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A short, effective therapy for posttraumatic stress disorder (PTSD) could decrease barriers to implementation and uptake, reduce dropout, and ameliorate distressing symptoms in military personnel and veterans. This non-inferiority RCT evaluated the efficacy of 2-week massed prolonged exposure (MPE) therapy compared to standard 10-week prolonged exposure (SPE), the current gold standard treatment, in reducing PTSD severity in both active serving and veterans in a real-world health service system.
Methods
This single-blinded multi-site non-inferiority RCT took place in 12 health clinics across Australia. The primary outcome was PTSD symptom severity measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks. 138 military personnel and veterans with PTSD were randomised. 71 participants were allocated to SPE, with 63 allocated to MPE.
Results
The intention-to-treat sample included 138 participants, data were analysed for 134 participants (88.1% male, M = 46 years). The difference between the mean MPE and SPE group PTSD scores from baseline to 12 weeks-post therapy was 0.94 [95% confidence interval (CI) −4.19 to +6.07]. The upper endpoint of the 95% CI was below +7, indicating MPE was non-inferior to SPE. Significant rates of loss of PTSD diagnosis were found for both groups (MPE 53.8%, SPE 54.1%). Dropout rates were 4.8% (MPE) and 16.9% (SPE).
Conclusions
MPE was non-inferior to SPE in significantly reducing symptoms of PTSD. Significant reductions in symptom severity, low dropout rates, and loss of diagnosis indicate MPE is a feasible, accessible, and effective treatment. Findings demonstrate novel methods to deliver gold-standard treatments for PTSD should be routinely considered.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Using a recent breakthrough of Smith [18], we improve the results of Fouvry and Klüners [4, 5] on the solubility of the negative Pell equation. Let
$\mathcal {D}$
denote the set of positive squarefree integers having no prime factors congruent to
$3$
modulo
$4$
. Stevenhagen [19] conjectured that the density of d in
$\mathcal {D}$
such that the negative Pell equation
$x^2-dy^2=-1$
is solvable with
$x, y \in \mathbb {Z}$
is
$58.1\%$
, to the nearest tenth of a percent. By studying the distribution of the
$8$
-rank of narrow class groups
$\operatorname {\mathrm {Cl}}^+(d)$
of
$\mathbb {Q}(\sqrt {d})$
, we prove that the infimum of this density is at least
$53.8\%$
.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus.
Aims
We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection.
Method
Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data.
Results
We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10−5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies.
Conclusions
We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.
Auditory Verbal Hallucinations (AVH) are a hallmark of psychosis, but affect many other clinical populations. Patients’ understanding and self-management of AVH may differ between diagnostic groups, change over time, and influence clinical outcomes.
We aimed to explore patients’ understanding and self-management of AVH in a young adult clinical population.
Method
35 participants reporting frequent AVH were purposively sampled from a youth mental health service, to capture experiences across psychosis and non-psychosis diagnoses. Diary and photo-elicitation methodologies were used – participants were asked to complete diaries documenting experiences of AVH, and to take photographs representing these experiences. In-depth, unstructured interviews were held, using participant-produced materials as a topic guide. Conventional content analysis was conducted, deriving results from the data in the form of themes.
Result
Three themes emerged:
(1) Searching for answers, forming identities – voice-hearers sought to explain their experiences, resulting in the construction of identities for voices, and descriptions of relationships with them. These identities were drawn from participants’ life-stories (e.g., reflecting trauma), and belief-systems (e.g., reflecting supernatural beliefs, or mental illness). Some described this process as active / volitional. Participants described re-defining their own identities in relation to those constructed for AVH (e.g. as diseased, 'chosen', or persecuted), others considered AVH explicitly as aspects of, or changes in, their personality.
(2) Coping strategies and goals – patients’ self-management strategies were diverse, reflecting the diverse negative experiences of AVH. Strategies were related to a smaller number of goals, e.g. distraction, soothing overwhelming emotions, 'reality-checking', and retaining agency.
