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The Best Flu Treatment For You - Consumer Reports
Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Influenza-related severe pneumonia and acute respiratory distress syndrome ARDS are severe threats to human health. The objective of this study was to assess the effects of systematic corticosteroid therapy in patients with pneumonia or ARDS.
Nineteen studies including individuals were identified, and fifteen studies patients were included in the meta-analysis of mortality. Eighteen were observational studies and one was a randomized controlled trial RCT.
The meta-analysis results showed that corticosteroid therapy was associated with significantly higher mortality OR 1. Subgroup analysis showed that among patients with unadjusted estimates, the odds of mortality were higher in patients receiving corticosteroid treatment OR 1. Current data do not support the routine use of corticosteroids in patients with influenza severe pneumonia or ARDS.
RCTs are needed to provide more robust evidence. Influenza is a viral infection that attacks the respiratory system.
Rapidly progressing viral pneumonia and acute respiratory distress syndrome are pulmonary manifestations that are commonly observed in patients with influenza and are associated with considerable mortality 123representing a severe threat and imparting a substantial financial burden worldwide 4.
Individuals with community-acquired pneumonia may benefit from systematic corticosteroid therapy, which may block the inflammatory cascade reaction 5. Corticosteroids could improve the lung tissue damage induced by influenza pneumonia and decrease the risk of mortality in animal models with influenza infections 67.
Many clinicians administer corticosteroids as an anti-inflammatory treatment for patients with severe influenza-related pneumonia to stop disease progression and improve clinical outcomes. A large cohort study of patients admitted to ICUs in Spain found that the frequency of corticosteroid treatment by study period was Recently, some studies have shown that corticosteroids may not be beneficial for patients with severe influenza and may even increase mortality 910 However, there is considerable uncertainty regarding whether patients with influenza-related ARDS or severe pneumonia can benefit from adjuvant corticosteroid therapy.
We aimed to systematically review all experimental and observational studies on corticosteroid use in patients with influenza-related ARDS and severe pneumonia. The effect of corticosteroid treatment on clinical outcomes was investigated. A study was excluded if it met any of the following criteria: a the study was a review article, conference abstract, case report or case series, case-control study; b the majority of included patients were immunocompromised; c insufficient data were available; d overlapping population; e studies with fewer than 20 participants.
There were no restrictions on influenza subtype, patient age or study setting. If only some of the individuals included in a study fit the eligibility criteria and these individuals had extractable results corresponding to the objective of this study, then the study was included.
Clinical outcomes including mortality, nosocomial infection, duration of mechanical ventilation, length of stay, time to fever alleviation and clinical stability and viral shedding were evaluated. The references of eligible studies were screened, and two authors independently reviewed all citations that met the inclusion criteria.
Study selection was performed in 2 stages: first, study title and abstract screening; second, full text examination. Outcome data were independently extracted from the included studies by two investigators using a previously piloted standardized pro forma. We obtained the following data: a characteristics of studies design, setting, country, period, methodological details for quality assessment ; b characteristics of participants demographics, co-morbid illnesses, disease severity, numbers in each group, influenza virus type ; c characteristics of interventions type, dose, timing and duration of corticosteroid use ; and d outcomes.
The quality of each study was independently assessed by two individuals according to the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for nonrandomized trials and comparative observational studies. Disagreements at any stage were resolved through discussion with the other authors until consensus was reached. We performed sensitivity analysis to assess the effect of the study design on clinical outcomes using stratification if the number of studies was sufficient.
Medians and interquartile ranges were generated in the analysis of continuous data that were not normally distributed. Subgroup analysis was performed in the following areas where possible: adult population versus child population; seasonal influenza versus outbreak influenza or pandemic influenza; ICU versus inpatient; adjusted estimates versus unadjusted estimates; and corticosteroid dose, timing and duration. A total of relevant articles were identified during the initial search.
After the removal of duplicates, articles remained. After screening the titles and abstracts of those articles, articles were excluded because of irrelevance. Of the 98 full-text articles reviewed, 81 were excluded for various reasons, and 19 articles remained. Details regarding the reasons for the exclusion of these studies are shown in Fig.
Ultimately, 15 studies were included in the meta-analysis of mortality, while 4 studies reported outcomes other than mortality in association with corticosteroid use. The characteristics of the participants in the included studies are summarized in Table 1 and Supplementary Table S3. The studies were published between and Eighteen of the studies had an observational design, while one had a randomized controlled trial design Outcome data were reported in 19 studies individuals, including in corticosteroid group and in the non-corticosteroid groupwhile mortality data were reported in 15 studies individuals.
Fourteen studies assessed individuals with H1N1pdm09 virus infection, 1 study assessed individuals with H7N9 virus infection, and 4 study assessed individuals with inter-pandemic influenza virus infection. Eight studies individuals had useable data related to patients with ARDS 9101415161718 The median ages varied from 2.
The proportion of male participants was higher than that of females Disease severity at baseline was reported in seven studies and in 4 studies individualsthe baseline disease severity was higher in individuals in the corticosteroid group than in those in the non-corticosteroid group 1920 Methylprednisolone Almost all patients The details of the therapies are described in Table 1. Because all studies included in the meta-analysis of mortality were observational cohort studies, selection bias was inevitable.
