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Individuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the ‘high risk of relapse’ group for whom longer antidepressant treatment durations are recommended.
Aims
In individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment.
Method
This was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures.
Results
We identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32–3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased – individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25–2.48). We found no interaction between polypharmacy and previous antidepressant duration.
Conclusions
Polypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment.
Recent higher-order explicit Runge–Kutta methods are compared with the classic fourth-order (RK4) method in long-term integration of both energy-conserving and lossy systems. By comparing quantity of function evaluations against accuracy for systems with and without known solutions, optimal methods are proposed. For a conservative system, we consider positional accuracy for Newtonian systems of two or three bodies and total angular momentum for a simplified Solar System model, over moderate astronomical timescales (tens of millions of years). For a nonconservative system, we investigate a relativistic two-body problem with gravitational wave emission. We find that methods of tenth and twelfth order consistently outperform lower-order methods for the systems considered here.
Current neurobiological models of post-traumatic stress disorder (PTSD) assume excessive medial frontal activation and hypoactivation of cortico-limbic regions as neural markers of post-traumatic dissociation. Script-driven imagery is an established experimental paradigm that is used to study acute dissociative reactions during trauma exposure. However, there is a scarcity of experimental research investigating neural markers of dissociation; findings from existing script-driven neuroimaging studies are inconsistent and based on small sample sizes.
Aims
The current aim was to identify the neural correlates of acute post-traumatic dissociation by employing the script-driven imagery paradigm in combination with functional magnetic resonance imaging.
Method
Functional neuroimaging data was acquired in 51 female patients with PTSD with a history of interpersonal childhood trauma. Blood-oxygen-level-dependent response during the traumatic (versus neutral) autobiographical memory recall was analysed, and the derived activation clusters were correlated with dissociation measures.
Results
During trauma recall, enhanced activation in the cerebellum, occipital gyri, supramarginal gyrus and amygdala was identified. None of the derived clusters correlated significantly with dissociative symptoms, although patients reported increased levels of acute dissociation following the paradigm.
Conclusions
The present study is one of the largest functional magnetic resonance imaging investigations of dissociative neural biomarkers in patients with PTSD undergoing experimentally induced trauma confrontation to elicit symptom-specific brain reactivity. In light of the current reproducibility crisis prominent in neuroimaging research owing to costly and time-consuming data acquisition, the current (null) findings highlight the difficulty of extracting reliable neurobiological biomarkers for complex subjective experiences such as dissociation.
We consider fully three-dimensional time-dependent outflow from a source into a surrounding fluid of different density. The source is distributed over a sphere of finite radius. The nonlinear problem is formulated using a spectral approach in which two streamfunctions and the density are represented as a Fourier-type series with time-dependent coefficients that must be calculated. Linearized theories are also discussed and an approximate stability condition for early stages in the outflow is derived. Nonlinear solutions are presented and different outflow shapes adopted by the fluid interface are investigated.
A classical problem in free-surface hydrodynamics concerns flow in a channel, when an obstacle is placed on the bottom. Steady-state flows exist and may adopt one of three possible configurations, depending on the fluid speed and the obstacle height; perhaps the best known has an apparently uniform flow upstream of the obstacle, followed by a semiinfinite train of downstream gravity waves. When time-dependent behaviour is taken into account, it is found that conditions upstream of the obstacle are more complicated, however, and can include a train of upstream-advancing solitons. This paper gives a critical overview of these concepts, and also presents a new semianalytical spectral method for the numerical description of unsteady behaviour.
To evaluate coronavirus disease 2019 (COVID-19) vaccine hesitancy among healthcare personnel (HCP) with significant clinical exposure to COVID-19 at 2 large, academic hospitals in Philadelphia, Pennsylvania.
Design, setting, and participants:
HCP were surveyed in November–December 2020 about their intention to receive the COVID-19 vaccine.
Methods:
The survey measured the intent among HCP to receive a COVID-19 vaccine, timing of vaccination, and reasons for or against vaccination. Among patient-facing HCP, multivariate regression evaluated the associations between healthcare positions (medical doctor, nurse practitioner or physician assistant, and registered nurse) and vaccine hesitancy (intending to decline, delay, or were unsure about vaccination), adjusting for demographic characteristics, reasons why or why not to receive the vaccine, and prior receipt of routine vaccines.
Results:
Among 5,929 HCP (2,253 medical doctors [MDs] and doctors of osteopathy [DOs], 582 nurse practitioners [NPs], 158 physician assistants [PAs], and 2,936 nurses), a higher proportion of nurses (47.3%) were COVID-vaccine hesitant compared with 30.0% of PAs and NPs and 13.1% of MDs and DOs. The most common reasons for vaccine hesitancy included concerns about side effects, the newness of the vaccines, and lack of vaccine knowledge. Regardless of position, Black HCP were more hesitant than White HCP (odds ratio [OR], ∼5) and females were more hesitant than males (OR, ∼2).
