Nota Técnica N. 3/2023 - SES/GVEDT: Nota técnica de Síndrome Gripal (SG) e Síndrome Respiratória Aguda Grave (SRAG) pelo vírus influenza / Technical Note N. 3/2023 - SES/GVEDT: Technical Note on Influenza Syndrome (SG) and Severe Acute Respiratory Syndrome (SARS) due to the influenza virus

A vigilância d influenza no Brasil é composta pela vigilância sentinela de Síndrome Gripal (SG), Síndrome Respiratória Grave (SRAG) em pacientes hospitalizados ou óbitos e em surtos de SG em instituições e de longa permanência. As unidade sentinelas de Síndrome Gripal têm como objetivo monitorar a circulação dos vírus respiratórios com ênfase em influenza e Sars-CoV-2, identificar as variações sazonais por faixa etária, prover cepas virais para formulação de vacinas de influenza, vigilância genômica do coronavírus, e identificar situações inusitadas

Influenza surveillance in Brazil is composed of sentinel surveillance of Influenza Syndrome (SG), Severe Respiratory Syndrome (SARS) in hospitalized or deceased patients and in SG outbreaks in institutions and long-term care facilities. The flu syndrome sentinel units aim to monitor the circulation of respiratory viruses with emphasis on influenza and Sars-CoV-2, identify seasonal variations by age group, provide viral strains for the formulation of influenza vaccines, genomic surveillance of the coronavirus, and identify unusual situations

Estatinas y mortalidad por influenza: revisión sistemática y meta-análisis / Statins and influenza mortality: systematic review and meta-analysis

INTRODUCCIÓN: Debido a sus propiedades antiinflamatorias, se ha planteado que el uso de las estatinas podría influir en la evolución de la infección por el virus de influenza. OBJETIVO: Evaluar el efecto de la terapia con estatinas sobre la mortalidad por influenza. MATERIAL y MÉTODOS: Se realizó un meta-análisis que incluyó estudios que evaluaron el uso de estatinas en pacientes con influenza e informaron los datos sobre mortalidad, después de buscar en las bases de datos PubMed/MEDLINE, Embase y Cochrane Controlled Trials. Se aplicó un modelo de efectos aleatorios. Se analizó el riesgo de sesgos y se desarrolló un análisis de sensibilidad. RESULTADOS: Se identificaron y se consideraron elegibles para el análisis ocho estudios (diez cohortes independientes), que incluyeron un total de 2.390.730 de pacientes. Un total de 1.146.995 de sujetos analizados recibieron estatinas mientras que 1.243.735 de sujetos formaron parte del grupo control. La terapia con estatinas se asoció con una menor mortalidad (OR: 0,66; IC 95%: 0,51-0,85). El análisis de sensibilidad mostró que los resultados fueron robustos. CONCLUSIONES: Nuestros datos sugieren que, en una población con influenza, el uso de estatinas se asoció con una reducción significativa de la mortalidad. Estos resultados deben confirmarse en futuros ensayos clínicos.

BACKGROUND: Due to their anti-inflammatory properties, it has been suggested that the use of statins could influence the evolution of influenza virus infection. AIM: To evaluate the effect of statin therapy on mortality from influenza. METHODS: A meta-analysis that included studies evaluating the use of statins in patients with influenza and reporting data on mortality, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases, was performed. A random effects model was applied. The risk of bias was analyzed and a sensitivity analysis was performed. RESULTS: Eight studies (10 independent cohorts), which included a total of 2,390,730 patients, were identified and eligible for analysis. A total of 1,146,995 subjects analyzed received statins, while 1,243,735 subjects were part of the control group. Statin therapy was associated with lower mortality (OR: 0.66; 95% CI: 0.51-0.85). The sensitivity analysis showed that the results were robust. CONCLUSION: Our data suggest that, in a population with influenza, the use of statins was associated with a significant reduction in mortality. These results must be confirmed in future clinical trials.