The risk of bias identified in the 19 included studies is shown in Supplementary Tables S4a,b. However, most included studies had substantial comparability bias because we could not adequately adjust for disease severity, and individuals with greater diseases severity tended to use corticosteroids. The pooled analysis of the crude results of the 15 included studies individuals suggested that those who used corticosteroids had a significantly higher mortality rate OR 2.
Five studies 810141526 reported adjusted effect estimates of day or inhospital mortality adjusted OR or adjusted hazard ratio aHRTable 2.
The pooled analysis of the crude results of ten included studies and five adjusted effect estimates suggested that those who used corticosteroids had a significantly higher mortality rate OR 1. The subgroup analysis of unadjusted effect estimates showed a similar result OR 1. However, the subgroup analysis of the five adjusted estimates showed no association between mortality and corticosteroid use HR 1.
There was no clear indication of publication bias in the funnel plot analysis Supplementary Fig. Meta-analysis of studies reporting mortality data. Abbreviations: CI, confidence interval; OR, odds ratio. Meta-analysis of unadjusted and adjusted estimates suggested that the difference in mortality between the corticosteroid and control groups was not statistically significant OR 1.
Li et al. However, Brun-Buisson et al. Cao et al. The other four studies 9161719 showed that corticosteroid use had no association with mortality Fig. Meta-analysis of studies mortality data in patients with ARDS. Considering the different management strategies for paediatric and adult patients, one study investigating paediatric patients was excluded The pooled analysis of 14 studies reporting adult individuals revealed a significant increase in the odds of mortality with corticosteroid use, with moderate statistical heterogeneity OR 2.
A subgroup analysis according to pure ICU patients 8 studies, individuals and mixed patients 7 studies, individuals including both ICU and wards patients was conducted. For the pure ICU subgroup, we found that corticosteroids were associated with an increased risk of mortality OR, 1.
A pooled analysis of these three studies showed no statistically significant association between corticosteroid use and mortality OR 1. The pooled analysis of these studies found corticosteroid use to be associated with greater odds of mortality OR 2. The number of studies was insufficient to perform subgroup analysis according to the various reported regimens. Two of the included studies reported outcomes related to children, but only one reported the risk of mortality OR 8. However, in that study, all children who received corticosteroids had ARDS, while the patients in the non-corticosteroid group had less severe disease conditions.
Another retrospective cohort study of children with pneumonia caused by the H1N1 influenza virus only reported length of hospital stay and duration of fever 28 and found a shorter length of stay and duration of fever in corticosteroid group Table 3.
Six studies reported an association between corticosteroid use and nosocomial infection. In four of these studies, corticosteroid use was associated with an increased risk of developing a nosocomial infection 15172021while the remaining two studies did not show a statistically significantly increased odds of developing infection 10 Overall, the pooled results revealed that the odds of nosocomial infection were significantly higher in patients who were administered corticosteroids than in those who were not OR 3.
Meta-analysis of studies reporting nosocomial infection data. CI, confidence interval; OR, odds ratio. Three studies reported the common pathogens isolated from patients with nosocomial infection. One study reported that the most common bacteria isolated was Acinetobacter baumannii In a study of patients with severe influenza pneumonia 15patients had nosocomial infection, and the most commonly isolated pathogens were Acinetobacter baumannii Seven studies reported length of stay according to corticosteroid use; all were unadjusted for disease severity Table 3.
Six studies found no statistically significant difference between the groups. One study 19 showed a longer length of ICU stay associated with corticosteroid use, while the total length of hospital stays was not significantly different between the groups.
Linko et al. Table 3. Two studies reported the time to fever alleviation according to corticosteroid use 28 Kudo et al. Notably, two studies found a shorter time to clinical stability in the corticosteroid group. The details of these outcomes are described in Table 3. The overall findings of this meta-analysis indicated that patients with pneumonia or acute respiratory distress syndrome who were administered corticosteroids had significantly higher mortality and incidence of nosocomial infection but the use of corticosteroids did not influence the length of hospital stay.
Our studies suggested a deleterious effect of steroids on mortality and nosocomial infection.
❿Prednisone works well for range of conditions, but can have many side effects - localhost
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In four of these studies, corticosteroid use was associated with an increased risk of developing a nosocomial infection 15 , 17 , 20 , 21 , while the remaining two studies did not show a statistically significantly increased odds of developing infection 10 , Overall, the pooled results revealed that the odds of nosocomial infection were significantly higher in patients who were administered corticosteroids than in those who were not OR 3.
Meta-analysis of studies reporting nosocomial infection data. CI, confidence interval; OR, odds ratio. Three studies reported the common pathogens isolated from patients with nosocomial infection.
One study reported that the most common bacteria isolated was Acinetobacter baumannii In a study of patients with severe influenza pneumonia 15 , patients had nosocomial infection, and the most commonly isolated pathogens were Acinetobacter baumannii Seven studies reported length of stay according to corticosteroid use; all were unadjusted for disease severity Table 3.
Six studies found no statistically significant difference between the groups. One study 19 showed a longer length of ICU stay associated with corticosteroid use, while the total length of hospital stays was not significantly different between the groups.
