Mpox: Keep it on the differential.

In its current global outbreak, mpox has exhibited several novel clinical presentations that clinicians should be aware of so they can recognize it if they see it. Although the case rate has decreased, mpox could linger at a low rate or resurface in other populations and thus should remain in the differential diagnosis in patients presenting with potential infections after intimate encounters.

Development and validation of a HILIC-MS/MS method for the quantitation of fructose in human urine in support of clinical programs.

In a previous publication [1], a 20-minute UPLC®-MS/MS method, employing a surrogate analyte approach, was developed and validated to measure fructose and sorbitol, as mechanistic biomarkers, in human plasma to support first-in-human (FIH) studies. Different from plasma which maintains its homeostasis, urine has no such homeostasis mechanisms [2], therefore it is expected to be able to accommodate more changes. Here we describe the development and validation of a LC-MS/MS method for the quantiation of fructose in human urine to support clinical trials. A hydrophilic interaction chromatography (HILIC) method using an Asahipak NH2P-50 column (Shodex, 4.6 × 250 mm, 5 µm) was developed. Acetone precipitation was utilized to extract fructose from urine. For validation, stable isotope-labeled 13C6-fructose was used as the surrogate analyte for fructose in the preparation of calibration curves. QCs were prepared using both the surrogate analyte (13C6-fructose) and the authentic analyte (fructose). Difficulties were encountered for post-extraction stability experiments especially for authentic fructose QCs at low concentrations. Extensive troubleshooting revealed that fructose's chromatography improved as the column aged. As a result, the response factor of fructose increased over time for low concentration samples, leading to failed post-extraction stability experiments. A column cleaning procedure was implemented to ensure consistency in chromatography performance. The HILIC-MS/MS method was successfully validated and applied to analyze clinical samples with a 91% overall run passing rate.

Home- and community-level predictors of social connection in nursing home residents: A scoping review.

Background and Aims: Social connection is associated with better physical and mental health and is an important aspect of the quality of care for nursing home residents. The primary objective of this scoping review was to answer the question: what nursing home and community characteristics have been tested as predictors of social connection in nursing home residents? The secondary objective was to describe the measures of social connection used in these studies. Methods: We searched MEDLINE(R) ALL (Ovid), CINAHL (EBSCO), APA PsycINFO (Ovid), Scopus, Sociological Abstracts (ProQuest), Embase and Embase Classic (Ovid), Emcare Nursing (Ovid), and AgeLine (EBSCO) for research that quantified associations between nursing home and/or community characteristics and resident social connection. Searches were limited to English-language articles published from database inception to search date (July 2019) and update (January 2021). Results: We found 45 studies that examined small-scale home-like settings (17 studies), facility characteristics (14 studies), staffing characteristics (11 studies), care philosophy (nine studies), and community characteristics (five studies). Eight studies assessed multiple home or community-level exposures. The most frequent measures of social connection were study-specific assessments of social engagement (11 studies), the Index of Social Engagement (eight studies) and Qualidem social relations (six studies), and/or social isolation (five studies) subscales. Ten studies assessed multiple social connection outcomes. Conclusion: Research has assessed small-scale home-like settings, facility characteristics, staffing characteristics, care philosophy, and community characteristics as predictors of social connection in nursing home residents. In these studies, there was no broad consensus on best approach(es) to the measurement of social connection. Further research is needed to build an evidence-base on how modifiable built environment, staffing and care philosophy characteristics-and the interactions between these factors-impact residents' social connection.

The relationship between quality and staffing in long-term care: A systematic review of the literature 2008-2020.

BACKGROUND: Higher staffing levels in long-term care have been associated with better outcomes for residents in several landmark studies. However previous systematic reviews found mixed results, calling into question the effectiveness of higher levels of staff. With persistent concerns about quality, rising resident acuity, and a growing demographic of seniors requiring more services, understanding the relationship between quality and long-term care staffing is a growing concern. OBJECTIVES: This review considered the following question: What is the influence of nursing and personal care staffing levels (registered nurse, licensed practical nurse, and nursing assistant) and / or skill mix on long-term care residents, measured by quality of care indicators? DESIGN: Preferred Reporting Items for Systematic Review and Meta-analysis Protocols guided the report of this systematic review. DATA SOURCES: Published articles focused on quality and nursing and personal care staffing in long-term care in peer-reviewed databases (MEDLINE, CINAHL, and AGELINE) and several Cochrane databases to retrieve studies published between January 2008 and June 2020. REVIEW METHODS: A systematic review was conducted. 11,096 studies were identified, of which 34 were included in this review. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used to evaluate study quality and risk of bias, and five quality measures were selected for in-depth analyses: pressure ulcers, hospitalizations, physical restraints, deficiencies and catherization. RESULTS: This review confirms previous review findings that evidence on the relationships between quality and long-term care staffing level and skill mix, remain mixed. Higher staffing levels and skill mix generally supported better rather than worse outcomes. Significant and consistent findings were more evident when staffing levels were further analyzed by indicator and staffing category. For example, registered nurses were consistently associated with significantly fewer pressure ulcers, hospitalizations, and urinary tract infections. Few studies examined the impact of total nursing and personal care hours compared to the impact of specific categories or classes of nursing staff on outcomes. CONCLUSIONS: Evidence on the relationship between quality and long-term care staffing remains mixed, however some categories of nursing staff may be more effective at improving the quality of certain indicators. Study quality has improved minimally over the last decade. Although research continues to standardize units of measurement, and longitudinal and instrumental variable analyses are increasingly being used, very few studies controlled for endogeneity, conducted adequate risk-adjustment, and used resident-level data. Additional strides must still be made to improve the rigor of long-term care staffing research.

