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To determine the impact of clinical decision support on guideline-concordant Clostridioides difficile infection (CDI) treatment.
Design:
Quasi-experimental study in >50 ambulatory clinics.
Setting:
Primary, specialty, and urgent-care clinics.
Patients:
Adult patients were eligible for inclusion if they were diagnosed with and treated for a first episode of symptomatic CDI at an ambulatory clinic between November 1, 2019, and November 30, 2020.
Interventions:
An outpatient best practice advisory (BPA) was implemented to notify prescribers that “vancomycin or fidaxomicin are preferred over metronidazole for C.difficile infection” when metronidazole was prescribed to a patient with CDI.
Results:
In total, 189 patients were included in the study: 92 before the BPA and 97 after the BPA. Their median age was 59 years; 31% were male; 75% were white; 30% had CDI-related comorbidities; 35% had healthcare exposure; 65% had antibiotic exposure; 44% had gastric acid suppression therapy within 90 days of CDI diagnosis. The BPA was accepted 23 of 26 times and was used to optimize the therapy of 16 patients in 6 months. Guideline-concordant therapy increased after implementation of the BPA (72% vs 91%; P = .001). Vancomycin prescribing increased and metronidazole prescribing decreased after the BPA. There was no difference in clinical response or unplanned encounter within 14 days after treatment initiation. Fewer patients after the BPA had CDI recurrence within 14–56 days of the initial episode (27% vs 7%; P < .001).
Conclusions:
Clinical decision support increased prescribing of guideline-concordant CDI therapy in the outpatient setting. A targeted BPA is an effective stewardship intervention and may be especially useful in settings with limited antimicrobial stewardship resources.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
What is faith? Is it just a matter of propositions, claims, such as “God is love”? Or is it more a matter of commitment, perhaps not fully articulated, of having a background awareness of God and his love? And what is the position of faith for the Christian? Is faith alone enough, or does one need to supplement it with reasoned argument and possibly appeal to outside evidence? The New Atheists argue that Christianity fails because it rests on faith, and, today, we see that reason and evidence, most notably science and its confirmed theories, negate faith claims. Faith therefore is seen as delusional, a function of the fact that people are scared of death and the apparent meaninglessness of their lives. Ruse and Davies raise and argue these questions, coming to very different conclusions.
The authors run through the major arguments for the existence of God: Anselm’s ontological argument (and also Descartes’s version), arguing that the very notion of God a priori proves hs existence; Aquinas’s cosmological (or causal) argument, that God is needed to stop an infinite regression of causes from the present to the past; and the teleological argument or the argument from design, that the design-like natural objects of this world demand a designer. Then they raise the standard objections: Gaunilo’s criticism that the ontological argument proves the existence of perfect islands, which is ridiculous, and Kant’s objection that you cannot infer matters of fact by a priori reasoning; Dawkins’s criticism that the cosmological argument raises the unanswered question of what causes God; and Hume’s criticism of the design argument, and Darwin’s subsequent demonstration that natural selection can explain final causes naturalistically, and so there is no need to invoke a Designer God.
Why do we disagree? Ultimately, it comes down to faith. The Christianity Ruse is rejecting is the Christianity of Kierkegaard. Faith demands a leap into the absurd. Reason and evidence backing up the faith commitment would render it inauthentic. Believe without seeing the scars! Hence, for Ruse, given that he thinks this the only authentic Christianity, all attempts to make sense of Christianity are pointless. You are trying to square the circle. Davies is a committed Christian, a Roman Catholic philosopher, and theologian. For him, faith and reason do not clash; they are complementary. Hence, for Davies it is legitimate – demanded – that he bring reason to bear on his faith beliefs, for instance, concerning the Trinity and the Incarnation. In the end, although there is sympathy for the beliefs of the other and much respect, Michael Ruse and Brian Davies are on different tracks, and they do not run in parallel.
The tensions between our two authors start to rise. Ruse dismisses natural theology and proofs for the existence of God. Faith or nothing, and that means nothing because faith does not work. Davies responds by pointing out that there is biblical evidence for natural theology, and turns to Aquinas for guidance. The saint agrees that faith trumps reason and is enough alone for Christian belief, but argues also that reason, natural theology, has its place. It can supplement and back up the commitments through faith. There is therefore no conflict between reason and faith. Both have their role. In any case, argues Davies, scientists make faith commitments, having to start somewhere without prior proof, so in the end science is in the same business as religion. Ruse responds that the commitments of science and the commitments of religion are entirely different. The Christian cannot end the case by using this line of argument.
