Functional Impairment Research Articles

Longitudinal Trajectories of Premorbid Social and Academic Adjustment in Youth at Clinical High Risk for Psychosis: Implications for Conversion.

Social and academic adjustment deteriorate in the years preceding a psychotic disorder diagnosis. Analyses of premorbid adjustment have recently been extended into the clinical high risk for psychosis (CHR) syndrome to identify risk factors and developmental pathways toward psychotic disorders. Work so far has been at the between-person level, which has constrained analyses of premorbid adjustment, clinical covariates, and conversion to psychosis. Growth-curve models examined longitudinal trajectories in retrospective reports of premorbid social and academic adjustment from youth at CHR (n = 498). Interaction models tested whether known covariates of premorbid adjustment problems (attenuated negative symptoms, cognition, and childhood trauma) were associated with different premorbid adjustment trajectories in converters vs non-converters (ie, participants who did/did not develop psychotic disorders within 2-year follow-up). Converters reported poorer social adjustment throughout the premorbid period. Converters who developed psychosis with an affective component reported poorer academic adjustment throughout the premorbid period than those who developed non-affective psychosis. Tentatively, baseline attenuated negative symptoms may have been associated with worsening social adjustment in the premorbid period for non-converters only. Childhood trauma impact was associated with fewer academic functioning problems among converters. Cognition effects did not differ based on conversion status. Premorbid social function is an important factor in risk for conversion to psychosis. Negative symptoms and childhood trauma had different relationships to premorbid functioning in converters vs non-converters. Mechanisms linking symptoms and trauma to functional impairment may be different in converters vs non-converters, suggesting possible new avenues for risk assessment.

The Neuropsychological Assessment Battery Driving Scenes Test in a Dementia Clinic.

In dementia research, the Driving Scenes test from the Neuropsychological Assessment Battery has been shown to relate to memory, dementia diagnosis, and functional impairment. The aim of the current study was to examine Driving Scenes and its component scores, and their relationships with cognition and daily functioning, in a mixed dementia clinic sample. One hundred U.S. military veterans between the ages of 55 and 88 were administered a full neuropsychological protocol that included Driving Scenes. The Driving Scenes score and its subscores were strongly related to memory skills, and there were additional subscore associations with language and visuospatial functions. Driving Scenes uniquely predicted reported bill payment difficulties and tendency to get lost while driving, which were not predicted by other performances across cognitive domains. Driving Scenes is a clinically and functionally relevant measure of memory. Although the Driving Scenes total score remains useful in dementia evaluations, component scores and error scores contribute additional practical information.

Non-invasive biomarkers of acute rejection in pediatric kidney transplantation: New targets and strategies.

Kidney transplantation is the preferred treatment for pediatric end-stage renal disease. However, pediatric recipients face unique challenges due to their prolonged need for kidney function to accommodate growth and development. The continual changes in the immune microenvironment during childhood development and the heightened risk of complications from long-term use of immunosuppressive drugs. The overwhelming majority of children may require more than one kidney transplant in their lifetime. Acute rejection (AR) stands as the primary cause of kidney transplant failure in children. While pathologic biopsy remains the "gold standard" for diagnosing renal rejection, its invasive nature raises concerns regarding potential functional impairment and the psychological impact on children due to repeated procedures. In this review, we outline the current research status of novel biomarkers associated with AR in urine and blood after pediatric kidney transplantation. These biomarkers exhibit superior diagnostic and prognostic performance compared to conventional ones, with the added advantages of being less invasive and highly reproducible for long-term graft monitoring. We also integrate the limitations of these novel biomarkers and propose a refined monitoring model to optimize the management of AR in pediatric kidney transplantation.

Granulocyte- Macrophage Colony-Stimulating Factor Reverses Immunosuppression Acutely Following a Traumatic Brain Injury and Hemorrhage Polytrauma in a Juvenile Male Rat Model.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 μg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment.

Functioning and neurocognition in very early and early-life onset bipolar disorders: the moderating role of bipolar disorder type.

