Cerebrospinal fluid galactomannan detection for the diagnosis of central nervous system aspergillosis: a diagnostic test accuracy systematic review and meta-analysis.

BACKGROUND: Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics. OBJECTIVES: To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis. METHODS: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023. STUDY ELIGIBILITY CRITERIA: Prospective and retrospective studies with one-group and two-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis. PARTICIPANTS: Adult and/or pediatric CNS aspergillosis patients. TEST(S): Galactomannan testing on CSF specimens. REFERENCE STANDARD: European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent. ASSESSMENT OF RISK OF BIAS: QUADAS-2 assessment in duplicate. METHODS OF DATA SYNTHESIS: Bivariate restricted maximum-likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver-operator characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none). RESULTS: We included eight studies (n=342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI: 57.2-78.7%) and 94.4% (95% CI: 82.8-98.3%), respectively. Using meta-regression, galactomannan cut-off (p=0.38), EORTC/MSGERC criteria version (p=0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p=0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analyzing the EORTC/MSGERC criteria reference standard used (e.g., 2002 versus 2008 definitions) or whether pediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and one-group design studies. DISCUSSION: CSF galactomannan is a highly specific but insensitive test for use as a component for CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations.

Different drugs, different sides: injection use of opioids alone, and not stimulants alone, predisposes to right-sided endocarditis.

OBJECTIVES: Many studies suggest that infective endocarditis (IE) in people who inject drugs is predominantly right sided, while other studies suggest left sided disease; few have differentiated by class of drug used. We hypothesised that based on differing physiological mechanisms, opioids but not stimulants would be associated with right sided IE. METHODS: A retrospective case series of 290 adult (age ≥18) patients with self-reported recent injection drug use, admitted for a first episode of IE to one of three hospitals in London Ontario between April 2007 and March 2018, stratified patients by drug class used (opioid, stimulant or both), and by site of endocarditis. Other outcomes captured included demographics, causative organisms, cardiac and non-cardiac complications, referral to addiction services, medical versus surgical management, and survival. RESULTS: Of those who injected only opioids, 47/71 (69%) developed right-sided IE, 17/71 (25%) developed left-sided IE and 4/71 (6%) had bilateral IE. Of those who injected only stimulants, 11/24 (46%) developed right-sided IE, 11/24 (46%) developed left-sided IE and 2/24 (8%) had bilateral IE. Relative to opioid-only users, stimulant-only users were 1.75 (95% CI 1.05 to 2.93; p=0.031) times more likely to have a left or bilateral IE versus right IE. CONCLUSIONS: While injection use of opioids is associated with a strong predisposition to right-sided IE, stimulants differ in producing a balanced ratio of right and left-sided disease. As the epidemic of crystal methamphetamine injection continues unabated, the rate of left-sided disease, with its attendant higher morbidity and mortality, may also grow.

Evaluating the safety and effectiveness of a nurse-led outpatient virtual IV vancomycin monitoring clinic: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) with vancomycin is a common treatment modality for certain Gram-positive infections. Data regarding the safety of various models of delivery are limited. OBJECTIVES: To review outcomes of a nurse-led OPAT vancomycin monitoring service. METHODS: This was a retrospective cohort study of consecutive patients referred to a nurse-led OPAT vancomycin clinic from December 2015 to March 2018. Patients were administered IV vancomycin in the home with active laboratory monitoring of vancomycin trough levels, renal function and complete blood count using an integrated electronic database linked with community laboratories (virtual vancomycin clinic, VVC). Monitoring was coordinated by nurses with physician approval of recommended dosing changes. Data were extracted from the electronic medical record. Demographics; clinical indication; microbial aetiology; culture source; antimicrobial regimen(s); serum creatinine and vancomycin trough values; initiation, discharge and completion dates; hospitalizations; adverse events; and outcomes were all evaluated. RESULTS: Two hundred and seventy-five patients underwent a total of 301 courses of OPAT with vancomycin; 285 courses were completed. The rate of treatment discontinuation due to adverse effects was 33/301 (11.0%), with 15/33 (45.5%) being due to renal adverse effects (15/301 [5.0%] of episodes). Two of 15 (18.2%) patients developed stage 2 acute kidney injury (AKI), and no patients had stage 3 AKI or required haemodialysis. Nine of 301 (3.0%) required readmission for treatment failure. Nursing costs associated with monitoring were $63.93 CAD/patient ($48.43 USD). CONCLUSIONS: A nurse-led VVC was a safe, effective and inexpensive modality for administering outpatient vancomycin.

The many faces of ocular syphilis: case-based update on recognition, diagnosis, and treatment.

In recent years, syphilis (Treponema pallidum) has become increasingly prevalent in Canada, and as a result, rates of ocular syphilis are also rising. Classically, syphilis was seen primarily in men who have sex with men; now, it is increasingly seen in people of all age groups, sexes, and sexual orientations. We present a series of 26 cases of ocular syphilis from London, Ontario, 5 of which are discussed in detail to illustrate the varied presentations and diagnostic challenges of ocular syphilis. The presentations include uveitis, iris granuloma (gumma), retinitis (acute syphilitic posterior placoid chorioretinitis), vasculitis, optic neuritis, and serous retinal detachment. The 5 cases are mostly middle-aged heterosexual men and women without the typical risk factors that would alert the examiner to suspect syphilis. We emphasize the importance of testing for syphilis when assessing and treating inflammatory eye disease, regardless of demographics and known risk factors, given the increasing prevalence of this disease. Diagnosis of syphilis relies on serologic testing, which is complex and has undergone significant changes from historical reliance on the Venereal Disease Research Laboratory test. We provide an overview of the strategy and rationale for modern serologic testing. The mainstay of treatment remains intravenous penicillin G, with alternative antibiotics (e.g., ceftriaxone) being less effective.