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Abstract Background Evidence suggests that coordination of care for people affected by rare diseases is poor. In order to improve the way that care is coordinated it is necessary to understand the preferences of people affected by these conditions, and providers. The aim of this study was to examine patient, parent and carer, and health care professional preferences for different attributes of care coordination for people affected by rare diseases. We conducted a discrete choice experiment using online surveys. There were no restrictions on participants in terms of rare conditions, demographic factors other than age, or geographical location within the UK. Choice scenarios were based on the following attributes: annual cost of attending appointments; access to health records; access to clinical expertise; support of a care coordinator; access to a specialist centre; and, the existence of a documented plan for emergency care. Data were analysed using alternative-specific conditional logit regression models. Results Valid responses were obtained from 996 individuals (528 patients, 280 carers, 188 health care professionals) between August and December 2019. All attributes significantly influenced the type of service respondents preferred. Patients, carers and health professionals’ preferences for care coordination were influenced by: the cost of attending appointments; access to health records; clinical expertise; role of care coordinators; access to specialist centres; and the existence of plan for emergency care. There were no statistically significant differences in the preferences between patients and carers. Preferences of health professionals differed to those of patients and carers. Both patients and carers selected responses which granted them a greater degree of autonomy in relation to the role of care coordinators, whereas health professionals preferred services where care coordinators had more autonomy. Health care professionals also expressed a stronger preference for a documented formal emergency plan to be in place. Conclusions The findings highlight that people value better coordinated care, in line with policy documents emphasising commitments to coordinated care for people affected by rare diseases. This study highlights the factors that could be included in service provision as ways of improving the coordination of care for people affected by rare diseases.

Abstract Background Relapsed or refractory follicular lymphoma (rrFL) is an incurable disease associated with shorter remissions and survival after each line of standard therapy. Many promising novel, chemotherapy-free therapies are in development, but few are licensed as their role in current treatment pathways is poorly defined. Methods The REFRACT trial is an investigator-initiated, UK National Cancer Research Institute, open-label, multi-centre, randomised phase II platform trial aimed at accelerating clinical development of novel therapies by addressing evidence gaps. The first of the three sequential novel therapy arms is epcoritamab plus lenalidomide, to be compared with investigator choice standard therapy (ICT). Patients aged 18 years or older with biopsy proven relapsed or refractory CD20 positive, grade 1-3a follicular lymphoma and assessable disease by PET-CT are eligible. The primary outcome is complete metabolic response by PET-CT at 24 weeks using the Deauville 5-point scale and Lugano 2014 criteria. Secondary outcomes include overall metabolic response, progression-free survival, overall survival, duration of response, and quality of life assessed by EQ-5D-5 L and FACT-Lym. The trial employs an innovative Bayesian design with a target sample size of 284 patients: 95 in the ICT arm and 189 in the novel therapy arms. Discussion Whilst there are many promising novel drugs in early clinical development for rrFL, understanding the relative efficacy and safety of these agents, and their place in modern treatment pathways, is limited by a lack of randomised trials and dearth of published outcomes for standard regimens to act as historic controls. Therefore, the aim of REFRACT is to provide an efficient platform to evaluate novel agents against standard therapies for rrFL. The adaptive Bayesian power prior methodology design will minimise patient numbers and accelerate trial delivery. Trial registration ClinicalTrials.gov: NCT05848765; 08-May-2023. EudraCT 2022-000677-75; 10-Feb-2022.

