Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review.

OBJECTIVE: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible. METHODS: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively. RESULTS: Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSION: The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.

Validation of a novel point-of-care test for alanine aminotransferase measurement: A pilot cohort study.

BACKGROUND: Alanine aminotransferase (ALT) measurement is essential for evaluation of liver disease. We validated a novel rapid point-of-care (POC) test for ALT1 against laboratory ALT. METHODS: Stored plasma samples from adults with chronic liver disease (Test cohort n = 240; Validation cohort n = 491) were analysed using the BioPoint® antigen immunoassay POC ALT1 lateral flow test, which provides quantitative ALT results (Axxin handheld reader) or semi-quantitative results (visual read, cut off 40 IU/ml). The accuracy of POC ALT1 to detect ALT > 40 IU/L was determined by ROC analysis. In patients with chronic hepatitis B, treatment eligibility (EASL criteria) was determined using POC ALT1 and compared to laboratory ALT. RESULTS: POC ALT1 test had good accuracy for laboratory ALT > 40 IU/L: AUROC 0.93 (95% CI: 0.89-0.96) in the Test cohort and AUROC 0.92 (95% CI: 0.88-0.95) in the Validation cohort. POC ALT1 cut off of 0.8 for ALT > 40 IU/L maximised sensitivity (97%) and specificity (71%) in the Test cohort (42% laboratory ALT > 40 IU/L) and yielded PPV 84% and NPV 91% in the Validation cohort (19% laboratory ALT > 40 IU/L). Semi-quantitative POC ALT1 had good accuracy for laboratory ALT in the Validation cohort (AUROC 0.85, 95% CI: 0.81-0.99; sensitivity 77% and specificity 93%). Combined with HBV DNA and transient elastography, both quantitative and semi-quantitative POC ALT1 tests had good accuracy for excluding hepatitis B treatment needs (sensitivity 96%, specificity 78% and NPV 99%). CONCLUSION: The POC ALT1 test had good accuracy for elevated ALT levels and for determining treatment eligibility among people with chronic hepatitis B.

Using social practice theory in measuring perceived stigma among female sex workers in Mombasa, Kenya.

BACKGROUND: Perceived stigma is a complex societal phenomenon that is harboured especially by female sex workers because of the interplay of a myriad of factors. As such, a precise measure of the contribution of different social practices and characteristics is necessary for both understanding and intervening in matters related to perceived stigma. We developed a Perceived Stigma Index that measures the factors that greatly contribute to the stigma among sex workers in Kenya, and thereby inform a framework for future interventions. METHODS: Social Practice Theory was adopted in the development of the Perceived Stigma Index in which three social domains were extracted from data collected in the WHISPER or SHOUT study conducted among female sex workers (FSW), aged 16-35 years in Mombasa, Kenya. The three domains included: Social demographics, Relationship Control and Sexual and Gender-based Violence, and Society awareness of sexual and reproductive history. The factor assessment entailed Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and the internal consistency of the index was measured using Cronbach's alpha coefficient. RESULTS: We developed a perceived stigma index to measure perceived stigma among 882 FSWs with a median age of 26 years. A Cronbach's alpha coefficient of 0.86 (95% confidence interval (CI) 0.85-0.88) was obtained as a measure of the internal consistency of our index using the Social Practice Theory. In regression analysis, we identified three major factors that contribute to the perceived stigma and consists of : (i) income and family support (ß = 1.69; 95% CI); (ii) society's awareness of the sex workers' sexual and reproductive history (ß = 3.54; 95% CI); and (iii) different forms of relationship control e.g. physical abuse (ß = 1.48; 95%CI that propagate the perceived stigma among the FSWs. CONCLUSION: Social practice theory has solid properties that support and capture the multi-dimensional nature of perceived stigma. The findings support the fact that social practices contribute or provoke this fear of being discriminated against. Thus, in offering interventions to curb perceived stigma, focus should fall on the education of the society on the importance of acceptance and integration of the FSWs as part of the society and the eradication of sexual and gender based violence meted out on them. TRIAL REGISTRATION: The trial was registered in the Australian New Zealand Clinical Trials Registry, ACTRN12616000852459.

