Cognitive functioning in patients with neuro-PASC: the role of fatigue, mood, and hospitalization status.

This study sought to characterize cognitive functioning in patients with neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) and investigate the association of subjective and objective functioning along with other relevant factors with prior hospitalization for COVID-19. Participants were 106 adult outpatients with Neuro-PASC referred for abbreviated neuropsychological assessment after scoring worse than one standard deviation below the mean on cognitive screening. Of these patients, 23 had been hospitalized and 83 had not been hospitalized for COVID-19. Subjective cognitive impairment was evaluated with the self-report cognition subscale from the Patient-Reported Outcome Measurement Information System. Objective cognitive performance was assessed using a composite score derived from multiple standardized cognitive measures. Other relevant factors, including fatigue and depression/mood symptoms, were assessed via the Patient-Reported Outcome Measurement Information System. Subjective cognitive impairment measures exceeded the minimal difficulties noted on objective tests and were associated with depression/mood symptoms as well as fatigue. However, fatigue independently explained the most variance (17.51%) in patients' subjective cognitive ratings. When adjusting for fatigue and time since onset of COVID-19 symptoms, neither objective nor subjective impairment were associated with prior hospitalization for COVID-19. Findings suggest that abbreviated neuropsychological assessment may not reveal objective difficulties beyond initial cognitive screening in patients with Neuro-PASC. However, subjective cognitive concerns may persist irrespective of hospitalization status, and are likely influenced by fatigue and depression/mood symptoms. The impact of concomitant management of fatigue and mood in patients with Neuro-PASC who report cognitive concerns deserve further study.

Multidimensional ADHD Symptom Profiles: Associations with Adverse Childhood Experiences.

OBJECTIVE: Adverse childhood experiences (ACEs) are associated with a range of negative health outcomes, including attention-deficit/hyperactivity disorder (ADHD) and neurocognitive deficits. This study identified symptom profiles in adult patients undergoing neuropsychological evaluations for ADHD and examined the association between these profiles and ACEs. METHODS: Utilizing unsupervised machine learning models, the study analyzed data from 208 adult patients. RESULTS: The Gaussian Mixture Model revealed two distinct symptom profiles: "Severely Impaired" and "Moderately Impaired". The "Severely Impaired" profile, 23.6% of the sample, was characterized by more severe ADHD symptomatology in childhood and worse neurocognitive performance. The "Moderately Impaired" profile, 76.4% of the sample, had scores in the average range for self-reported internalizing and externalizing psychopathology and better neurocognitive performance. There was a greater number of ACEs reported by patients in the Severely Impaired profile than the Moderately Impaired profile (p = .022). Specifically, using an ACEs cutoff of ≥4, 53.1% of patients in the Severely Impaired profile reported four or more ACEs, compared with 34.6% in the Moderately Impaired profile (p = .020). Profiles were not related to clinician-ascribed diagnosis. CONCLUSIONS: Findings underscore the association between ACEs and worse symptom profiles marked by impaired neurocognitive function, increased internalizing and externalizing psychopathology, and heightened perceived stress in adults with ADHD. Future research may explore the effect of ACEs on symptom profiles in diverse populations and potential moderators or mediators of these associations. Findings offers valuable insights for clinicians in their assessment and treatment planning.

Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes.

BACKGROUND: Kinases are intracellular signalling mediators and key to sustaining the inflammatory process in rheumatoid arthritis (RA). Oral inhibitors of Janus Kinase family (JAKs) are widely used in RA, while inhibitors of other kinase families e.g. phosphoinositide 3-kinase (PI3K) are under development. Most current biomarker platforms quantify mRNA/protein levels, but give no direct information on whether proteins are active/inactive. Phosphoproteome analysis has the potential to measure specific enzyme activation status at tissue level. METHODS: We validated the feasibility of phosphoproteome and total proteome analysis on 8 pre-treatment synovial biopsies from treatment-naive RA patients using label-free mass spectrometry, to identify active cell signalling pathways in synovial tissue which might explain failure to respond to RA therapeutics. RESULTS: Differential expression analysis and functional enrichment revealed clear separation of phosphoproteome and proteome profiles between lymphoid and myeloid RA pathotypes. Abundance of specific phosphosites was associated with the degree of inflammatory state. The lymphoid pathotype was enriched with lymphoproliferative signalling phosphosites, including Mammalian Target Of Rapamycin (MTOR) signalling, whereas the myeloid pathotype was associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling. This analysis also highlighted novel kinases not previously linked to RA, such as Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in the myeloid pathotype. Several phosphosites correlated with clinical features, such as Disease-Activity-Score (DAS)-28, suggesting that phosphosite analysis has potential for identifying novel biomarkers at tissue-level of disease severity and prognosis. CONCLUSIONS: Specific phosphoproteome/proteome signatures delineate RA pathotypes and may have clinical utility for stratifying patients for personalised medicine in RA.