As in-feed antibiotics are phased out of swine production, producers are seeking alternatives to facilitate improvements in growth typically seen from this previously common feed additive. Kazachstania slooffiae is a prominent commensal fungus in the swine gut that peaks in relative abundance shortly after weaning and has beneficial interactions with other bacteriome members important for piglet health. In this study, piglets were supplemented with K. slooffiae to characterize responses in piglet health as well as fungal and bacterial components of the microbiome both spatially (along the entire gastrointestinal tract and feces) and temporally (before, during, and after weaning). Litters were assigned to one of four treatments: no K. slooffiae (CONT); one dose of K. slooffiae 7 days before weaning (day 14; PRE); one dose of K. slooffiae at weaning (day 21; POST); or one dose of K. slooffiae 7 days before weaning and one dose at weaning (PREPOST). The bacteriome and mycobiome were analyzed from fecal samples collected from all piglets at day 14, day 21, and day 49, and from organ samples along the gastrointestinal (GI) tract at day 21 and day 49. Blood samples were taken at day 14 and day 49 for cytokine analysis, and fecal samples were assayed for antimicrobial resistance. While some regional shifts were seen in response to K. slooffiae administration in the mycobiome of the GI tract, no remarkable changes in weight gain or health of the animals were observed, and changes were more likely due to sow and the environment. Ultimately, the combined microbiome changed most considerably following the transition from suckling to nursery diets. This work describes the mycobiome along the piglet GI tract through the weaning transition for the first time. Based on these findings, K. slooffiae administered at this concentration may not be an effective tool to hasten colonization of K. slooffiae in the piglet GI tract around the weaning transition nor support piglet growth, microbial gut health, or immunity. However, diet and environment greatly influence microbial community development.

Background: We describe acoustic patterns across the five most prominent vocal types in typically developing infants (TD) and compare them with patterns in infants who develop autism (ASD) or a developmental disability (DD) not related to autism. Infant-directed speech (IDS) is a potentially important influence on such vocal acoustic patterns. Both acoustic patterns and effects of IDS are important for understanding the earliest origins of communication disorders., Aims: To compare duration, pitch and loudness of infant vocalizations for three groups of infants (TD, ASD, DD) in circumstances with high or low amounts of IDS., Methods and Procedures: Two five-minute segments from each of 1259 all-day recordings across the first year were coded and acoustically analyzed for three groups of infants (130 TD, 44 ASD, 21 DD). Duration, mean fundamental frequency, and root mean square amplitude were determined for >162,000 infant utterances., Outcomes and Results: Cries were longest and loudest, and vowel-like sounds were shortest of the five vocal types in all groups. TD infants showed significant alterations in vocal acoustics during periods of high IDS., Conclusions and Implications: Strong similarities in acoustic patterns occurred across the three groups, but only the TD group showed significant acoustic effects of IDS., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Colorectal cancer rates are increasing in older populations, who often have comorbidities and face higher surgical risks and mortality rates. Therefore, surgical outcomes, such as 5-year mortality rates, may not be appropriate, necessitating a focus on postoperative quality of life. However, determining optimal postoperative outcome measures for older colorectal cancer patients poses a challenge. This scoping review aimed to explore currently available data describing postoperative outcomes used to assess older patients undergoing elective colorectal cancer surgery., Method: We conducted a comprehensive literature search of major electronic databases from inception to March 2023. Studies exploring frail or older individuals with colorectal cancer undergoing elective surgical procedures, and which reported postoperative outcomes, were included. Outcomes were categorized as surgery-specific versus person-centred and summarized using narrative synthesis. The type and rate of surgery-specific outcomes were tabulated., Results: Of 1366 identified citations, 16 studies focused on person-centred outcomes and 66 reported exclusively on surgery-specific outcomes. Nine 'person-centred outcome' studies reported discharge destination, primarily home discharge. Postoperative delirium ranged from 8.2% to 18.1% in six studies. Four studies explored geriatric syndromes, three analysed activities of daily living, and three studies reported significant quality of life improvement. The 66 'surgery-specific outcome' studies assessed mortality (N = 61); length of stay (N = 40); postoperative complications (N = 47); readmission (N = 18); reoperation (N = 16); and survival (N = 42)., Conclusion: Person-centred outcomes are underreported, but crucial for guiding patient management. Older patients require adequate information about their postoperative recovery period to enhance wellbeing. Future research must address this gap to improve care for older people undergoing elective colorectal cancer surgery., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objective: Understanding of how oscillometric waveforms (OMW) vary between pregnant and nonpregnant individuals remains low. An exploratory analysis was completed to assess for quantitative and qualitative