Improved rapid diagnostic tests to detect syphilis and yaws: a systematic review and meta-analysis.

BACKGROUND: Current rapid tests for syphilis and yaws can detect treponemal and non-treponemal antibodies. We aimed to critically appraise the literature for rapid diagnostic tests (RDTs) which can better distinguish an active infection of syphilis or yaws. METHODS: We conducted a systematic review and meta-analysis, searching five databases between January 2010 and October 2021 (with an update in July 2022). A generalised linear mixed model was used to conduct a bivariate meta-analysis for the pooled sensitivity and specificity. Heterogeneity was assessed using the I2 statistic. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) to assess the risk of bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to evaluate the certainty of evidence. RESULTS: We included 17 studies for meta-analyses. For syphilis, the pooled sensitivity and specificity of the treponemal component were 0.93 (95% CI: 0.86 to 0.97) and 0.98 (95% CI: 0.96 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.90 (95% CI: 0.82 to 0.95) and 0.97 (95% CI: 0.92 to 0.99), respectively. For yaws, the pooled sensitivity and specificity of the treponemal component were 0.86 (95% CI: 0.66 to 0.95) and 0.97 (95% CI: 0.94 to 0.99), respectively. For the non-treponemal component, the pooled sensitivity and specificity were 0.80 (95% CI: 0.55 to 0.93) and 0.96 (95% CI: 0.92 to 0.98), respectively. CONCLUSIONS: RDTs that can differentiate between active and previously treated infections could optimise management by providing same-day treatment and reducing unnecessary treatment. PROSPERO REGISTRATION NUMBER: CRD42021279587.

Viral load monitoring for people living with HIV in the era of test and treat: progress made and challenges ahead - a systematic review.

BACKGROUND: In 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs. METHODS: A literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring (the proportion of PLHIV who received a follow-up VL after an initial elevated VL test), confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure). RESULTS: The search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12-93% median: 74% IQR: 46-82%) and study populations (adults (range: 25-96%, median: 67% IQR: 50-84%), children, adolescents/young people (range: 2-94%, median: 72% IQR: 47-85%), and pregnant women (range: 32-82%, median: 57% IQR: 43-71%)). Community-based models reported higher VL monitoring (median: 85%, IQR: 82-88%) compared to decentralised care at primary health facility (median: 64%, IRQ: 48-82%). Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed. CONCLUSIONS: Substantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the "failure cascade" in PLHIV on ART who fail to achieve viral suppression.

Field Performance and Diagnostic Accuracy of a Low-Cost Instrument-Free Point-of-Care CD4 Test (Visitect CD4) Performed by Different Health Worker Cadres among Pregnant Women.

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of ≥350 CD4 cells/mm3 The field performance and diagnostic accuracy of the test was assessed among HIV-infected pregnant women in South Africa. A nurse performed testing at the point-of-care using both venous and finger-prick blood, and a counselor and laboratory staff tested venous blood in the clinic laboratory (four Visitect CD4 tests/participant). Performance was compared to the mean CD4 count from duplicate flow cytometry tests on venous blood (FACSCalibur Trucount). In 2017, 156 patients were enrolled, providing a total of 624 Visitect CD4 tests (468 venous and 156 finger-prick samples). Of 624 tests, 28 (4.5%) were inconclusive. Generalized linear mixed modeling showed better performance of the test on venous blood (sensitivity = 81.7%; 95% confidence interval [CI] = 72.3 to 91.1]; specificity = 82.6%, 95% CI = 77.1 to 88.1) than on finger-prick specimens (sensitivity = 60.7%; 95% CI = 45.0 to 76.3; specificity = 89.5%, 95% CI = 83.2 to 95.8; P = 0.001). No difference in performance was detected by cadre of health worker (P = 0.113) or between point-of-care versus laboratory-based testing (P = 0.108). Adequate performance of Visitect CD4 with different operators and at the point of care, with no need of electricity or instrument, shows the potential utility of this device, especially for facilitating decentralization of CD4 testing services in rural areas.

Performance of a Novel Low-Cost, Instrument-Free Plasma Separation Device for HIV Viral Load Quantification and Determination of Treatment Failure in People Living with HIV in Malaysia: a Diagnostic Accuracy Study.

