Public involvement in an aggregate and individual participant data meta-analysis of mindfulness-based programmes for mental health promotion.

BACKGROUND: Involving the public in evidence synthesis research is challenging due to the highly analytic nature of the projects, so it is important that involvement processes are documented, reflected upon, and shared to devise best practices. There is a literature gap on the involvement of the public in individual participant data meta-analyses, particularly in public health projects. We aimed to document and reflect on our collective experiences of involving and being involved as public stakeholders at all stages of a systematic review and individual participant data meta-analysis project. METHODS: We formed a stakeholder group made of four members of the public at the beginning of our evidence synthesis project comprising a systematic review, an aggregate data meta-analysis, and an individual participant data meta-analysis of mindfulness-based programmes for mental health promotion in non-clinical adults. Following each group meeting, members and participating researchers completed written reflections; one group member collected and collated these. At the end of the project, a reflective writing workshop was held before all members completed their final reflections. Everyone completed an adapted, open-ended questionnaire which asked about what did and did not work well, the overall experience, what could be improved, and the felt impact the stakeholder group had on the research. RESULTS: Overall, the stakeholders and researchers reported a positive experience of working together. Positives from the stakeholders' point of view included learning new skills, experiencing research, and making new friends. For the researchers, stakeholders helped them focus on what matters to the public and were reinvigorating research partners. The challenges stakeholders experienced included having long gaps between meetings and feeling overwhelmed. The researchers found it challenging to strike the balance between asking stakeholders to be involved and for them to learn research-related skills without overburdening them and making sure that the learning was engaging. When looking back at their experience, stakeholders described seeing their impact on the project in hindsight but that this was not felt while the project was being carried out. CONCLUSION: Successfully involving the public in complex evidence synthesis projects is possible and valuable from the points of view of the researchers and the stakeholders. However, it requires a significant time, skill, and resource investment that needs to be factored in from project inception. Further guidance and stakeholder training materials would be helpful. Specific suggestions are provided.

Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with 11C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy.

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aß) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aß, and cognitive scores, and whether metabolites and Aß explained cognitive scores better than Aß alone. In the ACC, higher Aß was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aß deposition than by models that only included one of these variables. These findings identify preliminary associations between Aß, neurometabolites, and cognition.

Contribution of severe mental disorders to fatally harmful effects of physical disorders: national cohort study.

BACKGROUND: It remains unknown whether severe mental disorders contribute to fatally harmful effects of physical illness. AIMS: To investigate the risk of all-cause death and loss of life-years following the onset of a wide range of physical health conditions in people with severe mental disorders compared with matched counterparts who had only these physical health conditions, and to assess whether these associations can be fully explained by this patient group having more clinically recorded physical illness. METHOD: Using Czech national in-patient register data, we identified individuals with 28 physical health conditions recorded between 1999 and 2017, separately for each condition. In these people, we identified individuals who had severe mental disorders recorded before the physical health condition and exactly matched them with up to five counterparts who had no recorded prior severe mental disorders. We estimated the risk of all-cause death and lost life-years following each of the physical health conditions in people with pre-existing severe mental disorders compared with matched counterparts without severe mental disorders. RESULTS: People with severe mental disorders had an elevated risk of all-cause death following the onset of 7 out of 9 broadly defined and 14 out of 19 specific physical health conditions. People with severe mental disorders lost additional life-years following the onset of 8 out 9 broadly defined and 13 out of 19 specific physical health conditions. The vast majority of results remained robust after considering the potentially confounding role of somatic multimorbidity and other clinical and sociodemographic factors. CONCLUSIONS: A wide range of physical illnesses are more likely to result in all-cause death in people with pre-existing severe mental disorders. This premature mortality cannot be fully explained by having more clinically recorded physical illness, suggesting that physical disorders are more likely to be fatally harmful in this patient group.

Pulmonary Cytopathology: Current and Future Impact of Microscopy and Immunohistochemistry.

