Immediate initiation of antiretroviral treatment: knowledge, attitudes, and practices among clinic staff in New York City.

BACKGROUND: Immediate initiation of antiretroviral treatment (iART) is a proven intervention that significantly decreases time to viral suppression and increases patient retention. iART involves starting medication as early as possible, often after a reactive rapid HIV test or re-engagement in care, although it does not have a universal definition. We aimed to understand iART from an implementation science perspective in a wide range of New York City (NYC) clinics providing HIV primary care, including staff knowledge, attitudes, and practices, as well as clinic barriers and facilitators to iART. METHODS: We used a mixed-methods, convergent study design, with a quantitative survey and in-depth interview (IDI), to understand individual-level knowledge, attitudes, and practices, as well as clinic-level barriers and facilitators to iART. We recruited at least one medical and non-medical staff member from a diverse purposive sample of 30 NYC clinics. In quantitative analyses, we used separate binomial logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (95% CI). In qualitative analyses, we used codebooks created by thematic analyses structured using a Framework Model to develop descriptive analytic memos. RESULTS: Recruited staff completed 46 surveys and 17 IDIs. We found high levels of awareness of the viral suppression and retention in care benefits of iART. Survey respondents more commonly reported medication starts within three to four days of a reactive rapid HIV test rather than same-day initiation. Among survey respondents, compared to medical staff, non-medical staff were more likely to agree that medication should only be initiated after receiving confirmatory HIV test results (OR: 0.2, 95% CI: 0.06-0.8). Additionally, survey respondents from clinics serving a majority people of color were less likely to report iART on the same day as a reactive rapid HIV test (OR: 0.2, 95% CI: 0.02-1.0, p-value < 0.5). IDI results elucidated barriers to implementation, including perceived patient readiness, which potentially leads to added disparities in iART access. CONCLUSION: iART has proven benefits and support for its implementation among HIV clinic staff. Our findings indicate that barriers to expanding iART access may be overcome if implementation resources are allocated strategically, which can further progress towards health equity.

Simple triage and rapid treatment protocol for emergency department mass casualty incident victim triage.

OBJECTIVE: Triage plays an essential role in emergency medical care. It is crucial to adopt appropriate triage in a mass casualty incident (MCI) when resources are limited. The simple triage and rapid treatment (START) protocol is commonly used worldwide; however, the effectiveness of the START protocol for emergency department (ED) triage is unclear. This study aimed to examine the accuracy of START for the ED triage of victims following a MCI. METHODS: We retrospectively reviewed the records of victims who presented to our ED during a MCI response after a train crash. The ED nurses applied the START protocol upon patient arrival, and we used a consensus-based standard to determine the outcome-based categories of these same patients. We compared the START protocol and outcome-based categories. In addition, the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of START in terms of predicting surgery and ED disposition were determined. RESULTS: This study enrolled 47 patients (predominantly women, 68.1%; median age: 39.0years). Most victims were triaged into the START minor category (61.7%) and discharged from the ED (68.1%). Twenty-nine patients had matched START and outcome-based categories, whereas 2 patients were over-triaged and 16 patients were under-triaged. Additionally, the START system had acceptable AUC and sensitivities for predicting surgery and ED disposition (AUC/sensitivity/specificity for surgery: 0.850/100%/69.1%; AUC/sensitivity/specificity for admission: 0.917/93.3%/87.5%; AUC/sensitivity/specificity for intensive care unit (ICU)/ED death: 0.994/100%/97.8%). CONCLUSIONS: This study demonstrated poor agreement between START categories, as determined in the ED, and the consensus-based standard categories. However, the START protocol was acceptable in terms of identifying emergent patients (100% sensitivity for the immediate and deceased categories) and predicting ED disposition (surgery, admission, and ICU/ED mortality). Although START is not perfect, our findings suggest that it could be used for the ED triage of trauma-related MCI victims.

Rapid antiretroviral treatment start seems as vital and cost-effective strategy in Central and Eastern Europe.

