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Two independent temporal-spatial clusters of hospital-onset Rhizopus infections were evaluated using whole-genome sequencing (WGS). Phylogenetic analysis confirmed that isolates within each cluster were unrelated despite epidemiological suspicion of outbreaks. The ITS1 region alone was insufficient for accurate analysis. WGS has utility for rapid rule-out of suspected nosocomial Rhizopus outbreaks.
We explored experiences and perceptions surrounding the Self-Stewardship Time-Out Program (SSTOP) intervention across implementation sites to improve antimicrobial use. Semistructured qualitative interviews were conducted with Antibiotic Stewardship physicians and pharmacists, from which 5 key themes emerged. SSTOP may serve to achieve sustainable promotion of antibiotic use improvements.
To investigate factors that influence antibiotic prescribing decisions, we interviewed 49 antibiotic stewardship champions and stakeholders across 15 hospitals. We conducted thematic analysis and subcoding of decisional factors. We identified 31 factors that influence antibiotic prescribing decisions. These factors may help stewardship programs identify educational targets and design more effective interventions.
Perfectionism, low self-esteem and external locus of control are psychological constructs linked to insomnia, anxiety and depression. Examining how these constructs impact mental health and serve as risk factors for the development of clinically significant symptoms may help direct psychological support resources and preventative measures for university students.
To longitudinally examine associations between the aforementioned psychological constructs and symptoms of insomnia, anxiety and depression in a large representative sample of first-year university students.
Electronic surveys including validated measures of the predictors and outcomes were emailed to all first-year undergraduate students at entry to a major Canadian university, and followed up on at conclusion of the academic year.
Compared with healthy sleepers, students screening positive for insomnia had lower self-esteem, higher self-evaluative perfectionism and increased external locus of control (all P < 0.001). Self-evaluative perfectionism (standardised β = 0.13, P < 0.01), self-esteem (β = −0.30, P < 0.001) and external locus of control (β = 0.07, P = 0.02) measured at entry were significantly associated with insomnia symptoms at follow-up. Insomnia symptoms at entry were strong predictors of symptoms of depression (β = 0.15, P < 0.001) and anxiety (β = 0.16, P < 0.001) at follow-up, even after controlling for baseline symptoms of those disorders.
Perfectionism, low self-esteem and external locus of control may predispose the development of insomnia symptoms in university students. In turn, insomnia symptoms appear to be robust predictors for depressive and anxiety symptoms. Sleep may be an important prevention target in university students.
Pain is poorly identified in dementia due to complete or partial loss in communication, which is associated with progressive cognitive impairment. If it goes untreated, pain can lead to behavioral disturbances (e.g., agitation/aggression), delirium, inappropriate pharmacotherapy (e.g., psychotropics), hospitalizations and caregiver distress. There are limited prevalence data in the literature on pain in dementia subtypes.
This study aims to investigate the prevalence and intensity of pain in various dementia subtypes in aged care residents living with dementia (RLWD), using a technology-driven pain assessment tool.
A 1-year retrospective cross-sectional study was conducted on the presence and intensity of pain in referrals to Dementia Support Australia from residential aged care homes (RACHs), using PainChek®. PainChek® is a pain assessment tool that uses artificial intelligence algorithms (e.g., automated facial recognition and analysis) to identify facial expressions indicative of pain in conjunction with other digital checklists of pain behaviors such as vocalization and movement cues. Presence and intensity of pain were identified using PainChek® categories (scores): no pain (0-6), mild pain (7-11), moderate pain (12-15) and severe pain (16-42).
During the study period (01/11/2017-31/10/2018), a sample of 479 referrals (age: 81.9 ± 8.3 years old; 55.5% female) from 370 RACHs with Alzheimer’s disease (AD; 40.9%), vascular dementia (VaD; 12.7%), mixed dementia (MD; 5.9%), dementia with Lewy body (DLB; 2.9%), and frontotemporal dementia (FTD; 2.3%) were examined. Pain was prevalent in two-thirds (65.6%) of the referrals with almost half (48.4%) of these categorized as experiencing moderate-severe pain. MD and those with DLB (78.6% each) shared the highest prevalence of pain, followed by AD (64.3%) > VaD (62.3%) > FTD (54.6%). Prevalence of severe pain was as follow: MD (17.9%) > AD (12.3%) > VaD (11.5%) > FTD (9.1%) > DLB (7.1%).
