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Identify risk factors for central line-associated bloodstream infections (CLABSI) in pediatric intensive care settings in an era with high focus on prevention measures.
Design:
Matched, case–control study.
Setting:
Quaternary children’s hospital.
Patients:
Cases had a CLABSI during an intensive care unit (ICU) stay between January 1, 2015 and December 31, 2020. Controls were matched 4:1 by ICU and admission date and did not develop a CLABSI.
Methods:
Multivariable, mixed-effects logistic regression.
Results:
129 cases were matched to 516 controls. Central venous catheter (CVC) maintenance bundle compliance was >70%. Independent CLABSI risk factors included administration of continuous non-opioid sedative (adjusted odds ratio (aOR) 2.96, 95% CI [1.16, 7.52], P = 0.023), number of days with one or more CVC in place (aOR 1.42 per 10 days [1.16, 1.74], P = 0.001), and the combination of a chronic CVC with administration of parenteral nutrition (aOR 4.82 [1.38, 16.9], P = 0.014). Variables independently associated with lower odds of CLABSI included CVC location in an upper extremity (aOR 0.16 [0.05, 0.55], P = 0.004); non-tunneled CVC (aOR 0.17 [0.04, 0.63], P = 0.008); presence of an endotracheal tube (aOR 0.21 [0.08, 0.6], P = 0.004), Foley catheter (aOR 0.3 [0.13, 0.68], P = 0.004); transport to radiology (aOR 0.31 [0.1, 0.94], P = 0.039); continuous neuromuscular blockade (aOR 0.29 [0.1, 0.86], P = 0.025); and administration of histamine H2 blocking medications (aOR 0.17 [0.06, 0.48], P = 0.001).
Conclusions:
Pediatric intensive care patients with chronic CVCs receiving parenteral nutrition, those on non-opioid sedative infusions, and those with more central line days are at increased risk for CLABSI despite current prevention measures.
Anxiety is a common comorbid feature of late-life depression (LLD) and is associated with poorer global cognitive functioning independent of depression severity. However, little is known about whether comorbid anxiety is associated with a domain-specific pattern of cognitive dysfunction. We therefore examined group differences (LLD with and without comorbid anxiety) in cognitive functioning performance across multiple domains.
Method:
Older adults with major depressive disorder (N = 228, ages 65–91) were evaluated for anxiety and depression severity, and cognitive functioning (learning, memory, language, processing speed, executive functioning, working memory, and visuospatial functioning). Ordinary least squares regression adjusting for age, sex, education, and concurrent depression severity examined anxiety group differences in performance on tests of cognitive functioning.
Results:
Significant group differences emerged for confrontation naming and visuospatial functioning, as well as for verbal fluency, working memory, and inhibition with lower performance for LLD with comorbid anxiety compared to LLD only, controlling for depression severity.
Conclusions:
Performance patterns identified among older adults with LLD and comorbid anxiety resemble neuropsychological profiles typically seen in neurodegenerative diseases of aging. These findings have potential implications for etiological considerations in the interpretation of neuropsychological profiles.
The trace element selenium is known to protect against oxidative damage which is known to contribute to cognitive impairment with ageing (1,2). The aim of this study was to explore the association between selenium status (serum selenium and selenoprotein P (SELENOP)) and global cognitive performance at baseline and after 5 years in 85-year-olds living in the Northeast of England.
Serum selenium and SELENOP concentrations were measured at baseline by total reflection X-ray fluorescence (TXRF) and enzyme-linked immunosorbent assay (ELISA), respectively, in 757 participants from the Newcastle 85+ study. Global cognitive performance was assessed using the Standardized Mini-Mental State Examination (SMMSE) where scores ≤25 out of 30 indicated cognitive impairment. Logistic regressions explored the associations between selenium status and global cognition at baseline. Linear mixed models explored associations between selenium status and global cognition prospectively after 5 years. Covariates included sex, body mass index, physical activity, high sensitivity C-reactive protein, alcohol intake, self-rated health, medications and smoking status.
At baseline, in fully adjusted models, there was no increase in odds of cognitive impairment with serum selenium (OR 1.004, 95% CI 0.993-1.015, p = 0.512) or between SELENOP (OR 1.006, 95% CI 0.881-1.149, p = 0.930). Likewise, over 5 years, in fully adjusted models there was no association between serum selenium and cognitive impairment (β 7.20E-4 ± 5.57E-4, p = 0.197), or between SELENOP and cognitive impairment (β 3.50E-3 ± 6.85E-3, p = 0.610).
In this UK cohort of very old adults, serum selenium or SELENOP was not associated with cognitive impairment at baseline and 5 years. This was an unexpected finding despite SELENOP’s key role in the brain and the observed associations in other studies. Further research is needed to explore the effect of selenium on global cognition in very old adults.
Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aβ) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD.
Participants and Measurements:
Older adults with major depression (N = 121, Ages 65–91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aβ standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity.
Results:
Greater anxiety severity was associated with lower OFC volume (β = −68.25, t = −2.18, p = .031) and greater cognitive dysfunction (β = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aβ SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (β = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety.
Conclusions:
Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
Background: 5-Aminolevulinic acid (5-ALA) is a prodrug used to selectively illuminate high-grade glioma (HGG) tissue intra-operatively, shown to nearly double complete resection rates in a 2006 multicentre, phase III clinical trial. Here, we review the history of the 2020 approval of 5-ALA in Canada and present some of the first preliminary results on resection rates, survival analysis, and adverse effects from a single Canadian center. Methods: We enrolled 76 patients (median age 61 years, 42 male) with suspected HGG amenable to surgical resection between June 2020 and January 2023. Gross total resection was defined by the absence of enhancing lesions on postoperative MRI. We compared the survival distributions of confirmed HGG cases with complete vs. incomplete resection using a log-rank test and Kaplan-Meier statistic. Results: 52 patients were confirmed as having a HGG based on a pathological diagnosis. In 32 of these patients (60.3%) a gross total resection was achieved. 82.76% were still alive at 180 and 270 days, and 72.73% at 360 days. 47.8% had a survival of 600 or more days. Conclusions: 5-ALA fluorescence-guided surgery resulted in high complete resection rates, and improved overall survival comparable to the literature with no notable adverse side effects.
To compare clinical outcomes associated with appropriate and inappropriate management of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) among inpatients with neurogenic bladder (NB).
Design:
Multicenter, retrospective cohort.
Setting:
The study was conducted across 4 Veterans’ Affairs hospitals.
Participants:
The study included veterans with NB due to spinal cord injury or disorder (SCI/D), multiple sclerosis (MS), or Parkinson’s disease (PD) hospitalized between January 1, 2017, and December 31, 2018, with diagnosis of ASB or UTI.
Interventions:
In a medical record review, we classified ASB and UTI diagnoses and treatments as appropriate or inappropriate based on national guidelines.
Main outcome measures:
Frequencies of Clostridioides difficile infection, acute kidney injury, 90-day hospital readmission, postculture length-of-stay (LOS), and multidrug-resistant organisms in subsequent urine cultures were compared between those who received appropriate and inappropriate management.
Results:
We included 170 encounters with ASB (30%) or UTI (70%) diagnoses occurring for 166 patients. Overall, 86.1% patients were male, 47.6% had SCI/D and 77.6% used bladder catheters. All ASB encounters had appropriate diagnoses, and 96.1% had appropriate treatment. In contrast, 37 UTI encounters (31.1%) had inappropriate diagnoses and 61 (51.3%) had inappropriate treatment, including 30 encounters with true ASB. Among patients with SCI/D or MS, appropriate ASB or UTI diagnosis was associated with a longer postculture LOS (median, 14 vs 7.5 days; P = .02). We did not detect any significant associations between appropriate versus inappropriate diagnosis and treatment and other outcomes.
Conclusions:
Almost one-third of UTI diagnoses and half of treatments in hospitalized patients with NB are inappropriate. Opportunities exist to improve ASB and UTI management in patients with NB to minimize inappropriate antibiotic use.
To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Design:
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Setting:
Community settings and care homes in 26 UK centers.
Participants:
People with probable or possible Alzheimer’s disease and agitation.
Measurements:
Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.
Results:
One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.
Conclusions:
On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.
Using a simple, coarse-grained Poisson process model, we calculate – for seven types of astrophysical catastrophe – both their individual and combined threat to complex lifeforms (extraterrestrial intelligences (ETIs)) throughout the Milky Way Galaxy. In terms of cumulative effects, we calculate that ETIs are likely to be astrophysically driven extinct on timescales of roughly once every 100 million years. In terms of comparative effects, large bolide impactors represent the most significant type of astrophysical contribution to the galaxy-wide debilitation of hypothesized ETI civilizations. Nonetheless, we conclude that astrophysical existential threats – whether taken singly or in combination – are likely insufficient, alone, to explain the Fermi Paradox. Astrophysical catastrophes, while both deadly and ubiquitous, do not appear to be frequent enough to wipe out every species in the Galaxy before they can attain or utilize spacefaring status.
This paper reports on four of the sources observed in the KAGONMA (KAgoshima Galactic Object survey with the Nobeyama 45-m telescope by Mapping in Ammonia lines) project for which mapping observations have been completed (KAG35, KAG45, KAG64, and KAG71). In this study, we compiled the analysis results of four sources for which mapping observations were completed in the KAGONMA project and statistically investigated the range to which star formation activity affects the molecular gas. In order to investigate the affected range, we analyzed the heating range by focusing on the temperature distribution of the molecular cloud and found that it is within about 3 pc. This suggests that direct star formation feedback in molecular clouds is very spatially limited.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
Aims
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
Method
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
Results
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Conclusions
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Social functioning has increasingly become recognised as an important outcome in schizophrenia. While measures of symptom status are highly developed and widely used there has been only limited work on developing instruments for measuring social functioning in a reliable and consistent manner. We aimed to review the schizophrenia literature to identify the structured social functioning measures that have been used with any frequency and compare their features (1).
Method:
A detailed electronic literature search (1990 - 2006) using the key words schizophrenia and social function was carried out and those papers containing details of any structured assessment of social function were used. The most frequently used instruments were identified. A search was also conducted for the use of social function measures in trials of antipsychotics in schizophrenia.
Results:
301 articles employed 87 potential social function measures and of these only 20 were used 3 or more times. Only 14 RCTs of antipsychotics employed them.
Conclusions:
There is limited consensus on the definition and measurement of social functioning but two or three scales show promise for regular usage.
Data on the process of mental health care is scant. Most studies focus on services at their inception when activity may be atypical and then usually present data only mean values for the reported variables over the whole study period. We aimed to test whether care delivery changes over time, and to describe any changes at the individual patient and team levels.
Methods.
Process data on 272 patients in three new intensive case management (ICM) teams were collected over 2 years. Interventions were prospectively recorded using clinician-derived categories. Changes over time are described at both patient and team level.
Results.
The number of contacts and the proportion of face-to-face activity were remarkably constant after the first month at the patient level. The proportion of ‘psychiatric’ interventions (main focus on medication or a specific ‘mental health’ intervention performed) increased greatly after the first 6 months. The care activity received by individual patients varied considerably. Overall, teams varied significantly in the extent to which their activity rates were sustained over time.
Conclusions.
New ICM teams deliver highly individualised care with more marked differences in treatment patterns between patients in the same team than mean differences between teams. The early ‘engagement’ period is marked by a greater focus on social care. There is evidence of differences in sustainability of the services by site.
ICD-10 delineates Acute and Transient Psychotic Disorders (ATPD, F 23) as distinct from schizophrenia and affective psychosis. We investigated the descriptive epidemiology of ATPD and predictive validity of the diagnosis, compared its three-year outcomes with affective psychosis and schizophrenia, and explored whether acute onset and early remission identify a distinct good outcome subgroup in non-affective psychoses.
Method:
Between 1992-1994, all first-episode psychosis patients in Nottingham were identified and assigned an intake ICD-10 diagnosis. Patients were assessed three years later using established outcome measures and longitudinal diagnosis assigned. Multivariate analyses were conducted to determine whether acute onset and early remission predicted favourable three-year outcome in non-affective psychotic disorders.