The Making Change Test: Initial validation of a novel digitized performance validity test for tele-neuropsychology.

OBJECTIVE: The Making Change Test (MCT) is a brief, digitized freestanding performance validity test (PVT) designed for tele-neuropsychology (TeleNP). The objective of this study was to report the initial validation of the MCT in a mixed neuropsychiatric sample referred for neuropsychological evaluation using a known-groups design. METHOD: The sample consisted of 136 adult outpatients who underwent a neuropsychological evaluation. Patients were classified as valid (n = 115) or invalid (n = 21) based on several established PVTs. Two validity indicators were calculated and assessed, including an Accuracy Response-Score and an Abbreviated Index. The Accuracy Response-Score incorporated both response time and errors. The Abbreviated Index aggregated response time and errors across the most sensitive test items in terms of predicting performance validity status. RESULTS: Correlational analyses indicated that the MCT Accuracy Response-Score and Abbreviated Index were more similar to non-memory-based PVTs than memory-based PVTs. Both the MCT Accuracy Response-Score and Abbreviated Index indicated acceptable classification accuracy (area under the curve of .77). The optimal cut score for the MCT Accuracy Response-Score (≥24) yielded a sensitivity of .38 and specificity of .90. The optimal cut score associated with the Abbreviated Index yielded slightly better operating characteristics, with a sensitivity of .50 and specificity of .90. CONCLUSIONS: Initial findings provide support for the criterion and construct validity of the MCT and suggest a promising TeleNP future for this performance validity tool. However, additional support is necessary before the MCT can be used clinically.

Putting the ready in readiness: A post-hoc analysis of surgeon performance during a military MASCAL in Afghanistan.

BACKGROUND: All military surgeons must maintain trauma capabilities for expeditionary care contexts, yet most are not trauma specialists. Maintaining clinical readiness for trauma and mass casualty care is a significant challenge for military and civilian surgeons. We examined the effect of a prescribed clinical readiness program for expeditionary trauma care on the surgical performance of 12 surgeons during a 60-patient MASCAL event. METHODS: The sample included orthopaedic (4) and general surgeons (8) who cared for MASCAL victims at Hamad Karzai International Airport, Kabul, Afghanistan on 26 August 2021. One orthopaedic and two general surgeons had prior deployment experience. The prescribed program included three primary measures of clinical readiness: 1. expeditionary knowledge (exam score), 2. procedural skills competencies (performance assessment score), 3. clinical activity (operative practice profile metric). Data were attained from program records for each surgeon in the sample. Each of the 60 patient cases were reviewed and rated (performance score) by The Joint Trauma System's Performance Improvement Branch; a military-wide performance improvement organization. All scores were normalized to facilitate direct comparisons using effect size calculations between each pre-deployment measure and MASCAL surgical care. RESULTS: Pre-deployment knowledge and clinical activity measures met program benchmarks. Baseline pre-deployment procedural skills competency scores did not meet program benchmarks, however those gaps were closed through re-training, ensuring all surgeons met or exceeded the program benchmarks pre-deployment. There were very large effect sizes (Cohen's d) between all program measures and surgical care score, confirming the relationship between the program measures and MASCAL trauma care provided by the 12 surgeons. CONCLUSION: The prescribed program measures ensured all surgeons achieved pre-deployment performance benchmarks and provided high quality trauma care to our nation's servicemembers. LEVEL OF EVIDENCE: Prognostic, Level III/IV.

Evaluation of urological and gynecological surgeons as force multipliers for mass Casualty trauma care.

