Routine Testing Of Patients Research Articles

Factors associated with immune‑related severe adverse events (Review).

Immune checkpoint inhibitors (ICIs) are frequently used in cancer treatment. Despite their clinical benefits, they can also cause a wide range of immune-related adverse events (ir-AEs). The overall incidence of irAEs in cancer patients treated with immunotherapy ranges from 70-90%, while that of immune-related severe adverse events (ir-SAEs) is 10-43%. ir-SAEs pose a significant risk to patient safety as they are extremely frequent and lethal. Due to non-specific manifestations, rapid progression and significant morbidity, it is essential to identify factors associated with ir-SAEs early to predict high-risk groups for treatment safety. However, less information is available on the factors causing ir-SAEs, and further research is needed. The present study reviews the factors associated with ir-SAEs in terms of demographic characteristics, disease-related information and laboratory examinations to provide a clinical reference. In terms of demographic characteristics, age, body mass index, smoking, ethnicity and cancer family history may influence the incidence of ir-SAEs. Regarding disease-related information, the risks factors associated with ir-SAEs may include disease history, treatment regimen and cancer type. For laboratory examinations, risk factors associated with ir-SAEs include the laboratory examination parameters of peripheral blood cells, immunocytes, cytokines/chemokines, genetics, gut microbia, proteins and brain injury markers. All of these risk factors can stimulate the body's inflammatory response, leading to over proliferation of T cells and other inflammatory factors. In addition, the use of ICIs may disrupt gut microbial homeostasis and dysregulate the pre-existing intestinal ecology, which may therefore trigger inflammatory signaling pathways, affect overall immune function and increase the occurrence of ir-SAEs. In response to the aforementioned risk factors, it is recommended that medical professionals incorporate their analysis into routine patient testing for early identification of patient ir-SAEs and to create early individualized interventions to improve the safety for immunotherapy patients.

Evaluation of the analytical performance of four different manufacturer's reagent red blood cells in antibody detection and identification.

The detection/identification of clinically significant antibodies to red cell antigens form the foundation for safe transfusion practices. This study aimed to evaluate the diagnostic performance of commercially available 0.8% reagent red blood cells (RRBCs) in Australia. 166 patient-derived plasma samples with a positive indirect antiglobulin test (IAT) were tested using column agglutination technology (CAT) with Immulab, Bio-Rad, Grifols and QuidelOrtho screening and identification RRBCs with the respective manufacturer's proprietary CAT system. False-negative antibody screening and identification results were obtained with Bio-Rad (3/61), Grifols (14/68) and Quidel-Ortho (3/59) RRBCs when tested with the respective manufacturer's proprietary CAT system. Zero false-negative results were observed with Immulab RRBCs when tested with samples across all platforms. The sensitivity of the RRBCs used in this study were calculated to be 95.83% (95%CI 88.30-99.13%) for Bio-Rad RRBCs, 82.50% (95%CI 72.38-90.09%) for Grifols RRBCs and 95.65% (95%CI 87.82-99.09%) for QuidelOrtho RRBCs. The sensitivity of Immulab RRBCs were stratified based on performance in the 3 CAT platforms: Bio-Rad CAT (100%, 95%CI 95.01-100%), Grifols CAT (100%, 95%CI 95.49-100%) and QuidelOrtho CAT (100%, 95%CI 94.79-100%). RRBCs used in antibody detection and identification vary in diagnostic performance and should therefore be carefully considered before being implemented in routine patient testing.

Serum Protein Electrophoresis Bands As Biomarkers for Drug-Sensitive Pulmonary Tuberculosis.

