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Procalcitonin is a promising marker for identification of bacterial infections. We assessed the accuracy and clinical value of procalcitonin for diagnosis of sepsis in critically ill patients. We searched Medline, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, and Science Direct, from inception to Feb 21, 2012, and reference lists of identified primary studies. We included articles written in English, German, or French that investigated procalcitonin for differentiation of septic patients—those with sepsis, severe sepsis, or septic shock—from those with a systemic inflammatory response syndrome of non-infectious origin. Studies of healthy people, patients without probable infection, and children younger than 28 days were excluded. Two independent investigators extracted patient and study characteristics; discrepancies were resolved by consensus. We calculated individual and pooled sensitivities and specificities. We used I2 to test heterogeneity and investigated the source of heterogeneity by metaregression. Our search returned 3487 reports, of which 30 fulfilled the inclusion criteria, accounting for 3244 patients. Bivariate analysis yielded a mean sensitivity of 0·77 (95% CI 0·72–0·81) and specificity of 0·79 (95% CI 0·74–0·84). The area under the receiver operating characteristic curve was 0·85 (95% CI 0·81–0·88). The studies had substantial heterogeneity (I2=96%, 95% CI 94–99). None of the subgroups investigated—population, admission category, assay used, severity of disease, and description and masking of the reference standard—could account for the heterogeneity. Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment. Ministry of Education and Research, the Deutsche Forschungsgemeinschaft, Thuringian Ministry for Education, Science and Culture, the Thuringian Foundation for Technology, Innovation and Research, and the German Sepsis Society.

BackgroundNeonates are at major risk of sepsis, but data on neonatal sepsis incidence are scarce. We aimed to assess the incidence and mortality of neonatal sepsis worldwide.MethodsWe performed a systematic review and meta-analysis. 13 databases were searched for the period January 1979–May 2019, updating the search of a previous systematic review and extending it in order to increase data inputs from low-income and middle-income countries (LMICs). We included studies on the population-level neonatal sepsis incidence that used a clinical sepsis definition, such as the 2005 consensus definition, or relevant ICD codes. We performed a random-effects meta-analysis on neonatal sepsis incidence and mortality, stratified according to sepsis onset, birth weight, prematurity, study setting, WHO region and World Bank income level.ResultsThe search yielded 4737 publications, of which 26 were included. They accounted for 2 797 879 live births and 29 608 sepsis cases in 14 countries, most of which were middle-income countries. Random-effects estimator for neonatal sepsis incidence in the overall time frame was 2824 (95% CI 1892 to 4194) cases per 100 000 live births, of which an estimated 17.6% 9 (95% CI 10.3% to 28.6%) died. In the last decade (2009–2018), the incidence was 3930 (95% CI 1937 to 7812) per 100 000 live births based on four studies from LMICs. In the overall time frame, estimated incidence and mortality was higher in early-onset than late-onset neonatal sepsis cases. There was substantial between-study heterogeneity in all analyses. Studies were at moderate to high risk of bias.ConclusionNeonatal sepsis is common and often fatal. Its incidence remains unknown in most countries and existing studies show marked heterogeneity, indicating the need to increase the number of epidemiological studies, harmonise neonatal sepsis definitions and improve the quality of research in this field. This can help to design and implement targeted interventions, which are urgently needed to reduce the high incidence of neonatal sepsis worldwide.

Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale. To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies. We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years. The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually. Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.

Tonsillectomy is one of the most common operations. Tonsillectomy is also one of the most painful surgical procedures. However, there is still no satisfactory standard for postoperative pain management. Four databases (Cochrane Library, Ovid Technologies, PubMed, Web of Science) were searched for the period from 1908 to 2019. The systematic literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were pooled using random-effects and fixed-effects models. Randomized controlled trials, reviews and meta-analyses were included. Primary outcomes were quantitative pain intensity in the first 24 h after tonsillectomy and on days 1, 3, and 7 postoperatively. The search yielded 1594 publications, of which 111 publications with 7566 patients, both children and adults, could be included. Intraoperative medication with intravenous dexamethasone significantly reduced pain (mean difference [MD] -0.42; 95% confidence interval [CI]: -0.61- -0.24). Among the local anesthetics, only the preoperative injection of levobupivacaine into the tonsillar compartment was able to provide sufficient pain reduction up to three days after tonsillectomy (MD: -1.92; 95% CI: -2.73 - -1.11). Preoperative or intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) significantly reduced pain (MD: -0.75; 95% CI: -0.87- -0.63). Steroids and NSAIDs are an important part of pain management after tonsillectomy.

