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The efficacy of intensive group treatment programs for child maltreatment has been established. The aim of this qualitative study was to understand how women with a history of child maltreatment experienced the Women Recovering from Abuse Program (WRAP), an existing intensive group treatment program. Seven women were interviewed following their participation in WRAP. Three themes emerged: Breaking Trauma-Based Patterns, Doing Therapy, and The Healing Journey as a Continuous Process. These findings deepen our understanding about how participants view the recovery process. Theoretical and clinical implications are discussed. [ABSTRACT FROM AUTHOR]

Inclusion of adaptive design features in a clinical trial provides preplanned flexibility to dynamically modify a trial during its conduct while preserving validity and integrity. Adaptive trials are needed to accelerate the conduct of more efficient, informative, and ethical clinical research in the field of neurology. Stroke is a natural candidate for adoption of these innovative approaches to trial design. This Research Methods in Neurology article is informed by a scoping review that identified 45 completed or ongoing adaptive clinical trials in stroke that were appraised: 15 trials had published results with or without a published protocol and 30 ongoing trials (14 trials had a published protocol, and 16 trials were registered only). Interventions spanned acute (n = 28), rehabilitation (n = 8), prevention (n = 8), and rehabilitation and prevention (n = 1). A subsample of these trials was selected to illustrate the utility of adaptive design features and discuss why each adaptive feature was incorporated in the design to best achieve the aim; whether each individual feature was used and whether it resulted in expected efficiencies; and any learnings during preparation, conduct, or reporting. We then discuss the operational, ethical, and regulatory considerations that warrant careful consideration during adaptive trial planning and reflect on the workforce readiness to deliver adaptive trials in practice. We conclude that adaptive trials can be designed, funded, conducted, and published for a wide range of research questions and offer future directions to support adoption of adaptive trial designs in stroke and neurologic research more broadly.

Introduction: The prevalence of upper limb motor weakness early post-stroke may be changing, which can have clinical and research implications. Our primary aim was to describe the prevalence of upper limb motor weakness early post-stroke, with a secondary aim to contextualize this prevalence by describing pre-stroke outcomes, other post-stroke impairments, functional activities, and discharge destination., Methods: This cross-sectional observational study extracted clinical data from confirmed stroke patients admitted to a metropolitan stroke unit over 15-months. The primary upper limb weakness measure was Shoulder Abduction and Finger Extension (SAFE) score. Demographics (eg, age), clinical characteristics (eg, stroke severity), pre-stroke outcomes (eg, clinical frailty), other post-stroke impairments (eg, command following), functional activities (eg, ambulation), and discharge destination were also extracted., Results: A total of 463 participants had a confirmed stroke and SAFE score. One-third of patients received ≥1 acute medical intervention(s). Nearly one-quarter of patients were classified as frail pre-stroke. Upper limb weakness (SAFE≤8) was present in 35% [95% CI: 30%-39%] at a median of 1-day post-stroke, with 22% presenting with mild-moderate weakness (SAFE5-8). The most common other impairments were upper limb coordination (46%), delayed recall (41%), and upper limb sensation (26%). After a median 3-day acute stroke stay, 52% of the sample were discharged home., Conclusion: Upper limb weakness was present in just over a third (35%) of the sample early post-stroke. Data on pre-stroke outcomes and the prevalence of other post-stroke impairments highlights the complexity and heterogeneity of stroke recovery. Further research is required to tease out meaningful recovery phenotypes and their implications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was ranked easy to address and very important, "variability in usual care" was ranked hard to address and of low importance, and "understanding the content of the control and how it differs from the experimental intervention" was ranked very important but not easy to address. The CONtrol DeSIGN (CONSIGN) decision support tool was developed to address the identified challenges and enhance comparator selection, description, and reporting. CONSIGN is a web-based tool inclusive of seven steps that guide the user through control comparator design. The tool was refined through multiple rounds of pilot testing that included more than 130 people working in neurorehabilitation research. Four hypothetical exemplar trials, which span preclinical, mood, aphasia, and motor recovery, demonstrate how the tool can be applied in practice. Six consensus recommendations are defined that span research domains, professional disciplines, and international borders., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The objectives of this systematic review were to describe the current dose and content of usual care upper limb motor intervention for inpatients following stroke and examine if context factors alter dose and content., Data Sources: A systematic search (EMBASE, MEDLINE) was completed from January 2015 to February 2023 (PROSPERO CRD42021281986)., Methods: Studies were eligible if they reported non-protocolised usual care upper limb motor intervention dose data for stroke inpatients. Studies were rated using the Johanna Briggs Institute critical appraisal tool. Data were descriptively reported for dose dimensions of time (on task or, in therapy) and intensity (repetitions, repetition/minute), content (intervention type/mode), and context (e.g., severity strata)., Results: Eight studies were included from four countries, largely reflecting inpatient rehabilitation. Time in therapy ranged from 23 to 121 min/day. Time on task ranged from 8 to 44 min/day. Repetitions ranged from 36 to 57/session, and 15 to 282/day. Time on task was lowest in the stratum of people with severe upper limb impairment (8 min/day), the upper limit for this stratum was 41.5 min/day. There was minimal reporting of usual care content across all studies., Conclusion: Upper limb motor intervention dose appears to be increasing in usual care compared to prior reports (e.g., average 21 min/day and 23 to 32 repetitions/session). Context variability suggests that doses are lowest in the stratum of patients with a severely impaired upper limb. Consistent reporting of the multiple dimensions of dose and content is necessary to better understand usual care offered during inpatient rehabilitation.

