Clinical Utility Of Test Research Articles

Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study

Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening. In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without signs or symptoms of cancer consented to MCED testing. We collected blood, analysed cfDNA, and returned results to participants' doctors. If a methylation signature indicative of cancer was detected, predicted cancer signal origin(s) informed diagnostic assessment. The primary outcome was time to, and extent of, diagnostic testing required to confirm the presence or absence of cancer. This trial is registered at ClinicalTrials.gov, NCT04241796, and is completed. Between Dec 12, 2019, and Dec 4, 2020, we recruited 6662 participants. 4204 (63·5%) of 6621 participants with analysable results were women, 2417 (36·5%) were men, and 6071 (91·7%) were White. A cancer signal was detected in 92 (1·4%) of 6621 participants with analysable results. 35 (38%) participants were diagnosed with cancer (true positives) and 57 (62%) had no cancer diagnosis (false positives). Excluding two participants whose diagnostic assessments began before MCED test results were reported, median time to diagnostic resolution was 79 days (IQR 37-219): 57 days (33-143) in true-positive and 162 days (44-248) in false-positive participants. Most participants had both laboratory tests (26 [79%] of 33 with true-positive results and 50 [88%] of 57 with false-positive results) and imaging (30 [91%] of 33 with true-positive results and 53 [93%] of 57 with false-positive results). Fewer procedures were done in participants with false-positive results (17 [30%] of 57) than true-positive results (27 [82%] of 33) and few had surgery (one with a false-positive result and three with a true-positive result). This study supports the feasibility of MCED screening for cancer and underscores the need for further research investigating the test's clinical utility. GRAIL.

Determining the clinical utility of a breath test for screening an asbestos-exposed population for pleural mesothelioma: baseline results

Pleural mesothelioma (PM) is an aggressive cancer of the serosal lining of the thoracic cavity, predominantly caused by asbestos exposure. Due to nonspecific symptoms, PM is characterized by an advanced-stage diagnosis, resulting in a dismal prognosis. However, early diagnosis improves patient outcome. Currently, no diagnostic biomarkers or screening tools are available. Therefore, exhaled breath was explored as this can easily be obtained and contains volatile organic compounds, which are considered biomarkers for multiple (patho)physiological processes. A breath test, which differentiates asbestos-exposed (AEx) individuals from PM patients with 87% accuracy, was developed. However, before being implemented as a screening tool, the clinical utility of the test must be determined. Occupational AEx individuals underwent annual breath tests using multicapillary column/ion mobility spectrometry. A baseline breath test was taken and their individual risk of PM was estimated. PM patients were included as controls. In total, 112 AEx individuals and six PM patients were included in the first of four screening rounds. All six PM patients were correctly classified as having mesothelioma (100% sensitivity) and out of 112 AEx individuals 78 were classified by the breath-based model as PM patients (30% specificity). Given the large false positive outcome, the breath test will be repeated annually for three more consecutive years to adhere to the ‘test, re-test’ principle and improve the false positivity rate. A low-dose computed tomography scan in those with two consecutive positive tests will correlate test positives with radiological findings and the possible growth of a pleural tumor. Finally, the evaluation of the clinical value of a breath-based prediction model may lead to the initiation of a screening program for early detection of PM in Aex individuals, which is currently lacking. This clinical study received approval from the Antwerp University Hospital Ethics Committee (B300201837007).

