Age-adjusted Cut-off Value Research Articles

Distinct age-adjusted D-dimer threshold to rule out acute pulmonary embolism in outpatients and inpatients.

The diagnosis of acute pulmonary embolism (PE) is combinations of clinical probability assessments, plasma D-dimer (DD) test results, and/or computed tomographic pulmonary angiography (CTPA). The aim of this study is to explore the appropriate DD cutoff using the immunoturbidimetric method in outpatients and inpatients. We retrospectively enrolled 2689 patients with suspected PE between January 2014 and December 2019. All patients underwent clinical probability assessments, DD tests, and CTPA. We investigated the appropriate cutoff level for plasma DD tests in the correlation analysis and receiver operating characteristic (ROC) curves. Among all patients, 1263 were confirmed acute PE. The age-adjusted DD level was determined to be age × 10μg/L (for patients aged >50 years) in outpatients. This cutoff value resulted in a sensitivity of 96.75% and a specificity of 87.02%, with the area under the curve (AUC) of 0.908 and the number needed to treat (NNT) of 1.18. For inpatients, the age-adjusted cutoff values for the biomarker DD demonstrated poor specificity (13.34%) and NNT (9.88). However, when the DD cutoff was adjusted to 2 × the upper limit of normal (ULN), the sensitivity increased to 93.19%, while the specificity remained at 29.55%, with the AUC of 0.610 and the NNT of 4.76. The optimal DD cut-off value was 3010 μg/L (about 5 × ULN), resulting in a sensitivity of 75.22% and specificity of 61.72%, with the AUC of 0.727 and the NNT of 2.7. Using the immunoturbidimetric method to measure DD, an age-adjusted DD cutoff (age × 10μg/L, if aged >50 years) should be considered for outpatients with suspected PE. For inpatients, increasing the DD cutoff value to at least 2 × ULN yields the best test performance.

Reporting age-adjusted D-dimer cut-off values reduces radiology overuse in emergency department patients with suspected deep venous thrombosis

IntroductionVenous thromboembolism (VTE) is a leading cause of death, associated with substantial morbidity in the absence of treatment. Our aim was, first, to compare the diagnostic performance of D-dimer for the diagnosis of VTE in the emergency department (ED), when reporting conventional cut-off point versus when additionally reporting age-adjusted values. Second, we explored the ordering pattern of Doppler ultrasound (US) and computerized tomographic pulmonary angiogram (CTPA), before and after reporting of the aforementioned age-adjusted cut-off value. Materials and methodsWe conducted a cross-sectional study to compare the diagnostic performance of D-dimer as a screening for VTE when reporting the conventional cut-off value versus when additionally including the age-adjusted metrics, and a quasi-experimental study to explore the ordering of Doppler US and CTPA before the age-specific metrics were shared in the report in ED patients between 50 and 100 years-old with D-dimer ordering. ResultsThe cross-sectional study included 392 patients, 25 with VTE. The specificity using an age-adjusted cut-off value was significantly higher (0.51) compared to a single absolute cut-off (0.42), and the negative likelihood ratio was lower as well (0.08 vs. 0.19), but again not statistically significant. In the quasi-experimental study, there was a decrease in the rate of use of both CTPA and Doppler US (P < 0.05). ConclusionThe intervention improved the use of the D-dimer result in the ED and helped improve the request for imaging tests.

Scale for the assessment and rating of ataxia: Age-dependent performance of healthy adults.

The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale. The objective was to study the age dependence of SARA in healthy adults and to define age-specific cut-off values to differentiate healthy from ataxic individuals. Data from 390 healthy individuals and 119 spinocerebellar ataxia patients were analyzed. SARA scores were mapped on functional SARA (fSARA). Age-adjusted cut-off values were determined by receiver operating characteristic curve analysis. The cut-off value was 3 for SARA and 1.5 for fSARA. Older patients had higher SARA cut-off values (4.5 for 60-69 years and 6.5 for 70-79 years). Age-adjusted cut-off values for fSARA are 1 for 18-29, 30-39 and 50-59 years, 2 for 40-49 and 60-69 years and 3 for 70-79 years. Sensitivity and specificity were higher for SARA than for fSARA. In this study, age-dependent cut-off values were defined for SARA and fSARA. The results may be relevant for the design of future preventive trials in spinocerebellar ataxias that use conversion to ataxia as an outcome.

Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures

ObjectiveThis study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures.MethodsThis was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2016 and June 2019. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e., conventional 0.5 mg/L, previously well-established age-adjusted cutoff value (age × 0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein.ResultsThere were 2759 patients included, 887 males and 1872 females, with an average age of 78 years. In total, 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.17 mg/L, 1.62 mg/L, 1.665 mg/L, 1.69 mg/L and 1.985 mg/L, respectively, and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61%, clearly higher than those for conventional threshold (0.5 mg/L, 37%) or previously established age-adjusted D-dimer threshold (age × 0.01 mg/L, 22%). In contrast, the sensitivity was lower than that (59% vs 85% or 77%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age × 0.01 mg/L) was used. The other indexes as PPV (15%, 11% and 12%) and NPV (93%, 93% and 94%) were comparable when three different D-dimer thresholds were applied.ConclusionsWe developed a new age-adjusted D-dimer cutoff value (age × 0.02 mg/L) for a specified high-risk population of patients aged 65 years or older with hip fractures, and demonstrated the improved utility of the D-dimer test for exclusion of DVT. This formula can be considered for use in elderly hip fracture patients who meet the applicable standards as preoperative DVT screening, after its validity is confirmed by more well-evidenced studies.

Age-adjusted cut-off values of lipid accumulation product (LAP) for predicting hypertension

Among the many factors considered relevant to hypertension, obesity and metabolic disturbances play an important role in the development of this pathology. Therefore, lipid accumulation product (LAP), an index of visceral adiposity, is a simple and effective indicator of hypertension risk. To date, the reference and cut-off values for LAP have not been defined. The aim of the study was to determine the age-adjusted optimal cut-off values of LAP for the prediction of hypertension risk. This cross-sectional case–control study comprised 1960 subjects ranging from 20 to 64 years of age. The participants underwent anthropometric tests, blood pressure measurements, questionnaire surveys and laboratory examinations. The cut-off values of LAP were determined using receiver operating characteristic (ROC) curve analysis. According to our study results, LAP values in healthy subjects increased with age, whereas there was no effect of age on LAP values in patients with hypertension. These two findings determine the presence of age-adjusted cut-off values of LAP for diagnosing hypertension. Increasing age is associated with an increase in the cut-off values of LAP to detect hypertension. In conclusion, hypertension risk should be estimated using the age-adjusted cut-off values of LAP; otherwise, the risk of hypertension might be overestimated or underestimated.

Do age-adjusted sex-specific cut-off values improve the agreement between high sensitivity cardiac troponins I and T? A retrospective study

BackgroundMany reports noted a disagreement between High sensitivity cardiac Troponin (hs-cTn) assays on the diagnosis of Acute Coronary Syndrome (ACS). MethodsWe conducted a retrospective study aiming to assess the agreement between hs-cTn T (Roche) and hs-cTn I (Abbott) in patients presenting with a suspected ACS to the emergency department at Hotel-Dieu hospital between September 2017 and October 2019 using overall, sex-specific, and age-adjusted sex-specific cut-off values. This was measured using Cohen’s Kappa. We explored whether renal function, circadian rhythm, age and sex influenced the discordance. And we analyzed the trend of agreement between baseline and repeated measurements. Results4856 patients who had simultaneous hs-cTn I and T values were retained for the analysis. 53.5% had a hs-cTn T above the overall 99th percentile, compared to 19.9% for hs-cTn I. The numbers were significantly reduced when applying age-adjusted sex-specific 99th percentile.A disagreement was seen in 34% of cases using overall 99th percentile. Using sex-specific cut off values did not impact this discordance; however, age-adjusted sex-specific cut-off values reduced the percentage of discrepancies to 15.8%. The decreased renal function had a negative effect on the agreement while the circadian rhythm had minimal effect. This initial discordance was carried forward into repeated measurements. ConclusionThe disagreement between hs-cTn T and I assays could be imputed to the choice of cut-off values. The use of age-adjusted sex specific 99th percentile reduced majorly these discordances. Further studies are needed in order to evaluate their clinical utility in patients presenting with ACS.

Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing

In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern. To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE. This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019. The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing. Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from -2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were -22% (95% CI, -26 to -19) and -19% (95% CI, -22 to -16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing. The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.

Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Systematic Review and Meta-analysis.

Background:Pulmonary embolism (PE), depending on the severity, carries a high mortality and morbidity. Proper evaluation, especially in patients with low probability for PE, is important to avoid unnecessary diagnostic testing.Objective:To review the diagnostic utility of conventional versus age-adjusted D-dimer cutoff values in patients 50 years and older with suspected pulmonary embolism.Methods:Systematic review with univariant and bivariant meta-analysis.Data sources:We searched PubMed, MEDLINE, and EBSCO for studies published before September 20th, 2020. We cross checked the reference list of relevant studies that compares conventional versus age-adjusted D-dimer cutoff values in patients with suspected pulmonary embolism.Study selection:We included primary published studies that compared both conventional (500 µg/L) and age-adjusted (age × 10 µg/L) cutoff values in patients with non-high clinical probability for pulmonary embolism.Results:Nine cohorts that included 47 720 patients with non-high clinical probability were included in the meta-analysis. Both Age-adjusted D-dimer and conventional D-dimer have high sensitivity. However, conventional D-dimer has higher false positive rate than age-adjusted D-dimer.Conclusion:Age-adjusted D-dimer cutoffs combined with low risk clinical probability assessment ruled out PE diagnosis in suspected patients with a decreased rate of false positive tests.