(3) Outlook – participants formed an overall outlook reflecting their self-efficacy in managing AVH. Resignation and hopelessness in connection with disabling AVH are contrasted with outlooks of “acceptance” or integration, which were described as positive, ideal, or mature.
Conclusion
Trans-diagnostic commonalities in understanding and self-management of AVH are highlighted - answer-seeking and identity-formation processes; a diversity of coping strategies and goals; and striving to accept the symptom. Descriptions of “voices-as-self”, and dysfunctional relationships with AVH, could represent specific features of voice-hearing in personality disorder, whereas certain supernatural/paranormal identities and explanations were clearly delusional. However, no aspect of identity-formation was completely unique to psychosis or non-psychosis diagnostic groups. The identity-formation process, coping strategies, and outlooks can be seen as a framework both for individual therapies and further research.
The restrictions experienced due to the COVID-19 pandemic had impacts on how clinical teaching and assessment is conducted. The Royal College of Psychiatrists decided to run the final part of the membership exam, the Clinical Assessment of Skills and Competencies (CASC) online for the first time in September 2020. We aimed to prepare candidates in the Northern Ireland deanery for this by developing a virtual mock examination using the Zoom platform.
Method
In previous years, higher psychiatry trainees in the Northern Ireland deanery have run successful face to face mock examinations to help pre-membership trainees prepare for the CASC. We adapted some of this material to our virtual examination. 16 stations were run in total, in two circuits of eight. These stations were mapped to the Royal College CASC blueprint. Higher trainees were recruited to act as examiners, with core trainees acting as simulated patients. The mock examination was advertised through the local deanery and all candidates sitting in September availed of the opportunity (a total of 8 trainees).
Zoom was used as the platform due to ease of use, familiarity and breakout room function. Each station formed one breakout room, and a facilitator moved candidates between rooms and provided timing prompts. Instructions were emailed to candidates in advance.
A comfort break was provided between circuits. At the end of the mock examination, everyone was returned to the main room and examiners gave general feedback and tips. Individual feedback was provided by collating mark schemes for each candidate, which included free text feedback, and sending these via email.
Result
Despite the evident challenges involved, the mock CASC ran smoothly. There was one minor delay of approximately 3 minutes due to technical difficulties, which was easily recouped. We obtained qualitative feedback from candidates which was positive, with trainees commenting that they felt “more at ease … less worried” about a digital exam, and that it was “efficient and effective”.
All candidates who sat the mock examination were successful in the face to face CASC sitting which followed in September.
Conclusion
We were able to successfully adapt what was previously an in-person mock CASC exam to the new digital format in a way that reflected how the actual CASC exam will run, and it was considered beneficial preparation by the candidates who sat this mock. This has improved trainee experience at a time when many teaching opportunities have been suspended.
The British Columbia Farmers’ Market Nutrition Coupon Program (FMNCP) provides low-income households with coupons valued at $21/week for 16 weeks to purchase healthy foods in farmers’ markets. Our objective was to explore FMNCP participants’ experiences of accessing nutritious foods, and perceived programme outcomes.
Design:
The current study used qualitative description methodology. Semi-structured interviews were conducted with FMNCP participants during the 2019 farmers' market season. Directed content analysis was used to analyse the data, whereby the five domains of Freedman et al.’s framework of nutritious food access provided the basis for an initial coding scheme. Data that did not fit within the framework’s domains were coded inductively.
Setting:
One urban and two rural communities in British Columbia, Canada.
Participants:
Twenty-eight adults who were participating in the FMNCP.
Results:
Three themes emerged: autonomy and dignity, social connections and community building, and environmental and programmatic constraints. Firstly, the programme promoted a sense of autonomy and dignity through financial support, increased access to high-quality produce, food-related education and skill development and mitigating stigma and shame. Secondly, shopping in farmers' markets increased social connections and fostered a sense of community. Finally, participants experienced limited food variety in rural farmers' markets, lack of transportation and challenges with redeeming coupons.