Conclusions:
Although most clinical HCP intended to receive a COVID-19 vaccine, intention varied by healthcare position. Consistent with other studies, hesitancy was also significantly associated with race or ethnicity across all positions. These results highlight the importance of understanding and effectively addressing reasons for hesitancy, especially among frontline HCP who are at increased risk of COVID exposure and play a critical role in recommending vaccines to patients.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
Methods
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
Results
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Conclusions
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food-based, reduced rank regression (RRR)-derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34 940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years and dietary data through validated semi-quantitative FFQ every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) with the lowest quintile was 0·99 (95 % CI 0·89, 1·10, P-value for trend = 0·97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile with the lowest was 1·39 (95 % CI 0·98, 1·96, P-value for trend = 0·03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated, EDIP was significantly associated with increased risk of periodontitis only among non-smokers who were obese. Hence, this association must be interpreted with caution.
Background: Detection of unusual carbapenemase-producing organisms (CPOs) in a healthcare facility may signify broader regional spread. During investigation of a VIM-producing Pseudomonas aeruginosa (VIM-CRPA) outbreak in a long-term acute-care hospital in central Florida, enhanced surveillance identified VIM-CRPA from multiple facilities, denoting potential regional emergence. We evaluated infection control and performed screening for CPOs in skilled nursing facilities (SNFs) across the region to identify potential CPO reservoirs and improve practices. Methods: All SNFs in 2 central Florida counties were offered a facility-wide point-prevalence survey (PPS) for CPOs and a nonregulatory infection control consultation. PPSs were conducted using a PCR-based screening method; specimens with a carbapenemase gene detected were cultured to identify the organisms. Infection control assessments focused on direct observations of hand hygiene (HH), environmental cleaning, and the sink splash zone. Thoroughness of environmental cleaning was evaluated using fluorescent markers applied to 6 standardized high-touch surfaces in at least 2 rooms per facility. Results: Overall, 21 (48%) SNFs in the 2-county region participated; 18 conducted PPS. Bed size ranged from 40 to 391, 5 (24%) facilities were ventilator-capable SNFs (vSNFs), and 12 had short-stay inpatient rehabilitation units. Of 1,338 residents approached, 649 agreed to rectal screening, and 14 (2.2%) carried CPOs. CPO-colonized residents were from the ventilator-capable units of 3 vSNFs (KPC-CRE=7; KPC-CRPA=1) and from short-stay units of 2 additional facilities (VIM-CRPA, n = 5; KPC-CRE, n = 1). Among the 5 facilities where CPO colonization was identified, the prevalence ranged from 1.1% in a short-stay unit to 16.1% in a ventilator unit. All facilities had access to soap and water in resident bathrooms; 14 (67%) had alcohol-based hand rubs accessible. Overall, mean facility HH adherence was 52% (range, 37%–66%; mean observations per facility = 106) (Fig. 1). We observed the use of non–EPA-registered disinfectants and cross contamination from dirty to clean areas during environmental cleaning; the overall surface cleaning rate was 46% (n = 178 rooms); only 1 room had all 6 markers removed. Resident supplies were frequently stored in the sink splash zone. Conclusions: A regional assessment conducted in response to emergence of VIM-CRPA identified a relatively low CPO prevalence at participating SNFs; CPOs were primarily identified in vSNFs and among short-stay residents. Across facilities, we observed low adherence to core infection control practices that could facilitate spread of CPOs and other resistant organisms. In this region, targeting ventilator and short-stay units of SNFs for surveillance and infection control efforts may have the greatest prevention impact.
Understanding the effects of predicted rising sea levels, combined with changes in precipitation and freshwater inflow on key estuarine ecosystem engineers such as the eastern oyster would provide critical information to inform restoration design and predictive models. Using oyster ladders with shell bags placed at three heights to capture a range of inundation levels, oyster growth of naturally recruited spat was monitored over the course of 6 months. Oyster numbers and shell heights were consistently highest in bottom and mid bags experiencing greater than 50% inundation (mid: 63 ± 7%; bottom: 95 ± 3%). Identifying thresholds for optimal oyster growth and survival to enhance restoration engineering would require finer scale evaluation of inundation levels.
Rey’s Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.
Method:
This study advances the Mayo’s Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30–91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided.
Results:
From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8–10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex.
Conclusions:
Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.
Many plant bugs (Miridae) are generalist herbivores that feed on multiple host species. The reasons these bugs move across hosts and the behavioural mechanisms responsible for their retention at specific hosts remain elusive. Green mirids (Creontiades dilutus) are endemic to Australia. These insects are important pests of cotton (Gossypium hirsutum) and even in low numbers can cause substantial damage to crops. These bugs are also present in relatively much higher numbers on pigeon pea (Cajanus cajan) planted alongside cotton fields, and evidence shows they move across these crops in both directions. Observations of these highly mobile insects in the field are challenging, but indirect evidence suggests that they may be nocturnal. This study evaluated: (1) the diel (24 h) period in which C. dilutus adults were most active, (2) whether they respond to plant volatiles immediately prior to landing on host substrates, and (3) if their presence on a host is in response to attraction or arrestment cues. The results suggest that C. dilutus bugs are typically most active early in the evenings, after remaining motionless during the day (unless disturbed). Their movement (at night) was arrested by hosts prior to touching plant tissues. There was no evidence to suggest that these bugs are attracted by volatiles beyond 2 cm. These outcomes demonstrate that insect behaviours need to be investigated within their typical activity periods, and that arrestment cues possibly play a central role in the host finding process of generalist C. dilutus and probably, therefore, other mirid species.
Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
There is evidence that patients with persecutory delusions tend to attribute excessively hypothetical positive events to internal causes and hypothetical negative events to external causes, arrive at hasty conclusions and fail in gathering and assessing adequate feedback, particularly when emotionally salient material is involved. Research on the neural correlates of the corresponding neural correlates and even more so on the potential effects of cognitive behavioral therapy (CBT) on the associated cerebral networks is almost unavailable.
The first and preliminary results of a multicentre fMRI study will be presented.
In this study eighty schizophrenia patients from the POSITIVE clinical trial and eighty healthy subjects were recruited at six German university hospitals (Bonn, Duisburg-Essen, Düsseldorf, Frankfurt, Cologne, Tubingen). After nine months of therapy (either with CBT or Supportive Therapy) patients and controls were re-examined enabling the study correlates of cerebral reorganization processes.
We found reliable differences in brain activation relating to phenomena of decision making under uncertainty, and biased attribution (self- vs. external reference of emotional events).
The comparison of both groups revealed significant decreased activation in key areas for decision making, self-reflection, self-relevance and agency attribution of patients with schizophrenia.
The preliminary data analysis of the still blinded treatment arms shows significantly increased activations in these areas after nine months of CBT. This suggest neuroplasitic changes according to relearning strategies in psychotic patients with schizophrenia and will hopefully give rise to a more widespread application of CBT in treatment of schizophrenia.
This case report describes a patient on tranylcypromine who erroneously received a single dose of imipramine and subsequently developed a fatal serotonin syndrome. Both the clinical features and the pathophysiology of the serotonin syndrome are discussed.
Pedophilia is a disorder where sexual preferences of adults are directed towards children. This disorder impacts society with 1–2 out of every 10 children being sexually approached by an adult, often resulting in prolonged negative psychological effects. Prior research reported structural and functional amygdala alterations in pedophilia. As the neurophenomenological model of sexual arousal suggests the importance of the amygdala in the emotional component, we focused on amygdala functional connectivity in pedophilia.
Aims
To investigate amygdala functional connectivity (FC) modulated by expectancy and salient stimuli in pedophilic patients.
Methods
Thirteen pedophilic patients and 13 matched healthy controls underwent a salience expectancy task in a 7T ultra high fMRI study. Subjects perceived pictures of naked adults and children. Half of the pictures were preceded by an expectancy cue. Participants were instructed to actively expect the picture depending on the cue. We conducted psychophysiological analysis (PPI) to examine amygdala FC changes in two amygdala sub-regions for child/adult stimuli during the expectancy period and the visual stimuli consummation period using as seed regions the basolateral (BLA) and central nucleus of the amygdala (CeA).
Results
Healthy controls, relative to patients showed significant stronger left CeA to right post-central gyrus FC during expectancy of adult > child picture. For picture condition (adult > child picture) we found significant stronger left CeA to left dorsolateral prefrontal cortex FC in patients compared to healthy controls.
Conclusion
These findings add to the recent literature by indicating that amygdala dysfunctional connectivity is involved in development of deviant sexual behavior.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The development and maintenance of an alcohol addiction is a complex interaction between genetic and environmental factors. Genetic effects seem to contribute substantially to the risk of developing an addiction, but also to its course and patients’ responses to different treatments. Recent studies identified associations between polymorphisms in the genes of glutamate and μ-opioid receptors and addiction risk. Those receptors are of special interest, because they are targets of therapeutic agents, such as acamprosate and topiramate.
Objectives and aims
Several studies were conducted, in order to further determine the effects of genetic polymorphisms in glutamate and opioid receptor genes on addictive behavior, neural response to alcohol cues and relapse risk.
Methods
Genetic effects were investigated in samples of alcohol-dependent patients using functional imaging techniques, neuropsychological tests and follow-up investigation after standard clinical treatment. Data on clinical parameters, neuronal response to alcohol cues, functional neuronal connectivity and relapse risk were collected and analyzed.
Results
Results demonstrate effects of genetic polymorphisms in glutamate and opioid receptors on neuronal response to alcohol cues in frontal and mesolimbic brain areas, subjective craving and time to first relapse. Current findings will be discussed in the light of existing evidence on the contribution of genetic effects to treatment outcome and patient stratification.
Conclusions
The investigation of genetic risk factors and mechanisms by which they affect addiction related phenotypes seems to be a promising tool to identify molecular treatment targets and predictors for successful treatment strategies.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.
Objectives/aims
To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.
Methods
A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.
Results
The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.
Conclusions
The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.