Reviewing the role of emerging therapies in the ADHD armamentarium.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that can be treated with both pharmacologic and nonpharmacologic modalities. Effective drug treatments for ADHD have been available for more than six decades. However, initial treatments had limitations in duration of effect, need for multiple daily doses, requirement for patients to swallow intact tablets, adverse effects and risk for abuse and diversion. During the past 20 years, more than two dozen stimulant and nonstimulant drugs have been developed. Nonetheless, there remain unmet needs in the treatment of ADHD.Areas covered: New stimulant and nonstimulant formulations in development are reviewed with emphasis on drugs in phase II and III trials. Efficacy, mechanism of action and adverse effect data are described where available. Abuse liability studies are described for abuse-deterrent formulations in development.Expert opinion: The review found a robust pipeline of stimulants and nonstimulants. Medications in development are formulated to optimize onset and duration of effect, alter the time of administration, obviate the need to swallow whole capsules or tablets and to deter abuse. While each of these formulations may fill a unique niche, these incremental improvements based on new drug delivery technologies may lead to very significant clinical effects.

Frequent follow-up of suicidal youth assessed in the emergency room: Long-term trajectory and predictors of suicidality.

Suicide was the second­leading cause of US deaths in 2018 among 15-24-year-olds. Suicide attempts, a risk factor for completions, and suicide ideation have doubled among pediatric emergency room (ER) patients during the past decade. Borderline Personality Disorder (BPD), a comorbid condition, has a 10% suicide rate. We examined the 4-year outcome of a cohort of suicidal adolescents, many also suffering from BPD and having undergone some form of treatment, to identify baseline factors which could inform intervention that would minimize suicidality 4 years post-discharge. METHODS: We conducted a prospective longitudinal study of suicidality at twelve points (four assessment occasions) for 286 suicidal youth presenting to a pediatric ER, most suffering from BPD, with 36 suicide ratings from baseline to 2-, 6- and 48-month follow-up evaluations. We examined the trajectory and predictors of persisting suicidality. RESULTS: Suicidality rapidly decreased within 2 months post-ER-discharge, subsequently remaining low throughout 48 months. Baseline functioning, female sex, stressful life events and BPD impulsiveness were most predictive of persisting suicidality at 48-month follow-up. CONCLUSION: Most suicidal youth, many meeting BPD criteria, no longer feel suicidal 2 months after ER discharge. Management of participants' baseline poor functioning stressful life events and the impulsiveness component of BPD specifically in females could impact suicidality 4 years later, and guide treatment options. The absence of the BPD cognitive and affective subscales as predictors of suicidality at 4-year follow-up may reflect treatment received. Further investigation of treatment effects is warranted and under way.

ADHD and Exposure to Maltreatment in Children and Youth: a Systematic Review of the Past 10 Years.

PURPOSE OF THE REVIEW: The purpose of the current paper was to review and summarize the literature on ADHD and maltreatment over the past 10 years. RECENT FINDINGS: The majority of research on ADHD and exposure to maltreatment focuses on the high rates of comorbidity, including international studies from Asia, South America, North America, and Europe. Longitudinal studies showed that early exposure to maltreatment is a risk factor for ADHD symptoms later in development; however, this finding was not consistent. There were some preliminary studies on the neurological and genetic mechanisms underlying the link between ADHD and exposure to maltreatment. Finally, ADHD and exposure to maltreatment were found to have an additive effect on clinically salient outcomes (e.g., aggression, suicide attempts). Results from the review have direct clinical and future implications, including the need to understand the effect of comorbid ADHD and exposure to maltreatment in treatment studies.

Safety of Combination Laser or Intense Pulsed Light Therapies and Doxycycline for the Treatment of Rosacea.

