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Patients with major depressive disorder (MDD) with acute suicidal ideation or behavior (MDSI) require immediate intervention. Though oral antidepressants can be effective at reducing depressive symptoms, they can take 4–6 weeks to reach full effect.
Objectives
This study aimed to identify unmet needs in the treatment of patients with MDSI, specifically exploring the potential clinical benefits of rapid reduction of depressive symptoms.
Methods
A Delphi panel consisting of practicing psychiatrists (n=12) from the US, Canada and EU was conducted between December 2020–June 2021. Panelists were screened to ensure they had sufficient experience with managing patients with MDD and MDSI. Panelists completed two survey rounds, and a virtual consensus meeting.
Results
This research confirmed current unmet needs in the treatment of patients with MDSI.
Hopelessness, functional impairment, worsening of MDD symptoms, recurrent hospitalization and higher risk of suicide attempt were considered as key consequences of the slow onset of action of oral antidepressants.
Treatment with rapid acting antidepressant was anticipated by panelists to provide short-term benefit such as rapid reduction of core MDD symptoms which may contribute to shorter hospital stays and improved patient engagement/compliance, allowing for earlier interventions and improved patient outcomes. For long-term benefits, panelists agreed that improved daily functioning and increased trust/confidence in treatment options, constitute key benefits of rapid-acting treatments
Conclusions
There is need for rapid-acting treatments which may help address key unmet needs and provide clinically meaningful benefits driven by the rapid relief of depressive symptoms particularly in patients with MDSI.
Disclosure
SB, ED, KJ, MO’H, QZ, MM, MH, SR, JA and DZ are employees of Janssen and hold stock in Johnson & Johnson Inc. AN is currently employed by Neurocrine Biosciences Inc. RP is an employee of Adelphi Values PROVE hired by Janssen.
To determine whether a clinician-directed acute respiratory tract infection (ARI) intervention was associated with improved antibiotic prescribing and patient outcomes across a large US healthcare system.
Design:
Multicenter retrospective quasi-experimental analysis of outpatient visits with a diagnosis of uncomplicated ARI over a 7-year period.
Participants:
Outpatients with ARI diagnoses: sinusitis, pharyngitis, bronchitis, and unspecified upper respiratory tract infection (URI-NOS). Outpatients with concurrent infection or select comorbid conditions were excluded.
Intervention(s):
Audit and feedback with peer comparison of antibiotic prescribing rates and academic detailing of clinicians with frequent ARI visits. Antimicrobial stewards and academic detailing personnel delivered the intervention; facility and clinician participation were voluntary.
Measure(s):
We calculated the probability to receive antibiotics for an ARI before and after implementation. Secondary outcomes included probability for a return clinic visits or infection-related hospitalization, before and after implementation. Intervention effects were assessed with logistic generalized estimating equation models. Facility participation was tracked, and results were stratified by quartile of facility intervention intensity.
Results:
We reviewed 1,003,509 and 323,023 uncomplicated ARI visits before and after the implementation of the intervention, respectively. The probability to receive antibiotics for ARI decreased after implementation (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.78–0.86). Facilities with the highest quartile of intervention intensity demonstrated larger reductions in antibiotic prescribing (OR, 0.69; 95% CI, 0.59–0.80) compared to nonparticipating facilities (OR, 0.89; 95% CI, 0.73–1.09). Return visits (OR, 1.00; 95% CI, 0.94–1.07) and infection-related hospitalizations (OR, 1.21; 95% CI, 0.92–1.59) were not different before and after implementation within facilities that performed intensive implementation.
Conclusions:
Implementation of a nationwide ARI management intervention (ie, audit and feedback with academic detailing) was associated with improved ARI management in an intervention intensity–dependent manner. No impact on ARI-related clinical outcomes was observed.
Major depressive disorder (MDD) is a polygenic disorder associated with brain alterations but until recently, there have been no brain-based metrics to quantify individual-level variation in brain morphology. Here, we evaluated and compared the performance of a new brain-based ‘Regional Vulnerability Index’ (RVI) with polygenic risk scores (PRS), in the context of MDD. We assessed associations with syndromal MDD in an adult sample (N = 702, age = 59 ± 10) and with subclinical depressive symptoms in a longitudinal adolescent sample (baseline N = 3,825, age = 10 ± 1; 2-year follow-up N = 2,081, age = 12 ± 1).
