Normative Cut-offs Research Articles

Homonymous hemi-macular atrophy in multiple sclerosis

Background: Retrograde trans-synaptic degeneration (TSD) following retro-chiasmal pathology, typically retro-geniculate in multiple sclerosis (MS), may manifest as homonymous hemi-macular atrophy (HHMA) of the ganglion cell/inner plexiform layer (GCIPL). Objective: To determine the frequency, association with clinical outcomes, and retinal and radiological features of HHMA in people with MS (PwMS). Methods: In this cross-sectional study, healthy controls (HC) and PwMS underwent retinal optical coherence tomography scanning. For quantitative identification of HHMA, a normalized asymmetry ratio was used, and its normative cutoffs were established from the HC. HHMA PwMS were propensity score matched 1:2 to non-HHMA PwMS. Mixed-effects linear regression models were used in analyses. Results: Based on normative data from 238 HC (466 eyes), 79 out of 942 PwMS exhibited HHMA (8.4%; 143 eyes). Compared to non-HHMA eyes from matched PwMS (158 PwMS; 308 eyes), HHMA eyes had lower average GCIPL (diff: −5.7 μm (95% CI −7.6 to −3.8); p < 0.001) but also inner nuclear layer (diff: −0.9 μm (95% CI −1.6 to −0.1); p = 0.02), and outer nuclear layer (diff: −1.9 μm (95% CI −3.4 to −0.4); p = 0.02) thicknesses; in further analyses, these differences were exclusive to the homonymous side of HHMA. HHMA participants also exhibited higher expanded disability status scale scores (diff: 0.5 (95% CI 0.1 to 0.9); p = 0.02), worse 100% and 2.5% visual acuity scores (diff: −3.2 (95% CI −4.1 to −1.0); p = 0.002, −5.4 (95% CI −7.5 to −3.5); p < 0.001), and higher frequency of microcystoid macular changes (10.1% vs. 3.2%; p = 0.03) compared to non-HHMA participants. Conclusions: HHMA, possibly as a marker of TSD, may signify higher disability in MS.

Do children with dysphagia and normal esophageal motility according to Chicago Classification always have "normal" esophageal motility?

Internationally adopted Chicago Classification (CC) criteria based on adult normative data have been used to diagnose children with esophageal motility disorders undergoing high-resolution esophageal manometry (HREM). The aim of this study was to compare HREM parameters of children without dysphagia and children with dysphagia and normal findings according to CC. HREM metrics of 41 children (13.2 (9-18) years; 20 female) without dysphagia and 41 children (13.7 (8-18) years; 30 female) with dysphagia and normal diagnosis according to CC were compared. Analyzed data included resting and integrated relaxation pressures (IRP) of upper (UES) and lower (LES) esophageal sphincters, esophageal peristaltic contractile integrals, transition zone (TZ) gaps, distal latency (DL), and manometric esophageal length to height ratio (MELH). 95%ile normative cutoffs were calculated from the cohort without dysphagia. Proximal contractile integral (PCI), UES and LES mean resting and IRP were not significantly different between the cohorts (p > 0.3). On the contrary, distal contractile integral (DCI), TZ gap and MELH were notably different with p = 0.0002, p = 0.027, and p = 0.033 respectively. According to 95%ile normative cutoffs of DCI, TZ gap and MELH, in cohort with dysphagia 27%, 15%, and 22% of patients respectively were not normal. First study ever to compare HREM parameters of children without dysphagia to children with dysphagia. Considerable proportion of children with dysphagia may be underdiagnosed according to the adult criteria. This emphasizes the need for universally accepted child-specific diagnostic protocols and norms.

Montreal Cognitive Assessment’s auditory items (MoCA-22): Normative data and reliable change indices

Our objective was to establish normative data and reliable change indices (RCI) for the Montreal Cognitive Assessment’s auditory items (MoCA-22). 4,935 cognitively unimpaired participants were administered the MoCA during an in-person visit to an Alzheimer’s Disease Research Center (Mage = 67.9, Meducation = 16.2, 65.8% women, 75.9% non-Hispanic-White), with 2,319 unimpaired participants returning for follow-up. Normative values and cutoffs were developed using demographic predictions from ordinary and quantile regression. Test-retest reliability was calculated using Spearman and intraclass correlations. RCI values were calculated using Chelune and colleagues’ (1993) formula. Education, age, and sex were all statistically related to MoCA-22 scores, with education having the strongest relationship. Notably, these relationships were not consistent across MoCA-22 quantiles, with education becoming more important and sex becoming less important for predicting low scores. These models were integrated into a calculator for deriving normative scores for an individual case. Furthermore, there was adequate-to-good test-retest reliability (ϱ = 0.56 95% CI [.54, .59]; ICC = 0.75, 95% CI [.73, .77]) and changes of at least 2-3 points are necessary to identify reliable change at 1-3-year follow-up. These findings add to the literature regarding utility of the MoCA-22 in the cognitive screening of older adults.

