Search

Objective: Hemangioma is a common benign tumor in the head and neck. The therapeutic effect by conventional treatment was not very satisfactory. The purpose of this study is to explore the surgical strategy of low-temperature plasma radiofrequency in the treatment of hemangioma located in the nasal cavity, pharynx, and larynx. Methods: The clinical data of 29 cases with hemangioma in nasal cavity, pharynx, and larynx treated by low-temperature plasma radiofrequency ablation were retrospectively analyzed. The strategy of ablation before resection was performed for 16 cases of nasal capillary hemangioma. The other 13 cases of cavernous hemangioma in the pharynx and larynx were treated by the strategy of direct ablation. Results: All 29 patients underwent a successful operation with minimal intraoperative bleeding and no postoperative bleeding complications. There was no nasal septum perforation, dyspnea, dysphagia, dysphonia, or other complications. The patients were followed up for more than 3 years without recurrence. Conclusion: Low-temperature plasma radiofrequency is a practical, minimally invasive, and accurate method for treating hemangiomas in the nasal cavity, pharynx, and larynx. For capillary hemangiomas, the strategy of ablation before resection may be an effective way to reduce bleeding, and for cavernous hemangiomas, the strategy of direct ablation is a simple and efficient method. [ABSTRACT FROM AUTHOR]

Aim: To gain staff feedback on the implementation and impact of a novel ambulatory monitoring system to support coronavirus patient management on an isolation ward. Design: Qualitative service evaluation. Methods: Semi‐structured interviews were conducted with 15 multidisciplinary isolation ward staff in the United Kingdom between July 2020 and May 2021. Interviews were audio‐recorded, transcribed and analysed using thematic analysis. Findings: Adopting Innovation to Assist Patient Safety was identified as the overriding theme. Three interlinked sub‐themes represent facets of how the system supported patient safety. Patient Selection was developed throughout the pandemic, as clinical staff became more confident in choosing which patients would benefit most. Trust In the System described how nurses coped with discrepancies between the ambulatory system and ward observation machines. Finally, Resource Management examined how, once trust was built, staff perceived the ambulatory system assisted with caseload management. This supported efficient personal protective equipment resource use by reducing the number of isolation room entries. Despite these reported benefits, face‐to‐face contact was still highly valued, despite the risk of coronavirus exposure. Conclusion: Hospital wards should consider using ambulatory monitoring systems to support caseload management and patient safety. Patients in isolation rooms or at high risk of deterioration may particularly benefit from this additional monitoring. However, these systems should be seen as an adjunct to nursing care, not a replacement. Implications for the Profession and/or Patient Care: Nurses valued ambulatory monitoring as a means of ensuring the safety of patients at risk of deterioration and prioritizing their workload. Impact: The findings of this research will be useful to all those developing or considering implementation of ambulatory monitoring systems in hospital wards. Reporting Method: This manuscript follows the Consolidated criteria for Reporting Qualitative Research (COREQ) guidelines with inclusion of relevant SQUIRE guidelines for reporting quality improvement. Patient or Public Contribution: No Patient or Public Contribution. [ABSTRACT FROM AUTHOR]

Background: Helplines for post‐secondary students have emerged in the last decade to address the growing mental health needs and increasing help‐seeking of this population in ways that are responsive to their needs and preferences. However, there is no publicly available evidence of the effectiveness of helplines for post‐secondary students. Aims: This study evaluated the outcomes of Good2Talk, a helpline for post‐secondary students in Ontario, Canada, that offers professional counselling and information and referral services related to mental health, addictions and well‐being. Methods: In this cross‐sectional study, purposive sampling was used to recruit post‐secondary students who contacted Good2Talk between March 2016 and March 2020. Data were collected using post‐call questionnaires. Paired samples t‐tests and multinomial logistic regression analyses were used to analyse the data from 619 post‐secondary students. Results: Participants reported significant decreases in distress and increases in their ability to face their concern after contacting the helpline. Feeling understood and low pre‐call distress were significant predictors of low post‐call distress. Confidence in their abilities and having a better plan were significant predictors of high post‐call ability to face their concern. Age, gender and number of previous calls to the helpline were not significant predictors of positive outcomes. Most participants reported that they would recontact the helpline and recommend the helpline to a peer. Conclusion: The study indicates that counselling and information and referral services can be effective in reducing distress and increasing post‐secondary students' abilities to address their mental health concerns. [ABSTRACT FROM AUTHOR]

We examined the Life Model of residential care for trauma-affected foster youth with life-skill deficits. Staff interviews described implementation. The Community-Oriented Programs Environment Scale, completed by youth and staff, assessed the care environment. The Child Assessment of Needs and Strengths, the Life Assessment, and discharge data were available for 42 youth. Results from the COPES indicated moderate-high scores on relationship, personal growth, and system maintenance. Paired-samples t-tests showed improvements in functioning, behavioral/emotional needs, and strengths. RMANOVAs of the Life Assessment showed youth experienced growth in spirituality/culture, education, vocation, and overall development. Most youth discharged to family-based placements or independent living. [ABSTRACT FROM AUTHOR]

Currently, numerous population pharmacokinetic (popPK) models for methotrexate (MTX) have been published for estimating PK parameters and variability. However, it is unclear whether the accuracy of these models is sufficient for clinical application. The aim of this study is to evaluate published models and assess their predictive performance according to the standards of scientific research. A total of 237 samples from 74 adult patients who underwent high‐dose MTX (HDMTX) treatment at Shanghai Changzheng Hospital were collected. The software package NONMEM was used to perform an external evaluation for each model, including prediction‐based diagnosis, simulation‐based diagnosis, and Bayesian forecasting. The simulation‐based diagnosis includes normalized prediction distribution error (NPDE) and visual predictive check (VPC). Following screening, 7 candidate models suitable for external validation were identified for comparison. However, none of these models exhibited excellent predictive performance. Bayesian simulation results indicated that the prediction precision and accuracy of all models significantly improved when incorporating prior concentration information. The published popPK models for MTX exhibit significant differences in their predictive performance, and none of the models were able to accurately predict MTX concentrations in our data set. Therefore, before adopting any model in clinical practice, extensive evaluation should be conducted. [ABSTRACT FROM AUTHOR]

To manage the rising prevalence of type 2 diabetes mellitus, sustainable diabetes prevention programs are needed. In this study, a process evaluation was conducted to qualitatively understand perceived successes and challenges of a diabetes prevention program situated in the community. This study took place in the first year of a multiyear project. Semistructured interviews were conducted with a sample of women clients (n = 14) postprogram and trainers (n = 10) 9 months into program implementation. Interviews were audio-recoded, transcribed verbatim, and analyzed using a Template Approach. Data were first analyzed deductively into two categories that aligned with the study's purpose (successes and challenges). Second, an inductive analysis was used to understand program delivery processes within each category. Clients and trainers expressed (a) program successes related to recruitment strategy, outlook on making behavior changes, and communication style used within the program and (b) program challenges surrounding effort of learning and applying the communication strategy, usefulness of program applications and tools, and program fit. This evaluation provides practical implications and future directions for diabetes prevention programs, and has informed tailoring and expansion of the program of focus. Results demonstrate the success of motivational interviewing from both client and trainer perspectives and the impact of community partnerships to increase prediabetes awareness in the community. Overall, the program's diabetes prevention and behavior change strategies coupled with a client-centered approach facilitated women clients in making diet and exercise modifications. [ABSTRACT FROM AUTHOR]

An integrated medication management (IMM) model was implemented in a medical center ward to improve the delivery of clinical pharmaceutical services (CPSs). This model incorporated a ward-based clinical pharmacist who performed medication reconciliation and medication reviews. It was perceived to promote interprofessional collaboration between pharmacists and non-pharmacist healthcare professionals (NPHPs, including attending physicians, nurse practitioners, and registered nurses). This study aimed to evaluate the effects of the IMM on NPHPs' intentions to collaborate with pharmacists and understand the mechanism of the impact of the IMM on interprofessional collaboration. A sequential explanatory mixed methods design was employed in the study. Initially, a questionnaire was administered to assess the effects of the IMM on NPHPs' intentions to collaborate with pharmacists. The NPHPs' experiences with the IMM were then documented using semi-structured interviews with inductive thematic analysis. Fifty-eight NPHPs completed the questionnaire, and NPHPs from the intervention ward reported a higher intention to discuss patient-related medication issues with pharmacists, indicating collaboration. Eleven NPHPs were interviewed, and they stated having better working relationships with pharmacists, experiencing more effective CPSs, and noting improved communication with pharmacists. The integration of quantitative and qualitative findings demonstrates that the critical mechanism of the IMM in promoting collaborative relationships is to integrate pharmacists into medical practice, which familiarizes NPHPs with pharmacists' roles, improves communication, and enables pharmacists to identify NPHPs' needs. To summarize, allowing ward-based pharmacists to engage in medical teams on a regular basis appears vital for improving interprofessional teamwork. Furthermore, stakeholders aiming to promote CPS in their institutions should consider the needs and communication channels among NPHPs. [ABSTRACT FROM AUTHOR]

Introduction: With the purpose of supporting scientific professionals and helping them to better integrate the expertise of users in their work, a users' and relatives' panel (URP) was set up at the National Institute for Excellence in Health and Social Services in Quebec (INESSS), Canada for the social services and mental health directorate. URPs are advisory structures that mobilise the experiential knowledge of people affected by various issues. Objectives: The objective of this study is to assess from a diverse stakeholders' perceptions: (1) the experience of developing and implementing the URP within the context of an Agencies for Health Technology Assessment and Assessment of Social Services (AHTAASS), (2) the contribution of such a URP, (3) the challenges encountered and (4) the perspectives of improvement for the following years. Methodology: We conducted a qualitative descriptive evaluation study. Nineteen interviews were conducted: six with URP members and 13 with staff representatives. The documents related to the creation of the panel, the URP minutes summarising the discussions and the reports published during that period were collected and analysed. Following a preliminary round of data analysis, a debriefing meeting was conducted with a few participants to validate the results. Results: The panel was set up as part of the INESSS' desire to better integrate experiential knowledge into its recommendations. Twelve projects were presented to the panel on various themes. The URP enabled health professionals to consider dimensions they had not identified, to better integrate the experiential data collected from users into their work and to develop recommendations that made more sense to users. Panel members and INESSS professionals learned to work together, moving the working methods from consultation to collaboration and even coconstruction. Based on the panel's significant contribution, the INESSS decided to maintain it and to strengthen its place in its system to better integrate the experiential knowledge of users into its work. Conclusion: This research illustrates how AHTAASS can set up a URP composed exclusively of users, and how it can contribute and be evaluated. It shows that URPs are structures that value the sharing of experiential knowledge of its members, humanise decision‐making and give meaning to the work done by scientific professionals. Patient or Public Contribution: One patient–researcher has contributed to the preparation and writing of this manuscript. [ABSTRACT FROM AUTHOR]