Introduction: Broadening eligibility criteria has been a focus to increase the generalizability of trial findings. Using upper-limb motor trials conducted early post-stroke as the illustrative domain, we sought to (1) investigate whether the published aim and conclusion statements adequately reflect the generalizability of findings and (2) explore internal validity and feasibility as constraints to achieving generalizability., Methods: We systematically applied a conceptual model of a trial sampling process to published literature from systematic review and prospective cross-sectional data. The eligibility criteria reported and used to exclude patients were classified by consensus as related to safety, internal validity, feasibility, or a combination thereof. Categorical data were reported as counts/proportions, and continuous data were reported as median (interquartile range (IQR))., Results: Thirty trials ( n  = 1638 participants) were included in the published literature and 1013 patients in the prospective data set. Thirty-seven percent of trials did not describe their target population in the aim and conclusion, and 80% did not report all trial screening data. Eligibility criteria related to internal validity were the most common type reported and applied to exclude patients across both data sets. In the prospective data set, 70% of patients were excluded for more than one reason., Conclusion: Key information to support the generalizability of trial findings was insufficiently reported in published upper-limb motor research conducted early post-stroke. Broadening eligibility criteria alone is unlikely to sufficiently improve trial inclusivity due to internal validity constraints. Trials could achieve inclusivity through targeting multiple sub-populations, that in combination, produce clinically relevant results that are applicable to a broader population.

Background: To enable development of effective interventions, there is a need to complete systematic early-phase dose articulation research. This scoping review aimed to synthesize dose articulation research of behavioral motor interventions for stroke recovery., Methods: MEDLINE and EMBASE were systematically searched for dose articulation studies. Preclinical experiments and adult clinical trials were classified based on the discovery pipeline and analyzed to determine which dose dimensions were articulated (time, scheduling or intensity) and how they were investigated (unidimensional vs multidimensional approach). Reporting of dose, safety and efficacy outcomes were summarized. The intervention description, risk of bias, and quality was appraised., Results: We included 41 studies: 3 of preclinical dose preparation (93 rodents), 2 Phase I dose ranging (21 participants), 9 Phase IIA dose screening (198 participants), and 27 Phase IIB dose finding (1879 participants). All studies adopted a unidimensional approach. Time was the most frequent dimension investigated (53%), followed by intensity (29%), and scheduling (18%). Overall, 95% studies reported an efficacy outcome; however, only 65% reported dose and 45% reported safety. Across studies, 61% were at high risk of bias, and the average percentage reporting of intervention description and quality was 61% and 67%, respectively., Conclusion: This review highlights a need to undertake more high-quality, early-phase studies that systematically articulate intervention doses from a multidimensional perspective in the field of behavioral motor stroke recovery. To address this gap, we need to invest in adapting early phase trial designs, especially Phase I, to support multidimensional dose articulation., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22-66) and study sample size remains small (median n=30, IQR 20-48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute (<24 hours), 13 acute (1-7 days), 176 early subacute (8-90 days), 34 late subacute (91-180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600-1430) min/session, 1 (IQR, 1-1) session/d, 5 (IQR, 5-5) d/wk for 4 (IQR, 3-5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and sample size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629.