BACKGROUND: Current treatment options for rosacea include topical agents, oral therapies, phototherapy using lasers, or intense pulsed light (IPL). Combination therapy for rosacea often yields better results than monotherapy. The safety of laser/light treatments in combination with systemic doxycycline has been questioned because of the theoretical risk of photosensitivity. OBJECTIVE: The purpose of this study was to assess the incidence of phototoxicity or photosensitivity in rosacea patients receiving concomitant laser or light treatments and systemic doxycycline. METHODS: Treatment records of 36 patients receiving laser/light treatments while also being treated with standard dose or anti-inflammatory dose of doxycycline were retrospectively reviewed. RESULTS: No adverse reactions related to doxycycline combined with laser/light therapy were reported. Specifically, no photosensitivity or sensitivity to wavelengths in the pulsed dye laser (PDL), or IPL range was observed in this cohort. All patients achieved some degree of clearance. CONCLUSION: The results of this retrospective study demonstrate that doxycycline used in conjunction with laser or nonlaser light therapy is a valid combination therapy for improving signs and symptoms of rosacea. No photosensitivity reactions were observed to commonly used IPL or PDL devices.

Descriptive and psychometric properties of the Persian version of the Weiss functional impairment rating scale: parent report form in Iranian children.

BACKGROUND: This study evaluates the descriptive and psychometric properties of the Persian version of the Weiss Functional Impairment Rating Scale-Parent Report Form (WFIRS-P) in a normal sample of Iranian children. METHOD: Parents of 282 students (grades 1-6) completed the WFIRS-P. Means and standard deviations were computed for the total scale, each domain, and each item of the WFIRS-P. Internal consistency, interdomain correlations, and test-retest reliability were used to assess the reliability of the scale. RESULTS: Among the WFIRS-P domains, life skills had the highest rated impairment (M = 0.50, SD = 0.37) and risky activities had the lowest. Internal consistency (α = .88) and test-retest reliability (r = 0.77) were strong for the WFIRS-P total scale. The correlation between the WFIRS-P domains and the total scale ranged from 0.52 to 0.81. CONCLUSIONS: Results suggest that the Persian version of the WFIRS-P is a useful and psychometrically reliable measure for assessing functional skills in children.

Parent and Child ADHD Symptoms in Relation to Parental Attitudes and Parenting: Testing the Similarity-Fit Hypothesis.

OBJECTIVE: We tested the similarity-fit hypothesis that predicts more positive parenting when both parent and child have high levels of ADHD symptoms compared to when only one does. METHOD: Mothers and fathers of 156, 5 to 13 year old sons participated (110 boys with ADHD, 46 without). Parent inattentive and hyperactive-impulsive symptoms were examined, in interaction with child ADHD, as predictors of parental tolerance, empathy, encouragement of child autonomy, and positive parenting. RESULTS: Several interactions of parent ADHD symptoms and child ADHD were detected which suggested that for parents with low levels of symptoms, the presence of child ADHD was associated with less positive parenting attitudes and behavior, but this negative relation between positive parenting and child ADHD was dampened among parents with more ADHD symptoms. CONCLUSIONS: Considered alongside the well documented parenting difficulties associated with parental ADHD, our findings suggest that parental ADHD symptoms also may help to mitigate some of the challenges facing families of children with ADHD.

Estimating minimal important differences for several scales assessing function and quality of life in patients with attention-deficit/hyperactivity disorder.