Linko et al. Table 3. Two studies reported the time to fever alleviation according to corticosteroid use 28 , Kudo et al. Notably, two studies found a shorter time to clinical stability in the corticosteroid group. The details of these outcomes are described in Table 3.
The overall findings of this meta-analysis indicated that patients with pneumonia or acute respiratory distress syndrome who were administered corticosteroids had significantly higher mortality and incidence of nosocomial infection but the use of corticosteroids did not influence the length of hospital stay. Our studies suggested a deleterious effect of steroids on mortality and nosocomial infection.
Several factors need to be accounted for in interpreting these findings. First, most studies did not adjust the clinical outcomes for potential confounding factors. Clinically, more severe cases tended to be treated with corticosteroids, which may obscure the real value of this treatment regarding mortality 30 , Therefore, in this study, we preferred the use of adjusted estimates of the effect to minimize potential confounding between the treatment groups.
However, five studies reported adjusted estimates of mortality, and their inclusion in the meta-analysis still revealed a higher odds of mortality related to steroids use.
Good evidences indicated that secondary bacterial pneumonia is an important cause of mortality related to influenza 32 , Therefore, increasing risk of nosocomial infection due to corticosteroid treatment may partly account for the potential harm from corticosteroid use. Two included studies 8 , 15 found that secondary bacterial pneumonia such as due to Acinetobacter baumannii , Pseudomonas aeruginosa , Streptococcus pneumoniae , Staphylococcus aureus or invasive fungal infection, were more common in corticosteroid-treated patients.
Several studies showed that prolonged viral shedding and delayed viral clearance were noted in corticosteroid-treated patients 10 , 34 , whereas slower clearance of virus loads was associated with higher mortality in patients with ARDS due to H1N1pdm09 virus infection Thus, prolonged viral shedding and delayed viral clearance may also contribute to higher mortality.
Second, most of the included observational studies did not explain why some patients received systemic corticosteroid therapy and others did not. Different indication may easily confound the effect of the corticosteroid. Some evidences supported the use of corticosteroids for asthma or COPD or septic shock in the context of influenza infection 36 , 37 , However, the high level of statistical heterogeneity may result in unstable estimates of the meta-analysis.
Therefore, well-designed clinical trials should be conducted to decrease the heterogeneity of patients and to provide more robust evidence. The results from clinical studies of corticosteroid therapy in patients with influenza are conflicting. Many studies have shown a significant association between corticosteroid treatment and mortality in patients with influenza; however, several studies have reported that corticosteroids can provide benefits to patients under certain conditions 15 , 28 , 39 , Kil et al.
However, in another study, compared with no treatment, administration steroid therapy was initiated at a median daily dose equivalent to IQR, — mg of hydrocortisone, and a median duration of 11 IQR, 6—20 days within the first 3 days of MV was more strongly associated with an increased risk of death, whereas when administration was beyond the first 3 days of MV, the association was no longer significant Several recent systematic reviews and meta-analyses concluded that corticosteroid therapy is significantly associated with mortality 41 , 42 , However, in these studies, there were no special limitations on subject inclusion criteria, which means that the patients were very diverse.
Additionally, there was no subgroup analysis for these patients under different disease conditions. Compared to patients in those previous studies, we focused only on patients with pneumonia or ARDS, which is more specific and makes the outcomes more targeted.
Our study observed a different outcome according to corticosteroid use in patients with ARDS due to influenza. This study has some limitations, including the lack of sufficient data on the dose, duration, timing and rationales of corticosteroid administration and the timing and duration of antiviral therapy.
In addition, only one study included in this meta-analysis was an RCT, and 18 were observational in nature. Thus, it is possible that selection bias or comparability bias could have affected the quality of the analysed evidence.
There is insufficient evidence in this meta-analysis to make a firm determination about the effectiveness of corticosteroids for people with influenza-related pneumonia or ARDS. The small number of included studies and the small number of patients in the included studies might also make the effect size of some outcome indicators insufficient, and we were unable to analyse the effect of some factors on the outcome indicators by meta-regression or subgroup analysis.
Current data do not support the routine use of corticosteroids in patients with influenza pneumonia or ARDS. However, the data assessed in this meta-analysis were extracted from 18 observational studies and only one RCT; therefore, the limitations associated with study design are important to consider. There is a need for more robust evidence on the role of corticosteroids in the treatment of influenza-related ARDS and severe pneumonia before a firm recommendation for clinical practice can be made.
Abdel-Ghafar, A. Update on avian influenza A H5N1 virus infection in humans. Kumar, A. Critically ill patients with influenza A H1N1 infection in Canada. Simonsen, L. Peasah, S. Influenza cost and cost-effectiveness studies globally—a review. Article PubMed Google Scholar. Torres, A. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial.
Li, C. Corticosteroid treatment ameliorates acute lung injury induced by swine origin influenza A H1N1 virus in mice. Ottolini, M. Combination anti-inflammatory and antiviral therapy of influenza in a cotton rat model. Moreno, G. Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study.
Kim, S. Cao, B. Prednisone suppresses the immune system and adrenal function, so doctors say that if you stop cold turkey, the adrenal glands may not respond as they would normally.
