Genetic evidence for the presence of two distinct hantaviruses associated with Apodemus mice in Croatia and analysis of local strains

In Europe, Dobrava-Belgrade (DOBV), Saaremaa (SAAV), and Puumala (PUUV) viruses are known to cause hemorrhagic fever with renal syndrome (HFRS). All three hantaviruses are now found in Croatia. Lung tissue samples of 315 Apodemus mice trapped in 2003-2004 were screened for the presence of hantaviral N-Ag and 20 mice (6.3%) were found either strongly positive or weak/suspected-positive. Partial sequences of hantavirus M and S segments were recovered by RT-PCR from six mice and subjected to (phylo)genetic analysis that revealed the presence of four novel strains of DOBV and one of SAAV. Curiously, one of the newly described DOBV strains was found in Apodemus agrarius mouse, that is, not in the traditional host, A. flavicollis mice, suggesting a spillover event. S segment sequences recovered previously from HFRS cases [Markoti? et al., 2002] were confirmed as DOBV sequences; one of which appeared particularly close to the prototype Slovenian DOBV isolate. Taken together with earlier data on PUUV in Croatia, these results show a co-circulation of three European hantavirus pathogens in this country. So far, not a single SAAV sequence has been recovered from HFRS patients either in Croatia or neighboring Slovenia and Hungary nor in Slovakia suggesting a somewhat lower fequency of acute SAAV infection in humans in this part of Europe than for example in the Baltics.     

Viral load and humoral immune response in association with disease severity in Puumala hantavirus-infected patients—implications for treatment

Hantaviruses are the causative agents of haemorrhagic fever with renal syndrome (HFRS) in Eurasia and of hantavirus cardiopulmonary syndrome (HCPS) in the Americas. The case fatality rate varies between different hantaviruses and can be up to 40%. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely, both virus-mediated and host-mediated mechanisms are involved. The aim of the present study was to investigate the association among Puumala hantavirus (PUUV) viral RNA load, humoral immune response and disease severity in patients with HFRS. We performed a study of 105 PUUV-infected patients that were followed during the acute phase of disease and for up to 1–3 months later. Fifteen of the 105 patients (14%) were classified as having moderate/severe disease. A low PUUV-specific IgG response (p <0.05) and also a higher white blood cell count (p <0.001) were significantly associated with more severe disease. The PUUV RNA was detected in a majority of patient plasma samples up to 9 days after disease onset; however, PUUV RNA load or longevity of viraemia were not significantly associated with disease severity. We conclude that a low specific IgG response was associated with disease severity in patients with HFRS, whereas PUUV RNA load did not seem to affect the severity of HFRS. Our results raise the possibility of passive immunotherapy as a useful treatment for hantavirus-infected patients.     

Impact of guideline-concordant antibiotics and macrolide/β-lactam combinations in 3203 patients hospitalized with pneumonia: prospective cohort study

For patients hospitalized with pneumonia, guidelines provide empirical antibiotic recommendations and some studies suggest that macrolide/β-lactam combinations are preferable. We hypothesized that guideline-concordant regimens, particularly macrolide/β-lactams, would reduce mortality and ICU admissions. All patients hospitalized with pneumonia in Edmonton, Alberta, Canada, were managed according to a clinical pathway and enrolled in a population-based registry. Clinical data, Pneumonia Severity Index and treatments were collected. Guideline-concordant regimens were macrolides/β-lactams or respiratory fluoroquinolone monotherapy. The main outcome was in-hospital mortality. The study included 3203 patients and most had severe pneumonia (63% PSI Class IV-V). Three hundred and twenty-one (10.0%) patients died, 306 (9.6%) were admitted to the ICU and 570 (17.8%) achieved the composite of death or ICU admission. Most (n = 2506) patients received guideline-concordant antibiotics. Receipt of guideline-concordant antibiotics was not associated with a reduction in mortality alone (231 (9.2%) vs. 90 (12.9%); adjusted odds ratio (aOR), 0.82; 95% CI, 0.61–1.09; p 0.16), but was associated with decreased death or ICU admission (14.7% vs. 29.0%; aOR, 0.44; 95% CI, 0.36–0.54; p <0.0001). Within guideline-concordant subgroups, there was no difference in mortality between macrolide/β-lactams and respiratory fluoroquinolone monotherapy (22 (8.3%) vs. 209 (9.3%); aOR, 1.09; 95% CI, 0.66–1.81; p 0.73) but macrolide/β-lactams were associated with increased odds of death or ICU admission (17.4% vs. 14.4%; aOR, 1.58; 95% CI, 1.09–2.27; p 0.01). In conclusion, guideline-concordant antibiotics were not associated with decreased mortality for patients hospitalized with pneumonia, but were associated with a decrease in the composite endpoint of death or ICU admission. Our findings do not support any clinical advantage of macrolide/β-lactam compared with respiratory fluoroquinolone monotherapy.     

Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue

OBJECTIVES: This study examined the impact of depressive symptoms and social support on 2-year sudden cardiac death (SCD) risk, controlling for fatigue symptoms. METHODS: Myocardial infarction (MI) patients (N = 671) participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial completed measures of depression, hostility, and social support. RESULTS: After controlling for significant biological predictors, psychosocial predictors of increased SCD risk in the survival analysis were greater social network contacts (RR = 1.04; 95% CI = 1.01-1.06; p < .007), lower social participation (RR = 0.98; 95% CI = 0.96-1.00; p < .05), and, in placebo-treated patients, elevated depressive symptoms (RR = 2.45; 95% CI = 1.14-5.35; p < .02). Fatigue was associated with SCD (RR = 1.31; 95% CI = 1.11-1.53; p < .001), and, when included in the model, diminished the influence of depression (RR = 1.73; 95% CI = 0.75-3.98; p = .20). When the cognitive-affective depressive symptoms were examined separately from somatic symptoms, there was a trend for an association between cognitive-affective symptoms and SCD in placebo-treated patients after controlling for fatigue (RR = 1.09; 95% CI = 0.99-1.19, p < .06). CONCLUSIONS: Symptoms of depression and fatigue overlap in patients with MI. The trend for the cognitive-affective symptoms of depression to be associated with SCD risk, even after controlling for dyspnea/fatigue, suggests that the association between depression and mortality after AMI cannot be entirely explained as a confound of cardiac-related fatigue. The independent contribution of social participation suggests a role of both depressive symptomatology and social factors in influencing mortality risk after MI.     

Specific humoral reaction of hemorrhagic fever with renal syndrome (HFRS) patients in China to recombinant nucleocapsid proteins from European hantaviruses

Hemorrhagic fever with renal syndrome (HFRS) is endemic in East Asia and Europe. This study was initiated to investigate the reactivity of antibodies in sera of Chinese HFRS patients with the recombinant nucleocapsid proteins (rNPs) of Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), and Puumala virus (PUUV), which are the prevalent hantavirus strains in Europe. Forty-eight pairs of acute and convalescent sera were collected from HFRS patients in Hubei, China (1985-2002) and tested by indirect IgG, IgA, and IgM enzyme-linked immunosorbent assays with six rNPs of European hantaviruses as coated antigens, respectively. The results showed that the sensitivity of rNPs against IgG was HTNV-rNP > DOBV-rNP > PUUV-rNP, while the sensitivity against IgA was DOBV-rNP > HTNV-rNP > PUUV-rNP. Quantitative analysis revealed both acute and convalescent sera from HFRS patients predominantly exhibit high levels of IgA. Although PUUV-rNPs showed very weak reactivity to the three kinds of immunoglobulins in all samples, three pairs of sera unexpectedly cross-reacted strongly to all three PUUV-rNP subtypes. We first observe that HFRS patients’ sera from Hubei Province show new prevalent characteristics of cross-reacting with PUUV-rNPs and continued high level of IgA in convalescent phase, as well as in China.     

Clostridium difficile as a cause of healthcare-associated diarrhoea among children in Auckland,New Zealand: clinical and molecular epidemiology

We aimed to determine the incidence of Clostridium difficile infection (CDI), the molecular epidemiology of circulating C. difficile strains and risk factors for CDI among hospitalised children in the Auckland region. A cross-sectional study was undertaken of hospitalised children <15 years of age in two hospitals investigated for healthcare-associated diarrhoea between November 2011 and June 2012. Stool specimens were analysed for the presence of C. difficile using a two-step testing algorithm including polymerase chain reaction (PCR). C. difficile was cultured and PCR ribotyping performed. Demographic data, illness characteristics and risk factors were compared between children with and without CDI. Non-duplicate stool specimens were collected from 320 children with a median age of 1.2 years (range 3 days to 15 years). Forty-six patients (14 %) tested met the definition for CDI. The overall incidence of CDI was 2.0 per 10,000 bed days. The percentage of positive tests among neonates was only 2.6 %. PCR ribotyping showed a range of strains, with ribotype 014 being the most common. Significant risk factors for CDI were treatment with proton pump inhibitors [risk ratio (RR) 1.74, 95 % confidence interval (CI) 1.09–5.59; p?=?0.002], presence of underlying malignancy (RR 2.71, 95 % CI 1.65–4.62; p?=?0.001), receiving chemotherapy (RR 2.70, 95 % CI 1.41–4.83; p?=?0.003) and exposure to antibiotics (RR 1.17, 95 % CI 0.99–1.17; p?=?0.03). C. difficile is an important cause of healthcare-associated diarrhoea in this paediatric population. The notion that neonatal populations will always have high rates of colonisation with C. difficile may not be correct. Several risk factors associated with CDI among adults were also found to be significant.     

