Acute Effects of Parent Stimulant Medication Versus Behavioral Parent Training on Mothers' ADHD, Parenting Behavior, and At-Risk Children.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is present in 25%-50% of parents of children with ADHD, compromising parenting and child behavioral treatment. Efforts to treat multiplex ADHD families have not compared behavioral parenting interventions to parent psychopharmacology without confounds of other treatments. This report describes a pilot early intervention study directly comparing parent lisdexamfetamine dimesylate (LDX) to behavioral parent training (BPT) in families in which the mother had currently untreated ADHD and the young child displayed ADHD symptoms. METHODS: Mothers with ADHD (N = 35) of 4- to 8-year-old stimulant-naive children (N = 35) were randomly assigned to an 8-week trial of LDX (starting at 20 mg/d and titrated to a maximum of 70 mg/d) or BPT. Outcomes included multi-method, multi-informant measures of (1) maternal ADHD symptoms (Conners' Adult ADHD Rating Scales) and impairment (Clinical Global Impressions-Severity of Illness scale [CGI-S] and CGI-Improvement scale [CGI-I]), (2) parenting (Alabama Parenting Questionnaire [APQ] and Dyadic Parent-Child Interaction Coding System, Fourth Edition), and (3) child ADHD symptoms (Conners Parent Rating Scale Revised-Short Form and Conners Early Childhood Scale) and impairment (CGI-S, CGI-I, and Child Impairment Rating Scale). RESULTS: At 8 weeks, both treatments improved mothers' self-reported emotion regulation and mothers' functioning on the CGI, but only LDX improved mothers' self-reported core ADHD symptoms. LDX was associated with improvement in parents' perception of their own ADHD symptoms (Conners Inattention [P < .0001] and ADHD Index scores [P < .0001]) and their child's ADHD symptoms (P = .009). Fifty-six percent of the mothers treated with LDX (n = 10) were "much" or "very much" improved with regard to their adult ADHD based on the CGI-I scores versus 6% of mothers receiving BPT (n = 1; P = .003). BPT improved parenting on self-reported positive parenting (P = .007), inconsistent discipline (P > .0001), and corporal punishment (P = .001), while LDX improved reported inconsistent discipline (P = .001) and corporal punishment (P = .04) on the APQ, consistent with prior research. In contrast to parental LDX, which did not improve observed parenting, BPT was associated with increased positive parenting during child-directed play (P = .0002) and clean-up (P = .04) and less negative parenting (P = .04) during child-directed play. Six percent of children (n = 1) whose mothers were randomized to LDX (n = 18) were "much" or "very much" improved on the CGI-I compared to 35% (n = 16) of those treated with BPT (P = .04). CONCLUSIONS: LDX and BPT each had unique effects on maternal ADHD symptoms and parenting, but modest effects on at-risk children. In general, LDX was more effective at treating mothers' core ADHD symptoms, but both LDX and BPT improved mothers' emotion regulation, and BPT resulted in more consistent effects on parenting measures via both maternal report and direct observation. As most children remained significantly impaired after 8 weeks of unimodal treatment, combination treatment and/or longer treatment duration may be necessary to improve functioning of multiplex ADHD families. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01816074​.

Piloting a Sequential, Multiple Assignment, Randomized Trial for Mothers with Attention-Deficit/Hyperactivity Disorder and Their At-Risk Young Children.

Objective: Parental attention-deficit/hyperactivity disorder (ADHD) is associated with suboptimal parenting and reduces the effectiveness of child ADHD treatments. We conducted a Pilot Sequential, Multiple Assignment, Randomized Trial (SMART Pilot) to evaluate the feasibility and acceptability of sequencing medication and behavioral treatments for mothers with ADHD to target outcomes, including maternal ADHD, parenting, and child ADHD symptoms/impairment in multiplex ADHD families. Methods: Thirty-five mothers with ADHD and their 5- to 8-year-old child with ADHD symptoms were enrolled. Mothers were randomized to 8 weeks of individually titrated stimulant medication (MSM) or behavioral parent training (BPT), followed by rerandomization to 8 weeks of continued first-line treatment (with as-needed modifications) or combined treatment, leading to four treatment sequences (MSM-MSM, MSM-BPT, BPT-MSM, and BPT-BPT). Results: Recruitment of multiplex ADHD families came primarily from child providers. Mothers were adherent to medication and had high therapy session attendance. Mothers and clinicians found both treatments to be acceptable and preferred combination treatment, especially receiving medication before BPT. Monotherapy treatment visits were viewed as more burdensome (MSM-MSM, BPT-BPT). Conclusions: Maternal stimulant medication and BPT are acceptable and feasible interventions for families in which both the mother and child have ADHD symptoms. Mothers with concerns about their children's ADHD symptoms are receptive to receiving treatment themselves as an initial strategy for improving their children's health and functioning. Fully powered SMART designs show promise in evaluating the sequencing of interventions and helping clinicians develop algorithms for treating multiplex families in real-world practice settings.