On the Clinimetrics of the Montreal Cognitive Assessment: Cutoff Analysis in Patients with Mild Cognitive Impairment due to Alzheimer's Disease.

In the era of disease-modifying therapies, empowering the clinical neuropsychologist's toolkit for timely identification of mild cognitive impairment (MCI) is crucial. Here we examine the clinimetric properties of the Montreal Cognitive Assessment (MoCA) for the early diagnosis of MCI due to Alzheimer's disease (MCI-AD). Data from 48 patients with MCI-AD and 47 healthy controls were retrospectively analyzed. Raw MoCA scores were corrected according to the conventional Nasreddine's 1-point correction and demographic adjustments derived from three normative studies. Optimal cutoffs were determined while previously established cutoffs were diagnostically reevaluated. The original Nasreddine's cutoff of 26 and normative cutoffs (non-parametric outer tolerance limit on the 5th percentile of demographically-adjusted score distributions) were overly imbalanced in terms of Sensitivity (Se) and Specificity (Sp). The optimal cutoff for Nasreddine's adjustment showed adequate clinimetric properties (≤23.50, Se = 0.75, Sp = 0.70). However, the optimal cutoff for Santangelo's adjustment (≤22.85, Se = 0.65, Sp = 0.87) proved to be the most effective for both screening and diagnostic purposes according to Larner's metrics. The results of post-probability analyses revealed that an individual testing positive using Santangelo's adjustment combined with a cutoff of 22.85 would have 84% post-test probability of receiving a diagnosis of MCI-AD (LR+ = 5.06). We found a common (mal)practice of bypassing the applicability of normative cutoffs in diagnosis-oriented clinical practice. In this study, we identified optimal cutoffs for MoCA to be allocated in secondary care settings for supporting MCI-AD diagnosis. Methodological and psychometric issues are discussed.

Diagnostic criteria of anterior segment swept-source optical coherence tomography to detect gonioscopic angle closure

AimsTo compare the diagnostic performance of 360° anterior segment optical coherence tomography assessment by applying normative percentile cut-offs versus iris trabecular contact (ITC) for detecting gonioscopic angle closure.MethodsIn this multicentre...

Evaluating the Clinical Reliability and Reference Values of the International Outcome Inventory for Cochlear Implants in a DOD Population.

Hearing loss significantly affects an individual's well-being, communication, social interaction, and quality of life. Cochlear implants serve as a viable management option. Given the variability in the impact of impairment, self-report measures are crucial for evaluating the perceived benefits of management options. The study aims to assess the reliability of the International Outcome Inventory for Cochlear Implants (IOI-CI) and establish normative cutoffs. This questionnaire evaluates patient's satisfaction with cochlear implants and contributes to the understanding of their experiences, addressing the increasing interest among cochlear implant clinicians. The design relies on electronic medical databases within the Veterans Affairs (VA) and Department of Defense (DOD) systems. After identification of eligibility, recruitment was based on participants responding to mailed study documents. This research adopts a descriptive approach of the analysis of questionnaire responses as well as quantitatively evaluating the reliability. Forty-nine service members, Veterans, and their dependents, including 32 men and 17 women, participated in the study. The participants had a mean age of 68.0 years, with cochlear implants ranging from 6 months to 2 years post-initial stimulation. The majority had a unilateral cochlear implant with a hearing aid on the contralateral ear. Data collected involved mailing baseline study packets, including the IOI-CI questionnaire, to potential participants identified through medical databases. Participants indicated consent by returning the study packet. Follow-up packets were sent at a later time. Intraclass Correlation Coefficients (ICC) were utilized for test-retest reliability and Generalized Linear Models (GLM) for exploring the impact of clinical and demographic factors. Data were analyzed using R. The ICC revealed a good level of agreement (ICC=0.84) between baseline and follow-up assessments for the IOI-CI total score. The GLM did not identify significant factors influencing IOI-CI scores. Normative values were established, indicating total scores between 18 and 35 as within the normal range for this questionnaire. The study contributes valuable insights into the reliability of the IOI-CI and establishes normative cutoffs, aiding clinicians in assessing cochlear implant users' experiences and satisfaction.