changes in OMW and oscillometric envelope features in pregnancy., Design and Methods: Eighteen pregnant individuals (over 20 weeks gestational age) and healthy, nonpregnant (HNP) women were recruited. Six HNP were matched to six healthy pregnant (HP) women, and six pregnant women with a hypertensive disorder of pregnancy (HDP) by age, arm circumference, and cuff size. Blood pressure measurements were completed per the International Organization for Standardization (ISO) protocol using a custom-built oscillometric device as the test device and two-observer mercury auscultation as the reference measurement. Auscultatory blood pressure and blood pressure derived from slope-based and fixed ratio algorithms were determined. OMW and envelope features were compared among groups., Results: In HNP, HP, and HDP groups respectively: mean auscultatory blood pressure (systolic mean ± SD/diastolic mean ± SD) was 103.4 ± 12.2/67.1 ± 7.9; 109.5 ± 3.1/58.1 ± 6.4; 135.6 ± 18.9/85.1 ± 14.2 mmHg. HDP had significantly higher auscultatory systolic and diastolic blood pressure than the HP group ( P  = 0.001). The pregnant groups had a lower average pulse width (mean ± SD: HNP = 0.8 ± 0 s, HP = 0.6 ± 0.1 s, HDP = 0.6 ± 0.1 s; HP vs. HNP mean difference [adjusted P value]: 0.2 [ P  = 0.004], HDP vs. HNP 0.1 [ P  = 0.018]) compared with the HNP group. The HDP group had a larger area under the OMW envelope than the HNP group (mean ± SD: HNP = 22.6 ± 3.4; HDP = 28.5 ± 4.2; HDP vs. HNP mean difference [adjusted P value]: 5.9 P  = 0.05)., Conclusion: In this exploratory work, differences in the OMW morphology and parameters were found in pregnancy and in hypertensive disorders of pregnancy compared with healthy controls. Even small differences may have important implications in algorithm development; further work comparing OMW envelopes in pregnancy is needed to optimize the algorithms used to determine blood pressure in pregnancy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Non-random exploration of infant speech-like vocalizations (e.g., squeals, growls, and vowel-like sounds or "vocants") is pivotal in speech development. This type of vocal exploration, often noticed when infants produce particular vocal types in clusters, serves two crucial purposes: it establishes a foundation for speech because speech requires formation of new vocal categories, and it serves as a basis for vocal signaling of wellness and interaction with caregivers. Despite the significance of clustering, existing research has largely relied on subjective descriptions and anecdotal observations regarding early vocal category formation. In this study, we aim to address this gap by presenting the first large-scale empirical evidence of vocal category exploration and clustering throughout the first year of life. We observed infant vocalizations longitudinally using all-day home recordings from 130 typically developing infants across the entire first year of life. To identify clustering patterns, we conducted Fisher's exact tests to compare the occurrence of squeals versus vocants, as well as growls versus vocants. We found that across the first year, infants demonstrated clear clustering patterns of squeals and growls, indicating that these categories were not randomly produced, but rather, it seemed, infants actively engaged in practice of these specific categories. The findings lend support to the concept of infants as manifesting active vocal exploration and category formation, a key foundation for vocal language., Competing Interests: D. K. Oller is an unpaid member of the LENA Scientific advisory board. However, this does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Yoo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction Distractions in operating theatres prevent team members from concentrating on the complex tasks required for a successful operation. This can be a potential hazard to care for, and previously, correlations have been made between increased theatre distractions and adverse events. However, it remains unclear how frequently such events occur during routine care in theatres. The present study aims to quantify distractions and analyse any differences between staff groups, operative stages, and modes of operation. Methods A single-centre prospective study was conducted to assess disruptions in general surgical theatres. Events were recorded using a previously described categorization system on a proforma by a single researcher. The source and severity of distraction were recorded, as well as the mode of operation (elective/emergency), stage of operation, and staff team (scrubbed/floor). Results A total of 4,219 minutes of surgery were observed over four weeks, and 1,095 distraction events were recorded. Of the 14 elective and nine emergency procedures recorded, there was a mean of 54.8 distractions per procedure and a frequency of one distraction every three minutes and 51 seconds (15.6 hr -1 ). Irrelevant communication relating to the patient's case was the most common source, accounting for 24.7% of all distractions. The most frequently disrupted stage of the procedure for scrubbed staff was during anastomosis/resection for both elective and emergency procedures, with 16.9 and 32.6 distractions occurring per hour, respectively. Scrubbed staff were significantly more susceptible to distraction in emergency procedures than the floor staff. Discussion Our study reflects previous assessments with irrelevant communications and emergency procedures yielding the highest prevalence of distraction. This investigation provides novel information about the different stages of general surgery and the frequency of distractions that occur., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Raftery et al.)

