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We sought to determine if a novel online health tool, called Down Syndrome Clinic to You (DSC2U), could improve adherence to national Down syndrome (DS) guidelines. We also sought to determine if primary care providers (PCPs) and caregivers are satisfied with this personalized online health tool. In a national, randomized controlled trial of 230 caregivers who had children or dependents with DS without access to a DS specialist, 117 were randomized to receive DSC2U and 113 to receive usual care. The primary outcome was adherence to five health evaluations indicated by national guidelines for DS. DSC2U is completed electronically, in all mobile settings, by caregivers at home. The outputs—personalized checklists—are used during annual wellness visits with the patient’s PCP. A total of 213 participants completed a 7-month follow-up evaluation. In the intention-to-treat analysis, the intervention group had a 1.6-fold increase in the number of indicated evaluations that were recommended by the primary care provider or completed compared with controls. Both caregivers and PCPs reported high levels of satisfaction with DSC2U. DSC2U improved adherence to the national DS health-care guidelines with a novel modality that was highly valued by both caregivers and PCPs.

An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease. Since 2017, an international consortium of DS clinics assembled a database of patients with unexplained regression and age- and sex-matched controls. Standardized data on clinical symptoms and tiered medical evaluations were collected. Elements of the proposed definition of unexplained regression in DS were analyzed by paired comparisons between regression cases and matched controls. We identified 35 patients with DS and unexplained regression, with a mean age at regression of 17.5 years. Diagnostic features differed substantially between regression cases and matched controls (p

Background Insomnia and low iron stores are common in children with autism spectrum disorders, and low iron stores have been associated with sleep disturbance. Methods We performed a randomized placebo-controlled trial of oral ferrous sulfate to treat insomnia in children with autism spectrum disorders and low normal ferritin levels. Twenty participants who met inclusion criteria and whose insomnia did not respond to sleep education were randomized to 3 mg/kg/day of ferrous sulfate (n = 9) or placebo (n = 11) for three months. Results Iron supplementation was well tolerated, and no serious adverse events were reported. Iron supplementation improved iron status (+18.4 ng/mL active versus −1.6 ng/mL placebo, P = 0.044) but did not significantly improve the primary outcome measures of sleep onset latency (−11.0 minutes versus placebo, 95% confidence interval −28.4 to 6.4 minutes, P = 0.22) and wake time after sleep onset (−7.7 minutes versus placebo, 95% confidence interval −22.1 to 6.6 min, P = 0.29) as measured by actigraphy. Iron supplementation was associated with improvement in the overall severity score from the Sleep Clinical Global Impression Scale (−1.5 points versus placebo, P = 0.047). Changes in measures of daytime behavior did not differ between groups. Conclusion This trial demonstrated no improvement in primary outcome measures of insomnia in subjects treated with ferrous sulfate compared with placebo. Interpretation was limited by low enrollment.

Population reflective research enrollment improves study generalizability and disease knowledge. Nevertheless, the proportion of underrepresented groups (URGs) in Parkinson's disease (PD) research remains low. Hence, the current manuscript describes the process of designing a study to analyze the effectiveness of strategies to overcome barriers to URG recruitment in PD research.The Fostering Inclusivity in Research Engagement for Underrepresented Populations in Parkinson's Disease (FIRE-UP PD) study asked participating sites to identify a URG or geographical region to target to assess knowledge and attitudes toward PD research as well as increase Fox Insight (an online study with The Michael J. Fox Foundation) participation across eight months. URGs were defined as racial and ethnic minorities, women, rural populations, and low socioeconomic status groups. Participating sites were paired based on their proposed interventions and were randomly assigned to either the intervention or control condition.The FIRE-UP PD study was divided into pre-intervention, intervention, and post-intervention periods to measure changes in awareness and trust in PD research along with engagement and interest in PD protocols through the use of several surveys. Interventions included developing educational tools to engage local communities, building partnerships within local PD communities, and recruiting stakeholders to reimagine medical and research information for the community.Improving representation in research is a crucial step toward improving access to PD diagnoses and treatments. This is one of the first multi-site PD research studies to include community engagement to address barriers to research participation and improve research recruitment of URGs.

