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According to the International Continence Society (ICS) (2016), cystometry is the continuous fluid filling of the bladder via a transurethral catheter (or other route, e.g. suprapubic or mitrofanoff), with at least intravesical and abdominal pressure measurements and display of detrusor pressure, including cough (stress) testing. Cystometry ends with ‘permission to void’ or with incontinence of the total bladder content .
Clozapine is a dopamine receptor antagonist that blocks a range of other monoamine receptors and may have some effects on the glutamatergic system. There is evidence that it has better efficacy and effectiveness than other dopamine antagonists in treating schizophrenia that has failed to respond to other dopamine receptor antagonists. It appears to reduce impulsive behaviours such as violence (Frogley et al., 2011), self-harm (Meltzer et al., 2003) and substance misuse (Lalanne et al., 2016) and to have mood-stabilizing properties (Chang et al., 2006). In the UK it is licensed for three indications: (i) treatment-resistant schizophrenia, (ii) for treating schizophrenia when other antipsychotics have led to severe neurological adverse reactions and (iii) treating psychosis associated with Parkinson’s disease where standard treatment has failed (electronic Medicines Compendium, 2019).
Quantify the burden of chronic insomnia characterized by nighttime awakenings (CINA) among diabetes patients.
Database analyses of National Health and Wellness Survey, an annual cross-sectional study of U.S. adults. Data were collected across the U.S. through self-administered, Internet-based questionnaires. Patients included in this study self-reported physician-diagnosed diabetes. From this cohort, subjects were categorized as CINA patients if they experienced nighttime awakenings, but did not experience difficulty falling asleep or sleep apnea. Controls did not experience sleep difficulties, sleep apnea, or symptoms of insomnia in the past twelve months. Outcomes included resource utilization in the past six months, work productivity and activity impairment as measured by validated WPAI questionnaire, and summary scores of the SF-8. Regression models were developed to assess independent effects of CINA on outcomes, adjusting for demographics and physical and psychiatric comorbidity.
Among diabetes patients, 150 experienced CINA; 2,437 experienced no insomnia (projected 0.56MM adults with CINA and diabetes). After adjustments, diabetes patients with CINA had 1.9 (p< 0.001) more provider visits, 11.8% (p=0.013) greater work impairment (among full-time employed) 17.0% (p< 0.001) greater activity impairment, and SF-8 physical and mental summary scores that were 5.2 and 5.2 (p< 0.001 for both) points lower than those without insomnia, a projected $33MM in direct costs and a loss of nearly six weeks of work productivity per year.
Among patients with diabetes, CINA in relative isolation was associated with a significant negative impact on healthcare utilization and its associated costs, work productivity, and health-related quality of life.
A lack of empathy is associated with callous-unemotional behaviour, violence, aggression, criminality, and problems in social interaction. Empathy is, though, inconsistently defined and inadequately measured. We therefore set out to produce a new and rigorously developed empathy questionnaire that would have clinical and public-health relevance.
Sixty-five questions, themed around cognitive empathy (the ability to construct a working model of the emotional states of others) and affective empathy (the ability to be sensitive to and vicariously experience the feelings of others), were administered to two independent samples of healthy volunteers (N1=640, N2=383), which were used to explore and validate the factor structure.
Principal components analysis revealed five factors from thirty-seven items. Confirmatory factor analysis confirmed this structure. The hypothesised two-factor structure (cognitive and affective empathy) was tested by adding two second order factors, indicated by the five first-order factors, and provided the best and most parsimonious fit to the data (CFI=0.961, RMSEA=0.048). Cognitive Empathy encompassed Perspective Taking and Online Simulation; Affective Empathy encompassed Emotional Responsivity, Peripheral Responsivity and Emotional Contagion. Females scored significantly higher than males on Affective Empathy but not on Cognitive Empathy. The factors correlated significantly with measures of empathic anger, impulsivity, aggression, psychopathy, Machiavellianism and empathy as measured by the Basic Empathy Scale.
The QCAE measures the distinct and specific components that make up cognitive and affective empathy. The factor structure was confirmed in independent samples and represents a valid tool for assessing cognitive and affective empathy and its subcomponents.
5-HTTLPR (serotonin transporter linked polymorphic region) has long (l) and short (s) allelic variations. The s allele is linked to depression, anxiety, and slower response to selective serotonin reuptake inhibitors (SSRI). Both depression and SSRI's are associated with bone loss and fractures. We explored the relationship between the 5-HTTLPR and bone loss.
