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Interviews with 22 home-based primary care (HBPC) clinicians revealed that infectious disease physicians and clinical pharmacists facilitate infection management and antibiotic selection, respectively, and that local initiatives within programs support antibiotic prescribing decisions. Interventions that facilitate specialist engagement and tailored approaches that address the unique challenges of HBPC are needed.
The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI.
Methods
Our approach involved a two-step procedure. First, we conducted a review of prior studies utilizing the PAI, evaluating each study using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). We specifically assessed whether the studies adhered to two standards of predictive modeling: refraining from using leave-one-out cross-validation (LOO CV) and preventing data leakage. Second, we examined the impact of deviating from these methodological standards in real data. We employed both a traditional approach violating these standards and an advanced approach implementing them in two large-scale datasets, PANIC-net (n = 261) and Protect-AD (n = 614).
Results
The PROBAST-rating revealed a substantial risk of bias across studies, primarily due to inappropriate methodological choices. Most studies did not adhere to the examined prediction modeling standards, employing LOO CV and allowing data leakage. The comparison between the traditional and advanced approach revealed that ignoring these standards could systematically overestimate the utility of the PAI.
Conclusion
Our study cautions that violating standards in predictive modeling may strongly influence the evaluation of the PAI's utility, possibly leading to false positive results. To support an unbiased evaluation, crucial for potential clinical application, we provide a low-bias, openly accessible, and meticulously annotated script implementing the PAI.
Cannabis use severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.
Aims
Examine outcome data from the first 46 individuals to complete the CCP's intervention.
Method
The sample (N = 46) consisted of adults (aged ≥ 18) with psychosis under the care of the South London and Maudsley NHS Foundation Trust, referred to the CCP between January 2020 and February 2023, who completed their intervention by September 2023. Clinical and functional measures were collected before (T0) and after (T1) the CCP intervention (one-to-one sessions and peer group attendance). Primary outcomes were changes in the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) score and pattern of cannabis use. Secondary outcomes included T0–T1 changes in measures of delusions, paranoia, depression, anxiety and functioning.
Results
A reduction in the mean CUDIT-R score was observed between T0 (mean difference = 17.10, 95% CI = 15.54–18.67) and T1, with 73.91% of participants achieving abstinence and 26.09% reducing the frequency and potency of their use. Significant improvements in all clinical and functional outcomes were observed, with 90.70% being in work or education at T1 compared with 8.70% at T0. The variance in CUDIT-R scores explained between 34 and 64% of the variance in our secondary measures.
Conclusions
The CCP intervention is a feasible strategy to support cannabis use cessation/reduction and improve clinical and functional outcomes of people with psychotic disorders.
Somatic cells (SCs) in milk are a heterogeneous population composed of several subsets of cells. However, a complete understanding of this heterogeneity in cow’s milk remains elusive. This study aimed to characterize heterogeneity within mammary epithelial (MEC) and immune cell subpopulations from healthy Holstein cows. An initial cell characterization of SC populations was completed using a single milk collection (3.8 L) from a base population of 25 multiparous Holstein cows to identify MEC and immune cells using flow cytometry with Butyrophilin 1A1 (BTN) and CD45 as cell surface markers. From the base population, 5 multiparous cows (≥300 days in milk (DIM), ≤162 × 103 SC/mL, and milk yield (MY) ≥ 25 kg/d) were selected for fluorescence activated cell sorting and single-cell RNA sequencing (scRNA-seq) analysis. A single-cell-suspension of approximately 1,000 sorted cells was prepared from each cow for characterization using scRNA-seq. Gel beads and barcodes were generated, cDNA amplified, cDNA sequencing libraries constructed and sequenced. After data normalization, scaling, and filtering control, two CD45+ databases were generated. The CD45+ databases contained 923 and 851 single cells, each comprising 17,771 and 12,156 features, respectively. Principal component analysis revealed seven and eight distinguishing clusters. Based on marker expression, most immune cells present in the samples were T cells (CD3E and PTPRC). Three different T cell subpopulations were revealed: helpers (CD4), cytotoxic (CD8A and CD8B), and regulatory T cells (IL2RA). The remaining four clusters were composed of granulocytes (neutrophils, eosinophils, and basophils; TLR4 and CXCL8), macrophages (PTPRC, CD14, CD68, TL2, IL1B), and a small population of B cells (CD19, CD22, and MS4A1). The study and characterization of immune cell subpopulations present in milk provide a basis for developing greater insights into mammary gland immune function, offering potential avenues for enhancing animal health and milk production in the future.
Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations.
Methods:
In 410 male and female participants aged 17–35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites.