With the advancement of tissue procurement techniques, in-depth knowledge of morphology is crucial for cytopathologists to diagnose neoplastic and nonneoplastic lung diseases optimally. Cytopathologists must also be well versed in immunohistochemistry/immunocytochemistry markers and their interpretation for an accurate diagnosis.

Investigation of singlet-oxygen-responsive genes in the cyanobacterium Synechocystis PCC 6803.

Singlet oxygen (1O2) is an important reactive oxygen species whose formation by the type-II, light-dependent, photodynamic reaction is inevitable during photosynthetic processes. In the last decades, the recognition that 1O2 is not only a damaging agent, but can also affect gene expression and participates in signal transduction pathways has received increasing attention. However, contrary to several other taxa, 1O2-responsive genes have not been identified in the important cyanobacterial model organism Synechocystis PCC 6803. By using global transcript analysis we have identified a large set of Synechocystis genes, whose transcript levels were either enhanced or repressed in the presence of 1O2. Characteristic 1O2 responses were observed in several light-inducible genes of Synechocystis, especially in the hli (or scp) family encoding HLIP/SCP proteins involved in photoprotection. Other important 1O2-induced genes include components of the Photosystem II repair machinery (psbA2 and ftsH2, ftsH3), iron homeostasis genes isiA and idiA, the group 2 sigma factor sigD, some components of the transcriptomes induced by salt-, hyperosmotic and cold-stress, as well as several genes of unknown function. The most pronounced 1O2-induced upregulation was observed for the hliB and the co-transcribed lilA genes, whose deletion induced enhanced sensitivity against 1O2-mediated light damage. A bioreporter Synechocystis strain was created by fusing the hliB promoter to the bacterial luciferase (lux), which showed its utility for continuous monitoring of 1O2 concentrations inside the cell.

Pulmonary Cytopathology: Current and Future Impact on Patient Care.

Small biopsies of lung are routinely obtained by many methods, including several that result in cytologic specimens. Because lung cancer is often diagnosed at a stage for which primary resection is not an option, it is critical that all diagnostic, predictive, and prognostic information be derived from such small biopsy specimens. As the number of available diagnostic and predictive markers expands, cytopathologists must familiarize themselves with current requirements for specimen acquisition, handling, results reporting, and molecular and other ancillary testing, all of which are reviewed here.

Defining Suicidal Thought and Behavior Phenotypes for Genetic Studies.

Background: Standardized definitions of suicidality phenotypes, including suicidal ideation (SI), attempt (SA), and death (SD) are a critical step towards improving understanding and comparison of results in suicide research. The complexity of suicidality contributes to heterogeneity in phenotype definitions, impeding evaluation of clinical and genetic risk factors across studies and efforts to combine samples within consortia. Here, we present expert and data-supported recommendations for defining suicidality and control phenotypes to facilitate merging current/legacy samples with definition variability and aid future sample creation. Methods: A subgroup of clinician researchers and experts from the Suicide Workgroup of the Psychiatric Genomics Consortium (PGC) reviewed existing PGC definitions for SI, SA, SD, and control groups and generated preliminary consensus guidelines for instrument-derived and international classification of disease (ICD) data. ICD lists were validated in two independent datasets (N = 9,151 and 12,394). Results: Recommendations are provided for evaluated instruments for SA and SI, emphasizing selection of lifetime measures phenotype-specific wording. Recommendations are also provided for defining SI and SD from ICD data. As the SA ICD definition is complex, SA code list recommendations were validated against instrument results with sensitivity (range = 15.4% to 80.6%), specificity (range = 67.6% to 97.4%), and positive predictive values (range = 0.59-0.93) reported. Conclusions: Best-practice guidelines are presented for the use of existing information to define SI/SA/SD in consortia research. These proposed definitions are expected to facilitate more homogeneous data aggregation for genetic and multisite studies. Future research should involve refinement, improved generalizability, and validation in diverse populations.

Three novel missense variants in two families with JAG2-associated limb-girdle muscular dystrophy.

