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To investigate the influences of dietary riboflavin (RF) addition on nutrient digestion and rumen fermentation, eight rumen cannulated Holstein bulls were randomly allocated into four treatments in a repeated 4 × 4 Latin square design. Daily addition level of RF for each bull in control, low RF, medium RF and high RF was 0, 300, 600 and 900 mg, respectively. Increasing the addition level of RF, DM intake was not affected, average daily gain tended to be increased linearly and feed conversion ratio decreased linearly. Total tract digestibilities of DM, organic matter, crude protein (CP) and neutral-detergent fibre (NDF) increased linearly. Rumen pH decreased quadratically, and total volatile fatty acids (VFA) increased quadratically. Acetate molar percentage and acetate:propionate ratio increased linearly, but propionate molar percentage and ammonia-N content decreased linearly. Rumen effective degradability of DM increased linearly, NDF increased quadratically but CP was unaltered. Activity of cellulase and populations of total bacteria, protozoa, fungi, dominant cellulolytic bacteria, Prevotella ruminicola and Ruminobacter amylophilus increased linearly. Linear increase was observed for urinary total purine derivatives excretion. The data suggested that dietary RF addition was essential for rumen microbial growth, and no further increase in performance and rumen total VFA concentration was observed when increasing RF level from 600 to 900 mg/d in dairy bulls.
Bipolar disorder is associated with premature mortality, but evidence is mostly derived from Western countries. There has been no research evaluating shortened lifespan in bipolar disorder using life-years lost (LYLs), which is a recently developed mortality metric taking into account illness onset for life expectancy estimation. The current study aimed to examine the extent of premature mortality in bipolar disorder patients relative to the general population in Hong Kong (HK) in terms of standardised mortality ratio (SMR) and excess LYLs, and changes of mortality rate over time.
This population-based cohort study investigated excess mortality in 12 556 bipolar disorder patients between 2008 and 2018, by estimating all-cause and cause-specific SMRs, and LYLs. Trends in annual SMRs over the 11-year study period were assessed. Study data were retrieved from a territory-wide medical-record database of HK public healthcare services.
Patients had higher all-cause [SMR: 2.60 (95% CI: 2.45–2.76)], natural-cause [SMR: 1.90 (95% CI: 1.76–2.05)] and unnatural-cause [SMR: 8.63 (95% CI: 7.34–10.03)] mortality rates than the general population. Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Men and women with bipolar disorder had 6.78 (95% CI: 6.00–7.84) years and 7.35 (95% CI: 6.75–8.06) years of excess LYLs, respectively. The overall mortality gap remained similar over time, albeit slightly improved in men with bipolar disorder.
Bipolar disorder is associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to natural causes. Persistent mortality gap underscores an urgent need for targeted interventions to improve physical health of patients with bipolar disorder.
There is compelling evidence for gradient effects of household income on school readiness. Potential mechanisms are described, yet the growth curve trajectory of maternal mental health in a child's early life has not been thoroughly investigated. We aimed to examine the relationships between household incomes, maternal mental health trajectories from antenatal to the postnatal period, and school readiness.
Prospective data from 505 mother–child dyads in a birth cohort in Singapore were used, including household income, repeated measures of maternal mental health from pregnancy to 2-years postpartum, and a range of child behavioural, socio-emotional and cognitive outcomes from 2 to 6 years of age. Antenatal mental health and its trajectory were tested as mediators in the latent growth curve models.
Household income was a robust predictor of antenatal maternal mental health and all child outcomes. Between children from the bottom and top household income quartiles, four dimensions of school readiness skills differed by a range of 0.52 (95% Cl: 0.23, 0.67) to 1.21 s.d. (95% CI: 1.02, 1.40). Thirty-eight percent of pregnant mothers in this cohort were found to have perinatal depressive and anxiety symptoms in the subclinical and clinical ranges. Poorer school readiness skills were found in children of these mothers when compared to those of mothers with little or no symptoms. After adjustment of unmeasured confounding on the indirect effect, antenatal maternal mental health provided a robust mediating path between household income and multiple school readiness outcomes (χ2 126.05, df 63, p < 0.001; RMSEA = 0.031, CFI = 0.980, SRMR = 0.034).
