Search

Effective screening tools can help providers with treatment decisions, including when to refer patients for neuropsychological evaluations, which are the gold standard for cognitive assessment of neurodegenerative disease. The authors examined whether performance on the Addenbrooke's Cognitive Examination-Third Edition (ACE-III), a readily available cognitive screening tool for older adults, predicted performance on subsequent neuropsychological evaluations.In total, 217 patients referred for neurocognitive concerns completed a neuropsychological evaluation, including the ACE-III. Patients were diagnosed as having normal cognition (NC, N=67), mild neurocognitive disorder (mild NCD, N=105), or major NCD (N=45). Regression analyses were used to determine whether ACE-III subscale scores predicted performance on neuropsychological measures assessing similar constructs. Logistic regression was used to assess whether ACE-III total score and overall neuropsychological test performance predicted diagnosis. Separate analyses compared those with higher and lower educational attainments. ACE-III subscales and total scores were compared by diagnostic group.Across all groups, ACE-III subscale scores predicted within-construct neuropsychological performances with moderate to strong effects (p0.001) but were less predictive for those with lower educational attainment. ACE-III total score was less sensitive than overall neuropsychological test performance in predicting neurocognitive disorders. ACE-III subscale and total scores distinguished diagnostic groups (NCmild NCDmajor NCD, p0.001).ACE-III subscale scores predicted performance on neuropsychological measures assessing similar constructs. However, overall performance on neuropsychological testing was more sensitive than ACE-III total score in predicting neurocognitive disorder diagnosis. Total ACE-III score differed by level of cognitive impairment. Comprehensive neuropsychological testing is recommended for patients who have lower educational status or complex symptom presentations or are younger.

Previous studies have examined whether spiritual well-being is associated with cancer outcomes, but minority populations are under-represented. This study examines associations of baseline spiritual well-being and change in spiritual well-being with change in distress and quality of life, and explores potential factors associated with changes in spiritual well-being among Hispanic women undergoing chemotherapy.Participants completed measures examining spiritual well-being, distress, and quality of life prior to beginning chemotherapy and at weeks 7 and 13. Participants' acculturation and sociodemographic data were collected prior to treatment. Mixed models were used to examine the association of baseline spiritual well-being and change in spiritual well-being during treatment with change in distress and quality of life, and to explore whether sociodemographic factors, acculturation and clinical variables were associated with change in spiritual well-being.A total of 242 participants provided data. Greater baseline spiritual well-being was associated with less concurrent distress and better quality of life (p lt; 0.001), as well as with greater emotional and functional well-being over time (p values lt; 0.01). Increases in spiritual well-being were associated with improved social well-being during treatment, whereas decreases in spiritual well-being were associated with worsened social well-being (p lt; 0.01). Married participants reported greater spiritual well-being at baseline relative to non-married participants (p lt; 0.001).Greater spiritual well-being is associated with less concurrent distress and better quality of life, as well as with greater emotional, functional, and social well-being over time among Hispanic women undergoing chemotherapy. Future work could include developing culturally targeted spiritual interventions to improve survivors' well-being.

Authorization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines for children has ushered in a new phase of the immunization campaign to address the pandemic but has been received with mixed responses from parents, children, and opinion leaders. Herein we consider perceptions and attitudes towards pediatric SARS-CoV-2 vaccines from a Food and Drug Administration (FDA) public commentary reflecting more than 63 000 comments.

Objectives:To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.Design:Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.Setting:Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.Participants:HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic.Methods:Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection.Results:Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3–14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient’s bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs).Conclusions:In our study cohort of HCP working in an academic healthcare system