Results:
Of 168 cases of first-episode psychosis, 112 received an intake diagnosis of non-affective psychoses (F20-29) and 32 (19%) of ATPD (F23). ATPD diagnosis was stable in women over three years, but not in men. Outcomes of ATPD were better than schizophrenia and similar to affective psychosis. In non-affective psychoses, favourable outcomes were a function of gender and good premorbid functioning rather than acute onset and early remission.
Conclusion:
ICD-10 ATPD criteria identify a diagnostically unstable group of disorders consisting of ‘good outcome’ schizophrenia, affective psychosis and a very small group of ‘true’ non-affective, non-schizophrenic acute and transient psychoses. Although ATPD have a better outcome than schizophrenia, in non-affective psychoses, acute onset and early remission do not independently predict favourable outcome over three years.
Our group has pioneered research indicating that Developmental vitamin D (DVD) deficiency (a candidate risk factor for schizophrenia) alters both brain development and function. We have convergent evidence indicating a disturbance in dopamine signalling in this model. 1stly the superior colliculus (the proto-basal ganglia) is the initial site where the vitamin D receptor is expressed in foetal brain; 2ndly we show a reduction in Catechol-O-methyl transferase (a major metabolic enzyme for dopamine) in these foetal brains; 3rdly dopamine metabolites in the DVD deplete neonatal brain reflect this enzymatic change. When we allow these animals to mature under vitamin D normal conditions we repeatedly observe alterations in both spontaneous and psychomimetic enhanced locomotion. Consistent with the theme of persistent changes in dopamine signalling in this model we now present new data showing that dopamine transporter density and/or affinity are altered in DVD deplete female offspring whilst DA 1 receptor density and dopamine cell number are reduced in DVD deplete male offspring (all P< 0.05 n>8).
Our most recent studies indicate that Nurr-1, a nuclear transcription regulator important in both bone and dopamine neuron development and survival may be a molecular mediator of these processes. Nurr-1 is upregulated by parathyroid hormone (PTH). PTH levels are 2-3 fold greater in vitamin D deficient Dams across gestation. Most importantly we have just shown that Nurr-1 is dose-dependently upregulated by parathyroid hormone (PTH) in a neuroblastoma cell line.
Conclusions:
Our findings strongly suggest that vitamin D directly (or indirectly via PTH) mediates dopamine neuron development.
The idea of assessing needs both in individuals and in populations is popular in health and social care, but has serious conceptual shortcomings. The concept of needs does not distinguish between the identification of a problem and its solution. It inhibits a consideration of the probabilities as to how effective various interventions may be in any given case — nor does it reflect the iterative process that is the reality of most health and social care. It does not specify goals and oversimplifies evaluation of outcome because it does not take into account different degrees of
change. In assessing population needs, there is the special risk of equating service use with service need, thereby entrenching the status quo. Instead of assessing needs, it is proposed that we identify problems, specify goals and choose interventions on the basis of probabilities of effectiveness. The outcome of any given intervention can be repeatedly reviewed with respect to its goals, and priorities may be reset accordingly.
Most community mental health services have evolved in response to the downsizing and closing of mental hospitals. Their form varies in different health care settings and their evolution was rarely subjected to formal evaluation. The introduction of Assertive Community Treatment in 1980 lead to a flurry of research activity which yielded conflicting results. Examination of these results provides the opportunity to distinguish essential from redundant components of care.
Methods:
Two separate studies were conducted - a systematic review followed by cluster and regression analysis of reported components of care and a secondly a meta-regression analysis of published studies.
Results:
The meta-regression demonstrated that most of the variation in hospitalization outcome was due to differences in baseline hospital usage. Staffing levels (e.g. caseloads) were not found to be crucial but multi-disciplinary working and integrated psychiatrists were. The systematic review indicated the importance of integration of health and social care and outreach.
Conclusions:
Multidisciplinary teams which include both social workers and psychiatrists and which focus on visiting patients at home are highly successful in managing severely ill patients in the community. Many of the detailed requirements proposed for ACT teams are probably superfluous.