Development and its reliability and validity of the Knowledge, Attitude and Practice Scale for Informal Caregivers of Pressure Injury Patients. / åŽ‹åŠ›æ€§æŸä¼¤æ‚£è€ éžæ­£å¼ç §é¡¾è€ çŸ¥ä¿¡è¡Œé‡è¡¨çš„ç¼–åˆ¶åŠä¿¡æ•ˆåº¦æ£€éªŒ.

OBJECTIVES: There is a lack of scientifically validated tools to measure the knowledge attitude and practice (KAP) of informal caregivers for patients with pressure injury (PI). This study aims to develop a KAP Scale for Informal Caregivers of PI Patients and to evaluate its reliability and validity. METHODS: Based on the KAP theory framework and relevant literature, an initial pool of items was created through expert brainstorming sessions. The initial scale was formed after a Delphi expert consultation and a preliminary survey. From April to October 2023, a convenient sample of informal caregivers for PI patients was recruited from an inpatient department of the Third Xiangya Hospital of Central South University, as well as its associated community and nursing homes. The first round included 186 participants, and the second round included 213 participants, who were used for item analysis and reliability and validity testing. After a 3-week interval, 20 participants from the initial group were randomly selected for a retest to assess the test-retest reliability of the scale. RESULTS: The KAP Scale for informal caregivers of PI patients consists of 3 dimensions with 19 items. The overall internal consistency (Cronbach's α) of the scale was 0.916. The item-level content validity index (I-CVI) ranged from 0.826 to 1.000, and the scale level-content validity index/average (S-CVI/Ave) was 0.94. Exploratory factor analysis extracted 3 common factors, accounting for 64.643% of the total variance. Confirmatory factor analysis showed that the model fit the data well, with χ2/df=2.54, root mean square error of approximation (RMSEA)=0.085, comparative fit index (CFI)=0.920, and standardized root mean square residual (SRMR)=0.059. CONCLUSIONS: The KAP scale for informal caregivers of PI patients demonstrates good reliability and validity and can be used to assess the KAP levels of informal caregivers regarding PI.

Effectiveness of micro-lecture based cardiac rehabilitation education on health status in individuals with coronary artery disease: A randomized clinical trial.

OBJECTIVE: To explore the effectiveness of the micro-lecture education on the ability of self-management and lifestyle changes in patients with coronary artery disease. DESIGN: A randomized control trial with a 12-week follow-up. SETTING: Cardiology wards of a large Chinese University Hospital. SUBJECTS: One hundred eligible inpatients with coronary artery disease were recruited. INTERVENTION: Intervention group received the micro-lecture education, while the control group received the traditional cardiac rehabilitation education. MAIN MEASURES: Primary outcome of the ability of coronary self-management was assessed by the Coronary self-management scaleat baseline, 12-week after discharge. Secondary outcomes of smoking status, exercise status, and six-minute walk distance were evaluated at the baseline, week4 and week 12 after discharge. The chi-square test,Fisher's exact test, group t-test and the repeated measure variance were used for the data analysis. RESULTS: Eighty-nine of 100 eligible participants responded, and mean age was 60.2 ± 11.3 years.After the intervention, the mean score of the coronary self-management scale (3.84 ± 0.36) was higher than that in the control group (2.78 ± 0.57).At week 12, the rate of re-smoked in the intervention group (6%) was significantly lower than that in the control group (43%),the frequency of the exercise (85%), and the 6MWD (495.55 ± 85.94) in the intervention group were better than the control group. CONCLUSION: Micro-lecture education program presented a positive effect on promoting the ability of self-management, and apotential effect on the therapeutic lifestyle changes for the coronary artery disease patients.

Comparison of outcomes between postpartum and non-postpartum women with stress urinary incontinence treated with conservative therapy: A prospective cohort study.

