Treatment effect heterogeneity of cognitive behavioral therapy for insomnia - A meta-analysis.

Investigation of the heterogeneity of the treatment effect (HTE) might guide the optimization of cognitive behavioral therapy for insomnia (CBT-I). This study examined HTE in CBT-I thereby analyzing if treatment setting, control group, different CBT-I components, and patient characteristics drive HTE. Randomized controlled trials investigating CBT-I were included. Bayesian random effect meta-regressions were specified to examine variances between the intervention and control groups regarding post-treatment symptom severity. Subgroup analyses analyzing treatment setting and control groups and covariate analysis analyzing treatment components and patient characteristics were specified. No significant HTE in CBT-I was found for the overall data set, settings and control groups. The covariate analyses yielded significant results for baseline severity and the treatment component relaxation therapy. Thus, this study identified potential causes for HTE in CBT-I for the first time, showing that it might be worthwhile to further examine possibilities for precision medicine in CBT-I.

The predictive value of supervised machine learning models for insomnia symptoms through smartphone usage behavior.

Introduction: Digital phenotyping can be an innovative and unobtrusive way to improve the detection of insomnia. This study explores the correlations between smartphone usage features (SUF) and insomnia symptoms and their predictive value for detecting insomnia symptoms. Methods: In an observational study of a German convenience sample, the Insomnia Severity Index (ISI) and smartphone usage data (e.g., time the screen was active, longest time the screen was inactive in the night) for the previous 7 days were obtained. SUF (e.g., min, mean) were calculated from the smartphone usage data. Correlation analyses between the ISI and SUF were conducted. For the specification of the machine learning models (ML), 80 % of the data was allocated to training, 20 % to testing, and five-fold cross-validation was used. Six algorithms (support vector machine, XGBoost, Random Forest, k-Nearest-Neighbor, Naive Bayes, and Logistic Regressions) were specified to predict ISI scores ≥15. Results: 752 participants (51.1 % female, mean ISI = 10.23, mean age = 41.92) were included in the analyses. Small correlations between some of the SUF and insomnia symptoms were found. In the ML models, sensitivity was low, ranging from 0.05 to 0.27 in the testing subsample. Random Forest and Naive Bayes were the best-performing algorithms. Yet, their AUCs (0.57, 0.58 respectively) in the testing subsample indicated a low discrimination capacity. Conclusions: Given the small magnitude of the correlations and low discrimination capacity of the ML models, SUFs, as measured in this study, do not appear to be sufficient for detecting insomnia symptoms. Further research is necessary to explore whether examining intra-individual variations and subpopulations or employing alternative smartphone sensors yields more promising outcomes.

Are single nucleotide polymorphisms in the IL-2 gene biomarkers for Hashimoto's thyroiditis?

Background and aims: Hashimoto's thyroiditis (HT) is an autoimmune disorder that can lead to hypothyroidism. The pathophysiology of HT involves the production of antithyroid antibodies that attack the thyroid tissue, causing inflammation and progressive fibrosis. Recent studies demonstrated a strong correlation between Interleukin-2 (IL-2) levels and the development of autoimmune diseases, suggesting that this cytokine may play a crucial role in the pathogenesis of HT. Methods: In this study, we determined the presence of the point mutation +114T/G in the IL-2 gene in patients with HT compared with a control group, and also the serum level of anti-thyroid peroxidase (TPOAbs) and anti-thyroglobulin (TgAbs) antibodies in HT patients with vs. without the mutation. The sequences of the IL-2 gene obtained from subjects were determined by the Sanger sequencing method. Results: Our study did not reveal that the +114T/G polymorphism of the IL-2 gene is a susceptibility or protective factor for HT. No significant correlations were observed between the reference genotype, hetero- and homozygous +114T/G polymorphism and TPOAbs, respectively TgAbs serum levels in HT patients. Conclusions: Further studies of more cases are needed to identify more polymorphisms in the IL-2 gene and study their correlations with HT.

Role of RAPID score and surgery in the management of pleural infection: a single center retrospective study.

