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Exploring women's thoughts on self-weighing during pregnancy: results of the Self-Weighing in Pregnancy: Experiences (SWIPE) study
No full textBACKGROUND: Excess gestational weight gain is common and an important risk factor for adverse pregnancy outcomes. Regular weighing can be used to assess and manage weight gain, but NICE guidelines do not recommend routine weighing during antenatal care. Trials that have tested the effectiveness of self-weighing to manage GWG have been unsuccesful in engaging women in regular self-weighing, although the reasons for lack of engagement are not fully understood. This study aimed to understand why this lack of engagement occurred by exploring the naturally occurring thoughts and feelings of pregnant women (9 to 15 weeks gestational age) who were asked to weigh themselves at home. METHODS: Twenty-five women were recruited to take part. Participants completed short questionnaires at their first-trimester and 20-week scans. After recruitment, participants were asked to weigh themselves at roughly the same time each week for 8 weeks. Whilst they weighed themselves they were asked to audio-record their current weight and describe any thoughts or feelings that occurred as they weighed themselves. These audio recordings were then sent to researchers using a secure messaging service. RESULTS: Most of the recruited women (56%) were unaware of guidelines for gestational weight gain, and only 40% could identify the ideal rate of GWG for their BMI group. Thematic analysis of the think-aloud recordings resulted in three main themes: "understanding weight gain in pregnancy", "taking action to prevent weight gain" and "reactions to self-weighing". Overall, there was a relatively positive response to self-weighing and some participants used self-weighing to reflect on the reasons for weight gain and plan actions they could take to avoid excess gain. Negative emotional responses tended to be related to a lack of guidance about what level of weight gain or loss was "healthy", or to other worries about the pregnancy. Of the women recruited who submitted at least one think aloud recording (n 10), 80% found self-weighing to be useful, and said they would likely continue to self-weigh at home. CONCLUSIONS: Women had complex emotions about self-weighing during pregnancy but overall found it useful, suggesting it could be encouraged as part of self-regulatory interventions to control GWG. Clear guidelines about appropriate gestational weight gain could help to reduce anxiety. TRIAL REGISTRATION: The study was prospectively registered with ISRCTN ISRCTN10035244
A phase Ib/II study of ivosidenib with venetoclax plus /- azacitidine in IDH1-mutated myeloid malignancies
No full textBackground: Isocitrate dehydrogenase-1 (IDH1+) mutations are present in 5-15% of myeloid malignancies, promoting leukemogenesis through production of the oncometabolite 2-hydroxyglutarate resulting in arrested myeloid differentiation. IDH1+ malignancies demonstrate increased reliance on the anti-apoptotic protein BCL-2, enhancing susceptibility to the BCL-2 inhibitor venetoclax (VEN). We report an interim safety and efficacy analysis of the IDH1 inhibitor ivosidenib (IVO; 500 mg PO daily D15-continuous) combined with VEN (D1-14) +/- azacitidine (AZA; 75mg/m2 D1-7 every 28 days). Methods: Eligible patients age ≥18 with IDH1+ MDS, newly diagnosed AML (ND: treatment naïve [TN] or secondary/treated secondary AML [sAML]), or relapsed/refractory (R/R) AML enrolled into three dose levels (DL): DL1 (IVO+VEN 400 mg), DL2 (IVO+VEN 800 mg), DL3 (IVO+VEN 400 mg+AZA). Primary objectives included safety and tolerability, and IWG defined overall response (ORR: CR+CRi+CRh+PR+MLFS). Prior receipt of IVO or VEN was exclusionary.
Results: 25 evaluable patients (DL1: 6, DL2: 6, DL3: 13) enrolled with a median follow-up of 16.1 months. Median age was 67 (range: 44-84). 84% (N=21) of patients had AML (ND: N=13 [TN: 8, sAML: 5], R/R: N=8), while 16% (N=4) had MDS. ELN risk was intermediate and adverse in 16% (N=4) and 56% (N=14). Median IDH1 VAF at enrollment was 22.7% (range: 5.1%-47.8%). Two patients had received a prior IDH1 inhibitor. The ORR was 92% (DL1: 67%, DL2: 100%, DL3: 100%). Composite CR (CRc: CR+CRi+CRh) was 84% (DL1: 67%, DL2: 100%, DL3: 85%) including 92% (TN: 100%, sAML: 80%), 63%, and 100% of patients with ND-AML, R/R-AML, or MDS. Median number of cycles received was 4 (DL1: 8.5, DL2: 6, DL3: 4) with ongoing responses in 62% (DL1: 33%, DL2: 50%, DL3: 82%) at 1-year. 8 patients transitioned to SCT (DL1: 0, DL2: 2, DL3: 6), and 8 patients remain on study (DL1: 2, DL2: 1, DL3: 5). 1-year OS was 68% for the entire study population (DL1: 50%, DL2: 67%, DL3: 78%), 71% in ND-AML (TN: 86%, sAML: 60%), 50% in R/R-AML, and 100% in MDS. Measurable residual disease negative CRc by multiparameter flow cytometry was attained in 60% (ND-AML: 67%, R/R-AML: 60%, MDS: 33%) correlating with improved OS (median OS: NR vs. 8.5 months, p-value: 0.038). Common grade 3/4 adverse events included febrile neutropenia (28%) and pneumonia (24%). Tumor lysis and differentiation syndrome occurred in two and four patients; all cases resolved with medical management.
