GLP-1 receptor agonist use during hospitalisation: Better glycaemic control compared to premixed insulin.

INTRODUCTION: Glycaemic control associates with better outcomes for hospitalised patients. Whether GLP-1 receptor agonists (GLP-1 RA) are suitable and effective drugs for inpatients is unclear. METHODS: A retrospective, single centre, observational study using data from the electronic health record. Patients admitted using GLP-1 RA as outpatients, from 2016 to 2019, were identified. Outcomes were compared to those admitted using twice-daily (BD) mixed insulin. Capillary glucose, medication use, creatinine, and demographic data were collected. As drugs may be discontinued/not administered in hospital, days when GLP-1 RA was administered were 'GLP-1 RA active' and, for insulin, 'insulin active'. The primary comparison was rate of hypoglycaemia (<4 mmol/L) and severe hypoglycaemia (<3 mmol/L). A logistic regression model examined variables for hypoglycaemia. RESULTS: GLP-1 RA comprised n = 262 admissions and BD insulin n = 166. The 'insulin active' cohort (n = 957 patient days) had higher risk of hypoglycaemia than 'GLP-1 RA active' (n = 806 days); occurring on 14.7% of days; 95% confidence interval [CI] 12.6-17.1 versus 9.9% days; 95% CI 8.0-12.2; p = 0.002, and severe hypoglycaemia 4.0% of days (95% CI 2.8-5.4) versus 2.0% (95% CI 1.1%-3.2%; p = 0.005). Daily glucose (mean ± standard deviation) was 10.8 ± 5.2 mmol/L in insulin active versus 9.6 ± 4.7 mmol/L in GLP-1 RA active; p < 0.001. Insulin use, age, and acute admissions predicted hypoglycaemia. The odds ratio for hypoglycaemia was 2.15 times greater (95% CI, 1.14-4.08; p = 0.019) with insulin than with GLP-1 RA. CONCLUSIONS: GLP-1 RA provided better glycaemic control than BD mixed insulin and should be continued during hospitalisation unless there is a clear indication for cessation.

The effect of the electronic health record on consultants' responsibility for patients and their care in general medicine.

The electronic health record has dramatically improved the safety of medical care as well as the clarity and accessibility of the notes. An equally profound, but under-recognised consequence, is the effect it has had on 'patient ownership' and responsibility within the hospital. It is now very easy to access and read through patients notes, from a distance and at scale, to identify patients for attention. Automated alerts can be set for quantitative laboratory or physiological variables, for the same purpose, and artificial intelligence is being developed for alerts based on free text or radiographic interpretation. This article explores the risk of this approach to healthcare and the danger of a 'collusion of anonymity', whereby responsibility for care is sufficiently diffuse that no one has ownership of a patient's care.

Subarachnoid haemorrhage rules in the decision for acute CT of the head: external validation in a UK cohort.

BACKGROUND: The Ottawa subarachnoid haemorrhage (SAH) rule and the Emerald SAH rule are clinical decision tools to aid in the decision for computed tomography (CT) of the head in patients attending an emergency department (ED) with acute non-traumatic headache. The objective of this study was to analyse the performance of these rules in a contemporary UK cohort. METHODS: We performed a retrospective external validation study. Patients undergoing CT of the head for the evaluation and treatment of non-traumatic headaches over a 6-month period in the ED at two tertiary centres were assessed. Each patient's Ottawa rule and Emerald rule were calculated and compared with their final diagnosis. RESULTS: The cohort consisted of 366 patients and there were 16 cases of SAH (based on CT findings or the presence of xanthochromia in cerebrospinal fluid). The Ottawa rule identified 288 patients requiring CT of the head. The sensitivity of the Ottawa rule was 100% (95% confidence interval (CI) 71-100%) and the specificity was 22% (95% CI 18-27%). The Emerald rule identified 267 patients who required CT, and achieved a sensitivity of 81% (95% CI 54-96%) and a specificity of 27% (95% CI 23-32%). CONCLUSIONS: The Ottawa SAH rule correctly identified all patients with SAH in this contemporary cohort. The Emerald rule did not perform as well in this cohort and is unsuitable for clinical use. The Ottawa rule is a useful tool to aid in the decision for CT of the head in patients presenting with acute non-traumatic headache to the ED.

