The influence of related and unrelated co-infections on parasite dynamics and virulence.

Many parasitic infections increase the morbidity and mortality of host populations. Interactions between co-infecting parasites can influence virulence, the damage done to a host. Previous studies investigating the impacts of parasite co-infection on hosts have been limited by their inability to control parasite dosage, use consistent virulence metrics, or verify co-infection status. This study used molecular tools, known infection dosage, and multiple assessments over time to test whether parasite relatedness can predict virulence in co-infections, as well as whether competitive interactions between different parasite strains within a host are predictable over time. In addition, we examined the impacts of other parasite traits, such as infectivity, as alternative predictors of virulence and competition outcomes. Hosts with single-strain (related) parasite infections were found to have lower virulence in terms of host and parasite reproduction, supporting kin selection predictions. However, these infections also resulted in higher host mortality. We argue that mortality should not be used as a measurement of virulence in parasite systems that castrate hosts. Hosts were more susceptible to mixed strain (unrelated) parasite infections, indicating that co-infections may make resistance more costly to hosts. Co-infections were dynamic, with changes in parasite dominance over the course of the infection. The more infective parasite strain appeared to suppress the less infective strain, ultimately increasing host longevity. Our findings suggest that unrelated, or more diverse, parasite infections are associated with higher virulence, but that studies must consider their methodology and possible alternative explanations beyond kin selection to understand virulence outcomes.

[Sepsis masquerading as delirium]. / Listeriensepsis mit Leitsymptom Delir.

A previously healthy 60-year-old patient presented to the emergency department with severe headache, altered personality and fever. He was treated for bacterial meningitis with delirium of unknown cause but presumed to be due to alcohol withdrawal. Despite receiving the antibiotic therapy regimen recommended for bacterial meningitis the patient's condition rapidly deteriorated with profound delirium and tachypnea. The intensivist who was consulted immediately suspected sepsis-associated organ failure and admitted the patient to the intensive care unit (ICU). The blood culture was positive for Listeria. After 10 days the patient could be discharged from the ICU and ultimately recovered completely. In patients presenting with unexplained delirium or altered personality the suspicion of septic encephalopathy should always be considered. They should be admitted to the ICU and sepsis treatment should be initiated without delay.

[Sepsis: case numbers increasing worldwide but new strategies too]. / Sepsis - weltweit steigende Fallzahlen, aber auch neue Strategien.

With the numbers of cases rising worldwide and consistently high mortality, sepsis is one of the world's most significant health issues. The Jena Symposium was dedicated to the challenges in research and development, new approaches to treatment, internationally successful strategies, and a potentially successful new initiative for improving the quality of prophylaxis, early diagnosis, and therapy. The importance of intensifying efforts in the fight against sepsis is becoming increasingly recognized by health care policy. Knowledge of lay people/the public about sepsis is lacking and the standards of quality are in need of improvement.

Pre-procedure ultrasound increases the success and safety of central venous catheterization†.

BACKGROUND: Real-time ultrasound (US) in central venous catheterization is superior to pre-procedure US. However, moving real-time US into routine practice is impeded by its perceived expense and difficulty. Currently, pre-procedure US and landmark (LM) methods are most widely used. We investigated these techniques in internal jugular vein (IJV) catheterization in respect of operator experience, complications, and risk factors. METHODS: In an observational non-randomized study, we investigated 606 of ∼1300 procedures, that is, 200 patients were treated under pre-procedure US and 406 under LM [pathfinder (PF) n=202, direct cannulation (DC) n=204]. We recorded first needle pass success rate, success rate after the third attempt, and the cannulation time. Procedures were performed by inexperienced (<100) or experienced (>100 catheterizations) operators. RESULTS: Pre-procedure US was associated with more successful attempts and shorter cannulation times. Under pre-procedure US, 88% of first attempts were successful and 100% of third attempts. The median (range) cannulation time was 39 (10-330) s. Under PF, only 56% of first, and 87% of third, attempts were successful with a median (range) cannulation time of 100 (25-3600) s. Under DC, 61% of first and 89% of third attempts were successful; the median (range) cannulation time was 70 (10-3600) s. Remarkably, inexperienced operators using pre-procedure US (n=38) were significantly faster than experienced operators using PF or DC (n=343) (cannulation time: median 60 s, range 12-330, for inexperienced; 60 s, range 10-3600, for experienced). First puncture success rates were higher (pre-procedure US, inexperienced 84%, PF or DC, experienced 57%). CONCLUSIONS: Pre-procedure US for IJV catheterization is safe, quick, and superior to LM.