Dose-Response Effects of Long-Acting Liquid Methylphenidate in Children with Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD): A Pilot Study.

Attention deficit/hyperactivity disorder (ADHD) symptoms are common in youth with autism spectrum disorders (ASD) and are frequently treated with stimulant medications. Twenty-seven children were randomized to different dose titration schedules, and ADHD symptoms, tolerability, and aberrant behaviors were assessed weekly during a 6-week trial with long-acting liquid methylphenidate (MPH). MPH at low to moderate doses was effective in reducing ADHD symptoms and was well tolerated in young children with ASD and ADHD. Future studies are needed to assess generalization and maintenance of efficacy.

Parent ADHD and Evidence-Based Treatment for Their Children: Review and Directions for Future Research.

One fourth to one half of parents of children with attention-deficit/hyperactivity disorder (ADHD) have ADHD themselves, complicating delivery of evidence-based child behavioral and pharmacological treatments. In this article, we review the literature examining the relation between parent ADHD and outcomes following behavioral and pharmacological treatments for children with ADHD. We also review research that has incorporated treatment of parent ADHD (either alone or in combination with child treatment) with the goal of improving parenting and child outcomes. Finally, we offer recommendations for future research on the relation between parent ADHD and evidence-based treatment outcomes for their children, with the purpose of advancing the science and informing clinical care of these families.

Personalized Treatment of Mothers With ADHD and Their Young At-Risk Children: A SMART Pilot.

Young children of mothers with adult attention-deficit/hyperactivity disorder (ADHD) are at risk for ADHD by virtue of genetics and environmental factors. Moreover, parent ADHD is associated with maladaptive parenting and poor child behavioral treatment response. Thus, a combined approach consisting of behavioral parent training (BPT) and maternal stimulant medication (MSM) may be needed to effectively treat ADHD within families. However, providing combined BPT+MSM initially to all families may be unnecessarily burdensome because not all families likely need combined treatment. The purpose of this study is to examine how to combine, sequence, and personalize treatment for these multiplex families in order to yield benefits to both the parent and child, thereby impacting the course of child ADHD and disruptive behavior symptoms. This article presents our rationale for, design of, and preliminary experiences (based on 26 participants) with an ongoing pilot Sequential Multiple Assessment Randomized Trial (SMART) designed to answer questions regarding the feasibility and acceptability of study protocols and interventions. This article also describes how the subsequent full-scale SMART might change based on what is learned in the SMART pilot and illustrates how the full-scale SMART could be used to inform clinical decision making about how to combine, sequence, and personalize treatment for complex children and families in which a parent has ADHD.

Trends in drug use from urine drug testing of addiction treatment clients.

OBJECTIVE: Urine drug testing (UDT) can play an important role in the care of patients in recovery from addiction, and it has become necessary for providers and programs to utilize specific, accurate testing beyond what immunoassay (IA) provides. DESIGN: A database of addiction treatment and recovery programs was sampled to demonstrate national trends in drug abuse and to explore potential clinical implications of differing results due to the type of testing utilized. SETTING: Deidentified data was selected from a national laboratory testing company that had undergone liquid chromatography tandem mass spectrometry (LC-MS/MS). PATIENTS/PARTICIPANTS: A total of 4,299 samples were selected for study. INTERVENTIONS: Descriptive statistics of the trends are presented. RESULTS: In total, 48.5 percent (n = 2,082) of the samples were deemed in full agreement between the practice reports and the results of LC-MS/MS testing. The remaining 51.5 percent of samples fell into one of seven categories of unexpected results, with the most frequent being detection of an unreported prescription medication (n = 1,097). CONCLUSIONS: Results of UDT demonstrate that more than half of samples yield unexpected results from specimens collected in addiction treatment. When comparing results of IA and LC-MS/MS, it is important to consider the limits of IA in the detection of drug use by these patients.