Conclusions:
Participation in the FMNCP facilitated access to nutritious foods and enhanced participants’ diet quality, well-being and health. Strategies such as increasing the amount and duration of subsidies and expanding programmes may help improve participants’ experiences and outcomes of farmers' market food subsidy programmes.
Promulgating a continuum model of mental health and mental illness has been proposed as a way to reduce stigma by decreasing notions of differentness. This systematic review and meta-analysis examines whether continuum beliefs are associated with lower stigma, and whether continuum interventions reduce stigma.
Methods
Following a pre-defined protocol (PROSPERO: CRD42019123606), we searched three electronic databases (PubMed, Web of Science, and PsycINFO) yielding 6726 studies. After screening, we included 33 studies covering continuum beliefs, mental illness, and stigma. Of these, 13 studies were included in meta-analysis.
Results
Continuum beliefs are consistently associated with lower stigma. Interventions were effective at manipulating continuum beliefs but differ in their effects on stigmatising attitudes.
Conclusions
We discuss whether and to what extent attitudes towards people with mental illness can be improved by providing information on a mental health-mental illness continuum. It appeared to be relevant whether interventions promoted a feeling of ‘us’ and a process of identification with the person with mental illness. We discuss implications for the design of future interventions.
We present current methods for estimating treatment effects and spillover effects under “interference”, a term which covers a broad class of situations in which a unit’s outcome depends not only on treatments received by that unit, but also on treatments received by other units. To the extent that units react to each other, interact, or otherwise transmit effects of treatments, valid inference requires that we account for such interference, which is a departure from the traditional assumption that units’ outcomes are affected only by their own treatment assignment. Interference and associated spillovers may be a nuisance or they may be of substantive interest to the researcher. In this chapter, we focus on interference in the context of randomized experiments. We review methods for when interference happens in a general network setting. We then consider the special case where interference is contained within a hierarchical structure. Finally, we discuss the relationship between interference and contagion. We use the interference R package and simulated data to illustrate key points. We consider efficient designs that allow for estimation of the treatment and spillover effects and discuss recent empirical studies that try to capture such effects.
We propose using fully Bayesian Gaussian process emulation (GPE) as a surrogate for expensive computer experiments of transport infrastructure cut slopes in high-plasticity clay soils that are associated with an increased risk of failure. Our deterioration experiments simulate the dissipation of excess pore water pressure and seasonal pore water pressure cycles to determine slope failure time. It is impractical to perform the number of computer simulations that would be sufficient to make slope stability predictions over a meaningful range of geometries and strength parameters. Therefore, a GPE is used as an interpolator over a set of optimally spaced simulator runs modeling the time to slope failure as a function of geometry, strength, and permeability. Bayesian inference and Markov chain Monte Carlo simulation are used to obtain posterior estimates of the GPE parameters. For the experiments that do not reach failure within model time of 184 years, the time to failure is stochastically imputed by the Bayesian model. The trained GPE has the potential to inform infrastructure slope design, management, and maintenance. The reduction in computational cost compared with the original simulator makes it a highly attractive tool which can be applied to the different spatio-temporal scales of transport networks.
The World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) advise cancer survivors to follow their lifestyle recommendations for cancer prevention. Adhering to these recommendations may have beneficial effects on patient-reported outcomes after a cancer diagnosis, but evidence is scarce. We aimed to assess associations of the individual dietary WCRF/AICR recommendations regarding fruit and vegetables, fibre, fast foods, red and processed meat, sugar-sweetened drinks and alcohol consumption with patient-reported outcomes in colorectal cancer (CRC) survivors. Cross-sectional data of 150 stage I–III CRC survivors, 2–10 years post-diagnosis, were used. Dietary intake was measured by 7-d dietary records. Validated questionnaires were used to measure health-related quality of life (HRQoL), fatigue and neuropathy. Confounder-adjusted linear regression models were used to analyse associations of each WCRF/AICR dietary recommendation with patient-reported outcomes. Higher vegetable intake (per 50 g) was associated with better global QoL (β 2·6; 95 % CI 0·6, 4·7), better physical functioning (3·3; 1·2, 5·5) and lower levels of fatigue (−4·5; −7·6, −1·4). Higher fruit and vegetables intake (per 100 g) was associated with better physical functioning (3·2; 0·8, 5·5) and higher intake of energy-dense food (per 100 kJ/100 g) with worse physical functioning (−4·2; −7·1, −1·2). No associations of dietary recommendations with neuropathy were found. These findings suggest that adhering to specific dietary WCRF/AICR recommendations is associated with better HRQoL and less fatigue in CRC survivors. Although the recommendations regarding healthy dietary habits may be beneficial for the well-being of CRC survivors, longitudinal research is warranted to gain insight into the direction of associations.
