The role of routine SARS-CoV-2 screening of healthcare-workers in acute care hospitals in 2020: a systematic review and meta-analysis.

BACKGROUND: Healthcare workers (HCW) are at increased risk of infection with SARS-CoV-2. Vulnerable patient populations in particular must be protected, and clinics should not become transmission hotspots to avoid delaying medical treatments independent of COVID. Because asymptomatic transmission has been described, routine screening of asymptomatic HCW would potentially be able to interrupt chains of infection through early detection. METHODS: A systematic search was conducted in the Cochrane COVID-19 Study Register, Web of Science and WHO COVID-19 Global literature on coronavirus with regard to non-incident related testing of healthcare workers using polymerase chain reaction on May 4th 2021. Studies since January 2020 were included. An assessment of risk of bias and representativeness was performed. RESULTS: The search identified 39 studies with heterogeneous designs. Data collection of the included studies took place from January to August 2020. The studies were conducted worldwide and the sample size of the included HCW ranged from 70 to 9449 participants. In total, 1000 of 51,700 (1.9%) asymptomatic HCW were tested positive for SARS-CoV-2 using PCR testing. The proportion of positive test results ranged between 0 and 14.3%. No study reported on HCW-screening related reductions in infected person-days. DISCUSSION AND CONCLUSIONS: The heterogeneous proportions might be explained by different regional incidences, lock-downs, and pre-analytical pitfalls that reduce the sensitivity of the nasopharyngeal swab. The very high prevalence in some studies indicates that screening HCW for SARS-CoV-2 may be important particularly in geographical regions and pandemic periods with a high-incidence. With low numbers and an increasing rate of vaccinated HCW, a strict cost-benefit consideration must be made, especially in times of low incidences. Since we found no studies that reported on HCW-screening related reductions in infected person-days, re-evaluation should be done when these are available.

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: an abridged Cochrane network meta-analysis.

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

Impact of investigator initiated trials and industry sponsored trials on medical practice (IMPACT): rationale and study design.

BACKGROUND: The German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF) initiated large research programs to foster high quality clinical research in the academic area. These investigator initiated trials (IITs) cover important areas of medical research and often go beyond the scope of industry sponsored trials (ISTs). The purpose of this project was to understand to what extent results of randomized controlled IITs and ISTs have an impact on medical practice, measured by their availability for decisions in healthcare and their implementation in clinical practice. We aimed to determine study characteristics influencing a trial's impact such as type of sponsor and place of conduct. In this article, we describe the rationale and design of this project and present the characteristics of the trials included in our study cohort. METHODS: The research impact of the following sub-cohorts was compared: German IITs (funded by DFG and BMBF or by other German non-commercial organizations), international IITs (without German contribution), German ISTs, and international ISTs. Trials included were drawn from the DFG-/BMBF-Websites, the German Clinical Trials Register, and from ClinicalTrials.gov . Research impact was measured as follows: 1) proportion of published trials, 2) time to publication, 3) proportion of publications appropriately indexed in biomedical databases, 4) proportion of openly accessible publications, 5) broadness of publication's target group, 6) citation of publications by systematic reviews or meta-analyses, and 7) appearance of publications or citing systematic reviews or meta-analyses in clinical practice guidelines. We also aimed to identify study characteristics associated with the impact of trials. RESULTS: We included 691 trials: 120 German IITs, 200 International IITs, 171 German ISTs and 200 International ISTs. The median number of participants was 150, 30% were international trials and 70% national trials, 48% drug-trials and 52% non-drug trials. Overall, 72% of the trials had one pre-defined primary endpoint, 28% two or more (max. 36). CONCLUSIONS: The results of this project deepen our understanding of the impact of biomedical research on clinical practice and healthcare policy, add important insights for the efficient allocation of scarce research resources and may facilitate providing accountability to the different stakeholders involved.

Influence of experience and qualification on PET-based target volume delineation. When there is no expert--ask your colleague.