Usage during pregnancy of the antiseizure medication (ASM), phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT), has been associated with adverse pregnancy outcomes. While morphological effects on offspring are well-documented, inconsistent findings have been reported on neuropsychological development, possibly due to differences in attention to maternal demographics, and other design characteristics. Herein, we report the results of a carefully designed protocol used to examine the effects of gestational monotherapy with PB, CBZ, or PHT upon children's general mental abilities, when compared to age- and gender- matched children born to unexposed women of similar age, education, and socioeconomic status.For each ASM, we selected qualifying cases from children born to PB, CBZ, or PHT monotherapy-exposed and unexposed women. Following the application of inclusion, exclusion, and matching criteria, our sample included 34 PB-exposed, 40 PHT-exposed, and 41 CBZ-exposed children along with matched unexposed children for each drug group. Criteria were applied through examination of maternal medical and educational histories, parental socioeconomic characteristics, and child's age and gender. Each child's physical and neuropsychological characteristics were examined, using standardized protocols. We report on the cognitive performance of the children as assessed by the Wechsler Intelligence Scale for Children - III (WISC-III), the leading measure of mental ability in the U.S.An overall mixed model ANOVA of the adjusted performance of the children across all groups controlling for maternal IQ revealed significant effects on verbal IQ, but not full-scale IQ or performance IQ. In the individual drug and unexposed group comparisons, only reduced verbal and full-scale IQ scores in PB-exposed versus matched unexposed children were found. Comparisons between drug groups revealed a significant reduction in verbal IQ and full-scale IQ in PB-exposed versus PHT-exposed children, but not in other drug-drug comparisons.These results demonstrate effects on children's mental ability due to prenatal PB exposure, such that analyses adjusted for maternal IQ scores, revealed reduced verbal mental abilities and reduced full-scale IQ scores when scores in exposed children were compared to scores from children of the same age and sex born to demographically similar, healthy unexposed women. When comparisons were made between drug groups, children exposed prenatally to PB performed significantly worse than prenatally PHT-exposed children, but CBZ-exposed children's scores were not significantly different from those of PB or PHT-exposed groups. In light of shared effects on structural teratogenicity, these findings suggest that use of PB monotherapy for the management of seizures during pregnancy may be associated with increased risk in comparison to PHT when neurobehavioral functioning is considered, and that only PB-exposed children have reduced performance compared to matched controls. Attention to these effects is critical in the developing world where use of these older medications remains predominant, and prudent choices can be made to reduce impact on cognitive development.

Background: Epidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precursor inosine is currently under clinical development as a potential disease-modifying strategy for Parkinson's disease (PD). Methods: Our study takes advantage of a recently completed phase II trial evaluating oral inosine in de novo non-disabling early PD with no major cardiovascular and nephrological conditions, and of three lines of genetically engineered mice: urate oxidase (UOx) global knockout (gKO), conditional KO (cKO), and transgenic (Tg) mice with markedly elevated, mildly elevated, and substantially reduced serum urate, respectively, to systematically investigate effects of urate-modifying manipulation on BP. Findings: Among clinical trial participants, change in serum urate but not changes in systolic, diastolic and orthostatic BP differed by treatment group. There was no positive correlation between urate elevations and changes in systolic, diastolic and orthostatic BP. Between UOx gKO, cKO, or Tg mice and their respective wild type littermates there were no significant differences in systolic or diastolic BP or in their responses to BP-regulating interventions. Interpretation: Our complementary preclinical and human studies of urate modulation in animal models and in generally healthy early PD do not support a hypertensive effect of urate elevation or an association between urate and BP. Funding: U.S. Department of Defense, RJG Foundation, Michael J. Fox Foundation LEAPS program, National Institutes of Health, American Federation for Aging Research, Parkinson's Disease Foundation Advancing Parkinson's Therapies initiative. Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The study protocol of PD patients was approved by the institutional review boards of the Administrative Coordination Center at Massachusetts General Hospital (MGH), the Clinical Coordination Center at University of Rochester and all clinical sites, and participants provided written informed consent.