Pulmonary embolism in hospitalised patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer. Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19. OBJECTIVES: To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE. We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19. PATIENTS/METHODS: Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR). RESULTS: There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care. The diagnostic yield for PE was 37%. The overall proportion of PE in patients with COVID-19 was 5.4%. The proportions with Wells score of ≥4 ('PE likely') was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951). The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3-9) in PE group vs 4 (IQR 2-7) in those without PE (P = 0.133). D-dimer was higher in PE (median 8000 ng/mL; IQR 4665-8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210-4410 ng/mL, P < 0.001). In the 'low probability' group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE. CONCLUSIONS: Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common. Of note, approaching half of PE events were diagnosed on hospital admission. More data are needed to identify an optimal diagnostic pathway in patients with COVID-19. Randomised controlled trials of intensified thromboprophylaxis are urgently needed.

Multiplex PCR point of care testing versus routine, laboratory-based testing in the treatment of adults with respiratory tract infections: a quasi-randomised study assessing impact on length of stay and antimicrobial use.

BACKGROUND: Laboratory-based respiratory pathogen (RP) results are often available too late to influence clinical decisions such as hospitalisation or antibiotic treatment due to time delay in transport of specimens and testing schedules. Ward-based i.e. point of care (POC) testing providing rapid results may alter the clinical management pathway. METHODS: FilmArray® RP polymerase chain reaction (PCR) systems were placed in three in-patient and out-patient medical areas. Patients presenting with influenza-like illness /upper respiratory tract infection +/- lower RTI were recruited between January-July 2015. FilmArray® POC testing occurred on even days of the month (intervention) or routine, laboratory-based RP PCR testing +/- atypical serology on odd days (control). The primary outcome was length of hospital stay. The secondary outcomes were impact on the use of antimicrobials, readmissions, all-cause mortality, length of ward stay and turn-around time (TAT) (time to result from admission). RESULTS: Of 606 eligible patients, 545 (89.9%) were included; 211 in the control arm and 334 in the intervention arm. 20% of control arm patients and 24% of intervention arm patients had an RP detected. POC testing was not associated with the primary outcome measure, length of stay, but reduced the TAT from 39.5 h to 19.0 h, p < 0.001. Only the prescribing decision differed between study arms, p < 0.001. When antivirals were given, the intervention was associated with a reduction in the median time to the first dose of 36 h and allowed appropriate treatment of mycoplasma infection. CONCLUSIONS: We found no association between respiratory PCR POC testing and length of stay or most of the secondary outcomes except the antimicrobial prescribing decision. This was probably due to a delay in initiating FilmArray® testing. Despite this, POC testing allowed time-critical antivirals to be given significantly faster, appropriate mycoplasma treatment and results were available considerably faster than routine, laboratory-based testing. Ward-staff of all grades performed POC testing without difficulty suggesting potential use across many divergent healthcare settings. Further studies evaluating the implementation of rapid respiratory PCR POC testing and the effect on length of stay and antimicrobial use are required. TRIAL REGISTRATION: ISRCTN10470967 , Retrospectively Registered, 30/6/2015.

Autobiographical memory: a candidate latent vulnerability mechanism for psychiatric disorder following childhood maltreatment.

BackgroundAltered autobiographical memory (ABM) functioning has been implicated in the pathogenesis of depression and post-traumatic stress disorder and may represent one mechanism by which childhood maltreatment elevates psychiatric risk.AimsTo investigate the impact of childhood maltreatment on ABM functioning.MethodThirty-four children with documented maltreatment and 33 matched controls recalled specific ABMs in response to emotionally valenced cue words during functional magnetic resonance imaging.ResultsChildren with maltreatment experience showed reduced hippocampal and increased middle temporal and parahippocampal activation during positive ABM recall compared with peers. During negative ABM recall they exhibited increased amygdala activation, and greater amygdala connectivity with the salience network.ConclusionsChildhood maltreatment is associated with altered ABM functioning, specifically reduced activation in areas encoding specification of positive memories, and greater activation of the salience network for negative memories. This pattern may confer latent vulnerability to future depression and post-traumatic stress disorder.

Altered neural response to rejection-related words in children exposed to maltreatment.