Defining homogeneous subgroups of bipolar disorder (BD) is a major goal in personalized psychiatry and research. According to the neurodevelopmental theory, age at onset may be a key variable. As potential trait markers of neurodevelopment, cognitive and functional impairment should be greater in the early form of the disease, particularly type 1 BD (BD I). The age at onset was assessed in a multicenter, observational sample of 4190 outpatients with BD. We used a battery of neuropsychological tests to assess six domains of cognition. Functioning was measured using the Functioning Assessment Short Test (FAST). We studied the potential moderation of the type of BD on the associations between the age at onset and cognitive and functioning in a subsample of 2072 euthymic participants, controlling for potential clinical and socio-demographic covariates. Multivariable analyses showed cognition to not be impaired in individuals with early (21-30years) and very early-life (before 14years) onset of BD. Functioning was equivalent between individuals with early and midlife-onset of BD II and NOS but better for individuals with early onset of BD I. In contrast, functioning was not worse in individuals with very early-onset BD I but worse in those with very early-onset BD II and NOS. Early-life onset BDs were not characterized by poorer cognition and functioning. Our results do not support the neurodevelopmental view that a worse cognitive prognosis characterizes early-life onset BD. This study suggests that functional remediation may be prioritized for individuals with midlife-onset BD I and very early life onset BD 2 and NOS.

Effect of repetitive transcranial magnetic stimulation combined with balance training on improving balance function in patients with Parkinson’s disease: A randomized controlled trial

BACKGROUND: An increasing amount of research has supported the positive role of repetitive transcranial magnetic stimulation(rTMS) in improving functional impairments in Parkinson’s patients. PURPOSE: To explore the effectiveness of using rTMS n and Balance Apparatus training to improve the balance function of Parkinson’s patients. METHODS: Patients were divided into 3 groups of 20 patients in each. All patients received routine rehabilitation training. The rTMS group received low-frequency rTMS therapy, while the balance apparatus group incorporated balance apparatus exercises. The observation group received both interventions. The three groups of patients were assessed at baseline and after 8 weeks of treatment using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor section, Berg balance scale (BBS), Time up and go test (TUGT), and Activities-Specific Balance Confidence (ABC) scales. Additionally, all participants were tested for movement ellipse area, and Average Trace Error (ATE) using the balance apparatus. RESULTS: The observation group achieved better treatment results. The UPDRS score was better than that of the balance apparatus group after treatment, and the ABC score was superior to other two group. Moreover, the observation group outperformed the other two group in terms of motion length, and open-eye elliptical area, with statistical significance. CONCLUSION The combined application of TMS and Balance Apparatus training effectively improves enhances balance function, and boosts self-confidence in balance perception among Parkinson’s patients.

Functional alterations of the brain default mode network and somatosensory system in trigeminal neuralgia

Mapping the localization of the functional brain regions in trigeminal neuralgia (TN) patients is still lacking. The study aimed to explore the functional brain alterations and influencing factors in TN patients using functional brain imaging techniques. All participants underwent functional brain imaging to collect resting-state brain activity. The significant differences in regional homogeneity (ReHo) and amplitude of low frequency (ALFF) between the TN and control groups were calculated. After familywise error (FWE) correction, the differential brain regions in ReHo values between the two groups were mainly located in bilateral middle frontal gyrus, bilateral inferior cerebellum, right superior orbital frontal gyrus, right postcentral gyrus, left inferior temporal gyrus, left middle temporal gyrus, and left gyrus rectus. The differential brain regions in ALFF values between the two groups were mainly located in the left triangular inferior frontal gyrus, left supplementary motor area, right supramarginal gyrus, and right middle frontal gyrus. With the functional impairment of the central pain area, the active areas controlling memory and emotion also change during the progression of TN. There may be different central mechanisms in TN patients of different sexes, affected sides, and degrees of nerve damage. The exact central mechanisms remain to be elucidated.

