The Impact of Point-of-Care Polymerase Chain Reaction Testing on Prescribing Practices in Primary Care for Management of Strep A: A Retrospective Before-After Study.

Background: Rapid antigen detection tests (RADTs) are the standard of care (SOC) for testing in patients with suspected group A β-hemolytic Streptococcus (Strep A) infection. Due to lower sensitivity, guidelines recommend confirmatory microbiological culture following negative RADT results. This process is time-consuming, and adherence is often poor, resulting in high rates of inappropriate antibiotic prescribing. We sought to evaluate the impact of switching from RADTs to point-of-care (POC) polymerase chain reaction (PCR) testing on use of antibiotics in primary care, when used as part of an antibiotic stewardship initiative. Methods: In this retrospective before-after study, electronic medical records of any patients presenting with suspected acute pharyngitis (June 2018-May 2019) across 15 outpatient primary care clinics were evaluated. Strep A was detected using the cobas Strep A assay (cobas Liat system). Results: Analysis of 10 081 eligible patient records showed that POC PCR testing resulted in a 44.1% reduction in antibiotic prescribing for patients with a negative POC PCR test result (10.1% PCR vs 18.0% RADT; P < .0001). Rates of antibiotic prescription varied across clinical sites, ranging between 10.7% and 33.8% and 12.4% and 34.4% during the use of PCR tests and RADTs, respectively. POC PCR had no impact on prescription rates in patients with positive POC test results compared to RADTs (76.2% vs 76.5%, respectively). More than 99% of antibiotics were prescribed during the initial primary care encounter. Conclusions: As part of a broader antibiotic stewardship initiative, implementation of POC PCR as SOC in outpatients with acute pharyngitis symptoms reduced the volume of inappropriate antibiotic prescriptions.

US cost-effectiveness and budget impact of point-of-care NAAT for streptococcus.

OBJECTIVES: In the United States, approximately 12 million individuals seek medical care for pharyngitis each year, accounting for about 2% of ambulatory care visits. Although the gold standard for diagnosing group A streptococcus (GAS) is culture, it is time intensive. Rapid antigen detection tests (RADT) with or without culture confirmation are commonly used instead. Although RADT provide results quickly, they generally have lower test sensitivity. Recently, point-of-care nucleic acid amplification tests (POC NAAT) have emerged. This study evaluates the cost-effectiveness and budget impact to the US payer of adopting POC NAAT. STUDY DESIGN: This study was a cost-effectiveness analysis, with costs and outcomes calculated via a decision tree. METHODS: A decision-tree model quantified costs and outcomes associated with a GAS diagnostic strategy using POC NAAT compared with RADT + culture confirmation. Model inputs were derived from the published literature. Model outputs included costs and clinical effects: quality-adjusted life-days lost, GAS and antibiotic complications, number of patients appropriately treated, and antibiotic utilization. Sensitivity and scenario analyses were performed. RESULTS: Base-case analysis projected that a POC NAAT strategy would cost $44 per patient compared with $78 for RADT + culture. Compared with RADT + culture, POC NAAT would increase the number of appropriately treated patients and avert unnecessary use of antibiotics. The budget impact of POC NAAT was -0.4% relative to current budget over 5 years. Findings were robust in sensitivity analyses. CONCLUSIONS: Our results suggest that POC NAAT would be less costly and more effective than RADT + culture; POC NAAT adoption may yield cost savings to US third-party payers. Access to POC NAAT is important to optimize GAS diagnosis and treatment decisions in the United States.

Clinical Performance of the Point-of-Care cobas Liat for Detection of SARS-CoV-2 in 20 Minutes: a Multicenter Study.

