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Alan L. Peterson;
Joseph F. McGuire;
Sabine Wilhelm;
John Piacentini;
Douglas W. Woods;
John T. Walkup;
John P. Hatch;
Robert Villarreal;
Lawrence Scahill
Over the past six decades, behavior therapy has been a major contributor to the development of evidence-based psychotherapy treatments. However, a long-standing concern with behavior therapy among many nonbehavioral clinicians has been the potential risk for symptom substitution. Few studies have been conducted to evaluate symptom substitution in response to behavioral treatments, largely due to measurement and definitional challenges associated with treated psychiatric symptoms. Given the overt motor and vocal tics associated with Tourette's disorder, it presents an excellent opportunity to empirically evaluate the potential risk for symptom substitution associated with behavior therapy. The present study examined the possible presence of symptom substitution using four methods: (a) the onset of new tic symptoms, (b) the occurrence of adverse events, (c) change in tic medications, and (d) worsening of co-occurring psychiatric symptoms. Two hundred twenty-eight participants with Tourette's disorder or persistent motor or vocal tic disorders were randomly assigned to receive behavioral therapy or supportive therapy for tics. Both therapies consisted of eight sessions over 10 weeks. Results indicated that participants treated with behavior therapy were not more likely to have an onset of new tic symptoms, experience adverse events, increase tic medications, or have an exacerbation in co-occurring psychiatric symptoms relative to participants treated with supportive therapy. Further analysis suggested that the emergence of new tics was attributed with the normal waxing and waning nature of Tourette's disorder. Findings provide empirical support to counter the long-standing concern of symptom substitution in response to behavior therapy for individuals with Tourette's disorder.
We conducted a mail survey of practicing pediatricians in Georgia to assess their knowledge, attitudes, and behaviors regarding recording patients' environmental histories. Of 477 eligible pediatricians, 266 (55.8%) responded. Fewer than one in five reported having received training in environmental history-taking. Pediatricians reported that they strongly believe in the importance of environmental exposures in children's health, and 53.5% of respondents reported experience with a patient who was seriously affected by an environmental exposure. Pediatricians agreed moderately strongly that environmental history-taking is useful in identifying potentially hazardous exposures and in helping prevent these exposures. Respondents reported low self-efficacy regarding environmental history-taking, discussing environmental exposures with parents, and finding diagnosis and treatment resources related to environmental exposures. The probability of self-reported history-taking varied with the specific exposure, with environmental tobacco smoke and pets most frequently queried and asbestos, mercury, formaldehyde, and radon rarely queried. The pediatricians' preferred information resources include the American Academy of Pediatrics, newsletters, and patient education materials. Pediatricians are highly interested in pediatric environmental health but report low self-efficacy in taking and following up on environmental histories. There is considerable opportunity for training in environmental history-taking and for increasing the frequency with which such histories are taken.
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Carlton Dampier;
Wally R. Smith;
Hae-Young Kim;
Carrie Greene Wager;
Margaret C. Bell;
Caterina P Minniti;
Jeffrey Keefer;
Lewis Hsu;
Lakshmanan Krishnamurti;
A. Kyle Mack;
Donna McClish;
Sonja M. McKinlay;
Scott T. Miller;
Ifeyinwa Osunkwo;
Phillip Seaman;
Marilyn J. Telen;
Debra L. Weiner
Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.
Status epilepticus (SE) is a life-threatening neurological emergency often refractory to available treatment options. It is a very heterogeneous condition in terms of clinical presentation and causes, which besides genetic, vascular and other structural causes also include CNS or severe systemic infections, sudden withdrawal from benzodiazepines or anticonvulsants and rare autoimmune etiologies. Treatment of SE is essentially based on expert opinions and antiepileptic drug treatment per se seems to have no major impact on prognosis. There is, therefore, urgent need of novel therapies that rely upon a better understanding of the basic mechanisms underlying this clinical condition. Accumulating evidence in animal models highlights that inflammation ensuing in the brain during SE may play a determinant role in ongoing seizures and their long-term detrimental consequences, independent of an infection or auto-immune cause; this evidence encourages reconsideration of the treatment flow in SE patients.
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S Sam Lim;
Ian N. Bruce;
Aidan G O'Keeffe;
Vern Farewell;
John G Hanly;
Susan Manzi;
Li Su;
Dafna D Gladman;
Sang-Cheol Bae;
Jorge Sanchez-Guerrero;
Juanita Romero-Diaz;
Caroline Gordon;
Daniel J Wallace;
Ann E Clarke;
Sasha Bernatsky;
Ellen M Ginzler;
David A Isenberg;
Anisur Rahman
Background and aims We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. Methods The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. Results We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p < 0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point). Conclusions Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.
