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The association of COVID-19 with death in people with severe mental illness (SMI), and associations with multimorbidity and ethnicity, are unclear.
To determine all-cause mortality in people with SMI following COVID-19 infection, and assess whether excess mortality is affected by multimorbidity or ethnicity.
This was a retrospective cohort study using primary care data from the Clinical Practice Research Database, from February 2020 to April 2021. Cox proportional hazards regression was used to estimate the effect of SMI on all-cause mortality during the first two waves of the COVID-19 pandemic.
Among 7146 people with SMI (56% female), there was a higher prevalence of multimorbidity compared with the non-SMI control group (n = 653 024, 55% female). Following COVID-19 infection, the SMI group experienced a greater risk of death compared with controls (adjusted hazard ratio (aHR) 1.53, 95% CI 1.39–1.68). Black Caribbean/Black African people were more likely to die from COVID-19 compared with White people (aHR = 1.22, 95% CI 1.12–1.34), with similar associations in the SMI group and non-SMI group (P for interaction = 0.73). Following infection with COVID-19, for every additional multimorbidity condition, the aHR for death was 1.06 (95% CI 1.01–1.10) in the SMI stratum and 1.16 (95% CI 1.15–1.17) in the non-SMI stratum (P for interaction = 0.001).
Following COVID-19 infection, patients with SMI were at an elevated risk of death, further magnified by multimorbidity. Black Caribbean/Black African people had a higher risk of death from COVID-19 than White people, and this inequity was similar for the SMI group and the control group.
Adverse effects are a common concern when prescribing and reviewing medication, particularly in vulnerable adults such as older people and those with intellectual disability. This paper describes the development of an app giving information on side-effects, called Medichec, and provides a description of the processes involved in its development and how drugs were rated for each side-effect. Medications with central anticholinergic action, dizziness, drowsiness, hyponatraemia, QTc prolongation, bleeding and constipation were identified using the British National Formulary (BNF) and frequency of occurrence of these effects was determined using the BNF, product information and electronic searches, including PubMed.
Medications were rated using a traffic light system according to how commonly the adverse effect was known to occur or the severity of the effect.
Medichec can facilitate access to side-effects information for multiple medications, aid clinical decision-making, optimise treatment and improve patient safety in vulnerable adults.
People with psychosis in Malawi have very limited access to timely assessment and evidence-based care, leading to a long duration of untreated psychosis and persistent disability. Most people with psychosis in the country consult traditional or religious healers. Stigmatising attitudes are common and services have limited capacity, particularly in rural areas. This paper, focusing on pathways to care for psychosis in Malawi, is based on the Wellcome Trust Psychosis Flagship Report on the Landscape of Mental Health Services for Psychosis in Malawi. Its purpose is to inform Psychosis Recovery Orientation in Malawi by Improving Services and Engagement (PROMISE), a longitudinal study that aims to build on existing services to develop sustainable psychosis detection systems and management pathways to promote recovery.
Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model.
We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose–response relationship.
People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18–1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08–1.44) and TCAs (HR 1.33, 95% CI 1.13–1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE.
In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose–response fashion.
To compare people with diabetes developing severe mental illness (SMI) to those with diabetes alone with respect to risk status, diabetes care receipt, and diabetes-relevant outcomes in primary care.
Data from mental health care (Clinical Record Interactive Search; CRIS) linked to primary care (Lambeth DataNet; LDN) were used. From patients with a type 2 diabetes mellitus (T2DM) diagnosis in primary care, those with a new SMI diagnosis were matched (by age, gender, and practice) with up to five randomly selected controls. Mixed models were used to estimate associations with trajectories of recorded HbA1c levels; Poisson regression models compared total and cardiovascular comorbidity levels and number of diabetes complications; linear regression models compared BMI and total cholesterol levels; conditional logistic regression models investigated microalbuminuria, receipt of a foot or retinal examination, use of statins and receipt of insulin; Cox proportional hazards were used to model incident microvascular and macrovascular events, foot morbidity and mortality.
