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Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.
Design:
We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).
Results:
At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.
Conclusions:
Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.
People with intellectual disability are more likely to experience mental health difficulties, and their treatment responses may differ from those in the general population. This book, written by leading clinical practitioners from around the world, provides comprehensive guidance on prescribing for people with intellectual disability, as well as general information on their clinical care. The guidelines have been conceived and developed by clinicians working in intellectual disability services. Combining the latest evidence and expert opinion, they provide a consensus approach to prescribing as part of a holistic package of care, and include numerous case examples and scenarios. Now in its fourth edition, this update reflects the changes in prescribing practice; it places emphasis on clinical scenarios and case examples and includes input from service users and their families. This is a practical guide for busy clinicians, and a valuable reference for all primary and secondary healthcare professionals.
Prenatal glucocorticoid exposure has been negatively associated with infant neurocognitive outcomes. However, questions about developmental timing effects across gestation remain. Participants were 253 mother-child dyads who participated in a prospective cohort study recruited in the first trimester of pregnancy. Diurnal cortisol was measured in maternal saliva samples collected across a single day within each trimester of pregnancy. Children (49.8% female) completed the Bayley Mental Development Scales, Third Edition at 6, 12, and 24 months and completed three observational executive function tasks at 24 months. Structural equation models adjusting for sociodemographic covariates were used to test study hypotheses. There was significant evidence for timing sensitivity. First-trimester diurnal cortisol (area under the curve) was negatively associated with cognitive and language development at 12 months and poorer inhibition at 24 months. Second-trimester cortisol exposure was negatively associated with language scores at 24 months. Third-trimester cortisol positively predicted performance in shifting between task rules (set shifting) at 24 months. Associations were not reliably moderated by child sex. Findings suggest that neurocognitive development is sensitive to prenatal glucocorticoid exposure as early as the first trimester and underscore the importance of assessing developmental timing in research on prenatal exposures for child health outcomes.
The New Jersey Kids Study (NJKS) is a transdisciplinary statewide initiative to understand influences on child health, development, and disease. We conducted a mixed-methods study of project planning teams to investigate team effectiveness and relationships between team dynamics and quality of deliverables.
Methods:
Ten theme-based working groups (WGs) (e.g., Neurodevelopment, Nutrition) informed protocol development and submitted final reports. WG members (n = 79, 75%) completed questionnaires including de-identified demographic and professional information and a modified TeamSTEPPS Team Assessment Questionnaire (TAQ). Reviewers independently evaluated final reports using a standardized tool. We analyzed questionnaire results and final report assessments using linear regression and performed constant comparative qualitative analysis to identify central themes.
Results:
WG-level factors associated with greater team effectiveness included proportion of full professors (β = 31.24, 95% CI 27.65–34.82), team size (β = 0.81, 95% CI 0.70–0.92), and percent dedicated research effort (β = 0.11, 95% CI 0.09–0.13); age distribution (β = −2.67, 95% CI –3.00 to –2.38) and diversity of school affiliations (β = –33.32, 95% CI –36.84 to –29.80) were inversely associated with team effectiveness. No factors were associated with final report assessments. Perceptions of overall initiative leadership were associated with expressed enthusiasm for future NJKS participation. Qualitative analyses of final reports yielded four themes related to team science practices: organization and process, collaboration, task delegation, and decision-making patterns.
Conclusions:
We identified several correlates of team effectiveness in a team science initiative's early planning phase. Extra effort may be needed to bridge differences in team members' backgrounds to enhance the effectiveness of diverse teams. This work also highlights leadership as an important component in future investigator engagement.