Assessing the clinical utility of toxicology testing in the peripartum period

Toxicology testing is frequently used as a means of gathering objective data about substance use in pregnancy, but little is known about the clinical utility of testing in the peripartum setting. This study aimed to characterize the utility of obtaining maternal-neonatal dyad toxicology testing at the time of delivery. We performed a retrospective chart review of all deliveries in a single healthcare system in Massachusetts between 2016 and 2020, and identified deliveries with either maternal or neonatal toxicology testing at delivery. An unexpected result was defined as a positive test for a nonprescribed substance that was not known on the basis of clinical history, self-report, or previous toxicology testing within a week of delivery, excluding results for cannabis. We evaluated the characteristics of maternal-infant dyads with unexpected positive results, unexpected positive results by rationale for testing, changes in clinical management after an unexpected positive test, and maternal outcomes in the year after delivery using descriptive statistics. Of the 2036 maternal-infant dyads with toxicology tests performed during the study period, there were 80 (3.9%) with an unexpected positive result. Diagnosis of substance use disorder with active use in the last 2 years was the clinical rationale for testing that yielded the greatest number of unexpected positive results (10.7% of total tests ordered for this rationale). Inadequate prenatal care (5.8%), maternal use of medication for opioid use disorder (3.8%), maternal medical indications such as hypertension or placental abruption (2.3%), history of substance use disorder in remission (1.7%), or maternal cannabis use (1.6%) yielded lower rates of unexpected results compared with a recent substance use disorder (within the last 2 years). Solely on the basis of findings from unexpected test results, 42% of dyads were referred to child protective services, 30% of dyads had no documentation of maternal counseling during delivery hospitalization, and 31% did not receive breastfeeding counseling after an unexpected test; 22.8% had monitoring for neonatal opioid withdrawal syndrome. Postpartum, 26 (32.5%) were referred to substance use disorder treatment, 31 (38.8%) attended a postpartum mental health visit, and only 26 (32.5%) attended a postpartum visit. Fifteen individuals (18.8%) were readmitted in the year after delivery, all for substance-related medical complications. Unexpected positive toxicology results at delivery were uncommon, particularly when tests were sent for frequently used clinical rationales for testing, suggesting a need to revisit guidelines surrounding appropriateness of indications for toxicology testing. The poor maternal outcomes in this cohort highlight a missed opportunity for maternal connection to counseling and treatment in the peripartum period.

The Practice and Clinical Utility of Trace Metal Testing for Hematology Patients: A Retrospective Cohort Study

Introduction: Trace metals play a critical role in human physiology and pathology. Deficiencies or toxicities in trace metals are associated with hematologic abnormalities and disorders and are included in the investigation of some hematology patients. For example, lead, copper and zinc levels may be included in the work-up of patients with unexplained anemia. The practice and clinical utility of these trace metal testing in unselected patients referred to hematology, however, are not well described. We examined the current practice of trace metal testing including lead, copper, and zinc, in hematology patients at a single tertiary care centre with the goal of informing future laboratory utilization of these investigations by hematologists. Methods: We investigated all adult patients who underwent trace metal testing ordered by hematologists between January 1, 2017, to December 31, 2021, at London Health Science Centre in London, Ontario, Canada. A retrospective chart review was performed to extract clinical and laboratory data including lead (whole blood), copper (plasma) and zinc (plasma) levels. Abnormal trace metal results were defined based on standard laboratory reference ranges. Primary outcomes were indications for trace metal testing and frequency of abnormal tests. Secondary outcomes included associated occupational exposures and clinical utility of testing, defined as the proportion of patients with an abnormal result that impacted diagnosis or management (including interventions such as advice to reduce exposures or initiate treatment such as chelation therapy or supplementation). Results: Preliminary results on 102/189 patients within our defined cohort revealed mean age 58 years with 32 men and 70 women tested for trace metals (Table 1a). Common indications for testing of each metal included work up for cytopenias, most commonly anemia (Table 1b). The three most common trace metals tested were 48/102 (47%) lead, 91/102 (89%) zinc, and 93/102 (91%) copper. Abnormal results were identified in 49 (48%) of the 102 patients with 12/48 (25%) in lead, 39/91 (42.9%) in zinc, and 9/93 (9.7%) copper testing. For lead, all abnormal results were toxicities, all abnormal results for zinc were deficiencies, and abnormal results for copper had a mix of both deficiencies and toxicities. Clinical utility was identified in one patient (8.3%) with an abnormal lead level, three (5.1%) with abnormal zinc levels, but none in the copper group. The single occupational exposure identified was toxic lead (greater than 50 times the upper limit of normal) in a patient with normal blood counts who made lead bullets. Data analysis for the full cohort is in progress and will be presented in the future. Conclusion: In this single-centre retrospective study, we characterized the use of trace metal testing for lead, zinc and copper deficiencies and toxicities by hematologists. Abnormal levels in these three metals are relatively common (48% for the entire cohort) with the highest frequency in zinc (43%) and lead (25%). However, despite the identification of abnormal results, clinical utility was low as management of patients with abnormal levels were not affected. This may indicate that the level of abnormality was trivial and did not require intervention in the majority of these identified. With this preliminary data, we speculate that some trace metal testing may be ordered as a non-specific panel of laboratory investigations for various indications and slightly abnormal results do not lead to any change in clinical management. Further investigations to explore the degree of trace metal level abnormalities and the impact on clinical diagnosis and management in these hematology patients are underway. The role of trace metal testing, the relationship between abnormal trace metal results and cytopenias such as anemia and impact on management will help to inform future clinical practice in hematology. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Impact of COVID-19 on Laboratory Test Utilization at a Pediatric Medical Center.