Background Boys with autism spectrum disorder (ASD) have lower bone mineral density (BMD) than typically developing controls. Differences in diet and exercise may contribute to low BMD. Objective Our aim was to examine macro- and micronutrient intakes and self-reported physical activity in boys with ASD compared to TDC and the relationship of these variables with BMD. Design/methods We conducted a cross-sectional study of 49 boys (25 ASD, 24 typically developing controls) assessed for 3-day food records and physical activity records, and BMD of the whole body less head, hip, and spine using dual-energy x-ray absorptiometry. Fasting levels of 25(OH) vitamin D and calcium were obtained. Participants Participants were adolescent boys, aged 8 to 17 years, recruited from a clinic population (ASD) or community advertisements (ASD and typically developing controls) matched for age. Results ASD participants were approximately 9 months younger than typically developing control participants on average. Body mass index and serum vitamin D and calcium levels were similar. Boys with ASD consumed 16% fewer calories, with a larger percentage obtained from carbohydrates, and 37% less animal protein and 20% less fat than typically developing controls. A lower proportion of ASD participants were categorized as "very physically active" (27% vs 79%; P z scores were 0.7 to 1.2 standard deviations lower in ASD than typically developing controls at all locations. Higher animal protein, calcium, and phosphorus intakes were associated positively with bone density measures in boys with ASD. Conclusions Compared to typically developing controls, boys with ASD had lower protein, calcium, and phosphorus intakes, activity levels, and BMD z scores at the lumbar spine, femoral neck, total hip, and whole body less head. Protein, calcium, and phosphorus intakes were associated positively with BMD.

Supporting the health of growing numbers of frail older adults living in subsidized housing requires interventions that can combat frailty, improve residents’ functional abilities, and reduce their health care costs. Tai Chi is an increasingly popular multimodal mind–body exercise that incorporates physical, cognitive, social, and meditative components in the same activity and offers a promising intervention for ameliorating many of the conditions that lead to poor health and excessive health care utilization. The Mind Body-Wellness in Supportive Housing (Mi-WiSH) study is an ongoing two-arm cluster randomized, attention-controlled trial designed to examine the impact of Tai Chi on functional indicators of health and health care utilization. We are enrolling participants from 16 urban subsidized housing facilities (n=320 participants), conducting the Tai Chi intervention or education classes and social calls (attention control) in consenting subjects within the facilities for one year, and assessing these subjects at baseline, 6 months, and 1 year. Physical function (quantified by the Short Physical Performance Battery), and health care utilization (emergency visits, hospitalizations, skilled nursing and nursing home admissions), assessed at 12 months are co-primary outcomes. Our discussion highlights our strategy to balance pragmatic and explanatory features into the study design, describes efforts to enhance site recruitment and participant adherence, and summarizes our broader goal of post study dissemination if effectiveness and cost-effectiveness are demonstrated, by preparing training and protocol manuals for use in housing facilities across the U.S.

To systematically evaluate and quantify the effects of Tai Chi/Qigong (TCQ) on motor (UPDRS III, balance, falls, Timed-Up-and-Go, and 6-Minute Walk) and non-motor (depression and cognition) function, and quality of life (QOL) in patients with Parkinson's disease (PD).A systematic search in 7 electronic databases targeted clinical studies evaluating TCQ for individuals with PD published through August 2016. Meta-analysis was used to estimate effect sizes (Hedges's g) and publication bias for randomized controlled trials (RCTs). Methodological bias in RCTs was assessed by two raters.Our search identified 21 studies, 15 of which were RCTs with a total of 735 subjects. For RCTs, comparison groups included no treatment (n = 7, 47%) and active interventions (n = 8, 53%). Duration of TCQ ranged from 2 to 6 months. Methodological bias was low in 6 studies, moderate in 7, and high in 2. Fixed-effect models showed that TCQ was associated with significant improvement on most motor outcomes (UPDRS III [ES = -0.444, p 0.001], balance [ES = 0.544, p 0.001], Timed-Up-and-Go [ES = -0.341, p = 0.005], 6 MW [ES = -0.293, p = 0.06], falls [ES = -0.403, p = 0.004], as well as depression [ES = -0.457, p = 0.008] and QOL [ES = -0.393, p 0.001], but not cognition [ES = -0.225, p = 0.477]). IEvidence to date supports a potential benefit of TCQ for improving motor function, depression and QOL for individuals with PD, and validates the need for additional large-scale trials.