Purpose: To investigate potential reasons for the mismatch between laboratory/ clinic-based sentence-in-noise performance and real-world listening abilities, we recently developed a corpus of natural, spontaneously spoken speech with three vocal effort levels (Everyday Conversational Sentences in Noise [ECOSiN]). Here, we examined the feasibility of using the ECO-SiN corpus for adaptive speech-in-noise testing, which might be a desirable format in certain situations (e.g., during a clinical visit). Method: Ten young, normal-hearing adults, along with 20 older adults with hearing loss participated in the study. Speech reception thresholds (SRTs) were obtained using ECO-SiN sentences, which were systematically compared to the SRTs obtained using traditional Bamford-Kowal-Bench-like sentences. Results: Results demonstrated the properties of the test compared favorably with those of a standard test based on scripted and clearly spoken sentences. Moreover, whereas normal-hearing listeners received a benefit from an increase in vocal effort, the participants with hearing loss showed a disbenefit that increased with increasing hearing loss. Conclusion: The adaptive version of the ECO-SiN test is feasible for research and clinical testing. [ABSTRACT FROM AUTHOR]

Background: Due to the increasing burden of life-limiting illnesses, the need for palliative care has increased. Nurses' palliative care competence is a vital factor in improving its accessibility. A reliable instrument is needed to measure nurses' competence in providing palliative care. Objective: Our aim was to translate and culturally adapt the Palliative Care Nursing Self-Competence Scale (PCNSC) into the Palliative Care Nursing Self-Competence Scale–Simplified Chinese (PCNSC-SC). Methods: Two cross-sectional studies were conducted after content validity had been confirmed during the instrument's translation and adaption. The convergent validity, construct validity, internal consistency, and homogeneity were evaluated in both the first and second studies. Test-retest reliability was assessed only in the first study. Clinical nurses who had a registered nurse qualification certificate and at least 12 months of work experience from a tertiary hospital in Hubei, China participated in the 2 studies. Results: The PCNSC-SC contains 8 dimensions and 34 items, based on goodness-of-fit indices and confirmatory factor analysis. The Cronbach's alpha of the PCNSC-SC was.984 and.990 in the 2 studies, respectively. The test-retest reliability of the PCNSC-SC after 2 weeks was.717. Conclusion: The PCNSC-SC can be used to evaluate perceived self-competence in palliative care of Chinese nurses with good reliability and validity. [ABSTRACT FROM AUTHOR]

Objectives: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are often accompanied by neuropsychiatric symptoms (NPS; e.g. depression/apathy/irritability) causing challenges for people living with dementia/caregivers and predicting worse disease progression. Accurately assessing NPS is critical to research on AD/MCI. However, there are limitations to both self-reports and clinician evaluations; the field often relies on informants to assess NPS. Informants' perception of NPS are influenced by disease and caregiver factors that may lead to biased assessments. We aimed to assess the relationship between participants self-reported affective states (valence/arousal) and informant-reported NPS. Methods: Data from a double-blinded intervention design (primarily testing neurostimulation's effect on NPS) were used to examine the relationship between participant-reported affective states and informant-reported NPS over 1 month. Forty participants (24 females) with MCI and NPS (mean age = 71.7, SD = 7) were enrolled along with informants (primarily spouses/partners) who regularly interact with participants. NPS assessment occurred weekly and at pre- and post-intervention, and participant-reported affective states were assessed at 14 timepoints. Results: Generalized Estimating Equations showed that participant levels of arousal, but not valence, were significantly related to corresponding informant-reported NPS at weekly (arousal: B= −0.59, SE = 0.27, Wald's χ2 = 4.61, p=.032; valence: B = 0.17, SE = 0.19, Wald's χ2 = 0.80, p=.37) and pre-/post- (arousal: B= −4.00, SE = 1.58, Wald's χ2 = 6.42, p=.011; valence: B= −3.34, SE = 1.80, Wald's χ2 = 3.43, p=.06) assessments. Conclusion: The findings indicate that informant-reported NPS may be more strongly influenced by arousal, and informants may be less attuned to valence in people living with MCI. [ABSTRACT FROM AUTHOR]

Considered investment in health and medical research (HMR) is critical for fostering a healthcare system that is sustainable, effective, responsive, and innovative. While several tools exist to measure the impact of research, few assess the research environment that nurtures and supports impactful research and the strategic alignment of research with societal needs. This perspective article discusses the limitations of existing assessment tools and presents a novel Research Impact Assessment Framework designed to enable more strategic and targeted investment towards HMR, having the potential for significant public benefit. [ABSTRACT FROM AUTHOR]

Assessment of interprofessional education (IPE) frequently focuses on students' learning outcomes including changes in knowledge, skills, and/or attitudes. While a foundational education in the values and information of their chosen profession is critical, interprofessional learning follows a continuum from formal education to practice. The continuum increases in significance and complexity as learning becomes more relationship based and dependent upon the ability to navigate complex interactions with patients, families, communities, co-workers, and others. Integrating IPE into collaborative practice is critical to enhancing students' experiential learning, developing teamwork competencies, and understanding the complexity of teams. This article describes a project that linked students with a hospital-based quality-improvement effort to focus on the acquisition and practice of teamwork skills and to determine the impact of teamwork on patient and quality outcome measures. A hospital unit was identified with an opportunity for improvement related to quality care, patient satisfaction, employee engagement, and team behaviours. One hundred and thirty-seven students from six health profession colleges at the Medical University of South Carolina underwent TeamSTEPPS® training and demonstrated proficiency of their teamwork-rating skills with the TeamSTEPPS® Team Performance Observation Tool (T-TPO). Students observed real-time team behaviours of unit staff before and after staff attended formal TeamSTEPPS® training. The students collected a total of 778 observations using the T-TPO. Teamwork performance on the unit improved significantly across all T-TPO domains (team structure, communication, leadership, situation monitoring, and mutual support). Significant improvement in each domain continued post-intervention and at 15-month follow-up, improvement remained significant compared to baseline. Student engagement in TeamSTEPPS® training and demonstration of their reliability as teamwork-observers was a valuable learning experience and also yielded an opportunity to gather unique, and otherwise difficult to attain, data from a hospital unit for use by quality managers and administrators. [ABSTRACT FROM AUTHOR]

Background: Adults with intellectual disabilities often display behaviour that challenges that is a result of biological differences, psychological challenges, and lack of appropriate social support. Intensive Support Teams (IST) are recommended to support the care needs of this group and avoid hospitalisation. However, little attention has been paid to the perspectives of stakeholders who manage, work in, or use ISTs. Method: Interviews and focus groups were conducted with 50 stakeholders (IST service managers and professionals, adults with intellectual disabilities, and family and paid carers) of ISTs. Services operated according to one of two service models previously identified in ISTs in England (enhanced or independent). Results: Thematic analysis identified accessible and flexible support, individualised care, and the involvement of carers and other relevant agencies in management plans and reviews as features of good IST care highlighted by all stakeholder groups. IST managers and professionals described the key challenges of current IST provision as unclear referral criteria, limited interfaces with other local services, and perceived threats associated with funding and staff retention. Findings were similar between the two IST models. Conclusions: ISTs are able to offer care and specialist support that is valued by families, service users and other care providers. However, they face several operational challenges that should be addressed if ISTs are to reach their potential along with community intellectual disability services in supporting adults with intellectual disabilities who display behaviour that challenges in the community. [ABSTRACT FROM AUTHOR]

Sex therapy patients report high rates of childhood interpersonal trauma (CIT) and insecure attachment, which may negatively influence the quality of their alliance with the therapist. Poor therapeutic alliance is associated with weaker progress during treatment. However, the effect of CIT, attachment and alliance on progress in therapy has not yet been documented in patients consulting for sexual difficulties. With a pre and post-test design, a total of 74 adults (39 women; 35 men) seeking sex therapy completed questionnaires assessing CIT, attachment representations, and therapeutic alliance. The main outcome measure was evolution of sexual satisfaction over the course of therapy. Results showed that, on average, patients experienced an improvement in their sexual satisfaction. Patients showing the largest improvement reported less attachment anxiety and higher levels of therapeutic alliance at pre-test. Furthermore, although participants reporting four or more types of CIT showed lower sexual satisfaction at pre-test, they reached a level similar to patients with less CIT at post-test, and thus, they demonstrated the greatest level of improvement. These findings support the beneficial effect of sex therapy for patients with a CIT history, and that, with a strong therapeutic relationship and attachment, all patients can develop a more positive and enjoyable sexuality. [ABSTRACT FROM AUTHOR]