Abstract PO2-12-09: Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer

Abstract Background: SPPADE symptoms (Sleep disturbance, Pain, Physical function impairment, Anxiety, Depression/distress, and Energy deficits/fatigue) may result from cancer and its treatment. The aim of this analysis was to characterize SPPADE symptoms in patients with breast cancer. Methods. SPPADE data were drawn from the Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) study, a stepped-wedge pragmatic cluster-randomized trial designed to evaluate a symptom management intervention in routine practice (NCT03892967). Symptom severity was measured on a 0-10 scale via a survey administered by patient portal, in-clinic tablet, or interactive voice response system (by phone) prior to, during, or soon after an outpatient oncology encounter. Scores of 4-6 were categorized as “moderate” and ≥7 as “severe.” In this analysis, only the data from each patient’s initial survey were included. Results. A total of 9,651 patients with breast cancer completed an initial E2C2 survey between March 2019 and January 2023. The proportion of patients with moderate or severe SPPADE symptoms were as follows: 22% moderate and 10% severe for insomnia; 18% moderate and 7% severe for pain; 17% moderate and 7% severe for anxiety; 15% moderate and 5% severe for emotional distress; 25% moderate and 12% severe for fatigue; and 22% moderate and 8% severe for impaired physical function. Table 1 presents score means and standard deviations by demographic subgroup. Conclusions. SPPADE symptoms are common in patients with breast cancer. These observations warrant routine implementation of symptom surveillance and management in breast oncology. Funding acknowledgement: The Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium is a Cancer Moonshot Research Initiative under the authorization of the 2016 United States 21st Century Cures Act. This research was supported by the National Cancer Institute of the NIH, UM1CA233033 (Mayo Clinic, Rochester, MN). Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer Citation Format: Kathryn Ruddy, Veronica Grzegorczyk, Deirdre Pachman, Sandra Mitchell, Bolun Liu, Deanne Smith, Ciara O'Sullivan, Shawna Ehlers, Jeph Herrin, Parvez Rahman, Andrea Cheville. Insomnia, Pain, Anxiety, Distress, Fatigue, and Functional Impairment in Patients with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-09.

Abstract PO3-06-02: Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register study