Study objectives The study aimed to compare urinary biomarkers in patients with Down syndrome (DS) with and without obstructive sleep apnea (OSA) to those of age- and sex-matched neurotypically developing healthy controls (HC). We further investigated whether we could predict OSA in patients with DS using these biomarkers. Methods Urine samples were collected from 58 patients with DS the night before or the morning after their scheduled overnight polysomnogram or both, of whom 47 could be age- and sex-matched to a sample of 43 HC. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay. Log-transformed creatinine-corrected assay levels were normalized. Normalized z -scores were compared between patients with DS vs. HC, between patients with DS with vs. without OSA, and to derive composite models to predict OSA. Results Most night-sampled urinary biomarkers were elevated among patients with DS relative to matched HC. No urinary biomarker levels differed between patients with DS with vs. without OSA. A combination of four urinary biomarkers predicted AHI > 1 with a positive predictive value of 90% and a negative predictive value of 68%. Conclusions Having DS, even in the absence of concurrent OSA, is associated with a different urinary biomarker profile when compared to that of HC. Therefore, while urinary biomarkers may be predictive of OSA in the general pediatric population, a different approach is needed in interpreting urinary biomarker assays in patients with DS. Certain biomarkers also seem promising to be predictive of OSA in patients with DS. No clinical trial was indicated in the undertaking of this work.

Knee osteoarthritis (OA) is the most common joint disorder in the U.S. and a leading cause of disability. Depression and obesity are highly comorbid among knee OA patients, and the combination of obesity and depression is associated with decreased physical activity, higher pain and disability, and more rapid cartilage degradation. Depression, obesity and OA exacerbate one another and share a common pathophysiology involving systemic inflammation and pro-inflammatory cytokines, reflecting a complex mind-body interaction. Current treatments for knee OA offer little to no benefit over placebo, and do not emphasize mind-body practices or physical activity to target the underlying pathophysiology. Mind-body interventions to lessen depressive symptoms and increase physical activity offer the ability to target biological, mechanical and psychological mechanisms of OA progression. Our long-term goals are to evaluate the mechanisms by which the Relaxation Response Resiliency Program (3RP) delivered via secure telehealth, and adapted for patients with depression, obesity and knee OA (GetActive-OA) promotes increases in physical activity and improved knee health. We hypothesize that the synergistic interaction between mindfulness, adaptive thinking, positive psychology and healthy living skills of the GetActive-OA will slow the progression of symptomatic knee OA by reducing pro-inflammatory cytokine expression and promoting optimal mechanical loading of the cartilage. Here we present the protocol for a mixed methods study that will adapt the 3RP for the needs of knee OA patients with depression and obesity with a focus on increasing physical activity (GetActive-OA), and iteratively maximize the feasibility, credibility and acceptability of the programs and research procedures., Highlights • Depression, obesity and knee osteoarthritis (OA) exacerbate one another and share a common pathophysiology. • Treatments do not emphasize mind-body practices to increase physical activity to target the underlying pathophysiology. • We aim to adapt the GetActive for the needs of knee OA patients with depression and obesity. • Internet delivery of the GetActive-OA program bypasses many barriers to care.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background Neurofibromatoses (NF) are a group of genetically distinct disorders of the nervous system unified by the predisposition to nerve sheath tumors. Although adolescents with NF types 1 and 2 (NF1 and NF2) report poor quality of life and high psychosocial burden, there are no evidence-based interventions to address these needs. This paper presents the study design and protocol for the first randomized controlled trial (RCT) of a mind-body intervention for adolescents with NF, Resilient Youth with NF (RY-NF), versus an educational control group, Health Education for NF (HE-NF), both delivered in groups via secure live video. Methods This is an ongoing, single-blind efficacy RCT. Recruitment began in November 2019 and will continue until March 2022. We will enroll 200 English-speaking, geographically diverse adolescents (ages 12–17) with NF1 and NF2 who report significant distress or difficulty coping with their NF symptoms. We will use a shared-baseline, linear mixed model to compare the effect of RY-NF versus HE-NF on changes in quality of life (QoL) and psychosocial outcomes from baseline to post-intervention, and 6- and 12-month follow-ups. We will also develop NF-specific minimal clinically important difference (MCID) for QoL variables, and conduct mediation and moderation analyses to understand mechanisms of improvement. Discussion This study has important clinical and public health implications for the psychosocial functioning of adolescents with NF. It provides a model for efficient delivery of virtual psychosocial care for adolescents with rare diseases. Plans for dissemination and implementation of the RY-NF should efficacy be ascertained are also discussed.