Background: The adoption of digital health technologies can improve the quality of care for polypharmacy patients, if the underlying complex implementation mechanisms are better understood. Context effects play a critical role in relation to implementation mechanisms. In primary care research, evidence on the effects of context in the adoption of digital innovation for polypharmacy management is lacking. Study aim: This study aims to identify contextual factors relevant to physician behavior and how they might mediate the adoption process. Methods: The physicians who participated in this formative evaluation study (n = 218) were part of the intervention group in a cluster-randomized controlled trial (AdAM). The intervention group implemented a digital innovation for clinical decision making in polypharmacy. A three-step methodological approach was used: (1) a realist inquiry approach, which involves the description of a context-mechanism-outcome configuration for the primary care setting; (2) a belief elicitation approach, which involves qualitative content analysis and the development of a quantitative latent contextualized scale; and (3) a mediation analysis using structural equation modeling (SEM) based on quantitative survey data from physicians to assess the mediating role of the contextualized scale (n = 179). Results: The key dimensions of a (1) context-mechanism-outcome model were mapped and refined. A (2) latent construct of the physicians' innovation beliefs related to the effectiveness of polypharmacy management practices was identified. Innovation beliefs play a (3) mediating role between the organizational readiness to implement change (p < 0.01) and the desired behavioral intent of physicians to adopt digital innovation (p < 0.01; R2 = 0.645). Our contextualized model estimated significant mediation, with a relative size of 38% for the mediation effect. Overall, the model demonstrated good fit indices (CFI = 0.985, RMSEA = 0.034). Conclusion: Physician adoption is directly affected by the readiness of primary care organizations for the implementation of change. In addition, the mediation analysis revealed that this relationship is indirectly influenced by primary care physicians' beliefs regarding the effectiveness of digital innovation. Both individual physician beliefs and practice organizational capacity could be equally prioritized in developing implementation strategies. The methodological approach used is suitable for the evaluation of complex implementation mechanisms. It has been proven to be an advantageous approach for formative evaluation. Trial registration: NCT03430336. First registration: 12/02/2018. ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Background: Maternal healthcare service is the care given for the woman during her gestation, delivery and postpartum period. The Maternal Mortality Ratio (MMR) was remains high and a public health problem in Ethiopia. Sub-Saharan African (SSA) countries account two-thirds of the global total maternal deaths. To curb such high burden related with child births, comprehensive emergency obstetric care is designed as one of the strategies for maternal healthcare services. However, its implementation status was not well investigated. This study aims to evaluate the implementation of comprehensive emergency obstetric and new born care program in terms of Availability, compliance and acceptability dimensions at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. Methods: A single case study design was employed from 01 to 30 April 2021. A total of 265 mothers who gave birth at University of Gondar Comprehensive Specialized Hospital (UoGCSH) during the data collection period for acceptability, 13 key informant interviews (KIIs), 49 non-participatory observations (25 observations during C/S performance and 24 assisted spontaneous vaginal deliver) and 320 retrospective document review were conducted. Availability, compliance and acceptability dimensions were evaluated using 32 indicators. Binary logistic regression model was fitted to identify factors associated with acceptability of the services. Adjusted Odds Ratio (AOR) with 95% confidence interval (CI) and p-value < 0.05 were also used to identify associated variables with acceptability. The qualitative data were recorded using tape recorder, transcribed in Amharic and translated to English language. Thematic analysis was done to supplement the quantitative findings. Results: The overall implementation of comprehensive emergency obstetric and newborn care (CEmONC) was 81.6%. Moreover, acceptability, availability and care provider's compliance with the guideline accounted 81, 88.9 and 74.8%, respectively. There were stocked-out of some essential drugs, such as methyldopa, nifidipine, gentamycin and vitamin K injection. CEmONC training gaps, inadequate number of autoclaves, shortage of water supply and long-distance delivery ward to laboratory unit were also the barriers for the CEmONC service. Short waiting time of clients (AOR = 2.40; 95%CI: 1.16, 4.90) and maternal educational level (AOR = 5.50, 95%CI: 1.95, 15.60) were positively associated with acceptability of CEmONC services. Conclusion: The implementation status of CEmONC program was good as per our judgment parameter. Compliance of healthcare providers with the guideline was fair and needed improvement. Essential emergency drugs, equipment and supplies were stocked-out. The University of Gondar Comprehensive Specialized Hospital was therefore had better to give great emphasis to expand maternity rooms/ units. The hospital had better to avail the resources and provide continuous capacity building for healthcare providers to enhance the program implementation. Plain Language Summary: Maternal healthcare service is the care given for the woman during her gestation, delivery and postpartum period. The Maternal Mortality Ratio (MMR) was remains high and a public health problem in Ethiopia. Sub-Saharan African (SSA) countries account two-thirds of the total global maternal deaths. To curb such high burden related with child births, comprehensive emergency management obstetric and newborn care is designed as one of the strategies for maternal healthcare services. The implementation status of CEmONC program service at University of Gondar comprehensive specialized hospital was good as per the preset judgment parameter. Unavailability of resources such as delivery couch, operational table, maternity and labor ward beds, glove, gauze, blood, vital sign instruments, and essential drugs including methyldopa, nifidipine, gentamycin, and vitamin K were stocked out and the challenges to provide CEmONC services. Healthcare providers' compliance with the implementation protocol were also fairly affected. Moreover, acceptability CEmONC service was also judged as good as per the judgmental evaluation parameter. Hospital had better to fulfil the necessary equipment and drugs to enhance the implementation status of the hospitals. Capacity building of healthcare providers might also a better strategy to improve the compliance. Strengthening awareness creation for women and their husbands had a paramount importance to enhance the acceptability of the services. [ABSTRACT FROM AUTHOR]

In this systematic evaluation of intervention research for transition-age autistic youth, we examined quality indicators in 193 group and single-case design intervention studies, which tested effects on 1258 outcomes. Behaviorally based interventions were the most common intervention type. We found significant threats to internal validity for the majority of studies, including inadequate randomization, unmasked assessors, and too few data points to infer functional relations. The majority of outcomes were measured in contexts similar to the intervention and were conceptualized as behaviors directly addressed by intervention procedures. As such, they are of unclear long-term utility for autistic people entering adulthood. Adverse events were rarely reported. We suggest several avenues for improving intervention research for this age group. In this study, we assess the quality of intervention research that focuses on autistic youth who are 14–22 years old. We found 193 different studies on this topic, and carefully reviewed them. Most of these studies tested strategies that were behavioral. This means that they used procedures like prompting and rewards to change participants' behavior. We found that the majority of studies had problems that make it hard to determine whether or not the intervention worked. The problems related to how researchers designed their studies, and how they measured the study outcomes. We also found that researchers rarely tried to find out if the strategies they studied had unintended negative effects for participants. Because of these issues, we make suggestions for how researchers might design better studies that will let people know how well the strategies worked. [ABSTRACT FROM AUTHOR]

Introduction: Involving service users in health service design and delivery is considered important to improve the quality of healthcare because it ensures that the delivery of healthcare is adapted to the needs of the users. Co‐production is a process used to involve service users, but multiple papers have highlighted the need for the mechanisms and values guiding co‐production to be more clearly stated. The aim of this paper was to evaluate the mechanisms and values that guided the co‐production approach of the Stories for Change project, which used Public Narrative as part of the co‐design process to create change in National Health Service maternity services. Methods: This study was conducted using a rapid feedback evaluation approach. Semistructured interviews (n = 16) were the main source of data, six of which were maternity service users, with observations (5 h) and documentary analysis also carried out in parallel. RREAL sheets were used for data analysis to organize data based on key topics of interest. Results: This study identified three broad mechanisms and values underpinning the co‐production approach: creating an open and safe space to share ideas, learning how to tell stories using Public Narrative and having service providers who play a key role in strengthening the health system listen to stories compelling them to action. This study identified the main areas for improvement of the Stories for Change project related to recruitment, the inclusion of participants, the co‐design process, the Skills Session and the Learning Event. Conclusion: Our study provided a deeper understanding of the co‐production approach that addresses the need to uncover the mechanism and values underlying co‐production and co‐design approaches. This study expands on the literature pertaining to the influence of storytelling in creating meaningful change in health care. We propose a co‐design methodology that uses Public Narrative as a model for service user engagement to help inform future healthcare development processes. Patient or Public Contribution: The experiences and perceptions of maternity service users and health professionals informed this evaluation. The project organizers were involved in the manuscript preparation stage by providing feedback, and service users wrote a commentary on the project from the lived experience perspective. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine has analgesic properties, but the intraoperative analgesic effect of dexmedetomidine is often masked by the effects of other general anaesthetics. Therefore, the degree to which it reduces intraoperative pain intensity remains unclear. The objective of this double-blind, randomised controlled trial was to evaluate the independent intraoperative analgesic efficacy of dexmedetomidine in real-time. Methods: This single-centre study enrolled 181 patients who were hospitalised for below-knee orthopaedic surgeries between 19 January 2021 to 3 August 2021 were eligible for this is single-centre study. Peripheral neural block was performed on patients scheduled for below-knee orthopaedic surgeries. Patients were randomly assigned to the dexmedetomidine or midazolam group and were intravenously administered with 1.5 µg kg−1 h−1 dexmedetomidine or 50 µg kg−1 h−1 midazolam, respectively. The analgesic efficacy was evaluated using the real-time non-invasive nociception monitoring. The primary endpoint was the attainment rate of the nociception index target. The secondary endpoints included the occurrence of intraoperative hypoxemia, haemodynamic parameters, the consciousness index, electromyography and patient outcomes. Results: On Kaplan–Meier survival analysis, the defined nociception index target was attained in 95.45% and 40.91% of patients receiving dexmedetomidine and midazolam, respectively. Log-rank analysis revealed that the dexmedetomidine group attained the nociception index target significantly faster and the median attainment time of the nociception index target in the dexmedetomidine group was 15 min. Dexmedetomidine group was associated with a significantly lower incidence of hypoxemia. There was no significant difference in blood pressure between the dexmedetomidine and midazolam groups. Further, the dexmedetomidine group had a lower maximum visual analogue scale score and lower analgesic consumption postoperatively. Conclusions: Dexmedetomidine has independent analgesia and systemically administered as an adjuvant agent has better analgesic efficacy than midazolam without severe side effects. Trial registration: clinicaltrial.gov Registry Identifier: NCT-04675372.Registered on 19/12 /2020. [ABSTRACT FROM AUTHOR]