BACKGROUND: It is essential to deliver specialist human immunodeficiency virus (HIV) care with maximum effectiveness, but also minimum time delay. Therefore, we aimed to determine whether rapid linkage to care defined as starting combined antiretroviral therapy (cART) on the day of the first visit at the HIV clinic is a costeffective approach. METHODS: In the analysis, Markov's lifetime model presented in our previous study was implemented. The inputs used in the model were updated in the terms of costs, life expectancy, and patient characteristics. For the analysis we used information from the previous model about the additional costs of treatment and qualityadjusted life years (QALYs) lost in the life horizon for people newly infected with HIV. The number of newly infected persons was estimated based on available data. RESULTS: Input data was available for 344 men having sex with men (MSM) who registered in the HIV specialist care between 2016 and 2017. The estimated QALY loss due to lack of rapid treatment initiation, where the viral load is not (was) taken into account, equals 0·018 (0·022), 0·039 (0·047), 0·131 (0·158) respectively in low, medium and high risk transmission groups. Rapid cART initiation was dominant regardless of the chosen scenarios. CONCLUSIONS: Cost-effectiveness analysis considering the HIV transmission indicates that the rapid initiation of HIV treatment is a cost-effective and potentially cost-saving approach to improve HIV care and reduce HIV transmission in Central and Eastern Europe.

Morphological and functional cardiac consequences of rapid hypertension treatment: a cohort study.

BACKGROUND: Left ventricular (LV) hypertrophy (LVH) in uncontrolled hypertension is an independent predictor of mortality, though its regression with treatment improves outcomes. Retrospective data suggest that early control of hypertension provides a prognostic advantage and this strategy is included in the 2018 European guidelines, which recommend treating grade II/III hypertension to target blood pressure (BP) within 3 months. The earliest LVH regression to date was demonstrated by echocardiography at 24 weeks. The effect of a rapid guideline-based treatment protocol on LV remodelling, with very early BP control by 18 weeks remains controversial and previously unreported. We aimed to determine whether such rapid hypertension treatment is associated with improvements in LV structure and function through paired cardiovascular magnetic resonance (CMR) scanning at baseline and 18 weeks, utilising CMR mass and feature tracking analysis. METHODS: We recruited participants with never-treated grade II/III hypertension, initiating a guideline-based treatment protocol which aimed to achieve BP control within 18 weeks. CMR and feature tracking were used to assess myocardial morphology and function immediately before and after treatment. RESULTS: We acquired complete pre- and 18-week post-treatment data for 41 participants. During the interval, LV mass index reduced significantly (43.5 ± 9.8 to 37.6 ± 8.3 g/m2, p < 0.001) following treatment, accompanied by reductions in LV ejection fraction (65.6 ± 6.8 to 63.4 ± 7.1%, p = 0.03), global radial strain (46.1 ± 9.7 to 39.1 ± 10.9, p < 0.001), mid-circumferential strain (- 20.8 ± 4.9 to - 19.1 ± 3.7, p = 0.02), apical circumferential strain (- 26.0 ± 5.3 to - 23.4 ± 4.2, p = 0.003) and apical rotation (9.8 ± 5.0 to 7.5 ± 4.5, p = 0.003). CONCLUSIONS: LVH regresses following just 18 weeks of intensive antihypertensive treatment in subjects with newly-diagnosed grade II/III hypertension. This is accompanied by potentially advantageous functional changes within the myocardium and supports the hypothesis that rapid treatment of hypertension could improve clinical outcomes. TRIAL REGISTRATION: ISRCTN registry number: 57475376 (assigned 25/06/2015).

Implementation of an Immediate HIV Treatment Initiation Program in a Public/Academic Medical Center in the U.S. South: The Miami Test and Treat Rapid Response Program.

