Mode of Action of Kanglemycin A, an Ansamycin Natural Product that Is Active against Rifampicin-Resistant Mycobacterium tuberculosis.

Antibiotic-resistant bacterial pathogens pose an urgent healthcare threat, prompting a demand for new medicines. We report the mode of action of the natural ansamycin antibiotic kanglemycin A (KglA). KglA binds bacterial RNA polymerase at the rifampicin-binding pocket but maintains potency against RNA polymerases containing rifampicin-resistant mutations. KglA has antibiotic activity against rifampicin-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis (MDR-M. tuberculosis). The X-ray crystal structures of KglA with the Escherichia coli RNA polymerase holoenzyme and Thermus thermophilus RNA polymerase-promoter complex reveal an altered-compared with rifampicin-conformation of KglA within the rifampicin-binding pocket. Unique deoxysugar and succinate ansa bridge substituents make additional contacts with a separate, hydrophobic pocket of RNA polymerase and preclude the formation of initial dinucleotides, respectively. Previous ansa-chain modifications in the rifamycin series have proven unsuccessful. Thus, KglA represents a key starting point for the development of a new class of ansa-chain derivatized ansamycins to tackle rifampicin resistance.

Alpha-synuclein modulates the repair of genomic DNA double-strand breaks in a DNA-PKcs-regulated manner.

α-synuclein (αSyn) is a presynaptic and nuclear protein that aggregates in important neurodegenerative diseases such as Parkinson's Disease (PD), Parkinson's Disease Dementia (PDD) and Lewy Body Dementia (LBD). Our past work suggests that nuclear αSyn may regulate forms of DNA double-strand break (DSB) repair in HAP1 cells after DNA damage induction with the chemotherapeutic agent bleomycin1. Here, we report that genetic deletion of αSyn specifically impairs the non-homologous end-joining (NHEJ) pathway of DSB repair using an extrachromosomal plasmid-based repair assay in HAP1 cells. Notably, induction of a single DSB at a precise genomic location using a CRISPR/Cas9 lentiviral approach also showed the importance of αSyn in regulating NHEJ in HAP1 cells and primary mouse cortical neuron cultures. This modulation of DSB repair is regulated by the activity of the DNA damage response signaling kinase DNA-PKcs, since the effect of αSyn loss-of-function is reversed by DNA-PKcs inhibition. Together, these findings suggest that αSyn plays an important physiologic role in regulating DSB repair in both a transformed cell line and in primary cortical neurons. Loss of this nuclear function may contribute to the neuronal genomic instability detected in PD, PDD and LBD and points to DNA-PKcs as a potential therapeutic target.

Modulating Electrostatic Properties and Noncovalent Interactions via Structural Isomerism: The Microwave Spectra and Molecular Structures of (E)- and (Z)-1,2,3,3,3-Pentafluoropropene and Their Gas-Phase Heterodimers with the Argon Atom.

Microwave spectra of both the E and Z isomers of 1,2,3,3,3-pentafluoropropene along with all three of the singly substituted 13C isotopologues for each are obtained using broadband chirped-pulse Fourier transform microwave spectroscopy from 2.0-18.1 GHz. Associated quantum chemistry calculations show that the barrier to internal rotation of the CF3 group is significantly higher for the Z isomer, which is stabilized by an intramolecular hydrogen bond, although the barriers in both isomers are sufficiently high to prevent the observation of any effects due to internal rotation. The normal isotopologues of the argon heterodimers for both isomers are also observed in the broadband spectrum and a Balle-Flygare cavity Fourier transform microwave spectrometer is used to obtain the 5.0-20.6 GHz spectra of the corresponding 13C isotopologues. In each case, the argon atom locates so as to maximize its interactions with areas of significant electron density. However, mapped electrostatic potential surfaces indicate that the areas of greatest nucleophilicity are different for the two isomers, suggesting that they may interact differently in forming heterodimers with protic acids.

