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Parenteral and enteral nutrition support are key components of care for various medical and physiological conditions in infants, children, and adults. Nutrition support practices have advanced over time, driven by the goals of safe and sufficient delivery of needed nutrients and improved patient outcomes. These advances have been, and continue to be, dependent on research and development studies. Such studies address aspects of enteral and parenteral nutrition support: formulations, delivery devices, health outcomes, cost‐effectiveness, and related metabolism. The studies are supported by public funding from the government and by private funding from foundations and from the nutrition support industry. To build public trust in nutrition support research findings, it is important to underscore ethical research conduct and reporting of results for all studies, including those with industry sponsors. In 2019, American Society for Parenteral and Enteral Nutrition's (ASPEN's) Board of Directors established a task force to ensure integrity in nutrition support research that is done as collaborative partnerships between the public (government and individuals) and private groups (foundations, academia, and industry). In this ASPEN Position Paper, the Task Force presents principles of ethical research to guide administrators, researchers, and funders. The Task Force identifies ways to curtail bias and to minimize actual or perceived conflict of interests, as related to funding sources and research conduct. Notably, this paper includes a Position Statement to describe the Task Force's guidance on Public‐Private Partnerships for research and funding. This paper has been approved by the ASPEN Board of Directors. [ABSTRACT FROM AUTHOR]

Nurse‐led clinics are known to positively impact and benefit patients; however, there is little understanding of the role of the nurse in a nurse‐led male Lower Urinary Tract Symptoms (LUTS) clinic. LUTS affect up to 30% of males over 65 in the United Kingdom and can significantly impact the quality of life of the person experiencing them. LUTS can be managed with conservative changes, as well as with medication and surgical intervention. The aim of this scoping review is to map what is known about the role of the nurse in a nurse‐led male LUTS clinic and what research tells us regarding, the barriers and enablers in nurses leading a male LUTS clinic. This scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐SCR) checklist and the methodological guidelines set out by the Joanna Briggs institute. A literature search was carried out over three databases (CINAHL, Medline Ovid, ProQuest health and medical collection) and systematically searched from 2000 to 2021. Grey literature was also searched, and citation chaining was undertaken. Following a systematic review of the literature, four papers met the inclusion criteria for this scoping review. The emergent themes across the four papers consisted of structure, assessment and resources, and effectiveness of the nurse‐led male LUTS clinic. There was clear agreement across the literature regarding the investigations and assessment the nurse should carry out. Ongoing practical, theoretical, and observational training and education is required to ensure the nurse is competent in running a male LUTS clinic. The papers reviewed showed the nurse provided a supportive role to the consultant. However, there is evidence indicating there is a move towards autonomous practice. There is a dearth of the current research relating to the role of the nurse in nurse‐led male LUTS clinics and the enablers and barriers in nurses leading male LUTS clinics. Further research should be considered to gain a better understanding of where nurse‐led male LUTS clinics currently take place, what the role of the nurse is in leading a LUTS clinic and what enablers and barriers exist. [ABSTRACT FROM AUTHOR]

Background: Robotic surgery has gained widespread acceptance in elective interventions, yet its role in emergency procedures remains underexplored. While the 2021 WSES position paper discussed limited studies on the application of robotics in emergency general surgery, it recommended strict patient selection, adequate training, and improved platform accessibility. This prospective study aims to define the role of robotic surgery in emergency settings, evaluating intraoperative and postoperative outcomes and assessing its feasibility and safety. Methods: The ROEM study is an observational, prospective, multicentre, international analysis of clinically stable adult patients undergoing robotic surgery for emergency treatment of acute pathologies including diverticulitis, cholecystitis, and obstructed hernias. Data collection includes patient demographics and intervention details. Furthermore, data relating to the operating theatre team and the surgical instruments used will be collected in order to conduct a cost analysis. The study plans to enrol at least 500 patients from 50 participating centres, with each centre having a local lead and collaborators. All data will be collected and stored online through a secure server running the Research Electronic Data Capture (REDCap) web application. Ethical considerations and data governance will be paramount, requiring local ethical committee approvals from participating centres. Discussion: Current literature and expert consensus suggest the feasibility of robotic surgery in emergencies with proper support. However, challenges include staff training, scheduling conflicts with elective surgeries, and increased costs. The ROEM study seeks to contribute valuable data on the safety, feasibility, and cost-effectiveness of robotic surgery in emergency settings, focusing on specific pathologies. Previous studies on cholecystitis, abdominal hernias, and diverticulitis provide insights into the benefits and challenges of robotic approaches. It is necessary to identify patient populations that benefit most from robotic emergency surgery to optimize outcomes and justify costs. [ABSTRACT FROM AUTHOR]

Background: Early language delay is exacerbated by social disadvantage. Factors such as parents' low levels of literacy, confidence and self‐perception can affect the capacity to act on advice received, critical to empowerment. Methods used to achieve successful health outcomes in socially disadvantaged clinical populations may need enhancing. Aims: To compare the impact of standard parent‐based intervention (PBI) to enhanced PBI for young children with speech, language and communication needs (SCLN) and their families living in more socially disadvantaged populations. Methods and Procedures: A multicentre clustered blind randomised controlled trial was used to compare the effect of parent‐based group interventions to improve early language development with children (mean age 27.5 months) from more socially disadvantaged populations with an expressive vocabulary of 40 or less single words. Intervention sessions were delivered by a speech and language therapist, over a 20‐week period. Participants received one of two interventions: (1) Standard Care – indirect group PBI – (PBI) (2) Enhanced Care: indirect group enhanced PBI – (EPBI). Both standardised and non‐standardised measures were used as outcomes. Parent engagement in the intervention was captured through analysis of attendance and the Parent Activation Measure – Speech & Language Therapy (PAM‐SLT) (Insignia Health, 2014). The PAM measures a person's knowledge, skills and confidence to manage their own health and well‐being (NHS England, 2018). In this study, activation referred to parents' knowledge, skills and confidence to manage their child's language development. Outcomes and Results: One hundred fifty‐five participants were randomised at baseline. Children in both groups made significant improvements in the outcome on MacArthur‐Bates Communicative Development Inventories Sentence Length, from pre‐intervention to post‐intervention and 6 months post‐intervention (p < 0.05). Changes in vocabulary and expressive language skills were more equivocal, showing wide variation in confidence intervals for both groups. Where parents attended at least one intervention session almost all effect sizes were in favour of the EPBI intervention. Parents' activation levels significantly increased for both groups (EPBI p < 0.001, PBI p = 0.003), with a moderate effect size in favour of EPBI (Hedges' G 0.37, confidence interval –0.02 to 0.76), although wide variation was found. Conclusions and Implications: This trial provides some evidence of facilitating the language development of children with SLCN from more socially disadvantaged areas through supporting caregivers. However, we found variation in outcomes; some children made excellent progress, whilst others did not. Further exploration of parent engagement and its relationship to child language outcomes will be valuable to understanding more about mechanisms of change in interventions that involve parents. WHAT THIS PAPER ADDS: What is already known on the subject: Speech, language and communication needs (SLCN) have a knock‐on effect on emotional well‐being, school readiness, literacy and school attainment, putting children at increased risk of long‐term consequences such as poor literacy, mental health problems and unemployment. In disadvantaged areas, the prevalence of language difficulties is higher than elsewhere. Factors such as parents' low levels of literacy, confidence and self‐perception can affect the capacity to act on advice received, critical to empowerment. What this paper adds to existing knowledge: Children with SLCN from more socially disadvantaged areas can make improvements in their language development through parent intervention, although wide individual variation was found. There was some evidence that children achieve better outcomes with EPBI, which employed an interagency collaborative approach. Parent's engagement (activation levels) increased significantly over time with intervention, with the increase twice as big for EPBI. What are the potential or actual clinical implications of this work?: This trial provides some evidence that it is possible to facilitate the language development of children from more socially disadvantaged areas through supporting their caregivers. Further research would be useful to determine whether increases in parent engagement are related to adherence to intervention and change in child outcomes. [ABSTRACT FROM AUTHOR]