Abstract Background: Until 2012, breast cancer patients with micrometastases (pN1mi) or isolated tumor cells (pN0(i)) in the sentinel node (SN) received axillary lymph node dissection (ALND). ALND is associated with lymphedema, paresthesia, functional impairment, and pain. In 2012, national Danish guidelines for patients with pN1mi and pN0(i) were changed reflecting several randomized clinical trials showing non-inferior prognosis when ALND was omitted. Since 2012, appr. 450 Danish breast cancer patients have been spared ALND each year. Development of axillary recurrence(AR) from minimal metastatic disease left in the axilla may take longer than experienced after macrometastatic disease. Hence, long-term follow-up is needed to evaluate the safety of omitting ALND for patients with pN1mi and pN0(i). Therefore, we aimed to investigate these outcomes with 10 years of follow-up. Methods: In this national register-based study, we included all women with primary breast cancer surgery between 01.01.2008 and 31.12.2021, who had pN1mi and pN0(i) in the SN. Women treated between 01.01.2008-31.12.2011 had received ALND, while in women treated between 01.01.2012 and 31.12.202,1 ALND was omitted. The two groups were compared with SN-negative patients (pN0) without ALND. The primary outcome was AR, and the secondary outcome was overall survival (OS). Information on surgery, nodal status, and recurrence were retrieved from the national Danish breast cancer group (DBCG) database. The definitions of pN1mi, pN0(i) and pN0 were according to AJCC, 8TH edition. We analyzed patient- and tumor characteristics with descriptive statistics, χ2 and Fisher exact test. The cumulative incidence of AR was calculated. OS was estimated using the Kaplan-Meier method and compared with a log-rank test. The effect of ALND was estimated with a Cox proportional hazards model, adjusting for age at operation, histology, malignancy grade, hormone receptor, HER2 status, and whether they received adjuvant systemic treatment or radiation therapy. With all statistical analysis, a two-tailed α-level of 0.05 was used. Results: 22,790 patients were included in the study. Overall,14.3% had pN1mi, 8.6% had pN0(i) and 77.1% had pN0. Of pN1mi or pN0(i) patients, 1490 had an ALND; 1227 patients with pN1mi and 263 patients with pN0(i). In 3737 patients ALND was omitted: 2036 with pN1mi and 1701 with pN0(i). Regarding the primary outcome, 1.1% of patients with pN1mi or pN0(i) had an AR, while 0.5% of the pN0 patients had AR. Analyzing patients with pN1mi or pN0(i) with or without ALND, 0.2% and 1.5%, respectively, had an AR. In subanalysis of patients with pN1mi with or without ALND, 0.2% and 1.8%, respectively, had an AR. In a subanalysis of patients with pN0(i), no patients with pN0(i) and ALND had an AR, while 1.1% of patients with pN0(i) had an AR when ALND was omitted. OS after 10 years of follow-up for the group of patients with pN1mi or pN0(i) was 81.5%; 83.7% for patients with and 79.12% for patients without ALND. For pN0 patients without ALND OS was 82%. This difference between the three groups was statistically significant(p< 0,01). However, when adjusting for risk factors, there was no statistically significant difference in OS between the patients with pN1mi or pN0(i) with and without ALND (p=0.6). Likewise, no statistically significant difference was found in OS, when looking at the subgroups of pN1mi with or without ALND (p=0.5) and pN0(i) with and without ALND(p=0.41). Conclusion: In this large register-based nationwide study we found a slightly higher rate of AR after 10 years of follow-up in breast cancer patients with micrometastases or isolated tumor cells in the SN if ALND was omitted. However, the axillary recurrence rate was low (< 2%), and after adjusting for other risk factors the increased recurrence rate did not affect OS. These results confirm the safety of omitting ALND in these patients. Citation Format: Riazan Hawaz-ali, Frederikke Munck, Tove Tvedskov, Niels Kroman. Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-02.

Abstract GS02-01: Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: Results from TROPION-Breast01

Abstract Background: The global, phase 3 TROPION-Breast01 trial (NCT05104866) assessed the TROP2-directed antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) compared with investigator’s choice of chemotherapy (ICC) in patients (pts) with inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2‒) breast cancer (BC). Primary results were presented at ESMO 2023 (Bardia A, et al. Abstract LBA11). Here we report expanded data from TROPION-Breast01. Methods: Pts aged ≥18 years who had inoperable or metastatic HR+/HER2‒ BC, had disease progression on endocrine therapy (ET) and for whom ET was unsuitable, and had received 1‒2 prior lines of systemic chemotherapy (CT), were eligible. Pts were randomized 1:1 to Dato-DXd (6 mg/kg Q3W) or ICC (eribulin, vinorelbine, capecitabine, or gemcitabine) until progression or unacceptable toxicity. The dual primary endpoints were progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1, and overall survival (OS). Results: In total, 732 pts were randomized: 365 to the Dato-DXd arm and 367 to ICC. At data cut-off (Jul 17, 2023), 93/39 pts in the Dato-DXd/ICC groups were ongoing treatment. Pts receiving Dato-DXd had significantly improved PFS vs ICC (HR 0.63 [95% CI 0.52‒0.76]; p<0.0001). Hazard ratios for PFS favored Dato-DXd over ICC across prespecified pt subgroups, including prior lines of CT in the metastatic setting (1 vs 2), prior use of CDK4/6 inhibitor (≤12 months vs >12 months), prior use of endocrine therapy in the metastatic setting ( <6 months vs ≥6 months) and brain metastases (yes vs no). OS data were not mature at this data cut-off. In the Dato-DXd vs ICC arms, 192 (53%) vs 247 (67%) pts had received a subsequent therapy after study treatment discontinuation, including 15 (4%) vs 52 (14%) who received subsequent ADC therapy, and 165 (45%) vs 186 (51%) who received subsequent CT. Median time to first subsequent therapy was 8.2 months in the Dato-DXd arm vs 5.0 months in the ICC arm (HR 0.53 [95% CI 0.45–0.64). Overall, rate of grade ≥3 treatment-related adverse events (TRAEs) with Dato-DXd was less than half that with ICC. The secondary patient-reported outcome endpoints showed that time to deterioration in physical functioning, pain, and global health status/quality of life were delayed in the Dato-DXd arm compared with ICC. Conclusions: TROPION-Breast01 met its dual primary endpoint of PFS, demonstrating statistically significant and clinically meaningful improvement in PFS with Dato-DXd compared with ICC across all subgroups. Overall, the safety profile and QoL with Dato-DXd was favorable compared with ICC. These data support Dato-DXd as a potential new therapeutic option for pts with inoperable or metastatic HR+/HER2‒ BC who have received 1‒2 prior lines of CT. Citation Format: Aditya Bardia, Komal Jhaveri, Seock-Ah Im, Michelino De Laurentiis, Binghe Xu, Sonia Pernas, Giuliano Borges, David Cescon, Masaya Hattori, Yen-Shen Lu, Noelia Martínez-Jáñez, Erika Hamilton, Shusen Wang, Junji Tsurutani, Kevin Kalinsky, Lu Xu, Sabrina Khan, Neelima Denduluri, Hope Rugo, Barbara Pistilli. Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: Results from TROPION-Breast01 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-01.

