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Schuetz P.,Harvard University | Muller B.,University of Basel | Christ-Crain M.,University of Basel | Stolz D.,University of Basel | And 15 more authors.
Evidence-Based Child Health | Year: 2013

Background: Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs). Objectives: The aim of this systematic review based on individual patient data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May 2011) and EMBASE (1974 to May 2011) to identify suitable trials. Selection criteria: We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm or usual care/guidelines. Trials were excluded if they exclusively focused on paediatric patients or if they used procalcitonin for another purpose than to guide initiation and duration of antibiotic treatment. Data collection and analysis: Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days. For the primary care setting, treatment failure was defined as death, hospitalisation, ARI-specific complications, recurrent or worsening infection, and patients reporting any symptoms of an ongoing respiratory infection at follow-up. For the ED setting, treatment failure was defined as death, ICU admission, re-hospitalisation after index hospital discharge, ARI-associated complications, and recurrent or worsening infection within 30 days of follow-up. For the ICU setting, treatment failure was defined as death within 30 days of follow-up. Secondary endpoints were antibiotic use (initiation of antibiotics, duration of antibiotics and total exposure to antibiotics (total amount of antibiotic days divided by total number of patients)), length of hospital stay for hospitalised patients, length of ICU stay for critically ill patients, and number of days with restricted activities within 14 days after randomisation for primary care patients. For the two co-primary endpoints of all-cause mortality and treatment failure, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression. The hierarchical regression model was adjusted for age and clinical diagnosis as fixed-effect. The different trials were added as random-effects into the model. We fitted corresponding linear regression models for antibiotic use. We conducted sensitivity analyses stratified by clinical setting and ARI diagnosis to assess the consistency of our results. Main results: We included 14 trials with 4221 participants. There were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting, or ARI diagnosis. These results proved robust in various sensitivity analyses. Total antibiotic exposure was significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4 (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and across all the different clinical settings and diagnoses. Authors' conclusions: Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARI was not associated with higher mortality rates or treatment failure. Antibiotic consumption was significantly reduced across different clinical settings and ARI diagnoses. Further high-quality research is needed to confirm the safety of this approach for non-European countries and patients in intensive care. Moreover, future studies should also establish cost-effectiveness by considering country-specific costs of procalcitonin measurement and potential savings in consumption of antibiotics and other healthcare resources, as well as secondary cost savings due to lower risk of side effects and reduced antimicrobial resistance. Procalcitonin testing to initiate or discontinue antibiotics in acute respiratory tract infections: Unnecessary antibiotic use significantly contributes to increasing bacterial resistance, medical costs and the risk of drug-related adverse events. The blood marker procalcitonin increases in bacterial infections and decreases when patients recover from the infection. Hence, procalcitonin may be used to support clinical decision making for the initiation and discontinuation of antibiotic therapy in patients with a clinical suspicion of infection. Randomised controlled trials have demonstrated that such a strategy works, particularly in patients with an infection of the respiratory tract. However, most of these individual studies did not include enough patients to allow for a conclusive assessment about safety (low statistical power). Thus, the risk for mortality and severe complications associated with procalcitonin-guided decision making remained unclear. This systematic review included individual patient data from 14 randomised controlled trials with a total of 4211 participants. When looking at these combined data, we found no increased risk for all-cause mortality or treatment failure when procalcitonin was used to guide initiation and duration of antibiotic treatment in participants with acute respiratory infections compared to control participants. However, we found a consistent reduction of antibiotic use, mainly due to lower prescription rates in primary care and lower duration of antibiotic courses in emergency department and intensive care unit patients. This analysis is limited to adult patients with respiratory infections excluding patients who were immuno-compromised (i.e. HIV positive, those receiving immuno-suppressive therapies or chemotherapy). Most trials were conducted in Europe and China and similar studies in other countries including the United States are warranted. © 2013 The Cochrane Collaboration.

Shen T.,Shanghai JiaoTong University | Li C.,Shanghai JiaoTong University | Wang B.,Shanghai JiaoTong University | Yang W.-M.,Shanghai JiaoTong University | And 7 more authors.
Psychiatry Investigation | Year: 2015

Objective Evidence of the brain network involved in cognitive dysfunction has been inconsistent for major depressive disorder (MDD), especially during early stage of MDD. This study seeks to examine abnormal cognition connectivity network (CCN) in MDD within the whole brain. Methods Sixteen patients with MDD and 16 health controls were scanned during resting-state using 3.0 T functional magnetic resonance imaging (fMRI). All patients were first episode without any history of antidepressant treatment. Both the left and right dorsolateral prefrontal cortex (DLPFC) were used as individual seeds to identify CCN by the seed-target correlation analysis. Two sample t test was used to calculate between-group differences in CCN using fisher z-transformed correlation maps. Results The CCN was constructed by bilateral seed DLPFC in two groups separately. Depressed subjects exhibited significantly increased functional connectivity (FC) by left DLPFC in one cluster, overlapping middle frontal gyrus, BA7, BA43, precuneus, BA6, BA40, superior temporal gyrus, BA22, inferior parietal lobule, precentral gyrus, BA4 and cingulate gyrus in left cerebrum. Health controls did not show any cluster with significantly greater FC compared to depressed subjects in left DLPFC network. There was no significant dif-ference of FC in right DLPFC network between depressed subjects and the health controls. Conclusion There are differences in CCN during early stage of MDD, as identified by increased FCs among part of frontal gyrus, parietal cortex, cingulate cortex, and BA43, BA22, BA4 with left DLPFC. These brain areas might be involved in the underlying mechanisms of cognitive dysfunction in MDD. © 2015 Korean Neuropsychiatric Association.