Background: Kidney disease is a progressive, debilitating condition. Patients experience challenging physical and psychological symptoms and are at increased risk of anxiety, depression, and poor mental wellbeing. Access to specialist psychological or social support is limited, with inadequate provision of psychosocial support available across UK renal units. The COSMIC study (examining the acceptability and feasibility of the Compassionate Mindful Resilience programme for adult patients with chronic kidney disease) aimed to support a new service development project, in partnership with Kidney Care UK, by implementing the Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, and explore its feasibility for patients with stage 4 or 5 kidney disease and kidney transplant recipients. This paper reports on the qualitative exploratory work which examined the experiences of study participants, their adherence to practice, and the acceptability of the intervention. Method: Participants (n = 19) took part in semi-structured interviews, which were transcribed, coded, and thematically analysed. Results: Three themes (and nine subthemes) were reported: experiences of the CMR programme that facilitated subjective benefit, participants' lived and shared experiences, and the practicalities of CMR programme participation. All participants reported that they found taking part in the CMR programme to be a beneficial experience. Conclusion: The CMR programme was found to be an acceptable intervention for people living with kidney disease and provided tools and techniques that support the mental health and wellbeing of this patient group. Further qualitative exploration into participant experience should be integrated within future trials of this intervention. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorder is the most prevalent psychiatric disorder. Benzodiazepines, which are often used for anxiety in patients with anxiety disorder, have various side effects. Lavender, one of the most commonly used essential oils in aromatherapy, has the potential to reduce benzodiazepine use for anxiety disorders. Methods: This study is a multicenter, double-masked, randomized, placebo-controlled clinical trial. The study will recruit patients aged 20–59 years old with generalized anxiety disorder and panic disorder among anxiety disorders. The bottle containing the test solution (lavender aroma essential oil or distilled water) will be given to the patients. Patients will carry the bottles with them in their daily life and use the drops on tissue paper when anxious. The primary endpoint is the number of times anxiolytics used in 28 days. Discussion: If the use of benzodiazepines could be reduced by sniffing lavender aroma, which is inexpensive and safe, it would contribute not only to the risks associated with benzodiazepine use but also to the health care economy and could even be added as a standard treatment. Trial registration: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000034422 Registered 17 January 2019. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper is to provide a preliminary evaluation of treatment outcomes, retention and client satisfaction following a 12-week combined cognitive behavioural therapy (CBT) and motivational enhancement therapy (MET) group treatment for cannabis use disorder (CUD) delivered in an outpatient setting. Implementation of the program is also described. Methods: A retrospective observational cohort study was conducted using data collected from medical records and self-report assessments. Participants were treatment-seeking cannabis users at the Centre for Addiction and Mental Health, Toronto. Cannabis use, cannabis-related problems, craving, withdrawal symptoms, self-efficacy for remaining abstinent, depression and anxiety were assessed pre- and post-treatment. Treatment retention was calculated by inspecting clinic attendance records, and client satisfaction was evaluated using an anonymous feedback survey. Potential predictors of treatment outcomes and retention were investigated in exploratory analyses. Results: Cannabis use was lower and days of abstinence higher post-treatment (vs pre-treatment). Post-treatment improvements in cannabis-related problems, craving, withdrawal symptoms, self-efficacy and mood were also observed. Completion of group treatment (⩾75% of sessions attended) was 57% and moderate levels of treatment satisfaction were reported. Conclusions: This study provides preliminary evidence that a 12-week combined CBT and MET treatment for cannabis use disorder delivered in a novel group setting improves cannabis use outcomes. Potential predictors of reduced cannabis use and retention were identified. Future controlled studies are warranted, and strategies for increasing retention should be explored. [ABSTRACT FROM AUTHOR]

Simple Summary: Measurable residual disease monitoring is an important prognostic tool in haematological malignancies commonly performed by two modalities: flow cytometry and molecular methods. In this paper, we studied consecutive adult participants requiring flow cytometric measurable residual disease monitoring. This is one of the largest prospective Australian studies to date, providing a unique insight into the Australian context. We described five distinctive patterns associated with disease relapse and survival and also investigated correlation with molecular methods. Our results provide additional evidence that the correlation between molecular and flow cytometric methods is moderate in B-lymphoblastic leukaemia and poor in acute myeloid leukaemia. There was a strong association between flow cytometry results and relapse in acute myeloid leukaemia but less so for B-lymphoblastic leukaemia. Our novel data indicate that the pattern of change in measurable residual disease over time was associated with the risk of relapse, particularly in acute myeloid leukaemia and highlight the divergent ways measurable residual disease testing can be employed across different leukaemias. Measurable residual disease (MRD) detected by flow cytometry (FC) is well established in paediatric B- lymphoblastic leukaemia (B-ALL) and adult chronic lymphocytic leukaemia (CLL), but its utility in adult B-ALL and adult acute myeloid leukaemia (AML) is less clear. In this prospective MRD study, one of the largest in Australia to date, we examined consecutive bone marrow aspirates from adult participants with B-ALL (n = 47) and AML (n = 87) sent for FC-MRD testing at a quaternary referral hospital in Sydney. FC-MRD results were correlated to corresponding Mol-MRD testing where available and clinical outcomes at three-month intervals over 1 year. B-ALL showed a moderate positive correlation (rs = 0.401, p < 0.001), while there was no correlation between FC-MRD and Mol-MRD for AML (rs = 0.13, p = 0.237). Five FC-MRD patterns were identified which had significant associations with relapse (X2(4) = 31.17(4), p > 0.001) and survival (X2(4) = 13.67, p = 0.008) in AML, but not in B-ALL. The three-month MRD results were also strongly associated with survival in AML, while the association in B-ALL was less evident. There was a moderate correlation between FC-MRD and Mol-MRD in B-ALL but not AML. The association of FC-MRD with relapse and survival was stronger in AML than in B-ALL. Overall, these findings suggest divergent utilities of FC-MRD in AML and B-ALL. [ABSTRACT FROM AUTHOR]

The definition of Early Cholecystectomy (EC) is still debatable. This paper aims to find whether the timing of EC affects outcomes. The article reports a multicentric prospective observational study including patients with acute calculous cholecystitis (ACC) who had cholecystectomy within ten days from the onset of symptoms. Kruskall-Wallis test, Fisher's Exact test, and Spearman rank correlation were used for statistical analysis. The patients were divided into three groups depending on the timing of the operation: 0–3 days, 4–7 days, or 8–10 days from the onset of symptoms. 1117 patients were studied over a year. The time from the onset of symptoms to EC did not affect the post-operative complications and mortality, the conversion, and the reintervention rate. The time represented a significant risk factor for intraoperative complications (0–3 days, 2.8%; 4–7 days, 5.6%; 8–10 days, 7.9%; p = 0.01) and subtotal cholecystectomies (0–3 days, 2.7%; 4–7 days, 5.6%; 8–10 days, 10.9%; p < 0.001). ACC is an evolutive inflammatory process and, as the days go by, the local and systemic inflammation increases, making surgery more complex and difficult with a higher risk of intraoperative complications. We recommend performing EC for ACC as soon as possible, within the first ten days of the onset of symptoms. [ABSTRACT FROM AUTHOR]

Background: At the beginning of the 21st century, international adoptions of children with cleft lip and/or palate increased dramatically in Sweden. Many children arrived partially or totally unoperated, despite being at an age when palatoplasty has usually been performed. To date, the speech development of internationally adopted (IA) children has been described up to age 7–8 years, but later development remains unstudied. Aims: To investigate speech development between ages 5 and 10 years in children born with cleft lip and palate (CLP) adopted from China and to compare them with non‐adopted (NA) children with CLP. A secondary aim was to compare the frequencies of secondary palatal surgery and number of visits to a speech and language pathologist (SLP) between the groups. Methods & Procedures: In a longitudinal study, 23 IA children from China were included and matched with 23 NA children born in Sweden. Experienced SLPs blindly reassessed audio recordings from routine follow‐ups at ages 5 and 10 years. Velopharyngeal function (VPF) was assessed with the composite score for velopharyngeal competence (VPC‐Sum) for single words and rated on a three‐point scale (VPC‐Rate) in sentence repetition. Target sounds in words and sentences were phonetically transcribed. Per cent correct consonants (PCC) were calculated at word and sentence levels. For in‐depth analyses, articulation errors were divided into cleft speech characteristics (CSCs), developmental speech characteristics (DSCs) and s‐errors. Information on secondary palatal surgery and number of visits to an SLP was collected. Outcomes & Results: VPF differed significantly between the groups at both ages when assessed with VPC‐Sum, but not with VPC‐Rate. Regardless of the method for assessing VPF, a similar proportion in both groups had incompetent VPF but fewer IA than NA children had competent VPF at both ages. IA children had lower PCC at both ages at both word and sentence levels. More IA children had CSCs, DSCs and s‐errors at age 5 years, and CSCs and s‐errors at age 10. The development of PCC was significant in both groups between ages 5 and 10 years. The proportion of children receiving secondary palatal surgery did not differ significantly between the groups, nor did number of SLP visits. Conclusions & Implications: CSCs were more persistent in IA children than in NA children at age 10 years. Interventions should target both cleft and DSCs, be comprehensive and continue past the pre‐school years. WHAT THIS PAPER ADDS: What is already known on this subject: At the beginning of the 21st century, IA children with cleft lip and/or palate arrived in Sweden partially or totally unoperated, despite being at an age when palatoplasty has usually been performed. Studies up to age 7–8 years show that adopted children, compared with NA peers, have poorer articulation skills, demonstrate both cleft‐related and developmental articulation errors, and are more likely to have velopharyngeal incompetence. Several studies also report that adopted children more often require secondary palatal surgery due to fistulas, dehiscence or velopharyngeal incompetence compared with NA peers. What this paper adds to existing knowledge: This longitudinal study provides additional knowledge based on longer follow‐ups than previous studies. It shows that the proportion of children assessed to have incompetent VPF was similar among IA and NA children. It was no significant difference between the groups regarding the proportion that received secondary palatal surgery. However, fewer IA children were assessed to have a competent VPF. Developmental articulation errors have ceased in most IA and all NA children at age 10 years, but significantly more adopted children than NA children still have cleft‐related articulation errors. What are the potential or actual clinical implications of this work?: Speech and language therapy should target both cleft‐related and developmental articulation errors. When needed, treatment must be initiated early, comprehensive, and continued past the pre‐school years, not least for adopted children. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with multiple myeloma (MM) who become refractory to three or more lines of therapy (RRMM patients) have few valid therapeutic alternatives. Among them, drugs directed against the BCMA antigen expressed in plasma cells are very appealing. Belantamab-mafodotin (belamaf) is the first antibody-drug conjugate against BCMA ready for clinical use. In this paper, we report the Spanish experience of belamaf monotherapy in 156 patients with RRMM. The overall response rate was 41.8%, with 39.8% of patients achieving a partial response or better. Median progression-free survival was 3.61 months, but interestingly, it increased to 14.47 months in patients achieving a minimal response or better. Treatment was well tolerated, ocular events being the most reported toxicity (87.9%; grade ≥ 3, 33.7%), but only two patients discontinued treatment due to side effects. Overall, our results confirm the safety and efficacy of belamaf in this poor prognosis subset of patients. Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1–10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1–28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1–5.1) and 14.47 months (95% CI, 7.91–21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7–13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the introduction of effective systemic therapies (ESTs) (in the form of both targeted and immuno-based therapies) in the treatment of malignant melanoma, the prognosis of metastatic patients has dramatically changed. The role of metastasectomy in oligometastatic patients has rarely been addressed in this new pharmacological era. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM). In this study, we describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, and identified prognostic factors affecting survival in our multicentric experience. To the best of our knowledge, this is the first paper analyzing in detail the impact of metastasectomy of PmMM in the era of ESTs. In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed. [ABSTRACT FROM AUTHOR]