Pregnant mothers with mental health symptoms, particularly those from economically-challenged households, are potential targets for intervention to level the playing field of their children.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
For advanced operational aircraft, the two-dimensional (2-D) thrust-vectoring (TV) nozzle effectively improves the flight mobility and post-stall manoevrability. However, its flow capacity decreases when deflecting and cooling air is injected, which impacts the engine’s operating state, including decreasing the fan surge margin and increasing the turbine inlet temperature. Therefore, in order to improve engine performance in the whole flight envelope, this paper studies the matching mechanism of the engine and the cooled 2-D TV nozzle, performance characterisation and control schedule of the nozzle, and an integrated aeroengine/nozzle modeling method is put forward. Based on these, an engine performance simulation model is modified to include a cooled 2-D TV nozzle. The testing results show that applying the nozzle control schedules recommended in this paper avoids the performance degradation when the nozzle deflects. This work advances the field of engine/nozzle integrated modeling, and helps to instruct the simulation and experimentation to better fit the needs of engine modeling and engineering applications.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA−) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA− diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA− diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.
A disruption database characterizing the current quench of disruptions with ITER-like tungsten divertor has been developed on EAST. It provides a large number of plasma parameters describing the predisruptive plasma, current quench time, eddy current, and mitigation by massive impurity injection, which shows that the current quench time strongly depends on magnetic energy and post-disruption electron temperature. Further, the energy balance and magnetic energy dissipation during the current quench phase has been well analysed. Magnetic energy is also demonstrated to be dissipated mainly by ohmic reheating and inductive coupling, and both of the two channels have great effects on current quench time. Also, massive gas injection is an efficient method to speed up the current quench and increase the fraction of impurity radiation.
This study aimed to investigate the benefit of Bonebridge devices in patients with single-sided deafness.
Five patients with single-sided deafness who were implanted with Bonebridge devices were recruited in a single-centre study. Participants’ speech perception and horizontal sound localisation abilities were assessed at 6 and 12 months post-operatively. Speech intelligibility in noisy environments was measured in three different testing conditions (speech and noise presented from the front, speech and noise presented from the front and contralateral (normal ear) side separately, and speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side). Sound localisation was evaluated in Bonebridge-aided and Bonebridge-unaided conditions at different stimuli levels (65, 70 and 75 dB SPL).
All participants showed a better capacity for speech intelligibility in quiet environments with the Bonebridge device. The speech recognition threshold with the Bonebridge device was significantly decreased at both short- and long-term follow up in the speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side condition (p < 0.05). Additionally, participants maintained similar levels of sound localisation between the Bonebridge-aided and unaided conditions (p > 0.05). However, the accuracy of localisation showed some improvement at 70 dB SPL and 75 dB SPL post-operatively.
The Bonebridge device provides the benefit of improved speech perception performance in patients with single-sided deafness. Sound localisation abilities were neither improved nor worsened with Bonebridge implantation at the follow-up assessments.