Homeopathy for COVID-19 in primary care: A randomized, double-blind, placebo-controlled trial (COVID-Simile study) / 中西医结合学报

BACKGROUND@#Different homeopathic approaches have been used as supportive care for coronavirus disease 2019 (COVID-19) cases, but none has been tested in a clinical trial.@*OBJECTIVES@#To investigate the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19.@*DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS@#A randomized, double-blind, two-armed, parallel, single-center, placebo-controlled clinical trial was conducted from June 2020 to April 2021 in São-Carlos, Brazil. Participants aged > 18 years, with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized (1:1) into two groups that received different treatments during a period of at-home-isolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo.@*OUTCOME MEASURES@#The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures.@*RESULTS@#Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between two groups among participants who were reporting influenza-like symptoms at the beginning of monitoring (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score ≥ 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group.@*CONCLUSION@#Results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases. Although some secondary measures do not support the null hypothesis, the wide confidence intervals suggest that further studies with larger sample sizes and more symptomatic participants are needed to test the effectiveness of homeopathic Natrum muriaticum LM2 for COVID-19.@*TRIAL REGISTRATION@#UMIN Clinical Trials Registry ID: JPRN-UMIN000040602.

Clinical trials and evaluation of Chinese patent medicine for influenza / 中国中药杂志

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.

Efficacy of oseltamivir compared with zanamivir in COPD patients with seasonal influenza virus infection: a randomized controlled trial

Influenza viruses exacerbate chronic obstructive pulmonary disease (COPD) with considerable morbidity and mortality. Zanamivir and oseltamivir are effective in treating influenza. However, their efficacy in relieving influenza symptoms in COPD patients remains unknown, with the lack of controlled trials in this subject. Therefore, we conducted this randomized controlled trial to investigate the clinical efficacy of both interventions in this population. Patients were allocated to two groups (80 patients each): oseltamivir (OSELTA) and zanamivir (ZANA) groups. Oseltamivir (75 mg) was orally administered twice daily for 5 days, while zanamivir (10 mg) was inhaled twice daily for 5 days. Clinical parameters including body temperature, influenza symptoms (i.e., sore throat, cough, etc.), and serial blood tests were recorded on days 1, 3, and 7. We analyzed primary (changes in body temperature) and secondary outcomes (changes in non-specific symptoms) using the pre-protocol and intention-to-treat analyses. Differences between groups were assessed using t-test. Oseltamivir and zanamivir significantly reduced body temperature on the 3rd day after treatment; however, the number of patients who reported clinical improvement in influenza-like symptoms was significantly higher in the OSELTA group compared to the ZANA group on days 3 (85 vs 68.8%, P=0.015) and 7 (97.5 vs 83.8%, P=0.003). However, no significant changes in hematological (white blood cells and its subtypes) and inflammatory (C-reactive protein) parameters were noted (P>0.05). Our results suggested that oseltamivir and zanamivir are effective in reducing body temperature, while oseltamivir led to better clinical improvement regarding influenza-like symptoms in patients with COPD.

Expert consensus on Antiviral Oral Liquid in treatment of influenza in clinical practice / 中国中药杂志

Antiviral Oral Liquid is modified on the basis of Baihu Decoction in Treatise on Febrility Diseases by ZHANG Zhongjing and Qingwen Baidu Yin in Qing Dynasty, with effects in clearing toxic heat, repelling dampness and cooling blood. It is widely used in clinical treatment of common colds, influenza and upper respiratory tract infection, mumps, viral conjunctivitis and hand-foot-mouth disease, with a good clinical efficacy and safety. Based on a questionnaire survey of clinicians and a systematic review of study literatures on Antiviral Oral Liquid, the international clinical practice guidelines development method was adopted to analyze the optimal available evidences and expert experiences in the "evidence-based, consensus-based and experience-based" principles. The consensus was jointly reached by more than 30 multidisciplinary experts nationwide, including clinical experts of traditional Chinese and Western medicine in the field of respiratory diseases and infectious diseases, and methodological experts. In the study, literatures were retrieved based on clinical problems in the clinical survey as well as PICO clinical problems. The GRADE system was used for the classification and evaluation of evidence, and fully combined with clinical expert experience, so as to reach expert consensus by the nominal grouping method. This expert consensus recommended or suggested indications, usage and dosage, course of treatment, intervention time for treatment, and the safety and precautions of Antiviral Oral Liquid for treatment of influenza, and can provide reference for the rational use of this drug in clinical practice.