Background & Aim: To assess consonant proficiency and velopharyngeal function in 10‐year‐old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. Methods & Procedures: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B–Lip and soft palate closure at 3–4 months, hard palate closure at 36 months, Arm C–Lip closure at 3–4 months, hard and soft palate closure at 12 months, and Arm D–Lip closure at 3–4 months combined with a single‐layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A–Lip and soft palate closure at 3–4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non‐syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC‐Rate), and a composite measure (VPC‐Sum) were reported. Outcomes & Results: The mean levels of consonant proficiency (PCC score) in the trial arms were 86–92% and between 58% and 83% of the children had VPC (VPC‐Sum). Only 50–73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). Conclusions & Implications: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDS: What is already known on the subject: Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5‐year‐olds. What this study adds to the existing knowledge: Speech outcomes based on standardized assessment in a large group of 10‐year‐old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work?: Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed. [ABSTRACT FROM AUTHOR]

Aims: This study compared two dose frequency conditions of an explicit intervention with 50 trials per session designed to improve past tense marking in early school‐aged children with developmental language disorder (DLD). The influence of allomorphs on intervention effects was also examined. Methods: Data from previously conducted intervention studies were combined and analysed. Participants included nine children (mean age = 6;5 years) who received 20–30‐min intervention sessions provided twice per week for 10 weeks (1000 trials; 400–600 min) and 20 children (mean age = 6;6) who received 20–30‐min intervention sessions provided once per week for 10 weeks (500 trials; 200–300 min). Repeated measures included criterion‐referenced probes for production of untrained past tense verbs collected throughout baseline, intervention, and maintenance phases. The rate of progress in each phase was analysed using logistic regression. The proportion of participants who produced past tense allomorphs correctly at pre‐intervention, post‐intervention, and maintenance testing points was analysed. Results: Logistic regression showed a stable baseline, highly significant progress during the intervention phase, and a marginally significant shallow decline during the maintenance phase. Those in the twice per week group showed a greater rate of progress during the intervention phase leading to significantly higher scores in the maintenance period when compared with the once per week group. The allomorphic category of past tense verbs did not appear to influence outcomes. Conclusions: Participants receiving intervention twice per week appeared to demonstrate a greater rate of progress with intervention than those receiving it once per week, although once per week was also effective. However, these results should be interpreted with caution. Limitations to study design indicate that a larger randomised controlled trial is required. All past tense allomorphs improve to a similar degree when treated with this intervention. What this paper adds: What is already known on the subject: Understanding the parameters of dosage and intensity are important for clinical practice.Research evaluating the efficacy and/or effectiveness of interventions delivered in different dose/intensity conditions is scarce.There appears to be different interpretations of what constitutes dosage and intensity in published research. What this paper adds to existing knowledge: This study retrospectively compared dosage and intensity conditions of intervention provided twice per week to intervention provided once per week. Both dose frequencies could be delivered in clinical settings.Results from this study were analysed by grouping data from multiple testing points, rather than comparing pre‐post results. This approach demonstrated the variability of individual performance that would otherwise be lost with conventional methods of analysis.This study demonstrated that all past tense allomorphs improve to a similar degree when treated with this intervention. What are the potential or actual clinical implications of this work?: Parameters of dosage and intensity are still not clearly defined well enough for translation to clinical practice. In consideration of current research, this intervention may be more effective if delivered twice per week.If clinicians are treating past tense, all allomorphs should be considered as priorities for intervention targets. [ABSTRACT FROM AUTHOR]

The Sequential Intercept Model has helped conceptualize interventions for people with serious mental illness in the criminal/legal system. This paper operationalizes the Sequential Intercept Model into a 35-item scorecard of behavioral health and legal practices. Using interviews, survey, and observational methods, the scorecard assesses an exploratory sample of 19 counties over 27 independent data collections. A series of ordinary least squares regression models assessed the predictor scores on four jail outcomes: prevalence of serious mental illness, length of stay, connections to treatment, and recidivism. Increases in pre-booking scores showed significant decreases in jail prevalence of serious mental illness at the p < 0.05 level, and post-booking scores and overall scores showed significant positive associations with connections to treatment at the p < 0.05 level, though these were non-significant after correcting for multiple comparisons. Preliminary findings suggest a combination of practices across the Sequential Intercept Model could have synergistic impacts on key jail diversion outcomes. [ABSTRACT FROM AUTHOR]

Background: The subcutaneous implantable‐defibrillator (S‐ICD) is a relatively new alternative to the transvenous ICD system to minimize intravascular lead‐related complications. This paper presents outcome of SICD implantation in patients enrolled in Iran S‐ICD registry. Methods: Between October 2015 and June 2022, this prospective multicenter national registry included 223 patients with a standard indication for an ICD, who neither required bradycardia pacing nor needed cardiac resynchronization to evaluate the early post‐implant complications and long‐term follow‐up results of the S‐ICD system. Results: The mean age of the patients was 45 ± 17 years. The majority (79.4%) were male. Ischemic cardiomyopathy (39.5%) was the most common underlying disorder among patients selected for S‐ICD implant. Most study patients (68.6%) had ICD for primary prevention of sudden cardiac death. Seven patients (3.1%) were found to have suboptimal lead positions. Six patients (2.7%) developed a pocket hematoma; all were managed medically. During a mean follow‐up of 2 years, the appropriate therapy was recorded in 13% of the patients and inappropriate ICD intervention mainly due to supraventricular tachycardia in 8.9%. Pocket infection was observed in four patients (1.8%) and five patients (2.2%) died mainly due to heart failure. Conclusion: S‐ICDs were effective at detecting and treating both induced and spontaneous ventricular arrhythmias. Major clinical complications were rare. [ABSTRACT FROM AUTHOR]

Purpose: To compare the outcomes of immediate and delayed implant placement with bone-level tapered implants. Materials and Methods: In this post-market, multicenter prospective randomized controlled study with a primary endpoint of 1 year, 53 patients were randomized to receive either immediate implant placement (test group) or delayed implant placement (control group). The mean crestal bone level changes from implant loading to 12 months postloading were measured using standardized digital periapical radiographs. Changes in facial plate thickness (as measured on CBCT images), implant success and survival, implant stability, soft tissue changes, patient-centered outcomes, and adverse events were measured to assess outcomes between the test and control treatments at 12 months postloading. Results: Of the original 53 patients, 46 patients completed the study (23 in each group). Mean bone changes from loading to the 12-month follow-up were recorded with no statistically significant difference (P = .950) between the groups. The hypothesis was confirmed that immediate implant placement (test) in extraction sockets produces in similar outcomes as delayed placement (control). The test group was found to be similar to the control group (P = .022) in terms of mean changes in facial plate thickness. Implant survival and success were 95.8% in the test group and 92% in the control group. Stability in the control group was superior at the time of surgery, but there was no difference between the groups at implant loading, producing a nonsignificant P value of .563). Conclusions: This randomized controlled multicenter study showed comparable outcomes 1 year after prosthetic loading in the immediate and delayed implant placement groups. [ABSTRACT FROM AUTHOR]