Evolution of the prevalence of hepatitis C virus infection and hepatitis C virus genotype distribution in human immunodeficiency virus-infected patients in Italy between 1997 and 2015

ObjectivesTo analyse the variation of hepatitis C virus (HCV) prevalence and genotype distribution and their determinants in people living with human immunodeficiency virus (HIV) who entered care between 1997 and 2015.MethodsHIV-infected patients enrolled in ICONA who were tested for HCV antibodies (HCV-Ab) were included.ResultsOverall 3407 of 12 135 (28.1%) were HCV-Ab+; and 735 of 12 135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most represented were genotypes 1 and 3. The prevalence of HCV infection decreased from 49.2% (2565/5217) during 1997–2002 to 10.2% (556/5466) during 2009–2015. The frequency of genotype 1a increased from 29.0% (264/911) to 43.0% (129/300), whereas genotype 3 decreased from 38.5% (351/911) to 27.0% (81/300). Independent predictors of HCV-Ab+ status were being female (adjusted OR (AOR) 1.23, 95% CI 1.04–1.50, p = 0.01), risk category (versus injecting drug users: men who have sex with men AOR 0.01, 95% CI 0.01–0.01, p <0.001; heterosexuals AOR 0.01, 95% CI 0.01–0.01, p <0.001; other/unknown AOR 0.02, 95% CI 0.01–0.02, p <0.001), being cared for in Central Italy (versus being cared for in Northern Italy: AOR 0.85, 95% CI 0.73–0.98, p <0.001), being Italian-born (AOR 1.44, 95% CI 1.16–1.80, p = 0.001) and being enrolled in less recent calendar years (versus 1997–2002: 2009–2015 AOR 0.23, 95% CI 0.19–0.27, p <0.001; 2003–2008 AOR 0.49, 95% CI 0.41–0.61, p <0.001).ConclusionsThe prevalence of HCV infection in HIV-infected patients entering into care in Italy significantly declined in more recent calendar years. After adjusting for risk factors and calendar years, HCV co-infection was more frequent in females and in those born in Italy.     

Clinical prediction model for differentiation of disseminated Histoplasma capsulatum and Mycobacterium avium complex infections in febrile patients with AIDS

BACKGROUND: Disseminated infection with Histoplasma capsulatum and Mycobacterium avium complex (MAC) in patients with AIDS are frequently difficult to distinguish clinically. METHODS: We retrospectively compared demographic information, other opportunistic infections, medications, symptoms, physical examination findings and laboratory parameters at the time of hospital presentation for 32 patients with culture documented disseminated histoplasmosis and 58 patients with disseminated MAC infection. RESULTS: Positive predictors of histoplasma infection by univariate analysis included lactate dehydrogenase level, white blood cell (WBC) count, platelet count, alkaline phosphatase level, and CD4 cell count. By multivariate logistic regression analysis, those characteristics that remained significant included a lactate dehydrogenase value > or =500 U/L (risk ratio [RR], 42; 95% confidence interval [CI], 18.53-97.5; p < .001), alkaline phosphatase < or =300 U/L (RR, 9.35; 95% CI, 2.61-33.48; p = .008), WBC < or =4.5 x 10(6)/L (RR, 21.29; 95% CI, 6.79-66.75; p = .008), and CD4 cell count (RR, 0.958; 95% CI, 0.946-0.971; p = .001). CONCLUSIONS: A predictive model for distinguishing disseminated histoplasmosis from MAC infection was developed using lactate dehydrogenase and alkaline phosphatase levels as well as WBC count. This model had a sensitivity of 83%, a specificity of 91%, and a misclassification rate of 13%.     