This chapter deals with arguments against the existence of God, at least a God as is supposed by Christianity – Creator, omnipotent and omniscient, all-loving especially toward his special creation, humankind. Ruse thinks that the arguments are effective. Above all, he cannot reconcile the Christian God with the problem of evil. He sees that human free will, including the power to do great evil, can in some sensed be reconciled with the Creator. He sees also that natural evil can likewise be reconciled with the Creator. He just cannot see that the Creator, knowing it was going to happen, let it happen. The suffering of small children cannot ever be reconciled with the end, no matter how good. Davies, taking a position much influenced by the great theologians, especially Aquinas, thinks that people like Ruse have an altogether mistaken understanding of God and his nature. The Bible is far from portraying God as the friendly chap in the sky, as supposed by Ruse. And theology backs up this realization by showing that, properly understood, we can speak of God as all-powerful and all-loving.
The two authors come apart here, not simply because Ruse is a nonbeliever and Davies a practicing Christian. Ruse was raised a Quaker and so, thinking theologically, he thinks in a Quaker context. More than anything he is accepting (or he would be if he were still a believer) of apophatic theology. One cannot say what God is but rather what He is not. How one works out the details of the Trinity are not that important. One is committed to the Trinity on faith, and for the rest – “now we see through a glass darkly.” For Davies, by contrast, theology is grounded in the thinking of the great theologians. He believes one can make progress on understanding the Trinity. Here is where the clash comes, not so much because Ruse is a nonbeliever, but because his theology tells him that all such attempts as those of Davies are bound to fail. 1 + 1 + 1 ≠ 1.
Morality is about right and wrong. There is the question of what we should do, substantive ethics, and the question of why we should do what we do, metaethics. There is little if any real difference between Ruse and Davies at the substantive level. At the metaethical level, Ruse takes a subjective view and Davies an objective view, but in important respects there is shared belief. Both ground morality in human nature. Right and wrong at the substantive level is a matter of who and what we are. Kindness to children is a good thing, because that is natural for humans. Hate of the disabled is wrong, because that is unnatural. But whereas Ruse grounds human nature in Darwinian evolutionary theory, and believes that there is no extra appeal to authority, and so is subjective, Davies grounds human nature in God’s loving creation, and hence in this sense is objective. An action is good is because God made us that way, and to do the right thing is to do the (God-created) natural thing.
Is debate on issues related to faith and reason still possible when dialogue between believers and non-believers has collapsed? Taking God Seriously not only proves that it is possible, but also demonstrates that such dialogue produces fruitful results. Here, Brian Davies, a Dominican priest and leading scholar of Thomas Aquinas, and Michael Ruse, a philosopher of science and well-known non-believer, offer an extended discussion on the nature and plausibility of belief in God and Christianity. They explore key topics in the study of religion, notably the nature of faith, the place of reason in discussions about religion, proofs for the existence of God, the problem of evil, and the problem of multiple competing religious systems, as well as the core concepts of Christian belief including the Trinity and the justification of morality. Written in a jargon-free manner, avoiding the extremes of evangelical literalism and New Atheism prejudice, Taking God Seriously does not compromise integrity or shy from discussing important or difficult issues.
The aim of our study was to test the efficacy of the nominative technique for estimating the prevalence of wildlife part use within a small sample. We used the domestic consumption of bear Ursus thibetanus and Helarctos malayanus parts in Lao People's Democratic Republic (Laos) as a case study and performed 179 semi-structured interviews in Luang Prabang, northern Laos, in August 2017 and April 2019. We also assessed whether the specialized questioning of the nominative technique could be used for qualitative data collection methods, such as semi-structured interviews. The technique theoretically ensures more accurate statements of illegal wildlife consumption by maintaining the anonymity of an individual's sensitive behaviour through asking about the behaviour of peers. We also directly asked about participants’ use of bear parts. The nominative technique suggested that c. 11% of the participants’ peers used bear parts, whereas respondents’ direct admittance of using bear parts was approximately double, at 23%. Use of bear parts appears not to be sensitive in northern Laos. In addition, we found a strong association between responses to questioning using the nominative technique and direct questioning, indicating that users of bear parts have social networks with higher levels of use. This lends supports to theories that use of wildlife products is directly influenced by social group. The underreporting resulting from use of the nominative technique indicates the high variability of response that can occur within small samples. However, our results show that the nominative technique may be a simple, useful tool for triangulating data, assessing users’ integration into social networks of use, and assessing changes in behaviour prevalence.
In the current opioid epidemic, identifying high-risk patients among those with substance and opioid use may prevent deaths. The objective of this study was to determine whether frequent emergency department (ED) use and degree of frequent use are associated with mortality among ED patients with substance and opioid use.