Background PTCy is increasingly being used in MUD/MMURD, and haploidentical donor HCT for prevention of graft-versus-host disease (GVHD). PTCy has been associated with increased risk of infections including CMV viremia after HCT. It remains unclear if this observation is independent of graft type. This study aims to evaluate the incidence of clinically significant CMV infection (CS-CMVi) following PTCy in MUD/MMURD compared to haploidentical donor HCT. Methods We performed a single-center retrospective study of all adults undergoing HCT with PTCy between January 1, 2015 and July 1, 2021. CS-CMVi, defined as CMV viremia or disease requiring initiation of CMV therapy, was evaluated in two groups: haploidentical HCT (n=170) and MUD/MMURD HCT (n=137). We assessed the incidence of CMV viremia, CS-CMVi, and CMV disease, as well as incidence of letermovir breakthrough infections and late CMV events after cessation of prophylaxis. Cumulative Incidence Functions were calculated based on time to CS-CMVi using dates of infection-free death, disease relapse, and repeat HCT as competing risks. Results The one-year cumulative incidence of CS-CMVi accounting for competing risks was 25% (95% CI 19 – 32) in the haploidentical group and 18% (95% CI 12 – 25) in the MUD/MMURD group (HR 1.50; 95% CI 0.91 – 2.46; p=0.11). CMV disease was rare, (haploidentical n=1; MUD/MMURD n=1) and no patients died of CMV infection. CS-CMVi in CMV seropositive patients was more common in the haploidentical group (23% versus 9%; p=0.002). Notably, CMV D+/R- HCT patients had a significantly higher rate of CS-CMVi in the MUD/MMURD cohort than in the haploidentical cohort. Of the CS-CMVi, letermovir breakthrough constituted 26% in the haploidentical group and 29% in the MUD/MMURD group. Late infections after cessation of letermovir occurred in only 14% of cases in the haploidentical group and 25% of cases in the MUD/MMURD group. Conclusion Rates of CS-CMVi, CMV viremia, and CMV disease were similar following PTCy in haploidentical donor HCT and MUD/MMURD HCT. CS-CMVi in CMV seropositive patients was more common in the haploidentical donor HCT population and MUD/MMURD HCT recipients had a higher incidence of CS-CMVi in the D+/R- patients. Disclosures Roman M. Shapiro, M.D., Miltenyi Biotec: Honoraria Rizwan Romee, M.D., Crispr Therapeutics: Grant/Research Support|Glycostem Therapeutics: Advisor/Consultant|NK Therapeutics: Advisor/Consultant|Skyline Therapeutics: Grant/Research Support Robert J. Soiffer, M.D., CSL Behring: Advisor/Consultant|Gilead: Career Chair Development Award|Jasper Therapeutics: Advisor/Consultant|Jazz Pharmaceuticals: Advisor/Consultant|Juno (BMS): DSMB|Kiadis: Board Member|Vor: Advisor/Consultant Vincent T. T. Ho, M.D., Alexion Pharmaceuticals: Advisor/Consultant|Allovir: Advisor/Consultant|Allovir: DSMC|Jazz Pharmaceuticals: Grant/Research Support|Omeros: Advisor/Consultant Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Merck: Grant/Research Support.

Background SARS-CoV-2 vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), but immunogenicity may be reduced in patients undergoing hematopoietic stem cell transplantation (HSCT). The variables that impact the humoral response, such as age, gender, disease and transplant type, prior treatments, and vaccine type, have not been comprehensively described. Methods A retrospective review was conducted at a single-centre of HSCT recipients who received COVID-19 vaccinations between 2020 and 2021. Participants were included if >18 years and had received at least a single dose of Pfizer, Moderna or Johnson & Johnson (J&J) vaccine. Anti-Spike (S) IgG titers were quantitatively measured at provider discretion during routine care using the Roche Elecsys Anti-SARS-CoV-2 spike immunoassay and categorized as Responders (< 0.8U/mL) and Non-responder (>0.8). Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for Responders vs Non-responders. Controlled risk factors included; Age, disease, treatments, and history of graft-versus-host disease (GVHD). Results Of 117 HSCT patients assessed, 59 (50.4%) were female, 106 (90.6%) were white, and the median age was 62.5 years (interquartile range [IQR, 49.9-67.8). Vaccinations were administered at a median of 179 days post-transplant (IQR 319 - 105) and antibody responses were measured at a median of 135.5 days post-vaccination (IQR 190-50). 106(90.6%) were responders with a mean titre of 1141.5U/mL (SD=1095.3). 35% had Low (< 100U/mL) titres. Being Female (OR 0.02, 95%CI 0.003 - 0.6) was associated with a slightly higher odds of being a responder. Conclusion Hematopoietic stem cell transplant recipients demonstrated a high prevalence of anti-S IgG antibody positivity following COVID vaccination. However, neither patient characteristics nor treatment regimens were seen to be strongly associated with anti-S protein positivity among HSCT recipients. More studies are needed to further characterize patient and treatment characteristics that correlate with seroprotection among these patients. Disclosures Stephen R. Walsh, MD, Janssen Vaccines: Grant/Research Support|ModernaTX: Grant/Research Support|Sanofi Pasteur: Grant/Research Support.