Fetal heart rate variability (fHRV) of normal-to-normal (NN) beat intervals provides high-temporal resolution access to assess the functioning of the autonomic nervous system (ANS). To determine critical periods of fetal autonomic maturation. The developmental pace is hypothesized to change with gestational age (GA). Prospective longitudinal observational study. 60 healthy singleton fetuses were followed up by fetal magnetocardiographic heart rate monitoring 4-11 times (median 6) during the second half of gestation. FHRV parameters, accounting for differential aspects of the ANS, were studied applying linear mixed models over four predefined pregnancy segments of interest (SoI: <27; 27+0-31+0; 31+1-35+0; >35+1 weeks GA). Periods of fetal active sleep and quiescence were accounted for separately. Skewness of the NN interval distribution VLF/LF band power ratio and complexity describe a saturation function throughout the period of interest. A decreasing LF/HF ratio and an increase in pNN5 indicate a concurrent shift in sympathovagal balance. Fluctuation amplitude and parameters of short-term variability (RMSSD, HF band) mark a second acceleration towards term. In contrast, fetal quiescence is characterized by sequential, but low-margin transformations; ascending overall variability followed by an increase of complexity and superseded by fluctuation amplitude. An increase in sympathetic activation, connected with by a higher ability of parasympathetic modulation and baseline stabilization, is reached during the transition from the late 2nd into the early 3rd trimester. Pattern characteristics indicating fetal well-being saturate at 35 weeks GA. Pronounced fetal breathing efforts near-term mirror in fHRV as respiratory sinus arrhythmia.

Recent evidence suggests that the vagus nerve and autonomic dysfunction play an important role in the pathogenesis of Parkinson’s disease. Using heart rate variability analysis, the autonomic modulation of cardiac activity can be investigated. This meta-analysis aims to assess if analysis of heart rate variability may indicate decreased parasympathetic tone in patients with Parkinson’s disease. The MEDLINE, EMBASE and Cochrane Central databases were searched on 31 December 2020. Studies were included if they: (1) were published in English, (2) analyzed idiopathic Parkinson’s disease and healthy adult controls, and (3) reported at least one frequency- or time-domain heart rate variability analysis parameter, which represents parasympathetic regulation. We included 47 studies with 2772 subjects. Random-effects meta-analyses revealed significantly decreased effect sizes in Parkinson patients for the high-frequency spectral component (HFms2) and the short-term measurement of the root mean square of successive normal-to-normal interval differences (RMSSD). However, heterogeneity was high, and there was evidence for publication bias regarding HFms2. There is some evidence that a more advanced disease leads to an impaired parasympathetic regulation. In conclusion, short-term measurement of RMSSD is a reliable parameter to assess parasympathetically impaired cardiac modulation in Parkinson patients. The measurement should be performed with a predefined respiratory rate.

The prospective multicentre Phase II PTLD-2 trial (NCT02042391) tested modified risk-stratification in adult SOT recipients with CD20-positive PTLD based on principles established in the PTLD-1 trials: sequential treatment and risk-stratification. After rituximab monotherapy induction, patients in complete remission as well as those in partial remission with IPI < 3 at diagnosis (low-risk) continued with rituximab monotherapy and thus chemotherapy free. Most others (high-risk) received R-CHOP-21. Thoracic SOT recipients who progressed (very-high-risk) received alternating R-CHOP-21 and modified R-DHAOx. The primary endpoint was event-free survival (EFS) in the low-risk group. The PTLD-1 trials provided historical controls. Rituximab was applied subcutaneously. Of 60 patients enrolled, 21 were low-risk, 28 high-risk and 9 very-high-risk. Overall response was 45/48 (94%, 95% CI 83–98). 2-year Kaplan–Meier estimates of time to progression and overall survival were 78% (95% CI 65–90) and 68% (95% CI 55–80) – similar to the PTLD-1 trials. Treatment-related mortality was 4/59 (7%, 95% CI 2–17). In the low-risk group, 2-year EFS was 66% (95% CI 45–86) versus 52% in the historical comparator that received CHOP (p = 0.432). 2-year OS in the low-risk group was 100%. Results with R-CHOP-21 in high-risk patients confirmed previous results. Immunochemotherapy intensification in very-high-risk patients was disappointing.