Lower resting state functional connectivity partially mediates adverse effects of prenatal alcohol exposure on arithmetic performance in children.

Fetal alcohol spectrum disorders (FASD) include a range of neurocognitive and behavioral impairments resulting from prenatal alcohol exposure (PAE). Among the PAE-related cognitive deficits, number processing is particularly affected. This study examines alterations in number processing networks and whether changes in functional connectivity mediate the adverse effects of PAE on arithmetic performance. Magnetic resonance imaging (MRI) was acquired in 57 children (mean (SD) age = 11.3 (+0.9) yr), 38 with FASD (19 fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 heavily exposed (HE)) and 19 controls. Whole-brain correlation analyses were performed from five seeds located in regions involved in number processing. Children with FAS/PFAS showed dose-dependent reductions in resting state functional connectivity between the seed in the right (R) posterior superior parietal lobule and a cluster in the left (L) inferior frontal gyrus, and between a seed in the R horizontal intraparietal sulcus and clusters in the R precentral gyrus and L cerebellar lobule VI. HE children showed lower resting state functional connectivity in a subset of these regions. Lower functional connectivity in the two fronto-parietal connections partially mediated the adverse effects of PAE on arithmetic performance. This study demonstrates PAE-related functional connectivity impairments in functional networks involved in number processing. The weaker connectivity between the R posterior superior parietal lobule and the L inferior frontal gyrus suggests that impaired verbal processing and visuospatial working memory may play a role in number processing deficits, while weaker connectivity between the R intraparietal sulcus and the R precentral gyrus points to poorer finger-based numerical representation, which has been linked to arithmetic computational skills.

Hearing Impairment and Physical Activity and Physical Functioning in Older Adults: Baseline Results from the ACHIEVE Trial.

Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. Analyses included 845 participants aged ≥70 years (mean=76.6y) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA≥40 dB] vs. mild [PTA<40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR=2.17, 95% CI=1.29-3.67), vs. those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00pm-05:59pm). Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.

The relationship between patient-specific factors and functional progression of COVID-19 survivors admitted to an inpatient rehabilitation facility.