HIV viral load (VL) testing is the recommended method for monitoring the response of people living with HIV and receiving antiretroviral therapy (ART). The availability of standard plasma VL testing in low- and middle-income countries (LMICs), and access to this testing, are limited by the need to use fresh plasma. Good specimen collection methods for HIV VL testing that are applicable to resource-constrained settings are needed. We assessed the diagnostic performance of the filtered dried plasma spot (FDPS), created using the newly developed, instrument-free VLPlasma device, in identifying treatment failure at a VL threshold of 1,000 copies/ml in fresh plasma. Performance was compared with that of the conventional dried blood spot (DBS). Venous blood samples from 201 people living with HIV and attending an infectious disease clinic in Malaysia were collected, and HIV VL was quantified using fresh plasma (the reference standard), FDPS, and DBS specimens. VL testing was done using the Roche Cobas AmpliPrep/Cobas TaqMan v2.0 assay. At a threshold of 1,000 copies/ml, the diagnostic performance of the FDPS was superior (sensitivity, 100% [95% confidence interval {CI}, 89.1 to 100%]; specificity, 100% [95% CI, 97.8 to 100%]) to that of the DBS (sensitivity, 100% [95% CI, 89.4 to 100%]; specificity, 36.8% [95% CI, 29.4 to 44.7%]) (P < 0.001). A stronger correlation was observed between the FDPS VL and the plasma VL (r = 0.94; P < 0.001) than between the DBS VL and the plasma VL (r = 0.85; P < 0.001). The mean difference in VL measures between the FDPS and plasma (plasma VL minus FDPS VL) was 0.127 log10 copies/ml (standard deviation [SD], 0.32), in contrast to -0.95 log10 copies/ml (SD, 0.84) between the DBS and plasma. HIV VL measurement using the FDPS outperformed that with the DBS in identifying treatment failure at a threshold of 1,000 copies/ml and compared well with the quantification of VL in plasma. The FDPS can be an attractive alternative to fresh plasma for improving access to HIV VL monitoring among people living with HIV on ART in LMICs.

Glycosaminoglycans-Specific Cell Targeting and Imaging Using Fluorescent Nanodiamonds Coated with Viral Envelope Proteins.

Understanding virus-host interactions is crucial for vaccine development. This study investigates such interactions using fluorescent nanodiamonds (FNDs) coated with vaccinia envelope proteins as the model system. To achieve this goal, we noncovalently conjugated 100 nm FNDs with rA27(aa 21-84), a recombinant envelope protein of vaccinia virus, for glycosaminoglycans (GAGs)-specific targeting and imaging of living cells. Another recombinant protein rDA27(aa 33-84) that removes the GAGs-binding sequences was also used for comparison. Three types of A27-coated FNDs were generated, including rA27(aa 21-84)-FND, rDA27(aa 33-84)-FND, and hybrid rA27(aa 21-84)/rDA27(aa 33-84)-FND. The specificity of these viral protein-FND conjugates toward GAGs binding was examined by flow cytometry, fluorescence microscopy, and gel electrophoresis. Results obtained for normal and GAGs-deficient cells showed that the recombinant proteins maintain their GAG-targeting activities even after immobilization on the FND surface. Our studies provide a new nanoparticle-based platform not only to target specific cell types but also to track the fates of these immobilized viral proteins in targeted cells as well as to isolate and enrich GAGs-associated proteins on cell membrane.

Feasibility of antiretroviral treatment monitoring in the era of decentralized HIV care: a systematic review.