BACKGROUND: The clinical demands of mass casualty events strain even the most well-equipped trauma centers and are especially challenging in resource-limited rural, remote, or austere environments. Gynecologists and urologists care for patients with pelvic and abdominal injuries, but the extent to which they are able to serve as "force multipliers" for trauma care is unclear. This study examined the abilities of urologists and gynecologists to perform 32 trauma procedures after mentored training by expert trauma educators to inform the potential for these specialists to independently care for trauma patients. METHODS: Urological (6), gynecological surgeons (6), senior (PGY5) general surgery residents (6), and non-trauma trained general surgeons (8) completed a rigorous trauma training program (ASSET+). All participants were assessed in their trauma knowledge and surgical abilities performing 32 trauma procedures pre/post mentored training by expert trauma surgeons. Performance benchmarks were set for knowledge (80%) and independent, accurate completion of all procedural components within a realistic time window (90%). RESULTS: General surgery participants demonstrated greater trauma knowledge than gynecologists and urologists; however, none of the specialties reached the 80% benchmark. Pre-training, general surgery and urology participants outperformed gynecologists for overall procedural abilities. Post-training, only general surgeons met the 90% benchmark. Post-hoc analysis revealed no differences between the groups performing most pelvic and abdominal procedures, however knowledge associated with decision making and judgment in the provision of trauma care was significantly below the benchmark for gynecologists and urologists, even after training. CONCLUSION: For physiologically stable patients with traumatic injuries to the abdomen, pelvis or retroperitoneum, these specialists might be able to provide appropriate care; however, they would best benefit trauma patients in the capacity of highly skilled assisting surgeons to trauma specialists. These specialists should not be considered for solo resuscitative surgical care. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III/IV.

Empirically derived symptom profiles in adults with attention-Deficit/hyperactivity disorder: An unsupervised machine learning approach.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with various cognitive, behavioral, and mood symptoms that complicate diagnosis and treatment. The heterogeneity of these symptoms may also vary depending on certain sociodemographic factors. It is therefore important to establish more homogenous symptom profiles in patients with ADHD and determine their association with the patient's sociodemographic makeup. The current study used unsupervised machine learning to identify symptom profiles across various cognitive, behavioral, and mood symptoms in adults with ADHD. It was then examined whether symptom profiles differed based on relevant sociodemographic factors. METHODS: Participants were 382 adult outpatients (62% female; 51% non-Hispanic White) referred for neuropsychological evaluation for ADHD. RESULTS: Employing Gaussian Mixture Modeling, we identified two distinct symptom profiles in adults with ADHD: "ADHD-Plus Symptom Profile" and "ADHD-Predominate Symptom Profile." These profiles were primarily differentiated by internalizing psychopathology (Cohen's d = 1.94-2.05), rather than by subjective behavioral and cognitive symptoms of ADHD or neurocognitive test performance. In a subset of 126 adults without ADHD who were referred for the same evaluation, the unsupervised machine learning algorithm only identified one symptom profile. Group comparison analyses indicated that female patients were most likely to present with an ADHD-Plus Symptom Profile (χ2 = 5.43, p < .001). CONCLUSION: The machine learning technique used in this study appears to be an effective way to elucidate symptom profiles emerging from comprehensive ADHD evaluations. These findings further underscore the importance of considering internalizing symptoms and patients' sex when contextualizing adult ADHD diagnosis and treatment.

Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: a consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the presence of proliferative lesions throughout the body. Management of TSC is challenging because patients have a multifaceted systemic illness with prominent neurological and developmental impact as well as potentially severe kidney, heart and lung phenotypes; however, every organ system can be involved. Adequate care for patients with TSC requires a coordinated effort involving a multidisciplinary team of clinicians and support staff. This clinical practice recommendation was developed by nephrologists, urologists, paediatric radiologists, interventional radiologists, geneticists, pathologists, and patient and family group representatives, with a focus on TSC-associated kidney manifestations. Careful monitoring of kidney function and assessment of kidney structural lesions by imaging enable early interventions that can preserve kidney function through targeted approaches. Here, we summarize the current evidence and present recommendations for the multidisciplinary management of kidney involvement in TSC.

Comparing embedded performance validity indicators within the WAIS-IV Letter-Number sequencing subtest to Reliable Digit Span among adults referred for evaluation of attention-deficit/hyperactivity disorder.

