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Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr’s index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route.

Steam methane reforming (SMR) is one of the most widely used hydrogen (H2) production processes. In addition to its extensive utilization in industrial sectors, hydrogen is expanding it share as a clean energy carrier, and more sustainable and efficient H2 production methods are continuously being explored and developed. One method replaces conventional fossil fuel-based heating with electrical heating through the flow of electrons across the reformer. At UCLA, an experimental setup was built of an electrically heated steam methane reforming process. This paper describes the system components, explains the digitalization of the experimental setup and introduces methods for building a first-principles-based dynamic process model using parameters estimated via data-driven methods from process experimental data. The modeling approach uses a lumped parameter approximation and employs algebraic equations to solve for gas-phase variables. The reaction parameters are calculated from steady-state experimental data, and the temperature change is modeled with respect to change in electric current using a first-order dynamic model. The overall dynamic process model is then used in a computational model predictive control (MPC) scheme to drive the process to a new H2 production set-point under unperturbed and steam flowrate disturbance cases. The performance and robustness of the proposed MPC scheme are compared to the ones of a classical proportional–integral (PI) controller and are demonstrated to be superior in terms of closed-loop response, robustness, and constraint handling.

[This corrects the article DOI: 10.1371/journal.pone.0054193.].

Profiling the tumour microenvironment (TME) has been informative in understanding the underlying tumour–immune interactions. Multiplex immunohistochemistry (mIHC) coupled with molecular barcoding technologies have revealed greater insights into the TME. In this study, we utilised the Nanostring GeoMX Digital Spatial Profiler (DSP) platform to profile a non-small-cell lung cancer (NSCLC) tissue microarray for protein markers across immune cell profiling, immuno-oncology (IO) drug targets, immune activation status, immune cell typing, and pan-tumour protein modules. Regions of interest (ROIs) were selected that described tumour, TME, and normal adjacent tissue (NAT) compartments. Our data revealed that paired analysis (n = 18) of matched patient compartments indicate that the TME was significantly enriched in CD27, CD3, CD4, CD44, CD45, CD45RO, CD68, CD163, and VISTA relative to the tumour. Unmatched analysis indicated that the NAT (n = 19) was significantly enriched in CD34, fibronectin, IDO1, LAG3, ARG1, and PTEN when compared to the TME (n = 32). Univariate Cox proportional hazards indicated that the presence of cells expressing CD3 (hazard ratio (HR): 0.5, p = 0.018), CD34 (HR: 0.53, p = 0.004), and ICOS (HR: 0.6, p = 0.047) in tumour compartments were significantly associated with improved overall survival (OS). We implemented both high-plex and high-throughput methodologies to the discovery of protein biomarkers and molecular phenotypes within biopsy samples, and demonstrate the power of such tools for a new generation of pathology research.

Identifying and targeting specific oncogenic drivers has become standard of care in the routine management of patients with lung cancer. Research is ongoing to expand the number of drug targets that can offer clinically meaningful outcomes. Rearranged during transfection (RET) fusions are the latest oncogenic driver alterations that show potential as a drug target. RET fusions occur in 1−2% of non-small cell lung cancer (NSCLC) cases. They are more commonly associated with younger age, female gender, non-smokers and Asian ethnicity. The RET kinase is abnormally activated through fusion with a partner protein such as KIF5B, CCDC6 or NCOA4. This leads to downstream intracellular signalling and enhancement of gene transcription and cell proliferation. The effectiveness of multi-kinase inhibitors in RET positive NSCLC has been explored in early phase and retrospective studies. From these studies, the most effective agents identified include cabozantanib and vandetanib. Overall response rates (ORR) vary from 18−47% across studies. In general, these agents have a manageable toxicity profile, although there are a number of off-target toxicities. Similar to the increased activity in ALK rearranged disease, pemetrexed has demonstrated superior response rates in this patient group and should be considered. Selective RET inhibitors, including LOXO-292 and BLU-667, are progressing in clinical trials. LOXO-292 has demonstrated an impressive ORR of 77% in RET positive solid tumours. It is anticipated this agent will be an effective targeted therapeutic option for patients with RET positive lung cancer.

Incidental fisheries capture has been identified as having a major effect on shark populations throughout the world. However, factors that contribute to the mortality of shark bycatch during fisheries capture are not fully understood. Here, we investigated the effects of capture duration, sea surface temperature, and shark total length (snout to the tip of the upper caudal lobe) on the physiology and condition of longline-caught bronze whalers, Carcharhinus brachyurus. Plasma lactate and potassium concentration had a positive linear relationship with capture duration, indicating that this species experiences increasing physiological challenges while on fishing gear. Additionally, we used stereotype logistic regression models to determine variables that could predict the capture condition of sharks (categorized as healthy, sluggish, or moribund or dead). In these models, elevated plasma lactate concentration, plasma potassium concentration, and capture duration increased the likelihood of C. brachyurus being captured in a sluggish condition or in a moribund or dead condition. After plasma lactate concentration exceeded 27.4 mmol/L, plasma potassium concentration exceeded 8.3 mmol/L, or capture durations exceeded 293 minutes, the majority of captured sharks (>50%) were predicted to be moribund or dead. We recommend that a reduction in the amount of time longlines are left fishing (soak time) will reduce immediate and post-release mortality in C. brachyurus bycatch and that our methods could be applied to identify causes of fisheries-induced mortality in future studies. The identification of operational, environmental, and biological variables contributing to poor condition will be necessary to implement conservation strategies that reduce mortality during capture.

IntroductionInherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin.MethodsAn isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed.ResultsCharacterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines.ConclusionOur results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer.

Guided digital mental health interventions are more effective than unguided interventions. While research often emphasizes the frequency and intensity of guidance, less attention has been paid to the behaviors enacted by the therapists supporting clients using these interventions. A scoping review of the literature was conducted to systematically examine the evidence on therapist behaviors (i.e., the actions and feedback provided by supporters to patients). Applying broad eligibility criteria, a systematic search was conducted in PubMed, PsycInfo, the Cochrane Library, and Embase from their inception to January 1st 2024. Sixteen studies met inclusion criteria and were included in the review. Following data extraction, a descriptive analysis and synthesis of the results was performed. Most studies (n = 12; 75 %) focused on therapist behaviors in the context of internet-delivered Cognitive Behavioral Therapy for anxiety and depression. While earlier studies primarily focused on identifying therapist behaviors, later studies shifted towards examining the associations between therapist behaviors and different outcomes, as well as deriving research and clinical applications for improving guided internet-delivered treatments. Identified gaps and recommendations for clinical practice, research, training, and treatment development are discussed.

