Weighted Blankets as a Sleep Intervention: A Scoping Review.

IMPORTANCE: Sleep disorders are associated with a range of health conditions, with poor sleep often further exacerbating individuals' health, well-being, and ability to participate in daily occupations. Weighted blankets offer a potentially simple nonpharmacological sleep intervention option. OBJECTIVE: To summarize available literature on instrumentation and outcomes associated with overnight use of weighted blankets for therapeutic purpose. EVIDENCE REVIEW: A scoping review following the PRISMA review guidelines was conducted. Sources included MEDLINE, Cochrane Library, CINAHL, PsycINFO, Scopus, Embase, and Google. Included studies reported on overnight use of weighted blankets. Critical appraisal of studies was conducted with standardized tools. FINDINGS: Eighteen studies met the inclusion criteria. Positive outcomes were reported for adults, including improved sleep, reduction in medication use, and improved mood. Sleep outcomes were mixed for children and adolescents but included improved occupational performance. Methodological quality of included studies regarding effectiveness was variable. Ten studies included details of the intervention, whereas only one study reported on implementation. No specific guidelines for use were included. CONCLUSIONS AND RELEVANCE: Weighted blankets are used as a sleep intervention for individuals across the life span experiencing a range of health conditions. Currently, there is more evidence of effectiveness with adults, although parents are favorable regarding weighted blanket use for children. Implementation and recommendation of weighted blankets are typically led by occupational therapists, with knowledge of the intervention facilitating use. This review provides information to inform occupational therapists' clinical decision-making and continued implementation of weighted blankets for individuals with sleep problems. Plain-Language Summary: This scoping review summarizes what is known about the use of weighted blankets as a sleep intervention for people of all ages. There is more evidence for overnight use of weighted blankets for adults, with improvements reported in sleep, mood, medication use, and pain. Although there is little evidence of improvement in sleep for children, some children show improvement in everyday functioning, and parents report positive outcomes from overnight use of weighted blankets. These findings suggest that occupational therapists should consider offering or recommending weighted blankets as a sleep intervention option for people of all ages, alongside consideration of individuals' preferences. Development of practice guidelines that incorporate current research findings is urgently needed to support occupational therapists' use of weighted blankets.

A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli.

Bacterial specialized metabolites are increasingly recognized as important factors in animal-microbiome interactions: for example, by providing the host with chemical defenses. Even in chemically rich animals, such compounds have been found to originate from individual members of more diverse microbiomes. Here, we identified a remarkable case of a moderately complex microbiome in the sponge host Mycale hentscheli in which multiple symbionts jointly generate chemical diversity. In addition to bacterial pathways for three distinct polyketide families comprising microtubule-inhibiting peloruside drug candidates, mycalamide-type contact poisons, and the eukaryotic translation-inhibiting pateamines, we identified extensive biosynthetic potential distributed among a broad phylogenetic range of bacteria. Biochemical data on one of the orphan pathways suggest a previously unknown member of the rare polytheonamide-type cytotoxin family as its product. Other than supporting a scenario of cooperative symbiosis based on bacterial metabolites, the data provide a rationale for the chemical variability of M. hentscheli and could pave the way toward biotechnological peloruside production. Most bacterial lineages in the compositionally unusual sponge microbiome were not known to synthesize bioactive metabolites, supporting the concept that microbial dark matter harbors diverse producer taxa with as yet unrecognized drug discovery potential.

What is simulation-based medical education (SBME) debriefing in prehospital medicine? A qualitative, ethnographic study exploring SBME debriefing in prehospital medical education.

INTRODUCTION: Simulation-based medical education (SBME) debriefing - a construct distinct from clinical debriefing - is used following simulated scenarios and is central to learning and development in fields ranging from aviation to emergency medicine. However, little research into SBME debriefing in prehospital medicine exists. This qualitative study explored the facilitation and effects of prehospital SBME debriefing, and identified obstacles to debriefing, using the London's Air Ambulance Pre-Hospital Care Course (PHCC) as a model. METHOD: Ethnographic observations of moulages and debriefs were conducted over two consecutive days of the PHCC in October 2019. Detailed contemporaneous field notes were made and analysed thematically. Subsequently, seven one-to-one, semi-structured interviews were conducted with four PHCC debrief facilitators and three course participants to explore their experiences of prehospital SBME debriefing. Interview data were transcribed and analysed thematically. RESULTS: Four overarching themes were identified: approach to facilitation of debriefs, effects of debriefing, facilitator development, and obstacles to debriefing. The unpredictable debriefing environment was seen as both hindering and, paradoxically, benefitting SBME debriefing. Despite using varied debriefing structures, facilitators emphasised similar key debriefing components including exploring participants' reasoning and sharing experiences to improve learning and prevent future errors. Debriefing was associated with three effects: releasing emotion; learning and improving, particularly compound learning as participants progressed through sequential scenarios; and the application of learning to clinical practice. Facilitator training and feedback were central to facilitator learning and development. Several obstacles to debriefing were identified, including mismatch of participant and facilitator agendas, pressure and time. CONCLUSIONS: SBME debriefing in prehospital medicine is complex, requiring an understanding of participant agendas and facilitator experience to maximise participant learning. Aspects unique to prehospital SBME debriefing were identified, notably, the unpredictable debriefing environment, and the paradoxical benefit of educational obstacles for learning. Aspects of SBME debriefing not extensively detailed in the literature were also highlighted, such as compound participant learning, facilitator candour, and facilitator learning, which require further exploration.

