Spirituality in Parkinson's Disease within a Sample from the USA.

Spirituality and religious beliefs are important for coping with medical conditions. The dopaminergic system is involved in reward behavior, and its dysfunction in Parkinson Disease (PD) raises questions about religiosity and spirituality in people with PD. This study examines the association between levels of spirituality and religiosity and the severity of PD motor and non-motor symptoms. The secondary aim investigates the perceived impact of PD diagnosis on spirituality and religiosity. This was a cross-sectional analysis of demographic, physical, mental, and spirituality and religiosity status in patients with PD recruited for the Health Outcomes Measurement (HOME) Study at the University of Maryland Parkinson Disease and Movement Disorders Center, Baltimore, USA. Spirituality and religiosity were assessed using the Spiritual Well-being Scale, and the World Health Organization Quality of Life Spiritual Religious and Personal Belief field-test instrument. The sample size was 85 PD patients. The mean age (standard deviation) was 65.5 (9.4) years and 67.1% were male. Higher levels of spirituality and religiosity were associated with younger age, sex (female), less education, religious affiliation (Christian), and mental health status. After adjusting for age, education, gender, race, marital status, religion, physical health, mental health, and comorbidity, only anxiety was associated with all of the spirituality/religiosity assessments. The majority of patients reported no change in their religious or spiritual beliefs following diagnosis. Greater spirituality and religiosity were associated with less anxiety. Also, younger women with PD showed higher levels of spirituality and religiosity. Longitudinal studies on more diverse populations are needed.

Somatoform Symptoms in Parkinson Disease.

BACKGROUND: Co-occurring somatoform symptoms complicate the diagnosis and treatment of Parkinson disease (PD). OBJECTIVE: To learn more about the relationship between somatoform symptoms and PD by comparing demographic and clinical features across PD groups differing in somatoform symptom severity. METHOD: Using standardized Brief Symptom Inventory-18 (BSI-18) scores to measure somatoform symptom severity, we assigned 1093 individuals with PD to one of four subgroups using comparisons to normative means: low (M < -½ SD), average (M ± ½ SD), high (M +½ SD to +1 SD), very high (M > +1 SD). We used demographics and disease severity measures to assess each subgroup. RESULTS: Most of the individuals with PD (56%) had high or very high somatoform symptom levels. Increased somatoform symptom levels were associated with female gender, lower socioeconomic status, greater disease duration, increased PD severity (Total Unified Parkinson's Disease Rating Scale), greater disability (Older Americans Resource and Services Disability subscale), increased BSI-18 Depression and Anxiety subscale scores, lower cognitive function (Mini-Mental State Examination), lower self-efficacy scores (Self-Efficacy to Manage Chronic Disease Scale), lower quality of life scores (SF-12 Health Status Survey), and greater medical comorbidity (Cumulative Illness Rating Scale-Geriatrics) (all comparisons: P < 0.001). We found no significant between-group differences for age, race, or marital status. CONCLUSION: Somatoform symptom severity in individuals with PD is associated with greater PD severity and disability and is more common in females and in individuals with low socioeconomic status. Greater awareness of somatoform symptoms should help improve PD treatment.

Longitudinal Change in Quality of Life in Neurological Disorders Measures Over 3 Years in Patients with Early Parkinson's Disease.

BACKGROUND: The Quality of Life in Neurological Disorders (Neuro-QoL) is a publicly available health-related quality-of-life measurement system. OBJECTIVE: The aim of this study was to evaluate the utility of Neuro-QoL item banks as outcome measures for clinical trials in Parkinson's disease. METHODS: An analysis of Neuro-QoL responsiveness to change and construct validity was performed in a multicenter clinical trial cohort. RESULTS: Among 310 participants over 3 years, changes in five of eight Neuro-QoL domains were significant (P < 0.05) but very modest. The largest effect sizes were seen in the cognition and mobility domains (0.35-0.39). The largest effect size for change over the year in which levodopa was initiated was -0.19 for lower extremity function-mobility. For a similarly designed clinical trial, estimated sample size required to demonstrate a 50% reduction in worsening ranged from 420 to more than 1000 participants per group. CONCLUSIONS: More sensitive tools will be required to serve as an outcome measure in early Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society.