Thinking and practice of key links in design of clinical trial scheme for treatment of influenza with traditional Chinese medicine / 中国中药杂志

To sort out the key points in "PICOS" design of clinical trial scheme for influenza, and optimize the clinical trial scheme of Chinese patent medicine in the treatment of influenza by strictly following the principle of evidence-based medicine, focusing on the clinical practice of the disease, and highlighting the characteristics of traditional Chinese medicine. "The design of a randomized, double-blind, positive parallel control study of a certain herbal preparation for the treatment of non-severe influenza" was taken as an example in this study, and the key points in the clinical trial design of Chinese patent medicine for the treatment of influenza were specifically discussed from six aspects, including the type of study, object of study, intervention measures, control measures, outcome indicators and frequently asked questions in test design. From methodological suggestions, in the design scheme of clinical trial on efficacy and safety of Chinese patent medicine in the treatment of influenza, the randomized controlled study should be the first choice for type of study; the inclusion criteria should define both the diagnostic criteria of Western medicine and the syndromes of traditional Chinese medicine(TCM); the exclusion criteria should include a comprehensive list of confounding factors and special circumstances lea-ding to bias in the study results; the interventions should be based on a well-defined dosing programme; internationally recognized positive drugs or guidelines should be used as control measures, with median antipyretic time as the main outcome indicator. For the evalua-tion of curative effect, disease symptom scale can be set, and the TCM syndrome scoring scale was carefully used in this study, with time nodes set for the efficacy evaluation standard. The full name of the drugs should be written in the regulations on combined drug use and prohibited drug use.

Bayesian network Meta-analysis of traditional Chinese medicine injections combined with antiviral western medicine in treatment of influenza / 中国中药杂志

To systematically evaluate the efficacy and safety of traditional Chinese medicine injections combined with antiviral wes-tern medicine in the treatment of influenza by Bayesian network Meta-analysis. Four Chinese databases(CNKI, Wanfang, VIP, CBM) and three English databases(PubMed, EMbase, Cochrane Library) were retrieved by computer for randomized controlled trials(RCT) about the comparison between the combined administration of traditional Chinese medicine injections with antiviral western medicine(or with placebo) and the single administration of antiviral western medicine in the treatment of influenza, or the comparison between two different traditional Chinese medicine injections combined with antiviral western medicine in the treatment of influenza. The retrieval time was from the establishment of the databases to July 2020. Two researchers independently screen out the literatures and extracted the data according to the inclusion criteria and exclusion criteria. The included studies were evaluated by the Cochrane 5.1 bias risk assessment tool, and data analysis was conducted by ADDIS 1.16.8 and Stata 14.0. A total of 49 literatures about 5 061 cases were included finally, involving six traditional Chinese medicine injections, namely Reduning Injection, Xiyanping Injection, Tanreqing Injection, Yanhuning Injection, Qingkailing Injection and Shuanghuanglian Injection. The results of network Meta-analysis,(1)in terms of total effective rate, 6 traditional Chinese medicine injections combined with antiviral western medicine was better than antiviral western medicine alone. In terms of probability sorting, Shuanghuanglian Injection combined with antiviral western medicine ranked first.(2)There was no significant statistical difference in adverse reaction rate among all groups, but Reduning Injection ranked first in the probability sorting, due to the least side effects.(3)In terms of antipyretic time, Yanhuning Injection, Xiyanping Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Xiyanping Injection ranked first in the probability sorting.(4)In terms of cough relief time, Qingkailing Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Qingkailing Injection was superior to Yanhuning Injection. Qingkailing Injection combined with antiviral western medicine ranked first in the probability sorting.(5)In terms of the length of hospital stay, Xiyanping Injection, Tanreqing Injection and Reduning Injection combined with antiviral western medicine was superior to antiviral western medicine alone, and Reduning Injection ranked first in the probability sorting due to the shortest hospital stay. Because of the small quantity and low quality of included studies, the results of this study shall be regarded cautiously and comprehensively. In the future, multi-center, large-sample and clinical randomized controlled trials shall be conducted to verify the results.