Diagnostic Accuracy of the Tina-Quant D-Dimer Gen.2 Assay with Age-Adjusted Cut-Off Ranges for Evaluation of Patients with Suspected Deep Vein Thrombosis or Pulmonary Embolism

Introduction: Fibrin degradation products, D-Dimer and X-oligomers, are biomarkers for activation of coagulation. D-Dimer testing is recommended as an additional diagnostic tool for proximal deep vein thrombosis (DVT) and pulmonary embolism (PE), in conjunction with clinical presentation and pre-test probability (Lim, et al. Blood Adv. 2018). D-Dimer levels naturally increase in patients over the age of 50 years, which reduces the specificity of D-Dimer levels as a diagnostic aid for proximal DVT and PE in older patients. We conducted a study to assess the diagnostic accuracy of the Tina-quant® D-Dimer Gen.2 (D-DI2; Roche Diagnostics) assay in patients with a low or intermediate pretest probability for proximal DVT or PE (Bertsch, et al. ISTH 2020; abstract PB0600). An exploratory objective of the study was to evaluate the diagnostic accuracy of the D-DI2 assay in the total study population after applying an age-adjusted cut-off value for patients aged &amp;gt;50 years. Methods: This prospective, observational, multi-center study was conducted between July 2017 and August 2019. Samples were collected at six European hospitals or specialist referral centers, or purchased from a commercial vendor (BioPartners Inc.). The 3.2% citrated plasma samples were analyzed at a central site using the D-DI2 assay on the cobas t 711 analyzer (Roche Diagnostics). Eligible patients were aged ≥18 years, presenting with symptoms suggestive of proximal DVT and/or PE, and with a low or intermediate pretest probability of DVT or PE by Wells score. Main exclusion criteria included DVT and/or PE symptoms for &amp;gt;7 days or a previous diagnosis of DVT and/or PE. DVT and/or PE were diagnosed according to local imaging protocols and standard-of-care procedures, in line with current clinical guidelines. Patients were followed-up for ≥90 days after hospital discharge to verify the clinical diagnosis and record any adverse events. In the primary analysis, a D-DI2 assay cut-off value of 0.5 μg fibrinogen equivalent units (FEU)/mL was applied across all patients, regardless of age. For the purpose of this exploratory analysis, age-adjusted cut-off values were calculated by multiplying age by 0.01 μg FEU/mL for patients aged &amp;gt;50 years. Results: In total, 2516 patients were included in the analysis (1741 DVT cohort; 775 PE cohort); of these, 1538 patients were aged &amp;gt;50 years (996 DVT cohort; 542 PE cohort) and the D-DI2 assay cut-off values for these patients were age-adjusted accordingly. The parameters for diagnostic accuracy for both the DVT and PE cohorts, unadjusted and age-adjusted values, are provided in the Table. Both negative predictive value (NPV) and sensitivity remained high after adjustment for age across both cohorts; however, there were slight decreases compared with the unadjusted values. Positive predictive value (PPV) was increased in both cohorts after age adjustment when compared with the unadjusted values. A reduction in false positives were reported for both the DVT (27%) and PE (26%) cohorts when adjusted for age compared with the unadjusted values. After age-adjustment, the number of false negatives in the total study population increased slightly in the DVT cohort (from zero to one case) and in the PE cohort (from one to five cases). Overall, specificity was increased when the results were adjusted for age. Conclusions: In our study population, when used in conjunction with a low or intermediate pretest probability for DVT and/or PE according to Wells criteria, the D-DI2 assay identifies patients at very low risk for proximal DVT and PE. Adjustment of the cut-off value for age resulted in a slight decrease in NPV, though still below the diagnostic threshold. The benefit of a reduction in false positives observed after age adjustment has the potential to prevent further unnecessary diagnostic procedures for patients. Disclosures Bertsch: Nuremberg General Hospital/Paracelsus Medical University: Current Employment. Blaschke:BMBF: Research Funding; Innovationsfonds: Research Funding; DGINA: Membership on an entity's Board of Directors or advisory committees. Body:University of Manchester: Current Employment; Beckman Coulter: Consultancy; LumiraDx: Consultancy; Roche Diagnostics: Consultancy; Siemens Healthineers: Consultancy; Abbott Point of Care: Consultancy; Abbott Point of Care: Research Funding; Roche Diagnostics: Research Funding; American Association of Clinical Chemistry (sponsored session from Roche, Abbott, ET Healthcare, Ortho, Siemens, Beckman): Speakers Bureau; LumiraDx advisory committee: Membership on an entity's Board of Directors or advisory committees; Creavo (chair of Trial Steering Committee): Membership on an entity's Board of Directors or advisory committees. Davidson:Roche Diagnostics International: Current Employment. Rieger:Roche Diagnostics GmbH: Current Employment. Horner:Salford Royal NHS Foundation Trust: Current Employment. Sonner:Roche Diagnostics GmbH: Consultancy; TRIGA-S Scientific Solutions: Current Employment. Sun:Roche Diagnostics GmbH: Current Employment. Turnes:ICON Clinical Research UK Ltd: Current Employment. Hoffman:Roche Diagnostics GmbH, Germany: Current Employment.