BACKGROUND: Regular monitoring of HIV patients who are receiving antiretroviral therapy (ART) is required to ensure patient benefits and the long-term effectiveness and sustainability of ART programs. Prompted by WHO recommendations for expansion and decentralization of HIV treatment and care in low and middle income countries, we conducted a systematic review to assess the feasibility of treatment monitoring in these settings. METHODS: A comprehensive search strategy was developed using a combination of MeSH and free text terms relevant to HIV treatment and care, health service delivery, health service accessibility, decentralization and other relevant terms. Five electronic databases and two conference websites were searched to identify relevant studies conducted in LMICs, published in English between Jan 2006 and Dec 2015. Outcomes of interest included the proportion of patients who received treatment monitoring and health system factors related to monitoring of patients on ART under decentralized HIV service delivery models. RESULTS: From 5363 records retrieved, twenty studies were included in the review; all but one was conducted in sub-Saharan African countries. The majority of studies (15/20) had relatively short follow-up duration (≤24 months), and only two studies were specifically designed to assess treatment monitoring practices. The most frequently studied follow-up period was 12 months and a wide range of treatment monitoring coverage was observed. The reported proportions of patients on ART who received CD4 monitoring ranged from very low (6%; N = 2145) to very high (95%; N = 488). The median uptake of viral load monitoring was 86% with studies in program settings reporting coverage as low as 14%. Overall, the longer the follow-up period, the lower the proportion of patients who received regular monitoring tests; and programs in rural areas reported low coverage of laboratory monitoring. Moreover, uptake in the context of research had significantly better where monitoring was done by dedicated research staff. In the absence of point of care (POC) testing, the limited capacity for blood sample transportation between clinic and laboratory and poor quality of nursing staff were identified as a major barrier for treatment monitoring practice. CONCLUSIONS: There is a paucity of data on the uptake of treatment monitoring, particularly with longer-term follow-up. Wide variation in access to both virological and immunological regular monitoring was observed, with some clinics in well-resourced settings supported by external donors achieving high coverage. The feasibility of treatment monitoring, particularly in decentralized settings of HIV treatment and care may thus be of concern and requires further study. Significant investment in POC diagnostic technologies and, improving the quality of and training for nursing staff is required to ensure effective scale up of ART programs towards the targets of 90-90-90 by the year 2020.

Inactivation of the particulate methane monooxygenase (pMMO) in Methylococcus capsulatus (Bath) by acetylene.

Acetylene (HCCH) has a long history as a mechanism-based enzyme inhibitor and is considered an active-site probe of the particulate methane monooxygenase (pMMO). Here, we report how HCCH inactivates pMMO in Methylococcus capsulatus (Bath) by using high-resolution mass spectrometry and computational simulation. High-resolution MALDI-TOF MS of intact pMMO complexes has allowed us to confirm that the enzyme oxidizes HCCH to the ketene (C2H2O) intermediate, which then forms an acetylation adduct with the transmembrane PmoC subunit. LC-MS/MS analysis of the peptides derived from in-gel proteolytic digestion of the protein subunit identifies K196 of PmoC as the site of acetylation. No evidence is obtained for chemical modification of the PmoA or PmoB subunit. The inactivation of pMMO by a single adduct in the transmembrane PmoC domain is intriguing given the complexity of the structural fold of this large membrane-protein complex as well as the complicated roles played by the various metal cofactors in the enzyme catalysis. Computational studies suggest that the entry of hydrophobic substrates to, and migration of products from, the catalytic site of pMMO are controlled tightly within the transmembrane domain. Support of these conclusions is provided by parallel experiments with two related alkynes: propyne (CH3CCH) and trifluoropropyne (CF3CCH). Finally, we discuss the implication of these findings to the location of the catalytic site in pMMO.

Performance of point-of-care CD4 testing technologies in resource-constrained settings: a systematic review and meta-analysis.