India has the highest cases of tuberculosis worldwide. According to WHO (2022), the incidence of tuberculosis in India is 210 per 100,000 population. Their incidence of new positive smear cases is 75 per 100,000 population per year. In tuberculosis, the level of albumin decreases while globulin increases leading to a low albumin to globulin (A/G) ratio, and electrophoresisof serum proteins aregood diagnostic approach and provides essential information for monitoring treatment outcomes. The present study includes 50 cases of pulmonary tuberculosis and 50 age-sex-matched healthy controls. Initially, serum protein estimation and electrophoresis were performed in newly diagnosed patients and controls. All drugs were given as National Tuberculosis Elimination Programme (NTEP) guidelines and blood samples were collected at two-month, four-month, and six-month intervals, and different serum protein fractions were compared and analyzed. The total serum protein was significantly lower in the cases than in the controls; 6.12±0.61 vs. 7.02±0.56 g/dL (p˂0.0020, t-value=3.12). The mean serum albumin was also significantly lower in the cases compared to the controls; 1.65±0.69 vs. 3.87±0.47g/dL (p˂0.0001, t-value=10.98). The α1 globulin started to rise after four months of treatment and at six months level was 0.262±0.32 g/dL. The level of γ globulin continuously decreases after antituberculous treatment to 1.56±0.67 gm/dL at six months. The cause of the decrease in total protein and albumin may be due to malnutrition leading to low cellular immunity. Serum protein leveland protein electrophoresis should be analyzed as routine tests inpatients before, during, and after treatment.It helps us in identifying patients at risk of pulmonary tuberculosis as well prognosis of the disease.This study is avaluable guide in deciding the effective management of tuberculosis patients with drug treatment plans and appropriate dietary intake. Hence, it highlights the complex relationship that exists between poverty and disease.

Serological testing for syphilis in the differential diagnosis of cognitive decline and polyneuropathy in geriatric patients

BackgroundIn the 19th century, neurosyphilis was the most frequent cause of dementia in Western Europe. Now dementia caused by syphilis has become rare in Germany. We studied whether routine testing of patients with cognitive abnormalities or neuropathy for antibodies against Treponema pallidum has therapeutic consequences in geriatric patients.MethodsA Treponema pallidum electrochemiluminescence immunoassay (TP-ECLIA) is routinely performed in all in-patients treated at our institution with cognitve decline or neuropathy and no or insufficient previous diagnostic workup. Patients with a positive TP-ECLIA treated from October 2015 to January 2022 (76 months) were retrospectively evaluated. In cases of positive TP-ECLIA, further specific laboratory investigations were performed to assess whether antibiotic therapy was indicated.ResultsIn 42 of 4116 patients (1.0%), TP-ECLIA detected antibodies directed against Treponema in serum. Specifity of these antibodies was ensured by immunoblot in 22 patients (11 × positiv, 11 × borderline values). Treponema-specific IgM was detectable in the serum of one patient, in 3 patients the Rapid Plasma Reagin (RPR) test, a modified Venereal Disease Research Laboratory test (VDRL), in serum was positiv. CSF analysis was performed in 10 patients. One patient had CSF pleocytosis. In 2 other patients, the Treponema-specific IgG antibody index was elevated. 5 patients received antibiotic therapy (4 × ceftriaxone 2 g/d i.v., 1 × doxycycline 300 mg/d p.o.).ConclusionIn approx. 1‰ of patients with previously undiagnosed or not sufficiently diagnosed cognitive decline or neuropathy, the diagnostic workup for active syphilis resulted in a course of antibiotic treatment.

Optimized Detection of Unknown MET Exon 14 Skipping Mutations in Routine Testing for Patients With Non-Small-Cell Lung Cancer.

MET exon 14 (METex14) skipping is an actionable biomarker in non-small-cell lung cancer. However, MET variants are highly complex and diverse, and not all variants lead to exon 14 skipping. Assessing the skipping effect of unknown variants is still a key issue in molecular diagnosis. We retrospectively collected MET variants around exon 14 from 4,233 patients with non-small-cell lung cancer who underwent next-generation sequencing testing using DNA, as well as two published data sets. Among the 4,233 patients, 44 unique variants including 29 novel variants (65.9%) were discovered from 53 patients. Notably, 31 samples (58.5%) failed RNA verification. Using RNA verification, nine novel skipping variants and five nonskipping variants were confirmed. We further used SpliceAI with the delta score cutoff of 0.315 to aid the classification of novel variants (sensitivity = 98.88% and specificity = 100%). When applied to the reported variants, we also found three wrongly classified nonskipping variants. Finally, an optimized knowledge-based interpretation procedure for clinical routine was built according to the mutation type and location, and five more skipping mutations from the 13 unknown variants were determined, which improved the population determination rate to 0.92%. This study discovered more METex14 skipping variants and optimized an innovative approach that could be adapted for the interpretation of infrequent or novel METex14 variants timely without experimental validation.