Caregiver-reported characteristics of children diagnosed with pathogenic variants in KDM5C.

Loss of function variants in the lysine demethylase 5C (KDM5C) gene account for approximately 0.7-2.8% of X-linked intellectual disability (ID) cases and pose significant burdens for patients and their caregivers. To date, 45 unique variants in KDM5C have been reported in individuals with ID. As a rare disorder, its etiology and natural history remain an area of active investigation, with treatment limited to symptom management. Previous studies have found that males present with moderate to severe ID with significant syndromic comorbidities such as epilepsy, short stature, and craniofacial abnormalities. Although not as well characterized, females have been reported to predominantly display mild to moderate ID with approximately half being asymptomatic. Here, we present caregiver-reported data for 37 unrelated individuals with pathogenic variants in KDM5C; the largest cohort reported to-date. We find that up to 70% of affected females were reported to display syndromic features including gastrointestinal dysfunction and hearing impairment. Additionally, more than half of individuals reported a diagnosis of autism spectrum disorder or described features consistent with this spectrum. Our data thus provide further evidence of sexually dimorphic heterogeneity in disease presentation and suggest that pathogenic variants in KDM5C may be more common than previously assumed.

Emotional Traumatic Brain Injury.

The definition of traumatic brain injury (TBI) has expanded to include mild TBI and postconcussive syndrome. This evolution has resulted in difficulty disentangling the physical trauma of mild TBI from the emotional trauma of posttraumatic stress disorder (PTSD). Advances in stress neurobiology and knowledge of brain injury at the macroscopic, microscopic, biochemical, and molecular levels call for a redefinition of TBI that encompasses both physical and emotional TBI. Conceptualizing a spectrum of TBI with both physical and emotional causation resolves the irreconcilable tangle between diagnostic categories and acknowledges overlapping forms of brain injury and shared systemic effects due to hormonal and inflammatory mediators. Recognizing emotional TBI shifts the interpretation of emotional trauma from a confound to a comorbid, related cause of brain injury. The mechanism of emotional TBI includes the intricate actions of stress hormones on diverse brain functions due to changes in synaptic plasticity, where chronically elevated hormone levels reduce neurogenesis, resulting in dendritic atrophy and impaired cognition. The overlapping effects of physical and emotional trauma are seen in neuropathology (ie, reduction of hippocampal volume in TBI and PTSD); fMRI (similar regional activations in physical and emotional pain); and systemic sequelae, including changes in proinflammatory cytokine levels and immune cell function. Accumulating evidence favors a change in the definition of TBI to encompass emotional TBI. The definition of TBI will be strengthened by the inclusion of both physical and emotional trauma that result in diverse and overlapping forms of brain injury with sequelae for physical and mental health.

Parkinson's disease age at onset genome-wide association study: Defining heritability, genetic loci, and α-synuclein mechanisms.

BACKGROUND: Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age at onset are largely unknown. OBJECTIVES: To identify the genetic determinants of PD age at onset. METHODS: Using genetic data of 28,568 PD cases, we performed a genome-wide association study based on PD age at onset. RESULTS: We estimated that the heritability of PD age at onset attributed to common genetic variation was ∼0.11, lower than the overall heritability of risk for PD (∼0.27), likely, in part, because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni-corrected significant effect at other known PD risk loci, GBA, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. Notably, SNCA, TMEM175, SCARB2, BAG3, and GBA have all been shown to be implicated in α-synuclein aggregation pathways. Remarkably, other well-established PD risk loci, such as GCH1 and MAPT, did not show a significant effect on age at onset of PD. CONCLUSIONS: Overall, we have performed the largest age at onset of PD genome-wide association studies to date, and our results show that not all PD risk loci influence age at onset with significant differences between risk alleles for age at onset. This provides a compelling picture, both within the context of functional characterization of disease-linked genetic variability and in defining differences between risk alleles for age at onset, or frank risk for disease. © 2019 International Parkinson and Movement Disorder Society.

Comparative study of PROMISⓇ self-efficacy for managing chronic conditions across chronic neurologic disorders.