AIM: This study aimed to compare the outcomes of pelvic floor muscle training (PFMT) between postpartum and non-postpartum women with stress urinary incontinence (SUI) and to detect potential factors that may influence these outcomes. METHODS: A total of 54 and 79 participants were recruited into postpartum (PP group) and non-postpartum (non-PP group) groups, respectively. A physiotherapist treated the participants twice a week for 6-8 weeks. At baseline and 6 and 12 months after treatment, the 1-h pad weight test (PWT), vaginal contraction pressure (VCP), and Incontinence Impact Questionnaire Short Form (IIQ-7) were assessed by an evaluator or physiotherapist. The primary outcome was PWT improvement. The participants whose PWT improvement reached a >50% reduction relative to baseline were considered responders. Secondary outcomes included VCP, IIQ-7 score, and patient satisfaction rate. RESULTS: The PWT improvement was 87.04% (95%CI: 0.78, 0.96) in the PP group at 1-year follow-up, which was significantly better than the 72.15% improvement (95%CI: 0.62, 0.82) in the non-PP group (OR = 2.591, 95%CI: 1.018, 6.595, P = 0.041). Changes in VCP and BMI were significant predictors of responders in the regression analysis. As the change in VCP increased by 1 cmH2 O, the efficiency increased by 4.2% (OR = 1.042, 95%CI: 1.010, 1.070). The change in BMI increased by 1 kg/m2 , and the efficiency decreased 23.0% (OR = 0.770, 95%CI: 0.633, 0.937). CONCLUSIONS: The outcome of PFMT in postpartum participants with SUI was better than that in non-postpartum participants. Women with more improvements in VCP and weight loss showed better amelioration of SUI symptoms after PFMT.

The Research and Evaluation of Antipsychotic Treatment in Community Behavioral Health Organizations, Outcomes (REACH-OUT) study: real-world clinical practice in schizophrenia.

BACKGROUND: Outpatient facilities, such as community behavioral health organizations (CBHOs), play a critical role in the care of patients with serious mental illness, but there is a paucity of "real-world" patient outcomes data from this health care setting. Therefore, we conducted The Research and Evaluation of Antipsychotic Treatment in Community Behavioral Health Organizations, Outcomes (REACH-OUT) trial, a real-world, prospective, noninterventional observational study of patients with mental illness treated at CBHOs across the United States. We describe demographic and clinical characteristics, antipsychotic therapy (APT) treatment patterns, and health care resource utilization in patients with schizophrenia undergoing medical care as usual. METHODS: This study enrolled adults with schizophrenia or bipolar I disorder who initiated APT treatment at various time points: 1) within 8 weeks of initiating risperidone long-acting injectables (RLAIs) or other APTs except paliperidone palmitate (PP), 2) after more than 24 weeks of continuous RLAI treatment, or 3) at any time after initiating PP LAI treatment (schizophrenia only). Study assessments were performed via participant interview, medical chart abstraction, and clinical survey at enrollment and at month 12. RESULTS: A total of 1065 patients from 46 CBHOs were enrolled. Of these, 944 (88.6%) had a diagnosis of schizophrenia and 121 (11.4%) had bipolar I disorder. At enrollment, 599 (63.5%) of patients with schizophrenia were receiving RLAIs or PP LAI, 281 (29.8%) were receiving oral APTs, and 64 (6.8%) were receiving other injectable APTs. A number of differences in patient characteristics and outcomes were observed between patients in the LAI APT cohort and the oral APT cohort. CONCLUSION: Descriptive analyses from this observational study suggest differences in the patient characteristics, treatment patterns, and clinical and economic outcomes among those with schizophrenia treated at CBHOs with LAI APT or oral APTs. Additional analyses will be conducted to delineate the impact of LAI APT versus oral APTs on patient outcomes. TRIAL REGISTRATION: Clinical Trial Registry: NCT01181960 . Registered 12 August 2010.

Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia.

OBJECTIVE: This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs). METHODS: PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity. RESULTS: Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%. CONCLUSIONS: Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Factors impacting the behavior of phytoremediation in pesticide-contaminated environment: A meta-analysis.