BackgroundThe epidemiology and clinical manifestation of coronavirus disease 2019 (COVID-19) in the pediatric population is different from the adult population. The purpose of this study is to identify effects of the COVID-19 pandemic on laboratory test utilization in a pediatric hospital.MethodsWe performed retrospective analysis on test utilization data from Ann & Robert H. Lurie Children’s Hospital of Chicago, an academic pediatric medical center. Data between two 100-day periods prior to (prepandemic) and during the pandemic (mid-pandemic) were analyzed to evaluate changes in test volume, lab utilization, and test positivity rate. We also evaluated these metrics based on in- vs outpatient testing and performed modeling to determine what variables significantly impact the test positivity rate.ResultsDuring the pandemic period, there was an expected surge in COVID-19 testing, while over 84% of lab tests studied decreased in ordering volume. The average number of tests ordered per patient was not significantly different during the pandemic for any of the laboratories (adjusted P value > 0.05). Thirty-three studied tests showed significant change in positivity rate during the pandemic. Linear modeling revealed test volume and inpatient status as the key variables associated with change in test positivity rate.ConclusionsExcluding severe acute respiratory syndrome coronavirus 2 tests, the COVID-19 pandemic has generally led to decreased test ordering volume and laboratory utilization. However, at this pediatric hospital, the average number of tests performed per patient and test positivity rates were comparable between pre- and mid-pandemic periods. These results suggest that, overall, clinical test utilization at this site remained consistent during the pandemic.

Exploring the effects of genomic testing on fear of cancer recurrence among breast cancer survivors.

Fear of cancer recurrence (FCR) is the greatest unmet psychosocial need among breast cancer survivors (BCS). The Oncotype Dx® test predicts the 10-year risk of distant recurrence and benefit of adjuvant chemotherapy among women with early stage hormone receptor-positive breast cancer. Despite the test's clinical utility, psychosocial responses are poorly understood. A descriptive cross-sectional study was conducted to explore associations between Oncotype Dx® test results (Recurrence Score [RS]) and FCR, health-related quality of life (HRQOL), distress, anxiety, depression, illness representation and perceived risk. Bivariate analyses were used to examine the associations between variables followed by multiple linear regression to examine predictors of FCR. Greater FCR was associated with higher distress, anxiety, depression, illness representation and poorer HRQOL. BCS's with a high Oncotype Dx® RS reported higher overall fear (p=0.013) and greater perceived consequences of their cancer (p=0.034) compared to BCS's with a low RS. Using multiple linear regression, anxiety ( =0.21, p=0.016), greater emotional response =0.45, p<0.001) and perceived consequences ( =0.18, p=0.039) of illness explained 58% of the variance (p<0.001) in FCR. BCS's with higher risk of recurrence may experience higher FCR. However, for FCR, modifiable factors such as anxiety and illness representation (greater emotional response and perceived consequences of illness) may be more important than non-modifiable factors such as Oncotype Dx® test results and age. Further research is needed to develop personalized interventions to improve BCS's outcomes.