Background: Contaminated surfaces within patient rooms and on shared equipment is a major driver of healthcare-acquired infections (HAIs). The emergence of Candida auris in the New York City metropolitan area, a multidrug-resistant fungus with extended environmental viability, has made a standardized assessment of cleaning protocols even more urgent for our multihospital academic health system. We therefore sought to create an environmental surveillance protocol to detect C. auris and to assess patient room contamination after discharge cleaning by different chemicals and methods, including touch-free application using an electrostatic sprayer. Surfaces disinfected using touch-free methods may not appear disinfected when assessed by fluorescent tracer dye or ATP bioluminescent assay. Methods: We focused on surfaces within the patient zone which are touched by the patient or healthcare personnel prior to contact with the patient. Our protocol sampled the over-bed table, call button, oxygen meter, privacy curtain, and bed frame using nylon-flocked swabs dipped in nonbacteriostatic sterile saline. We swabbed a 36-cm2 surface area on each sample location shortly after the room was disinfected, immediately inoculated the swab on a blood agar 5% TSA plate, and then incubated the plate for 24 hours at 36°C. The contamination with common environmental bacteria was calculated as CFU per plate over swabbed surface area and a cutoff of 2.5 CFU/cm2 was used to determine whether a surface passed inspection. Limited data exist on acceptable microbial limits for healthcare settings, but the aforementioned cutoff has been used in food preparation. Results: Over a year-long period, terminal cleaning had an overall fail rate of 6.5% for 413 surfaces swabbed. We used the protocol to compare the normal application of either peracetic acid/hydrogen peroxide or bleach using microfiber cloths to a new method using sodium dichloroisocyanurate (NaDCC) applied with microfiber cloths and electrostatic sprayers. The normal protocol had a fail rate of 9%, and NaDCC had a failure rate of 2.5%. The oxygen meter had the highest normal method failure rate (18.2%), whereas the curtain had the highest NaDCC method failure rate (11%). In addition, we swabbed 7 rooms previously occupied by C. auris–colonized patients for C. auris contamination of environmental surfaces, including the mobile medical equipment of the 4 patient care units that contained these rooms. We did not find any C. auris, and we continue data collection. Conclusions: A systematic environmental surveillance system is critical for healthcare systems to assess touch-free disinfection and identify MDRO contamination of surfaces.
There are several published echo-derived scores to help predict successful biventricular versus univentricular palliation in neonates with critical aortic stenosis. This study aims to determine whether any published scoring system accurately predicted outcomes in these neonates.
Methods:
Single centre, retrospective cohort study including neonates who underwent aortic valve intervention (surgical valvotomy or balloon valvuloplasty) with the intention of biventricular circulation. Primary outcome was survival with biventricular circulation at hospital discharge. Data from their initial neonatal echocardiogram were used to compute the following scores – Rhodes, CHSS 1, Discriminant, CHSS 2, and 2 V.
