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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).
Multicenter, retrospective cohort.
The study was conducted across 4 Veterans’ Affairs hospitals.
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.
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.
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.
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.
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Community settings and care homes in 26 UK centers.
People with probable or possible Alzheimer’s disease and agitation.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Many patients with schizophrenia show major difficulties in performing basic social roles. Occupational and social functioning (and independent living) are considered domains of functioning. Improvement in functioning is recognized as an important aim in treatment guidelines and as an outcome by regulatory agencies.
The Europe, Middle East and Africa (EMEA) functioning survey canvassed opinions of psychiatrists (and neurologists with psychiatric backgrounds in Germany) across the region.
To ascertain psychiatrists' perceptions of the clinical importance, assessment and management of functioning amongst their patients with schizophrenia.
The survey comprised 17 questions and was conducted from March-April 2011, in 39 EMEA countries. Respondents' demographics and their opinions regarding personal and social functioning in patients with schizophrenia were collected.
Results were obtained from 3610 clinicians. Psychiatrists reported that they perceived more than two in three of their patients show impaired/very poor levels of functioning. 91% believed that personal and social functioning was an important treatment goal for patients with schizophrenia and 90% believed it was an important goal for patients' families. The majority of psychiatrists assess the personal and social functioning of their patient at each visit but 81% determine the level of functioning through clinical interview. To manage personal and social functioning in their patients, 26% of psychiatrists prefer pharmacological interventions while 47% prefer psychosocial interventions.
Although psychiatrists recognize that functioning is impaired/very poor in patients with schizophrenia, there is still a need to address it as a main treatment goal for patients with schizophrenia.
Patients diagnosed with glioblastoma (GBM) are treated with surgery followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. Patients are monitored with serial magnetic resonance imaging (MRI). However, treatment-related changes frequently mimic disease progression. We reviewed a series of patients undergoing surgery for presumed first-recurrence GBM, where pathology reports were available for tissue diagnosis, in order to better understand factors associated with a diagnosis of treatment-related changes on final pathology.
Patient records at a single institution between 2005 and 2015 were retrospectively reviewed. Pathology reports were reviewed to determine diagnosis of recurrent GBM or treatment effect. Survival analysis was performed interrogating overall survival (OS) and progression-free survival (PFS). Correlation with radiation treatment plans was also examined.
One-hundred-twenty-three patients were identified. One-hundred-sixteen patients (94%) underwent resection and seven underwent biopsy. Treatment-related changes were reported in 20 cases (16%). These patients had longer median OS and PFS from the time of recurrence than patients with true disease progression. However, there was no significant difference in OS from the time of initial diagnosis. Treatment effect was associated with surgery within 90 days of completing radiation. In patients receiving radiation at our institution (n = 53), larger radiation target volume and a higher maximum dose were associated with treatment effect.
Treatment effect was associated with surgery nearer to completion of radiation, a larger radiation target volume, and a higher maximum point dose. Treatment effect was associated with longer PFS and OS from the time of recurrence, but not from the time of initial diagnosis.
