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To retrospectively observe procalcitonin (PCT) and antibiotic ordering practices in patients hospitalized with community-acquired pneumonia (CAP).
Design:
Retrospective, exact matched, multicenter cohort study from October 1, 2018 – March 31, 2023.
Setting:
All hospitals across the Mayo Clinic Enterprise.
Participants:
Adult patients with CAP, identified using pneumonia diagnosis codes and receipt of systemic antibiotics with an indication of “respiratory tract infection” within 48 hours of hospitalization.
Methods:
PCT testing within the first 7 days of hospitalization was compared to non-PCT care (nPCT). The primary outcomes were treatment duration, antibiotic days of therapy (DOT), and length of stay (LOS).
Results:
15364 patients met inclusion criteria. PCT testing occurred in 42.4% (6515/15364) of encounters, totaling 8214 PCT results. 12880 unique patient encounters were matched 1:1, 6440 in each group. Treatment duration was longer in the PCT group compared to the nPCT group (5.1 vs 4.6 days, respectively, P < 0.001). Patients in the PCT group also received more DOT (8.6 vs 7.6 DOT, P < 0.001) and had a longer LOS (6.8 vs 5.9 days, P < 0.001), respectively. There was no difference in 30-day all-cause mortality or C. difficile infection between groups. In a sensitivity analysis of nPCT patients compared to those with a peak value <0.25 ng/mL (i.e. normal result) there was no difference in treatment duration (4.6 days nPCT vs 4.7 days normal PCT, P = 0.104) or LOS (5.9 days nPCT vs 6.0 days normal PCT, P = 0.134).
Conclusion:
PCT testing in patients hospitalized with CAP was not associated with reduced antimicrobial utilization, LOS, or 30-day all-cause mortality.
Diagnosis in psychiatry faces familiar challenges. Validity and utility remain elusive, and confusion regarding the fluid and arbitrary border between mental health and illness is increasing. The mainstream strategy has been conservative and iterative, retaining current nosology until something better emerges. However, this has led to stagnation. New conceptual frameworks are urgently required to catalyze a genuine paradigm shift.
Methods
We outline candidate strategies that could pave the way for such a paradigm shift. These include the Research Domain Criteria (RDoC), the Hierarchical Taxonomy of Psychopathology (HiTOP), and Clinical Staging, which all promote a blend of dimensional and categorical approaches.
Results
These alternative still heuristic transdiagnostic models provide varying levels of clinical and research utility. RDoC was intended to provide a framework to reorient research beyond the constraints of DSM. HiTOP began as a nosology derived from statistical methods and is now pursuing clinical utility. Clinical Staging aims to both expand the scope and refine the utility of diagnosis by the inclusion of the dimension of timing. None is yet fit for purpose. Yet they are relatively complementary, and it may be possible for them to operate as an ecosystem. Time will tell whether they have the capacity singly or jointly to deliver a paradigm shift.
Conclusions
Several heuristic models have been developed that separately or synergistically build infrastructure to enable new transdiagnostic research to define the structure, development, and mechanisms of mental disorders, to guide treatment and better meet the needs of patients, policymakers, and society.
The UK population is ageing and becoming more ethnically diverse(1). Nutrition is a key modifiable determinant of healthy ageing but there is little published data of dietary patterns in ethnic minority groups. The reasons for poor dietary habits of older adults from ethnic minority groups could be attributed to cost of living, language barriers, age, availability of traditional foods(2). As part of a larger research study to improve nutritional health in older adults (TANGERINE: nuTritional heAlth aNd aGeing in oldER ethnIc miNoritiEs), the aim of this study was to investigate vegetable intake in different older ethnic groups compared with a white (British) reference population.
We used food frequency questionnaire (FFQ) data drawn from Wave 2 (2010-2012) and Wave 13 (2021-2022) of Understanding Society, a UK household panel survey(3). We calculated the proportions of vegetable intake by ethnic group for each wave, weighted for population representativeness, and used (weighted) logistic regression for intake (everyday vs less than every day) to adjust for potential confounders. Data from the WHO food insecurity questionnaire in wave 13 was used to evaluate the ethnic group differences in food insecurity.