Ovarian follicle selection is a natural biological process in the pre-ovulatory hierarchy in birds that drives growing follicles to be selected within the ovulatory cycle. Follicle selection in birds is strictly regulated, involving signaling pathways mediated by dietary nutrients, gonadotrophic hormones and paracrine factors. This study aimed to test the hypothesis that dietary Ca may participate in regulating follicle selection in laying ducks through activating the signaling pathway of cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/extracellular signal-regulated kinase (ERK), possibly mediated by gonadotrophic hormones. Female ducks at 22 weeks of age were initially fed one of two Ca-deficient diets (containing 1.8% or 0.38% Ca) or a Ca-adequate control diet (containing 3.6% Ca) for 67 days (depletion period), then all birds were fed the Ca-adequate diet for an additional 67 days (repletion period). Compared with the Ca-adequate control, ducks fed 0.38% Ca during the depletion period had significantly decreased (P < 0.05) numbers of hierarchical follicles and total ovarian weight, which were accompanied by reduced egg production. Plasma concentration of FSH was decreased by the diet containing 1.8% Ca but not by that containing 0.38%. The ovarian content of cAMP was increased with the two Ca-deficient diets, and phosphorylation of PKA and ERK1/2 was increased with 0.38% dietary Ca. Transcripts of ovarian estradiol receptor 2 and luteinizing hormone receptor (LHR) were reduced in the ducks fed the two Ca-deficient diets (P < 0.05), while those of the ovarian follicle stimulating hormone receptor (FSHR) were decreased in the ducks fed 0.38% Ca. The transcript abundance of ovary gap junction proteins, A1 and A4, was reduced with the Ca-deficient diets (P < 0.05). The down-regulation of gene expression of gap junction proteins and hormone receptors, the increased cAMP content and the suppressed hierarchical follicle numbers were reversed by repletion of dietary Ca. These results indicate that dietary Ca deficiency negatively affects follicle selection of laying ducks, independent of FSH, but probably by activating cAMP/PKA/ERK1/2 signaling pathway.
The risk factors of criminal behavior in patients with schizophrenia are not well explored. This study is to explore the risk factors for criminal behavior in patients with schizophrenia in rural China.
We used data from a 14-year prospective follow-up study (1994-2008) of criminal behavior among a cohort (n=510) of patients with schizophrenia in Xinjin County, Chengdu, China.
There were 489 patients (95.9%) who were followed up from 1994 to 2008. The rate of criminal behavior was 13.5% among these patients with schizophrenia during the follow-up period. Compared with female subjects (6 cases, 20.0%), male patients had significantly higher rate of violent criminal behavior (e.g., arson, sexual assault, physical assault, and murder) (24 cases, 80.0%) (p< 0.001). Bivariate analyses showed that the risk of criminal behavior was significantly associated with being unmarried, of younger age, previous violent behavior, homelessness, lower family economic status, no family caregivers, and higher scores on measures (PANSS) of positive, negative, and total symptoms of illness. In multiple logistic regression analyses being unmarried and previous violent behavior were identified as independent predictors of increased criminal behavior in persons with schizophrenia.
The risk factors for criminal behavior among patients with schizophrenia should be understood within a particular social context. Criminal behavior may be predicted by specific characteristics of patients with schizophrenia in rural community. The findings of risk factors for criminal behavior should be considered in planning community mental health care and interventions for high-risk patients and their families.
There seems to be geographical differences in decisions about breast conserving surgery (BCS) in breast cancer patients. This study was to evaluate patients’ attitude to BCS and to assess the factors affecting cancer practice in West China.
A structured questionnaire was distributed to 184 patients, eliciting information about the patients’ characteristics, occupation, education, family life, recognition of illness, knowledge about BCS, the main means of gaining surgery information, selecting surgery approaches, preferences to breast reservation.
In all, 163 patients completed the questionnaire. The results indicated that only 7.4% of patients received BCS and 23% of the remaining patients desired to have BCS and the affecting factors were significantly associated with their family life, recognition of illness and the main means of gaining surgery information (P < 0.05). No associations were between BCS selecting and the other variables studied. The most frequent reasons for selecting BCS were keeping the female shape and improving quality of life (71%), the second most were postoperative recovery, minimal influence of physical function (47%) and patients’ knowledge about BCS (42%). The most frequent reasons for not selecting BCS were uncertainty about BCS results and worry about recurrence (81%), the second most was the elderly age unnecessary for BCS (40%).
The findings indicate that breast cancer patients in West China do not take BCS as the first choice as the best treatment method. It is warranted that further study of more patients, attitude of patients’ partners and physicians to BCS.
To get a more robust DNA methylation profile from the data given by a published article of a MZ study of psychiatry.
Considering the relevance of birth weight with DNA methylation profiles, we reanalyzed the data from the paper of Mill etc. (DOI: 10.1002/ajmg.b.30316) with rearrangement of the group order within twin pair, prior if lighter in birth weight. Statistical methods used are including mean, correlation and paired-samples t-test (considering twins’ particularity).