Methods
MDD-RVIs quantify the correlation of the individual’s corresponding brain metric with the expected pattern for MDD derived in an independent sample. Using the same methodology across samples, subject-specific MDD-PRS and six MDD-RVIs based on different brain modalities (subcortical volume, cortical thickness, cortical surface area, mean diffusivity, fractional anisotropy, and multimodal) were computed.
Results
In adults, MDD-RVIs (based on white matter and multimodal measures) were more strongly associated with MDD (β = 0.099–0.281, PFDR = 0.001–0.043) than MDD-PRS (β = 0.056–0.152, PFDR = 0.140–0.140). In adolescents, depressive symptoms were associated with MDD-PRS at baseline and follow-up (β = 0.084–0.086, p = 1.38 × 10−4−4.77 × 10−4) but not with any MDD-RVIs (β < 0.05, p > 0.05).
Conclusions
Our results potentially indicate the ability of brain-based risk scores to capture a broader range of risk exposures than genetic risk scores in adults and are also useful in helping us to understand the temporal origins of depression-related brain features. Longitudinal data, specific to the developmental period and on white matter measures, will be useful in informing risk for subsequent psychiatric illness.
Electric vertical take-off and landing aircraft (eVTOLs) have been accessed on various configurations over the past decade. This literature review deals with the issue of determining the appropriate design for an Autonomous Passenger Drone (APD). APDs have been compared with VTOLs on their pros and cons. The authors analysed aerodynamics and propulsion systems of multiple APDs. Further, the comparative analysis aids in designing the best framework for the exterior form of APDs based on human capacity, flying technology, fuel type, travel distance, door type, size, material, safety, cost, etc.
Urban Air Mobility (UAM) can provide new air mobility faster and avoid city traffic with the growth of new technologies. But they need to be co-developed with the city infrastructure. Thus, understanding the working scenarios of UAM and how they will interact with the city and the other modes of transport systems is vital. Storyboarding helps policymakers, city planners, designers, and investors better understand the product's contextual interaction over time. This process allows the design team to be implicit or express a design that is easy to understand, reflect upon, or modify.
Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8–2.3], externalizing (RR = 4.8, 95% CI 3.6–6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2–2.9), and suicidality (2.3, 95% CI 1.8–2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.
Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner.
Methods
Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N = 3212–5369 per phenotype).
Results
The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints [β = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; β = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls.
Conclusions
Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific.
In recent years, the Tooth Cementum Annulations method has been demonstrated to be highly effective at estimating age at death in permanent teeth. Prior to this study, no validation studies have attempted to use TCA to age deciduous teeth. Deciduous teeth provide unique challenges for anthropologists seeking to use the TCA method. Among these are the constraint that cementum annulations are only countable immediately before and after the root apex closes, and the fact that in healthy teeth the cementum record is destined to be destroyed by rhizolysis, so cementum annulations will only be available in teeth that are surgically extracted, or in teeth from juvenile decedents. From a practical standpoint, we found that methods that had previously yielded good results in permanent teeth worked much less well in deciduous teeth. The use of high magnification, bright-field illumination, and analyzing multiple regions of interest per tooth are all recommended for best results.
Although exposure therapy (ET) is an effective treatment for anxiety disorders and obsessive-compulsive disorder, many clinicians report not utilizing it. The present study targeted common utilization barriers by evaluating an intensive ET training experience in a relatively inexperienced sample of pre-professionals. Thirty-two individuals at the undergraduate or college graduate level without formal clinical experience participated as camp counsellors in a 5day exposure-based therapeutic summer camp for youth with anxiety disorders and/or obsessive-compulsive disorder. Participants were trained in ET through a progressive cascading model and answered questionnaires before and after camp. Repeated measure MANOVA revealed significantly increased feelings of self-efficacy conducting exposures, and significantly decreased feelings of disgust sensitivity and contamination-related disgust from pre-camp to post-camp. A subset of individuals providing data 1 month after the camp maintained a significant gain in ET self-efficacy. Regression analyses revealed that contamination-related disgust, but not disgust sensitivity, significantly predicted post-camp ET self-efficacy. These findings suggest that individuals early into their post-secondary education can learn ET, and the progressive cascading model holds promise in its utility across experience levels and warrants further investigation. Disgust may also play a role in feelings of competency conducting ET. Implications on dissemination and implementation efforts are also discussed.