BACKGROUND: Point-of-care (POC) CD4 testing increases patient accessibility to assessment of antiretroviral therapy eligibility. This review evaluates field performance in low and middle-income countries (LMICs) of currently available POC CD4 technologies. METHODS: Eight electronic databases were searched for field studies published between January 2005 and January 2015 of six POC CD4 platforms: PointCare NOW™, Alere Pima™ CD4, Daktari™ CD4 Counter, CyFlow® CD4 miniPOC, BD FACSPresto™, and MyT4™ CD4. Due to limited data availability, meta-analysis was conducted only for diagnostic performance of Pima at a threshold of 350 cells/µl, applying a bivariate multi-level random-effects modelling approach. A covariate extended model was also explored to test for difference in diagnostic performance between capillary and venous blood. RESULTS: Twenty seven studies were included. Published field study results were found for three of the six POC CD4 tests, 24 of which used Pima. For Pima, test failure rates varied from 2 to 23 % across study settings. Pooled sensitivity and specificity were 0.92 (95 % CI = 0.88-0.95) and 0.87 (95 % CI = 0.85-0.88) respectively. Diagnostic performance by blood sample type (venous vs. capillary) revealed non-significant differences in sensitivity (0.94 vs 0.89) and specificity (0.86 vs 0.87), respectively in the extended model (Wald χ2(2) = 4.77, p = 0.09). CONCLUSIONS: POC CD4 testing can provides reliable results for making treatment decision under field conditions in low-resource settings. The Pima test shows a good diagnostic performance at CD4 cut-off of 350 cells/µl. More data are required to evaluate performance of POC CD4 testing using venous versus capillary blood in LMICs which might otherwise influence clinical practice.

Acceptability and feasibility of point-of-care CD4 testing on HIV continuum of care in low and middle income countries: a systematic review.

BACKGROUND: CD4 testing is, and will remain an important part of HIV treatment and care in low and middle income countries (LMICs). We report the findings of a systematic review assessing acceptability and feasibility of POC CD4 testing in field settings. METHODS: Electronic databases were searched for studies published in English between 2005 and 2015 that describe POC CD4 platforms. Studies conducted in LMICs and under field conditions outside a laboratory environment were eligible. Qualitative and descriptive data analysis was used to present the findings. RESULTS: Twelve studies were included, 11 of which were conducted in sub-Saharan countries and used one POC CD4 test (The Alere Pima CD4). Patients reported positively regarding the implementation of POC CD4 testing at primary health care and community level with ≥90 % of patients accepting the test across various study settings. Health service providers expressed preference toward POC CD4 testing as it is easy-to-use, efficient and satisfied patients' needs to a greater extent as compared to conventional methods. However, operational challenges including preference toward venous blood rather than finger-prick sampling, frequent device failures and operator errors, quality of training for test operators and supervisors, and increased staff workload were also identified. CONCLUSIONS: POC CD4 testing seems acceptable and feasible in LIMCs under field conditions. Further studies using different POC CD4 tests available on the market are required to provide critical data to support countries in selection and implementation of appropriate POC CD4 technologies.

Improved mass spectrometric analysis of membrane proteins based on rapid and versatile sample preparation on nanodiamond particles.

We have developed a novel streamlined sample preparation procedure for mass spectrometric (MS) analysis of membrane proteins using surface-oxidized nanodiamond particles. The platform consists of solid-phase extraction and elution of the membrane proteins on nanodiamonds, concentrating the membrane proteins on the nanodiamonds and separating out detergents, chaotropic agents, and salts, and other impurities that are often present at high concentrations in solubilized membrane preparations. In this manner, membrane-protein extracts are transformed into MS-ready samples in minutes. The protocol is not only fast, but also widely adaptable and highly effective for preparing generic membrane protein samples for both MALDI-MS studies of membrane-protein complexes and shotgun membrane proteomics studies. As proof of concept, we have demonstrated substantial improvements in the MALDI-MS analysis of the particulate methane monooxygenase (pMMO) complex, a three-subunit transmembrane protein solubilized in various detergent buffers. Enzymatic digestions of membrane proteins are also greatly facilitated since the proteins extracted on to the nanodiamonds are exposed on the surface of the nanoparticles rather than in SDS gels or in detergent solutions. We illustrate the effectiveness of nanodiamonds for SDS removal in the preparation of membrane proteins for MS analysis on the proteome level by examining the quality of the tryptic peptides prepared by on-surface nanodiamond digestion of an E. coli membrane fraction for shotgun proteomics.

A novel point-of-care test for cirrhosis based on dimeric to monomeric IgA ratio in blood: a pilot cohort study.

