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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
The origins and timing of inpatient room sink contamination with carbapenem-resistant organisms (CROs) are poorly understood.
Methods:
We performed a prospective observational study to describe the timing, rate, and frequency of CRO contamination of in-room handwashing sinks in 2 intensive care units (ICU) in a newly constructed hospital bed tower. Study units, A and B, were opened to patient care in succession. The patients in unit A were moved to a new unit in the same bed tower, unit B. Each unit was similarly designed with 26 rooms and in-room sinks. Microbiological samples were taken every 4 weeks from 3 locations from each study sink: the top of the bowl, the drain cover, and the p-trap. The primary outcome was sink conversion events (SCEs), defined as CRO contamination of a sink in which CRO had not previously been detected.
Results:
Sink samples were obtained 22 times from September 2020 to June 2022, giving 1,638 total environmental cultures. In total, 2,814 patients were admitted to study units while sink sampling occurred. We observed 35 SCEs (73%) overall; 9 sinks (41%) in unit A became contaminated with CRO by month 10, and all 26 sinks became contaminated in unit B by month 7. Overall, 299 CRO isolates were recovered; the most common species were Enterobacter cloacae and Pseudomonas aeruginosa.
Conclusion:
CRO contamination of sinks in 2 newly constructed ICUs was rapid and cumulative. Our findings support in-room sinks as reservoirs of CRO and emphasize the need for prevention strategies to mitigate contamination of hands and surfaces from CRO-colonized sinks.
Various water-based heater-cooler devices (HCDs) have been implicated in nontuberculous mycobacteria outbreaks. Ongoing rigorous surveillance for healthcare-associated M. abscessus (HA-Mab) put in place following a prior institutional outbreak of M. abscessus alerted investigators to a cluster of 3 extrapulmonary M. abscessus infections among patients who had undergone cardiothoracic surgery.
Methods:
Investigators convened a multidisciplinary team and launched a comprehensive investigation to identify potential sources of M. abscessus in the healthcare setting. Adherence to tap water avoidance protocols during patient care and HCD cleaning, disinfection, and maintenance practices were reviewed. Relevant environmental samples were obtained. Patient and environmental M. abscessus isolates were compared using multilocus-sequence typing and pulsed-field gel electrophoresis. Smoke testing was performed to evaluate the potential for aerosol generation and dispersion during HCD use. The entire HCD fleet was replaced to mitigate continued transmission.
Results:
Clinical presentations of case patients and epidemiologic data supported intraoperative acquisition. M. abscessus was isolated from HCDs used on patients and molecular comparison with patient isolates demonstrated clonality. Smoke testing simulated aerosolization of M. abscessus from HCDs during device operation. Because the HCD fleet was replaced, no additional extrapulmonary HA-Mab infections due to the unique clone identified in this cluster have been detected.
Conclusions:
Despite adhering to HCD cleaning and disinfection strategies beyond manufacturer instructions for use, HCDs became colonized with and ultimately transmitted M. abscessus to 3 patients. Design modifications to better contain aerosols or filter exhaust during device operation are needed to prevent NTM transmission events from water-based HCDs.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
We assessed Oxivir Tb wipe disinfectant residue in a controlled laboratory setting to evaluate low environmental contamination of SARS-CoV-2. Frequency of viral RNA detection was not statistically different between intervention and control arms on day 3 (P=0.14). Environmental contamination viability is low; residual disinfectant did not significantly contribute to low contamination.
This retrospective review of 4-year surveillance data revealed a higher central line-associated bloodstream infection (CLABSI) rate in non-Hispanic Black patients and higher catheter-associated urinary tract infection (CAUTI) rates in Asian and non-Hispanic Black patients compared with White patients despite similar catheter utilization between the groups.
