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Pre-exposure prophylaxis (PrEP) is highly effective at reducing HIV acquisition. We aimed to estimate usage of oral-PrEP, and factors associated with adherence among female sex workers (FSWs) in Nairobi, Kenya, using a novel point-of-care urine tenofovir lateral flow assay (LFA). The Maisha Fiti study randomly selected FSWs from Sex Worker Outreach Program clinics in Nairobi. Data were collected from 1003 FSWs from June-October 2019, including surveys on self-reported oral-PrEP adherence. Adherence was also measured using the LFA for HIV-negative FSWs currently taking oral-PrEP. Informed by a social-ecological theoretical framework, we used hierarchical multivariable logistic regression models to estimate associations between individual, interpersonal/community, and structural/institutional-level factors and either self-reported or LFA-assessed adherence. Overall, 746 HIV-negative FSWs aged 18-40 participated in the study, of whom 180 (24.1%) self-reported currently taking oral-PrEP. Of these, 56 (31.1%) were adherent to oral-PrEP as measured by LFA. In the multivariable analyses, associations with currently taking oral-PrEP included having completed secondary education, high alcohol/substance use, feeling empowered to use PrEP, current intimate partner, no recent intimate partner violence, having support from sex worker organisations, experiencing sex work-related stigma, and seeking healthcare services despite stigma. Associations with oral-PrEP LFA-measured adherence measured included having only primary education, experience of childhood emotional violence, belonging to a higher wealth tertile, and being nulliparous. Oral-PrEP adherence, measured by self-report or objectively, is low among FSWs in Nairobi. Programs to improve oral-PrEP usage among FSWs should work to mitigate social and structural barriers and involve collaboration between FSWs, healthcare providers and policymakers.

Successful integration of point-of-care testing (POCT) into clinical settings requires improved assay sensitivity and precision to match laboratory standards. Here, we show how innovations in amplified biosensing, imaging, and data processing, coupled with deep learning, can help improve POCT. To demonstrate the performance of our approach, we present a rapid and cost-effective paper-based high-sensitivity vertical flow assay (hs-VFA) for quantitative measurement of cardiac troponin I (cTnI), a biomarker widely used for measuring acute cardiac damage and assessing cardiovascular risk. The hs-VFA includes a colorimetric paper-based sensor, a portable reader with time-lapse imaging, and computational algorithms for digital assay validation and outlier detection. Operating at the level of a rapid at-home test, the hs-VFA enabled the accurate quantification of cTnI using 50 μL of serum within 15 min per test and achieved a detection limit of 0.2 pg/mL, enabled by gold ion amplification chemistry and time-lapse imaging. It also achieved high precision with a coefficient of variation of

Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDCs LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance.

BACKGROUND: Adherence challenges with oral tenofovir-based pre-exposure prophylaxis (PrEP) are common. We developed a point-of-care assay to objectively assess tenofovir in urine and conducted a pilot trial examining the impact of counselling informed by use of this urine assay on long-term PrEP adherence. METHODS: This randomised trial enrolled women not in serodiscordant partnerships 3 months after PrEP initiation at the Kenya Medical Research Institute to compare standard-of-care adherence counselling versus counselling informed by the urine assay (urine-test counselling group) every 3 months for 12 months. In the standard of care group, urine samples were stored and tested at study end without participant feedback. Here we report the adherence primary outcome of hair concentrations of tenofovir at 12 months as a long-term metric (undetectable levels defined long-term non-adherence), as well as urine concentrations of tenofovir at each visit as a short-term adherence metric and acceptability of the assay assessed by quantitative surveys. Data were analysed by randomisation group. This completed trial was registered with ClinicalTrials.gov (NCT03935464). FINDINGS: From March 17, 2021 to Jan 18, 2022 we enrolled 49 women in the urine-test counselling group and 51 in the standard of care group; retention was 86 (86%) of 100. Nine (21%) of 42 in the urine-test counselling group had hair samples at 12 months with tenofovir concentrations below the limit of quantification compared with 15 (37%) of 41 in the standard of care group. The relative odds of long-term non-adherence in the standard of care group compared with urine-test counselling were 3·53 (95% CI 1·03-12·03; p=0·044). Pre-intervention, urine tenofovir was detectable in 65% in the urine-test counselling group and 71% in the standard of care group (p=0·68). At 12 months, 31 (72%) of 43 in the intervention group had detectable urine tenofovir compared with 19 (45%) of 42 in the standard of care group (p=0·0015). 40 (93%) of 43 participants liked the test very much and only one disliked the test. One participant in the standard of care group was withdrawn at the 6-month visit due to HIV seroconversion. INTERPRETATION: A low-cost urine tenofovir assay to inform PrEP counselling resulted in improvement in both short-term and long-term metrics of adherence. This urine tenofovir assay could help to improve long-term PrEP adherence. FUNDING: National Institute of Allergy and Infectious Diseases and National Institutes of Health.