Despite an increase in the amount of published stroke recovery research, interventions have failed to markedly affect the trajectory of recovery poststroke. We argue that early-phase research to systematically investigate dose is an important contributor to advance the science underpinning stroke recovery. In this article, we aim to ( a ) define the problem of insufficient use of a systematic approach to early-phase, multidimensional dose articulation research and ( b ) propose a solution that applies this approach to design a multidimensional phase I trial to identify the maximum tolerated dose (MTD). We put forward a design template as a decision support tool to increase knowledge of how to develop a phase I dose-ranging trial for nonpharmaceutical stroke recovery interventions. This solution has the potential to advance the development of efficacious stroke recovery interventions, which include activity-based rehabilitation interventions.

Dose articulation is a universal issue of intervention development and testing. In stroke recovery, dose of a nonpharmaceutical intervention appears to influence outcome but is often poorly reported. The challenges of articulating dose in nonpharmacological stroke recovery research include: (1) the absence of specific internationally agreed dose reporting guidelines; (2) inadequate conceptualization of dose, which is multidimensional; and (3) unclear and inconsistent terminology that incorporates the multiple dose dimensions. To address these challenges, we need a well-conceptualized and consistent approach to dose articulation that can be applied across stroke recovery domains to stimulate critical thinking about dose during intervention development, as well as promote reporting of planned intervention dose versus actually delivered dose. We followed the Design Research Paradigm to develop a framework that guides how to articulate dose, conceptualizes the multidimensional nature and systemic linkages between dose dimensions, and provides reference terminology for the field. Our framework recognizes that dose is multidimensional and comprised of a duration of days that contain individual sessions and episodes that can be active (time on task) or inactive (time off task), and each individual episode can be made up of information about length, intensity, and difficulty. Clinical utility of this framework was demonstrated via hypothetical application to preclinical and clinical domains of stroke recovery. The suitability of the framework to address dose articulation challenges was confirmed with an international expert advisory group. This novel framework provides a pathway for better articulation of nonpharmacological dose that will enable transparent and accurate description, implementation, monitoring, and reporting, in stroke recovery research.

The purpose of this study was to develop and validate a self-report measure of body image and sexual adjustment in breast cancer patients: the Sexual Adjustment and Body Image Scale (SABIS). Three hundred and fifty three women diagnosed with primary breast cancer that had completed initial surgical treatment completed the SABIS and five measures of psychological, psychosocial, and sexual functioning. Psychometric properties of the SABIS were examined and it was found to be a reliable and valid means of assessing body image and sexuality in breast cancer patients following surgery.

The systemic-constructivist approach to studying and benefiting couples was derived from qualitative and quantitative research on distressed couples over the past 10 years. Systemic-constructivist couple therapy (SCCT) is the clinical intervention that accompanies the approach. SCCT guides the therapist to work with both the intrapersonal and the interpersonal aspects of marriage while also integrating the social-environmental context of the couple. The theory that underlies SCCT is explained, including concepts such as we-ness and interpersonal processing. The primary components of the therapy are described. Findings described previously in an inaugural monograph containing extensive research demonstrating the long-term utility of SCCT are reviewed. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Changes in partners' sense of self-in-relationship, which a systemic-constructivist couple therapy (SCCT) induced, led to robust improvement in satisfaction in 2 studies and a follow-up study. In each study, 13 referred couples completed measures of satisfaction, mutuality, similarities, and other-in-self construal pre-post 12 hours of SCCT. The authors reliably coded transcripts of 1st and final sessions for each partner's we-ness, the identity that each partner establishes in relationship to the other. Having met the criteria for the rigorous study of change in single group process-outcome design, changes in we-ness accompanied large posttherapy dyadic increments on all variables in each study. Therapeutic gains appeared at follow-up and correlated with increased we-ness obtained at end of therapy 2 years earlier. The authors raise theoretical implications for all types of couple therapies and explain clinical techniques.