Objectives: This study investigated the Wechsler Adult Intelligence Scale-Fourth Edition Letter-Number Sequencing (LNS) subtest as an embedded performance validity indicator among adults undergoing an attention-deficit/hyperactivity disorder (ADHD) evaluation, and its potential incremental value over Reliable Digit Span (RDS). Method: This cross-sectional study comprised 543 adults who underwent neuropsychological evaluation for ADHD. Patients were divided into valid (n = 480) and invalid (n = 63) groups based on multiple criterion performance validity tests. Results: LNS total raw scores, age-corrected scaled scores, and age- and education-corrected T-scores demonstrated excellent classification accuracy (area under the curve of .84, .83, and .82, respectively). The optimal cutoff for LNS raw score (≤16), age-corrected scaled score (≤7), and age- and education-corrected T-score (≤36) yielded .51 sensitivity and .94 specificity. Slightly lower sensitivity (.40) and higher specificity (.98) was associated with a more conservative T-score cutoff of ≤33. Multivariate models incorporating both LNS and RDS improved classification accuracy (area under the curve of .86), and LNS scores explained a significant but modest proportion of variance in validity status above and beyond RDS. Chaining LNS T-score of ≤33 with RDS cutoff of ≤7 increased sensitivity to .69 while maintaining ≥.90 specificity. Conclusions: Findings provide preliminary evidence for the criterion and construct validity of LNS as an embedded validity indicator in ADHD evaluations. Practitioners are encouraged to use LNS T-score cutoff of ≤33 or ≤36 to assess the validity of obtained test data. Employing either of these LNS cutoffs with RDS may enhance the detection of invalid performance.

The Impact of Adverse Childhood Experiences on Symptom and Performance Validity Tests Among a Multiracial Sample Presenting for ADHD Evaluation.

OBJECTIVE: Adverse childhood experiences (ACEs) are commonly reported in individuals presenting for attention-deficit hyperactivity disorder (ADHD) evaluation. Performance validity tests (PVTs) and symptom validity tests (SVTs) are essential to ADHD evaluations in young adults, but extant research suggests that those who report ACEs may be inaccurately classified as invalid on these measures. The current study aimed to assess the degree to which ACE exposure differentiated PVT and SVT performance and ADHD symptom reporting in a multi-racial sample of adults presenting for ADHD evaluation. METHOD: This study included 170 adults referred for outpatient neuropsychological ADHD evaluation who completed the ACE Checklist and a neurocognitive battery that included multiple PVTs and SVTs. Analysis of variance was used to examine differences in PVT and SVT performance among those with high (≥4) and low (≤3) reported ACEs. RESULTS: Main effects of the ACE group were observed, such that high ACE group reporting demonstrated higher scores on SVTs assessing ADHD symptom over-reporting and infrequent psychiatric and somatic symptoms on the Minnesota Multiphasic Personality Inventory-2-Restructured Form. Conversely, no significant differences emerged in total PVT failures across ACE groups. CONCLUSIONS: Those with high ACE exposure were more likely to have higher scores on SVTs assessing over-reporting and infrequent responses. In contrast, ACE exposure did not affect PVT performance. Thus, ACE exposure should be considered specifically when evaluating SVT performance in the context of ADHD evaluations, and more work is needed to understand factors that contribute to different patterns of symptom reporting as a function of ACE exposure.

Neurocognitive change over the course of a multiday external lumbar drain trial in patients with suspected normal pressure hydrocephalus.

Objective: To characterize neurocognitive response to cerebrospinal fluid (CSF) diversion during a multiday external lumbar drainage (ELD) trial in patients with suspected normal pressure hydrocephalus (NPH). Methods: Inpatients (N = 70) undergoing an ELD trial as part of NPH evaluation participated. Cognition and balance were assessed using standardized measures before and after a three-day ELD trial. Cognitive change pre- to post-ELD trial was assessed in relation to change in balance, baseline neuroimaging findings, NPH symptoms, demographics, and other disease-relevant clinical parameters. Results: Multiday ELD resulted in significant cognitive improvement (particularly on measures of memory and language). This improvement was independent of demographics, test-retest interval, number of medical and psychiatric comorbidities, NPH symptom duration, estimated premorbid intelligence, baseline level of cognitive impairment, cerebrovascular disease burden, degree of ventriculomegaly, or other NPH-related morphological brain alterations. Balance scores evidenced a greater magnitude of improvement than cognitive scores and were weakly, but positively correlated with cognitive change scores. Conclusions: Findings suggest that cognitive improvement associated with a multiday ELD trial can be sufficiently captured with bedside neurocognitive testing. These findings support the utility of neuropsychological consultation, along with balance assessment, in informing clinical decision-making regarding responsiveness to temporary CSF diversion for patients undergoing elective NPH evaluation. Implications for the understanding of neuroanatomical and cognitive underpinnings of NPH are discussed.