IRB-approved retrospective chart review of adult psychiatric patients during a 10-year period with both 5-HTTLPR genotype and bone mineral density (BMD) assessment (hip and spine BMD stratified by age, Z-scores < 50, T-scores ≥50 years). Age, gender, and BMD scores were compared between the 5-HTTLPR categories of s allele (l/s and s/s genotypes) versus l/l genotype using one-way ANOVA.
Of 3016 with 5-HTTLPR genotyping, 239 had BMD, with 157 (66%) s allele and 82 (34%) l/l genotypes. Among men and women < 50 years, s allele had lower Z-scores in the hip (−0.6628/n=43 vs −0.1306/n=36, p=0.012) and spine (−0.9762/n=42 vs -0.1000/n=41, p=0.0019) than l/l. There were no differences in T-scores between the s allele and l/l genotypes for men and women ≥50 years. Gender analysis (n=198 women, n=41 men) showed women with s allele had lower Z-scores in the hip (−0.68182/n=33 vs −0.08788/n=33, p=0.0146) and spine (−1.0250/n=32 vs − 0.0586/n=29, p=0.0020) than the l/l genotype.
The s allele is associated with lower bone density at the hip and spine in younger adults, particularly in younger women. Our results suggest 5-HTTLPR variants may mediate serotonin effects on bone in a gender-specific or hormonal/ menopausal-dependent interaction.
There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive Ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology.
This was a 12 week rater blind placebo controlled study. All to gather 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using PANSS, CGI, GAF and AIMS.
Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual (TAU) on PANSS total score, although, this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS.
Anti-inflammatory treatments have shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. This study has led to a larger SMRI-funded, double blind, randomized control trial.
Quality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT.
Predictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial.
Change in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before.
Improving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.
Immune mechanisms have been implicated in the pathogenesis of schizophrenia. This has lead to clinical trials of re-purposing drugs with off-target anti-inflammatory actions. They include the antibiotic minocycline and simvastatin (HMP-Co reductase inhibitor), which decrease microglial activation, and ondansetron a 5-HT3-receptor antagonist that has limited effects on cytokine production. This presentation will address their efficacy and mechanism of action.
1) Update on trials with minocycline including our own positive finding on negative symptoms (PMID: 16959472)
2) Present new results with ondansetron and simvastatin summarised below.
Ondansetron (8mg) and simvastatin (40mg) vs placebos in 2x2 design (PMID: 23782463). Patients aged 18-65, stable treatment, DSM IV schizophrenia-related diagnosis. PANSS and cognition at 0,3,6 months.
The four cells of the 2x2 design contained 302 patients. The interaction between ondansetron and simvastatin was significant at p=.006 reflecting the lower scores in the 3 active treatment groups than in the P+P group. Ondansetron improved verbal (p=.007) and visual list learning (p=.02) with no other treatment effects on cognition.
Minocycline appears to benefit negative symptoms in early psychosis with a minor effect on cognition. Simvastatin had limited effects in our patients with established schizophrenia but its anti-inflammatory effects could be worth investigating in early psychosis. Ondansetron has a significant effect on new learning, which might be expected from its 5-HT3 antagonist properties. This may underlie a benefit on negative symptoms reported by others and us.
Cognitive impairment in schizophrenia is a strong predictor of the functional outcome and no effective treatments are available. MATRICS Consensus Cognitive Battery (MCCB) is approved by the FDA as outcome measure for trials of cognitive-enhancing drugs in schizophrenia. CogState Schizophrenia Battery (CSB) provides a briefer cognition assessment with minimal practice effects and a strong correlation between the CSB and MCCB composite scores. We tested the sensitivity of CSB as a cognitive outcome measure in a clinical trial in schizophrenia, where a cognitive-enhancing drug and cognitive training were combined.
49 participants with schizophrenia were enrolled in a double-blind, placebo-controlled study. Participants were randomised to modafinil (200mg/day) or placebo and underwent a cognitive training program for 10 weekdays. CSB was administered twice at baseline to minimise practice effects, at the last day of the intervention and two weeks after the completion of the intervention.
There was a significant time effect at the end of the intervention on the CSB composite score (p=0.042). There was no significant treatment effect on CSB composite score at the end of the intervention (p=0.686) or at follow up (p=0.120).
Multiple administrations of CSB were well tolerated by participants. The significant time effects on the composite score may suggest the operation of practice effects. Several factors could have contributed to the lack of treatment effects on CSB, such as the burden of multiple neuropsychological testing in a relatively brief study, the duration of modafinil treatment and also the intensive nature of cognitive training.