OBJECTIVE: Defining minimal important difference (MID) is critical to interpreting patient-reported outcomes data and treatment efficacy in clinical trials. This study estimates the MID for the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) and the Child Health and Illness Profile-Parent Report (CHIP-CE-PRF76) among parents of young people with attention-deficit/hyperactivity disorder (ADHD) in the UK. METHODS: Parents of children (6-12 years; n=100) and adolescents (13-17 years; n=117) with ADHD completed a socio-demographic form, the CHIP-CE-PRF76, the WFIRS-P, and the Pediatric Quality of Life scale at baseline and 4 weeks later. At follow-up, a subset of parents completed anchor questions measuring change in the child/adolescent from baseline. MIDs were estimated using anchor-based and distribution-based methods, and separately for children and adolescents. RESULTS: The MID estimates for overall change in the WFIRS-P total score ranged from 11.31 (standard error of measurement) to 13.47 (anchor) for the total sample. The range of MID estimates for the CHIP-CE-PRF76 varied by domain: 6.80-7.41 (satisfaction), 6.18-7.34 (comfort), 5.60-6.72 (resilience), 6.06-7.57 (risk avoidance), and 4.00-5.63 (achievement) for the total sample. Overall, MID estimates for WFIRS-P MID and CHIP-CE-PRF76 were slightly higher for adolescents than for children. CONCLUSION: This study estimated MIDs for these instruments using several methods. The observed convergence of the MID estimates increases confidence in their reliability and could assist clinicians and decision makers in deriving meaningful interpretations of observed changes in the WFIRS-P and CHIP-CE in clinical trials and practice.

The Weiss Functional Impairment Rating Scale-Parent Form for assessing ADHD: evaluating diagnostic accuracy and determining optimal thresholds using ROC analysis.

PURPOSE: The Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) is a 50-item scale that assesses functional impairment on six clinically relevant domains typically affected in attention-deficit/hyperactivity disorder (ADHD). As functional impairment is central to ADHD, the WFIRS-P offers potential as a tool for assessing functional impairment in ADHD. These analyses were designed to examine the overall performance of WFIRS-P in differentiating ADHD and non-ADHD cases using receiver operating characteristics (ROC) analysis. This is the first attempt to empirically determine the level of functional impairment that differentiates ADHD children from normal controls. METHODS: This observational study comprised 5-19-year-olds with physician-diagnosed ADHD (n = 476) and non-ADHD controls (n = 202). ROC analysis evaluated the ability of WFIRS-P to discriminate between ADHD and non-ADHD, and identified a WFIRS-P cut-off score that optimises correct classification. Data were analysed for the complete sample, for males versus females and for participants in two age groups (5-12 versus 13-19 years). RESULTS: Area under the curve (AUC) was 0.91 (95% confidence interval 0.88-0.93) for the overall WFIRS-P score, suggesting highly accurate classification of ADHD distinct from non-ADHD. Sensitivity (0.83) and specificity (0.85) were maximal for a mean overall WFIRS-P score of 0.65, suggesting that this is an appropriate threshold for differentiation. DeLong's test found no significant differences in AUCs for males versus females or 5-12 versus 13-19 years, suggesting that WFIRS-P is an accurate classifier of ADHD across gender and age. CONCLUSIONS: When assessing function, WFIRS-P appears to provide a simple and effective basis for differentiating between individuals with/without ADHD in terms of functional impairment. CLASSIFICATION: Disease-specific applications of QOL research.

Safety and efficacy of a novel diffractive lens array using a picosecond 755 nm alexandrite laser for treatment of wrinkles.

INTRODUCTION: Picosecond lasers have been reported to be effective for removal of tattoo pigment. This prospective study evaluated the efficacy and safety of the treatment of peri-oral and -ocular wrinkles using a novel diffractive lens array coupled with a picosecond 755 nm alexandrite laser. METHODS: Forty female subjects presenting with wrinkles from photodamage were enrolled in an IRB approved study. Subjects received four picosecond diffractive lens array treatments to the full face at 1 month intervals. Six subjects were biopsied (two subjects at 1 month, two subjects at 3 months, and two subjects at 6 months). Digital photographic images were taken at 1, 3, and 6 months post-final treatment visits. Images were graded by blinded physicians for fine lines/wrinkles, erythema, dyschromia, and global improvement. Data on discomfort level, satisfaction, and side effects were recorded. RESULTS: Overall blinded physician rated global improvement ranged from improved to much improved at 1-, 3-, and 6-month time points. At baseline the average Fitzpatrick wrinkle score was 5.48. At the 6-month follow-up the average score was 3.47. The overall average change in score from pre-treatment to post-treatment was 1.97. Subject self-assessment at 6 months indicated that 90% of subjects were extremely or satisfied with their results. Unanticipated adverse events were absent with anticipated post-treatment erythema lasting for just several hours. CONCLUSIONS: A novel diffractive lens array used with a picosecond 755 nm alexandrite laser for treatment of wrinkles is highly effective and safe for wrinkles and other signs of photoaging. Lasers Surg. Med. 49:40-44, 2017. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Leg Rejuvenation: A Combination Approach: A Review and Our Experience.