BACKGROUND AND AIMS: Dimeric IgA to monomeric IgA ratio (dIgA ratio) is a biomarker of gut mucosal leakage in liver cirrhosis. We evaluated the diagnostic performance of a novel point-of-care (POC) dIgA ratio test for cirrhosis. METHODS: Plasma samples from people with chronic liver disease were analyzed using the BioPoint POC dIgA ratio antigen immunoassay lateral flow test. Cirrhosis was defined by Fibroscan>12.5 kPa, clinical evidence of cirrhosis or liver histopathology. POC dIgA test diagnostic accuracy was determined in a test cohort using receiver operating characteristic curve analysis; optimal cutoffs for sensitivity and specificity were then applied to a validation cohort. RESULTS: A total of 1478 plasma samples from 866 patients with chronic liver disease were included (test cohort n = 260, validation cohort n = 606). In all, 32% had cirrhosis; 44% Child-Pugh A, 26% Child-Pugh B, and 29% Child-Pugh C. Median POC dIgA ratio was higher in cirrhosis (0.9) compared with no cirrhosis (0.4, p < 0.001), and in Child-Pugh class B/C compared with A cirrhosis (1.4 Child-Pugh B/C vs. 0.6 Child-Pugh A, p < 0.001). POC dIgA ratio test had good diagnostic accuracy for liver cirrhosis in the test cohort (area under the receiver operating characteristic curve=0.80); a dIgA ratio cutoff of 0.6 had a sensitivity of 74% and specificity of 86%. POC dIgA test accuracy was moderate in the validation cohort (area under the receiver operating characteristic curve=0.75; positive predictive value 64%, negative predictive value 83%). Using a dual cutoff approach, 79% of cirrhosis cases were correctly diagnosed and further testing was avoided in 57%. CONCLUSIONS: POC dIgA ratio test had moderate accuracy for cirrhosis. Further studies evaluating the accuracy of POC dIgA ratio testing for cirrhosis screening are warranted.

Foregone health care in adolescents from school and community settings in Indonesia: a cross-sectional study.

Background: Adolescence is a development period marked by the onset of a new set of health needs. The present study sought to quantify the prevalence of foregone care (not seeking medical care when needed) and identify which adolescents are at greater risk of having unmet healthcare needs. Methods: A multi-stage random sampling strategy was used to recruit school participants (grade 10-12) in two provinces in Indonesia. Respondent driven sampling was used to recruit out-of-school adolescents in the community. All participants completed a self-reported questionnaire which measured healthcare seeking behaviours, psychosocial wellbeing, use of healthcare services, and perceived barriers to accessing healthcare. Multivariable regression analysis was performed to examine factors associated with foregone care. Findings: A total of 2161 adolescents participated in the present study and nearly one in four adolescents reported foregone care in the past year. Experiences of poly-victimisation and seeking care for mental health needs increased the risk of foregone care. In-school adolescents who reported psychological distress [adjusted risk ratio (aRR) = 1.88, 95%CI = 1.48-2.38] or had high body mass index (aRR = 1.25, 95%CI = 1.00-1.57) were at greater risk of foregone care. The leading reason for foregone care was lack of knowledge of available services. In-school adolescents predominantly reported non-access barriers to care (e.g., perception of the health concern or anxiety about accessing care) whereas most out-of-school adolescents reported access barriers (e.g., did not know where to get care or could not pay). Interpretation: Foregone care is common among Indonesian adolescents, especially in adolescents with mental and physical health risks. Differences between in-school and out-of-school adolescents suggest that interventions to promote appropriate healthcare use will need tailoring. Further research is needed to determine causal relationships around barriers in access to healthcare. Funding: Australia-Indonesia Centre.

Digital Healthy Diet Literacy and Fear of COVID-19 as Associated with Treatment Adherence and Its Subscales among Hemodialysis Patients: A Multi-Hospital Study.

