Inappropriate laboratory test utilization in outpatient tertiary care: Implications for value-based healthcare.

OBJECTIVES: To assess the rate of inappropriate repetition of laboratory testing and estimate the cost of such testing for thyroid stimulating hormone (TSH), total cholesterol, vitamin D, and vitamin B12 tests. METHODS: A retrospective cohort study was carried out in the Family Medicine and Polyclinic Department at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Clinical and laboratory data were collected between 2018-2021 for the 4 laboratory tests. The inappropriate repetition of tests was defined according to international guidelines and the costs were calculated using the hospital prices. RESULTS: A total of 109,929 laboratory tests carried out on 23,280 patients were included in this study. The percentage of inappropriate tests, as per the study criteria, was estimated to be 6.1% of all repeated tests. Additionally, the estimated total cost wasted amounted to 2,364,410 Saudi Riyals. Age exhibited a weak positive correlation with the total number of inappropriate tests (r=0.196, p=0.001). Furthermore, significant differences were observed in the medians of the total number of inappropriate tests among genders and nationalities (p<0.001). CONCLUSION: The study identified significantly high rates of inadequate repetitions of frequently requested laboratory tests. Urgent action is therefore crucial to overcoming such an issue.

HIT-It or Quit It: Heparin-Induced Thrombocytopenia Testing Appropriateness Using 4T Scoring and Inappropriate Testing Cost Analysis.

OBJECTIVES: The American Society of Hematology's 4T scoring system is a validated tool to assess a patient's probability of having heparin-induced thrombocytopenia (HIT) before testing is performed. There is no benefit to testing patients with a low probability 4T score for HIT. This study aimed to assess for inappropriate HIT testing at our institution based on 4T scoring. METHODS: We retrospectively reviewed 201 patient charts and calculated 4T scores and testing costs to assess for inappropriate testing and the economic impact of such testing. RESULTS: HIT testing often occurred in the least appropriate patients and resulted in tens of thousands of dollars of waste for unnecessary testing. CONCLUSIONS: Inappropriate testing for HIT is still a prevalent issue despite literature supporting the 4T score for guidance in testing appropriateness.

Laboratory and Field Evaluation of the Crystal VC-O1 Cholera Rapid Diagnostic Test.

Cholera is a severe acute, highly transmissible diarrheal disease which affects many low- and middle-income countries. Outbreaks of cholera are confirmed using microbiological culture, and additional cases during the outbreak are generally identified based on clinical case definitions, rather than laboratory confirmation. Many low-resource areas where cholera occurs lack the capacity to perform culture in an expeditious manner. A simple, reliable, and low-cost rapid diagnostic test (RDT) would improve identification of cases allowing rapid response to outbreaks. Several commercial RDTs are available for cholera testing with two lines to detect either serotypes O1 and O139; however, issues with sensitivity and specificity have not been optimal with these bivalent tests. Here, we report an evaluation of a new commercially available cholera dipstick test which detects only serotype O1. In both laboratory and field studies in Kenya, we demonstrate high sensitivity (97.5%), specificity (100%), and positive predictive value (100%) of this new RDT targeting only serogroup O1. This is the first field evaluation for the new Crystal VC-O1 RDT; however, with these high-performance metrics, this RDT could significantly improve cholera outbreak detection and improve surveillance for better understanding of cholera disease burden.

Creating a novel strategy to reduce unnecessary laboratory testing based on healthcare cost analysis in high-risk pregnancies and delivery ward.

INTRODUCTION: Inappropriate request for laboratory tests is a challenging problem and an important cause for additional healthcare costs. Indeed, it may have further ambiguity for the clinicians. This study aimed to design an education-based program to reduce unnecessary laboratory testing orders and the associated costs. MATERIALS AND METHODS: In this interventional prospective study that took place in an educational hospital, the type and frequency of selected laboratory testing requested by gynecology, and obstetrics residents in the patients with gestational diabetes mellitus, preeclampsia, preterm labor, and premature preterm rupture of the membrane as well as cesarean section and normal vaginal delivery were analyzed periodically in a 1-year interval. At the same time, continuous educational supports and monitoring were performed. The results were compared before and after interventions. RESULTS: The educational intervention regardless of the etiologies of the admission, decreased the requested laboratory testing significantly (p < 0.001), except for CBC. Indeed, no near misses or delays in treatment were observed. Cost analysis showed a 31.3% reduction of expenses per inpatient day due to the decrease in the number of daily laboratory testing ordered. CONCLUSIONS: Appropriate education and continuous monitoring of the residents could reduce the unrequired laboratory testing as well as healthcare costs.