Phytoremediation provides substantial advantages, including eco-friendliness, cost-effectiveness, efficiency, and visual appeal. However, the current knowledge of the factors influencing phytoremediation in pesticide-contaminated environments remains limited. It is critical to understand phytoremediation and the factors affecting the variation in removal efficiency. In this study, we compiled 72 previous research articles to quantify plant-induced improvements in removal efficiency and identify factors that influence variations in phytoremediation behavior through meta-analysis. We observed a significant increase in the removal efficiency of phytoremediation compared to the control group which did not involve phytoremediation. Pesticides significantly affect removal efficiency in terms of their modes of action, substance group, and properties. Plants demonstrated higher efficiency in remediating environments contaminated with pesticides possessing lower molecular masses and log Kow values. Plant species emerged as a crucial determinant of variations in removal efficiency. Annual plants exhibited a 1.45-fold higher removal efficiency than perennial plants. The removal efficiencies of different plant types decreased in the following order: agri-food crops > aquatic macrophytes > turfgrasses > medicinal plants > forage crops > woody trees. The Gramineae family, which was the most prevalent, demonstrated a robust and consistent phytoremediation ability. This study offers a more comprehensive triangular relationship between removal efficiency, pesticides, and plants, expanding the traditional linear model. Our findings offer valuable insights into the behavior of phytoremediation in pesticide-contaminated environments and the factors determining its success, ultimately guiding further research toward developing strategies for higher removal efficiency in phytoremediation.

Evaluation of Traumatic Subdural Hematoma Volume by Using Image Segmentation Assessment Based on Deep Learning.

Rapid and accurate evaluations of hematoma volume can guide the treatment of traumatic subdural hematoma. We aim to explore the consistency between the measurement results of traumatic subdural hematoma (TSDH) using a deep learn-based image segmentation algorithm. A retrospective study was conducted on 90 CT images of patients diagnosed with TSDH in our hospital from January 2019 to January 2022. All image data were measured by manual segmentation, convolutional neural networks (CNN) algorithm segmentation, and ABC/2 volume formula. With manual segmentation as the "golden standard," a consistency test was carried out with CNN algorithm segmentation and ABC/2 volume formula, respectively. The percentage error of CNN algorithm segmentation is less than ABC/2 volume formula. There is no significant difference between CNN algorithm segmentation and manual segmentation (P > 0.05). The area under curve of the ABC/2 volume formula, manual segmentation, and CNN algorithm segmentation is 0.811 (95% CI: 0.717~0.905), 0.840 (95% CI: 0.753~0.928), and 0.832 (95% CI: 0.742~0.922), respectively. From our results, the algorithm based on CNN has a good efficiency in segmentation and accurate calculation of TSDH hematoma volume.

Resource utilization in patients with schizophrenia who initiated risperidone long-acting therapy: results from the Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE).

BACKGROUND: Schizophrenia is a chronic mental health disorder associated with increased hospital admissions and excessive utilization of outpatient services and long-term care. This analysis examined health care resource utilization from a 24-month observational study of patients with schizophrenia initiated on risperidone long-acting therapy (RLAT). METHODS: Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation (SOURCE) was a 24-month observational study designed to examine real-world treatment outcomes by prospectively following patients with schizophrenia initiated on RLAT. At baseline visit, prior hospitalization and ER visit dates were obtained for the previous 12 months and subsequent hospitalization visit dates were obtained at 3-month visits, if available. The health care resource utilization outcomes measures observed in this analysis were hospitalizations for any reason, psychiatric-related hospitalizations, and emergency room (ER) visits. Incidence density analysis was used to assess pre-event and postevent rates per person-year (PY). RESULTS: The primary medical resource utilization analysis included 435 patients who had a baseline visit, ≥1 postbaseline visits after RLAT initiation, and valid hospitalization dates. The number of hospitalizations and ER visits per PY declined significantly (p < .0001) after initiation with RLAT. A 41% decrease (difference of -0.29 hospitalizations per PY [95% CI: -0.39 to -0.18] from baseline) in hospitalizations for any reason, a 56% decrease (a difference of -0.35 hospitalizations per PY [95% CI: -0.44 to -0.26] from baseline) in psychiatric-related hospitalizations, and a 40% decrease (-0.26 hospitalizations per PY [95% CI: -0.44 to -0.10] from baseline) in ER visits were observed after the baseline period. The percentage of psychiatric-related hospitalizations decreased significantly after RLAT initiation, and patients had fewer inpatient hospitalizations and ER visits (all p < .0001). CONCLUSION: The results suggest that treatment with RLAT may result in decreased hospitalizations for patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00246194.