Functional lower extremity strength influences stepping strategy in community-dwelling older adults during single and dual-task walking

As age increases, a decline in lower extremity strength leads to reduced mobility and increased fall risks. This decline outpaces the age-related reduction in muscle mass, resulting in mobility limitations. Older adults with varying degrees of mobility-disability use different stepping strategies. However, the link between functional lower extremity strength and stepping strategy is unknown. Therefore, understanding how age-related reductions in functional lower extremity strength influence stepping strategy is vital to unraveling mobility limitations. Twenty participants (17F, 72 ± 6 years) were recruited and tested at a local community event. Participants were outfitted with inertial measurement units (IMU) and walked across a pressurized walkway under single and dual motor task conditions (walking with and without carrying a tray with water) at their usual and fast speeds. Participants were dichotomized into normal (11) or low functional strength groups (9) based on age-specific normative cutoffs using the instrumented 5-repetition Sit-to-Stand test duration. Our study reveals that older adults with normal strength prefer adjusting their step time during walking tasks, while those with reduced strength do not exhibit a preferred stepping strategy. This study provides valuable insights into the influence of functional lower extremity strength on stepping strategy in community-dwelling older adults during simple and complex walking tasks. These findings could aid in diagnosing gait deviations and developing appropriate treatment or management plans for mobility disability in older adults.

A Prospective Study on Neural Biomarkers in Patients with Long-COVID Symptoms.

this prospective observational study aims to assess serum levels of glial fibrillary acidic protein (GFAP), s100b, and total Tau in long-COVID patients, exploring correlations with symptoms, cognitive decline, mental health, and quality of life. Long-COVID patients visiting our outpatient clinic (February 2021-December 2022) were screened alongside age- and sex-matched controls. GFAP, s100b, and total Tau in serum were measured with ELISA. Cognitive function, depression, anxiety, post-traumatic stress disorder, and quality of life were evaluated using MoCA, HADS (depression and anxiety), IES-R, and SF-36, respectively. Sixty-five long-COVID patients and 20 controls were included. GFAP levels were significantly higher in long-COVID patients (p = 0.031), though not correlating with the presence of long-COVID symptoms. S100b and total Tau showed no significant differences between patients and controls. Nervous system-related symptoms were reported in 47% of patients. High rates of cognitive decline (65.9%), depression (32.2%), anxiety (47.5%), and post-traumatic stress disorder (44.1%) were observed. Over 80% of the study population scored below normative cutoffs for SF-36, indicating a significant impact on quality of life. in this long-COVID cohort with substantial psychological and cognitive symptoms, GFAP levels were elevated compared to controls, though not correlating with the presence of long-COVID symptoms.

Household food insecurity is associated with greater autonomic dysfunction testing score in Latinos with type 2 diabetes.

We examined household food insecurity (HFI) and autonomic nervous system (ANS) function in a subset of low-income Latinos with type 2 diabetes with data from a stress management trial. InclusionLatino or Hispanic, Spanish speaking, age less than 18 years, ambulatory status, type 2 diabetes more than 6 months, A1c less than 7.0%. ExclusionPain or dysfunction in hands (e.g., arthritis) precluding handgrip testing; medical or psychiatric instability. HFI was assessed with the 6-item U.S. household food security survey module; with responses to > = 1 question considered HFI. An ANS dysfunction index was calculated from xix autonomic function tests which were scored 0 = normal or 1 = abnormal based on normative cutoffs and then summed. Autonomic function tests were: 1) 24-hour heart rate variability as reflected in standard deviation of the normal-to-normal (SDNN) heart rate acquired with 3-channel, 7-lead ambulatory electrocardiogram (Holter) monitors; 2) difference between the highest diastolic blood pressure (DBP) during sustained handgrip and the average DBP at rest; 3) difference between baseline supine and the minimal BP after standing up; and, from 24-hour urine specimens 4) cortisol, 5) normetanephrine, and, 6) metanephrine. Thirty-five individuals participated, 23 (65.7%) of them were women, age mean = 61.6 (standard deviation = 11.2) years, HbA1c mean = 8.5% (standard deviation = 1.6) and 20 participants (57.1%) used insulin. Twenty-two participants (62.9%) reported HFI and 25 (71.4%) had one or more abnormal ANS measure. Independent t-tests showed that participants with HFI had a higher ANS dysfunction index (mean = 1.5, standard deviation = 0.9) than patients who were food secure (mean = 0.7, standard deviation = 0.8), p = 0.02. Controlling for financial strain did not change significance. Total ANS index was not related to glycemia, insulin use or other socioeconomic indicators. In this sample, HFI was associated with ANS dysfunction. Policies to improve food access and affordability may benefit health outcomes for Latinos with diabetes.