"You may think that the consultants are great, and they know everything, but they don't": exploring how new emergency medicine consultants experience uncertainty.

BACKGROUND: Uncertainty is particularly obvious in emergency medicine (EM) due to the characteristics of the patient cohort, time constraints, and busy environment. Periods of transition are thought to add to uncertainty. Managing uncertainty is recognised as a key ability for medical practice, but is often not addressed explicitly. This study explored how new consultants in EM experience uncertainty, with the aim of making explicit what is often hidden and potentially informing support for doctors to manage the uncertainty they face. METHODS: This was a qualitative study using interpretive phenomenological analysis (IPA). Five consultants working in the UK within one year of achieving a certificate of completion of training were interviewed online during 2021, these were transcribed and analysed using IPA. RESULTS: Three superordinate themes were identified: 'transition and performance as a source of uncertainty', 'uncertainty and decision-making in the context of the emergency department' and 'sharing uncertainty and asking for help'. The transition created uncertainty related to their professional identity that was compounded by a lack of useful feedback. There was tension between perceived expectations of certainty and the recognition of uncertainty in practice. EM doctors were seen as experts in managing uncertainty, with responses to uncertainty including gathering information, sharing uncertainty and seeking help. Expressing uncertainty was viewed as necessary for good patient care but could be risky to credibility, with psychological safety and role modelling behaviour making it easier for the participants to express uncertainty. CONCLUSION: This study highlights the need for new consultants to have psychologically safe, reflective spaces to think through uncertainties with others. This appears to reduce uncertainty, and also act as a source of feedback. The study adds to the existing calls to address uncertainty more explicitly in training, and challenge the expectations of certainty that exist within medicine.

A Novel Spinel Ferrite-Hexagonal Ferrite Composite for Enhanced Magneto-Electric Coupling in a Bilayer with PZT.

The magnetoelectric effect (ME) is an important strain mediated-phenomenon in a ferromagnetic-piezoelectric composite for a variety of sensors and signal processing devices. A bias magnetic field, in general, is essential to realize a strong ME coupling in most composites. Magnetic phases with (i) high magnetostriction for strong piezomagnetic coupling and (ii) large anisotropy field that acts as a built-in bias field are preferred so that miniature, ME composite-based devices can operate without the need for an external magnetic field. We are able to realize such a magnetic phase with a composite of (i) barium hexaferrite (BaM) with high magnetocrystalline anisotropy field and (ii) nickel ferrite (NFO) with high magnetostriction. The BNx composites, with (100 - x) wt.% of BaM and x wt.% NFO, for x = 0-100, were prepared. X-ray diffraction analysis shows that the composites did not contain any impurity phases. Scanning electron microscopy images revealed that, with an increase in NFO content, hexagonal BaM grains become prominent, leading to a large anisotropy field. The room temperature saturation magnetization showed a general increase with increasing BaM content in the composites. NFO rich composites with x ≥ 60 were found to have a large magnetostriction value of around -23 ppm, comparable to pure NFO. The anisotropy field HA of the composites, determined from magnetization and ferromagnetic resonance (FMR) measurements, increased with increasing NFO content and reached a maximum of 7.77 kOe for x = 75. The BNx composite was cut into rectangular platelets and bonded with PZT to form the bilayers. ME voltage coefficient (MEVC) measurements at low frequencies and at mechanical resonance showed strong coupling at zero bias for samples with x ≥ 33. This large in-plane HA acted as a built-in field for strong ME effects under zero external bias in the bilayers. The highest zero-bias MEVC of ~22 mV/cm Oe was obtained for BN75-PZT bilayers wherein BN75 also has the highest HA. The Bilayer of BN95-PZT showed a maximum MEVC ~992 mV/cm Oe at electromechanical resonance at 59 kHz. The use of hexaferrite-spinel ferrite composite to achieve strong zero-bias ME coupling in bilayers with PZT is significant for applications related to energy harvesting, sensors, and high frequency devices.

