Background and aims To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). Methods We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. Results We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13–3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. Conclusions Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-023-11768-1.

The term multiplex PCR refers to simultaneous amplification of more than one target in a single PCR. This method has some advantages but presents the possibility of competition between multiple targets for a finite number of reagents, which may invalidate the assay.The Roche Cobas AMPLICOR multiplex PCR for Chlamydia trachomatis and Neisseria gonorrhoeae, a U.S. Food and Drug Administration-approved assay, can detect both C. trachomatis and N. gonorrhoeae from a single specimen. PCR amplification of C. trachomatis and N. gonorrhoeae proceeds in one tube with a shared enzyme and shared nucleotides but independent biotinylated primers. An optional internal control (IC) permits detection of amplification inhibition. The IC DNA has primer binding sequences identical to those of the C. trachomatis target. Detection is accomplished by using oligonucleotide probes that are unique for C. trachomatis, N. gonorrhoeae, and IC, respectively, with colorimetric quantification by spectophotometer. A negative assay result is valid if the IC optical density (OD) is Ն0.2, indicating successful amplification (Method Manual, Cobas Amplicor, Roche Diagnostics, 12/1999, Revision 3.0).We performed 580 multiplex PCRs on endocervical and urethral swab specimens, and 58 assays yielded positive results for C. trachomatis alone (OD Ն 2.0), 13 assays yielded positive results for N. gonorrhoeae alone (OD Ն 3.5), and 4 assays yielded positive results for both. Of the 58 assays positive for C. trachomatis, 13 (22.4%) had IC OD values that were Ͻ0.2 (mean OD, 0.059). The results of these 13 assays were correctly interpreted as C. trachomatis positive (mean C. trachomatis OD, 3.187). Because of the failure of the IC to amplify, the N. gonorrhoeae OD values for these 13 were invalid. The limiting reagent could be the primer, shared by C. trachomatis and IC. In the absence of IC amplification, it was not clear that there were a sufficient number of reagents, aside from the primer, to amplify N. gonorrhoeae. Of these 13 assays, 11 had OD values interpreted as negative for N. gonorrhoeae (mean N. gonorrhoeae OD, 0.047). Five of these specimens from the 11 assays were cultured and yielded negative results. Two additional specimens that turned out to be N. gonorrhoeae culture positive had equivocal N. gonorrhoeae OD values of 2.013 and 3.492, respectively, resolvable as positive by duplicate repeat testing.A Roche Molecular Systems study suggested that competitive inhibition occurs when the relative concentration of one target is extremely high and that the competition is for reagents other than the primer. This Roche paper discusses the optional use of the IC for increased sensitivity as well as retesting of existing specimens to eliminate nonspecific, labile polymerase inhibition, which we saw in five specimens not discussed here (1). However, we had a very high rate of competitive inhibition not correctable by repetition. Experimental dilution of the specimens did result in IC amplification, but also, in one case, converted a positive C. trachomati...

Managers at Kino Community Hospital in Tucson, AZ, were growing concerned about patient violence and its effects. This worry resulted from an increasing number of injuries to staff caused by patients in addition to the escalating costs of workers' compensation claims. Managers theorized that staff injuries could be decreased by changing staffing patterns, practicing crisis intervention techniques more frequently, and establishing continuing education classes. The hospital therefore implemented a step-by-step violence prevention program for its inpatient psychiatric department, an action that led to markedly fewer staff injuries by the end of 1996. A detailed account of this program follows.

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