Moral Injury: How It Affects Us and Tools to Combat It.

Introduction: Moral injury comprises feelings of guilt, despair, shame, and/or helplessness from having one's morals transgressed. Those underrepresented in health care are more likely to experience moral injury arising from micro- and macroaggressions. This workshop was designed for interprofessional health care providers ranging from students to program leadership to raise awareness about moral injury and provide tools to combat it. Methods: This 75-minute interactive workshop explored moral injury through a health care lens. It included components of lecture, case-based learning, small-group discussion, and individual reflection. Participants completed anonymous postworkshop evaluations, providing data on satisfaction and intention to change practice. We used descriptive statistics to analyze the quantitative data and applied content analysis to the qualitative data. Results: The workshop was presented at two local academic conferences. Data were collected from 34 out of 60 participants, for a response rate of 57%. Ninety-seven percent of participants felt the workshop helped them define and identify moral injury and was a valuable use of their time, as well as indicating they would apply the information learned in their daily life. One hundred percent would recommend the workshop to a friend or colleague. Almost half felt they could implement strategies to address moral injury after participating in the workshop. Discussion: This workshop proved to be a valuable tool to define and discuss moral injury. The materials can be adapted to a broad audience.

Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder.

BACKGROUND: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses. METHODS: We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4-15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions-Improvement (CGI-I) was a secondary endpoint. RESULTS: Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (- 12.5 ± 3.18 [mean ± SE]) vs. placebo (- 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65). CONCLUSION: Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27-0419-6116. CLINICALTRIALS: Gov registration ID is NCT06058962, last update posted 2023-09-28.

Para-Methoxybenzylidene Acetal-Protected D-Glucosamine Derivatives as pH-Responsive Gelators and Their Applications for Drug Delivery.

Carbohydrate-based low molecular weight gelators (LMWGs) are compounds with the capability to self-assemble into complex molecular networks within a solvent, leading to solvent immobilization. This process of gel formation depends on noncovalent interactions, including Van der Waals, hydrogen bonding, and π-π stacking. Due to their potential applications in environmental remediation, drug delivery, and tissue engineering, these molecules have emerged as an important area of research. In particular, various 4,6-O-benzylidene acetal-protected D-glucosamine derivatives have shown promising gelation abilities. In this study, a series of C-2-carbamate derivatives containing a para-methoxy benzylidene acetal functional group were synthesized and characterized. These compounds exhibited good gelation properties in several organic solvents and aqueous mixtures. Upon removal of the acetal functional group under acidic conditions, a number of deprotected free sugar derivatives were also synthesized. Analysis of these free sugar derivatives revealed two compounds were hydrogelators while their precursors did not form hydrogels. For those protected carbamates that are hydrogelators, removal of the 4,6-protection will result in a more water-soluble compound that produces a transition from gel to solution. Given the ability of these compounds to form gels from solution or solution from gels in situ in response to acidic environments, these compounds may have practical applications as stimuli-responsive gelators in an aqueous medium. In turn, one hydrogelator was studied for the encapsulation and release of naproxen and chloroquine. The hydrogel exhibited sustained drug release over a period of several days, with the release of chloroquine being faster at lower pH due to the acid lability of the gelator molecule. The synthesis, characterization, gelation properties, and studies on drug diffusion are discussed.

Barriers to Telemedicine Video Visits for Older Adults in Independent Living Facilities: Mixed Methods Cross-sectional Needs Assessment.

