Multidisciplinary Protocol for the Management of Violent Patients and Promotion of Workplace Safety in the Intensive Care Unit

Introduction: Workplace violence is a prevalent issue in healthcare, yet limited evidence informs management options to improve workplace safety associated with violent patients and families. Even less is known about reducing violence in intensive care units (ICUs), a healthcare setting that commonly serves patients at high risk of aggressive behaviors. Multifaceted, interdisciplinary and institution-specific interventions are recommended to address workplace safety. Methods: Our institution developed four interventions to address the issue of violent patients in our ICUs. The interventions included a Disruptive/Aggressive Behavior Algorithm, Code Grey Box, Rapid Sedation Protocol and a Customer Service Representative. Security calls to the ICUs were the primary measure used to assess effectiveness of the interventions. Results: Security calls to the ICUs decreased from October 2013 to August 2016, after the implementation of the four interventions. Discussion: The implementation of four interventions decreased the calls to security, despite encouraging early escalation to security for potentially violent patients. The trend may represent a decrease in violent episodes, increased staff confidence in managing violent patients, or improved early recognition of high-risk patients. Conclusions: Violent patients and families in the ICU is an understudied workplace safety issue. Our institution used a multifaceted interdisciplinary approach to create and implement interventions which led to a reduction in the need for security personnel response to threats of ICU staff safety. These interventions serve as a guide for other institutions with the aim to decrease workplace violence and promote workplace safety

Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136503/1/phar1912-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136503/2/phar1912_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136503/3/phar1912.pd

Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Testing for sexually transmitted infections and blood borne viruses on admission to Western Australian prisons

<p>Abstract</p> <p>Background</p> <p>Prison populations are known to be at high risk of sexually transmitted infections (STIs) and blood borne viruses (BBVs). In accordance with State health guidelines, the Western Australian Department of Correctional Services' policy is to offer testing for STIs and BBVs to all new prison entrants. This audit was undertaken to assess the completeness and timeliness of STI and BBV testing among recent prison entrants in Western Australia, and estimate the prevalence of STIs and BBVs on admission to prison.</p> <p>Methods</p> <p>A retrospective audit of prison medical records was conducted among 946 individuals admitted to prison in Western Australia after the 1^stJanuary 2005, and discharged between the 1^stJanuary and 31^stDecember 2007 inclusive. Quota sampling was used to ensure adequate sampling of females, juveniles, and individuals from regional prisons. Main outcomes of interest were the proportion of prisoners undergoing STI and BBV testing, and the prevalence of STIs and BBVs.</p> <p>Results</p> <p>Approximately half the sample underwent testing for the STIs chlamydia and gonorrhoea, and almost 40% underwent testing for at least one BBV. Completeness of chlamydia and gonorrhoea testing was significantly higher among juveniles (84.1%) compared with adults (39.8%; p < 0.001), and Aboriginal prisoners (58.3%) compared with non-Aboriginal prisoners (40.4%; p < 0.001). Completeness of BBV testing was significantly higher among adults (46.5%) compared with juveniles (15.8%; p < 0.001) and males (43.3%) compared with females (33.1%; p = 0.001). Among prisoners who underwent testing, 7.3% had a positive chlamydia test result and 24.8% had a positive hepatitis C test result.</p> <p>Conclusion</p> <p>The documented coverage of STI and BBV testing among prisoners in Western Australia is not comprehensive, and varies significantly by age, gender and Aboriginality. Given the high prevalence of STIs and BBVs among prisoners, increased test coverage is required to ensure optimal use of the opportunity that prison admission presents for the treatment and control of STIs and BBVs among this high risk group.</p

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570