Behavioral Treatment of Insomnia and Sleep Disturbances in School-Aged Children and Adolescents.

Insomnia and related sleep disturbances are prevalent among youth and are associated with adverse consequences, including poorer psychiatric functioning. Behavioral sleep interventions, ranging from brief educational interventions to behavioral therapies (cognitive behavior therapy-insomnia), are associated with positive outcomes for pediatric sleep health. In addition, sleep interventions may improve psychiatric health for children and adolescents with neurodevelopmental and internalizing disorders. Additional research is necessary to clarify the efficacy of these interventions over the long-term and across demographic groups; however, evidence suggests incorporating behavioral sleep strategies may prove beneficial to pediatric patients with sleep disturbances and related psychiatric complaints.

Industry Perspective on Temperature Cycling Studies to Meet Regulatory Temperature Excursion Support Requirements: Survey Outcome and Recommendations.

Temperature cycling stability studies can be appropriately designed and utilized to ensure that drug product quality, efficacy, and safety are not compromised when materials are subjected to short term temperature excursions from intended storage that may occur during e.g., shipping, transport, or patient use. Some countries, such as Australia and Brazil, impose specific regulations that specify the need to conduct stability studies that are supportive of "real world" excursions as part of licensing approval requirements. These temperature cycling stability studies extend beyond what is described in ICH Guidelines Q1A(R2) and Q5C, and companies may be challenged in designing studies that not only satisfy country specific regulations, but also satisfy all global regulatory health authority expectations. This article focuses on responses to a cross-industry survey conducted within the International Consortium for Innovation and Quality (iqconsortium.org) member companies, regarding practices related to temperature cycling stability studies, in order to determine how these requirements are being interpreted and met. The results indicate that while there is no one-size-fits-all approach to performing temperature cycling stability studies, there are common and best practices that can be followed to satisfy global health authority regulatory guidelines and requirements. PURPOSE: The purpose of this paper is to describe the outcome of an industry survey and common/best practices on temperature cycling stability studies performed on drug product (DP) to satisfy the requirements established for marketing authorizations in Australia and Brazil or any other countries that may have similar requirements. The framework is proposed within the context of late phase and commercial development of common biological and/or large molecule modalities, such as monoclonal antibodies (mAbs, including bispecific antibodies), fusion proteins, complex proteins, oligonucleotides, and antibody-drug conjugates (ADCs), but many of the general principles involved may be applied to other therapeutics, such as Virus Like Particles (VLP), gene or cell therapies (GTx or CTx), or vaccines. For the purposes of this paper, temperature cycling stability studies refer to studies that are designed, in part, to support short term temperature excursions that drug product may be subjected to during shipping and storage activities and is outside of the labeled storage condition of the product.

Using the multiple sclerosis resiliency scale to identify psychological distress in persons with multiple sclerosis.

BACKGROUND: The Multiple Sclerosis Resiliency Scale (MSRS) is the first resilience measure that is specific to multiple sclerosis (MS)-related challenges. In order for the MSRS to be a valuable tool for clinicians, it is important to identify what is a meaningful score. As such, this study aimed to examine the MSRS' ability to identify persons with MS experiencing depression or anxiety symptoms, as determined using clinically significant scores on the Hospital Anxiety and Depression Scale (HADS). METHODS: Participants (n = 884) were persons with MS who were recruited electronically primarily through the North American Research Committee on MS (NARCOMS). In addition to the MSRS, participants completed the HADS, which was used to categorize them into possible depression and anxiety groups using two criteria from the literature: ≥8 and ≥11. Receiver-operating-characteristic (ROC) curves were run to determine the MSRS total and subscale scores' classification accuracies, with optimal scores for detecting possible depression and anxiety cases determined using the Youden index. RESULTS: The MSRS total score's classification accuracy ranged between 86.2% and 92.2% for depression, with scores of 70 and 68 for the ≥8 and ≥11 criteria, respectively. For anxiety, the MSRS total score's classification accuracy ranged between 78.1% and 82.8%, with scores of 72 and 71 for the ≥8 and ≥11 criteria, respectively. The Emotional and Cognitive Strategies subscale had the strongest classification accuracy of all the subscales. CONCLUSIONS: The MSRS can be used to identify persons with MS experiencing mental health difficulties with relatively good classification accuracy, which may help clinicians to triage who needs additional assistance or support.

Behavioral Treatment of Insomnia and Sleep Disturbances in School-Aged Children and Adolescents.