A realist evaluation of a London general practitioner trainer course.

Clinicians with teaching and training roles should be adequately trained and assessed. However, some debate exists as to what the nature of this training should be. Historically, a postgraduate certificate in education was a pre-requisite to becoming a GP trainer but this is changing with growing concern that such a pre-requisite might act as a deterrent to potential GP trainers. This research examines the impact of a scheme designed to provide an alternative, more practical and focused, pathway to becoming a GP trainer. We interviewed 26 course participants and stakeholders of the London GP Training Course (LGPTC), observed teaching sessions, and analysed course materials. We asked what elements of the course were and weren't effective, for whom, and under what circumstances. Here, we present a summary of our main findings - that GP trainers want to know practically, not theoretically, how to be a trainer; formative assessment boosts trainees' confidence in their own skills and abilities; short, practical GP training courses can help enhance the numbers of GP trainers; important questions remain about the role and value of educational theory in education faculty development.

Contemporary perspectives on the genetics and clinical use of lipoprotein(a) in preventive cardiology.

PURPOSE OF REVIEW: The pathogenicity of lipoprotein(a) [Lp(a)] as a risk factor for atherosclerotic cardiovascular disease (ASCVD) is well evidenced and recognized by international consensus-based guidelines. However, the measurement of Lp(a) is not routine clinical practice. Therapeutic agents targeting Lp(a) are now progressing through randomised clinical trials, and it is timely for clinicians to familiarize themselves with this complex and enigmatic lipoprotein particle. RECENT FINDINGS: Recent developments in the understanding of genetic influences on the structure, plasma concentration and atherogenicity of Lp(a) have contextualized its clinical relevance. Mendelian randomization studies have enabled estimation of the contribution of Lp(a) to ASCVD risk. Genotyping individual patients with respect to Lp(a)-raising single nucleotide polymorphisms predicts ASCVD, but has not yet been shown to add value beyond the measurement of Lp(a) plasma concentrations, which should be done by Lp(a) isoform-independent assays capable of reporting in molar concentrations. Contemporary gene-silencing technology underpins small interfering RNA and antisense oligonucleotides, which are emerging as the leading Lp(a)-lowering therapeutic agents. The degree of Lp(a)-lowering required to achieve meaningful reductions in ASCVD risk has been estimated by Mendelian randomization, providing conceptual support. SUMMARY: Measurement of Lp(a) in the clinical setting contributes to the assessment of ASCVD risk, and will become more important with the advent of specific Lp(a)-lowering therapies. Knowledge of an individual patient's genetic predisposition to increased Lp(a) appears to impart little or not additional clinical value beyond Lp(a) particle concentration.

Hydrated Rubrolides from the New Zealand Tunicate Synoicum kuranui.

LCMS analysis of an extract of the New Zealand tunicate Synoicum kuranui showed evidence for numerous new rubrolides. Following a mass spectrometry-guided isolation procedure, new hydrated rubrolides V and W (5 and 6), along with previously reported rubrolide G (3), were isolated and characterized using MS and NMR. The anti-bacterial and cell cytotoxic activity of the compounds were compared to the potent anti-MRSA compound rubrolide A; hydration across the C-5/C-6 bond was shown to abrogate antibacterial activity.

Lipoprotein apheresis and PCSK9 inhibitors for severe familial hypercholesterolaemia: Experience from Australia and New Zealand.

INTRODUCTION: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA. MATERIALS AND METHODS: We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres. RESULTS: LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors. CONCLUSION: While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.

Approach to the diagnosis of secondary hypertension in adults.

Presentations that should raise suspicion of secondary hypertension include early-onset, severe or resistant hypertension. A suggestive family history or clinical clues can point to a specific secondary cause. The most common causes and associations are renal disease, primary aldosteronism and obstructive sleep apnoea. Medicines, illicit substances and alcohol may also be responsible. The assessment of patients begins with history taking and examination, to look for clinical clues. Laboratory tests include electrolytes, urea, creatinine and the aldosterone:renin ratio, urinalysis and the urine albumin:creatinine ratio. Abnormal results should prompt further investigation. Initial testing for primary aldosteronism is best done before starting potentially interfering antihypertensive drugs. If the patient is already taking interfering antihypertensive drugs that cannot be stopped, the interpretation of the aldosterone:renin ratio must consider the presence of those drugs. Specialist advice can be sought if needed.

Widening the spectrum of genetic testing in familial hypercholesterolaemia: Will it translate into better patient and population outcomes?