Background: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts., Result: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8 + cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles., Conclusion: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract., (© 2024. The Author(s).)

Aim: Temporary stoma formation remains a common part of modern-day colorectal surgical operations. At the time of reversal, a second procedure is required when the bowel is anastomosed and the musculature is closed. The rate of incisional hernia at these sites is 30%-35% with conventional suture closure. Mesh placement at this site is therefore an attractive option to reduce hernia risk, particularly as new mesh types, such as biosynthetic meshes, are available. The aim of this work was to conduct a systematic review and meta-analysis assessing the use of mesh for prophylaxis of incisional hernia at stoma closure and to explore the outcome measures used by each of the included studies to establish whether they are genuinely patient-centred., Method: This is a systematic review and meta-analysis assessing the published literature regarding the use of mesh at stoma site closure operations. Comprehensive literature searches of major electronic databases were performed by an information specialist. Screening of search results was undertaken using standard systematic review principles. Data from selected studies were input into an Excel file. Meta-analysis of the results of included studies was conducted using RevMan software (v.5.4). Randomized controlled trial (RCT) and non-RCT data were analysed separately., Results: Eleven studies with a total of 2008 patients were selected for inclusion, with various mesh types used. Of the included studies, one was a RCT, seven were nonrandomized comparative studies and three were case series. The meta-analysis of nonrandomized studies shows that the rate of incisional hernia was lower in the mesh reinforcement group compared with the suture closure group (OR 0.21, 95% CI 0.12-0.37) while rates of infection and haematoma/seroma were similar between groups (OR 0.7, 95% CI 0.41-1.21 and OR 1.05, 95% CI 0.63-1.80, respectively). The results of the RCT were in line with those of the nonrandomized studies., Conclusion: Current evidence indicates that mesh is safe and reduces incisional hernia. However, this is not commonly adopted into current clinical practice and the literature has minimal patient-reported outcome measures. Future work should explore the reasons for such slow adoption as well as the preferences of patients in terms of outcome measures that matter most to them., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

The present study compared the infant's tendency in the first year of life to produce clusters of particular vocal types (squeals, vocants, and growls) in typically developing (TD) and autistic infants. Vocal clustering provides evidence of vocal category formation and may establish a foundation for speech development. Specifically, we compared the extent of vocal clustering across outcome groups and age groups. We also examined the associations between the extent of vocal clustering and later outcomes at 2 years within the autistic group. Randomly selected 5-min segments (27,153 5-min segments total) from 1293 all-day home recordings from 103 TD infants and 44 autistic infants across the first year were humancoded (about 9.75 h of data coded per infant on average) to derive vocal clustering patterns. Fisher's exact tests were used to compare the occurrence of squeals versus vocants, as well as growls versus vocants, across coded segments. Infants in both groups demonstrated clear clustering patterns of squeals and growls across all age groups. The extent of vocal clustering in the autistic group did not correlate significantly with later language, repetitive behavior, or autism severity outcomes. These findings highlight the robustness of the systematic production of vocal categories across the first year of life. The similarity of the clustering patterns in the TD and autistic groups suggests that vocal category formation through active infant vocal exploration is a robust feature of early speech development., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)