To date, this is the largest study that presented data on pain prevalence and intensity in major dementia subtypes in the RACH setting. Moderate-severe pain is highly prevalent in RLWD, which appears to differ by dementia subtypes. This may reveal the impact of neuropathological etiology of those subtypes on the neurobiology of pain.
People living with dementia (PLWD) in residential aged care homes (RACHs) are frequently prescribed psychotropic medications due to the high prevalence of neuropsychiatric symptoms, also known as behaviors and psychological symptoms of dementia (BPSD). However, the gold standard to support BPSD is using psychosocial/non-pharmacological therapies.
This study aims to describe and evaluate services and neuropsychiatric outcomes associated with the provision of psychosocial person-centered care interventions delivered by national multidisciplinary dementia-specific behavior support programs.
A 2-year retrospective pre-post study with a single-arm analysis was conducted on BPSD referrals received from Australian RACHs to the two Dementia Support Australia (DSA) programs, the Dementia Behavior Management Advisory Service (DBMAS) and the Severe Behavior Response Teams (SBRT). Neuropsychiatric outcomes were measured using the Neuropsychiatric Inventory (NPI) total scores and total distress scores. The questionnaire version “NPI-Q” was administered for DBMAS referrals whereas the nursing home version “NPI-NH” was administered for SBRT referrals. Linear mixed effects models were used for analysis, with time, baseline score, age, sex, and case length as predictors. Clinical significance was measured using Cohen’s effect size (d; ≥0.3), the mean change score (MCS; 3 points for the NPI-Q and 4 points for the NPI-NH) and the mean percent change (MPC; ≥30%) in NPI parameters.
A total of 5,914 referrals (55.9% female, age 82.3 ± 8.6 y) from 1,996 RACHs were eligible for analysis. The most common types of dementia were Alzheimer’s disease (37.4%) and vascular dementia (11.7%). The average case length in DSA programs was 57.2 ± 26.3 days. The NPI scores were significantly reduced as a result of DSA programs, independent of covariates. There were significant reductions in total NPI scores as a result of the DBMAS (61.4%) and SBRT (74.3%) programs. For NPI distress scores, there were 66.5% and 69.1% reductions from baseline for the DBMAS and SBRT programs, respectively. All metrics (d, MCS, MPC) were above the threshold set for determining a clinically significant effect.
Multimodal psychosocial interventions delivered by DSA programs are clinically effective as demonstrated by positive referral outcomes, such as improved BPSD and related caregiver distress.
We evaluated adverse drug events (ADEs) by chart review in a random national sample of 428 veterans with coronavirus disease 2019 (COVID-19) who received tocilizumab (n = 173 of 428). ADEs (median time, 5 days) occurred in 51 of 173 (29%) and included hepatoxicity (n = 29) and infection (n = 13). Concomitant medication discontinuation occurred in 22% of ADE patients; mortality was 39%.
Unemployment and being not in the labour force (NILF) are risk factors for suicide, but their association with self-harm is unclear, and there is continuing debate about the role of confounding by prior mental health conditions. We examine associations between employment status and self-harm and suicide in a prospective cohort, taking into account prior mental-health-related factors.
We used linked data from the New Zealand Integrated Data Infrastructure. The outcomes were chosen to be hospital presentation for self-harm and death by suicide. The exposure was employment status, defined as employed, unemployed, or NILF, measured at the 2013 Census. Confounders included demographic factors and mental health history (use of antidepressant medication, use of mental health services, and prior self-harm). Logistic regression was used to model effects. Analyses were stratified by gender.
For males, unemployment was associated with an increased risk of suicide [odds ratio (OR): 1.48, 95% confidence interval (CI): 1.20–1.84] and self-harm (OR: 1.55, 95% CI: 1.45–1.68) after full adjustment for confounders. NILF was associated with an increased risk of self-harm (OR: 1.43, 95% CI: 1.32–1.55), but less of an association was seen with suicide (OR: 1.19, 95% CI: 0.94–1.49). For females, unemployment was associated with an increased risk of suicide (OR: 1.30, 95% CI: 0.93–1.80) and of self-harm (OR: 1.52, 95% CI: 1.43–1.62), and NILF was associated with a similar increase in risk for suicide (OR: 1.31, 95% CI: 0.98–1.75) and self-harm (OR: 1.32, 95% CI: 1.26–1.40).
Exclusion from employment is associated with a considerably heightened risk of suicide and self-harm for both men and women, even among those without prior mental health problems.