Background: The RAPID [Renal (urea level), Age, Pleural fluid purulence, source of Infection and Denutrition (albumin level)] score classifies patients with pleural infection according to mortality risk at 3 months. This study aims to assess the applicability of this score in a thoracic surgery department and to determine the impact of surgery in the management of pleural infection depending on the Rapid score. Methods: In this single center retrospective study, patients managed for pleural infection, from January 1st 2013 to June 30th 2019, were included. The primary endpoint was the probability of survival at 6 months and 12 months depending on the RAPID score. Secondary endpoint was the probability of survival at 6 and 12 months in patients who had surgeries (surgical treatment group) and patients who didn't have surgery (medical treatment group). Results: Seventy-four patients were included, with a median age of 54.5 years. According to the RAPID score, the low-, medium- and high-risk groups had 30, 30 and 14 patients respectively. The probability of survival at 6 and 12 months in the low- and medium-risk groups were both 0.967 [95% confidence index (CI95): 0.905-1] whereas, the probabilities of survival at 6 and 12 months in the high-risk group was significantly lower at 0.571 (CI95: 0.363-0.899) and 0.357 (CI95: 0.177-0.721) respectively (P<0.0001). The probabilities of survival at 6 months and 12 months in the medical treatment group was 0.875 (CI95: 0.786-0.974) and 0.812 (CI95: 0.704-0.931) respectively compared to the surgical treatment group where probabilities of survival at 6 and 12 months were both 0.923 (CI95: 0.826-1) (P=0.26). Conclusions: In our study, patients with pleural infection, classified as high-risk according to the RAPID score, had a lower survival rate compared to low- and medium-risk patients. No difference in survival rate was found between patients classified as low- and medium-risk. In selected patients, surgical management seems to decrease mortality compared to exclusive medical management: this result should be confirmed in larger prospective studies.

Quantifying brain connectivity signatures by means of polyconnectomic scoring.

A broad range of neuropsychiatric disorders are associated with alterations in macroscale brain circuitry and connectivity. Identifying consistent brain patterns underlying these disorders by means of structural and functional MRI has proven challenging, partly due to the vast number of tests required to examine the entire brain, which can lead to an increase in missed findings. In this study, we propose polyconnectomic score (PCS) as a metric designed to quantify the presence of disease-related brain connectivity signatures in connectomes. PCS summarizes evidence of brain patterns related to a phenotype across the entire landscape of brain connectivity into a subject-level score. We evaluated PCS across four brain disorders (autism spectrum disorder, schizophrenia, attention deficit hyperactivity disorder, and Alzheimer's disease) and 14 studies encompassing ~35,000 individuals. Our findings consistently show that patients exhibit significantly higher PCS compared to controls, with effect sizes that go beyond other single MRI metrics ([min, max]: Cohen's d = [0.30, 0.87], AUC = [0.58, 0.73]). We further demonstrate that PCS serves as a valuable tool for stratifying individuals, for example within the psychosis continuum, distinguishing patients with schizophrenia from their first-degree relatives (d = 0.42, p = 4 × 10-3, FDR-corrected), and first-degree relatives from healthy controls (d = 0.34, p = 0.034, FDR-corrected). We also show that PCS is useful to uncover associations between brain connectivity patterns related to neuropsychiatric disorders and mental health, psychosocial factors, and body measurements.

The C55A Single Nucleotide Polymorphism in CTLA-4 Gene, a New Possible Biomarker in Thyroid Autoimmune Pathology Such as Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is a chronic autoimmune disorder characterized by the production of autoantibodies against the thyroid gland. Different studies have shown that several genes may be associated with HT, which explains why patients often have family members with thyroiditis or other autoimmune diseases. The aim of this case-control study was to evaluate the correlation between polymorphisms at the level of exon 1 from the CTLA-4 gene and the susceptibility to developing HT. In this study, we found that there is no statistically significant association between the polymorphism rs231775 (A22G in exon 1) of the CTLA-4 gene and a genetic predisposition to HT. In contrast, a strong association was discovered for the first time between C55A in exon 1 of the CTLA-4 gene and HT. Our findings suggest that there is a genetic relationship between the CTLA-4 (+55A/C) genotype and the seropositivity against thyroid autoantigens, such as anti-thyroid peroxidase (ATPO) and anti-thyroglobulin antibodies (ATG).

Acceptance of smart sensing: a barrier to implementation-results from a randomized controlled trial.