The published literature on depression in multiple sclerosis (MS) is reviewed quantitatively. The authors report mean effect sizes for 20 studies comparing depression scores of MS patients with those of healthy participants (d=1.07) and 21 studies comparing depression scores of MS patients with those of patients who have other chronic conditions (d=-0.14). The confidence interval for the mean overall MS-medical comparison included 0. However, subgroups of patients with chronic fatigue and spinal-neuromuscular conditions were more and less depressed than MS patients, respectively. Results indicate that a majority of MS patients with mild to moderate disability levels are distinguishable from healthy people in terms of depressive symptoms. However, the depression-disease link is complex and not specific to this form of demyelinating illness., (((c) 2005 APA, all rights reserved).)

Objective: Bipolar disorder is associated with a high frequency of both completed suicides and suicide attempts. The primary aim of this study was to identify clinical predictors of suicide attempts in subjects with bipolar disorder., Methods: We studied 336 subjects with a diagnosis of bipolar I, bipolar II, or schizoaffective disorder (bipolar type). The Structured Clinical Interview for DSM-IV (SCID-I) was administered and subsequently two expert psychiatrists established a diagnosis. Predictors of suicide attempts were examined in attempters and non-attempters., Results: The lifetime rate of suicide attempts for the entire sample was 25.6%. A lifetime co-morbid substance use disorder was a significant predictor of suicide attempts: bipolar subjects with co-morbid substance use disorders (SUD) had a 39.5% lifetime rate of attempted suicide, while those without had a 23.8% rate (odds ratio = 2.09, 95% CI = 1.03-4.21, chi2 = 4.33, df = 1, p = 0.037)., Conclusions: Lifetime co-morbid SUD were associated with a higher rate of suicide attempts in patients with bipolar disorder. This relationship may have a genetic origin and/or be explained by severity of illness and trait impulsivity.

There is evidence for the involvement of glutamatergic transmission in the pathogenesis of major psychoses. The two most commonly used mood stabilizers (ie lithium and valproate) have been found to act via the N-methyl-D-aspartate receptor (NMDAR), suggesting a specific role of NMDAR in the pathogenesis of bipolar disorder (BP). The key subunit of the NMDAR, named NMDA-1 receptor, is coded by a gene located on chromosome 9q34.3 (GRIN1). We tested for the presence of linkage disequilibrium between the GRIN1 (1001-G/C, 1970-A/G, and 6608-G/C polymorphisms) and BP. A total of 288 DSM-IV Bipolar I, Bipolar II, or schizoaffective disorder, manic type, probands with their living parents were studied. In all, 73 triads had heterozygous parents for the 1001-G/C polymorphism, 174 for the 1970-A/G, and 48 for the 6608-G/C. These triads were suitable for the final analyses, that is, the transmission disequilibrium test (TDT) and the haplotype-TDT. For the 1001-G/C and the 6608-G/C polymorphisms, we found a preferential transmission of the G allele to the affected individuals (chi(2)=4.765, df=1, P=0.030 and chi(2)= 8.395, df=1, P=0.004, respectively). The 1001G-1970A-6608A and the 1001G-1970A-6608G haplotypes showed the strongest association with BP (global chi(2)=14.12, df=4, P=0.007). If these results are replicated there could be important implications for the involvement of the GRIN1 in the pathogenesis of BP. The role of the gene variants in predicting the response to mood stabilizers in BP should also be investigated.