We calculated twin difference by lighter twin's methylation percentage minus that of heavier twin. The mean of CpG1 methylation differences is -7.08% while -7.17% for CpG2. The two means have no statistical significant difference in a paired-samples t-test (t=0.027, p=0.979, 2-tailed). These results are different from the original paper: 10.3% for CpG1 and 16.1% for CpG2, which are statistical significantly different (t=-2.792, p=0.018, 2-tailed). Besides, we found that in the lighter twin group, the methylation percentage are statistical significantly different between CpG1 and CpG2 (t=2.627, p=0.024, 2-tailed). As to correlation analysis, we got a slightly different result: correlation between MZ differences in two sites is weaker after rearrangement (r=0.875, while r=0.913 before arrangement, both p< 0.001).
According to our study, the results imply that twin differences may not be the only thing worthy of investigation. Different patterns among CpGs in certain kinds of subgroups should also need attention. We need conduct a robust data analysis strategy in our researches on the epigenetic aspects of psychiatry, where monozygotic twins have a favorable utility.
Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs.
Metabolic abnormality is common among schizophrenia patients. Some metabolic traits were found associated with subgroups of schizophrenia patients.
We examined a possible relationship between metabolic abnormality and psychosis profile in schizophrenia patients.
Three hundred and seventy-two chronic schizophrenia patients treated with antipsychotics for more than 2 years were assessed with the Positive and Negative Syndrome Scale. A set of metabolic traits was measured at scheduled checkpoints between October 2004 and September 2006.
Multiple regressions adjusted for sex showed negative correlations between body mass index (BMI) and total score and all subscales; triglycerides (TG) was negatively correlated with total score and negative syndrome, while HDLC was positively correlated with negative syndrome. When sex interaction was concerned, total score was negatively correlated with BMI but not with others; negative syndrome was negatively correlated with BMI and positively with HDLC. No metabolic traits were correlated with positive syndrome or general psychopathology.
Loss of body weight is a serious health problem in schizophrenia patients with severe psychosis syndrome, especially the negative syndrome. Schizophrenia patients with severe negative syndrome may have a distinct lipid pathophysiology in comparison with those who were less severe in the domain.
Patients with chronic kidney disease (CKD) have more cognitive impairments. However, the etiologies are not fully clear. Plasma homocysteine levels and vascular burden rise in CKD; meanwhile, high homocysteine levels and vascular factors are known risk factors of dementia in non-CKD patients. Thus, we aimed to investigate the association between homocysteine, vascular burden and cognitive impairment in CKD and to see if the effect of elevated homocysteine on cognitive impairment mediated by vascular factor.
146 patients with CKD and 69 normal comparisons were recruited. Cognitive function was evaluated by comprehensive neuropsychological tests assessing processing speed, executive function, language, visuospatial function, memory, and attention domains. Vascular burden was assessed by Framinghan cardiovascular risk scale (FCRS) which indicates risk of atherosclerotic diseases including stroke.
In controlled analysis, patients with CKD had lower scores in all cognitive domains, and had higher homocysteine levels (18.5±6.4 vs. 9.8±2.9, p< 0.0001) and FCRS(17.0±4.7 vs. 14.0±4.7, p< 0.0001). Among patients with CKD, higher homocysteine levels (p=0.026) were associated with lower score on digit symbol task which is related to processing speed and executive function with controlling for age, sex, education and stage of CKD. The association persisted (p=0.047) after controlling for vascular risks.
Patients with CKD had extensive cognitive impairments. Elevated homocysteine levels may be an risk factor, which is independent of vascular burden, of cognitive impairment on processing speed and executive function. Further studies to investigate if normalization of homocysteine can improve cognitive function will be suggested.