Perceived clinical utility of a test for predicting inadequate response to TNF inhibitor therapies in rheumatoid arthritis: results from a decision impact study

Tumor necrosis factor inhibitor (TNFi) therapies are often the first biologic therapy used to treat rheumatoid arthritis (RA) patients. However, a substantial fraction of patients do not respond adequately to TNFi therapies. A test with the ability to predict response would inform therapeutic decision-making and improve clinical and financial outcomes. A 32-question decision-impact survey was conducted with 248 rheumatologists to gauge the perceived clinical utility of a novel test that predicts inadequate response to TNFi therapies in RA patients. Participants were informed about the predictive characteristics of the test and asked to indicate prescribing decisions based on four result scenarios. Overall, rheumatologists had a favorable view of the test: 80.2% agreed that it would improve medical decision-making, 92.3% said it would increase their confidence when making prescribing decisions, and 81.5% said it would be useful when considering TNFi therapies. Rheumatologists would be more likely to prescribe a TNFi therapy when the test reported that no signal of non-response was detected (79.8%) and less likely to prescribe a TNFi therapy when a signal of non-response was detected (11.3%–25.4%). Rheumatologists (84.7%) agreed that payers should provide coverage for such a test. This study shows that rheumatologists support the clinical need for a test to predict inadequate response to TNFi therapies. Test results were perceived to lead to changes in prescribing behaviors as results instill confidence in the ordering rheumatologist.

Abstract P6-08-12: Feasibility of a nation-wide family-based study to assess cancer risks in families with a predicted pathogenic variant identified through hereditary breast and ovary multi-gene panel testing: The TUMOSPEC study

Abstract Background. Assessment of the age-dependent cancer risk conferred by germline predicted pathogenic variants (PPV) in cancer susceptibility genes is often hampered by the way the data are collected. Cohort-based data frequently contain an overrepresentation of patients carrying a gene variant of interest and an underrepresentation of cancer-free gene variant carriers. In order to overcome this problem, penetrance estimates can be grounded on family-based study designs, through the evaluation of index patients (IP) and their family relatives. The purpose of the TUMOSPEC study is to estimate the penetrance of PPV in genes whose literature data are currently inaccurate or limited and to determine their associated tumour spectrum. This will lead to an appropriate assessment of the clinical utility of testing these genes. Methods. IP are enrolled consecutively among patients who are being offered a germline genetic test in a hereditary breast and ovary cancer (HBOC) context in a participating cancer genetics clinics. A panel of 24 genes (ATM, BAP1, BARD1, BRIP1, CHEK2, FANCM, FAM175A, MRE11A, NBN, STK11, RINT1, XRCC2, PALB2, MLH1, MSH2, MSH6, PMS2, CDH1, PTEN, RAD50, RAD51B, RAD51C, RAD51D, TP53) is tested in parallel of BRCA1 and BRCA2. If a PPV is identified, the IP is asked to give her/his first- and second-degree relatives and cousins address, regardless of their health status. Each relative is then contacted by the study coordinating centre (CC) to be invited. Each participant completes an epidemiological questionnaire addressing personal medical history and exposure to various risk factors, and provides a saliva sample to determine if he/she carries the familial PPV. The CC collects questionnaires, family history, clinical and genetic data. Results. Enrolment for the feasibility study takes place between Sep. 2017 and Dec. 2019 at each of the 46 participating french clinics. In June 2019, the study included 3,298 IP. So far, the CC received 1,241 TUMOSPEC panel results (37.6%) with a mean delay of 5 months [0.7 -17.5]. Among them, 169 carried a PPV in at least one of the genes (totalizing 183 PPV). Additionally, 44 IP with PPV identified beforehand were enrolled (table 1). Relatives’ invitation of these 213 IP began in June 2018. Among the relatives of the first 29 index cases contacted so far, 4.6 relatives per family consented to participate. Conclusions. The feasibility study showed that inclusion process is well adapted and that the communication between the various partners (clinicians, biologists, investigators and study participants) is quite smooth. Rates of inclusion for invited relatives (50%), for IP questionnaire completion (45%) and relatives biological sample collection (50%) are also very satisfactory and yet underestimated due to the recent start of relatives inclusions. Overall, this study shows that it is feasible to conduct a large-scale study to gather sufficient number of positive families for each gene included in the panel in a reasonable interval of time. This on-going national effort will allow to appropriately assess cancer risks cancer in families with a PPV in a gene often included in HBOC multi-gene panels. This is an essential step to optimize clinical management guidelines specific to each gene, and will represent a valuable resource for future research on the genetics of breast and ovary cancers. Number of PPV identified in IPGeneATMCHEK2PALB2RAD51CBRIP1RAD51DMSH6RAD50PMS2MRE11ANBNMSH2MLH1CDH1BARD1TP53STK11XRCC2RINT1BAP1RAD51BFAM175AFANCMPTENNumber of PPV512019161111111010999865544322110 Citation Format: Olivier Caron, Séverine Eon-Marchais, Sarah Bonnet-Boissinot, Juana Beauvallet, Marie-Gabrielle Dondon, Chrystelle Colas, Florence Coulet, Capucine Delnatte, Claude Houdayer, Christine Lasset, Jérôme Lemonnier, Michel Longy, Catherine Nogues, Dominique Stoppa-Lyonnet, Dominique Vaur, Fabienne Lesueur, Nadine Andrieu, TUMOSPEC Investigators Group, UNICANCER Groupe Génétique et Cancer. Feasibility of a nation-wide family-based study to assess cancer risks in families with a predicted pathogenic variant identified through hereditary breast and ovary multi-gene panel testing: The TUMOSPEC study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-12.