Insomnia and related sleep disturbances are prevalent among youth and are associated with adverse consequences, including poorer psychiatric functioning. Behavioral sleep interventions, ranging from brief educational interventions to behavioral therapies (cognitive behavior therapy-insomnia), are associated with positive outcomes for pediatric sleep health. In addition, sleep interventions may improve psychiatric health for children and adolescents with neurodevelopmental and internalizing disorders. Additional research is necessary to clarify the efficacy of these interventions over the long-term and across demographic groups; however, evidence suggests incorporating behavioral sleep strategies may prove beneficial to pediatric patients with sleep disturbances and related psychiatric complaints.

The influence of trait mindfulness on depression in multiple sclerosis: potential implications for treatment.

PURPOSE: This study seeks to add to existing literature on depression and illness intrusiveness in chronic disorders by examining, (1) how the perceived intrusiveness of multiple sclerosis (MS) leads to depression, (2) and the mediating role trait mindfulness plays in this relationship METHODS: Participants (N = 755) were persons with MS (PwMS) recruited through the North American Research Committee on MS (NARCOMS) registry (a larger study). Participants completed the Illness Intrusiveness Ratings Scale, the Hospital Anxiety and Depression Scale and the Mindful Attention Awareness Scale. A mediation model assessed if trait mindfulness mediates the relationship between illness intrusiveness and depression RESULTS: Illness intrusiveness predicted trait mindfulness (a = - 4.54; p < .001), trait mindfulness predicted depression (b = - .04; p < .001); there was a direct effect of illness intrusiveness on depression (c' = 2.53; p < .001) and an indirect effect on depression (ab = .17, 95% BCa CI [.10, .25]) when trait mindfulness was in the model, which represented a medium size effect, R2med = .10 [95% CI .07, .14] CONCLUSION: Trait mindfulness mediates the relationship between illness intrusiveness and depression in PwMS. Providers could provide psychoeducation on the benefits of mindfulness and mindfulness-based interventions.

Short Report: Adherence to Neuropsychological Recommendations in Patients with Multiple Sclerosis.

BACKGROUND: Adherence to nonmedication recommendations is typically low, as seen in various health populations. Because literature on adherence to treatment recommendations made after neuropsychological testing in multiple sclerosis (MS) is lacking, this study evaluated adherence and reasons for nonadherence. Relationships between adherence to recommendations and various other factors in patients with MS were also evaluated. METHODS: Of 66 adult patients seen for neuropsychological testing at an MS center, 55 were eligible for this study. Forty-five patients (mean age, 43.4 years; 75.6% women) were reached by phone, and all agreed to an interview involving questions regarding adherence to treatment recommendations. Other information was obtained through retrospective medical record review. RESULTS: Overall self-reported adherence to recommendations made from neuropsychological testing was 38%. Adherence rates varied by recommendation type: psychopharmacological management had the highest rate (80%), and referrals for cognitive rehabilitation had the lowest (6.5%). Reasons for nonadherence included needing more information and wanting to speak with one's physician regarding the recommendations. Adherence was associated with patients' ability to spontaneously recall at least some of their recommendations and with receiving both a written report and a phone call with test results. CONCLUSIONS: Adherence to recommendations made after neuropsychological testing for patients with MS is low. Points of intervention may be to give directed feedback for each recommendation and to provide both a written report and a phone call with results and recommendations. Asking patients to repeat back the recommendations may be a simple and efficient way to increase understanding and improve adherence.

Sex differences in predictors of illness intrusiveness in persons with multiple sclerosis.

PURPOSE: Multiple sclerosis (MS) is a complex, chronic disease that can have debilitating effects on daily activities and well-being, compromising health-related quality of life. One underlying determinant of quality of life (QOL) is perceived illness intrusiveness, which examines the disruptiveness of the condition and/or its related treatment on engagement in interest and activities, in turn affecting psychological functioning. There is evidence that persons with MS (PwMS) have higher level of illness intrusiveness compared to those with other chronic conditions; however, limited research exists on differences by sex. This study aimed to explore these possible differences between men and women, hypothesizing that men with MS will have overall higher illness intrusiveness (lower QOL) when compared to women with MS. METHODS: A total of 922 PwMS were primarily recruited through the North American Research Committee on MS Registry. The participants completed a one-time anonymous online survey. Illness intrusiveness was measured using the Illness Intrusiveness Ratings Scale (IIRS) total score and three subscales. Independent t-tests determined differences in demographics, disease characteristics, and IIRS outcomes. Hierarchical regressions were then used to further assess whether sex was a significant predictor of illness intrusiveness. RESULTS: Men exhibited greater overall, intimacy, and relationship and personal development-related perceived illness intrusiveness. However, sex was only a significant predictor of the Intimacy IIRS subscale after accounting for age, disability, and depression. CONCLUSIONS: These findings highlight the intrusiveness of MS on intimacy and sexual functioning, particularly among men. Potential clinical implications and future directions are discussed.