Context: The purpose of this study was to compare short-term clinical outcomes between meniscus procedures performed with anterior cruciate ligament reconstruction (ACLR), ACLR (ACLR-only), ACLR with meniscectomy/resection (ACLR-resect), and ACLR with meniscal repair (ACLR-repair) for bone patellar tendon bone grafts (BPTB) and hamstring tendon grafts, separately. Design: This was a cross-sectional study conducted in a controlled laboratory setting as part of a large point-of-care collaborative research program. Methods: This study included 314 participants (168 females; mean [SD]: age, 19.7 [4.8]) with primary unilateral ACLR with a BPTB or hamstring tendon. Patients were divided into 3 groups depending on meniscal procedure (ACLR-only, ACLR-resect, and ACLR-repair). Postsurgical testing included: isokinetic assessment of knee extension and flexion, single-leg hop tests, and patient-reported outcomes. Multivariate analysis of covariance compared differences between meniscal procedures on the battery of tests, and for each statistically significant variable an analysis of covariance assessed the effect of meniscal procedure within each graft type. Chi-square analysis assessed the influence of meniscal procedure on tests' pass rates defined as 90% of limb symmetry index. Results: BPTB: ACLR-only had greater hamstring strength than ACLR-resect (P = .05) and ACLR-repair (P = .005). ACLR-only had the highest proportion of participants to pass the hamstring strength test (P=.02). amstring tendon: ACLR-only (P=.03) and ACLR-resect (P=.003) had higher International Knee Documentation Committee scale scores than ACLR-repair. There was a significant difference in the proportion of participants who scored >90% limb symmetry index on the timed hop test (P = .05). Conclusions: The influence of meniscal repair on clinical outcomes is dependent on the graft choice. Following an ACLR with BPTB and a meniscal procedure, hamstring function should be more closely monitored for optimal short-term recovery. [ABSTRACT FROM AUTHOR]

BackgroundHousehold contact investigations are effective for finding tuberculosis (TB) cases but are hindered by low referral uptake for clinic-based evaluation and testing. We assessed the acceptability and feasibility of in-home testing of household contacts (HHC) using the GeneXpert Edge platform.MethodsWe conducted a 2-arm, randomized study in Eastern Cape, South Africa. HHCs were verbally assessed using the World Health Organization-recommended 4-symptom screen. Households with ≥1 eligible symptomatic contact were randomized. Intervention households received in-home GeneXpert MTB/RIF molecular testing. GeneXpert-positive HHCs were referred for clinic-based treatment. Standard-of-care households were referred for clinic-based sputum collection and testing. We defined acceptability as agreeing to in-home testing and feasibility as generation of valid Xpert MTB/RIF results. The proportion and timeliness of test results received was compared between groups.ResultsEighty-four households were randomized (n = 42 per arm). Of 100 eligible HHCs identified, 98/100 (98%) provided consent. Of 51 HHCs allocated to the intervention arm, all accepted in-home testing; of those, 24/51 (47%) were sputum productive and 23/24 (96%) received their test results. Of 47 HCCs allocated to standard-of-care, 7 (15%) presented for clinic-based TB evaluation, 6/47 (13%) were tested, and 4/6 (67%) returned for their results. The median (interquartile range) number of days from screening to receiving test results was 0 (0) and 16.5 (11-15) in the intervention and standard-of-care arms, respectively.ConclusionsIn-home testing for TB was acceptable, feasible, and increased HHCs with a molecular test result. In-home testing mitigates a major limitation of household contact investigations (dependency on clinic-based referral), revealing new strategies for enhancing early case detection.

As a progressive disease process, early diagnosis and ongoing monitoring and treatment of lower limb peripheral artery disease (PAD) is critical to reduce the risk of diabetes-related foot ulcer (DFU) development, non-healing of wounds, infection and amputation, in addition to cardiovascular complications. There are a variety of non-invasive tests available to diagnose PAD at the bedside, but there is no consensus as to the most diagnostically accurate of these bedside investigations or their reliability for use as a method of ongoing monitoring. Therefore, the aim of this systematic review was to first determine the diagnostic accuracy of non-invasive bedside tests for identifying PAD compared to an imaging reference test and second to determine the intra- and inter-rater reliability of non-invasive bedside tests in adults with diabetes. A database search of Medline and Embase was conducted from 1980 to 30 November 2022. Prospective and retrospective investigations of the diagnostic accuracy of bedside testing in people with diabetes using an imaging reference standard and reliability studies of bedside testing techniques conducted in people with diabetes were eligible. Included studies of diagnostic accuracy were required to report adequate data to calculate the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) which were the primary endpoints. The quality appraisal was conducted using the Quality Assessment of Diagnostic Accuracy Studies and Quality Appraisal of Reliability quality appraisal tools. From a total of 8517 abstracts retrieved, 40 studies met the inclusion criteria for the diagnostic accuracy component of the review and seven studies met the inclusion criteria for the reliability component of the review. Most studies investigated the diagnostic accuracy of ankle -brachial index (ABI) (N = 38). In people with and without DFU, PLRs ranged from 1.69 to 19.9 and NLRs from 0.29 to 0.84 indicating an ABI 1.3, TBI of

ObjectivePregnant and postpartum women (PPW) in Southern Africa are at increased risk of acquiring HIV and curable sexually transmitted infections (STIs). Oral pre-exposure prophylaxis (PrEP) is safe and effective to use during pregnancy to reduce HIV acquisition and vertical transmission. Point-of-care (POC) STI testing can identify PPW at risk of HIV and facilitate risk-differentiated and person-centred counselling to improve PrEP initiation, persistence and adherence. We evaluated the impact of POC STI testing compared with STI syndromic management on PrEP outcomes among PPW in Cape Town, South Africa.MethodsThe STI and PrEP in Pregnancy Study enrolled PPW without HIV and ≤34 weeks pregnant at their regular antenatal care visit with follow-up after 1 month. PPW were randomised to receive POC STI testing or STI syndromic management. PPW randomised to POC STI testing self-collected vaginal swabs for Chlamydia trachomatis, Neisseria gonorhoeae and Trichomonas vaginalis (Cepheid GeneXpert) testing and were offered same-day treatment if diagnosed. We compared PrEP initiation at baseline, PrEP prescription refill at 1 month (persistence) and adherence through tenofovir-diphosphate detection in dried blood spots by randomisation arm. In a secondary analysis, we evaluated the association between an STI diagnosis (positive STI test or reporting STI symptoms) with PrEP outcomes.ResultsWe enrolled and randomised 268 pregnant women. Twenty-eight per cent of women were diagnosed with ≥1 STI. Overall, 65% of women initiated and 79% persisted on PrEP with no significant differences by randomisation arm. Secondary analysis demonstrated that an STI diagnosis (positive STI test or reporting STI symptoms) was associated with higher PrEP initiation (adjusted relative risk=1.28; 95% CI 1.08 to 1.52), controlling for arm, maternal and gestational age.ConclusionsPOC STI testing was not associated with PrEP initiation or persistence relative to syndromic management. However, improving STI diagnosis by supplementing syndromic management with POC STI testing could improve PrEP initiation among PPW.Trial registration numberNCT03902418; Clinical Trials.gov; 1 April 2019.

Background: The cannulation of the internal jugular vein (IJV) is a frequent procedure in critically ill patients. According to the guidelines, real-time ultrasound navigation is recommended. Traditional techniques pose several disadvantages, such as suboptimal needle visualization. Therefore, this non-inferiority trial aimed to describe the novel approach and compare the novel lateral in-plane short-axis approach for IJV access with the conventional short-axis out-of-plane approach. Objectives: The primary objective of the trial was to prove that the first attempt success rate in the novel technique is non-inferior to the conventional technique. The secondary objectives were to demonstrate that the complication rate and the functional duration of the catheter in the novel technique are not inferior to those in the conventional technique. Methods: Patients eligible for IJV cannulation were randomly assigned to either the novel technique (Group A) or the conventional one (Group B). The procedure duration, success rate and the number of attempts required were documented. The functionality of the catheter and complications were monitored from insertion until the catheter removal. Standard descriptive statistical methods were employed for the analysis. Results: A total of 200 subjects were equally divided between Group A and Group B. For the primary outcome, there was no significant difference in first attempt success rate (Group A: 79, Group B: 77, p = 0.434). Secondary outcomes, including complications and catheter functional time, did not differ significantly between the groups. However, the novel technique demonstrated a significantly faster procedure time (Group A: 315 s, Group B: 330 s, p = 0.016). Notably, the novel approach was linked with significantly larger IJV diameter measured during the procedure (Group A: 18.2 mm, Group B: 12.1 mm, p < 0.001). Conclusion: The novel lateral in-plane short-axis approach for IJV cannulation is a non-inferior alternative with a lower incidence of posterior vessel wall puncture compared to the conventional approach. [ABSTRACT FROM AUTHOR]

Background: Chest pain is a common reason patients are admitted to the hospital. The most clinically significant cases are those in which the pain is due to an immediate life-threatening condition, such as acute aortic dissection (AAD). A prompt and correct diagnosis is crucial to patient survival. This case report of a patient who presented with chest pain confirms the appropriateness of urgent imaging tests e.g. POCUS when AAD is suspected in high-risk patients, regardless of the results of additional laboratory tests such as the D-dimer (DD) assay. Case report: A 72-year-old female patient was brought by the emergency medical team to the emergency room due to fainting without loss of consciousness and severe chest pain. Owing to worsening hypotonia and recurrent chest pain, a thoracic computed tomography (CT scan) was performed and subsequently revealed aortic dissection within the ascending segment with bleeding into the pericardial sac. The results of previously ordered laboratory tests, including the DD assay, were unremarkable and were obtained only after the thoracic CT scan had been acquired. Despite prompt medical intervention, the patient died. Conclusion: Vigilance is required when diagnosing chest pain in high-risk patients who are suspected of having AAD. The case presented in this report confirms the importance of a thorough history and physical examination as well as prompt diagnostic imaging e.g. POCUS or CT scan. Dedicated laboratory tests such as the DD assay, while often helpful, may fail to reveal remarkable abnormalities in time for medical intervention. [ABSTRACT FROM AUTHOR]

The pathogenic oomycete Pythium insidiosum causes a fatal infectious illness known as pythiosis, impacting humans and certain animals in numerous countries in the tropics and subtropics. Delayed diagnosis is a primary factor contributing to the heightened morbidity and mortality associated with the disease. Several new serodiagnostic methods have been developed to improve the identification of pythiosis. However, these assays provide only indirect evidence of pythiosis and are not readily available in the commercial market. Here, we have developed an affordable point-of-care test (POCT) kit based on an immunochromatographic assay to detect P. insidiosum antigens directly. Our recent findings reveal that the lateral flow sandwich immunological testing cassette can accurately identify vascular pythiosis antigens using a small volume of patient's plasma, accomplishing diagnostic efficiency, with a limit of detection (LOD) of 8 ng/mL. This prototype cartridge represents a significant stride toward advancing enriched POCT for pythiosis serodiagnosis. [ABSTRACT FROM AUTHOR]

A novel hybridization chain reaction (HCR) powered optical fiber-embedded microfluidic biochip (HCR-FMB) has been constructed for ultrafast and sensitive detection of lethal-7a (let-7a) in serum. By integrating HCR, fluorescence energy resonant transfer, and evanescent wave fluorescence principle, the HCR-FMB enables detecting let-7a with satisfactory limit of detection of 100.0 pM within 6 min at room temperature, and demonstrates excellent specificity. The HCR-FMB can directly detect let-7a in serum with high sensitivity and without any pre-treatment, and good recoveries were observed for let-7a in serum samples, demonstrating their potential application to the analysis of serum samples. The HCR-FMB exhibits several advantages, including rapidity, enzyme-free, miniaturization, ease-of-operation, field-deployment applicability, minimal-equipment, and cost-effectiveness. The HCR-FMB can be considered a revolutionary detection device that rapidly adapts and deploys in various settings, especially in low medical resource regions. [ABSTRACT FROM AUTHOR]