Age specific reference intervals for plasma biomarkers of neurodegeneration and neurotrauma in a Canadian population

IntroductionIn this study, we aimed to create reference intervals (RI) using a large Canadian population-based cohort, for plasma protein biomarkers with potential utility to screen, diagnosis, prognosticate and manage a variety of neurological diseases and disorders. RIs were generated for: the ratio of amyloid beta 42 over 40 (Aβ42/40), phosphorylated tau-181 (p-tau-181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Methods900 plasma specimens from male and female participants aged 3–79 years old were obtained from the Statistics Canada Biobank, which holds specimens from the Canadian Health Measures Survey. Analysis of Aβ42/40, p-tau-181, NfL and GFAP was performed on the Quanterix Simoa HD-X analyzer using the Neurology 4-plex E and p-tau-181 assays. Discrete RIs were produced according to Clinical Laboratory Standards Institute guidelines (EP28-A3c). Continuous RIs were created using quantile regression. ResultsFor discrete RIs, significant age partitions were determined for each biomarker. No significant sex partitions were found. The following ranges and age partitions were determined: Aβ42/40: 3–<55y = 0.053–0.098, 55–<80y = 0.040–0.090; p-tau-181: 3–<12y = 1.4–5.6 pg/ml, 12–<60y = 0.8–3.1 pg/ml, 60–<80y = 0.9–4.0 pg/ml; NfL: 3–<40y = 2.6–11.3 pg/ml, 40–<60y = 4.6–17.7 pg/ml, 60–<80y = 8.1–47.1 pg/ml; GFAP; 3–<10y = 47.0–226 pg/ml, 10–<60y = 21.2–91.9 pg/ml, 60–<80y = 40.7–228 pg/ml. Continuous RIs produced smooth centile curves across the age range, from which point estimates for each year of age were calculated. ConclusionsDiscrete and continuous RIs for neurological plasma biomarkers will help refine normative cut-offs across the lifespan and improve the precision of interpretating biomarker levels. Continuous RIs are recommended for use in age groups, such as pediatrics and older adults, that experience rapid concentration changes by age.

THU649 PCOS Phenotype In Unselected Populations (P-PUP) Study: Defining And Comparing Hirsutism Across Various Ethnic Groups In Unselected Populations

Abstract Disclosure: S. Kiconco: None. A.E. Joham: None. L.V. Suturina: None. X. Zhao: None. A. Gambineri: None. F.R. Tehrani: None. B.O. Yildiz: None. J. Kim: None. H.J. Teede: None. R. Azziz: None. Introduction Hirsutism is defined as the male pattern distribution of terminal hair in a female. It is one of the diagnostic features of polycystic ovary syndrome (PCOS), reflecting clinical hyperandrogenism, as measured by the modified Ferriman-Gallwey score (mFG). However, whether the mFG scores and the normative cut-off varies by ethnicity is unclear. We aimed to describe and compare the distribution of mFG score in different ethnic groups from eight countries using data from unselected (medically unbiased) populations to determine and compare the normative cut-off values between the different ethnic groups and the prevalence of hirsutism thereby defined. Methods We utilised data of 10,919 participants aged 15 to 80 years. Data were obtained from epidemiologic studies assessing unselected women conducted in different countries including China, Iran, Italy, Nigeria, Russia, South Korea, Turkey, and the United States of America. The distribution of mFG between ethnic groups was determined descriptively as medians. Cluster analysis (k means, k=2) and the receiver operating characteristics curve were used to determine the normative cut-offs for the mFG score. All medians, cut-offs and percentile values were compared between ethnic groups using the Kruskal-Wallis test at a 95% level of significance. Results Our data consisted of 11 ethnic groups from 8 countries. The Persian (4.8±4.7) and Italian (4.8±4.7) populations had higher median mFG scores than the rest of the ethnic groups, whilst Asian populations (Chinese, Korean and Buryat) had the lowest scores. Overall, the median distribution of mFG differed significantly by ethnicity. Using cluster analysis, the mFG cut offs range from 4 to 9, with the Persian ethnic group having the highest, followed by the Italian group, with cut-offs differing by ethnicity overall; however cut offs are similar for Black American, Turkish, Asian and Russian groups. Conclusion The distribution and normal cut off values for hirsutism differ significantly by ethnicity, with the Persian population having the highest cut offs. Ethnicity needs to be considered when assessing women for clinical hyperandrogenism. Presentation: Thursday, June 15, 2023