Abstract Background In recent years, exponential growth in digital innovations and internet access has provided opportunities to deliver health services at a much greater scale than previously possible. Evidence-based technology-enabled interventions can provide cost-effective, accessible, and resource-efficient solutions for addressing mental health issues. This study evaluated the first year of a supported digital cognitive behavioral therapy (CBT) service provided by the national health service in Ireland, which has been accessible to individuals who receive a referral from one of five referring groups: General Practitioners, Primary Care Psychology, Counselling Primary Care, Community Mental Health, and Jigsaw (a nationwide youth mental health service). Methods A retrospective, observational study examining data from the service between April 2021 to April 2022 was conducted. Descriptive statistics on referrals, account activations, user demographics, program usage, and user satisfaction were extracted, and pre-to-post clinical outcomes for depression measured by the Patient Health Questionnaire-9 and for anxiety measured by the Generalised Anxiety Disorder-7 were analysed using linear mixed effect models. Results There were 5,298 referrals and 3,236 (61%) account activations within the year. Most users were female (72.9%) and aged between 18 and 44 years (75.4%). The CBT programs were associated with significant reductions in both depression (β = 3.34, 95% CI [3.03, 3.65], p 0.8). Time spent using the programs was also found to be a predictor of the variability in these clinical outcomes (p

Abstract Background Citizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this. Citizen science is a potential way to involve patients and the public in improving clinical guideline implementation. We aimed to explore the application of citizen science methods to involve patients and the public in the dissemination and implementation of clinical guidelines in oral health and dentistry. Methods We developed GUIDE (GUideline Implementation in oral health and DEntistry), a citizen science online platform, using a participatory approach with researchers, oral health professionals, guideline developers and citizens. Recruitment was conducted exclusively online. The platform focused on prespecified challenges related to oral health assessment guidelines, and asked citizens to generate ideas, as well as vote and comment on other citizens' ideas to improve those challenges. Citizens also shared their views via surveys and two online synchronous group meetings. Data were collected on participant's demographics, platform engagement and experience of taking part. The most promising idea category was identified by an advisory group based on engagement, feasibility and relevance. We presented quantitative data using descriptive statistics and analysed qualitative data using inductive and deductive thematic analysis. Results The platform was open for 6 months and we recruited 189 citizens, from which over 90 citizens actively engaged with the platform. Most citizens were over 34 years (64%), female (58%) and had a university degree (50%). They generated 128 ideas, 146 comments and 248 votes. The challenge that led to most engagement was related to prevention and oral health self‐care. To take this challenge forward, citizens generated a further 36 ideas to improve a pre‐existing National Health Service oral care prevention leaflet. Citizens discussed motivations to take part in the platform (understanding, values, self‐care), reasons to stay engaged (communication and feedback, outputs and impact, and relevance of topics discussed) and suggestions to improve future platforms. Conclusion Citizen science is an effective approach to generate and prioritise ideas from a group of citizens to improve oral health and dental services. Prevention and oral health self‐care were of particular interest to citizens. More research is needed to ensure recruitment of a diverse group of citizens and to improve retention in citizen science projects. Patient or Public Contribution This project was inherently conducted with the input of public partners (citizen scientists) in all key aspects of its conduct and interpretation. In addition, two public partners were part of the research team and contributed to the design of the project, as well as key decisions related to its conduct, analysis, interpretation and dissemination and are co‐authors of this manuscript.

Prior studies have found metacognitive biases are linked to a transdiagnostic dimension of anxious-depression, manifesting as reduced confidence in performance. However, previous work has been cross-sectional and so it is unclear if under-confidence is a trait-like marker of anxious-depression vulnerability, or if it resolves when anxious-depression improves. Data were collected as part of a large-scale transdiagnostic, four-week observational study of individuals initiating internet-based cognitive behavioural therapy (iCBT) or antidepressant medication. Self-reported clinical questionnaires and perceptual task performance were gathered to assess anxious-depression and metacognitive bias at baseline and 4-week follow-up. Primary analyses were conducted for individuals who received iCBT (n=649), with comparisons between smaller samples that received antidepressant medication (n=82) and a control group receiving no intervention (n=88). Prior to receiving treatment, anxious-depression severity was associated with under-confidence in performance in the iCBT arm, replicating previous work. From baseline to follow-up, levels of anxious-depression were significantly reduced, and this was accompanied by a significant increase in metacognitive confidence in the iCBT arm (β=0.17, SE=0.02, p

Abstract Background Evidence-based treatments for depression exist but not all patients benefit from them. Efforts to develop predictive models that can assist clinicians in allocating treatments are ongoing, but there are major issues with acquiring the volume and breadth of data needed to train these models. We examined the feasibility, tolerability, patient characteristics, and data quality of a novel protocol for internet-based treatment research in psychiatry that may help advance this field. Methods A fully internet-based protocol was used to gather repeated observational data from patient cohorts receiving internet-based cognitive behavioural therapy (iCBT) (N = 600) or antidepressant medication treatment (N = 110). At baseline, participants provided > 600 data points of self-report data, spanning socio-demographics, lifestyle, physical health, clinical and other psychological variables and completed 4 cognitive tests. They were followed weekly and completed another detailed clinical and cognitive assessment at week 4. In this paper, we describe our study design, the demographic and clinical characteristics of participants, their treatment adherence, study retention and compliance, the quality of the data gathered, and qualitative feedback from patients on study design and implementation. Results Participant retention was 92% at week 3 and 84% for the final assessment. The relatively short study duration of 4 weeks was sufficient to reveal early treatment effects; there were significant reductions in 11 transdiagnostic psychiatric symptoms assessed, with the largest improvement seen for depression. Most participants (66%) reported being distracted at some point during the study, 11% failed 1 or more attention checks and 3% consumed an intoxicating substance. Data quality was nonetheless high, with near perfect 4-week test retest reliability for self-reported height (ICC = 0.97). Conclusions An internet-based methodology can be used efficiently to gather large amounts of detailed patient data during iCBT and antidepressant treatment. Recruitment was rapid, retention was relatively high and data quality was good. This paper provides a template methodology for future internet-based treatment studies, showing that such an approach facilitates data collection at a scale required for machine learning and other data-intensive methods that hope to deliver algorithmic tools that can aid clinical decision-making in psychiatry.

