To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.
This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.
A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.
The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.
This study considers the textiles made, traded, and exchanged across Eurasia from late antiquity to the late Middle Ages with special attention to the socio-political and cultural aspects of this universal medium. It presents a wide range of textiles used in both domestic and religious settings, as dress and furnishings, and for elite and ordinary owners. The introduction presents historiographical background to the study of textiles and explains the conditions of their survival in archaeological contexts and museums. A section on the materials and techniques used to produce textiles if followed by those outlining textile production, industry, and trade across Eurasia. Further sections examine the uses for dress and furnishing textiles and the appearance of imported fabrics in European contexts, addressing textiles' functions and uses in medieval societies. Lastly, a concluding section on textile aesthetics connects fabrics to their broader visual and material context.
Illicit substance use is dangerous in both acute and chronic forms, frequently resulting in lethal poisoning, addiction, and other negative consequences. Similar to research in other psychiatric conditions, whose ultimate goal is to enable effective prevention and treatment, studies in substance use are focused on factors elevating the risk for the disorder. The rapid growth of the substance use problem despite the effort invested in fighting it, however, suggests the need in changing the research approach. Instead of attempting to identify risk factors, whose neutralization is often infeasible if not impossible, it may be more promising to systematically reverse the perspective to the factors enhancing the aspect of liability to disorder that shares the same dimension but is opposite to risk, that is, resistance to substance use. Resistance factors, which enable the majority of the population to remain unaffected despite the ubiquity of psychoactive substances, may be more amenable to translation. While the resistance aspect of liability is symmetric to risk, the resistance approach requires substantial changes in sampling (high-resistance rather than high-risk) and using quantitative indices of liability. This article provides an overview and a practical approach to research in resistance to substance use/addiction, currently implemented in a NIH-funded project. The project benefits from unique opportunities afforded by the data originating from two longitudinal twin studies, the Virginia Twin Study of Adolescent and Behavioral Development and the Minnesota Twin Family Study. The methodology described is also applicable to other psychiatric disorders.
Adequate dietary protein intake is important in human subjects for maintaining muscle turnover, determining the protein content of tissues and thus the preservation of muscle mass and function as we age. A screening tool to assess if an older individual is likely to have a lower dietary protein intake (predicted probability of protein intake ≤1⋅0 g/kg per d), has been developed for a Netherlands dietary profile, but this has not been validated in a UK population. This study aimed to adapt and then validate the protein screening tool for use in a UK population. Amendment of the tool was undertaken using data from UK BioBank and the UK National Diet and Nutrition Survey to reflect protein sources in the UK diet. Validation of the amended version of the protein screener screening tool was conducted using protein intake derived from a food frequency questionnaire (FFQ) in a sample of UK adults (n = 184) (age range 18–91 years) as the reference standard. Using the FFQ, 40 % of respondents (n = 74) reported a protein intake of ≤1⋅0 g per kg body mass. The discriminative accuracy of the amended screener was tested using receiver operating characteristic (ROC) curves. The area under the curve for the ROC was 0⋅731 (95 % CI 0⋅657, 0⋅805), indicating that the amended screener may be a valid tool to screen for individuals consuming ≤1⋅0 g/kg adjusted BM/d in an adult UK population. This protein screener tool is a potential method to screen individuals with a likelihood of habitually consuming protein intakes of ≤1⋅0 g/kg per d. Further validation is needed using a more robust dietary intake methodology and for specific groups, such as older adults. The screener may be applicable across healthcare, clinical and research applications.