The percentage vegetable intake at least every day was reduced between Waves 2 and 13 in all ethnic groups. At both Waves all ethnic groups, except Indian ethnicity have lower vegetable intakes than white (British) reference group. The age and sex adjusted odds ratios (OR) (95% confidence intervals) at Wave 2 were 0.60 (0.51, 0.71) for Caribbean, 0.67 (0.56, 0.79) for African, 0.36 (0.28, 0.44) for Pakistani, 0.78 (0.62, 0.98) for Bangladeshi and 1.10 (0.94, 1.28) for Indian. The differences could be largely explained by lower income and greater area deprivation for Bangladeshi, less so for Caribbean, African and Pakistani groups. Results were similar for Wave 13. All ethnic groups, except Indian had higher odds of greater food insecurity than the white (British) reference group, largely attributed to income and area deprivation, for example, the OR for Pakistani group compared with white (British) reference group decreased from 1.74 (1.18, 2.56) to 1.05 (0.70, 1.58). However, for the African group, the OR remained greater than white reference population at 2.55 (1.73, 3.76) even after accounting for socioeconomic position.
The findings suggest differences in vegetable intake between different ethnic groups which have been maintained between 2010-2012 and 2021-2022 and may be explained to some extent by socioeconomic disadvantage. Whilst we used cross-sectional analyses of self-reported data, there remains a need for further large-scale studies using longitudinal and experimental designs in older ethnic groups considering socioeconomic position, recognising the importance of heterogeneity and the need to analyse ethnic groups individually, rather than as a group for measurements of dietary intake.
Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders.
Methods
The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration.
Results
Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006).
Conclusions
Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.
Do parties face an electoral penalty when they nominate candidates of colour? We employ a regression discontinuity design using state legislative election data from 2018, 2019, and 2020 to isolate the effect of nominating a candidate of colour on a party's general election performance. Utilising this approach with real-world data heightens external validity relative to existing racial penalty studies, largely supported by surveys and experiments. We find no evidence that candidates of colour are disadvantaged in state legislative general elections relative to narrowly nominated white candidates from the same party. These findings challenge the leading explanations for the underrepresentation of racial/ethnic minority groups, with implications for candidate selection across the United States.
In light of a history of categorical exclusion, it is critical that pregnant people are included in research to help improve the knowledge base and interventions needed to address public health. Yet the volatile legal landscape around reproductive rights in the United States threatens to undue recent progress made toward the greater inclusion of pregnant people in research. We offer ethical and practical guidance for researchers, sponsors, and institutional review boards to take specific steps to minimize legal risks and ensure the ethical conduct of research with pregnant people in an evolving legal environment.
Washington State established a Memorandum of Understanding (MOU) and operational plan in 2012 to coordinate pharmacy infrastructure and workforce during a public health emergency. The objectives of this study were to adapt the MOU operational plan to the context of the coronavirus disease 2019 (COVID-19) pandemic and assess community pharmacies’ organizational readiness to implement COVID-19 testing and vaccination.
Methods:
This mixed methods study was conducted June-August 2020. Three facilitated discussions were conducted with community pharmacists and local health jurisdiction (LHJ) representatives to test the MOU operational plan. Facilitated discussions were thematically analyzed to inform adaptations to the operational plan. Pharmacists were surveyed to assess their organization’s readiness for COVID-19 testing and vaccination before and after the facilitated discussions using the Organizational Readiness for Implementing Change (ORIC) measure. Survey responses were analyzed using descriptive statistics.
Results:
Six pharmacists from 5 community pharmacy organizations and 4 representatives from 2 LHJs participated in at least 1 facilitated discussion. Facilitated discussions resulted in 3 themes and 16 adaptations to the operational plan. Five of 6 community pharmacists (83% response rate) completed both surveys. Mean organizational readiness decreased from baseline to follow-up for COVID-19 testing and vaccination.
Conclusions:
Operational plan adaptations highlight opportunities to strengthen MOUs between local and state health departments and community pharmacies to support future emergency preparedness and readiness efforts.
A survey was conducted among Canadian tertiary neonatal intensive care units. Of the 27 sites who responded, 9 did not have any form of antimicrobial stewardship, and 11 used vancomycin for empirical coverage in late-onset-sepsis evaluations. We detected significant variations in the diagnostic criteria for urinary tract infection and ventilator-associated pneumonia.