In a cohort of 693 cases with SMI (122 bipolar disorder, 571 schizophrenia and related) and T2DM compared to 3366 controls, all-cause mortality was increased substantially in the cohort with SMI (adjusted hazard ratio 4.52, 95% CI 3.73–5.47; for bipolar 5.59, 3.37–9.28; for schizophrenia 4.42, 3.60–5.44). However, for all the other outcome comparisons, the only significant findings were of reduced foot examination (adjusted odds ratio 0.75, 0.54–0.98) and reduced retinal screening (0.77, 0.61–0.96).
Higher mortality suggests increased risk of adverse outcomes for people with pre-existing T2DM who develop SMI, and reduced foot/retinal examinations suggest disadvantaged healthcare receipt. However, other potential explanations for the mortality difference could not be identified from the outcomes analysed, so further investigation is needed into underlying causal pathways.
This chapter provides an overview of operational risk modeling techniques used by industry participants and regulators in the USA, recommendations for how modeling techniques can be improved, and a summary of the model risk tools necessary for any operational risk modeling framework.
The current coronavirus disease (COVID-19) pandemic has placed unprecedented strain on underfunded public health resources in the Southeastern United States. The Memphis, TN, metropolitan region has lacked infrastructure for health data exchange.
This manuscript describes a multidisciplinary initiative to create a community-focused COVID-19 data registry, the Memphis Pandemic Health Informatics System (MEMPHI-SYS). MEMPHI-SYS leverages test result data updated directly from community-based testing sites, as well as a full complement of public health data sets and knowledge-based informatics. It has been guided by relationships with community stakeholders and is managed alongside the largest publicly funded community-based COVID-19 testing response in the Mid-South. MEMPHI-SYS has supported interactive Web-based analytic resources and informs federally funded COVID-19 outreach directed toward neighborhoods most in need of pandemic support.
MEMPHI-SYS provides an instructive case study of how to collaboratively establish the technical scaffolding and human relationships necessary for data-driven, health equity-focused pandemic surveillance, and policy interventions.
Patients diagnosed with mental health problems are more predisposed to cardiovascular disease, including cardiac surgery. Nevertheless, health outcomes after cardiac surgery for patients with mental health problems as a discrete group are unknown. This study examined the association between secondary care mental health service use and postoperative health outcomes following cardiac surgery.
We conducted a retrospective observational research, utilizing data from a large South London mental healthcare supplier linked to national hospitalization data. OPCS-4 codes were applied to classify cardiac surgery. Health results were compared between those individuals with a mental health disorder diagnosis from secondary care and other local residents, including the length of hospital stay (LOS), inpatient mortality, and 30-day emergency hospital readmission.
Twelve thousand three hundred and eighty-four patients received cardiac surgery, including 1,481 with a mental disorder diagnosis. Patients with mental health diagnosis were at greater risk of emergency admissions for cardiac surgery (odds ratio [OR] 1.60; 1.43, 1.79), longer index LOS (incidence rate ratio 1.28; 1.26, 1.30), and at higher risk of 30-day emergency readmission (OR 1.53; 1.31, 1.78). Those who underwent pacemaker insertion and major open surgery had worse postoperative outcomes during index surgery hospital admission while those who had major endovascular surgery had worse health outcomes subsequent 30-day emergency hospital readmission.
People with a mental health disorder diagnosis undertaking cardiac surgery have significantly worse health outcomes. Personalized guidelines and policies to manage preoperative risk factors require consideration and evaluation.
Amiodarone may be considered for patients with junctional ectopic tachycardia refractory to treatment with sedation, analgesia, cooling, and electrolyte replacements. There are currently no published pediatric data regarding the hemodynamic effects of the newer amiodarone formulation, PM101, devoid of hypotensive agents used in the original amiodarone formulation. We performed a single-center, retrospective, descriptive study from January 2012 to December 2020 in a pediatric ICU. Thirty-three patients were included (22 male and 11 female) between the ages of 1.1 and 1,460 days who developed post-operative junctional ectopic tachycardia or other tachyarrhythmias requiring PM101. Data analysis was performed on hemodynamic parameters (mean arterial pressures and heart rate) and total PM101 (mg/kg) from hour 0 of amiodarone administration to hour 72. Adverse outcomes were defined as Vasoactive-Inotropic Score >20, patients requiring ECMO or CPR, or patient death. There was no statistically significant decrease in mean arterial pressures within the 6 hours of PM101 administration (p > 0.05), but there was a statistically significant therapeutic decrease in heart rate for resolution of tachyarrhythmia (p < 0.05). Patients received up to 25 mg/kg in an 8-hour time for rate control. Average rate control was achieved within 11.91 hours and average rhythm control within 62 hours. There were four adverse events around the time of PM101 administration, with three determined to not be associated with the medication. PM101 is safe and effective in the pediatric cardiac surgical population. Our study demonstrated that PM101 can be used in a more aggressive dosing regimen than previously reported in pediatric literature with the prior formulation.