Methods
This cohort study used linked population-based ED (National Ambulatory Care Reporting System) and mortality data from Alberta. All adults ≥ 18 years with substance or opioid use-related visits based on diagnostic codes from April 1, 2012, to March 31, 2013, were included (n = 16,389). Frequent use was defined by ≥ 5 visits in the previous year. Outcomes were unadjusted and adjusted (for age, sex, income) mortality within 90 days (primary), and 30 days, 365 days, and 2 years (secondary). To examine degree, frequent use was subcategorized into 5–10, 11–15, 16–20, and > 20 visits.
Results
Frequent users were older, lower income, and made lower acuity visits than non-frequent users. Frequent users with substance use had higher mortality at 365 days (hazard ratio [HR] 1.36 [1.04, 1.77]) and 2 years (HR 1.32 [1.04, 1.67]), but not at 90 or 30 days. Mortality did not differ for frequent users with opioid use overall. By degree, patients with substance use and > 20 visits/year and with opioid use and 16–20 visits/year demonstrated a higher 365-day and 2-year mortality.
Conclusions
Among patients with substance use, frequent ED use and extremely frequent use (> 20 visits/year) were associated with long-term but not short-term mortality. These findings suggest a role for targeted screening and preventive intervention.
OBJECTIVES/SPECIFIC AIMS: 1) Determine the mutational landscape, including translocation, mutations and mutational signatures as well as copy number variations of pPCL and identify significant differences to non pPCL MM. 2) Determine whether genetic changes pertinent to pPCL could be explored as therapeutic targets to improve the dismal prognosis of this patient population. METHODS/STUDY POPULATION: Samples from overall 19 pPCL patients that presented to the Myeloma Center, UAMS between 2000-2018 were used for this study. We performed gene expression profiling (GEP; Affymetrix U133 Plus 2.0) of matched circulating peripheral PCs and bone marrow (BM) PCs from 13 patients. Whole exome sequencing (WES) was performed on purified CD138+ PCs from BM aspirates from 19 pPCL patients with a median depth of 61x. CD34+ sorted cells, taken at the time of stem cell harvest from the same 19 patients, were used as controls. Translocations and mutations were called using Manta and Strelka and annotated as previously reported. Copy number was determined by Sequenza. RESULTS/ANTICIPATED RESULTS: 1) GEP from the BM and circulating peripheral PCs showed that the expression patterns of the two samples from each individual clustered together, indicating that circulating PCs and BM PCs in pPCL result from the same clone and are biologically clearly related. 2) The clinical characteristics from the patient cohort used for WES analysis were as follows: median age was 58 years (range 36–77), females accounted for 74% (14/19), an elevated creatinine level was found in 78% (14/18) and an elevated LDH level in 71% (10/14). All patients presented with an ISS stage of III. Median OS of the whole dataset was poor at 22 months, which is consistent with OS from previously reported pPCL cohorts. 3) Primary Immunoglobulin translocations were common and identified in 63% (12/19) of patients, including MAF translocations, which are known to carry high risk in 42% (8/19) of patients [t(14;16), 32% and t(14;20), 10%] followed by t(11;14) (16%) and t(4;14) (10%). Furthermore, 32% (6/19) of patients had at least one MYC translocation, which are known to play a crucial role in disease progression. 4) The mutational burden of pPCL consisted of a median of 98 non-silent mutations per sample, suggesting that the mutational landscape of pPCL is highly complex and harbors more coding mutations than non-pPCL MM. 5) Driver mutations, that previously have been described in non-pPCL MM showed a different prevalence and distribution in pPCL, including KRAS and TP53 with 47% (9/19) and 37% (7/19) affected patients respectively compared to 21% and 5% in non-PCL MM. PIK3CA (5%), PRDM1 (10%), EP300 (10%) and NF1 (10%) were also enriched in the pPCL group compared to previously reported cases in non-pPCL MM. 6) Biallelic inactivation of TP53 – a feature of Double Hit myeloma - was found in 6/19 (32%) samples, indicating a predominance of high risk genomic features compared to non-pPCL MM. Furthermore, analysis of mutational signatures in pPCL showed that aberrant APOBEC activity was highly prevalent only in patients with a MAF translocation, but not in other translocation groups. DISCUSSION/SIGNIFICANCE OF IMPACT: In conclusion we present one of the first WES datasets on pPCL with the largest patient cohort reported to date and show that pPCL is a highly complex disease. The aggressive disease behavior can, at least in part, be explained by a high prevalence of MAF and MYC translocations, TP53 and KRAS mutations as well as bi-allelic inactivation of TP53. It is of interest that only KRAS but not NRAS mutations are highly enriched in pPCL. From all highly prevalent genomic alterations in pPCL, only KRAS mutations offer a potential for already available therapeutically targeting with MEK inhibitors, which should be further explored.