BACKGROUND: Children exposed to maltreatment show neural sensitivity to facial cues signalling threat. However, little is known about how maltreatment influences the processing of social threat cues more broadly, and whether atypical processing of social threat cues relates to psychiatric risk. METHODS: Forty-one 10- to 14-year-old children underwent a social rejection-themed emotional Stroop task during functional magnetic resonance imaging: 21 children with a documented history of maltreatment (11 F) and 19 comparison children with no maltreatment history (11 F). Groups were matched on age, pubertal status, gender, IQ, socioeconomic status, ethnicity and reading ability. Classic colour Stroop stimuli were also administered in the same paradigm to investigate potential differences in general cognitive control. RESULTS: Compared with their peers, children who had experienced maltreatment showed reduced activation in the Rejection versus Neutral condition, across circuitry previously implicated in abuse-related posttraumatic stress disorder (PTSD), including the left anterior insula, extending into left ventrolateral prefrontal cortex/orbitofrontal cortex; left amygdala; left inferior parietal cortex (STS); and bilateral visual association cortex, encompassing the cuneus and lingual gyrus. No group differences in neural or behavioural responses were found for the classic colour Stroop conditions. Significant negative associations between activity in bilateral cuneus and STS during the rejection-themed Stroop and higher self-reported PTSD symptomatology, including dissociation, were observed in children exposed to maltreatment. CONCLUSION: Our findings indicate a pattern of altered neural response to social rejection cues in maltreated children. Compared to their peers, these children displayed relative hypoactivation to rejection cues in regions previously associated with PTSD, potentially reflecting an avoidant coping response. It is suggested that such atypical processing of social threat may index latent vulnerability to future psychopathology in general and PTSD in particular.

The sexually dimorphic impact of maltreatment on cortical thickness, surface area and gyrification.

An extensive literature has detailed how maltreatment experience impacts brain structure in children and adolescents. However, there is a dearth of studies on the influence of maltreatment on surface based indices, and to date no study has investigated how sex influences the impact of maltreatment on cortical thickness, surface area and local gyrification. We investigated sex differences in these measures of cortical structure in a large community sample of children aged 10-14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 matched non-maltreated controls. The maltreated group relative to the controls presented with a pattern of decreased cortical thickness within a region of right anterior cingulate, orbitofrontal cortex and superior frontal gyrus; decreased surface area within the right inferior parietal cortex; and increased local gyrification within left superior parietal cortex. This atypical pattern of cortical structure was similar across males and females. An interaction between maltreatment exposure and sex was found only in local gyrification, within two clusters: the right tempo-parietal junction and the left precentral gyrus. These findings suggest that maltreatment impacts cortical structure in brain areas associated with emotional regulation and theory of mind, with few differences between the sexes.

Sex differences in socioemotional functioning, attentional bias, and gray matter volume in maltreated children: A multilevel investigation.

While maltreatment is known to impact social and emotional functioning, threat processing, and neural structure, the potentially dimorphic influence of sex on these outcomes remains relatively understudied. We investigated sex differences across these domains in a large community sample of children aged 10 to 14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 well-matched nonmaltreated peers. The maltreated group relative to the nonmaltreated comparison group exhibited poorer social and emotional functioning (more peer problems and heightened emotional reactivity). Cognitively, they displayed a pattern of attentional avoidance of threat in a visual dot-probe task. Similar patterns were observed in males and females in these domains. Reduced gray matter volume was found to characterize the maltreated group in the medial orbitofrontal cortex, bilateral middle temporal lobes, and bilateral supramarginal gyrus; sex differences were observed only in the supramarginal gyrus. In addition, a disordinal interaction between maltreatment exposure and sex was found in the postcentral gyrus. Finally, attentional avoidance to threat mediated the relationship between maltreatment and emotional reactivity, and medial orbitofrontal cortex gray matter volume mediated the relationship between maltreatment and peer functioning. Similar mediation patterns were observed across sexes. This study highlights the utility of combining multiple levels of analysis when studying the "latent vulnerability" engendered by childhood maltreatment and yields tentative findings regarding a neural basis of sex differences in long-term outcomes for maltreated children.

Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability?