Exploring rates of abnormal pharmacogenetic findings in a pain practice.

Pharmacogenetic testing (PGT) is part of increasing efforts to personalize medicine, hopefully leading to better medication selection with more effective, less toxic therapies. Pharmacogenetic testing has relevance for chronic pain treatment, given the frequent comorbidities and polypharmacy. This retrospective study explored the prevalence of polymorphisms in a specialty pain practice in Louisiana. Pharmacogenetic testing was conducted for the cytochrome P450 (CYP) enzymes CYP2B6, CYP2C19, and CYP2D6, or the uridine diphosphate-glucuronosyltransferase 2 family polypeptide B15 (UGT2B15) enzyme utilizing a noninvasive, saliva-based test based on clinical decision-making. The sample consisted of 61 men (58.7%) and 41 women (39.4%), with an average age of 46.7 years (range = 23-83, SD = 11.5 years). Across all tests, 164 (42.3%) were extensive, 99 (25.5%) were intermediate, 28 (7.2%) were ultrarapid, and 27 (7%) were poor metabolizers. Only three patients who had been tested were found to be extensive (normal) for all four genes. These data demonstrate that genetic polymorphisms were frequently encountered. Consideration should be given to obtaining PGT as an aspect of evaluation and treatment planning when working with patients in need of specialty pain consultation and care. Caution is needed, as this brief report encompasses results from a single pain practice in one geographic location with a potentially distinct prevalence of genetic polymorphisms. Further prospective study is needed.

Mother-teacher agreement on preschoolers' symptoms of ODD and CD: does context matter?

The aims of this study were to examine mother-teacher agreement on oppositional defiant disorder (ODD) and conduct disorder (CD) symptoms and diagnoses in preschool children; to determine if context is a source of disagreement; and to explore if sex, referral status, and age moderated agreement rates. Participants included 158 male and 139 female 3- to 5-year old preschool children, their mothers, and teachers. A structured interview, the Kiddie-Disruptive Behavior Disorder Schedule was used for maternal report and teachers completed the Early Childhood Inventory. Results indicated that mothers reported more symptoms and diagnoses of ODD and CD than teachers, and mother-teacher agreement on both ODD and CD symptoms and diagnoses was low. Level of mother-teacher agreement increased when reporting on behavior in the same context; however, the rates remain modest. Referral status increased the likelihood of mother and teacher agreement on several ODD and CD symptoms, as well as ODD and CD diagnosis. These data suggest that context plays a role in mother-teacher agreement in the assessment of young children's ODD and CD symptoms.

Consensus recommendations from the strategic planning summit for pain and palliative care pharmacy practice.

Pain and symptoms related to palliative care (pain and palliative care [PPC]) are often undertreated. This is largely owing to the complexity in the provision of care and the potential discrepancy in education among the various health care professionals required to deliver care. Pharmacists are frequently involved in the care of PPC patients, although pharmacy education currently does not offer or require a strong curriculum commitment to this area of practice. The Strategic Planning Summit for the Advancement of Pain and Palliative Care Pharmacy was convened to address opportunities to improve the education of pharmacists and pharmacy students on PPC. Six working groups were charged with objectives to address barriers and opportunities in the areas of student and professional assessment, model curricula, postgraduate training, professional education, and credentialing. Consensus was reached among the working groups and presented to the Summit Advisory Board for adoption. These recommendations will provide guidance on improving the care provided to PPC patients by pharmacists through integrating education at all points along the professional education continuum.

Interpretation of urine drug testing in pain patients.