Background: Compassionate Communities have been put forward as a new model for community-based palliative care to positively impact the health and wellbeing of those experiencing challenges of serious illness, death, dying, and loss. Despite the growing international movement to develop these public health initiatives to end-of-life care, only a handful of initiatives have undergone some form of evaluation. Aim: To provide guidance on designing evaluation research by identifying theoretical frameworks to understand the development, implementation, and underlying mechanisms of Compassionate Communities. Methods: To identify suitable theoretical frameworks for the study of Compassionate Communities, we applied two steps. The first step examined the characteristics of Compassionate Communities and translated them into assessment criteria for the selection of theoretical frameworks. The second step consisted of applying the identified assessment criteria to a list of widely used and highly cited theoretical frameworks. Results: Three well-established theoretical frameworks were identified as being most suitable to study the development, implementation, and underlying mechanisms of Compassionate Communities: The Consolidated Framework for Implementation Research (CFIR), the integrated-Promoting Action on Research Implementation in Health Services framework (i-PARIHS), and the Extended Normalization Process Theory (ENPT). Conclusions: The article supports and encourages the use of theoretical frameworks to evaluate the complex processes behind public health palliative care initiatives. The complementary use of two determinant frameworks and an implementation theory provides theoretical grounding to gain rich insights into the emergent and shifting interplays between agency, social processes, and contextual factors that shape the development and implementation of Compassionate Communities. [ABSTRACT FROM AUTHOR]

Over the last decades, the negative effects of intimate partner violence (IPV) directed at men in abusive different-sex and same-sex relationships have been increasingly investigated. Men who are the targets of IPV face many barriers to help-seeking, and to overcome them, public awareness campaigns have been developed. Women who experienced IPV have found campaigns targeting them to be harmful and misleading, and previous research suggests that following the principles of formative evaluation research may improve campaigns' effectiveness and reduce unwanted negative effects. This article documents the theory-based formative evaluation research conducted with 14 men abused in different-sex and same-sex relationships for the creation of targeted campaigns. Through semi-structured interviews, men were asked about their overall knowledge of campaigns, their thoughts about specific pictorial IPV campaigns, and their suggestions for the development of new campaigns. Thematic analysis and a theoretically grounded coding scheme were used to analyze the content of the interviews with high interrater reliability. Overall, our results indicate that most men were not aware of campaigns in Portugal, and their impressions about the ones they recalled were mixed. Most men praised clear messages informing forms of violence, while some responded negatively to the inclusion of words such as "shame" and "victim" and the depiction of bruises. They also considered that future campaigns targeting men should portray "real people" like them and provide information on self-efficacy, the efficacy of recommended responses, and threat susceptibility. Our findings are consistent with previous evidence with women who experienced IPV but also provide theoretically grounded novel contributions and highlight the importance of considering the population of interest's insights when developing and testing new campaigns. [ABSTRACT FROM AUTHOR]

Background: Universal mental health screening and psychosocial assessment during pregnancy have been recommended as best practice, but uptake of universal programs in the private hospital system has been slow. Aim: The aim of this study was to evaluate the Pre‐admission Midwife Appointment Program (PMAP), an antenatal mental health screening program at the Mater Hospital, Sydney. Materials and Methods: In this mixed‐methods design study, PMAP interview data were collected for a consecutive series of 485 women who attended the PMAP during a 10‐month period. Women also completed two postnatal telephone interviews (10 weeks and 9 months postpartum). The interviews involved depression screening and questions about the program. Results: Of the 485 participants, 4.1% screened positive for depression on the Edinburgh Postnatal Depression Scale. In total, 19% were identified as currently suffering from, or at risk of developing, perinatal mental health issues; referrals to support services were provided for the 13% who were not already linked in with appropriate supports. All women displayed a decrease in depressive symptom severity from pregnancy to 10 weeks and 9 months postpartum. The PMAP was viewed positively by consumers, with >93% viewing the program as helpful and >98% saying that they would recommend the program to others. Additional program benefits identified included opportunities to gain practical information and prepare for motherhood and to think/reflect on their emotional well‐being. Conclusions: Given the observed rates of psychosocial risk among this sample, related referral opportunities and positive consumer feedback, we recommend other Australian private hospitals consider implementing PMAP or similar programs. [ABSTRACT FROM AUTHOR]

Objective: To describe the development of a web-based, theory-guided narrative intervention that replaces conventional pre-test genetic counseling for women at elevated breast cancer risk.Methods: We used an iterative process that was guided by health behavior theory and feedback from multiple stakeholder groups including: 1) content input from genetic experts; 2) study team input; 3) review of video storyboards, video example, study logo, recruitment materials, post-test patient preference counseling survey, and additional study surveys; 4) video series development; and 5) intervention review and finalization of study-related materials.Results: The intervention is patient-centered providing convenience and an opportunity for an individual's preferences for post-test counseling delivery. The intervention's efficacy is being determined in a randomized controlled trial compared to conventional genetic counseling for adherence to recommended guidelines and changes in knowledge, perception of breast cancer risk, breast cancer-specific worry, and satisfaction with counseling.Conclusion: If efficacious, the intervention may improve the delivery of the genetic testing and counseling process, inform best practices, and reduce the genetic counseling workforce burden.Practice Implications: The developed intervention has the potential to improve the genetic testing and counseling experience for women at elevated risk for breast cancer, inform best practices, and reduce genetic counseling workforce burden. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate whether calcitriol supplementation enhances CD4+ T cell count and prognosis in patients with tuberculosis and low 25(OH)D levels.Methods: This randomized controlled clinical trial enrolled treatment-naïve patients with tuberculosis admitted to Zigong First People's Hospital (June 2016 to April 2017). The patients were grouped as the serum 25(OH)D ≥ 75 nmol/L (Normal-25(OH)D) and 25(OH)D < 75 nmol/L (Low-25(OH)D) groups. The Low-Vit-D group was randomized to the Low-25(OH)D and Low-25(OH)D-Calcitriol groups. All patients were treated with the 2HRZE/4HR regimen. The patients in the Low-25(OH)D-Calcitriol group received calcitriol 0.25 µg bid. The main endpoints were CD4+ T cell count during treatment, time to sputum culture conversion, time to 50% lesion absorption, and a 6-month cure rate.Results: This study included 30 patients in each group. Baseline 25-(OH) D levels and CD4+ T cell counts were higher in the Normal-25(OH)D group than in the Low-25(OH)D and Low-25(OH)D-Calcitriol groups (25(OH)D: 79.3 ± 3.4 vs. 37.8 ± 13.4 vs. 11.9 nmol/L, P < 0.05; 671 ± 287 vs. 200 ± 110 vs. 194 ± 119 cell/µL, P < 0.05). 25-(OH) D levels and CD4+ T cell counts increased in the Low-25(OH)D-Calcitriol group during treatment to reach higher levels than in the Low-25(OH)D group at 1, 4, 8, and 24 weeks (all P < 0.05). Compared with the Low-25(OH)D group, the Low-25(OH)D-Calcitriol group showed shorter time to sputum culture conversion (3.2 ± 1.4 vs. 5.9 ± 2.5 days, P < 0.001) and time to 50% lesion absorption (7.4 ± 1.5 vs. 10.9 ± 4.0 days, P = 0.014) and similar to those in the Normal-25(OH)D group (3.1 ± 1.2 and 7.3 ± 1.5 days, respectively. The cure rate was 86.7% in the Low-25(OH)D group and 96.7% in the two other groups.Conclusions: Calcitriol supplementation can elevate CD4+ T cell levels, shorten the time to sputum culture conversion, and accelerate lesion absorption in patients with tuberculosis and 25(OH)D deficiency. Trial registration The study is registered at the Chinese Clinical Trial Registry (ChiCTR2000039832). [ABSTRACT FROM AUTHOR]

Background: Teens with attention deficit-hyperactivity disorder (ADHD) are at increased risk for motor vehicle collisions. A computerized skills-training program to reduce long glances away from the roadway, a contributor to collision risk, may ameliorate driving risks among teens with ADHD.Methods: We evaluated a computerized skills-training program designed to reduce long glances (lasting ≥2 seconds) away from the roadway in drivers 16 to 19 years of age with ADHD. Participants were randomly assigned in a 1:1 ratio to undergo either enhanced Focused Concentration and Attention Learning, a program that targets reduction in the number of long glances (intervention) or enhanced conventional driver's education (control). The primary outcomes were the number of long glances away from the roadway and the standard deviation of lane position, a measure of lateral movements away from the center of the lane, during two 15-minute simulated drives at baseline and at 1 month and 6 months after training. Secondary outcomes were the rates of long glances and collisions or near-collisions involving abrupt changes in vehicle momentum (g-force event), as assessed with in-vehicle recordings over the 1-year period after training.Results: During simulated driving after training, participants in the intervention group had a mean of 16.5 long glances per drive at 1 month and 15.7 long glances per drive at 6 months, as compared with 28.0 and 27.0 long glances, respectively, in the control group (incidence rate ratio at 1 month, 0.64; 95% confidence interval [CI], 0.52 to 0.76; P<0.001; incidence rate ratio at 6 months, 0.64; 95% CI, 0.52 to 0.76; P<0.001). The standard deviation of lane position (in feet) was 0.98 SD at 1 month and 0.98 SD at 6 months in the intervention group, as compared with 1.20 SD and 1.20 SD, respectively, in the control group (difference at 1 month, -0.21 SD; 95% CI, -0.29 to -0.13; difference at 6 months, -0.22 SD; 95% CI, -0.31 to -0.13; P<0.001 for interaction for both comparisons). During real-world driving over the year after training, the rate of long glances per g-force event was 18.3% in the intervention group and 23.9% in the control group (relative risk, 0.76; 95% CI, 0.61 to 0.92); the rate of collision or near-collision per g-force event was 3.4% and 5.6%, respectively (relative risk, 0.60, 95% CI, 0.41 to 0.89).Conclusions: In teens with ADHD, a specially designed computerized simulated-driving program with feedback to reduce long glances away from the roadway reduced the frequency of long glances and lessened variation in lane position as compared with a control program. During real-world driving in the year after training, the rate of collisions and near-collisions was lower in the intervention group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02848092.). [ABSTRACT FROM AUTHOR]

