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The hallmark neuropathological changes associated with Alzheimer's disease (AD) include extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Because NFTs are strongly associated with clinical impairment, multiple therapeutic programs focused on reducing tau pathology have been initiated, necessitating the development of biomarkers specific to tau pathology. Current tau blood‐based biomarkers (e.g., phosphorylated tau 181 [p‐tau181] and 217 [p‐tau217]) are more closely associated with amyloid pathology than tau pathology and may not allow specific assessment of the presence of, or therapeutic impact on, neuropathological tau. BIIB080 is a microtubule associated protein tau ( MAPT )–targeting antisense oligonucleotide that reduces production of tau protein. Exploratory analysis from the BIIB080 Phase 1b trial (NCT03186989) demonstrated that BIIB080 treatment was associated with a dose‐dependent and sustained reduction in soluble tau protein in cerebrospinal fluid (CSF), and exploratory analysis evaluating the change in soluble p ‐tau in plasma is in progress. Moreover, BIIB080 impacted aggregated parenchymal tau pathology, as measured by tau positron emission tomography, demonstrating a reduction of tau pathology from baseline across all brain composites assessed at the end of the long‐term extension. These data were the first to show this magnitude of treatment response on this pathological hallmark of AD. The ongoing Phase 2 CELIA trial (NCT05399888) will further evaluate impacts of BIIB080 on these biomarkers, as well as the safety and efficacy of BIIB080 in a larger and broader AD population. Emerging candidates for tau‐specific biomarkers include p ‐tau205 and a portion of the microtubule binding region of tau containing the residue 243 (MTBR‐tau243). Evaluation of the impact of BIIB080 on these measures and other novel biomarkers of tau pathology is ongoing. However, these biomarkers are currently measured in CSF only, and evidence for their use as treatment‐response measures is limited. Based on emerging tau biomarker advances and biomarker results from BIIB080, this presentation will provide future directions on the use and importance of tau biomarkers for development of therapies targeting tau.

Purpose: The purpose of this study was to compare the effect of speech intervention provided with a low intensity with speech intervention provided with a high intensity on the speech and health-related quality of life (HRQoL) in Dutch-speaking children with a cleft palate with or without a cleft lip (CP ± L) between 4 and 12 years. Method: A longitudinal, prospective, randomized controlled trial with a multiple baseline design was used. Twelve children with a CP ± L (M[subscript age] = 8.0 years, SD = 1.54) were divided into two groups using block randomization stratified by age and gender: One group received low-intensity speech intervention (LISI; n = 6) and one group received high-intensity speech intervention (HISI; n = 6). Children in the LISI group received intervention with a session duration of 1 hr, a dose frequency of 1 session per week, and a total intervention duration of 10 weeks. Children in the HISI group received intervention with a session duration of 1 hr, a dose frequency of 5 sessions per week, and a total intervention duration of 2 weeks. The cumulative intervention intensity was kept constant. Both groups received identical therapy programs provided by the same experienced speech therapist. Perceptual speech assessments were performed on baseline and posttreatment data points. Changes in HRQoL were assessed using the Velopharyngeal Insufficiency Effects on Life Outcomes (VELO) questionnaire. Both groups were compared over time using (generalized) linear mixed models. Results: No significant Time × Group interactions were observed for the percentage of correctly produced consonants at the word and sentence levels, indicating no differences in evolution over time among the two groups. The variables speech understandability, speech acceptability, and the total VELO scores significantly improved following HISI, but not following LISI. Conclusions: Children in the HISI group made equal and, for some variables, even superior progress in only 2 weeks of therapy compared to children in the LISI group who received 10 weeks of therapy. HISI is a promising strategy to improve speech outcomes and HRQoL in a shorter time period.