Results:
Between 01/1999 and 12/2017, 68 neonates underwent aortic valve intervention at a median age of 4 days (range 1–29 days); 35 surgical valvotomy and 33 balloon valvuloplasty. Survival with biventricular circulation was maintained in 60/68 patients at hospital discharge. Of the remaining eight patients, three were converted to univentricular palliation, four died, and one underwent heart transplant prior to discharge. None of the binary score predictions of biventricular versus univentricular (using that score’s proposed cut-offs) were significantly associated with the observed outcome in this cohort. A high percentage of those predicted to need univentricular palliation had successful biventricular repair: 89.4% by Rhodes, 79.3% by CHSS 1, 85.2% by Discriminant, and 66.7% by CHSS 2 score. The 2 V best predicted outcome and agreed with the local approach in most cases.
Conclusion:
This study highlights the limitations of and need for alternative scoring systems/cut-offs for consistently accurate echocardiographic prediction of early outcome in neonates with critical aortic stenosis.
This study examined psychological constructs (delay discounting, grit, future time perspective and subjective social status) in relation to food security status and body weight.
Design:
A simultaneous triangulation mixed methods design was used to collect quantitative and qualitative data. Quantitative data were collected in fifty-six adults. Independent variables included food security status (food secure or food insecure) and BMI category (normal weight or overweight/obese). Participants, matched on race (African American and White), were categorised into four food security status by BMI category groups. Psychological constructs were measured via validated questionnaires. Qualitative data were collected in a subsample of twelve participants via in-depth interviews.
Setting:
This study was conducted in Baton Rouge, Louisiana.
Participants:
The sample was 66 % female and 48 % African American with a mean age of 32·3 (sd 9·2) years and BMI of 28·8 (sd 7·7) kg/m2.
Results:
Quantitative results showed that food-insecure participants with overweight/obesity had greater delay discounting (–3·78 v. –6·16, P = 0·01; –3·78 v. –5·75, P = 0·02) and poorer grit (3·37 v. 3·99, P = 0·02; 3·37 v. 4·02, P = 0·02 ) than their food-secure counterparts and food-insecure participants with normal weight. Food-insecure participants with overweight/obesity also had a shorter time period for financial planning (0·72 v. 4·14, P = 0·02) than food-secure participants with normal weight. Qualitative data largely supported quantitative findings with participants discussing varied perceptions of psychological constructs.
Conclusions:
This study found differences in delaying gratification, grit and financial planning between food security status and body weight groups.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
Methods:
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
Results:
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Conclusion:
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
This research communication addresses the hypothesis that Southeast dairy producers' self-reported bulk tank somatic cell count (BTSCC) was associated with producers' response to three statements (1) ‘a troublesome thing about mastitis is the worries it causes me,’ (2) ‘a troublesome thing about mastitis is that cows suffer,’ and (3) ‘my broad goals include taking good care of my cows and heifers.’ Surveys were mailed to producers in Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee, and Virginia (29% response rate, N = 596; final analysis N = 574), as part of a larger survey to assess Southeastern dairy producers' opinions related to BTSCC. Surveys contained 34 binomial (n = 9), Likert scale (n = 7), and descriptive (n = 18) statements targeted at producer self-assessment of herd records, management practices, and BTSCC. Statements 1 and 2 were assessed on a 5-point Likert scale from ‘strongly disagree’ to ‘strongly agree.’ Statement 3 was assessed on a 5-point Likert scale from ‘very unimportant’ to ‘very important.’ Reported mean BTSCC for all participants was 254 500 cells/ml. Separate univariable logistic regressions using generalized linear mixed models (SAS 9.4, Cary, NC, USA) with a random effect of farm, were performed to determine if BTSCC was associated with probability for a producer's response to statements. If BTSCC was significant, forward manual addition was performed until no additional variables were significant (P ≤ 0.05), but included BTSCC, regardless of significance. Bulk tank somatic cell count was associated with ‘a troublesome thing about mastitis is the worries it causes me,’ but not with Statements 2 or 3. This demonstrates that >75% of Southeastern dairy producers are concerned with animal care and cow suffering, regardless of BTSCC. Understanding Southeast producers' emphasis on cow care is necessary to create targeted management tools for herds with elevated BTSCC.