Test and Rapid Response Treatment (TRRT) linkage programs have demonstrated improved HIV suppression rates. This paper describes the design and implementation of the Miami TRRT initiative and its clinical impact. Assisted by a dedicated care navigator, patients receiving a reactive HIV rapid test at the Florida Department of Health STD Clinic were offered same-day HIV care at the University of Miami/Jackson Memorial Medical Center Adult HIV Outpatient Clinic. Patient retention and labs were tracked for 12 months. Of the 2337 individuals tested, 46 had a reactive HIV test; 41 (89%) consented to participate. For the 36 patients in continued care for a year, 33 (91.7%) achieved virological suppression (< 200 copies/mL) within 70 days of their reactive HIV rapid test; at 12 months, 35 (97.2%) remained suppressed, and mean CD4 T cell counts increased from 452 ± 266 to 597 ± 322 cells/mm3. The Miami TRRT initiative demonstrated that immediate linkage to care is feasible and improves retention and suppression in a public/academic medical center in the U.S. South.

Platelet-rich plasma with keratinocytes and fibroblasts enhance healing of full-thickness wounds.

Advances in tissue engineering led to the development of various tissue-engineered skin substitutes (TESS) for the treatment of skin injuries. The majority of the autologous TESS required lengthy and costly cell expansion process to fabricate. In this study, we determine the possibility of using a low density of human skin cells suspended in platelet-rich plasma (PRP)-enriched medium to promote the healing of full-thickness skin wounds. To achieve this, full-thickness wounds of size 1.767 cm2 were created at the dorsum part of nude mice and treated with keratinocytes (2 × 104 cells/cm2) and fibroblasts (3 × 104 cells/cm2) suspended in 10% PRP-enriched medium. Wound examination was conducted weekly and the animals were euthanized after 2 weeks. Gross examination showed that re-epithelialization was fastest in the PRP+cells group at both day 7 and 14, followed by the PRP group and NT group receiving no treatment. Only the PRP+cells group achieved complete wound closure by 2 weeks. Epidermal layer was presence in the central region of the wound of the PRP+cells and PRP groups but absence in the NT group. Comparison between the PRP+cells and PRP groups showed that the PRP+cells-treated wound was more mature as indicated by the presence of thinner epidermis with single cell layer thick basal keratinocytes and less cellular dermis. In summary, the combination of low cell density and diluted PRP creates a synergistic effect which expedites the healing of full-thickness wounds. This combination has the potential to be developed as a rapid wound therapy via the direct application of freshly harvested skin cells in diluted PRP.

Rapid amelioration of severe manic episodes with right unilateral ultrabrief pulse ECT: a case series of four patients.

OBJECTIVE: The aim of this small case series is to describe four cases of severe mania, where ultrabrief pulse electroconvulsive therapy (ECT) was used as a primary mode of treatment. METHODS: A retrospective file review was undertaken of four patients identified as having received ultrabrief pulse ECT for severe mania. The outcome measures for treatment efficacy were the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI). RESULTS: All the patients showed significant clinical improvement. A comparison of pre- and post-treatment YMRS and CGI scores showed a dramatic decrease in all four cases. However, one patient was shifted to brief pulse ECT due to inadequate response. CONCLUSIONS: Ultrabrief pulse ECT may be an effective treatment in cases of severe mania. Due to the very small number of cases in the current case series, no specific conclusions regarding efficacy may be drawn; however, larger, controlled studies would be indicated.

A modified simple triage and rapid treatment algorithm from the New York City (USA) Fire Department.