PURPOSE: Self-efficacy (SE) for managing chronic conditions is the belief that one can carry out behaviors to reach health goals. The study objective is to investigate (1) SE for managing chronic conditions across diverse neurologic conditions, (2) demographic and disease determinants of SE, and (3) SE as a predictor of health and disability. METHODS: Patients with chronic neurologic conditions (epilepsy, multiple sclerosis, neuropathy, Parkinson disease, stroke; n = 834) completed five SE for Managing Chronic Conditions instruments (Patient-Reported Outcomes Measurement Information System®; PROMIS®). Other assessments included PROMIS depression, fatigue, physical function, and global health. RESULTS: Two of the five SE domains showed differences across the five disorders (ANOVA; SE for Managing Daily Activities p < .001 and Managing Symptoms p < .01). The three domains with no differences were Managing Medications/Treatments, Emotions, and Social Interactions. Lowest SE was in neuropathy, and highest in epilepsy (Managing Activities) and stroke (Managing Symptoms). Multivariate regression showed SE measures to be better predictors of mental health, global health, and disability than either disease severity or diagnosis. CONCLUSIONS: SE for managing chronic conditions differs across neurologic disorders, with lowest SE for managing activities and symptoms in neuropathy, and highest in patients with epilepsy and stroke. PROMIS SE measures are better predictors of mental health, disability, and quality of life than disease severity or diagnosis.

Multidimensionality of the PROMIS self-efficacy measure for managing chronic conditions.

PURPOSE: This study investigated the PROMIS Self-Efficacy Measure for Managing Chronic Conditions (PROMIS-SE) domain distributions and examined the factor structure of the PROMIS-SE. METHODS: A total of 1087 individuals with chronic conditions participated in this study. PROMIS-SE's item banks and two short forms (eight-item and four-item) measuring five behavioral domains (daily activities(DA), Emotions(EM), medications and treatments(MT), social interactions(SS), and Symptoms(SX)) were examined. PROMIS-SE's T-score ranges and distributions were examined to identify domain metric distributions and confirmatory factor analysis (CFA) was conducted to test a multidimensional model fit to the PROMIS-SE. RESULTS: PROMIS-SE domains showed different T-score ranges and distributions for item banks and two short forms across all five domains. While PROMIS-SE EM demonstrated the highest T-scores (least negatively skewed), MT had the lowest T-scores (most negatively skewed) for all three forms. In general, respondents were more likely to achieve highest self-efficacy ratings (very confident) for domains DA, MT, and SS as compared to domains EM and SX. CFA confirmed that a multidimensional model adequately fit all three PROMIS-SE forms. CONCLUSION: Our results indicate that self-efficacy T-distributions are not consistent across domains (i.e., managing medications and treatments domain was more negatively skewed difficult than other domains), which is a requirement for making inter-domain comparisons. A multidimensional model could be used to enhance the PROMIS-SE's estimate accuracy and clinical utility.

Parkinson's Disease: Patients' Knowledge, Attitudes, and Interest in Genetic Counseling.

The objective of this study was to assess the genetics knowledge of patients with Parkinson's disease (PD), and to explore their attitudes on genetic testing and interest in genetic counseling. We surveyed 158 patients from the University of Maryland Parkinson's Disease and Movement Disorders Center. Patients averaged a score of 63% on general genetics knowledge and 73% on PD genetics knowledge. Participants had an overall positive attitude toward genetic testing: 80% believed that the use of genetic tests among people should be promoted, and 83% would undertake genetic test for PD if it was available. Patients reported a high interest to discuss the benefits, risks, and impacts of genetic testing for PD (mean sum score = 26, range = 9-35), and 43% patients expressed interest in meeting with a genetic counselor. Multivariate regression analysis showed that patients who had more positive attitudes toward genetic testing for PD were more interested in meeting with a genetic counselor (ß = 0.6, p < 0.001). This study is the first to demonstrate an interest in genetic counseling among patients with PD. Our findings demonstrate a new niche for genetic counselors to support patients in clarifying gaps or misconceptions in knowledge about PD genetics as well as the possible risks, benefits, and limitations of genetic testing.

High pH instability of quaternary ammonium surfactant coatings in capillary electrophoresis.