Abstract Background Many refugees suffer from mental health problems due to stressful and traumatic events before, during, and after migration. However, refugees are facing a wide variety of barriers, limiting their access to mental health care. Internet-based tools, available in several languages, could be one way to increase the availability of mental health services for refugees. The present study aimed to develop and test a screening tool to screen for clinically relevant symptoms of psychiatric disorders common among refugees (i.e. Depression, Anxiety, Post-traumatic stress disorder, and Insomnia). We, designed, translated, and adapted an internet-based tiered screening procedure suitable for use with the largest refugee populations residing in Sweden. The tool aims to accurately identify symptoms of mental distress (Tier 1), differentiate between symptoms of specific psychiatric disorders (Tier 2), and assess symptom severity (Tier 3). We tested the overall efficiency of using a tiered screening procedure. Methods Seven hundred fifty-seven refugees residing in Sweden, speaking any of the languages Arabic, Dari, Farsi, English, or Swedish, completed an online questionnaire following a three-tiered procedure with screening instruments for each tier. In this study, the Tier 3 scales were used as reference standards for clinically relevant symptoms, to evaluate screening efficiency in terms of accuracy and reduction of item burden in previous tiers. Results The results show that the tiered procedure could reduce the item burden while maintaining high accuracy, with up to 86% correctly assessed symptoms and few false negatives with moderate symptoms and above (at most 9%), and very few with severe symptoms (at most 1.3%). Discussion This study generated an accurate screening tool that efficiently identifies clinically relevant symptoms of common psychiatric disorders among refugees. Using an adapted online tiered procedure to screen for multiple mental health issues among refugees has the potential to facilitate screening and increase access to mental health services for refugees. We discuss the utility of the screening tool and the necessity of further evaluation.

BackgroundThis study consisted of a qualitative exploration of stakeholder experience regarding the implementation of internet-delivered cognitive behavioral therapy (iCBT) as part of routine service provision within the UK's Improving Access to Psychological Therapies program.MethodsStakeholder groups included service providers (n = 6), commercial iCBT representatives (n = 6) and patients who received a course of iCBT as part of treatment at the service (n = 7). Participants took part in a semi-structured interview over the telephone, and subsequent data were qualitatively analyzed using the descriptive-interpretive approach.ResultsService providers highlighted the importance of effective leadership and management, training initiatives, the provision of feedback to commercial iCBT representatives and creating work structures around iCBT to facilitate iCBT supporting staff in their use of it. Commercial iCBT representatives similarly reported the importance of training clinicians in iCBT use, identifying the appropriate individuals at all levels of the service to drive iCBT implementation, and the importance of being responsive to any problems or needs that arise from the service. Patients reported an overall positive experience of receiving iCBT but highlighted a need for more information from their supporter and the intervention to better structure their usage. Contextual factors, in terms of barriers and facilitators, were also highlighted by service provider and commercial participants; citing negative clinician attitudes and technological issues/bugs as barriers to implementation, and the exposure to iCBT created by COVID-19 and perseverance in using iCBT over time as facilitators.DiscussionThe findings contribute to a growing field of literature that seeks to understand the experience of relevant stakeholders who are involved with and contribute to iCBT implementation, including commercial iCBT representatives who, to our knowledge, have not been accounted for as part of published research to date.

BackgroundResearch suggests there is heterogeneity in treatment response for internet-delivered cognitive behavioral therapy (iCBT) users, but few studies have investigated the trajectory of individual symptom change across iCBT treatment. Large patient data sets using routine outcome measures allows the investigation of treatment effects over time as well as the relationship between outcomes and platform use. Understanding trajectories of symptom change, as well as associated characteristics, may prove important for tailoring interventions or identifying patients who may not benefit from the intervention. ObjectiveWe aimed to identify latent trajectories of symptom change during the iCBT treatment course for depression and anxiety and to investigate the patients’ characteristics and platform use for each of these classes. MethodsThis is a secondary analysis of data from a randomized controlled trial designed to examine the effectiveness of guided iCBT for anxiety and depression in the UK Improving Access to Psychological Therapies (IAPT) program. This study included patients from the intervention group (N=256) and followed a longitudinal retrospective design. As part of the IAPT’s routine outcome monitoring system, patients were prompted to complete the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) after each supporter review during the treatment period. Latent class growth analysis was used to identify the underlying trajectories of symptom change across the treatment period for both depression and anxiety. Differences in patient characteristics were then evaluated between these trajectory classes, and the presence of a time-varying relationship between platform use and trajectory classes was investigated. ResultsFive-class models were identified as optimal for both PHQ-9 and GAD-7. Around two-thirds (PHQ-9: 155/221, 70.1%; GAD-7: 156/221, 70.6%) of the sample formed various trajectories of improvement classes that differed in baseline score, the pace of symptom change, and final clinical outcome score. The remaining patients were in 2 smaller groups: one that saw minimal to no gains and another with consistently high scores across the treatment journey. Baseline severity, medication status, and program assigned were significantly associated (P

This article investigates how floor plan layout of a printed circuit board (PCB) influences the reliability of the component’s solder joint connections when operated in a vibrating environment. A random vibration profile as seen in an automotive environment was used in full lifetime tests. An industry-standard FR4 PCB with electroless nickel immersion gold (ENIG) surface finish was manufactured with double-sided component placement including 14 flip chips, eight on the top side and six on the bottom side. Ultrasound scans were used as a nondestructive test to assess the integrity of solder joints from manufacture to failure. This enabled monitoring of the important interface between solder joints and flip chip where failure mostly occurs. The initial failure pattern was found by experiment where 86 cycles of random vibration caused all flip chips to mechanically fail. Failure followed a Weibull probability with a value of $\beta = 1.297$ , indicating that failure rates increase with time. The results show that the reliability of a flip chip varies with its position on a PCB with some marked differences to component lifetimes. The results also show that for two-sided flip-chip placements on a PCB, back-to-back, overlapped, and single-sided orientations have subtle effects on flip-chip lifetimes. Similarly, reliability varied with solder joint positions since joints on the sides of a flip chip nearest the PCB edges were less reliable than those on sides on a flip chip furthest away. Finally, design guidelines are offered to effect the most reliable flip-chip placement on a two-sided PCB when operated in a vibrating environment. [ABSTRACT FROM AUTHOR]