Background: Accurate and timely diagnostics are essential for effective mental healthcare. Given a resource- and time-limited mental healthcare system, novel digital and scalable diagnostic approaches such as smart sensing, which utilizes digital markers collected via sensors from digital devices, are explored. While the predictive accuracy of smart sensing is promising, its acceptance remains unclear. Based on the unified theory of acceptance and use of technology, the present study investigated (1) the effectiveness of an acceptance facilitating intervention (AFI), (2) the determinants of acceptance, and (3) the acceptance of adults toward smart sensing. Methods: The participants (N = 202) were randomly assigned to a control group (CG) or intervention group (IG). The IG received a video AFI on smart sensing, and the CG a video on mindfulness. A reliable online questionnaire was used to assess acceptance, performance expectancy, effort expectancy, facilitating conditions, social influence, and trust. The self-reported interest in using and the installation of a smart sensing app were assessed as behavioral outcomes. The intervention effects were investigated in acceptance using t-tests for observed data and latent structural equation modeling (SEM) with full information maximum likelihood to handle missing data. The behavioral outcomes were analyzed with logistic regression. The determinants of acceptance were analyzed with SEM. The root mean square error of approximation (RMSEA) and standardized root mean square residual (SRMR) were used to evaluate the model fit. Results: The intervention did not affect the acceptance (p = 0.357), interest (OR = 0.75, 95% CI: 0.42-1.32, p = 0.314), or installation rate (OR = 0.29, 95% CI: 0.01-2.35, p = 0.294). The performance expectancy (γ = 0.45, p < 0.001), trust (γ = 0.24, p = 0.002), and social influence (γ = 0.32, p = 0.008) were identified as the core determinants of acceptance explaining 68% of its variance. The SEM model fit was excellent (RMSEA = 0.06, SRMR = 0.05). The overall acceptance was M = 10.9 (SD = 3.73), with 35.41% of the participants showing a low, 47.92% a moderate, and 10.41% a high acceptance. Discussion: The present AFI was not effective. The low to moderate acceptance of smart sensing poses a major barrier to its implementation. The performance expectancy, social influence, and trust should be targeted as the core factors of acceptance. Further studies are needed to identify effective ways to foster the acceptance of smart sensing and to develop successful implementation strategies. Clinical Trial Registration: identifier 10.17605/OSF.IO/GJTPH.

Adherence to sleep restriction therapy - An evaluation of existing measures.

Sleep restriction, a key element of cognitive behavioural therapy for insomnia, involves considerable behavioural changes in patients' lives, leading to side-effects like increased daytime sleepiness. Studies on sleep restriction rarely report adherence, and when assessed it is often limited to the average number of therapy sessions attended. This study aims to systematically evaluate different measures of adherence to cognitive behavioural therapy for insomnia and their relationship with treatment outcome. This is a secondary analysis of data from a randomized controlled trial investigating cognitive behavioural therapy for insomnia (Johann et al. (2020) Journal of Sleep Research, 29, e13102). The sample included 23 patients diagnosed with insomnia according to DSM-5 criteria who underwent 8 weeks of cognitive behavioural therapy for insomnia. The following adherence measures based on sleep diary data were used: number of sessions completed; deviations from agreed time in bed; average percentage of patients deviating from bedtime by 15, 30 or 60 min; variability of bedtime and wake-up time; change in time in bed from pre- to post-assessment. Treatment outcome was assessed using the Insomnia Severity Index. Multiple regression models were employed, and insomnia severity was controlled for. Results showed that none of the adherence measures predict insomnia severity. Baseline insomnia severity, dysfunctional thoughts and attitudes about sleep, depression or perfectionism did not predict adherence. The limited variance in the outcome parameter due to most patients benefiting from treatment and the small sample size may explain these findings. Additionally, using objective measures like actigraphy could provide a better understanding of adherence behaviour. Lastly, the presence of perfectionism in patients with insomnia may have mitigated adherence problems in this study.

Prevalence of rhinitis and associated factors in adolescents and adults: a Global Asthma Network study.

OBJECTIVE: To determine the prevalence of allergic rhinitis and associated factors in adolescents and in their parents/guardians. METHODS: A cross-sectional study, applying a standardized and validated written questionnaire. Adolescents (13-14 years old; n=1,058) and their parents/guardians (mean age=42.1 years old; n=896) living in the city of Uruguaiana, southern Brazil, responded to the Global Asthma Network standard questionnaires. RESULTS: The prevalence of allergic rhinitis in adolescents was 28.0%, allergic rhinoconjunctivitis, 21.3%, and severe forms of allergic rhinitis, 7.8%. In the adults, the prevalence of allergic rhinitis was 31.7%. Some associated factors with allergic rhinitis in adolescents include low physical exercise (OR 2.16; 95%CI 1.15-4.05), having only one older sibling (OR 1.94; 95CI 1.01-3.72) and daily meat consumption (OR 7.43; 95% CI 1.53-36.11). In contrast, consuming sugar (OR 0.34; 95%CI 0.12-0.93) or olive oil (OR 0.33; 95%CI 0.13-0 .81) once or twice a week, and eating vegetables daily (OR 0.39; 95%CI 0.15-0.99) were considered factors negatively associated. In adults, exposure to fungi at home (OR 5.25; 95%CI 1.01-27.22) and consumption of meat once or twice a week (OR 46.45; 95CI 2.12-1020.71) were factors associated with the medical diagnosis of allergic rhinitis, while low education (OR 0.25; 95%CI 0.07-0.92) was found to be a factor negatively associated. CONCLUSIONS: The prevalence of allergic rhinitis in adolescents is high, as well as its medical diagnosis in adults living in Uruguaiana. Environmental factors, especially food habits, were associated with findings in both groups.