BACKGROUND: Despite the increasing availability of telemedicine video visits during the COVID-19 pandemic, older adults have greater challenges in getting care through telemedicine. OBJECTIVE: We aim to better understand the barriers to telemedicine in community-dwelling older adults to improve the access to and experience of virtual visits. METHODS: We conducted a mixed methods needs assessment of older adults at two independent living facilities (sites A and B) in Northern California between September 2020 and March 2021. Voluntary surveys were distributed. Semistructured interviews were then conducted with participants who provided contact information. Surveys ascertained participants' preferred devices as well as comfort level, support, and top barriers regarding telephonic and video visits. Qualitative analysis of transcribed interviews identified key themes. RESULTS: Survey respondents' (N=249) average age was 84.6 (SD 6.6) years, and 76.7% (n=191) of the participants were female. At site A, 88.9% (111/125) had a bachelor's degree or beyond, and 99.2% (124/125) listed English as their preferred language. At site B, 42.9% (51/119) had a bachelor's degree or beyond, and 13.4% (16/119) preferred English, while 73.1% (87/119) preferred Mandarin. Regarding video visits, 36.5% (91/249) of all participants felt comfortable connecting with their health care team through video visits. Regarding top barriers, participants at site A reported not knowing how to connect to the platform (30/125, 24%), not being familiar with the technology (28/125, 22.4%), and having difficulty hearing (19/125, 15.2%), whereas for site B, the top barriers were not being able to speak English well (65/119, 54.6%), lack of familiarity with technology and the internet (44/119, 36.9%), and lack of interest in seeing providers outside of the clinic (42/119, 35.3%). Three key themes emerged from the follow-up interviews (n=15): (1) the perceived limitations of video visits, (2) the overwhelming process of learning the technology for telemedicine, and (3) the desire for in-person or on-demand help with telemedicine. CONCLUSIONS: Substantial barriers exist for older adults in connecting with their health care team through telemedicine, particularly through video visits. The largest barriers include difficulty with technology or using the video visit platform, hearing difficulty, language barriers, and lack of desire to see providers virtually. Efforts to improve telemedicine access for older adults should take into account patient perspectives.

Conformational Clusters of Phosphorylated Tyrosine.

Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters ( Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999 , 294 , 1351 - 1362 ). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the n + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases.

A Mobile Phone-Based Health Coaching Intervention for Weight Loss and Blood Pressure Reduction in a National Payer Population: A Retrospective Study.

BACKGROUND: The prevalence of obesity and associated metabolic conditions continue to be challenging and costly to address for health care systems; 71% of American adults were overweight, with 35% of men and 40% of women diagnosed with obesity in 2014. Digital health coaching is an innovative approach to decreasing the barriers of cost and accessibility of receiving health coaching for the prevention and management of chronic disease in overweight or obese individuals. OBJECTIVE: To evaluate the early impact of a mobile phone-based health coaching service on weight loss and blood pressure management in a commercially insured population. METHODS: This was a retrospective study using existing registry data from a pilot commercial collaboration between Vida Health and a large national insurance provider, which enrolled adult members who were overweight (body mass index >25 kg/m2) and able to engage in a mobile phone-based coaching intervention. Participants received 4 months of intensive health coaching via live video, phone, and text message through the Vida Health app. Participants were also provided with a wireless scale, pedometer, and blood pressure cuff. Of the 1012 enrolled, 763 (75.40%) participants had an initial weight upon enrollment and final weight between 3 and 5 months from enrollment; they served as our intervention group. There were 73 participants out of the 1012 (7.21%) who had weight data 4 months prior to and after Vida coaching, who served as the matched-pair control group. RESULTS: Participants in the intervention group lost an average of 3.23% total body weight (TBW) at 4 months of coaching and 28.6% (218/763) intervention participants achieved a clinically significant weight loss of 5% or more of TBW, with an average of 9.46% weight loss in this cohort. In the matched-pair control group, participants gained on average 1.81% TBW in 4 months without Vida coaching and lost, on average, 2.47% TBW after 4 months of Vida coaching, demonstrating a statistically significant difference of 4.28% in mean percentage weight change (P<.001). Among 151 intervention participants with blood pressure data, 112 (74.2%) had a baseline blood pressure that was above the goal (systolic blood pressure >120 mmHg); 55 out of 112 (49.1%) participants improved their blood pressure at 4 months by an entire hypertensive stage-as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. CONCLUSIONS: Mobile phone app-based health coaching interventions can be an acceptable and effective means to promote weight loss and improve blood pressure management in overweight or obese individuals. Given the ubiquity of mobile phones, digital health coaching may be an innovative solution to decreasing barriers of access to much-needed weight management interventions for obesity.