Diagnostic accuracy of clinical tests directed to the long head of biceps tendon in a surgical population: a combination of old and new tests

Our objective was to examine the clinical utility of old and new clinical tests directed to the long head of the biceps tendon (LHBT) and to quantify the importance of proper test interpretation. A consecutive 65 patients scheduled to undergo arthroscopic surgery were selected. Before surgery, 5 clinical tests were performed: Speed, Yergason, upper cut, biceps resisted flexion (BRF), and modified BRF (mBRF) using a dumbbell. Pain in an area other than the bicipital groove was noted. The presence of LHBT disease was assessed at arthroscopy, and the clinical utility of the tests was calculated. The upper cut test was the most sensitive test and the one with the lowest negative likelihood ratio (0.90 and 0.26, respectively); the Yergasontest was the most specific and the one with the highest positive likelihood ratio (0.83 and 2.20, respectively). BRF strength did not correlate with an LHBT lesion. The mBRF test has a sensitivity of 0.34 and a specificity of 0.75. Higher age predicted an increased risk of an LHBT lesion (1.2 times). Different interpretations of the tests can result in a difference of up to 29 percentage points in performance (ie, sensitivity). Our results suggest that the upper cut test should be used as a screening test and that after a positive result, the Speedand the Yergasontests should be used as confirmatory tests.

Is stratification testing for treatment of chronic obstructive pulmonary disease exacerbations cost-effective in primary care? an early cost-utility analysis.

Patients with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations usually require treatment with oral steroids or antibiotics, depending on the etiology of the exacerbation. Current management is based on clinician's assessment and judgement, which lacks diagnostic accuracy and results in overtreatment. A test to guide these decisions in primary care is in development. We developed an early decision model to evaluate the cost-effectiveness of this treatment stratification test in the primary care setting in the United Kingdom. A combined decision tree and Markov model was developed of COPD progression and the exacerbation care pathway. Sensitivity analysis was carried out to guide technology development and inform evidence generation requirements. The base case test strategy cost GBP 423 (USD 542) less and resulted in a health gain of 0.15 quality-adjusted life-years per patient compared with not testing. Testing reduced antibiotic prescriptions by 30 percent, potentially lowering the risk of antimicrobial resistance developing. In sensitivity analysis, the result depended on the clinical effects of treating patients according to the test result, as opposed to treating according to clinical judgement alone, for which there is limited evidence. The results were less sensitive to the accuracy of the test. Testing may be cost-saving in primary care, but this requires robust evidence on whether test-guided treatment is effective. High quality evidence on the clinical utility of testing is required for early modeling of diagnostic tests generally.

Coronary artery calcium scoring: Its practicality and clinical utility in primary care.

Coronary artery calcium scoring is useful as a risk-stratification tool in coronary artery disease, and it outperforms other risk-assessment methods. American College of Cardiology/American Heart Association guidelines give the test a IIB recommendation in clinical scenarios in which risk stratification is uncertain. However, if the test is not used in the appropriate clinical setting, misinterpretation of the results can lead to unnecessary cardiac testing. This review provides the primary care provider with basic knowledge about the test's clinical utility, interpretation, risks, and limitations.

Pathways from autism spectrum disorder diagnosis to genetic testing.