A number of genomic conditions caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders (ND-CNVs). Although these patients also tend to have cognitive impairments, few studies have investigated the range of emotion and behaviour problems in young people with ND-CNVs using measures that are suitable for those with learning difficulties.
A total of 322 young people with 13 ND-CNVs across eight loci (mean age: 9.79 years, range: 6.02–17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC).
Of the total, 69% of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR = 0.71, CI = 0.55–0.91, p = .008) were less likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (χ2 = 39.99, p < 0.001), with the lowest rate in young people with 22q11.2 deletion (45.7%) and the highest in those with 1q21.1 deletion (93.8%). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 9–16% of the variance, depending on DBC subdomain.
Emotion and behaviour problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in emotion and behaviour problems not accounted for by genotype.
The present study aims to assess associations between parental depression and parental and child nutritional status and diets in Nepal.
A cross-sectional survey conducted from June to September 2017.
This monitoring survey was conducted in sixteen of forty-two Suaahara intervention districts spanning mountains, hills and plains in Nepal. Multi-stage cluster sampling was used to sample communities in this survey.
Women and men with a child 6–59 months of age were randomly selected (n 3158 mothers and children; n 826 fathers).
Overall, 36 % of mothers, 37 % of fathers and 55 % of children met minimum dietary diversity, indicating that they consumed foods from at least four of seven food groups (children) and at least five of ten food groups (adults) in the 24 h prior to the interview. The percentage of children stunted, wasted and underweight was 28, 11 and 23, respectively. Only 5 % of mothers and 3 % of fathers screened positive for moderate or severe depression (Patient Health Questionnaire-9 score ≥ 10). In adjusted models, we found maternal depression was positively associated with maternal underweight (OR = 1·48, 95 % CI 1·01, 2·17). Maternal and paternal depression, however, were not associated with other indicators of anthropometric status or dietary diversity.
Maternal and paternal depression, measured by the Patient Health Questionnaire-9, were not associated with dietary diversity or anthropometric status of fathers or children in Nepal, whereas depressed mothers were at increased risk of being underweight. Additional studies are needed to further assess relationships between mental health and nutritional outcomes.
Vitamin B12 deficiency is common among older adults, even with dietary intakes well in excess of current recommendations. Severe clinical B12 deficiency (i.e. pernicious anaemia) leads to irreversible neurological damage, but once diagnosed, can be treated effectively with B12 injections. A much more common cause of low vitamin B12 status in older adults is food-bound malabsorption owing to atrophic gastritis. This in turn leads to reduced gastric acid secretion, thus limiting B12 absorption from food (given the essential role of gastric acid in releasing B12 from food proteins). Proton pump inhibitor (PPI) drugs reduce gastric acid secretion, similar to atrophic gastritis, thus there is a concern that these medications may lead to vitamin B12 malabsorption. Therefore, the aim of this study was to investigate biomarker status of vitamin B12 in relation to atrophic gastritis and PPI usage. Data were accessed from The Trinity Ulster Department of Agriculture (TUDA) Ageing Cohort Study, a cross-sectional study of community-dwelling adults (n 5186, ≥ 60 years) recruited across Northern Ireland and the Republic of Ireland (2008–2012). TUDA participants were classified into 3 groups; ‘healthy’ controls, atrophic gastritis and PPI users. Vitamin B12 status was assessed using a total of four biomarkers: serum total B12; serum holotranscobalamin, holoTC; plasma methylmalonic acid, MMA; plasma homocysteine. Atrophic gastritis was identified using pepsinogen analysis (via ELISA), with a pepsinogen I : II ratio of < 3 considered indicative of atrophic gastritis. Based on results from all four biomarkers, participants with atrophic gastritis were found to have significantly lower B12 status compared to healthy controls: e.g. mean (95% CI) serum total vitamin B12, 188 (156, 218) pmol/L vs. 262 (252, 272) pmol/L P < 0.001; holoTC, 46.0 (38.1, 53.8) pmol/L vs. 60.3 (57.8, 62.8) pmol/L P < 0.001; plasma MMA, 0.65 (0.52, 0.78) μmol/L vs. 0.37 (0.32, 0.42) μmol/L P = 0.001. No differences in B12 biomarker concentrations were observed between PPI users and healthy controls. Regular consumption of fortified foods (i.e. ≥ 5 portions per week) compared to non-regular consumption (i.e. 0–4 portions per week) impacted positively on B12 biomarker status in all participants. This effect however appeared insufficient to restore normal vitamin B12 status in those with atrophic gastritis. These results show that older adults with atrophic gastritis have significantly lower vitamin B12 biomarker status, particularly in those who did not regularly consume fortified foods. Further investigations of the effect of atrophic gastritis and PPI usage on B12 status are warranted.
Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts.
To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes.
Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders.
In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being.
Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.
Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence.
To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence.
Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes.
13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender.
Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p < 0.05) but not OPRK1 gene. The rs2281285 - rs199794 haplotype showed significant association (p = 0.0236) with negative craving, while rs2235749 - rs10485703 haplotype showed marginally significant association (p = 0.055). This replicates previous findings of association between these haplotypes and alcohol dependence. Negative craving was also associated with PDYN rs2281285 variant (p = 0.012) with estimated effect size of 6.95 (SE = 2.75). This new association finding was not significant after correction for multiple testing (p = 0.18).
Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.
We recently identified association between GRIN2B rs2058878 variant and abstinence length in acamprosate-treated alcoholics (Karpyak et al. 2014). Here we present results of additional analyses exploring associations in the same sample (225 alcoholics treated with acamprosate for three months) at the gene and gene-set levels, for 12 genes involved in glycine signaling, 4 genes involved in glutamate reuptake, synthesis and degradation and 7 genes encoding NMDA receptor subunits.
After adjustment for relevant covariates, gene-level tests were performed using principal components (PC) analysis. Gene-set analyses were performed using the PC-Gamma approach with varying soft truncation threshold (STT) for the Gamma method for combining gene-level p-values.
Shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between last drink and initiation of acamprosate treatment. After adjustment for covariates, we observed nominally significant association of abstinence length with variation in the AMT (p=0.024), GRIN3A (p=0.016) and SHMT2 (p=0.039) genes, and marginally significant evidence for association with the GRIN2B (p=0.067) and GLRB (p=0.060) genes. At the gene-set level, association of abstinence length with variation in the glycine pathway was nominally significant (p=0.042 with STT=0.37). Marginal evidence of association with abstinence length was also observed for variation in the NMDA-receptor subunits (p<0.1 for STT<0.15).
Our findings suggest association of abstinence length in acamprosate-treated alcoholics with variation in the glycine signaling pathway and genes encoding NMDA receptor subunits. Investigation of the mechanisms underlying these associations and their usefulness for individualized treatment selection should follow.
The prevalence and impact of motor coordination difficulties in children with copy number variants associated with neurodevelopmental disorders (ND-CNVs) remains unknown. This study aims to advance understanding of motor coordination difficulties in children with ND-CNVs and establish relationships between intelligence quotient (IQ) and psychopathology.
169 children with an ND-CNV (67% male, median age = 8.88 years, range 6.02–14.81) and 72 closest-in-age unaffected siblings (controls; 55% male, median age = 10.41 years, s.d. = 3.04, range 5.89–14.75) were assessed with the Developmental Coordination Disorder Questionnaire, alongside psychiatric interviews and standardised assessments of IQ.
The children with ND-CNVs had poorer coordination ability (b = 28.98, p < 0.001) and 91% of children with an ND-CNV screened positive for suspected developmental coordination disorder, compared to 19% of controls (OR = 42.53, p < 0.001). There was no difference in coordination ability between ND-CNV genotypes (F = 1.47, p = 0.184). Poorer coordination in children with ND-CNV was associated with more attention deficit hyperactivity disorder (ADHD) (β = −0.18, p = 0.021) and autism spectrum disorder trait (β = −0.46, p < 0.001) symptoms, along with lower full-scale (ß = 0.21, p = 0.011), performance (β = −0.20, p = 0.015) and verbal IQ (β = 0.17, p = 0.036). Mediation analysis indicated that coordination ability was a full mediator of anxiety symptoms (69% mediated, p = 0.012), and a partial mediator of ADHD (51%, p = 0.001) and autism spectrum disorder trait symptoms (66%, p < 0.001) as well as full scale IQ (40%, p = 0.002), performance IQ (40%, p = 0.005) and verbal IQ (38%, p = 0.006) scores.
The findings indicate that poor motor coordination is highly prevalent and closely linked to risk of mental health disorder and lower intellectual function in children with ND-CNVs. Future research should explore whether early interventions for poor coordination ability could ameliorate neurodevelopmental risk.