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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
There is substantial variation in patient symptoms following psychological therapy for depression and anxiety. However, reliance on endpoint outcomes ignores additional interindividual variation during therapy. Knowing a patient's likely symptom trajectories could guide clinical decisions. We aimed to identify latent classes of patients with similar symptom trajectories over the course of psychological therapy and explore associations between baseline variables and trajectory class.
Methods
Patients received high-intensity psychological treatment for common mental health problems at National Health Service Improving Access to Psychological Therapies services in South London (N = 16 258). To identify trajectories, we performed growth mixture modelling of depression and anxiety symptoms over 11 sessions. We then ran multinomial regressions to identify baseline variables associated with trajectory class membership.
Results
Trajectories of depression and anxiety symptoms were highly similar and best modelled by four classes. Three classes started with moderate-severe symptoms and showed (1) no change, (2) gradual improvement, and (3) fast improvement. A final class (4) showed initially mild symptoms and minimal improvement. Within the moderate-severe baseline symptom classes, patients in the two showing improvement as opposed to no change tended not to be prescribed psychotropic medication or report a disability and were in employment. Patients showing fast improvement additionally reported lower baseline functional impairment on average.
Conclusions
Multiple trajectory classes of depression and anxiety symptoms were associated with baseline characteristics. Identifying the most likely trajectory for a patient at the start of treatment could inform decisions about the suitability and continuation of therapy, ultimately improving patient outcomes.
While studies from the start of the COVID-19 pandemic have described initial negative effects on mental health and exacerbating mental health inequalities, longer-term studies are only now emerging.
Method
In total, 34 465 individuals in the UK completed online questionnaires and were re-contacted over the first 12 months of the pandemic. We used growth mixture modelling to identify trajectories of depression, anxiety and anhedonia symptoms using the 12-month data. We identified sociodemographic predictors of trajectory class membership using multinomial regression models.
Results
Most participants had consistently low symptoms of depression or anxiety over the year of assessments (60%, 69% respectively), and a minority had consistently high symptoms (10%, 15%). We also identified participants who appeared to show improvements in symptoms as the pandemic progressed, and others who showed the opposite pattern, marked symptom worsening, until the second national lockdown. Unexpectedly, most participants showed stable low positive affect, indicating anhedonia, throughout the 12-month period. From regression analyses, younger age, reporting a previous mental health diagnosis, non-binary, or self-defined gender, and an unemployed or a student status were significantly associated with membership of the stable high symptom groups for depression and anxiety.
Conclusions
While most participants showed little change in their depression and anxiety symptoms across the first year of the pandemic, we highlight the divergent responses of subgroups of participants, who fared both better and worse around national lockdowns. We confirm that previously identified predictors of negative outcomes in the first months of the pandemic also predict negative outcomes over a 12-month period.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.
Method
Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.
Results
Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.
Conclusions
We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
In cognitive models of adult psychosis, schematic beliefs about the self and others are important vulnerability and maintaining factors, and are therefore targets for psychological interventions. Schematic beliefs have not previously been investigated in children with distressing unusual, or psychotic-like, experiences (UEDs). The aim of this study was firstly to investigate whether a measure of schematic beliefs, originally designed for adults with psychosis, was suitable for children; and secondly, to examine the association of childhood schematic beliefs with internalising and externalising problems and with UEDs.
Method
Sixty-seven children aged 8–14 years, with emotional and behavioural difficulties, completed measures of UEDs, internalising (depression and anxiety), and externalising (conduct and hyperactivity-inattention) problems, together with the Brief Core Schema Scales (BCSS).
Results
The BCSS was readily completed by participants, and scale psychometric properties were good. Children tended to view themselves and others positively. Internalising and externalising problems and UEDs were all associated with negative schematic beliefs; effect sizes were small to medium.
Conclusions
Schematic beliefs in young people can be measured using the BCSS, and negative schematic beliefs are associated with childhood psychopathology and with UEDs. Schematic beliefs may therefore form a useful target in psychological interventions for young people with UEDs.
The German version of the Conners Adult ADHD Rating Scales (CAARS) has proven to show very high model fit in confirmative factor analyses with the established factors inattention/memory problems, hyperactivity/restlessness, impulsivity/emotional lability, and problems with self-concept in both large healthy control and ADHD patient samples. This study now presents data on the psychometric properties of the German CAARS-self-report (CAARS-S) and observer-report (CAARS-O) questionnaires.
Methods
CAARS-S/O and questions on sociodemographic variables were filled out by 466 patients with ADHD, 847 healthy control subjects that already participated in two prior studies, and a total of 896 observer data sets were available. Cronbach's-alpha was calculated to obtain internal reliability coefficients. Pearson correlations were performed to assess test-retest reliability, and concurrent, criterion, and discriminant validity. Receiver Operating Characteristics (ROC-analyses) were used to establish sensitivity and specificity for all subscales.