A Community-Based Study on the Prevalence of Olfactory Dysfunction.

Olfactory dysfunction (OD) is common, affecting an estimated 13 million adults in the United States. Prior studies may underestimate OD prevalence due to use of brief smell identification tests or age-adjusted cutoff values, which concede that it is acceptable for older people to have a decreased sense of smell. To determine OD prevalence in the healthy community when the goal and expectation is ideal olfactory function, rather than age-based population norms. Secondary goals were to explore factors associated with OD. Subjects without otolaryngic complaints were recruited from the community surrounding the Medical University of South Carolina. Olfactory-specific information was collected, and olfactory function was assessed using the Sniffin' Sticks test (Burghardt, Wedel, Germany) to measure threshold, discrimination, and identification (TDI). OD was defined as a TDI score < 31. Bivariate analysis and linear regression were used to determine factors associated with OD. In total, 176 subjects were included with mean age of 52 years (range: 20-93), 111 (63%) female, and 127 (72%) white. Mean TDI score was 28.8 (6.9) and OD was present in 94 (53%) subjects. Multivariate linear regression revealed that TDI decreased an average of 1 point every 5 years. TDI was also associated with Mini-Mental Status Examination (MMSE) score, asthma, and gastroesophageal reflux disease. Threshold was associated with age, heart problems, and gastroesophageal reflux disease. Discrimination was associated with age and MMSE scores. Identification was associated with age, heart problems, and anxiety. In a community-based sample, OD affects greater than 50% of subjects. Aging impacts all aspects of olfaction, while the effects of factors such as asthma, MMSE scores, gastroesophageal reflux disease, heart problems, and anxiety may only be evident in specific olfactory subtests.

The Diagnostic Efficacy of Age-Adjusted D-Dimer Cutoff Value and Pretest Probability Scores for Deep Venous Thrombosis.

This study seeks to evaluate the diagnostic value of D-Dimer Plus and Innovance D-Dimer as well as the age-adjusted cutoff value for D-dimer detection in combination with 4 pretest probability (PTP) scores for deep venous thrombosis (DVT). A total of 688 patients referred for lower extremity vascular compression venous ultrasonography for suspected DVT from January 2016 to May 2018 in the First Affiliated Hospital of Sun Yat-sen University underwent D-dimer tests combining with 4 PTP scores. The diagnostic efficacy of the Wells score was the highest of the 4 PTP scores. The diagnostic efficacy of Innovance D-Dimer for DVT was greater than that of D-Dimer Plus, with better sensitivity and negative predictive value, which were both greater than 98%. If the cutoff values were adjusted by age, the Innovation D-Dimer could further improve both the specificity and the positive predictive value, providing better diagnostic performance. When the 2 D-dimer detections were used in combination with 4 PTP scores for DVT diagnosis, separately, both the positive predictive value and the negative predictive value significantly improved for D-Dimer Plus, and the positive predictive values significantly improved for Innovance D-Dimer. However, the sensitivity, specificity, and negative predictive values did not obviously change. For our patients, Wells score had the best diagnostic efficacy for our patients with suspected DVT among the 4 PTP scores. Innovance D-Dimer in combination with age-adjusted cutoff values exhibited increased sensitivity and negative predictive value for DVT diagnosis and was equivalent to the diagnostic efficacy of the Innovance D-Dimer in combination with PTP scores.

Safety of D-Dimer As a Stand-Alone Test for the Exclusion of Deep Vein Thrombosis Compared to Other Strategies