Genetic deletion of Polo-like kinase 2 reduces alpha-synuclein serine-129 phosphorylation in presynaptic terminals but not Lewy bodies.

Phosphorylation of alpha-synuclein at serine-129 is an important marker of pathologically relevant, aggregated forms of the protein in several important human diseases, including Parkinson's disease, Dementia with Lewy bodies, and Multiple system atrophy. Although several kinases have been shown to be capable of phosphorylating alpha-synuclein in various model systems, the identity of the kinase that phosphorylates alpha-synuclein in the Lewy body remains unknown. One member of the Polo-like kinase family, PLK2, is a strong candidate for being the Lewy body kinase. To examine this possibility, we have used a combination of approaches, including biochemical, immunohistochemical, and in vivo multiphoton imaging techniques to study the consequences of PLK2 genetic deletion on alpha-synuclein phosphorylation in both the presynaptic terminal and preformed fibril-induced Lewy body pathology in mouse cortex. We find that PLK2 deletion reduces presynaptic terminal alpha-synuclein serine-129 phosphorylation, but has no effect on Lewy body phosphorylation levels. Serine-129 mutation to the phosphomimetic alanine or the unphosphorylatable analog aspartate does not change the rate of cell death of Lewy inclusion-bearing neurons in our in vivo multiphoton imaging paradigm, but PLK2 deletion does slow the rate of neuronal death. Our data indicate that inhibition of PLK2 represents a promising avenue for developing new therapeutics, but that the mechanism of neuroprotection by PLK2 inhibition is not likely due to reducing alpha-synuclein serine-129 phosphorylation and that the true Lewy body kinase still awaits discovery.

Etiology, Comorbidities, and Health Service Use in a Clinical Cohort of Children With Hearing Loss.

OBJECTIVE: To examine etiology, comorbidities, and health service use in a cohort of children with permanent hearing loss. Receiving an etiological diagnosis can inform reproductive planning, rehabilitation outcomes, predict additional disabilities, and direct intervention or management decisions. DESIGN: Retrospective audit of 518 deaf/hard-of-hearing children attending a tertiary pediatric outpatient clinic (2016-2019) using descriptive statistics. We used linear regression to investigate the relationship between degree of hearing loss, comorbidities, and health service use. RESULTS: Of the 518 children who attended the clinic, 481 (92.9%) proceeded with testing for etiology. Most children (399/518, 77.0%) were diagnosed with hearing loss by 3 mo of age. Of the children tested, the cause of hearing loss was confirmed in 234/481 (48.6%), suspected in 113/481 (23.5%), and unknown in 134/481 (27.9%); 17/341 (5.0%) had congenital cytomegalovirus (CMV), 17/320 (5.3%) had enlarged vestibular aqueducts, 67/213 (31.5%) of children with bilateral hearing loss had connexin mutation, and 25/72 (34.7%) of children with unilateral loss had hypoplastic/absent cochlear nerve on imaging. The odds of having a definitive/suspected diagnosis were twice as likely for indivduals with profound hearing loss than mild hearing loss (OR 2.1; 95% CI, 1.2-3.9; P = 0.02). The majority (348/518, 67.2%) of children had medical comorbidities, and most children attended otolaryngology (453/518, 87.5%), early intervention (358/518, 69.1%), and genetic (287/518, 55.4%) services. CONCLUSIONS: Children with hearing loss have diverse etiologies, most have comorbidities, and attend multiple services. Most families elected to proceed with diagnostic testing for etiology. Current guidelines and expanded access to genetic testing identified a confirmed/suspected etiological diagnosis in 72.1% of children tested. The number of comorbidities correlated with service use, regardless of hearing loss severity.

Back pain occurred due to changes in routinary activities among Brazilian schoolteachers during the COVID-19 pandemic.