BACKGROUND AND PURPOSE: The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates the dependency of manual delineation on experience and qualification. PATIENTS AND METHODS: A total of 44 international interdisciplinary observers each defined a [(18)F]fluorodeoxyglucose (FDG)-PET based gross tumor volume (GTV) using the same PET/CT scan from a patient with lung cancer. The observers were "experts" (E; n = 3), "experienced interdisciplinary pairs" (EP; 9 teams of radiation oncologist (RO) + nuclear medicine physician (NP)), "single field specialists" (SFS; n = 13), and "students" (S; n = 10). Five automatic delineation methods (AM) were also included. Volume sizes and concordance indices within the groups (pCI) and relative to the experts (eCI) were calculated. RESULTS: E (pCI = 0.67) and EP (pCI = 0.53) showed a significantly higher agreement within the groups as compared to SFS (pCI = 0.43, p = 0.03, and p = 0.006). In relation to the experts, EP (eCI = 0.55) showed better concordance compared to SFS (eCI = 0.49) or S (eCI = 0.47). The intermethod variability of the AM (pCI = 0.44) was similar to that of SFS and S, showing poorer agreement with the experts (eCI = 0.35). CONCLUSION: The results suggest that interdisciplinary cooperation could be beneficial for consistent contouring. Joint delineation by a radiation oncologist and a nuclear medicine physician showed remarkable agreement and better concordance with the experts compared to other specialists. The relevant intermethod variability of the automatic algorithms underlines the need for further standardization and optimization in this field.

Reirradiation plus EGFR inhibition in locally recurrent and unresectable head and neck cancer: final results from a single institution.

PURPOSE: For some patients with recurrent, unresectable, and previously irradiated head and neck squamous cell carcinoma (HNSCC), reirradiation (re-RT) may be a curative option. Chemotherapy with epidermal growth factor receptor (EGFR) inhibition is established as palliative management. This retrospective single-institutional study investigates feasibility, toxicity, and outcome of reirradiation (re-RT) combined with EGFR blockade for these patients. PATIENTS AND METHODS: Between June 2008 and June 2012, 23 patients with inoperable and previously irradiated HNSCC were reirradiated. Concomitant EGFR blockade (cetuximab) was given initially at 400 mg/m2 two days prior to re-RT and weekly (250 mg/m2) thereafter. PET/CT imaging was fused with planning CT in 8 patients. RESULTS: One patient died of anaphylactic shock during the first cetuximab administration; two discontinued treatment on their own request. In all, 20 patients completed re-RT (50.4-66.6 Gy) and received cetuximab as prescribed. Grade 3 acute side effects were documented for dermatitis (35%), dysphagia (30%), acneiform rash (30%), and mucositis (15%). The 1-year overall survival rate was 34.8% Median overall and progression-free survival times were 9 and 4.3 months, respectively. A multivariable analysis using the Cox regression model showed significant positive impact of acneiform rash (hazard ratio [HR] 0.1531, 95% confidence interval [CI] 0.0383-0.6111), while a period from first radiation to re-RT longer than 120 months negatively (HR 0.1633, 95% CI 0.0305-0.8734) influenced patient survival. CONCLUSION: re-RT with concurrent cetuximab was feasible. Compared to platinum-based chemotherapy with fluorouracil and cetuximab, this therapeutic approach did not demonstrate survival benefit. Prolonged intervals from first treatment to re-RT seem to be unfavorable.

Performance of a novel microarray multiplex PCR for the detection of 23 respiratory pathogens (SYMP-ARI study).

Symptoms of acute febrile respiratory tract infection are often unspecific, but the rapid identification of pathogens allows optimised patient management. The objective of this study was to evaluate a novel multiplex polymerase chain reaction (PCR) suspension microarray which detects 19 viral and four atypical bacterial targets. A comprehensive set of sensitive monoplex real-time PCR assays was used for each pathogen as the gold standard. A panel of archived as well as 300 prospectively collected clinical samples was analysed by both methods. At least one target was detected in 165/300 (55 %) samples by monoplex PCR and in 140/300 (46 %) samples by multiplex PCR, respectively. The positivity rate was significantly higher in paediatric patients compared to adults [126/154 (82 %) vs. 39/146 (27 %) by monoplex and 114/154 (74 %) vs. 26/146 (18 %) by multiplex PCR, respectively]. Among all samples, 17/300 (5.6 %) were positive for atypical bacteria by monoplex and 8/300 (2.6 %) by multiplex PCR, respectively. Multiple detections were recorded in 35/300 (11.6 %) samples by monoplex and 26/300 (8.7 %) by multiplex PCR. For the most common pathogens, the sensitivity ranged from 57 to 93 % and the specificity ranged from 95 to 100 %. The overall concordance between both methods was 77 % [95 % confidence interval (CI) 72-81 %]. False-negative results by multiplex PCR were mainly due to the low target concentration. Compared to monoplex PCR, the novel microarray assay proved its principle but displayed overall lower sensitivities, potentially restricting its use to paediatric patients. For some targets, only small numbers of positive samples were available, requiring larger studies to firmly assess the sensitivity and specificity.