BackgroundTogether with clinical decision rules, D-dimer testing has long been the mainstay of diagnostic work-up of suspected deep vein thrombosis (DVT). Advantages of D-dimer measurement include wide availability, low costs and high sensitivity. Age-adjusted D-dimer cut-off values have been suggested to improve specificity of D-dimer testing, defining a positive D-dimer as age multiplied by 0.01 mg/L at or over fifty years of age. Age-adjusted cut-off values have been found to increase specificity without compromising safety in the setting of acute pulmonary embolism, but have not been extensively evaluated in DVT.In this study, we aimed to evaluate and compare the diagnostic performance of fixed versus age-adjusted D-dimer thresholds in patients with suspected DVT, as a stand-alone test or in combination with pre-test probability assessment.MethodsWe included 973 consecutive outpatients referred to Østfold Hospital, Norway, with suspected first or recurrent lower extremity DVT, between 2015 and 2017. STA®-Liatest® Plus D-Dimer assay was performed and Wells clinical score assessed in all patients. Patients with positive fixed D-dimer (≥0.5 mg/L) were referred for whole-leg compression ultrasonography (CUS), whereas patients with negative D-dimer were not, irrespective of the clinical pre-test probability. Failure rate was defined as patients with negative D-dimer at baseline remaining untreated and diagnosed with symptomatic venous thromboembolism during 3-month follow-up. We compared diagnostic indices of both D-dimer thresholds with or without initial pre-test probability assessment.ResultsDVT was diagnosed in 177 out of 973 patients (18%).The fixed D-dimer cut-off was associated with a sensitivity of 99.4% (95% CI 96.9 to 99.9%) for one diagnostic failure (0.3%) (not adjudicated as of print). Adding the Wells score would have detected this one case at a cost of 90 additional CUS examinations. Age-adjusted D-dimer as a stand-alone test was associated with 6 diagnostic failures (1.5%) for a sensitivity of 96.6% (95% CI 92.8 to 98.8%). Age-adjusted D-dimer combined with Wells score yielded a sensitivity of 99.4% (95% CI 96.9 to 99.9%), with one diagnostic failure (0.4%) and 714 patients referred for CUS.ConclusionOur results suggest that the fixed D-dimer as a stand-alone test without Wells score is a safe and efficient diagnostic strategy. Combining age-adjusted D-dimer with Wells score was equally safe, but was not associated with a lower number of necessary CUS examinations. DisclosuresFronas:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant in conducting the study. Tøvik Jørgensen:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant for conducting the study. Ghanima:Bayer, BMS, Novartis: Research Funding; Amgen, Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Pre-surgery age-adjusted Charlson Comorbidity Index is associated with worse outcomes in acute cholecystitis

BackgroundBeneficial effects of cholecystectomy in acute cholecystitis (AC) might be weakened by complications. The age-adjusted Charlson Comorbidity Index (CCI) assesses disease relevance in the prediction of one-year mortality. AimsTo evaluate whether age-adjusted CCI predicted complications (including surgical complications, intensive care unit [ICU] admission, and in-hospital death) among patients undergoing cholecystectomy for AC. Associations between age-adjusted CCI and the length of hospital stay have been also evaluated. Methods271 patients were enrolled at Ospedale Policlinico San Martino (Genoa, Italy) between 2005 and 2013. Clinical data and blood samples were collected. ResultsPatients’ median age was 67 years. They underwent more frequently video-laparoscopic cholecystectomy with a limited rate of conversion to open cholecystectomy. Surgical complications occurred in 23 patients (8.5%). 6 patients (2.2%) needed ICU admission, while death occurred in 4 patients (1.5%). According to the cut-off point identified by ROC curve, an age-adjusted CCI cut-off value of 5 was found predictive for in-hospital complications also when confounders were considered (OR 1.35, 95% CI 1.02–1.79, p = 0.035). No association between adjusted CCI and the length of hospital stay was found. ConclusionsIn patients surgically treated for AC, age-adjusted CCI could represent an additional tool, along with available risk scores, to help surgeons in choosing the best therapeutic option.

Digit Triplet Test Hearing Screening With Broadband and Low-Pass Filtered Noise in a Middle-Aged Population.

This study investigated whether age affects Flemish Digit Triplet Test (DTT) scores, as well as sensitivity and specificity of the test to detect high-frequency hearing impairment in middle age. DTT performance in broadband and low-pass filtered noise was assessed for 21 young and 61 middle-aged persons with normal-hearing sensitivity. Cutoff values based on their performance were used to evaluate sensitivity and specificity of the DTT as a screening tool in 145 middle-aged persons, with varying audiometric profiles. DTT performance for normal-hearing persons depended on age in both noise conditions. For low-pass filtered noise, the trade-off between sensitivity and specificity also increased when age-adjusted cutoff values were applied for screening in middle age. The Flemish DTT with broadband noise had high sensitivity and specificity to detect high-frequency hearing impairment in middle age. Similar results were obtained for low-pass filtered noise when cutoff values for referral were age adjusted.

Age-dependent effects of homocysteine and dimethylarginines on cardiovascular mortality in claudicant patients with lower extremity arterial disease