Abstract Background Research has shown that internet-based cognitive behavioural therapy (iCBT) can be a very promising solution to increase access to and the dissemination of evidence-based treatments to all of the population in need. However, iCBT is still underutilized in clinical contexts, such as primary care. In order to achieve the effective implementation of these protocols, more studies in ecological settings are needed. The Unified Protocol (UP) is a transdiagnostic CBT protocol for the treatment of emotional disorders, which includes depression, anxiety and related disorders, that has shown its efficacy across different contexts and populations. An internet-based UP (iUP) programme has recently been developed as an emerging internet-based treatment for emotional disorders. However, the internet-delivered version of the UP (iUP) has not yet been examined empirically. The current project seeks to analyse the effectiveness of the iUP as a treatment for depression, anxiety and related emotional disorders in a primary care public health setting. Methods The current study will employ a parallel-group, randomized controlled trial design. Participants will be randomly assigned to (a) the internet-based Unified Protocol (iUP), or (b) enhanced waiting list control (eWLC). Randomization will follow a 2:1 allocation ratio, with sample size calculations suggesting a required sample of 120 (iUP=80; eWLC=40). The Mini-International Neuropsychiatric Interview (M.I.N.I.) will be used for assessing potential participants. The Overall Anxiety Severity and Impairment Scale (OASIS) and the Overall Depression Severity and Impairment Scale (ODSIS) as well as other standardized questionnaires will be used for assessments at baseline, 4 weeks, 8 weeks and 12 weeks from baseline and for the iUP condition during the follow-up. Discussion Combining the advantages of a transdiagnostic treatment with an online delivery format may have the potential to significantly lower the burden of emotional disorders in public health primary care setting. Anxiety and depression, often comorbid, are the most prevalent psychological disorders in primary care. Because the iUP allows for the treatment of different disorders and comorbidity, this treatment could represent an adequate choice for patients that demand mental health care in a primary care setting. Trial registration ISRCTN18056450 https://doi.org/10.1186/ISRCTN18056450 .

Abstract Background Major depressive disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM only. But 77% of US MDD patients are nonetheless treated with ADM only despite strong patient preferences for psychotherapy. This mismatch is due at least in part to a combination of cost considerations and limited availability of psychotherapists, although stigma and reluctance of PCPs to refer patients for psychotherapy are also involved. Internet-based cognitive behaviorial therapy (i-CBT) addresses all of these problems. Methods Enrolled patients (n = 3360) will be those who are beginning ADM-only treatment of MDD in primary care facilities throughout West Virginia, one of the poorest and most rural states in the country. Participating treatment providers and study staff at West Virginia University School of Medicine (WVU) will recruit patients and, after obtaining informed consent, administer a baseline self-report questionnaire (SRQ) and then randomize patients to 1 of 3 treatment arms with equal allocation: ADM only, ADM + self-guided i-CBT, and ADM + guided i-CBT. Follow-up SRQs will be administered 2, 4, 8, 13, 16, 26, 39, and 52 weeks after randomization. The trial has two primary objectives: to evaluate aggregate comparative treatment effects across the 3 arms and to estimate heterogeneity of treatment effects (HTE). The primary outcome will be episode remission based on a modified version of the patient-centered Remission from Depression Questionnaire (RDQ). The sample was powered to detect predictors of HTE that would increase the proportional remission rate by 20% by optimally assigning individuals as opposed to randomly assigning them into three treatment groups of equal size. Aggregate comparative treatment effects will be estimated using intent-to-treat analysis methods. Cumulative inverse probability weights will be used to deal with loss to follow-up. A wide range of self-report predictors of MDD heterogeneity of treatment effects based on previous studies will be included in the baseline SRQ. A state-of-the-art ensemble machine learning method will be used to estimate HTE. Discussion The study is innovative in using a rich baseline assessment and in having a sample large enough to carry out a well-powered analysis of heterogeneity of treatment effects. We anticipate finding that self-guided and guided i-CBT will both improve outcomes compared to ADM only. We also anticipate finding that the comparative advantages of adding i-CBT to ADM will vary significantly across patients. We hope to develop a stable individualized treatment rule that will allow patients and treatment providers to improve aggregate treatment outcomes by deciding collaboratively when ADM treatment should be augmented with i-CBT. Trial registration ClinicalTrials.gov NCT04120285 . Registered on October 19, 2019.

Abstract Background Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent among university students and predict impaired college performance and later life role functioning. Yet most students do not receive treatment, especially in low-middle-income countries (LMICs). We aim to evaluate the effects of expanding treatment using scalable and inexpensive Internet-delivered transdiagnostic cognitive behavioral therapy (iCBT) among college students with symptoms of MDD and/or GAD in two LMICs in Latin America (Colombia and Mexico) and to investigate the feasibility of creating a precision treatment rule (PTR) to predict for whom iCBT is most effective. Methods We will first carry out a multi-site randomized pragmatic clinical trial (N = 1500) of students seeking treatment at student mental health clinics in participating universities or responding to an email offering services. Students on wait lists for clinic services will be randomized to unguided iCBT (33%), guided iCBT (33%), and treatment as usual (TAU) (33%). iCBT will be provided immediately whereas TAU will be whenever a clinic appointment is available. Short-term aggregate effects will be assessed at 90 days and longer-term effects 12 months after randomization. We will use ensemble machine learning to predict heterogeneity of treatment effects of unguided versus guided iCBT versus TAU and develop a precision treatment rule (PTR) to optimize individual student outcome. We will then conduct a second and third trial with separate samples (n = 500 per arm), but with unequal allocation across two arms: 25% will be assigned to the treatment determined to yield optimal outcomes based on the PTR developed in the first trial (PTR for optimal short-term outcomes for Trial 2 and 12-month outcomes for Trial 3), whereas the remaining 75% will be assigned with equal allocation across all three treatment arms. Discussion By collecting comprehensive baseline characteristics to evaluate heterogeneity of treatment effects, we will provide valuable and innovative information to optimize treatment effects and guide university mental health treatment planning. Such an effort could have enormous public-health implications for the region by increasing the reach of treatment, decreasing unmet need and clinic wait times, and serving as a model of evidence-based intervention planning and implementation. Trial status IRB Approval of Protocol Version 1.0; June 3, 2020. Recruitment began on March 1, 2021. Recruitment is tentatively scheduled to be completed on May 30, 2024. Trial registration ClinicalTrials.gov NCT04780542 . First submission date: February 28, 2021.