Results
Coefficient alphas ranged from .74 to .95, and test-retest reliability from .85 to .92 for the CAARS-S, and from .65 to .85 for the CAARS-O. All CAARS subscales, except problems with self-concept correlated significantly with the Barrett Impulsiveness Scale (BIS), but not with the Wender Utah Rating Scale (WURS). Criterion validity was established with ADHD subtype and diagnosis based on DSM-IV criteria. Sensitivity and specificity were high for all four subscales.
Conclusion
The reported results confirm our previous study and show that the German CAARS-S/O do indeed represent a reliable and cross-culturally valid measure of current ADHD symptoms in adults.
After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.
DESIGN
Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.
METHODS
We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.
RESULTS
Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.
CONCLUSIONS
Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.
Surgical site infections (SSIs) following colorectal surgery (CRS) are among the most common healthcare-associated infections (HAIs). Reduction in colorectal SSI rates is an important goal for surgical quality improvement.
OBJECTIVE
To examine rates of SSI in patients with and without cancer and to identify potential predictors of SSI risk following CRS
DESIGN
American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data files for 2011–2013 from a sample of 12 National Comprehensive Cancer Network (NCCN) member institutions were combined. Pooled SSI rates for colorectal procedures were calculated and risk was evaluated. The independent importance of potential risk factors was assessed using logistic regression.
SETTING
Multicenter study
PARTICIPANTS
Of 22 invited NCCN centers, 11 participated (50%). Colorectal procedures were selected by principal procedure current procedural technology (CPT) code. Cancer was defined by International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes.
MAIN OUTCOME
The primary outcome of interest was 30-day SSI rate.
RESULTS
A total of 652 SSIs (11.06%) were reported among 5,893 CRSs. Risk of SSI was similar for patients with and without cancer. Among CRS patients with underlying cancer, disseminated cancer (SSI rate, 17.5%; odds ratio [OR], 1.66; 95% confidence interval [CI], 1.23–2.26; P=.001), ASA score ≥3 (OR, 1.41; 95% CI, 1.09–1.83; P=.001), chronic obstructive pulmonary disease (COPD; OR, 1.6; 95% CI, 1.06–2.53; P=.02), and longer duration of procedure were associated with development of SSI.
CONCLUSIONS
Patients with disseminated cancer are at a higher risk for developing SSI. ASA score >3, COPD, and longer duration of surgery predict SSI risk. Disseminated cancer should be further evaluated by the Centers for Disease Control and Prevention (CDC) in generating risk-adjusted outcomes.
Studies have shown that specific cognitions and behaviours play a role in maintaining chronic fatigue syndrome (CFS). However, little research has investigated illness-specific cognitive processing in CFS. This study investigated whether CFS participants had an attentional bias for CFS-related stimuli and a tendency to interpret ambiguous information in a somatic way. It also determined whether cognitive processing biases were associated with co-morbidity, attentional control or self-reported unhelpful cognitions and behaviours.
Method
A total of 52 CFS and 51 healthy participants completed self-report measures of symptoms, disability, mood, cognitions and behaviours. Participants also completed three experimental tasks, two designed specifically to tap into CFS salient cognitions: (i) visual-probe task measuring attentional bias to illness (somatic symptoms and disability) v. neutral words; (ii) interpretive bias task measuring positive v. somatic interpretations of ambiguous information; and (iii) the Attention Network Test measuring general attentional control.
Results
Compared with controls, CFS participants showed a significant attentional bias for fatigue-related words and were significantly more likely to interpret ambiguous information in a somatic way, controlling for depression and anxiety. CFS participants had significantly poorer attentional control than healthy individuals. Attention and interpretation biases were associated with fear/avoidance beliefs. Somatic interpretations were also associated with all-or-nothing behaviour and catastrophizing.
Conclusions
People with CFS have illness-specific biases which may play a part in maintaining symptoms by reinforcing unhelpful illness beliefs and behaviours. Enhancing adaptive processing, such as positive interpretation biases and more flexible attention allocation, may provide beneficial intervention targets.
Patients are frequently discharged with central venous catheters (CVCs) for home infusion therapy.
OBJECTIVE
To study a prospective cohort of patients receiving home infusion therapy to identify environmental and other risk factors for complications.
DESIGN
Prospective cohort study between March and December 2015.
SETTING
Home infusion therapy after discharge from academic medical centers.
PARTICIPANTS
Of 368 eligible patients discharged from 2 academic hospitals to home with peripherally inserted central catheters and tunneled CVCs, 222 consented. Patients remained in the study until 30 days after CVC removal.