This is a condition called "adrenal insufficiency. Gradually weaning from prednisone allows the adrenals to begin functioning as they did before the patient began taking the steroid. People who are taking prednisone for months or years suffer not only from long-term side effects, but may continue to suffer from the short-term "nuisance" symptoms.
Those can have a deleterious effects on a person's life and personality -- and on the people around them. If a person does have a serious reaction, doctors can instead opt for one of seven subclasses of nonsteroidal anti-inflammatory drugs, or NSAIDs. Examples include meloxicam or even aspirin or ibuprofen. That's why it's important to talk to your doctor if your body is reacting badly. Treatment was sought for rheumatoid arthritis. Prednisone has been dubbed "a 20th-century wonder drug.
Before prednisone, doctors say, there weren't effective treatments for conditions or illnesses such as lupus, severe psoriasis, asthma, bacterial meningitis or a serious case of pneumonia. Prednisone was developed in a long process that was originally connected to the search for a treatment for rheumatoid arthritis, says Abelson.
More than a century ago, doctors knew that women with rheumatoid arthritis felt significantly better when they were pregnant. And, notes Heather Free, Pharm D. Homeopathic products , which are classified by the FDA as medications and may sit on drugstore shelves next to over-the-counter drugs, are a different matter. In homeopathy, a presumed active ingredient—in Oscillococcinum, it's an extract of wild duck heart and liver—is diluted to the point where it's virtually undetectable.
According to Lipman, there's no good evidence that homeopathy works. Consumer Reports reached out to Boiron, the manufacturers of Oscillococcinum. In an emailed statement, a Boiron representative wrote, "Oscillococcinum has remarkable customer satisfaction and a money-back guarantee.
The statement also said: "Oscillococcinum has been shown in two placebo-controlled, double-blind, randomized clinical trials to help reduce the severity and shorten the duration of flu-like symptoms. What should you do if you've got the flu? Unless you're a candidate for an antiviral, our experts recommend strategies such as rest, getting plenty of fluids, and the use of OTC pain relievers as directed by your doctor. You can also follow the Consumer Reports' day-by-day guide to treating colds and flu.
While most studies on masks have been done in healthcare settings, some suggest they may help stave off flu in other situations, too. It may also help prevent you from passing the virus from your hands to your mouth or nose. And wear one if you're sick and are going to be around other people, or are caring for someone with the flu.
Last, consider a mask if you're going to a doctor's office, or if you're traveling on an airplane, especially if people around you seem sick. Two types of masks are currently available: surgical masks available at drugstores and online , designed to block large particles that may carry viruses, and N respirators available at some hardware, medical supply, and office supply stores and online , which block even smaller particles. Both appear to work equally well, according to a study in JAMA.
Because there was no randomized trial available, we included both cohort studies and case—control studies. We included cohort studies fulfilling the following selection criteria: enrolled patients had confirmed, probable, or suspected influenza A H1N1 ; all of the subjects were inpatient, or admitted to the ICU, or critically ill; corticosteroid treatment was compared with noncorticosteroid treatment within the cases; and data about hospital mortality were accessible.
For case—control studies, the inclusion criteria were that: enrolled patients had confirmed, or had probable or were suspected of having influenza A H1N1 ; all of the subjects were inpatient, or admitted to the ICU, or critically ill; deaths were cases and survivors were controls; and the numbers of patients who received or did not receive steroid treatment were presented in two groups.
There were no restrictions on studies with respect to age groups. Studies were excluded if they: included seasonal influenza infection cases; were in vitro tests, animal experiments, case studies, case series, and review or letter articles; and targeted special crowds, such as pregnant women and patients with HIV infections.
Additionally, confirmed influenza A H1N1 cases were defined as an acute respiratory illness with laboratory confirmation by real-time PCR or viral culture. Corticosteroid treatment was defined as: systemic corticosteroid use; and nonstandardized corticosteroid use, which was decided by the attending physician and was regardless of type, dosage, and frequency of administration. All full articles were reviewed for the selection and exclusion of publications with predefined inclusion criteria by two researchers independently.
We also contacted the corresponding author of 12 studies by email to ask for additional details. However, only three authors responded. For case—control studies, we collected information about the numbers of patients treated with steroids in each group. With regard to cohort studies, information about the number of patients who died in each group and other clinical outcomes were collected.
Disagreements were resolved by consensus. The Newcastle-Ottawa Scale scoring system was used to assess the methodology and quality of both cohort studies and case—control studies [ 29 ]. The Newcastle-Ottawa Scale assigns a maximum score of 4 for selection, 2 for comparability, and 3 for exposure case—control studies or outcome cohort studies. Hence, a score of 9 is the highest possible and reflects the best quality.
Two investigators independently assessed the risk of bias of each study. The detailed evaluation criteria are shown in Additional file 1. Inter-rater agreement was assessed using Cohen's kappa statistics and disagreements were resolved by consensus. We calculated the relative risk for death within cohort studies, while the odds ratio OR was used for case—control studies.
Heterogeneity of treatment effects among studies was assessed by examining forest plots, and statistically using Cochran Q and I 2 statistics. If a significant heterogeneity was identified, subgroup analyses were carried out. Studies were categorized by sample size, by whether the subjects from two groups are comparable in terms of age and antiviral treatment, and by whether the studies included probable and suspected A H1N1 cases.