Background: Treatment fidelity refers to the degree to which an intervention is implemented as intended. Promoting treatment fidelity is important to achieve a valid comparison in intervention research. However, it is often underreported: few studies detail the use and development of fidelity measures. This study aims to promote the treatment fidelity of a modified version of the Derbyshire Language Scheme (M‐DLS), a manualised intervention for children with language difficulties, by exploring participants' opinions on training and intervention delivery. Results inform development of a checklist and scoring system to monitor and promote treatment fidelity in a comparison trial. Method: Ten student speech and language therapists (SLTs) and two research assistants (RAs) participated in the study. All received training on the M‐DLS, and 10 were video‐recorded completing role‐plays of an M‐DLS session in small groups. Feedback was gathered after training and role‐plays in focus groups and interviews. Feedback was interpreted using the constructs of the Theoretical Domains Framework (TDF). A treatment fidelity checklist was then developed using the feedback. The first author and two RAs rated role‐play videos using the checklist to trial it to inform amendments and to promote interrater reliability. Interrater agreement was calculated using Spearman's test of correlation. Results: Participants discussed the importance of having clear materials and time to practise sessions. They suggested amendments to the materials and training to promote treatment fidelity. The checklist and scoring system accounted for participants' suggestions, with amendments detailed in a log. Spearman's correlation results suggested agreement between the raters was strong. Conclusions: Results emphasise the importance of training quality, practice and reflective opportunities and clear materials to promote treatment fidelity. The construction of the checklist and scoring system was described in detail, informing the development of future checklists. After further trialling, the checklist can be used to ensure the M‐DLS is delivered with high treatment fidelity in the comparison trial. What this paper adds: What is already known on this subject: Treatment fidelity is an essential component of intervention effectiveness and efficacy studies, ensuring the intervention is delivered as intended. It is also an essential component of evidence-based clinical practice. However, few research studies report the treatment fidelity process or publish the checklists used, depriving clinicians of useful information for implementation. What this study adds: This study describes in detail the iterative process of treatment fidelity checklist development, engaging those implementing the intervention in development. This ensured clarity and interrater reliability of the checklist. Furthermore, a novel scoring system was developed so that accuracy of implementation can be easily compared across users and across practice attempts. What are the clinical implications of this work?: The importance of treatment fidelity when implementing effective and efficacious interventions cannot be overstated. The treatment fidelity checklist developed for research can be easily adopted to support accurate implementation in clinical practice through an audit process. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vision impairments affect the ability to navigate environments and gain spatial perception of one's surroundings. Existing navigation aids typically provide close-range information, but not feedback on farther distances (i.e., beyond 5 m from the user). OBJECTIVE: To address this gap, the OptiBand, a custom assistive device, was previously designed with a stakeholder who is blind. The OptiBand uses Lidar sensing and haptic feedback to relay information on objects up to 15 m away. In this paper, we sought to evaluate the efficacy of the OptiBand with an in situ user study. METHODS: N = 9 participants (eight blind and one low-vision) used the OptiBand for a period of three months. Users periodically rated spatial perception workload and trust of their assistive navigation aids (at first as a baseline without the OptiBand, and then with the OptiBand). RESULTS: The OptiBand tended to yield lower workload requirements and similar trust levels compared to existing navigation aids. Interview data demonstrated the usefulness of the OptiBand in selected day-to-day tasks such as navigating outdoors and maintaining appropriate interpersonal spacing. CONCLUSIONS: This work provides evidence on benefits of and potential uses of assistive navigation aids like the OptiBand. Researchers interested in similar devices can benefit from our efforts. [ABSTRACT FROM AUTHOR]

Chronic primary low back pain (CPLBP) is a prevalent and disabling condition that often requires rehabilitation interventions to improve function and alleviate pain. This paper aims to advance future research, including systematic reviews and randomized controlled trials (RCTs), on CPLBP management. We provide methodological and reporting recommendations derived from our conducted systematic reviews, offering practical guidance for conducting robust research on the effectiveness of rehabilitation interventions for CPLBP. Our systematic reviews contributed to the development of a WHO clinical guideline for CPLBP. Based on our experience, we have identified methodological issues and recommendations, which are compiled in a comprehensive table and discussed systematically within established frameworks for reporting and critically appraising RCTs. In conclusion, embracing the complexity of CPLBP involves recognizing its multifactorial nature and diverse contexts and planning for varying treatment responses. By embracing this complexity and emphasizing methodological rigor, research in the field can be improved, potentially leading to better care and outcomes for individuals with CPLBP. [ABSTRACT FROM AUTHOR]

Treatment success is the desired outcome in aphasia rehabilitation. However, to date, there is a lack of consensus on what defines a 'successful' result on a given aphasia outcome measurement instrument (OMI). In this methodological paper, we present strategies for how to define and measure treatment success on a given OMI at the group-level, as well as for an individual person with aphasia. The latter is particularly important when research findings from group studies are clinically implemented for individuals in rehabilitation. We start by presenting methods to calculate the average statistically significant change across several (group) studies (e.g., standardised mean difference, raw unstandardised mean difference) for a given OMI. Such metrics are useful to summarise the overall effect of the intervention of interest, particularly in meta-analyses. However, benchmarks based on group effects are not feasible for assessing an individual participant's treatment success and thus for determining the proportion of patients who had a beneficial response to therapy (overall response rate of an intervention). We therefore recommend a distribution-based approach to determine benchmarks of a statistically significant treatment response at the individual level, i.e., the 'smallest detectable change' for a given OMI, which refers to the smallest change that can be detected by the OMI beyond measurement error. However, the statistical significance of an individual treatment effect does not necessarily correspond to its clinical impact. This requires an additional indicator. The benchmark to determine a clinically relevant improvement on a given OMI is the 'minimal important change'. The minimally important change is defined as the smallest OMI change score perceived as important by the relevant stakeholder group (i.e., people with aphasia, their relatives/caregivers, clinicians). It therefore requires relating the individual OMI change scores to 'anchors', i.e., meaningful external criteria, preferably based on patient-perceived therapy success. Currently, there is no consensus regarding the optimal 'anchors' and their respective definition of clinically important change in aphasia outcome research. Operationalising individual treatment success based on both statistically significant and (patient-reported) clinically meaningful benchmarks is a key priority in aphasia rehabilitation. Availability of such measures will (a) facilitate estimates of therapy response rate in intervention studies and thus optimise therapeutic decisions and (b) provide stakeholder groups (e.g., the society, the stroke team, people with aphasia, family, clinicians, healthcare professionals) with objective, statistically reliable and meaningful feedback on individual treatment response in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Several medications have been applied to Alzheimer's dementia patients (AD) but their efficacies have been insufficient. The efficacy and safety of 4 weeks of repetitive transcranial magnetic stimulation (rTMS) in Japanese AD were evaluated in this exploratory clinical trial. Methods: Forty-two patients, aged 60-93 years (average, 76.4 years), who were taking medication (> 6 months) and had Mini-Mental State Examination (MMSE) scores ≤ 25 and Clinical Dementia Rating Scale scores (CDR-J) of 1 or 2, were enrolled in this single-center, prospective, randomized, three-arm study [i.e., 120% resting motor threshold (120% RMT), 90% RMT for the bilateral dorsolateral prefrontal cortex, and Sham]. Alzheimer's Disease Assessment Scale-Japanese Cognitive (ADAS-J cog), Montreal Cognitive Assessment (MoCA-J), Clinical Global Impression of Change (CGIC), Neuropsychiatric inventory (NPI), and EuroQOL 5 Dimensions 5-Level (EQ-5D-5L) were administered. The primary endpoint was the mean change from baseline in the MMSE score (week 4). An active rTMS session involved applying 15 trains bilaterally (40 pulses/train at 10 Hz; intertrain interval, 26 s). Participants received ≥ 8 interventions within the first 2 weeks and at least one intervention weekly in the 3rd and 4th weeks. Full Analysis set (FAS) included 40 patients [120% RMT (n = 15), 90% RMT (n = 13), and Sham (n = 12)]. Results: In the FAS, MMSE, ADAS-J cog, MoCA-J, CDR-J, CGIC, NPI, and EQ-5D-5L scores between the three groups were not significantly different. Two patients were erroneously switched between the 120% RMT and 90% RMT groups, therefore, "as treated" patients were mainly analyzed. Post hoc analysis revealed significant treatment efficacy in participants with MMSE scores ≥ 15, favoring the 120% RMT group over the Sham group. Responder analysis revealed 41.7% of the 120% RMT group had a ≥ 3-point improvement in the ADAS-J cog versus 0% in the Sham group (Fisher's exact test, p = 0.045). The MoCA-J showed the same tendency but was not significant. Efficacy disappeared in week 20, based on the ADAS-cog and MoCA-J. No intervention-related serious adverse events occurred. Conclusion: This paper is the first report of using rTMS in Japanese AD patients. The treatment seems safe and moderate-mild stage AD should be target population of pivotal clinical trial with 120% RMT rTMS. [ABSTRACT FROM AUTHOR]