METHODS
Patients underwent chart abstraction and monthly telephone surveys while the CVC was in place, focusing on complications and environmental exposures. Multivariable analyses estimated adjusted odds ratios and adjusted incident rate ratios between clinical, demographic, and environmental risk factors and 30-day readmissions or CVC complications.
RESULTS
Of 222 patients, total parenteral nutrition was associated with increased 30-day readmissions (adjusted odds ratio, 4.80 [95% CI, 1.51–15.21) and CVC complications (adjusted odds ratio, 2.41 [95% CI, 1.09–5.33]). Exposure to soil through gardening or yard work was associated with a decreased likelihood of readmissions (adjusted odds ratio, 0.09 [95% CI, 0.01–0.74]). Other environmental exposures were not associated with CVC complications.
CONCLUSIONS
complications and readmissions were common and associated with the use of total parenteral nutrition. Common environmental exposures (well water, cooking with raw meat, or pets) did not increase the rate of CVC complications, whereas soil exposures were associated with decreased readmissions. Interventions to decrease home CVC complications should focus on total parenteral nutrition patients.
Large volumes of data and multiple computing platforms are now universal components of paediatric cardiovascular medicine, but are in a constant state of evolution. Often, multiple sets of related data reside in disconnected “silos”, resulting in clinical, administrative, and research activities that may be duplicative, inefficient, and at times inaccurate. Comprehensive and integrated data solutions are needed to facilitate these activities across congenital heart centres. We describe methodology, key considerations, successful use cases, and lessons learnt in developing an integrated data platform across our congenital heart centre.
Toxoplasmosis causes complications during pregnancy that have serious effects on fetal development. Thus far, toxocariasis has been reported to spread only via vertical transmission. Nonetheless, the population of pregnant women is also exposed to this infection. Co-infection with both Toxoplasma gondii and Toxocara spp. has been reported in children, but there are no reports of co-infection in the population of pregnant women. The aim of this study was to determine the prevalence of co-infection with T. gondii and Toxocara spp. in pregnant women at a university hospital in southern Brazil, and to identify the risk factors associated with infection by both parasites. Two hundred pregnant women were tested for the presence of anti-T. gondii and anti-Toxocara spp. antibodies and were asked to complete an epidemiological questionnaire. In this study, the co-infection rate observed in the total population of pregnant women was 8%. In addition, women with a positive result for a serology test for Toxocara spp. were at increased risk of infection by T. gondii (P = 0.019). Co-infection with both parasites in pregnant women was associated with low birth weights in neonates. The similar modes of transmission of both parasites could explain the co-infection. Only a few previous studies have investigated this phenomenon. The findings of the present study emphasize the importance of serological diagnosis during prenatal care and further research in this area to identify risk factors associated with this co-infection, and the possible implications of this co-infection during pregnancy and on the health of newborns.
Cognitive models of adult psychosis propose that negative schematic beliefs (NSBs) mediate the established association between victimisation and psychotic symptoms. In childhood, unusual, or psychotic-like, experiences are associated with bullying (a common form of victimisation) and NSBs. This study tests the mediating role of NSBs in the relationship between bullying and distressing unusual experiences (UEDs) in childhood.
Method
Ninety-four 8–14 year olds referred to community Child and Adolescent Mental Health Services completed self-report assessments of UEDs, bullying, and NSBs about the self (NS) and others (NO).
Results
Both NS and NO were associated with bullying (NS: r = .40, P < .001; NO: r = .33, P = .002), and with UEDs (NS: r = .51, P < .001; NO: r = .43, P < .001). Both NS and NO significantly mediated the relationship between bullying and UEDs (NS: z = 3.15, P = .002; NO: z = 2.35, P = .019).
Conclusions
Children's NSBs may mediate the adverse psychological impact of victimisation, and are appropriate treatment targets for young people with UEDs. Early educational intervention to reduce negative appraisals of the self and others may increase resilience to future adverse experiences and reduce later mental health risk.
We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.
We consider Euclidean first passage percolation on a large family of connected random geometric graphs in the d-dimensional Euclidean space encompassing various well-known models from stochastic geometry. In particular, we establish a strong linear growth property for shortest-path lengths on random geometric graphs which are generated by point processes. We consider the event that the growth of shortest-path lengths between two (end) points of the path does not admit a linear upper bound. Our linear growth property implies that the probability of this event tends to zero sub-exponentially fast if the direct (Euclidean) distance between the endpoints tends to infinity. Besides, for a wide class of stationary and isotropic random geometric graphs, our linear growth property implies a shape theorem for the Euclidean first passage model defined by such random geometric graphs. Finally, this shape theorem can be used to investigate a problem which is considered in structural analysis of fixed-access telecommunication networks, where we determine the limiting distribution of the length of the longest branch in the shortest-path tree extracted from a typical segment system if the intensity of network stations converges to 0.