Objective To determine the prevalence of overweight/obese status in children with autism spectrum disorders (ASD), identify associated characteristics, and develop a model to predict weight status. Methods The prevalence of overweight and obesity was determined in 2769 children with ASD enrolled in the Autism Speaks Autism Treatment Network, a collaboration of 17 academic centers, and compared with a national sample matched for age, sex, and race. Associations in the ASD sample between weight status and demographic and clinical variables, such as age, race, head circumference, and adaptive functioning, were tested using ordinal logistic regression. The accuracy of a final model that predicted weight status based on early life variables was evaluated in a validation sample. Results The prevalence of overweight and obesity were 33.9% and 18.2%, respectively; ASD was associated with a higher risk of obesity (but not overweight) relative to the national sample (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.05–1.28; P = .003). In the adjusted analysis, overweight/obese status was significantly associated with Hispanic ethnicity (OR, 1.99; 95% CI, 1.37–2.89), parental high school education (OR, 1.56; 95% CI, 1.09–2.21), high birth weight (OR, 1.56; 95% CI, 1.11–2.18), macrocephaly (OR, 4.01; 95% CI, 2.96–5.43), and increased somatic symptoms (OR, 1.41; 95% CI, 1.01–1.95). A prediction model designed to have high sensitivity predicted low risk of overweight/obesity accurately, but had low positive predictive value. Conclusions The prevalence of obesity in children with ASD was greater than a national sample. Independent associations with increased weight status included known risk factors and macrocephaly and increased level of somatic symptoms. A model based on early life variables accurately predicted low risk of overweight/obesity.

Background The duration of untreated psychosis is well recognised as an independent predictor of symptomatic and functional outcome in the short term and has facilitated the development of worldwide early intervention programmes. However, the extent and mechanisms by which it might influence prognosis beyond a decade remain poorly understood. Methods The authors examined the relationship between duration of untreated psychosis and outcome 12 years after a first episode of psychosis and assessed whether its relationship with function is affected by symptoms in a prospective, 12-year follow-up of an epidemiologically-based inception cohort. Results Longer duration of untreated psychosis predicted poorer remission status, more severe positive and negative symptoms, and greater impairment in general functioning, social functioning and quality of life at 12 years on standardised measures, independent of other factors at baseline. It was not associated with gainful employment, for which education was the only predictor, or independent living, for which age was the only predictor. The relationship between duration of untreated psychosis and functional outcome was mediated by concurrent psychopathology, particularly negative symptoms. Conclusions These results provide qualified support for the potential long-term benefit of reduction in the duration of untreated psychosis in terms of improvement in symptoms and functional outcome. Its failure to predict real-life outcomes such as independent living and gainful employment could reflect the importance of pre-existing socio-cultural factors such as individual opportunity. The relationship between duration of untreated psychosis and negative symptoms was largely responsible for its effect on function, suggesting a possible long-term protective mechanism against disability.