Introduction: The coronavirus disease 2019 (COVID-19) led to the worldwide closure of dental practices or reduction of dental services. By the end of April 2020, governments and professional organisations were publishing recommendations or guidance for the reopening/restructuring of dental services. The aim of this study was to assess how dental aerosol-generating procedures (AGPs) were defined in international dental guidelines, what mitigation processes were advised, and whether they were linked to COVID-19 epidemiology. Methods: Electronic searches of a broad range of databases, along with grey literature searches, without language restriction were conducted up to 13 July 2020. Recommendations for the use of face masks and fallow times with patients without COVID-19 were assessed against the deaths per 1 million population in the included countries and country income level using Pearson Chi-squared statistics. Results: Sixty-three guidance documents were included. Most (98%) indicated that AGPs can be performed with patients without COVID-19 with caveats, including advice to restrict AGPs where possible, with 21% only recommending AGPs for dental emergencies. Face masks were recommended by most documents (94%), with 91% also specifying the use of goggles or face shields. Fallow periods for patients without COVID-19 were mentioned in 48% of documents, ranging from 2 to 180 minutes. There were no significant differences in recommendations for face masks or fallow time in patients without COVID-19 by country death rate (P = .463 and P = .901) or World Bank status (P = .504 and P = .835). Most documents recommended procedural or environmental mitigations such as preprocedural mouthwash (82%) and general ventilation (52%). Few documents provided underpinning evidence for their recommendations. Conclusions: While the amount of high-quality direct evidence related to dentistry and COVID-19 remains limited, it is important to be explicit about the considered judgements for recommendations as well as generate new evidence to face this challenge.

Background/Aims: The oxidative stress sensor transient receptor potential melastatin-2 (TRPM2) ion channel has recently gained attention in many types of cancer. The lung tissue is highly susceptible to oxidative stress-mediated injury and diseases; therefore, we aimed to determine whether TRPM2 plays an essential role in protecting lung cancer cells from oxidative damage while promoting cancer cell survival and metastasis. Methods: We used two non-small cell lung (NSCLC) cell lines A549 and H1299 as a lung cancer model. We investigated the functional expression of TRPM2 using electrophysiology, qRT-PCR and Western blots. CFSE and flow cytometry were used to study TRPM2 role in proliferation, cell cycle and apoptosis. Gap closure chambers and Three-Tiered Chemotaxis Chamber were used to study the role of TRPM2 in metastasis. SCID mice were used to study the role of TRPM2 in lung tumor growth and metastasis. Results: We demonstrate that TRPM2 is functionally expressed in NSCLC cells and that its downregulation significantly inhibits cell proliferation and promotes apoptosis. These results were concomitant with an induction in DNA damage and G2/M cell cycle arrest. TRPM2 silencing inhibits also lung cancer cells invasion ability and alters EMT processes. Mechanistically, TRPM2 downregulation causes an increase in the intracellular levels of reactive oxygen (ROS) and nitrogen (RNS) species, which in turn causes DNA damage and JNK activation leading to G2/M arrest, and an ultimate cell death. Finally, TRPM2 downregulation suppresses the growth of human lung tumour xenograft in SCID mice and TRPM2 depleted tumours exhibited a significant reduction in the mRNA expression level of EMT markers compared to the control tumors. Conclusion: Our data provide new insights on the functional expression of TRPM2 in lung cancer, its essential role in tumour growth and metastasis through the control of JNK signaling pathway, and that TRPM2 could be exploited for targeted lung cancer therapies. [ABSTRACT FROM AUTHOR]

BackgroundMental health difficulties in children and adolescents are highly prevalent; however, only a minority receive adequate mental health care. Internet-delivered interventions offer a promising opportunity to increase access to mental health treatment. Research has demonstrated their effectiveness as a treatment for depression and anxiety in adults. This work provides an up-to-date examination of the available intervention options and their effectiveness for children and young people (CYP). ObjectiveIn this systematic review and meta-analysis, we aimed to determine the evidence available for the effectiveness of internet-delivered interventions for treating anxiety and depression in CYP. MethodsSystematic literature searches were conducted throughout November 2020 using PubMed, PsycINFO, and EBSCO academic search complete electronic databases to find outcome trials of internet-delivered interventions treating symptoms of anxiety and/or depression in CYP by being either directly delivered to the CYP or delivered via their parents. Studies were eligible for meta-analysis if they were randomized controlled trials. Risk of bias and publication biases were evaluated, and Hedges g between group effect sizes evaluating intervention effects after treatment were calculated. Meta-analyses used random-effects models as per protocol. ResultsA total of 23 studies met the eligibility criteria for the systematic review, of which 16 were included in the meta-analyses, including 977 participants in internet-delivered treatment conditions and 1008 participants in control conditions across 21 comparisons. Random-effects models detected a significant small effect for anxiety symptoms (across 20 comparisons; Hedges g=−0.25, 95% CI −0.38 to −0.12; P

BackgroundPrevious research has shown a strong relationship between financial difficulties and mental health problems. Psychological factors such as hope and worry about finances appear to be an important factor in this relationship.ObjectiveTo develop an online based psychological intervention (Space from Money Worries) to tackle the psychological mechanisms underlying the relationship between poor mental health and financial difficulties, and to conduct an initial evaluation of the acceptability and preliminary efficacy of the intervention.Materials and Methods30 participants accessing Increasing Access to Psychological Therapies (IAPT) services completed GAD-7 to measure anxiety and PHQ-9 to measure depression upon signing up to the online intervention and again 4 to 8 weeks after this. Participants also completed a measure of perceived financial distress/wellbeing and a “Money and Mental Health Scale” constructed for the evaluation.ResultsOverall, 77% (n = 23) completed the intervention and follow-up assessments. Intent to Treat Analysis showed that there were statistically significant improvements in symptoms of depression, anxiety, improved perceived financial wellbeing and reduced scores on the money and mental health scale. The vast majority of participants rated each module positively.ConclusionsSpace from Money Worries appears to be acceptable and may lead to improvements in mental health, perceived financial wellbeing and a reduced relationship between financial difficulties and poor mental health. However, future research with a larger sample and a control group are needed to confirm that these changes are due to the intervention.