Dietary therapies have revolutionised treatment for irritable bowel syndrome (IBS). However, response rates to the diet with the highest evidence of efficacy (the low FODMAP diet) remain at 50-75%, suggesting other potential drivers of symptom onset. A low food chemical elimination-rechallenge diet targeting bioactive food chemicals (including salicylates, amines, glutamate and other additives), is commonly applied in Australia in patients exhibiting both gastrointestinal and extra-intestinal symptoms. One key food chemical, salicylate, has been shown to elicit symptoms in IBS patients with aspirin-sensitivity(1), and 77% of IBS patients have reported amine-rich foods trigger symptoms(2). However, data supporting the full low chemical diet is scant, and safety concerns exist due to its restrictive nature potentially causing nutritional deficiencies and disordered eating. This cross-sectional survey aimed to evaluate the frequency of co-existing extra-intestinal symptoms, as well as explore patient perceptions and use of the low chemical diet in those with IBS and healthy controls. Participants with IBS (IBS-Severity Scoring System (IBS-SSS) >75), and healthy controls (not meeting Rome IV and IBS-SSS ≤75) were recruited via online advertisement. Validated questionnaires were used to assess gastrointestinal symptoms (IBS-SSS), extraintestinal symptoms (extended PHQ-12), nutrient (Comprehensive Nutritional Assessment Tool) and food additive intake (IBD-Food additive questionnaire). Additional questionnaires assessed use of dietary therapies with specific focus on food chemicals. Data was analysed using independent samples t-test and chi-square test. 204 IBS (Total IBS-SSS, 277 ± 79) and 22 healthy controls (36 ± 28, p<0.01) completed the study. IBS participants were more likely to report extra-intestinal symptoms including headaches (p<0.01), migraines (p = 0.03), fatigue (p<0.01), difficulty sleeping (p = 0.03), rhinitis (p = 0.02), urticaria (p = 0.04) and mood disturbance (p<0.01). IBS participants were more likely to report at least one food chemical as a trigger for gastrointestinal (38% vs 13%, p = 0.03) and/or extra-intestinal (30% vs 9%, p = 0.04) symptoms. In the IBS group, the most common suspected dietary triggers for gastrointestinal symptoms were salicylates (19%) followed by MSG (17%) and artificial colours (14%); while for extra-intestinal symptoms, MSG (15%) was most common, followed by amines (14%), and sulphites (12%). There was no significant difference in consumption of ultra-processed, additive containing foods. Twenty-one (10%) IBS participants were following a low chemical diet, with dietary advice provided by a dietitian (n = 13), general practitioner (n = 6), gastroenterologist (n = 6), naturopath (n = 3), family/friend (n = 4) and/or the diet was self-initiated (n = 7). Fourteen of the 21 (67%) reported following both a low food chemical and low FODMAP diet. Patients with IBS are more likely to report extra-intestinal symptoms compared to healthy controls. Despite limited evidence, a low food chemical diet is utilised to manage both gastrointestinal and extra-intestinal symptoms. Of concern, many respondents following a low food chemical diet reported also following a low FODMAP diet, which may have implications for nutritional adequacy.
At least 200 billion black soldier fly (Hermetia illucens) larvae (BSFL) are reared each year as food and feed, and the insect farming industry is projected to grow rapidly. Despite interest by consumers, producers, and legislators, no empirical evidence exists to guide producers in practicing humane – or instantaneous – slaughter for these novel mini-livestock. BSFL may be slaughtered via freezing, boiling, grinding, or other methods; however standard operating procedures (SOPs) and equipment design may affect the likelihood of instantaneous death using these methods. We tested how larval body size and particle size plate hole diameter affect the likelihood of instantaneous death for black soldier fly larvae that are slaughtered using a standard meat grinder. Larval body size did not affect the likelihood of instantaneous death for larvae that are 106–175 mg in mass. However, particle size plate hole diameter had a significant effect on the likelihood of instantaneous death, with only 54% of larvae experiencing an instant death when using the largest particle size plate (12-mm hole diameter) compared to 84% using the smallest particle size plate (2.55 mm). However, a higher percentage of instantaneous death (up to 99%) could be achieved by reducing the proportion of larvae that become stuck in the machine. We conclude by outlining specific recommendations to support producers in achieving a 99% instantaneous death rate through specific SOPs to be used with similarly designed machines. We also develop a protocol for producers that wish to test their own grinding SOPs.
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:
The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:
APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:
Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
Background: Our aim was to develop a National Quality Indicators Set for the Care of Adults Hospitalized for Neurological Problems, to serve as a foundation to build regional or national quality initiatives in Canadian neurology centres. Methods: We used a national eDelphi process to develop a suite of quality indicators and a parallel process of surveys and patient focus groups to identify patient priorities. Canadian content and methodology experts were invited to participate. To be included, >70% of participants had to rate items as critical and <15% had to rate it as not important. Two rounds of surveys and consensus meetings were used identify and rank indicators, followed by national consultation with members of the Canadian Neurological Society. Results: 38 neurologists and methodologists and 56 patients/caregivers participated in this project. An initial list of 91 possible quality indicators was narrowed to 40 indicators across multiple categories of neurological conditions. 21 patient priorities were identified. Conclusions: This quality indicators suite can be used regionally or nationally to drive improvement initiatives for inpatient neurology care. In addition, we identified multiple opportunities for further research where evidence was lacking or patient and provider priorities did not align.