Estimation of Reference Intervals from Routine Data Using the refineR Algorithm-A Practical Guide.

Accurate reference intervals are essential for the interpretation of laboratory test results. Typically, they are determined by the central 95% range of test results from a predefined reference population. As these direct studies can face practical and ethical challenges, indirect methods using routine measurements offer an alternative approach. We provide step-by-step guidance on how to apply an indirect method in practice using refineR, the most recently published indirect method, and showcase the application by evaluating real-world data of 12 prespecified analytes. Measurements were retrieved from ARUP Laboratories' data warehouse, and were obtained from routine patient testing on cobas c502 or e602 analyzers. Test results were prefiltered and cleaned and, if necessary, physiologically partitioned prior to estimating reference intervals using refineR. Estimated reference intervals were then compared to established intervals provided by the manufacturer. For most analytes, the reference intervals estimated by refineR were comparable to those provided by the manufacturer, shown by overlapping confidence intervals at both reference limits, or only the upper or lower limit. For thyroid-stimulating hormone, refineR estimated higher reference limits, while estimates for prealbumin were lower compared to the established reference interval. We applied the refineR algorithm to a variety of real-world data sets resulting in reference intervals similar to intervals previously established by direct methods. We further provide practical guidance and a code example on how to apply an indirect method in a real-world scenario facilitating their access and thus their use in laboratory settings.

Prevalence and Associated Factors of Cryptococcal Antigenemia in HIV-Infected Patients with CD4 < 200 Cells/µL in São Paulo, Brazil: A Bayesian Analysis

Cryptococcosis is a severe life-threatening disease and a major cause of mortality in people with advanced AIDS and CD4 ≤ 100 cells/µL. Considering the knowledge gap regarding the benefits of routine application of antigenemia tests in HIV-infected patients with 100−200 CD4 cells/µL for the prevention of cryptococcal meningitis (CM), we aimed to evaluate the prevalence of positive antigenemia through lateral flow assay (LFA) and associated factors in HIV-infected patients with CD4 < 200 cells/µL. Our findings of 3.49% of positive LFA (LFA+) patients with CD4 < 100 cells/µL and 2.24% with CD4 between 100−200 cells/µL have been included in a Bayesian analysis with 12 other studies containing similar samples worldwide. This analysis showed a proportion of 3.6% LFA+ patients (95% credible interval-Ci [2.5−5.7%]) with CD4 < 100 cells/µL and 1.1% (95%Ci [0.5−4.3%]) with CD4 between 100−200 cells/µL, without statistical difference between these groups. The difference between mortality rates in LFA+ and negative LFA groups was e = 0.05013. Cryptococcoma and CM were observed in the LFA+ group with 100−200 and <100 CD4 cells/µL, respectively. Considering the benefits of antifungal therapy for LFA+ patients, our data reinforced the recommendation to apply LFA as a routine test in patients with 100−200 CD4 cells/µL aiming to expand cost-effectiveness studies in this group.

EP16.03-011 The European Program for ROutine Testing of Patients with Advanced Lung Cancer (EPROPA) 1 Year Activity

To fill the gap affecting the relevant heterogeneity of molecular testing and cancer care across Europe, the Women Against Lung Cancer Europe (WALCE) Association promoted the European Program for Routine testing of Patients with Advanced lung cancer (EPROPA) and provides a molecular screening platform for NSCLC samples characterization with the aim of increasing the detection of targetable drivers and optimizing patients’ access to clinical trials.

Public Interest in Population Genetic Screening for Cancer Risk.