Objective: Over half of the world's forcibly displaced persons are under the age of 25, with many suffering from symptoms of psychological disorders. Many refugees from Afghanistan or Iran speak either Dari or Farsi, which are mutually intelligible dialects of the Persian language. Previous research on adult refugees and immigrants have shown that internet-based cognitive behavioural therapy (ICBT) can be a valuable complement to other forms of treatment. However, there is a lack of knowledge if ICBT is a feasible and acceptable treatment for adolescents and young adults with a refugee background. Method: Fifteen Dari/Farsi-speaking adolescents and young adults between 15 and 26 years of age participated in a feasibility study of a novel individually tailored guided ICBT intervention targeting symptoms of common mental disorders such as anxiety and depression. Self-reported symptoms of anxiety and depression were assessed using the Hopkins Symptom Checklist-25 (HSCL-25) as the primary outcome measure. Four of the treatment participants and three additional non-treatment participants consented to be interviewed regarding the programme's acceptability. The interviews were analysed using Thematic Analysis. Results: The intervention suffered from low adherence, with only 3 participants completing the post-treatment assessment and with participants completing 0.9 modules on average, which meant that the intended quantitative analysis of the pre to post change was not possible. The thematic analysis resulted in two overarching categories, barriers and facilitators, that each contained four themes and related subthemes. Overall, the intervention was deemed culturally relevant and easy to understand. The most salient barriers to participation across interviews concerned interference of symptoms such as concentration difficulties, low energy, and a lack of human contact and support. Conclusion: The current version of the ICBT program demonstrated low feasibility and acceptability in the target population, which mainly seemed to be related to the delivery format. Future studies should investigate if a blended treatment format with regular phone/video calls with a therapist can increase adherence to the intervention.

Abstract Utilization of internet-delivered cognitive behavioural therapy (iCBT) for treating depression and anxiety disorders in stepped-care models, such as the UK’s Improving Access to Psychological Therapies (IAPT), is a potential solution for addressing the treatment gap in mental health. We investigated the effectiveness and cost-effectiveness of iCBT when fully integrated within IAPT stepped-care settings. We conducted an 8-week pragmatic randomized controlled trial with a 2:1 (iCBT intervention: waiting-list) allocation, for participants referred to an IAPT Step 2 service with depression and anxiety symptoms (Trial registration: ISRCTN91967124). The primary outcomes measures were PHQ-9 (depressive symptoms) and GAD-7 (anxiety symptoms) and WSAS (functional impairment) as a secondary outcome. The cost-effectiveness analysis was based on EQ-5D-5L (preference-based health status) to elicit the quality-adjust life year (QALY) and a modified-Client Service Receipt Inventory (care resource-use). Diagnostic interviews were administered at baseline and 3 months. Three-hundred and sixty-one participants were randomized (iCBT, 241; waiting-list, 120). Intention-to-treat analyses showed significant interaction effects for the PHQ-9 (b = −2.75, 95% CI −4.00, −1.50) and GAD-7 (b = −2.79, 95% CI −4.00, −1.58) in favour of iCBT at 8-week and further improvements observed up to 12-months. Over 8-weeks the probability of cost-effectiveness was 46.6% if decision makers are willing to pay £30,000 per QALY, increasing to 91.2% when the control-arm’s outcomes and costs were extrapolated over 12-months. Results indicate that iCBT for depression and anxiety is effective and potentially cost-effective in the long-term within IAPT. Upscaling the use of iCBT as part of stepped care could help to enhance IAPT outcomes. The pragmatic trial design supports the ecological validity of the findings.

Insomnia is a highly prevalent, often comorbid disorder associated with difficulties sleeping, remaining awake, and impaired quality of life. Internet-delivered Cognitive Behavioral Therapy for insomnia (ICBT-I11 ICBT-I, internet-delivered cognitive behavioral therapy for insomnia.) has the potential to help large numbers of people with sleep disorders. This study investigated the preliminary effects of an 8-week guided ICBT-I intervention within a routine stepped-care service. Fifty-six (N = 56) patients consented to participate. The primary outcome was assessed using the Insomnia Severity Index (ISI) and secondary outcome measures included the Patient Health Questionnaire 9-item (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), and the Work and Social Adjustment Scale (WSAS), each administered at baseline and weekly thereafter. Intention-to-treat analyses indicated that ICBT-I produced statistically significant pre- to post- reductions in symptoms of insomnia, yielding within-group effects of d = 0.82 suggesting a potential for improved outcomes. Similar improvements were seen across secondary outcomes, with small-to-medium post-treatment within-group effects observed: depression (d = 0.63), anxiety (d = 0.39), and functional impairment (d = 0.31). These findings are supportive of the intervention's potential effectiveness and speak to the importance of several implementation factors that could enhance the effects of the intervention. The results contribute to the growing evidence base for digital interventions designed to help those with sleep difficulties and will inform the design of a future controlled evaluation of ICBT-I under routine clinical settings.

BackgroundTreatment dropout continues to be reported from internet-delivered cognitive behavioral therapy (iCBT) interventions, and lower completion rates are generally associated with lower treatment effect sizes. However, evidence is emerging to suggest that completion of a predefined number of modules is not always necessary for clinical benefit or consideration of the needs of each individual patient. ObjectiveThe aim of this study is to perform a qualitative analysis of patients’ experiences with an iCBT intervention in a routine care setting to achieve a deeper insight into the phenomenon of dropout. MethodsA total of 15 purposively sampled participants (female: 8/15, 53%) from a larger parent randomized controlled trial were interviewed via telephone using a semistructured interview schedule that was developed based on the existing literature and research on dropout in iCBT. Data were analyzed using a descriptive-interpretive approach. ResultsThe experience of treatment leading to dropout can be understood in terms of 10 domains: relationship to technology, motivation to start, background knowledge and attitudes toward iCBT, perceived change in motivation, usage of the program, changes due to the intervention, engagement with content, experience interacting with the supporter, experience of web-based communication, and termination of the supported period. ConclusionsPatients who drop out of treatment can be distinguished in terms of their change in motivation: those who felt ready to leave treatment early and those who had negative reasons for dropping out. These 2 groups of participants have different treatment experiences, revealing the potential attributes and nonattributes of dropout. The reported between-group differences should be examined further to consider those attributes that are strongly descriptive of the experience and regarded less important than those that have become loosely affiliated.