The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis – and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.
We describe severe acute respiratory coronavirus virus 2 (SARS-CoV-2) IgG seroprevalence and antigenemia among patients at a medical center in January–March 2021 using residual clinical blood samples. The overall seroprevalences were 17% by infection and 16% by vaccination. Spent or residual samples are a feasible alternative for rapidly estimating seroprevalence or monitoring trends in infection and vaccination.
Delays in the diagnosis and therapy of benign paroxysmal positional vertigo can greatly impact quality of life and increase healthcare costs for patients. This study aimed to appraise the quality of clinical practice guidelines for the diagnosis and management of benign paroxysmal positional vertigo.
Methods
A comprehensive database search of clinical practice guidelines was completed up to 30 October 2021. Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation II instrument in the quality appraisal.
Results
The highest score was in ‘clarity and presentation’ (58.33 ± 22.7). The lowest score was in ‘applicability’ (13.96 ± 30.1). Overall, four clinical practice guidelines were ‘low quality’ and only one guideline was ‘high quality’.
Conclusion
This review identified a significant lack of quality in clinical practice guideline development for benign paroxysmal positional vertigo, highlighting the need for a more rigorous approach for future guideline development.
To design a meditation protocol and test its feasibility, acceptability and efficacy in conjunction with yoga training (YT) for persons with schizophrenia (SZ).
Methods:
The meditation protocol consisted of Anapana (observing normal respiration) and Yoga Nidra (supine, restful awareness). In a single-blind randomised controlled trial, medicated and clinically stable outpatients diagnosed with SZ were randomised to receive treatment as usual (TAU), TAU augmented with YT or TAU augmented with meditation and yoga training (MYT) for 3 weeks (N = 145). Acceptability, clinical, social and cognitive functions were assessed after 3-week and 3-month post-randomisation using within-group and between-group analyses with repeated measures multivariate tests.
Results:
No group-wise differences in compliance, study discontinuation, major/serious side effects or adverse events were noted. For six assessed clinical variables, the direction of changes were in the desired direction and the effect sizes were greater in the MYT group compared with the TAU group at both time points. Changes in social function variables were greater at 3 months than at 3 weeks. Nominally significant improvement in individual cognitive domains were noted in all groups at both time points. All effect sizes were in the small to medium range.
Conclusion:
MYT is feasible and acceptable and shows modest benefits for persons with SZ. MYT can also improve quality of life and clinical symptoms. Larger studies of longer duration are warranted.
OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.
OBJECTIVES/GOALS: For patients suffering from respiratory failure there are limited options to support gas exchange aside from mechanical ventilation. Our goal is to design, investigate, and refine a novel device for extrapulmonary gas exchange via peritoneal perfusion with perfluorocarbons (PFC) in an animal model. METHODS/STUDY POPULATION: Hypoxic respiratory failure will be modeled using 50 kg swine mechanically ventilated with subatmospheric (10-12%) oxygen. Through a midline laparotomy, two cannulas, one for inflow and one for outflow, will be placed into the peritoneal space. After abdominal closure, the cannulas will be connected to a device capable of draining, oxygenating, regulating temperature, filtering, and pumping perfluorodecalin at a rate of 3-4 liters per minute. During induced hypoxia, the physiologic response to PFC circulation through the peritoneal space will be monitored with invasive (e.g. arterial and venous blood gases) and non-invasive measurements (e.g. pulse oximetry). RESULTS/ANTICIPATED RESULTS: We anticipate that the initiation of oxygenated perfluorocarbons perfusion through the peritoneal space during induced hypoxia will create an increase in hemoglobin oxygen saturation and partial pressure of oxygen in arterial blood. As we expect gas exchange to be occurring in the microvascular beds of the peritoneal membrane, we expect to observe an increase in the venous blood oxygen content sampled from the inferior vena cava. Using other invasive hemodynamic measures (e.g. cardiac output) and blood samples taken from multiple venous sites, a quantifiable rate of oxygen delivery will be calculable. DISCUSSION/SIGNIFICANCE: Peritoneal perfluorocarbon perfusion, if able to deliver significant amounts of oxygen, would provide a potentially lifesaving therapy for patients in respiratory failure who are unable to be supported with mechanical ventilation alone, and are not candidates for extracorporeal membrane oxygenation.