INTRODUCTION: The objective of this study was to determine if modification of the Simple Triage and Rapid Treatment (START) system by the addition of an Orange category, intermediate between the most critically injured (Red) and the non-critical, non-ambulatory injured (Yellow), would reduce over- and under-triage rates in a simulated mass-casualty incident (MCI) exercise. METHODS: A computer-simulation exercise of identical presentations of an MCI scenario involving a 2-train collision, with 28 case scenarios, was provided for triaging to two groups: the Fire Department of the City of New York (FDNY; n=1,347) using modified START, and the Emergency Medical Services (EMS) providers from the Eagles 2012 EMS conference (Lafayette, Louisiana USA; n=110) using unmodified START. Percent correct by triage category was calculated for each group. Performance was then compared between the two EMS groups on the five cases where Orange was the correct answer under the modified START system. RESULTS: Overall, FDNY-EMS providers correctly triaged 91.2% of cases using FDNY-START whereas non-FDNY-Eagles providers correctly triaged 87.1% of cases using unmodified START. In analysis of the five Orange cases (chest pain or dyspnea without obvious trauma), FDNY-EMS performed significantly better using FDNY-START, correctly triaging 86.3% of cases (over-triage 1.5%; under-triage 12.2%), whereas the non-FDNY-Eagles group using unmodified START correctly triaged 81.5% of cases (over-triage 17.3%; under-triage 1.3%), a difference of 4.9% (95% CI, 1.5-8.2). CONCLUSIONS: The FDNY-START system may allow providers to prioritize casualties using an intermediate category (Orange) more properly aligned to meet patient needs, and as such, may reduce the rates of over-triage compared with START. The FDNY-START system decreases the variability in patient sorting while maintaining high field utility without needing computer assistance or extensive retraining. Comparison of triage algorithms at actual MCIs is needed; however, initial feedback is promising, suggesting that FDNY-START can improve triage with minimal additional training and cost.

A Simple Graphical Method for Quantification of Disaster Management Surge Capacity Using Computer Simulation and Process-control Tools.

INTRODUCTION: Surge capacity, or the ability to manage an extraordinary volume of patients, is fundamental for hospital management of mass-casualty incidents. However, quantification of surge capacity is difficult and no universal standard for its measurement has emerged, nor has a standardized statistical method been advocated. As mass-casualty incidents are rare, simulation may represent a viable alternative to measure surge capacity. Hypothesis/Problem The objective of the current study was to develop a statistical method for the quantification of surge capacity using a combination of computer simulation and simple process-control statistical tools. Length-of-stay (LOS) and patient volume (PV) were used as metrics. The use of this method was then demonstrated on a subsequent computer simulation of an emergency department (ED) response to a mass-casualty incident. METHODS: In the derivation phase, 357 participants in five countries performed 62 computer simulations of an ED response to a mass-casualty incident. Benchmarks for ED response were derived from these simulations, including LOS and PV metrics for triage, bed assignment, physician assessment, and disposition. In the application phase, 13 students of the European Master in Disaster Medicine (EMDM) program completed the same simulation scenario, and the results were compared to the standards obtained in the derivation phase. RESULTS: Patient-volume metrics included number of patients to be triaged, assigned to rooms, assessed by a physician, and disposed. Length-of-stay metrics included median time to triage, room assignment, physician assessment, and disposition. Simple graphical methods were used to compare the application phase group to the derived benchmarks using process-control statistical tools. The group in the application phase failed to meet the indicated standard for LOS from admission to disposition decision. CONCLUSIONS: This study demonstrates how simulation software can be used to derive values for objective benchmarks of ED surge capacity using PV and LOS metrics. These objective metrics can then be applied to other simulation groups using simple graphical process-control tools to provide a numeric measure of surge capacity. Repeated use in simulations of actual EDs may represent a potential means of objectively quantifying disaster management surge capacity. It is hoped that the described statistical method, which is simple and reusable, will be useful for investigators in this field to apply to their own research.

Recent advances in medical device triage technologies for chemical, biological, radiological, and nuclear events.