Results:
Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake.
Conclusions:
Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.
People with schizophrenia (PSZ) are impaired in attentional prioritization of non-salient but relevant stimuli over salient distractors during visual working memory (VWM) encoding. Conversely, guidance of top–down attention by external predictive cues is intact. Yet, it is unknown whether this preserved ability can help PSZ encode more information in the presence of salient distractors.
Methods
We employed a visuospatial change-detection task using four Gabor patches with differing orientations in 66 PSZ and 74 healthy controls (HCS). Two Gabor patches flickered which were designated either as targets or distractors and either a predictive or a non-predictive cue was displayed to manipulate top–down attention, resulting in four conditions.
Results
We observed significant effects of group, salience and cue as well as significant interactions of salience by cue, group by salience and group by cue. Across all conditions, PSZ stored significantly less information in VWM than HCS. PSZ stored significantly less non-flickering than flickering information with a non-predictive cue. However, PSZ stored significantly more flickering and non-flickering information with a predictive cue.
Conclusions
Our findings indicate that control of attentional selection is impaired in schizophrenia. We demonstrate that additional top–down information significantly improves performance in PSZ. The observed deficit in attentional control suggests a disturbance of GABAergic inhibition in early visual areas. Moreover, our findings are indicative of a mechanism for enhancing attentional control in PSZ, which could be utilized by pro-cognitive interventions. Thus, the current paradigm is suitable to reveal both preserved and compromised cognitive component processes in schizophrenia.
Coercive measures such as involuntary psychiatric admission are considered a last resort in the treatment of people with psychiatric disorders. So far, numerous factors have been identified that influence their use. However, the link between a pandemic – in particular, restrictions such as lockdowns – and the use of involuntary psychiatric admission is unclear.
Aim
To examine the association between COVID-19 lockdowns and involuntary psychiatric admissions in Austria.
Method
This retrospective exploratory study assessed all involuntary psychiatric admissions and use of mechanical restraint in Austria, except for the federal state of Vorarlberg, between 1 January 2018 and 31 December 2020. Descriptive statistics and regression models were used.
Results
During the 3-year study period, 40 012 individuals (45.9% females, mean age 51.3 years) had 66 124 involuntary psychiatric admissions for an average of 10.9 days. Mechanical restraint was used during 33.9% of these admissions. In weeks of nationwide COVID-19 lockdowns (2020 v. 2018/2019), involuntary psychiatric admissions were significantly fewer (odds ratio = 0.93, P = 0.0001) but longer (11.6 (s.d.: 16) v. 10.9 (s.d.: 15.8) days). The likelihood of involuntary admission during lockdowns was associated with year (2020 v. 2018–2019; adjusted odds ratio = 0.92; P = 0.0002) but not with sex (P = 0.814), age (P = 0.310), use of mechanical restraint (P = 0.653) or type of ward (P = 0.843).
Conclusions
Restrictions such as lockdowns affect coercive measures and resulted in fewer but longer involuntary psychiatric admissions during weeks of lockdown in Austria. These results strengthen previous findings that showed the dependence of coercive measures on external factors, highlighting the need to further clarify causality and desired prevention effects when using coercive measures.
We propose a new, unified approach for comparative research on citizens’ satisfaction with democracy (SWD). It starts with a well-specified individual-level model of the considerations citizens draw upon when answering the SWD survey question. Then we specify the relationship from contextual factors (especially institutions) through these individual-level mediating considerations and on to the SWD attitude. Multilevel structural equation estimation is applied to a merged dataset of European Social Survey (ESS) and country-level contextual data. The results add solidity to theoretical and empirical findings that citizens’ judgments of democracy are driven mostly by policy outputs and lived experience and not much by institutional variation or its political consequences.
In this introduction to the special issue on methodology, we provide background on its original motivation and a systematic overview of the contributions. The latter are discussed with correspondence to the phase of the scientific process they (most strongly) refer to: Theory construction, design, data analysis, and cumulative development of scientific knowledge. Several contributions propose novel measurement techniques and paradigms that will allow for new insights and can thus avail researchers in JDM and beyond. Another set of contributions centers around how models can best be tested and/or compared. Especially when viewed in combination, the papers on this topic spell out vital necessities for model comparisons and provide approaches that solve noteworthy problems prior work has been faced with.