Purpose To identify prognostic and predictive factors of overall survival (OS), relapse-free survival (RFS) and toxicity for patients with uterine papillary serous carcinoma (UPSC). Materials and methods Patient, tumor, treatment and relapse characteristics of 135 women with Stages I–IVA UPSC treated between 1980 and 2006 at Dana–Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed using Cox regression models to determine prognostic and predictive factors for OS, RFS and toxicity. Results Mean follow-up was 5.5years (range, 0.01–25.2). Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression analysis, increasing age, stage, and myometrial invasion were prognostic factors associated with shorter OS and RFS. A paclitaxel–platinum chemotherapy regimen was significantly associated with longer OS (hazard ratio [HR]=0.34, 95% confidence interval [CI] 0.15–0.74, p=0.007) and RFS (HR=0.45, 95% CI 0.22–0.92, p=0.03). RFS was improved for patients treated with RT (HR=0.44, 95% CI 0.25–0.77, p=0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received RT and was 2.9% for those who did not (p=NS). Conclusion Uterine papillary serous cancer can be an aggressive tumor type with a poor prognosis. RFS was improved by radiation and chemotherapy with few grade 3 or higher complications. Using radiation and paclitaxel–platinum chemotherapy should be attempted whenever feasible for patients with UPSC who do not have distant metastases at diagnosis.

Rationale Sedation is a common side effect of clozapine treatment and may exacerbate metabolic consequences of poor diet and exercise habits that are common in patients with schizophrenia. Modafinil has been proposed as a treatment for clozapine-induced sedation and metabolic abnormalities. Objective To estimate the effect sizes and person-to-person variation in anthropometric measures, glucose and lipid metabolism, and diet on modafinil treatment for future randomized control trials. Methods A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted, adding modafinil up to 300 mg/day to stabilized schizophrenia outpatients receiving clozapine. Blood pressure, weight, BMI, laboratory assays, and dietary intake were tracked to monitor changes in metabolic markers. Results Thirty-five participants were randomly assigned to treatment with study drug or placebo and were included in the analysis. Modafinil did not improve blood pressure, weight, BMI, glucose or lipid metabolism compared to placebo. Modafinil was well tolerated and did not worsen psychosis. Conclusions Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine. However, the effects of modafinil on weight and insulin regulation warrant further investigation with effect sizes of 0.4 to 0.6.

Purpose To assess the dose to the organs at risk (OARs) and utility of repeated OAR dose–volume histogram calculations in multifraction high–dose-rate vaginal cylinder brachytherapy using 3-dimensional imaging. Methods and Materials Thirty-eight patients (125 fractions) received high–dose-rate brachytherapy to the vaginal vault between January 2005 and October 2005. All patients emptied their bladders before insertion. After each insertion, a CT scan with 2.5-mm slices and contours of the bladder, rectum, and sigmoid was performed. Dose–volume histograms were generated for the D0.1cc and D2cc for the OAR using a software program created at our institution. Variance component models estimated the within-patient variance of the dose to the OAR between fractions. Predictors of dose to the OAR were identified using linear mixed models. Results The within-patient coefficients of variation of total D0.1cc dose were bladder 14.0%, rectum 7.9%, and sigmoid 27.6%; for D2cc, these were 8.1%, 5.9%, and 20.3%, respectively. Intraclass correlations ranged from 0.27 to 0.79. Larger OAR predicted greater total D0.1cc and D2cc. Other predictors of total D0.1cc and D2cc dose included the size of the cylinder and the length of the treatment field for rectum. Conclusions CT simulation provides a noninvasive assessment of the dose to the bladder, rectum, and sigmoid. The small within-patient variation in doses to the bladder and rectum do not support reporting doses to the OARs beyond the initial fraction.