Background: Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies. Methods: An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the 'Think Aloud' method with patient advisory group members and Research Nurses to assess the usability of the system. Results: Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials. Conclusion: By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development. Trial registration: ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507 Plain English summary: More and more patients tell clinicians how they feel by completing questionnaires electronically. Therefore, it is important to assess how easy it is for patients to do this. In this study, we describe how we developed an electronic platform for patients to report their symptoms and how we tested the usability of this platform with patient partners and research nurses. Once the electronic platform was developed, quality of life and symptoms questionnaires were programmed onto it. Alerts were sent to the clinical team if specific scores were obtained on the symptoms questionnaires. Although two patient partners were not able to finish the testing session because of technical issues, the ones who completed the session liked its simplicity and responsiveness. The research nurses also liked the system and only suggested minor modifications. Following this testing, we refined the electronic platform to test it further in a larger study which investigates the safety and use of a drug. We hope that thanks to this electronic platform, we will obtain useful information on the safety and efficacy of treatment. [ABSTRACT FROM AUTHOR]

A co-design project, consisting of individual and collective design activities, was organized with clients of a mental health service, in order to explore its potential to support people with psychosis. The group met for approximately two hours, weekly, for six months, participating in design activities and collectively deciding on the project purpose and outcome – a boardgame. The experience of one group participant (Anthony) is explored, selected as the first case study within an Interpretative Phenomenological Analytical (IPA) framework. Following IPA's ideographic focus, Anthony's case was purposefully selected, as it portrayed a detailed picture, informing theoretical reflection on designing as therapeutic. The paper includes Anthony's first-hand account, combined with an analysis of data from three semi-structured interviews, photographic evidence and a reflective diary kept by the lead researcher. Results suggest that, for Anthony, design activity: a) helps developing a sense of agency b) is experienced as grounding in reality c) contributes to the development of inter-personal relationships, and d) has a different sense of rhythm than artistic practice. These results are contextualized within literature on the lived experience of psychosis and suggest that designing can be beneficial for people with psychosis, providing the backdrop for further research and practice. [ABSTRACT FROM AUTHOR]

Background: Violence exacts staggering personal and financial costs – a burden disproportionally born by adolescents and young adults. This may be partially due to an increased sensitivity to social rejection during this critical phase of development. Irritability, a transdiagnostic symptom, is often elicited by social interactions. Yet, little is known about age differences in social rejection‐elicited aggression and irritability. Progress toward testing such relations has been hindered by a lack of ecologically‐valid tasks that enable the measurement of in‐the‐moment social rejection‐elicited aggression. Methods: In this paper, we describe an initial study of young adults (n = 55) that demonstrates the efficacy of a novel Virtual School and Aggression Paradigm (VS‐AP). Next, we replicate these results in a second study of adolescents and young adults (ages 11–25 years; n = 173) and examine relations between social rejection‐elicited aggression, irritability, and age. Results: We found that aggressive behavior in the VS‐AP differed for accepting, rejecting, and unpredictable peer types (Study 1: F(2, 108) = 20.57, p <.001, ε2 =.28; Study 2: F(2, 344) = 152.13, p <.001, ε2 =.47), demonstrating that the VS‐AP successfully models social rejection‐elicited aggression. In Study 2, age was negatively correlated with aggressive behavior (r = −.29, p <.001) and irritability (r = −.28, p <.001), while irritability was positively correlated with aggressive behavior (r =.28, p <.001). Age moderated the relation between social rejection‐elicited aggression and irritability. Specifically, irritability was more predictive of aggression in young adults than in adolescents (F(3, 167) = 7.07, p <.001). Conclusions: Data suggest mechanisms promoting rejection‐elicited aggression may differ across development and vary for those with and without high levels of irritability. The VS‐AP is a promising tool for probing neurocognitive, developmental, and clinically relevant mechanisms underlying social rejection‐elicited aggression. [ABSTRACT FROM AUTHOR]

Pectus excavatum is the most common congenital anterior chest wall deformity, with an incidence of 1:400 to 1:1000. Surgical strategy has evolved with the revolutionary idea of Donald Nuss, who was a pioneer in the operative correction of this deformity using minimally invasive surgery. The aim of this paper is to compare the preliminary results of pectus excavatum repair in two University Centers with a moderate number of patients using the standard Nuss procedure and its modification, the extrapleural thoracoscopic approach. The statistical analysis showed no significant difference for the patient's age (14.52 ± 3.70 vs. 14.57 ± 1.86; p = 0.95) and the CT Haller index (4.17 ± 1.58 vs. 3.78 ± 0.95; p = 0.32). A statistically significant difference was noted for the duration of a pectus bar implant (2.16 ± 0.24 vs. 2.48 ± 0.68; p = 0.03) between the Maribor and Novi Sad Center. We report 14 complications (28%), including dislocation of the pectus bar (10%), pleural effusion (8%), wound inflammation (6%), pericarditis (2%) and an allergic reaction to the pectus bar (2%). Standard and thoracoscopic extrapleural Nuss procedures are both safe and effective procedures used to correct a pectus excavatum deformity. The choice of surgical procedure should be made according to a surgeon's reliability in performing a particular procedure. Our study found no advantages of one procedure over the other. [ABSTRACT FROM AUTHOR]

Physical activity is a factor by which mental health can be improved. However, the association between mental health and physical exercise, in a "team-based sport" setting within the community, remains unclear. The current paper aims to provide an evaluation of a football programme, implemented by Time to Change Wales, funded by the Welsh Government, to improve mental health. Participants attended weekly 90–120 minute football sessions, held in local community venues across Wales, UK, with no requirement on the number of sessions that participants had to attend. A qualitative method was employed to explore the experiences of those who took part. Individuals who participated in the programme reported psychosocial and physical benefits, such as improved physical and mental health, improved social confidence and having a sense of purpose added to their day-to-day living. Factors affecting participation were also identified within the data, such as environmental barriers. Conclusion: The findings provide both support and contextual extension to previous research in this area; demonstrating the positive effects of sport-based therapy for those with mental health difficulties. Implications and conclusions should be used to inform future research into developing community sport-based programmes to improve mental health. [ABSTRACT FROM AUTHOR]

Introduction: This paper provides a report of social validity and its usefulness in understanding study effects. Social validity data were drawn from a larger single-case study designed to investigate the effectiveness of the Matrix Approach in the practice of early intervention visual impairment professionals. Methods: Qualitative measures were used to assess social validity. According to Wolf (1978), validation of a study should encompass the significance of goals, appropriateness of procedures, and importance of outcomes. Therefore, data sources were created to provide evidence of social validity in these areas including pre- and post-intervention interviews of parents and professionals. Results: Three themes emerged from the social validity data. These are organized under the topics introduced by Wolf (1978) and identified as measures of quality by Horner et al. (2005). The themes are (a) Goals: role of the parent as learner and the professional as expert before using the Matrix Approach, (b) Procedures: helpfulness of coaching and the structure of the Matrix Approach, and (c) Outcomes: personal and professional growth as a result of using the Matrix Approach. Discussion: Evaluation of social validity in single-case research is an important component in a study's design and in interpreting the study's outcomes. Wolf's framework proved valuable in promoting a robust evaluation of study effectiveness, especially when incorporated into the study design. Intentionally planning to measure social validity held the researchers accountable to the practical needs of the participants. In fact, there is value in gathering social validity data at various points in a study. Further, hearing the perspective of stakeholders can provide valuable insights as researchers seek to understand the complexities of change evident in the outcomes of a study. Implications for Practitioners: Collaborative planning is an essential component of early intervention. The Matrix Approach shows promise as a mechanism to foster such collaboration. [ABSTRACT FROM AUTHOR]

The relationship between self-awareness (insight) and outcome following acquired brain injury (ABI) is well recognised, but evidence suggests that information regarding brain injury and its cognitive impact is not adequately conveyed to social workers, or appropriately considered when assessing support needs and a person's capacity to make decisions about their care. The Brain Injury Needs Indicator (BINI) provides a solution, by enabling the valid assessment of the needs of those with brain injuries living in a community setting. This paper investigated associations between impaired insight, functional outcome of brain injury, and level of risk, and validated the use of the BINI as an indicator of need. A high prevalence of severe disability (73 per cent) and low insight (30 per cent) was found in a sample of thirty individuals with ABI. The composite BINI score was the measure most strongly related with a clinical assessment of risk (rs = 0.72, N  =   26). Self-report methods may underestimate support needs, especially in those with low levels of insight into their difficulties. The BINI, which combines outcome post-ABI with a measure of insight, provides a more accurate estimate of risk than either measure individually. It is important to include both areas in individual needs assessments. [ABSTRACT FROM AUTHOR]