Comparative efficacy of onsite, digital, and other settings for cognitive behavioral therapy for insomnia: a systematic review and network meta-analysis.

Given the limited availability and accessibility of onsite cognitive behavioral therapy for insomnia (CBT-I), other CBT-I settings, such as internet-delivered CBT-I (iCBT-I), have been proposed. The primary aim of the study was to compare the efficacy of available CBT-I settings on insomnia severity. A systematic review and frequentist network meta-analysis of available CBT-I settings was performed. PsycINFO, PsycARTICLES, MEDLINE, PubMed, and CINAHL were searched for randomized controlled trials (RCTs) investigating any CBT-I settings in adults with insomnia disorder. The systematic literature search (3851 references) resulted in 52 RCTs. For the primary outcome insomnia severity, all examined CBT-I settings except smartphone-delivered CBT-I yielded significant effects when compared to WL. Large standardized mean differences were found for individual onsite CBT-I (- 1.27;95%CI - 1.70, - 0.84), group-delivered CBT-I (- 1.00;95%CI - 1.42. - 0.59), telehealth (- 1.28;95%CI - 2.06, - 0.50), and guided bibliotherapy (- 0.99;95%CI - 1.67, - 0.32). Both guided iCBT-I (- 0.71;95%CI - 1.18, - 0.24) and unguided iCBT-I (- 0.78;95%CI - 1.18, - 0.38) yielded medium effect sizes. The results underline that health care systems should intensify their efforts to provide synchronously-delivered CBT-I (individual onsite, group-delivered, and telehealth), and particularly individual onsite CBT-I, given its solid evidence base. Medium to large effect sizes for iCBT-I and guided bibliotherapy indicate that self-help settings may be a viable alternative when synchronously-delivered CBT-I is not available.

Help for insomnia from the app store? A standardized rating of mobile health applications claiming to target insomnia.

A large number of mobile health applications claiming to target insomnia are available in commercial app stores. However, limited information on the quality of these mobile health applications exists. The present study aimed to systematically search the European Google Play and Apple App Store for mobile health applications targeting insomnia, and evaluate the quality, content, evidence base and potential therapeutic benefit. Eligible mobile health applications were evaluated by two independent reviewers using the Mobile Application Rating Scale-German, which ranges from 1 - inadequate to 5 - excellent. Of 2236 identified mobile health applications, 53 were included in this study. Most mobile health applications (68%) had a moderate overall quality. Concerning the four main subscales of the Mobile Application Rating Scale-German, functionality was rated highest (M = 4.01, SD = 0.52), followed by information quality (M = 3.49, SD = 0.72), aesthetics (M = 3.31, SD = 1.04) and engagement (M = 3.02, SD = 1.03). While scientific evidence was identified for 10 mobile health applications (19%), only one study employed a randomized controlled design. Fifty mobile health applications featured sleep hygiene/psychoeducation (94%), 27 cognitive therapy (51%), 26 relaxation methods (49%), 24 stimulus control (45%), 16 sleep restriction (30%) and 24 sleep diaries (45%). Mobile health applications may have the potential to improve the care of insomnia. Yet, data on the effectiveness of mobile health applications are scarce, and this study indicates a large variance in the quality of the mobile health applications. Thus, independent information platforms are needed to provide healthcare seekers and providers with reliable information on the quality and content of mobile health applications.