Limb-girdle muscular dystrophy recessive 27 is associated with biallelic variants in JAG2, encoding the JAG2 notch ligand. Twenty-four affected individuals from multiple families have been described in two reports. We present two Australian families with three novel JAG2 missense variants: (c.1021G>T, p.(Gly341Cys)) homozygous in two siblings of Pakistani origin, and compound heterozygous variants (c.703T>C, p.(Trp235Arg); c.2350C>T, p.(Arg784Cys)) in a proband of European ancestry. Patients presented with childhood-onset limb-girdle-like myopathy with difficulty or inability walking. MRI revealed widespread torso and limb muscle involvement. Muscle pathology showed myopathic changes with fatty infiltration. Muscle RNA sequencing revealed significant downregulation of myogenesis genes PAX7, MYF5, and MEGF10 similar to previous JAG2-related muscular dystrophy cases or Jag2-knockdown cells. In absence of functional assays to characterise JAG2 variants, clinical, MRI and transcriptomic profiling collectively may help discern JAG2-related muscular dystrophy, diagnosis of which is essential for patients and families given the severity of disease and reoccurrence risk.

Probing CP Violation with Neutrino Disappearance Alone.

The best way to probe CP violation in the lepton sector is with long-baseline accelerator neutrino experiments in the appearance mode: the appearance of ν_{e} in predominantly ν_{µ} beams. Here we show that it is possible to discover CP violation with disappearance experiments only, by combining JUNO for electron neutrinos and DUNE or Hyper-Kamiokande for muon neutrinos. While the maximum sensitivity to discover CP is quite modest (1.6σ with 6 years of JUNO and 13 years of DUNE), some values of δ may be disfavored by >3σ depending on the true value of δ.

Revisiting Differences in Fourth-Year Orthopaedic Away Rotation Opportunities and Fees Among Allopathic and Osteopathic Medical Students.

Introduction: Fourth-year away rotations are an important modifiable variable proven to increase students' opportunities to match into orthopaedic surgery. The purpose of this study was to determine differences in away rotation eligibility requirements and cost of rotation between allopathic and osteopathic students during the 2023 application cycle. Eligibility requirements and fees were then compared with the 2021 application cycle. Methods: A cross-sectional study was performed during the 2023 application cycle of all nonmilitary, Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery residency programs (n = 194). Each program's website, affiliated school of medicine's website, visiting student application service portal, and Residency Explorer tool were searched for eligibility criteria, associated rotation fees, and other rotation requirements. Two-sample Z tests for proportions were utilized to compare differences in programs with differing requirements for students based on academic degree type. Data were compared statistically with previously reported data from the 2021 application cycle. Results: In 2023, there were more programs that restricted osteopathic medical students from away rotations than programs that restricted allopathic medical students (12/194, 6.2% vs. 0/194, 0.0%; p < 0.001). All 12 programs were formerly ACGME-accredited before the integration into a single accreditation system. There was a decrease in the number of programs restricting osteopathic medical students from away rotations compared with the 2021 application cycle (18/194, 9.3% vs. 12/194, 6.2%; p = 0.254). Fees associated with away rotations ranged from $25 to $4,000 for both allopathic and osteopathic students. The number of programs that charged osteopathic medical students higher rotation fees than programs that charged allopathic students when compared with the 2021 application cycles decreased (1/194, 0.5% vs. 5/194, 2.6%; p = 0.049). Conclusions: While some programs continue to have away rotation eligibility requirements that prohibit osteopathic medical students from rotating, only one residency program currently charges osteopathic medical students a higher fee to rotate than allopathic medical students.

Association between adolescent alcohol use and cognitive function in young adulthood: A co-twin comparison study.