Predictive values of multiple serum biomarkers for suicidal behaviours (SBs) have rarely been tested. This study sought to evaluate and develop a panel of multiple serum biomarkers for predicting SBs in outpatients receiving a 12-month pharmacotherapy programme for depressive disorders.
At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics including previous suicidal attempt and present suicidal severity were evaluated in 1094 patients with depressive disorders without a bipolar diagnosis. Of these, 884 were followed for increased suicidal severity and fatal/non-fatal suicide attempt outcomes over a 12-month treatment period. Individual and combined effects of serum biomarkers on these two prospective SBs were estimated using logistic regression analysis after adjustment for relevant covariates.
Increased suicidal severity and fatal/non-fatal suicide attempt during the 12-month pharmacotherapy were present in 155 (17.5%) and 38 (4.3%) participants, respectively. Combined cortisol, total cholesterol, and folate serum biomarkers predicted fatal/non-fatal suicide attempt, and these with interleukin-1 beta and homocysteine additionally predicted increased suicidal severity, with clear gradients robust to adjustment (p values < 0.001).
Application of multiple serum biomarkers could considerably improve the predictability of SBs during the outpatient treatment of depressive disorders, potentially highlighting the need for more frequent monitoring and risk appraisal.
People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population.
People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012–2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership.
The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: ‘substance related’ (24.9%), ‘atopic’ (24.2%), ‘pure affective’ (30.4%), ‘cardiovascular’ (14.1%), and ‘complex multimorbidity’ (6.4%). Patients had on average 7–9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the ‘pure affective’. Compared to the largest cluster (‘pure affective’), the ‘substance related’ and the ‘atopic’ clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98–1.00) and 0.96 (0.95–0.97) respectively], and the ‘cardiovascular’ and ‘complex multimorbidity’ clusters were older (ORs 1.09 (1.07–1.10) and 1.16 (1.14–1.18) respectively). The ‘substance related’ cluster was more likely to be White, the ‘cardiovascular’ cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10–2.79), and both more likely to have schizophrenia, compared to other clusters.
The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.
Deutetrabenazine is FDA-approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal trials (ARM-TD/AIM-TD), deutetrabenazine significantly improved Abnormal Involuntary Movement Scale (AIMS) scores and was well-tolerated. This post hoc analysis examined the efficacy and safety of long-term deutetrabenazine treatment in TD patients with comorbid psychiatric illness, including schizophrenia/schizoaffective disorder and mood disorders (bipolar/depression/other).
Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study. Deutetrabenazine was titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse events (AEs) were analyzed in subgroups by comorbid psychiatric illness.
A total of 337 patients in the OLE study were included in the analysis: 205 patients with schizophrenia/schizoaffective disorder (mean age, 55 years; 50% male; 6.4 years since diagnosis; 92% taking DRA) and 131 patients with mood disorders (mean age, 60 years; 35% male; 4.6 years since diagnosis; 50% taking DRA). At week 145, mean ± SE dose was 40.4 ± 1.1 mg/day for schizophrenia/schizoaffective disorder (n = 88) and 38.5 ± 1.2 mg/day for mood disorders (n = 72). Mean ± SE change from baseline in AIMS score at week 145 was −6.3 ± 0.49 and −7.1 ± 0.58, 56% and 72% achieved PGIC treatment success, and 66% and 82% achieved CGIC treatment success in schizophrenia/schizoaffective disorder and mood disorder patients, respectively. Overall AE incidence (exposure-adjusted incidence rates [incidence/patient-years]) was low: any, 1.02 and 1.71; serious, 0.10 and 0.12; leading to discontinuation, 0.07 and 0.05).