Prevalence of rhinitis and associated factors in adolescents and adults: a Global Asthma Network study / Prevalência de rinite e fatores associados em adolescentes e adultos: um estudo da Global Asthma Network

Abstract Objective: To determine the prevalence of allergic rhinitis and associated factors in adolescents and in their parents/guardians. Methods: A cross-sectional study, applying a standardized and validated written questionnaire. Adolescents (13-14 years old; n=1,058) and their parents/guardians (mean age=42.1 years old; n=896) living in the city of Uruguaiana, southern Brazil, responded to the Global Asthma Network standard questionnaires. Results: The prevalence of allergic rhinitis in adolescents was 28.0%, allergic rhinoconjunctivitis, 21.3%, and severe forms of allergic rhinitis, 7.8%. In the adults, the prevalence of allergic rhinitis was 31.7%. Some associated factors with allergic rhinitis in adolescents include low physical exercise (OR 2.16; 95%CI 1.15-4.05), having only one older sibling (OR 1.94; 95CI 1.01-3.72) and daily meat consumption (OR 7.43; 95% CI 1.53-36.11). In contrast, consuming sugar (OR 0.34; 95%CI 0.12-0.93) or olive oil (OR 0.33; 95%CI 0.13-0 .81) once or twice a week, and eating vegetables daily (OR 0.39; 95%CI 0.15-0.99) were considered factors negatively associated. In adults, exposure to fungi at home (OR 5.25; 95%CI 1.01-27.22) and consumption of meat once or twice a week (OR 46.45; 95CI 2.12-1020.71) were factors associated with the medical diagnosis of allergic rhinitis, while low education (OR 0.25; 95%CI 0.07-0.92) was found to be a factor negatively associated. Conclusions: The prevalence of allergic rhinitis in adolescents is high, as well as its medical diagnosis in adults living in Uruguaiana. Environmental factors, especially food habits, were associated with findings in both groups.

Resumo Objetivo: Determinar a prevalência de rinite alérgica e fatores associados em adolescentes e em seus pais/responsáveis. Métodos: Estudo transversal, com aplicação de questionário escrito padronizado e validado. Adolescentes (13-14 anos; n=1.058) e seus pais/responsáveis (média de idade=42,1 anos; n=896) residentes na cidade de Uruguaiana, Sul do Brasil, responderam aos questionários padrão da Global Asthma Network. Resultados: A prevalência de rinite alérgica em adolescentes foi de 28,0%, a de rinoconjuntivite alérgica foi de 21,3% e a de formas graves de rinite alérgica, de 7,8%. Nos adultos, a prevalência de rinite alérgica foi de 31,7%. Alguns fatores associados à rinite alérgica em adolescentes incluem fazer pouco exercício físico (odds ratio — OR 2,16; intervalo de confiança — IC95% 1,15-4,05), ter apenas um irmão mais velho (OR 1,94; IC95% 1,01-3,72) e consumir carne diariamente (OR 7,43; IC95% 1,53-36,11). Por outro lado, consumir açúcar (OR 0,34; IC5% 0,12-0,93) ou azeite de oliva (OR 0,33 IC95% 0,13-0,81) uma ou duas vezes por semana e comer vegetais diariamente (OR 0,39; IC95% 0,15-0,99) foram considerados fatores associados negativamente. Em adultos, a exposição a fungos no domicílio (OR 5,25; IC95% 1,01-27,22) e o consumo de carne uma ou duas vezes por semana (OR 46,45; IC95 2,12-1020,71) foram fatores associados ao diagnóstico médico de rinite alérgica, enquanto a baixa escolaridade (OR 0,25; IC95% 0,07-0,92) se mostrou como fator associado negativamente. Conclusões: A prevalência de rinite alérgica em adolescentes é alta, assim como seu diagnóstico médico em adultos residentes em Uruguaiana. Fatores ambientais, especialmente hábitos alimentares, foram associados aos achados em ambos os grupos.

Prevalence and factors associated with depression and anxiety among medical students in an inland university in Brazil / Prevalência e fatores associados à depressão e ansiedade entre estudantes de medicina de uma universidade do interior do Brasil

Medical schools are known to be stressful environments for students, and hence medical students have been believed to experience greater incidences of depression and anxiety than the general population or students from other spe-cialties. The present study investigates the prevalence of anxiety and depressive symptoms together with factors as-sociated with them among medical students in a federal public university in the south of Brazil. A descriptive study was performed using self-administered questionnaires to access socio-demographic, institutional, and health variables in association with two scales - Beck's Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) - designed to assess depressive and anxiety symptoms, respectively. The research sample consisted of 152 subjects. The depres-sive symptoms prevalence was 65.1% (BDI > 9), state-anxiety was 98.6%, and trait-anxiety was 97.4% (STAI > 33). Among women, 37.8% demonstrated moderate/severe depressive symptoms. High levels of state-anxiety symptoms and trait-anxiety symptoms were found in 44.7% of students under the age of 20. In the group with the lowest month-ly income, it was observed the highest distributions for moderate/severe depressive symptoms, high state and high trait-anxiety symptoms, corresponding to 47.4%, 57.9%, and 47.4%, respectively. Students attending the third term of medical school had the highest percentage of moderate/severe depressive symptoms (62.5%) and high state-anxiety symptoms (50%). In addition, students who had both financial aid programs presented the highest percentages of moderate/severe depressive symptoms (46.2%), highstate-anxiety symptoms (61.5%), and high trait-anxiety symptoms (46.2%). We also observed a correlationbetween depression and trait-anxiety symptoms (P = 0.037). In conclusion, it was identified as risk factors for depressive symptoms the previous depression diagnosis, previous search for health service due to psychological symptoms, being in financial aid programs, dissatisfaction with the medical school, and inadequate psychological help offered by it. For state-anxiety symptoms and trait-anxiety outcome, there is an increased risk among low-income or students who have financial help from financial aid programs and younger age students. (AU)