Prevalence of flat lesions in a large screening population and their role in colonoscopy quality improvement.

BACKGROUND AND STUDY AIMS: Flat lesions pose new challenges for endoscopists, but the importance of detecting them is still controversial. Most screening studies do not survey macroscopic polyp morphology. The aims were to evaluate the percentage of flat polyp findings in a large asymptomatic adult screening population (n = 52 521), to assess the impact of shape and size on malignant transformation, and to assess the role of flat lesions regarding quality assurance in colorectal cancer prevention. MATERIAL AND METHODS: Retrospective analysis of screening colonoscopies performed between 2007 and 2011 according to the Austrian "Quality management for colon cancer prevention" program. RESULTS: 17 771 patients with polyps were included in the study. Patients with flat polyps represented 24.2 % (n = 4293), 62.4 % (n = 11 097) were classified as having sessile and 13.4 % (n = 2381) as pedunculated polyps. Among those with flat polyps 51.4 % had adenomas (n = 2207). High grade dysplasia (HGD) was found in 2.1 % (n = 47) of flat adenomas, in 1.5 % (n = 89) of sessile adenomas and 4.7 % (n = 92) of pedunculated adenomas (P < 0.0001. The risk for containing HGD was 1.0 % for flat lesions ≤ 10 mm in size compared with 10.3 % for lesions > 10 mm, and 1.0 % for polypoid lesions ≤ 10 mm compared with 9.3 % for lesions > 10 mm (P < 0.0001). Multivariable logistic regression showed that polyp size (P < 0.0001) but not polyp shape (P = 0.438) is an independent predictor for HGD. Adenoma detection rate (ADR) correlated weakly with the flat polyp detection rate (Pearson r = 0.24). CONCLUSION: Malignant potential of polyps is mostly affected by size but not by shape. Since flat polyp detection rate only correlates poorly with ADR we do not recommend its incorporation in quality assured screening colonoscopy.

Ventilatory strategies in septic patients. Results from a nationwide observational trial.

BACKGROUND: Mortality in intensive care unit (ICU) patients is affected by multiple variables. The possible impact of the mode of ventilation has not yet been clarified; therefore, a secondary analysis of the "epidemiology of sepsis in Germany" study was performed. The aims were (1) to describe the ventilation strategies currently applied in clinical practice, (2) to analyze the association of the different modes of ventilation with mortality and (3) to investigate whether the ratio between arterial partial pressure of oxygen and inspired fraction of oxygen (PF ratio) and/or other respiratory variables are associated with mortality in septic patients needing ventilatory support. METHODS: A total of 454 ICUs in 310 randomly selected hospitals participated in this national prospective observational 1-day point prevalence of sepsis study including 415 patients with severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine criteria. RESULTS: Of the 415 patients, 331 required ventilatory support. Pressure controlled ventilation (PCV) was the most frequently used ventilatory mode (70.6 %) followed by assisted ventilation (AV 21.7 %) and volume controlled ventilation (VCV 7.7 %). Hospital mortality did not differ significantly among patients ventilated with PCV (57 %), VCV (71 %) or AV (51 %, p=0.23). A PF ratio equal or less than 300 mmHg was found in 83.2 % of invasively ventilated patients (n=316). In AV patients there was a clear trend to a higher PF ratio (204±70 mmHg) than in controlled ventilated patients (PCV 179±74 mmHg, VCV 175±75 mmHg, p=0.0551). Multiple regression analysis identified the tidal volume to pressure ratio (tidal volume divided by peak inspiratory airway pressure, odds ratio OR=0.94, 95 % confidence interval 95% CI=0.89-0.99), acute renal failure (OR=2.15, 95% CI=1.01-4.55) and acute physiology and chronic health evaluation (APACHE) II score (OR=1.09, 95% CI=1.03-1.15) but not the PF ratio (univariate analysis OR=0.998, 95 % CI=0.995-1.001) as independent risk factors for in-hospital mortality. CONCLUSIONS: This representative survey revealed that severe sepsis or septic shock was frequently associated with acute lung injury. Different ventilatory modes did not affect mortality. The tidal volume to inspiratory pressure ratio but not the PF ratio was independently associated with mortality.