Previously, we reported the clinical efficacy of MPH-LA in adult ADHD evaluated in a 40-week, randomised, double-blind, placebo-controlled, multicentre core study [comprising of dose confirmation (9-week), real-life dose optimisation (5-week) and maintenance of effect phases (6- month)] (Atten Defic Hyperact Disord. 2013;(5):219–220). Here, we report the long-term efficacy from the 26-week extension phase of the same study.
During the extension phase, patients initiated treatment with MPH-LA 20 mg/day (oral, once daily capsules); uptitrated to optimal dose of 40, 60 or 80 mg/day in increments of 20 mg/week. Change in DSM-IV ADHD rating scale (RS) and SDS total scores at the end of study, were evaluated from the baseline of maintenance of effect phase of the core study and the baseline of extension phase.
At the end of the extension phase, the mean change in DSM-IV ADHD RS and SDS total scores from baseline of the maintenance of effect phase was −0.9 and −1.4 points respectively; and from baseline of extension phase was −7.2 and −4.8 respectively (Table). No new or unexpected safety concerns were observed during the extension phase.
MPH-LA continued to maintain clinical efficacy in adult ADHD patients over long-term.
Table DSM-IV ADHD RS, SDS total scores and change from baseline at the end of extension phase
Previous studies have shown that the polymorphisms in COMT gene and environmental factors affect the risk of drug dependence, but there’s no research shown in relapse of heroin dependence, and the mechanism underlying remains uncertain.
Examine the interaction between allelic variants of the catechol-O- methlytransferase (COMT) gene and environmental factors (encountering drug-related environmental situations, social support) in contribution to relapse in heroin dependence.
Construct the gene-environment interaction model in order to understand the mechanism for relapse in heroin dependence.
The 249 heroin dependent subjects who followed up at one year after abstinent by using the natural history interview (NHI), social support rateing Scale (SSRS), and other questionnaires were genotyped for eight tagging single nucleotide polymorphisms (SNP) on the COMT gene. General Multifactor Dimensionality Reduction (GMDR) was used to construct the gene-environment interaction model which impacting relapse in heroin dependence.
The relapse group had higher frequencies of encountering drug-related environment (EDE) and G allele and GG genotype frequencies on COMT gene rs4680 locus and less Social Support Scale scores than that in the abstinence group. Logistic regression analysis showed that encountering more drug-related environment and GG genotype carriers were the risk factors for relapse in heroin dependence. GMDR analysis showed that the COMT gene was interact with the frequency of EDE and social support level to impact the relapse in heroin dependence.
Gene-environment interaction between COMT gene and the frequency of EDE and social support were related to heroin dependence relapse.
Recent epidemiology studies have reported the prevalence of adult ADHD to be approximately 4%, however approved treatments are limited.
Primary objectives were to confirm the clinically-effective and safe dosage range of MPH-LA in adults with ADHD and evaluate the 6-month maintenance of effect.
Treatment Period (TP) 1: Patients were randomized to double-blind placebo, MPH-LA 40, 60, or 80 mg/day for 9- weeks (3-week titration, 6-week fixed-dose) to evaluate change in DSM-IV ADHD-RS and Sheehan Disability Scale (SDS) total score in TP1. TP2: 5-week titration to individual optimal dose. TP3: Patients were randomized to their optimal dose or placebo for 6-months double-blind withdrawal period to evaluate percentage of treatment failures during TP3.
Improvement from baseline in total score on the DSM-IV ADHD-RS and SDS was significantly greater than placebo for all MPH-LA dose levels (table). Patients treated with MPH-LA had significantly lower treatment failure rates (21.34%) compared to placebo in TP3 (49.6%; odds-ratio (95%CI=0.3 (0.2, 0.4); p< 0.0001). The safety results were consistent with the established safety profile for MPH-LA.
[Improvement by week 9: DSM-IV ADHD-RS and SDS].
N=Full Analysis Set for TP1 (All randomized patients receiving one dose of study drug in TP1)
MPH-LA administered at 40-80mg/day demonstrated superior ADHD symptom control and reduction in functional impairment compared to placebo and demonstrated maintenance of effect over 6 months. No unexpected adverse events were observed.