Conclusions: IVO+VEN +/- AZA is an effective treatment regimen in patients with IDH1+myeloid malignancies. The combination therapy is associated with an acceptable and expected toxicity profile with notable efficacy and high rates of MRD-negative CRc in AML. Enrollment into the study continues. Clinical trial information: NCT03471260
Ethics of early intervention in Alzheimer's disease
No full textAlzheimer’s disease (AD) research, treatment, and prevention focus increasingly on developing personalized interventions based on personal genetic, biological, phenotypic data, for early intervention (EI) to limit harm. This approach has much to recommend it, but important ethical and philosophical challenges follow that should be considered, which we analyze here. We argue that advancing understanding of the causes of AD undermines the clarity of the distinction between primary and secondary prevention. This makes it increasingly unclear how primary and secondary categories can be appealed to as the basis for making judgements about what interventions are permissible, and for distinguishing between acceptably vs unacceptably early points in life to intervene. Timely efforts at prevention are vital for limiting harm from AD and given the logic of EI is that, in presence of risk, earlier is better, one might assume that earliest is best. This may or may not be the case; however, the permissibility of intervening in different ways at different stages of life is complex and turns on numerous contextual factors. We consider the particular ethical implications of intervening at different points in the life course, presenting a valuable resource for negotiating clinical and policy implications of EI in AD
Disentangling contextual effects from musculoskeletal treatments
No full textWhen a patient receives a treatment for a musculoskeletal pain condition, the outcome they experience (total effect) is made up of the specific treatment effect and non-specific effects that may include natural history, regression to the mean, and contextual effects 1. Understanding the specific effect of the treatment is important for research consumers; patients, clinicians and policy makers, as some treatments have harms or costs that could outweigh any positive specific effects. In this article we 1) discuss challenges in identifying and removing contextual effects in pragmatic trials, 2) introduce a way to isolate contextual effects of treatments using causal mediation analysis, and 3) highlight the importance of explicitly defining the contextual effect we want to estimate or control
Feeding design in free-living mesostigmatid chelicerae (Acari: Anactinotrichida)
No full textA model based upon mechanics is used in a re-analysis of historical acarine morphological work augmented by an extra seven zoophagous mesostigmatid species. This review shows that predatory mesostigmatids do have cheliceral designs with clear rational purposes. Almost invariably within an overall body size class, the switch in predatory style from a worm-like prey feeding (‘crushing/mashing’ kill) functional group to a micro-arthropod feeding (‘active prey cutting/slicing/slashing' kill) functional group is matched by: an increased cheliceral reach, a bigger chelal gape, a larger morphologically estimated chelal crunch force, and a drop in the adductive lever arm velocity ratio of the chela. Small size matters. Several uropodines (Eviphis ostrinus, the omnivore Trachytes aegrota, Urodiaspis tecta and, Uropoda orbicularis) have more elongate chelicerae (greater reach) than their chelal gape would suggest, even allowing for allometry across mesostigmatids. They may be: plesiosaur-like high-speed strikers of prey, scavenging carrion feeders (like long-necked vultures), probing/burrowing crevice feeders of cryptic nematodes, or small morsel/fragmentary food feeders. Some uropodoids have chelicerae and chelae which probably work like a construction-site mechanical excavator-digger with its small bucket. Possible hoeing/bulldozing, spore-cracking and tiny sabre-tooth cat-like striking actions are discussed for others. Subtle changes lead small mesostigmatids to be predator–scavengers (mesocarnivores) or to be predator–fungivores (hypocarnivores). Some uropodines (e.g., the worm-like prey feeder Alliphis siculus and, Uropoda orbicularis) show chelae similar in design to astigmatids and cryptostigmatids indicating possible facultative saprophagy. Scale matters—obligate predatory designs (hypercarnivory) start for mesostigmatids with chelal gape > 150 μm and cheliceral reach > 350 μm (i.e., about 500–650 μm in body size). Commonality of trophic design in these larger species with solifugids is indicated. Veigaia species with low chelal velocity ratio and other morphological strengthening specialisms, appear specially adapted in a concerted way for predating active soft and fast moving springtails (Collembola). Veigaia cerva shows a markedly bigger chelal gape than its cheliceral reach would proportionately infer suggesting it is a crocodile-like sit-and-wait or ambush predator par excellence. A small chelal gape, low cheliceral reach, moderate velocity ratio variant of the worm-like feeding habit design is supported for phytoseiid pollenophagy. Evidence for a resource partitioning model in the evolution of gnathosomal development is found. A comparison to crustacean claws and vertebrate mandibles is made. Alliphis siculus and Rhodacarus strenzkei are surprisingly powerful mega-cephalics for their small size. Parasitids show a canid-like trophic design. The chelicera of the nematophagous Alliphis halleri shows felid-like features. Glyphtholaspis confusa has hyaena-like cheliceral dentition. The latter species has a markedly smaller chelal gape than its cheliceral reach would suggest proportionately, which together with a high chelal velocity ratio and a high estimated chelal crunch force matches a power specialism of feeding on immobile tough fly eggs/pupae by crushing (durophagy). A consideration of gnathosomal orientation is made. Predatory specialisms appear to often match genera especially in larger mesostigmatids, which may scale quite differently. Comparison to holothyrids and opilioacarids indicates that the cheliceral chelae of the former are cutting-style and those of the latter are crushing-style. A simple validated easy-to-use ‘2:1 on’ predictive algorithm of feeding habit type is included based on a strength-speed tradeoff in chelal velocity ratio for ecologists to test in the field
Changes in paediatric respiratory infections at a UK teaching hospital 2016-2021; impact of the SARS-CoV-2 pandemic
No full textObjective: To describe the impact of the SARS-CoV-2 pandemic on the incidence of paediatric viral respiratory tract infection in Oxfordshire, UK.
Methods: Data on paediatric Emergency Department (ED) attendances (0-15 years inclusive), respiratory virus testing, vital signs and mortality at Oxford University Hospitals were summarised using descriptive statistics.
Results: Between 1-March-2016 and 30-July-2021, 155,056 ED attendances occurred and 7,195 respiratory virus PCRs were performed. Detection of all pathogens was suppressed during the first national lockdown. Rhinovirus and adenovirus rates increased when schools reopened September-December 2020, then fell,
before rising in March-May 2021. The usual winter RSV peak did not occur in 2020/21, with an interseasonal rise (32/1,000 attendances in 0-3yr olds) in July 2021. Influenza remained suppressed throughout. A higher Paediatric Early Warning Score (PEWS) was seen for attendees with adenovirus during the pandemic compared to pre-pandemic (p=0.04, Mann-Witney U test), no other differences in PEWS were seen.
Conclusions: SARS-CoV-2 caused major changes in the incidence of paediatric respiratory viral infection in Oxfordshire, with implications for clinical service demand, testing strategies, timing of palivizumab RSV prophylaxis, and highlighting the need to understand which public health interventions are most effective for preventing respiratory virus infections
Carbon capture and storage at the end of a lost decade
No full textFollowing the landmark 2015 United Nations Paris Agreement, a growing number of countries are committing to the transition to net-zero emissions. Carbon capture and storage (CCS) has been consistently heralded to directly address emissions from the energy and industrial sectors and forms a significant component of plans to reach net-zero. However, despite the critical importance of the technology and substantial research and development to date, CCS deployment has been slow. This review examines deployment efforts over the last decade. We reveal that facility deployment must increase dramatically from current levels, and much work remains to maximize storage of CO2 in vast subsurface reserves. Using current rates of deployment, CO2 storage capacity by 2050 is projected to be around 700 million tons per year, just 10% of what is required. Meeting the net-zero targets via CCS ambitions seems unlikely unless worldwide coordinated efforts and rapid changes in policy take place
Economic evaluation of new models of care: does the decision change between cost-utility analysis and multi-criteria decision analysis?
No full textObjectives: To experiment with new approaches of collaboration in healthcare delivery, local authorities implement new models of care. Regarding the local decision-context of these models, Multi-Criteria Decision Analysis (MCDA) may be of added value to Cost-Utility Analysis (CUA), as it covers a wider range of outcomes. This study compares the two methods using a side-by-side application.
Methods: A new Dutch model of care, Primary Care Plus (PC+), was used as case study to compare the results of CUA and MCDA. Data of patients referred to PC+ or care-as-usual was retrieved by questionnaires and administrative databases with a three-month follow-up. Propensity score matching together with generalised linear regression models was used to reduce confounding. Univariate and probabilistic sensitivity analyses were performed to explore uncertainty in the results.