[Sepsis : putting knowledge into practice]. / Sepsis : Wissen für die Praxis.

Sepsis is a complex systemic inflammatory reaction in response to an infection and must be treated as an emergency. The diagnosis of sepsis is often delayed even though early goal-directed resuscitation and therapy with antibiotics within the first hours can reduce sepsis-related mortality. This article presents the most important points concerning the pathophysiology, diagnosis and therapy of sepsis.

[Sepsis incidence in Germany and worldwide : Current knowledge and limitations of research using health claims data]. / Inzidenz der Sepsis in Deutschland und weltweit : Aktueller Wissensstand und Limitationen der Erhebung in Abrechnungsdaten.

Sepsis is the life-threatening organ dysfunction caused by a dysregulated host response to infection. With an estimated 48.9 million patients being affected by sepsis every year, sepsis is one of the most common diseases worldwide. Approximately 20% of global deaths are considered as sepsis-related. In Germany, a study based on nationwide hospital discharge data of almost all German hospitals found a sepsis incidence of 158 per 100,000 inhabitants. Estimates based on clinical patient data from other industrialized countries were 780/100,000 (Sweden) and 517/100,000 (USA). However, the comparability of incidence rates is limited due to the different data sources and sepsis case identification strategies used. In all, 41.7% of sepsis patients died in hospital, and 17.9% of intensive care unit patients are affected by sepsis. Case identification of sepsis in health claims data has a low sensitivity; therefore, it is likely that sepsis incidence is underestimated using these data, as many sepsis cases are not coded as such. For the purpose of epidemiological surveillance, health claims data should be complemented by other data sources such as registries or electronic health records.

Optimized method for correct left-sided central venous catheter placement under electrocardiographic guidance.

BACKGROUND: Central venous catheter (CVC) placement under ECG guidance in the left thoracocervical area can lead to catheter misplacement. The aim of this study was to identify the cause and quantify the magnitude of this error. METHODS: CVCs were sited in either the left or right internal jugular (IJ), subclavian (SC), or innominate (brachiocephalic) vein using the Seldinger technique and a total of 227 insertions were studied. The position of the catheter tip was confirmed with two different intra-atrial ECG monitoring methods (Seldinger's wire vs 10% saline solution). Measurements were compared between the two methods and correlated to the different access sites. RESULTS: All right-sided CVC had the line tip in the optimal position and both intra-atrial ECG recording by Seldinger's wire or 10% saline delivered correct results. For left-sided lines, however, the two methods gave significantly different results regarding the position of the line tip for each insertion site. When using the Seldinger wire as intravascular ECG lead, the results differed from the saline method by a mean of 21 mm for the IJ and 10 mm for the SC. CONCLUSIONS: CVC placement under ECG guidance is a reliable method to site the line tip at the optimal position. However, when using a left-sided thoracocervical access point, the Seldinger wire-conducted ECG delivered a constant error. This could be adjusted for by advancing the CVC 20 mm in addition to the wire-based measurement of the insertion depth at the left IJ vein and 10 mm at the left SC vein.

Antiplatelet agents for the prevention of arteriovenous fistula and graft thrombosis: a meta analysis.

