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Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e−14) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.
Our research group demonstrated that vitamin A restriction affected meat quality of Angus cross and Simmental steers. Therefore, the aim of this study is to highlight the genotype variations in response to dietary vitamin A levels. Commercial Angus and Simmental steers (n = 32 per breed; initial BW = 337.2 ± 5.9 kg; ~8 months of age) were fed a low-vitamin A (LVA) (1017 IU/kg DM) backgrounding diet for 95 days to reduce hepatic vitamin A stores. During finishing, steers were randomly assigned to treatments in a 2 × 2 factorial arrangement of genotype × dietary vitamin A concentration. The LVA treatment was a finishing diet with no supplemental vitamin A (723 IU vitamin A/kg DM); the control (CON) was the LVA diet plus supplementation with 2200 IU vitamin A/kg DM. Blood samples were collected at three time points throughout the study to analyze serum retinol concentration. At the completion of finishing, steers were slaughtered at a commercial abattoir. Meat characteristics assessed were intramuscular fat concentration, color, Warner-Bratzler shear force, cook loss and pH. Camera image analysis was used for determination of marbling, 12th rib back fat and longissimus muscle area (LMA). The LVA steers had lower (P < 0.001) serum retinol concentration than CON steers. The LVA treatment resulted in greater (P = 0.03) average daily gain than the CON treatment, 1.52 and 1.44 ± 0.03 kg/day, respectively; however, there was no effect of treatment on final BW, DM intake or feed efficiency. Cooking loss and yield grade were greater and LMA was smaller in LVA steers (P < 0.05). There was an interaction between breed and treatment for marbling score (P = 0.01) and percentage of carcasses grading United States Department of Agriculture (USDA) Prime (P = 0.02). For Angus steers, LVA treatment resulted in a 16% greater marbling score than CON (683 and 570 ± 40, respectively) and 27% of LVA Angus steers graded USDA Prime compared with 0% for CON. Conversely, there was no difference in marbling score or USDA Quality Grades between LVA and CON for Simmental steers. In conclusion, feeding a LVA diet during finishing increased marbling in Angus but not in Simmental steers. Reducing the vitamin A level of finishing diets fed to cattle with a high propensity to marble, such as Angus, has the potential to increase economically important traits such as marbling and quality grade without negatively impacting gain : feed or yield grade.
Se can enhance lactation performance by improving nutrient utilization and antioxidant status. However, sodium selenite (SS) can be reduced to non-absorbable elemental Se in the rumen, thereby reducing the intestinal availability of Se. The study investigated the impacts of SS and coated SS (CSS) supplementation on lactation performance, nutrient digestibility, ruminal fermentation and microbiota in dairy cows. Sixty multiparous Holstein dairy cows were blocked by parity, daily milk yield and days in milk and randomly assigned to five treatments: control, SS addition (0.3 mg Se/kg DM as SS addition) or CSS addition (0.1, 0.2 and 0.3 mg Se/kg DM as CSS addition for low CSS (LCSS), medium CSS (MCSS) and high CSS (HCSS), respectively). Experiment period was 110 days with 20 days of adaptation and 90 days of sample collection. Dry matter intake was higher for MCSS and HCSS compared with control. Yields of milk, milk fat and milk protein and feed efficiency were higher for MCSS and HCSS than for control, SS and LCSS. Digestibility of DM and organic matter was highest for CSS addition, followed by SS addition and then control. Digestibility of CP was higher for MCSS and HCSS than for control, SS and LCSS. Higher digestibility of ether extract, NDF and ADF was observed for SS or CSS addition. Ruminal pH decreased with dietary Se addition. Acetate to propionate ratio and ammonia N were lower, and total volatile fatty acids (VFAs) concentration was greater for SS, MCSS and HCSS than control. Ruminal H ion concentration was highest for MCSS and HCSS and lowest for control. Activities of cellobiase, carboxymethyl-cellulase, xylanase and protease and copies of total bacteria, fungi, Ruminococcus flavefaciens, Fibrobacter succinogenes and Ruminococcus amylophilus increased with SS or CSS addition. Activity of α-amylase, copies of protozoa, Ruminococcus albus and Butyrivibrio fibrisolvens and serum glucose, total protein, albumin and glutathione peroxidase were higher for SS, MCSS and HCSS than for control and LCSS. Dietary SS or CSS supplementation elevated blood Se concentration and total antioxidant capacity activity. The data implied that milk yield was elevated due to the increase in total tract nutrient digestibility, total VFA concentration and microorganism population with 0.2 or 0.3 mg Se/kg DM from CSS supplementation in dairy cows. Compared with SS, HCSS addition was more efficient in promoting lactation performance of dairy cows.