Background The global population of senior citizens is growing rapidly, contributing to a rising prevalence of neurodegenerative diseases, including synucleinopathies such as Parkinson’s disease (PD), Lewy Body Dementia (LBD), and Alzheimer’s disease (AD). Drug development for synucleinopathies has been particularly inefficient. Progress in developing therapies targeting underlying mechanisms has been hindered by the poor translatability of animal models, which often fail to accurately reflect human synucleinopathy pathology, and the limited availability of cognitive biomarkers for predicting treatment outcomes. Our work aims to develop a comprehensive preclinical drug discovery pipeline that integrates humanized mice, neurochemical, imaging, and cognitive biomarkers to enhance predictive accuracy. This approach combines advanced behavioral assessments, imaging modalities, and real‐time neurochemical monitoring in behaving mice to better understand disease pathogenesis, identify therapeutic efficacy, and detect adverse effects. Method We combined preformed fibril (PFF) injections of wild‐type human synuclein into mouse models expressing human synuclein with high‐throughput touchscreen‐based cognitive tasks relevant to synucleinopathies to investigate cognitive deficits. In parallel, fibre photometry recordings were used to measure dopamine dynamics and calcium signaling in freely behaving mice. Pathological changes were assessed using immunofluorescence, lightsheet microscopy, and MRI. We also initiated experiments to test the ability of different treatments, including drugs and genetic manipulations targeting chaperones, and a vaccine to mitigate alpha‐synuclein (a‐Syn) toxicity in these models. Result Mice unilaterally injected with PFFs in the striatum exhibited significant cognitive deficits in touchscreen‐based tasks including pairwise visual discrimination (PVD) and visuomotor conditional learning (VMCL), which appear before motor impairments. Fibre photometry recordings revealed altered dopamine dynamics in freely behaving PFF‐injected mice. These cognitive and neurochemical changes were associated with elevated phosphorylated a‐Syn levels that spreads through cortical‐striatal‐thalamic networks, confirmed through immunofluorescence, Western blotting, and lightsheet microscopy. MRI analysis showed spatial atrophy patterns in PFF‐injected mice that mimic human synucleinopathy atrophy. Preliminary results indicate that treatments mitigate a‐Syn toxicity and improve cognitive deficits. Conclusion We aim to establish a robust cost‐effective pipeline that improves the translation of preclinical discoveries to clinical success, ultimately accelerating the development of effective treatments for synucleinopathies and reducing the risk of late‐stage drug failures.

Multi-month dispensing (MMD) has been widely adopted by national HIV programs as a key strategy for improving the quality of HIV care and treatment services while meeting the unique needs of diverse client populations. We assessed the clinical outcomes of clients receiving MMD in Kenya by conducting a retrospective cohort study using routine programmatic data in 32 government health facilities in Kenya. We included clients who were eligible for multi-month antiretroviral therapy (ART) dispensing for ≥ 3 months (≥ 3MMD) according to national guidelines. The primary exposure was enrollment into ≥ 3MMD. The outcomes were lost to follow-up (LTFU) and viral rebound. Multilevel modified-Poisson regression models with robust standard errors were used to compare clinical outcomes between clients enrolled in ≥ 3MMD and those receiving ART dispensing for less than 3 months (< 3MMD). A total of 3,501 clients eligible for ≥ 3MMD were included in the analysis, of whom 65% were enrolled in ≥ 3MMD at entry into the cohort. There was no difference in LTFU of ≥ 180 days between the two types of care (aRR 1.1, 95% CI 0.7–1.6), while ≥ 3MMD was protective for viral rebound (aRR 0.1 95% CI 0.0-0.2). As more diverse client-focused service delivery models are being implemented, robust evaluations are essential to guide the implementation, monitor progress, and assess acceptability and effectiveness to deliver optimal people-centered care.

