Comparative safety and efficacy of vasopressors for mortality in septic shock: A network meta-analysis

© 2015, © The Intensive Care Society 2015.Introduction: Septic shock is a life-threatening condition requiring vasopressor agents to support the circulatory system. Several agents exist with choice typically guided by the specific clinical scenario. We used a network meta-analysis approach to rate the comparative efficacy and safety of vasopressors for mortality and arrhythmia incidence in septic shock patients. Methods: We performed a comprehensive electronic database search including Medline, Embase, Science Citation Index Expanded and the Cochrane database. Randomised trials investigating vasopressor agents in septic shock patients and specifically assessing 28-day mortality or arrhythmia incidence were included. A Bayesian network meta-analysis was performed using Markov chain Monte Carlo methods. Results: Thirteen trials of low to moderate risk of bias in which 3146 patients were randomised were included. There was no pairwise evidence to suggest one agent was superior over another for mortality. In the network meta-analysis, vasopressin was significantly superior to dopamine (OR 0.68 (95% CI 0.5 to 0.94)) for mortality. For arrhythmia incidence, standard pairwise meta-analyses confirmed that dopamine led to a higher incidence of arrhythmias than norepinephrine (OR 2.69 (95% CI 2.08 to 3.47)). In the network meta-analysis, there was no evidence of superiority of one agent over another. Conclusions: In this network meta-analysis, vasopressin was superior to dopamine for 28-day mortality in septic shock. Existing pairwise information supports the use of norepinephrine over dopamine. Our findings suggest that dopamine should be avoided in patients with septic shock and that other vasopressor agents should continue to be based on existing guidelines and clinical judgement of the specific presentation of the patient

Quantifying the impact of AI recommendations with explanations on prescription decision making

The influence of AI recommendations on physician behaviour remains poorly characterised. We assess how clinicians' decisions may be influenced by additional information more broadly, and how this influence can be modified by either the source of the information (human peers or AI) and the presence or absence of an AI explanation (XAI, here using simple feature importance). We used a modified between-subjects design where intensive care doctors (N=86) were presented on a computer for each of 16 trials with a patient case and prompted to prescribe continuous values for two drugs. We used a multi-factorial experimental design with four arms, where each clinician experienced all four arms on different subsets of our 24 patients. The four arms were (i) baseline (control), (ii) peer human clinician scenario showing what doses had been prescribed by other doctors, (iii) AI suggestion and (iv) XAI suggestion. We found that additional information (peer, AI or XAI) had a strong influence on prescriptions (significantly for AI, not so for peers) but simple XAI did not have higher influence than AI alone. There was no correlation between attitudes to AI or clinical experience on the AI-supported decisions and nor was there correlation between what doctors self-reported about how useful they found the XAI and whether the XAI actually influenced their prescriptions. Our findings suggest that the marginal impact of simple XAI was low in this setting and we also cast doubt on the utility of self-reports as a valid metric for assessing XAI in clinical experts

Gaps in patient reported outcome measures in randomised clinical trials of cardiac catheter ablation: a systematic review

Aims: To systematically evaluate randomised clinical trials of cardiac catheter ablation and to assess the prevalence, characteristics and reporting standards of clinically relevant patient reported outcome measures (PROMs). / Methods and Results: Electronic database searches of Medline, Embase, CENTRAL and the WHO Trial Registry were conducted in March 2019. The study protocol was registered on PROSPERO (CRD42019133086). Of 7,125 records identified, 237 RCTs were included for analysis, representing 35,427 patients with a mean age of 59 years. Only 43 RCTs (18%) reported PROMs of which 27 included a generic PROM that measured health-related quality of life (HRQL) necessary to conduct comparative effectiveness research. There was notable under-representation of certain patient groups - only 31% were women and only 8% were of non-Caucasian ethnicity, in trials which reported such data. The reporting standard of PROMs was highly variable with 8-62% adherence against CONSORT PRO specific items. / Conclusion: PROMs play a crucial role in determining the clinical and cost effectiveness of treatments which primarily offer symptomatic improvement, such as cardiac catheter ablation (CCA). Their underuse significantly limits evaluation of the comparative effectiveness of treatments. Using CCA as an exemplar, there are additional issues of infrequent assessment, poor reporting and under-representation of many population groups. Greater use of PROMs, and specifically validated HRQL questionnaires, is paramount in giving patients a voice in studies, generating more meaningful comparisons between treatments and driving better patient-centred clinical and policy-level decision making

The diagnostic certainty levels of junior clinicians: A retrospective cohort study