Assessment of effectiveness measures in patients with schizophrenia initiated on risperidone long-acting therapy: the SOURCE study results.

BACKGROUND: To evaluate effectiveness outcomes in a real-world setting in patients with schizophrenia initiating risperidone long-acting therapy (RLAT). METHODS: This was a 24-month, multicenter, prospective, longitudinal, observational study in patients with schizophrenia who were initiated on RLAT. Physicians could change treatment during the study as clinically warranted. Data were collected at baseline and subsequently every 3 months up to 24 months. Effectiveness outcomes included changes in illness severity as measured by Clinical Global Impression-Severity (CGI-S) scale; functional scores as measured by Personal and Social Performance (PSP) scale, Global Assessment of Functioning (GAF), and Strauss-Carpenter Levels of Functioning (LOF); and health status (Medical Outcomes Survey Short Form-36 [SF-36]). Life-table methodology was used to estimate the cumulative probability of relapse over time. Adverse events were evaluated for safety. RESULTS: 532 patients were enrolled in the study; 209 (39.3%) completed the 24-month study and 305 (57.3%) had at least 12 months of follow-up data. The mean (SD) age of patients was 42.3 (12.8) years. Most patients were male (66.4%) and either Caucasian (60.3%) or African American (23.7%). All changes in CGI-S from baseline at each subsequent 3-month follow-up visit were statistically significant (p < .0001), indicating improvement in disease severity. Improvements were also noted for the PSP, GAF, and total LOF, indicating improvement in daily functioning and health outcome. CONCLUSIONS: Patients with schizophrenia who were initiated on RLAT demonstrated improvements in measures of effectiveness within 3 months, which persisted over 24 months. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00246194.

A novel mutation within the 2B rod domain of keratin 9 in a Chinese pedigree with epidermolytic palmoplantar keratoderma combined with knuckle pads and camptodactyly.

Knuckle pads and camptodactyly are overlapping symptoms associated with many genetic and environmental factors. To the best of our knowledge, all reported cases of epidermolytic palmoplantar keratoderma (EPPK) with knuckle pads have been without accompanying camptodactyly. We here report a novel KRT9 mutation-EPPK family with combined knuckle pads and camptodactyly. All the EPPK-affected individuals in this southern Chinese pedigree suffered severe diffuse palmar and plantar hyperkeratosis including hyperhidrosis and cuticle splitting: 3 females presented EPPK only, 8 adult males had notably severe knuckle pads and camptodactyly as well as EPPK, and one 6-year-old boy manifested EPPK with knuckle pads. Haplotype analysis excluded the known candidate loci for camptodactyly and/or knuckle pad-like phenotypes on chromosomes 13q12, 3q11.2-q13.12, 1q24-q25, 4p16.3 and 16q11.1-q22, while only the markers D17S1787 and D17S579 flanking KRT9 showed co-segregation with EPPK. Then a novel c.T1373C (p.L458P) mutation within the sixth exon of KRT9 was validated, and this mutation presented a more severe pathogenicity than the previously reported p.L458F. We speculated that KRT9 plays a complicated role in the genesis of EPPK with knuckle pads and camptodactyly, which needs to be further investigated.

Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium.