Background: Depression and anxiety are common problems among breast cancer survivors. Carer support is one of the most important determinants of women's psychological wellbeing. Survivors' distress can be alleviated by giving carers access to survivors' evidence-based treatment, which will help carers understand what survivors have been going through and help survivors feel more supported. Given the limited access to evidence-based treatments, an adapted internet-delivered cognitive behavioural therapy (iCBT) intervention for breast cancer survivors, but also open for carers' access, has the potential to decrease survivors' depression and anxiety symptoms and improve cancer-related communication and relationship quality between survivors and carers. Objectives: This study evaluates (1) the effectiveness of a guided iCBT intervention for depression and/or anxiety symptoms among breast cancer survivors with and without main carer access, and (2) the acceptability and satisfaction with the iCBT programme. Method: In this pilot study comparing the effectiveness of an adapted 7-week iCBT without main carer access against the iCBT with main carer access and treatment-as-usual control, 108 breast cancer survivors will be recruited and then randomised to either (1) treatment (n = 72) or (2) treatment-as-usual control group (n = 36) with a 2:1 ratio. The participants in the treatment group will be assigned to either iCBT alone or iCBT with the main carer also having access to the same content based on their preference. The primary outcome measure is the Hospital Anxiety and Depression Scale, and alongside secondary measures such as Cancer-Related Quality of Life, Breast Cancer Worry Scale, Brief COPE, and Medical Outcomes Study Social Support Survey will be completed by the survivors at baseline, post-treatment, and 2-month follow-up. Survivors who have carers will also complete Survivor-Carer Cancer Communication and Relationship Quality measures to provide insights into the effects of carer access. To assess the acceptability and satisfaction with the programme, survivors and their main carers will fill out the Helpful Aspects of Therapy Form (HAT) and Satisfaction with Online Treatment (SAT). Programme effectiveness and the effects of carer access on primary and secondary outcome measures will be evaluated on intention-to-treat and per-protocol basis using Linear-Mixed-Models. Discussion: This is the first trial comparing the effectiveness and acceptability of iCBT with and without carer access for depression and anxiety among breast cancer survivors. The findings of this study will provide novel data on the acceptability of iCBT programmes for breast cancer survivors and the impact of carer access on them and their carers.

Background: Culturally adapted psychotherapy (CAP) studies are limited and until now there are few published examples that illustrate the process of cultural adaptation with internet-delivered treatments. Aim: This paper aims to illustrate an integrative approach to the cultural adaptation of an evidence-based internet-delivered cognitive-behavioural therapy intervention for depression (Space from Depression programme). Method: Mixed method approach utilising quantitative and qualitative methods to assist in the cultural adaptation of the Space from Depression programme was used. The adaptation involved a framework for cultural sensitivity (CSF), alongside an ecological validity framework (EVF) and principles from cross-cultural assessment research. The method included the development of a theory-informed measure, the Cultural Relevance Questionnaire (CRQ), designed specifically for this research. Results: The adaptation included an establishment of CSF, which included the incorporation of Colombian cultural expressions. College students' (n = 5) and experts' (n = 7) evaluated the EVF based on cross-cultural assessment principles of a preliminary adapted version through the CRQ, showing reliability in the sample (Cronbach's Alpha 0.744). Qualitative analysis supported the culturally sensitive changes or incorporations made to the programme, such as: personal stories and textual translations from English and these were considered ecologically valid and representative. Conclusions: The research provided support for the idea that CAP can be conducted systematically for internet-delivered interventions. Keywords: Culturally adapted psychotherapy, Internet-delivered treatment, Cultural sensitivity framework, Ecological validity framework, Cultural equivalence, Depression

Background: The UK’s Improving Access to Psychological Therapies (IAPT) program is a stepped-care model treating individuals with depression and anxiety disorders. Internet-delivered cognitive behavioral therapy (iCBT) is routinely offered to individuals with mild to moderate symptoms, but its applicability to individuals with severe clinical symptoms and requiring a high-intensity intervention is relatively unknown. The current study sought to investigate the potential impacts of using iCBT as a prequel for patients requiring high-intensity treatment (HIT; face-to-face) for depression and anxiety in IAPT.Methods: The study utilized an open study design. One hundred and twenty-four participants who were on a waiting list for high-intensity, face-to-face psychological treatment were offered iCBT. Psychometric data on symptoms of depression, anxiety, and functioning were collected from participants before starting and on finishing iCBT and at the point of service exit. Therapeutic alliance data were collected from patients and clinicians during treatment. Patient pathway data, such as number of treatment sessions and time in treatment, was also collected and incorporated into the analysis.Results: Significant reductions across primary outcome measures of depression and anxiety, as well as improved functioning, were observed from baseline to iCBT treatment exit, and from iCBT exit to service exit. Analysis of the therapeutic alliance data for patients and clinicians illustrated differences in outcome for those who dropped out and those who completed treatment.Discussion: This study illustrates the potential for using iCBT as a prequel to high-intensity therapy for depression and anxiety disorders and is the first of its kind to do so within IAPT stepped care. The results show that iCBT is a valuable option reducing waiting times and enhancing clinical efficiency. The study contributes to the well-established evidence on online psychological treatments worldwide, but further clinical and service development research is necessary to scale these treatments appropriately.

Abstract Background Depression and anxiety are common mental health disorders worldwide. The UK’s Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT. Methods The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis. Discussion This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services. Trial registration Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124. Web: http://www.isrctn.com/ISRCTN91967124. Clinicaltrials.gov: NCT03188575. Trial registration date: June 8, 2017 (prospectively registered).