Most patients with uncomplicated depression can be treated as an outpatient, while inpatient care is generally reserved for people with severe or treatment-resistant depressive symptoms, significantly impaired reality testing due to accompanying psychosis, high suicide risk, and/or impaired self-care . Many patients whose initial presentation is so severe as to warrant hospitalization will have “failed” outpatient treatment. Even though such patients already have an established outpatient team, the inpatient psychiatrist should be prepared to reevaluate the patient’s diagnosis and overall plan as part of a “fresh look,” and attempt to understand why the patient is not responding well to outpatient treatment.
Treatment-refractory depression patients are also sometimes referred for hospital admission with a specific plan for initiation of a course of electroconvulsive therapy (ECT) .
Dementia, or Major Neurocognitive Disorder per the DSM-V, is an umbrella term used to describe a group of clinical syndromes defined by deterioration in intellectual functioning. In order to diagnose dementia, an individual must have a significant decline in cognitive functioning from baseline, with deficits in at least one cognitive domain. Common domains affected include reasoning ability, visual–spatial processing, mathematical ability, language, and executive function. As dementia progresses, individuals have increasing difficulties with the “4 As”: amnesia (inability to use or retain memory), aphasia (difficulty with receptive and/or expressive language), apraxia (loss of ability to perform previously learned tasks) and agnosia (misidentification of familiar people, objects, or places). In its later stages, basic functioning ceases and individuals become totally dependent on others for care.
The clinical syndrome of dementia can be caused by a number of different underlying disease processes, varying from nutritional deficiencies to neurodegenerative disorders.
Over the past decade, a growing interest has developed on the archaeology, palaeontology, and palaeoenvironments of the Arabian Peninsula. It is now clear that hominins repeatedly dispersed into Arabia, notably during pluvial interglacial periods when much of the peninsula was characterised by a semiarid grassland environment. During the intervening glacial phases, however, grasslands were replaced with arid and hyperarid deserts. These millennial-scale climatic fluctuations have subjected bones and fossils to a dramatic suite of environmental conditions, affecting their fossilisation and preservation. Yet, as relatively few palaeontological assemblages have been reported from the Pleistocene of Arabia, our understanding of the preservational pathways that skeletal elements can take in these types of environments is lacking. Here, we report the first widespread taxonomic and taphonomic assessment of Arabian fossil deposits. Novel fossil fauna are described and overall the fauna are consistent with a well-watered semiarid grassland environment. Likewise, the taphonomic results suggest that bones were deposited under more humid conditions than present in the region today. However, fossils often exhibit significant attrition, obscuring and fragmenting most finds. These are likely tied to wind abrasion, insolation, and salt weathering following fossilisation and exhumation, processes particularly prevalent in desert environments.
Poor school connectedness (SC), defined as students’ feelings of belonging, safety, and fairness at school, is a risk factor for negative psychosocial outcomes. Few studies have examined the specific relationship between SC and anxiety. This study examined the relation between SC and anxiety within a group of 114 clinically anxious youth (mean age = 10.82; SD = 2.93; 48.2% female; 70.2% White, non-Hispanic); age differences were also examined. Results indicated that SC was significantly negatively associated with age but unrelated to gender, race/ethnicity, socio-economic status, parent education, or presence of a comorbid disorder. Findings generally revealed that low SC was associated with greater total and domain specific anxiety. SC may play a unique role in the maintenance of global and domain specific anxiety symptoms.
Field surveys were conducted across the Blacklands region of Texas during 2016 and 2017 to document the distribution of herbicide-resistant Lolium spp. infesting winter wheat production fields in the region. A total of 68 populations (64 Italian ryegrass, four perennial ryegrass) were evaluated in a greenhouse for sensitivity to herbicides of three different modes of action: an acetolactate synthase (ALS) inhibitor (mesosulfuron-methyl), two acetyl-coenzyme-A carboxylase (ACCase) inhibitors (diclofop-methyl and pinoxaden), and a 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibitor (glyphosate). Herbicides were applied at twice the label-recommended rates for mesosulfuron-methyl (29 g ai ha−1), diclofop-methyl (750 g ai ha−1), and pinoxaden (118 g ai ha−1); and at the recommended rate for glyphosate (868 g ae ha−1). The herbicide screenings were followed by dose-response assays of the most-resistant ryegrass population for each herbicide at eight rates (0.5, 1, 2, 4, 8, 16, 32, and 64×), compared with a susceptible population at six rates (0.0625, 0.125, 0.25, 0.5, 1, and 2×). The initial screening and dose-response experiments were conducted in a completely randomized design with three replications and two experimental runs. Survivors (<80% injury) were characterized as highly resistant (0% to 20% injury) or moderately resistant (21% to 79%). Results showed that 97%, 92%, 39%, and 3% of the Italian ryegrass populations had survivors to diclofop-methyl, mesosulfuron-methyl, pinoxaden, and glyphosate treatments, respectively. Of the four perennial ryegrass populations, three were resistant to diclofop-methyl and mesosulfuron-methyl, and one was resistant to pinoxaden as well. Perennial ryegrass populations did not exhibit any resistance to glyphosate. Dose-response assays revealed 37-, 196-, and 23-fold resistance in Italian ryegrass to mesosulfuron-methyl, diclofop-methyl, and pinoxaden, respectively, compared with a susceptible standard. One Italian ryegrass population exhibited three-way multiple resistance to ACCase-, ALS-, and EPSPS-inhibitors. The proliferation of multiple herbicide–resistant ryegrass is a challenge to sustainable wheat production in Texas Blacklands and warrants diversified management strategies.