BACKGROUND: Patients increasingly seek to enhance the appearance of their legs. Elimination of unwanted leg veins, reduction of epidermal photo-aging changes such as solar lentigines and keratoses, tightening of skin laxity and reduction of adipose tissue are among the most commonly requested goals. Many patients require a combination approach to address their concerns. It is important for dermatologists to be aware of the multitude of procedures that can be performed, often in combination, to rejuvenate the leg. OBJECTIVE: The purpose of this review article was to discuss procedures for improving the appearance of the leg and to share the authors experience, especially in the combination approach to leg rejuvenation. METHODS: A literature search was performed to investigate cosmetic procedures being performed on the leg, with an emphasis on controlled or randomized studies. In addition, the authors contributed their personal experience. RESULTS: Our discussion of the literature review highlights the treatments for leg veins, unwanted fat, cellulite, and photodamage of the legs that are most supported in peer-reviewed publications. CONCLUSION: A synergistic, combination approach to leg rejuvenation works best. This includes the use of injectable agents, energy-based devices, and more invasive surgical procedures.

ASDS Cosmetic Dermatologic Surgery Fellowship Milestones.

BACKGROUND: The American Council of Graduate Medical Education, which oversees much of postgraduate medical education in the United States, has championed the concept of "milestones," standard levels of achievement keyed to particular time points, to assess trainee performance during residency. OBJECTIVE: To develop a milestones document for the American Society for Dermatologic Surgery (ASDS) Cosmetic Dermatologic Surgery (CDS) fellowship program. METHODS: An ad hoc milestone drafting committee was convened that included members of the ASDS Accreditation Work Group and program directors of ASDS-approved Cosmetic Dermatologic Surgery (CDC) fellowship training programs. Draft milestones were circulated through email in multiple rounds until consensus was achieved. RESULTS: Thirteen milestones were developed in the 6 Accreditation Council for Graduate Medical Education (ACGME) competency areas, with 8 of these being patient-care milestones. Additional instructions for milestone administration more specific to the CDS fellowship than general ACGME instructions were also approved. Implementation of semiannual milestones was scheduled for the fellowship class entering in July 2018. CONCLUSION: Milestones are now available for CDS fellowship directors to implement in combination with other tools for fellow evaluation.

Comparative outcomes of different endovenous thermal ablation systems on great and small saphenous vein insufficiency: Long-term results.