BACKGROUND: Childhood maltreatment has been shown to significantly elevate the risk of psychiatric disorder. Previous neuroimaging studies of children exposed to maltreatment have reported atypical neural structure in several regions, including the prefrontal cortex and temporal lobes. These studies have exclusively investigated volumetric differences rather than focusing on genetically and developmentally distinct indices of brain structure. METHODS: Here we used surface-based methods to examine cortical thickness, surface area, and local gyrification in a community sample of children with documented experiences of abuse (n = 22) and a group of carefully matched nonmaltreated peers (n = 21). RESULTS: Reduced cortical thickness in the maltreated compared with the nonmaltreated group was observed in an extended cluster that incorporated the anterior cingulate, superior frontal gyrus, and orbitofrontal cortex. In addition, reduced cortical surface area was observed within the parcellated regions of the left middle temporal area and lingual gyrus. Local gyrification deficits within the maltreated group were located within two clusters, the lingual gyrus and the insula extending into pars opercularis. CONCLUSIONS: This is the first time structural abnormalities in the anterior cingulate and lingual gyrus have been detected in children exposed to maltreatment. Surface-based methods seem to capture subtle, previously undetected, morphological abnormalities associated with maltreatment. We suggest that these approaches detect developmental precursors of brain volume differences seen in adults with histories of abuse. Because the reported regions are implicated in several clinical disorders, they might constitute biological markers of vulnerability, linking exposure to early adversity and psychiatric risk.

Amygdala activation in maltreated children during pre-attentive emotional processing.

BACKGROUND: Childhood adversity is associated with significantly increased risk of psychiatric disorder. To date, functional magnetic resonance imaging (fMRI) studies of children have mainly focused on institutionalisation and investigated conscious processing of affect. AIMS: To investigate neural response to pre-attentively presented affect cues in a community sample of children with documented experiences of maltreatment in the home. METHOD: A masked dot-probe paradigm involving pre-attentive presentation of angry, happy and neutral facial expressions was employed. Eighteen maltreated children were compared with 23 carefully matched non-maltreated peers. RESULTS: Increased neural response was observed in the right amygdala for pre-attentively presented angry and happy faces in maltreated v. non-maltreated children. Level of amygdala activation was negatively associated with age at onset for several abuse subtypes. CONCLUSIONS: Maltreatment is associated with heightened neural response to positive and negative facial affect, even to stimuli outside awareness. This may represent a latent neural risk factor for future psychiatric disorder.

Reduced orbitofrontal and temporal grey matter in a community sample of maltreated children.

BACKGROUND: Childhood maltreatment is strongly associated with increased risk of psychiatric disorder. Previous neuroimaging studies have reported atypical neural structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and cerebellum in maltreated samples. It has been hypothesised that these structural differences may relate to increased psychiatric vulnerability. However, previous studies have typically recruited clinical samples with concurrent psychiatric disorders, or have poorly characterised the range of maltreatment experiences and levels of concurrent anxiety or depression, limiting the interpretation of the observed structural differences. METHODS: We used voxel-based morphometry to compare grey matter volume in a group of 18 children (mean age 12.01 years, SD = 1.4), referred to community social services, with documented and well-characterised experiences of maltreatment at home and a group of 20 nonmaltreated children (mean age 12.6 years, SD = 1.3). Both groups were comparable on age, gender, cognitive ability, ethnicity and levels of anxiety, depression and posttraumatic stress symptoms. We examined five a priori regions of interest: the prefrontal cortex, temporal lobes, amygdala, hippocampus and cerebellum. RESULTS: Maltreated children, compared to nonmaltreated peers, presented with reduced grey matter in the medial orbitofrontal cortex and the left middle temporal gyrus. CONCLUSIONS: The medial orbitofrontal cortex and the middle temporal gyrus have been implicated in reinforcement-based decision-making, emotion regulation and autobiographical memory, processes that are impaired in a number of psychiatric disorders associated with maltreatment. We speculate that grey matter disturbance in these regions in a community sample of maltreated children may represent a latent neurobiological risk factor for later psychopathology and heightened risk taking.

Positron emission tomography in the diagnosis and management of intracranial germ cell tumours.

Positron emission tomography (PET) with (18)F-fluorodeoxy-glucose indicates metabolically active tissue. When investigating enhancing intracranial tumours, we have suggested that PET positivity might suggest an intracranial germ cell tumour (IGCT). Here, we present a case with dicentric IGCT where PET was initially discordant between the lesions and where PET then became negative despite clearly aggressive clinical behaviour. A cautionary note is introduced with respect to the interpretation of negative (18)F-FDG PET when investigating enhancing intracranial lesions.