Objective: To examine antidepressant augmentation with and hypnotic effects of slow-release melatonin (SR-melatonin) in patients with treatment-resistant depression., Design: Open-label trial., Setting: Tertiary care outpatient depression clinic., Patients: Nine outpatients who had failed to respond to 2 or more 8-week trials of antidepressant medication., Interventions: Patients received SR-melatonin 5 mg per day for the first 2 weeks and 10 mg per day for the final 2 weeks, in addition to their antidepressant medication., Outcome Measures: Structured Clinical Interview for DSM-IV, Axis 1 Disorders, Hamilton Rating Scale for Depression (HRSD), Beck Depression Inventory, Response Style Questionnaire, sleep and fatigue measures., Results: One patient was excluded after 1 week because of the development of a mixed affective state. In the remaining 8 patients there was a 20% mean decrease in HRSD scores after 4 weeks of treatment, with no individual achieving an improvement of 50% or more. There was a 36% decrease on the 3-item HRSD related to insomnia, with 4 of 8 patients showing at least a 50% improvement on this measure. The greatest decrease in insomnia occurred during the last 2 weeks of the study, following the increase in dosage to 10 mg per day of SR-melatonin. Patients also reported significantly lower levels of fatigue post-treatment., Conclusions: SR-melatonin may be a useful adjunct for sleep, but does not substantially augment existing antidepressant therapies in some patients with treatment-resistant depression.

By use of stopped-flow kinetic data, we have measured the kinetics of mononitrated neurophysin I monomer binding to oxytocin. The association constant was 1.3(+/-0.3) x 10(5) M-1s-1 and the dissociation rate constant was 2.0(+/-0.5)s-1 for protonated oxytocin binding. Both rates are significantly slower than those observed for neurophysin dimer. These data suggest that the binding process by which the monomer binds oxytocin is not identical to that of dimer.

Donkey IgGa was isolated in purified form from normal and immune donkey sera by column chromatography on DEAE-cellulose. Isolated donkey IgGa and mixtures of (IgGa+IgGb) were used as antigens to prepare rabbit reagents specific for equine IgGa or IgGb. Antibodies present in sera obtained from a single donkey at various times during the course of hyperimmunization with BSA were isolated by immuno-adsorption. The class or subclass of immunoglobulins present among isolated, donkey anti-BSA antibodies was determined by use of specific rabbit anti-equine immunoglobulin reagents. The homologues of horse IgGa, IgGb, IgGc and IgA were identified in normal donkey, mule, hinny and zebra serum.

Thermodynamic binding constants for the interactions of mononitrated neurophysins with oxytocin, vasopressin, and peptide analogues of the hormones were determined by using a spectrophotometric titration technique. The data were fit to a binding model which included all known interactions in these systems. From an examination of the free energies for the binding reaction, we concluded that residues 1-3 contribute 84% of the binding energy for formation of the neurophysin dimer mono complex and 79% for the formation of the bis complex. Rate constants for complex formation and dissociation with native bovine neurophysin were determined by using temperature-jump relaxation. The association rate constants for neurophysin dimer binding to oxytocin, vasopressin, and the peptide analogues were all in the range of 1.3 X 10(6) M-1 s-1 for mono complexation and 1.5 X 10(6) M-1 s-1 for bis complexation. Thus, formation rate constants are identical for both mono and bis complexation, and no significant differences exist between formation constants for hormones and peptides. On the other hand, a clear distinction in dissociation rate constants is apparent when one compares the hormones (kr = 4 to 16 s-1) with the peptide analogues (kr = 54 to 182 s-1). There is rougly a tenfold increase in overall dissociation rate constant when one compares the peptides to the hormones. From these data, we conclude that the rate-determining step in the association reaction involves the first two or three residues on the hormone. After the initial binding takes place, only with intact hormone, i.e., oxytocin or vasopressin, can additional bonding interactions in the complex take place. These additional interactions are reflected in the slower off-rate of the hormone complexes relative to the peptide complexes.