Background: Renin-angiotensin system (RAS) inhibitors - including angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) - slow the progression of mild or moderate chronic kidney disease. However, the results of some studies have suggested that the discontinuation of RAS inhibitors in patients with advanced chronic kidney disease may increase the estimated glomerular filtration rate (eGFR) or slow its decline.Methods: In this multicenter, open-label trial, we randomly assigned patients with advanced and progressive chronic kidney disease (eGFR, <30 ml per minute per 1.73 m2 of body-surface area) either to discontinue or to continue therapy with RAS inhibitors. The primary outcome was the eGFR at 3 years; eGFR values that were obtained after the initiation of renal-replacement therapy were excluded. Secondary outcomes included the development of end-stage kidney disease (ESKD); a composite of a decrease of more than 50% in the eGFR or the initiation of renal-replacement therapy, including ESKD; hospitalization; blood pressure; exercise capacity; and quality of life. Prespecified subgroups were defined according to age, eGFR, type of diabetes, mean arterial pressure, and proteinuria.Results: At 3 years, among the 411 patients who were enrolled, the least-squares mean (±SE) eGFR was 12.6±0.7 ml per minute per 1.73 m2 in the discontinuation group and 13.3±0.6 ml per minute per 1.73 m2 in the continuation group (difference, -0.7; 95% confidence interval [CI], -2.5 to 1.0; P = 0.42), with a negative value favoring the outcome in the continuation group. No heterogeneity in outcome according to the prespecified subgroups was observed. ESKD or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). Adverse events were similar in the discontinuation group and continuation group with respect to cardiovascular events (108 vs. 88) and deaths (20 vs. 22).Conclusions: Among patients with advanced and progressive chronic kidney disease, the discontinuation of RAS inhibitors was not associated with a significant between-group difference in the long-term rate of decrease in the eGFR. (Funded by the National Institute for Health Research and the Medical Research Council; STOP ACEi EudraCT number, 2013-003798-82; ISRCTN number, 62869767.). [ABSTRACT FROM AUTHOR]

Objective: Binge-eating disorder, the most prevalent eating disorder, is a serious public health problem associated with obesity, psychiatric and medical comorbidities, and functional impairments. Binge-eating disorder remains underrecognized and infrequently treated, and few evidence-based treatments exist. The authors tested the effectiveness of naltrexone-bupropion and behavioral weight loss therapy (BWL), alone and combined, for binge-eating disorder comorbid with obesity.Methods: In a randomized double-blind placebo-controlled trial conducted from February 2017 to February 2021, using a 2×2 balanced factorial design, 136 patients with binge-eating disorder (81.6% women; mean age, 46.5 years; mean BMI, 37.1) were randomized to one of four 16-week treatments: placebo (N=34), naltrexone-bupropion (N=32), BWL+placebo (N=35), or BWL+naltrexone-bupropion (N=35). Overall, 81.7% of participants completed independent posttreatment assessments.Results: Intention-to-treat binge-eating remission rates were 17.7% in the placebo group, 31.3% in the naltrexone-bupropion group, 37.1% in the BWL+placebo group, and 57.1% in the BWL+naltrexone-bupropion group. Logistic regression of binge-eating remission revealed that BWL was significantly superior to no BWL, and that naltrexone-bupropion was significantly superior to placebo, but there was no significant interaction between BWL and medication. Mixed models of complementary measures of binge-eating frequency also indicated that BWL was significantly superior to no BWL. The rates of participants attaining 5% weight loss were 11.8% in the placebo group, 18.8% in the naltrexone-bupropion group, 31.4% in the BWL+placebo group, and 38.2% in the BWL+naltrexone-bupropion group. Logistic regression of 5% weight loss and mixed models of percent weight loss both revealed that BWL was significantly superior to no BWL. Mixed models revealed significantly greater improvements for BWL than no BWL on secondary measures (eating disorder psychopathology, depression, eating behaviors, and cholesterol and HbA1c levels).Conclusions: BWL and naltrexone-bupropion were associated with significant improvements in binge-eating disorder, with a consistent pattern of BWL being superior to no BWL. [ABSTRACT FROM AUTHOR]

Objective: Intravenous ketamine, which displays rapid antidepressant properties, is posited to reverse depression by rapidly enhancing neuroplasticity. The authors tested whether an automated, computer-based approach could efficiently leverage enhanced neuroplasticity to extend the durability of rapid clinical response.Methods: A total of 154 adults (ages 18-60) with treatment-resistant unipolar depression were randomized in a double-blind, parallel-arm design to receive an active/active treatment combination (ketamine plus active "automated self-association training" [ASAT]; N=53) or one of two control arms that lacked either the active drug component (saline plus active ASAT; N=51) or the active behavioral component (ketamine plus sham ASAT; N=50). One day after a single infusion of intravenous ketamine (0.5 mg/kg over 40 minutes) or inert placebo (saline), active ASAT-targeting self-worth through automated "evaluative conditioning" training delivered by computer-or sham ASAT (consisting of identical computer tasks that included no positive or self-referential stimuli) was given, delivered twice daily over 4 consecutive days (eight sessions, ≤20 minutes per session). The prespecified primary outcome measure throughout the main (30-day) study period was score on the Montgomery-Åsberg Depression Rating Scale (MADRS).Results: Ketamine rapidly and significantly reduced depression scores at 24 hours postinfusion (group-by-time interaction: standardized beta [β]=-1.30, 95% CI=-1.89, -0.70; t=-4.29, df=150). In intent-to-treat linear mixed models, depression scores in the ketamine+ASAT group remained significantly and stably low over the 30-day study period relative to those of the saline+ASAT group (β=-0.61, 95% CI=-0.95, -0.28; t=-3.62, df=148). By contrast, depression scores following ketamine+sham treatment followed a significant, increasing linear trajectory from 24 hours to 30 days, approaching the levels observed in the saline+ASAT group (group-by-time interaction relative to the saline+ASAT group: β=0.015, 95% CI=0.003, 0.03; t=2.35, df=568).Conclusions: After priming the brain with ketamine, training positive self-associations could provide an efficient, low-cost, portable, noninvasive, and highly dissemination-ready strategy for leveraging and extending ketamine's rapid antidepressant effects. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we explored chronic airways disease (CAD) patients' responses to health literacy (HL) communication domain questions within disease self-management scenarios, as part of a larger CAD HL measurement tool development study.Methods: Adult asthma and chronic obstructive pulmonary disease (COPD) patients from specialty care respiratory clinics were initially presented with realistic disease management scenarios and asked to share information they would communicate. Participants' responses were grouped into response categories that were reviewed and verified by key informants. A new cohort of CAD patients then responded to the same scenarios and had their answers placed into the developed response categories by trained interviewers.Results: 19 initial stage participants' responses informed response categories for the following self-management topics: Inhaler Use (n = 20); Prednisone Use (n = 30); Flu (Influenza) (n = 35); and Weather Forecasting & Air Quality Index (n = 29). 141 participants' responses were categorised during the second stage.Conclusions: Specialty care CAD patients displayed an understanding of key information to communicate across disease self-management topic. Our two-step, patient-driven approach may interest researchers investigating health-related communication from patients' perspectives.Practice Implications: Findings may illuminate potential areas to investigate communication gaps among CAD patients; further investigation is warranted among non-specialty care patients. [ABSTRACT FROM AUTHOR]

Objective: To examine the Curriculum of England's Personalised Care Institute as a national initiative to promote person-centred practice.Method: Analysis of Curriculum content and discourse RESULTS: The Curriculum describes an educational framework which aspires to unify approaches and universalize provision of Personalised Care. It presents 8 "models and approaches" and 6 "components" within the "whole" of Personalised Care. It locates their unity in an underlying common core repertoire of professional capabilities and values and an anchoring belief in people's strengths, resourcefulness and ability to develop their own solutions with appropriate support. The Curriculum indicates some complexity in the provision of Personalised Care but leaves unanswered questions about the theoretical coherence of the concept. It also neglects some important aspects of person-centredness (especially values beyond empowerment and choice); the implications of entrenched social inequalities and systemic prejudices; and other practical-ethical implementation challenges that can be difficult for health professionals.Conclusion: The Curriculum signals a national commitment to person-centred practice, but its practical potential is limited by its neglect of the value tensions and diverse situational challenges involved.Practice Implications: The Curriculum and similar policy-education initiatives could be strengthened by more explicit attention to the normative complexities of person-centred practice. [ABSTRACT FROM AUTHOR]

Investigators of previous cross-sectional epigenome-wide association studies (EWAS) in adults have reported hundreds of 5'-cytosine-phosphate-guanine-3' (CpG) sites associated with type 2 diabetes mellitus (T2DM) and glycemic traits. However, the results from EWAS have been inconsistent, and longitudinal observations of these associations are scarce. Furthermore, few studies have investigated whether DNA methylation (DNAm) could be modified by smoking, drinking, and glycemic traits, which have broad impacts on genome-wide DNAm and result in altering the risk of T2DM. Twin studies provide a valuable tool for epigenetic studies, as twins are naturally matched for genetic information. In this study, we conducted a systematic literature search in PubMed and Embase for EWAS, and 214, 33, and 117 candidate CpG sites were selected for T2DM, HbA1c, and fasting blood glucose (FBG). Based on 1,070 twins from the Chinese National Twin Registry, 67, 17, and 16 CpG sites from previous studies were validated for T2DM, HbA1c, and FBG. Longitudinal review and blood sampling for phenotypic information and DNAm were conducted twice in 2013 and 2018 for 308 twins. A cross-lagged analysis was performed to examine the temporal relationship between DNAm and T2DM or glycemic traits in the longitudinal data. A total of 11 significant paths from T2DM to subsequent DNAm and 15 paths from DNAm to subsequent T2DM were detected, suggesting both directions of associations. For glycemic traits, we detected 17 cross-lagged associations from baseline glycemic traits to subsequent DNAm, and none were from the other cross-lagged direction, indicating that CpG sites may be the consequences, not the causes, of glycemic traits. Finally, a longitudinal mediation analysis was performed to explore the mediation effects of DNAm on the associations of smoking, drinking, and glycemic traits with T2DM. No significant mediations of DNAm in the associations linking smoking and drinking with T2DM were found. In contrast, our study suggested a potential role of DNAm of cg19693031, cg00574958, and cg04816311 in mediating the effect of altered glycemic traits on T2DM. [ABSTRACT FROM AUTHOR]

