Book Review

Review of: FRED BLOSSER, PRIMER ON OCCUPATIONAL SAFETY AND HEALTH. (The Bureau of National Affairs, Inc. 1992) [374 pp.] Appendices (e.g., forms, OSHA Inspection Procedures, OSHA/EPA Memorandum of Understanding, statute), glossary, index, preface, table of cases. LC 91-43769; ISBN 0-87179-741-0. [$46.00 paper. 1250 23d Street, NW, Ste. 300B; Washington DC 20037.

Analysis of Functional Correlations

Technological advances have led to an increase in the collection of high-dimensional, nearly continuously sampled signals. Evolutionary correlations between such signals are salient to many studies, as they provide important information about associations between different dynamic processes and can be used to understand how these processes relate to larger complex mechanisms. Despite the large number of methods for analyzing functional data that have been explored in the past twenty-five years, there is a dearth of methods for analyzing functional correlations. This dissertation introduces new methods for addressing three questions pertaining to functional correlations. First, we address the problem of estimating a single functional correlation by developing a smoothing spline estimator and accompanying bootstrap procedure for forming confidence intervals. Next, we consider the problem of testing the equivalence of two functional correlations from independent samples by developing a novel adaptive Neyman testing procedure. Lastly, we address the problem of testing the equivalence of two functional correlations from dependent samples by extending the adaptive Neyman test to this more complicated setting, and by embedding the problem in a state-space framework to formulate a practical Kalman filter-based algorithm for its implementation. These methods are motivated by questions in sleep medicine and chronobiology and are used to analyze the dynamic coupling between delta EEG power and high frequency heart rate variability during sleep

EINAQ - A European educational initiative on Attention-Deficit Hyperactivity Disorder and associated problems

BACKGROUND: Continuing Medical Education (CME) plays an important role in quality management, especially as quality assurance, for the improvement of healthcare in child and adolescent psychiatry. This requires responsibility regarding quality standards of clinical practice throughout Europe as outlined by the European Union of Medical Specialists (UEMS). OBJECTIVE: Therefore, steps should be undertaken to improve specialists' medical care and harmonize it in Europe. Attention-Deficit Hyperactivity Disorder (ADHD) with its many co-existing developmental disorders/problems is the central healthcare problem in child and adolescent psychiatry with high impact on society. Therefore, it was chosen as the target. METHOD: A European Interdisciplinary Network for ADHD Quality Assurance (EINAQ) was founded, didactic material was developed and a faculty of experts from several European countries established to offer all over Europe harmonized courses on ADHD and associated problems. RESULTS: Pilot courses were given in Germany in 2003/2004 and were highly appreciated by the participants. Further courses in Germany and other European countries will take place in 2004. CONCLUSION: EINAQ seems to be on the right track to be part of CME and specialized networks for healthcare in ADHD to improve the provision for mental health problems in children and adolescents in Europe. Cooperative projects with official European bodies like the UEMS -- Section on Child and Adolescent Psychiatry/Psychotherapy and the European Society of Child and Adolescent Psychiatry could strengthen the impact of EINAQ

My care manager, my computer therapy and me: the relationship triangle in computerized cognitive behavioural therapy

Previous research has reported mixed findings regarding the relationship between therapeutic alliance, engagement and outcomes in e-mental health. This study aims to overcome some of the methodological limitations of previous research and extend our understanding of alliance-outcome relationships in e-mental health by exploring the nature of the relationship triangle between the patient, their care manager and their computerized cognitive behavioural therapy (CCBT) program, accessed with or without an Internet Support Group (ISG). Positive patient-rated alliance with both their care manager and the CCBT program itself was found and these were significantly associated with measures of engagement and clinical outcome. The magnitude of this association was moderate, and within the range of that reported for traditional face-to-face psychotherapies in recent meta-analyses. Limitations of the study, including the reliance on completer data and a cross-sectional design, and directions for future research are presented. Our findings suggest that both the training and supervision of support staff and the optimization of CCBT interventions themselves to enhance alliance and experience may lead to improved engagement and outcomes