The two-tailed cationic surfactant dioctadecyldimethyl ammonium bromide (DODAB) produces semi-permanent coatings that yield strongly reversed electroosmotic flow (EOF), for example -0.31 ± 0.01 cm2 kV-1 s-1 at pH 3.5. Moreover, these coatings are easy to prepare, regenerable, cost effective, and yield high efficiency (520 000-900 000 plates per m) separations of cationic proteins over many runs under acidic (pH 3.5) conditions. Given the quaternary amine functionality of DODAB, we were surprised to observe that DODAB coatings become unstable at pH > 7. At pH 7.2, the EOF of a DODAB coated capillary drifted from reversed to cathodic over only 5 runs, and protein separations became severely compromised. By pH 12, no EOF reversal was observed. Electrophoretic and mass spectrometric studies demonstrate that the coating decomposition involves a surface conversion of the quaternary amine in DODAB to a variety of products, although the exact mechanism remains elusive. Regardless, the results herein demonstrate that semi-permanent coatings based on cationic two-tailed surfactants such as DODAB are limited to separations using acidic buffers.

Discordance Between Physician Assessment and Patient-Reported Depressive Symptoms in Parkinson Disease.

OBJECTIVE: To assess concordance between physician assessment and patient-reported symptoms when screening for depression in Parkinson disease (dPD). BACKGROUND: Depression in Parkinson disease is highly prevalent (∼40%) and has a significant impact on quality of life and disability, yet physician recognition and treatment remain inadequate. METHODS: One thousand seventy-six patients with PD completed the Brief Symptom Inventory-18 (BSI-18), a screening questionnaire for psychiatric symptoms, which was compared to item #3 (depression) on the Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: The mean BSI-18 depression score was 51.4 (9.7). Of the 170 (16%) patients screening positive for dPD on the BSI-18, 104 (61%) were not recognized as depressed by neurologists on the UPDRS. Factors associated with lower neurologist recognition included male gender, better mental health quality of life, and lack of antidepressant use. CONCLUSION: More than 60% of patients screening positive for depression on self-report were not recognized by neurologists on the UPDRS. A patient-reported screening tool for depression may improve recognition and management of dPD.

Validation of the PROMIS® measures of self-efficacy for managing chronic conditions.

PURPOSE: The Patient-Reported Outcomes Measurement Information System® (PROMIS®) was designed to develop, validate, and standardize item banks to measure key domains of physical, mental, and social health in chronic conditions. This paper reports the calibration and validation testing of the PROMIS Self-Efficacy for Managing Chronic Conditions measures. METHODS: PROMIS Self-Efficacy for Managing Chronic Conditions item banks comprise five domains, Self-Efficacy for Managing: Daily Activities, Symptoms, Medications and Treatments, Emotions, and Social Interactions. Banks were calibrated in 1087 subjects from two data sources: 837 patients with chronic neurologic conditions (epilepsy, multiple sclerosis, neuropathy, Parkinson disease, and stroke) and 250 subjects from an online Internet sample of adults with general chronic conditions. Scores were compared with one legacy scale: Self-Efficacy for Managing Chronic Disease 6-Item scale (SEMCD6) and five PROMIS short forms: Global Health (Physical and Mental), Physical Function, Fatigue, Depression, and Anxiety. RESULTS: The sample was 57% female, mean age = 53.8 (SD = 14.7), 76% white, 21% African American, 6% Hispanic, and 76% with greater than high school education. Full-item banks were created for each domain. All measures had good internal consistency and correlated well with SEMCD6 (r = 0.56-0.75). Significant correlations were seen between the Self-Efficacy measures and other PROMIS short forms (r > 0.38). CONCLUSIONS: The newly developed PROMIS Self-Efficacy for Managing Chronic Conditions measures include five domains of self-efficacy that were calibrated across diverse chronic conditions and show good internal consistency and cross-sectional validity.

Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

Clinical subtypes and genetic heterogeneity: of lumping and splitting in Parkinson disease.