Influenza A (H1N1): outbreak management in a dialysis unit and clinical outcomes of infection in chronic hemodialysis patients / Influenza A (H1N1): controle de surto em unidade de diálise e desfechos clínicos da infecção em pacientes em hemodiálise crônica

ABSTRACT Introduction: Chronic hemodialysis (HD) patients are considered to be at high risk for infection. Here, we describe the clinical outcomes of chronic HD patients with influenza A (H1N1) infection and the strategies adopted to control an outbreak of influenza A in a dialysis unit. Methods: Among a total of 62 chronic HD patients, H1N1 infection was identified in 12 (19.4%). Of the 32 staff members, four (12.5%) were found to be infected with the H1N1 virus. Outcomes included symptoms at presentation, comorbidities, occurrence of hypoxemia, hospital admission, and clinical evaluation. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction. Results: The 12 patients who had H1N1 infection did not differ significantly from the other 50 non-infected patients with respect to age, sex, dialysis vintage, dialysis modality, or proportion of comorbidities. Obesity was higher in the H1N1-infected group (41.5 vs. 4%, p<0.002). The most common symptoms were fever (92%), cough (92%), and rhinorrhea (83%). Early empirical antiviral treatment with oseltamivir was started in symptomatic patients and infection control measures, including the intensification of contact-reduction measures by the staff members, antiviral chemoprophylaxis to asymptomatic patients undergoing HD in the same shift of infected patients, and dismiss of staff members suspected of being infected, were implemented to control the spread of infection in the dialysis unit. Conclusion: The clinical course of infection with H1N1 in our patients was favorable. None of the patients developed severe disease and the strategies adopted to control the outbreak were successful.

RESUMO Introdução: Pacientes em hemodiálise (HD) crônica apresentam risco elevado para infecções. O presente estudo descreve os desfechos clínicos de pacientes em HD crônica com infecção pelo vírus influenza A (H1N1) e as estratégias adotadas para controlar um surto de influenza A numa unidade de diálise. Métodos: Doze (19,4%) de 62 pacientes em HD crônica e quatro (12,5%) de 32 funcionários desta unidade de diálise apresentaram infecção pelo vírus H1N1. Os desfechos incluíram sintomas à apresentação, comorbidades, ocorrência de hipoxemia, internação hospitalar e avaliação clínica. A presença de infecção foi confirmada por reação em cadeia da polimerase via transcriptase reversa (RT-PCR) em tempo real. Resultados: Os 12 pacientes com infecção por H1N1 não diferiram significativamente dos 50 pacientes sem infecção no tocante a idade, sexo, tempo em diálise, modalidade de diálise e percentual de comorbidades. O percentual de obesidade foi mais elevado no grupo com infecção por H1N1 (41,5% vs. 4%, p<0,002). Os sintomas mais comuns foram febre (92%), tosse (92%) e rinorreia (83%). Os pacientes foram submetidos a tratamento antiviral com oseltamivir e medidas de controle (intensificação das medidas de redução de contato pelos funcionários da clínica, quimioprofilaxia com antiviral para pacientes assintomáticos em HD na mesma sala dos pacientes com infecção e afastamento de funcionários da clínica com suspeita de infecção) para controlar a disseminação da infecção pela unidade de diálise. Conclusão: O curso clínico da infecção por H1N1 em nossos pacientes foi favorável. Nenhum evoluiu para doença grave e as estratégias adotadas foram efetivas no controle do surto.

