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Cognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.
A randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.
Intention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).
Group IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
In response to advancing clinical practice guidelines regarding concussion management, service members, like athletes, complete a baseline assessment prior to participating in high-risk activities. While several studies have established test stability in athletes, no investigation to date has examined the stability of baseline assessment scores in military cadets. The objective of this study was to assess the test–retest reliability of a baseline concussion test battery in cadets at U.S. Service Academies.
All cadets participating in the Concussion Assessment, Research, and Education (CARE) Consortium investigation completed a standard baseline battery that included memory, balance, symptom, and neurocognitive assessments. Annual baseline testing was completed during the first 3 years of the study. A two-way mixed-model analysis of variance (intraclass correlation coefficent (ICC)3,1) and Kappa statistics were used to assess the stability of the metrics at 1-year and 2-year time intervals.
ICC values for the 1-year test interval ranged from 0.28 to 0.67 and from 0.15 to 0.57 for the 2-year interval. Kappa values ranged from 0.16 to 0.21 for the 1-year interval and from 0.29 to 0.31 for the 2-year test interval. Across all measures, the observed effects were small, ranging from 0.01 to 0.44.
This investigation noted less than optimal reliability for the most common concussion baseline assessments. While none of the assessments met or exceeded the accepted clinical threshold, the effect sizes were relatively small suggesting an overlap in performance from year-to-year. As such, baseline assessments beyond the initial evaluation in cadets are not essential but could aid concussion diagnosis.
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.
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.
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.
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.
Guidelines recommend empowering patients and families to remind healthcare workers (HCWs) to perform hand hygiene (HH). The effectiveness of empowerment tools for patients and their families in Southeast Asia is unknown.
We performed a prospective study in a pediatric intensive care unit (PICU) of a Vietnamese pediatric referral hospital. With family and HCW input, we developed a visual tool for families to prompt HCW HH. We used direct observation to collect baseline HH data. We then enrolled families to receive the visual tool and education on its use while continuing prospective collection of HH data. Multivariable logistic regression was used to identify independent predictors of HH in baseline and implementation periods.
In total, 2,014 baseline and 2,498 implementation-period HH opportunities were observed. During the implementation period, 73 families were enrolled. Overall, HCW HH was 46% preimplementation, which increased to 73% in the implementation period (P < .001). The lowest HH adherence in both periods occurred after HCW contact with patient surroundings: 16% at baseline increased to 24% after implementation. In multivariable analyses, the odds of HCW HH during the implementation period were significantly higher than baseline (adjusted odds ratio [aOR], 2.94; 95% confidence interval [CI], 2.54–3.41; P < .001) after adjusting for observation room, HCW type, time of observation (weekday business hours vs evening or weekend), and HH moment.
The introduction of a visual empowerment tool was associated with significant improvement in HH adherence among HCWs in a Vietnamese PICU. Future research should explore acceptability and barriers to use of similar tools in low- and middle-income settings.
Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Evidence from high-income countries suggests that childhood trauma is associated with schizophrenia. Studies of childhood trauma and schizophrenia in low and middle income (LMIC) countries are limited. This study examined the prevalence of childhood traumatic experiences among cases and controls and the relationship between specific and cumulative childhood traumatic experiences and schizophrenia in a sample in South Africa.
Data were from the Genomics of Schizophrenia in the South African Xhosa people study. Cases with schizophrenia and matched controls were recruited from provincial hospitals and clinics in the Western and Eastern Cape regions in South Africa. Childhood traumatic experiences were measured using the Childhood Trauma Questionnaire (CTQ). Adjusted logistic regression models estimated associations between individual and cumulative childhood traumatic experiences and schizophrenia.
Traumatic experiences were more prevalent among cases than controls. The odds of schizophrenia were 2.44 times higher among those who experienced any trauma than those who reported no traumatic experiences (95% CI 1.77–3.37). The odds of schizophrenia were elevated among those who experienced physical/emotional abuse (OR 1.59, CI 1.28–1.97), neglect (OR 1.39, CI 1.16–1.68), and sexual abuse (OR 1.22, CI 1.03–1.45) compared to those who did not. Cumulative physical/emotional abuse and neglect experiences increased the odds of schizophrenia as a dose–response relationship.