Acceptability of Routine Point-of-Care Early Infant Diagnosis in Eight African Countries: Findings From a Qualitative Assessment of Clinical and Laboratory Personnel.

BACKGROUND: The Elizabeth Glaser Pediatric AIDS Foundation introduced point-of-care (POC) testing for early infant diagnosis (EID) of HIV in 8 African countries. Understanding experiences and opinions of users can help facilitate introduction and sustainability. SETTING: Cameroon, Côte d'Ivoire, Eswatini, Kenya, Lesotho, Mozambique, Rwanda, and Zimbabwe. METHODS: Structured interviews with health care workers (HCWs) providing EID services and semistructured interviews with national and regional laboratory managers or EID program managers were conducted before and after the implementation of POC EID. Survey responses were analyzed and compared; open-ended responses were analyzed by theme. RESULTS: In total, 234 and 175 interviews with HCWs and 28 and 14 interviews with laboratory or program managers were conducted before and after the introduction of POC EID, respectively. In preintervention interviews, challenges identified with laboratory-based EID testing included distance from patients' residence to the health facility, time-consuming sample transportation to central laboratories, stockout of testing kits, and long wait times for results. Postintervention data revealed that HCWs found POC EID easy to use and were very satisfied with the fast turnaround time and ability to initiate treatment for HIV-infected infants sooner. Laboratory managers were also supportive of scaling-up POC testing although cautious of the need for reliable infrastructure to operate platforms. The recommendation was that POC EID be integrated within the national diagnostic testing network. CONCLUSIONS: Support for POC EID from key stakeholders is essential for sustainability. Overall, participants supported the rollout of POC testing for EID, noting challenges and opportunities for scaling-up POC EID and recommending integration into the overall EID system.

Screening Algorithms to Reduce Burden of Pediatric HIV Testing: A Systematic Review and Meta-analysis.

BACKGROUND: The accuracy of symptom screening to identify children eligible for further HIV testing in generalized epidemics has been examined in several studies. We performed a systematic review and meta-analysis of these studies. METHODS: We screened 5 databases and abstracts from 4 HIV/AIDS conferences. Studies were included if they were performed in clinical settings, included children of 0-15 years old, and used a signs/symptoms screen to determine eligibility for HIV testing. The primary outcomes were sensitivity and specificity of the screening tools. A meta-analysis was performed to evaluate the utility of a screening tool in the outpatient setting. RESULTS: Our search returned 5529 database results and approximately 6700 conference abstracts, of which 36 articles were reviewed and 7 met criteria for inclusion. All were prospective or cross-sectional studies that developed and/or validated a screening tool to identify children at higher risk for being HIV infected. Sensitivity of the screening tools ranged from 71% to 96%, whereas specificity ranged from 25% to 99%. Meta-analysis of studies evaluating outpatient screening tools revealed a sensitivity of 81.4%, with a specificity of 69.4% for detecting HIV infection. CONCLUSIONS: Few studies have evaluated the use of screening tools for HIV diagnosis in children. Screening tools that exist showed only moderate sensitivity and specificity and missed a substantial number of HIV-infected children in high-prevalence areas. In outpatient settings, the use of a screening tool may help reduce the number of HIV tests needed to identify an HIV-infected child, but at the cost of missed diagnoses. Further studies are needed to determine whether this represents a resource-saving mechanism.

Development and validation of a quantitative ultra performance LC® hydrophilic interaction liquid chromatography MS/MS method to measure fructose and sorbitol in human plasma.

AIM: Fructose and sorbitol are utilized as biomarkers for nonalcoholic steatohepatitis. Measurement of fructose and sorbitol levels helps understanding disease progression, drug response and underlying mechanism. MATERIALS & METHODS: Stable isotope-labeled fructose and sorbitol were used as surrogate standards and internal standards. Human plasma samples were processed and analyzed by ultra performance LC®-MS/MS via chromatographic separation on a hydrophilic interaction liquid chromatography analytical column without derivatization. Assay was validated with biomarker fit-for-purpose concept. RESULTS: A 12-min ultra performance LC®-MS/MS method was developed and validated to directly measure fructose and sorbitol in human plasma with acceptable intra- and inter-assay precision and accuracy. CONCLUSION: This sensitive, selective, and high-throughput assay with suitable dynamic ranges was successfully applied to clinical studies to provide reliable fructose and sorbitol biomarker data.

A fully automated and validated human plasma LC-MS/MS assay for endogenous OATP biomarkers coproporphyrin-I and coproporphyrin-III.

AIM: A validated LC-MS/MS assay for the quantitation of coproporphyrin-I and -III (CP-I, CP-III) in human plasma has been developed to understand the utility of both as possible endogenous biomarkers for organic anion-transporting polypeptides (OATP)-mediated drug-drug interactions (DDIs). MATERIALS AND METHODS:  Human plasma extracts were analyzed for CP-I and CP-III using a Sciex API 6500+ mass spectrometer. Results: The assay was utilized for plasma samples from a clinical DDI study involving a new chemical entity that presented as an OATP inhibitor in vitro. A formal DDI study, with a probe drug (atorvastatin), was also included as part of the clinical study. CONCLUSION: Changes in CP-I area under the plasma concentration versus time curve (AUC0-48 h) were observed, which were similar to the AUC ratio obtained with atorvastatin. These results support the idea that plasma CP-I may have utility in Phase I by supporting the rapid assessment of OATP inhibition risk.