OBJECTIVE: This study's main objective was to investigate the emergence of back pain as a consequence to changes in usual activities due to the COVID-19 pandemic among teachers in public schools in the state of Minas Gerais, Brazil. METHODS: A cross-sectional study was conducted among 15,276 schoolteachers using an online questionnaire. The variables included sociodemographic and occupational data, health situation, habits and behaviors during the COVID-19 pandemic. Bivariate analyses using Pearson's chi-square test and multiple analyses using Poisson regression were performed to identify the associated factors. RESULTS: About 58% of schoolteachers reported back pain due to changes in routine activities during the pandemic. The adjusted model showed a correlation between back pain and female sex, longer working hours, overwork, difficulties concerning distance working, negative changes in health status and quality of sleep; frequent feeling of sadness, depression, or anxiety; use of medications to relax, sleep or against stress/anxiety/depression; physical inactivity or negative changes in the practice of physical activities; increased body weight; reduction of leisure time; increased time of use of computer or tablet and overload of housework. CONCLUSION: During the COVID-19 pandemic, schoolteachers reported a high prevalence of emergence of back pain, which delineates a contradiction in terms: on the one hand, distance education allows social distancing that contributes to the preservation of teachers' health by reducing the risk of contamination by COVID-19. On the other hand, it imposes new demands that-in disagreement with working conditions-can threaten the health of these workers.

Strengthening research capacity through an intensive training program for biomedical investigators from low- and middle-income countries: the Vanderbilt Institute for Research Development and Ethics (VIRDE).

BACKGROUND: Capacity strengthening initiatives aimed at increasing research knowledge and skills of investigators in low- and middle-income countries (LMICs) have been implemented over the last several decades. With increased capacity, local investigators will have greater leadership in defining research priorities and impact policy change to help improve health outcomes. Evaluations of models of capacity strengthening programs are often limited to short-term impact. Noting the limitations of traditional output-based evaluations, we utilized a broader framework to evaluate the long-term impact of the Vanderbilt Institute in Research Development and Ethics (VIRDE), a decade-old intensive grant development practicum specifically tailored for investigators from LMICs. METHODS: To assess the impact of VIRDE on the research careers of alumni over the past 10 years, we surveyed alumni on research engagement, grant productivity, career trajectory, and knowledge gained in grant writing. Descriptive statistics, including means and total counts, and paired sample t-tests were used to analyze the data. RESULTS: Forty-six of 58 alumni completed the survey. All respondents returned to their home countries and are currently engaged in research. Post-VIRDE grant writing knowledge ratings were significantly greater than pre-VIRDE. The number of respondents submitting grants post-VIRDE was 2.6 times higher than before the program. Eighty-three percent of respondents submitted a total of 147 grants post-VIRDE, of which 45.6% were awarded. Respondents acknowledged VIRDE's positive impact on career growth and leadership, with 88% advancing in career stage. CONCLUSIONS: Gains in grant writing knowledge and grant productivity suggest that VIRDE scholars built skills and confidence in grant writing during the program. A substantial proportion of respondents have advanced in their careers and continue to work in academia in their country of origin. Results show a sustained impact on the research careers of VIRDE alumni. The broader framework for research capacity strengthening resulted in an expansive assessment of the VIRDE program and alumni, illuminating successful program elements and implications that can inform similar capacity strengthening programs.

Utilization of combination bowel preparation (CBP) is protective against the development of post-operative Clostridium difficile infection (CDI), decreases septic complications, and provides a survival benefit.