Treatment adherence (TA) is a critical issue and is under-investigated in hemodialysis patients. A multi-center study was conducted from July 2020 to March 2021 on 972 hemodialysis patients in eight hospitals in Vietnam to explore the factors associated with TA during the COVID-19 pandemic. Data were collected, including socio-demographics, an End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ), 12-item short-form health literacy questionnaire (HLS-SF12), 4-item digital healthy diet literacy scale (DDL), 10-item hemodialysis dietary knowledge scale (HDK), 7-item fear of COVID-19 scale (FCoV-19S), and suspected COVID-19 symptoms (S-COVID19-S). Bivariate and multivariate linear regression models were used to explore the associations. Higher DDL scores were associated with higher TA scores (regression coefficient, B, 1.35; 95% confidence interval, 95%CI, 0.59, 2.12; p = 0.001). Higher FCoV-19S scores were associated with lower TA scores (B, -1.78; 95%CI, -3.33, -0.24; p = 0.023). In addition, patients aged 60-85 (B, 24.85; 95%CI, 6.61, 43.11; p = 0.008) with "very or fairly easy" medication payment ability (B, 27.92; 95%CI, 5.89, 44.95; p = 0.013) had higher TA scores. Patients who underwent hemodialysis for ≥5 years had a lower TA score than those who received <5 years of hemodialysis (B, -52.87; 95%CI, -70.46, -35.28; p < 0.001). These findings suggested that DDL and FCoV-19S, among other factors, should be considered in future interventions to improve TA in hemodialysis patients.

A profile of the Visitect® CD4 and Visitect® CD4 advanced disease for management of people living with HIV.

INTRODUCTION: CD4 testing plays an important role in clinical management and epidemiological surveillance of HIV disease. Rapid, point-of-care (POC) CD4 tests can improve patients' access to CD4 testing, enabling decentralization of HIV services. AREAS COVERED: We conducted a profile review of the Visitect®CD4 and the Visitect®CD4 Advanced Disease (Omega Diagnostics, UK) - the two lateral flow, equipment-free POC CD4 tests, which can be used to identify people with HIV who have CD4 of less than 350 and 200 cells/µl, respectively. Using published data from independent studies, we discussed the performance and utility of these tests, highlighting the advantages as well as their limitations. EXPERT OPINION: The tests are user-friendly, acceptable to health care workers, and feasible to implement in primary health care settings and can provide reliable results for clinical decision-making. Hands-on training with pictorial instructions for use is needed to enhance test's operator confidence in interpretation of test results. Quality assurance program should be in place to ensure the quality of testing. Development of a next-generation test with a cutoff of 100 cells/µl is recommended to identify patients with advanced immunosuppression for initiation of prophylaxis to reduce HIV-related death. Operational research is also needed to identify cost-effective implementation strategies in real-world settings.

Point-of-Care Diagnostics for Diagnosis of Active Syphilis Infection: Needs, Challenges and the Way Forward.

Syphilis, a curable sexually transmitted infection, has re-emerged as a global public health threat with an estimated 5.6 million new cases every year. Pregnant women and men who have sex with men are key target populations for syphilis control and prevention programs. Frequent syphilis testing for timely and accurate diagnosis of active infections for appropriate clinical management is a key strategy to effectively prevent disease transmission. However, there are persistent challenges in the diagnostic landscape and service delivery/testing models that hinder global syphilis control efforts. In this commentary, we summarise the current trends and challenges in diagnosis of active syphilis infection and identify the data gaps and key areas for research and development of novel point-of-care diagnostics which could help to overcome the present technological, individual and structural barriers in access to syphilis testing. We present expert opinion on future research which will be required to accelerate the validation and implementation of new point-of-care diagnostics in real-world settings.

Fear of COVID-19, healthy eating behaviors, and health-related behavior changes as associated with anxiety and depression among medical students: An online survey.