Although anterograde memory deficits are well documented in patients with epilepsy, the extent to which remote memory deficits occur is less clear. This is due in part to a lack of reliable methods for assessment. The present study examined the feasibility of using the Transient News Events Test (TNET) to assess remote memory in subjects status post anterior temporal lobectomy (ATL) for the treatment of refractory seizures. Results indicated significantly poorer performance of the patient group compared to healthy controls. The decrement in performance within the patient group was evident only for items from more recent time periods. Reasons for an apparent stability of the most remote memories with ATL and implications regarding hippocampal function are reviewed. In conclusion, the TNET provides a feasible method for assessment of remote memory function in patients with epilepsy, with decrements in performance noted in comparison to a healthy control group in this retrospective study.

Wayne PM, Krebs DE, Macklin EA, Schnyer R, Kaptchuk TJ, Parker SW, Scarborough DM, McGibbon CA, Schaechter JD, Stein J, Stason WB. Acupuncture for upper-extremity rehabilitation in chronic stroke: a randomized sham-controlled study. Objective To compare the effects of traditional Chinese acupuncture with sham acupuncture on upper-extremity (UE) function and quality of life (QOL) in patients with chronic hemiparesis from stroke. Design A prospective, sham-controlled, randomized controlled trial (RCT). Setting Patients recruited through a hospital stroke rehabilitation program. Participants Thirty-three subjects who incurred a stroke 0.8 to 24 years previously and had moderate to severe UE functional impairment. Interventions Active acupuncture tailored to traditional Chinese medicine diagnoses, including electroacupuncture, or sham acupuncture. Up to 20 treatment sessions (mean, 16.9) over a mean of 10.5 weeks. Main Outcome Measures UE motor function, spasticity, grip strength, range of motion (ROM), activities of daily living, QOL, and mood. All outcomes were measured at baseline and after treatment. Results Intention-to-treat (ITT) analyses found no statistically significant differences in outcomes between active and sham acupuncture groups. Analyses of protocol-compliant subjects revealed significant improvement in wrist spasticity ( P P P P =.09) and digit ROM ( P =.06). Conclusions Based on ITT analyses, we conclude that acupuncture does not improve UE function or QOL in patients with chronic stroke symptoms. However, gains in UE function observed in protocol-compliant subjects suggest traditional Chinese acupuncture may help patients with chronic stroke symptoms. These results must be interpreted cautiously because of small sample sizes and multiple, unadjusted, post hoc comparisons. A larger, more definitive RCT using a similar design is feasible and warranted.

Hypertension is a major public health problem with serious medical and financial consequences. Barriers to successful conventional pharmacological treatment include side effects, out-of-pocket expenses, patient noncompliance and insufficient dosages. Acupuncture has been studied as an alternative therapy for controlling blood pressure (BP) but previous studies have serious methodological limitations. This paper describes the design of the Stop Hypertension with the Acupuncture Research Program (SHARP) trial, a pilot randomized clinical trial designed to gather preliminary data regarding the efficacy of traditional Chinese medicine (TCM)-based acupuncture for control of essential hypertension. The design of the SHARP trial balanced rigorous clinical trial methodology with principles of TCM. Eligible participants had systolic BP (SBP) 140-179 mm Hg and diastolic BP (DBP) 90-109 mm Hg in the absence of antihypertensive therapy. Following screening, participants were randomized to one of three groups: individualized, standardized or control acupuncture. Treatments were designed according to principles of TCM; nonspecific effects associated with the interventions were standardized across the randomized groups. For individualized acupuncture, points were tailored to each participant. Standardized acupuncture used a prespecified set of points. The invasive sham control acupuncture regimen was designed to be non-active. Each participant received a "prescription" for individualized acupuncture from an acupuncturist who was masked to treatment assignment, and was subsequently treated by an independent acupuncturist. Patients and those assessing BP were masked to treatment group. Acupuncture was delivered twice a week for 6 weeks. Follow-up visits were every 2 weeks to week 10 and then at months 4, 6, 9 and 12. The primary endpoint will be change in SBP from baseline to 10 weeks. DBP, BP trajectories over the 12-month follow-up and antihypertensive medication requirements will also be examined. Initial contact was documented for 1442 prospective participants from March 2001 to April 2002; 424 provided informed consent and 192 were ultimately randomized.