Stigma of mental illness contributes to silence, denial and delayed help seeking. Existing stigma reduction strategies seldom consider gender and cultural contexts. The Strengths in Unity study was a multi-site Canadian study that engaged Asian men in three stigma reduction interventions (ACT, CEE, psychoeducation) and mobilized them as Community Mental Health Ambassadors. Our participants included both men living with or affected by mental illness (LWA) as well as community leaders (CL). This paper will: (1) describe the baseline characteristics of the Toronto participants including their sociodemographic information, mental illness stigma (CAMI and ISMI), attitudes towards social change (SJS), and intervention-related process variables (AAQ-II, VLQ, FMI, Empowerment); (2) compare the differences among these variables between LWA and CL; and (3) explore factors that may correlate with socio-economic status and mental health stigma. A total of 609 Asian men were recruited in Toronto, Canada. Both CL and LWA had similar scores on measures of external and internalized stigma and social change attitudes, except that LWA had more positive views about the acceptance and integration of those with mental illness into the community on the CAMI, while CL had a higher level of perceived behavioral control on the SJS. Group differences were also observed between LWA and CL in some process-related variables. Exploratory analysis suggests that younger and more educated participants had lower stigma. Our findings underscore the importance of engaging both community leaders and people with lived experience as mental health advocates to address stigma. [ABSTRACT FROM AUTHOR]

Background: Melanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial.Methods: This paper reports on process evaluation. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved.Results: Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up.Conclusion: Melanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool.Trial Registration: Clinical Trials.gov , NCT03328247 . Registered on 1 November 2017. [ABSTRACT FROM AUTHOR]

Purpose: Age, sex, and type of fracture have traditionally been described as prognostic factors for proximal humeral fractures (PHFs). Some non-medical patient-related factors may play a role in the outcome. This paper evaluates the association of comorbidities and socioeconomic factors with clinical outcomes for PHF.Methods: A total of 217 patients with PHF were evaluated according to Neer's classification with X-ray. Comorbidities were assessed through the Charlson comorbidity index and, non-medical patient-related factors were determined with a 52-item questionnaire concerning personal behaviors such as social activities, family support, economic solvency, and leisure-time activities. The clinical outcome was assessed with the Constant-Murley Score (CMS), with a minimum 1-year follow-up. The minimal clinically relevant difference for the CMS was set at 10 points. A multivariable analysis was performed to adjust for comorbidities and non-medical patient-related factors, such as age, sex, fracture classification, and treatment.Results: One hundred and eighty-three patients completed the initial research protocol, while 126 of them completed the 1-year follow-up. The mean age was 71.6 years (SD ± 13.3), and 79.3% of the patients were women. In the bivariable analysis, age and comorbidities were correlated with the CMS (correlation coefficient: - 0.34 [- 0.49, 0.17] and 0.35 [0.18, 0.50], respectively), as well as non-medical patient-related factors and the fracture pattern (p value ANOVA < 0.001). In the multivariable regression model, the effects of considering oneself socially active, without economic problems, and self-sufficient were associated with a higher CMS than the effect of the fracture pattern (beta coefficient: 11.69 [6.09-17.30], 15.54 [8.32-22.75], and 10.61 [3.34-17.88], respectively).Conclusion: Socioeconomic status had a higher impact on functional outcomes than fracture pattern in patients with PHF. [ABSTRACT FROM AUTHOR]

Background - Histoplasmosis is a soil based rare air borne fungal infection and mostly documented in HIV positive patients. They are common in people living near valley region. Materials and methods- This is a multiinstitutional study. We report 3 cases of asian women from different regions of Southern Rajasthan who died due to delayed diagnosis of Histoplasmosiswithin few days of admission. They all had complaints of fatigue and fever since 1 month. One presented with decreased urine output and pancytopenia. Others had complaints of prolonged fever with pancytopenia and fatigue. All were diagnosed on Bone marrow examination for presence of Histoplasma Capsulatum, diagnosis was supported by special stains used for reporting. Treatment was started but patients deteriorated and died within 10 days of admission. Conclusion- Delay in diagnosis of Histoplasmosis leads to death of patients. So, Histoplasmosis is considered as a differential diagnosis of prolonged fever with pancytopenia and chronic infections. [ABSTRACT FROM AUTHOR]

Background: Misophonia is a condition marked by dysregulated emotions and behaviors in response to trigger sounds, often chewing, breathing, or coughing. Evidence suggests that misophonia develops in adolescence and the emotions and behaviors are a conditioned response to distress, resulting in social avoidance, stress, and family conflict. In addition, co-occurrence with other psychiatric illnesses such as anxiety, OCD, and Tourette syndrome is common. A transdiagnostic cognitive behavioral therapeutic (CBT) approach appears appropriate. There are currently no controlled studies of youth with misophonia. The current paper describes the approach to a pilot randomized, blinded family-based treatment study for youth ages 8-16 years. Preliminary results from a pilot open trial also are described.Methods: A 2-phase dual site telehealth treatment study using a transdiagnostic CBT approach, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children and Adolescents (UP-C/A; Ehrenreich-May et al., 2018), is proposed. Phase 1 consisted of a 4-case pilot of UP-C/A. Phase 2 includes a randomized trial comparing the UP-C/A to a standard relaxation and education protocol.Results: Preliminary results from the pilot show modest improvements in evaluator-rated misophonia symptoms on the Clinical Global Impression Severity and Improvement scales.Limitations: There is little research to inform evidence-based practice for youth with misophonia. Study limitations include lack of standardized misophonia assessment instruments and an absence of formal diagnostic criteria.Conclusions: The current paper describes proposed methods for the first randomized controlled trial for youth with misophonia and their families along with results from a 4-case pilot. [ABSTRACT FROM AUTHOR]

Aims and objectives: Investigate evidence available on the efficacy, safety and acceptability of devices for the management of female urinary incontinence, in which clinical settings and specific female populations they have been tested. Learn more about healthcare professionals' perspectives and experiences regarding female urinary incontinence devices. Background: Urinary incontinence is defined as the involuntary leakage of urine, estimated to affect 25%–45% of women. Urinary incontinence predisposes the skin to urinary incontinence dermatitis, it is one of the most common documented causes of inappropriate urinary catheterisation, favouring catheter‐associated infection. Several products for managing female urinary incontinence are available, no accurate and systematic data on usability, effectiveness and associated outcomes of these products are available. Design and Methods: A scoping review was conducted, using a methodological framework including the following five steps: identification of the research question; identification of relevant documents; selection of documents included in the review; tracking of information and data; synthesis and reporting of results. Twenty‐one articles were selected. PRISMA‐ScR Checklist was followed. Results: The devices explored in the studies were as follows: female external urinary catheter; disposable sanitary pads, diapers or sanitary pads used to manage urinary incontinence in women; mechanical devices; a new prototype of underwear that tracks where pads lose; reusable underwear for light incontinence; a new intelligent system pad. Conclusions: New smart pads, urine suction systems and female external catheters appear to be effective in preventing and reducing urinary incontinence dermatitis. The female external catheter reduces the days of indwelling catheterisation and could reduce the incidence of catheter associated urinary tract infection; therefore, it should be recommended. [ABSTRACT FROM AUTHOR]

Background: Psychotherapy for borderline personality disorder is often extensive and resource-intensive. Mentalisation-based therapy is a psychodynamically oriented treatment option for borderline personality disorder, which includes a case formulation, psychoeducation, and group and individual therapy. The evidence on short-term compared with long-term mentalisation-based therapy is currently unknown.Methods/design: The Short-Term MBT Project (MBT-RCT) is a single-centre, parallel-group, investigator-initiated, randomised clinical superiority trial in which short-term (20 weeks) will be compared with long-term (14 months) mentalisation-based therapy for outpatients with subthreshold or diagnosed borderline personality disorder. Outcome assessors, data managers, the data safety and monitoring committee, statisticians, and decision-makers will be blinded to treatment allocation. Participants will be assessed before randomisation and at 8, 16, and 24 months after randomisation. The primary outcome will be the severity of borderline symptomatology assessed with the Zanarini Rating Scale for Borderline Personality Disorder. Secondary outcomes will be functional impairment (Work and Social Adjustment Scale), quality of life (Short-Form Health Survey 36-mental component), global functioning (Global Assessment of Functioning), and proportion of participants with severe self-harm. In this paper, we present a detailed statistical analysis plan including a comprehensive explanation of the planned statistical analyses, methods to handle missing data, and assessments of the underlying statistical assumptions. Final statistical analyses will be conducted independently by two statisticians following the present plan.Discussion: We have developed this statistical analysis plan before unblinding of the trial results in line with the Declaration of Helsinki and the International Conference on Harmonization of Good Clinical Practice Guidelines, which should increase the validity of the MBT-RCT trial by mitigation of analysis bias.Trial Registration: ClinicalTrials.gov NCT03677037 . Registered on 19 September 2018. [ABSTRACT FROM AUTHOR]

Aim: To evaluate an innovative paediatric neurorehabilitation model in relation to improving quality of neurorehabilitation and reducing length of stay (LOS) for children with acquired brain injury.Method: A process evaluation approach was conducted in line with Medical Research Council evaluation of complex interventions guidance. Analysis was conducted on routinely collected patient data from 2017 to 2018, including LOS and family feedback. Descriptive and inferential statistics were used for quantitative analysis and qualitative data was analysed thematically.Results: Outcomes for 70 children (0-16y, median age 5y, IQR 1-11y, 46 males, 24 females) referred to the service indicated improved function and reduced complexity of need. The mean LOS was 10.6 days compared to baseline mean LOS of 41 days (2011-2012). High satisfaction from the families was recorded; however, ongoing needs and service gaps regarding long-term support were identified.Interpretation: This service model is effective in delivering quality paediatric neurorehabilitation, demonstrating a sustained impact on LOS, and positive patient outcome data and family feedback for this group of patients. What this paper adds Investment in early intensive neurorehabilitation and supported discharge impacts length of stay (LOS) for children with acquired brain injury. Early intensive neurorehabilitation and supported discharge is effective. This is demonstrated by a sustained reduction in LOS, positive patient outcomes, and family feedback. [ABSTRACT FROM AUTHOR]