International institutions underpinning the ‘liberal international order’ are increasingly contested by established Western powers. This article contributes to a better understanding of this novel challenge ‘from within’. We conceptualize four types of contestation frames according to (1) whether contesting states attribute the source of grievances to specific practices or the underlying principles of an international institution; and (2) whether they present their own nation or the international community as the subject of grievances. Combining these two dimensions, we distinguish between globalist-reformist, nationalist-reformist, globalist-revisionist and nationalist-revisionist contestation frames. These contestation frames are consequential as they open up or shrink the discursive space for contested institutions’ re-legitimation. Drawing on the Trump Administration’s contestation of the World Bank, NATO, the UNHRC, and the WTO, we demonstrate that contestation frames and defenders’ responses varied greatly across institutions, ranging from accommodative deliberations about institutional reforms to principled rejection and the justification of the status quo.
Autoimmune mechanisms are related to disease development in a subgroup of patients with psychosis. The contribution of immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein (MOG) is mainly unclear in this context.
Methods:
Therefore, two patients with psychosis and anti-MOG antibodies – detected in fixed cell-based and live cell-based assays – are presented.
Results:
Patient 1 suffered from late-onset psychosis with singular white matter lesions in magnetic resonance imaging (MRI) and intermittent electroencephalography (EEG) slowing. Patient 2 suffered from a chronic paranoid–hallucinatory disorder with intermittent confusional states, non-specific white matter alterations on MRI, a disorganised alpha rhythm on EEG, and elevated cerebrospinal fluid protein. Both patients had anti-MOG antibody titres of 1 : 320 in serum (reference < 1 : 20).
Conclusions:
The arguments for and against a causal role for anti-MOG antibodies are discussed. The antibodies could be relevant, but due to moderate titres, they may have caused a rather ‘subtle clinical picture’ consisting of psychosis instead of ‘classical’ MOG encephalomyelitis.
Older adults exhibit heightened vulnerability for alcohol-related health impairments. Increases in the proportion of older adults within the European Union’s total population and prevalence rates of alcohol use disorders in this age group are being observed. This large scale international study was conducted to identify those older adults with an increased risk to engage in hazardous drinking behaviour.
Methods
Socio-demographic, socio-economic, personality characteristics (Big Five Inventory, BFI-10), and alcohol consumption patterns of 13,351 individuals from 12 different European countries, collected by the Survey of Health, Aging, and Retirement in Europe, were analyzed using regression models.
Results
Age, nationality, years of education, as well as personality traits, were significantly associated with alcohol intake. For males, extraversion predicted increased alcohol intake (RR = 1.11, CI = 1.07–1.16), whereas conscientiousness (RR = 0.93, CI = 0.89–0.97), and agreeableness (RR = 0.94, CI = 0.90–0.99), were associated with a reduction. For females, openness to new experiences (RR = 1.11, CI = 1.04–1.18) predicted increased alcohol intake. Concerning excessive drinking, personality traits, nationality, and age-predicted consumption patterns for both sexes: Extraversion was identified as a risk factor for excessive drinking (OR = 1.15; CI = 1.09–1.21), whereas conscientiousness was identified as a protective factor (OR = 0.87; CI = 0.823–0.93).
Conclusion
Hazardous alcohol consumption in the elderly was associated with specific personality characteristics. Preventative measures, crucial in reducing deleterious health consequences, should focus on translating the knowledge of the association of certain personality traits and alcohol consumption into improved prevention and treatment.
Evidence-based infection control strategies are needed for healthcare workers (HCWs) following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). In this study, we evaluated the negative predictive value (NPV) of a home-based 7-day infection control strategy.
Methods:
HCWs advised by their infection control or occupational health officer to self-isolate due to a high-risk SARS-CoV-2 exposure were enrolled between May and October 2020. The strategy consisted of symptom-triggered nasopharyngeal SARS-CoV-2 RNA testing from day 0 to day 7 after exposure and standardized home-based nasopharyngeal swab and saliva testing on day 7. The NPV of this strategy was calculated for (1) clinical coronavirus disease 2019 (COVID-19) diagnosis from day 8–14 after exposure, and for (2) asymptomatic SARS-CoV-2 detected by standardized nasopharyngeal swab and saliva specimens collected at days 9, 10, and 14 after exposure. Interim results are reported in the context of a second wave threatening this essential workforce.
Results:
Among 30 HCWs enrolled, the mean age was 31 years (SD, ±9), and 24 (80%) were female. Moreover, 3 were diagnosed with COVID-19 by day 14 after exposure (secondary attack rate, 10.0%), and all cases were detected using the 7-day infection control strategy: the NPV for subsequent clinical COVID-19 or asymptomatic SARS-CoV-2 detection by day 14 was 100.0% (95% CI, 93.1%–100.0%).