An emerging role for DNA sequencing is to identify people at risk for an inherited cancer syndrome in order to prevent or ameliorate the manifestation of symptoms. Two cancer syndromes, Hereditary Breast and Ovarian Cancer and Lynch Syndrome meet the “Tier 1” evidence threshold established by the Centers for Disease Control and Prevention (CDC) for routine testing of patients with a personal or family history of cancer. Advancements in genomic medicine have accelerated public health pilot programs for these highly medically actionable conditions. In this brief report, we provide descriptive statistics from a survey of 746 US respondents from a Qualtrics panel about the public’s awareness of genetic testing, interest in learning about their cancer risk, and likelihood of participating in a population genetic screening (PGS) test. Approximately of half the respondents were aware of genetic testing for inherited cancer risk (n = 377/745, 50.6%) and would choose to learn about their cancer risk (n-309/635, 48.7%). Characteristics of those interested in learning about their cancer risk differed by educational attainment, age, income, insurance status, having a primary care doctor, being aware of genetic testing, and likelihood of sharing information with family (p < 0.05). A sizeable majority of the respondents who were interested in about learning their cancer risk also said that they were likely to participate in a PGS test that involved a clinical appointment and blood draw, but no out-of-pocket cost (n = 255/309, 82.5%). Reasons for not wanting to participate included not finding test results interesting or important, concerns about costs, and feeling afraid to know the results. Overall, our results suggest that engaging and educating the general population about the benefits of learning about an inherited cancer predisposition may be an important strategy to address recruitment barriers to PGS.

Cyclopentane peptide nucleic acid: Gold nanoparticle conjugates for the detection of nucleic acids in a microfluidic format.

Routine patient testing for viral infections is critical to identify infected individuals for treatment and to prevent spreading of infections to others. Developing robust and reliable diagnostic tools to detect nucleic acids of viruses at the point-of-care could greatly assist the clinical management of viral infections. The remarkable stability and high binding affinity of peptide nucleic acids (PNAs) to target nucleic acids could make PNA-based biosensors an excellent starting point to develop new nucleic acid detection technologies. We report the application of cyclopentane-modified PNAs to capture target nucleic acids in a microfluidic channel, and the use of bioorthogonal PNAs conjugated to gold nanoparticles as probes to semi-quantitatively signal the presence of a target nucleic acid derived from HIV-1. The basic results presented could be used to develop more advanced devices to detect nucleic acids from viruses such as HIV, SARS-CoV-2, and a wide range of other human diseases.

1368TiP EPROPA: The European program for routine testing of patients with advanced lung cancer

Lung cancer represents a successful example of precision medicine application in medical oncology, since the introduction of routine molecular testing and targeted therapies into clinical practice has significantly contributed to decrease non-small cell lung cancer (NSCLC) patients’ mortality worldwide. International guidelines recommend the routine use of next generation sequencing (NGS) as new standard approach to profile advanced lung adenocarcinoma samples, with the aim of identifying targetable driver mutations that allow patients’ access to effective targeted drugs either available in daily practice or in the context of clinical trials.

Antiphospholipid Antibodies and Infection: Non Nova Sed Nove.

The clinical significance of antiphospholipid antibodies (aPL) in the context of infections has attracted attention since their first discovery in patients with syphilis. In fact, the recognition of aPL in patients with infections has been described in parallel to the understating of the syndrome. Since the first description of aPL-positive tests in three patients with COVID-19 diagnosed in January 2020 in Wuhan, China, a large number of studies took part in the ongoing debate on SARS-2-Cov 2 induced coagulopathy, and many following reports speculated a potential role for aPL. In order to get further insights on the effective role of detectable aPL in the pro-thrombotic status observed in COVID-19 patients, we performed an observational age-sex controlled study to compare the aPL profile of hospitalized patients with COVID with those observed in a) patients with thrombotic APS and b) patients with cultural/serologically-proved infections. Our data showed positive aPL testing in about half of the patients (53%) with COVID-19 and patients with other viral/bacterial infections (49%). However, aPL profile was different when comparing patients with overt APS and patients with aPL detected in the contest of infections. Caution is therefore required in the interpretation and generalization of the role of aPL s in the management of patients with COVID-19. Before introducing aPL testing as a part of the routine testing in patients with COVID-19, larger well-designed clinical studies are required. While the pro-thrombotic status in patients with COVID-19 is now unquestionable, different mechanisms other than aPL should be further investigated.