THU645 Comparison Of LC-MS/MS Testosterone Assays Towards Standardization Of Lower Testosterone Ranges

Abstract Disclosure: M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Eli-Lilly, Amino Co. S. Ottey: None. K.D. Sherif: None. O. Sugahara: None. F. Pokuah: None. A.N. Lyle: None. V. Hubert: None. Objective: Polycystic ovary syndrome (PCOS) is a common disorder in women. The diagnosis of PCOS often includes elevated concentrations of serum testosterone. Previous work has harmonized the higher range of the testosterone assay and normative cut-offs for low and high testosterone concentrations for the male gender. However, similar work is needed to better align existing Liquid Chromatography Tandem Mass Spectroscopy (LC-MS/MS) methods in the lower range of testosterone and determine upper limits of normal for females. Methods: This is a secondary analysis of a pooled cohort of 60 obese adolescents with and without PCOS, enrolled in 1 of three studies (NCT02157974; NCT03041129; NCT03717935) at the University of Colorado, Anschutz. None of the participants were taking hormonal medication to treat PCOS. Frozen plasma samples collected between 6-7 AM were analyzed by Esoterix hormone branch of LabCorp (Agoura Hills, CA) and by the Centers for Disease Control (CDC) Clinical Standardization Programs with LC-MS/MS. Samples were selected from the available participants to encompass the full range of testosterone concentrations available within the cohort. Results: Within the entire cohort (N=60, Age = 15.8, SD: ± 1.7 years, BMI 35.4, SD: ± 5.5 kg/m2), the means between the assays were statistically, but not clinically different (CDC 48.4 SD: ±24.4 ng/dL vs OL 45.4 SD: ±22.1, p=0.013).Deming regression indicated that the assays were not different with an intercept of 2.05 (-3.69 to 7.79, 95% confidence interval) and slope of 0.895 (0.753 to 1.04, 95% confidence interval). The two assays were highly correlated via linear regression (R2=0.859, p&amp;lt;0.001) and with a Bland-Altman comparison, the CDC assay only had a slight positive bias of 3.04, SD: ± 9.18 ng/dL relative to Esoterix. When divided by PCOS status (PCOS N=52, Hirsutism score 6.5±5.9, Control N=8, Hirsutism score 2.1±4.5), the CDC assay ROC demonstrated discrimination of PCOS status with an AUC of 0.903 (0.800-1.00), p&amp;lt;0.001 and the Youden index was &amp;lt;27.1 ng/dL with a sensitivity of 87.5% and a specificity of 86.5%. However, when the sensitivity was at 100%, the specificity was 57.7% and the cut-off &amp;lt;43.0 ng/dL. Conclusions: The Esoterix, a major commercial lab, assay is very similar to that of CDC LC-MS/MS, and able to discriminate PCOS status at 43.0 ng/dL. Future work is needed to 1) align more clinical assays to the CDC standard and 2) define a common cut-off to describe hyperandrogenism in females across the weight and age spectrum. Presentation: Thursday, June 15, 2023

Behavioral and Emotional Problems among School Children in Tripoli, Libya: What Impact does it have on Community Public Health?

Objective: to detect the prevalence of mental health problems, including behavioral and emotional difficulties among school children (6-15 years) in Tripoli, Libya as observed by their parents and teachers. Methods: The study took place in Tripoli, Libya. Data was collected over three months period between January and March 2022 from parents and teachers. The Arabic version of Strengths and Difficulties Questionnaire (SDQ. Goodman 2002) were used. The sample size was 300 children aged between 6 and 15 years who were attending compulsory education. Four schools were randomly selected and then children were randomly sampled from each class. Parents were asked to hand over the questionnaire to their child’s teacher and collect them later. Data was analyzed to describe normative scores, bandings and cut-offs for normal, borderline and abnormal scores. Only public schools were included in the study. Results: When it came to the perception of teachers and parents, it was found that the response rate for parents and teachers were almost the same only 245 questionnaires were returned (134 male and 111 female) giving a response rate of 81.6%. out of these, 208, both the parents and teacher questionnaires were returned (84.8%),26 filled in only the parents' questionnaires (10.6%), and 11 returned only the teacher’s questionnaire (4.4%). TEACHERS rated their pupils consistently as showing difficulties in all areas with (23.0 %) of the children considered to be displaying abnormal behavior (Total Difficulties Score). The highest proportion of abnormal behavior was for peer relation (17.0%) and conduct problems (18.0%). PARENTS rated their children as having fewer problems than rated by teachers, but rates were still high with (15%) of the children receiving total difficulty scores in the abnormal band. The most problematic areas as assessed by parents were peer relations (29%) followed by emotion problems (22%). Conclusion: Parent SDQs revealed high rates of children with conduct, emotional and peer problems falling above the 90th centile established in the UK sample. Teachers SDQs revealed higher rates of children with conduct problems. Comparison with UK and Egypt data showed abnormal total difficulties score of 11.9% which is a bit higher than UK (10.1%) but lower than that of Egypt (20.6%). Much greater investment in child mental health care is needed. More efforts are needed to identify those children and decide what we can usefully do to help the many-not only the few. Keywords: Tripoli, Libya, behavioral problems, school children, SDQ, mental health

Association of Neuroimaging Markers on Clinical CT Scans With Domain-Specific Cognitive Impairment in the Early and Later Post-Stroke Stages.

Post-stroke cognitive impairment (PSCI) is associated with neuroimaging markers, including cortical atrophy and white matter lesions (WMLs), on clinically acquired CT neuroimaging. To investigate the association between cortical atrophy/WMLs and PSCI in specific cognitive domains in the acute/subacute and chronic stages after stroke, in order to provide clarity on the relationship between these neuroimaging markers and the temporal evolution of PSCI. We visually assessed cortical atrophy using the Global Cortical Atrophy (GCA) scale and WMLs using the Fazekas scale. Oxford Cognitive Screen (OCS) or Birmingham Cognitive Screen (BCoS) assessed PSCI at two timepoints (acute/subacute and chronic) in six domains (language, memory, number processing, executive function, attention, praxis). We binarised domain-specific performance as impaired/unimpaired using normative cut-offs. Multivariable linear and logistic regression analyses evaluated associations between GCA/Fazekas scores with acute/subacute/chronic global and domain-specific PSCI, and ANCOVAs examined whether these scores were significantly different in patients with recovered versus persistent PSCI. Age, sex, education, NIHSS, lesion volume, and recurrent stroke were covariates in these analyses. Among 411 stroke patients (Mdn/IQR age= 76.16/16.64; 193 female; 346 ischaemic stroke; 107 recurrent stroke), GCA and Fazekas scores were not associated with global cognitive impairment in the acute/subacute stage after stroke, but GCA score was associated with chronic global PSCI (B = 0.01, p < .001, 95% CI [0.00 0.01]). In domain-specific analyses, GCA score was associated with chronic impairment in the memory (B = 0.06, p < .001, 95% CI [0.03 0.10]) and attention (B = 0.05, p = .003, 95% CI [0.02 0.09]) domains, and patients with persistent PSCI these domains showed significantly higher GCA scores than patients who had recovered (Memory: F(1,157) = 6.63, p = .01, η 2 G = .04; Attention: F(1,268) = 10.66, p = .001, η 2 G = .04). The present study highlights the potential impact of cortical atrophy on the cognitive recovery process after stroke and demonstrates the prognostic utility of CT neuroimaging for post-stroke cognitive outcomes. Clinical neuroimaging could help identify patients at long-term risk of PSCI during acute hospitalisation.

Normative cut-offs for polycystic ovary syndrome diagnostic features in adolescents using cluster analysis.