BACKGROUND: Because wide variations in mental health care utilization exist throughout the world, determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients. The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy (RLAT) for schizophrenia across countries. METHODS: This was a pragmatic analysis of data from two prospective observational studies conducted in the US (Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [SOURCE]; ClinicalTrials.gov registration number for the SOURCE study: NCT00246194) and Spain, Australia, and Belgium (electronic Schizophrenia Treatment Adherence Registry [eSTAR]). Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation. Clinical improvement was evaluated using the Clinical Global Impressions-Severity (CGI-S) and Global Assessment of Functioning (GAF) scales, and change from baseline was evaluated using paired t tests. Psychiatric hospitalization rates were analyzed using incidence densities, and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods. RESULTS: The initial sample comprised 3,069 patients (US, n = 532; Spain, n = 1,345; Australia, n = 784; and Belgium, n = 408). In all, 24 months of study participation, completed by 39.3% (n = 209), 62.7% (n = 843), 45.8% (n = 359), and 64.2% (n = 262) of patients from the US, Spain, Australia, and Belgium, respectively, were included in the clinical analysis. Improvements compared with baseline were observed on both clinical assessments across countries (P < 0.001 at all post-baseline visits). The mean improvement was approximately 1 point on the CGI-S and 15 points on the GAF. A total of 435 (81.8%), 1,339 (99.6%), 734 (93.6%), and 393 (96.3%) patients from the US, Spain, Australia, and Belgium, respectively, had ≥1 post-baseline visit and were included in the analysis of psychiatric hospitalization rates. Hospitalization rates decreased significantly in all countries regardless of hospitalization status at RLAT initiation (P < 0.0001) and decreased significantly in the US and Spain (P < 0.0001) when the analysis was limited to outpatients only. CONCLUSIONS: RLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US, Spain, Australia, and Belgium, despite differences in health care delivery systems.

Promoting resilience and lower stress in nurses and improving inpatient experience through emotional intelligence training in China: A randomized controlled trial.

BACKGROUND: Emotional intelligence training relieves stress and promotes resilience among nurses. Previous studies have not sufficiently explored the effect of emotional intelligence training among nurses on the experience of inpatients under their care. OBJECTIVE: To explore the effects of emotional intelligence training on emotional intelligence, resilience, and perceived stress among nurses and examine how training affects inpatient experience. DESIGN: Randomized controlled trial. SETTING: A tertiary general hospital in Changsha, China. PARTICIPANTS: A total of 103 nurses were randomly selected from 20 wards. METHODS: The wards were randomized into two groups. The intervention group (n = 53 nurses) received emotional intelligence training in two phases: Phase I-system training phase, twice a week for one month; Phase II-a consolidated learning phase, once a week for 11 months. The control group (n = 50) received daily briefings in meetings between head nurses, which were held regularly to discuss specific problems. There was no emotional intelligence training conducted with the control group. Data were collected at baseline and after the intervention. RESULTS: Emotional intelligence training improved emotional intelligence, resilience, and stress in the intervention group. The control group scored lower on the Wong and Law's Emotional Intelligence Scale and all subscales, showed stability in the scores on the Connor-Davidson Resilience Scale and its subscales, and very little change in stress scores. Repeated measures analysis of variance showed significantly greater beneficial changes in the intervention group on all but the optimism subscale. There were suggestive differences in the predicted direction between the emotional intelligence training wards and the control wards at post-test on the patient experience scale and the four subscales. CONCLUSION: Our study suggests that emotional intelligence training improves emotional intelligence, resilience, and stress among nurses and leads to improvements in inpatient experience. Emotional intelligence training should be part of nurse education to improve the quality of care nurses provide and their ability to work without increased stress.

New Enantiomers of a Nor-Bisabolane Derivative and Two New Phthalides Produced by the Marine-Derived Fungus Penicillium chrysogenum LD-201810.

Marine-derived fungi are a treasure house for the discovery of structurally novel secondary metabolites with potential pharmaceutical value. In this study, a pair of new nor-bisabolane derivative enantiomers (±)-1 and two new phthalides (4 and 5), as well as four known metabolites, were isolated from the culture filtrate of the marine algal-derived endophytic fungus Penicillium chrysogenum LD-201810. Their structures were established by detailed interpretation of spectroscopic data (1D/2D NMR and ESI-MS). The optical resolution of compound (±)-1 by chiral HPLC successfully afforded individual enantiomers (+)-1 and (-)-1, and their absolute configurations were determined by TDDFT-ECD calculations. Compound (±)-1 represents the first example of bisabolane analogs with a methylsulfinyl substituent group, which is rare in natural products. All of the isolated compounds 1-7 were evaluated for their cytotoxic activity against A549, BT-549, HeLa, HepG2, MCF-7, and THP-1 cell lines, as well as for antifungal activity against four plant pathogenetic fungi (Alternaria solani, Botrytis cinerea, Fusarium oxysporum, and Valsa mali). Compound 2, a bisabolane-type sesquiterpenoid, was shown to possess excellent activity for control of B. cinerea with half-maximal inhibitory concentration (IC50) of 13.6 µg/mL, whereas the remaining investigated compounds showed either weak or no cytotoxic/antifungal activity in this study.