PURPOSE OF REVIEW: Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years. RECENT FINDINGS: New and innovative clinical diagnostic criteria for Parkinson disease have been proposed and await validation. Studies using functional imaging or wearable biosensors, as well as biomarker studies, provide new support for the validity of the traditional clinical subtypes of Parkinson disease (tremor-dominant versus akinetic-rigid or postural instability/gait difficulty). A recent cluster analysis (as unbiased data-driven approach to subtyping) included a wide spectrum of nonmotor variables, and showed correlation of the proposed subtypes with disease progression in a longitudinal analysis. New genetic factors contributing to Parkinson disease susceptibility continue to be identified, including rare mutations causing monogenetic disease, common variants with small effect size and risk factors (like mutations in the gene for glucocerebrosidase) that fall in between the two other categories. Recent studies show some limited correlation between genetic factors and clinical heterogeneity. Despite some variations in patterns of pathology, Lewy bodies are still the hallmark of Parkinson disease, including the vast majority of genetic subgroups. SUMMARY: Evidence of clinical, genetic and pathological heterogeneity of Parkinson disease continues to emerge, but clearly defined subtypes that hold up in more than one of these domains remain elusive. For research to identify such subtypes, splitting is likely the way forward; until then, for clinical practice, lumping remains the more pragmatic approach.

Disability Rating Scales in Parkinson's Disease: Critique and Recommendations.

INTRODUCTION: PD is associated with impairments that progress over time to disability. A large number of disability scales exist with little information on the best choice in PD. METHODS: Following methodology adopted by the International Parkinson and Movement Disorder Society Task Force, a review of disability scales used in PD was completed. Based on prespecified criteria, the review categorized scales into: "Recommended"; "Recommended with Further Validation in PD Required" when well-validated scales have not been specifically tested for clinimetric properties in PD; "Suggested"; and "Listed." RESULTS: Twenty-nine disability instruments were identified with nine scales fulfilling criteria for "Recommended" and 7 "Recommended with Further Validation in PD Required." Eight scales are "Suggested" and five scales are "Listed" for use in PD. The nine Recommended scales (Functional Status Questionnaire, Lawton-Brody Activities of Daily Living, Nottingham Activities of Daily Living, Schwab and England Activities of Daily Living, Self-Assessment PD Disability, Short Parkinson's Evaluation Scale/Scales for Outcomes in PD, Unified PD Rating Scale-II: Activities of Daily Living, Movement Disorders Society UPDRS Motor Experiences of Daily Living, PROMIS® and Neuro-QoL Physical Function), and the seven Recommended with Further Validation in PD Required are reviewed. CONCLUSION: Many disability measures are available and recommended for application in PD. The Task Force does not recommend the development of a new scale. Selection of the most appropriate instrument for a particular objective requires consideration of the characteristics of each scale and the goals of the assessment. © 2016 International Parkinson and Movement Disorder Society.

Asymmetric responsiveness of disability and health-related quality of life to improvement versus decline in Parkinson's disease.

PURPOSE: Clinical trials in Parkinson's disease commonly employ outcome measures of disability and quality of life. Responsiveness of these outcomes measures to symptomatic decline versus improvement has not been studied. We wanted to study the responsiveness of Schwab & England Activities of Daily Living Scale (SE) and Short Form-12 (SF-12) to symptomatic decline versus improvement in Parkinson's disease over a 4-year period among a naturalistic cohort of patients. METHODS: Parkinson's disease patients (N = 228, disease duration 6.1 years) were followed for 4 years with assessments of disease severity, Unified Parkinson's Disease Rating Scale (UPDRS), health-related quality of life (SF-12 physical/mental health), and disability (SE). The sample was subdivided into those who declined (N = 118) or improved (N = 102) on total-UPDRS. Responsiveness was assessed with Cohen's effect size and standardized response mean. RESULTS: At baseline, patients who improved over 4 years had greater disease severity and worse quality of life than decliners (p < .05). Decliners had a 13.5-point worsening on total-UPDRS, 26.3-39.8; p < .001) associated with concomitant decline on the SF-12 (physical health 42.9-39.2, mental health 50.0-46.6; both p < .001) and the SE (85-74 %; p < .001). Improvers had a 13.0-point improvement on total-UPDRS (39.8-26.8; p < .001) associated with minimal change on the SF-12 (physical health 40.8-39.5, mental health 47.1-46.3) and SE (79-79 %). Based on effect size, the rank order of responsiveness of measures for decliners from high to low was SE (-0.78), Short Form-12 mental health (-0.45), and SF-12 physical health (-0.34). Rank order of responsiveness for improvers was Short Form-12 physical health (-0.11), SF-12 mental health (-0.10), and SE (-0.03). CONCLUSIONS: Among decliners, measures of disability and quality of life were moderate to highly responsive to change in disease severity. Among improvers, both disability and quality of life were poorly responsive despite UPDRS improvement of comparable magnitude.