Sensitivity analysis excluded studies one by one to investigate the heterogeneity. The sponsor of this study had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the paper for publication. The corresponding authors had full access to all data in the study and had final responsibility for the decision to submit the paper for publication.
Of the 2, references screened, 23 studies were included in the final analysis Figure 1. Fourteen studies were case—control studies [ 15 , 31 - 43 ], and nine studies were cohort studies [ 44 - 52 ].
In total, 6, subjects were analyzed, with 4, subjects in case—control studies and 1, subjects in cohort studies.
Among these studies, seven studies were conducted in China [ 36 , 39 , 41 - 44 , 50 ], three in Spain [ 33 , 45 , 49 ], three in India [ 31 , 35 , 46 ], two in Korea [ 18 , 28 ], two in Argentina [ 15 , 40 ], and one study each was conducted in Mexico [ 37 ], Turkey [ 38 ], Saudi Arabia [ 48 ], France [ 51 ], and Finland [ 52 ], while the remaining study was multicenter and conducted in several countries European Society of Intensive Care Medicine [ 47 ].
The characteristics of the included studies are summarized in Table 1. Participants in all studies were inpatients. Eighteen studies only included patients in the ICU or critically ill cases [ 15 , 32 - 36 , 38 - 40 , 42 , 44 , 46 - 52 ], and three studies included children [ 35 , 36 , 40 ]. There was only one study that did not mention antiviral treatment use in patients [ 44 ]. Corticosteroid treatment varied among these studies, with most using methylprednisolone or hydrocortisone; doses varied from 80 to mg daily.
However, there were still several studies which did not describe the tapering doses in detail, or the precise duration of treatment. Two Spanish studies showed that corticosteroid administrations were not standardized and were decided by the attending physician without detailed data [ 33 , 49 ]. Another six studies did not provide any detailed information about dose, duration, and treatment mode [ 34 , 40 , 42 - 44 , 52 ]. The overall quality of the included studies was moderate and the analyses are presented in Figure 2 and Figure 3.
Most studies were retrospective and observational studies, and the most common bias was lack of comparability in terms of age or antiviral therapy between study groups. In addition, some studies did not provide detailed data with regard to corticosteroid use. Most of the study data were obtained either from the registration systems or by reviewing hospital records, and the response rate was not reported. They were therefore judged as high risk in this respect.
Only a few studies demonstrated that they excluded steroid-use cases for underlining diseases, while other studies did not mention this at all. Effect of corticosteroids on influenza A H1N1 cases from case—control studies.
Diamond, overall estimate from the meta-analysis; square, point estimate of the result of each study; horizontal line that runs through the square and the width of the diamond represents the CI. Red dot, high risk of bias; green dot, low risk of bias; A to I, see Additional file 1. Effect of corticosteroids on influenza A H1N1 cases from cohort studies. The random-effects model was therefore used and the combined OR was 4.
Subgroup analysis was conducted to investigate the heterogeneity, and the results are shown in Additional file 2. The plots show that the sample size of studies, as well as comparability in terms of age and antiviral treatment, did not significantly influence the final mortality outcome.
The heterogeneity was not statistically significant, after studies were categorized according to whether they enrolled suspected or probable cases, and the pooled OR was 5. Subgroup analyses, as shown in Additional file 3 , revealed that the relative risk was higher in studies of poor quality than that of the good quality studies.
However, the difference was not statistically significant. Besides, the inclusion of probable and suspected cases did not significantly change the result, consistently showing steroid treatment was a risk factor of mortality. Similarly, another Chinese study indicated that patients in steroid treatment groups have a shorter duration of fever and a shorter duration of inflammation [ 50 ].
Also, Linko and colleagues study showed that the length of ICU and hospital stay was significantly longer in the patients treated with corticosteroids [ 52 ].
Regarding the duration of mechanical ventilation, Diaz and colleagues displayed that there was no difference between the corticosteroid and noncorticosteroid groups [ 49 ]. However, the funnel plots provided evidence of publication bias for both types of studies Additional file 4. During the influenza pandemic, the debate over whether to use corticosteroid treatment in severe influenza H1N1-infected patients resurfaced and was disputed by clinicians [ 26 ].
According to our review, corticosteroid administration is likely to increase mortality in patients with influenza A H1N1 , and the trend is consistent regardless of the quality as well as the sample size of studies. Apart from the studies included in this meta-analysis, there are many studies that refer to the steroids used and the outcomes, and most of them reported that corticosteroids have negative effects or no effect on H1N1 treatment.
For example, Balaganesakumar and colleagues found that corticosteroid treatment would cause a higher risk of poor patient outcomes [ 54 ]. Other reports showed that patients who received corticosteroids were more likely to develop secondary bacterial pneumonia [ 47 , 55 ] or were associated with an increased risk of developing critical illness, with ICU admission, or had more prolonged ICU stays [ 17 , 55 - 57 ].
The possible explanation for the negative effectiveness of corticosteroids might be that corticosteroids could inhibit immune reactions. However, immune systems should be activated in order to eliminate the virus [ 58 ]. Altered immune reactions thus might lead to prolonged virus viremia [ 59 ] and delay viral clearance [ 60 ], and ultimately increase the risk of mortality.