Development of the Multiple Sclerosis Resiliency Scale (MSRS).

OBJECTIVES: While resilience has been an area of increasing research, there are no measures that are specific to the psychological, social, and physical factors associated with resilience in persons with multiple sclerosis (PwMS). This study aimed to develop the MS Resiliency Scale (MSRS), a multidimensional measure. Items were created based on a review of the literature, with five hypothesized subscales, and then evaluated in a large sample of PwMS. METHOD: Participants (N = 932) were primarily recruited through the North American Research Committee on MS (NARCOMS) and completed the study electronically. Principal components analysis was utilized to determine the number of factors and whether they aligned with the theorized model. RESULTS: Using an unforced solution with oblique (promax) rotation and Kaiser normalization, and suppressing items with coefficients below 0.4, 25 items were retained in five subscales that accounted for 42.75% of the variance: Emotional and Cognitive Strategies (13 items; α = .92), Physical Activity and Diet (3 items; α = .77), MS Peer Support (2 items; α = .82), Support from Family and Friends (5 items; α = .79), and Spirituality (2 items; α = .91). The total score was negatively correlated with depression, r = -.72, p < .001 and anxiety, r = -.56, p < .001. IMPLICATIONS: The 25-item MSRS assesses several psychological, social, and physical factors associated with resilience in PwMS, and may be a helpful tool in identifying individuals in need of additional assistance or support. (PsycINFO Database Record

Assessing the criterion validity of four highly abbreviated measures from the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS).

OBJECTIVE: Cognitive dysfunction is prevalent in multiple sclerosis. As self-reported cognitive functioning is unreliable, brief objective screening measures are needed. Utilizing widely used full-length neuropsychological tests, this study aimed to establish the criterion validity of highly abbreviated versions of the Brief Visuospatial Memory Test - Revised (BVMT-R), Symbol Digit Modalities Test (SDMT), Delis-Kaplan Executive Function System (D-KEFS) Sorting Test, and Controlled Oral Word Association Test (COWAT) in order to begin developing an MS-specific screening battery. METHOD: Participants from Holy Name Medical Center and the Kessler Foundation were administered one or more of these four measures. Using test-specific criterion to identify impairment at both -1.5 and -2.0 SD, receiver-operating-characteristic (ROC) analyses of BVMT-R Trial 1, Trial 2, and Trial 1 + 2 raw data (N = 286) were run to calculate the classification accuracy of the abbreviated version, as well as the sensitivity and specificity. The same methods were used for SDMT 30-s and 60-s (N = 321), D-KEFS Sorting Free Card Sort 1 (N = 120), and COWAT letters F and A (N = 298). RESULTS: Using these definitions of impairment, each analysis yielded high classification accuracy (89.3 to 94.3%). CONCLUSIONS: BVMT-R Trial 1, SDMT 30-s, D-KEFS Free Card Sort 1, and COWAT F possess good criterion validity in detecting impairment on their respective overall measure, capturing much of the same information as the full version. Along with the first two trials of the California Verbal Learning Test - Second Edition (CVLT-II), these five highly abbreviated measures may be used to develop a brief screening battery.

Structural characterization of recombinant alpha-1-antitrypsin expressed in a human cell line.

Human alpha-1-antitrypsin (A1PI) is a plasma protein with the function of protecting lung tissues from proteolytic destruction by enzymes from inflammatory cells. A1PI deficiency is an inherited disorder associated with pulmonary emphysema and a higher risk of chronic obstructive pulmonary disease (COPD). Here we present the structural characterization of a recombinant form of human A1PI (Hu-recA1PI) expressed in the human PER.C6 cell line using an array of analytical and biochemical techniques. Hu-recA1PI had the same primary structure as plasma-derived A1PI (pd-A1PI) except reduced N-terminal heterogeneity. The secondary and tertiary structures were indistinguishable from pd-A1PI. Like pd-A1PI, Hu-recA1PI was modified by N-linked glycosylation on N46, N83, and N246. Unlike pd-A1PI, most glycans on recA1P1 were core fucosylated via α(1-6) linkage. In addition, significantly higher amounts of tri- and tetraantennary glycans were observed. These differences in glycosylation contributed to the apparent higher molecular weight and lower isoelectric point (pI) of Hu-recA1PI than pd-A1PI. Hu-recA1PI contained both α(2-3)- and α(2-6)-linked sialic acids and had very similar sialylation levels as pd-A1PI. Hu-recA1PI glycans were differentially distributed, with N46 containing mostly biantennary glycans, N83 containing primarily tri- and tetraantennary glycans, and N247 containing exclusively biantennary glycans.