Of the many links generated by the Crown, military connectivity was one of the most potent. As they forged England into a ‘war state’, the three Edwards with their bellicose ambitions mobilised the people and resources of their realm on a scale that dwarfed anything attempted by their predecessors. Inevitably, Cornwall was drawn into the war effort. Between the battles of Falkirk in 1298 and Agincourt in 1415 there were no fewer than 452 instances of named Cornish men-at-arms and mounted archers fighting in major royal expeditions. Yet there were wide variations in the degree of participation. While no fewer than twenty-seven Cornishmen served at Crecy-Calais, for example, only two enlisted in 1373 to go with John of Gaunt on his ‘great march’.
The changing demands of war greatly influenced the nature and scale of Cornish military service. While the large Falkirk and Bannockburn campaigns drew about eighteen gentlemen to Scotland, the smaller armies operating north of the border in the 1330s were more poorly attended. The Hundred Years’ War was to result in a dramatic expansion of the county's service. In 1340 some eight Cornishmen served at Sluys-Tournai, but just two years later twice that number fought in Brittany, a campaign for which the peninsula was more conveniently sited. With some twelve Cornishmen contesting the field at Poitiers, the county was well placed for expeditions to Aquitaine too. From 1369 royal demands for troops grew more regular, as ‘the Edwardian War was intermittent; the Caroline War (1369–89) unremitting’. In a war which favoured the county's strong military-maritime tradition, England and France increasingly fought for command of the sea routes. It is illustrative of this that the earl of Arundel's ‘cruising war-fleets’ of 1387 and 1388 contained as many as fifty-six Cornish men-at-arms and archers. Since England and France increasingly drew other kingdoms into this phase of the war, in 1386 some nine Cornishmen campaigned with John of Gaunt in his bid for the Castilian throne. In these years Princess Joan can even be found paying her steward an addition £13 6s. 8d. for raising recruits to fight in France and Spain.
For each port: (S) relates to the number of ships; (C) records the crew size; and (T) represents the average tonnage of the vessels. The average tonnage (T) is only a loose approximation as often these figures were recorded only for a few ships. In the ‘total section’ at the bottom of each table, the crew size may only include the shipmasters themselves because the size of crews often went unrecorded.
It is a fact universally acknowledged that medieval Cornwall was a county quite unlike any other. Distant from the political and social heartlands of England, lamented as ‘the very ends of the earth’ by its bishops, overseen by a powerful lordship and inhabited by men and women who at times were labelled an ‘obdurate folk’, believing that their county formed ‘a large land long ago bearing the name of a kingdom’, Cornwall was viewed as somewhere curiously distinctive by many contemporaries and historians alike. The county's leading lineages, bearing names the like of which you find nowhere else, among them Bodrugan, Carminow and l’Ercedekne, exercised great influence over Cornish affairs, not least through office-holding in the peninsula. By the fourteenth century, when royal government had come to reach out into the entire realm, Cornwall ranked as one of the country's great seigniorial enclaves. Together, myths, saints, government and lordship were to endow the name and notion of Cornwall with authority in the minds of its inhabitants. Combined with the continued currency of the local Cornish language and the circulation of chivalric literature that marked out the county as historically different, the land of King Arthur, it is not difficult to explain the trope of Cornish otherness.
Yet, despite the peninsula forming a remote and idiosyncratic corner of the kingdom, the county most emphatically still held a place in the realm of England. In this respect, the position of Cornwall contrasted sharply with that in parts of Ireland and Wales, where power remained fractured and an English elite attempted to rule over people whom blood, birth, administration and law regarded as inferior. Since the king's writ always extended to west of the Tamar, constitutionally Cornwall did not even correspond to an English palatinate, which enjoyed the status of a liberty. Indeed, the common law regarded all Cornishmen and women as English; Cornwall's residents like those of every other county paid parliamentary subsidies for the common good; the county possessed a substantial voice in the parliamentary Commons; the king directly appointed nearly all local government officials; and Cornishmen owed military service for the defence of the realm.