Perspectives of low-income chronically ill patients on complex care management.

INTRODUCTION: Low-income, chronically ill adults disproportionately experience poor health outcomes despite increased health care use and costs. Complex care management (CCM) programs are an innovative approach to improving outcomes for these patients, but little is known about the patients' experiences in CCM programs in safety net primary care settings. METHOD: The authors conducted semistructured interviews with 13 CCM participants in a safety net primary care clinic to explore their perceptions of their health and their experiences with CCM. Interviews were recorded, transcribed, independently coded, and analyzed through an iterative process using grounded theory methodology to identify themes in the participants' experiences. RESULTS: From our interviews, 3 themes emerged-(a) participants mourned the loss of physical function and social well-being as a result of poor health; (b) participants reported increased health-related motivation due to relationships with the care team; and (c) participants experienced a newfound sense of control as a result of improved care navigation and self-management. DISCUSSION: Complex care management improved health-related motivation and provided a renewed sense of control for study participants, who were experiencing the loss of physical function and social well-being due to their chronic diseases. These findings support the importance of relationship-centered care models in programs for low-income, chronically ill patients. Future research should focus on identifying and spreading best practices that effectively empower patients to feel more in control of their health. (PsycINFO Database Record

Comorbidities in adult attention-deficit/hyperactivity disorder: a practical guide to diagnosis in primary care.

Diagnosis and management of attention-deficit/hyperactivity disorder (ADHD) in adults is complex and challenging because of the frequent comorbidity of other psychiatric disorders that have symptoms overlapping with those of ADHD. The presence of comorbidities can create challenges to making an accurate diagnosis and also impact treatment options and outcomes. This review discusses disorders that may be comorbid with ADHD in adults, including anxiety, mood, substance use disorder, antisocial personality disorder, and borderline personality disorder. Suggestions for recognizing these comorbidities and distinguishing them from ADHD and perspectives on their possible impact on ADHD treatment are included. Adjunctive nonpharmacologic modalities may be especially helpful in the case of comorbid mood, anxiety, substance abuse, or personality disorders.

Tumor necrosis factor-α produced in the kidney contributes to angiotensin II-dependent hypertension.

Immune system activation contributes to the pathogenesis of hypertension and the resulting progression of chronic kidney disease. In this regard, we recently identified a role for proinflammatory Th1 T-lymphocyte responses in hypertensive kidney injury. Because Th1 cells generate interferon-γ and tumor necrosis factor-α (TNF-α), we hypothesized that interferon-γ and TNF-α propagate renal damage during hypertension induced by activation of the renin-angiotensin system. Therefore, after confirming that mice genetically deficient of Th1 immunity were protected from kidney glomerular injury despite a preserved hypertensive response, we subjected mice lacking interferon-γ or TNF-α to our model of hypertensive chronic kidney disease. Interferon deficiency had no impact on blood pressure elevation or urinary albumin excretion during chronic angiotensin II infusion. By contrast, TNF-deficient (knockout) mice had blunted hypertensive responses and reduced end-organ damage in our model. As angiotensin II-infused TNF knockout mice had exaggerated endothelial nitric oxide synthase expression in the kidney and enhanced nitric oxide bioavailability, we examined the actions of TNF-α generated from renal parenchymal cells in hypertension by transplanting wild-type or TNF knockout kidneys into wild-type recipients before the induction of hypertension. Transplant recipients lacking TNF solely in the kidney had blunted hypertensive responses to angiotensin II and augmented renal endothelial nitric oxide synthase expression, confirming a role for kidney-derived TNF-α to promote angiotensin II-induced blood pressure elevation by limiting renal nitric oxide generation.

A physician's guide to helping patients with ADHD find success in the workplace.