BACKGROUND AND AIMS: Studies on adolescent alcohol use and cognition are often unable to separate the potential causal effects of alcohol use on cognition from shared etiological influences, including genetic influences or other substance use comorbidities also known to be associated with cognition, such as nicotine use. The present study aimed to fill this gap and clarify the relationship between adolescent alcohol use and young adult cognition by accounting for both measured and unmeasured confounders. DESIGN: A random effects model accounting for nesting in families was used to control for measured confounders. Next, co-twin comparisons were conducted within the full sample and in monozygotic twin pairs (MZ) to control for unmeasured genetic and environmental confounders shared by co-twins. PARTICIPANTS/SETTING: Participants were 812 individuals (58.6% female, 361 complete pairs, 146 MZ pairs) from the longitudinal FinnTwin12 study in Finland. MEASUREMENTS: Adolescent alcohol use was indexed with measures of frequency of use and intoxication averaged across ages 14 and 17. Cognitive outcomes were measured at average age 22 and included Trail Making Test, California Stroop test, Wechsler Adult Intelligence subtests (Vocabulary, Block Design, Digit Symbol), Digit Span subtest of Wechsler Memory Scale, Mental Rotation Test and Object Location Memory test. Covariates included sex, parental education, general cognitive ability, current alcohol use and nicotine use. FINDINGS: Greater frequency of alcohol use and frequency of intoxication across adolescence was associated with decreased vocabulary scores in the co-twin control [freq: stnd beta = -0.12, 95% confidence interval (CI) = -0.234, -0.013] and MZ only co-twin control models (freq: stnd beta = -0.305, 95% CI = -0.523, -0.087; intox: stnd beta = -0.301, 95% CI = -0.528, -0.074). CONCLUSIONS: In Finland, there appears to be little evidence that adolescent alcohol use causes cognitive deficits in young adulthood, except modest evidence for association of higher adolescent alcohol use with lower young adult vocabulary scores.

Aboveground and belowground biodiversity have complementary effects on ecosystem functions across global grasslands.

Grasslands are integral to maintaining biodiversity and key ecosystem services and are under threat from climate change. Plant and soil microbial diversity, and their interactions, support the provision of multiple ecosystem functions (multifunctionality). However, it remains virtually unknown whether plant and soil microbial diversity explain a unique portion of total variation or shared contributions to supporting multifunctionality across global grasslands. Here, we combine results from a global survey of 101 grasslands with a novel microcosm study, controlling for both plant and soil microbial diversity to identify their individual and interactive contribution to support multifunctionality under aridity and experimental drought. We found that plant and soil microbial diversity independently predict a unique portion of total variation in above- and belowground functioning, suggesting that both types of biodiversity complement each other. Interactions between plant and soil microbial diversity positively impacted multifunctionality including primary production and nutrient storage. Our findings were also climate context dependent, since soil fungal diversity was positively associated with multifunctionality in less arid regions, while plant diversity was strongly and positively linked to multifunctionality in more arid regions. Our results highlight the need to conserve both above- and belowground diversity to sustain grassland multifunctionality in a drier world and indicate climate change may shift the relative contribution of plant and soil biodiversity to multifunctionality across global grasslands.

The "future" pain clinician: Competencies needed to provide psychologically informed care.

BACKGROUND & OBJECTIVE: Psychologically informed care has been proposed to improve treatment outcomes for chronic pain and aligns with a person-centered approach. Yet implementation lags behind, and studies suggest that a lack of competency leads to poor results. It is unclear what training clinicians require to deliver this care. We examine how we might improve psychologically informed care guided by the needs of the patient and in congruence with the scientific literature with a particular focus on how competencies might be upgraded and implementation enhanced. METHODS: We selectively review the literature for psychologically informed care for pain. The patient's view on what is needed is contrasted with the competencies necessary to meet these needs and how treatment should be evaluated. RESULTS: Patient needs and corresponding competencies are delineated. A number of multi-professional skills and competencies are required to provide psychologically informed care. Single-subject methodologies can determine whether the care has the desired effect for the individual patient and facilitate effectiveness. We argue that becoming a competent "pain clinician" requires a new approach to education that transcends current professional boundaries. CONCLUSIONS: Providing person-centered care guided by the needs of the patient and in line with the scientific literature shows great potential but requires multiple competencies. We propose that training the pain clinician of the future should focus on psychologically informed care and the competencies required to meet the individual's needs. Single-subject methodology allows for continual evaluation of this care.

Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age.