Blurred vision and myopic shift in Puumala virus infections are independent of disease severity

Puumala virus infection causes epidemic nephropathia (NE), a certain type of haemorrhagic fever with renal syndrome (HFRS). Myopic shift is considered a pathognomonic sign of NE and HFRS but rates of ocular involvement vary. The aim of the study was to evaluate whether clinical and laboratory findings are associated with ophthalmic involvement in NE in Austria. We found that blurred vision and myopic shift are frequent in Puumala virus infections in Austria but are independent of disease severity.     

Ⅰ型出血热患者中性粒细胞与淋巴细胞功能变化研究

目的研究肾综合征出血热（ＨＦＲＳ）患者的淋巴细胞和中性粒细胞免疫功能变化及其相互间关系，进一步阐明发病机理。方法采用Ｅａ、Ｅｔ花环形成、ＰＨＡ皮肤试验及中性粒细胞趋化、吞噬、ＮＢＴ还原等多种试验方法同时对３２例由Ｈａｎｔａａｎ病毒引起的姬鼠型ＨＦＲＳ患者的淋巴细胞和中性粒细胞免疫功能变化及其相互间关系进行动态测定。结果ＨＦＲＳ患者早期前五项指标均明显低于正常人（Ｐ＜０．０１）；病程中，淋巴细胞损伤程度较粒细胞更加突出；中性粒细胞ＮＢＴ还原能力在恢复期反降至最低（Ｐ＜０．０５）。此外，患者这两种细胞的免疫功能在恢复期并未能完全达到正常水平。结论ＨＦＲＳ患者淋巴细胞免疫功能损伤程度与病程密切相关，可能是Ｈａｎｔａａｎ病毒直接作用的结果；而中性粒细胞免疫功能变化比较复杂，有待进一步研究。恢复期患者细胞免疫功能未能完全恢复提示临床治疗应予以关注。     

Puumala and Dobrava viruses cause hemorrhagic fever with renal syndrome in Bosnia-Herzegovina: Evidence of highly cross-neutralizing antibody responses in early patient sera

Hantavirus infection was diagnosed serologically by μ-capture IgM and IgG ELISAs in hemorrhagic fever with renal syndrome (HFRS) patients admitted to Tuzla Hospital, Bosnia-Herzegovina. The results indicated that more than one hantavirus caused the outbreak. To address the question of which hantavirus serotypes were involved, sequentially drawn sera were analyzed by focus reduction neutralization test (FRNT) for antibodies against Puumala, Hantaan, Dobrava, and Seoul hantaviruses. The data revealed that acute- or early convalescent-phase sera, even when drawn as late as 3 weeks after the onset of disease, could not be used for typing of the causative hantavirus; a significant number of these samples showed similar reactivity of neutralizing antibodies to several different hantavirus serotypes. Moreover, although several acute-phase sera showed the highest FRNT titer to Hantaan virus, convalescent sera from these patients in all cases showed high specificity for Puumala or Dobrava viruses. This phenomenon, interpreted as a cross-neutralizing primary antibody response, makes several earlier reports concerning causative agents of HFRS questionable. Serological examination of small rodents trapped in the endemic area identified Puumala- and Dobrava-like virus infections. RT-PCR and sequencing of rodent lung samples identified Dobrava virus in one yellow-necked field mouse (Apodemus flavicollis). Cross-FRNT data, using polyclonal rabbit antibodies, clearly confirmed Dobrava virus as a unique hantavirus serotype. In conclusion, the results revealed that both Puumala- and Dobrava-like viruses caused HFRS in Bosnia-Herzegovina, whereas no signs of Hantaan or Seoul virus involvement were found. J. Med. Virol. 53:51–59, 1997. © 1997 Wiley-Liss, Inc.     

Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: meta-analysis of randomised controlled trials