Background: Preoperative chemoradiotherapy (CRT) with CROSS regimen has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to preoperative CRT may further improve oncologic results. Preoperative camrelizumab plus chemotherapy has been demonstrated as a promising treatment modality based on results of the phase II NICE study (ChiCTR1900026240).Methods: The NICE-2 study is designed as a three-arm, multicenter, prospective, randomized, phase II clinical trial, comparing camrelizumab plus chemotherapy (IO-CT) and camrelizumab plus CRT (IO-CRT) versus CRT as preoperative treatment for locally advanced ESCC. A total of 204 patients will be recruited from 8 Chinese institutions within 1.5 years. The primary endpoint is pathological complete response (pCR) rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events.Discussion: This is the first prospective randomized controlled trial to explore commonly used neoadjuvant treatments in clinical practice, which will provide high-level evidence of neoadjuvant treatment for patients with locally advanced ESCC. The purpose of this study is to establish the optimal modality of IO-CT, IO-CRT and CRT as preoperative treatment for locally advanced ESCC. The Institution Review Committee approved this study protocol in August 2021 and patient enrollment was started in September 2021.Trial Registration: ClinicalTrial.gov: NCT05043688 (August 29, 2021). The trial was prospectively registered. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a network meta-analysis to evaluate potential differences in patient outcomes when different meshes, especially biological meshes, were used for ventral hernia repair.Methods: PubMed, Embase, Cochrane Library, and Clinical Trials.gov databases were searched for studies comparing biological meshes with biological or synthetic meshes for ventral hernia repair. The outcomes were hernia recurrence rate, surgical site infection, and seroma. We performed a two-step network meta-analysis to investigate the outcomes of several biological meshes: non-cross-linked human acellular dermal matrix (NCHADM), non-cross-linked porcine ADM (NCPADM), non-cross-linked bovine ADM (NCBADM), cross-linked porcine ADM (CPADM), and porcine small intestinal submucosa (PSIS).Results: From 6304 publications, 23 studies involving 2603 patients were finally included. We found no differences between meshes in recurrence at 1-year follow-up and in surgical site infection rate. NCBADM was associated with the lowest recurrence rate and the lowest surgical site infection rate. NCHADM implantation was associated with the lowest rate of seroma. PSIS was associated with a higher risk of seroma than NCHADM (pooled risk ratio 3.89, 95% confidence interval 1.13-13.39) and NCPADM (RR 3.42, 95% CI 1.29-9.06).Conclusions: Our network meta-analysis found no differences in recurrence rate or surgical site infection among different biological meshes. The incidence of postoperative seroma was higher with PSIS than with acellular dermal matrices. We observed large heterogeneity in the studies of ventral hernia repair using biological meshes, and, therefore, well-designed randomized clinical trials are needed. [ABSTRACT FROM AUTHOR]

Background: Health information exchange (HIE) notifications when patients experience cross-system acute care encounters offer an opportunity to provide timely transitions interventions to improve care across systems.Objective: To compare HIE notification followed by a post-hospital care transitions intervention (CTI) with HIE notification alone.Design: Cluster-randomized controlled trial with group assignment by primary care team.Patients: Veterans 65 or older who received primary care at 2 VA facilities who consented to HIE and had a non-VA hospital admission or emergency department visit between 2016 and 2019.Interventions: For all subjects, real-time HIE notification of the non-VA acute care encounter was sent to the VA primary care provider. Subjects assigned to HIE plus CTI received home visits and telephone calls from a VA social worker for 30 days after arrival home, focused on patient activation, medication and condition knowledge, patient-centered record-keeping, and follow-up.Measures: Primary outcome: 90-day hospital admission or readmission.Secondary Outcomes: emergency department visits, timely VA primary care team telephone and in-person follow-up, patients' understanding of their condition(s) and medication(s) using the Care Transitions Measure, and high-risk medication discrepancies.Key Results: A total of 347 non-VA acute care encounters were included and assigned: 159 to HIE plus CTI and 188 to HIE alone. Veterans were 76.9 years old on average, 98.5% male, 67.8% White, 17.1% Black, and 15.1% other (including Hispanic). There was no difference in 90-day hospital admission or readmission between the HIE-plus-CTI and HIE-alone groups (25.8% vs. 20.2%, respectively; risk diff 5.6%; 95% CI - 3.3 to 14.5%, p = .25). There was also no difference in secondary outcomes.Conclusions: A care transitions intervention did not improve outcomes for veterans after a non-VA acute care encounter, as compared with HIE notification alone. Additional research is warranted to identify transitions services across systems that are implementable and could improve outcomes. [ABSTRACT FROM AUTHOR]

Objective: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet.Research Design and Methods: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage.Results: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis.Conclusions: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction. [ABSTRACT FROM AUTHOR]

Background: Physical activity is a cornerstone in diabetes management; however, evidence synthesis on the association between physical activity and long-term diabetes-related complications is scarce.Purpose: To summarize and evaluate findings on physical activity and diabetes-related complications, we conducted a systematic review and meta-analysis.Data Sources: We searched PubMed, Web of Science, and the Cochrane Library for articles published up to 6 July 2021.Study Selection: We included prospective studies investigating the association between physical activity and incidence of and mortality from diabetes-related complications, i.e., cardiovascular disease (CVD), coronary heart disease, cerebrovascular events, heart failure, major adverse cardiovascular events, and microvascular complications such as retinopathy and nephropathy, in individuals with diabetes.Data Extraction: Study characteristics and risk ratios with 95% CIs were extracted. Random-effects meta-analyses were performed, and the certainty of evidence and risk of bias were evaluated with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools.Data Synthesis: Overall, 31 studies were included. There was moderate certainty of evidence that high versus low levels of physical activity were inversely associated with CVD incidence, CVD mortality (summary risk ratio 0.84 [95% CI 0.77, 0.92], n = 7, and 0.62 [0.55, 0.69], n = 11), and microvascular complications (0.76 [0.67, 0.86], n = 8). Dose-response meta-analyses showed that physical activity was associated with lower risk of diabetes-related complications even at lower levels. For other outcomes, similar associations were observed but certainty of evidence was low or very low.Limitations: Limitations include residual confounding and misclassification of exposure.Conclusions: Physical activity, even below recommended amounts, was associated with reduced incidence of diabetes-related complications. [ABSTRACT FROM AUTHOR]

Study Question: Does the type of incubator used to culture human preimplantation embryos affect development to the blastocyst stage and alter amino acid utilization of embryos in assisted reproduction?Summary Answer: Culturing embryos in a time lapse system (TLS) was associated with a higher Day 5 blastocyst formation rate and altered amino acid utilization when measured from Day 3 to Day 5 compared to the standard benchtop incubator.What Is Known Already: Culture environment is known to be important for the developing preimplantation embryo. TLSs provide a stable milieu allowing embryos to be monitored in situ, whereas embryos cultured in standard benchtop incubators experience environmental fluctuations when removed for morphological assessment.Study Design, Size, Duration: A prospective clinical trial randomizing 585 sibling embryos to either the TLS (289 embryos) or the standard benchtop incubator (296 embryos) over a 23-month period in a UK University Hospital Fertility Clinic.Participants/materials, Setting, Methods: Participants were aged 42 years or under, had an antral follicle count of ≥12 and ≥6 2 pronucleate zygotes. Zygotes were cultured individually in 25 µl of medium. Randomized embryos were graded and selected for transfer or cryopreservation on Day 5. For those embryos produced by women who underwent stimulation with recombinant FSH injections and were triggered with hCG, spent medium was collected on Day 5 for amino acid analysis by high pressure liquid chromatography. Clinical pregnancy was defined as the presence of a foetal heart beat on ultrasound scan at 7 weeks.Main Results and the Role Of Chance: Overall, blastocyst formation rate on Day 5 was significantly higher in embryos cultured in the TLS (55%) compared to the standard incubator (45%; P = 0.013). Similarly, there was an increase in the number of blastocysts suitable for cryopreservation in the TLS (31%) compared to the standard incubator (23%; P = 0.032). There was a significant difference in the utilization of 12 amino acids by blastocysts cultured from Day 3 to Day 5 in the TLS compared to the standard incubator. Embryos cultured in the TLS displayed an increased total amino acid utilization (P < 0.001) and reduced amino acid production (P < 0.001) compared to those in the standard incubator. Irrespective of incubator used, embryos fertilized by ICSI depleted significantly more amino acids from the medium compared to those fertilized by conventional IVF. There was no difference in the mean score of blastocysts transferred, or the clinical pregnancy rate after transfer of embryos from either of the incubators.Limitations, Reasons For Caution: The study was not powered to discern significant effects on clinical outcomes.Wider Implications Of the Findings: The metabolism and development of preimplantation embryos is impacted by the type of incubator used for culture. Further research is required to investigate the long-term implications of these findings.Study Funding/competing Interest(s): NIHR Southampton Biomedical Research Centre Commercial and Enterprise Incubator Fund funded this study. The TLS was provided on loan for the study by Vitrolife. The authors declare no conflict of interests.Trial Registration Number: ISRCTN73037149.Trial Registration Date: 12 January 2012.Date Of First Patient’s Enrolment: 21 January 2012. [ABSTRACT FROM AUTHOR]