BACKGROUND: The current standard recommended by the American Society of Colon and Rectal Surgeons (ASCRS) is to utilize a combined bowel preparation (CBP) that involves both mechanical (MBP) and oral antibiotic (ABP) components. The current literature is equivocal on whether ABP predisposes to post-operative Clostridium difficile infection (CDI). CDI following colorectal surgery is a significant complication leading to increase in significant morbidity and mortality. Objective was to further delineate the association between CBP and CDI. METHODS: Retrospective review of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) registry was performed. Specifically the main and targeted colectomy/proctectomy databases for 2015 and 2016 were analyzed. 64,449 colorectal surgeries were contained. Exclusion of non-elective cases and cases that did not utilize a bowel preparation or used ABP alone resulted in 24,000 cases for final analysis. Primary endpoint was post-operative CDI development. Secondary analysis involved surgical site infections (SSIs), anastomotic leaks, and sepsis development. 30-day mortality rates, rapidity of return of bowel function, and length of stay were also evaluated. RESULTS: Approximately two-thirds of the cases analyzed involved CBP and the remaining third used MBP alone. Cases that utilized CBP had statistically significant lower rates of all infectious complications evaluated. CBP was found to be protective in regard to the development of CDI with an odds ratio (OR) of 0.58. Our results collaborate the current literature that CBP decreases SSIs and anastomotic leaks with ORs of 0.58 and 0.79, respectively. CBP had its most profound effect on lowering septic shock and mortality rates halving the incidence of both. CONCLUSION: Our findings support the ASCRS guidelines for routine utilization of CBP to optimize post-operative outcomes. CBP does not increase the risk of CDI and in fact is significantly protective. CBP potentially also provides decreased risk of sepsis and mortality.

Probiotics, Prebiotics and Epithelial Tight Junctions: A Promising Approach to Modulate Intestinal Barrier Function.

Disruptions in the intestinal epithelial barrier can result in devastating consequences and a multitude of disease syndromes, particularly among preterm neonates. The association between barrier dysfunction and intestinal dysbiosis suggests that the intestinal barrier function is interactive with specific gut commensals and pathogenic microbes. In vitro and in vivo studies demonstrate that probiotic supplementation promotes significant upregulation and relocalization of interepithelial tight junction proteins, which form the microscopic scaffolds of the intestinal barrier. Probiotics facilitate some of these effects through the ligand-mediated stimulation of several toll-like receptors that are expressed by the intestinal epithelium. In particular, bacterial-mediated stimulation of toll-like receptor-2 modulates the expression and localization of specific protein constituents of intestinal tight junctions. Given that ingested prebiotics are robust modulators of the intestinal microbiota, prebiotic supplementation has been similarly investigated as a potential, indirect mechanism of barrier preservation. Emerging evidence suggests that prebiotics may additionally exert a direct effect on intestinal barrier function through mechanisms independent of the gut microbiota. In this review, we summarize current views on the effects of pro- and prebiotics on the intestinal epithelial barrier as well as on non-epithelial cell barrier constituents, such as the enteric glial cell network. Through continued investigation of these bioactive compounds, we can maximize their therapeutic potential for preventing and treating gastrointestinal diseases associated with impaired intestinal barrier function and dysbiosis.

Evidence for the Validity of the Children's Attraction to Physical Activity (CAPA) Scale in Iranian Preschool Children.

PURPOSE: The escalating trend of overweight and obesity is a major global health challenge and needs particular attention. There are a number of reasons for this increase, but the dominant one appears to be the pandemic of physical inactivity. It is now clear that children's attraction to physical activity is an important promising factor in children's physical activity involvement. In this study, we aimed to cross-validate the long version of children's attraction to physical activity (CAPA) scale in Iranian preschool children. DESIGN AND METHODS: Evidence for the validity of the scale was based on face validity, content validity, and internal consistency. The scale was translated into Persian and underwent forward translation, synthesis of the translation and backward translation. Face and content validity were subsequently assessed on individuals and expert panels. A sample of 30 preschool children (5-6 years of age) were randomly selected from three kindergartens. Children were interviewed by their kindergarten teachers. RESULTS: Internal consistency for each of the five subscales of the CAPA scale was evaluated through Cronbach's alpha. The internal consistency was acceptable for most of the subscales when negative statements were excluded from the analyses. CONCLUSIONS: The results supported the use of modified version of Persian-language long CAPA scale for Iranian preschool children, with the deletion of negatively worded items. PRACTICE IMPLICATIONS: Health care professionals may use the CAPA when assessing the attraction of children toward physical activity and its potential involvement in childhood obesity.

A critique of the historical-fire-regime concept in conservation.