Some estrogen metabolites are associated with increased breast cancer risk, while others are protective. Research efforts have focused on modifiable factors, including bioactive compounds found in food or supplements, promoting estrogen profiles with anti-cancer properties. EstroSense® is a nutraceutical product with bioactive compounds, including Indole-3-carbinol and green-tea catechins, which may favourably affect estrogen profiles. This study was conducted to determine if EstroSense use, compared to placebo, promotes a higher urinary 2-hydroxyestrone:16α-hydroxyestrone ratio (2-OHE1:16α-OHE1), a biomarker associated with a lowered risk of breast cancer. A total of 148 premenopausal women were recruited from British Columbia, Canada to participate in a randomized, double-blind, cross-over, multicentre, placebo-controlled study in which women were randomized to a treatment sequence that consisted of either EstroSense®, followed by placebo or vice-versa. The women were instructed to consume three capsules per day of EstroSense® or the placebo for three menstrual cycles (∼12 weeks). The primary outcome was the measurement of 2-OHE1:16α-OHE1 in casual samples at baseline and after each treatment phase. After 12 weeks of intervention, the mean (95% CI) urinary 2-OHE1:16α-OHE1 was 4.55 (2.69, 6.42) (p<0.001) higher following EstroSense than placebo adjusted for baseline values. EstroSense use led to markedly higher urinary 2-OHE1:16α-OHE1 than the placebo, a biomarker associated with a lower risk of breast cancer. http://clinicaltrials.gov (NCT02385916). [ABSTRACT FROM AUTHOR]

Background The high costs of novel anticancer drugs have caused concern among healthcare stakeholders. To address the knowledge gap on the proportion of survival benefit with the related economic expenditure, we aimed to assess the correlation between the costs and value of innovative drugs targeted to specific tumours, before and after price negotiation policy implementation. Methods We identified new drugs for lung and breast cancer that entered the National Reimbursement Drug List (NRDL) through price negotiation from 2016 to 2023. Therapeutic value consisted of traditional clinical endpoints, like the percentage improvement of overall survival (≥OS%) and progression-free survival (≥PFS%), and the quantified gains of the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated monthly drug costs and used Spearman's correlation coefficient and Cohen's kappa statistics for statistical analysis. Results Twenty-nine innovative price-negotiated drugs were collected between 2016 and 2023. The median monthly costs were US$3381.31 out of NRDL and US$1095.88 within NRDL, with an ≥OS% of 22.24% (IQR = 6.45-29.48) and a ≥PFS% of 83.82% (IQR = 50.41-104.05). The median ASCO-VF score was 40.98, and 17 drugs scored the meaningful benefit of ESMO-MCBS. We found no association between clinical benefits and their costs before and after NRDL, either overall or for specific cancers. The agreement between the two frameworks was stable. Conclusions The negotiation policy decreased medication costs, but did not generate the expected correlation between the value and costs of anticancer drugs. Comprehensive value assessments need to be performed in the future to explore more in-depth findings and promote the affordability and availability of effective anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non‐small cell lung cancer (NSCLC) in real‐world settings. Methods: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first‐line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow‐up data were obtained using medical records from diagnosis to March 1, 2018. Results: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3‐year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3‐year progression‐free survival (PFS) and disease‐free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29–0.81]), PFS (0.62 [0.39–0.96]), and DFS (0.62 [0.39–0.97]) versus surgery alone. Conclusions: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC. [ABSTRACT FROM AUTHOR]

Background: In recent years, an increasing number of studies have examined the potential efficacy of cognitive training procedures in individuals with normal ageing and mild cognitive impairment (MCI). Objective: The aims of this study were to (i) evaluate the efficacy of the cognitive Virtual Reality Rehabilitation System (VRRS) combined with anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex compared to placebo tDCS stimulation combined with VRRS and (ii) to determine how to prolong the beneficial effects of the treatment. A total of 109 subjects with MCI were assigned to 1 of 5 study groups in a randomized controlled trial design: (a) face-to-face (FTF) VRRS during anodal tDCS followed by cognitive telerehabilitation (TR) (clinic-atDCS-VRRS+Tele@H-VRRS); (b) FTF VRRS during placebo tDCS followed by TR (clinic-ptDCS-VRRS+Tele@H-VRRS); (c) FTF VRRS followed by cognitive TR (clinic-VRRS+Tele@H-VRRS); (d) FTF VRRS followed by at-home unstructured cognitive stimulation (clinic-VRRS+@H-UCS); and (e) FTF cognitive treatment as usual (clinic-TAU). Results: An improvement in episodic memory was observed after the end of clinic-atDCS-VRRS (p < 0.001). We found no enhancement in episodic memory after clinic-ptDCS-VRRS or after clinic-TAU. Moreover, the combined treatment led to prolonged beneficial effects (clinicatDCS- VRRS+Tele@H-VRRS vs. clinic-ptDCS-VRRS+Tele@H-VRRS: p = 0.047; clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-VRRS+Tele@H-VRRS: p = 0.06). Discussion: The present study provides preliminary evidence supporting the use of individualized VRRS combined with anodal tDCS and cognitive telerehabilitation for cognitive rehabilitation. [ABSTRACT FROM AUTHOR]

Introduction: Patients experiencing an out-of-hospital cardiac arrest (OHCA) frequently do not receive bystander cardiopulmonary resuscitation (CPR), especially in low- and middle-income countries (LMIC). In this study we sought to determine the prevalence of OHCA patients in Vietnam who received bystander CPR and its effects on survival outcomes. Methods: We performed a multicenter, retrospective observational study of patients (≥18 years) presenting with OHCA at three major hospitals in an LMIC from February 2014-December 2018. We collected data on the hospital and patient characteristics, the cardiac arrest events, the emergency medical services (EMS) system, the therapy methods, and the outcomes and compared these data, before and after pairwise 1:1 propensity score matching, between patients who received bystander CPR and those who did not. Upon admission, we assessed factors associated with good neurological survival at hospital discharge in univariable and multivariable logistic models. Results: Of 521 patients, 388 (74.5%) were men, and the mean age was 56.7 years (SD 17.3). Although most cardiac arrests (68.7%, 358/521) occurred at home and 78.8% (410/520) were witnessed, a low proportion (22.1%, 115/521) of these patients received bystander CPR. Only half of the patients were brought by EMS (8.1%, 42/521) or private ambulance (42.8%, 223/521), 50.8% (133/262) of whom had resuscitation attempts. Before matching, there was a significant difference in good neurological survival between patients who received bystander CPR (12.2%, 14/115) and patients who did not (4.7%, 19/406; P < .001). After matching, good neurological survival was absent in all OHCA patients who did not receive CPR from a bystander. The multivariable analysis showed that bystander CPR (adjusted odds ratio: 3.624; 95% confidence interval 1.629-8.063) was an independent predictor of good neurological survival. Conclusion: In our study, only 22.1% of total OHCA patients received bystander CPR, which contributed significantly to a low rate of good neurological survival in Vietnam. To improve the chances of survival with good neurological functions of OHCA patients, more people should be trained to perform bystander CPR and teach others as well. A standard program for emergency first-aid training is necessary for this purpose. [ABSTRACT FROM AUTHOR]

Background According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. Methods We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. Results In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P  < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P  = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P  < .001). HER2E showed increased PCR rates compared to non-HER2E (P  = .004). Conclusions Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential. [ABSTRACT FROM AUTHOR]

Introduction: Metronomic oral cyclophosphamide (MOC) presents many potential advantages, such as significantly less severe side effects than standard regimens, ease of administration, and the delivery of a dose-dense but not necessarily dose-intense treatment. These observations prompted us to evaluate in a retrospective, multicenter study the efficacy and toxicity of MOC in a real-life series of pretreated cancer patients. Methods: The study is a multicenter, retrospective analysis of the activity of single-agent MOC in patients with recurrent or residual epithelial ovarian, fallopian tube, or primary. Eligible patients were continuously treated with MOC at 50 mg/day until progression, toxicity, or death. Overall response rate (ORR), stable disease (SD), and disease control rate (DCR) were reported. Results: The study included 62 patients. Three patients reached a complete response rate (5%), 11 had a partial response rate (18), and 15 had stabilization of disease (24) for an ORR of 23% and a DCR of 47%. Patients with low-grade indolent tumors showed an ORR and an SD rate higher than that observed in non-indolent ones (33% vs. 18% and 28% vs. 14%, respectively). Overall, progression-free survival was 3.5 months (range 1–9 months). Conclusion: Single-agent MOC is active and very well tolerated in a significant fraction of patients with refractory, recurrent, or residual epithelial ovarian, fallopian tube, or primary peritoneal cancer. In the vision of a practical approach, single-agent MOC may be a useful palliative treatment option for patients with poor tolerance to high-dose regimens or widely pretreated. Further studies are needed better to characterize the role of such an approach in clinical practice. [ABSTRACT FROM AUTHOR]