SARS-CoV-2 diagnostics: Towards a more comprehensive approach to routine patient testing

The SARS-CoV-2 pandemic has provided the stimulus for the rapid development of a variety of diagnostic testing methods. Initially these were deployed as screening tools to evidence spread of the virus within populations. The recent availability of vaccines against the virus and the need to better understand the parameters of post-infection protective immunity requires development of methods, suitable for use in the routine diagnostic laboratory, capable of characterising the viral immune response in greater detail. Such methods need to consider both cellular and humoral immunity. Toward this aim we have investigated use of a commercial multiplex assay (COVID Plus Assay, One Lambda), providing assessment of the SARS-CoV-2 response at structural level, and developed an in-house cell stimulation assay using commercially available viral peptides (Miltenyi). This paper reports our experience in use of these methods in extended investigation of a cohort of healthcare workers with prior screening results indicative of viral infection. The antibody response generated is shown to be both qualitatively and quantitatively different in different individuals. Similarly a recall response to SARS-CoV-2 antigen involving the T cell compartment can be readily demonstrated in recovered individuals but is of variable magnitude.

Future-proof Radiation therapist (RTT) practice in a pandemic - Lessons learnt from COVID-19.

The European SocieTy for Radiotherapy and Oncology Radiation Therapist Committee (ESTRO RTTC) published a guidance document and infographic providing recommendations to minimise risk of COVID-19 transmission in radiotherapy (RT) departments. The purpose of this study was to investigate the changes embedded in RT practice in the COVID-19 era and to recommend proactive measures to protect RT practice in future pandemics. The study was initiated by the ESTRO Radiation Oncology Safety and Quality Committee (ROSQC). A survey consisting of multiple choice, open ended and Likert scale questions was created to analyse the extent of changes embedded in RT practice in response to the COVID-19 pandemic under the four domains: patient care, RTT workflow, remote working and RT practice. This online survey was distributed globally in May 2020. 229 respondents across 27 countries completed the survey. 60% of respondents reported continuing/commencing RT in COVID-19 patients. Routine testing of patients and RTTs was not common. Split teams' procedures, hot linacs and separate entrances were implemented by 50% of respondents. Remote working was implemented for RT team members where face to face patient contact was not essential. Lack of staff, connectivity issues and lack of confirmed positive cases in the department were the main reasons cited for not implementing recommended measures. It is suggested that RT departments have responded to the COVID-19 pandemic and implemented certain changes in RT practice. RT departments should act now to implement recommended proactive measures to protect patients and RTTs - frontline healthcare workers.

Use of point-of-care testing for respiratory viruses in hospital

In The Lancet Respiratory Medicine, Tristan Clark and colleagues report the results of a randomised controlled trial of point-of-care testing for influenza in patients in two UK hospitals in Hampshire, UK.1 Before the emergence of COVID-19, influenza was the most important cause of admission to hospital with a respiratory virus. In England, influenza is estimated to have caused an average of 11 300 deaths per year between the 2015–16 and 2019–20 influenza seasons.2 Influenza often goes undiagnosed in hospital, in part because of an absence of routine testing of patients with respiratory illness in this setting.

Primary Diagnostic Tools for SARS-Cov-2 Infection (COVID-19): Current Challenge

Pandemic outbreaks are always a challenge for the health care management to hold the mortality rate when preventive measures are not established. The only solution is to control the spread by conducting massive screening and isolating affected ones from the healthy ones. The research concentration is to develop rapid diagnostics and screening at lower cost. Rapid diagnostic methods are being used and developed worldwide.Multiple studies suggest that RT-PCR, protein testing and CT should be the principal diagnostic instrument for routine testing in patients with COVID-19. But three factors are still indistinct in those diagnostic methods such as rapidity, sensitivity, and specificity. Thus, alternative approaches that provide higher efficiency and lower time requirement are highly appreciated for switching the super spread infectious disease detection.Moderntimes, microfluidics alternatively called lab on a chip or POCT have been widely used in cancer and viral detection, specifically for virus detection in very recent days. The ability of POCT tests to provide short time results,suitable in low resource clinics even at home. So, we saw the importance of miniaturized tools suitable for COVID-19 detection will endure the current expensive methods. Despite the limitations, approved tests are still experiencing good results against a great pandemic. We reviewed and highlighted the point of care testing (PCOT) method is not less than any other screening method by reviewing a wide research setting.