In 2010, the US Food and Drug Administration (Silver Spring, Maryland USA) created the Medical Countermeasures Initiative with the mission of development and promoting medical countermeasures that would be needed to protect the nation from identified, high-priority chemical, biological, radiological, or nuclear (CBRN) threats and emerging infectious diseases. The aim of this review was to promote regulatory science research of medical devices and to analyze how the devices can be employed in different CBRN scenarios. Triage in CBRN scenarios presents unique challenges for first responders because the effects of CBRN agents and the clinical presentations of casualties at each triage stage can vary. The uniqueness of a CBRN event can render standard patient monitoring medical device and conventional triage algorithms ineffective. Despite the challenges, there have been recent advances in CBRN triage technology that include: novel technologies; mobile medical applications ("medical apps") for CBRN disasters; electronic triage tags, such as eTriage; diagnostic field devices, such as the Joint Biological Agent Identification System; and decision support systems, such as the Chemical Hazards Emergency Medical Management Intelligent Syndromes Tool (CHEMM-IST). Further research and medical device validation can help to advance prehospital triage technology for CBRN events.

Potential Utility of C-reactive Protein for Tuberculosis Risk Stratification Among Patients With Non-Meningitic Symptoms at HIV Diagnosis in Low- and Middle-income Countries.

Background: The World Health Organization recommends initiating same-day antiretroviral therapy (ART) while tuberculosis (TB) testing is under way for patients with non-meningitic symptoms at HIV diagnosis, though safety data are limited. C-reactive protein (CRP) testing may improve TB risk stratification in this population. Methods: In this baseline analysis of 498 adults (>18 years) with TB symptoms at HIV diagnosis who were enrolled in a trial of rapid ART initiation in Haiti, we describe test characteristics of varying CRP thresholds in the diagnosis of TB. We also assessed predictors of high CRP as a continuous variable using generalized linear models. Results: Eighty-seven (17.5%) participants were diagnosed with baseline TB. The median CRP was 33.0 mg/L (interquartile range: 5.1, 85.5) in those with TB, and 2.6 mg/L (interquartile range: 0.8, 11.7) in those without TB. As the CRP threshold increased from ≥1 mg/L to ≥10 mg/L, the positive predictive value for TB increased from 22.4% to 35.4% and negative predictive value decreased from 96.9% to 92.3%. With CRP thresholds varying from <1 to <10 mg/L, a range from 25.5% to 64.9% of the cohort would have been eligible for same-day ART and 0.8% to 5.0% would have untreated TB at ART initiation. Conclusions: CRP concentrations can be used to improve TB risk stratification, facilitating same-day decisions about ART initiation. Depending on the CRP threshold, one-quarter to two-thirds of patients could be eligible for same-day ART, with a reduction of 3- to 20-fold in the proportion with untreated TB, compared with a strategy of same-day ART while awaiting TB test results.

Provider Perspectives on Rapid Treatment Initiation Among People Newly Diagnosed With HIV: A New Message of "Urgency"?

BACKGROUND: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program. METHODS: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo. RESULTS: Providers believed earlier initiation would signal an "extra sense of urgency" about the importance of antiretroviral therapy-a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability. CONCLUSION: Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments.

Doctor and clinic staff perspectives on a program to immediately start HIV treatment among patients newly diagnosed with HIVTreating human immunodeficiency virus (HIV) is easier than ever. Starting newly diagnosed persons on HIV medication as soon as possible is a now recommended goal. However, starting patients right away can be challenging. This study interviewed doctors and clinic staff to better understand their perspectives prior to implementing a program that would provide newly diagnosed patients with HIV treatment immediately. Results showed that some doctors are worried patients will not return after receiving their medications. Providers want support for linking patients to the clinic and ensuring they will be able to receive their next dose of medication when they come in. Other providers saw the benefits of reducing HIV stigma if the program can more quickly start patients on treatment. Some providers explained that when you go to the doctor and are sick you receive medications immediately, yet for newly diagnosed patients living with HIV, patients can be told to come back a month later to start treatment. Some providers believe shifting this messaging may also help patients take their medications better. Most providers saw the need for clinics to have more same-day appointment availability to meet the needs of the new program. Overall, providers were excited about the opportunity to improve the HIV care by offering HIV medications to newly diagnosed patients immediately.

Delay prior to expedited carotid endarterectomy: a prospective audit of practice.