Familial hypercholesterolaemia (FH) is caused by pathogenic variants in LDLR, APOB or PCSK9. Impaired low-density lipoprotein (LDL) receptor function leads to decreased LDL catabolism and premature atherosclerotic cardiovascular disease (ASCVD). Thousands of LDLR variants are known, but assignation of pathogenicity requires accurate phenotyping, family studies and assessment of LDL receptor function. Precise, genetic diagnosis of FH using targeted next generation sequencing allows for optimal treatment, distinguishing FH from pathogenically distinct disorders requiring different treatment. Polygenic hypercholesterolaemia resulting from an accumulation of LDL cholesterol-raising single nucleotide polymorphisms (SNPs) could also be suspected by this approach. Similarly, ASCVD risk could be estimated by broader sequencing of cholesterol and non-cholesterol-related genes. Both of these areas require further research. The clinical management of FH, focusing on the primary or secondary prevention of ASCVD, has been boosted by PCSK9 inhibitor therapy. The efficacy of PCSK9 inhibitors in homozygous FH may be partly predicted by the LDLR variants. While expanded genetic testing in FH is clinically useful in providing an accurate diagnosis and enabling cost-effective testing of relatives, further research is needed to establish its value in improving clinical outcomes.

Intrastromal bevacizumab in the management of corneal neovascularization: a retrospective review.

PURPOSE: To evaluate the long-term safety and efficacy of intrastromal bevacizumab for treatment of deep corneal neovascularization in candidates for high-risk cornea grafting. METHODS: A single-center retrospective study involving 14 eyes of 14 patients with chronic deep corneal neovascularization, treated with intrastromal bevacizumab by a single provider from 2011 to present. Intrastromal bevacizumab (0.05-0.1 mL of 2.5 mg/0.1 mL) was administered every 4-8 weeks. On average 1-3 intrastromal injections were performed prior to corneal grafting (penetrating keratoplasty or deep anterior lamellar keratoplasty). RESULTS: 64.2% patients had neurotrophic keratitis secondary to herpes zoster or simplex. Neovascularization was encroaching the visual axis in 50% and was paracentral in 42.8%. After intrastromal bevacizumab injection, 14.2% had complete regression of neovascularization, avoiding the need of future corneal transplant. Persistent neovascularization was noticed in 21.4%. Successful penetrating keratoplasty was performed in 57% of patients. Minimal adverse effects were noted; temporary epithelial defect was seen in two eyes and self-limited intrastromal hemorrhage in one. There was no evidence of recurrence of neovascularization or graft rejection in the transplant group (mean follow-up 3 years). CONCLUSION: Intrastromal bevacizumab appears to be a safe and effective modality in the treatment of chronic corneal neovascularization, producing durable regression of corneal neovascularization and allowing for durable success of subsequent corneal transplants in high-risk patients.

Targeted Isolation of Rubrolides from the New Zealand Marine Tunicate Synoicum kuranui.

Global natural products social (GNPS) molecular networking is a useful tool to categorize chemical space within samples and streamline the discovery of new natural products. Here, we demonstrate its use in chemically profiling the extract of the marine tunicate Synoicum kuranui, comprised of many previously reported rubrolides, for new chemical entities. Within the rubrolide cluster, two masses that did not correspond to previously reported congeners were detected, and, following MS-guided fractionation, led to the isolation of new methylated rubrolides T (3) and (Z/E)-U (4). Both compounds showed strong growth inhibitory activity against the Gram-positive bacteria Bacillus subtilis, with minimum inhibitory concentration (MIC) values of 0.41 and 0.91 µM, respectively.

Teaching medical professionalism: a qualitative exploration of persuasive communication as an educational strategy.

BACKGROUND: Across the world, local standards provide doctors with a backbone of professional attitudes that must be embodied across their practice. However, educational approaches to develop attitudes are undermined by the lack of a theoretical framework. Our research explored the ways in which the General Medical Council's (GMC) programme of preventative educational workshops (the Duties of a Doctor programme) attempted to influence doctors' professional attitudes and examined how persuasive communication theory can advance understandings of professionalism education. METHODS: This qualitative study comprised 15 ethnographic observations of the GMC's programme of preventative educational workshops at seven locations across England, as well as qualitative interviews with 55 postgraduate doctors ranging in experience from junior trainees to senior consultants. The sample was purposefully chosen to include various geographic locations, different programme facilitators and doctors, who varied by seniority. Data collection occurred between March to December 2017. Thematic analysis was undertaken inductively, with meaning flowing from the data, and deductively, guided by persuasive communication theory. RESULTS: The source (educator); the message (content); and the audience (participants) were revealed as key influences on the persuasiveness of the intervention. Educators established a high degree of credibility amongst doctors and worked to build rapport. Their message was persuasive, in that it drew on rational and emotional communicative techniques and made use of both statistical and narrative evidence. Importantly, the workshops were interactive, which allowed doctors to engage with the message and thus increased its persuasiveness. CONCLUSIONS: This study extends the literature by providing a theoretically-informed understanding of an educational intervention aimed at promoting professionalism, examining it through the lens of persuasive communication. Within the context of interactive programmes that allow doctors to discuss real life examples of professional dilemmas, educators can impact on doctors' professional attitudes by drawing on persuasive communication techniques to enhance their credibility to demonstrate expertise, by building rapport and by making use of rational and emotional appeals.