The association among serum homocysteine (HCY), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) is of interest in endothelial dysfunction, although the underlying pathology is not fully elucidated. We investigated the relationship of HCY with SDMA and ADMA regarding their long-time outcome and the age dependency of HCY, SDMA, and ADMA values in claudicant patients with lower extremity arterial disease. 120 patients were included in a prospective observational study (observation time 7.96 ± 1.3 years) with cardiovascular mortality as the main outcome parameter. Patients with intermittent claudication prior to their first endovascular procedure were included. HCY, SDMA, and ADMA were measured by high-performance liquid chromatography. Cutoff values for HCY (≤/>15 µmol/l), SDMA (≤/>0.75 µmol/l), and ADMA (≤/>0.8 µmol/l) differed significantly regarding cardiovascular mortality (p < 0.001, p < 0.001, p = 0.017, respectively). Age correlated significantly with HCY (r = 0.393; p < 0.001), SDMA (r = 0.363; p < 0.001), and ADMA (r = 0.210; p = 0.021). HCY and SDMA (r = 0.295; p = 0.001) as well as SDMA and ADMA (r = 0.380; p < 0.001) correlated with each other, while HCY and ADMA did not correlate (r = 0.139; p = 0.130). Patients older than 65 years had higher values of HCY (p < 0.001) and SDMA (p = 0.01), but not of ADMA (p = 0.133). In multivariable linear regression, age was the only significant independent risk factor for cardiovascular death (beta coefficient 0.413; 95% CI 0.007–0.028; p = 0.001). Age correlated significantly with HCY, SDMA, and ADMA. However, only age was an independent predictor for cardiovascular death. Older patients have higher values of HCY and SDMA than younger subjects suggesting age-adjusted cutoff values of HCY and SDMA due to strong age dependency.

Usefulness of D-Dimer Testing in Predicting Recurrence in Elderly Patients with Unprovoked Venous Thromboembolism

BackgroundWhether post-anticoagulation D-dimer levels are useful in predicting recurrence in elderly patients with unprovoked venous thromboembolism is unknown. MethodsWe followed up 157 patients aged ≥65 years with acute symptomatic, unprovoked venous thromboembolism in a prospective, multicenter cohort study. All patients completed 3-12 months of anticoagulation and then underwent quantitative D-dimer testing (enzyme-linked immunosorbent assay) 12 months after the index venous thromboembolism. The outcome was recurrent symptomatic venous thromboembolism after D-dimer measurement. We examined associations between log-transformed and dichotomized D-dimer values and the time to venous thromboembolism recurrence using competing risk regression, adjusting for age, sex, and overt pulmonary embolism. ResultsThere was no statistically significant association between quantitative or dichotomized D-dimer levels and venous thromboembolism recurrence. The area under the receiver operating characteristic curve for predicting recurrent venous thromboembolism was moderate (0.66; 95% confidence interval [CI], 0.51-0.82). The negative likelihood ratios were 0.34 (95% CI, 0.05-2.38) at the usual and 0.34 (95% CI, 0.09-1.29) at the age-adjusted cutoff values. Among patients with normal D-dimer results, venous thromboembolism recurrence rates were 6.8 (95% CI, 2.2-21.2) per 100 patient-years using the usual and 7.1 (95% CI, 3.2-15.8) per 100 patient-years using the age-adjusted cutoff values. ConclusionD-dimer testing alone may not be useful in identifying elderly patients with unprovoked venous thromboembolism who are at low risk of recurrent venous thromboembolism and in whom anticoagulants may be safely stopped.

Age-adjusted PSA-density cut off values. Can the underdiagnosis and overdiagnosis of prostate cancer (PCa) and negative prostate biopsies be reduced at no cost?