Indeed, there are several studies that reveal the positive role of corticosteroids, but most of them used animal models [ 61 ] or case series that lacked a control group [ 22 , 24 ].
Critical Care volume 19Article number: 46 Cite this article. Metrics details. Corticosteroids are used empirically in influenza A H1N1 treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection.
Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection.
Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. In total twenty-three eligible studies were included. The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality.
However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza.
We conclude that further research is required. Novel influenza A H1N1 spread around the world in spring Although influenza A H1N1 infection has a mild clinical course, the pandemic virus is capable of leading to severe illness, requiring hospitalization. As an example, the hospital admission rate for children with H1N1 influenza was twofold the rate for seasonal influenza [ 1 ]. The disease causeddeaths globally [ 67 ]. Accordingly, there is an increasing need for the development of an effective therapy and treatment to improve upon the prognosis of severe cases.
In severe influenza infectious cases, cytokine dysregulation was observed in patients [ 8 ] and corticosteroids had been proven to be able to reduce systemic inflammation by inhibition of proliferation and cytokine production [ 8 - 11 ]. Previous meta-analyses of patients with acute long injury and acute respiratory distress syndrome indicated that prolonged glucocorticoid treatment is safe and is associated with significant reductions in markers of systemic inflammation, multiple organ dysfunction score, duration of mechanical ventilation, and ICU length of stay [ 1112 ].
Although corticosteroids are widely used, the effect of corticosteroids on pandemic A H1N1 influenza patients has not been studied adequately and, thus, is still controversial. For example, in several studies a remarkable effect was observed of early treatment with oseltamivir and steroids for patients with severe pneumonia in preventing disease progression [ 19 - 21 ].
Additionally, a number of clinical case series and case reports have shown that patients with severe respiratory complications, pneumonia, improved after the use of corticosteroids [ 22 - 24 ]. However, the USA Centers for Disease Control and Prevention does not recommend the use of corticosteroids as a primary medicine for H1N1 infection, with the exception that a reasonable dose is indicated for a specific reason; for example, pulmonary obstruction or septic shock [ 25 ].
Moreover, World Health Organization guidelines for Pharmacological Management of Pandemic Influenza A H1N1 and other Influenza Viruses recommend that systemic corticosteroids should not be administrated to patients who have severe or progressive clinical illness unless in some exceptional circumstances [ 2627 ].
Severe influenza treatment guidelines for Korea also indicate that systemic corticosteroid administration should not be performed for the treatment of severe influenza patients unless the therapeutic effect has already been proven [ 28 ]. None of the guidelines above recommend systematic corticosteroid use regularly with H1N1 infection. However, lack of clinical evidence makes these recommendations or guidelines unconvincing. Until now, many studies involving the treatment of severe H1N1 cases have been published, but the results are inconsistent, which could be due to insufficient sample sizes, complicated clinical status, or study design.
To our knowledge, there has been no systematic literature review evaluating the benefit of corticosteroids to severe H1N1 infection. A principal resource for the optimal clinical therapy of influenza A H1N1 patients and directions for future research are warranted.
We therefore conducted the present study to determine whether corticosteroids can treat severe H1N1 infection. To clarify the association of corticosteroids with H1N1 mortality taking into account clinical status and study design, we examined the associations in larger, prospective cohort studies in global settings, using existing literature, and assessed the effect of corticosteroids treatment on mortality through meta-analysis.
We conducted a comprehensive literature search both for English-language and Chinese-language articles examining the effect of corticosteroid treatment in influenza A H1N1 published up until October We contacted article authors for further information or clarification when necessary. No attempt was made to include unpublished data.
All searches were executed independently by two skilled researchers. In addition, the reference lists of retrieved original articles and of relevant systematic reviews were manually checked. No ethics board approval was deemed necessary for a meta-analysis of previously published studies.
Because there was no randomized trial available, we included both cohort studies and case—control studies. We included cohort studies fulfilling the following selection criteria: enrolled patients had confirmed, probable, or suspected influenza A H1N1 ; all of the subjects were inpatient, or admitted to the ICU, or critically ill; corticosteroid treatment was compared with noncorticosteroid treatment within the cases; and data about hospital mortality were accessible.
For case—control studies, the inclusion criteria were that: enrolled patients had confirmed, or had probable or were suspected of having influenza A H1N1 ; all of the subjects were inpatient, or admitted to the ICU, or critically ill; deaths were cases and survivors were controls; and the numbers of patients who received or did not receive steroid treatment were presented in two groups.
There were no restrictions on studies with respect to age groups. Studies were excluded if they: included seasonal influenza infection cases; were in vitro tests, animal experiments, case studies, case series, and review or letter articles; and targeted special crowds, such as pregnant women and patients with HIV infections. Additionally, confirmed influenza A H1N1 cases were defined as an acute respiratory illness with laboratory confirmation by real-time PCR or viral culture.
Corticosteroid treatment was defined as: systemic corticosteroid use; and nonstandardized corticosteroid use, which was decided by the attending physician and was regardless of type, dosage, and frequency of administration. All full articles were reviewed for the selection and exclusion of publications with predefined inclusion criteria by two researchers independently.