Highly accurate testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the point of care (POC) is an unmet diagnostic need in emergency care and time-sensitive outpatient care settings. Reverse transcription-PCR (RT-PCR) technology is the gold standard for SARS-CoV-2 diagnostics. We performed a multisite U.S. study comparing the clinical performance of the first U.S. Food and Drug Administration (FDA)-authorized POC RT-PCR for detection of SARS-CoV-2 in 20 min, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test, to the most widely used RT-PCR laboratory test, the cobas 68/8800 SARS-CoV-2 test. Clinical nasopharyngeal swab specimens from 444 patients with 357 evaluable specimens at five U.S. clinical laboratories were enrolled from 21 September 2020 to 23 October 2020. The overall agreement between the Liat and 68/8800 systems for SARS-CoV-2 diagnostics was 98.6% (352/357). Using Liat, positive percent agreement for SARS-CoV-2 was 100% (162/162) and the negative percent agreement was 97.4% (190/195). The Liat is an RT-PCR POC test that provides highly accurate SARS-CoV-2 results in 20 min with performance equivalent to that of high-throughput laboratory molecular testing. Rapid RT-PCR testing at the POC can enable more timely infection control and individual care decisions for coronavirus disease 2019.

Molecular point-of-care testing for influenza A/B and respiratory syncytial virus: comparison of workflow parameters for the ID Now and cobas Liat systems.

AIMS: Point-of-care (POC) tests for influenza and respiratory syncytial virus (RSV) offer the potential to improve patient management and antimicrobial stewardship. Studies have focused on performance; however, no workflow assessments have been published comparing POC molecular tests. This study compared the Liat and ID Now systems workflow, to assist end-users in selecting an influenza and/or RSV POC test. METHODS: Staffing, walk-away and turnaround time (TAT) of the Liat and ID Now systems were determined using 40 nasopharyngeal samples, positive for influenza or RSV. The ID Now system requires separate tests for influenza and RSV, so parallel (two instruments) and sequential (one instrument) workflows were evaluated. RESULTS: The ID Now ranged 4.1-6.2 min for staffing, 1.9-10.9 min for walk-away and 6.4-15.8 min for TAT per result. The Liat ranged 1.1-1.8 min for staffing, 20.0-20.5 min for walk-away and 21.3-22.0 min for TAT. Mean walk-away time comprised 38.0% (influenza positive) and 68.1% (influenza negative) of TAT for ID Now and 93.7% (influenza/RSV) for Liat. The ID Now parallel workflow resulted in medians of 5.9 min for staffing, 9.7 min for walk-away and 15.6 min for TAT. Assuming prevalence of 20% influenza and 20% RSV, the ID Now sequential workflow resulted in medians of 9.4 min for staffing, 17.4 min for walk-away, and 27.1 min for TAT. CONCLUSIONS: The ID Now and Liat systems offer different workflow characteristics. Key considerations for implementation include value of both influenza and RSV results, clinical setting, staffing capacity, and instrument(s) placement.

Evaluation of the Liat Cdiff Assay for Direct Detection of Clostridioides difficile Toxin Genes within 20 Minutes.

Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea. Prompt diagnosis is required for initiation of timely infection control measures and appropriate adjustment of antibiotic treatment. The cobas Cdiff assay for use on the cobas Liat system enables a diagnostic result in 20 minutes. A total of 252 prospective (n = 150) and retrospective (n = 102) stool specimens from The Netherlands, France, and Switzerland were tested on the cobas Cdiff assay using the Xpert C. difficile assay as a reference method. The overall positive and negative percent agreement (PPA and NPA, respectively) of the cobas Cdiff assay compared with the Xpert C. difficile assay was 98.0% (100/102; 95% confidence interval [CI], 93.1% to 99.5%) and 94.0% (141/150; 95% CI, 89.0% to 96.8%), respectively. When comparing the PPAs of cobas Cdiff and Xpert C. difficile with culture, the results were 91.7% (55/60; 95% CI, 81.9% to 96.4%) and 85.0% (51/60; 95% CI, 73.9% to 91.9%), respectively. The difference was not statistically significant. The cobas Cdiff assay offers a very rapid alternative for diagnosing C. difficile infection. The 20-minute turnaround time provides the potential for point-of-care testing so that adequate infection control measures can be initiated promptly.

Diagnosis and Management of Group a Streptococcal Pharyngitis in the United States, 2011-2015.