Outcomes of patients with COVID-19 and coronary artery disease and heart failure: findings from the Philippine CORONA study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) and coronary artery disease (CAD) or heart failure (HF) are more likely to have poor outcomes. This study aimed to determine the characteristics and outcomes of COVID-19 patients with CAD/HF across various institutions in the Philippines. METHODS: We utilized the data from the Philippine CORONA Study and compared the outcomes of admitted COVID-19 patients with CAD/HF versus those without. The Student's t test, Mann-Whitney U test, binary logistic regression and multivariate regression analysis were utilized. Odds ratios (OR) and Kaplan-Meier curves were generated. RESULTS: We included a total of 512 patients with COVID-19 had CAD/HF and 10,369 were without. CAD/HF was significantly associated with COVID severity, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. After adjusting for confounders, the presence of CAD/HF was still associated with death from a cardiac cause (OR 2.22, 95% CI 1.49-3.3, p < 0.01). CONCLUSIONS: The presence of CAD or HF was significantly associated with severity of COVID disease, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization.

Perceived cognitive impairment is related to internalizing psychopathology but unrelated to objective cognitive performance among nongeriatric adults presenting for outpatient neuropsychological evaluation.

Objective: This study investigated the relationship between perceived cognitive impairment, objective cognitive performance, and intrapersonal variables thought to influence ratings of perceived cognitive impairment. Method: Study sample comprised 194 nongeriatric adults who were seen in a general outpatient neuropsychology clinic for a variety of referral questions. The cognition subscale score from the WHO Disability Assessment Schedule served as the measure of perceived cognitive impairment. Objective cognitive performance was indexed via a composite score derived from a comprehensive neuropsychological battery. Internalizing psychopathology was indexed via a composite score derived from anxiety and depression measures. Medical and neuropsychiatric comorbidities were indexed by the number of different ICD diagnostic categories documented in medical records. Demographics included age, sex, race, and years of education. Results: Objective cognitive performance was unrelated to subjective concerns, explaining <1% of the variance in perceived cognitive impairment ratings. Conversely, internalizing psychopathology was significantly predictive, explaining nearly one-third of the variance in perceived cognitive impairment ratings, even after accounting for test performance, demographics, and number of comorbidities. Internalizing psychopathology was also highly associated with a greater discrepancy between scores on perceived and objective cognitive measures among participants with greater cognitive concerns. Clinically significant somatic symptoms uniquely contributed to the explained variance in perceived cognitive impairment (by ∼13%) when analyzed in a model with internalizing symptoms. Conclusions: These findings suggest that perceived cognitive impairment may be more indicative of the extent of internalizing psychopathology and somatic concerns than cognitive ability.

Needs assessment of global pharmaceutical development goals: an explanatory mixed-methods study of 21 countries.

OBJECTIVES: Investment in the development of the pharmacy workforce has been recognized as crucial for achieving universal health coverage. The 21 International Pharmaceutical Federation (FIP) Development Goals (DGs) have been used when conducting national needs assessments in several countries to provide evidence-based policy on workforce development. This study aimed to explore factors contributing to education and training in a FIP sample of mainly low- to middle-income countries (LMICs), and current national policy initiatives and priorities, mapped against the FIP DGs. METHODS: The study employed a mixed-methods approach, including an online survey questionnaire and interviews with representatives from 26 national professional organizations from 21 countries. A Multiple Correspondence Analysis (MCA), descriptive analysis, and thematic analysis were carried out to analyse the data. KEY FINDINGS: A total of 26 national professional organizations from 21 countries participated in this study. The quantitative MCA results indicated categorical correlations with variables related to the maintenance of licensed pharmacy practice and mechanisms for personal career development and advancement, such as the availability of competency development frameworks. Six themes emerged from the qualitative analysis of ongoing national programmes in the sampled countries: strengthening initial education and training, competency and career development programmes, initiatives related to pharmacists' role in patient safety, communicable diseases, and antimicrobial stewardship, pharmaceutical care and medicines access, strengthening research to improve pharmacists' impact, and outcomes and policy review and development. CONCLUSION: This study provided an evidence-based needs assessment exploring factors contributing to workforce development and identifying pharmaceutical development priorities mapped to the FIP DGs across a cohort of nations.