Trichoderma: A Treasure House of Structurally Diverse Secondary Metabolites With Medicinal Importance.

Fungi play an irreplaceable role in drug discovery in the course of human history, as they possess unique abilities to synthesize diverse specialized metabolites with significant medicinal potential. Trichoderma are well-studied filamentous fungi generally observed in nature, which are widely marketed as biocontrol agents. The secondary metabolites produced by Trichoderma have gained extensive attention since they possess attractive chemical structures with remarkable biological activities. A large number of metabolites have been isolated from Trichoderma species in recent years. A previous review by Reino et al. summarized 186 compounds isolated from Trichoderma as well as their biological activities up to 2008. To update the relevant list of reviews of secondary metabolites produced from Trichoderma sp., we provide a comprehensive overview in regard to the newly described metabolites of Trichoderma from the beginning of 2009 to the end of 2020, with emphasis on their chemistry and various bioactivities. A total of 203 compounds with considerable bioactivities are included in this review, which is worth expecting for the discovery of new drug leads and agrochemicals in the foreseeable future. Moreover, new strategies for discovering secondary metabolites of Trichoderma in recent years are also discussed herein.

Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: a randomized double-blind clinical trial.

PURPOSE: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new-onset epilepsy. METHODS: Randomized, double-blind, 28-day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new-onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure. RESULTS: At day 28, the estimated seizure-free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment-related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047). CONCLUSION: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new-onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new-onset epilepsy requiring rapid treatment initiation.

Long-term, open-label safety study of oral almotriptan 12.5 mg for the acute treatment of migraine in adolescents.

OBJECTIVES: This study evaluated the long-term safety of oral almotriptan 12.5 mg for the treatment of multiple migraine episodes in adolescents over a 12-month period. Efficacy outcomes were assessed as a secondary objective. METHODS: Adolescent migraineurs aged 12-17 years were enrolled in this 12-month, open-label study (Study ID CR002827). Patients were instructed to record their assessments on paper headache records whenever they experienced a migraine headache that they treated with study medication. Safety was assessed descriptively and assessments included adverse event (AE) recording, change in laboratory values, vital signs, and electrocardiogram parameters. Efficacy outcomes were assessed descriptively and outcomes included rates for 2- and 24-hour pain relief and sustained pain relief, 2- and 24-hour pain-free and sustained pain-free, and presence of migraine-associated symptoms of photophobia, phonophobia, nausea and vomiting. RESULTS: Overall, 67.1% of patients reported >or=1 AE over the course of the trial, 7.6% had an AE judged by the study investigator to be related to treatment with almotriptan, 2.4% discontinued because of an AE, and 1.9% reported serious AEs. The most commonly reported treatment-related AEs (occurring in >or=1% of patients) were nausea (1.4%) and somnolence (1.4%). Pain relief responses for treated migraines of moderate or severe intensity at baseline were 61.7% and 68.6%, at 2 and 24 hours, respectively; the sustained pain relief rate was 55.5%. Pain-free responses were reported for 40.5% of all treated migraines at 2 hours and 65.9% of treated migraines at 24 hours; the sustained pain-free rate was 38.4%. The proportion of migraines that achieved the pain relief, sustained pain relief, pain-free and sustained pain-free endpoints were similar in the 12- to 14-year and 15- to 17-year age groups. Treating with almotriptan 12.5 mg when headache pain was mild was associated with higher rates of pain relief and pain-free at 2 and 24 hours, and sustained pain relief and sustained pain-free, compared with treatment initiated when pain was severe. CONCLUSIONS: Almotriptan 12.5 mg was well tolerated in this adolescent population over a 12-month period. No unexpected safety or tolerability concerns were revealed over the course of this study. The results are consistent with almotriptan 12.5 mg being effective for the acute treatment of pain and symptoms associated with migraine in both younger and older adolescents.

