Debate: Transfusing to normal haemoglobin levels will not improve outcome

Recent evidence suggests that critically ill patients are able to tolerate lower levels of haemoglobin than was previously believed. It is our goal to show that transfusing to a level of 100 g/l does not improve mortality and other clinically important outcomes in a critical care setting. Although many questions remain, many laboratory and clinical studies, including a recent randomized controlled trial (RCT), have established that transfusing to normal haemoglobin concentrations does not improve organ failure and mortality in the critically ill patient. In addition, a restrictive transfusion strategy will reduce exposure to allogeneic transfusions, result in more efficient use of red blood cells (RBCs), save blood overall, and decrease health care costs

Field-Induced Magnetization Steps in Intermetallic Compounds and Manganese Oxides: The Martensitic Scenario

Field-induced magnetization jumps with similar characteristics are observed at low temperature for the intermetallic germanide Gd5Ge4and the mixed-valent manganite Pr0.6Ca0.4Mn0.96Ga0.04O3. We report that the field location -and even the existence- of these jumps depends critically on the magnetic field sweep rate used to record the data. It is proposed that, for both compounds, the martensitic character of their antiferromagnetic-to-ferromagnetic transitions is at the origin of the magnetization steps.Comment: 4 pages,4 figure

Variation in red cell transfusion practice in the intensive care unit: a multicentre cohort study

OBJECTIVES: To determine the degree of interinstitutional transfusion practice variation and reasons why red cells are administered in critically ill patients. STUDY DESIGN: Multicentre cohort study combined with a cross-sectional survey of physicians requesting red cell transfusions for patients in the cohort. STUDY POPULATION: The cohort included 5298 consecutive patients admitted to six tertiary level intensive care units in addition to administering a survey to 223 physicians requesting red cell transfusions in these units. MEASUREMENTS: Haemoglobin concentrations were collected, along with the number and reasons for red cell transfusions plus demographic, diagnostic, disease severity (APACHE II score), intensive care unit (ICU) mortality and lengths of stay in the ICU. RESULTS: Twenty five per cent of the critically ill patients in the cohort study received red cell transfusions. The overall number of transfusions per patient-day in the ICU averaged 0.95 ± 1.39 and ranged from 0.82 ± 1.69 to 1.08 ± 1.27 between institutions (P < 0.001). Independent predictors of transfusion thresholds (pre-transfusion haemoglobin concentrations) included patient age, admission APACHE II score and the institution (P < 0.0001). A very significant institution effect (P < 0.0001) persisted even after multivariate adjustments for age, APACHE II score and within four diagnostic categories (cardiovascular disease, respiratory failure, major surgery and trauma) (P < 0.0001). The evaluation of transfusion practice using the bedside survey documented that 35% (202 of 576) of pre-transfusion haemoglobin concentrations were in the range of 95-105 g/l and 80% of the orders were for two packed cell units. The most frequent reasons for administering red cells were acute bleeding (35%) and the augmentation of O(2) delivery (25%). CONCLUSIONS: There is significant institutional variation in critical care transfusion practice, many intensivists adhering to a 100g/l threshold, and opting to administer multiple units despite published guidelines to the contrary. There is a need for prospective studies to define optimal practice in the critically ill

Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: The ARIPI randomized trial