Assessment of the psychometrics of a PROMIS item bank: self-efficacy for managing daily activities.

PURPOSE: The aim of this study is to investigate the psychometrics of the Patient-Reported Outcomes Measurement Information System self-efficacy for managing daily activities item bank. METHODS: The item pool was field tested on a sample of 1087 participants via internet (n = 250) and in-clinic (n = 837) surveys. All participants reported having at least one chronic health condition. The 35 item pool was investigated for dimensionality (confirmatory factor analyses, CFA and exploratory factor analysis, EFA), item-total correlations, local independence, precision, and differential item functioning (DIF) across gender, race, ethnicity, age groups, data collection modes, and neurological chronic conditions (McFadden Pseudo R (2) less than 10 %). RESULTS: The item pool met two of the four CFA fit criteria (CFI = 0.952 and SRMR = 0.07). EFA analysis found a dominant first factor (eigenvalue = 24.34) and the ratio of first to second eigenvalue was 12.4. The item pool demonstrated good item-total correlations (0.59-0.85) and acceptable internal consistency (Cronbach's alpha = 0.97). The item pool maintained its precision (reliability over 0.90) across a wide range of theta (3.70), and there was no significant DIF. CONCLUSION: The findings indicated the item pool has sound psychometric properties and the test items are eligible for development of computerized adaptive testing and short forms.

The role of technical advances in the adoption and integration of patient-reported outcomes in clinical care.

BACKGROUND: Patient-reported outcomes (PROs) are gaining recognition as key measures for improving the quality of patient care in clinical care settings. Three factors have made the implementation of PROs in clinical care more feasible: increased use of modern measurement methods in PRO design and validation, rapid progression of technology (eg, touchscreen tablets, Internet accessibility, and electronic health records), and greater demand for measurement and monitoring of PROs by regulators, payers, accreditors, and professional organizations. As electronic PRO collection and reporting capabilities have improved, the challenges of collecting PRO data have changed. OBJECTIVES: To update information on PRO adoption considerations in clinical care, highlighting electronic and technical advances with respect to measure selection, clinical workflow, data infrastructure, and outcomes reporting. METHODS: Five practical case studies across diverse health care settings and patient populations are used to explore how implementation barriers were addressed to promote the successful integration of PRO collection into the clinical workflow. The case studies address selecting and reporting of relevant content, workflow integration, previsit screening, effective evaluation, and electronic health record integration. CONCLUSIONS: These case studies exemplify elements of well-designed electronic systems, including response automation, tailoring of item selection and reporting algorithms, flexibility of collection location, and integration with patient health care data elements. They also highlight emerging logistical barriers in this area, such as the need for specialized technological and methodological expertise, and design limitations of current electronic data capture systems.

Interplay of donor-acceptor interactions in stabilizing boron nitride compounds: insights from theory.

The stability of a variety of linear and cyclic (BN)n (n = 1-3) adducts with N-heterocyclic carbene (ImMe2; ImMe2 = [(HCNMe)2C:]), N-heterocyclic olefin (ImMe2CH2) and Wittig (Me3PCH2) donors has been examined using M05-2X/cc-pVTZ computations. The strength and nature of the bonds have been investigated using natural bond orbital (NBO) and atoms-in-molecules (AIM) analyses. Complementary energy decomposition analysis (EDA-NOCV) has been carried out based on BP86/TZ2P computations. In agreement with NBO and AIM analyses, the orbital interaction energy obtained from EDA contributes at least 50% to the total attractive interactions for the carbon-boron bonds indicating their largely covalent nature. The feasibility of isolating monomeric (BN)n units using a donor/acceptor protocol was also investigated in a series of adducts of the general form: LB·(BN)n·BH3 and LB·(BN)n·W(CO)5 (n = 1-3; LB = Lewis bases). Moreover, EDA-NOCV analysis of ImMe2·BN·W(CO)5 and ImMe2·B3N3·W(CO)5 shows that the carbene-boron bonds are stronger in the presence of W(CO)5 as a Lewis acid mainly because of a dramatic decrease in the amount of Pauli repulsion rather than an increase in the electrostatic/orbital attraction terms.