Predicting hospital admission and discharge with symptom or function scores in patients with schizophrenia: pooled analysis of a clinical trial extension.

BACKGROUND: The purpose of this analysis was to evaluate relationships between hospital admission or discharge and scores for symptom or functioning in patients with schizophrenia. METHODS: Data were from three 52-week open-label extensions of the double-blind pivotal trials of paliperidone extended-release (ER). Symptoms and patient function were measured every 4 weeks using the Personal and Social Performance (PSP) scale and the Positive and Negative Syndrome Scale (PANSS). The intent-to-treat analysis set was defined as open-label patients who had at least one post-baseline PSP and PANSS measurement. Time until first hospitalization was evaluated using the Cox proportional hazard model with categorical time-dependent measures for the PSP (1 to 30, 31 to 70, 71 to 100) or PANSS (< 75, >/= 75 to < 95, >/= 95), as well as age, gender, schizophrenia duration, and country. Similar analyses were performed for time to discharge. RESULTS: Of the 1,077 enrolled patients, 1,028 (95.5%) met study criteria; of these, 382 (37.2%) were hospitalized at open-label baseline. Compared with patients with PSP >/= 71 group, the hazard for new hospitalization was 8.351 times greater (P = 0.0001) for patients with the poorest functioning (PSP 1 to 30) and 1.977 times greater (P = 0.0295) for patients with PSP of 31-70 compared to the >/= 71 group. The hazard for new hospitalization was 5.457 times greater (P < 0.0001) for patients PANSS >/= 95 and 2.316 times greater (P = 0.0027) for the >/= 75 to < 95 group compared with the < 75 group. For patients hospitalized at baseline, the PANSS >/= 95 patients had a discharge hazard that was 0.456 times lower than for the < 75 patients (P < 0.0001). The hazard for discharge was 0.646 times lower (P = 0.0012) for the PANSS >/= 75 to < 95 group compared with the < 75 group. A patient's country was a significant predictor variable, with US patients being admitted and discharged faster. CONCLUSIONS: Better functioning or being less symptomatic is associated with reduced risk for hospitalization and greater chance for early discharge. Treatments or programs that reduce symptoms or improve function decrease the risk of hospitalization in community patients or increase the chance of discharge for hospitalized patients.

[Effects of RNA interference targeting angiotensin 1 receptor and angiotensin-converting enzyme on blood pressure and myocardial remodeling in spontaneous hypertensive rats].