Prescribed fire is widely accepted as a conservation tool because fire is essential to the maintenance of native biodiversity in many terrestrial communities. Approaches to this land-management technique vary greatly among continents, and sharing knowledge internationally can inform application of prescribed fire worldwide. In North America, decisions about how and when to apply prescribed fire are typically based on the historical-fire-regime concept (HFRC), which holds that replicating the pattern of fires ignited by lightning or preindustrial humans best promotes native species in fire-prone regions. The HFRC rests on 3 assumptions: it is possible to infer historical fire regimes accurately; fire-suppressed communities are ecologically degraded; and reinstating historical fire regimes is the best course of action despite the global shift toward novel abiotic and biotic conditions. We examined the underpinnings of these assumptions by conducting a literature review on the use of historical fire regimes to inform the application of prescribed fire. We found that the practice of inferring historical fire regimes for entire regions or ecosystems often entails substantial uncertainty and can yield equivocal results; ecological outcomes of fire suppression are complex and may not equate to degradation, depending on the ecosystem and context; and habitat fragmentation, invasive species, and other modern factors can interact with fire to produce novel and in some cases negative ecological outcomes. It is therefore unlikely that all 3 assumptions will be fully upheld for any landscape in which prescribed fire is being applied. Although the HFRC is a valuable starting point, it should not be viewed as the sole basis for developing prescribed fire programs. Rather, fire prescriptions should also account for other specific, measurable ecological parameters on a case-by-case basis. To best achieve conservation goals, researchers should seek to understand contemporary fire-biota interactions across trophic levels, functional groups, spatial and temporal scales, and management contexts.

A Standard Set of Outcome Measures for the Comprehensive Appraisal of Cleft Care.

Care of the patient with cleft lip and/or palate remains complex. Prior attempts at aggregating data to study the effectiveness of specific interventions or overall treatment protocols have been hindered by a lack of data standards. There exists a critical need to better define the outcomes-particularly those that matter most to patients and their families-and to standardize the methods by which these outcomes will be measured. This report summarizes the recommendations of an international, multidisciplinary working group with regard to which outcomes a typical cleft team could track, how those outcomes could be measured and recorded, and what strategies may be employed to sustainably implement a system for prospective data collection. It is only by agreeing on a common, standard set of outcome measures for the comprehensive appraisal of cleft care that intercenter comparisons can become possible. This is important for quality-improvement endeavors, comparative effectiveness research, and value-based health-care reform.

Polo-like kinase inhibition leads to neuroprotection of neurons bearing alpha-synuclein Lewy body-like inclusions in vivo.

α-synuclein (αSyn) and S129 phosphorylated αSyn (pSyn) define synucleinopathies like Parkinson's disease (PD). Targeting S129 αSyn kinases, like the Polo-like kinase (PLK) family, could provide a therapeutic strategy to limit degeneration of cells bearing aggregated αSyn inclusions. Using longitudinal in vivo multiphoton imaging in mouse cortex after αSyn inclusion induction, we find an increase in cell survival of inclusion-bearing neurons after PLK inhibition. PLK inhibition is associated with increased αSyn levels within inclusions and increased nuclear DNA damage repair markers. Overall, these findings suggest that PLK inhibition may serve as a potential therapeutic strategy for limiting neurodegeneration in PD.

Alpha-synuclein regulates the repair of genomic DNA double-strand breaks in a DNA-PKcs-dependent manner.