PurposeThis study examines challenges faced by families and health providers related to genetic testing for autism spectrum disorder (ASD).MethodsThis qualitative study of 14 parents and 15 health providers identified an unstandardized three-step process for families who pursue ASD genetic testing.ResultsStep 1 is the clinical diagnosis of ASD, confirmed by providers practicing alone or in a team. Step 2 is the offer of genetic testing to find an etiology. For those offered testing, step 3 involves the parents’ decision whether to pursue testing. Despite professional guidelines and recommendations, interviews describe considerable variability in approaches to genetic testing for ASD, a lack of consensus among providers, and questions about clinical utility. Many families in our study were unaware of the option for genetic testing; testing decisions by parents appear to be influenced by both provider recommendations and insurance coverage.ConclusionConsideration of genetic testing for ASD should take into account different views about the clinical utility of testing and variability in insurance coverage. Ideally, policy makers from the range of clinical specialties involved in ASD care should revisit policies to clarify the purpose of genetic testing for ASD and promote consensus about its appropriate use.

A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios.

BackgroundSperm DNA fragmentation (SDF) is recognized as a leading cause of male infertility because it can impair the paternal genome through distinct pathophysiological mechanisms. Current evidence supports SDF as a major factor in the pathophysiology of several conditions, including varicocele, unexplained infertility, assisted reproductive technology failure, and environmental lifestyle factors, although the mechanisms involved have not been fully described yet. Measurement of the levels of DNA fragmentation in semen provides valuable information on the integrity of paternal chromatin and may guide therapeutic strategies. A recently published clinical practice guideline (CPG) highlighted how to use the information provided by SDF testing in daily practice, which triggered a series of commentaries by leading infertility experts. These commentaries contained an abundance of information and conflicting views about the clinical utility of SDF testing, which underline the complex nature of SDF.MethodsA search of papers published in response to the CPG entitled “Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios” was performed within the Translational Andrology and Urology (TAU) website (http://tau.amegroups.com/). The start and end dates for the search were May 2017 and August 2017, respectively. Each commentary meeting our inclusion criteria was rated as “supportive without reservation”, “supportive with reservation”, “not supportive” or “neutral”. We recorded whether articles discussed either SDF characteristics as a laboratory test method or clinical scenarios, or both. Subsequently, we extracted the particulars from each commentary and utilized the ‘Strengths-Weaknesses-Opportunities-Threats’ (SWOT) analysis to understand the perceived advantages and drawbacks of SDF as a specialized sperm function method in clinical practice.ResultsFifty-eight fertility experts from six continents and twenty-two countries contributed commentaries. Overall, participants (87.9%; n=51) were supportive of the recommendations provided by the CPG on the utility of SDF testing based on clinical scenarios. The majority of participants made explicit remarks about both the clinical scenarios and SDF assays’ characteristics. Among ‘not supportive’ and ‘supportive with reservation’ participants, 75% (n=30/40) and 77.5% (n=31/40) expressed concerns related to technical limitations of SDF testing methods and clinical utility of the test in one or more clinical scenarios discussed in the CPG, respectively. The SWOT analysis revealed that the CPG provides a reasonable evidence-based proposal for integration of SDF testing in the routine daily practice. It also uncovered gaps of knowledge and threats limiting the widespread application of SDF in everyday practice, thus allowing the identification of opportunities to further refine SDF testing and its clinical utility.ConclusionsThe understanding of the role of SDF in male infertility requires an in-depth analysis of the multifactorial pathophysiological processes and the theories involved. The SWOT analysis allowed an objective evaluation of CPG on the clinical utility of SDF testing based on clinical scenarios and its accompanying commentaries written by global experts in all possible angles. Implementation of SDF testing in the clinic may not only increase the outcome of ART but more importantly improve the health of both fathers to be and resulting offspring.

Carpal tunnel syndrome: Analyzing efficacy and utility of clinical tests and various diagnostic modalities.