Preoperative laboratory testing among low-risk patients prior to elective ambulatory endocrine surgeries: A review of the 2015-2018 NSQIP cohorts.

BACKGROUND: Preoperative laboratory tests (PLTs) are not associated with complications among healthy patients in various ambulatory procedures. This association has not been studied in ambulatory endocrine surgery. METHODS: The 2015-2018 NSQIP datasets were queried for elective outpatient thyroid and parathyroid procedures in ASA class 1 and 2 patients. Outcomes were compared between those with and without PLTs. Multivariate regression examined factors predictive of receiving PLTs. Testing costs were calculated. RESULTS: 58.7% of the cohort received PLTs. There were no differences in outcomes between those who were and those who were not tested. Non-white ethnicity, dyspnea, and non-general anesthesia were strongly predictive of receiving PLTs. Over $2.6 million is spent annually on PLTs in this population. CONCLUSIONS: Over half of healthy patients undergoing elective thyroid and parathyroid surgery receive PLTs. Complication rates did not differ between those with and without PLTs. Preoperative testing should be used more judiciously in these patients, which may lead to cost savings.

Rapid detection of SARS-CoV-2 antibodies using electrochemical impedance-based detector.

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was classified as a pandemic by the World Health Organization and has caused over 550,000 deaths worldwide as of July 2020. Accurate and scalable point-of-care devices would increase screening, diagnosis, and monitoring of COVID-19 patients. Here, we demonstrate rapid label-free electrochemical detection of SARS-CoV-2 antibodies using a commercially available impedance sensing platform. A 16-well plate containing sensing electrodes was pre-coated with receptor binding domain (RBD) of SARS-CoV-2 spike protein, and subsequently tested with samples of anti-SARS-CoV-2 monoclonal antibody CR3022 (0.1 µg/ml, 1.0 µg/ml, 10 µg/ml). Subsequent blinded testing was performed on six serum specimens taken from COVID-19 and non-COVID-19 patients (1:100 dilution factor). The platform was able to differentiate spikes in impedance measurements from a negative control (1% milk solution) for all CR3022 samples. Further, successful differentiation and detection of all positive clinical samples from negative control was achieved. Measured impedance values were consistent when compared to standard ELISA test results showing a strong correlation between them (R2=0.9). Detection occurs in less than five minutes and the well-based platform provides a simplified and familiar testing interface that can be readily adaptable for use in clinical settings.

The cost-effectiveness of isavuconazole compared to voriconazole, the standard of care in the treatment of patients with invasive mould diseases, prior to differential pathogen diagnosis in Spain.

BACKGROUND: Invasive mould diseases are associated with high morbidity, mortality and economic impact. Its treatment is often started prior to differential pathogen diagnosis. Isavuconazole is approved for treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM) when amphotericin-B is not indicated. OBJECTIVES: To estimate the cost-effectiveness of isavuconazole vs voriconazole for the treatment of adult patients with possible IA prior to differential pathogen diagnosis, in Spain. METHODS: A decision tree analysis was performed using the Spanish Healthcare System perspective. Among all patients with possible IA, it was considered that 7.81% actually had IM. Costs for laboratory analysis, management of adverse events, hospitalisation and drugs per patient, deaths and long-term effects in life years (LYs) and quality-adjusted LYs (QALYs) were considered. Efficacy data were obtained from clinical trials and utilities from the literature. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: In patients with possible IA and when compared to voricanozole, isavuconazole showed an incremental cost of 4758.53€, besides an incremental effectiveness of +0.49 LYs and +0.41 QALYs per patient. The Incremental Cost Effectiveness Ratio was 9622.52€ per LY gained and 11,734.79€ per QALY gained. The higher cost of isavuconazole was due to drug acquisition. Main parameters influencing results were mortality, treatment duration and hospitalisation days. The PSA results showed that isavuconazole has a probability of being cost-effective of 67.34%, being dominant in 24.00% of cases. CONCLUSIONS: Isavuconazole is a cost-effective treatment compared to voriconazole for patients with possible IA for a willingness to pay threshold of 25,000€ per additional QALY.