We developed an agent-based model using a trial emulation approach to quantify effect measure modification of spillover effects of pre-exposure prophylaxis (PrEP) for HIV among men who have sex with men (MSM) in the Atlanta-Sandy Springs-Roswell metropolitan area, Georgia. PrEP may impact not only the individual prescribed, but also their partners and beyond, known as spillover. We simulated a two-stage randomised trial with eligible components (≥3 agents with ≥1 HIV+ agent) first randomised to intervention or control (no PrEP). Within intervention components, agents were randomised to PrEP with coverage of 70%, providing insight into a high PrEP coverage strategy. We evaluated effect modification by component-level characteristics and estimated spillover effects on HIV incidence using an extension of randomisation-based estimators. We observed an attenuation of the spillover effect when agents were in components with a higher prevalence of either drug use or bridging potential (if an agent acts as a mediator between ≥2 connected groups of agents). The estimated spillover effects were larger in magnitude among components with either higher HIV prevalence or greater density (number of existing partnerships compared to all possible partnerships). Consideration of effect modification is important when evaluating the spillover of PrEP among MSM.
Consumption of unpasteurised milk in the United States has presented a public health challenge for decades because of the increased risk of pathogen transmission causing illness outbreaks. We analysed Foodborne Disease Outbreak Surveillance System data to characterise unpasteurised milk outbreaks. Using Poisson and negative binomial regression, we compared the number of outbreaks and outbreak-associated illnesses between jurisdictions grouped by legal status of unpasteurised milk sale based on a May 2019 survey of state laws. During 2013–2018, 75 outbreaks with 675 illnesses occurred that were linked to unpasteurised milk; of these, 325 illnesses (48%) were among people aged 0–19 years. Of 74 single-state outbreaks, 58 (78%) occurred in states where the sale of unpasteurised milk was expressly allowed. Compared with jurisdictions where retail sales were prohibited (n = 24), those where sales were expressly allowed (n = 27) were estimated to have 3.2 (95% CI 1.4–7.6) times greater number of outbreaks; of these, jurisdictions where sale was allowed in retail stores (n = 14) had 3.6 (95% CI 1.3–9.6) times greater number of outbreaks compared with those where sale was allowed on-farm only (n = 13). This study supports findings of previously published reports indicating that state laws resulting in increased availability of unpasteurised milk are associated with more outbreak-associated illnesses and outbreaks.
Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined.
Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith–Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart.
Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment.
These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.
Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.
To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.
We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.
The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.
In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.
OBJECTIVES/GOALS: To describe and evaluate an innovative university-community vaccination and food access model for minority, immigrant, and underserved individuals experiencing food insecurity during a global pandemic. METHODS/STUDY POPULATION: The Purdue University Center for Health Equity and Innovation (CHEqI) partnered with the two largest food banks in the Midwest and Walgreens to offer free COVID-19 and Flu vaccinations alongside food distribution. Goals included addressing food insecurity, increasing vaccine access, and decreasing vaccine hesitancy. CHEqI acquired funding, recruited volunteers and interpreters, assessed interest and addressed vaccine hesitancy. Food bank/pantry partners distributed food and provided access to clientele and marketing assistance. Walgreens procured, administered, and documented vaccinations. The Model accommodated drive-through and indoor processes. Unidentifiable observational and self-report data were collected. Descriptive statistics were computed to characterize program outcomes. RESULTS/ANTICIPATED RESULTS: A total of 11 vaccination events occurred between June and October 2021 at three food bank/pantry locations. Of these 11 events, nine (82%) were drive-through and two (18%) took place indoors, eight (72%) offered COVID-19 vaccinations only, and three (27%) offered both COVID-19 and Flu vaccinations. Food was distributed to a total of 5,108 families and 416 vaccines (314 COVID, 102 Flu) were administered. Of the 396 individuals who received at least one vaccine, 20 (5%) received both a COVID and Flu vaccine. Of the 386 individuals who received at least one vaccine and reported their sex, 194 (50%) identified as female and the average age of those who received at least one vaccine was 45 years old. Of those who reported race (N = 228) or ethnicity (N = 253), 43% identified as Black or African American and 53% identified as LatinX. DISCUSSION/SIGNIFICANCE: Findings offer an innovative vaccination and food access model for diverse individuals experiencing food insecurity during a global pandemic. By drawing on cost effective, accessible, and culturally contextualized practices to optimize the reach and quality of vaccination services we can improve access barriers and mitigate health disparities.