Conclusions:
Among HCWs with high-risk exposure to SARS-CoV-2, a home-based 7-day infection control strategy may have a high NPV for subsequent COVID-19 and asymptomatic SARS-CoV-2 detection. Ongoing data collection and data sharing are needed to improve the precision of the estimated NPV, and here we report interim results to inform infection control strategies in light of a second wave threatening this essential workforce.
Mental health problems are prevalent among therapists and may have a negative impact on therapist effectiveness. To counteract such problems, therapist self-care (for example, striking a balance between personal and professional demands and seeking personal therapy), has received increased attention. Conceptually, self-care can be considered as part of a personal practice model, focusing on techniques that therapists engage with self-experientially with a focus on their personal and/or professional development. However, studies of the self-application of specific treatment techniques are lacking. We aimed to explore the use, and perceived usefulness, of cognitive behavioural therapy (CBT) techniques for self-care to prevent or treat own mental health problems among practising therapists. Participants were therapists (n = 228) of various professional backgrounds in Sweden. Data were collected using a web-based survey. Descriptive statistics were calculated, and non-parametric analyses conducted to investigate associations of 13 CBT techniques with therapist characteristics. Use of CBT techniques for self-care was highly prevalent among participants, and they perceived the techniques as useful, irrespective of characteristics such as gender, age, profession, years since graduation, clinical experience, level of training in CBT, and previous experience of personal CBT. The high prevalence among therapists of the use of treatment techniques for self-care is very encouraging. Therapist self-care, including the self-application of treatment techniques, may be an important factor for therapist effectiveness, which calls for further development of personal practice models with respect to self-care, and future studies investigating associations between therapist mental health, self-care, effectiveness and patient outcome.
Key learning aims
(1) Therapist self-care using cognitive behavioural therapy (CBT) techniques to prevent or treat own mental health problems may influence therapist effectiveness. However, studies of self-application of treatment techniques are lacking.
(2) In the present survey study, the use of CBT techniques for self-care was highly prevalent among practising therapists, and they perceived the techniques as useful, irrespective of characteristics such as gender, age, profession, years since graduation, clinical experience, level of training in CBT, and previous experience of personal CBT.
(3) Almost all therapists believed that it was a good idea to self-apply CBT techniques for their own sake and for the benefit of their patients.
Background: Estimating the burden of intestinal colonization with antibiotic-resistant gram-negative bacteria (AR-GNB) is critical to understanding their global epidemiology and spread. We aimed to determine the prevalence of, and risk factors for, intestinal colonization due to AR-GNB in population-based hospital and community settings in Chile. Methods: Between December 2018 and May 2019, we enrolled randomly selected hospitalized adults in 4 tertiary-care public hospitals (Antofagasta, Santiago, Curico and Puerto Montt), and adults residing in a community-based cohort in the rural town of Molina. Following informed consent, we collected rectal swabs and epidemiological information through a standardized questionnaire. Swabs were plated onto MacConkey agar with 2 µg/mL ciprofloxacin or ceftazidime. All recovered morphotypes were identified, and antibiotic susceptibility testing was performed via disk diffusion. The primary outcome was the prevalence of colonization with fluoroquinolone (FQ)- or third-generation cephalosporin (3GC)–resistant GNB. The secondary outcome was the prevalence of colonization with multidrug-resistant (MDR) GNB, defined as GNB resistant to ≥3 antibiotic classes. Categories were not mutually exclusive. Bivariate and multivariate analyses were performed to describe risk factors for colonization with these categories. Results: In total, 775 hospitalized adults and 357 community participants were enrolled, with a median age of 60 years (IQR, 42–72) and 55 years (IQR, 48–62) years, respectively. Among hospitalized participants, the prevalence of colonization with FQ- or 3GC-resistant GNB was 47% (95% CI, 43%–50%) and 41% (95% CI, 38%–45%), respectively, whereas the prevalence of MDR-GNB colonization was 27% (95% CI, 24%–31%). In the community setting, the prevalence of colonization with either FQ-, 3GC-resistant GNB, or MDR-GNB was 40% (95% CI, 34%–45%), 29% (95% CI, 24%– 34%), and 5% (95% CI, 3%–8%), respectively. Independent risk factors for hospital MDR-GNB colonization included the hospital of admission, unit of hospitalization (intensive care units carried the highest risk), in-hospital antimicrobial exposure, comorbidities (Charlson index), and length of stay. In the community setting, recent antibiotic exposure (<3 months) predicted colonization with either FQ- or 3GC-resistant GNB, and alcohol consumption was inversely associated with MDR GNB colonization. Conclusions: A high burden of colonization with AR-GNB was observed in this sample of hospitalized and community-dwelling adults in Chile. The high burden of colonization with GNB resistant to commonly used antibiotics such as FQ and 3GC found in community dwellers, suggests that the community may be a relevant source of antibiotic resistance. Efforts to understand relatedness between resistant strains circulating in the community and the hospital are needed.