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial pneumonia. Compared with glycopeptide antibiotics, linezolid achieves higher lung epithelial lining fluid concentrations, which may have an advantage in treating nosocomial pneumonia patients. The objective of this study was to evaluate the efficacy and safety of linezolid versus vancomycin or teicoplanin for the treatment of nosocomial pneumonia. Data were obtained from the Cochrane Central Register of Controlled Trials and the EMBASE and MEDLINE databases. Randomised controlled studies involving the use of linezolid versus vancomycin or teicoplanin in nosocomial pneumonia patients were included in the study. Twelve linezolid trials were included. There was no statistically significant difference between the two groups in the treatment of nosocomial pneumonia regarding the clinical cure rate [relative risk (RR)?=?1.08, 95 % confidence interval (CI)?=?1.00–1.17, p?=?0.06]. Linezolid was associated with better microbiological eradication rate in nosocomial pneumonia patients compared with glycopeptide antibiotics (RR?=?1.16, 95 % CI?=?1.03–1.31, p?=?0.01). There were no differences in the all-cause mortality (RR?=?0.95, 95 % CI?=?0.83–1.09, p?=?0.46) between the two groups. However, the risks of rash (RR?=?0.41, 95 % CI?=?0.24–0.71, p?=?0.001) and renal dysfunction (RR?=?0.41, 95 % CI?=?0.27–0.64, p?<?0.0001) were higher with glycopeptide antibiotics. Although linezolid was more effective in eradicating microbiology than glycopeptide antibiotics for nosocomial pneumonia patients, it did not demonstrate superiority in clinical cure. The incidences of renal dysfunction and rash are higher in the glycopeptide antibiotics group.     

Incidence and outcomes of infective endocarditis after transcatheter aortic valve implantation versus surgical aortic valve replacement

ObjectivesTranscatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR) in aortic stenosis (AS). Infective endocarditis (IE) in patients with prosthetic heart valves is associated with significant morbidity and mortality. Data on the incidence, risk factors, and outcomes of IE after TAVI are conflicting. We evaluated these issues in patients with percutaneous TAVI vs. isolated surgical AVR (SAVR) at a nationwide level.MethodsBased on the administrative hospital discharge database, the study collected information for all patients with aortic stenosis treated with AVR in France between 2010 and 2018.ResultsA total of 47 553 patients undergoing TAVI and 60 253 patients undergoing isolated SAVR were identified. During a mean follow-up of 2.0 years (median (25th to 75th percentile) 1.2 (0.1–3.4) years), the incidence rates of IE were 1.89 (95% confidence interval (CI) 1.78–2.00) and 1.40 (95% CI 1.34–1.46) events per 100 person-years in unmatched TAVI and SAVR patients, respectively. In 32 582 propensity-matched patients (16 291 with TAVI and 16 291 with SAVR), risk of IE was not different in patients treated with TAVI vs. SAVR (incidence rates of IE 1.86 (95% CI 1.70–2.04) %/year vs 1.71 (95% CI 1.58–1.85) %/year respectively, relative risk (RR) 1.09, 95% CI 0.96–1.23). In these matched patients, total mortality was higher in TAVI patients with IE (43.0% 95% CI 37.3–49.3) than in SAVR patients with IE (32.8% 95% CI 28.6–37.3; RR 1.32, 95% CI 1.08–1.60).DiscussionIn a nationwide cohort of patients with AS, treatment with TAVI was associated with a risk of IE similar to that following SAVR. Mortality was higher for patients with IE following TAVI than for those with IE following SAVR.     

Efficacy and safety of umifenovir for coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

We conducted this systemic review and meta‐analysis in an attempt to evaluate the efficacy and safety of umifenovir in coronavirus disease 2019 (COVID‐19). We searched PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, and medRxiv database. We included both retrospective and prospective studies. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were applied to assess the effectiveness of umifenovir for COVID‐19. A total of 12 studies with 1052 patients were included in our final studies. Compared with control group, umifenovir was associated with higher negative rate of PCR on day 14 (RR:1.27; 95% CI: 1.04 to 1.55). However, umifenovir is not related to nucleus acid negative conversion time (MD: 0.09; 95% CI: ?1.48 to 1.65), negative rate on day 7 (RR:1.09; 95% CI: 0.91 to 1.31), incidence of composite endpoint (RR:1.20; 95% CI: 0.61 to 2.37), rate of fever alleviation on day 7 (RR:1.00; 95% CI: 0.91 to 1.10), rate of cough alleviation on day 7 (RR:1.00; 95% CI: 0.85 to 1.18), or hospital length of stay (MD: 1.34; 95% CI: ‐2.08 to 4.76). Additionally, umifenovir was safe in COVID‐19 patients (RR for incidence of adverse events: 1.29; 95% CI: 0.57 to 2.92). The results of sensitivity analysis and subgroup analysis were similar to pooled results. There is no evidence to support the use of umifenovir for improving patient‐important outcomes in patients with COVID‐19.     

Stem cell dose and tumorbiologic parameters as prognostic markers for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous blood stem cell support.