Objective To test the hypothesis that bone accrual over a 4-year period is reduced in boys with autism spectrum disorder (ASD) compared with typically developing controls. Study design Twenty-five boys with ASD and 24 controls were assessed for bone outcomes. Fourteen boys with ASD and 11 controls were assessed both at baseline and after 4 years. The mean subject age was 11.0 ± 1.6 years at study initiation and 14.9 ± 1.6 years at follow-up. Bone mineral density (BMD) was measured at the spine, hip, and whole body using dual-energy X-ray absorptiometry and normalized for age, race, and sex (BMD z-scores). Height adjustments were performed as well. We assessed medical history, physical activity using questionnaires, vitamin D and calcium intake using food records, and serum calcium, phosphorus, 25(OH)-vitamin D, and pubertal hormone levels. Results Boys with ASD had lower spine, hip, and whole body BMD z-scores compared with controls. In those subjects assessed both at baseline and after 4 years, bone accrual rates did not differ between the 2 groups; however, spine and hip BMD z-scores remained lower in the boys with ASD than in controls at follow-up. Notably, the ASD group was less physically active at both time points. Conclusion Although pubertal bone accrual was similar to that in controls, BMD in children with ASD remained low over a 4-year follow-up period, suggesting that low BMD is a consequence of prepubertal factors, such as low physical activity. Studies are needed to investigate the causes and consequences of decreased BMD, to assess BMD in females and adults with ASD, and to evaluate therapeutic interventions.

Objective: To determine whether children with homozygous sickle cell anemia (SCD) who have silent infarcts on magnetic resonance imaging (MRI) of the brain are at increased risk for overt stroke. Methods: We selected patients with homozygous SCD who (1) enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) before age 6 months, (2) had at least 1 study-mandated brain MRI at age 6 years or older, and (3) had no overt stroke before a first MRI. MRI results and clinical and laboratory parameters were tested as predictors of stroke. Results: Among 248 eligible patients, mean age at first MRI was 8.3 ± 1.9 years, and mean follow-up after baseline MRI was 5.2 ± 2.2 years. Five (8.1%) of 62 patients with silent infarct had strokes compared with 1 (0.5%) of 186 patients without prior silent infarct; incidence per 100 patient-years of follow-up was increased 14-fold (1.45 per 100 patient-years vs 0.11 per 100 patient-years, P = .006). Of several clinical and laboratory parameters examined, silent infarct was the strongest independent predictor of stroke (hazard ratio=7.2, P = .027). Conclusions: Silent infarct identified at age 6 years or older is associated with increased stroke risk. (J Pediatr 2001;139:385-90)

patients treated with stable doses of antipsychotics were randomly assigned to two groups that received an infusion of either sodium nitroprusside or placebo for four hours. Psychiatric symptoms were assessed at baseline and every hour during the infusion with the Brief Psychiatric Rating Scale (BPRS) and the negative subscale of the Positive and Negative Syndromes Scale (PANNS-n). Additional assessments were made 12 hours after the infusion, daily for seven days, and weekly for four weeks. Cognitive tests (Stroop Color Word Test, N-back, and FAS) were administered at baseline and 12 hours after the end of the infusion. No side effects were reported by the participants. All the clinical and demographic characteristics of the sample including age, education, duration of disease, gender, diagnostic subtype, and type of antipsychotic in use were matched across groups. Symptom ratings were significantly reduced in the group treated with sodium nitroprusside, but not in the placebo group. Cognitive performance was also significantly improved in the nitroprusside group compared to placebo. There were no significant differences between the two groups regarding the physiological parameters analyzed (systolic and diastolic blood pressure, cardiac rhythm, and oxygen saturation). The strategy of treating schizophrenia patients for four hours with 0,5 mcg/kg/min sodium nitroprusside improved psychopathology and cognitive function. Our findings support the hypothesis that the NMDA-NO-GMPc pathway is affected in schizophrenia and that nitric oxide donors such as sodium nitroprusside could thus be a promising approach in the management of the disorder. Although exciting, these results are preliminary and must be replicated by future studies.