The impact of untreated adult attention-deficit/hyperactivity disorder (ADHD) in the workplace can be substantial, and employees with ADHD often confront frustration, employer disappointment, and low performance ratings. As a result, adults with ADHD may seek treatment from primary care providers to improve occupational performance. Previously considered a behavior disorder primarily affecting children and adolescents, ADHD in adulthood presents primarily as a cognitive disorder. Self-management deficits play a greater role in adult ADHD, particularly with respect to occupational and interpersonal functioning. Although specialized resources are available to assist adults with ADHD, many afflicted individuals may be unaware or unable to access them. Primary care providers who may be treating adults with ADHD are in a unique position to help them obtain the care and support needed to build appropriate skills and manage occupational issues. In this review, a literature search of the past 10 years was conducted to identify articles concerning ADHD and its impact on individuals in the workplace. The influence of ADHD on occupational functioning is discussed in the context of self-management impairments, diagnosis and assessment, and management strategies. With early and successful intervention, adults with ADHD may be able to become more aware of the impact of ADHD on work performance and achieve successful occupational experiences.

ADHD in adults: current treatment trends with consideration of abuse potential of medications.

OBJECTIVE: To review the literature describing impairments in educational, occupational, and social functioning in adults with attention-deficit/hyperactivity disorder (ADHD), current treatment trends, and factors that may influence the abuse potential of long-acting medications used to treat ADHD in adults. METHODS: A MEDLINE search was conducted to identify articles relating to functional impairments and treatment options for adults with ADHD, as well as the abuse potential of ADHD medications. RESULTS: ADHD is one of the most common psychiatric behavioral disorders in children, and its symptoms have been shown to persist into adulthood. Symptoms of ADHD may occur at home, school, work, or in social situations, and symptom occurrence in these different settings can have a profound negative impact for adults with ADHD. Impairments in educational, occupational, and social functioning in adults with ADHD have been described and are summarized in this review article. Although long-acting medications are more frequently prescribed for children with ADHD than short-acting medications, adults with ADHD are equally likely to be treated with short- and long-acting medications. While all medications used to treat ADHD in adults have potential for abuse, there are a number of factors that may contribute to a lower potential for abuse for long-acting agents compared with immediate-release medications. CONCLUSION: Impairments from ADHD can be chronic and persistent and they can affect daily educational, occupational, and personal functioning. Adults, in particular, have responsibilities that can extend into the late evening hours so that clinicians need to consider medication duration of action when selecting a pharmacotherapy intervention for adults with ADHD.

Improving Communication in ADHD Care: Results from In-office Linguistic Research.

UNLABELLED: IntroductionAn in-office linguistic study was conducted to help improve understanding of how to better evaluate and treat attention-deficit/hyperactivity disorder (ADHD). METHODS: Naturally occurring interactions were recorded among 7 psychiatrists and 23 patients and 8 pediatricians along with 22 patients and their parents. Participants were interviewed separately post-visit. Transcripts of interactions and interviews were analyzed using sociolinguistic techniques. RESULTS: Visits were variable in length and lacked concrete treatment plans. In the pediatric setting, children were typically excluded from dialogues, accounting for only 8% of words spoken. School was the primary metric used to evaluate symptoms. Pediatricians allayed parents' concerns about stimulant therapy by promising to prescribe the lowest possible dose, rather than discussing titrating to an optimal dose. Adults were evaluated idiosyncratically without the use of scales or tools. Stimulants were positioned as short-term "trials" without strong physician recommendations.DiscussionConversations about stimulant therapy lacked goal- and expectation-setting. Also missing from conversations was a definitive treatment plan based on the core symptoms of ADHD. Incorporating open-ended questions and tools or rating scales may result in a more effective and efficient in-office dialogue. CONCLUSION: Further research is warranted to assess the efficacy of communication strategies to enhance in-office discussions of ADHD and stimulant therapy.

Psychopathology, families, and culture: autism.

Autism spectrum disorders (ASDs) are now considered to be the most common of the developmental disorders, although the effect of cultural influences on the diagnosis and treatment of ASDs has received limited attention. The existing literature on this topic suggests that both macro-level and microlevel cultural factors can affect the characterization, diagnosis, and treatment of ASDs. As a result, it is important for clinicians to consider cultural factors throughout the diagnostic, treatment planning, and intervention implementation processes. In this article, cultural influences on the prevalence of autism and the diagnostic and treatment processes are reviewed and synthesized through a consideration of the developmental context and through clinical practice suggestions.

Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) adversely impacts the educational achievement, mood and emotion processing, and interpersonal relationships of children and adolescents. Effective treatments include a number extended-release (ER) methylphenidate-(MPH) and amphetamine-based drugs. Some formulations release a comparatively larger bolus after dosing and can result in different onset and duration of efficacy. OBJECTIVE: Provide an evidence-based description of the time course of efficacy of psychostimulant medications used in ADHD treatment of children and adolescents. DATA SOURCES: A literature search from 1998 to 2008 was conducted using a MEDLINE database and the keywords "attention-deficit/hyperactivity disorder," "extended-release," "sustained-release," "methylphenidate," "amphetamine," "randomized," "controlled," "placebo," "efficacy," "time course," and "classroom study." DATA EXTRACTION: Selection criteria included randomized, blinded, placebo- or active comparator-controlled clinical studies that evaluated an ER formulation of a psychostimulant treatment for ADHD in at least 30 children and adolescents aged 6 to 17 years. STUDY SELECTION: Eighteen clinical trials met the chosen criteria and evaluated: d, l-MPH, long-acting (d, l-MPH-LA); d, l-MPH-OR; d, l-MPH-CD (MCD); d-MPH-ER; MPH transdermal system (MTS); mixed amphetamine salts, ER (MAS-XR); and lisdexamfetamine dimesylate (LDX). DATA SYNTHESIS: Onset of efficacy was earliest for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5 hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and LDX at approximately 2 hours. Duration of efficacy for each treatment was: MCD 7.5 hours; d, l-MPH-LA 8 to 12 hours; and 12 hours for MTS, d-MPH-ER, d, l-MPH-OR, MAS-XR, and LDX. However, data should be interpreted with caution given the different trial designs and assessment time points. CONCLUSIONS: d-MPH-ER has the earliest onset of efficacy at 0.5 hours postdose, and MTS, d-MPH-ER, d, l-MPH-OR, MAS-XR, and LDX have a long duration of action at 12 hours postdose. Clinicians should consider differences in the onset of efficacy of each drug in the context of individual patient needs.

A randomized, double-blind, crossover study of once-daily dexmethylphenidate in children with attention-deficit hyperactivity disorder: rapid onset of effect.

BACKGROUND: Long-acting methylphenidate formulations provide control of attention-deficit hyperactivity disorder (ADHD) symptoms for up to 12 hours; however, not all formulations have rapid onset of therapeutic effect, which is essential for providing symptom control during morning hours. The primary objective of this randomized, double-blind, crossover study was to assess the efficacy of dexmethylphenidate extended release (ER) versus placebo by measuring the change from pre-dose to 0.5 hours post-dose on the Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) rating scale. METHODS: Eighty-six children (6-12 years) with ADHD diagnosed using the DSM-IV criteria were randomized to receive dexmethylphenidate ER 20 mg/day or placebo, sequentially, for 7 days, with the final dose administered in a laboratory classroom setting on day 7 of each treatment period. The primary efficacy comparison was change in the SKAMP-Combined score from pre-dose to 0.5 hours post-dose, with additional secondary assessments at 1, 2, 4, 6 and 8 hours post-dose. Secondary efficacy measures included change from pre-dose at all timepoints in the SKAMP-Attention and SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores, and change from baseline on the Conners' ADHD/DSM-IV Scale for Parents (CADS-P). In an exploratory analysis, a daily diary card was completed by parents on the children's in-home behaviour before school. Safety was assessed by occurrence of adverse events, monitoring of vital signs and interpretation of ECGs. RESULTS: Significant improvements were noted at 0.5 hours and at all timepoints post-dose throughout the 8-hour laboratory classroom day for dexmethylphenidate ER vs placebo in the primary outcome measure of the SKAMP-Combined scores (p < 0.001), as well as SKAMP-Attention, SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores (p < 0.05). The changes from baseline in CADS-P scores were significantly greater with dexmethylphenidate ER than placebo (-16.382 vs -4.622; p < 0.001). Responses to all diary questions indicated significant improvement with dexmethylphenidate ER treatment versus placebo (all p < 0.001). The most common adverse events were abdominal pain (dexmethylphenidate ER 3.5%; placebo 4.7%), headache (dexmethylphenidate ER 3.5%; placebo 2.3%) and increased appetite (dexmethylphenidate ER 0%; placebo 3.5%). CONCLUSION: Compared with placebo, once-daily dexmethylphenidate ER 20 mg provided rapid and significant improvement at 0.5 hours post-dose in attention, deportment and academic performance, which was sustained for 8 hours post-dose. Overall, once-daily dexmethylphenidate ER 20 mg was well tolerated. In an analysis of parental assessment of diary responses, children appeared more organized, and morning preparation for school was smoother and less frustrating with once-daily dexmethylphenidate ER compared with placebo.