Objetivo: Investigar a prevalência de sintomas de ansiedade e depressão e fatores associados a eles entre es-tudantes de medicina de uma universidade pública do sul do Brasil. Métodos: Foi realizado um estudo descritivo através de questionários autoaplicáveis para avaliar variáveis sociodemográficas, institucionais e de saúde, associa-das a duas escalas - Inventário de Depressão de Beck (BDI) e Inventário de Traço-Estado de Ansiedade (STAI) - para avaliar os sintomas de depressão e ansiedade, respectivamente. Resultados: A prevalência de sintomas depres-sivos foi de 65,1% (BDI > 9), estado de ansiedade foi de 98,6% e traço de ansiedade de 97,4% (STAI > 33). Uma correlação significativa foi encontrada entre depressão e traço de ansiedade. Diagnóstico prévio de depressão, busca prévia por serviços de saúde, insatisfação com o curso de medicina e ter auxílio de baixa renda e bolsa de iniciação científica foram identificados como fatores de risco para depressão. Estudantes com baixa renda mensal e menores de 25 anos apresentaram maior risco para estado de ansiedade. Idade, ano da faculdade de medicina e programa de ajuda financeira provaram ser um fator de risco para traço de ansiedade. Conclusão: Esses resultados mostram fatores significativos relacionados à saúde mental de estudantes de uma faculdade de medicina recém-fundada no interior do Brasil. (AU)

Comparative effectiveness of three versions of a stepped care model for insomnia differing in the amount of therapist support in internet-delivered treatment: study protocol for a pragmatic cluster randomised controlled trial (GET Sleep).

INTRODUCTION: It is unclear how internet-delivered cognitive-behavioural therapy for insomnia (CBT-I) can be integrated into healthcare systems, and little is known about the optimal level of therapist guidance. The aim of this study is to investigate three different versions of a stepped care model for insomnia (IG1, IG2, IG3) versus treatment as usual (TAU). IG1, IG2 and IG3 rely on treatment by general practitioners (GPs) in the entry level and differ in the amount of guidance by e-coaches in internet-delivered CBT-I. METHODS AND ANALYSIS: In this randomised controlled trial, 4268 patients meeting International Classification of Diseases, Tenth Revision (ICD-10) criteria for insomnia will be recruited. The study will use cluster randomisation of GPs with an allocation ratio of 3:3:3:1 (IG1, IG2, IG3, TAU). In step 1 of the stepped care model, GPs will deliver psychoeducational treatment; in step 2, an internet-delivered CBT-I programme will be used; in step 3, GPs will refer patients to specialised treatment. Outcomes will be collected at baseline, and 4 weeks, 12 weeks and 6 months after baseline assessment. The primary outcome is insomnia severity at 6 months. An economic evaluation will be conducted and qualitative interviews will be used to explore barriers and facilitators of the stepped care model. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Medical Centre-University of Freiburg. The results of the study will be published irrespective of the outcome. TRIAL REGISTRATION NUMBER: DRKS00021503.

A systematic quality rating of available mobile health apps for borderline personality disorder.