Survivors of hospitalization for severe acute COVID-19 infection faced significant functional impairments necessitating discharge to inpatient rehabilitation facilities (IRFs) for intensive rehabilitation prior to discharge home. There remains a lack of large cohort studies of the functional outcomes of patients admitted to IRFs with COVID-19-related impairments and the relationship to patient-specific factors. To characterize functional outcomes of patients admitted to IRFs for COVID-19-related debility and to investigate associations between functional outcomes and patient-specific factors. Multisite retrospective cohort study. Multiple IRFs in a large urban city. Adult patients admitted to IRFs for rehabilitation after hospitalization for acute COVID-19 infection. Not applicable. Primary outcomes included change in GG Self-Care and Mobility Activities subscales and Functional Independence Measure scores from admission to discharge from inpatient rehabilitation. Linear regression analysis was used to relate functional changes to demographic, medical, and hospitalization-specific factors. Secondary outcomes included discharge destination from the IRF. The analysis included n = 362 patients admitted to IRFs for COVID-19-related rehabilitation needs. This cohort showed significant improvements in mobility, self-care, and cognition congregate scores (216.0%, 174.3%, 117.6% respectively). Patient-specific factors associated with functional improvement, included age, body mass index, premorbid employment status, history of diabetes and cardiac disease and medications received in acute care, and muscle strength upon admission to IRF. Patients admitted to inpatient rehabilitation for COVID-19-related functional deficits made significant functional improvements in mobility, self-care, and cognition. Many significant associations were found between patient-specific factors and functional improvement, which support further investigation of these factors as possible predictors of functional improvement in an IRF for COVID-19-related deficits.

Effects on Child Development and Parent–Child Interaction of the FACAM Intervention: A Randomized Controlled Study of an Interdisciplinary Intervention to Support Women in Vulnerable Positions through Pregnancy and Early Motherhood

Health inequality can have a profound impact on a child’s life. Maternal mental health challenges can hinder bonding, leading to impaired functioning and poorer child outcomes. To provide extra support for vulnerable pregnant women, the FACAM intervention offers the services of a health nurse or family therapist from pregnancy until the child starts school. This study examined the effects of FACAM intervention on pregnant women in vulnerable positions and their children until the child turned two years old. We randomly assigned 331 pregnant women to either FACAM intervention or care as usual and assessed them at baseline and when the infant was 3–6, 12–13.5, and 24 months old. The primary outcome was maternal sensitivity measured by Coding Interactive Behavior (CIB). Secondary outcomes included the parent–child relationship, child social–emotional development, child developmental progress, parent–child interaction, and child development. Our findings indicate that care-as-usual children were significantly more involved than FACAM children when the child was 4–6 months old (b = −0.25, [−0.42; −0.08] d = −0.42). However, we suspect this result is due to a biased dropout. We did not find any significant differences in any other outcomes. Therefore, the study suggests that the FACAM intervention is not superior to care as usual regarding child development and parent–child interaction outcomes.

Depression in Persons With Epilepsy: Lessons From Case Review.

Major depressive disorder is highly prevalent among persons with epilepsy (PWEs). Between 30% and 50% of PWEs suffer from depression. Many factors contribute to this prevalence, including the psychosocial impact of the diagnosis, restrictions on driving and certain types of work, and adverse effects associated with antiseizure medications. Without proper treatment, depressed PWEs have increased risks for suicide, strained relationships, lowered seizure control, and impairment in functioning. Our objective was to use the existing literature and insights from our experience in treating depression and anxiety in PWEs within an academic mood disorders center. We aimed to provide practical guidance for health care professionals who treat depression in this population. Persons with epilepsy and depression were identified by their treating psychiatrists. Their electronic health records were reviewed and compiled for this report, with a total of 12 included in this review. Records were reviewed regarding antiseizure medications, psychotropic medications, light therapy, psychotherapy, other interventions, and treatment response. Based on our review of literature, as well as review of cases of individuals with epilepsy and comorbid psychiatric conditions, we recommend a step-wise evidence-based approach of optimizing psychiatric medication doses, augmenting with additional medication and/or implementing nonpharmacological interventions such as light therapy and psychotherapy. In PWEs, improvement in depression, other psychiatric symptoms, and function are the goals of drug and nondrug interventions. Depression care has the potential to significantly improve the quality of life of PWEs and reduce both morbidity and mortality.

Structural neuroimaging of skin-picking disorder.