Key learning aims
(1) How can training of CBT techniques such as exposure occur prior to graduate education?
(2) Can self-efficacy in conducting exposures meaningfully increase in an experiential training of pre-professionals?
(3) How does an individual’s tolerance of disgust impact feelings of competence conducting exposures?
People who use drugs (PWUD) are now at the intersection of two public health emergencies – the Covid-19 pandemic and the overdose crisis. They may be at heightened risk of overdose due to increased isolation, worsened mental health, and changes to the illicit drug supply. The province of British Columbia (BC) in Canada is anticipated to experience a record-breaking year of overdose deaths as over 1,500 people (32.9 deaths per 100,000) have died from overdose in 2020. In response, BC released new clinical guidelines in March to allow the prescribing of pharmaceutical alternatives aiming to reduce PWUD’s risk of overdose and contracting Covid-19.
Objectives
We examined the risk and protective factors for overdose during these dual crises. We explored how the Covid-19 pandemic has impacted the mental health and substance use of PWUD and their access to treatment and harm reduction services.
Methods
We are conducting a survey among patients with opioid use disorder at a major hospital in Vancouver, BC. It includes the following domains: sociodemographic characteristics; mental and physical health; substance use patterns; opioid overdose history; access to treatment, harm reduction services; impacts of Covid-19.
Results
We anticipate collecting data from 200 participants. Descriptive statistics and regression analysis will be conducted to describe the sample and determine the risk, protective factors for overdose.
Conclusions
We will gain a better understanding of overdose risk in PWUD who are now navigating the complex challenges created by the dual crises. This will in turn inform the establishment of evidence-based strategies to reduce their overdose risk.
This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States and other exemptions as specified by federal or state law. The consensus statement also supports COVID-19 vaccination of nonemployees functioning at a healthcare facility (eg, students, contract workers, volunteers, etc).
Transcranial direct current stimulation (tDCS) could be a side-effect-free alternative to psychostimulants in attention-deficit/hyperactivity disorder (ADHD). Although there is limited evidence for clinical and cognitive effects, most studies were small, single-session and stimulated left dorsolateral prefrontal cortex (dlPFC). No sham-controlled study has stimulated the right inferior frontal cortex (rIFC), which is the most consistently under-functioning region in ADHD, with multiple anodal-tDCS sessions combined with cognitive training (CT) to enhance effects. Thus, we investigated the clinical and cognitive effects of multi-session anodal-tDCS over rIFC combined with CT in double-blind, randomised, sham-controlled trial (RCT, ISRCTN48265228).
Methods
Fifty boys with ADHD (10–18 years) received 15 weekday sessions of anodal- or sham-tDCS over rIFC combined with CT (20 min, 1 mA). ANCOVA, adjusting for baseline measures, age and medication status, tested group differences in clinical and ADHD-relevant executive functions at posttreatment and after 6 months.
Results
ADHD-Rating Scale, Conners ADHD Index and adverse effects were significantly lower at post-treatment after sham relative to anodal tDCS. No other effects were significant.
Conclusions
This rigorous and largest RCT of tDCS in adolescent boys with ADHD found no evidence of improved ADHD symptoms or cognitive performance following multi-session anodal tDCS over rIFC combined with CT. These findings extend limited meta-analytic evidence of cognitive and clinical effects in ADHD after 1–5 tDCS sessions over mainly left dlPFC. Given that tDCS is commercially and clinically available, the findings are important as they suggest that rIFC stimulation may not be indicated as a neurotherapy for cognitive or clinical remediation for ADHD.