Efficacy and safety of extended-release dexmethylphenidate compared with d,l-methylphenidate and placebo in the treatment of children with attention-deficit/hyperactivity disorder: a 12-hour laboratory classroom study.

OBJECTIVE: This study compared the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) 20 mg/day and 30 mg/day with extended-release racemic methylphenidate hydrochloride (d,l-MPH-ER) 36 mg/day and 54 mg/day, and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. METHODS: This multicenter, double-blind, crossover study included children (N = 84) 6-12 years of age, stabilized on total daily doses of 40 mg to 60 mg d,l-MPH or 20 mg/day or 30 mg/day d-MPH who were randomized to different treatment sequences. Primary efficacy was measured by the change from pre-dose in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2 hours post-dose (d-MPH-ER 20 mg/day versus d,l-MPH- ER 36 mg/day). Adverse events were monitored throughout the study period. RESULTS: Mean change in SKAMP-Combined score at 2 hours post-dose was significantly larger for d-MPH-ER 20 mg/day versus d,l-MPH-ER 36 mg/day (p < 0.001). Both doses of d-MPH-ER had a more rapid onset and greater morning effect relative to d,l-MPH-ER while d,l-MPH-ER had a greater effect at the end of the 12-hour day. All active treatments provided a significant benefit over placebo at most time points to 12 hours post-dosing. Both treatments were well tolerated. CONCLUSIONS: d-MPH-ER and d,l-MPH-ER improved ADHD symptoms and were well tolerated. While d-MPH-ER had a faster onset of action, d,l-MPH-ER retained greater effect at the end of the 12- hour classroom day.

Treatment of children with attention-deficit/hyperactivity disorder: results of a randomized, multicenter, double-blind, crossover study of extended-release dexmethylphenidate and D,L-methylphenidate and placebo in a laboratory classroom setting.

The purpose of this study was to compare the efficacy and safety of extended-release dexmethylphenidate (d-MPH-ER) to that of d,l-MPH-ER and placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. This multicenter, double-blind, crossover study randomized 82 children, 6 to 12 years of age, stabilized on a total daily dose to the nearest equivalent of 40 to 60 mg of d,l-MPH or 20 or 30 mg/day of d-MPH. Patients participated in a screening day and practice day, and were randomized to 1 of 10 sequences of all five treatments in five separate periods. Treatments included d-MPH-ER (20 mg/day), d-MPH-ER (30 mg/day), d,l-MPH-ER (36 mg/day), d,l-MPH-ER (54 mg/day), and placebo. Primary efficacy was measured by the change from predose on the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores at 2-h postdose during the 12-h laboratory assessment (d-MPH-ER 20 mg/day vs. d,l-MPH-ER 36 mg/day). Adverse events were monitored throughout the study period. d-MPH-ER (20 mg/day) was significantly more effective than d,l-MPH-ER (36 mg/day) in the primary efficacy variable, change from predose to 2-h postdose in SKAMP-combined score. In general, d-MPH-ER had an earlier onset of action than d,l-MPH-ER, while d,l-MPH-ER had a stronger effect at 12-h postdose. No serious adverse events were reported. Treatment with either agent was associated with significant improvements in ADHD symptoms. d-MPH-ER and d,l-MPH-ER can be differentiated on what part of the day each is more effective.