AIMS: The aim of this study was to evaluate the impact of antiplatelet agents on the thrombosis rates of arteriovenous fistulae and grafts used for haemodialysis access. METHODS: In this meta analysis, a systematic search of the literature was used to identify randomised controlled trials evaluating the effect of antiplatelet agents in graft or fistula thrombosis or bleeding. Two authors identified eligible trials and abstracted data on outcomes and study characteristics. The incidence of thrombosis was the primary outcome of interest and was calculated separately for studies evaluating grafts and those evaluating fistulae. A random-effects model was used for statistical pooling. RESULTS: Ten trials were included in the analysis, nine of which reported outcomes on graft or fistula thrombosis. Antiplatelet agents reduced the rate of arteriovenous fistulae thrombosis (OR 0.54, 95% CI 0.31-0.94) but not grafts (OR 0.50, 95% CI 0.16-1.53). Both analyses had a moderate degree of statistical heterogeneity, likely because of differences in study design, antiplatelet agent and dose, as well as other possible factors. Review of bleeding events did not reveal a concerning risk of bleeding, but could not be statistically evaluated. CONCLUSIONS: Antiplatelet agents reduce the rate of arteriovenous fistula thrombosis; however, at this time, research does not support the use of these agents for preventing arteriovenous graft thrombosis.

[Prevention and follow-up care of sepsis. 1st revision of S2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V., DSG) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin, DIVI)]. / Prävention und Nachsorge der Sepsis. 1. Revision der S2k-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

The 1st revision of the S2k guideline on the prevention and follow-up care of sepsis, provided by the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information on the effective and appropriate medical care of critically ill patients with severe sepsis or septic shock. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis.

PURPOSE: To investigate the global burden of sepsis in hospitalized adults by updating and expanding a systematic review and meta-analysis and to compare findings with recent Institute for Health Metrics and Evaluation (IHME) sepsis estimates. METHODS: Thirteen electronic databases were searched for studies on population-level sepsis incidence defined according to clinical criteria (Sepsis-1, -2: severe sepsis criteria, or sepsis-3: sepsis criteria) or relevant ICD-codes. The search of the original systematic review was updated for studies published 05/2015-02/2019 and complemented by a search targeting low- or middle-income-country (LMIC) studies published 01/1979-02/2019. We performed a random-effects meta-analysis with incidence of hospital- and ICU-treated sepsis and proportion of deaths among these sepsis cases as outcomes. RESULTS: Of 4746 results, 28 met the inclusion criteria. 21 studies contributed data for the meta-analysis and were pooled with 30 studies from the original meta-analysis. Pooled incidence was 189 [95% CI 133, 267] hospital-treated sepsis cases per 100,000 person-years. An estimated 26.7% [22.9, 30.7] of sepsis patients died. Estimated incidence of ICU-treated sepsis was 58 [42, 81] per 100,000 person-years, of which 41.9% [95% CI 36.2, 47.7] died prior to hospital discharge. There was a considerably higher incidence of hospital-treated sepsis observed after 2008 (+ 46% compared to the overall time frame). CONCLUSIONS: Compared to results from the IHME study, we found an approximately 50% lower incidence of hospital-treated sepsis. The majority of studies included were based on administrative data, thus limiting our ability to assess temporal trends and regional differences. The incidence of sepsis remains unknown for the vast majority of LMICs, highlighting the urgent need for improved epidemiological sepsis surveillance.

Polyester fiber: from its invention to its present position.

The use of polyester fibers has grown more rapidly than that of any other man-made fiber. Many factors have contributed to this growth. Polyester's unique physical properties of strength, high modulus, elasticity, and durability are the basis for its success. The tailorability of the fiber makes it possible to generate a whole family of property variants for a wide variety of end uses. The ready availability and low cost of the raw materials, the continuing advances in polymerization technology, and the versatility of the melt spinning process have also been major factors in establishing polyester as the leading man-made fiber. New end uses have had a major impact on the growth of polyester. Most notable was the introduction of durable press fabrics for clothing and home furnishings. The consumer preference for easy-care fabrics and garments makes the durable press area one of continuing growth. Two relatively new areas where growth is expected to continue at a rapid rate are tire cord and textured knits for women's and men's outerwear.

Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry.

BACKGROUND: The PROGRESS Registry (Promoting Global Research Excellence in Severe Sepsis) was designed to provide comparative data reflecting everyday clinical practice, thereby allowing participating institutions to explore and benchmark medical interventions in severe sepsis. MATERIALS AND METHODS: PROGRESS was an international, noninterventional, prospective, observational registry collecting data that describe the management and outcomes of severe sepsis patients in intensive care units (ICUs). Patients were enrolled who had been diagnosed with severe sepsis (suspected or proven infection and >or= 1 acute sepsis-induced organ dysfunction) at the participating institutions, where de-identified data were entered directly into a secured website. PROGRESS was governed by an independent international medical advisory board. RESULTS: PROGRESS took place in 276 ICUs in 37 countries, and 12,881 patients were identified as having severe sepsis. There was considerable variation among countries in enrollment levels, provision of standard treatment and supportive therapies, and ICU and hospital outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU admission in 29.1% of patients, and after ICU admission in the remainder. Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively. The mean length of ICU and hospital stay was 14.6 days and 28.2 days, respectively. CONCLUSIONS: The PROGRESS international sepsis registry demonstrates that a large web-based sepsis registry is feasible. Wide variations in outcomes and use of sepsis therapies were observed between countries. These results also suggest that additional opportunities exist across countries to improve severe sepsis outcomes.

Effects of staff training on the care of mechanically ventilated patients: a prospective cohort study.

BACKGROUND: Adherence to guidelines to avoid complications associated with mechanical ventilation is often incomplete. The goal of this study was to assess whether staff training in pre-defined interventions (bundle) improves the quality of care in mechanically ventilated patients. METHODS: This study was performed on a 50-bed intensive care unit of a tertiary care university hospital. Application of a ventilator bundle consisting of semirecumbent positioning, lung protective ventilation in patients with acute lung injury (ALI), ulcer prophylaxis, and deep vein thrombosis prophylaxis (DVTP) was assessed before and after staff training in post-surgical patients requiring mechanical ventilation for at least 24 h. RESULTS: A total of 133 patients before and 141 patients after staff training were included. Overall bundle adherence increased from 15 to 33.8% (P<0.001). Semirecumbent position was achieved in 24.9% of patient days before and 46.9% of patient days after staff training (P<0.001). Administration of DVTP increased from 89.5 to 91.5% (P=0.048). Ulcer prophylaxis of >90% was achieved in both groups. Median tidal volume in patients with ALI remained unaltered. Days on mechanical ventilation were reduced from 6 (interquartile range 2.0-15.0) to 4 (2.0-9.0) (P=0.017). Rate of ventilator-associated pneumonia (VAP), ICU length of stay, and ICU mortality remained unaffected. In patients with VAP, the median ICU length of stay was reduced by 9 days (P=0.04). CONCLUSIONS: Staff training by an ICU change team improved compliance to a pre-defined ventilator bundle. This led to a reduction in the days spent on mechanical ventilation, despite incomplete bundle implementation.

Adding a dopamine agonist to preexisting levodopa therapy vs. levodopa therapy alone in advanced Parkinson's disease: a meta analysis.