Introduction - Purpose: Investigation of the usefulness of age-adjusted PSA-density cut off values for performing prostate biopsies. Focus on reducing the number of biopsies and the improvement of the overdiagnosis/underdiagnosis ratio of low-risk PCa. Material & Method: In a series of 560 consecutive patients with transrectal ultrasound (TRUS) guided biopsy, we performed a series of calculations with different PSAD cut off values and the age-adjusted PSAD cut off values proposed by the authors (PSAD ≥ 0.10 for age ≤ 69, PSAD ≥ 0.15 for age 70-75 and PSAD ≥0.20 for age ≥ 76). Results: The overall diagnosis of PCa reached 41.6%. PCa was found in 10.13%, 23.48%, 53.33%, 73.16% , and a Gleason pattern of 4 or 5 was found in 6.6%, 6.46%, 20.83% and 53.24%, for PSAD values of < 0.1, ≥ 0.1 - <0.15, ≥0.15 - < 0.20 and ≥ 0.20 respectively. The reduction of TRUS biopsies was calculated at 37.32% for the age-adjusted values (PSAD≥ 0.10 for age ≤ 69, PSAD ≥ 0.15 for age 70-75 and PSAD ≥ 0.20 for age ≥ 76) and at 26.42%, 50.00%, 66.07%, for PSAD cut off values of 0.1, 0.15 and 0.20 respectively. The estimated negative biopsies that could have been avoided per one non-diagnosis of low-risk PCa in men ≤ 69 years was 16 for age-adjusted values, 12.1, 8.35 and 5.75 for PSAD cut off values of 0.10, 0.15 and 0.20 respectively. The ratio of non-diagnosis of low-risk PCa under 70 years to the non-diagnosis of low-risk PCa over 75 years was 1.1 for age-adjusted values and 5.5, 6.67, 7.0, 5.6 and 4.8 for PSAD cut off values of 0.1, 0.12, 0.14, 0.15 and 0.2 respectively. Conclusion: According to our analysis, we recommend age-adjusted PSAD cut off values. In this way, we can greatly reduce negative TRUS biopsies, the related complications and the subsequent cost of overtreatment, with only a minimal loss of low-risk PCa diagnosis, in groups with theoretically treatable disease. Σκοπός: Σκοπός η δίχως κόστος eλάττωση του ολικού αριθμού των βιοψιών του προστάτη, η eλάττωση των αρνητικών βιοψιών αλλά και η eλάττωση της διάγνωσης χαμηλού κινδύνου καρκίνου σe υπeρήλικeς (υπeρδιάγνωση-υπeρθeραπeία) μe την μικρότeρη δυνατή υποδιάγνωση χαμηλού κινδύνου καρκίνου σe νeαρούς eνήλικeς μe δυνητικά θeραπeύσιμη νόσο. Μέθοδος: Σe μια σeιρά διαδοχικών ασθeνών μe διορθικά καθοδηγούμeνη βιοψία του προστάτη (TRUS), πραγματοποιήσαμe μια σeιρά από υπολογισμούς μe διαφορeτικές eλάχιστeς τιμές PSAD αλλά και των προτeινόμeνων ηλικιακά προσαρμοσμένων κατώτeρων τιμών PSAD (≥ 0,10 για ηλικία ≤ 69 , ≥ 0,15 για 70-75 και ≥0,20 για ≥ 76 eτών ). Αποτeλέσματα: Η μeίωση των TRUS βιοψιών υπολογίστηκe στο 37,32% για τις ηλικιακά προσαρμοσμένeς τιμές του PSAD και στο 26,42%, 50,00%, 66,07% για eλάχιστeς τιμές PSAD 0,1, 0,15 και 0,20 αντίστοιχα. Οι υπολογιζόμeνeς αρνητικές βιοψίeς που θα μπορούσαν να έχουν αποφeυχθeί ανά μια μη διάγνωση χαμηλού κινδύνου CaP σe άντρeς ≤ 69 eτών, ήταν 16 για τις ηλικιακά προσαρμοσμένeς τιμές, 12,1, 8,35 και 5,75 για eλάχιστeς τιμές PSAD 0,10, 0,15 και 0,20, αντίστοιχα. Συμπέρασμα: Προτeίνουμe eλάχιστeς τιμές PSAD ηλικιακά προσαρμοσμένeς μe σκοπό την μeίωση των αρνητικών βιοψιών ,των eπιπλοκών, αλλά και του κόστους της υπeρθeραπeίας σe υπeρήλικeς μe μόνο μια eλάχιστη απώλeια του χαμηλού κινδύνου PCa, στις ηλικίeς μe θeωρητικά θeραπeύσιμη νόσο.

Age-Adjusted D-Dimer Cut-Off Levels to Rule-out Venous Thromboembolism in Patients with Non-High Pre-Test Probability. Clinical Performance and Cost-Effectiveness Analysis

BackgroundD-dimer levels below a well-defined cut-off level enable to safely rule out VTE in patients with a low or intermediate pre-test probability (PTP), as the test negative predictive value (NPV) was high. As ageing is associated with increased D-dimer levels, the question was raised of the usefulness of their measurement to rule out VTE in elderly patients. Various attempts were made in the recent years to address that issue, particularly the use of age-adjusted cut-off values calculated by multiplying the patient's age by 10, in patients aged over 50.Aim of that studyThe aim of the study was to validate such a strategy, and to evaluate its economic impact in unselected outpatients referred to the emergency departments of 5 French centres (2 university hospitals, and 3 general hospitals).Patients, Materials and MethodsAfter exclusion of those on anticoagulant treatment at the time of the diagnosis (n=23), a total of 1255 consecutive patients with a non-high PTP of VTE were included in the study. The same standardized procedure was used in the 5 centres, i.e. D-dimer measurement in patients with a non-high PTP, and imaging techniques (usually computed pulmonary angiography in case of suspected PE and Doppler ultrasonography in case of suspected DVT) only when D-dimer was above the cut-off level.D-dimer was evaluated using the same latex-based fully automated assay (HemosIL D-dimer HS500 assay, Instrumentation Laboratory). Test results were expressed in ng/mL fibrinogen equivalent units (FEU), and the traditional cut-off level for VTE exclusion was 500 ng/mL.ResultsVTE was diagnosed in 105 patients of the 1255 included patients (8.4%): 88 patients were diagnosed out of the 1082 patients referred for suspected PE and 27 out the 173 referred for suspected DVT. D-dimer levels were above 500 ng/mL in all patients with VTE and in 521 of the 1150 patients without VTE (45.3%). The test NPV was 100% as well as its sensitivity. If the overall test specificity was 54.7%, it significantly decreased in an age-dependent manner over 70 years, related to a high percentage of increased D-dimer levels in elderly patients, particularly in those above 80 years.Using age-adjusted cut-off levels, calculated by multiplying the patient's age by 10, induced a significantly improvement in test specificity, particularly in very old patients with an overall NPV=60.2% vs. 54.7% using the fixed cut-off value. The overall NPV remained high (99.9%), even if a 78 y-old female with a low PTP of PE would have been misdiagnosed as her D-dimer level (540 ng/mL) was above 500 ng/mL but below the age-adjusted cut-off value. Such an improvement in test performance was found both in patients with suspected PE and DVT (Table).As this increase in test specificity would have led to exclude VTE in a higher percentage of patients in the studied population, we evaluated the cost-effectiveness of that strategy, taking into account the local cost of D-dimer testing, angiography and Doppler US (16.20, 58.72, and 75.60 Euros respectively). In the case of suspected PE, the economic impact of the proposed diagnosis strategy was a decreased of 6.9% of total costs (45,023.4 vs. 48,356.4 Euros). In the case of DVT, the overall saving was 5.1% (9,909 vs. 10,438.2 Euros). If such an analysis was used in the US, where angiography and Doppler US were more expensive (648 and 226 US$ respectively), and D-dimer less costly (14 US$), the cost savings would have been even higher (-11.0% for PE, and -6.3% for DVT).ConclusionsThe use age-adjusted cut-off levels for D-dimer, in patients aged over 50 years old, leaded to a significant increase in the test specificity, but correlatively to slightly decreased NPV and sensitivity, as some patients with D-dimer levels above 500 ng/mL but below the age-adjusted cut-off value could be misdiagnosed. However such a strategy was found to be safe in our studied populations, as the NPV remained high (99.9%), and cost-effective. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life in patients with lumbar degenerative disc disease.