Skin-picking disorder (SPD) is conceptualized as an obsessive-compulsive and related disorder (OCRD). Patients with SPD excessively manipulate their skin, which leads to skin lesions, psychological distress, and functional impairment. The neuroanatomical facets of this disorder are still poorly understood. A total of 220 participants (123 patients with a primary diagnosis of SPD and 97 healthy controls; mean age = 30 years, 80% female) were recruited for a voxel-based morphometry (VBM) study. VBM data were compared between patients and controls, and between three SPD subgroups, each characterized by a distinct age of symptom onset (before puberty, during puberty, adulthood). Relative to the healthy comparison group, patients with SPD had significantly less grey matter volume (GMV) in regions of interest (ROIs: insula, orbitofrontal cortex, pallidum, cerebellum, supramarginal gyrus) and in the frontal pole and occipital regions (whole-brain findings). Early onset of symptoms (before puberty) was associated with elevated levels of focused skin-picking, in addition to less GMV in specific ROIs (insula, orbitofrontal cortex) as well as in paracingulate/ superior temporal regions (whole-brain findings). SPD-related reductions in GMV were identified in brain regions involved in interoception, emotion regulation, and motor control. This partially aligns with findings for OCD. The detection of different age-of-onset groups based on clinical as well as morphometric data points to the heterogeneity of the disorder and warrants further investigation.

Sensory over-responsivity and orbitofrontal cortex connectivity in obsessive-compulsive disorder

BackgroundSensory over-responsivity (SOR) in obsessive-compulsive disorder (OCD) is associated with illness severity and functional impairment. However, the neural substrates of SOR in OCD have not yet been directly probed. MethodsWe examined resting-state global functional connectivity markers of SOR in 119 adults with OCD utilizing the CONN-fMRI Functional Connectivity Toolbox for SPM (v21a). We quantified SOR with the sensory sensitivity and sensory avoiding subscales of the Adult and Adolescent Sensory Profile (AASP). We also measured: OCD severity, with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Obsessive-Compulsive Inventory-Revised (OCI-R); sensory phenomena with the Sensory Phenomena Scale (SPS); general anxiety, with the Beck Anxiety Inventory (BAI); and depressive symptomatology, with Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR). ResultsThere was a significant positive relationship of SOR with global connectivity in anterior and medial OFC (Brodmann's area 11, k = 154, x = 14, y = 62, z = −18, whole-brain corrected at FWE p < 0.05). LimitationsFuture investigations should explore neural responses to sensory stimulation tasks in OCD and compare findings with those obtained in other conditions also characterized by high SOR, such as autism spectrum disorder. ConclusionsThis study implicates OFC functional connectivity as a neurobiological mechanism of SOR in OCD and suggests that the substrates of SOR in OCD may be dissociable from both that of other symptoms in OCD, and SOR in other disorders. With replication and extension, the finding may be leveraged to develop and refine treatments for OCD and investigate the pathophysiology of SOR in other conditions.

Persistent Impairment in Immune Reconstitution and Worse Survival Outcomes Among Allogeneic Stem Cell Transplant Patients with Early COVID-19 Infection.

Patients undergoing allogenic hematopoietic stem cell transplantation (HSCT) are at an increased risk of mortality due to transplant-related complications in the first year following transplantation, in part due to the profound immune dysregulation with T- and B-cell lymphopenia and functional impairment. Although several large studies have described higher mortality rates from the coronavirus disease 2019 (COVID-19) in HSCT recipients, no reports have focused on the impact of early COVID-19 infection on immune reconstitution post-transplant and correlation with transplant outcomes. We retrospectively analyzed 61 consecutive adult patients who underwent their first allogeneic HSCT at our institution. Thirteen patients (21.3%) experienced early COVID-19 infection with a median time to diagnosis of 100 days. In multivariable analysis, patients with early COVID-19 infection had significantly worse overall survival (adjusted hazard ratio [aHR], 4.06; 95% CI, 1.26 to 13.05; P=.019) and progression-free survival (aHR, 6.68; 95% CI, 2.11 to 21.11; P=.001).This was mainly attributed to higher non-relapse mortality (NRM) among early COVID(+) patients (P=.042). Allogeneic HSCT patients with early COVID-19 infection had significant delays in absolute lymphocyte count (95% CI, -703.69 to -56.79; P=.021), CD3+CD4+ (95% CI, -105.35 to -11.59; P=.042), CD3+CD8+ (95% CI, -324.55 to -57.13; P=.038), and CD3-CD56+ (95% CI, -193.51 to -47.31; P=.014) recovery compared to those without early COVID-19 infection. Our findings suggest that patients with early COVID-19 infection after allogeneic HSCT have higher NRM and worse survival, at least in part due to impairment in immune reconstitution post-transplantation.

Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa

Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV. We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021at Chris Hani Baragwanath Academic Hospital, South Africa. We collected data on comorbidities, and COVID-19 severity using the World Health Organization (WHO) clinical progression scale. Prospectively, we followed up all participants within 40-days post-discharge to assess body mass index (BMI), COVID-19 symptoms and quality of life using St George's Respiratory Questionnaire (SGRQ), 6-min walking-test (6MWT), and spirometry. A subsequent in-depth visit assessed plethysmography, diffusing capacity for the lung for carbon monoxide (DLCO), and high-resolution chest-CT. We followed up 111 participants, where 65.8% were female, median age 50.5 years, and predominantly black-African (92.8%). Relevant comorbidities included TB disease (18.9%) and HIV infection (36%). SGRQ total scores were elevated in 78.9%, median 6MWT distance was reduced at 300m (IQR 210-400), and nearly half (49.5%) exhibited spirometry findings below the lower limit of normal (LLN). In-depth pulmonary assessment for 61 participants revealed abnormalities in total lung capacity (31.6%<80% predicted), DLCO (53.4%<80% predicted), and chest-CT (86.7% abnormal). Significant risk factors for individual abnormal outcomes, adjusted for age and sex, were TB disease, HIV with CD4 <200cells/mm3, BMI <18.5kg/m2 and >35kg/m2, and initial COVID-19 severity. This study demonstrates substantial lung and functional morbidity within the first weeks post-COVID-19, particularly in individuals with pre-existing comorbidities including TB, HIV, and low or high BMI. Chest-CT and DLCO show best early potential at reflecting COVID-19-related pathologies. The Bavarian State Ministry of Science and Arts.

Psychological impact on the quality-of-life in patients of psoriasis vulgaris: A systemic review

Living with a chronic condition like psoriasis can significantly affect the individual involved. Psoriasis patients have difficulties with their physical, psychological, occupational, and social functioning. These impairments can result in psychiatric morbidity depression and anxiety disorders. This systematic review (SR) assessed the impact of psychological factors in life of psoriasis patients. The literature search comprised Medline through PubMed, Web of Science, the Cochrane Library, Wiley Online Library, and additional sources such as Google Scholar, spanning the period from 2014 to 2023. Thorough examination of the most important electronic databases was conducted. Various study designs, including observational studies, trials, and commentaries, were incorporated to ensure a comprehensive examination of the research topic. The risk of bias was evaluated using established methodology. This SR comprised 13 studies, with the Cochrane Risk of Bias Tool employed to assess biases in randomized trials across five domains. The majority of the studies demonstrated a low risk (57.69%), indicating their reliability while those categorized as unclear (37.17%) exhibited some ambiguity without compromising the validity of results. Studies categorized as high risk (5.12%) suggested significant bias and potential errors. The findings indicate an association between psoriasis and various psychological factors, including depression, anxiety, suicidal ideation, impaired emotional functioning, negative body image, and self-perception. The significant impact of depression and anxiety on individuals with psoriasis underscores the need for greater awareness of its psychological aspects. Incorporating psychological interventions into care and management strategies is crucial for addressing this chronic condition and enhancing overall well-being, thus improving quality of life.