Preoperative skin preparation is an effective method to prevent surgical site infections (SSI). Alcoholic chlorhexidine (CHG) and povidone iodine (PV-I) are the most widely used antiseptic agents. This meta-analysis aims to determine their efficacy in reducing natural bacterial skin flora in clean orthopedic surgery. A systematic search was conducted through current literature up to June 2021 to identify clinical randomized trials that compared the efficacy of alcoholic chlorhexidine and povidone iodine in reducing bacterial skin colonization after preoperative skin preparation. A meta-analysis was conducted. Of 235 screened articles, 8 randomized controlled trials were included. The results of the meta-analysis demonstrate a significantly lower positive culture rate in the chlorhexidine group than in the povidone iodine group (RR = 0.53, 95% Cl: 0.32–0.88). The present data show the superiority of chlorhexidine in reducing the normal bacterial flora compared to povidone iodine in clean orthopedic surgery.

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Annually, sepsis leads to approx. 90.000 deaths in Germany. Risk factors include amongst others older age (>60), innate or acquired dysfunction of the immune system, and underlying chronic diseases of the lung, heart, liver, or kidneys. The manifestation of sepsis is a medical emergency, and patient outcomes depend on timely diagnosis and immediate treatment. In addition, vaccinations e.g., against pneumococci or influenza virus, are a highly effective public health tool to prevent the most common underlying infections that may lead to sepsis. However, a lack of public awareness for the relevance of vaccination and detecting sepsis as an emergency underlines the need for public health interventions that address these issues. SepWiss aims to evaluate the effects of a multimodal information campaign designed to address this lack of awareness among the risk population in Germany. SepWiss is an intervention at state level, consisting of a multimodal information campaign targeting risk groups in the German federal states of Berlin and Brandenburg (intervention region). Based on available evidence, various information formats were developed and implemented by outdoor advertising, social media, educational formats and through stakeholders' platforms, starting in August 2021. The control region comprises of the remaining 14 German federal states. We will analyze vaccination coverage (primary outcome), and sepsis knowledge, the ability to detect sepsis as an emergency, and attitude towards vaccination (secondary outcomes) amongst the risk population in a controlled before-after comparison. The implementation is accompanied by a mixed-method process evaluation. SepWiss is the first project of its kind to evaluate a complex multi-faceted evidence-based information campaign with regards to the topics of vaccination coverage, and the importance of sepsis detection and prevention for the most vulnerable populations in Germany. Results will be valuable for informing further nationwide campaigns. German Registry for Clinical Trials: DRKS00024475. Registered February 24th, 2021.

In times of globalization there is an increasing use of English in the medical literature. The aim of this study was to analyze the influence of English-language articles in multi-language medical journals on their international recognition--as measured by a lower rate of self-citations and higher impact factor (IF). We analyzed publications in multi-language journals in 2008 and 2009 using the Web of Science (WoS) of Thomson Reuters (former Institute of Scientific Information) and PubMed as sources of information. The proportion of English-language articles during the period was compared with both the share of self-citations in the year 2010 and the IF with and without self-citations. Multivariable linear regression analysis was performed to analyze these factors as well as the influence of the journals' countries of origin and of the other language(s) used in publications besides English. We identified 168 multi-language journals that were listed in WoS as well as in PubMed and met our criteria. We found a significant positive correlation of the share of English articles in 2008 and 2009 with the IF calculated without self-citations (Pearson r=0.56, p = <0.0001), a correlation with the overall IF (Pearson r = 0.47, p = <0.0001) and with the cites to years of IF calculation (Pearson r = 0.34, p = <0.0001), and a weak negative correlation with the share of self-citations (Pearson r = -0.2, p = 0.009). The IF without self-citations also correlated with the journal's country of origin--North American journals had a higher IF compared to Middle and South American or European journals. Our findings suggest that a larger share of English articles in multi-language medical journals is associated with greater international recognition. Fewer self-citations were found in multi-language journals with a greater share of original articles in English.