A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a newly emerging human infectious disease. Because no specific antiviral drugs or vaccines are available to treat COVID-19, early diagnostics, isolation, and prevention are crucial for containing the outbreak. Molecular diagnostics using reverse transcription polymerase chain reaction (RT-PCR) are the current gold standard for detection. However, viral RNAs are much less stable during transport and storage than proteins such as antigens and antibodies. Consequently, false-negative RT-PCR results can occur due to inadequate collection of clinical specimens or poor handling of a specimen during testing. Although antigen immunoassays are stable diagnostics for detection of past infection, infection progress, and transmission dynamics, no matched antibody pair for immunoassay of SARS-CoV-2 antigens has yet been reported. In this study, we designed and developed a novel rapid detection method for SARS-CoV-2 spike 1 (S1) protein using the SARS-CoV-2 receptor ACE2, which can form matched pairs with commercially available antibodies. ACE2 and S1-mAb were paired with each other for capture and detection in a lateral flow immunoassay (LFIA) that did not cross-react with SARS-CoV Spike 1 or MERS-CoV Spike 1 protein. The SARS-CoV-2 S1 (<5 ng of recombinant proteins/reaction) was detected by the ACE2-based LFIA. The limit of detection of our ACE2-LFIA was 1.86 × 105 copies/mL in the clinical specimen of COVID-19 Patients without no cross-reactivity for nasal swabs from healthy subjects. This is the first study to detect SARS-CoV-2 S1 antigen using an LFIA with matched pair consisting of ACE2 and antibody. Our findings will be helpful to detect the S1 antigen of SARS-CoV-2 from COVID-19 patients.

One-step rapid quantification of SARS-CoV-2 virus particles via low-cost nanoplasmonic sensors in generic microplate reader and point-of-care device.

The spread of SARS-CoV-2 virus in the ongoing global pandemic has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemic. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. As low as 370 vp/mL were detected in one step within 15 min and the virus concentration can be quantified linearly in the range of 0 to 107 vp/mL. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.

The Utility of Preoperative Labs in Predicting Postoperative Complications Following Primary Total Hip and Knee Arthroplasty.

BACKGROUND: Preoperative testing costs billions of dollars despite little evidence supporting its utility. The purpose of this study was to determine the relationship between abnormal preoperative laboratory tests and postoperative complications following total joint arthroplasty. METHODS: The NSQIP database was used to identify 45,936 primary total hip arthroplasty (THA) and 76,041 pri-mary total knee arthroplasty (TKA) cases performed between 2006 and 2013. Complications within 30 days of surgery were collected and multivariable regression modeling was performed incorporating all significant laboratory values as well as demographics and preoperative comorbidities. RESULTS: For THA patients, abnormal sodium (p = 0.016, OR = 1.89), white count (p = 0.043, OR = 1.73), and partial thromboplastin time (p = 0.028, OR = 1.43) were significantly associated with complications. For TKA patients, abnormal alkaline phosphatase (p = 0.04, OR = 2.12), creatinine (p = 0.003, OR = 1.56), and INR (p = 0.008, OR = 1.99) were significantly predictive of complications. CONCLUSION: Of the 13 laboratory values, only six were significantly associated with complications. These findings may have implications for risk stratification in the inpatient setting.

Test Utilization and Value in the Evaluation of Peripheral Neuropathies.

Peripheral neuropathies can be classified as typical or atypical. Patients with atypical neuropathy have one or more of the following features: acute/subacute onset, non-length dependence, motor predominance, or asymmetry. This classification is important because it informs the appropriate diagnostic evaluation of this highly prevalent condition. The evaluation of a typical peripheral neuropathy, also known as distal symmetric polyneuropathy, requires a thorough history, neurologic examination, and focused laboratory testing. Electrodiagnostic testing and MRI account for the majority of costs but rarely lead to changes in diagnosis or management. These costs are increasingly being passed on to patients, especially those with high-deductible health plans. In contrast, patients with atypical neuropathy require more extensive testing, including electrodiagnostic tests. These tests are much more likely to lead to the use of disease-modifying therapies in these patients compared to in those with typical peripheral neuropathy. This article describes two cases to illustrate the appropriate diagnostic workup of those with typical or atypical neuropathy.

Cost-benefit of limited isolation and testing in COVID-19 mitigation.