BACKGROUND: There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). AIMS: This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. METHODS: This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. CONCLUSIONS: These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern.Trial registration number: ClinicalTrials.gov Identifier: NCT01689909.

Development and initial evaluation of a clinical prediction model for risk of treatment resistance in first-episode psychosis: Schizophrenia Prediction of Resistance to Treatment (SPIRIT).

BACKGROUND: A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication. AIMS: To develop and evaluate a model that could predict the risk of TRS in routine clinical practice. METHOD: We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis. Using sociodemographic and clinical predictors, a model for predicting risk of TRS was developed based on penalised logistic regression, with missing data handled using multiple imputation. Internal validation was undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. Interviews and focus groups with clinicians were conducted to establish clinically relevant risk thresholds and understand the acceptability and perceived utility of the model. RESULTS: We included seven factors in the prediction model that are predominantly assessed in clinical practice in patients with FEP. The model predicted treatment resistance among the 1081 patients with reasonable accuracy; the model's C-statistic was 0.727 (95% CI 0.723-0.732) prior to shrinkage and 0.687 after adjustment for optimism. Calibration was good (expected/observed ratio: 0.999; calibration-in-the-large: 0.000584) after adjustment for optimism. CONCLUSIONS: We developed and internally validated a prediction model with reasonably good predictive metrics. Clinicians, patients and carers were involved in the development process. External validation of the tool is needed followed by co-design methodology to support implementation in early intervention services.

Unveiling the intricacy of gapmer oligonucleotides through advanced tandem mass spectrometry approaches and scan accumulation for 2DMS.

Antisense oligonucleotides (ASOs) are crucial for biological applications as they bind to complementary RNA sequences, modulating protein expression. ASOs undergo synthetic modifications like phosphorothioate (PS) backbone and locked nucleic acid (LNA) to enhance stability and specificity. Tandem mass spectrometry (MS) techniques were employed to study gapmer ASOs, which feature a DNA chain within RNA segments at both termini, revealing enhanced cleavages with ultraviolet photodissociation (UVPD) and complementary fragment ions from collision-induced dissociation (CID) and electron detachment dissociation (EDD). 2DMS, a data-independent analysis technique, allowed for comprehensive coverage and identification of shared fragments across multiple precursor ions. EDD fragmentation efficiency correlated with precursor ion charge states, with higher charges facilitating dissociation due to intramolecular repulsions. An electron energy of 22.8 eV enabled electron capture and radical-based cleavage. Accumulating multiple scans and generating average spectra improved signal intensity, aided by denoising algorithms. Data analysis utilised a custom Python script capable of handling modifications and generating unique mass lists.

Photosynthetic capacity in middle-aged larch and spruce acclimates independently to experimental warming and elevated CO2.

Photosynthetic acclimation to both warming and elevated CO2 of boreal trees remains a key uncertainty in modelling the response of photosynthesis to future climates. We investigated the impact of increased growth temperature and elevated CO2 on photosynthetic capacity (Vcmax and Jmax) in mature trees of two North American boreal conifers, tamarack and black spruce. We show that Vcmax and Jmax at a standard temperature of 25°C did not change with warming, while Vcmax and Jmax at their thermal optima (Topt) and growth temperature (Tg) increased. Moreover, Vcmax and Jmax at either 25°C, Topt or Tg decreased with elevated CO2. The Jmax/Vcmax ratio decreased with warming when assessed at both Topt and Tg but did not significantly vary at 25°C. The Jmax/Vcmax increased with elevated CO2 at either reference temperature. We found no significant interaction between warming and elevated CO2 on all traits. If this lack of interaction between warming and elevated CO2 on the Vcmax, Jmax and Jmax/Vcmax ratio is a general trend, it would have significant implications for improving photosynthesis representation in vegetation models. However, future research is required to investigate the widespread nature of this response in a larger number of species and biomes.

Impact of patient habitus and acquisition protocol on iodine quantification in dual-source photon-counting computed tomography.