Purpose: The aim of this study was to compare the effect of a short-term intensive voice therapy (IVT) with a long-term traditional voice therapy (TVT) on the vocal quality, vocal capacities, psychosocial impact, vocal tract discomfort, laryngological anatomy/physiology, and session attendance of patients with dysphonia. An additional comparison was made between an individual IVT (IVT-I) and a group IVT (IVT-G). Method: A longitudinal, prospective controlled trial was used. Forty-six adults diagnosed with dysphonia were assigned to 1 of the 3 treatment groups. The IVT groups practiced with a frequency of 1 hr 20 min a day and a duration of 2 weeks. The TVT group practiced with a frequency of two 30-min sessions a week and a duration of 6 months. Both therapy programs were content-identical and guided by the same voice therapist. A multidimensional voice assessment consisting of both objective (maximum performance task, aerodynamic measurements, voice range profile, acoustic analysis, multiparametric voice quality indices) and subjective (subject's self-report, auditory-perceptual evaluation, flexible videolaryngostroboscopy) outcomes was used to evaluate the participants' voice. Results: IVT made an equal progress in only 2 weeks and 12 hr of therapy compared with TVT that needed 6 months and 24 hr of therapy. IVT-I and IVT-G showed comparable results. Session attendance was clearly higher in IVT compared with TVT. Long-term follow-up results (1 year) were positive for the 3 groups, except for the self-reported psychosocial impact that increased in the IVT-I group. Conclusions: Short-term IVT is at least equally effective in treating patients with dysphonia as long-term TVT. Group treatment seemed as effective as individual treatment. Attendance and cost-effectiveness are important advantages of IVT. A potential drawback might be an insufficient psychosocial progress. The golden mean between intensive and traditional treatment might therefore be an achievable, effective, and efficient solution for everyday clinical practice.

Purpose Recent years have seen remarkable progress in cancer therapy, although treatment-induced adverse reactions and complications are not uncommon. Approximately 40 % of patients undergoing chemotherapy for cancer experience adverse reactions in the oral cavity, with nearly half of them developing severe oral mucositis that necessitates postponing therapy and/or changing the drug dosage. The objective of this study was to assess the usefulness of prophylactic professional oral health care (POHC) for preventing mucositis in patients undergoing chemotherapy. Methods Twenty-six female patients scheduled for chemotherapy for breast cancer were included in this study and randomized to the self-care or POHC groups. Assessment parameters included oral cavity photographs, plaque control records, Saxon test scores, Oral Assessment Guide scores, and grading using the Common Terminology Criteria for Adverse Events. Beginning before surgery and continuing through the completion of chemotherapy, the POHC patient group received weekly professional oral health care, including scaling, professional cleaning of the tooth surfaces, brushing instructions, and nutritional and lifestyle guidance. Results More patients in the self-care group developed oral mucositis than in the POHC group. The Oral Assessment Guide score, which was used as an index of oral mucositis, was also significantly lower in the POHC group. Based on the Oral Assessment Guide and plaque control records, there was almost no deterioration of the oral environment in the POHC group, whereas deterioration was observed in the self-care group. Conclusions These findings demonstrate the efficacy of regular POHC in reducing the risk of oral mucositis in breast cancer patients undergoing chemotherapy.

Purpose A notable number of young people self-harm, with only a minority receiving professional support. Evidence suggests that therapy can help recovery from self-harm, but little is known about the experiences of those who self-harm and participate in therapy delivered via videoconferencing. Design/methodology/approach Risk assessments were examined for evidence of self-harm and used to identify two groups for analysis: young people who had self-harmed in the past six months and those who had not. A mixed methods analysis was then conducted to examine process and outcome data for these two groups. Data included a number of sessions attended, late-cancelled and missed without notice; and patient-reported outcome measure scores (Young Person-Clinical Outcomes in Routine Evaluation and Revised Children’s Anxiety and Depression Scale). End-of-treatment reports were subsequently analysed using thematic analysis. Findings Those with current self-harm risk appeared to start therapy with lower well-being. No notable differences in progress were found between groups on quantitative outcomes. There was greater reporting of poorer clinical outcomes in the reports of those with current self-harm risk, including two unique types of barriers to effective therapy: “general difficulties” (e.g. poor well-being limiting engagement, specific components of therapy being challenging) and “CBT was not preferred”. Originality/value Lower baseline well-being could explain the greater ongoing care needs and lower well-being post-therapy among those with current self-harm risk, despite both groups appearing to make similar levels of therapeutic progress quantitatively. Recent self-harm does not appear to reduce the utility of videoconferencing cognitive behavioural therapy; however, clients’ individual needs should be carefully considered.