Background Cytomegalovirus (CMV) disease is associated with increased morbidity and mortality following solid organ and hematopoietic cell transplantation. Currently, standard of care CMV treatments often have significant myelosuppressive or renal toxicities. Given letermovir’s favorable safety profile when used prophylactically, it may be a safe and efficacious alternative agent for CMV treatment. Methods A proof-of-concept, open-label trial was conducted in patients who lacked effective therapeutic options or presented with baseline organ dysfunction. Participants were eligible for enrollment if they were ≥12 years old and had documented CMV infection refractory to treatment defined as failure to achieve >1 log reduction in CMV viral load (VL) (when VL > 500 IU/mL) or lack of clinical improvement for CMV end-organ disease after ≥14 days of standard CMV treatment. Alternatively, patients with severe myelosuppression and renal dysfunction at baseline or genotypic antiviral resistance were also eligible. Participants were excluded if their current CMV infection developed while receiving letermovir for CMV prophylaxis. Letermovir was administered daily (480 mg PO/IV) for up to 12 weeks, with optional additional 12 weeks of treatment for secondary prophylaxis if clinically indicated. Results Ten patients met eligibility criteria and were enrolled. Reasons for enrollment included ganciclovir resistance (1/10), refractory CMV infection (6/10), renal dysfunction (7/10), and myelosuppression (7/10). The median baseline CMV VL was 1272 IU/ml [interquartile range (IQR); 925, 2546]. Six patients completed the study, three died due to complications of primary disease, and one discontinued due to diarrhea. Five patients (50%) had documented CMV viremia clearance, with a median time to first unquantifiable/undetectable CMV VL of 13 days [IQR; 9,18] and a median treatment duration of 53 days [IQR; 15,84]. Infections and GI disorders were the most common adverse events (AE), none considered related to study drug. No unexpected AE were observed during letermovir treatment. Conclusion Letermovir may be a safe and tolerable alternative for patients with treatment refractory CMV infection or for patients with severe baseline myelosuppression and renal dysfunction. Disclosures Matthew Cheng, MD, AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|Scynexis Inc.: Grant/Research Support Sandra Burchett, MD, MSc, merck: Grant/Research Support Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|pfizer: Advisor/Consultant|Scynexis: Grant/Research Support Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Merck: Grant/Research Support Francisco M. Marty, MD, SM, AlloVir: Advisor/Consultant|Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Ansun: Grant/Research Support|Avir: Advisor/Consultant|Chimerix: Grant/Research Support|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Kyorin: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Regeneron: Advisor/Consultant|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Scynexis: Grant/Research Support|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|United Medical: Advisor/Consultant|WHISCO: Grant/Research Support.

Purpose This research investigated the nature of cognitive decline in prodromal Alzheimer's disease (AD), particularly in mild cognitive impairment, amnestic type (aMCI). We assessed language in aMCI as compared with healthy aging (HA) and healthy young (HY) with new psycholinguistic assessment of complex sentences, and we tested the degree to which deficits on this language measure relate to performance in other general cognitive domains such as memory. Method Sixty-one individuals with aMCI were compared with 24 HA and 10 HY adults on a psycholinguistic measure of complex sentence production (relative clauses). In addition, HA, HY, and a subset of the aMCI participants ( n = 22) were also tested on a multidomain cognitive screen, the Addenbrooke's Cognitive Examination–Revised (ACE-R), and on a verbal working memory Brown–Peterson (BP) test. General and generalized linear mixed models were used to test psycholinguistic results and to test whether ACE-R and BP performance predicted performance on the psycholinguistic test similarly in the aMCI and HA groups. Results On the psycholinguistic measure, sentence imitation was significantly deficited in aMCI in comparison with that in HA and HY. Experimental factorial designs revealed that individuals with aMCI had particular difficulty repeating sentences that especially challenged syntax–semantics integration. As expected, the aMCI group also performed significantly below the HY and HA groups on the ACE-R. Neither the ACE-R Memory subtest nor the BP total scores predicted performance on the psycholinguistic task for either the aMCI or the HA group. However, the ACE-R total score significantly predicted psycholinguistic task performance, with increased ACE-R performance predicting increased psycholinguistic task performance only for the HA group, not for the aMCI group. Conclusions Results suggest a selective deterioration in language in aMCI, specifically a weakening of syntax–semantics integration in complex sentence processing, and a general independence of this language deficit and memory decline. Results cohere with previous assessments of the nature of difficulty in complex sentence formation in aMCI. We argue that clinical screening for prodromal AD can be strengthened by supplementary testing of language, as well as memory, and extended evaluation of strength of their relation.