We report on the prognostic significance of tumorbiologic parameters and CD34(+) cell dose in 120 patients with metastatic breast cancer (MBC) who received high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation as first-line treatment. Her2/neu, p53, Ki67, and bcl-2 protein expression were studied using immunohistochemical staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA-index) and tumor cell proliferation (S-phase fraction) were measured by DNA flow cytometry. The relationship between these parameters and the CD34(+) cell dose and progression free (PFS) and overall survival (OS) was analyzed. With a median follow-up period of 40 months (range, 7-89 months), no more than two metastatic sites (relative risk [RR] = 3.84 [95% confidence interval (CI) 1.49-10]; p =.005) and hyperploidy (RR = 2.58 [95% CI 1.26-5.26]; p =.009) were independent predictors of longer PFS according to multivariate analysis. Independent prognostic factors of longer OS included one or two metastatic sites (RR = 4.16 [95% CI 1.96-4.16]; p <.001), a positive combined hormone receptor status (RR = 2.45 [95% CI 1.45-4.14]; p =.001) and a high number of infused stem cells (>7.8 x 10(6) CD34(+) cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p =.01). In conclusion, positive hormone receptors, < or =2 metastatic sites, high DNA-index and high CD34(+) cell dose (>7.8 x 10(6) CD34(+) cells per kg) are predictors for a favorable outcome after autotransplantation for MBC. Our observation might indicate a favorable effect of HDCT in MBC patients with overexpression of Her2/neu who might have a worse prognosis when treated with conventional chemotherapy.     

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20–64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20–0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD −19.14; 95% CI −22.80 to −15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89–1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78–0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10–1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD −15.65; 95% CI −16.16 to −15.13), with increased TAE (RR 1.73; 95% CI 0.60–5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64–0.94) and improving QoL (MD −13.3; 95% CI −23.93 to −2.67) and smell (MD +0.7; 95% CI −0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41–6.50). The evidence for reslizumab is very uncertain.     

Fluoroquinolone prophylaxis in patients with neutropenia: a meta-analysis of randomized placebo-controlled trials

A recent meta-analysis, which included non-placebo open-labeled trials, showed that fluoroquinolone prophylaxis reduces mortality in neutropenic patients, whereas two recent large trials failed to show a similar benefit. Therefore, we performed a meta-analysis of randomized, blinded, placebo-controlled trials of fluoroquinolone prophylaxis in neutropenic patients. We searched several databases for relevant trials in any language. We used random effects models for pooling dichotomous data and assessed the between-study inconsistency with I (2). Two investigators independently assessed the eligibility and quality of the included trials. A total of 2,721 patients were randomized in eight eligible trials. Compared to the placebo, there was a statistically non-significant but consistent decrease in mortality with fluoroquinolone prophylaxis (4.5% vs. 3.9%, relative risk (RR) 0.76, 95% confidence interval (CI) 0.54, 1.08, p = 0.13, I (2) = 0%). Significant inconsistency, however, accompanied the pooled analysis of febrile episode (39% vs. 31%, RR 0.76, 95% CI 0.55, 1.03, p = 0.08, I (2) = 96.5%). To an extent, this inconsistency was explained in the subgroup analyses by the type of patient population studied and the type of fluoroquinolone used (p for interaction 相似文献   

Dolutegravir(DTG,S/GSK1349572) combined with other ARTs is superior to RAL- or EFV-based regimens for treatment of HIV-1 infection: a meta-analysis of randomized controlled trials

Background

The first-generation integrase inhibitors (INIs) raltegravir (RAL) and elvitegravir (EVG) have shown efficacy against HIV infection, but they have the limitations of once-more daily dosing and extensive cross-resistance. Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such shortcomings, is under spotlight. The purpose of this study is to review the evidence for DTG use in clinical settings, including its efficacy and safety.

Methods

PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted.

Results

Four unique studies were included with the use of DTG in antiretroviral therapy-naive patients. In therapy-naive patients, DTG combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence interval (95 % CI 1.03–1.12). Evidence further supported use of DTG had a better virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03–1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03–1.15; RR 1.06, 95 % CI 0.98–1.15, respectively). In the matter of safety of DTG-based regimen, the risk of any event was RR 0.98 (95 % CI 0.94–1.01), the risk of serious adverse events (AEs) was RR 0.84 (95 % CI 0.62–1.15), and the risk of drug-related serious AEs was RR 0.33 (95 % CI 0.13–0.79).

Conclusion

In general, DTG 50 mg given once daily combined with an active background drug is a better choice in terms of both efficacy and safety.