OBJECTIVE: To quantify the Hawthorne effect of hand hygiene performance among healthcare workers using direct observation.DESIGN: Prospective observational study.SETTING: Intensive care unit, university hospital.METHODS: Direct observation of hand hygiene compliance over 48 audits of 2 hours each. Simultaneously, hand hygiene events (HHEs) were recorded using electronic alcohol-based handrub dispensers. Directly observed and electronically recorded HHEs during the 2 hours of direct observation were compared using Spearman correlations and Bland-Altman plots. To quantify the Hawthorne effect, we compared the number of electronically recorded HHEs during the direct observation periods with the re-scaled electronically recorded HHEs in the 6 remaining hours of the 8-hour working shift.RESULTS: A total of 3,978 opportunities for hand hygiene were observed during the 96 hours of direct observation. Hand hygiene compliance was 51% (95% CI, 49%–53%). There was a strong positive correlation between directly observed compliance and electronically recorded HHEs (ρ=0.68 [95% CI, 0.49–0.81], P<.0001). In the 384 hours under surveillance, 4,180 HHEs were recorded by the electronic dispensers. Of those, 2,029 HHEs were recorded during the 96 hours in which direct observation was also performed, and 2,151 HHEs were performed in the remaining 288 hours of the same working shift that were not under direct observation. Healthcare workers performed 8 HHEs per hour when not under observation compared with 21 HHEs per hour during observation.CONCLUSIONS: Directly and electronically observed HHEs were in agreement. We observed a marked influence of the Hawthorne effect on hand hygiene performance.Infect Control Hosp Epidemiol 2015;36(8):957–962

To identify new tumor-suppressor gene candidates relevant for human hepatocarcinogenesis, we performed genome-wide methylation profiling and vertical integration with array-based comparative genomic hybridization (aCGH), as well as expression data from a cohort of well-characterized human hepatocellular carcinomas (HCCs). Bisulfite-converted DNAs from 63 HCCs and 10 healthy control livers were analyzed for the methylation status of more than 14,000 genes. After defining the differentially methylated genes in HCCs, we integrated their DNA copy-number alterations as determined by aCGH data and correlated them with gene expression to identify genes potentially silenced by promoter hypermethylation. Aberrant methylation of candidates was further confirmed by pyrosequencing, and methylation dependency of silencing was determined by 5-aza-2′-deoxycytidine (5-aza-dC) treatment. Methylation profiling revealed 2,226 CpG sites that showed methylation differences between healthy control livers and HCCs. Of these, 537 CpG sites were hypermethylated in the tumor DNA, whereas 1,689 sites showed promoter hypomethylation. The hypermethylated set was enriched for genes known to be inactivated by the polycomb repressive complex 2, whereas the group of hypomethylated genes was enriched for imprinted genes. We identified three genes matching all of our selection criteria for a tumor-suppressor gene (period homolog 3 [PER3], insulin-like growth-factor–binding protein, acid labile subunit [IGFALS], and protein Z). PER3 was down-regulated in human HCCs, compared to peritumorous and healthy liver tissues. 5-aza-dC treatment restored PER3 expression in HCC cell lines, indicating that promoter hypermethylation was indeed responsible for gene silencing. Additionally, functional analysis supported a tumor-suppressive function for PER3 and IGFALS in vitro . Conclusion: The present study illustrates that vertical integration of methylation data with high-resolution genomic and transcriptomic data facilitates the identification of new tumor-suppressor gene candidates in human HCC.

For patients with bacteraemia caused by methicillin-sensitive Staphylococcus aureus anti-staphylococcal penicillins (ASPs) or cefazolin are agents of choice. While ASPs are potentially nephrotoxic, cefazolin may be less effective in some S. aureus strains due to an inoculum effect. To perform a systematic literature review and meta-analysis assessing current evidence comparing cefazolin with ASPs for patients with S. aureus bacteraemia (SAB). We searched MEDLINE, ISI Web of Science (Science Citation Index Expanded) and the Cochrane Database as well as clinicaltrials.gov from inception to 26 June 2018. All studies investigating the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB were eligible for inclusion regardless of study design, publication status or language. Additional information was requested by direct author contact. A meta-analysis to estimate relative risks (RRs) with the corresponding 95% confidence intervals (CIs) was performed. Statistical heterogeneity was estimated using I2. The primary endpoint was 90-day all-cause mortality. The Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for study and data quality assessment. Fourteen non-randomized studies were included. Seven reported the primary endpoint (RR 0.71 (0.50, 1.02), low quality of evidence). Cefazolin treatment may be associated with lower 30-day mortality rates (RR 0.70 (0.54, 0.91), low quality of evidence) and less nephrotoxicity (RR 0.36 (0.21, 0.59), (low quality of evidence)). We are uncertain whether cefazolin and ASP differ regarding treatment failure/relapse as the quality of the evidence has been assessed as very low (RR of 0.84 (0.59, 1.18)). For patients with endocarditis (RR 0.71 (0.12, 4.05)) or abscesses (RR 1.17 (0.30, 4.63)), cefazolin treatment may be associated with equal 30-day and 90-day mortality (low quality of evidence). Cefazolin seemed to be at least equally as effective as ASPs while being associated with less nephrotoxicity.