PCSK9 inhibition 2018: riding a new wave of coronary prevention.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates the low-density lipoprotein cholesterol (LDL-c) receptor and thus circulating LDL-c levels. With overwhelming evidence now supporting the reduction in LDL-c to lower the risk of cardiovascular disease, PCSK9 inhibitors represent an important therapeutic target, particularly in high-risk populations. Here, we summarise and update the science of PCSK9, including its discovery and the development of various inhibitors, including the now approved monoclonal antibodies. In addition, we summarise the clinical applications of PCSK9 inhibitors in a range of patient populations, as well as the major randomised controlled trials investigating their use in coronary prevention.

Clinical guidance on the contemporary use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies.

There is now significant evidence for the benefits of lowering low-density lipoprotein cholesterol (LDL-c) to reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Although statins are the most widely prescribed lipid-lowering therapy that effectively lower LDL-c, especially in combination with ezetimibe, some patients require adjunctive therapy to further lower LDL-c and mitigate attendant risk of ASCVD. The gap can be filled by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies whose use is currently supported by two recent cardiovascular outcome studies and new treatment guidelines. We provide an overview of extant studies investigating PCSK9 monoclonal antibodies in various patient populations, an update of the guidelines regarding their use and a case-based discussion.

An Acetylenic Lipid from the New Zealand Ascidian Pseudodistoma cereum: Exemplification of an Improved Workflow for Determination of Absolute Configuration of Long-Chain 2-Amino-3-alkanols.

An acetylenic 2-amino-3-alcohol, distaminolyne B (2), isolated from the New Zealand ascidian Pseudodistoma cereum, is reported. The isolation and structure elucidation of 2 and assignment of 2S,3S absolute configuration (AC) using the exciton coupled circular dichroism technique are described. Using a methodologically facile workflow, the same AC was also established by analysis of specific rotation, terminal methyl C-1 δC chemical shift, and NH δH and J values of the N,O-diacetate derivative.

Lamellarin Sulfates from the Pacific Tunicate Didemnum ternerratum.

Six new lamellarin sulfates (1-6) were isolated from the methanolic extract of the Pacific tunicate Didemnum ternerratum, collected from the Kingdom of Tonga. Mass spectrometric molecular networking through the GNPS platform was used to target the isolation of 1-6. Planar structures were elucidated through a combination of NMR and MS experiments. Through comparison of experimental and calculated ECD spectra, the absolute configurations of atropisomers 2-5 were determined, with their energetic barriers to racemization also determined computationally. The cytotoxicity of the compounds was tested against the human colon carcinoma cell line HCT-116, where lamellarin D-8-sulfate (5) exhibited moderate activity with an IC50 of 9.7 µM.

Pharmacokinetics of Benzylpenicillin (Penicillin G) during Prolonged Intermittent Renal Replacement Therapy.

Prolonged intermittent renal replacement therapy (PIRRT) is an increasingly adopted method of renal replacement in critically ill patients. Like continuous renal replacement therapy, PIRRT can alter the pharmacokinetics (PK) of many drugs. In this setting, dosing data for antibiotics like benzylpenicillin are lacking. In order to enable clinicians to prescribe benzylpenicillin safely and effectively, knowledge of the effects of PIRRT on the plasma PK of benzylpenicillin is required. Herein, we describe the PK of benzylpenicillin in 2 critically ill patients on PIRRT for the treatment of penicillin-susceptible Staphylococcus aureus bacteremia complicated by infective endocarditis. Blood samples were taken for each patient taken over dosing periods during PIRRT and off PIRRT. Two-compartment PK models described significant differences in the mean clearance of benzylpenicillin with and without PIRRT (6.61 vs. 3.04 L/h respectively). We would suggest a benzylpenicillin dose of 1,800 mg (3 million units) every 6-h during PIRRT therapy as sufficient to attain PK/pharmacodynamic target.