BACKGROUND: To perform a meta analysis of randomised placebo-controlled trials evaluating the use of dopamine agonist (DA) or placebo to preexisting levodopa therapy for the treatment of advanced Parkinson's disease (PD). We focused on clinically important efficacy [Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as change in 'off' time and levodopa dose] and safety outcomes (withdrawal because of adverse drug events (ADEs), dyskinesias, hallucinations and mortality). METHODS: A systematic literature search was performed between January 1990 and July 2007. The primary outcome measures assessed were the reduction in scores of Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as reduction in 'off' time and reductions in levodopa dose from baseline. Safety end-points were also evaluated. RESULTS: A total of 15 trials (n = 4380 subjects) were included in the meta analysis. Adjunctive DA use resulted in greater improvement as measured by the UPDRS ADL [weighted mean difference (WMD) -2.20, 95% confidence interval (CI) -2.64 to -1.76; p < 0.0001] and motor score reduction (WMD -5.56, 95% CI -6.82 to -4.31; p < 0.0001) as well as reduction in 'off' time measured in hours/day (WMD -1.20, 95% CI -1.78 to -0.62; p < 0.0001) and reduction in levodopa dose (WMD -128.5 mg, 95% CI -175.0 to -82.1; p < 0.0001) vs. placebo. Incidence of dyskinesia and hallucinations was higher with DAs [odds ratio (OR) 3.27, 95% CI 2.65-4.03; p < 0.0001] and (OR 3.34, 95% CI 2.44-4.58; p < 0.0001). Non-ergot DAs were qualitatively better, although both ergot and non-ergot DAs showed statistically significant improvements in all UPDRS scores. CONCLUSION: Adjunctive DA use to levodopa is superior to levodopa alone in reducing PD symptoms in patients not controlled with monotherapy. DAs seem especially useful amongst PD patients with wearing-off phenomenon from levodopa therapy, but can cause some adverse events.

[Ultrasound guidance for placement control of central venous catheterization. Survey of 802 anesthesia departments for 2007 in Germany]. / Ultraschall und Lagekontrolle bei der Anlage zentraler Venenkatheter. Umfrage unter 802 Anästhesieabteilungen im Jahr 2007 in Deutschland.

OBJECTIVES AND METHODS: In 2007 a survey on the development of the current practice of using ultrasound to assist central venous catheter (CVC) placement was carried out in 802 departments of anesthesiology and intensive care medicine in hospitals with more than 200 beds in Germany. These data were compared to data from a survey in 2003. Additionally, data regarding control of CVC positioning were collected. RESULTS: The response rate was 58%. In these 468 departments approximately 340,000 CVCs are placed annually and 317 departments have access to an ultrasound machine. Ultrasound guidance is used by 188 (40%) departments for central venous cannulation. Of these only 24 (12.7%) use ultrasound routinely and 114 (60.6%) use it when faced with a difficult cannulation. Approximately one-third of the users perform continuous ultrasound guidance for CVC placement. Equipment was not at disposal in 115 (41.1%) departments not using ultrasound for CVC placement did not possess the equipment and 93 (33.2%) did not consider ultrasound necessary. Positioning of CVCs was controlled either by electrocardiogram (ECG) guidance and/or chest radiograph in 92%. CONCLUSION: In Germany placement of central venous catheters is still usually based on anatomical landmarks. However, compared to 2003, ultrasound guidance for CVC placement is gradually being introduced (40% compared to 19%). Given the well-documented advantages of ultrasound guidance compared to landmark based approaches for central venous cannulation, acquisition of this technology should belong to the training programme of an anesthesiologist.

[Diagnosis and causal treatment of sepsis]. / Diagnose und kausale Therapie der Sepsis.

The high mortality and morbidity of severe sepsis and septic shock had not been reduced during the two recent decades, despite a number of advances in the field of supportive and adjunctive sepsis therapies. The reason might be that important steps towards overcoming of sepsis - early diagnosis, the surgical resection of the infectious focus and an adequate antibiotic treatment - at present are still suboptimal and have to be improved. However, worldwide growing resistances of pathogens against the common antibiotics are detected. In opposite, no major progress in the development of new antibiotics, mainly for the treatment of Gram-negative non-fermenter infections like Pseudomonas aeruginosa, can be predicted for the next years. Therefore, sepsis treatment must be focused on prevention of infection, and on an optimised application of current antibiotic substances. The key factors are a broad, high dose, and early applicated initial treatment, a de-escalation strategy according to the clinical course supported by the application of novel molecular markers, and - with exceptions - a limitation of treatment to 7 to 10 days. A closer cooperation between microbiologists, infection control specialists and clinical infectious disease consultants may be a key factor to overcome the raising problems in the future.