The juvenile justice system in the USA adjudicates over seven hundred thousand youth in the USA annually with significant behavioral offenses. This study aimed to test the effect of juvenile justice involvement on adult criminal outcomes.
Analyses were based on a prospective, population-based study of 1420 children followed up to eight times during childhood (ages 9–16; 6674 observations) about juvenile justice involvement in the late 1990 and early 2000s. Participants were followed up years later to assess adult criminality, using self-report and official records. A propensity score (i.e. inverse probability) weighting approach was used that approximated an experimental design by balancing potentially confounding characteristics between children with v. without juvenile justice involvement.
Between-groups differences on variables that elicit a juvenile justice referral (e.g. violence, property offenses, status offenses, and substance misuse) were attenuated after applying propensity-based inverse probability weights. Participants with a history of juvenile justice involvement were more likely to have later official and violent felony charges, and to self-report police contact and spending time in jail (ORs from 2.5 to 3.3). Residential juvenile justice involvement was associated with the highest risk of both, later official criminal records and self-reported criminality (ORs from 5.1 to 14.5). Sensitivity analyses suggest that our findings are likely robust to potential unobserved confounders.
Juvenile justice involvement was associated with increased risk of adult criminality, with residential services associated with highest risk. Juvenile justice involvement may catalyze rather than deter from adult offending.
The aim of the social and behavioral sciences is to understand human behavior across a wide array of contexts. Our theories often make sweeping claims about human nature, assuming that our ancestors or offspring will be prone to the same biases and preferences. Yet we gloss over the fact that our research is often based in a single temporal context with a limited set of stimuli. Political and moral psychology are domains in which the context and stimuli are likely to matter a great deal (Van Bavel, Mende-Siedlecki, Brady, & Reinero, 2016). In response to Yarkoni (see BBS issue), we delve into topics related to political and moral psychology that likely depend on features of the research. These topics include understanding differences between liberals and conservatives, when people are willing to sacrifice someone to save others, the behavior of political leaders, and the dynamics of intergroup conflict.
Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.
Inpatient surgical site infections (SSIs) cause morbidity in children. The SSI rate among pediatric ambulatory surgery patients is less clear. To fill this gap, we conducted a multiple-institution, retrospective epidemiologic study to identify incidence, risk factors, and outcomes.
We identified patients aged <22 years with ambulatory visits between October 2010 and September 2015 via electronic queries at 3 medical centers. We performed sample chart reviews to confirm ambulatory surgery and adjudicate SSIs. Weighted Poisson incidence rates were calculated. Separately, we used case–control methodology using multivariate backward logistical regression to assess risk-factor association with SSI.
In total, 65,056 patients were identified by queries, and we performed complete chart reviews for 13,795 patients; we identified 45 SSIs following ambulatory surgery. The weighted SSI incidence following pediatric ambulatory surgery was 2.00 SSI per 1,000 ambulatory surgeries (95% confidence interval [CI], 1.37–3.00). Integumentary surgeries had the highest weighted SSI incidence, 3.24 per 1,000 ambulatory surgeries (95% CI, 0.32–12). The following variables carried significantly increased odds of infection: clean contaminated or contaminated wound class compared to clean (odds ratio [OR], 9.8; 95% CI, 2.0–48), other insurance type compared to private (OR, 4.0; 95% CI, 1.6–9.8), and surgery on weekend day compared to weekday (OR, 30; 95% CI, 2.9–315). Of the 45 instances of SSI following pediatric ambulatory surgery, 40% of patients were admitted to the hospital and 36% required a new operative procedure or bedside incision and drainage.
Our findings suggest that morbidity is associated with SSI following ambulatory surgery in children, and we also identified possible targets for intervention.