Biopsy-derived oral keratinocytes - A model to potentially test for oral mucosa radiation sensitivity.

Purpose: To establish stable in vitro growth of keratinocytes from very small biopsy specimens and successfully apply new test systems to determine their radiosensitivity. Materials and Methods: Oral mucosa biopsies (diameter: 1.7 mm) from 15 subjects were immobilized with custom-made cups onto culture plates. Outgrowing cells were tested for cytokeratin 5/14 and Ki67, expanded, radiated at different doses, and seeded onto circumscribed areas before being allowed to spread centrifugally. In this newly developed spreading assay, cell-covered areas were measured by image analysis. For statistical analysis, a linear mixed regression model was used; additionally, results were correlated to the radiation dose applied. Colony forming efficiency (CFE) was used to validate the results. DNA damage repair was analysed by gammaH2AX and 53BP1 foci quantification using immunofluorescence microscopy 24 h and 96 h after irradiation. Results: Stable keratinocyte growth continued for up to 7 weeks in 14 biopsies. Cells spread reliably from an initial 16.6 mm2 up to a median of 119.2 mm2 (range: 54.4-290). Radiated cells spread to only 100.7 mm2 (2 Gy; range: 55.3-266.7); 73.2 mm2 (4 Gy; 15-240.4); 47 mm2 (6 Gy; 2-111.9), and 22.7 mm2 (8 Gy; 0-80). Similarly, CFE decreased from 0.223 (0 Gy) to 0.0028 (8 Gy). Using an individual donor as a random factor, cell spread correlated with CFE, where radiation dose was the main driver (decrease by 0.50, adjusted for area). Upon irradiation with 6 Gy, radiation-induced DNA damage was increased after 24 h in all samples, and even after 96 h in 5 out of 7 samples, as detected by a higher number of gammaH2AX/53BP1 foci in irradiated cells (mean 3.7 for 24 h; mean 0.6 for 96 h). Conclusion: In vitro propagation of keratinocytes derived from a small biopsy is feasible. Radiation impairs cellular migration and proliferation, and the newly described spreading assay allows ranking for cellular radioresistance. The keratinocyte model also supports classical functional assays such as clonogenic survival and DNA double strand repair. The clinical relevance awaits upcoming investigations.

Are KISS data representative of German intensive care units? Statistical issues.

OBJECTIVES: Data collected within the German nosocomial infection surveillance system KISS are recommended as reference data for judging nosocomial infection rates in German intensive care units (ICUs). It is unknown whether the KISS data tend to under- or overestimate the true infection incidence rates. In this article, methodological aspects of the SIR1 study on the incidence of nosocomial infections are discussed, with the aim of estimating unbiased incidence rates of nosocomial infections in interdisciplinary German ICUs and examining whether the KISS data are representative. METHODS: We discuss the following methodological issues: 1) Sample size estimation. 2) Stratified random sampling of German ICUs. 3) Investigation of seasonal effects. 4) Statistical modeling of incidence rates using a negative binomial regression model. 5) Comparison of weighted incidence rates with the standardized rate ratio (SRR). RESULTS: Random sampling proved difficult to realize in practice since many ICUs refused to participate, particularly those in small hospitals. Analysis was adjusted for hospital size. No seasonal trends were found in the KISS data. Due to marked differences between ICUs, the number of infections is over-dispersed compared to a Poisson model, so negative binomial regression was used. Fifty ICUs were observed for two consecutive months each, corresponding to 21,832 patient days, during which 262 infections occurred. Infections were more frequent in large hospitals. The incidence rates provided by the SIR study are on average (SRR) 1.89 (1.63-2.20) times as large as those estimated by the KISS system. CONCLUSION: For estimating nosocomial infection incidence rates, random sampling and statistical modeling of over-dispersion were successfully performed. The study provides evidence that the KISS surveillance system tends to underestimate the true incidence rates of nosocomial infections in German ICUs.