BACKGROUND AND OBJECTIVE: This study examined the outcomes of over a decade of endovenous thermal ablation (EVTA) treatments for great and small saphenous vein (GSV and SSV) insufficiency, utilizing three different endovenous thermal ablation systems. MATERIALS AND METHODS: This retrospective study reviewed EVTA treatments performed at an outpatient clinic (MDLSVI) from April 1999 to February 2013. Systems included 810 nm diode (hemoglobin targeting), 1,320 nm laser (water targeting) and a radiofrequency (direct thermal transfer) (RF) device. Clinical and ultrasonographic evaluation were performed before treatment and at each follow-up visit. Patients were examined yearly by Duplex ultrasonography. Success was defined as complete absence of reflux. RESULTS: Analysis of 934 treatments demonstrated that although recanalization could occur over time, endovenous ablation has a very high success rate. Ablation rates were 92.5%, 85.9%, and 71.9% at 6-months, 1-year, and 5-years after procedures. Recanalization occurred in 156 out of 934 treatments (16.7%) during the follow-up period. Among three difference systems, the total ablation success rate was significantly different (P < 0.001). The 1,320 nm Nd:YAG laser (n = 502) provided the highest ablation rate compared to the radiofrequency (n = 398) and 810 nm diode (n = 34) throughout their follow-up period, which were 8, 13, and 9 years, respectively. At 1-year follow-up, successful ablation rates of RF, 810 nm, and 1,320 nm were 78.2%, 80.8%, and 93.7%, respectively. At 5-year follow-up, successful ablation rates of RF, 810 nm, and 1,320 nm were 61.7%, 65.7%, and 84.7%, respectively. CONCLUSION: EVTA is very effective for ablation of the GSV and SSV. Complete ablation varied significantly among different systems with water targeting 1,320 nm providing the highest incidence saphenous vein ablation. This remained durable at 8-year follow-up by Duplex ultrasound.

Treatment of Acne Scars With High Intensity Focused Radio Frequency.

In this multi-site case series, the efficacy of high intensity focused radiofrequency (RF) delivered to the dermis was evaluated for treating acne scars. A novel delivery system that uses insulated microneedles to deliver a desired thermal effect to multiple depths of the dermis while sparing the epidermis from RF injury was used. Four (4) healthy subjects from four different practices were evaluated and used in this case report. The subjects were treated between 3 or 4 times depending on the severity of the acne scars presented. The depth of thermal delivery was adjusted before each pass and all subjects received at a minimum, three passes to the treated area. Before and after photographs along with adverse effects were recorded. The theory behind the use of insulated needles with the active RF delivery at the distal tip is to allow for significant thermal injury to several layers of the dermis while avoiding thermal injury to the epidermis. This case report demonstrates significant improvement on acne scars and that all skin types should be safely treatable with minimum downtime realized.

Consensus for sclerotherapy.

BACKGROUND: The American Society for Dermatologic Surgery (ASDS) periodically develops consensus documents for its members concerning various aspects of dermatologic surgery. Unwanted and painful leg veins are a very widespread problem. Many advances in sclerotherapy of varicose and telangiectatic leg veins have occurred since the previous consensus documents. OBJECTIVE: In 2013, the ASDS Board of Directors voted to have a committee of experts in the field to develop consensus documents on sclerotherapy. MATERIALS AND METHODS: An expert panel reviewed the literature on sclerotherapy and discussed the findings. A consensus was reached with evidence-based recommendations on diagnostic evaluation and treatment of varicose and telangiectatic leg veins. RESULTS: The consensus documents include discussion of indications for treatment, patient selection, contraindications, diagnostic testing, treatment approaches, use of compression, and expected outcome. Common sclerosants and their mechanisms of action, advantages and disadvantages of foam sclerotherapy, and minimizing and treating complications are presented. CONCLUSION: The ASDS consensus documents on sclerotherapy will be helpful in educating their members on safe and effective sclerotherapy of varicose and telangiectatic leg veins.

Evaluation of a novel anti-aging topical formulation containing cycloastragenol, growth factors, peptides, and antioxidants.