Context: Even though red blood cells (RBCs) are lifesaving in neonatal intensive care, transfusing older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and length of hospital stay. Objective: To determine if RBCs stored for 7 days or less compared with usual standards decreased rates of major nosocomial infection and organ dysfunction in neonatal intensive care unit patients requiring at least 1 RBC transfusion. Design, Setting, and Participants: Double-blind, randomized controlled trial in 377 premature infants with birth weights less than 1250 g admitted to 6 Canadian tertiary neonatal intensive care units between May 2006 and June 2011. Intervention: Patients were randomly assigned to receive transfusion of RBCs stored 7 days or less (n=188) vs standard-issue RBCs in accordance with standard blood bank practice (n=189). Main Outcome Measures: The primary outcome was a composite measure of major neonatal morbidities, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, and intraventricular hemorrhage, as well as death. The primary outcome was measured within the entire period of neonatal intensive care unit stay up to 90 days after randomization. The rate of nosocomial infection was a secondary outcome. Results: The mean age of transfused blood was 5.1 (SD, 2.0) days in the fresh RBC group and 14.6 (SD, 8.3) days in the standard group. Among neonates in the fresh RBC group, 99 (52.7%) had the primary outcome compared with 100 (52.9%) in the standard RBC group (relative risk, 1.00; 95% CI, 0.82-1.21). The rate of clinically suspected infection in the fresh RBC group was 77.7% (n=146) compared with 77.2% (n=146) in the standard RBC group (relative risk, 1.01; 95% CI, 0.90-1.12), and the rate of positive cultures was 67.5% (n=127) in the fresh RBC group compared with 64.0% (n=121) in the standard RBC group (relative risk, 1.06; 95% CI, 0.91-1.22). Conclusion: In this trial, the use of fresh RBCs compared with standard blood bank practice did not improve outcomes in premature, very low-birth-weight infants requiring a transfusion. Trial Registration: clinicaltrials.gov Identifier: NCT00326924; Current Controlled Trials Identifier: ISRCTN65939658. ©2012 American Medical Association. All rights reserved

Adrenoceptors in GtoPdb v.2021.3

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [60, 186]. Adrenoceptors, &#945;1 The three &#945;1-adrenoceptor subtypes &#945;1A, &#945;1B and &#945;1D are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. -(-)phenylephrine, methoxamine and cirazoline are agonists and prazosin and doxazosin antagonists considered selective for &#945;1- relative to &#945;2-adrenoceptors. [3H]prazosin and [125I]HEAT (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy FLprazosin- QAPB) are used to examine cellular localisation of &#945;1-adrenoceptors. &#945;1-Adrenoceptor agonists are used as nasal decongestants; antagonists to treat symptoms of benign prostatic hyperplasia (alfuzosin, doxazosin, terazosin, tamsulosin and silodosin, with the last two compounds being &#945;1A-adrenoceptor selective and claiming to relax bladder neck tone with less hypotension); and to a lesser extent hypertension (doxazosin, terazosin). The &#945;1- and &#946;2-adrenoceptor antagonist carvedilol is used to treat congestive heart failure, although the contribution of &#945;1-adrenoceptor blockade to the therapeutic effect is unclear. Several anti-depressants and anti-psychotic drugs are &#945;1-adrenoceptor antagonists contributing to side effects such as orthostatic hypotension. Adrenoceptors, &#945;2 The three &#945;2-adrenoceptor subtypes &#945;2A, &#945;2B and &#945;2C are activated by (-)-adrenaline and with lower potency by (-)-noradrenaline. brimonidine and talipexole are agonists and rauwolscine and yohimbine antagonists selective for &#945;2- relative to &#945;1-adrenoceptors. [3H]rauwolscine, [3H]brimonidine and [3H]RX821002 are relatively selective radioligands. There are species variations in the pharmacology of the &#945;2A-adrenoceptor. Multiple mutations of &#945;2-adrenoceptors have been described, some associated with alterations in function. Presynaptic &#945;2-adrenoceptors regulate many functions in the nervous system. The &#945;2-adrenoceptor agonists clonidine, guanabenz and brimonidine affect central baroreflex control (hypotension and bradycardia), induce hypnotic effects and analgesia, and modulate seizure activity and platelet aggregation. clonidine is an anti-hypertensive (relatively little used) and counteracts opioid withdrawal. dexmedetomidine (also xylazine) is increasingly used as a sedative and analgesic in human [31] and veterinary medicine and has sympatholytic and anxiolytic properties. The &#945;2-adrenoceptor antagonist mirtazapine is used as an anti-depressant. The &#945;2B subtype appears to be involved in neurotransmission in the spinal cord and &#945;2C in regulating catecholamine release from adrenal chromaffin cells. Although subtype-selective antagonists have been developed, none are used clinically and they remain experimental tools. Adrenoceptors, &#946; The three &#946;-adrenoceptor subtypes &#946;1, &#946;2 and &#946;3 are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. Isoprenaline is selective for &#946;-adrenoceptors relative to &#945;1- and &#945;2-adrenoceptors, while propranolol (pKi 8.2-9.2) and cyanopindolol (pKi 10.0-11.0) are relatively selective antagonists for &#946;1- and &#946;2- relative to &#946;3-adrenoceptors. (-)-noradrenaline, xamoterol and (-)-Ro 363 show selectivity for &#946;1- relative to &#946;2-adrenoceptors. Pharmacological differences exist between human and mouse &#946;3-adrenoceptors, and the 'rodent selective' agonists BRL 37344 and CL316243 have low efficacy at the human &#946;3-adrenoceptor whereas CGP 12177 (low potency) and L 755507 activate human &#946;3-adrenoceptors [88]. &#946;3-Adrenoceptors are resistant to blockade by propranolol, but can be blocked by high concentrations of bupranolol. SR59230A has reasonably high affinity at &#946;3-adrenoceptors, but does not discriminate between the three &#946;- subtypes [320] whereas L-748337 is more selective. [125I]-cyanopindolol, [125I]-hydroxy benzylpindolol and [3H]-alprenolol are high affinity radioligands that label &#946;1- and &#946;2- adrenoceptors and &#946;3-adrenoceptors can be labelled with higher concentrations (nM) of [125I]-cyanopindolol together with &#946;1- and &#946;2-adrenoceptor antagonists. Fluorescent ligands such as BODIPY-TMR-CGP12177 can be used to track &#946;-adrenoceptors at the cellular level [8]. Somewhat selective &#946;1-adrenoceptor agonists (denopamine, dobutamine) are used short term to treat cardiogenic shock but, chronically, reduce survival. &#946;1-Adrenoceptor-preferring antagonists are used to treat cardiac arrhythmias (atenolol, bisoprolol, esmolol) and cardiac failure (metoprolol, nebivolol) but also in combination with other treatments to treat hypertension (atenolol, betaxolol, bisoprolol, metoprolol and nebivolol) [507]. Cardiac failure is also treated with carvedilol that blocks &#946;1- and &#946;2-adrenoceptors, as well as &#945;1-adrenoceptors. Short (salbutamol, terbutaline) and long (formoterol, salmeterol) acting &#946;2-adrenoceptor-selective agonists are powerful bronchodilators used to treat respiratory disorders. Many first generation &#946;-adrenoceptor antagonists (propranolol) block both &#946;1- and &#946;2-adrenoceptors and there are no &#946;2-adrenoceptor-selective antagonists used therapeutically. The &#946;3-adrenoceptor agonist mirabegron is used to control overactive bladder syndrome. There is evidence to suggest that &#946;-adrenoceptor antagonists can reduce metastasis in certain types of cancer [189]

PROTOCOL: In‐person interventions to reduce social isolation and loneliness: An evidence and gap map

Abstract This is the protocol for an evidence and gap map. The objectives are as follows: This EGM aims to map available evidence on the effects of in‐person interventions to reduce social isolation and/or loneliness across all age groups in all settings

Adrenoceptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [58], see also [180]. Adrenoceptors, &#945;1&#945;1-Adrenoceptors are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. phenylephrine, methoxamine and cirazoline are agonists and prazosin and cirazoline antagonists considered selective for &#945;1- relative to &#945;2-adrenoceptors. [3H]prazosin and [125I]HEAT (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy PLprazosin- QAPB) are used to examine cellular localisation of &#945;1-adrenoceptors. Selective &#945;1-adrenoceptor agonists are used as nasal decongestants; antagonists to treat hypertension (doxazosin, prazosin) and benign prostatic hyperplasia (alfuzosin, tamsulosin). The &#945;1- and &#946;2-adrenoceptor antagonist carvedilol is used to treat congestive heart failure, although the contribution of &#945;1-adrenoceptor blockade to the therapeutic effect is unclear. Several anti-depressants and anti-psychotic drugs are &#945;1-adrenoceptor antagonists contributing to side effects such as orthostatic hypotension and extrapyramidal effects.Adrenoceptors, &#945;2 &#945;2-Adrenoceptors are activated by (-)-adrenaline and with lower potency by (-)-noradrenaline. brimonidine and talipexole are agonists and rauwolscine and yohimbine antagonists selective for &#945;2- relative to &#945;1-adrenoceptors. [3H]rauwolscine, [3H]brimonidine and [3H]RX821002 are relatively selective radioligands. There is species variation in the pharmacology of the &#945;2A-adrenoceptor. Multiple mutations of &#945;2-adrenoceptors have been described, some associated with alterations in function. Presynaptic &#945;2-adrenoceptors regulate many functions in the nervous system. The &#945;2-adrenoceptor agonists clonidine, guanabenz and brimonidine affect central baroreflex control (hypotension and bradycardia), induce hypnotic effects and analgesia, and modulate seizure activity and platelet aggregation. clonidine is an anti-hypertensive and counteracts opioid withdrawal. dexmedetomidine (also xylazine) is used as a sedative and analgesic in human and veterinary medicine with sympatholytic and anxiolytic properties. The &#945;2-adrenoceptor antagonist yohimbine has been used to treat erectile dysfunction and mirtazapine as an anti-depressant. The &#945;2B subtype appears to be involved in neurotransmission in the spinal cord and &#945;2C in regulating catecholamine release from adrenal chromaffin cells.Adrenoceptors, &#946;&#946;-Adrenoceptors are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. Isoprenaline is selective for &#946;-adrenoceptors relative to &#945;1- and &#945;2-adrenoceptors, while propranolol (pKi 8.2-9.2) and cyanopindolol (pKi 10.0-11.0) are relatively &#946;1 and &#946;2 adrenoceptor-selective antagonists. (-)-noradrenaline, xamoterol and (-)-Ro 363 show selectivity for &#946;1- relative to &#946;2-adrenoceptors. Pharmacological differences exist between human and mouse &#946;3-adrenoceptors, and the 'rodent selective' agonists BRL 37344 and CL316243 have low efficacy at the human &#946;3-adrenoceptor whereas CGP 12177 and L 755507 activate human &#946;3-adrenoceptors [88]. &#946;3-Adrenoceptors are resistant to blockade by propranolol, but can be blocked by high concentrations of bupranolol. SR59230A has reasonably high affinity at &#946;3-adrenoceptors, but does not discriminate well between the three &#946;- subtypes whereas L 755507 is more selective. [125I]-cyanopindolol, [125I]-hydroxy benzylpindolol and [3H]-alprenolol are high affinity radioligands that label &#946;1- and &#946;2- adrenoceptors and &#946;3-adrenoceptors can be labelled with higher concentrations (nM) of [125I]-cyanopindolol together with &#946;1- and &#946;2-adrenoceptor antagonists. [3H]-L-748337 is a &#946;3-selective radioligand [474]. Fluorescent ligands such as BODIPY-TMR-CGP12177 can be used to track &#946;-adrenoceptors at the cellular level [8]. Somewhat selective &#946;1-adrenoceptor agonists (denopamine, dobutamine) are used short term to treat cardiogenic shock but, chronically, reduce survival. &#946;1-Adrenoceptor-preferring antagonists are used to treat hypertension (atenolol, betaxolol, bisoprolol, metoprolol and nebivolol), cardiac arrhythmias (atenolol, bisoprolol, esmolol) and cardiac failure (metoprolol, nebivolol). Cardiac failure is also treated with carvedilol that blocks &#946;1- and &#946;2-adrenoceptors, as well as &#945;1-adrenoceptors. Short (salbutamol, terbutaline) and long (formoterol, salmeterol) acting &#946;2-adrenoceptor-selective agonists are powerful bronchodilators used to treat respiratory disorders. Many first generation &#946;-adrenoceptor antagonists (propranolol) block both &#946;1- and &#946;2-adrenoceptors and there are no &#946;2-adrenoceptor-selective antagonists used therapeutically. The &#946;3-adrenoceptor agonist mirabegron is used to control overactive bladder syndrome

The reporting of theoretical health risks by the media: Canadian newspaper reporting of potential blood transmission of Creutzfeldt-Jakob disease

BACKGROUND: The media play an important role at the interface of science and policy by communicating scientific information to the public and policy makers. In issues of theoretical risk, in which there is scientific uncertainty, the media's role as disseminators of information is particularly important due to the potential to influence public perception of the severity of the risk. In this article we describe how the Canadian print media reported the theoretical risk of blood transmission of Creutzfeldt-Jakob disease (CJD). METHODS: We searched 3 newspaper databases for articles published by 6 major Canadian daily newspapers between January 1990 and December 1999. We identified all articles relating to blood transmission of CJD. In duplicate we extracted information from the articles and entered the information into a qualitative software program. We compared the observations obtained from this content analysis with information obtained from a previous policy analysis examining the Canadian blood system's decision-making concerning the potential transfusion transmission of CJD. RESULTS: Our search identified 245 relevant articles. We observed that newspapers in one instance accelerated a policy decision, which had important resource and health implication, by communicating information on risk to the public. We also observed that newspapers primarily relied upon expert opinion (47 articles) as opposed to published medical evidence (28 articles) when communicating risk information. Journalists we interviewed described the challenges of balancing their responsibility to raise awareness of potential health threats with not unnecessarily arousing fear amongst the public. CONCLUSIONS: Based on our findings we recommend that journalists report information from both expert opinion sources and from published studies when communicating information on risk. We also recommend researchers work more closely with journalists to assist them in identifying and appraising relevant scientific information on risk

In‐person interventions to reduce social isolation and loneliness: An evidence and gap map

BackgroundSocial isolation and loneliness can occur in all age groups, and they are linked to increased mortality and poorer health outcomes. There is a growing body of research indicating inconsistent findings on the effectiveness of interventions aiming to alleviate social isolation and loneliness. Hence the need to facilitate the discoverability of research on these interventions.ObjectivesTo map available evidence on the effects of in-person interventions aimed at mitigating social isolation and/or loneliness across all age groups and settings.Search MethodsThe following databases were searched from inception up to 17 February 2022 with no language restrictions: Ovid MEDLINE, Embase, EBM Reviews—Cochrane Central Register of Controlled Trials, APA PsycInfo via Ovid, CINAHL via EBSCO, EBSCO (all databases except CINAHL), Global Index Medicus, ProQuest (all databases), ProQuest ERIC, Web of Science, Korean Citation Index, Russian Science Citation Index, and SciELO Citation Index via Clarivate, and Elsevier Scopus.Selection CriteriaTitles, abstracts, and full texts of potentially eligible articles identified were screened independently by two reviewers for inclusion following the outlined eligibility criteria.Data Collection and AnalysisWe developed and pilot tested a data extraction code set in Eppi-Reviewer. Data was individually extracted and coded. We used the AMSTAR2 tool to assess the quality of reviews. However, the quality of the primary studies was not assessed.Main ResultsA total of 513 articles (421 primary studies and 92 systematic reviews) were included in this evidence and gap map which assessed the effectiveness of in-person interventions to reduce social isolation and loneliness. Most (68%) of the reviews were classified as critically low quality, while less than 5% were classified as high or moderate quality. Most reviews looked at interpersonal delivery and community-based delivery interventions, especially interventions for changing cognition led by a health professional and group activities, respectively. Loneliness, wellbeing, and depression/anxiety were the most assessed outcomes. Most research was conducted in high-income countries, concentrated in the United States, United Kingdom, and Australia, with none from low-income countries. Major gaps were identified in societal level and community-based delivery interventions that address policies and community structures, respectively. Less than 5% of included reviews assessed process indicators or implementation outcomes. Similar patterns of evidence and gaps were found in primary studies. All age groups were represented but more reviews and primary studies focused on older adults (≥60 years, 63%) compared to young people (≤24 years, 34%). Two thirds described how at-risk populations were identified and even fewer assessed differences in effect across equity factors for populations experiencing inequities