We aimed to assess the incidence of obstructive sleep apnoea (OSA) in people with schizophrenia, to explore clinical associates with OSA and how well OSA screening tools perform in this population.
All patients registered in a community outpatient Clozapine clinic, between January 2014 and March 2016, were consecutively approached to participate. Participants were screened for OSA using at home multichannel polysomnography (PSG) and were diagnosed with OSA if the apnoea-hypopnoea index (AHI) was >10 events/hr. Univariate comparison of participants to determine whether AHI > 10 events/hr was associated with demographic factors, anthropometric measures and psychiatric symptoms and cognition was performed. The sensitivity, specificity, positive predictive value and negative predictive value of the commonly used sleep symptoms scales and OSA screening tools were also determined.
Thirty participants were recruited, 24 men and 6 women. Mean age was 38.8 (range: 25–60), and mean body mass index (BMI) was 35.7 (range 19.9–62.1). The proportion of participants with OSA (AHI > 10 events/hr) was 40%, 18 (60%) had no OSA, 4 (13%) had mild OSA (AHI 10.1–20), zero participants had moderate OSA (AHI 20.1–30) and 8 (27%) had severe OSA (AHI > 30). Diagnosis of OSA was significantly associated with increased weight, BMI, neck circumference and systolic blood pressure. Diagnosis of OSA was not significantly associated with Positive and Negative Symptoms Scale, Montgomery Asperger’s Depression Rating Scale, Personal and Social Performance scale or Brief Assessment of Cognition for Schizophrenia scores. All OSA screening tools demonstrated poor sensitivity and specificity for a diagnosis of OSA.
OSA was highly prevalent in this cohort of people with schizophrenia and was associated with traditional anthropometric OSA risk factors.
Thermal barrier coating is a high-temperature protective technology widely used in industrial gas turbines. However, the failure of coating peeling because of the generation of thermally grown oxide (TGO) at the interface during service hinders its further application. In this study, Raman spectroscopy and wedge indentation are used to determine the TGO residual stress and the interface energy release rate, respectively. The effect of TGO on the interfacial fracture toughness during the growth process was discussed. Raman spectroscopy test results show that the residual stress of TGO is about 0.5 GPa. Wedge indentation test results illustrate that high-temperature heat treatment could accelerate the interface degradation of thermal barrier coatings. Stress analysis and test research demonstrate that the microcracks induced by compressive stress of TGO will propagate with increasing heating time, ending with failure of barrier coatings.
Longitudinal studies predictably experience non-random attrition over time. Among older adults, risk factors for attrition may be similar to risk factors for outcomes such as cognitive decline and dementia, potentially biasing study results.
To characterize participants lost to follow-up which can be useful in the study design and interpretation of results.
In a longitudinal aging population study with 10 years of annual follow-up, we characterized the attrited participants (77%) compared to those who remained in the study. We used multivariable logistic regression models to identify attrition predictors. We then implemented four machine learning approaches to predict attrition status from one wave to the next and compared the results of all five approaches.
Multivariable logistic regression identified those more likely to drop out as older, male, not living with another study participant, having lower cognitive test scores and higher clinical dementia ratings, lower functional ability, fewer subjective memory complaints, no physical activity, reported hobbies, or engagement in social activities, worse self-rated health, and leaving the house less often. The four machine learning approaches using areas under the receiver operating characteristic curves produced similar discrimination results to the multivariable logistic regression model.
Attrition was most likely to occur in participants who were older, male, inactive, socially isolated, and cognitively impaired. Ignoring attrition would bias study results especially when the missing data might be related to the outcome (e.g. cognitive impairment or dementia). We discuss possible solutions including oversampling and other statistical modeling approaches.
The aim of this study was to clarify effects of Clozapine and its metabolites on insulin resection and expression of glucose transporter 2 (GLUT2) located in cell membrane of isolated rat's islets.
The cells of isolated rat's islets were prepared by a modified collagenase digestion methods. At 5.5 mmol/L glucose, the cells of islets was treated with 1mmol/L clozapine, desmethyl-clozapine(DCLO), clozapine N-oxide(CNO), respectively, blank control group was also set.
1. After incubation 48h, the insulin in supernatant was assayed by radioimmunoassay.
2. The cells of isolated rat's islets in each group were detected GLUT2 mRNA level with RT-PCR and its protein expression with Western-blot.