α-synuclein (αSyn) is a presynaptic and nuclear protein that aggregates in important neurodegenerative diseases such as Parkinson's Disease (PD), Parkinson's Disease Dementia (PDD) and Lewy Body Dementia (LBD). Our past work suggests that nuclear αSyn may regulate forms of DNA double-strand break (DSB) repair in HAP1 cells after DNA damage induction with the chemotherapeutic agent bleomycin1. Here, we report that genetic deletion of αSyn specifically impairs the non-homologous end-joining (NHEJ) pathway of DSB repair using an extrachromosomal plasmid-based repair assay in HAP1 cells. Importantly, induction of a single DSB at a precise genomic location using a CRISPR/Cas9 lentiviral approach also showed the importance of αSyn in regulating NHEJ in HAP1 cells and primary mouse cortical neuron cultures. This modulation of DSB repair is dependent on the activity of the DNA damage response signaling kinase DNA-PKcs, since the effect of αSyn loss-of-function is reversed by DNA-PKcs inhibition. Using in vivo multiphoton imaging in mouse cortex after induction of αSyn pathology, we find an increase in longitudinal cell survival of inclusion-bearing neurons after Polo-like kinase (PLK) inhibition, which is associated with an increase in the amount of aggregated αSyn within inclusions. Together, these findings suggest that αSyn plays an important physiologic role in regulating DSB repair in both a transformed cell line and in primary cortical neurons. Loss of this nuclear function may contribute to the neuronal genomic instability detected in PD, PDD and DLB and points to DNA-PKcs and PLK as potential therapeutic targets.

Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine.

Intestinal ischemic injury damages the epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age-dependency of intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier versus older patients. We have developed a pig model that demonstrates age-dependent failure of intestinal barrier restitution in neonatal pigs which can be rescued by the direct application of juvenile pig mucosal tissue, but the mechanisms of rescue remain undefined. We hypothesized that by identifying a subpopulation of restituting enterocytes by their expression of cell migration transcriptional pathways, we can then predict novel upstream regulators of age-dependent restitution response programs. Superficial mucosal epithelial cells from recovering ischemic jejunum of juvenile pigs were processed for single cell RNA sequencing analysis, and predicted upstream regulators were assessed in a porcine intestinal epithelial cell line (IPEC-J2) and banked tissues. A subcluster of absorptive enterocytes expressed several cell migration pathways key to restitution. Differentially expressed genes in this subcluster predicted their upstream regulation included colony stimulating factor-1 (CSF-1). We validated age-dependent induction of CSF-1 by ischemia and documented that CSF-1 and CSF1R co-localized in ischemic juvenile, but not neonatal, wound-adjacent epithelial cells and in the restituted epithelium of juveniles and rescued (but not control) neonates. Further, the CSF1R inhibitor BLZ945 reduced restitution in scratch wounded IPEC-J2 cells. These studies validate an approach to inform potential novel therapeutic targets, such as CSF-1, to improve outcomes in neonates with intestinal injury in a unique pig model. NEW & NOTEWORTHY: These studies validate an approach to identify and predict upstream regulation of restituting epithelium in a unique pig intestinal ischemic injury model. Identification of potential molecular mediators of restitution, such as CSF-1, will inform the development of targeted therapeutic interventions for medical management of patients with ischemia-mediated intestinal injury.

Musculoskeletal pain among healthcare workers: an exploratory study on gender differences.

BACKGROUND: Musculoskeletal disorder rates among healthcare workers are high compared to other occupational groups. Studies indicate a higher prevalence of musculoskeletal pain in women as compared to men in most productive sectors. The objectives of our study were to assess the prevalence of upper-limb musculoskeletal pain in male and female employees of the Belo Horizonte municipal Health Department, and to identify associated factors, considering individual and occupational characteristics, by gender. METHODS: This cross-sectional study of a proportional sample of 1,721 subjects from a universe of 13,602 workers in the municipal health system evaluated the prevalence of self-reported upper-limb musculoskeletal pain. The magnitude of the associations was estimated by Poisson regression. RESULTS: The prevalence of upper-limb musculoskeletal pain was 24.1% among women and 11.0% among men. Women who had high domestic workloads, and performed tasks under high strain showed high prevalence of musculoskeletal pain. For women and men, a high prevalence of upper-limb pain was reported by those who performed highly physically demanding tasks, and those exposed to poor environmental conditions. CONCLUSIONS: The findings suggest gender differences in the distribution of upper-limb musculoskeletal pain across occupational groups. It also support initiatives that focus on the need to give visibility to the different effects of working conditions on the health of occupational groups and suggest the importance of developing specific measures to promote women's health. The higher prevalence of pain observed among women with high domestic workloads suggests the importance of these activities when evaluating workload in occupational studies.