This multi-center study examined the safety and effectiveness of cochlear implantation of children between 9 and 11 months of age. The intended impact was to support practice regarding candidacy assessment and prognostic counseling of pediatric cochlear implant candidates. Data in the clinical chart of children implanted at 9–11 months of age with Cochlear Ltd devices at five cochlear implant centers in the United States and Canada were included in analyses. The study included data from two cohorts implanted with one or two Nucleus devices during the periods of January 1, 2012–December 31, 2017 (Cohort 1, n = 83) or between January 1, 2018 and May 15, 2020 (Cohort 2, n = 50). Major adverse events (requiring another procedure/hospitalization) and minor adverse events (managed with medication alone or underwent an expected course of treatment that did not require surgery or hospitalization) out to 2 years post-implant were monitored and outcomes measured by audiometric thresholds and parent-reports on the IT-MAIS and LittlEARS questionnaires were collected. Results revealed 60 adverse events in 41 children and 227 ears implanted (26%) of which 14 major events occurred in 11 children; all were transitory and resolved. Improved hearing with cochlear implant use was shown in all outcome measures. Findings reveal that the procedure is safe for infants and that they show clear benefits of cochlear implantation including increased audibility and hearing development. [ABSTRACT FROM AUTHOR]

Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation. This framework overcomes the limitations of traditional rating scales and offers an efficient and accurate method that is rater-independent for evaluating and monitoring dystonia patients. To evaluate the framework, we leveraged semi-standardized clinical video data collected in three retrospective, longitudinal cohort studies across seven academic centres. We extracted static head angle excursions for clinical validation and derived kinematic variables reflecting naturalistic head dynamics to predict dystonia severity, subtype, and neuromodulation effects. The framework was also applied to a fully independent cohort of generalised dystonia patients for comparison between dystonia sub-types. Computer vision-derived measurements of head angle excursions showed a strong correlation with clinically assigned scores. Across comparisons, we identified consistent kinematic features from full video assessments encoding information critical to disease severity, subtype, and effects of neural circuit interventions, independent of static head angle deviations used in scoring. Our visual perceptive machine learning framework reveals kinematic pathosignatures of dystonia, potentially augmenting clinical management, facilitating scientific translation, and informing personalized precision neurology approaches. [ABSTRACT FROM AUTHOR]

Background: Evidence for the management of pregnant women with acute hypoxaemic respiratory failure (AHRF) is currently lacking. The likelihood of avoiding intubation and the risks of continuing the pregnancy under invasive ventilation remain undetermined. We report the management and outcome of pregnant women with pneumonia related to SARS-CoV-2 admitted to the ICU of tertiary maternity hospitals of the Paris area. Methods: We studied a retrospective cohort of pregnant women admitted to 15 ICUs with AHRF related to SARS-CoV-2 defined by the need for O2 ≥ 6 L/min, high-flow nasal oxygen (HFNO), non-invasive or invasive ventilation. Trajectories were assessed to determine the need for intubation and the possibility of continuing the pregnancy on invasive ventilation. Results: One hundred and seven pregnant women, 34 (IQR: 30–38) years old, at a gestational age of 27 (IQR: 25–30) weeks were included. Obesity was present in 37/107. Intubation was required in 47/107 (44%). Intubation rate according to respiratory support was 14/19 (74%) for standard O2, 17/36 (47%) for non-invasive ventilation and 16/52 (31%) for HFNO. Factors significantly associated with intubation were pulmonary co-infection: adjusted OR: 3.38 (95% CI 1.31–9.21), HFNO: 0.11 (0.02–0.41) and non-invasive ventilation: 0.20 (0.04–0.80). Forty-six (43%) women were delivered during ICU stay, 39/46 (85%) for maternal pulmonary worsening, 41/46 (89%) at a preterm stage. Fourteen non-intubated women were delivered under regional anaesthesia; 9/14 ultimately required emergency intubation. Four different trajectories were identified: 19 women were delivered within 2 days after ICU admission while not intubated (12 required prolonged intubation), 23 women were delivered within 2 days after intubation, in 11 intubated women pregnancy was continued allowing delivery after ICU discharge in 8/11, 54 women were never intubated (53 were delivered after discharge). Timing of delivery after intubation was mainly dictated by gestational age. One maternal death and one foetal death were recorded. Conclusion: In pregnant women with AHRF related to SARS-CoV-2, HFNO and non-invasive mechanical ventilation were associated with a reduced rate of intubation, while pulmonary co-infection was associated with an increased rate. Pregnancy was continued on invasive mechanical ventilation in one-third of intubated women. Study registration retrospectively registered in ClinicalTrials (NCT05193526). [ABSTRACT FROM AUTHOR]

Introduction: The optimal strategy for differentiated thyroid cancer (DTC) patients treated with radioiodine (RAI) following thyroidectomy remains controversial. Multi-centre clinical studies are essential to identify strategies to improve patient outcomes while minimising treatment-induced toxicity. Materials and Methods: The INSPIRE clinical trial (ClinicalTrials.gov Identifier: NCT04391244) aims to investigate patient-specific dosimetry for DTC patients and to determine the range of absorbed doses delivered to target and nontarget tissues and their relationship with treatment outcome and toxicity. Results: We report here initial results of the first 30 patients enrolled onto the INSPIRE trial. A large range of absorbed doses are observed for both thyroid remnants and salivary glands, with median values of 4.8 Gy (Range 0.2 - 242 Gy) and 0.3 Gy (Range 0.1 to 1.7 Gy), respectively. Discussion: The preliminary study results are encouraging and could help to improve our understanding of absorbed doses to thyroid remnants and normal organs following RAI therapy. Such knowledge could potentially enable patientspecific treatment planning with improved clinical outcomes and quality-of-life of patients. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to determine the effect of music on the pain, anxiety, and comfort levels of patients who underwent bone marrow aspiration and biopsy. Methods: This study was conducted on patients with hematological malignancies. Music was used with the intervention group. Patients' pain, anxiety, and comfort levels were measured. In addition, qualitative data were obtained through in-depth interviews with patients. Results: A significant difference (p < 0.05) was found between the experimental and control groups regarding pain, comfort and anxiety levels following the application of music. It was found that there was a negative correlation between comfort and pain (r=-0.442 p < 0.001) and between comfort and anxiety (r=-0.544 p < 0.001). As a result of qualitative interviews, patients mentioned the relaxing effect of music and the reduction of anxiety and pain levels. They also stated that music can be utilized as an alternative method. Conclusion: According to the results of the present study, music reduced the pain and anxiety levels of the patients in bone marrow aspiration and biopsy and increased their comfort levels. We can say that music can be used in the clinic as a non-pharmacological method for pain, anxiety and comfort. Clinical Trials Number: NCT05895357 (Date:08/06/2023). [ABSTRACT FROM AUTHOR]

Purpose: Literature suggests a dependency of the acoustic metrics, smoothed cepstral peak prominence (CPPS) and harmonics-to-noise ratio (HNR), on human voice loudness and fundamental frequency (F0). Even though this has been explained with different oscillatory patterns of the vocal folds, so far, it has not been specifically investigated. In the present work, the influence of three elicitation levels, calibrated sound pressure level (SPL), F0 and vowel on the electroglottographic (EGG) and time-differentiated EGG (dEGG) metrics hybrid open quotient (OQ), dEGG OQ and peak dEGG, as well as on the acoustic metrics CPPS and HNR, was examined, and their suitability for voice assessment was evaluated. Method: In a retrospective study, 29 women with a mean age of 25 years (± 8.9, range: 18–53) diagnosed with structural vocal fold pathologies were examined before and after voice therapy or phonosurgery. Both acoustic and EGG signals were recorded simultaneously during the phonation of the sustained vowels /ɑ/, /i/, and /u/ at three elicited levels of loudness (soft/comfortable/loud) and unconstrained F0 conditions. Results: A linear mixed-model analysis showed a significant effect of elicitation effort levels on peak dEGG, HNR, and CPPS (all p < .01). Calibrated SPL significantly influenced HNR and CPPS (both p < .01). Furthermore, F0 had a significant effect on peak dEGG and CPPS (p < .0001). All metrics showed significant changes with regard to vowel (all p < .05). However, the treatment had no effect on the examined metrics, regardless of the treatment type (surgery vs. voice therapy). Conclusions: The value of the investigated metrics for voice assessment purposes when sampled without sufficient control of SPL and F0 is limited, in that they are significantly influenced by the phonatory context, be it speech or elicited sustained vowels. Future studies should explore the diagnostic value of new data collation approaches such as voice mapping, which take SPL and F0 effects into account. [ABSTRACT FROM AUTHOR]