OBJECTIVE: To investigate the effects of RNA interference (RNAi) targeting angiotensin II Type 1 receptor (ATlR) and angiotensin-converting enzyme (ACE) on blood pressure and myocardial remodeling in spontaneous hypertensive rats (SHRs). METHODS: Saline (control), adenovirus (Ad5) and recombinant adenoviral vectors (Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA expressing ACE, AT1R, ACE and AT1R gene-specific shRNA, respectively) were randomly administered by caudal intravasation to SHRs (n = 12 each group) at day 1 and 17. Normotensive Wistar-Kyoto rats (WKY) served as normal controls. Systolic blood pressure (SBP) of the caudal artery was measured daily. Expression of ACE and AT1R at mRNA levels in ventricle and aorta were evaluated by fluorescence quantitative PCR. Angiotension II serum concentration was measured by ELISA at day 3 (n = 6 each group). The ratio of left ventricular to body weight (LVW/BW) and myocardial collagen content were measured, myocardial ultrastructure observed under transmission electron microscope at the study end. RESULTS: The caudal artery pressure of saline and Ad5 group was equally increased by about 26 mm Hg(1 mm Hg = 0.133 kPa) compared to baseline (both P < 0.05). Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA injection significantly reduced SBP (-24 mm Hg, -22 mm Hg and -26 mm Hg respectively, all P < 0.05 vs. baseline) and the antihypertensive effect could last at least 15 days post each injection. SBP was not affected by saline and Ad5 injections. ACE and AT1 mRNA expressions at ventricle and aorta were significantly decreased in Ad5-ACE-shRNA, Ad5-ACE-AT1R-shRNA and Ad5-AT1R-shRNA, Ad5-ACE-AT1R-shRNA treated SHRs compared to those in saline and Ad5 groups (all P < 0.05) and was comparable to that in WKY group (P > 0.05). The LVW/BW ratio [(2.22 +/- 0.18) microg/mg, (2.23 +/- 0.19) microg/mg, (2.17 +/- 0.16) microg/mg] and myocardial collagen content [(1.291 +/- 0.019) microg/mg, (1.298 +/- 0.019) microg/mg, (1.276 +/- 0.019) microg/mg] in Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA treated SHRs were also significantly lower than those in saline treated [(3.23 +/- 0.13) microg/mg and(1.683 +/- 0.013) microg/mg, both P < 0.05] and Ad5 treated SHRs [(3.25 +/- 0.12) microg/mg and(1.693 +/- 0.013) microg/mg, both P < 0.05], but still higher than those of WKY group [(2.06 +/- 0.12) microg/mg and (1.258 +/- 0.019) microg/mg, both P < 0.05]. Myocardial ultrastructure was also significantly improved in all SHRs underwent RNAi treatments compared to saline and Ad5 treated SHRs. CONCLUSION: RNAi targeting ACE and AT1R gene significantly inhibited myocardial and aortic ACE and AT1R mRNA expressions and resulted in prolonged antihypertensive effects and myocardial ultrastructure improvements in SHRsl. The RNAi technology may be a potential new strategy of gene therapy for hypertension.

Tissue kallikrein: A potential serum biomarker to predict delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) is a severe complication after aneurysmal subarachnoid hemorrhage (aSAH). Tissue kallikrein (TK), a subgroup of serine proteinases, is an important component of the kallikrein-kinin system. Exogenous TK attenuated cerebral vasospasm in a rabbit model of subarachnoid hemorrhage. We intended to discern association of serum TK levels with aSAH-related DCI. METHODS: Serum TK levels were detected in a total of 92 aSAH patients and 92 healthy controls. A multivariate logistic regression model was configured to investigate relationship between TK levels and occurrence of DCI. RESULTS: TK levels were substantially lower in aSAH patients than in controls. TK levels were strongly correlated with World Federation of Neurological Surgeons (WFNS) score and modified Fisher score. Serum TK, WFNS score and modified Fisher score retained as the three independent predictors for DCI. Under receiver operating characteristic curve, predictive capability of TK levels was in the range of WFNS score and modified Fisher score, as well as TK levels could remarkably improve predictive abilities of WFNS score and modified Fisher score. CONCLUSIONS: Serum TK emerges as a potential biomarker for assessment of hemorrhagic severity and prediction of DCI following aSAH.

Identification of potential metabolic biomarkers in Yin deficiency syndrome using LC-MS.

Yin and Yang are the two counter-balancing aspects in ancient Chinese philosophy. In traditional Chinese medicine, Yin deficiency syndrome (YDS) is a common sub-health state with complex causes. While the syndrome may be treated to various degrees of effectiveness with traditional Chinese medicine, efficient modern methods are yet to be developed for diagnosing and treating the YDS. Here we performed a metabolomics study on YDS in rats. Serum metabolites in rats were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method to identify potential biomarkers for YDS. The rats were divided randomly into the healthy control group, the untreated YDS group, and the anemarrhena treated YDS group. Compared with the control group, significant increase in the metabolites such as dihydrotestosterone (DHT) and 5ß-DHT, 4-imidazolone-5-propanoate, 4-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde, and 5-(L-alanin-3-yl)-2-hydroxy-cis,cis-muconate 6-semialdehyde were observed in the serum of untreated YDS group, which returned to normal in the anemarrhena treated group. Therefore, these metabolites may serve as potential biomarkers for YDS, and may facilitate the diagnosis and treatment of YDS.