Purpose: Evaluation of iodine quantification accuracy with varying iterative reconstruction level, patient habitus, and acquisition mode on a first-generation dual-source photon-counting computed tomography (PCCT) system. Approach: A multi-energy CT phantom with and without its extension ring equipped with various iodine inserts (0.2 to 15.0 mg/ml) was scanned over a range of radiation dose levels ( CTDI vol 0.5 to 15.0 mGy) using two tube voltages (120, 140 kVp) and two different source modes (single-, dual-source). To assess the agreement between nominal and measured iodine concentrations, iodine density maps at different iterative reconstruction levels were utilized to calculate root mean square error (RMSE) and generate Bland-Altman plots by grouping radiation dose levels (ultra-low: < 1.5 ; low: 1.5 to 5; medium: 5 to 15 mGy) and iodine concentrations (low: < 5 ; high: 5 to 15 mg/mL). Results: Overall, quantification of iodine concentrations was accurate and reliable even at ultra-low radiation dose levels. RMSE ranged from 0.25 to 0.37, 0.20 to 0.38, and 0.25 to 0.37 mg/ml for ultra-low, low, and medium radiation dose levels, respectively. Similarly, RMSE was stable at 0.31, 0.28, 0.33, and 0.30 mg/ml for tube voltage and source mode combinations. Ultimately, the accuracy of iodine quantification was higher for the phantom without an extension ring (RMSE 0.21 mg/mL) and did not vary across different levels of iterative reconstruction. Conclusions: The first-generation PCCT allows for accurate iodine quantification over a wide range of iodine concentrations and radiation dose levels. Stable accuracy across iterative reconstruction levels may allow further radiation exposure reductions without affecting quantitative results.

Monitoring and Outcomes of Central Line-Associated Bloodstream Infections in a Tertiary Care Intensive Care Unit.

Background Central line-associated bloodstream infections (CLABSIs) are significant healthcare-associated infections that increase morbidity, mortality, and healthcare costs. This study aims to analyze the frequency, microbiology, risk factors, and outcomes of CLABSI in an adult intensive care unit. Methods We conducted a hospital-based, prospective surveillance study in the critical care unit of a tertiary care hospital. We included patients with a central line (CL) from admission until discharge or line removal. Data collection focused on patient demographics, comorbidities, CL insertion site, and CLABSI rates. The incidence of CLABSI was calculated per 1,000 CL-days, and statistical analysis was performed using the Chi-square test. Results Of the 169 patients enrolled, 123 episodes of bloodstream infections were recorded, 56 (45.5%) of which were CLABSIs. The organisms most frequently isolated were Klebsiella pneumoniae (n = 14; 24.6%), Enterobacter cloacae complex (n = 11; 19.3%), Klebsiella species (n = 7; 12.28%), and Acinetobacter baumannii (n = 7; 12.28%). The overall CLABSI rate was 24.70 per 1,000 CL-days. No significant association was found between CLABSI and patient age, gender, or the site of CL insertion. However, a significant relationship was observed between CLABSI and the presence of comorbid conditions (p = 0.001). The study also noted a high rate of antibiotic resistance among the isolated pathogens. Conclusions Our results emphasize the need for stringent infection control measures and suggest that comorbid conditions significantly increase the risk of CLABSI. Addressing antibiotic resistance and implementing effective prevention strategies are essential for reducing the burden of CLABSIs.

Deaths with COVID-19 and from all-causes following first-ever SARS-CoV-2 infection in individuals with preexisting mental disorders: A national cohort study from Czechia.