Suicide risk in patients is markedly elevated during psychiatric inpatient care, as well as after discharge. However, it is unclear whether, and to what extent, this increased suicide risk varies between sex. Thus, the aim of this study was to analyze sex differences for suicides during and after psychiatric hospitalization in various countries.
Methods.
National suicide mortality rates and inpatient-related suicide rates (three intervals: during psychiatric inpatient treatment, 1 month, and 1 year after discharge) from 12 countries for 2000–2016 were analyzed, and a logistic model was used to quantify the effect of sex.
Results.
Persons admitted to or discharged from psychiatric inpatient care exhibited significantly increased rates of suicide compared to those in the general population. Furthermore, increase of suicide risk was significantly higher for females than for males for all investigated time intervals (inpatient suicide odds ratio [OR] 1.85; suicide within 1 month after discharge—OR 1.94; suicide within 1 year after discharge—OR 2.04).
Conclusion.
Analysis confirmed the time during and after psychiatric inpatient care to be significantly associated with an elevated risk for suicide. Further, a significant sex effect was observed, with females in this population being at a proportionally higher risk for suicide during psychiatric inpatient treatment as well as the year following discharge. Our study implicates that more effective suicide preventive measures during inpatient stay, focusing on female patients, are needed.
Quantum set theory (QST) and topos quantum theory (TQT) are two long running projects in the mathematical foundations of quantum mechanics (QM) that share a great deal of conceptual and technical affinity. Most pertinently, both approaches attempt to resolve some of the conceptual difficulties surrounding QM by reformulating parts of the theory inside of nonclassical mathematical universes, albeit with very different internal logics. We call such mathematical universes, together with those mathematical and logical structures within them that are pertinent to the physical interpretation, ‘Q-worlds’. Here, we provide a unifying framework that allows us to (i) better understand the relationship between different Q-worlds, and (ii) define a general method for transferring concepts and results between TQT and QST, thereby significantly increasing the expressive power of both approaches. Along the way, we develop a novel connection to paraconsistent logic and introduce a new class of structures that have significant implications for recent work on paraconsistent set theory.
Patients diagnosed with glioblastoma (GBM) are treated with surgery followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. Patients are monitored with serial magnetic resonance imaging (MRI). However, treatment-related changes frequently mimic disease progression. We reviewed a series of patients undergoing surgery for presumed first-recurrence GBM, where pathology reports were available for tissue diagnosis, in order to better understand factors associated with a diagnosis of treatment-related changes on final pathology.
Methods:
Patient records at a single institution between 2005 and 2015 were retrospectively reviewed. Pathology reports were reviewed to determine diagnosis of recurrent GBM or treatment effect. Survival analysis was performed interrogating overall survival (OS) and progression-free survival (PFS). Correlation with radiation treatment plans was also examined.
Results:
One-hundred-twenty-three patients were identified. One-hundred-sixteen patients (94%) underwent resection and seven underwent biopsy. Treatment-related changes were reported in 20 cases (16%). These patients had longer median OS and PFS from the time of recurrence than patients with true disease progression. However, there was no significant difference in OS from the time of initial diagnosis. Treatment effect was associated with surgery within 90 days of completing radiation. In patients receiving radiation at our institution (n = 53), larger radiation target volume and a higher maximum dose were associated with treatment effect.
Conclusion:
Treatment effect was associated with surgery nearer to completion of radiation, a larger radiation target volume, and a higher maximum point dose. Treatment effect was associated with longer PFS and OS from the time of recurrence, but not from the time of initial diagnosis.
Recent events have led to a renewed conversation surrounding the relevance and potential removal of Confederate monuments around the country, and several monuments have already been removed. However, we have little insight to explain why some monuments have been removed while others remain. This article seeks to understand the social and political determinants that can better explain the recent removal of Confederate monuments throughout the United States. Analyzing results from an original dataset of Confederate monuments, we identify which local government structures and racial and civic characteristics best predict the removal of these monuments. Ultimately, although we find that other factors contribute to monument removal, the size of the black population, the presence of a National Association for the Advancement of Colored People chapter, and the percentage of Democrats in a county in which a monument exists—as well as whether the monument exists in a state that constrains removal by legislative decree—best predict whether a Confederate monument will be taken down. This project elucidates the interplay of race, partisanship, and local and statewide politics as it relates to the dismantling of Confederate monuments.