Study Question: Can animation videos on how to optimize the chances of pregnancy influence stress, anxiety, depression and sexual functioning of individuals trying to conceive (TTC)?Summary Answer: There were no differences between those educated to have intercourse every other day, on the fertile window and a control group (CG), and depression and sexual dysfunction significantly increased over time for all arms.What Is Known Already: Recent findings indicate that time to pregnancy can be significantly shortened by targeting the fertile period, but some reproductive care guidelines recommend instead the practice of intercourse every other day on the basis that it is less stressful to the couple. Evidence to support guidelines on how to preserve well-being and psychosocial adjustment and optimize pregnancy chances is lacking.Study Design, Size, Duration: We conducted a prospective, double-blinded, three-arm randomized controlled trial between July 2016 and November 2019. Participants were randomized to either not having any stimulus (CG) or visualizing a short animated video explaining how to improve chances of pregnancy by having intercourse every other day (EOD group), or by monitoring the fertile window (FWM group). Assessments were made before the intervention (T0), and 6 weeks (T1), 6 months (T2) and 12 months after (T3), with follow-ups censored in case of pregnancy.Participants/materials, Setting, Methods: Participants were childless individuals of reproductive age actively TTC and not diagnosed or unaware of a condition that could prevent spontaneous pregnancy. Individuals were excluded from recruitment if they had previous children or had a condition preventing spontaneous pregnancy. Our primary outcome was stress and secondary outcomes included anxiety, depression, sexual functioning and pregnancy. Primary analyses were performed according to intention-to-treat principle.Main Results and the Role Of Chance: Of the 450 randomized participants 127 were educated to use an every-other-day strategy, 135 to monitor the fertile window, and 134 received no intervention. Groups were similar regarding demographics and months TTC. Repeated measures analysis revealed that there were no significant interaction effects of psychological and sexual well-being between groups over time (P > 0.05). Significant time effects were revealed for stress (F(3,855) = 4.94, P < 0.01), depression (F(3,855) = 14.22, P < 0.01) and sexual functioning (time effects P values <0.001 for female sexual functioning dimensions and <0.002 for male dimensions), but not for anxiety (F(2,299) = 0.51, P > 0.05). Stress levels lowered after 6 months (P < 0.001) and returned to baseline levels at the 1-year follow-up. Depressive symptomatology significantly increased at 6 weeks (P = 0.023), and again 1 year after (P = 0.001). There were also significant decreases in all female sexual functioning dimensions (desire, satisfaction, arousal, pain, orgasm and lubrication). In men, there were significant variations in orgasm, intercourse satisfaction and erectile function, but not desire and sexual satisfaction. Revealed pregnancy rates were 16% for participants in the EOD group, 30% for the FWM group and 20% for the CG. Pregnancies were not significantly different between arms: EOD vs FWM (odds ratio (OR) 2.32; 95% CI 0.92-5.83); EOD vs CG (OR 0.74; 95% CI 0.30-1.87); and FWM vs CG (OR 1.71; 95% CI 0.70-4.18).Limitations, Reasons For Caution: Participants were recruited after transitioning to procreative sex. The study might be prone to bias as almost 30% of our sample fulfilled the chronological criterion for infertility, and other reproductive strategies could have been tried over time before recruitment.Wider Implications Of the Findings: Our data suggest that stress does not arise from feeling pressured on the fertile period and that advice on timing of intercourse might have to be personalized. The increasing levels of depression and sexual dysfunction over a year emphasize the crucial role of preconception care and fertility counseling in promoting psychological and sexual well-being.Study Funding/competing Interest(s): This work was supported by European Union Funds (FEDER/COMPETE-Operational Competitiveness Programme) and by national funds (FCT-Portuguese Foundation for Science and Technology) under the projects PTDC/MHC-PSC/4195/2012 and SFRH/BPD/85789/2012.Trial Registration Number: NCT02814006.Trial Registration Date: 27 June 2016.Date Of First Patient’s Enrollment: 19 July 2016. [ABSTRACT FROM AUTHOR]

Study Question: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births?Summary Answer: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births.What Is Known Already: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain.Study Design, Size, Duration: We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins.Participants/materials, Setting, Methods: We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis.Main Results and the Role Of Chance: Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: -30% to -9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD -24%, 90% CI -36% to -13%) in line with inferiority of EM.Limitations, Reasons For Caution: Our trial did not reach the planned sample size, therefore the results are limited by the number of participants.Wider Implications Of the Findings: This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS.Study Funding/competing Interest(s): The trial was supported by a grant of the SEENEZ healthcare initiative. The subsidizing parties were The Dutch Organisation for Health Research and Development (ZonMW 837004023, www.zonmw.nl) and the umbrella organization of 10 health insurers in The Netherlands. E.R.G. receives personal fees from Titus Health care outside the submitted work. M.G. declares unrestricted research and educational grants from Guerbet, Merck and Ferring not related to the presented work, paid to their institution VU medical centre. A.B.H. reports receiving travel and speakers fees from Nordic Pharma and Merck and he is member of the Nordic Pharma ANGEL group and of the Safety Monitoring Board of Womed. C.B.L. reports speakers fee from Inmed and Yingming, and his department receives research grants from Ferring, Merck and Guerbet paid to VU medical centre. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy for ObsEva and Merck. M.v.W. received a grant from the Netherlands Organisation for Health Research and Development ZonMW (80-8520098-91072). F.M. received two grants from the Netherlands Organisation for Health Research and Development ZonMW (NTR 5599 and NTR 6590). The other authors report no competing interest.Trial Registration Number: Dutch Trial register NL5455 (NTR5599).Trial Registration Date: 18 December 2015.Date Of First Patient’s Enrolment: 26 January 2017. [ABSTRACT FROM AUTHOR]

Background: Few data exist on early-life metabolic perturbations in newborns with perinatal HIV and antiretroviral (ARV) exposure but uninfected (HEU) compared to those perinatally HIV unexposed and uninfected (HUU).Methods: We enrolled pregnant persons with HIV (PWH) receiving tenofovir (TDF)/emtricitabine or lamivudine (XTC) plus dolutegravir (DTG) or efavirenz (EFV), and pregnant individuals without HIV, as well as their liveborn infants. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Preprandial homeostasis model assessment for insulin resistance (HOMA-IR) was assessed at birth and 1 month. Linear mixed models were fit to assess the association between in utero HIV/ARV exposure and average HOMA-IR from birth to 1 month, adjusting for confounders.Results: Of 450 newborns, 306 were HEU. HOMA-IR was higher in newborns HEU versus HUU after adjusting for confounders (mean difference of 0.068 in log HOMA-IR, P = .037). Among newborns HEU, HOMA-IR was not significantly different between TDF/XTC/DTG versus TDF/XTC/EFV in utero ARV exposure and between AZT versus NVP newborn postnatal prophylaxis arms.Conclusions: Newborns HEU versus HUU had lower insulin sensitivity at birth and at 1 month of life, raising potential concern for obesity and other metabolic perturbations later in life for newborns HEU.Clinical Trials Registration: NCT03088410. [ABSTRACT FROM AUTHOR]

Background: Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett's neoplasia in human subjects.Methods: Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800. This near-infrared (NIR) contrast agent was topically administered to patients with Barrett's esophagus (BE) undergoing either endoscopic therapy or surveillance. Fluorescence images were collected using a flexible fiber accessory passed through the instrument channel of an upper gastrointestinal endoscope. Fluorescence images were collected from 31 BE patients. A deep learning model was used to segment the target (T) and background (B) regions.Results: The mean target-to-background (T/B) ratio was significantly greater for high grade dysplasia (HGD) and EAC versus BE, low grade dysplasia (LGD), and squamous epithelium. At a T/B ratio of 1.5, sensitivity and specificity of 94.1 % and 92.6 %, respectively, were achieved for the detection of Barrett's neoplasia with an area under the curve of 0.95. No adverse events attributed to the heterodimer were found. EGFR and ErbB2 expression were validated in the resected specimens.Conclusions: This "first-in-human" clinical study demonstrates the feasibility of detection of early Barrett's neoplasia using a NIR-labeled peptide heterodimer. [ABSTRACT FROM AUTHOR]

Background: Active surveillance after neoadjuvant treatment is increasingly implemented. The success of this strategy relies on the accurate detection of residual cancer. This study aimed to assess the diagnostic value of a second (bite-on-bite) biopsy for the detection of residual esophageal cancer and to correlate outcomes to the distribution of residual cancer found in the resection specimen.Methods: A multicenter prospective study of esophageal cancer patients undergoing active surveillance after neoadjuvant chemoradiotherapy was performed. At clinical response evaluations, an upper gastrointestinal (GI) endoscopy was performed with at least four bite-on-bite biopsies of the primary tumor site. First and second biopsies were analyzed separately. Patients with histopathological evidence of residual cancer were included in the primary analysis. Two pathologists blinded for biopsy outcome examined all resection specimens.Results: Between October 2017 and July 2020, 626 upper GI endoscopies were performed in 367 patients. Of 138 patients with residual cancer, 112 patients (81 %) had at least one positive biopsy. In 14 patients (10 %) only the first biopsy was positive and in 25 patients (18 %) only the second biopsy (P = 0.11). Remarkably, the rates of patients with tumor-free mucosa and deeper located tumors were higher in patients detected by the first biopsy. The second biopsy increased the false-positive rate by 3 percentage points. No adverse events occurred.Conclusions: A second (bite-on-bite) biopsy improves the detection of residual esophageal cancer by almost 20 percentage points, at the expense of increasing the false-positive rate by 3 percentage points. The higher detection rate is explained by the higher number of biopsies obtained rather than by the penetration depth. [ABSTRACT FROM AUTHOR]

Purpose: To find a new approach of pan-retinal photocoagulation (PRP) with less damage to the retina in the treatment of severe non-proliferative diabetic retinopathy (NPDR), this study compared functional changes in the retina after subthreshold and threshold PRP treatment in severe NPDR eyes.Methods: Post hoc analysis of a randomized clinical trial was conducted in this study. Seventy eyes of 35 patients with bilateral, symmetric, severe NPDR were enrolled. Two eyes from the same patient were randomized into two groups, one eye received subthreshold PRP (S-PRP) and the other eye received threshold PRP (T-PRP). Comprehensive ophthalmological evaluations were performed on the baseline and every 3 months for 1 year. Visual field (VF) and full-field electroretinography (ERG) were performed on the baseline and repeated at month 12.Results: During the 12-month follow-up, 4 eyes (11.4%) in the S-PRP group and 3 eyes (8.6%) in the T-PRP group progressed to proliferative diabetic retinopathy (PDR) stage, and there was no statistical difference in PDR progression rate between the two groups (P = 0.69). In addition, the changes in best-corrected visual acuity (BCVA) from baseline to month 12 between the two groups had no statistical difference (P = 0.30). From baseline to month 12, changes in central VF between the two groups had no statistical difference (P = 0.25), but changes in total score points of peripheral VF in the S-PRP group (- 242.1 ± 210.8 dB) and the T-PRP group (- 308.9 ± 209.7 dB) were statistically significant (P = 0.03). At month 12, ERG records showed that the amplitude of dark-adapted 0.01 ERG, dark-adapted 3.0 ERG, oscillatory potentials, light-adapted 3.0 ERG, and 30 Hz flicker ERG of both groups were significantly decreased from the baseline (P < 0.05). In addition, the amplitude of each ERG record in the S-PRP group decreased significantly less than those in the T-PRP group (P < 0.05).Conclusions: Subthreshold PRP is as effective as threshold PRP for preventing severe NPDR progress to PDR within 1 year with less damage to periphery VF and retinal function.Trial Registration: Clinicaltrials: gov Identifier: NCT01759121. [ABSTRACT FROM AUTHOR]

Background: Pre-treatment HIV drug resistance (PDR) may result in increased risk of virological failure and acquisition of new resistance mutations. With recently increasing ART coverage and periodic modifications of the guidelines for HIV treatment, there is a need for an updated systematic review to assess the levels of the PDR among adults newly initiating ART in Eastern Africa.Methods: We conducted a systematic search for studies published between 1 January 2017 and 30 April 2022 in the MEDLINE Complete and CINAHL Complete, searched simultaneously using EBSCOhost, and Web of Science. To determine the overall PDR prevalence estimates, we extracted data from eligible articles and analysed prevalence estimates using Stata 14.2.Results: A total of 22 eligible observation studies were selected. The studies included a total of 5852 ART-naive people living with HIV. The overall pooled prevalence of PDR was 10.0% (95% CI: 7.9%-12.0%, I2 = 88.9%) and 9.4% (95% CI: 7.0%-11.9%, I2 = 90.4%) for NNRTIs, 2.6% (95% CI: 1.8%-3.4%, I2 = 69.2%) for NRTIs and 0.7% (95% CI: 0.3%-1.2%, I2 = 29.0%) for PIs. No major integrase strand transfer inhibitors (INSTI)-related mutations were identified.Conclusions: We observed a moderate overall PDR prevalence among new ART initiators in this study. PDR to NNRTIs is more prevalent, underscoring the importance of the current WHO recommendation for replacement of NNRTIs by INSTIs. PDR to NRTIs was low but notable, which warrants continuous surveillance of pre-existing resistance to the dolutegravir co-administered NRTI in Eastern Africa. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of general practice-level prescribing feedback on antibiotic prescribing in a real-world pragmatic cluster randomized controlled trial.Methods: Three hundred and forty general practices in four territorial Health Boards in NHS Scotland were randomized in Quarter 1, 2016 to receive four quarterly antibiotic-prescribing feedback reports or not, from Quarter 2, 2016 to Quarter 1, 2017. Reports included different clinical topics, benchmarking against national and health board rates, and behavioural messaging with improvement actions. The primary outcome was total antibiotic prescribing rate. There were 16 secondary prescribing outcomes and 5 hospital admission outcomes (potential adverse effects of reduced prescribing). The main evaluation timepoint was 1 year after the final report (Quarter 1, 2018), with an additional evaluation in the quarter after the final report (Quarter 2, 2017). Routine administrative NHS data were used to generate the feedback reports and analyse the effects.Results: Total antibiotic prescribing rates were lower at the main evaluation timepoint in both intervention (1.83 versus baseline 1.93 prescriptions/1000 patients/day) and control (1.90 versus baseline 1.98) practices, with no evidence of intervention effect [adjusted rate ratio (ARR) 0.98 (95% CI 0.94-1.02; P = 0.35)]. At the additional timepoint, adjusted total antibiotic prescribing rates were 1.67 and 1.73 prescriptions/1000 patients/day, with evidence of a small intervention effect, ARR 0.99 (0.98-1.00; P = 0.03).Conclusions: This well-designed, practice-level antibiotic-prescribing feedback had limited evidence of additional effects in the context of decreasing antibiotic prescribing and an established national stewardship programme. [ABSTRACT FROM AUTHOR]

Aim: To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy (CP).Method: Ninety-one children (52 males, 39 females; median age 3 years 7 months [range 2-5 years]) with CP due to hypoxic-ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 × 107 AlloCB total nucleated cells (TNC) per kilogram at baseline (n = 31); (2) the hCT-MSC group received 2 × 106 hCT-MSC at baseline, 3 months, and 6 months (n = 28); (3) the natural history control group received 10 × 107 AlloCB TNC per kilogram at 12 months (n = 31). Motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66) and Peabody Developmental Motor Scale, Second Edition.Results: Infusions (n = 143) were well tolerated, with eight infusion reactions (three in the AlloCB group, five in hCT-MSC) and no other safety concerns. At 12 months, the mean differences (95% confidence intervals [CI]) between actual and expected changes in GMFM-66 score were AlloCB 5.8 points (3.4-8.2), hCT-MSC 4.3 (2.2-6.4), and natural history 3.1 (1.4-5.0). In exploratory, post hoc analysis, the mean GMFM-66 score (95% CI) of the hCT-MSC group was 1.4 points higher than natural history (-1.1 to 4.0; p = 0.27), and the AlloCB group was 3.3 points higher than natural history (0.59-5.93; p = 0.02) after adjustment for baseline Gross Motor Function Classification System level, GMFM-66 score, and etiology.Interpretation: High-dose AlloCB is a potential cell therapy for CP and should be further tested in a randomized, blinded, placebo-controlled trial.What This Paper Adds: Unrelated donor allogeneic umbilical cord blood (AlloCB) and human umbilical cord tissue-derived mesenchymal stromal cell infusion is safe in young children with cerebral palsy. Significant changes in motor function were not observed 6 months after treatment. One year later, treatment with AlloCB was associated with greater increases in Gross Motor Function Measure-66 scores. [ABSTRACT FROM AUTHOR]

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is an important malaria control strategy in sub-Saharan Africa. Indeed, it overcomes the risk of misdiagnosis due to low peripheral parasitemia during pregnancy by treating women with SP on predetermined schedules. However, over time, the spread of Plasmodium-resistant strains has threatened this strategy in many countries. As an alternative, the intermittent screening and treatment for pregnancy (ISTp) aims at a monthly screening of pregnant women, preferably by using very sensitive tests such as ultrasensitive rapid diagnostic tests (us-RDTs) and the treatment of positive cases with artemisinin-based combination therapy (ACT) regardless of the presence of symptoms. Unlike IPTp-SP, ISTp prevents overuse of antimalarials limiting the drug pressure on parasites, an advantage which can be potentiated by using an ACT like pyronaridine-artesunate (Pyramax®) that is not yet used in pregnant women in the field.Methods: This study aims to compare the non-inferiority of ISTp using us-RDTs and Pyramax® versus IPTp-SP on malaria in pregnancy through a randomized clinical trial performed in Kisenso, Kinshasa, the Democratic Republic of the Congo, a malaria perennial transmission area.Discussion: The results will be essential for the National Malaria Control Program to update the malaria prevention policy in pregnant women in the Democratic Republic of the Congo.Trial Registration: ClinicalTrials.gov NCT04783051. [ABSTRACT FROM AUTHOR]

Background: People with Parkinson's disease (PD) have a high fall rate and many falls are associated with turns. Despite this, there is minimal research on effects of rehabilitation on the quality of turns. Further, quantifying turns in the home may have broader implications since rehabilitation of turns would ideally improve turning in real world mobility.Methods: Sixty people with PD and a history of falls will be randomized to receive either a novel TURNing InTervention (TURN-IT) or no intervention (control group). The TURN-IT group will be seen for 6 weeks (18 visits) for an individualized, progressive program that is based on the specific constraints of turning in PD. Wearable sensors will be used to measure 7 days of mobility, including turns, before and after intervention or control period. In addition, blinded assessments of gait, mobility and turns will occur before and after intervention for both groups and falls will be monitored for twelve months post intervention with bimonthly email questionnaires.Discussion: This study has the potential to change how we rehabilitate and assess turning in people with PD and falls. There are several novel aspects to our study including a comprehensive turning-focused intervention that is tailored to the underlying constraints that impair turning in people with PD. Further, our outcome measure of turning quality during 7 days of daily life is novel and has implications for determining real-life changes after rehabilitation. The ultimate goal of this rehabilitation intervention is to improve how patients turn in daily life and to reduce falls.Trials Registration: This protocol is registered at clinicaltrials.gov; #NCT04897256; https://clinicaltrials.gov/ct2/show/NCT04897256?term=Horak&cond=Parkinson+Disease&draw=2&rank=4 . [ABSTRACT FROM AUTHOR]

Background: Health systems are increasingly attempting to intervene on social adversity as a strategy to improve health care outcomes. To inform health system efforts to screen for social adversity, we sought to explore the stability of social risk and interest in assistance over time and to evaluate whether the social risk was associated with subsequent healthcare utilization.Methods: We surveyed Kaiser Permanente members receiving subsidies from the healthcare exchange in Southern California to assess their social risk and desire for assistance using the Accountable Health Communities instrument. A subset of initial respondents was randomized to be re-surveyed at either three or six months later.Results: A total of 228 participants completed the survey at both time points. Social risks were moderate to strongly stable across three and six months (Kappa range = .59-.89); however, social adversity profiles that included participants' desire for assistance were more labile (3-month Kappa = .52; 95% CI = .41-.64 & 6-month Kappa = .48; 95% CI = .36-.6). Only housing-related social risks were associated with an increase in acute care (emergency, urgent care) six months after initial screening; no other associations between social risk and utilization were observed.Conclusions: This study suggests that screening for social risk may be appropriate at intervals of six months, or perhaps longer, but that assessing desire for assistance may need to occur more frequently. Housing risks were associated with increases in acute care. Health systems may need to engage in screening and referral to resources to improve overall care and ultimately patient total health. [ABSTRACT FROM AUTHOR]