Access to diagnostic tools like chest radiography (CXR) is challenging in resource-limited areas. Despite reduced reliance on CXR due to the need for quick clinical decisions, its usage remains prevalent in the approach to neonatal respiratory distress syndrome (NRDS). To assess CXR's role in diagnosing and grading NRDS severity compared to current clinical features and laboratory standards. A review of studies with NRDS diagnostic criteria was conducted across six databases (MEDLINE, EMBASE, BVS, Scopus-Elsevier, Web of Science, Cochrane) up to 3 March 2023. Independent reviewers selected studies, with discrepancies resolved by a senior reviewer. Data were organised into descriptive tables to highlight the use of CXR and clinical indicators of NRDS. Out of 1,686 studies screened, 23 were selected, involving a total of 2,245 newborns. All selected studies used CXR to diagnose NRDS, and 21 (91%) applied it to assess disease severity. While seven reports (30%) indicated that CXR is irreplaceable by other diagnostic tools for NRDS diagnosis, 10 studies (43%) found that alternative methods surpassed CXR in several respects, such as severity assessment, monitoring progress, predicting the need for surfactant therapy, foreseeing Continuous Positive Airway Pressure failure, anticipating intubation requirements, and aiding in differential diagnosis. CXR remains an important diagnostic tool for NRDS. Despite its continued use in scientific reports, the findings suggest that the study's outcomes may not fully reflect the current global clinical practices, especially in low-resource settings where the early NRDS approach remains a challenge for neonatal survival. PROSPERO number CRD42022336480.

Despite significant social and legal progress, LGBTQ+ (lesbian, gay, bisexual, transgender, and other sexual and gender minority) populations continue to experience higher rates of mental health and substance use disorders than their heterosexual and cisgender counterparts. Effective LGBTQ+ affirmative mental health care is essential for addressing these disparities but is often limited and difficult to access. The shortage of LGBTQ+ affirmative mental health care providers results from the absence of required and accessible LGBTQ+-focused training and technical assistance opportunities for mental health care professionals. This study evaluates the implementation of our COVID-19 adapted, completely virtual, organization- and therapist-focused training program to improve the mental health workforce’s cultural competence in working with the LGBTQ+ community: the Sexual and Gender Diversity Learning Community (SGDLC). Guided by an expanded RE-AIM model, we used administrator and therapist feedback to assess SGDLC implementation factors to understand how it may be best translated for scaled-up promotion and widespread adoption. Assessment of the initial reach, adoption, and implementation of the SGDLC indicated that it had strong feasibility; reports on satisfaction and relevance support the SGDLC’s acceptability. Maintenance could not be fully assessed from the short study follow-up period. Still, administrators and therapists expressed an intent to continue their newfound practices, a desire for continued training and technical assistance in this area, but also concerns about finding additional opportunities for this education.

Prescriptions for biologic therapy for treatment of Crohn’s disease (CD) and ulcerative colitis (UC) have increased during the past two decades; however, trends are less clear regarding corticosteroid prescriptions in this context. We designed a cross-sectional study using the IQVIA Ambulatory Electronic Medical Records databases. Weighted linear regressions by age group were used to estimate annual percentage change from 2011 to 2020 in prescriptions for biologics and for corticosteroids among patients with or without biologic prescriptions within the same calendar year. Using 2019 data, we compared patient demographic and lifestyle risk factors using χ2 test for biologic prescriptions and corticosteroids with or without biologics prescriptions. There was an 11% (CD) and 16% (UC) annual increase in the percentage of patients prescribed biologics during the study period. The percentage of patients with biologics prescriptions prescribed corticosteroids decreased by 2% (CD) and 3% (UC) annually after 2015, while the percentage remained unchanged for corticosteroid prescriptions among patients without biologics. In 2019, differences in medication prescriptions existed by patient’s demographic and lifestyle factors for patients with CD (n=52,892) and UC (n=52,280), including a higher percentage prescribed biologics among younger patients, men, those with fewer comorbidities, and current alcohol drinkers, and a higher percentage prescribed corticosteroids without biologics among women, those with more comorbidities, and a history of smoking. While medications continue to evolve during the biologic era, it is important to continue to monitor trends and differences in prescription patterns to assess progress toward optimizing treatment for patients with CD or UC.