The spread of carbapenem-non-susceptible Klebsiella pneumoniae strains bearing different resistance determinants is a rising problem worldwide. Especially infections with KPC (Klebsiella pneumoniae carbapenemase) - producers are associated with high mortality rates due to limited treatment options. Recent clinical studies of KPC-blood stream infections revealed that colistin-based combination therapy with a carbapenem and/or tigecycline was associated with significantly decreased mortality rates when compared to colistin monotherapy. However, it remains unclear if these observations can be transferred to K. pneumoniae harboring other mechanisms of carbapenem resistance. A three-dimensional synergy analysis was performed to evaluate the benefits of a triple combination with meropenem, tigecycline and colistin against 20 K. pneumoniae isolates harboring different β-lactamases. To examine the mechanism behind the clinically observed synergistic effect, efflux properties and outer membrane porin (Omp) genes (ompK35 and ompK36) were also analyzed. Synergism was found for colistin-based double combinations for strains exhibiting high minimal inhibition concentrations against all of the three antibiotics. Adding a third antibiotic did not result in further increased synergistic effect in these strains. Antagonism did not occur. These results support the idea that colistin-based double combinations might be sufficient and the most effective combination partner for colistin should be chosen according to its MIC.

Interscalene brachial plexus (ISB) block is often associated with phrenic nerve block and diaphragmatic paresis. The goal of our study was to test if the anterior or the posterior ultrasound guided approach of the ISB is associated with a lower incidence of phrenic nerve blocks and impaired lung function. This was a prospective, randomized and single-blinded study of 84 patients scheduled for elective shoulder surgery who fullfilled the inclusion and exclusion critereria. Patients were randomized in two groups to receive either the anterior (n = 42) or the posterior (n = 42) approach for ISB. Clinical data were recorded. In both groups patients received ISB with a total injection volume of 15 ml of ropivacaine 1 %. Spirometry was conducted at baseline (T0) and 30 min (T30) after accomplishing the block. Changes in spirometrical variables between T0 and T30 were investigated by Wilcoxon signed-rank test for each puncture approach. The temporal difference between the posterior and the anterior puncture approach groups were again analyzed by the Wilcoxon-Mann-Whitney test. The spirometric results showed a significant decrease in vital capacity, forced expiratory volume per second, and maximum nasal inspiratory breathing after the Interscalene brachial plexus block; indicating a phrenic nerve block (p <0.001, Wilcoxon signed-rank). A significant difference in the development of the spirometric parameters between the anterior and the posterior group could not be identified (Wilcoxon-Mann-Whitney test). Despite the changes in spirometry, no cases of dyspnea were reported. A different site of injection (anterior or posterior) did not show an effect in reducing the cervical block spread of the local anesthetic and the incidence of phrenic nerve blocks during during ultrasound guided Interscalene brachial plexus block. Clinical breathing effects of phrenic nerve blocks are, however, usually well compensated, and subjective dyspnea did not occur in our patients. German Clinical Trials Register (DRKS number 00009908 , registered 26 January 2016).

Background: Sequelae of COVID-19 can be severe and longlasting. We compared frequencies of fatigue, depression and cognitive dysfunction in survivors of SARS-CoV-2-infection and sepsis. Methods: We performed a prospective cohort study of 355 symptomatic post-COVID patients who visited our out-patient clinic for post-COVID-19 care. We compared them with 272 symptomatic patients from the Mid-German Sepsis Cohort, which investigates the long-term courses of sepsis survivors. Possible predictors for frequent clinical findings (fatigue, signs of depression, cognitive dysfunction) in post-COVID were investigated with multivariable logistic regression. Results: Median age of the post-COVID patients was 51 years (range 17–86), 60.0% were female, and 31.8% required hospitalization during acute COVID-19. In the post-COVID patients (median follow-up time: 163 days) and the post-sepsis patients (180 days), fatigue was found in 93.2% and 67.8%, signs of depression were found in 81.3% and 10.9%, and cognitive dysfunction was found in 23.5% and 21.3%, respectively. In post-COVID, we did not observe an association between fatigue or depression and the severity of acute COVID-19. In contrast, cognitive dysfunction was associated with hospitalization (out-patient versus in-patient) and more frequent in post-COVID patients treated on an ICU compared to the MSC patients. Conclusion: In post-COVID patients, fatigue and signs of depression are more common than in sepsis survivors, independent from the acute SARS-CoV-2-infection. In contrast, cognitive dysfunction is associated with hospitalization. Despite the differences in frequencies, owing to the similarity of post-COVID and post-sepsis sequelae, this knowledge may help in implementing follow-up approaches after SARS-CoV-2 infection.