Characteristics differentiating problem representation synthesis between novices and experts

Background: Formulating a thoughtful problem representation (PR) is fundamental to sound clinical reasoning and an essential component of medical education. Aside from basic structural recommendations, little consensus exists on what characterizes high-quality PRs. Objectives: To elucidate characteristics that distinguish PRs created by experts and novices. Methods: Early internal medicine residents (novices) and inpatient teaching faculty (experts) from two academic medical centers were given two written clinical vignettes and were instructed to write a PR and three-item differential diagnosis for each. Deductive content analysis described the characteristics comprising PRs. An initial codebook of characteristics was refined iteratively. The primary outcome was differences in characteristic frequencies between groups. The secondary outcome was characteristics correlating with diagnostic accuracy. Mixed-effects regression with random effects modeling compared case-level outcomes by group. Results: Overall, 167 PRs were analyzed from 30 novices and 54 experts. Experts included 0.8 fewer comorbidities (p &lt;.01) and 0.6 more examination findings (p =.01) than novices on average. Experts were less likely to include irrelevant comorbidities (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2–0.8) or a diagnosis (OR = 0.3, 95% CI = 0.1–0.8) compared with novices. Experts encapsulated clinical data into higher-order terms (e.g., sepsis) than novices (p &lt;.01) while including similar numbers of semantic qualifiers (SQs). Regardless of expertise level, PRs following a three-part structure (e.g., demographics, temporal course, and clinical syndrome) and including temporal SQs were associated with diagnostic accuracy (p &lt;.01). Conclusions: Compared with novices, expert PRs include less irrelevant data and synthesize information into higher-order concepts. Future studies should determine whether targeted educational interventions for PRs improve diagnostic accuracy.</p

Characteristics differentiating problem representation synthesis between novices and experts

Background: Formulating a thoughtful problem representation (PR) is fundamental to sound clinical reasoning and an essential component of medical education. Aside from basic structural recommendations, little consensus exists on what characterizes high-quality PRs. Objectives: To elucidate characteristics that distinguish PRs created by experts and novices. Methods: Early internal medicine residents (novices) and inpatient teaching faculty (experts) from two academic medical centers were given two written clinical vignettes and were instructed to write a PR and three-item differential diagnosis for each. Deductive content analysis described the characteristics comprising PRs. An initial codebook of characteristics was refined iteratively. The primary outcome was differences in characteristic frequencies between groups. The secondary outcome was characteristics correlating with diagnostic accuracy. Mixed-effects regression with random effects modeling compared case-level outcomes by group. Results: Overall, 167 PRs were analyzed from 30 novices and 54 experts. Experts included 0.8 fewer comorbidities (p &lt;.01) and 0.6 more examination findings (p =.01) than novices on average. Experts were less likely to include irrelevant comorbidities (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2–0.8) or a diagnosis (OR = 0.3, 95% CI = 0.1–0.8) compared with novices. Experts encapsulated clinical data into higher-order terms (e.g., sepsis) than novices (p &lt;.01) while including similar numbers of semantic qualifiers (SQs). Regardless of expertise level, PRs following a three-part structure (e.g., demographics, temporal course, and clinical syndrome) and including temporal SQs were associated with diagnostic accuracy (p &lt;.01). Conclusions: Compared with novices, expert PRs include less irrelevant data and synthesize information into higher-order concepts. Future studies should determine whether targeted educational interventions for PRs improve diagnostic accuracy.</p

Indications and Relative Utility of Lower Endoscopy in the Management of Clostridium difficile Infection