Despite the existence of a large Indian diaspora, there has been relatively little scholarly attention paid to India's relations with overseas Indians after its independence in 1947. The common narrative is that India abruptly cut ties with overseas Indians at independence, as it adhered to territorially based understandings of sovereignty and citizenship. Re-examining India's relations with Indian communities in Ceylon and Burma between the 1940s and the 1960s, this article demonstrates that, despite its rhetoric, independent India did not renounce responsibility for its diaspora. Instead, because of pre-existing social connections that spanned the former British empire, the Government of India faced regular demands to assist overseas Indians, and it responded on several fronts. To understand this continued engagement with overseas Indians, this article introduces the idea of ‘post-imperial sovereignty'. This type of sovereignty was layered, as imperial sovereignty had been, but was also concerned with advancing norms designed to protect minority communities across the world. India’s strategy to argue for these norms was simultaneously multilateral, regional, and bilateral. It sought to use the United Nations, the Commonwealth, and the 1947 Asian Relations Conference to secure rights for overseas Indians. As those attempts failed, India negotiated claims for citizenship with governments in Burma and Ceylon, and shaped the institutions and language through which Indians voiced demands for their rights in these countries. Indian expressions of sovereignty beyond the space of the nation-state, therefore, impacted on practices of citizenship, even during the process of de-recognition in Asia.

Background The COVID-19 pandemic has led to pervasive social and economic disruptions. This cross-sectional investigation aimed to evaluate associations between religious/spiritual factors and mental health symptoms among community residents in a southern US state. In particular, we focused on perceptions of God's distance, a salient aspect of religious/spiritual struggle that has received little scrutiny in health research. Methods Participants included 551 respondents assessed during a period of gradual reopening but rising infection rates. Mental health outcomes were assessed using standardized measures of generalized anxiety, depression, and trauma symptoms. Perceptions of an affirming relationship with God, anger at God, and disappointment at God's distance were evaluated using an adapted version of the Attitudes-Toward-God Scale-9. Results In multivariate analyses that accounted for pandemic-related and demographic factors, positive relationships with God were related to diminished symptoms on all three mental heatlh indices (all p's ≤.003), whereas disappointment with God's distance was associated with more pronounced difficulties (all p's ≤.014). Limtations The cross-sectional design precludes causal conclusions. Conclusions Findings suggest that perceived relationships with God are tied to clinically relevant mental health outcomes during periods of major upheaval. Disappointment with God's distance may be an important, understudied dimension of religious/spiritual struggle meriting further investigation.

Objective: Cognitive dysfunction is one of the most frequently reported symptoms in post-acute sequelae of COVID-19 (PASC) and has become a common reason for neuropsychological referral. While data are emerging, we aimed to address possible cross-cultural patterns of neuropsychological outcomes that remain underexplored. Methods: In this cross-sectional, retrospective study, we characterize the cognitive performance, demographic makeup, and clinical characteristics of 84 PASC patients (Mage = 57 years) referred for neuropsychological evaluation to three USA sites and one in Germany. Neuropsychological data (mean demographically adjusted z-scores and frequencies of impairment) were examined across six cognitive domains. Independent t-tests compared performances of previously hospitalized and non-hospitalized patients. Results: Patients were assessed on average seven months post-COVID-19 infection. The majority were women and non-hospitalized. Mean cognitive performance was within the normative range, but high variability existed within and between sites. Deficits were generally mild and most frequent in processing speed (range across sites: 9–57% of patients), executive functioning (range across sites: 4–43% of patients) and attention/working memory (range across sites: 0–43% of patients). Hospitalized patients showed greater cognitive impairment than those not requiring hospitalization. Mood symptoms and fatigue/sleep disturbance were more frequent than objective cognitive impairments. At the time of assessment, most patients were unable to return to work. Conclusions: Cognitive performance in clinically referred PASC patients was, overall, within the normative range. Mild deficits were most frequent in time-based attentional/executive tasks. Other factors, such as affective symptoms and fatigue, were frequent and may significantly impact functioning, perhaps more than cognition. Further work with larger samples and longitudinal measures is needed to clarify the impact of COVID-19 on cognitive function and psychiatric distress.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine. Eleven of 13 participants showed detectable levels of SARS-CoV-2 protein as early as day 1 after first vaccine injection. Clearance of detectable SARS-CoV-2 protein correlated with production of immunoglobulin G (IgG) and immunoglobulin A (IgA).

The 1950s are often derided in the scholarship as a period of welfarist policies which reinforced women’s role in the family and entrenched women’s economic dependence. This paper examines the Central Social Welfare Board, and in particular its Welfare Extension Projects, to provide a new characterisation of the approach to women’s issues during the period. It argues that the Central Social Welfare Board, with its unique administrative structure, its preference for voluntary activity, and its adherence to persuasion as a mode of action reflected many of the characteristics of Indian socialism of the time. It also sketches, from this angle, a partial picture of state feminism in India. In the Central Social Welfare Board, state feminism was concerned with the gradual transformation of women and a radical, if short-lived, makeover of the state.