BACKGROUND: Traditionally, urine drug screens have only been concerned with positive or negative results. Those results provide physicians treating patients for pain with chronic opioid therapy with information about medication compliance, use of nonprescribed medications, and use of illicit drugs. However, the analysis of urine for drugs offers additional information that, when compiled and accurately interpreted, may also be of great value to these doctors. PURPOSE: The aim of this article was to discuss the interpretation of urine drug tests and their application to pain physician practices. METHOD: We utilized a selection of recent articles on urine drug screening applicable to the pain patient population. RESULTS AND CONCLUSIONS: The article provides pertinent information about interpretation of urine drug testing, which is separated into six categories: which drugs and metabolites to test for; which analytical cutoffs to use; pain medication metabolism; identification of alcohol use; determination of patient compliance; and which patient groups to consider for more frequent testing.

Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression.

Tumor cells release several factors that can help the progression of the tumor by directly supporting tumor growth and/or suppressing host antitumor immunity. Here, we report that human primary breast tumor cells not only express elevated levels of heat shock protein 27 (Hsp27) at the intracellular level but also release extremely high levels of Hsp27 compared with the same patients' serum Hsp27 levels, predicting an acutely increased concentration of soluble Hsp27 in the human breast tumor microenvironment (HBTM). We demonstrate that Hsp27 levels in the HBTM can be extremely elevated as evidenced by high soluble Hsp27 levels in patients' tumor interstitial fluid. Because increasing numbers of tumor-associated macrophages (TAM) in the HBTM negatively correlate to patients' clinical outcomes and we have previously reported the immunoregulatory activity of soluble Hsp27, here, we tested for any specific effects of soluble Hsp27 on human monocyte to macrophage differentiation. We demonstrate that soluble Hsp27 causes the differentiation of monocytes to macrophages with immuno-tolerizing phenotypes (HLA-DRlow, CD86low, PD-L1high, ILT2high, and ILT4high). We detected the presence of TAMs with similar phenotypes in breast cancer patients. Hsp27-differentiated macrophages induce severe unresponsiveness/anergy in T cells. Moreover, these macrophages lose tumoricidal activity but become extremely proangiogenic, inducing significant neovascularization, a process that is critically important for tumor growth. Thus, our data demonstrate a novel immune escape and tumor growth-supporting mechanism mediated by soluble Hsp27 that may be operative in human breast cancer.

The structure of psychopathology in a community sample of preschoolers.

Despite growing interest in the development of alternative diagnostic classification systems for psychopathology in young children, little is known about the adequacy of the DSM symptom structure for describing psychopathology in this population. This paper examines the fit of the DSM-IV emotional (ED) and disruptive behavior disorder (DD) symptom structure in a community sample of 796 4-year-old children. Using the parent-report Child Symptom Inventory (CSI), the best model fit for ED included separate factors for Social Phobia, Separation Anxiety Disorder, Generalized Anxiety Disorder, and Major Depressive Disorder. For DD, the best model included separate Attention Deficit Hyperactivity Disorder-Inattentive type (ADHD-I), Attention Deficit Hyperactivity Disorder-Hyperactive/Impulsive type (ADHD-HI), and Oppositional Defiant Disorder diagnoses. These findings support using DSM-IV nosology to classify EDs in a community sample of preschool children, and suggest differentiation of ADHD into ADHD-I and ADHD-HI.

Predictive validity of DSM-IV oppositional defiant and conduct disorders in clinically referred preschoolers.

BACKGROUND: Diagnostic validity of oppositional defiant and conduct disorders (ODD and CD) for preschoolers has been questioned based on concerns regarding the ability to differentiate normative, transient disruptive behavior from clinical symptoms. Data on concurrent validity have accumulated, but predictive validity is limited. Predictive validity is critical to refuting the hypothesis that diagnosing ODD and CD in young children leads to pathologizing normal behavior. ODD and CD have emerged as gateway disorders to many forms of adult psychopathology. Establishing how early we can identify symptoms and disorders that herald poor prognosis is one of the most important goals for research on etiology and prevention. METHODS: Subjects were 3-5-year-old consecutive referrals to a child psychiatry clinic (n=123) and demographically matched children from a pediatric clinic (n=100). A diagnostic interview was used to assess DSM-IV ODD and CD in a prospective follow-up design from preschool to school age. Stability of ODD and CD diagnoses and level of impairment were tested as a function of preschool diagnosis. RESULTS: Over 80% of preschoolers diagnosed with ODD and approximately 60% of preschoolers diagnosed with CD met criteria for the same disorder during follow-up. Impairment over time varied significantly as a function of stability of diagnosis across three years. CONCLUSIONS: These results provide the first evidence of the predictive validity of DSM-IV ODD and CD in clinically referred preschool children. The findings challenge the assumption that symptoms of disruptive behavior disorders that occur during the preschool period tend to be transient.