We also contacted the corresponding author of 12 studies by email to ask for additional details. However, only three authors responded. For case—control studies, we collected information about the numbers of patients treated with steroids in each group. With regard to cohort studies, information about the number of patients who died in each group and other clinical outcomes were collected.
Disagreements were resolved by consensus. The Newcastle-Ottawa Scale scoring system was used to assess the methodology and quality of both cohort studies and case—control studies [ 29 ]. The Newcastle-Ottawa Scale assigns a maximum score of 4 for selection, 2 for comparability, and 3 for exposure case—control studies or outcome cohort studies. Hence, a score of 9 is the highest possible and reflects the best quality. Two investigators independently assessed the risk of bias of each study.
The detailed evaluation criteria are shown in Additional file 1. Inter-rater agreement was assessed using Cohen's kappa statistics and disagreements were resolved by consensus. We calculated the relative risk for death within cohort studies, while the odds ratio OR was used for case—control studies.
Heterogeneity of treatment effects among studies was assessed by examining forest plots, and statistically using Cochran Q and I 2 statistics. If a significant heterogeneity was identified, subgroup analyses were carried out. Studies were categorized by sample size, by whether the subjects from two groups are comparable in terms of age and antiviral treatment, and by whether the studies included probable and suspected A H1N1 cases.
Sensitivity analysis excluded studies one by one to investigate the heterogeneity. The sponsor of this study had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the paper for publication.
The corresponding authors had full access to all data in the study and had final responsibility for the decision to submit the paper for publication. Of the 2, references screened, 23 studies were included in the final analysis Figure 1. Fourteen studies were case—control studies [ 1531 - 43 ], and nine studies were cohort studies [ 44 - 52 ].
In total, 6, subjects were analyzed, with 4, subjects in case—control studies and 1, subjects in cohort studies.
Among these studies, seven studies were conducted in China [ 363941 - 4450 ], three in Spain [ 334549 ], three in India [ 313546 ], two in Korea [ 1828 ], two in Argentina [ 1540 ], and one study each was conducted in Mexico [ 37 ], Turkey [ 38 ], Saudi Arabia [ 48 ], France [ 51 ], and Finland [ 52 ], while the remaining study was multicenter and conducted in several countries European Society of Intensive Care Medicine [ 47 ].
The characteristics of the included studies are summarized in Table 1. Participants in all studies were inpatients. Eighteen studies only included patients in the ICU or critically ill cases [ 1532 - 3638 - 40424446 - 52 ], and three studies included children [ 353640 ]. There was only one study that did not mention antiviral treatment use in patients [ 44 ]. Corticosteroid treatment varied among these studies, with most using methylprednisolone or hydrocortisone; doses varied from 80 to mg daily.
However, there were still several studies which did not describe the tapering doses in detail, or the precise duration of treatment. Two Spanish studies showed that corticosteroid administrations were not standardized and were decided by the attending physician without detailed data [ 3349 ]. Another six studies did not provide any detailed information about dose, duration, and treatment mode [ 344042 - 4452 ]. The overall quality of the included studies was moderate and the analyses are presented in Figure 2 and Figure 3.
Most studies were retrospective and observational studies, and the most common bias was lack of comparability in terms of age or antiviral therapy between study groups. In addition, some studies did not provide detailed data with regard to corticosteroid use. Most of the study data were obtained either from the registration systems or by reviewing hospital records, and the response rate was not reported.
They were therefore judged as high risk in this respect. Only a few studies demonstrated that they excluded steroid-use cases for underlining diseases, while other studies did not mention this at all. Effect of corticosteroids on influenza A H1N1 cases from case—control studies.
Diamond, overall estimate from the meta-analysis; square, point estimate of the result of each study; horizontal line that runs through the square and the width of the diamond represents the CI. Red dot, high risk of bias; green dot, low risk of bias; A to I, see Additional file 1. Effect of corticosteroids on influenza A H1N1 cases from cohort studies. The random-effects model was therefore used and the combined OR was 4. Subgroup analysis was conducted to investigate the heterogeneity, and the results are shown in Additional file 2.
The plots show that the sample size of studies, as well as comparability in terms of age and antiviral treatment, did not significantly influence the final mortality outcome. The heterogeneity was not statistically significant, after studies were categorized according to whether they enrolled suspected or probable cases, and the pooled OR was 5. Subgroup analyses, as shown in Additional file 3revealed that the relative risk was higher in studies of poor quality than that of the good quality studies.
However, the difference was not statistically significant. Besides, the inclusion of probable and suspected cases did not significantly change the result, consistently showing steroid treatment was a risk factor of mortality. Similarly, another Chinese study indicated that patients in steroid treatment groups have a shorter duration of fever and a shorter duration of inflammation [ 50 ].
Also, Linko and colleagues study showed that the length of ICU and hospital stay was significantly longer in the patients treated with corticosteroids [ 52 ].
Regarding the duration of mechanical ventilation, Diaz and colleagues displayed that there was no difference between the corticosteroid and noncorticosteroid groups [ 49 ]. However, the funnel plots provided evidence of publication bias for both types of studies Additional file 4.
During the influenza pandemic, the debate over whether to use corticosteroid treatment in severe influenza H1N1-infected patients resurfaced and was disputed by clinicians [ 26 ].
