peptides and cytokines to discriminate between ATBD and LTBI. We studied 54 patients with ATBD disease and 51 with LTBI infection. Cell culture supernatant from cells stimulated with overlapping Mycobacterium tuberculosis novel peptides and 40 cytokines/chemokines were analyzed using the Luminex technology. To summarize longitudinal measurements of analyte levels, we calculated the area under the curve (AUC). Our results indicate that in vitro cell stimulation with a novel combination of peptides (Rv0849-12, Rv2031c-14, Rv2031c-5, and Rv2693-06) and IL-1RA detection in culture supernatants can discriminate between LTBI and ATBD.

Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital.

OBJECTIVES: To determine the risk factors for in-hospital mortality in patients with COVID-19 from a Peruvian national hospital. METHODS: Retrospective cohort study of medical records of patients with COVID-19 hospitalized at Hospital Nacional Hipólito Unanue (HNHU) during the months of April to August 2020. The dependent variable was in-hospital mortality. Independent variables included sociodemographic and clinical characteristics, physical examination findings, oxygen saturation (SaO2) at admission, treatment received during hospitalization and laboratory results at admission. A Cox regression model was used to evaluate the crude and adjusted hazard ratios for associated factors. RESULTS: We included 1418 patients. Median age was 58 years (IQR 47-68 years) and 944 (66.6%) were male. The median length of hospitalization was 7 (4-13) days, and the mortality rate was 46%. The most frequent comorbidities were type 2 diabetes mellitus, hypertension, and obesity. In the adjusted analysis, mortality was associated with age (HR 1.02; 95%CI 1.02-1.03), history of surgery (HR 1.89; 95%CI 1.31-2.74), lower oxygen saturation at admission (HR 4.08; CI95% 2.72-8.05 for SaO2<70% compared to SaO2>94%), the presence of poor general condition (HR 1.81; 95% CI 1.29-2.53), altered state of consciousness (HR 1.58; 95%CI 1.18-2.11) and leukocyte levels (HR 1.01; 95%CI 1.00-1. 02). Treatment with ivermectin (HR 1.44; 95%CI 1.18-1.76) and azithromycin (HR 1.25; 95%CI 1.03-1.52) were associated with higher mortality. Treatment with corticosteroids at low to moderate doses was associated with lower mortality (HR 0.56 95%CI 0. 37-0. 86) in comparison to no steroid use. CONCLUSION: A high mortality was found in our cohort. Low oxygen saturation at admission, age, and the presence of hematological and biochemical alterations were associated with higher mortality. The use of hydroxychloroquine, ivermectin or azithromycin was not useful and was probably associated with unfavorable outcomes. The use of corticosteroids at moderate doses was associated with lower mortality.

Protocol for a controlled before-after quasi-experimental study to evaluate the effectiveness of a multi-component intervention to reduce gaps in hypertension care and control in low-income communes of Medellin, Colombia.

INTRODUCTION: Research on public health interventions to improve hypertension care and control in low-income and middle-income countries remains scarce. This study aims to evaluate the effectiveness and assess the process and fidelity of implementation of a multi-component intervention to reduce the gaps in hypertension care and control at a population level in low-income communes of Medellin, Colombia. METHODS AND ANALYSIS: A multi-component intervention was designed based on international guidelines, cross-sectional population survey results and consultation with the community and institutional stakeholders. Three main intervention components integrate activities related to (1) health services redesign, (2) clinical staff training and (3) patient and community engagement. The effectiveness of the intervention will be evaluated in a controlled before-after quasi-experimental study, with two deprived communes of the city selected as intervention and control arms. We will conduct a baseline and an endline survey 2 years after the start of the intervention. The primary outcomes will be the gaps in hypertension diagnosis, treatment, follow-up and control. Effectiveness will be evaluated with the difference-in-difference measures. Generalised estimation equation models will be fitted considering the clustered nature of data and adjusting for potential confounding variables. The implementation process will be studied with mixed methods. Implementation fidelity will be documented to assess to which degree the intervention components were implemented as intended. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Research Committee of Metrosalud in Colombia (reference 1400/5.2), the Medical Ethics Committee of the Antwerp University Hospital (reference 18/40/424) and the Institutional Review Board of the Antwerp Institute of Tropical Medicine (reference 1294/19). We will share and discuss the study results with the community, institutional stakeholders and national health policymakers. We will publish them in national and international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05011838.

Evaluation of clinical prediction rules for respiratory isolation of inpatients with suspected pulmonary tuberculosis.

BACKGROUND: In the framework of hospital infection control, various clinical prediction rules (CPRs) for respiratory isolation of patients with suspected pulmonary tuberculosis (PTB) have been developed. Our aim was to evaluate their performance in an emergency department setting with a high prevalence of PTB. METHODS: We searched the MEDLINE and OVID databases to identify CPRs to predict PTB. We used a previously collected database containing clinical, radiographical, and microbiological information on patients attending an emergency department with respiratory complaints, and we applied each CPR to every patient and compared the result with culture for Mycobacterium tuberculosis as the reference standard. We also simulated the proportion of isolated suspects and missed cases for PTB prevalences of 5% and 30%. RESULTS: We withheld 13 CPRs for evaluation. We had complete data on 345 patients. Most CPRs achieved a high sensitivity but very low specificity and very low positive predictive value. Mylotte's score, which includes results of sputum smear as a predictive finding, was the best-performing CPR. It attained a sensitivity of 88.9% and a specificity of 63.9%. However, at a 30% PTB prevalence, 498 of 1000 individuals with suspected PTB would have to be isolated; 267 of these cases would be true PTB cases, and 33 cases would be missed. Two consecutive sputum smears had a sensitivity of 75.6% and a specificity of 99.7%. CONCLUSIONS: In a setting with a high prevalence of PTB, only 1 of the 13 assessed CPRs demonstrated high sensitivity combined with satisfactory specificity. Our results highlight the need for local validation of CPRs before their application.

Performance of an algorithm based on WHO recommendations for the diagnosis of smear-negative pulmonary tuberculosis in patients without HIV infection.

OBJECTIVE: To evaluate the performance of an algorithm based on WHO recommendations for diagnosis of smear-negative pulmonary tuberculosis in HIV-negative patients. METHODS: We recruited HIV-negative patients with clinical suspicion of tuberculosis who had had three negative sputum smears in Lima, Peru. All included subjects underwent a complete anamnesis, physical examination and chest X-ray, and had a sputum specimen cultured in Ogawa, Middlebrook 7H9 media and MGIT®. We applied an algorithm based on WHO recommendations to classify patients as having tuberculosis or not. The diagnostic performance of the algorithm was evaluated comparing its results against the reference standard of a positive culture for M. tuberculosis in either of the media used. RESULTS: A total of 264 of the 285 patients included (92.6%) completed evaluation and follow up. Of these, 70 (26.5%) had a positive culture for M. tuberculosis. Clinical response to a broad spectrum course of antibiotics was good in 32 of these 70 patients (45.7; 95%CI 34.0-57.4%). Overall, the algorithm attained a sensitivity of 22.9% (95% CI 13.1-32.7%) and a specificity of 95.4 % (95% CI 92.4-98.3%) compared to culture results. The positive likelihood ratio was 4.93 and the negative likelihood ratio was 0.81. CONCLUSIONS: The sensitivity and negative likelihood ratio of the algorithm is poor. It should be re-evaluated, and possibly adapted to local circumstances before further use. The clinical response to an antibiotic trial is the most important component to reassess. We also suggest considering performing chest X-ray earlier in the diagnostic work-up.

Sleep Quality and Perinatal Depression in Pregnant Women Treated in a Primary Care Centre in Lima, Peru. / Calidad del sueño y depresión perinatal en gestantes atendidas en un centro de atención primaria en Lima, Perú.

OBJECTIVE: The aim is to evaluate the association between sleep quality and perinatal depression in pregnant women between the 12th week of gestation and the 36th week of gestation in a maternity and child centre in Lima. METHODS: Analytical cross-sectional study in pregnant women cared for in a primary care centre between August and December 2019. The data were collected through a self-administered survey. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The evaluation of perinatal depression was performed with the Edinburgh Postnatal Depression Scale (EPDS). For the multivariate analysis, Poisson regression with robust variances was used to calculate the crude and adjusted prevalence ratios and their respective confidence intervals. RESULTS: The sample was composed of 200 participants. The median [IQR] age was 26 [22-32] years, and 111 (55.5%) pregnancies were unplanned. 52% presented a poor quality of sleep and the risk of perinatal depression was 31.5%. Poor quality of sleep was associated with a significantly higher frequency of perinatal depression (aPR=4.8 for those with poor quality of sleep warranting medical attention, and aPR=6.6 for those with poor quality of sleep warranting medical attention and treatment). CONCLUSIONS: There is a possible association between poor sleep quality and perinatal depression in pregnant women between weeks 12 and 36 of gestation. Operational research should be promoted to assess whether interventions to improve sleep quality could have a positive impact on reducing perinatal depression.

Factors associated with mortality in hospitalized elders in an internal medicine department. / Factores asociados a mortalidad de adultos mayores hospitalizados en un servicio de Medicina Interna.

The aim of this prospective cohort study was to determine the factors associated with mortality in elders admitted to an Internal Medicine Department of a public hospital in Lima. During 2019, 360 patients over 60 years of age were consecutively evaluated by applying the Comprehensive Geriatric Assessment tools and reviewing their medical records. During hospitalization, 45 (12.5%) died. There was a higher frequency of anemia (p = 0.043), hypoalbuminemia (p = 0.006), pressure ulcers (p = 0.003), high comorbidity (p < 0.001), functional dependence (p < 0.001) and malnutrition (p = 0.002) among deceased patients compared to non-deceased. In the multivariate model, the presence of delirium on admission was associated with a higher risk of hospital mortality (RR = 3.64; 95% CI: 1.51 - 8.76, p = 0.004). Additional studies are required in our country to assess the prognostic value of delirium and other geriatric syndromes on mortality and other adverse outcomes.

El presente estudio prospectivo de cohorte tuvo como objetivo determinar los factores asociados a la mortalidad de los adultos mayores admitidos en un servicio de Medicina Interna de un hospital público de Lima. Durante el 2019 se evaluaron consecutivamente 360 pacientes mayores de 60 años mediante la aplicación de las herramientas de la Valoración Geriátrica Integral y la revisión de sus historias clínicas. Del total, 45 (12,5%) fallecieron durante el internamiento. En el modelo multivariado, la presencia de delirio al ingreso se asoció con un mayor riesgo de mortalidad hospitalaria (RR = 3,64; IC95%: 1,51-8,76, p = 0,004). Hubo una mayor frecuencia de anemia (p = 0,043), hipoalbuminemia (p = 0,006), úlceras por presión (p = 0,003), comorbilidad alta (p < 0,001), dependencia funcional (p < 0,001) y malnutrición (p = 0,002) entre los pacientes fallecidos respecto a los no fallecidos. Se requieren estudios adicionales en nuestro país para evaluar el valor pronóstico del delirio, otros síndromes geriátricos sobre la mortalidad y otros desenlaces adversos.

Development and validation of an instrument to evaluate medical students' lifestyle. / Desarrollo y validación de un instrumento para medir el estilo de vida de estudiantes de medicina.

INTRODUCTION: It is required to have validated instruments in health science students that identify unhealthy habits and assess the impact of educational interventions and programs aimed at promoting a healthy lifestyle. OBJECTIVE: To evaluate the validity and reliability of an instrument to measure medical students' lifestyles. METHODS: A lifestyle questionnaire was developed using the Delphi technique by a group of experts. The final questionnaire was applied to 332 students of the School of Medicine of the Ricardo Palma University in 2017. A preliminary examination was carried out to assess preconditions for construct validityincluding the correlation matrix, the Kaiser Meyer Olkin statistic, and the Bartlett sphericity test. Factor analysis was used for construct validity, and the possible resulting factors were extracted through the principal component analysis. Cronbach's alpha coefficient was calculated to assess the instrument reliability. RESULTS: In this study, 41.6% of participants were men with a mean age of 20 years (standard deviation = 3). The preconditions for the factor analysis were a Kaiser Meyer Olkin coefficient = 0.773 and a significant Bartlett sphericity test. For the 47 items of the final questionnaire, the factor analysis showed an explained variance of 56.7% with eigenvalues greater than one. Cronbach's alpha was 0.78. The final questionnaire could assume values between -23 to 151 points. Based on a cut point of 71 points, the prevalence of students with an unhealthy lifestyle was 73.6%. CONCLUSION: The developed instrument has acceptable validity and reliability to measure lifestyle in medical students. For external validation, studies in other university populations are suggested.

INTRODUCCIÓN: Se requiere contar con instrumentos validados en estudiantes de ciencias de la salud que permitan identificar hábitos no saludables, junto con evaluar el impacto de intervenciones y programas educativos destinados a promover un estilo de vida saludable. OBJETIVO: Evaluar la validez y fiabilidad de un instrumento para medir el estilo de vida en estudiantes de la carrera de medicina humana. MÉTODO: Se elaboró un cuestionario sobre estilos de vida desarrollado mediante la técnica Delphi entre un grupo de expertos. El cuestionario final resultante fue aplicado a una población de 332 estudiantes de la Facultad de Medicina Humana de una universidad peruana en el año 2017. Se realizó una exploración para evaluar las condiciones previas para ejecutar la validez de constructo, incluyendo la evaluación de la matriz de correlaciones, el estadístico Kaiser Meyer Olkin y la prueba de esfericidad de Bartlett. Para la validez de constructo se empleó el análisis factorial y se extrajeron los posibles factores resultantes por medio del análisis de componentes principales. Para demostrar la fiabilidad del instrumento se calculó el coeficiente α de Cronbach. RESULTADOS: El 41,6% de los participantes fueron varones. La edad media fue de 20 años (desviación estándar 3). Las condiciones previas al análisis factorial fueron un coeficiente Kaiser Meyer Olkin de 0,773 y una prueba de esfericidad de Bartlett significativa. El análisis factorial sobre los 47 ítems del cuestionario final obtuvo una varianza explicada de 56,7% con autovalores superiores a 1. El valor del α de Cronbach fue de 0,78. El cuestionario final puede tomar valores entre -23 hasta 151 puntos. Sobre la base de un punto de corte de 71 puntos, la prevalencia de estudiantes con un estilo de vida no saludable fue de 73,6%. CONCLUSIÓN: El instrumento desarrollado tiene validez y fiabilidad aceptable para medir el estilo de vida en estudiantes de medicina. Se sugiere la validación externa en otras poblaciones universitarias.

Detection of Viral and Bacterial Respiratory Pathogens Identified by Molecular Methods in COVID-19 Hospitalized Patients and Its Impact on Mortality and Unfavorable Outcomes.

PURPOSE: The purpose of this study is to evaluate the frequency of viral and bacterial respiratory pathogens detected by molecular methods in sputum samples of patients hospitalized for COVID-19 and to evaluate its impact on mortality and unfavorable outcomes (in-hospital death or mechanical ventilation). PATIENTS AND METHODS: The prospective cohort included patients with diagnosis of COVID-19 hospitalized at Hospital Nacional Hipólito Unanue. Sociodemographic and clinical data were collected from clinical records. Sputum samples were analyzed with the Biofire Filmarray Pneumonia plus® respiratory panel. Crude and adjusted associations with unfavorable outcomes were evaluated using logistic regression models. RESULTS: Ninety-three patients who were able to collect sputum samples were recruited between September 8 and December 28, 2020. The median age was 61.7 years (IQR 52.3-69-8) and 66 (71%) were male. The most frequent symptoms were dyspnea, cough, fever, and general malaise found in 80 (86%), 76 (82%), 45 (48%), and 34 (37%) patients, respectively. Fifty-three percent of patients had comorbidities. Seventy-six (82%) patients received antibiotics prior to admission and 29 (31%) developed unfavorable outcome. Coinfection was evidenced in 38 (40.86%) cases. The most frequently found bacteria were Staphylococcus aureus, Streptococcus agalactiae, Haemophilus influenzae and Klebsiella pneumoniae in 11 (11.83%), 10 (10.75%), 10 (10.75%), and 8 (8.6%) cases, respectively. Streptococcus pneumoniae was found in one case (1.08%). We neither identify atypical bacteria nor influenza virus. No association was found between the presence of viral or bacterial microorganisms and development of unfavorable outcomes (OR 1.63; 95% CI 0.45-5.82). CONCLUSION: A high frequency of respiratory pathogens was detected by molecular methods in patients with COVID-19 pneumonia but were not associated with unfavorable outcomes. No atypical agents or influenza virus were found. The high use antibiotics before admission is a concern. Our data suggest that the use of drug therapy against atypical bacteria and viruses would not be justified in patients hospitalized for COVID-19.

Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients.

BACKGROUND: We determined the frequency of genetic polymorphisms in three anti-TB drug metabolic proteins previously reported: N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. METHODS: We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. RESULTS: Seventy-four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug-induced liver injuries. Sixty-four percent are homozygous for the wild-type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug-resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. CONCLUSIONS: This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies.

Evaluation of the humoral response induced by BBIBP-CorV vaccine by determining neutralizing antibodies in peruvian healthcare personnel. / Evaluación de la respuesta humoral inducida por la vacuna BBIBP-CorV mediante la determinación de anticuerpos neutralizantes en personal sanitario peruano.

OBJECTIVE.: To determine the titer of antibodies against the receptor binding domain (RBD) of the spike protein (S) in health personnel between the 4th and 12th week after receiving the BBIBP-CorV vaccine (Sinopharm). MATERIALS AND METHODS.: We included a total of 168 healthcare workers from two hospitals in the region, who complied with the complete Sinopharm vaccine schedule; serum antibodies were measured using the Elecsys® Anti-SARS-CoV-2 test. RESULTS.: All participants developed antibodies to the RBD domain. The lowest antibody titer level was 1.78 U/mL. Levels equal to or above 250 were found in 70 (41.7%) participants. The geometric mean was 82.6 (95% CI: 67.8-100.6). Women had higher antibody levels. Participants whose antibodies were measured between 4- and 7-weeks post-vaccination showed significantly higher antibody levels than patients whose antibody levels were measured between 10- and 12-weeks post-vaccination. Among patients with a history of COVID-19, antibody levels were found to be at or above 250 U/mL in 88% of cases, compared to 6% among those without a history of COVID-19, (p<0.001). CONCLUSION.: All participants immunized with BBIBPCorV vaccine were positive for antibodies against the SARS-CoV-2 spike protein RBD. The correlation between the titer level and protection against COVID-19, as well as the length of the protection provided by the vaccine, needs to be evaluated.

OBJETIVO.: Determinar el título de anticuerpos frente al dominio de unión al receptor (RBD) de la proteína espiga (S) en personal de salud entre la 4.ª y 12.ª semana luego de haber recibido la vacuna BBIBP-CorV (Sinopharm). MATERIALES Y MÉTODOS.: Se incluyeron 168 trabajadores de salud de dos hospitales de la región, quienes cumplían el esquema completo con vacuna de Sinopharm, y se realizó la medición de anticuerpos en suero mediante la prueba Elecsys® Anti-SARS-CoV-2. RESULTADOS.: Todos los participantes desarrollaron anticuerpos frente al dominio RBD. El valor mínimo fue de 1,78 U/mL. En 70 (41,7%) participantes se encontraron niveles iguales o por encima de 250. La media geométrica fue de 82,6 (IC 95% 67,8-100,6). Las mujeres presentaron un mayor nivel de anticuerpos. El grupo de participantes en los que se midieron anticuerpos entre las semanas 4 y 7 posvacunación mostró niveles de anticuerpos significativamente mayores que los pacientes cuyas determinaciones fueron realizadas entre las 10 y 12 semanas posvacunación. Entre los pacientes con antecedente de COVID-19, los niveles de anticuerpos se encontraron en cifras iguales o por encima de 250 U/mL en el 88% de casos, en comparación con 6% entre aquellos sin antecedente de COVID-19, (p<0,001). CONCLUSIÓN.: Todos los participantes inmunizados con la vacuna BBIBP-CorV presentaron positividad a anticuerpos frente al RBD de la proteína S del SARS-CoV-2. Es necesario evaluar la correlación entre la magnitud de los títulos y la protección frente a COVID-19 y el tiempo de protección conferido por la vacuna.

Randomized clinical trial to evaluate safety and efficacy of convalescent plasma use among hospitalized patients with COVID-19 (PERUCONPLASMA): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The general objective of this study is to test the hypothesis that administration of convalescent plasma from donors with previous diagnosis of severe COVID-19 pneumonia is safe and associated with a decrease in all-cause in-hospital mortality among hospitalized patients with COVID-19 at 30 days in comparison with standard treatment alone. The secondary objectives are as follows: (1) to assess the efficacy of convalescent plasma to reduce the length of hospitalization, (2) to assess the efficacy of convalescent plasma to reduce the length of ICU stay, and (3) to assess the efficacy of convalescent plasma on reducing the requirement of invasive mechanical ventilation or ICU stay. TRIAL DESIGN: PERUCONPLASMA is a IIb phase open label, randomized, superiority clinical trial with 1:1 allocation taking place in real life routine clinical practice at public hospitals in Lima, Peru. Participants will be randomized to receive convalescent plasma along with local standard treatment or local standard treatment alone. After allocation, all participants will be followed for a total of 30 days or until hospital discharge, whichever occurs first. PARTICIPANTS: The population for the study are patients with severe disease with a confirmed laboratory test for SARS-CoV-2 infection hospitalized in 3 tertiary-care hospitals in Lima, Peru. Subjects are eligible for the trial if they meet all of the following inclusion criteria: 1. Age 18 or older 2. Hospitalization due to COVID-19 with laboratory confirmation (either with serologic, molecular, or antigen test along with a compatible clinical presentation) 3. Severe or critical COVID-19 disease Severe illness was defined by 2 or more of the following: Respiratory rate of 22 or more Hypoxemia with oxygen saturation equal or less than 93% Abnormal blood gas analysis (PaO2 < 60 mmHg, PaCO2 > 50 mmHg, or Pa/FiO2 < 300) Critical disease was defined by either: Mechanical ventilation requirement less than 72 h. Shock. 4. Capacity to provide informed consent (patient or patient's direct relative) 5. Availability of convalescent plasma units compatible with ABO blood type of the subject. EXCLUSION CRITERIA: Subjects are not eligible for the trial if they meet any of the following criteria: 1. Contraindication for transfusion (e.g., prior anaphylaxis, congestive heart failure) 2. Hemodynamic instability (PA < 60 mmHg refractory to vasopressors) 3. Uncontrolled concomitant infections\ 4. Stupor or coma 5. Platelets < 50,000/µL or disseminated intravascular coagulation 6. Serum creatinine > 3.5 mg/dL or dialysis requirement 7. Total bilirubin > 6 mg/dL or jaundice of unknown etiology 8. Myocardial infarction or acute coronary syndrome 9. Active or recent (< 7 days) intracranial hemorrhage 10. Pregnancy Donors: The donors have to meet the following criteria: male between 30 and 60 years with a previous diagnosis of severe COVID-19-associated pneumonia within the last 3 months, with resolution of symptoms of at least 28 days. The rationale for including donors with severe disease is to maximize the probability of collecting convalescent plasma units with high titer of neutralizing antibodies, as the technology to measure this specific type of antibodies is not routinely available in Peru. Aliquots of plasma will be stored for future quantification of neutralizing antibodies. INTERVENTION AND COMPARATOR: Convalescent plasma from donors with previous severe COVID-19 is the investigational medical product. The experimental group will receive 1 to 2 units of 200 to 250 ml of convalescent plasma along with local standard treatment. The control group will receive local standard treatment alone. The participants randomized to plasma will have evaluations at 6 h and 24 h to specifically evaluate possible post transfusion events. All the participants will be evaluated at day 3, day 7, and day 30 after enrolment. MAIN OUTCOMES: Safety outcome: Incidence of serious adverse reactions related to convalescent plasma transfusion within 24 h after convalescent plasma administration. Efficacy outcomes: Mortality from any cause during hospitalization at 30 days post randomization. Length of hospitalization at 30 days post randomization or until hospital discharge. Duration of mechanical ventilation at 30 days post randomization or until hospital discharge. Length of hospitalization in an intensive care unit at 30 days post randomization or until hospital discharge. Exploratory: Oxygen requirement evolution at days 3 and 7. Score Sequential Organ Failure Assessment (SOFA) evolution at days 3 and 7. Dynamics of inflammatory marker (lymphocyte, C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH)) evolution at days 3 and 7. Proportion of patients progressing to multi-organ failure at 30 days post randomization or until hospital discharge. Proportion of transfusion related adverse reactions at 30 days post randomization or until hospital discharge. RANDOMIZATION: Randomization will be carried out within the electronic case report form (eCRF) in 1:1 ratio (receive plasma/control) in a randomization process established by blocks of size 2, 4, and 6. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomization process. Randomization blocks will be performed with "ralloc", Stata's randomization process v.16.0. Randomization through the eCRF will be available 24 h every day. BLINDING (MASKING): Both the participants and study staff will be aware of the allocated intervention. Blinded statistical analysis will be performed. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The sample size was calculated using the Fleiss formula with continuity correction to detect a mortality reduction from 50 to 20% between the two treatment arms with a confidence level of 95% and a power of 80%. Based on this information, a total of 45 patients per arm would be needed. After adjustment for a drop-out rate of 10% after enrolment, a total of 50 patients per arm (100 patients in total) will be enrolled. TRIAL STATUS: Current protocol version: 5.0 dated January 04, 2021. Recruitment started on September 21, 2020, and is expected to finish by the end of March 2021. TRIAL REGISTRATION: Peruvian Register of Clinical Trials (REPEC) ID: PER-016-20, registered on June 27, 2020. Clinicaltrials.gov ID: NCT04497324 , registered on August 4, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.