BACKGROUND: Clinical decision-making is influenced by many factors, including clinicians' perceptions of the certainty around what is the best course of action to pursue. OBJECTIVE: To characterise the documentation of working diagnoses and the associated level of real-time certainty expressed by clinicians and to gauge patient opinion about the importance of research into clinician decision certainty. METHOD: This was a single-centre retrospective cohort study of non-consultant grade clinicians and their assessments of patients admitted from the emergency department between 01 March 2019 and 31 March 2019. De-identified electronic health record proformas were extracted that included the type of diagnosis documented and the certainty adjective used. Patient opinion was canvassed from a focus group. RESULTS: During the study period, 850 clerking proformas were analysed; 420 presented a single diagnosis, while 430 presented multiple diagnoses. Of the 420 single diagnoses, 67 (16%) were documented as either a symptom or physical sign and 16 (4%) were laboratory-result-defined diagnoses. No uncertainty was expressed in 309 (74%) of the diagnoses. Of 430 multiple diagnoses, uncertainty was expressed in 346 (80%) compared to 84 (20%) in which no uncertainty was expressed. The patient focus group were unanimous in their support of this research. CONCLUSION: The documentation of working diagnoses is highly variable among non-consultant grade clinicians. In nearly three quarters of assessments with single diagnoses, no element of uncertainty was implied or quantified. More uncertainty was expressed in multiple diagnoses than single diagnoses. IMPLICATIONS: Increased standardisation of documentation will help future studies to better analyse and quantify diagnostic certainty in both single and multiple working diagnoses. This could lead to subsequent examination of their association with important process or clinical outcome measures

Financial performance of English NHS trusts and variation in clinical outcomes: a longitudinal observational study

OBJECTIVES: To examine the association between financial performance as measured by operating margin (surplus/deficit as a proportion of turnover) and clinical outcomes in English National Health Service (NHS) trusts. SETTING: Longitudinal, observational study in 149 acute NHS trusts in England between the financial years 2011 and 2016. PARTICIPANTS: Our analysis focused on outcomes at individual NHS Trust-level (composed of one or more acute hospitals). PRIMARY AND SECONDARY OUTCOMES: Outcome measures included readmissions, inpatient satisfaction score and the following process measures: emergency department (Accident and Emergency (A&E)) waiting time targets, cancer referral and treatment targets and delayed transfers of care (DTOCs). RESULTS: There was a progressive increase in the proportion of trusts in financial deficit: 22% in 2011, 27% in 2012, 28% in 2013, 51% in 2014, 68% in 2015 and 91% in 2016. In linear regression analyses, there was no significant association between operating margin and clinical outcomes (readmission rate or inpatient satisfaction score). There was, however, a significant association between operating margin and process measures (DTOCs, A&E breaches and cancer waiting time targets). Between the best and worst financially performing Trusts, there was an approximately 2-fold increase in A&E breaches and DTOCs overall although this variation decreased over the 6 years. Between the best and worst performing trusts on cancer targets, the magnitude of difference was smaller (1.16 and 1.15-fold), although the variation slowly rose during the 6 years. CONCLUSIONS: Operating margins in English NHS trusts progressively worsened during 2011-2016, and this change was associated with poorer performance on several process measures but not with hospital readmissions or inpatient satisfaction. Significant variation exists between the best and worst financially performing Trusts. Further research is needed to examine the causal nature of relationships between financial performance, process measures and outcomes

N-[3-(2,6-Dimethylanilino)-1-methylbut-2-enylidene]-2,6-dimethylanilinium chloride1

The title salt, C21H27N2 +·Cl− resulted from the condensation between 2,6-dimethyl­aniline and acetyl­acetone in acidified ethanol. The bulky cation is stabilized in a β-imino­enamine tautomeric form, and presents a W-shaped conformation. The benzene rings are arranged almost parallel, with a dihedral angle of 6.58 (4)° between the mean planes. Both N—H groups in the cation form strong hydrogen bonds with two symmetry-related chloride anions. The resulting supra­molecular structure is a one dimensional polymer running along [001], alternating cations and anions. The π–π inter­action observed in the mol­ecule, characterized by a centroid–centroid separation of 4.298 (4) Å, is thus extended to the chains, with separations of 5.222 (4) Å between benzene rings of neighbouring cations in the crystal

The Actinome of Dictyostelium discoideum in Comparison to Actins and Actin-Related Proteins from Other Organisms

Actin belongs to the most abundant proteins in eukaryotic cells which harbor usually many conventional actin isoforms as well as actin-related proteins (Arps). To get an overview over the sometimes confusing multitude of actins and Arps, we analyzed the Dictyostelium discoideum actinome in detail and compared it with the genomes from other model organisms. The D. discoideum actinome comprises 41 actins and actin-related proteins. The genome contains 17 actin genes which most likely arose from consecutive gene duplications, are all active, in some cases developmentally regulated and coding for identical proteins (Act8-group). According to published data, the actin fraction in a D. discoideum cell consists of more than 95% of these Act8-type proteins. The other 16 actin isoforms contain a conventional actin motif profile as well but differ in their protein sequences. Seven actin genes are potential pseudogenes. A homology search of the human genome using the most typical D. discoideum actin (Act8) as query sequence finds the major actin isoforms such as cytoplasmic beta-actin as best hit. This suggests that the Act8-group represents a nearly perfect actin throughout evolution. Interestingly, limited data from D. fasciculatum, a more ancient member among the social amoebae, show different relationships between conventional actins. The Act8-type isoform is most conserved throughout evolution. Modeling of the putative structures suggests that the majority of the actin-related proteins is functionally unrelated to canonical actin. The data suggest that the other actin variants are not necessary for the cytoskeleton itself but rather regulators of its dynamical features or subunits in larger protein complexes

β3-Adrenoceptor Antagonist SR59230A Attenuates the Imbalance of Systemic and Myocardial Oxygen Transport Induced by Dopamine in Newborn Lambs

Background In neonates, the increase in O 2 -delivery (DO 2 ) by dopamine is offset by a greater increase in O 2 -consumption (VO 2 ). This has been attributed to β 3 -adrenergic receptors in neonatal brown fat tissue. β 3 receptors in the heart have negative inotropic properties. We evaluated the effects of SR59230A, a β 3 -antagonist, on the balance of systemic and myocardial O 2 -transport in newborn lambs treated with dopamine. Methods Lambs (2-5 days old, n = 12) were anesthetized and mechanically ventilated. Heart rate (HR) and rectal temperature were monitored. VO 2 was measured by respiratory mass spectrometry and cardiac output (CO) by a pulmonary artery transonic flowmeter. Arterial, jugular bulb venous and coronary sinus blood gases and lactate were measured to calculate DO 2 , O 2 extraction ratio (ERO 2 ), myocardial O 2 and lactate extraction ratios (mERO 2 , mERlac). After baseline measurements, lambs were randomized to receive SR59230A at 5 mg/kg iv (SRG) or placebo. Both groups received incremental doses of a dopamine infusion (0-5-10-15-20 mcg/kg/min) every 15 min. Measurements were repeated at the end of each dose. Results After SR59230A infusion, CO and HR trended to decrease ( P = 0.06), but no significant changes occurred in other parameters. Over the incremental doses of dopamine, temperature increased in both groups ( P 0.1). DO 2 trended to a small increase ( P = 0.08). VO 2 increased in both groups ( P < 0.0001) but to a lesser degree in SRG ( P < 0.0001). As a result, ERO 2 increased in both groups ( P < 0.0001), but to a lesser degree in SRG ( P < 0.0001). mERO 2 was lower in SRG ( P = 0.01) with a faster increase ( P < 0.0001). mERlac was higher in SRG ( P = 0.06) with a faster decrease ( P = 0.04). Conclusion Although SR59230A tends to induce an initial drop in CO, it significantly attenuates the rise in VO 2 and hence the imbalance of systemic and myocardial O 2 transport induced by dopamine at higher doses. Studies are warranted to examine the effect of SR59230A in cases of cardiac dysfunction and increased VO 2 , observed after cardiac surgery

TECHNIQUES FOR REARING AND RELEASING NONMIGRATORY CRANES: LESSONS FROM THE MISSISSIPPI SANDHILL CRANE PROGRAM

Captive-reared Mississippi sandhill cranes (Grus canadensis pulla) reared at the Patuxent Wildlife Research Center (patuxent) have been released at the Mississippi Sandhill Crane National Wildlife Refuge (MSCNWR) since 1981. Of 131 birds released through December 1990, 103 were reared by foster parents. The remaining 28 were experimentally hand-reared in 1989 and 1990. After refining release procedures, parent-reared birds have integrated into the wild flock, many have survived, and some have bred. Releases of hand-reared cranes elsewhere in the 1970\u27s were largely unsuccessful. at least in part due to the lack of a lengthy acclimation period. A new hand-rearing protocol holds promise in producing release-worthy birds. The technique employs some features first used in the 1960\u27s (e.g., a costume for the human caretaker and model crane heads used to train chicks to feed). In the mid-1980\u27s, the following features were added: (1) the costumed caretaker was given a visor and feathers, (2) a taxidermic crane head or a hand puppet was held or suspended from the ceiling for use in stimulating chicks to feed, (3) a taxidermic mount of a brooding crane supplied warmth, (4) a full-sized live crane was maintained in an adjacent pen and in visual contact with neonatal young to provide an imprinting model, and (5) a small group of adult (or subadult) cranes was penned adjacent to the outdoor chick pens to provide socialization models. Recent releases of Mississippi sandhill cranes hand-reared according to this protocol and released in Mississippi have had high first-year survival rates. The now-operational technique holds promise for producing large numbers of release-worthy birds