1. Compared to control group, clozapine significantly inhibited insulin secretion (P=0.007< 0.01); DCLO has a tendency to inhibit insulin secretion after 48h of incubation, but no significant difference was found (P=0.154>0.05). There was no difference of insulin secretion between CNO group and the control group after 48h of incubation (P>0.05).
2. The mRNA and protein expression of GLUT2 located in cell membrane of slets: clozapine group was significantly lower than control group (P=0.017< 0.05, P=0.035< 0.05), DCLO group was also lower than control group, but no significant difference was found (P>0.05), and no significant difference between CNO group and control group (P>0.05).
Clozapine can inhibit GLUT2 expression of cells of islets, and then hamper glucose transport through cell membrane, which was one of mechanisms to explain the effect of clozapine on insulin secretion.
To investigate the executive function and learning ability of the patients with first-episode schizophrenia, and its relationship with the patients’ clinical symptoms.
50 schizophrenia patients and 50 healthy controls were tested by the Tower of London (TOL). All the subjects received two phases of the test of TOL continuously, with a break of 1 minute. And Positive and Negative Symptom Scale (PANSS) was used to assess the clinical symptoms of the patients.
Compared with the control group, the number of reply during the 1st phase (x1) and the 2nd phase (x2)of the patients group, was lower (P<0.01); the reaction time during the 1st phase (t1) and the 2nd phase (t2) was longer (P<0.01); while the rate of correct answer during the 1st phase (p1) and the 2nd phase (p2) do not differ. For the control group, x2 was higher than x1 (P<0.01), and t2 was shorter than t1 (P<0.01). However, for the schizophrenia group, there were no difference between x1 and x2, t1 and t2. The value of x1, p1, x2 of the patients were correlated negatively with the PANSS negative subscale score (P< 0.05), and t1 and t2 were correlated positively with the the negative subscale score (P< 0.01). The performance of the TOL did not correlated with the PANSS positive subscale score and general psychopathology subscale score.
The executive function and learning ability of the schizophrenics are impaired and the impairment of the cognitive function is significantly correlated with the negative symptoms of schizophrenia patients.
The aim of this study was to compare the clinical efficacy and the safety of venlafaxine and fluoxetine in the treatment of obsessive-compulsive disorder (OCD).
One hundred and Eight inpatients who met the Diagnostic and Statistical Manual of Mental Disorders, the Forth Edition(DSM-IV) for OCD were involved in this study. The subjects were randomly divided into venlafaxine group or fluoxetine group. Efficacy of venlafaxine and fluoxetine in treatment of OCD were assessed with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression-Severity(CGI-S), the side effects were evaluated with Treatment Emergent Symptom Scale (TESS).
The therapeutic efficacy in venlafaxine group was similar to that in fluoxetine (70.36%vs68.29%, P>0.05) after eight weeks’ therapy. The improve-rates of Y-BOCS after 2 weeks’ therapy of venlafaxine were significant higher than those of baseline, while the improve-rates of Y-BOCS after 4 weeks’ therapy of fluoxetine were significant higher than those of baseline(P< 0.05). The side effects of venlafaxine group were similar to fluoxetine group (P>0.05).
The results indicate that both venlafaxine and fluoxetine is effective in the treatment of OCD, but venlafaxine work faster than fluoxutine.
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.
This unique study of treatment of the mixed state of bipolar I disorder using simultaneous depression and mania response criteria compared divalproex monotherapy versus olanzapine augmentation in a 6-week, randomized, double-blind trial.
Patients (age 18-60 years) with 14-28 days of divalproex monotherapy (blood levels of 75-125 μg/mL) were randomized to augmentation with olanzapine 5-20 mg/day or placebo. Data collected included: Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Clinical Global Impression for Bipolar Illness (CGI-BP), hospitalizations, concomitant medications, and adverse events (AEs). Primary co-objectives were comparisons of baseline to endpoint changes in HDRS and YMRS. Secondary objectives included comparisons of times to onset (25% reduction) and response (50% reduction) in both HDRS and YMRS, change in CGI-BP, hospitalizations, and safety.