We present WALLABY pilot data release 1, the first public release of H i pilot survey data from the Wide-field ASKAP L-band Legacy All-sky Blind Survey (WALLABY) on the Australian Square Kilometre Array Pathfinder. Phase 1 of the WALLABY pilot survey targeted three
$60\,\mathrm{deg}^{2}$
regions on the sky in the direction of the Hydra and Norma galaxy clusters and the NGC 4636 galaxy group, covering the redshift range of
$z \lesssim 0.08$
. The source catalogue, images and spectra of nearly 600 extragalactic H i detections and kinematic models for 109 spatially resolved galaxies are available. As the pilot survey targeted regions containing nearby group and cluster environments, the median redshift of the sample of
$z \approx 0.014$
is relatively low compared to the full WALLABY survey. The median galaxy H i mass is
$2.3 \times 10^{9}\,{\rm M}_{{\odot}}$
. The target noise level of
$1.6\,\mathrm{mJy}$
per 30′′ beam and
$18.5\,\mathrm{kHz}$
channel translates into a
$5 \sigma$
H i mass sensitivity for point sources of about
$5.2 \times 10^{8} \, (D_{\rm L} / \mathrm{100\,Mpc})^{2} \, {\rm M}_{{\odot}}$
across 50 spectral channels (
${\approx} 200\,\mathrm{km \, s}^{-1}$
) and a
$5 \sigma$
H i column density sensitivity of about
$8.6 \times 10^{19} \, (1 + z)^{4}\,\mathrm{cm}^{-2}$
across 5 channels (
${\approx} 20\,\mathrm{km \, s}^{-1}$
) for emission filling the 30′′ beam. As expected for a pilot survey, several technical issues and artefacts are still affecting the data quality. Most notably, there are systematic flux errors of up to several 10% caused by uncertainties about the exact size and shape of each of the primary beams as well as the presence of sidelobes due to the finite deconvolution threshold. In addition, artefacts such as residual continuum emission and bandpass ripples have affected some of the data. The pilot survey has been highly successful in uncovering such technical problems, most of which are expected to be addressed and rectified before the start of the full WALLABY survey.
To describe the epidemiology of complex colon surgical procedures (COLO), stratified by present at time of surgery (PATOS) surgical-site infections (SSIs) and non-PATOS SSIs and their impact on the epidemiology of colon-surgery SSIs.
Design:
Retrospective cohort study.
Methods:
SSI data were prospectively collected from patients undergoing colon surgical procedures (COLOs) as defined by the National Healthcare Safety Network (NHSN) at 34 community hospitals in the southeastern United States from January 2015 to June 2019. Logistic regression models identified specific characteristics of complex COLO SSIs, complex non-PATOS COLO SSIs, and complex PATOS COLO SSIs.
Results:
Over the 4.5-year study period, we identified 720 complex COLO SSIs following 28,188 COLO surgeries (prevalence rate, 2.55 per 100 procedures). Overall, 544 complex COLO SSIs (76%) were complex non-PATOS COLO SSIs (prevalence rate [PR], 1.93 per 100 procedures) and 176 (24%) complex PATOS COLO SSIs (PR, 0.62 per 100 procedures). Age >75 years and operation duration in the >75th percentile were independently associated with non-PATOS SSIs but not PATOS SSIs. Conversely, emergency surgery and hospital volume for COLO procedures were independently associated with PATOS SSIs but not non-PATOS SSIs. The proportion of polymicrobial SSIs was significantly higher for non-PATOS SSIs compared with PATOS SSIs.
Conclusions:
Complex PATOS COLO SSIs have distinct features from complex non-PATOS COLO SSIs. Removal of PATOS COLO SSIs from public reporting allows more accurate comparisons among hospitals that perform different case mixes of colon surgeries.
After implementing a coronavirus disease 2019 (COVID-19) infection prevention bundle, the incidence rate ratio (IRR) of non–severe acute respiratory coronavirus virus 2 (non–SARS-CoV-2) hospital-acquired respiratory viral infection (HA-RVI) was significantly lower than the IRR from the pre–COVID-19 period (IRR, 0.322; 95% CI, 0.266–0.393; P < .01). However, HA-RVIs incidence rates mirrored community RVI trends, suggesting that hospital interventions alone did not significantly affect HA-RVI incidence.
We present the most sensitive and detailed view of the neutral hydrogen (
${\rm H\small I}$
) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal
${\rm H\small I}$
in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K (
$1.6\,\mathrm{mJy\ beam}^{-1}$
)
$\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$
spectral channel with an angular resolution of
$30^{\prime\prime}$
(
${\sim}10\,\mathrm{pc}$
). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire
${\sim}25\,\mathrm{deg}^2$
field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes
${\rm H\small I}$
test observations.
Sleep disturbances are important symptoms to monitor in people with bipolar disorder (BD) but the precise longitudinal relationships between sleep and mood remain unclear. We aimed to examine associations between stable and dynamic aspects of sleep and mood in people with BD, and assess individual differences in the strength of these associations.
Methods
Participants (N = 649) with BD-I (N = 400) and BD-II (N = 249) provided weekly self-reports of insomnia, depression and (hypo)mania symptoms using the True Colours online monitoring tool for 21 months. Dynamic structural equation models were used to examine the interplay between weekly reports of insomnia and mood. The effects of clinical and demographic characteristics on associations were also assessed.
Results
Increased variability in insomnia symptoms was associated with increased mood variability. In the sample as a whole, we found strong evidence of bidirectional relationships between insomnia and depressive symptoms but only weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. We found substantial variability between participants in the strength of prospective associations between insomnia and mood, which depended on age, gender, bipolar subtype, and a history of rapid cycling.
Conclusions
Our results highlight the importance of monitoring sleep in people with BD. However, researchers and clinicians investigating the association between sleep and mood should consider subgroup differences in this relationship. Advances in digital technology mean that intensive longitudinal data on sleep and mood are becoming increasingly available. Novel methods to analyse these data present an exciting opportunity for furthering our understanding of BD.
Ensuring equitable access to health care is a widely agreed-upon goal in medicine, yet access to care is a multidimensional concept that is difficult to measure. Although frameworks exist to evaluate access to care generally, the concept of “access to genomic medicine” is largely unexplored and a clear framework for studying and addressing major dimensions is lacking.
Methods:
Comprised of seven clinical genomic research projects, the Clinical Sequencing Evidence-Generating Research consortium (CSER) presented opportunities to examine access to genomic medicine across diverse contexts. CSER emphasized engaging historically underrepresented and/or underserved populations. We used descriptive analysis of CSER participant survey data and qualitative case studies to explore anticipated and encountered access barriers and interventions to address them.
Results:
CSER’s enrolled population was largely lower income and racially and ethnically diverse, with many Spanish-preferring individuals. In surveys, less than a fifth (18.7%) of participants reported experiencing barriers to care. However, CSER project case studies revealed a more nuanced picture that highlighted the blurred boundary between access to genomic research and clinical care. Drawing on insights from CSER, we build on an existing framework to characterize the concept and dimensions of access to genomic medicine along with associated measures and improvement strategies.
Conclusions:
Our findings support adopting a broad conceptualization of access to care encompassing multiple dimensions, using mixed methods to study access issues, and investing in innovative improvement strategies. This conceptualization may inform clinical translation of other cutting-edge technologies and contribute to the promotion of equitable, effective, and efficient access to genomic medicine.
We performed surveillance for hospital-acquired COVID-19 (HA-COVID-19) and compared time-based, electronic definitions to real-time adjudication of the most likely source of acquisition. Without real-time adjudication, nearly 50% of HA-COVID-19 cases identified using electronic definitions were misclassified. Both electronic and traditional contact tracing methods likely underestimated the incidence of HA-COVID-19.
The paradoxical relationship between standardized infection ratio and standardized utilization ratio for catheter-associated urinary tract infections (CAUTIs) in contrast to central-line–associated bloodstream infections (CLABSIs), in addition to CAUTI definition challenges, incentivizes hospitals to focus their prevention efforts on urine culture stewardship rather than catheter avoidance and care.
To determine the impact of electronic health record (EHR)–based interventions and test restriction on Clostridioides difficile tests (CDTs) and hospital-onset C. difficile infection (HO-CDI).
Design:
Quasi-experimental study in 3 hospitals.
Setting:
957-bed academic (hospital A), 354-bed (hospital B), and 175-bed (hospital C) academic-affiliated community hospitals.
Interventions:
Three EHR-based interventions were sequentially implemented: (1) alert when ordering a CDT if laxatives administered within 24 hours (January 2018); (2) cancellation of CDT orders after 24 hours (October 2018); (3) contextual rule-driven order questions requiring justification when laxative administered or lack of EHR documentation of diarrhea (July 2019). In February 2019, hospital C implemented a gatekeeper intervention requiring approval for all CDTs after hospital day 3. The impact of the interventions on C. difficile testing and HO-CDI rates was estimated using an interrupted time-series analysis.