The timing and duration of the coldest period in the last glacial stage, often referred to as the last glacial maximum (LGM), has been observed to vary spatially and temporally. In Australia, this period is characterised by colder, and in some places more arid, climates than today. We applied Monte-Carlo change point analysis to all available continuous proxy records covering this period, primarily pollen records, from across Australia (n = 37) to assess this change. We find a significant change point occurred (within uncertainty) at 28.6 ± 2.8 ka in 25 records. We interpret this change as a shift to cooler climates, associated with a widespread decline in biological productivity. An additional change point occurred at 17.7 ± 2.2 ka in 24 records. We interpret this change as a shift towards warmer climates, associated with increased biological productivity. We broadly characterise the period between 28.6 (± 2.8) – 17.7 (± 2.2) ka as an extended period of maximum cooling, with low productivity vegetation that may have occurred as a combined response to reduced temperatures, lower moisture availability and atmospheric CO2. These results have implications for how the spatial and temporal coherence of climate change, in this case during the LGM, can be best interrogated and interpreted.
ABSTRACT IMPACT: This is the first study to use QUINT analyses to examine heterogeneity of treatment effect for group medical visits among individuals with type 2 diabetes. QUINT is a data driven method that assumes no a priori assumptions regarding effect moderators - an important step in the path towards personalized medicine. OBJECTIVES/GOALS: To examine heterogeneity of treatment effect (HTE) in Jump Start, a trial that compared the effectiveness of group medical visits (GMVs) focused on medication management only versus the addition of intensive weight management (WM) on glycemic control for patients with type 2 diabetes and body mass index >=27kg/m^2. METHODS/STUDY POPULATION: Jump Start patients (n=263) were randomized to a GMV-based medication management plus low carbohydrate diet-focused WM program (WM/GMV; n = 127) or GMV-based medication management only (GMV; n = 136) for diabetes control. We used QUalitative INteraction Trees (QUINT), a tree-based clustering method, to determine if there were subgroups of patients who derived greater benefit from either WM/GMV or GMV. Subgroup predictors included 32 baseline demographic, clinical, and psychosocial factors. Outcome was hemoglobin A1c (HbA1c). We conducted internal validation via bootstrap resampling to estimate bias in the range of mean outcome differences among arms. RESULTS/ANTICIPATED RESULTS: QUINT analyses indicated that for patients who had not previously attempted weight loss, WM/GMV resulted in better glycemic control than GMV alone (mean difference in HbA1c improvement = 1.48%). For patients who had previously attempted weight loss and had lower cholesterol and blood urea nitrogen levels, GMV alone was better than WM/GMV (mean difference in HbA1c improvement = 1.51%). Internal validation resulted in moderate corrections in the mean HbA1c differences between arms; however, differences remained in the clinically significant range. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among patients with diabetes and BMI>=27kg/m^2, a low-carbohydrate, weight loss focus may better improve HbA1c in those who have never attempted weight loss. A medication management focus may be better in those who have attempted weight loss and have lower cholesterol and blood urea nitrogen.
Emerging from the warehouse of knowledge about terrestrial ecosystem functioning and the application of the systems ecology paradigm, exemplified by the power of simulation modeling, tremendous strides have been made linking the interactions of the land, atmosphere, and water locally to globally. Through integration of ecosystem, atmospheric, soil, and more recently social science interactions, plausible scenarios and even reasonable predictions are now possible about the outcomes of human activities. The applications of that knowledge to the effects of changing climates, human-caused nitrogen enrichment of ecosystems, and altered UV-B radiation represent challenges addressed in this chapter. The primary linkages addressed are through the C, N, S, and H2O cycles, and UV-B radiation. Carbon dioxide exchanges between land and the atmosphere, N additions and losses to and from lands and waters, early studies of SO2 in grassland ecosystem, and the effects of UV-B radiation on ecosystems have been mainstays of research described in this chapter. This research knowledge has been used in international and national climate assessments, for example the IPCC, US National Climate Assessment, and Paris Climate Accord. Likewise, the knowledge has been used to develop concepts and technologies related to sustainable agriculture, C sequestration, and food security.
This study aimed to evaluate and compare simultaneous integrated boost-based volumetric modulated arc therapy (SIB-VMAT) of head-and-neck plans optimised using segmented and non-segmented intermediate-risk target volumes.
Materials and methods:
CT data of 20 patients with locally advanced laryngeal cancer treated with radical chemoradiation were included retrospectively. Both segmented [planning target volume (PTV) IR!] and non-segmented PTV (PTV IR) volumes were created for the intermediate-risk volume. Correspondingly, two VMAT plans were generated for every CT dataset. Dosimetry parameters obtained from cumulative dose volume histogram and the quality indices such as conformity and homogeneity indices were evaluated for both plans and were statistically analysed.