Successful use of undersized donors for orthotopic heart transplantation--with a caveat.

Accepted clinical practice has been to require body weights to be within 20% as a criterion for matching donor to recipient for cardiac transplantation. From November 1989 through September 1993 we began accepting larger differences in body weight between donor and recipient with 80 orthotopic heart transplants performed. Twenty-eight of these transplants used undersized donors (donor-to-recipient body weight ratio [DRBW] of 0.6 to 0.8) with the remaining donors being either size matched (DRBW = 0.8 to 1.0) or oversized (DRBW > 1.0). Thirty-three of the 80 transplant recipients (41%) were classified preoperatively as United Network for Organ Sharing (UNOS) status I and the remaining patients were classified as UNOS status II. Hospital survival for status I recipients was 9 of 14 (64%) for undersized donors, 7 of 8 (87.5%) for sized-matched donors, and 11 of 11 (100%) for oversized donors (p < 0.05). Hospital survival for status II recipients was 12 of 14 (85.7%) for undersized donors, 24 of 24 (100%) for sized-matched donors, and 8 of 9 (88.8%) for oversized donors. Our data support the continued use of hearts from undersized donors in status II recipients. The use of hearts from undersized donors in status I recipients is associated with increased mortality compared with size-matched donors and must be undertaken with caution.

Triterpenoid glycosides from Stauntonia hexaphylla.

From Stauntonia hexaphylla, two new 3,28-bisglycosidic triterpenoid glycosides named staunosides A and B, were isolated along with three known triterpenoid glycosides, one of which was isolated from nature of the first time, though it had previously been obtained from the acid hydrolysate of kizuta saponin K12. On the basis of chemical and physicochemical evidence, the structures of staunosides A and B were elucidated as 3-O-(beta-D-glucopyranosyl)-hederagenin-28-O-[beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl]ester and 28-O-[alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)- beta-D-glucopyranosyl]ester, respectively.

Triterpenoid glycosides from Stauntonia hexaphylla.

On the basis of spectroscopic and chemical methods, the structures of two new bisdesmosidic triterpenoid glycosides, named staunoside D and E, which were isolated from Stauntonia hexaphylla, were established as 3-O-(beta-D-glucopyranosyl(1-->2)-[beta-D- glucopyranosyl(1-->3)]-beta-D-glucopyranosyl)-hederagenin-28- O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] ester and 28-O-[alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl]ester, respectively. Three known triterpenoid glycosides were also isolated. A new proglycoside was isolated from the cleavage of the ester-glycosidic linkage and its structure characterized.

Reduction of ischaemic rest pain in advanced peripheral arterial occlusive disease. A double blind placebo controlled trial with iloprost.

Severe pain at rest is a major symptom of advanced peripheral arterial occlusive disease (PAOD). Preliminary studies of treatment with iloprost, a prostacyclin analogue, showed encouraging results in patients with ischaemic rest pain. Therefore a randomized, placebo-controlled multicentre study was undertaken in 113 patients admitted to hospital with rest pain of at least 2 weeks duration caused by severe PAOD. The patients were randomly assigned to receive 2-week placebo or iloprost infusions for 6 hours per day at a dose of 0.5-0.2 ng/kg/min in addition to conventional care. Demographic data and arteriographic findings were similar in the two groups. Eleven patients withdrew from the study before completion and 102 patients could be included in the final analysis. Significantly more patients in the iloprost group (62.5% of 48) than in the placebo group (42.6% of 54) had complete relief of pain without analgesic therapy during at least five consecutive days at the end of the treatment period (p less than 0.05, chi 2-test). Facial flush, headache and nausea were the most common side effects during iloprost infusion. Serious adverse reactions did not occur. Thus, a 2-week iloprost infusion was shown to be safe and effective as a treatment for ischaemic rest pain caused by PAOD.

Laser Tissue Welding - Poised for the New Millenium.