Background: Medical students' health and wellbeing are highly concerned during the COVID-19 pandemic. This study examined the impacts of fear of COVID-19 (FCoV-19S), healthy eating behavior, and health-related behavior changes on anxiety and depression. Methods: We conducted an online survey at 8 medical universities in Vietnam from 7th April to 31st May 2020. Data of 5,765 medical students were collected regarding demographic characteristics, FCoV-19S, health-related behaviors, healthy eating score (HES), anxiety, and depression. Logistic regression analyses were used to explore associations. Results: A lower likelihood of anxiety and depression were found in students with a higher HES score (OR = 0.98; 95%CI = 0.96, 0.99; p = 0.042; OR = 0.98; 95%CI = 0.96, 0.99; p = 0.021), and in those unchanged or more physical activities during the pandemic (OR = 0.54; 95%CI = 0.44, 0.66; p < 0.001; OR = 0.44; 95%CI = 0.37, 0.52; p < 0.001) as compared to those with none/less physical activity, respectively. A higher likelihood of anxiety and depression were reported in students with a higher FCoV-19S score (OR = 1.09; 95%CI = 1.07, 1.12; p < 0.001; OR = 1.06; 95%CI = 1.04, 1.08; p < 0.001), and those smoked unchanged/more during the pandemic (OR = 6.67; 95%CI = 4.71, 9.43; p < 0.001; OR = 6.77; 95%CI = 4.89, 9.38; p < 0.001) as compared to those stopped/less smoke, respectively. In addition, male students had a lower likelihood of anxiety (OR = 0.79; 95%CI = 0.65, 0.98; p = 0.029) compared to female ones. Conclusions: During the pandemic, FCoV-19S and cigarette smoking had adverse impacts on medical students' psychological health. Conversely, staying physically active and having healthy eating behaviors could potentially prevent medical students from anxiety and depressive symptoms.

Osteoporosis Risk in Hemodialysis Patients: The Roles of Gender, Comorbidities, Biochemical Parameters, Health and Diet Literacy.

Osteoporosis is a common bone health disorder in hemodialysis patients that is linked with a higher morbidity and mortality rate. While previous studies have explored the associated factors of osteoporosis, there is a lack of studies investigating the impacts of health literacy (HL) and digital healthy diet literacy (DDL) on osteoporosis. Therefore, we aimed to investigate the associations of HL, DDL, and other factors with osteoporosis among hemodialysis patients. From July 2020 to March 2021, a cross-sectional study was conducted on 675 hemodialysis patients in eight hospitals in Vietnam. The data were collected by using the osteoporosis self-assessment tool for Asians (OSTA) and the 12-item short form of the health literacy questionnaire (HLS-SF12) on digital healthy diet literacy (DDL) and hemodialysis dietary knowledge (HDK). In addition, we also collected information about the socio-demographics, the clinical parameters, the biochemical parameters, and physical activity. Unadjusted and adjusted multinomial logistic regression models were utilized in order to investigate the associations. The proportion of patients at low, medium, and high levels of osteoporosis risk was 39.6%, 40.6%, and 19.8%, respectively. In the adjusted models, women had a higher likelihood of osteoporosis risk than men (odds ratio, OR, 3.46; 95% confidence interval, 95% CI, 1.86, 6.44; p < 0.001; and OR, 6.86; 95% CI, 2.96, 15.88; p < 0.001). The patients with rheumatoid arthritis (OR, 4.37; 95% CI, 1.67, 11.52; p = 0.003) and stomach ulcers (OR, 1.95; 95% CI, 1.01, 3.77; p = 0.048) were more likely to have a higher likelihood of osteoporosis risk than those without. The patients who had a higher waist circumference (WC), HL, and DDL were less likely to have a medium level of osteoporosis risk (OR, 0.95; 95% CI, 0.92, 0.98; p = 0.004; OR, 0.92; 95% CI, 0.88, 0.96; p < 0.001; OR, 0.96; 95% CI, 0.93, 0.99; p = 0.017, respectively) and a high level of osteoporosis risk (OR, 0.93; 95% CI, 0.89, 0.97; p = 0.001; OR, 0.89; 95% CI, 0.84, 0.94; p < 0.001; OR, 0.95; 95% CI, 0.91, 0.99; p = 0.008, respectively) compared with a low level of osteoporosis risk and to those with a lower WC, HL, and DDL. In addition, higher levels of hemoglobin (Hb) (OR, 0.79; 95% CI, 0.66, 0.95; p = 0.014), hematocrit (Hct) (OR, 0.95; 95% CI, 0.92, 0.99; p = 0.041), albumin (OR, 0.91; 95% CI, 0.83, 0.99; p = 0.030), and education (OR, 0.37; 95% CI, 0.16, 0.88; p = 0.025) were associated with a lower likelihood of a high level of osteoporosis risk. In conclusion, osteoporosis risk is highly prevalent in hemodialysis patients. Improved HL, DDL, education, WC, albumin, Hb, and Hct levels should be considered in preventing hemodialysis patients from developing osteoporosis.