Biosafety Risk Assessment of a Clinical Biochemistry Laboratory for SARS-CoV-2 Infection

INTRODUCTION: Clinical laboratories are a transfer point for infected patient samples. According to the World Health Organization (WHO) Biosafety Guideline, a risk assessment approach is the backbone of laboratory biosafety. In laboratories, risk assessment is recommended at predetermined periods and in the event of new circumstances. On February 12, 2020, the WHO published an interim guidance document, Laboratory biosafety guidance related to the novel coronavirus (2019-nCoV) and it was highly recommended that all coronavirus 2019 (COVID-19) testing procedures be performed based on a local risk assessment. This study was designed to evaluate the biosafety risk in a biochemistry laboratory where routine testing of patients diagnosed with COVID-19 is performed. METHODS: Risk assessment for tests performed on analyzers and a complete urinalysis was performed using the risk assessment template included in the subsequent WHO interim guidance document, “Laboratory biosafety guidance related to coronavirus disease (COVID-19).” RESULTS: The overall initial risk for tests performed on analyzers and a complete urinalysis test was determined to be very high. Processes such as pipetting a sample and checking a sample tube by scanning the barcode during tests performed on analyzers were suspended until additional risk control measures could be implemented. The manual microscopic urinalysis process was also discontinued. To reduce the risk, surgical masks, surgical caps, eye protection, and disposable laboratory coats were added to the previously mandated personal protective equipment. After implementing additional risk control measures, the total residual risk of both processes was graded medium. DISCUSSION AND CONCLUSION: Since there is as yet no effective treatment for COVID-19, exposure risk is considered severe. Therefore, the probability of exposure is important in determining the level of risk. Measures put in place reduced the total residual risk.

SAT-733 Improving the Diagnosis, Treatment, and Prevention of Endocrine Diseases Through Accurate and Reliable Laboratory Measurements with CDC’s Clinical Standardization Programs

Laboratory measurements are critical for the correct diagnosis and treatment of patients as well as in the investigation of chronic diseases such as hypogonadism, PCOS, and bone-and kidney-related diseases. Inaccurate measurements can lead to misclassification of patients and incorrect treatment. Furthermore, the effective use of research findings in patient care is prevented. The CDC Clinical Standardization Programs (CDC CSP) assess the analytical performance of assays against performance goals defined by clinical and medical organizations. The CDC CSP assist with assay calibration, the certification of analytical performance, and the monitoring of analytical performance during the measurement of patient and/or study samples. CDC CSP have programs in place for the calibration and certification of commercial assays and laboratory developed tests (LDTs) for total testosterone (TT), estradiol (E2), vitamin D (VD), free thyroxine (FT4), total cholesterol (TC), total glycerides (TG), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C). The programs available for monitoring analytical performance during routine testing include TT, VD, TC, TG, HDL-C, apolipoprotein AI and B. CDC CSP also support accuracy-based external quality assurance surveys such as those offered by the College of American Pathologists. Enrollment of assays and LDTs in CDC’s certification programs has resulted in improvements in calibration accuracy; i.e. the absolute mean bias of assays participating in the CDC Vitamin D Standardization Certification Program was well below the allowable bias of 5% each year. Assays standardized in CDC’s certification programs also demonstrated higher accuracy in routine patient testing; i.e. CDC VD certified assays have a lower bias compared to non-certified assays. Similar observations were made with assays certified in the CDC’s program for TT. Monitoring data over the past 10 years from the CDC Lipid Standardization Program indicated that the majority of TC measurements performed in routine testing were consistently within the recommended bias limits of ±3%. CDC CSP continue to improve the analytical performance of assays by addressing measurement bias caused by factors other than incorrect calibration such as interfering compounds. The programs are responding to new clinical and public health needs with the addition of new analytes such as PTH and glucose. The CDC CSP support projects aiming at establishing reference intervals and other research studies. The CDC CSP work with stakeholders, such as the Partnership for the Accurate Testing of Hormones and the Endocrine Society, to educate the clinical and laboratory communities about the importance of using standardized assays in patient care, research, and public health.

Frequency of Sexually Transmitted Infection/HIV Testing Among Commercially Insured Patients With International Classification of Disease Tenth Revision Specified Sex Partners.