Miocarditis fulminante en adultos por el virus de la influenza B: reporte de dos casos y revisión de la literatura / Fulminant myocarditis due to the influenza B virus in adults: Report of two cases and literature review

Resumen La miocarditis es una enfermedad inflamatoria del miocardio. Las infecciones virales son la causa más común, aunque también puede deberse a reacciones de hipersensibilidad y de etiología autoinmunitaria, entre otras. El espectro clínico de la enfermedad es variado y comprende desde un curso asintomático, seguido de dolor torácico, arritmias y falla cardiaca aguda, hasta un cuadro fulminante. El término 'fulminante' se refiere al desarrollo de un shock cardiogénico con necesidad de soporte vasopresor e inotrópico o dispositivos de asistencia circulatoria, ya sea oxigenación por membrana extracorpórea o balón de contrapulsación intraaórtico. Cerca del 10 % de los casos de falla cardiaca por miocarditis corresponde a miocarditis fulminante. La miocarditis por influenza se considera una condición infrecuente; no obstante, su incidencia ha aumentado desde el 2009 a raíz de la pandemia de influenza por el virus AH1N1. Por su parte, la miocarditis por influenza de tipo B sigue siendo una condición infrecuente. Se describen aquí dos casos confirmados de miocarditis fulminante por el virus de la influenza B atendidos en un centro cardiovascular, que requirieron dispositivos de asistencia circulatoria mecánica.

Abstract Myocarditis is an inflammatory disease of the myocardium. Viral infections are the most common cause, although it can also be due to hypersensitivity reactions and autoimmune etiology, among other causes. The clinical spectrum of the disease is varied, from an asymptomatic course, followed by chest pain, arrhythmias, and acute heart failure, to a fulminant episode. The term fulminant refers to the development of cardiogenic shock with a need for vasopressor support and inotropic or assisted circulation devices either extracorporeal membrane oxygenation (ECMO) or intra-aortic counterpulsation balloon. About 10% of cases of heart failure due to myocarditis correspond to fulminant myocarditis. Influenza myocarditis has been considered an infrequent condition. However, its incidence has increased since 2009 as a result of the AH1N1 pandemic; otherwise, myocarditis due to the Influenza type B virus remains an infrequent entity. We describe the experience in a cardiovascular center of two confirmed cases of fulminant myocarditis due to influenza B that required circulatory assistance devices.

Cómo interpretar guías de práctica clínica elaboradas con metodología GRADE / Clinical guidelines using the GRADE system (Grading of Recommendations Assessment, Development and Evaluation)

The Ministry of Health of Chile, aiming to improve the quality of clinical practice guidelines, gradually incorporated the GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) to develop evidence based recommendations. This system summarizes and evaluates the certainty of the available evidence. It moves from evidence to decision in a systematic and transparent manner, based on four main dimensions: balance between benefits and harms, certainty of evidence, patient's values and preferences and use of resources. The GRADE system produces strong and conditional recommendations. Strong recommendations provide confidence that the favorable consequences of an intervention clearly outweigh the adverse consequences, or vice versa. These recommendations apply to a broad range of patients and circumstances. Conditional recommendations, however, indicate that there is a close balance between favorable and unfavorable consequences of the intervention, there is uncertainty in the magnitude of benefits or adverse effects, there is uncertainty or variability in values and preferences of individuals or costs are not justified. These recommendations apply to many patients, but not all of them: ideally they should be discussed with each person. To achieve a better implementation of the recommendations made with GRADE methodology, health professionals should know the meaning of strong and conditional recommendations and they should be able to critically assess of them.

Surveillance of antiviral resistance markers in Argentina: detection of E119V neuraminidase mutation in a post-treatment immunocompromised patient

Although vaccines are the best means of protection against influenza, neuraminidase inhibitors are currently the main antiviral treatment available to control severe influenza cases. One of the most frequent substitutions in the neuraminidase (NA) protein of influenza A(H3N2) viruses during or soon after oseltamivir administration is E119V mutation. We describe the emergence of a mixed viral population with the E119E/V mutation in the NA protein sequence in a post-treatment influenza sample collected from an immunocompromised patient in Argentina. This substitution was identified by a real-time reverse transcriptase polymerase chain reaction (RT-PCR) protocol and was confirmed by direct Sanger sequencing of the original sample. In 2014, out of 1140 influenza samples received at the National Influenza Centre, 888 samples (78%) were A(H3N2) strains, 244 (21.3%) were type B strains, and 8 (0.7%) were A(H1N1)pdm09 strains. Out of 888 A(H3N2) samples, 842 were tested for the E119V substitution by quantitative RT-PCR: 841 A(H3N2) samples had the wild-type E119 genotype and in one sample, a mixture of viral E119/ V119 subpopulations was detected. Influenza virus surveillance and antiviral resistance studies can lead to better decisions in health policies and help in medical treatment planning, especially for severe cases and immunocompromised patients.