The Relationship Between Perceptions of Physical Self-Worth, Subdomain Importance, and Physical Fitness in Adolescents With Low Motor Competence: An Exploratory Study.

Purpose: Adolescent perceptions of their physical self-worth (PSW) and the component domains draw upon physical attributes, such as motor competence, physical fitness, and self-perceptions, which in turn enhance the desire to engage in physical activity. Whilst these relationships have been researched in populations with typical motor development, little is known of the interplay of these contributors to PSW with those with low motor competence (LMC). Even less is known of how importance placed on particular physical subdomains may be used by the adolescent with LMC to mitigate negative effects on their perceptions of PSW. Method: Thirty-four adolescents with low motor competence, 25 boys and 9 girls (Mage = 13.89 yrs, SD = 1.49), completed the McCarron Assessment of Neuromuscular Development (MAND), the Children's Physical Self-Perception Questionnaire (C-PSPP) and a range of physical fitness tests. Results: All self-perception subdomain score was lower than importance ratings. Physical fitness measures were also low but were not significantly associated with PSW. However, the higher importance scores relative to physical self-perceptions resulted in greater discrepancy scores in all subdomains. Conclusion: Adolescents with LMC have low PSW, and low self-perceptions relative to importance ratings for most physical self-subdomains. These discrepancies, rather than actual fitness, potentially reduce their motivation to be physically active.

Modelling admission lengths within psychiatric intensive care units.

OBJECTIVES: To examine whether discharge destination is a useful predictor variable for the length of admission within psychiatric intensive care units (PICUs). METHODS: A clinician-led process separated PICU admissions by discharge destination into three types and suggested other possible variables associated with length of stay. Subsequently, a retrospective study gathered proposed predictor variable data from a total of 368 admissions from four PICUs. Bayesian models were developed and analysed. RESULTS: Clinical patient-type grouping by discharge destination displayed better intraclass correlation (0.37) than any other predictor variable (next highest was the specific PICU to which a patient was admitted (0.0585)). Patients who were transferred to further secure care had the longest PICU admission length. The best model included both patient type (discharge destination) and unit as well as an interaction between those variables. DISCUSSION: Patient typing based on clinical pathways shows better predictive ability of admission length than clinical diagnosis or a specific tool that was developed to identify patient needs. Modelling admission lengths in a Bayesian fashion could be expanded and be useful within service planning and monitoring for groups of patients. CONCLUSION: Variables previously proposed to be associated with patient need did not predict PICU admission length. Of the proposed predictor variables, grouping patients by discharge destination contributed the most to length of stay in four different PICUs.

Sexual and reproductive health needs assessment and interventions in a female psychiatric intensive care unit.

AIMS AND METHOD: To assess the sexual and reproductive health (SRH) needs of women admitted to a psychiatric intensive care unit (PICU), and acceptability of delivering specialist SRH assessments and interventions in this setting. Within a quality improvement framework, staff were trained, a clinical protocol developed and clinical interventions made accessible. RESULTS: Thirty per cent of women were identified as having unmet SRH needs and proceeded to a specialist appointment, representing a 2.5-fold increase in unmet need detection. Forty-two per cent of women were assessed, representing a 3.5-fold increase in uptake. Twenty-one per cent of women initiated SRH interventions, of which 14% had all their SRH needs met. Staff, patients and carers highlighted the acceptability and importance of SRH care, if interventions were appropriately timed and patients' individual risk profiles were considered. Barriers to access included lack of routine enquiry, illness acuity and impact of the COVID-19 pandemic. CLINICAL IMPLICATIONS: SRH needs for PICU admissions are greater than previously realised. Providing a nurse-led SRH assessment is acceptable, feasible and beneficial for PICU patients.