BACKGROUND/OBJECTIVE: This study investigates the efficacy, tolerance, and usability of a single product containing cycloastragenol, growth factors, peptides, and antioxidants to decrease the visible signs of aging, including fine lines, and wrinkles, texture, pore size, elasticity, skin color/clarity, redness, hydration, and overall skin quality. METHODS: Twenty subjects were enrolled in a 12-week, open-label, patient-assessment study. Subjects used a gentle cleanser, cycloastragenol, growth factors, peptides, and antioxidants (Regeneration Booster™, Jan Marini Skin Research (San Jose, CA) and a broad spectrum SPF for the duration of the 12-week study. Assessments were taken at baseline, 2, 4, 8, and 12 weeks. All assessments were compared against baseline for statistical significance. RESULTS: Eighteen of the twenty subjects completed the 12-week study. Improvement was significant after just 2 weeks of use for all measured categories except erythema and significant for all categories at 12 weeks. One hundred percent of study subjects noted improvement in at least 3 or more of the 8 assessed categories with an average improvement in 6.7 categories. Improvement response rate for individual categories ranged from 67% to 100% of study subjects. There were zero cases of sensitivity or irritation and product smell, feel and ease of application were rated "positive" by 100% of study subjects. Photographic improvement was most notable in texture and lines on the cheeks and eye area. CONCLUSION: Regeneration Booster, when used as a stand-alone anti-aging solution, delivers rapid and significant reduction in the visible signs of aging. Subject satisfaction was extremely high and there were zero reported cases of sensitivity or irritation. Based on these observations, Regeneration Booster is a safe and effective topical product for individuals seeking significant improvement in the appearance of aging skin.

Two-treatment protocol for skin laxity using 90-Watt dynamic monopolar radiofrequency device with real-time impedance intelligence monitoring.

UNLABELLED: Multiple devices are currently on the market that employ radiofrequency to non-invasively treat skin laxity and wrinkle reduction. The study device was a unique monopolar radiofrequency device FDA cleared for the treatment of wrinkles and rhytids. The delivery system allows constant monitoring of the real-time local skin impedance changes, which allows radiofrequency energy to be more uniformly dosed over an entire treatment area. OBJECTIVE: The objective was to validate effectiveness of a modified treatment protocol for a unique monopolar radiofrequency device, which has been engineered with greater power and self-monitoring circuitry. METHODS: Twenty-four female subjects received bilateral monopolar radiofrequency treatments to the mid and lower face from the sub malar region to the submentum. Subjects completed 1 and 3 month follow ups with digital imaging. Skin biopsies (on 4 subjects) and ultrasound measurements (on 12 subjects) were completed. RESULTS: Assessments demonstrated a reduction in skin laxity of 35%, a reduction in fine lines/wrinkles of 42%, and a reduction in the appearance of global photodamage of 33%. Expert photograding demonstrated 92% of subjects showing at least a mild improvement in skin laxity at three months post treatment. 50 MHz ultrasound measurements in 12 subjects showed an increase of 19% in skin density. Histology showed a marked increase in dermal collagen and elastin fibers in two subjects who demonstrated a clinically noticeable reduction in skin laxity and minimal changes in two subjects who demonstrated minimal clinical improvements. There were no significant adverse events reported. CONCLUSION: This modified radiofrequency device and treatment protocol was well tolerated and produced improvements in the appearance of skin laxity and overall anti-aging effects in the majority of subjects. Objective measurements including ultrasound and histology help explain the clinical outcome.

A Scoping Review of the Intersectionality of Autism and Intellectual and Developmental Disability with Social Inequity on Diagnosis and Treatment of Youth.

Objective: To describe how the intersectionality of race, ethnicity, and language with autism and intellectual and developmental disability (IDD) impacts mental health inequities in psychopharmacological management of youth. Method: This was a scoping review in which a series of searches were conducted in PubMed, Web of Science, Google Scholar, and manual review of the articles collected. Results: Although autism and/or IDD increases the risk for poor physical and mental health, social determinants of health such as race, ethnicity, and language account for approximately a third of poor outcomes. Minoritized children with autism/IDD experience significantly greater delays to diagnosis and misdiagnosis and are less likely to receive appropriate services. Access to psychological testing and psychosocial services is often limited by availability, skilled practitioners, a shortage of non-English-language providers or interpreters, and poor reimbursement. Conclusion: The intersectionality of autism and/or IDD with race, ethnicity, and language compounds the health inequities associated with either of these challenges independently.

From Consensus Statement to Pills to Pixels: New Innovations in Attention-Deficit/Hyperactivity Disorder Care.

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations.