A feasibility randomised controlled trial of a motivational interviewing-based intervention for weight loss maintenance in adults

Background Obesity has significant health and NHS cost implications. Relatively small reductions in weight have clinically important benefits, but long-term weight loss maintenance (WLM) is challenging. Behaviour change interventions have been identified as key for WLM. Motivation is crucial to supporting behaviour change, and motivational interviewing (MI) has been identified as a successful approach to changing health behaviours. The study was designed as an adequately powered, pragmatic randomised controlled trial (RCT); however, owing to recruitment issues, the study became a feasibility trial. Objectives To assess recruitment, retention, feasibility, acceptability, compliance and delivery of a 12-month intervention to support WLM. Secondary objectives were to assess the impact of the intervention on body mass index (BMI) and other secondary outcomes. Design Three-arm individually randomised controlled trial comprising an intensive arm, a less intensive arm and a control arm. Setting Community setting in South Wales and the East Midlands. Participants Individuals aged 18�70 years with a current or previous BMI of ??30 kg/m2 who could provide evidence of at least 5% weight loss during the previous 12 months. Intervention Participants received individually tailored MI, which included planning and self-monitoring. The intensive arm received six face-to-face sessions followed by nine telephone sessions. The less intensive arm received two face-to-face sessions followed by two telephone sessions. The control arm received a leaflet advising them on healthy lifestyle. Main outcome measures Feasibility outcomes included numbers recruited, retention and adherence. The primary effectiveness outcome was BMI at 12 months post randomisation. Secondary outcomes included waist circumference, waist-to-hip ratio, physical activity, proportion maintaining weight loss, diet, quality of life, health service resource usage, binge eating and well-being. A process evaluation assessed intervention delivery, adherence, and participants� and practitioners� views. Economic analysis aimed to assess cost-effectiveness in terms of quality-adjusted life-years (QALYs). Results A total of 170 participants were randomised. Retention was good (84%) and adherence was excellent (intensive, 83%; less intensive, 91%). The between-group difference in mean BMI indicated the intensive arm had BMIs 1.0?kg/m2 lower than the controls [95% confidence interval (CI) �2.2 kg/m2 to 0.2?kg/m2]. Similarly, a potential difference was found in weight (average difference of 2.8?kg, 95% CI �6.1 kg to 0.5?kg). The intensive arm had odds of maintaining on average 43% [odds ratio(OR) 1.4, 95% CI 0.6 to 3.5] higher than controls. None of these findings were statistically significant. Further analyses controlling for level of adherence indicated that average BMI was 1.2?kg/m2 lower in the intensive arm than the control arm (95% CI �2.5?kg/m2 to 0.0?kg/m2). The intensive intervention led to a statistically significant difference in weight (mean �3.7?kg, 95% CI �7.1?kg to �0.3?kg). The other secondary outcomes showed limited evidence of differences between groups. The intervention was delivered as planned, and both practitioners and participants were positive about the intervention and its impact. Although not powered to assess cost-effectiveness, results of this feasibility study suggest that neither intervention as currently delivered is likely to be cost-effective in routine practice. Conclusion This is the first trial of an intervention for WLM in the UK, the intervention is feasible and acceptable, and retention and adherence were high. The main effectiveness outcome showed a promising mean difference in the intensive arm. Owing to the small sample size, we are limited in the conclusions we can draw. However, findings suggest that the intensive intervention may facilitate long-term weight maintenance and, therefore, further testing in an effectiveness trial may be indicated. Research examining WLM is in its infancy, further research is needed to develop our understanding of WLM and to expand theory to inform the development of interventions to be tested in rigorously designed RCTs with cost-effectiveness assessed

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Comparison of pulsed-field gel electrophoresis and randomly amplified DNA polymorphism analysis for typing extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae

The incidence and transmission patterns of extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella pneumoniae in patients admitted to the intensive care unit (ICU) of a university hospital were investigated over a 3-year period. K. pneumoniae isolates were characterized by antibiotic susceptibility, capsular serotyping, plasmid profiles, and pulsed-field gel electrophoresis (PFGE) of genome macrorestriction patterns with XbaI, and the results were compared with those obtained by typing with the randomly amplified polymorphic DNA (RAPD) patterns. The discriminatory power of RAPD typing was evaluated for three primers. The incidence of isolation of ESBL-producing K. pneumoniae was 2.5 cases per 1,000 admissions to the ICU versus 0.35 cases per 1,000 admissions to other units (relative risk, 7.03; 95% confidence interval, 3.89 to 12.69). Infection developed in 53% of evaluable patients. Thirty-six percent of the cases were possibly acquired in other institutions. Isolates from ICU patients were subdivided into six capsular serotypes and into four clonal groups based on antibiotype, plasmid content, and PFGE and RAPD patterns. Two clones were associated with clusters of cross-infection, involving 5 and 12 patients, respectively. Following implementation of contact isolation precautions, the incidence of nosocomial acquisition of ESBL-producing K. pneumoniae decreased from 0.55 to 0.26 cases per 1,000 admissions (P = 0.03). PFGE and RAPD analysis showed concordant results and comparable discrimination for differentiation between groups of epidemiologically related strains of ESBL-producing K. pneumoniae. More subclonal variants were determined among epidemic clones by PFGE analysis than by RAPD analysis. Both methods are useful for typing K. pneumoniae strains in epidemiological investigations, although RAPD analysis is more efficient

Post-mortem Characterisation of a Case With an ACTG1 Variant, Agenesis of the Corpus Callosum and Neuronal Heterotopia

Cytoplasmic Actin Gamma 1 (ACTG1) gene variant are autosomal dominant and can cause CNS anomalies (Baraitser Winter Malformation Syndrome; BWMS). ACTG1 anomalies in offspring include agenesis of the corpus callosum (ACC) and neuronal heterotopia which are ectopic nodules of nerve cells that failed to migrate appropriately. Subcortical and periventricular neuronal heterotopia have been described previously in association with ACC. In this case report, we investigated a neonatal brain with an ACTG1 gene variant and a phenotype of ACC, and neuronal heterotopia (ACC-H) which was diagnosed on antenatal MR imaging and was consistent with band heterotopia seen on post-mortem brain images. Histologically clusters of neurons were seen in both the subcortical and periventricular white matter (PVWM) brain region that coincided with impaired abnormalities in glial formation. Immunohistochemistry was performed on paraffin-embedded brain tissue blocks from this case with ACTG1 variant and an age-matched control. Using tissue sections from the frontal lobe, we examined the distribution of neuronal cells (HuC/HuD, calretinin, and parvalbumin), growth cone (drebrin), and synaptic proteins (synaptophysin and SNAP-25). Additionally, we investigated how the ACTG1 variant altered astroglia (nestin, GFAP, vimentin); oligodendroglia (OLIG2) and microglia (Iba-1) in the corpus callosum, cortex, caudal ganglionic eminence, and PVWM. As predicted in the ACTG1 variant case, we found a lack of midline radial glia and glutamatergic fibers. We also found disturbances in the cortical region, in glial cells and a lack of extracellular matrix components in the ACTG1 variant. The caudal ganglionic eminence and the PVWM regions in the ACTG1 variant lacked several cellular components that were identified in a control case. Within the neuronal heterotopia, we found evidence of glutamatergic and GABAergic neurons with apparent synaptic connections. The data presented from this case study with BWMS with variants in the ACTG1 gene provides insight as to the composition of neuronal heterotopia, and how disturbances of important migratory signals may dramatically affect ongoing brain development

Time-dependent visibility modelling of a relativistic jet in the X-ray binary MAXI J1803-298

Tracking the motions of transient jets launched by low-mass X-ray binaries (LMXBs) is critical for determining the moment of jet ejection, and identifying any corresponding signatures in the accretion flow. However, these jets are often highly variable and can travel across the resolution element of an image within a single observation, violating a fundamental assumption of aperture synthesis. We present a novel approach in which we directly fit a single time-dependent model to the full set of interferometer visibilities, where we explicitly parameterise the motion and flux density variability of the emission components, to minimise the number of free parameters in the fit, while leveraging information from the full observation. This technique allows us to detect and characterize faint, fast-moving sources, for which the standard time binning technique is inadequate. We validate our technique with synthetic observations, before applying it to three Very Long Baseline Array (VLBA) observations of the black hole candidate LMXB MAXI J1803-298 during its 2021 outburst. We measured the proper motion of a discrete jet component to be $1.37\pm0.14$ mas/hr, and thus we infer an ejection date of MJD $59348.08_{-0.06}^{+0.05}$, which occurs just after the peak of a radio flare observed by the Australia Telescope Compact Array (ATCA) and the Atacama Large Millimeter/Sub-Millimeter Array (ALMA), while MAXI J1803-298 was in the intermediate state. Further development of these new VLBI analysis techniques will lead to more precise measurements of jet ejection dates, which, combined with dense, simultaneous multi-wavelength monitoring, will allow for clearer identification of jet ejection signatures in the accretion flow.Comment: 15 pages, 9 figures, 4 tables; Accepted for publication in MNRA

Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals’ views and experiences

Copyright \ua9 2024 Peter, Mellis, McInnes-Dean, Daniel, Walton, Fisher, Leeson-Beevers, Allen, Baple, Beleza-Meireles, Bertoli, Campbell, Canham, Cilliers, Cobben, Eason, Harrison, Holder-Espinasse, Male, Mansour, McEwan, Park, Smith, Stewart, Tapon, Vasudevan, Williams, Wu, Chitty and Hill.Introduction: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS. Methods: A survey (n = 159) and semi-structured interviews (n = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future. Results: Overall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions. Conclusion: Healthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals

‘Something that helped the whole picture’: Experiences of parents offered rapid prenatal exome sequencing in routine clinical care in the English National Health Service

Objectives: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery. Methods: In this qualitative study, semi-structured interviews were conducted with 42 women and 6 male partners and 63 fetal medicine and genetic health professionals. Interviews were transcribed verbatim and analysed using thematic analysis. Results: Overall views about pES were positive and parents were grateful to be offered the test. Highlighted benefits of pES included the value of the additional information for pregnancy management and planning for future pregnancies. An anxious wait for results was common, often associated with the need to make decisions near to 24 weeks in pregnancy when there are legal restrictions for late termination. Descriptions of dealing with uncertainty were also common, even when results had been returned. Many parents described pES results as informing decision-making around whether or not to terminate pregnancy. Some professionals were concerned that a non-informative result could be overly reassuring and highlighted that careful counselling was needed to ensure parents have a good understanding of what the result means for their pregnancy. Emotional support from professionals was valued; however, some parents felt that post-test support was lacking. Conclusion: Parents and professionals welcomed the introduction of pES. Results inform parents' decision-making around the termination of pregnancy. When there are no diagnostic findings or uncertain findings from pES, personalised counselling that considers scans and other tests are crucial. Directing parents to reliable online sources of information and providing emotional support throughout could improve their experiences of care

Atmospheric deposition as a source of heavy metals in urban stormwater

Atmospheric deposition is one of the most important pathways of urban stormwater pollution. Atmospheric deposition which can be in the form of either wet or dry deposition have distinct characteristics in terms of associated particulate sizes, pollutant types and influential parameters. This paper discusses the outcomes of a comprehensive research study undertaken to identify important traffic characteristics and climate factors such as antecedent dry period and rainfall characteristics which influences the characteristics of wet and dry deposition of solids and heavy metals. The outcomes confirmed that Zinc (Zn) is correlated with traffic volume whereas Lead (Pb), Cadmium (Cd), Nickel (Ni), and Copper (Cu) are correlated with traffic congestion. Consequently, reducing traffic congestion will be more effective than reducing traffic volume for improving air quality particularly in relation to Pb, Cd, Ni, and Cu. Zn was found to have the highest atmospheric deposition rate compared to other heavy metals. Zn in dry deposition is associated with relatively larger particle size fractions (>10 µm), whereas Pb, Cd, Ni and Cu are associated with relatively smaller particle size fractions (<10 µm). The analysis further revealed that bulk (wet plus dry) deposition which is correlated with rainfall depth and contains a relatively higher percentage of smaller particles compared to dry deposition which is correlated with the antecedent dry period. As particles subjected to wet deposition are smaller, they disperse over a larger area from the source of origin compared to particles subjected to dry deposition as buoyancy forces become dominant for smaller particles compared to the influence of gravity. Furthermore, exhaust emission particles were found to be primarily associated with bulk deposition compared to dry deposition particles which mainly originate from vehicle component wear

Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial

Background Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and response to olaparib in metastatic castration-resistant prostate cancer. Methods In this open-label, investigator-initiated, randomised phase 2 trial following a selection (or pick-the-winner) design, we recruited participants from 17 UK hospitals. Men aged 18 years or older with progressing metastatic castration-resistant prostate cancer previously treated with one or two taxane chemotherapy regimens and with an Eastern Cooperative Oncology Group performance status of 2 or less had tumour biopsies tested with targeted sequencing. Patients with DDR gene aberrations were randomly assigned (1:1) by a computer-generated minimisation method, with balancing for circulating tumour cell count at screening, to receive 400 mg or 300 mg olaparib twice daily, given continuously in 4-week cycles until disease progression or unacceptable toxicity. Neither participants nor investigators were masked to dose allocation. The primary endpoint of confirmed response was defined as a composite of all patients presenting with any of the following outcomes: radiological objective response (as assessed by Response Evaluation Criteria in Solid Tumors 1.1), a decrease in prostate-specific antigen (PSA) of 50% or more (PSA50) from baseline, or conversion of circulating tumour cell count (from ≥5 cells per 7·5 mL blood at baseline to <5 cells per 7·5 mL blood). A confirmed response in a consecutive assessment after at least 4 weeks was required for each component. The primary analysis was done in the evaluable population. If at least 19 (43%) of 44 evaluable patients in a dose cohort responded, then the dose cohort would be considered successful. Safety was assessed in all patients who received at least one dose of olaparib. This trial is registered at ClinicalTrials.gov, NCT01682772. Recruitment for the trial has completed and follow-up is ongoing. Findings 711 patients consented for targeted screening between April 1, 2015, and Aug 30, 2018. 161 patients had DDR gene aberrations, 98 of whom were randomly assigned and treated (49 patients for each olaparib dose), with 92 evaluable for the primary endpoint (46 patients for each olaparib dose). Median follow-up was 24·8 months (IQR 16·7–35·9). Confirmed composite response was achieved in 25 (54·3%; 95% CI 39·0–69·1) of 46 evaluable patients in the 400 mg cohort, and 18 (39·1%; 25·1–54·6) of 46 evaluable patients in the 300 mg cohort. Radiological response was achieved in eight (24·2%; 11·1–42·3) of 33 evaluable patients in the 400 mg cohort and six (16·2%; 6·2–32·0) of 37 in the 300 mg cohort; PSA50 response was achieved in 17 (37·0%; 23·2–52·5) of 46 and 13 (30·2%; 17·2–46·1) of 43; and circulating tumour cell count conversion was achieved in 15 (53·6%; 33·9–72·5) of 28 and 13 (48·1%; 28·7–68·1) of 27. The most common grade 3–4 adverse event in both cohorts was anaemia (15 [31%] of 49 patients in the 300 mg cohort and 18 [37%] of 49 in the 400 mg cohort). 19 serious adverse reactions were reported in 13 patients. One death possibly related to treatment (myocardial infarction) occurred after 11 days of treatment in the 300 mg cohort. Interpretation Olaparib has antitumour activity against metastatic castration-resistant prostate cancer with DDR gene aberrations, supporting the implementation of genomic stratification of metastatic castration-resistant prostate cancer in clinical practice