Mao F.,Xinjiang Karamay Central Hospital | Zhang D.-H.,Xinjiang Karamay Central Hospital | Peng X.-C.,Shanghai Sixth Peoples Hospital | Liao Y.,Shanghai Fifth Peoples Hospital
Journal of Investigative Surgery | Year: 2015

Purpose/Aim: This meta-analysis compares the clinical outcomes of surgical versus conservative treatment of displaced, 3- or 4-part, proximal humeral fractures. Materials and Methods: Medline, Cochrane, EMBASE, and Google Scholar were searched for studies published until October 2013, reporting functional outcomes of 3- or 4-part fractures of the proximal humerus in skeletally mature patients. Only randomized controlled trials were included. The treatments that were evaluated included non-surgical, open surgery, intramedullary pin, locking plate, arthroplasty, and minimally invasive surgical treatments. A meta-analysis was performed on the difference in functional outcomes and quality of life (QoL) between participants undergoing surgical versus non-surgical treatment. Results: Out of 254 participants in the studies who were analyzed, 127 were treated surgically. The difference in mean values of functional score showed similar results between surgical and non-surgical treatments (difference in mean values = 0.015, 95% CI = -0.232 to 0.261, p =.908).The difference in mean values of QoL showed that surgical treatment provided better post-operative QoL than non-surgical treatment (difference in mean values = 0.146, 95% CI = 0.052 to 0.240, p =.002). Conclusions: Surgical treatment of displaced, multi-fragment fractures of the proximal humerus did not improve shoulder functional outcome, based on the Constant-Murley Score, when compared with conservative and non-surgical treatments. However, health-related QoL was significantly improved with surgical treatment compared with conservative treatment. © 2015 © 2015 Informa Healthcare USA, Inc.

Schuetz P.,Beth Israel Deaconess Medical Center | Schuetz P.,University of Basel | Briel M.,Basel Institute for Clinical Epidemiology and Biostatistics | Briel M.,McMaster University | And 18 more authors.
Clinical Infectious Diseases | Year: 2012

Background.Procalcitonin algorithms may reduce antibiotic use for acute respiratory tract infections (ARIs). We undertook an individual patient data meta-analysis to assess safety of this approach in different ARI diagnoses and different clinical settings.Methods.We identified clinical trials in which patients with ARI were assigned to receive antibiotics based on a procalcitonin algorithm or usual care by searching the Cochrane Register, MEDLINE, and EMBASE. Individual patient data from 4221 adults with ARIs in 14 trials were verified and reanalyzed to assess risk of mortality and treatment failure - overall and within different clinical settings and types of ARIs.Results.Overall, there were 118 deaths in 2085 patients (5.7) assigned to procalcitonin groups compared with 134 deaths in 2126 control patients (6.3; adjusted odds ratio, 0.94; 95 confidence interval CI,. 71-1.23)]. Treatment failure occurred in 398 procalcitonin group patients (19.1) and in 466 control patients (21.9; adjusted odds ratio, 0.82; 95 CI,. 71-.97). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting or ARI diagnosis. Total antibiotic exposure per patient was significantly reduced overall (median [interquartile range], from 8 [5-12] to 4 [0-8] days; adjusted difference in days, -3.47 [95 CI, -3.78 to -3.17]) and across all clinical settings and ARI diagnoses.Conclusions.Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs was effective in reducing antibiotic exposure across settings without an increase in the risk of mortality or treatment failure. Further high-quality trials are needed in critical-care patients. © The Author 2012.

Xu X.,Wannan Medical College | Zhang J.,Shanghai Fifth Peoples Hospital | Wu J.-B.,Shanghai Fifth Peoples Hospital | Han F.,Shanghai Chest Hospital
Tumor | Year: 2011

Objective: To investigate the clinical significance of various genotypes of human papillomavirus (HPV) infection in cervical intraepithelial neoplasia (CIN). Methods: PCR-reverse dot blot (PCR-RDB) genotyping chip was used to examine HPV genotype in various cervical lesions (including 100 cases of histological biopsy specimens and 70 matched cases of cytological brushing specimens). Results: The positive rate of HPV infection in the 100 cases of histological biopsy specimens was 82%. Fifteen HPV genotypes were detected in these cases. HPV-16 (37%), HPV-58 (11%), HPV-33 (11%) and HPV-52 (7%) were most common genotypes of high risk (HR)-HPV. There was a trend of increased positive rates of HR-HPV with the increased grade of cervical lesion (P <0.05). It was observed that the positive rates of HR-HPV genotypes were 16.67% in squamous metaplasia and hyperplasia, 57.14% in CIN I, 68.18% in CIN II, and 75.68% in CIN III and 85.71% in invasive cervical cancer. The significant difference was found in HPV16 infection among CIN I, CIN II and CIN III groups (P <0.05). The positive rate of HPV detected in 70 cases of cytological brushing specimens was 64.28%, whereas it was 80.00% in the matched cases of histological biopsy specimens. The consistency of HPV genotyping between the cytological brushing specimens and histological biopsy specimens was dissatisfied (kappa<0.40). Conclusion: The grade of cervical lesion was significantly associated with HR-HPV infection especially for HPV-16. The patients infected with low risk (LR)-HPV frequently have a mixed infection of HR-HPV. The detection of HPV by using cervical histological biopsy specimens was more sensitive than by using cytological brushing specimens. Copyright@2009-2010 Tumor All rights reserved.

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