Patients were 59% female, 51% Caucasian, 33% African American, and 14% Hispanic with mean standard deviation (SD) HDRS and YMRS scores of 22.2 (4.5) and 20.9 (4.4). Mean standard error (SE) score changes for the olanzapine (n=100) or placebo (n=101) arms, respectively, were: HDRS, -9.37 (.55) and -7.69 (.54), p=.022; YMRS, -10.15 (.44) and -7.68 (.44), p< .001; and CGI-BP, -1.34 (.11) and -1.06 (.11), p=.056. Times-to-onset (median 7 vs 14 days) and response (median 25 vs 49 days) were significantly shorter for olanzapine augmentation. One olanzapine patient required hospitalization (p=1.0). Treatment-emergent AEs were consistent with previously-published rates.
Six-week olanzapine treatment augmentation was associated with greater and earlier reduction of manic and depressive symptoms in mixed episode patients on divalproex treatment.
Effectiveness of medication treatment is determined by three components: treatment efficacy (symptom reduction), tolerability/safety, and adherence. Compared with efficacy and safety, research into adherence has been lacking. Nevertheless, medication non-adherence is a risk factor for relapse and for aggressive behavior in association with substance abuse in schizophrenia patients. Non-adherence has been estimated to cause approximately 40% of relapses in patients with schizophrenia. High rates of treatment discontinuation in all arms of the CATIE study illustrate the widespread nature of non-adherence. Most of previous research has defined non-adherence as a complete discontinuation of medication. However, many schizophrenia patients show partial adherence: they do not completely discontinue their medication, but they do not take all that has been prescribed. Partial adherence is more difficult to define and study than complete non-adherence.
e had the opportunity to study partial adherence in the context of a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10mg/d, 20 mg/d and 40 mg/d for patients with schizophrenia or schizoaffective disorder (N=599). Medication non-adherence was measured by pill counts. Baseline characteristics including demographics, illness history and symptom severity were investigated as potential risk factors for treatment non-adherence.
Results and conclusion
Approximately 1/3 of patients were non-adherent with their medication at least once during the 8-week study. These non-adherent patients had significantly less improvement compared to adherent patients. Adherent patients had greater weight gain than the non-adherent ones. Among the available baseline measures, greater baseline depression severity appeared to be a significant risk factor for non-adherence.
Cognitive dysfunction was thought to be one of the core features of schizophrenia. And the executive function of the patients was paid more attention by more and more researchers and clinicians.
To investigate the executive function and the learning ability of the patients with first-episode schizophrenia, and their relationships with psychiatric symptoms.
Fifty cases of first-episode schizophrenia patients and fifty age- and gender-matched healthy controls were tested by a computerized version of Tower of London (TOL) test. The scores of the Positive and Negative Syndrome Scale(PANSS) in the group of schizophrenia patients were over 60.
The numbers of the correct answer [x1 :(14.62 ± 4.12), x2: (14.80 ± 4.70)] during the first session and the second session of the TOL test of the patients group were significantly lower than that of the control group [x1: (17.48 ± 3.79), x2:(18.68 ± 3.19)], and the reaction times [t1: (9.27 ± 4.37) seconds, t2: (9.51 ± 5.58) seconds] of the two sessions of TOL were longer than the control group [t1: (7.28 ± 2.04) seconds, t2: (6.67 ± 1.51) seconds], P < 0.01. For the control group, x2 was significantly greater than x1, and t2 shorter than t1 (P < 0.01), while for the patients group, there was no difference between the performances of the first session and the second session. The scores of TOL in the schizophrenia patients were correlated with the negative symptom score of PANSS (P < 0.05) and were not correlated with the scores of other subscales of PANSS (P > 0.05).
The executive function and the learning ability of schizophrenia are impaired and the cognitive dysfunction is correlated with negative symptoms.
To compare therapeutic efficacy, social function, discontinue rate, relapse and recurrence rate of the depression outpatients with first episode between Venlafaxine extended release and Fluoxertine hydrochloride treatment. Methods In this 48 week natural parallel follow-up study, total 188 patients who meet ICD-10 criteria for a major depressive episode were admitted and assigned to receive either Venlafaxine Extended Release (Venlafaxine XR group) (n=89) or Fluoxertine hydrochloride(Fluoxertine group) (n=99).At baseline,week2,8,12,16,24,32,48,Hamilton Rating Scale for Depression (HAMD)-17 item was used to value disease severity, and Social Disability Screening Schedule(SDSS)for social disability, and the discontinue, relapse and recurrence rates were compared. Results (1) At week 24 Venlafaxine XR group had much lower HAMD17 total score than Fluoxertine group (P<0.05). (2)The remission rate and response rate between two groups had no statistical difference (P>0.05). (3) At week 12, Venlafaxine XR group had a higher SDSS score than Fluoxertine group (P<0.05).(4)At week 12, 16, 24, 32,48,Venlafaxine XR group displayed lower discontinue rates (P<0.05). Venlafaxine XR group had a longer treatment course than Fluoxertine did [(30.99±15.98) weeks vs. [(22.57±15.26) weeks] (P<0.01). (5) The relapse and recurrence rates of two groups had no statistical difference (P>0.05). Conclusions In the acute phase, Venlafaxine XR has a better effect for social function and treatment adherence than Fluoxertine hydrochloride. In the continued phase and sustained phase, Venlafaxine XR performs better for symptoms relief and treatment adherence.Venlafaxine XR has parallel performance with Fluoxertine hydrochloride by the terms of therapeutic efficacy, social function restore, relapse and recurrence rate.