The number of people over the age of 65 attending Emergency Departments (ED) in the United Kingdom (UK) is increasing. Those who attend with a mental health related problem may be referred to liaison psychiatry for assessment. Improving responsiveness and integration of liaison psychiatry in general hospital settings is a national priority. To do this psychiatry teams must be adequately resourced and organised. However, it is unknown how trends in the number of referrals of older people to liaison psychiatry teams by EDs are changing, making this difficult.
We performed a national multi-centre retrospective service evaluation, analysing existing psychiatry referral data from EDs of people over 65. Sites were selected from a convenience sample of older peoples liaison psychiatry departments. Departments from all regions of the UK were invited to participate via the RCPsych liaison and older peoples faculty email distribution lists. From departments who returned data, we combined the date and described trends in the number and rate of referrals over a 7 year period.
Referral data from up to 28 EDs across England and Scotland over a 7 year period were analysed (n = 18828 referrals). There is a general trend towards increasing numbers of older people referred to liaison psychiatry year on year. Rates rose year on year from 1.4 referrals per 1000 ED attenders (>65 years) in 2011 to 4.5 in 2019 . There is inter and intra site variability in referral numbers per 1000 ED attendances between different departments, ranging from 0.1 - 24.3.
To plan an effective healthcare system we need to understand the population it serves, and have appropriate structures and processes within it. The overarching message of this study is clear; older peoples mental health emergencies presenting in ED are common and appear to be increasingly so. Without appropriate investment either in EDs or community mental health services, this is unlikely to improve.
The data also suggest very variable inter-departmental referral rates. It is not possible to establish why rates from one department to another are so different, or whether outcomes for the population they serve are better or worse. The data does however highlight the importance of asking further questions about why the departments are different, and what impact that has on the patients they serve.
A single high-fat, high-carbohydrate meal (HFHC) results in elevated postprandial glucose (GLU), triglycerides (TAG) and metabolic load index (MLI; TAG (mg/dl) + GLU (mg/dl)) that contributes to chronic disease risk. While disease risk is higher in older adults (OA) compared to younger adults (YA), the acute effects of exercise on these outcomes in OA is understudied. Twelve YA (age 23.3 ± 3.9 yrs, n = 5 M/7 F) and 12 OA (age 67·7 ± 6.0 yrs, n = 8 M/4 F) visited the laboratory in random order to complete a HFHC with no exercise (NE) or acute exercise (EX) condition. EX was performed 12 hours prior to HFHC at an intensity of 65 % of maximal heart rate to expend 75 % of the kcals consumed in HFHC (Marie Callender’s Chocolate Satin Pie; 12 kcal/kgbw; 57 % fat, 37 % CHO). Blood samples were taken at 0, 30, 60, 90 minutes, and then every hour until 6 hours post-meal. TAG levels increased to a larger magnitude in OA (Δ∼61 ± 31 %) compared to YA (Δ∼37 ± 34 %, P < 0·001), which were attenuated in EX compared to NE (P < 0·05) independent of age. There was no difference in GLU between OA and YA after the HFM, however, EX had attenuated GLU independent of age (NE: Δ∼21 ± 26 %; EX: Δ∼12 ± 18 %, P = 0·027). MLI was significantly lower after EX compared to NE in OA and YA (P < 0·001). Pre-prandial EX reduced TAG, GLU and MLI post-HFHC independent of age.
Novel endometrial cancer (EC) early-detection approaches may reduce racial disparities in mortality. We conducted six community-based focus groups with White and Black women (N = 57 participants) in February-March 2020 to explore acceptability of a home-based tampon sampling approach for EC. Participants also completed a survey. Data were analyzed using qualitative content analysis. Awareness of EC and risk factors was low. Acceptability regarding home sampling was high, but participants expressed concerns about instruction complexity and potential risks. Black women reported lower comfort with tampons. Increasing EC awareness, self-efficacy, and familiarization with tampons would advance prospects for at-home sample collection for EC testing.