Sensitivity of flow cytometric assay for measurement of human intracellular heat shock protein 27.

Increased expression of heat shock protein 27 (hsp27) is related to enhanced resistance of breast tumor cells to cytotoxic drugs and radiation therapy. Therefore, development of a rapid and sensitive method for detection of hsp27 may be useful for correlating tumor cell expression of hsp27 to breast cancer patients' clinical outcome. We have simultaneously assessed hsp27 levels in three different human cell lines (MCF-7, MDA-MB-231, and Jurkat) by both Western blotting and flow cytometry. MCF-7 hsp27 levels were consistently detected at higher levels, while MDA-MB-231 hsp27 levels were detected at very low levels when immunoblotting was performed. Hsp27 was not detected in Jurkat cells by immunoblotting. In contrast, hsp27 levels were detected by flow cytometry in all the cell lines, indicating a better sensitivity of this method. Although hsp27 was expressed in almost equal percentage of MCF-7 (93+/-3.4%), MDA-MB-231 (97+/-1%), and Jurkat (95.5+/-1.9) cells, the fluorescence intensity of intracellular hsp27 protein was significantly lower in MDA-MB-231 and Jurkat cells as compared to MCF-7 cells. The flow cytometry data further demonstrated that reduced hsp27 expression in both MDA-MB-231 and Jurkat cells was not due to a lack of hsp27 expression in a subset of cells, but rather due to reduced expression of hsp27 in all individual cells.

Pharmacist-physician collaboration in pain management practice.

Pain is one of the most common reasons patients seek out healthcare and management typically requires complex medication regimens. Pharmacists have become increasingly more involved in pain management. Historically, pharmacists and physicians have often had adversarial relationships because of regulatory influence. However, as medication experts, pharmacists can play a key role in optimizing outcomes in the management of pain and can be critical to the success of the medication regimen. Numerous opportunities for collaboration exist for pharmacists and physicians in various settings. One example is the VIGIL process, an effective risk management strategy that requires collaboration between pharmacists and physicians. The success of pharmacist-physician collaboration will depend on numerous factors, including strong physician and administrative support. A clear strategy and stepwise approach to developing a pain management pharmacist-physician collaborative practice is the key to its success. Once the collaboration is formalized, a management strategy should also be defined and should include regular chart review and regular feedback from the physician. Through physician-pharmacist collaboration, pain management outcomes can be optimized and risk can be managed.

The efficacy and safety of pain management before and after implementation of hospital-wide pain management standards: is patient safety compromised by treatment based solely on numerical pain ratings?

UNLABELLED: Inadequate analgesia in hospitalized patients prompted the Joint Commission on Accreditation of Healthcare Organizations in 2001 to introduce standards that require pain assessment and treatment. In response, many institutions implemented treatment guided by patient reports of pain intensity indexed with a numerical scale. Patient safety associated with treatment of pain guided by a numerical pain treatment algorithm (NPTA) has not been examined. We reviewed patient satisfaction with pain control and opioid-related adverse drug reactions before and after implementation of our NPTA. Patient satisfaction with pain management, measured on a 1-5 scale, significantly improved from 4.13 to 4.38 (P < 0.001) after implementation of an NPTA. The incidence of opioid over sedation adverse drug reactions per 100,000 inpatient hospital days increased from 11.0 pre-NPTA to 24.5 post-NPTA (P < 0.001). Of these patients, 94% had a documented decrease in their level of consciousness preceding the event. Although there was an improvement in patient satisfaction, we experienced a more than two-fold increase in the incidence of opioid over sedation adverse drug reactions in our hospital after the implementation of NPTA. Most adverse drug reactions were preceded by a documented decrease in the patient's level of consciousness, which emphasizes the importance of clinical assessment in managing pain. IMPLICATIONS: Although patient satisfaction with pain management has significantly improved since the adoption of pain management standards, adverse drug reactions have more than doubled. For the treatment of pain to be safe and effective, we must consider more than just a one-dimensional numerical assessment of pain.