OBJECTIVES: To identify reasons for delay before carotid endarterectomy (CEA) in a reconfigured "fast-track" system where patients were admitted from the TIA (transient ischaemic attack) Clinic for urgent CEA. METHODS: Prospective audit in 89 recently symptomatic patients. RESULTS: Ten patients (11%) suffered recurrent symptoms between admission and surgery. Two strokes were sufficiently severe that CEA was cancelled. The median delay from index symptom to CEA was 8 days. 74/87 (85%) underwent CEA <14 days from the index symptom; 39/87 (45%) within 7 days. Forty-five (51%) were ready for CEA <24 hours of admission; 74 (83%) <72 hours. The most common reasons for delay to CEA were logistical, especially a failure to plan for access to weekend operating. Two-thirds of the Tuesday/Friday theatre lists that were reserved for urgent CEAs were actually used for CEA; 27 (33%) were not used for CEA but were utilized for another vascular procedure, and five (4%) were cancelled the day before and went unused. CONCLUSIONS: The vast majority of patients (85%) underwent CEA <14 days from the index symptom, but 11% still suffered recurrent symptoms prior to surgery. Transferring patients directly from the TIA Clinic reduced overall delays, but Vascular Units adopting such an approach might then be vulnerable to criticisms regarding prolonged lengths of pre-operative in-patient stay while patients were worked up for theatre. Protected theatre lists both optimized (and delayed) access to CEA, but the most important cause of delay was that we had not planned for weekend operating using specialist anaesthetic and theatre staff.

Procedural risk following carotid endarterectomy in the hyperacute period after onset of symptoms.

OBJECTIVES: There have been concerns that performing carotid endarterectomy (CEA) in the hyperacute period after onset of a transient ischaemic attack (TIA) or stroke may be associated with a significant increase in the procedural risk that could offset any long-term benefit to the patient. The aim of this audit was to determine the 30-day risk of stroke/death after CEA in symptomatic patients, stratified for delay from the most recent neurological event, mode of presentation, and age. METHODS: Retrospective audit in 475 recently symptomatic patients between October 1, 2008, and April 24, 2013. RESULTS: Forty-one patients (9%) underwent surgery <48 hours of their most recent event, with a 30-day death/stroke rate of 2.4% (1/41). The procedural risk was 1.8% in 167 patients who underwent surgery within 3-7 days (3/167), falling to 0.8% in 133 patients who underwent surgery between 8 and 14 days (1/133) and 0.8% in 134 patients whose surgery took place after >14 days had elapsed (1/134). Overall, 208 (44%) underwent surgery within 7 days of their most recent neurological event (30-day risk = 1.9%), while 341 (72%) underwent CEA within 14 days (30 day risk = 1.5%). There was no evidence of any systematic differences in procedural risk by operating in the hyperacute period relating to mode of presentation (TIA, stroke, amaurosis) or age (<80 years; >80 years). CONCLUSIONS: This audit found no evidence that the procedural risk was increased when CEA was performed in the hyperacute period whether this time period was defined as <48 hours, <7 days, or <14 days.

Rapid treatments for depression: Endocannabinoid system as a therapeutic target.

Current first-line treatments for major depressive disorder (MDD), i.e., antidepressant drugs and psychotherapy, show delayed onset of therapeutic effect as late as 2-3 weeks or more. In the clinic, the speed of beginning of the actions of antidepressant drugs or other interventions is vital for many reasons. Late-onset means that depression, its related disability, and the potential danger of suicide remain a threat for some patients. There are some rapid-acting antidepressant interventions, such as sleep deprivation, ketamine, acute exercise, which induce a significant response, ranging from a few hours to maximally one week, and most of them share a common characteristic that is the activation of the endocannabinoid (eCB) system. Activation of this system, i.e., augmentation of eCB signaling, appears to have anti-depressant-like actions. This article puts the idea forward that the activation of eCB signaling represents a critical mechanism of rapid-acting therapeutic interventions in MDD, and this system might contribute to the development of novel rapid-acting treatments for MDD.