Abstract Background Depression is the principal cause of disability in the world. High prevalence rates of depression in general populations and college students have been found worldwide and in various cultural groups. Low-intensity cognitive behavioural internet-delivered treatment has demonstrated efficacy in high-income-countries (HICs). However little is known of their potential for adaptation and efficacy in low and middle-income countries. Methods Study (1) involves the cultural adaptation of the Space from Depression cognitive-behaviour internet-delivered programme with an asynchronous support for depressive symptoms. This includes initial researcher/clinician adaptation and the integration of cultural assessment feedback of the programme by a panel of experts and users through the theoretically-based Cultural Relevance Questionnaire (CRQ). Study (2) describes the implementation of the culturally adapted intervention using a randomised controlled trial methodology. The efficacy trial will include an active treatment group and a waiting-list control group of participants meeting eligibility criteria (mild to moderate depression symptoms). The active condition will consist of 7 weekly modules of internet-delivered cognitive behavioural therapy (iCBT) Space from Depression, with post-session feedback support. The primary outcome will be the Patient Health Questionnaire (PHQ-9). The study also involves collection of client reported significant events and client satisfaction with the internet-delivered treatment. Data will be collected at baseline and at post-treatment (week 7), and at follow-up (week 20/3 months). Analysis will be conducted on the intention-to-treat basis. Discussion The study seeks to establish a theoretically robust methodology for culturally adapting internet-delivered interventions for mental health disorders and to evaluate the efficacy of a culturally adapted internet-delivered treatment for depression in Colombia, with support. The study will be a first contribution to a method for culturally adapting internet-delivered interventions and also a first to examine the efficacy of such an adapted intervention in Latin America. Trial registration Clinical trials NCT03062215. Retrospectively registered 14th February 2017.

Abstract Background Obesity and dental caries are global public health problems which can impact in childhood and throughout the life course. In simple terms, childhood dental caries and body weight are linked via the common risk factor of diet. An association between dental caries and obesity has been described in a number of studies and reviews. However, similarly, a relationship has also been noted between low body weight and caries experience in children. This protocol will provide the framework for an umbrella review to address the following question: Does the available evidence support a relationship between dental caries experience and body weight in the child population? Methods This review protocol outlines the process to carry out an umbrella systematic review which will synthesise previous reviews of childhood dental caries experience and body weight. An umbrella review methodology will be used to examine the methodological and reporting quality of existing reviews. Discussion The final umbrella review aims to aggregate the available evidence in order to provide a summary for policymakers and to inform healthcare interventions. Systematic review registration PROSPERO CRD42016047304

Abstract Background This is a protocol for a systematic review of the impact of health coaching on changing the health behaviour of offenders. Prisoners are more likely to suffer from health-related issues when compared to the general population. Health coaching has been shown to influence health outcomes of patients with chronic conditions. This review, therefore, aims to assess the effectiveness of health coaching interventions on the health of adolescent and adult offenders in custodial institutions. Methods We plan to conduct a systematic review of the current literature on health coaching interventions delivered in the prison setting. We will include randomised controlled trials and observational studies that compare health coaching to the usual care or other alternative interventions. The ideal interventions will be delivered either by health professionals or peer coaches, and the outcomes extracted in the data collection will be disease-specific, clients’ life and self-management skills, behavioural and psychosocial outcomes. If appropriate, a meta-analysis of the data collected will be carried out on the last stage of the review. Discussion This systematic review will identify and gather evidence on the impact of health coaching interventions delivered in the prison setting and can function as a supporting material for health professionals, prison staff, the healthcare system, and public health departments when considering delivering health coaching. Systematic review registration PROSPERO CRD42016053237 .

Abstract Background Continuing advances in medical care and nutrition have prolonged the lifespan and expanded the elderly demographic world-wide. Despite increasing elderly populations within Taiwanese nursing homes, there has been a lack of dermatologic surveys, and the prevalence of skin conditions within this group is unknown. Methods To establish the prevalence of skin disease within nursing homes in southern Taiwan, we undertook a dermatologic and epidemiologic investigation of 398 patients in Tainan City, southern Taiwan, between November 1999 and February 2000. Results This study revealed that more than half of all nursing home patients suffered from fungus (61.6%) and xerosis (58.3%), while other pruritic skin diseases, such as dermatitis and scabies, were less prevalent at 7.3% and 3.3%, respectively. Risk factors for fungal infection included bedridden status (risk ratio (RR), 1.2; 95% confidence interval (CI), 1.1–1.4) and male gender (RR, 1.2; 95% CI, 1.0–1.3). Xerosis was statistically correlated with an age range of 80–90 years (RR, 1.2; 95% CI, 1.0–1.4) when compared to other age ranges. Current scabies diagnosis was strongly associated with a previous history of scabies (RR, 8.9; 95% CI, 1.7–21.1). Conclusions Our study provides clinically relevant data regarding the prevalence of skin diseases in institutionalized Taiwanese patients for the first time. The results suggest that scabies persists within some nursing homes despite treatment, and that some patients remain undiagnosed. The dermatologic needs of these Taiwanese patients are not currently being satisfied. [ABSTRACT FROM AUTHOR]

Background: There are clear advantages to internet-delivered interventions for depression. Users' perspectives on the acceptability, satisfaction, and efficacy of an internet-delivered treatment for depression can inform future developments in the area. Methods: Respondents (n = 281) were participants in an 8 week supported internet-delivered Cognitive Behaviour Therapy treatment for depressive symptoms. Self-report online questionnaires gathered quantitative and qualitative data on the user experience. Principle findings: Most respondents were satisfied with the programme (n = 191), felt supported (n = 203), reported positive gains and impact resulting from use of the programme, and perceived these to be likely to be lasting effects (n = 149). Flexibility and accessibility were the most liked aspects. A small number of respondents felt their needs were not met by the intervention (n = 64); for this group suggestions for improvements centred on the programme's structure and how supporter feedback is delivered. Conclusion: Results will deepen the understanding of users' experience and inform the development and implementation of evidence-based internet-delivered interventions.

Antecedentes/Objetivo : La depresión es uno de los trastornos de salud mental más co - munes y un incipiente problema de salud pública. Pocos estudios han investigado la prevalencia y factores predictivos de su gravedad en el contexto irlandés. El objetivo del estudio fue investigar los factores de riesgo que predicen la gravedad de la depresión en una muestra de adultos en Irlanda en búsqueda de tratamiento. Método : Los participan - tes auto-referidos accedieron a una intervención en línea para la depresión. Los partici - pantes ( N = 641) completaron cuestionarios, incluyendo el BDI-II, e información asociada con predictores comunes de la depresión. Resultados : Se encontraron varios factores que predijeron la gravedad de la depresión: el sexo, ser mujer, ser joven, situación laboral, estar soltero o con pareja pero no casado, diagnóstico previo de depresión y experiencias de estrés recientes. Conclusiones : El estudio contribuye a la elaboración de perfiles de incidencia y factores predictivos en la gravedad de la depresión. Los resultados confir - man algunos de los factores de riesgo conocidos y ponen en relieve la necesidad de nue - vas investigaciones que lleven a cabo la detección de la depresión así como un mayor acceso a las intervenciones.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.