Rapid multiplex PCR for respiratory viruses reduces time to result and improves clinical care: Results of a systematic review and meta-analysis.

OBJECTIVES: The clinical impact of rapid sample-to-answer "syndromic" multiplex polymerase chain reaction (PCR) testing for respiratory viruses is not clearly established. We performed a systematic literature review and meta-analysis to evaluate this impact for patients with possible acute respiratory tract infection in the hospital setting. METHODS: We searched EMBASE, MEDLINE, and Cochrane databases from 2012 to present and conference proceedings from 2021 for studies comparing clinical impact outcomes between multiplex PCR testing and standard testing. RESULTS: Twenty-seven studies with 17,321 patient encounters were included in this review. Rapid multiplex PCR testing was associated with a reduction of - 24.22 h (95% CI -28.70 to -19.74 h) in the time to results. Hospital length of stay was decreased by -0.82 days (95% CI -1.52 to -0.11 days). Among influenza positive patients, antivirals were more likely to be given (RR 1.25, 95% CI 1.06-1.48) and appropriate infection control facility use was more common with rapid multiplex PCR testing (RR 1.55, 95% CI 1.16-2.07). CONCLUSIONS: Our systematic review and meta-analysis demonstrates a reduction in time to results and length of stay for patients overall along with improvements in appropriate antiviral and infection control management among influenza-positive patients. This evidence supports the routine use of rapid sample-to-answer multiplex PCR testing for respiratory viruses in the hospital setting.

Epidemiology, methods of diagnosis, and clinical management of patients with arginase 1 deficiency (ARG1-D): A systematic review.

BACKGROUND: Arginase 1 Deficiency (ARG1-D) is a rare, progressive, metabolic disorder that is characterized by devastating manifestations driven by elevated plasma arginine levels. It typically presents in early childhood with spasticity (predominately affecting the lower limbs), mobility impairment, seizures, developmental delay, and intellectual disability. This systematic review aims to identify and describe the published evidence outlining the epidemiology, diagnosis methods, measures of disease progression, clinical management, and outcomes for ARG1-D patients. METHODS: A comprehensive literature search across multiple databases such as MEDLINE, Embase, and a review of clinical studies in ClinicalTrials.gov (with results reported) was carried out per PRISMA guidelines on 20 April 2020 with no date restriction. Pre-defined eligibility criteria were used to identify studies with data specific to patients with ARG1-D. Two independent reviewers screened records and extracted data from included studies. Quality was assessed using the modified Newcastle-Ottawa Scale for non-comparative studies. RESULTS: Overall, 55 records reporting 40 completed studies and 3 ongoing studies were included. Ten studies reported the prevalence of ARG1-D in the general population, with a median of 1 in 1,000,000. Frequently reported diagnostic methods included genetic testing, plasma arginine levels, and red blood cell arginase activity. However, routine newborn screening is not universally available, and lack of disease awareness may prevent early diagnosis or lead to misdiagnosis, as the disease has overlapping symptomology with other diseases, such as cerebral palsy. Common manifestations reported at time of diagnosis and assessed for disease progression included spasticity (predominately affecting the lower limbs), mobility impairment, developmental delay, intellectual disability, and seizures. Severe dietary protein restriction, essential amino acid supplementation, and nitrogen scavenger administration were the most commonly reported treatments among patients with ARG1-D. Only a few studies reported meaningful clinical outcomes of these interventions on intellectual disability, motor function and adaptive behavior assessment, hospitalization, or death. The overall quality of included studies was assessed as good according to the Newcastle-Ottawa Scale. CONCLUSIONS: Although ARG1-D is a rare disease, published evidence demonstrates a high burden of disease for patients. The current standard of care is ineffective at preventing disease progression. There remains a clear need for new treatment options as well as improved access to diagnostics and disease awareness to detect and initiate treatment before the onset of clinical manifestations to potentially enable more normal development, improve symptomatology, or prevent disease progression.

Efficiency of Different Endodontic Irrigation and Activation Systems, Self-Adjusting File Instrumentation/Irrigation System, and XP-Endo Finisher in Removal of the Intracanal Smear Layer: An Ex vivo Scanning Electron Microscope Study.

AIM: This ex vivo study was designed to evaluate and compare different endodontic irrigation and activation systems, the self-adjusting file (SAF) instrumentation/irrigation system, and XP-endo finisher for removal of intracanal smear layer. MATERIALS AND METHODS: Fifty recently extracted, noncarious human intact single-rooted premolars were selected and divided into five groups (n = 10) according to the root canal irrigation systems; syringe and needle irrigation, passive ultrasonic irrigation (PUI), EndoVac irrigation system, SAF system, and XP-endo finisher. All groups were prepared to apical size F4 file except for the SAF group which was prepared to apical size 20 K-file and then instrumented with the SAF file. Each sample was subjected to final irrigation using different irrigation/activation systems. After splitting the samples, one half of each root was selected for examination under scanning electron microscope. The irrigation systems were compared using the Fisher's exact test with significance set at P < 0.05. RESULTS: In the coronal part, there was no difference among the groups. In the mid-root section, the results of the PUI, EndoVac, SAF, and XP-endo finisher groups tended to be better than syringe and needle irrigation, but the difference was not significant. The apical part of the canal, the SAF system, and XP-endo finisher group seemed to be cleaner than those of the EndoVac group, but this difference was not significant. CONCLUSIONS: Within the limitations of the present study, SAF system and XP-endo finisher group cleaned the apical part of the canal more efficiently than EndoVac, PUI, and syringe and needle irrigation.

Role of patient-reported outcomes and other efficacy endpoints in the drug approval process in Europe (2008-2012).

The present study aimed at systematically reviewing the role and extent of patient-reported outcomes (PROs) usage within the package of scientific evidence considered for marketing authorization (MA). All regulatory information published by the European Medicines Agency (EMA) for products authorized between January 2008 and December 2012 and appearing in the European Public Assessment Report (EPAR) database was examined for efficacy endpoints. The endpoints here considered included: PROs, clinician reported outcomes (CROs), and laboratory reported outcomes (LROs). LROs were the most frequently reported endpoints. Out of the 180 products here selected, 99 (55%), 67 (37%), and 30 (17%), respectively, used LROs, CROs and PROs as primary endpoints (PEs). PROs as any endpoints were used in 82 (46%) products. Out of these, PROs were documented as PE in 30 (37%), with 27 (33%) products having used PROs both as primary and non-PEs. PRO usage was most frequently identified with nervous system and antineoplastic agents. During the study period, the use of all the three types of endpoints appeared to be static. Both the regulatory bodies and the industry should ensure complete and clear reporting of all endpoints used, including PROs, to improve transparency.