Predictors of non-home discharge after pancreatoduodenectomy in patients aged 80 years and above.

BACKGROUND: Pancreatic cancer has the highest growth in incidence among patients aged ≥80 years. Discharge destination after hospitalization is increasingly recognized as a marker of return to baseline functional status. Our aim was to identify the preoperative and intraoperative predictors of non-home discharge in those aged 80 or older. METHODS: The ACS-NSQIP pancreas-targeted database was queried to identify patients aged ≥80 years who underwent pancreatoduodenectomy (PD) from 2014 to 2020. Home discharge (HD) versus non-HD cohorts were compared using univariate logistic regression. Multivariable logistic regression was used to identify predictors of non-HD. RESULTS: Non-HD was over twice as likely to occur in patients aged ≥80 years than in those aged 65-79 years (p < 0.01). Comorbidity factors significantly associated with non-HD in patients aged ≥80 years included COPD, hypertension, HF, lower preoperative albumin, but not obesity. Non-comorbidity factors included older age, female gender, ASA III-IV, preoperative dependent functional status, and transfer origin before PD. CONCLUSION: Individuals ≥80 years have possibly delayed or lower rate of return to baseline functional status following PD compared to those aged 65-79 years. Predictors of non-HD can be identified to facilitate preoperative counseling and discharge planning, thus enhancing care workflow efficiency.

Cross-validating the Clinical Assessment of Attention Deficit-Adult symptom validity scales for assessment of attention deficit/hyperactivity disorder in adults.

INTRODUCTION: The Clinical Assessment of Attention Deficit-Adult is among the few questionnaires that offer validity indicators (i.e., Negative Impression [NI], Infrequency [IF], and Positive Impression [PI]) for classifying underreporting and overreporting of attention-deficit/hyperactivity disorder (ADHD) symptoms. This is the first study to cross-validate the NI, IF, and PI scales in a sample of adults with suspected or known ADHD. METHOD: Univariate and multivariate analyses were conducted to examine the independent and combined value of the NI, IF, and PI scores in predicting invalid symptom reporting and neurocognitive performance in a sample of 543 adults undergoing ADHD evaluation. RESULTS: The NI scale demonstrated better classification accuracy than the IF scale in discriminating patients with and without valid scores on measures of overreporting. Only NI scores significantly predicted validity status when used in combination with IF scores. Optimal cut-scores for the NI (≤51; 30% sensitivity / 90% specificity) and IF (≥4; 18% sensitivity / 90% specificity) scales were consistent with those reported in the original manual; however, these indicators poorly discriminated patients with invalid and valid neurocognitive performance. The PI scale demonstrated acceptable classification accuracy in discriminating patients with invalid and valid scores on measures of underreporting, albeit with an optimal cut-score (≥27; 36% sensitivity / 90% specificity) lower than that described in the manual. CONCLUSION: Findings provide preliminary evidence of construct validity for these scales as embedded validity indicators of symptom overreporting and underreporting. However, these scales should not be used to guide clinical judgment regarding the validity of neurocognitive test performance.

Multivariate examination of embedded indicators of performance validity for ADHD evaluations: A targeted approach.

This study investigated the individual and combined utility of 10 embedded validity indicators (EVIs) within executive functioning, attention/working memory, and processing speed measures in 585 adults referred for an attention-deficit/hyperactivity disorder (ADHD) evaluation. Participants were categorized into invalid and valid performance groups as determined by scores from empirical performance validity indicators. Analyses revealed that all of the EVIs could meaningfully discriminate invalid from valid performers (AUCs = .69-.78), with high specificity (≥90%) but low sensitivity (19%-51%). However, none of them explained more than 20% of the variance in validity status. Combining any of these 10 EVIs into a multivariate model significantly improved classification accuracy, explaining up to 36% of the variance in validity status. Integrating six EVIs from the Stroop Color and Word Test, Trail Making Test, Verbal Fluency Test, and Wechsler Adult Intelligence Scale-Fourth Edition was as efficacious (AUC = .86) as using all 10 EVIs together. Failing any two of these six EVIs or any three of the 10 EVIs yielded clinically acceptable specificity (≥90%) with moderate sensitivity (60%). Findings support the use of multivariate models to improve the identification of performance invalidity in ADHD evaluations, but chaining multiple EVIs may only be helpful to an extent.

Unrepaired base excision repair intermediates in template DNA strands trigger replication fork collapse and PARP inhibitor sensitivity.

DNA single-strand breaks (SSBs) disrupt DNA replication and induce chromosome breakage. However, whether SSBs induce chromosome breakage when present behind replication forks or ahead of replication forks is unclear. To address this question, we exploited an exquisite sensitivity of SSB repair-defective human cells lacking PARP activity or XRCC1 to the thymidine analogue 5-chloro-2'-deoxyuridine (CldU). We show that incubation with CldU in these cells results in chromosome breakage, sister chromatid exchange, and cytotoxicity by a mechanism that depends on the S phase activity of uracil DNA glycosylase (UNG). Importantly, we show that CldU incorporation in one cell cycle is cytotoxic only during the following cell cycle, when it is present in template DNA. In agreement with this, while UNG induces SSBs both in nascent strands behind replication forks and in template strands ahead of replication forks, only the latter trigger fork collapse and chromosome breakage. Finally, we show that BRCA-defective cells are hypersensitive to CldU, either alone and/or in combination with PARP inhibitor, suggesting that CldU may have clinical utility.

Development and Evaluation of the Psychometric Properties of the Tamil Version of Eating Assessment Tool - 10 (EAT-10): Preliminary Findings from Persons with Head and Neck Cancer.

Aims: This study aimed to develop and evaluate the psychometric properties of the Tamil version of the Eating Assessment Tool (EAT-10). Setting & Study Design: Prospective cross-sectional study on persons with Head and Neck Cancer (HNC) during their follow-up for oncological and swallowing consultation at a tertiary care hospital and healthy individuals recruited from the community. Methods: The study was conducted in two phases: (1) translation and development of the Tamil version of EAT-10 and (2) administration of Tamil EAT-10 to assess internal consistency reliability, test-retest reliability and known-group validity. 92 participants with HNC in the clinical group and 149 healthy adults in the control group completed the Tamil EAT-10. In addition, a subgroup of 20 participants with HNC repeated the questionnaire within a week to assess test-retest reliability. Results: The Cronbach alpha for the 10 items was 0.96 indicating high internal consistency reliability. The test-retest reliability of the individual items and the total scores (r = 0.98) of the Tamil version of EAT-10 were high. The total EAT-10 scores for the HNC group (14.4 ± 11.5) were significantly higher (p < 0.001) than the scores for healthy adults (0.72 ± 2.0). Conclusion: The Tamil version of the EAT-10 developed in this study is a reliable and valid self-administered tool for identifying concerns related to swallowing among persons treated for HNC and healthy adults. This tool can be implemented for clinical practice and research in dysphagia among a Tamil-speaking population. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03376-8.

Does comorbid depression impact executive functioning (EF) in adults diagnosed with ADHD?: a comparison of EF across diagnoses in clinically-referred individuals.

INTRODUCTION: Executive functioning (EF) is a salient factor in both ADHD as well as depressive disorders. However, sparse literature has examined whether depression severity impacts EF concurrently among adults with ADHD. The goal of this study was to examine differences in EF between adult patients diagnosed with ADHD and those diagnosed with a non-ADHD primary psychopathological condition, as a function of both ADHD presentation and depression severity in a diverse clinical sample. METHOD: This crosssectional study included 404 adult patients clinically referred for neuropsychological evaluation to assist with differential diagnosis and/or treatment planning related to known or suspected ADHD. Various EF tasks and a measure of depression severity were administered. One-way MANOVA analyses were conducted to compare EF performance between individuals diagnosed with ADHD or a non-ADHD primary psychopathological condition, with additional analyses examining group differences based on ADHD presentation and depression severity. Regression analyses also examined the potential contribution of depression severity to each EF measure within each group. RESULTS: No significant EF performance differences were found when comparing individuals diagnosed with ADHD and those with a non-ADHD primary psychopathological condition, nor based on ADHD presentation. When comparing across groups using cut-offs for high or low depression, only one EF measure showed significant differences between groups. Further, depression severity generally did not predict reduced EF performances with the exception of verbal fluency and working memory performances in select groups. CONCLUSIONS: This study demonstrated that individuals with ADHD generally perform comparably on EF measures regardless of the presence or absence of comorbid depression. These results suggest further examination of EF deficits when they emerge for adults with ADHD, especially beyond comorbid depression severity.