Background:Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, but not adequately studied in India.Objectives:To study clinical tests, nerve conduction studies (NCS), ultrasonography (USG), and magnetic resonance imaging (MRI) in diagnosing CTS.Materials and Methods:We diagnosed CTS in 54 patients (93 hands) out of 60 screened patients with symptoms compatible with CTS, including 19 control patients (23 hands). We conducted provocative tests and calculated Boston Carpal tunnel Questionnaire (BCTQ) symptom (S) and function (F) scores. NCS positive patients were classified into mild, mild-to-moderate, moderate, severe, and all-CTS groups. Median nerve anteroposterior, transverse, circumference (CIR), and cross-sectional area (CSA) at inlet (I), middle (M), and outlet (O) each was measured by USG in all patients. MRI was done in 26 patients (39 hands).Results:Phalen, hand elevation and pressure provocation tests had higher sensitivity, Tinel's test had higher specificity and tethered median nerve and tourniquet tests had low sensitivity and moderate specificity. USG had low sensitivity but high specificity, and MRI had moderate sensitivity. USG in patients compared to controls was significantly abnormal in CSA-I, CIR-I, and CSA-O. Significant correlation was found between BCTQ-S and NCS and BCTQ-S and CIR-O. CIR-M, CIR-O, CSA-M, and CSA-I had correlation with NCS. MRI was significant in moderate and in moderate + severe groups combined and associated pathologies were detected in 59% patients.Conclusion:NCS remain gold standard but USG and MRI help increase sensitivity and detect mass lesions amenable to surgery.

Carpal tunnel syndrome: Analyzing efficacy and utility of clinical tests and various diagnostic modalities

Carpal tunnel syndrome: Analyzing efficacy and utility of clinical tests and various diagnostic modalities

Public attitudes toward genetic risk testing and its role in healthcare.

Developments in genomics continue to increase the number of disorders for which genetic testing is available, whether in the primary healthcare system, through direct-to-consumer testing, or as part of expanded newborn screening panels. This paper reviews a robust literature on public attitudes toward genetics and genetic testing. In general, attitudes are positive about genetic research and new genomic technologies, with majorities indicating an interest in genetic testing. However, complex beliefs comprise the public's thinking about genetics. Attitudes are driven by beliefs about the type of genetic research, the personal and clinical utility of tests, and the area of genetics in which testing is applied. Limitations of current research are noted and suggestions made for future research.

To Investigate DVT for Thrombophilic Factors, or Not To

Thrombophilia is an inherited predisposition to Venous Thromboembolism (VTE) of Deep Vein Thrombosis (DVT), with or without associated Pulmonary Embolus (PE). Ever since the deficiency antithrombin was reported as inherited risk factor for venous thromboembolism, the gamut of test has increased seeking causal association for familial venous thrombosis including F5G1691A (FVR506Q, factor V Leiden) and the F2G20210A gene mutations. In the 1980s and 1990s thrombophilia testing became common in unselected patients and their relatives. According to recent guidelines, testing is clearly not mandatory in situations where the clinical utility of testing is not proven, (clinical utility defined as the ability of a test to influence or alter clinical outcome). However, many clinicians still have used thrombophilia test results to determine clinical management. [1] Clinicians in developing countries continue showing unprecedented enthusiasm in ordering tests for cases of arterial or venous thrombosis as well as their family members in absence of family history of thrombosis, sometimes without giving any consideration to very important issues such as time since thrombotic event, patient on anticoagulant therapy as well as when an obvious plausible provoking factor already identified. Venous thromboembolism is commonly encountered by gynecologists, obstetricians, Orthopedicians, surgeons and they do not have the best of knowledge about thrombophilic factors, their limitations, and relevance and this could be a reason for excessive demand for thrombophilic tests. Also the health system in many developing countries is such that the laboratory experts have no active role in advising the clinicians or modifying the test requests from clinicians. The high cost of these tests at questionable benefit is also overlooked. Thrombophilia testing in patients with a first VTE do not reduce the incidence of recurrence in clinical practice [2]. Thus knowledge of the thrombophilia status of affected patients fails to substantially help clinicians to prevent any recurrence. Most evidences currently suggest that the intensity and duration of anticoagulation treatment after a thrombotic event should not be altered based on most thrombophilic risk factors status [3].

Conveying genomic recurrence risk estimates to patients with early-stage breast cancer: oncologist perspectives

The development and increased use of genomic profiling has led to refinement of breast cancer treatment. This study sought to examine medical and surgical oncologists' perceptions of factors related to the translation and integration of Oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA) into routine clinical care. Twenty oncologists (10 medical and 10 surgical oncologists) participated in qualitative interviews. Questions centered on the following themes: oncologists' perceptions about the clinical utility of testing, the impact of patient preferences on the decision to test and use results to inform treatment decisions, methods of communicating risk associated with test results to patients, and benefits of and barriers to incorporating testing into multidisciplinary care settings. Oncologists found Oncotype DX test results useful in their practice but had concerns as well. These included that some oncologists either used testing inappropriately or placed undue emphasis on the results at the expense of other clinical information. The use of intermediate test results, which have less clear clinical implications, incorporating results with patient treatment preferences, and the use of testing in multidisciplinary teams were noted as specific challenges. Oncologists noted several benefits of testing and also many challenges, despite wide dissemination and common use. Education for health providers should include specific training in how to interpret and communicate the uncertainty inherent in genomic tests while integrating patient preferences to inform treatment decision making.

Predictive Ability of Direct-to-Consumer Pharmacogenetic Testing: When is Lack of Evidence Really lack of Evidence?

For several years personal genome tests have been offered directly to consumers via the internet. Based on single genome scans, these direct-toconsumer (DTC) tests predict susceptibility to common multifactorial diseases, such as Type 2 diabetes, coronary heart disease and nonfamilial cancer, inform about predisposition to drug response, report carrier status for monogenic diseases, or provide all of the above. The market is served by a few major players, such as 23andMe and deCODEme, and numerous lesser-known companies such as YouScript, GenePlanet and Theranostics [101–105]. The market for DTC personal genome testing is steadily increasing, even though the evidence on the predictive ability and clinical utility of these tests is limited. The few available studies have shown that predicted risks of multifactorial diseases differed between companies and were sometimes even contradictory for the same individual [1,106], but large-scale studies on the predictive ability are lacking. From prediction studies that investigated genetic risk models based on different but comparable selections of SNPs, we know that the predictive ability of genetic testing for multifactorial diseases is low to moderate, except when one or more SNPs had substantial impact on disease risk [2]. From this indirect evidence it is concluded that the DTC offer of genetic testing for multifactorial diseases is premature. To date, most of the discussion about DTC personal genome tests has focused on the prediction of these multifactorial diseases and less attention has been given to the predictive ability and clinical utility of pharmacogenetic testing. Yet, many companies offer pharmacogenetic testing to inform about the genetic susceptibility to drug response and side effects of treatment [3], such as the efficacy of clopidogrel and the risk

Early recurrence in standard-risk medulloblastoma patients with the common idic(17)(p11.2) rearrangement

Medulloblastoma is diagnosed histologically; treatment depends on staging and age of onset. Whereas clinical factors identify a standard- and a high-risk population, these findings cannot differentiate which standard-risk patients will relapse and die. Outcome is thought to be influenced by tumor subtype and molecular alterations. Poor prognosis has been associated with isochromosome (i)17q in some but not all studies. In most instances, molecular investigations document that i17q is not a true isochromosome but rather an isodicentric chromosome, idic(17)(p11.2), with rearrangement breakpoints mapping within the REPA/REPB region on 17p11.2. This study explores the clinical utility of testing for idic(17)(p11.2) rearrangements using an assay based on fluorescent in situ hybridization (FISH). This test was applied to 58 consecutive standard- and high-risk medulloblastomas with a 5-year minimum of clinical follow-up. The presence of i17q (ie, including cases not involving the common breakpoint), idic(17)(p11.2), and histologic subtype was correlated with clinical outcome. Overall survival (OS) and disease-free survival (DFS) were consistent with literature reports. Fourteen patients (25%) had i17q, with 10 (18%) involving the common isodicentric rearrangement. The presence of i17q was associated with a poor prognosis. OS and DFS were poor in all cases with anaplasia (4), unresectable disease (7), and metastases at presentation (10); however, patients with standard-risk tumors fared better. Of these 44 cases, tumors with idic(17)(p11.2) were associated with significantly worse patient outcomes and shorter mean DFS. FISH detection of idic(17)(p11.2) may be useful for risk stratification in standard-risk patients. The presence of this abnormal chromosome is associated with early recurrence of medulloblastoma.