High-risk sexual behaviors (HRSB) are associated with sexually transmitted infections (STIs). The Centers for Disease Control and Prevention and US Preventive Services Task Force recommend routine testing for patients with HRSB. Providers can classify patients with HRSB based on the sex of their sex partners using the International Classification of Disease Tenth Revision. We analyzed STI/human immunodeficiency virus (HIV) testing frequencies among patients with HRSB. This study used a large US administrative outpatient medical claims data set from 2015 to 2017. Patients aged 15 to 64 years were identified with HRSB using International Classification of Disease Tenth Revision codes. An initial HRSB diagnosis in 2016 served as the index date. We assessed chlamydia, gonorrhea, syphilis, and HIV testing by HRSB at the index date, and 4 time intervals of 1 to 6 months, and 7 to 12 months before and after the index date. We identified 52,160 patients with HRSB: 90.3% were patients with opposite-sex partners, 7.7% patients with same-sex partners, and 2.1% patients with same- and opposite-sex partners. There were 77.5% and 82.1% of the patients insured 6 months before and after the index, respectively. On the index date, patients with opposite-sex partners tested most for chlamydia (65.3%) and gonorrhea (65.2%), patients with same-sex partners tested most for syphilis (51.5%) and HIV (57.8%). Among insured patients, follow-up STI/HIV testing was 89.5% during 1 to 6 months and 33.1% during 7 to 12 months after the index date. Patients tested on the index date were more likely to have an STI/HIV test within 1 to 6 months after the index date. The STI/HIV testing among patients with HRSB could improve. It is important for patients identified as HRSB to get tested and continue testing patients based on recommendations.

Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules.

Thyroid nodules are very common in general medical practice, but rarely turn out to be a medullary thyroid carcinoma (MTC). Calcitonin is a sensitive tumour marker for the detection of MTC (basal calcitonin). Sometimes a stimulation test is used to improve specificity (stimulated calcitonin). Although the European Thyroid Association's guideline advocates calcitonin determination in people with thyroid nodules, the role of routine calcitonin testing in individuals with thyroid nodules is still questionable. The objective of this review was to determine the diagnostic accuracy of basal and/or stimulated calcitonin as a triage or add-on test for detection of MTC in people with thyroid nodules. We searched CENTRAL, MEDLINE, Embase and Web of Science from inception to June 2018. We included all retrospective and prospective cohort studies in which all participants with thyroid nodules had undergone determination of basal calcitonin levels (and stimulated calcitonin, if performed). Two review authors independently scanned all retrieved records. We extracted data using a standard data extraction form. We assessed risk of bias and applicability using the QUADAS-2 tool. Using the hierarchical summary receiver operating characteristic (HSROC) model, we estimated summary curves across different thresholds and also obtained summary estimates of sensitivity and specificity at a common threshold when possible. In 16 studies, we identified 72,368 participants with nodular thyroid disease in whom routinely calcitonin testing was performed. All included studies performed the calcitonin test as a triage test. Median prevalence of MTC was 0.32%. Sensitivity in these studies ranged between 83% and 100% and specificity ranged between 94% and 100%. An important limitation in 15 of the 16 studies (94%) was the absence of adequate reference standards and follow-up in calcitonin-negative participants. This resulted in a high risk of bias with regard to flow and timing in the methodological quality assessment. At the median specificity of 96.6% from the included studies, the estimated sensitivity (95% confidence interval (CI)) from the summary curve was 99.7% ( 68.8% to 100%). For the median prevalence of MTC of 0.23%, the positive predictive value (PPV) for basal calcitonin testing at a threshold of 10 pg/mL was 7.7% (4.9% to 12.1%). Summary estimates of sensitivity and specificity for the threshold of 10 pg/mL of basal calcitonin testing was 100% (95% CI 99.7 to 100) and 97.2% (95% CI 95.9 to 98.6), respectively. For combined basal and stimulated calcitonin testing, sensitivity ranged between 82% and 100% with specificity between 99% and 100%. The median specificity was 99.8% with an estimated sensitivity of 98.8% (95% CI 65.8 to 100) . Both basal and combined basal and stimulated calcitonin testing have a high sensitivity and specificity. However, this may be an overestimation due to high risk of bias in the use and choice of reference standard The value of routine testing in patients with thyroid nodules remains questionable, due to the low prevalence, which results in a low PPV of basal calcitonin testing. Whether routine calcitonin testing improves prognosis in MTC patients remains unclear.