Sex differences in pain perception are known to exist; however, the exact pathomechanism remains unclear. This work aims to elucidate sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life (HRQoL) in patients with lumbar degenerative disc disease. In a prospective 2-center study, back and leg pain (visual analogue scale [VAS]), functional disability (Oswestry Disability Index and Roland-Morris Disability Index), and HRQoL (EuroQol-5D and Short Form [SF12]) were collected for consecutive patients undergoing lumbar spine surgery. Objective functional impairment (OFI) was estimated using age-adjusted and sex-adjusted cutoff values for the timed-up-and-go (TUG) test. A healthy cohort of n = 110 subjects served as the control group. Univariate and multivariate analyses were performed to test the association between sex and pain, subjective and OFIs, and HRQoL. The study comprised n = 305 patients (41.6% females). Female patients had more VAS back pain (P = 0.002) and leg pain (P = 0.014). They were more likely to report higher functional impairment in terms of Oswestry Disability Index (P = 0.005). Similarly, HRQoL measured with the EuroQol-5D index (P = 0.012) and SF12 physical composite score (P = 0.005) was lower in female patients. Female patients reported higher VAS back and leg pain, functional impairment, and reduced HRQoL than male patients. However, there were no sex differences with respect to the presence and degree of OFI measured by the TUG test using age-adjusted and sex-adjusted cutoff values. As such, the TUG may be a good test to overcome sex bias for the clinical assessment of patients with degenerative disc disease.

Age-Adjusted Cutoff D-Dimer Level to Rule Out Acute Pulmonary Embolism: A Validation Cohort Study

BackgroundThe diagnosis of pulmonary embolism in the Emergency Room setting is challenging. Multiple patients have to undergo radiologic assessment with its inherent shortcomings. The D-dimer test with accepted cutoff level of 500 μg/L is associated with a high proportion of false-positive results. The present study aimed to validate the advantages of using an age-adjusted D-dimer cutoff level, compared with 500-μg/L value in the diagnosis of acute pulmonary embolism. MethodsThis study evaluated patients admitted to the Rambam Emergency Room between 2011 and 2014 with a suspected diagnosis of pulmonary embolism. Patient data, D-dimer plasma levels, and imaging results were collected. The study cohort was subdivided according to the D-dimer levels below and above 500 μg/L. The group with levels above 500 μg/L was further assessed using the newly suggested age-adjusted D-dimer cutoff level, defined as age multiplied by 10. ResultsFiles of 1241 patients were reviewed; 654 patients with low or intermediate risk for pulmonary embolism had a D-dimer level above 500 μg/L. Two hundred eight (208) patients had a D-dimer level above 500 μg/L but below the age-adjusted cutoff value; one of them was diagnosed with pulmonary embolism (0.48% [95% confidence interval 0%-2.6%]). Four hundred forty-six (446) patients had a D-dimer level above the age-adjusted cutoff value, and 28 of them were diagnosed with pulmonary embolism (6.28% [95% confidence interval 4.2%-8.9%]), representing a negative predictive value of 99.5% for the age-adjusted cutoff level. ConclusionsAn age-adjusted D-dimer cutoff level may be safely used to exclude pulmonary embolism in patients with a low or intermediate probability for acute pulmonary embolism, alleviating the need to perform unnecessary imaging evaluations.