The diagnosis of polycystic ovary syndrome (PCOS) remains challenging with international guidelines prioritising accurate cut-offs for individual diagnostic features. These diagnostic cut-offs are currently based on arbitrary percentiles, often from poorly characterised cohorts, and are dependent on variable laboratory ranges defined by assay manufacturers, limiting diagnostic accuracy. Cluster analysis is the recommended approach for defining normative cut-offs within populations for clinical syndromes. Few PCOS adult studies have applied cluster analysis, with no studies in adolescents. We aimed to define normative cut-offs for individual PCOS diagnostic features in a community-based population of adolescents using cluster analysis. This analysis utilised data from the Menstruation in Teenagers Study, a subgroup of the Raine Study, which is a population based prospective cohort of 244 adolescents whose mean age at PCOS assessment was 15.2 years. K-means cluster analysis and receiver operating characteristics curves were used to define normative cut-offs for modified Ferriman-Gallwey (mFG) score, free testosterone (free T), free androgen index (FAI), and menstrual cycle length. Normative cut-offs for mFG, free T, FAI, and menstrual cycle lengths were 1.0, 23.4 pmol/L, 3.6, and 29 days, respectively. These corresponded to the 65th, 71st, 70th, and 59th population percentiles, respectively. In this novel study, we define the normative diagnostic criteria cut-offs in this unselected adolescent population and show that these cut-offs correspond to lower percentiles than conventional cut-offs. These findings highlight the pertinent need to re-define PCOS diagnostic cut-offs in adolescents. Validation is required in larger, multi-ethnic, and well-characterised adolescent cohorts.

Survey of exercise testing and training in cystic fibrosis clinics in the UK: a decade of progress

ObjectivesRegular exercise testing is recommended for people with cystic fibrosis (pwCF), as is the provision and regular review of exercise training programmes. A previous survey on exercise testing and training...

Reference Intervals for Plasma Biomarkers of Alzheimer’s Disease

AbstractBackgroundSeveral blood‐based biomarkers are emerging as potential screening, diagnostic, and prognostic tools for Alzheimer’s disease (AD), including: the ratio of amyloid beta 42 over 40 (Aβ42/40), reflecting the pathology of amyloid plaques; phosphorylated tau‐181 (p‐tau‐181), reflecting the formation of neurofibrillary tangles; neurofilament light (NF‐L), reflecting axonal damage observed in neurodegeneration; and glial fibrillary acidic protein (GFAP), reflecting neuroinflammation through astrocyte activation. A critical step in the translation of these biomarkers from research to clinical implementation is establishment of reference intervals derived from an appropriate population.Methods900 plasma samples from male and female participants aged 3‐79 years old were analyzed for Aβ42/40, p‐tau‐181, NF‐L and GFAP to create reference intervals (RI). Samples are obtained from the Canadian Health Measures Survey (CHMS), a national study that collects demographics, health questionnaires, clinical data and biospecimens from participants. Analysis was preformed on the Quanterix Simoa HD‐X analyzer using the Neurology 4‐plex E and p‐tau‐181 assay. Discrete and continuous RIs were produced for each biomarker. Discrete RIs are produced according to the Clinical Laboratory Standards Institute guidelines (EP20‐A3c). Continuous RIs are created using quantile regression.ResultsParticipant samples were selected from the following age bins designated by the CHMS biobank: 3 to 5 years (N=56), 6 to 11 years (N=58), 12 to 19 years (N=58), 20 to 39 years (102), 40 to 59 years (N= 102), 60 to 79 years (N=140). After analysis, age partitions for discrete RI were created, resulting in two to five age‐bins per biomarker which reference intervals were generated for. Continuous RIs produced smooth centile curves across all ages, from which point estimates for any age can be calculated.ConclusionsBoth discrete and continuous RIs for plasma Aβ42/40, p‐tau‐181, NF‐L and GFAP may help refine normative cut offs for each biomarker across the lifespan.

Normative cutoffs of muscle mass, muscle strength, and frailty for healthy Indian population.