Long-term deutetrabenazine treatment provided clinically meaningful improvements in TD-related movements, with a favorable safety profile, regardless of underlying comorbid psychiatric illness.
Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Tardive dyskinesia (TD) is an involuntary movement disorder that can result from exposure to dopamine-receptor antagonists (DRAs). Deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores in the 12-week pivotal trials (ARM-TD/AIM-TD). This post hoc analysis assessed the long-term efficacy and safety of deutetrabenazine by baseline DRA use.
Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse event (AE) rates were analyzed in subgroups by baseline DRA use.
Of 337 patients in the OLE study, 254 were taking DRAs at baseline (mean age, 56 years; 48% male; 6.0 years since diagnosis) and 83 were not (mean age, 60 years; 31% male; 4.9 years since diagnosis). Mean ± SE dose at week 145 was 39.9 ± 1.0 mg/day in patients taking DRAs (n = 108) and 38.5 ± 1.5 mg/day in patients not taking DRAs (n = 53). At week 145, mean ± SE change from baseline in AIMS score was −6.1 ± 0.43 and −7.5 ± 0.71; 64% and 62% achieved PGIC treatment success; and 69% and 81% achieved CGIC treatment success, respectively. Overall AE incidence was low (exposure-adjusted incidence rates [incidence/patient-years]: any, 1.08 and 1.97; serious, 0.10 and 0.12; leading to discontinuation, 0.06 and 0.05).
This analysis suggests that deutetrabenazine for long-term treatment of TD is beneficial, with a favorable safety profile, regardless of concomitant DRA use.
Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
One prominent criticism of the abstractionist program is the so-called Bad Company objection. The complaint is that abstraction principles cannot in general be a legitimate way to introduce mathematical theories, since some of them are inconsistent. The most notorious example, of course, is Frege’s Basic Law V. A common response to the objection suggests that an abstraction principle can be used to legitimately introduce a mathematical theory precisely when it is stable: when it can be made true on all sufficiently large domains. In this paper, we raise a worry for this response to the Bad Company objection. We argue, perhaps surprisingly, that it requires very strong assumptions about the range of the second-order quantifiers; assumptions that the abstractionist should reject.
To investigate factors associated with suicidal ideation (SI) around the time of dementia diagnosis. We hypothesised relatively preserved cognition, co-occurring physical and psychiatric disorders, functional impairments, and dementia diagnosis subtype would be associated with a higher risk of SI.
Cross-sectional study using routinely collected electronic mental healthcare records.
National Health Service secondary mental healthcare services in South London, UK, serving a population of over 1.36 million residents.
Patients who received a diagnosis of dementia (Alzheimer’s, vascular, mixed Alzheimer’s/vascular, or dementia with Lewy bodies) between 1 Nov 2007–31 Oct 2021: 18,252 people were identified during the observation period.
A natural language processing algorithm was used to identify recorded clinician recording of SI around the time of dementia diagnosis. Sociodemographic and clinical characteristics were also measured around the time of diagnosis. We compared people diagnosed with non-Alzheimer’s dementia to those with Alzheimer’s and used statistical models to adjust for putative confounders.
15.1% of patients had recorded SI, which was more common in dementia with Lewy bodies compared to other dementia diagnoses studied. After adjusting for sociodemographic and clinical factors, SI was more frequent in those with depression and dementia with Lewy bodies and less common in those with impaired activities of daily living and in vascular dementia. Agitated behavior and hallucinations were not associated with SI in the final model.
Our findings highlight the importance of identifying and treating depressive symptoms in people with dementia and the need for further research into under-researched dementia subtypes.
The rate of normal birth outcomes (i.e. full-term births without intervention) for women with severe mental illness (SMI – psychotic and bipolar disorders) is not known. We examined rates of birth without intervention (spontaneous labour onset, spontaneous vaginal delivery without instruments, no episiotomy and no indication of pre- or post-delivery anaesthesia) in women with SMI (584 pregnancies) compared with a control population (70 942 pregnancies). Outcome ratios were calculated standardising for age. Women with SMI were less likely to have a birth without intervention (29.5%) relative to the control population (36.8%) (standardised outcome ratio 0.74, 95% CI 0.63–0.87).