BACKGROUND: Mobile health apps (MHAs) may offer a mean to overcome treatment barriers in Borderline Personality Disorder (BPD) mental health care. However, MHAs for BPD on the market lack transparency and quality assessment. METHODS: European app stores were systematically searched, and two independent trained reviewers extracted relevant MHAs. Employed methods and privacy and security details documentation of included MHAs were extracted. MHAs were then assessed and rated using the German version of the standardized Mobile Application Rating Scale (MARS-G). Mean values and standard deviations of all subscales (engagement, functionality, aesthetics, information, and therapeutic gain) and correlations with user ratings were calculated. RESULTS: Of 2977 identified MHAs, 16 were included, showing average quality across the four main subscales (M = 3.25, SD = 0.68). Shortcomings were observed with regard to engagement (M = 2.87, SD = 0.99), potential therapeutic gain (M = 2.67, SD = 0.83), existing evidence base (25.0% of included MHAs were tested empirically), and documented privacy and security details. No significant correlations were found between user ratings and the overall total score of the MARS-G or MARS-G main subscales. CONCLUSIONS: Available MHAs for BPD vary in quality and evidence on their efficacy, effectiveness, and possible adverse events is scarce. More substantial efforts to ensure the quality of MHAs available for patients and a focus on transparency, particularly regarding privacy and security documentation, are necessary.

Retrospective review of three-fractioned accelerated partial breast irradiation.

METHODS: This retrospective study evaluated patients who received three-fraction accelerated partial breast irradiation (APBI) via brachytherapy for breast cancer between January 2016 and April 2020. Inclusion criteria included age ≥18 years and early-stage unilateral breast cancer with negative lymph nodes. We evaluated acute toxicity (<6 weeks), late toxicity (≥6 weeks), and cosmetic outcomes. Frequencies of each variable were calculated. Cancer-specific outcomes were determined via the Kaplan-Meier method. RESULTS: Thirty consecutive patients received three-fraction APBI of 2,250 cGy over 2 d. All cancers were stage T2 or less. Median time to last follow-up was 22 months. Local recurrence-free survival was 95.8% at 22 months. Seventeen (56.7%) patients reported an acute toxicity event. All were grade 1 except one patient with grade 2 (fatigue). No patient experienced ≥ grade 3 acute toxicity. One (3.3%) patient reported grade 3 late toxicity (tissue fibrosis). No patients had breast edema, fat necrosis, or non-healing wounds. There were no ≥ grade 3 cosmetic events. DISCUSSION: Three-fraction APBI via brachytherapy was successful in preventing disease recurrence and death in this study, with still limited follow-up. Although acute and late toxicities or adverse cosmetic outcomes were seen, very few were grade 2 or higher and compare favorably to those reported in prior 10-fraction APBI studies. CONCLUSIONS: This study provides early single institutional evidence that three-fraction APBI may become a feasible treatment alternative.

Automated Network Assembly of Mechanistic Literature for Informed Evidence Identification to Support Cancer Risk Assessment.

BACKGROUND: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data. OBJECTIVES: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated approach that combines machine reading of publications with network visualization tools. METHODS: We chose 13 chemicals that were evaluated by the International Agency for Research on Cancer (IARC) Monographs program incorporating the key characteristics of carcinogens (KCCs) approach. Using established literature search terms for KCCs, we retrieved and analyzed literature using Integrated Network and Dynamical Reasoning Assembler (INDRA). INDRA combines large-scale literature processing with pathway databases and extracts relationships between biomolecules, bioprocesses, and chemicals into statements (e.g., "benzene activates DNA damage"). These statements were subsequently assembled into networks and compared with the KCC evaluation by the IARC, to evaluate the informativeness of our approach. RESULTS: We found, in general, larger networks for those chemicals which the IARC has evaluated the evidence to be strong for KCC induction. Larger networks were not directly linked to publication count, given that we retrieved small networks for several chemicals with little support for KCC activation according to the IARC, despite the significant volume of literature for these specific chemicals. In addition, interpreting networks for genotoxicity and DNA repair showed concordance with the IARC KCC evaluation. DISCUSSION: Our method is an automated approach to condense mechanistic literature into searchable and interpretable networks based on an a priori ontology. The approach is no replacement of expert evaluation but, instead, provides an informed structure for experts to quickly identify which statements are made in which papers and how these could connect. We focused on the KCCs because these are supported by well-described search terms. The method needs to be tested in other frameworks as well to demonstrate its generalizability. https://doi.org/10.1289/EHP9112.

Complications of peripherally inserted central catheters in pregnancy: a systematic review and meta-analysis.