Population-derived cutoffs for low skeletal muscle mass, skeletal muscle strength, and frailty among Indians are lacking. Studies describing sarcopenia and frailty among patients with chronic liver diseases have used cutoffs derived from Caucasian populations giving erroneous results. We aimed to derive gender-specific cutoffs for low skeletal muscle mass and skeletal muscle strength from healthy Indians. Healthy Indian population consisted of two groups. Group 1 (GpI) included 242 healthy liver donors and group 2 (GpII) 272 healthy health care workers. Skeletal muscle index (SMI) was calculated from computed tomography (CT) abdomen performed prior to donor hepatectomy only in GpI. Liver frailty index (LFI) was computed using the online calculator, after recording hand grip strength (HGS), chair stand-up test (CSUT), and balance test in both groups. HGS was measured using the Smedley handgrip dynamometer. CSUT was noted as time to complete 5 chair stand-ups with subjects' arms folded across the chest. Gender-specific cutoffs of SMI and HGS were derived as <5th percentile of the distribution values and as >95th percentile for CSUT and LFI values. The SMI was measured from GpI subjects (n=242; 120 males [mean age 31.13] and 122 females [mean age 36.60]). The HGS, CSUT, and LFI were measured in GpI and GpII subjects (n=514; 272 males [mean age 34.30] and 242 females [mean age 37.52]). The cutoffs for SMI, HGS, CSUT, and LFI were <27.72 cm2/m2, <25.63 kg, >10 s, and >3.49, respectively for healthy males. The corresponding cutoffs for healthy females were <24.4 cm2/m2, <16.7 kg, > 10 s, and >3.68, respectively. We derived gender-specific cutoffs for SMI, HGS, CSUT, and LFI from healthy adult Indian population, which can be used to detect sarcopenia and frailty among patients with liver diseases, as well as other conditions.

Diagnostic properties of the Italian ECAS Carer Interview (ECAS-CI)

BackgroundThis study aimed at providing diagnostic properties and normative cut-offs for the Italian ECAS Carer Interview (ECAS-CI).MaterialsN = 292 non-demented ALS patients and N = 107 healthy controls (HCs) underwent the ECAS-CI and the Frontal Behavioural Inventory (FBI). Two ECAS-CI measures were addressed: (1) the number of symptoms (NoS; range = 0–13) and (2) that of individual symptom clusters (SC; range = 0–6). Diagnostics were explored against an FBI score ≥ than the 95th percentile of the patients’ distribution.ResultsBoth the NoS and SC discriminated patient from HCs. High accuracy, sensitivity, and specificity were detected for both the NoS and SC; however, at variance with SC, the NoS showed better post-test features and did not overestimate the occurrence of behavioural changes. The ECAS-CI converged with the FBI and diverged from the cognitive section of the ECAS.DiscussionThe ECAS-CI is a suitable screener for behavioural changes in ALS patients, with the NoS being its best outcome measure (cut-off: ≥ 3).

What Is a Normal Testosterone Level for Young Men? Rethinking the 300 ng/dL Cutoff for Testosterone Deficiency in Men 20-44 Years Old.

There is an age-related decline in male testosterone production. It is therefore surprising that young men are evaluated for testosterone deficiency with the same cutoff of 300 ng/dL that was developed from samples of older men. Our aim is to describe normative total testosterone levels and age-specific cutoffs for low testosterone levels in men 20 to 44 years old. We analyzed the 2011-2016 National Health and Nutrition Examination Surveys, which survey nationally representative samples of United States residents. Men 20 to 44 years old with testosterone levels were included. Men on hormonal medications, with a history of testicular cancer or orchiectomy, and with afternoon/evening laboratory values were excluded. We separated men into 5-year intervals and evaluated the testosterone levels of each age group, and for all men 20 to 44 years old. We used the American Urological Association definition of a "normal testosterone level" (the "middle tertile") to calculate age-specific cutoffs for low testosterone levels. Our final analytic cohort contained 1,486 men. Age-specific middle tertile levels were 409-558 ng/dL (20-24 years old), 413-575 ng/dL (25-29 years old), 359-498 ng/dL (30-34 years old), 352-478 ng/dL (35-39 years old), and 350-473 ng/dL (40-44 years old). Age-specific cutoffs for low testosterone levels were 409, 413, 359, 352, and 350 ng/dL, respectively. Diagnosis of testosterone deficiency has traditionally been performed in an age-indiscriminate manner. However, young men have different testosterone reference ranges than older men. Accordingly, age-specific normative values and cutoffs should be integrated into the evaluation of young men presenting with testosterone deficiency.