Childhood trauma is common in this population. Among many other benefits, interventions to prevent childhood trauma may contribute to a decreasing occurrence of schizophrenia.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
In product design engineering (PDE), ideation involves the generation of technical behaviours and physical structures to address specific functional requirements. This differs from generic creative ideation tasks, which emphasise functional and technical considerations less. To advance knowledge about the neural basis of PDE ideation, we present the first fMRI study on professional product design engineers practising in industry. We aimed to explore brain activation during ideation, and compare activation in open-ended and constrained tasks. Imagery manipulation tasks were contrasted with ideation tasks in a sample of 29 PDE professionals. The key findings were: (1) PDE ideation is associated with greater activity in left cingulate gyrus; (2) there were no significant differences between open-ended and constrained tasks; and (3) a preliminary association with activity in the right superior temporal gyrus was also observed. The results are consistent with existing fMRI work on generic creative ideation, suggesting that PDE ideation may share a number of similarities at the neural level. Future work includes: functional connectivity analysis of open-ended and constrained ideation to further investigate potential differences; investigating the effects of aspects of design expertise/training on processing; and the use of novelty measures directly linked to the designer’s internal processing in fMRI analysis.
Early identification of infants with CHD at heightened risk of developmental delays can inform surveillance priorities. This study investigated pre-operative and post-operative neuromotor performance in infants undergoing open-heart surgery, and their developmental status at 6 months of age, to identify risk factors and inform care pathways.
Infants undergoing open-heart surgery before 4 months of age were recruited into a prospective cohort study. Neuromotor performance was assessed pre-operatively and post-operatively using the Test of Infant Motor Performance and Prechtl’s Assessment of General Movements. Development was assessed at 6 months of age using the Ages and Stages Questionnaire third edition. Pre-operative and post-operative General Movements performance was compared using McNemar’s test and test of infant motor performance z-scores using Wilcoxon’s signed rank test. Risk factors for delayed development at 6 months were explored using logistic regression.
Sixty infants were included in this study. In the 23 (38%) infants. A total of 60 infants were recruited. In the 23 (38%) infants assessed pre-operatively, there was no significant difference between pre- and post-operative performance on the GMs (p=0.63) or TIMP (p=0.28). At discharge, 15 (26%) infants presented with abnormal GMs, and the median TIMP z-score was −0.93 (IQR: −1.4 to −0.69). At 6 months, 28 (52.8%) infants presented with gross motor delay on the ASQ-3, significantly negatively associated with gestational age (p=0.03), length of hospital stay (p=0.04) and discharge TIMP score (p=0.01).
Post-operative assessment using the GMs and TIMP may be useful to identify infants requiring individualised care and targeted developmental follow-up. Long-term developmental surveillance beyond 6 months of age is recommended.
Indigenous women and children experience some of the most profound health disparities globally. These disparities are grounded in historical and contemporary trauma secondary to colonial atrocities perpetuated by settler society. The health disparities that exist for chronic diseases may have their origins in early-life exposures that Indigenous women and children face. Mechanistically, there is evidence that these adverse exposures epigenetically modify genes associated with cardiometabolic disease risk. Interventions designed to support a resilient pregnancy and first 1000 days of life should abrogate disparities in early-life socioeconomic status. Breastfeeding, prenatal care and early child education are key targets for governments and health care providers to start addressing current health disparities in cardiometabolic diseases among Indigenous youth. Programmes grounded in cultural safety and co-developed with communities have successfully reduced health disparities. More works of this kind are needed to reduce inequities in cardiometabolic diseases among Indigenous women and children worldwide.