Rapid Treatment Initiation for Hepatitis C Virus Infection: Potential Benefits, Current Limitations, and Real-World Examples.

The science for rapid treatment initiation for hepatitis C virus infection is in place. Easy and quick diagnostic tools can provide results within an hour. Necessary assessment before treatment initiation is now minimal and manageable. Treatment has a low dose burden and high tolerability. Although the critical components for rapid treatment are accessible, certain barriers prevent wider utilization, including insurance restrictions and delays in the health care system. Rapid treatment initiation can improve linkage to care by addressing many barriers to care at once, which is essential for achieving a care plateau. Young people with low health care engagement, finitely engaged people (eg, those who are incarcerated), or people with high-risk injection drug behavior, and thereby high risk for transmission of hepatitis C virus, can benefit the most from rapid treatment. Several innovative care models have demonstrated the potential for rapid treatment initiation by overcoming barriers to care with rapid diagnostic testing, decentralization, and simplification. Expanding these models is likely to be an important component for the elimination of hepatitis C virus infection. This article reviews the current motivation for rapid treatment initiation for hepatitis C virus infection and published literature describing rapid treatment initiation models.

Rapid Detection of Extensively Drug-Resistant Tuberculosis in Clinical Samples Using a Novel Tabletop Platform: Protocol for a Prospective Clinical Study.

BACKGROUND: The lack of accurate and efficient diagnostic devices for extensively drug-resistant tuberculosis (XDR-TB) makes it a severe threat to global public health. A prospective clinical study in an intended-use cohort was designed to evaluate the Akonni Biosystems XDR-TB TruArray and lateral flow cell (XDR-LFC) to address this gap in tuberculosis diagnostics. OBJECTIVE: This paper presents the protocol for a study that aims to document the conceptualization and design of this evaluation method for early dissemination while data collection and analysis are ongoing. METHODS: The clinical study was conducted in three phases. The first phase was to observe changes in bacterial load and culture positivity in patient sputa over time and better understand the diversity of prospective clinical samples. The second phase was to prospectively collect clinical samples for sensitivity and specificity testing of the Akonni Biosystems XDR-LFC device. Lastly, the third phase was to explore the anti-TB drug concentrations in serum throughout the drug-resistant tuberculosis treatment. RESULTS: The methodology described includes the study design, laboratory sample handling, data collection, and the protection elements of human subjects of this clinical study to evaluate a potential new XDR-TB diagnostic device. A total of 664 participants were enrolled across the three phases. The implemented complex systems facilitated a thorough clinical data collection for an objective evaluation of the device. The study is closed to recruitment. The follow-up data collection and analysis are in progress. CONCLUSIONS: This paper outlined a prospective cohort study protocol to evaluate a rapid XDR-TB detection device, which may be informative for other researchers with similar goals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26748.

Early treatment of acute promyelocytic leukaemia is accurately guided by the PML protein localisation pattern: real-life experience from a tertiary New Zealand centre.

Current guidelines recommend that a rapid test be used to assist diagnosis of acute promyelocytic leukaemia (APL), but the choice of an assay is discretionary. PML immunofluorescence (PML IF) identifies the microparticulate pattern of the PML protein localisation, highly specific for APL. The aim of this study was to evaluate clinical utility of PML IF in a real-life setting based on a retrospective records review for all patients who had PML IF performed in our centre between 2000 and 2017. Final analysis included 151 patients, 70 of whom had APL. PML IF was reported on average 3 days faster than cytogenetics. Compared with genetic results, PML IF showed sensitivity of 96% and specificity of 100%. PML IF accurately predicted APL in four APL cases with cryptic karyotype/FISH and excluded APL in 98% cases tested based on the suspicious immunophenotype alone, 21/28 of whom had mutated NPM1. Results of PML IF influenced decision to start ATRA in 25 (36%) APL patients and led to its termination in six non-APL patients. In conclusion, PML IF is a fast and reliable test that facilitates accurate treatment decisions when APL is suspected. This performance of PML IF remains hard to match in a real-life setting.