BACKGROUND: Clinical guidelines for the diagnosis of group A streptococcal (GAS) pharyngitis recommend the use of a rapid antigen detection test (RADT) and/or bacterial culture. This study evaluated the overall diagnosis and treatment of acute pharyngitis in the United States, including predictors of test type and antibiotic prescription. METHODS: A retrospective analysis of pharyngitis events from 2011 through 2015 was conducted using the MarketScan commercial/Medicare databases. A pharyngitis event was defined as occurring within 2 weeks from the index visit. Patient and provider characteristics were examined across 5 testing categories: RADT, RADT plus culture, other tests, nucleic acid amplification testing (NAAT), and no test. Multivariate models were used to identify significant predictors of NAAT use and antibiotic prescription. RESULTS: A total of 18.8 million acute pharyngitis events were identified in 11.6 million patients. Roughly two-thirds of events (68.2%) occurred once, and roughly a third of patients (29.1%) required additional follow-up, but hospitalization was rare (0.3%). Across all events, 43% were diagnosed by RADT, while 20% were diagnosed by RADT plus culture. The proportion of events diagnosed by NAAT increased 3.5-fold from 2011 to 2015 (0.06% vs 0.27%). Antibiotic use was frequent (49.3%), less often in combination with RADT plus culture (31.2%) or NAAT alone (34.5%) but significantly more often with RADT alone (53.4%) or no test (57.1%). Pediatricians were significantly less likely than other providers to prescribe antibiotics in their patients, regardless of patient age (p < 0.0001). CONCLUSIONS: Antibiotic use for sore throat remains common, with many clinicians not following current guidelines for diagnosis of GAS pharyngitis. Diagnosis of GAS pharyngitis using RADT plus culture or NAAT alone was associated with lower use of antibiotics. Diagnostic testing can help lower the incidence of inappropriate antibiotic use, and inclusion of NAAT in the clinical guidelines for GAS pharyngitis warrants consideration.

Diagnosis and antibiotic treatment of group a streptococcal pharyngitis in children in a primary care setting: impact of point-of-care polymerase chain reaction.

BACKGROUND: To compare the sensitivity and specificity of the recommended 2-step rapid antigen detection test (RADT) with confirmatory culture vs the point-of-care (POC) polymerase chain reaction (PCR) Roche cobas® Liat® Strep A test for detection of group A Streptococcus (GAS) in pediatric patients with pharyngitis, and to investigate the impact of these tests on antibiotic use in a large pediatric clinic. METHODS: This prospective, open-label study was conducted at a single site during fall/winter 2016-2017. A total of 275 patients aged 3 to 18 years with symptoms of pharyngitis had a throat-swab specimen analyzed using RADT, POC PCR, and culture. The sensitivity, specificity, and percentage agreement (95% CI) between assays and a laboratory-based nucleic acid amplification test were calculated. DNA sequencing was used to adjudicate discrepancies. The RADT or POC PCR result was provided to clinicians on alternating weeks to compare the impact on antibiotic use. RESULTS: A total of 255 samples were evaluated; 110 (43.1%) were GAS positive. Sensitivities (95% CI) for POC PCR, RADT, and culture were 95.5% (89.7-98.5%), 85.5% (77.5-1.5%), and 71.8% (62.4-80.0%), respectively. Specificities (95% CI) for POC PCR, RADT, and culture were 99.3% (96.2-99.98%), 93.7% (88.5-97.1%), and 100% (97.5-100%), respectively. Compared with RADT, POC PCR resulted in significantly greater appropriate antibiotic use (97.1% vs 87.5%; P = .0065). CONCLUSION: Under real-world conditions, RADT results were less specific and culture results were less sensitive than found in established literature and led to increased rates of inappropriate antibiotic use. POC PCR had high sensitivity and specificity and rapid turnaround times, and led to more appropriate antibiotic use. TRIAL REGISTRATION: ID number ISRCTN84562679 . Registered October 162,018, retrospectively registered.

Performance comparison of the cobas Liat and Cepheid GeneXpert systems for Clostridium difficile detection.