INTRODUCTION: Complication rates associated with peripherally inserted central catheters (PICCs) in the general population are variable, and rates specific to pregnant women are unclear. We conducted a systematic review and meta-analysis to estimate the rate of PICC-associated complications in pregnant women. METHODS: We searched published literature for records discussing PICC use in pregnant or postpartum women. We included studies with primary data regarding rates of maternal complications from PICC use. The primary outcomes were maternal infection (cellulitis, sepsis), venous thromboembolism (VTE), or combined major complication rate. Secondary outcomes were superficial thrombophlebitis or mechanical failure. Meta-analysis was performed using STATA 12 with the METAN and METAPROP software routines. Pooled estimates with 95%CI were calculated using random-effects models. RESULTS: After the removal of duplicates, the primary search yielded 318 articles, with 5 being included for final analysis. The pooled rate of combined infectious and thromboembolic complications was 26% (95%CI = 6-53%). For secondary outcomes the pooled rate of infectious complications was 18% (95%CI = 4-39%), VTE 6% (95%CI = 0-18%), mechanical failure 7% (95%CI = 3-12%), and superficial thrombophlebitis 1% (95%CI = 0-3%). There was significant statistical heterogeneity between studies for all outcomes calculated. CONCLUSION: There are limited data regarding complication rates due to PICC use in pregnancy, with a high level of heterogeneity among existing studies. The risk of VTE appears comparable to PICC-associated VTE in the non-pregnant hospitalized population. The risk of infection associated with PICC use was the most variable, with rates ranging from 4% to 37%. This suggests that infection risk may be modifiable and further studies are needed to assess interventions that may lower this risk.

Systematic Review of the Use of Power Doppler Ultrasound in the Imaging of Peripheral Nerve Compression Neuropathy.

BACKGROUND: Power Doppler ultrasonography has been used as an adjunct in the diagnosis of peripheral nerve compression neuropathy. To better characterize its sensitivity and specificity, the authors performed a systematic review of its use in carpal and cubital tunnel syndrome diagnosis. METHODS: The authors systematically reviewed published literature on the use of power Doppler ultrasound to diagnose peripheral compression neuropathy using Ovid MEDLINE, Embase.com, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, NHS Economic Evaluation Database, World Health Organization International Clinical Trial Repository Platform, and Clinicaltrials.gov. No filters for language, date, or publication type were used. RESULTS: After reviewing 1538 identified studies, 27 publications were included involving 1751 participants with compression neuropathy (2048 median and 172 ulnar). All but three studies examined patients with carpal tunnel syndrome. Heterogeneity between study design and methodology was a noted limitation. Sensitivity and specificity of power Doppler ultrasound in the diagnosis of carpal tunnel syndrome ranged from 2.2 to 93.4 percent, and 89 to 100 percent, respectively, whereas sensitivity for cubital tunnel syndrome was 15.3 to 78.9 percent. There was variability in power Doppler signal detection based on location, with higher sensitivities at the carpal tunnel inlet and in areas of increased nerve swelling. CONCLUSIONS: Power Doppler ultrasound is unreliable as a screening test but appears to increase diagnostic accuracy of ultrasonography in compression neuropathies. It is most beneficial in moderate to severe disease and may be valuable in detecting early cases and in disease surveillance.

Graded Coronary Risk Stratification for Emergency Department Patients With Chest Pain: A Controlled Cohort Study.

Background Resource utilization among emergency department (ED) patients with possible coronary chest pain is highly variable. Methods and Results Controlled cohort study amongst 21 EDs of an integrated healthcare system examining the implementation of a graded coronary risk stratification algorithm (RISTRA-ACS [risk stratification for acute coronary syndrome]). Thirteen EDs had access to RISTRA-ACS within the electronic health record (RISTRA sites) beginning in month 24 of a 48-month study period (January 2016 to December 2019); the remaining 8 EDs served as contemporaneous controls. Study participants had a chief complaint of chest pain and serum troponin measurement in the ED. The primary outcome was index visit resource utilization (observation unit or hospital admission, or 7-day objective cardiac testing). Secondary outcomes were 30-day objective cardiac testing, 60-day major adverse cardiac events (MACE), and 60-day MACE-CR (MACE excluding coronary revascularization). Difference-in-differences analyses controlled for secular trends with stratification by estimated risk and adjustment for risk factors, ED physician and facility. A total of 154 914 encounters were included. Relative to control sites, 30-day objective cardiac testing decreased at RISTRA sites among patients with low (≤2%) estimated 60-day MACE risk (-2.5%, 95% CI -3.7 to -1.2%, P<0.001) and increased among patients with non-low (>2%) estimated risk (+2.8%, 95% CI +0.6 to +4.9%, P=0.014), without significant overall change (-1.0%, 95% CI -2.1 to 0.1%, P=0.079). There were no statistically significant differences in index visit resource utilization, 60-day MACE or 60-day MACE-CR. Conclusions Implementation of RISTRA-ACS was associated with better allocation of 30-day objective cardiac testing and no change in index visit resource utilization or 60-day MACE. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03286179.