Laser tissue welding is a relatively new technique, which was initially described only about 30 years ago. Over the past 10 years, the implementation of protein solders has redefined the field. Alternative methods of wound closure and of tissue approximation have been quickly accepted in clinical medicine. The techniques and theory involved in performing laser tissue welding may soon be essential knowledge for all surgeons. Just as laparoscopy has become a mainstay for general surgeons and urologists, novel mechanisms of tissue approximation will continue to replace older, less efficacious techniques.

Laser tissue welding - poised for the new millenium.

Laser tissue welding is a relatively new technique, which was initially described only about 30 years ago. Over the past 10 years, the implementation of protein solders has redefined the field. Alternative methods of wound closure and of tissue approximation have been quickly accepted in clinical medicine. The techniques and theory involved in performing laser tissue welding may soon be essential knowledge for all surgeons. Just as laparoscopy has become a mainstay for general surgeons and urologists, novel mechanisms of tissue approximation will continue to replace older, less efficacious techniques.

[Quantitative determination of alpha-peroxyachifolide in yarrow by HPLC with amperometric detection]. / Quantitative Bestimmung von alpha-Peroxyachifolid in der Schafgarbe durch HPLC mit amperometrischer Detektion.

A HPLC method with amperometric detection is established for the contact allergen alpha-peroxyachifolid (1) from yarrow (Achillea millefolium L., s. str.). The amounts of 1 are between 0.25 and 0.60% in blossoms, dried 2 h at room temperature, and between 0.01 and 0.05% in the leaves. In completely dried material and in some preparations from the market 1 could also be quantified.

[Freiburg intervention program for ambulatory therapy of obesity in childhood (FITOC)]. / Freiburger Interventionsprogramm zur ambulanten Therapie der Adipositas im Kindesalter (FITOC).

In this study we first try to answer the question, whether it is possible to make a successful treatment for obese children in an interdisciplinary program. Second it is asked whether a transfer of this program to further regions in Germany leads to comparable results. In FITOC children from the age of 8-11 years and over the 97. BMI-percentile are integrated in this program. The goals weight management, increased physical fitness and improvement of the cardiac risk profile are checked by weight, height, fasting blood serum, a standardized cycle ergometry and a medical measurement at the beginning, after treatment and at all check-ups. The recorded medical data show clearly that the intervention leads to a significant improvement in almost all checked parts. The successful treatment can be recorded after 8 months, likewise after 2.5 years as a long-term result. The further cornerstones of FITOC nutrition and psychology are not subject of this publication. In future the psychological part in FITOC will be evaluated by standardized inventories. The group from Düren has a success in therapy according to the definition of the program. Thereby it is shown that FITOC is extendable, if teams are trained intensively and the conditions are comparable. FITOC is able to treat obese children successfully over a long period of time. In consideration of the rising prevalence of obesity in childhood and the limited financial resources in health care this outpatient interdisciplinary program is an effective choice of treatment.

Measuring inter-observer agreement in contour delineation of medical imaging in a dummy run using Fleiss' kappa.

BACKGROUND: In medical imaging used for planning of radiation therapy, observers delineate contours of a treatment volume in a series of images of uniform slice thickness. OBJECTIVE: To summarize agreement in contouring between an arbitrary number of observers by a single number, we generalized the kappa index proposed by Zijdenbos et al. (1994). METHODS: Observers characterized voxels by allocating them to one of two categories, inside or outside the contoured region. Fleiss' kappa was used to measure association between n indistinguishable observers. Given the number Vi of voxels contoured by exactly i observers (i = 1, ..., n ), the resulting overall kappa is representable as a ratio of weighted sums of the Vi . RESULTS: Overall kappa was applied to analyze inter-center variations in a multicenter trial on radiotherapy planning in patients with locally advanced lung cancer. A contouring dummy run was performed within the quality assurance program. Contouring was done twice, once before and once after a training program. Observer agreement was enhanced from 0.59 (with a 95% confidence interval (CI) of 0.51-0.67) to 0.69 (95% CI 0.59-0.78). CONCLUSION: By contrast to average pairwise indices, overall kappa measures observer agreement for more than two observers using the full information about overlapping volumes, while not distinguishing between observers. It is particularly adequate for measuring observer agreement when identification of observers is not possible or desirable and when there is no gold standard.