Background: When measuring young Duchenne Muscular Dystrophy (DMD) patients’ health-related quality of life (HRQoL), parent-proxy reports are heavily relied on. Therefore, it is imperative that the relationship between parent-proxy and child self-report HRQoL is understood. This study examined the level of agreement between children and their parent-proxy rating of the child’s HRQoL. Methods: We used FOR-DMD clinical trial baseline data. HRQoL, measured using the PedsQL inventory, was reported by 178 parent and child (ages 4 to 7 years) dyads. Intracorrelation coefficients (ICC) measured absolute agreement while paired t-tests determined differences in the average HRQoL ratings between groups. Results: The level of agreement between child and parent-proxy ratings of HRQoL was poor for the generic PedsQL scale (ICC: 0.29) and its subscales; and, similarly low for the neuromuscular disease module (ICC:0.16). On average, parents rated their child’s HRQoL as poorer than the children rated themselves in all scales except for psychosocial and school functioning. Conclusions: Child and parent-proxy HRQoL ratings are discordant in this study sample, as occurs in other chronic pediatric diseases. This should be taken into account when interpreting clinical and research HRQoL findings in this population. Future studies should examine reasons for parents’ perception of poorer HRQoL than that reported by their children.
Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. In June 2017, Health Canada approved Nusinersen, currently the only available drug for SMA. Since 2016, patients in Ontario have been treated clinically with Nusinersen through different access programs. Methods: Retrospective case series of patients with SMA treated clinically with Nusinersen in Ontario, describing clinical characteristics and logistics of intrathecal Nusinersen administration. Results: Twenty patients have been treated across four centres. To date, we have reviewed 8 cases at one centre (seven SMA Type I, one SMA Type II). Age at first dose ranged from 3-156 months and disease duration 9-166 months. Patients had received 4-7 doses at last evaluation. Three patients with scoliosis (2 with spinal rods) required fluoroscopy-guided radiologist administration, and 4 required general anesthesia. No complications/adverse events were reported. At last follow up, 5/8 families reported improved daily activities. Of 5 patients with baseline and follow up motor function testing, 3 demonstrated improved scores. One patient died due to respiratory decline at age 9 months, despite improved motor outcome scores. Conclusions: We describe the first Canadian post-marketing experience with Nusinersen. Timely dissemination of this information is needed to guide clinicians, hospital administrators, and policy-makers.
The effect of transportation and lairage on the faecal shedding and post-slaughter contamination of carcasses with Escherichia coli O157 and O26 in young calves (4–7-day-old) was assessed in a cohort study at a regional calf-processing plant in the North Island of New Zealand, following 60 calves as cohorts from six dairy farms to slaughter. Multiple samples from each animal at pre-slaughter (recto-anal mucosal swab) and carcass at post-slaughter (sponge swab) were collected and screened using real-time PCR and culture isolation methods for the presence of E. coli O157 and O26 (Shiga toxin-producing E. coli (STEC) and non-STEC). Genotype analysis of E. coli O157 and O26 isolates provided little evidence of faecal–oral transmission of infection between calves during transportation and lairage. Increased cross-contamination of hides and carcasses with E. coli O157 and O26 between co-transported calves was confirmed at pre-hide removal and post-evisceration stages but not at pre-boning (at the end of dressing prior to chilling), indicating that good hygiene practices and application of an approved intervention effectively controlled carcass contamination. This study was the first of its kind to assess the impact of transportation and lairage on the faecal carriage and post-harvest contamination of carcasses with E. coli O157 and O26 in very young calves.
Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan–Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.
The Molonglo Observatory Synthesis Telescope (MOST) is an 18000 m2 radio telescope located 40 km from Canberra, Australia. Its operating band (820–851 MHz) is partly allocated to telecommunications, making radio astronomy challenging. We describe how the deployment of new digital receivers, Field Programmable Gate Array-based filterbanks, and server-class computers equipped with 43 Graphics Processing Units, has transformed the telescope into a versatile new instrument (UTMOST) for studying the radio sky on millisecond timescales. UTMOST has 10 times the bandwidth and double the field of view compared to the MOST, and voltage record and playback capability has facilitated rapid implementaton of many new observing modes, most of which operate commensally. UTMOST can simultaneously excise interference, make maps, coherently dedisperse pulsars, and perform real-time searches of coherent fan-beams for dispersed single pulses. UTMOST operates as a robotic facility, deciding how to efficiently target pulsars and how long to stay on source via real-time pulsar folding, while searching for single pulse events. Regular timing of over 300 pulsars has yielded seven pulsar glitches and three Fast Radio Bursts during commissioning. UTMOST demonstrates that if sufficient signal processing is applied to voltage streams, innovative science remains possible even in hostile radio frequency environments.