Introduction: Point-of-Care Ultrasound (PoCUS) is being increasingly utilized during cardiac arrests for prognosis. Following the publication of recent studies, the goal of this study was to systematically review and analyze the literature to evaluate the accuracy of PoCUS in predicting return of spontaneous circulation (ROSC), survival to hospital admission (SHA), and survival to hospital discharge (SHD) in adult patients with non-traumatic, non- shockable out- of-hospital or emergency department cardiac arrest. Methods: A systematic review and meta-analysis was completed. A search of Medline, EMBASE, Cochrane, CINAHL, ClinicalTrials.gov and the World Health Organization Registry was completed from 1974 until August 24th 2018. Adult randomized controlled trials and observational studies were included. The QUADAS-2 tool was applied by two independent reviewers. Data analysis was completed according to PRISMA guidelines and with a random effects model for the meta-analysis. Heterogeneity was assessed using I-squared statistics. Results: Ten studies (1,485 participants) were included. Cardiac activity on PoCUS had a pooled sensitivity of 59.9% (95% confidence interval 36.5%-79.4%) and specificity of 91.5% (80.8%-96.5%) for ROSC; 74.7% (58.3%-86.2%) and 80.5% (71.7%-87.4%) for SHA; and 69.4% (45.5%-86.0%) and 74.6% (59.8%-85.3%) for SHD. The sensitivity of cardiac activity on PoCUS for predicting ROSC was 24.7%(6.8%-59.4%) in the asystole subgroup compared with 77% (59.4%-88.5%) within the PEA subgroup. Cardiac activity on PoCUS, compared to an absence had an odd ratio of 15.9 (5.9-42.5) for ROSC, 9.8 (4.9-19.4) for SHA and 5.7 (2.1-15.6) for SHD. Positive likelihood ratio (LR) was 6.65 (3.16-14.0) and negative LR was 0.27 (0.12-0.61) for ROSC. Conclusion: Cardiac activity on PoCUS was associated with improved odds for ROSC, SHA, and SHD among adults with non-traumatic asystole and PEA. We report lower sensitivity and higher negative likelihood ratio, but with greater heterogeneity compared to previous systematic reviews. PoCUS may provide valuable information in the management of non-traumatic PEA or asystole, but should not be viewed as the sole predictor in determining outcomes in these patients.
The objective was to determine the longitudinal associations between callous-unemotional (CU) and oppositional defiant (OD) behaviors from the first to fourth grades for Spanish children. Four possible outcomes were evaluated: (a) CU behaviors in the first grade predict increases in OD behaviors in the fourth grade, controlling for OD behaviors in the first grade; (b) OD behaviors in the first grade predict increases in CU behaviors in the fourth grade, controlling for CU behaviors in the first grade; (c) both unique effects are significant; and (d) neither unique effect is significant. A longitudinal panel model with two latent variables (CU and OD behaviors), three sources (mothers, fathers, teachers), and two occasions (spring of the first and fourth grades) was used to evaluate the four possibilities among 758 (54% boys) first grade and 469 (53% boys) fourth grade Spanish children. For mother-, father-, and teacher-reports, OD behaviors in the first grade predicted increases in CU behaviors in the fourth grade, after controlling for CU behaviors in the first grade, whereas CU behaviors in the first grade did not predict increases in OD behaviors in the fourth grade, after controlling for OD behaviors in the first grade. OD behaviors thus conferred independent vulnerability to increases in CU behaviors 3 years later among young children.
Objectives: As the number of adolescents and young adults (AYAs) surviving congenital heart disease (CHD) grows, studies of long-term outcomes are needed. CHD research documents poor executive function (EF) and cerebellum (CB) abnormalities in children. We examined whether AYAs with CHD exhibit reduced EF and CB volumes. We hypothesized a double dissociation such that the posterior CB is related to EF while the anterior CB is related to motor function. We also investigated whether the CB contributes to EF above and beyond processing speed. Methods: Twenty-two AYAs with CHD and 22 matched healthy controls underwent magnetic resonance imaging and assessment of EF, processing speed, and motor function. Volumetric data were calculated using a cerebellar atlas (SUIT) developed for SPM. Group differences were compared with t tests, relationships were tested with Pearson’s correlations and Fisher’s r to z transformation, and hierarchical regression was used to test the CB’s unique contributions to EF. Results: CHD patients had reduced CB total, lobular, and white matter volume (d=.52–.99) and poorer EF (d=.79–1.01) compared to controls. Significant correlations between the posterior CB and EF (r=.29–.48) were identified but there were no relationships between the anterior CB and motor function nor EF. The posterior CB predicted EF above and beyond processing speed (ps<.001). Conclusions: This study identified a relationship between the posterior CB and EF, which appears to be particularly important for inhibitory processes and abstract reasoning. The unique CB contribution to EF above and beyond processing speed alone warrants further study. (JINS, 2018, 24, 939–948)