Several guidelines have been produced for the management of nutrition in patients with head and neck cancer. However, no systematic evaluation of the quality of these guidelines has been performed to date.
Method
A comprehensive search was conducted up to August 2020. The quality of guidelines was assessed by four independent reviewers using the Appraisal of Guidelines for Research and Evaluation, 2nd edition.
Results
Nine guidelines were assessed for critical evaluation. Only two guidelines were classified as ‘high quality’. The ‘scope and purpose’ domain achieved the highest mean score (75.5 ± 17.0 per cent), and the lowest domain mean score was ‘applicability’ (37.6 ± 23.0 per cent).
Conclusion
These findings highlight the variability in the methodological quality of guidelines for the management of nutrition in head and neck cancer. These results may help to improve the reporting of future guidelines and guide the selection for use in clinical practice.
To describe the incidence of seasonal respiratory viral infections (s-RVIs) before and during the coronavirus disease 2019 (COVID-19) pandemic and to compare virus-specific patient outcomes in pediatric patients.
Design:
A retrospective cross-sectional study including patient admissions to the Children’s National Hospital between October 1, 2015, and December 31, 2020.
Results:
Among 12,451 patient admissions between March 15 and December 31, 2020 (cohort 1), 8,162 (66%) were tested for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and 249 (2.0%) were positive. Among 10,986 patient admissions between April 1 and December 31, 2020 (cohort 2), 844 (8%) were tested for s-RV upon admission and 160 were positive. Thus, 1.5% of patient admissions were associated with laboratory-confirmed s-RVIs. Among the 49,901 patient admissions during a viral season between October 1, 2015, and March 31, 2020 (cohort 3), 7,539 (15%) were tested for s-RV upon admission and 4,531 were positive; thus, 9.0% of patient admissions were associated with laboratory-confirmed s-RVIs. hHRV/rENT was the most detected virus, but the detection rate decreased substantially (31% vs 18%; P < .001) during the COVID-19 pandemic. No patients had RSV, influenza, hMPV, hPIV, or hCoV detected upon admission after April 21, 2020. The 3 patient cohorts had no statistically significant difference in the percentage of ICU admissions (10.8% vs 15.0% vs 14.2%; P > .05) or death at discharge (0.8% vs 0.6% vs 0.5%; P > .05).
Conclusions:
Compared to COVID-19, s-RVI cases were associated with a higher proportion of inpatient admissions but were similar in ICU admission and death rates in hospitalized pediatric patients. Public health interventions for preventing COVID-19 were highly effective in preventing pediatrics s-RVIs.
Rapid progression from the first identifiable symptom to the onset of first-episode psychosis (FEP) allows less time for early intervention. The aim of this study was to examine the association between the first identifiable symptom and the subsequent speed of illness progression.
Methods
Data were available for 390 patients attending a catchment-based early intervention service for FEP. Exposure to non-psychotic and subthreshold psychotic symptoms was retrospectively recorded using semi-structured interviews. Outcomes following the onset of the first identifiable symptom were (1) time to onset of FEP and (2) symptom incidence rate (i.e. number of symptoms emerging per person-year until FEP onset). These outcomes were respectively analyzed with Cox proportional hazards and negative binomial regressions.
Results
After Bonferroni correction, having a subthreshold psychotic (v. non-psychotic) symptom as the first symptom was not associated with time to FEP onset [hazard ratio (HR) = 1.39; 95% CI 0.94–2.04] but was associated with higher symptom incidence [incidence rate ratio (IRR) = 1.92; 95% CI 1.10–3.48]. A first symptom of suspiciousness was associated with shorter time to FEP onset (HR = 2.37; 95% CI 1.38–4.08) and higher symptom incidence rate (IRR = 3.20; 95% CI 1.55–7.28) compared to other first symptoms. In contrast, a first symptom of self-harm was associated with lower symptom incidence rate (IRR = 0.06; 95% CI 0.01–0.73) compared to other first symptoms. Several associations between symptoms and illness progression were moderated by the age at symptom onset.
Conclusions
Appreciating the content and timing of early symptoms can identify windows and treatment targets for early interventions in psychosis.