According to our review, corticosteroid administration is likely to increase mortality in patients with influenza A H1N1and the trend is consistent regardless of the quality as well as the sample size of studies.
We reviewed the evidence regarding the effect of additional ('adjunctive') steroid treatment in individuals with influenza infection. Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. People who are taking prednisone for months or years suffer not only from a number of people suffered not only from flu, but respiratory. Recently, some studies have shown that corticosteroids may not be beneficial for patients with severe influenza and may even increase mortality. Corticosteroids are deeply involved in the initial events of the inflammatory response, being involved in the resolution of inflammation. Corticosteroids can. Rhodes, A. Epidemiological and clinical characteristics of childhood pandemic H1N1 virus infection: an observational cohort study. Morens, D. Therefore, well-designed clinical trials should be conducted to decrease the heterogeneity of patients and to provide more robust evidence.Photo illustration of the possible side effects to prednisone. Ted Crow, The Plain Dealer. They are among the wildly diverse conditions for which doctors prescribe the corticosteroid prednisone. All of these ailments involve inflammation, and as a steroid, prednisone is a potent anti-inflammatory.
If you talk to friends and acquaintances, you'll likely find a few who are taking prednisone, or just having got off it, or whose child or other family member is taking it. This winter especially, a number of people suffered not only from flu, but respiratory viruses, including respiratory syncytial virus, or RSV, and parainfluenza 3.
For patients whose lungs were already compromised by asthma, for example, doctors say they often prescribed prednisone. One of the reasons taking this steroid becomes a frequent topic of conversation is because of the pronounced side effects that some people who take it experience.
Physicians prescribe a drug that makes some people feel awful with such significant side effects for one reason. You'd be hard-pressed to find one that doesn't. Often, a patient's first introduction to prednisone is when a child or adult has a severe upper respiratory infection, asthma or pneumonia.
He has found that parents are often upset because children can have dramatic reactions to it. If they are already somewhat hyperactive, their behavior can become worse, Craven said. So he tells parents of that possibility upfront. If a patient -- a child or adult -- takes prednisone for more than a few weeks or months, the side effects can be far more serious.
Taking the drug long-term, as, for example, people with MS or lupus might, increases the risk of cataracts and, more commonly, of bone loss. Diminished bone density and osteoporosis are well-known complications of oral prednisone treatment. A study of injected corticosteroids found that a single shot into the spine for back pain reduced bone mineral density of the hip. Whether administered by injection, in pills or through an inhaler, steroids weaken bones.
So, doctors often advise patients on prednisone to take extra vitamin D and calcium; osteoporosis medications may even be prescribed to prevent fractures. They also recommend that people take prednisone with food or milk to limit stomach discomfort. Because of prednisone's side effects, doctors often prescribe it in a step-down dosage -- a blast of higher doses at the beginning, then tapering off. Prednisone suppresses the immune system and adrenal function, so doctors say that if you stop cold turkey, the adrenal glands may not respond as they would normally.
This is a condition called "adrenal insufficiency. Gradually weaning from prednisone allows the adrenals to begin functioning as they did before the patient began taking the steroid.
People who are taking prednisone for months or years suffer not only from long-term side effects, but may continue to suffer from the short-term "nuisance" symptoms.
Those can have a deleterious effects on a person's life and personality -- and on the people around them. If a person does have a serious reaction, doctors can instead opt for one of seven subclasses of nonsteroidal anti-inflammatory drugs, or NSAIDs. Examples include meloxicam or even aspirin or ibuprofen. That's why it's important to talk to your doctor if your body is reacting badly. Treatment was sought for rheumatoid arthritis.
Prednisone has been dubbed "a 20th-century wonder drug. Before prednisone, doctors say, there weren't effective treatments for conditions or illnesses such as lupus, severe psoriasis, asthma, bacterial meningitis or a serious case of pneumonia. Prednisone was developed in a long process that was originally connected to the search for a treatment for rheumatoid arthritis, says Abelson. More than a century ago, doctors knew that women with rheumatoid arthritis felt significantly better when they were pregnant.
They began to wonder if a naturally occurring hormone could be the reason for that. Research began to be conducted in a number of countries, including the United States and Canada, in the s. Clinical trials in the U. In , a team at a major pharmaceutical company, Schering, converted cortisone into the stronger prednisone. The team's leader, Arthur Nobile, was granted the patent in , when production of the new drug got under way. But it wasn't until the s that the drug began to be far more widely prescribed, says Dr.
Inflammation a factor in many conditions. Ernie Boyd, executive director of the Ohio Pharmaceutical Association, says there is another explanation, too. After, they began prescribing prednisone to deal with the inflammation. Its effectiveness began to make it a go-to drug. That it was an inexpensive generic made it even more popular as a prescription, doctors say. Michael Wascovich, director of the Cleveland Clinic's pharmacies, says prednisone is among the top medicines prescribed by doctors.
Certainly, some patients feel the unpleasant effects. Every drug has risks and benefits, and so too does prednisone, he says. Patients have to weigh their concerns against the severity of the condition that's being treated. To reach this Plain Dealer reporter:etheiss plaind. If you purchase a product or register for an account through one of the links on our site, we may receive compensation.
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