The international community has been put in an unprecedented situation by the COVID-19 pandemic. Creating models to describe and quantify alternative mitigation strategies becomes increasingly urgent. In this study, we propose an agent-based model of disease transmission in a society divided into closely connected families, workplaces, and social groups. This allows us to discuss mitigation strategies, including targeted quarantine measures. We find that workplace and more diffuse social contacts are roughly equally important to disease spread, and that an effective lockdown must target both. We examine the cost-benefit of replacing a lockdown with tracing and quarantining contacts of the infected. Quarantine can contribute substantially to mitigation, even if it has short duration and is done within households. When reopening society, testing and quarantining is a strategy that is much cheaper in terms of lost workdays than a long lockdown. A targeted quarantine strategy is quite efficient with only 5 days of quarantine, and its effect increases when testing is more widespread.

Facile biosensors for rapid detection of COVID-19.

Currently the world is being challenged by a public health emergency caused by the coronavirus pandemic (COVID-19). Extensive efforts in testing for coronavirus infection, combined with isolating infected cases and quarantining those in contact, have proven successful in bringing the epidemic under control. Rapid and facile screening of this disease is in high demand. This review summarises recent advances in strategies reported by international researchers and engineers concerning how to tackle COVID-19 via rapid testing, mainly through nucleic acid- and antibody- testing. The roles of biosensors as powerful analytical tools are emphasized for the detection of viral RNAs, surface antigens, whole viral particles, antibodies and other potential biomarkers in human specimen. We critically review in depth newly developed biosensing methods especially for in-field and point-of-care detection of SARS-CoV-2. Additionally, this review describes possible future strategies for virus rapid detection. It helps researchers working on novel sensor technologies to tailor their technologies in a way to address the challenge for effective detection of COVID-19.

Cost analysis of implementing HIV drug resistance testing in Kenya: a case study of a service delivery site at a tertiary level hospital in Kenya.

Background: HIV drug resistance (HIVDR) threatens progress achieved in response to the HIV epidemic. Understanding the costs of implementing HIVDR testing programs for patient management and surveillance in resource-limited settings is critical in optimizing resource allocation. Here, we estimate the unit cost of HIVDR testing and identify major cost drivers while documenting challenges and lessons learnt in implementation of HIVDR testing at a tertiary level hospital in Kenya. Methods: We employed a mixed costing approach to estimate the costs associated with performing a HIVDR test from the provider's perspective. Data collection involved a time and motion study of laboratory procedures and interviewing laboratory personnel and the management personnel. Cost analysis was based on estimated 1000 HIVDR tests per year. Data entry and analysis were done using Microsoft Excel and costs converted to US dollars (2019). Results: The estimated unit cost for a HIVDR test was $271.78 per test. The main cost drivers included capital ($102.42, 37.68%) and reagents (101.50, 37.35%). Other costs included: personnel ($46.81, 17.22%), utilities ($14.69, 5.41%), equipment maintenance costs ($2.37, 0.87%) and quality assurance program ($4, 1.47%). Costs in relation to specific laboratory processes were as follows: sample collection ($2.41, 0.89%), RNA extraction ($22.79, 8.38%), amplification ($56.14, 20.66%), gel electrophoresis ($10.34, 3.80%), sequencing ($160.94, 59.22%), and sequence analysis ($19.16, 7.05%). A user-initiated modification of halving reagent volumes for some laboratory processes (amplification and sequencing) reduced the unit cost for a HIVDR test to $233.81 (13.97%) reduction.  Conclusions: Capital expenditure and reagents remain the most expensive components of HIVDR testing. This cost is bound to change as the sequencing platform is utilized towards maximum capacity or leveraged for use with other tests. Cost saving in offering HIVDR testing services is also possible through reagent volume reduction without compromising on the quality of test results.

Evaluation of pooled sample analysis strategy in expediting case detection in areas with emerging outbreaks of COVID-19: A pilot study.

Timely diagnosis of COVID-19 infected individuals and their prompt isolation are essential for controlling the transmission of SARS-CoV-2. Though quantitative reverse transcriptase PCR (qRT-PCR) is the method of choice for COVID-19 diagnostics, the resource-intensive and time-consuming nature of the technique impairs its wide applicability in resource-constrained settings and calls for novel strategies to meet the ever-growing demand for more testing. In this context, a pooled sample testing strategy was evaluated in the setting of emerging disease outbreak in 3 central Indian districts to assess if the cost of the test and turn-around time could be reduced without compromising its diagnostic characteristics and thus lead to early containment of the outbreak. From 545 nasopharyngeal and oropharyngeal samples received from the three emerging districts, a total of 109 pools were created with 5 consecutive samples in each pool. The diagnostic performance of qRT-PCR on pooled sample was compared with that of individual samples in a blinded manner. While pooling reduced the cost of diagnosis by 68% and the laboratory processing time by 66%, 5 of the 109 pools showed discordant results when compared with induvial samples. Four pools which tested negative contained 1 positive sample and 1 pool which was positive did not show any positive sample on deconvolution. Presence of a single infected sample with Ct value of 34 or higher, in a pool of 5, was likely to be missed in pooled sample analysis. At the reported point prevalence of 4.8% in this study, the negative predictive value of qRT-PCR on pooled samples was around 96% suggesting that the adoption of this strategy as an effective screening tool for COVID-19 needs to be carefully evaluated.

Optimising triage procedures for patients with cancer needing active anticancer treatment in the COVID-19 era.

BACKGROUND: Immunosuppression induced by anticancer therapy in a COVID-19-positive asymptomatic patient with cancer may have a devastating effect and, eventually, be lethal. To identify asymptomatic cases among patients receiving active cancer treatment, the Federico II University Hospital in Naples performs rapid serological tests in addition to hospital standard clinical triage for COVID-19 infection. METHODS: From 6 to 17 April 2020, all candidates for chemotherapy, radiotherapy or target/immunotherapy, if negative at the standard clinical triage on the day scheduled for anticancer treatment, received a rapid serological test on peripheral blood for COVID-19 IgM and IgG detection. In case of COVID-19 IgM and/or IgG positivity, patients underwent a real-time PCR (RT-PCR) SARS-CoV-2 test to confirm infection, and active cancer treatment was delayed. RESULTS: Overall 466 patients, negative for COVID-19 symptoms, underwent serological testing in addition to standard clinical triage. The average age was 61 years (range 25-88 years). Most patients (190, 40.8%) had breast cancer, and chemotherapy with or without immunotherapy was administered in 323 (69.3%) patients. Overall 433 (92.9%) patients were IgG-negative and IgM-negative, and 33 (7.1%) were IgM-positive and/or IgG-positive. Among the latter patients, 18 (3.9%), 11 (2.4%) and 4 (0.9%) were IgM-negative/IgG-positive, IgM-positive/IgG-negative and IgM-positive/IgG-positive, respectively. All 33 patients with a positive serological test, tested negative for RT-PCR SARS-CoV-2 test. No patient in our cohort developed symptoms suggestive of active COVID-19 infection. CONCLUSION: Rapid serological testing at hospital admission failed to detect active asymptomatic COVID-19 infection. Moreover, it entailed additional economic and human resources, delayed therapy administrationand increased hospital accesses.

Active testing of groups at increased risk of acquiring SARS-CoV-2 in Canada: costs and human resource needs.

BACKGROUND: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely passive, which impedes epidemic control. We defined active testing strategies for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) for groups at increased risk of acquiring SARS-CoV-2 in all Canadian provinces. METHODS: We identified 5 groups who should be prioritized for active RT-PCR testing: contacts of people who are positive for SARS-CoV-2, and 4 at-risk populations - hospital employees, community health care workers and people in long-term care facilities, essential business employees, and schoolchildren and staff. We estimated costs, human resources and laboratory capacity required to test people in each group or to perform surveillance testing in random samples. RESULTS: During July 8-17, 2020, across all provinces in Canada, an average of 41 751 RT-PCR tests were performed daily; we estimated this required 5122 personnel and cost $2.4 million per day ($67.8 million per month). Systematic contact tracing and testing would increase personnel needs 1.2-fold and monthly costs to $78.9 million. Conducted over a month, testing all hospital employees would require 1823 additional personnel, costing $29.0 million; testing all community health care workers and persons in long-term care facilities would require 11 074 additional personnel and cost $124.8 million; and testing all essential employees would cost $321.7 million, requiring 25 965 added personnel. Testing the larger population within schools over 6 weeks would require 46 368 added personnel and cost $816.0 million. Interventions addressing inefficiencies, including saliva-based sampling and pooling samples, could reduce costs by 40% and personnel by 20%. Surveillance testing in population samples other than contacts would cost 5% of the cost of a universal approach to testing at-risk populations. INTERPRETATION: Active testing of groups at increased risk of acquiring SARS-CoV-2 appears feasible and would support the safe reopening of the economy and schools more broadly. This strategy also appears affordable compared with the $169.2 billion committed by the federal government as a response to the pandemic as of June 2020.