Results:
Maximum dose of PTV IR! was observed to be higher in the non-segmented plans (7281·45 versus 7075·75 cGy) and was statistically significant (p = 0·002). Homogeneity index (HI) of PTV IR! in segmented plans fared better compared to non-segmented plans (0·1 versus 0·12, p = 0·01). All other dosimetry parameters were found to be similar in both plans.
Conclusion:
This study shows that using segmented volumes for planning will lead to more homogenous plans with regard to intermediate- and low-risk volumes, especially under controlled settings.
Salivary duct carcinoma (SDC) is an extremely rare and aggressive subtype of salivary gland cancer with high morbidity and mortality and poor response to treatment. The current options of treatment include radical surgery followed by radiotherapy (RT) with or without chemotherapy. The aim of this study was to analyse the patterns of recurrences, possible predictors of outcome and role of RT in a cohort of patients with non-metastatic SDC.
Methods:
A retrospective review of patients treated between 2010 and 2019 with histologically proven non-metastatic SDC was conducted.
Results:
Sixteen patients were included in the series. Median follow-up was 25 months. Progression-free survival (PFS) and overall survival (OS) at 12 months were 61% and 80%, respectively. Seven out of the 16 patients had disease progression, distant metastases being most frequent. Four patients died due to disease progression. PFS was significantly worse for patients with pathological neck node positivity (p = 0·036) and peri-parotid nodes (p = 0·007). Local control was significantly associated with RT (p = 0·011). Addition of any chemotherapy, regardless of either concurrent or adjuvant, had no impact on the PFS or OS. Pathological neck node positivity with nodal stage of N2 or higher correlated significantly with worse OS (p = 0·031).
Conclusion:
Salivary ductal carcinoma is an aggressive malignancy with high metastatic potential. Inferior prognosis was observed among patients who had metastatic deposits in either cervical nodes or peri-parotid nodes on histopathology. As systemic failures are more predominant among these patients, larger prospective trials are needed to formulate an optimum strategy for choice and sequencing of first-line systemic therapy.
The aim of this study was to establish arytenoid asymmetry as a pre-operative predictive parameter for arytenoid adduction surgery in unilateral vocal fold paralysis and thereafter identify the most predictive parameter for arytenoid adduction among the established parameters.
Methods
A retrospective comparative study was undertaken. The ‘arytenoid asymmetry angle’ formed between skewed ‘glottic’ and ‘interarytenoid’ axes (traced along the plane of closure of the membranous and cartilaginous glottis, respectively) was quantified in pre-operative laryngoscopic images of 85 adults with unilateral vocal fold paralysis who underwent either type 1 thyroplasty (group 1) or type 1 thyroplasty with arytenoid adduction (group 2). The need for arytenoid adduction was determined intra-operatively based on subjective voice improvement and laryngoscopic results.
Results
Arytenoid asymmetry (p < 0.0001), posterior phonatory gap (p = 0.001) and vertical level difference (p = 0.004) were significantly greater in group 2 (descending order of parameters). Arytenoid asymmetry angle showed a significant positive correlation with the latter two parameters.
Conclusion
Arytenoid asymmetry is the most predictive parameter for arytenoid adduction. An arytenoid asymmetry angle of more than or equal to 33.9⁰ is an indication for arytenoid adduction. This aids in pre-operative planning of arytenoid adduction.
To highlight the importance of imaging in reducing an accidental injury to the anomalous brachiocephalic trunk and its branches during tracheal surgery.
Case report
This paper reports two cases of accidental injury to the great vessels in the neck during tracheal surgery. The first incident occurred during a repeat tracheostomy, when the right common carotid artery was injured. On reviewing the computed tomography images, the bifurcation of the brachiocephalic artery was seen to the left of the midline, and the right common carotid artery was adherent just below the tracheostomy site. The second incident happened during surgery for tracheal stenosis, when there was an inadvertent injury to the main brachiocephalic trunk, which was adherent to the trachea in the lower neck region.
Conclusion
For airway surgeons, radiological assessment of vascular structures in relation to the trachea prior to surgery is as important as the endoluminal airway assessment for the best outcome.