Clostridium difficile infection (CDI) is a high burden and significant cause of healthcare-acquired infectious diarrhea in the United States (US). Timely and accurate diagnosis of CDI enables the rapid initiation of antibiotic therapy and infection control policies to minimize disease transmission. Polymerase chain reaction (PCR) assays have become a preferred modality for diagnosing CDI in the US. The cobas Liat Cdiff PCR test is a novel assay that can be performed on-demand for hospital-based testing with a rapid 20-minute turnaround time from specimen collection to result reporting. We compared the clinical performance of the cobas Liat Cdiff test to the previously introduced Xpert C. difficile/Epi test; both tests are FDA-cleared PCR assays that detect the toxin B (tcdB) gene of C. difficile. Prospectively collected and remnant stool specimens from 310 patients with suspected CDI were obtained for analysis. The cobas Liat Cdiff and Xpert PCR tests showed an overall percent agreement of 97.4% (302/310; 95% CI: 95.0-98.9). Low bacterial burdens of toxigenic C. difficile, indicated by significantly delayed PCR cycle threshold (Ct) values, explained most of the discordance. Positive and negative percent agreement of the cobas Liat Cdiff test compared to the Xpert PCR test were 94.5% (52/55) and 98.0% (250/255), respectively. The clinical performance of the cobas Liat Cdiff test, combined with its simplicity of use and rapid result reporting, provides a reliable option for clinical laboratory use.

Diagnostic accuracy of the real-time PCR cobas® Liat® Influenza A/B assay and the Alere i Influenza A&B NEAR isothermal nucleic acid amplification assay for the detection of influenza using adult nasopharyngeal specimens.

BACKGROUND: Accurate detection of influenza requires diagnostic testing; however, methods such as RADTs and central laboratory-based tests are limited by low sensitivity and time constraints, respectively. OBJECTIVE: To compare the performances of the cobas® Liat® Influenza A/B and Alere™ i Influenza A&B point-of-care (POC) assays for detecting influenza A and B viruses using fresh nasopharyngeal specimens with the GenMark Dx® Respiratory Viral Panel as the reference method, a FDA cleared IVD PCR test. STUDY DESIGN: A total of 87 samples collected in viral transport medium from adults ≥18 years of age were re-tested on both POC assays (based on the reference PCR method, 29 were influenza A and 18 were influenza B virus positive). RESULTS: The overall sensitivity and specificity of the cobas Influenza A/B for the detection of influenza A and B relative to reference PCR was 97.9% (95% confidence interval [CI] 88.9%, 99.6%) and 97.5% (95% CI: 87.1%, 99.6%), respectively, while the sensitivity of the Alere i Influenza A&B assay relative to the reference PCR method was 63.8% (95% CI: 49.5%, 76.0%) and the specificity was 97.5% (95% CI: 87.1%, 99.6%). The individual sensitivities and specificities of the cobas Influenza A/B assay for influenza A alone and influenza B alone were comparable to those of the reference PCR method (influenza A: sensitivity of 100% [95% CI: 88.3%, 100.0%] and specificity of 98.3% [95% CI: 90.9%, 99.7%]; influenza B: sensitivity of 94.4% [95% CI: 74.2%, 99.0%] and specificity of 100% [95% CI: 94.7%, 100.0%]). For the Alere i Influenza A&B assay, the individual specificities for influenza A and B were comparable to those of the reference PCR method (98.3% [95% CI: 90.9%, 99.7%] and 97.1% [95% CI: 90.0%, 99.2%], respectively), while the individual sensitivities were low relative to reference PCR (55.2% [95% CI: 37.5%, 71.6%] and 72.2% [95% CI: 49.1%, 87.5%], respectively). CONCLUSION: The cobas Influenza A/B assay demonstrated performance equivalent to laboratory-based PCR, and could replace rapid antigen tests.

Lab-in-a-tube: Real-time molecular point-of-care diagnostics for influenza A and B using the cobas® Liat® system.