Results: Although both methods indicated PC+ as dominant alternative, complementary differences were observed. MCDA provided additional evidence that PC+ improved access to care (standardised performance score of 0.742 versus 0.670), improvement in health-related quality of life was driven by the psychological well-being component (standardised performance score of 0.710 versus 0.704), estimated the budget required for the PC+ to be affordable in addition to preferable (€521.42 per patient). Additionally, MCDA was less sensitive to the utility measures used.
Conclusions: MCDA may facilitate an auditable and transparent evaluation of new models of care by providing additional information on a wider range of outcomes and incorporating affordability. However, more effort is needed to increase the usability of MCDA among local decision makers
Coinage metal aluminyl complexes: probing regiochemistry and mechanism in the insertion and reduction of carbon dioxide
No full textThe synthesis of coinage metal aluminyl complexes, featuring M–Al covalent bonds, is reported via a salt metathesis approach employing an anionic Al(I) (‘aluminyl’) nucleophile and group 11 electrophiles. This approach allows access to both bimetallic (1 : 1) systems of the type (tBu3P)MAl(NON) (M = Cu, Ag, Au; NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene) and a 2 : 1 di(aluminyl)cuprate system, K[Cu{Al(NON)}2]. The bimetallic complexes readily insert heteroallenes (CO2, carbodiimides) into the unsupported M–Al bonds to give systems containing a M(CE2)Al bridging unit (E = O, NR), with the μ-κ1(C):κ2(E,E′) mode of heteroallene binding being demonstrated crystallographically for carbodiimide insertion in the cases of all three metals, Cu, Ag and Au. The regiochemistry of these processes, leading to the formation of M–C bonds, is rationalized computationally, and is consistent with addition of CO2 across the M–Al covalent bond with the group 11 metal acting as the nucleophilic partner and Al as the electrophile. While the products of carbodiimide insertion are stable to further reaction, their CO2 analogues have the potential to react further, depending on the identity of the group 11 metal. (tBu3P)Au(CO)2Al(NON) is inert to further reaction, but its silver counterpart reacts slowly with CO2 to give the corresponding carbonate complex (and CO), and the copper system proceeds rapidly to the carbonate even at low temperatures. Experimental and quantum chemical investigations of the mechanism of the CO2 to CO/carbonate transformation are consistent with rate-determining extrusion of CO from the initially-formed M(CO)2Al fragment to give a bimetallic oxide that rapidly assimilates a second molecule of CO2. The calculated energetic barriers for the most feasible CO extrusion step (ΔG‡ = 26.6, 33.1, 44.5 kcal mol−1 for M = Cu, Ag and Au, respectively) are consistent not only with the observed experimental labilities of the respective M(CO)2Al motifs, but also with the opposing trends in M–C (increasing) and M–O bond strengths (decreasing) on transitioning from Cu to Au
Self-worth and bonding emotions are related to well-being in health-care providers: a cross-sectional study
No full textBackground: Interacting with patients can elicit a myriad of emotions in health-care providers. This may result in satisfaction or put providers at risk for stress-related conditions such as burnout. The present study attempted to identify emotions that promote provider well-being. Following eudaimonic models of well-being, we tested whether certain types of emotions that reflect fulfilment of basic needs (self-worth, bonding with patients) rather than positive emotions in general (as suggested by hedonic models) are linked to well-being. Specifically, we hypothesized that well-being is associated with positive emotions directed at the self, which reflect self-worth, and positive as well as negative emotions (e.g., worry) directed at the patient, which reflect bonding. However, we expected positive emotions directed at an object/situation (e.g., curiosity for a treatment) to be unrelated to well-being, because they do not reflect fulfilment of basic needs.
Methods: 58 physicians, nurses, and psychotherapists participated in the study. First, in qualitative interviews, they reported their emotions directed at the self, the patient, or an object/situation during distressing interactions with patients. These emotions were categorised into positive emotions directed towards the self, the patient, and an object/situation, and negative emotions directed towards the patient that reflect bonding. Second, providers completed questionnaires to assess their hedonic and eudaimonic well-being. The well-being scores of providers who did and did not experience these emotions were compared.
Results: Providers who experienced positive emotions directed towards the self or the patient had higher well-being than those who did not. Moreover, for the first time, we found evidence for higher well-being in providers reporting negative patient-directed emotions during distressing interactions. There was no difference between providers who did and did not experience positive object/situation-directed emotions.
Conclusions: These findings may point towards the importance of “eudaimonic” emotions rather than just positive emotions in interactions with patients. Emotions such as contentment with oneself, joy for the patient’s improvement, and, notably, grief or worry for the patient may build a sense of self-worth and strengthen bonding with the patient. This may explain their association with provider well-being