Background. Diagnosis and management of Clostridium difficile infection (CDI) rely upon clinical assessments and diagnostic studies. Among diagnostic tests, lower gastrointestinal (GI) endoscopy in the setting of CDI remains controversial. Objective. To describe the role of lower endoscopy in CDI management. Methods. Retrospective study of lower endoscopies in CDI at four metropolitan hospitals, July 2005 through December 2007. Results. Of 1760 CDI inpatients, 45 lower endoscopies were performed on 43 patients. Most common indications were ruling out other etiologies (42%), inconclusive stool studies (36%), and worsening course (11%). Most endoscopies (73%) had positive findings, including pseudomembranous colitis (49%) and nonspecific colitis (24%). Biopsies were performed in 31 cases, more with nonspecific colitis (10/11, 92%) compared to pseudomembranous colitis (14/22, 64%). Conclusion. While not recommended as a primary screening tool, lower GI endoscopy can add valuable information in CDI when other colonic pathologies may exist, studies are inconclusive, or clinical status worsens

Relationship between quality of life and psychopathological profile: data from an observational study in children with ADHD

Although ADHD significantly affects the quality of life (QoL) of patients and their families, QoL in children with ADHD has rarely been investigated in association with psychopathological profile, and the relationship remains unclear. The open-label OBSEER study evaluated the effectiveness and tolerability of Equasym XL®, a modified-release methylphenidate, in routine care of children and adolescents (aged 6–17 years) with ADHD. At baseline, questionnaires assessing psychopathological profile (Strengths and Difficulties Questionnaire, SDQ; parental ratings) and QoL (KINDL; parent, child or adolescent versions) were completed; QoL was reassessed at final visit. We analysed the relationship between psychopathology and parent/patient-rated QoL in ADHD at baseline. Data from 721 consecutively referred children and adolescents were analysed. QoL was similarly low from parent and self-ratings and independent of severity on the SDQ subscale hyperactivity/inattention. Self-ratings indicated that additional conduct disorder was associated with further reduction in QoL. Similarly, children with high scores from parent and adolescent ratings on the SDQ subscale conduct problems had reduced QoL on some KINDL subscales. Adolescents with ADHD not receiving medication at baseline reported lower QoL than those already on medication. Results show that children and adolescents with ADHD have low QoL, independent of core symptom severity. Additional conduct problems may further impact QoL negatively, while ADHD medication use may show a trend towards improved QoL. Not all psychopathological problems associated with ADHD affect QoL similarly. As parents appear to have a less critical view of QoL compared with children’s self-ratings, both parent and child ratings should be included in clinical assessments

Team-focused implementation strategies to improve implementation of mental health screening and referral in rural Children\u27s Advocacy Centers: Study protocol for a pilot cluster randomized hybrid type 2 trial

BACKGROUND: Children\u27s Advocacy Centers (CACs) use multidisciplinary teams to investigate and respond to maltreatment allegations. CACs play a critical role in connecting children with mental health needs to evidence-based mental health treatment, especially in low-resourced rural areas. Standardized mental health screening and referral protocols can improve CACs\u27 capacity to identify children with mental health needs and encourage treatment engagement. In the team-based context of CACs, teamwork quality is likely to influence implementation processes and outcomes. Implementation strategies that target teams and apply the science of team effectiveness may enhance implementation outcomes in team-based settings. METHODS: We will use Implementation Mapping to develop team-focused implementation strategies to support the implementation of the Care Process Model for Pediatric Traumatic Stress (CPM-PTS), a standardized screening and referral protocol. Team-focused strategies will integrate activities from effective team development interventions. We will pilot team-focused implementation in a cluster-randomized hybrid type 2 effectiveness-implementation trial. Four rural CACs will implement the CPM-PTS after being randomized to either team-focused implementation (n = 2 CACs) or standard implementation (n = 2 CACs). We will assess the feasibility of team-focused implementation and explore between-group differences in hypothesized team-level mechanisms of change and implementation outcomes (implementation aim). We will use a within-group pre-post design to test the effectiveness of the CPM-PTS in increasing caregivers\u27 understanding of their child\u27s mental health needs and caregivers\u27 intentions to initiate mental health services (effectiveness aim). CONCLUSIONS: Targeting multidisciplinary teams is an innovative approach to improving implementation outcomes. This study will be one of the first to test team-focused implementation strategies that integrate effective team development interventions. Results will inform efforts to implement evidence-based practices in team-based service settings. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05679154 . Registered on January 10, 2023

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)