To observe the changes of glucocorticoid receptors(GR) in the nucleus raphes magnus (NRM)neurons of PTSD-like rats.
25 male Wistar rats were randomly divided into PTSD model 1d, 4d, 7d, 14d groups and a normal group with 5 rats in each group. Rats in model groups were treated with SPS procedure to reproduce PTSD model.The changes of expression of GR in NRM of rats were detected by immunohistochemistry and PCR in each group, and image analysis and statistical analysis were performed in each group.
GR was distributed in the nucleus of neurons. The expression of GR was sharply decreased on 1d, but gradually increased on 4d and 7d, then decreased on 14d. All of 4d, 7d, 14d are higher than the normal (P < 0.05).
The lasting dysfunction of GR in the nucleus raphes magnus (NRM) may play an important role in post-traumatic stress disorder rats.
Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
Depression and anxiety disorders are prevalent mental disorders in China. But some those patients do not seek help from psychiatrists firstly but see internists first.
Objectives and aims
This study aimed to investigate the prevalence of depressive - anxiety disorders in gastroenterology outpatients and assess the detection rate provided by physicians in China.
A multicenter, hospital-based cross-sectional study was carried on in the 15 large general hospitals of five cities cross China. A total of 1995 gastroenterological outpatients were screened by Hospital Anxiety and Depression Scale (HADS). Subjects whose HADS scores ≥ 8 were interviewed by psychiatrists, using Mini International Neuropsychiatric Interview (M.I.N.I) to make further diagnoses. Physicians’ diagnoses and treatment were recorded.
The adjusted prevalence of depressive disorder and anxiety disorders was 14.39% and 9.42% respectively.
The prevalence of depressive-anxiety disorder is high in gastroenterology outpatients in China, which suggests the related training of detecting these mental disorders is needed to gastroenterologists.
This double-blind (DB), relapse prevention, phase-3 study was designed to evaluate the efficacy and safety of paliperidone palmitate long-acting 3-monthly formulation (PP3M) versus placebo in delaying time-to-relapse of schizophrenia symptoms.
Adults (18-70 years old) with schizophrenia (DSM-IV-TR) were treated with PP (17-week, open-label [OL] transition phase: 50, 75, 100, or 150 mg eq, once-monthly, [PP1M]; 12-week OL maintenance phase: 3.5-fold PP1M stabilized dose, single injection), and then randomized (1:1) to PP3M fixed doses (175, 263, 350 or 525 mg eq.) or placebo.
305/506 patients enrolled were randomized (PP3M: n=160; placebo: n=145); majority were men (75%), white (59%), mean age 38.4 years. Interim analysis results favored PP3M vs. placebo (p = 0.0002, two-sided log-rank test; HR: 3.45, 95% CI: 1.73; 6.88); median time-to-relapse was 274 days in placebo and not estimable in PP3M group. Final results were consistent with interim analysis. Both PANSS total score and CGI-S score showed a significant effect over time in PP3M- vs. placebo-treated patients (p>0.001). 330/506 (65.2%) patients in OL phase and 183/305 (60.0%) in DB phase (PP3M: 61.9% vs. placebo: 57.9%) had ≥1 treatment-emergent adverse event (TEAE). The TEAEs noted more frequently in PP3M-vs. placebo (DB phase) were nasopharyngitis (5.6% vs. 1.4%), weight gain (8.8% vs. 3.4%), headache (8.8% vs.4.1%) and akathisia (4.4% vs. 0.7%).
Compared with placebo, PP3M significantly delayed time to first relapse in patients with schizophrenia, previously treated for 4 months with PP1M. PP3M was tolerable with a safety profile generally consistent with other marketed formulations of paliperidone.