BACKGROUND: Evidence suggests reduced survival rates following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in people with preexisting mental disorders, especially psychotic disorders, before the broad introduction of vaccines. It remains unknown whether this elevated mortality risk persisted at later phases of the pandemic and when accounting for the confounding effect of vaccination uptake and clinically recorded physical comorbidities. METHODS AND FINDINGS: We used data from Czech national health registers to identify first-ever serologically confirmed SARS-CoV-2 infections in 5 epochs related to different phases of the pandemic: 1st March 2020 to 30th September 2020, 1st October 2020 to 26th December 2020, 27th December 2020 to 31st March 2021, 1st April 2021 to 31st October 2021, and 1st November 2021 to 29th February 2022. In these people, we ascertained cases of mental disorders using 2 approaches: (1) per the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes for substance use, psychotic, affective, and anxiety disorders; and (2) per ICD-10 diagnostic codes for the above mental disorders coupled with a prescription for anxiolytics/hypnotics/sedatives, antidepressants, antipsychotics, or stimulants per the Anatomical Therapeutic Chemical (ATC) classification codes. We matched individuals with preexisting mental disorders with counterparts who had no recorded mental disorders on age, sex, month and year of infection, vaccination status, and the Charlson Comorbidity Index (CCI). We assessed deaths with Coronavirus Disease 2019 (COVID-19) and from all-causes in the time period of 28 and 60 days following the infection using stratified Cox proportional hazards models, adjusting for matching variables and additional confounders. The number of individuals in matched-cohorts ranged from 1,328 in epoch 1 to 854,079 in epoch 5. The proportion of females ranged from 34.98% in people diagnosed with substance use disorders in epoch 3 to 71.16% in individuals diagnosed and treated with anxiety disorders in epoch 5. The mean age ranged from 40.97 years (standard deviation [SD] = 15.69 years) in individuals diagnosed with substance use disorders in epoch 5 to 56.04 years (SD = 18.37 years) in people diagnosed with psychotic disorders in epoch 2. People diagnosed with or diagnosed and treated for psychotic disorders had a consistently elevated risk of dying with COVID-19 in epochs 2, 3, 4, and 5, with adjusted hazard ratios (aHRs) ranging from 1.46 [95% confidence intervals (CIs), 1.18, 1.79] to 1.93 [95% CIs, 1.12, 3.32]. This patient group demonstrated also a consistently elevated risk of all-cause mortality in epochs 2, 3, 4, and 5 (aHR from 1.43 [95% CIs, 1.23, 1.66] to 1.99 [95% CIs, 1.25, 3.16]). The models could not be reliably fit for psychotic disorders in epoch 1. People diagnosed with substance use disorders had an increased risk of all-cause mortality 28 days postinfection in epoch 3, 4, and 5 (aHR from 1.30 [95% CIs, 1.14, 1.47] to 1.59 [95% CIs, 1.19, 2.12]) and 60 days postinfection in epoch 2, 3, 4, and 5 (aHR from 1.22 [95% CIs, 1.08, 1.38] to 1.52 [95% CIs, 1.16, 1.98]). Cases ascertained based on diagnosis of substance use disorders and treatment had increased risk of all-cause mortality in epoch 2, 3, 4, and 5 (aHR from 1.22 [95% CIs, 1.03, 1.43] to 1.91 [95% CIs, 1.25, 2.91]). The models could not be reliably fit for substance use disorders in epoch 1. In contrast to these, people diagnosed with anxiety disorders had a decreased risk of death with COVID-19 in epoch 2, 3, and 5 (aHR from 0.78 [95% CIs, 0.69, 0.88] to 0.89 [95% CIs, 0.81, 0.98]) and all-cause mortality in epoch 2, 3, 4, and 5 (aHR from 0.83 [95% CIs, 0.77, 0.90] to 0.88 [95% CIs, 0.83, 0.93]). People diagnosed and treated for affective disorders had a decreased risk of both death with COVID-19 and from all-causes in epoch 3 (aHR from 0.87 [95% CIs, 0.79, 0.96] to 0.90 [95% CIs, 0.83, 0.99]), but demonstrated broadly null effects in other epochs. Given the unavailability of data on a number of potentially influential confounders, particularly body mass index, tobacco smoking status, and socioeconomic status, part of the detected associations might be due to residual confounding. CONCLUSIONS: People with preexisting psychotic, and, less robustly, substance use disorders demonstrated a persistently elevated risk of death following SARS-CoV-2 infection throughout the pandemic. While it cannot be ruled out that part of the detected associations is due to residual confounding, this excess mortality cannot be fully explained by lower vaccination uptake and more clinically recorded physical comorbidities in these patient groups.