Nest design is one factor contributing to floor-laying in farmed poultry. We investigated: (i) if ducks (Anas platyrhynchos) prefer a particular nest substrate; and (ii) how important that preference is to them, indicated by stress-induced hyperthermia, egg albumen corticosterone, and behaviour. Twelve female ducks that were trained in a push-door task had temperature data loggers implanted. Preference testing identified the most and least preferred nest substrates between sawdust, astroturf, and hemp fibres. A behavioural demand test then required the ducks to use push-doors to access nests containing either the most or least preferred substrate. The preferred substrate door was loaded with increasing weight (0–120% of bodyweight, four nights per workload) and eventually blocked to prevent nest access. The least preferred substrate door remained unweighted. The overall rank order of substrate preferences was sawdust > hemp > astroturf. Six of the 12 birds pushed all workloads and attempted to push the blocked door. The area under the curve (AUC) of hyperthermia was larger when the preferred substrate door was blocked compared with 0%. The AUC did not differ between nights 2–4 of the blocked door compared with night 1. Egg albumen corticosterone was unaffected. We conclude that laying Pekin ducks prefer manipulatable nest substrates and accessing one is important enough to pay a cost. The results indicate that a manipulatable substrate should be provided to commercially farmed nesting ducks.
As the incidence of human papillomavirus related oropharyngeal cancer continues to rise, it is increasingly important for public understanding to keep pace. This study aimed to identify areas of patient interest and concern regarding human papillomavirus and oropharyngeal cancer.
Method
This study was a retrospective survey of search queries containing the keywords ‘HPV cancer’ between September 2015 and March 2021.
Results
There was 3.5-fold more interest in human papillomavirus related oropharyngeal cancer (15 800 searches per month) compared with human papillomavirus related cervical cancer (4500 searches per month). Among searches referencing cancer appearance, 96.8 per cent pertained to the head and neck region (3050 searches per month). Among vaccination searches, 16 of 47 (34.0 per cent; 600 searches per month) referenced human papillomavirus vaccines as being a cause of cancer rather than preventing cancer.
Conclusion
The vast majority of online searches into human papillomavirus cancer pertain to the oropharynx. There are relatively few search queries on the topic of vaccination preventing human papillomavirus associated oropharyngeal cancer, which highlights the continued importance of patient education and awareness campaigns.
To conduct a contemporary detailed assessment of outpatient antibiotic prescribing and outcomes for positive urine cultures in a mixed-sex cohort.
Design:
Multicenter retrospective cohort review.
Setting:
The study was conducted using data from 31 Veterans’ Affairs medical centers.
Patients:
Outpatient adults with positive urine cultures.
Methods:
From 2016 to 2019, data were extracted through a nationwide database and manual chart review. Positive urine cultures were reviewed at the chart, clinician, and aggregate levels. Cases were classified as cystitis, pyelonephritis, or asymptomatic bacteriuria (ASB) based upon documented signs and symptoms. Preferred therapy definitions were applied for subdiagnoses: ASB (no antibiotics), cystitis (trimethoprim-sulfamethoxazole, nitrofurantoin, β-lactams), and pyelonephritis (trimethoprim-sulfamethoxazole, fluoroquinolone). Outcomes included 30-day clinical failure or hospitalization. Odds ratios for outcomes between treatments were estimated using logistic regression.
Results:
Of 3,255 cases reviewed, ASB was identified in 1,628 cases (50%), cystitis was identified in 1,156 cases (36%), and pyelonephritis was identified in 471 cases (15%). Of all 2,831 cases, 1,298 (46%) received preferred therapy selection and duration for cases where it could be defined. The most common antibiotic class prescribed was a fluoroquinolone (34%). Patients prescribed preferred therapy had lower odds of clinical failure: preferred (8%) versus nonpreferred (10%) (unadjusted OR, 0.74; 95% confidence interval [CI], 0.58–0.95; P = .018). They also had lower odds of 30-day hospitalization: preferred therapy (3%) versus nonpreferred therapy (5%) (unadjusted OR, 0.55; 95% CI, 0.37–0.81; P = .002). Odds of clinical treatment failure or hospitalization was higher for β-lactams relative to ciprofloxacin (unadjusted OR, 1.89; 95% CI, 1.23–2.90; P = .002).
Conclusions:
Clinicians prescribed preferred therapy 46% of the time. Those prescribed preferred therapy had lower odds of clinical failure and of being hospitalized.
Delays in the diagnosis and therapy of benign paroxysmal positional vertigo can greatly impact quality of life and increase healthcare costs for patients. This study aimed to appraise the quality of clinical practice guidelines for the diagnosis and management of benign paroxysmal positional vertigo.
Methods
A comprehensive database search of clinical practice guidelines was completed up to 30 October 2021. Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation II instrument in the quality appraisal.
Results
The highest score was in ‘clarity and presentation’ (58.33 ± 22.7). The lowest score was in ‘applicability’ (13.96 ± 30.1). Overall, four clinical practice guidelines were ‘low quality’ and only one guideline was ‘high quality’.
Conclusion
This review identified a significant lack of quality in clinical practice guideline development for benign paroxysmal positional vertigo, highlighting the need for a more rigorous approach for future guideline development.