Rapid diagnosis of influenza A and B is important for direct treatment decisions in patient care and for the reduction of in-hospital transmissions. The new real-time PCR based molecular point-of-care (POC) assay, the cobas® Influenza A/B test on the cobas® Liat® System (cobas® Liat® Influenza A/B assay), generated a PCR result in less than 20 min, was evaluated for the detection of influenza A and B. One hundred twenty-one retrospectively collected respiratory specimens, previously analyzed with a routine influenza A/B test (Diagenode) were tested using the cobas® Liat® Influenza A/B assay. The cobas® Liat® Influenza A/B assay allows influenza A and B testing by RT-PCR within 20 min. This assay detected influenza A in 51 of 56 samples positive by the Diagenode test. The five discrepant results were retested with the Cepheid Influenza A/B test, confirming two positive cases. All 30 influenza B Diagenode positive samples were found positive by the cobas® Liat® Influenza A/B assay. Control samples (viral negative and non-influenza pathogens) were all negative by the cobas® Liat® Influenza A/B assay. The cobas® Liat® Influenza A/B assay showed a sensitivity for influenza A/B of 96% and 100%, respectively, and 100% specificity for both targets. The cobas® Liat® Influenza A/B assay is a useful tool for accurate, rapid, and sensitive detection of influenza A and B, offering timely and personalized patient management and infection control when implemented at the point-of-care.

Accurate Detection of Streptococcus pyogenes at the Point of Care Using the cobas Liat Strep A Nucleic Acid Test.

The performance of a polymerase chain reaction-based point-of-care assay, the cobas Strep A Nucleic Acid Test for use on the cobas Liat System (cobas Liat Strep A assay), for the detection of group A Streptococcus bacteria was evaluated in primary care settings. Throat swab specimens from 427 patients were tested with the cobas Liat Strep A assay and a rapid antigen detection test (RADT) by existing medical staff at 5 primary care clinics, and results were compared with bacterial culture. The cobas Liat Strep A assay demonstrated equivalent sensitivity (97.7%) and specificity (93.3%) to reference culture with a 15-minute turnaround time. In comparison to RADTs, the cobas Liat Strep A assay showed improved sensitivity (97.7% Liat vs 84.5% RADT). The Clinical Laboratory Improvement Amendments-waived cobas Liat Strep A assay demonstrated the ease of use and improved turnaround time of RADTs along with the sensitivity of culture.

Optimizing antiretroviral product selection: a sample approach to improving patient outcomes, saving money, and scaling-up health services in developing countries.

Over the last decade, increased funding to support HIV treatment programs has enabled millions of new patients in developing countries to access the medications they need. Today, although demand for antiretrovirals continues to grow, the financial crisis has severely constrained funding leaving countries with difficult choices on program prioritization. Product optimization is one solution countries can pursue to continue to improve patient care while also uncovering savings that can be used for further scale up or other health system needs. Program managers can make procurement decisions that actually reduce program costs by considering additional factors beyond World Health Organization guidelines when making procurement decisions. These include in-country product availability, convenience, price, and logistics such as supply chain implications and laboratory testing requirements. Three immediate product selection opportunities in the HIV space include using boosted atazanavir in place of lopinovir for second-line therapy, lamivudine instead of emtricitabine in both first-line and second-line therapy, and tenofovir + lamivudine over abacavir + didanosine in second-line therapy. If these 3 opportunities were broadly implemented in sub-Saharan Africa and India today, approximately $300 million of savings would be realized over the next 5 years, enabling hundreds of thousands of additional patients to be treated. Although the discussion herein is specific to antriretrovirals, the principles of product selection are generalizable to diseases with multiple treatment options and fungible commodity procurement. Identifying and implementing approaches to overcome health system inefficiencies will help sustain and may expand quality care in resource-limited settings.

Lesbians over sixty: the consistency of findings from twenty years of survey data.

This article reports on a previously unpublished survey of a community of elder lesbians collected in 1984 by Dr. Monika Kehoe and colleagues, which described the social life, family relationships, relationships with women, sexuality, health, and health care services of elder lesbians. We report the findings of this study now not only because they have historical importance, but also because they remain relevant to the current life experiences and needs of elder lesbians. Specifically, this article describes the results of the original survey and discusses these findings in light of subsequent research findings. This comparison sheds light on the consistency of the attitudes, behaviors, and relationships of elder lesbians over the past 20 years. Recent and current research about elder lesbians largely confirms the observations of the Kehoe survey that older lesbians have: (1) often created a variety of social, sexual, and domestic experiences during their lives; (2) focused their social lives around a network of friends; (3) often not maintained close familial ties; and (4) avoided using conventional senior services often due to perceived discrimination.