Results:
C. difficile testing was already declining in the preintervention period (annual change in incidence rate [IR], 0.79; 95% CI, 0.72–0.87) and did not decrease further with the EHR interventions. The laxative alert was temporally associated with a trend reduction in HO-CDI (annual change in IR from baseline, 0.85; 95% CI, 0.75–0.96) at hospitals A and B. The gatekeeper intervention at hospital C was associated with level (IRR, 0.50; 95% CI, 0.42-0.60) and trend reductions in C. difficile testing (annual change in IR, 0.91; 95% CI, 0.85–0.98) and level (IRR 0.42; 95% CI, 0.22–0.81) and trend reductions in HO-CDI (annual change in IR, 0.68; 95% CI, 0.50–0.92) relative to the baseline period.
Conclusions:
Test restriction was more effective than EHR-based clinical decision support to reduce C. difficile testing in our 3-hospital system.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
We describe the frequency of pediatric healthcare-associated infections (HAIs) identified through prospective surveillance in community hospitals participating in an infection control network. Over a 6-year period, 84 HAIs were identified. Of these 51 (61%) were pediatric central-line–associated bloodstream infections, and they often occurred in children <1 year of age.
Background: Surgical site infections (SSIs) among cardiothoracic (CT) patients are associated with high rates of morbidity and mortality. Data are limited regarding SSI incidence among pediatric patients undergoing primary reparative procedures for congenital cardiac disease. Published evidence on targeted interventions to prevent pediatric CT-surgery SSI is lacking. We aimed to establish standard metrics for measuring CT-surgery SSI incidence and to implement bundled interventions for SSI prevention. Methods: A dedicated CT-surgery SSI prevention workgroup was established, consisting of hospital leadership, CT surgeons, cardiac critical care unit staff, anesthesia, perfusion, environmental services, instrument sterile processing, risk management, infection prevention and antibiotic stewardship. We created a standard definition for CT-surgery SSI and calculated retrospective SSI rates over a 24-month period (2017–2019). The outcome measured was incidence of CT-surgery SSI per 100 primary cardiac procedures with delayed ( 3 days after primary surgery) or non-delayed chest closure. The difference in proportion of SSI was reported separately for delayed closure and non-delayed closure; statistical significance was tested using a Fisher’s Exact test. We identified many potential improvement opportunities, including gaps in SSI surveillance, poor compliance with daily bathing, inconsistent perioperative antimicrobial prophylaxis, lack of controlled environment for bedside chest closures, and lapses in environmental cleaning. These issues informed the enhanced SSI prevention bundle, which included education on sterility with the operating room (OR) staff. Protocols for care of cardiac patients with delayed chest closures focused on universal daily and preoperative chlorhexidine baths. In addition, the bundle incorporated stringent environmental cleaning interventions including scheduled decluttering of patient rooms and clinical spaces, terminal cleaning of patient rooms prior to returning from the OR, and use of adjunctive ultraviolet light for the daily cleaning of operating rooms and patient rooms at discharge. Results: Surveillance definition of microbiological growth from a clinical sample obtained within 30 days of primary cardiac procedure sufficiently captured all CT-surgery SSIs. Of 551 CT-surgery procedures prior to intervention, 91 (17%) had delayed final operative closures. Prior to the intervention, 16 SSIs were identified from July 2017 – May 2019 for a rate of 2.90 per /100 procedures, and was higher among patients with delayed chest closure 6.59 per /100 procedures (6 SSIs/91 procedures) versus those with primary chest closure 2.17 per /100 procedures (10 SSIs/460 procedures; P = 0.034). Gram-positive organisms, including coagulase coagulase-negative Staphylococci, were most frequently identified as the causative organisms for SSIs. Compliance with bundled intervention, rolled out over a 2-month period, was associated with an immediate decrease in the number of SSIs for primary and delayed chest closures 6SSIs /185 procedures in the initial quarters (August – December 2019) of the post-intervention period. However, this decrease was not reflected in the overall rate (3.24 per /100 procedures) due to fewer procedures performed. Data collection to measure sustainability is ongoing. Conclusions: Bundled interventions targeting skin antisepsis and environmental cleaning may be associated with a decrease in SSIs among pediatric CT-surgery patients. Ongoing surveillance is required to determine sustainability of these interventions.
We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful. Although our protocol was resource intensive, it prevented exposures to healthcare team members.