Purpose: We elicited patient experiences from clinical trial simulations to aid in future trial development and to improve patient recruitment and retention. Patients and methods: Two simulations of draft Phase II and Phase III anifrolumab studies for systemic lupus erythematosus (SLE)/lupus nephritis (LN) were performed involving African-American patients from Grady Hospital, an indigent care hospital in Atlanta, GA, USA, and white patients from Altoona Arthritis and Osteoporosis Center in Altoona, PA, USA. The clinical trial simulation included an informed consent procedure, a mock screening visit, a mock dosing visit, and a debriefing period for patients and staff. Patients and staff were interviewed to obtain sentiments and perceptions related to the simulated visits. Results: The Atlanta study involved 6 African-American patients (5 female) aged 27–60 years with moderate to severe SLE/LN. The Altoona study involved 12 white females aged 32–75 years with mild to moderate SLE/LN. Patient experiences had an impact on four patient-centric care domains: 1) information, communication, and education; 2) responsiveness to needs; 3) access to care; and 4) coordination of care; and continuity and transition. Patients in both studies desired background material, knowledgeable staff, family and friend support, personal results, comfortable settings, shorter wait times, and greater scheduling flexibility. Compared with the Altoona study patients, Atlanta study patients reported greater preferences for information from the Internet, need for strong community and online support, difficulties in discussing SLE, emphasis on transportation and child care help during the visits, and concerns related to financial matters; and they placed greater importance on time commitment, understanding of potential personal benefit, trust, and confidentiality of patient data as factors for participation. Using these results, we present recommendations to improve study procedures to increase retention, recruitment, and compliance for clinical trials. Conclusion: Insights from these two studies can be applied to the development and implementation of future clinical trials to improve patient recruitment, retention, compliance, and advocacy.
Cardiomyocytes (CMs) derived from human pluripotent stem cells (hPSCs) are considered a most promising option for cell-based cardiac repair. Hence, various protocols have been developed for differentiating hPSCs into CMs. Despite remarkable improvement in the generation of hPSC-CMs, without purification, these protocols can only generate mixed cell populations including undifferentiated hPSCs or non-CMs, which may elicit adverse outcomes. Therefore, one of the major challenges for clinical use of hPSC-CMs is the development of efficient isolation techniques that allow enrichment of hPSC-CMs. In this review, we will discuss diverse strategies that have been developed to enrich hPSC-CMs. We will describe major characteristics of individual hPSC-CM purification methods including their scientific principles, advantages, limitations, and needed improvements. Development of a comprehensive system which can enrich hPSC-CMs will be ultimately useful for cell therapy for diseased hearts, human cardiac disease modeling, cardiac toxicity screening, and cardiac tissue engineering.
by
Julia J. Scialla;
Rulan S. Parekh;
Joseph A. Eustace;
Brad C. Astor;
Laura Plantinga;
Bernard. G Jaar;
Tariq Shafi;
Josef Coresh;
Neil R. Powe;
Michal L. Melamed
Background: Abnormalities in mineral homeostasis are ubiquitous in patients on dialysis, and influenced by race. In this study, we determine the race-specific relationship between mineral parameters and mortality in patients initiating hemodialysis.
Methods: We measured the levels of fibroblast growth factor 23 (FGF23) and 25-hydroxyvitamin D (25 D) in 184 African American and 327 non-African American hemodialysis patients who enrolled between 1995 and 1998 in the Choices for Healthy Outcomes in Caring for ESRD Study. Serum calcium, phosphorus, parathyroid hormone (PTH) and total alkaline phosphatase levels were averaged from clinical measurements during the first 4.5 months of dialysis. We evaluated the associated prospective risk of mortality using multivariable Cox proportional hazards models stratified by race.
Results: PTH and total alkaline phosphatase levels were higher, whereas calcium, phosphorus, FGF23 and 25 D levels were lower in African Americans compared to those of non-African Americans. Higher serum phosphorus and FGF23 levels were associated with greater mortality risk overall; however, phosphorus was only associated with risk among African Americans (HR 5.38, 95% CI 2.14-13.55 for quartile 4 vs. 1), but not among non-African Americans (p-interaction = 0.04). FGF23 was associated with mortality in both groups, but more strongly in African Americans (HR 3.91, 95% CI 1.74-8.82 for quartiles 4 vs. 1; p-interaction = 0.09). Serum calcium, PTH, and 25 D levels were not consistently associated with mortality. The lowest and highest quartiles of total alkaline phosphatase were associated with higher mortality risk, but this did not differ by race (p-interaction = 0.97).
Conclusions: Aberrant phosphorus homeostasis, reflected by higher phosphorus and FGF23, may be a risk factor for mortality in patients initiating hemodialysis, particularly among African Americans.
by
Ruben A. Mesa;
Jason Gotlib;
Vikas Gupta;
John V. Catalano;
Michael W. Deininger;
Alan L. Shields;
Carole B. Miller;
Richard T. Silver;
Moshe Talpaz;
Elliott Winton;
Jimmie H. Harvey;
Thomas Hare;
Susan Erickson-Viitanen;
William Sun;
Victor Sandor;
Richard S. Levy;
Hagop M. Kantarjian;
Srdan Verstovsek