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVE: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. METHODS Search methods: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. Selection criteria: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. Data collection and analysis: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage ...

Clinical Profile of the H1N1 Influenza.

The H1N1 influenza A infection initially pandemic started in Mexico in March 2009 and spread as per WHO phases of pandemic alert all over the world. It was in late march 2009 an outbreak of a respiratory illness and later to proved to be caused by novel swine origin influenza A (S-OIV) identified in Mexico. Aims & Objectives : The aim of the present study was to describe first clinical presentation, various organ damage, treatment outcome duration of hospital stay and mortality and impact on high risk group patients. This is retrospective study hospital based Bharati Vidyapeeth Deemed University Medical College and Hospital, Sangli. Material and Methods: During post-pandemic period in 2010 the patients were admitted in hospitals which were suspected cases of H1N1 influenza “A” infection. 118 cases were studied August 2010 to 31st January 2011. Results : One hundred eighteen (118) patients were admitted in hospital. Of the 118 patients 32 patients were H1N1 positive and 86 patients H1N1 negative. RT- PCR test was done for confirmation of infection. X- Ray chest in positive cases of H1N1 influenza “A” infection bilateral extensive Pneumonititis other organ damage suggestive ECG, STT were changes renal failure common symptoms cough, fever, breathlessness in 28 cases sex-wise and age-wise distribution is not significant. Hospital stay all admitted patients and hospital stay in expired patients p value < 0.00 and < 0.005 highly significant. Statistics – percentage, ratio Chi- square tests used. Conclusion : Mortality in risk (Comorbid condition) with and without risk (ventilator required) The Mortality was 18.50 % more during the winter season (Chilly and cold atmosphere August to October during this season feverable for viability of the virus) significantly mortality is seen in young age group. This infection can be prevented by vaccination. The tablet tamiflu 75 mg 1 BD for 10 days no other adverse effects observed in our study the drug is safe and no resistance was observed.

The Association between Influenza Treatment and Hospitalization-Associated Outcomes among Korean Children with Laboratory-Confirmed Influenza

There are limited data evaluating the relationship between influenza treatment and hospitalization duration. Our purpose assessed the association between different treatments and hospital stay among Korean pediatric influenza patients. Total 770 children < or = 15 yr-of-age hospitalized with community-acquired laboratory-confirmed influenza at three large urban tertiary care hospitals were identified through a retrospective medical chart review. Demographic, clinical, and cost data were extracted and a multivariable linear regression model was used to assess the associations between influenza treatment types and hospital stay. Overall, there were 81% of the patients hospitalized with laboratory-confirmed influenza who received antibiotic monotherapy whereas only 4% of the patients received oseltamivir monotherapy. The mean treatment-related charges for hospitalizations treated with antibiotics, alone or with oseltamivir, were significantly higher than those treated with oseltamivir-only (P < 0.001). Influenza patients treated with antibiotics-only and antibiotics/oseltamivir combination therapy showed 44.9% and 28.2%, respectively, longer duration of hospitalization compared to those treated with oseltamivir-only. Patients treated with antibiotics, alone or combined with oseltamivir, were associated with longer hospitalization and significantly higher medical charges, compared to patients treated with oseltamivir alone. In Korea, there is a need for more judicious use of antibiotics, appropriate use of influenza rapid testing.

Fatores relacionados ao óbito pela Influenza Pandêmica A (H1N1) 2009 em pacientes tratados com Oseltamivir / Factors related to death by the Pandemic Influenza A (H1N1) 2009 in patients treated with Oseltamivir / Factores relacionados con la muerte por la Influenza Pandémica A (H1N1) 2009 en pacientes tratados con Oseltamivir

Este estudo pretende identificar os fatores relacionados ao óbito na Influenza Pandêmica A(H1N1) 2009 em pacientes tratados com Oseltamivir. Trata-se de um estudo observacional e retrospectivo, realizado com dados de pacientes que apresentaram diagnóstico laboratorial da doença. Os dados foram coletados dos formulários de notificação da doença, pertencentes a uma base de dados do Ministério da Saúde. As análises estatísticas foram realizadas pelos testes de qui-quadrado, t de Student e por regressão logística, considerando significativos os valores de p<0,05. A maior ocorrência de óbitos foi observada nos pacientes com idade entre 20 e 59 anos, de baixa escolaridade, com a presença de comorbidades, não vacinados, tratados tardiamente e que apresentavam sintomas mais severos da infecção. A identificação de fatores de risco para o óbito reforça a necessidade de prevenção e assistência precoce, principalmente na presença de fatores que aumentam a gravidade clínica da doença.

This study aimed to identify factors related to death in Pandemic Influenza A(H1N1)2009 in patients treated with Oseltamivir. It is an observational and retrospective study, carried out with data of patients who had presented laboratorial diagnosis of the illness. Data were collected from the notification forms of the disease, belonging to a database of the Ministry of Health. Statistical analysis was performed by chi-square, Student t test and logistic regression, considering significant p values <0,05. The highest mortality was observed in patients aged between 20 and 59 years, low schooling, with the presence of comorbidities, not vaccinated, treated late and had more severe symptoms of infection. The identification of risk factors for death reinforces the need for prevention and early care, especially in the presence of factors that increase the clinical severity of disease.

Este estudio se propone identificar los factores relacionados con la muerte dela influenza pandémica A(H1N1)2009 en pacientes tratados con Oseltamivir. Es un estudio observacional y retrospectivo, realizado con datos de los pacientes que presentan diagnóstico de laboratorio. Los datos fueron recogidos de los formularios de notificación de la enfermedad, pertenecientes a una base de datos del Ministerio de Salud. Los análisis estadísticos se realizó mediante las pruebas del qui-cuadrado, t de Student y regresión logística, en vista de significativo los valores de p<0,05. La mayor mortalidad se observó en pacientes con edades entre 20 y 59 años, baja escolaridad, con la presencia de comorbilidades, no vacunados, tratados tardíamente y que habían síntomas más graves de la infección. La identificación de factores de riesgo para la muerte refuerza la necesidad de la prevención y atención temprana, especialmente en la presencia de factores que aumentan la gravedad de la enfermedad.

Pandemic H1N1 illness prognosis: evidence from clinical and epidemiological data from the first pandemic wave in São Paulo, Brazil

OBJECTIVES: The pandemic of 2009 H1N1 influenza A emerged in February 2009, with high morbidity and mortality, and rapidly spread globally. São Paulo was among the most affected areas in Brazil. This study compares the clinical and epidemiological characteristics of influenza-like illness between outpatients and hospitalized patients and evaluates the impact of oseltamivir therapy on the outcome of 2009 H1N1 influenza A patients. METHODS: This is a case series study comparing the clinical and epidemiological characteristics of influenza-like illness between outpatients attended at Hospital São Paulo in August 2009 (the peak of the first pandemic wave) and those patients hospitalized between May and September 2009 (the entire first pandemic wave). RESULTS: The 1651 patients evaluated were predominantly female (927×686, p<0.001) and aged 31.71±16.42 years, with 148 reporting chronic pulmonary disease. Dyspnea was presented by 381 (23.4%) patients and was more frequent among those aged 30 years or more (p<0.001). Hospitalization occurred at 3.73±2.85 days, and antiviral treatment started 2.27±2.97 days after the onset of first symptoms. A delay of more than 5 days in starting oseltamivir therapy was independently associated with hospitalization (p<0.001), a stay in the ICU (p<0.001) and a higher risk of dying (OR = 28.1, 95% CI 2.81-280.2, p = 0.007). CONCLUSION: The 2009 pandemic of H1N1 influenza A affected young adults, presented a significant disease burden and produced severe cases with a significant fatality rate. However, promptly starting specific therapy improved the outcome. .