Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial.

BACKGROUND: Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. OBJECTIVE: To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis. METHODS: DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. RESULTS: Patients were randomized to apremilast (n = 143) or placebo (n = 146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P = .0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. LIMITATIONS: Lack of active-comparator. CONCLUSIONS: Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis.

Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behçet's Syndrome.

BACKGROUND: Since US FDA approval in 2014, apremilast has consistently demonstrated a favorable benefit-risk profile in 706,585 patients (557,379 patient-years of exposure) worldwide across approved indications of plaque psoriasis, psoriatic arthritis, and Behçet's syndrome; however, long-term exposure across these indications has not been reported. OBJECTIVE: The aim of this study was to conduct a pooled analysis of apremilast data from 15 clinical studies with open-label extension phases, focusing on long-term safety. METHODS: We analyzed longer-term safety and tolerability of apremilast 30 mg twice daily across three indications for up to 5 years, focusing on adverse events of special interest, including thrombotic events, malignancies, major adverse cardiac events (MACE), serious infections, and depression. Data were pooled across 15 randomized, placebo-controlled studies and divided into placebo-controlled or all-apremilast-exposure groups. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Overall, 4183 patients were exposed to apremilast (6788 patient-years). Most TEAEs were mild to moderate in the placebo-controlled period (96.6%) and throughout all apremilast exposure (91.6%). TEAE rates of special interest were similar between treatment groups in the placebo-controlled period and remained low throughout all apremilast exposure. Exposure-adjusted incidence rates per 100 patient-years during all apremilast exposure were MACE, 0.30; thrombotic events, 0.10; malignancies, 1.0; serious infections, 1.10; serious opportunistic infections, 0.21; and depression, 1.78. Safety findings were consistent across indications and regions. No new safety signals were identified. CONCLUSIONS: The incidence of serious TEAEs and TEAEs of special interest was low despite long-term exposure, further establishing apremilast as a safe oral option for long-term use across indications with a favorable benefit-risk profile. CLINICAL TRIAL REGISTRATION: NCT00773734, NCT01194219, NCT01232283, NCT01690299, NCT01988103, NCT02425826, NCT03123471, NCT03721172, NCT01172938, NCT01212757, NCT01212770, NCT01307423, NCT01925768, NCT00866359, NCT02307513.

Impact of apremilast on quality of life in Behçet's syndrome: analysis of the phase 3 RELIEF study.

OBJECTIVE: To assess apremilast's impact on patient quality of life (QoL) in active Behçet's syndrome and correlations between improvement in patients' QoL and efficacy measures in the phase 3 RELIEF study. METHODS: QoL measures included Behçet's Disease QoL (BDQoL), 36-Item Short-Form Health Survey V.2 (SF-36v2) Physical/Mental Component Summary (PCS/MCS) and eight subscale scores, focusing on Physical Functioning (PF). Pearson's correlation coefficients assessed relationships between efficacy endpoints (oral ulcer count, oral ulcer pain, Behçet's Syndrome Activity Scale (BSAS), Behçet's Disease Current Activity Form (BDCAF)) and QoL endpoints for apremilast at Week 12. RESULTS: Apremilast (n=104) demonstrated significantly greater improvements versus placebo (n=103) in SF-36v2 PCS (3.1 vs 0.9), MCS (4.6 vs ─0.7) and PF (2.9 vs 0.14), respectively (all p<0.05). Mild correlations were observed in improvements of SF-36v2 measures (PCS, MCS, PF) with oral ulcer count (r=-0.11, PCS), and change in oral ulcer pain from baseline (r=-0.28, PCS; r=-0.10, PF) and BSAS (r=-0.38, PCS; r=-0.20, PF; r=-0.16, MCS). Correlations among BDCAF and SF-36v2 components and BDQoL were variable. BDQoL showed mild/moderate correlations with SF-36v2 components (r=-0.18, PCS; r=-0.13, PF; r=-0.45, MCS). CONCLUSIONS: Apremilast was associated with significant improvements in QoL measures of SF-36v2 PCS, MCS and PF and BDQoL in patients with Behçet's syndrome. Correlations of improvement among QoL endpoints support the beneficial clinical effects of apremilast in Behçet's syndrome. TRIAL REGISTRATION NUMBER: NCT02307513.

Apremilast in a Japanese subgroup with Behçet's syndrome: Results from a Phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVES: Apremilast efficacy and safety was assessed in a prespecified subgroup of Japanese patients with oral ulcers associated with Behçet's syndrome from a Phase 3 randomized, placebo-controlled, double-blind study of apremilast (RELIEF). METHODS: The primary end point was area under the curve for number of oral ulcers during the 12-week placebo-controlled phase (AUCWk0-12). Key secondary end points were change from baseline in oral ulcer pain, complete oral ulcer resolution, and measures of disease activity and quality of life (QoL). RESULTS: Thirty-nine Japanese patients were randomised (apremilast 30 mg BID: n = 19; placebo: n = 20). Improvements at Week 12 were observed for apremilast vs. placebo in AUCWk0-12 for the number of oral ulcers (115.9 vs. 253.3; nominal P = 0.0168); 57.9% vs. 25.0% achieved complete oral ulcer resolution, 47.4% vs. 0.0% achieved oral ulcer resolution by Week 6 and maintained oral ulcer-free status for ≥6 additional weeks; mean change from baseline in BSAS was -10.5 vs. 0.5. Favourable effects were observed for apremilast vs. placebo in other secondary end points, including QoL. Clinical benefits were sustained over 28 weeks of continued apremilast treatment. Adverse events were consistent with apremilast's known safety profile. CONCLUSIONS: Apremilast reduced the number of oral ulcers and overall disease activity in this Japanese subgroup with Behçet's syndrome.

Apremilast for oral ulcers associated with active Behçet's syndrome over 68 weeks: long-term results from a phase 3 randomised clinical trial.

OBJECTIVES: This study assessed the efficacy and safety of apremilast for the oral ulcers associated with Behçet's syndrome (BS) up to 64 weeks. METHODS: The phase 3, double-blind, placebo-controlled RELIEF study randomised adult patients with active BS to placebo or apremilast 30 mg twice daily for 12 weeks, followed by an extension phase with all patients receiving apremilast through Week 64 and 4-week post-treatment follow-up (upon treatment discontinuation). The primary endpoint was area under the curve for the number of oral ulcers over 12 weeks (AUCWk0-12), reflecting the number of oral ulcers over time and accounting for their recurring-remitting course. Oral ulcer number, complete and partial responses, pain and disease activity and quality of life (QoL) were also assessed throughout the study. RESULTS: A total of 207 participants were randomised and received at least one dose of study medication; 178 entered the extension phase and 143 completed Week 64. AUCWk0-12 was significantly lower with apremilast versus placebo (p<0.0001), and oral ulcers number, pain, complete/partial responses, disease activity and QoL with apremilast versus placebo showed improvements at Week 12, which were maintained through Week 64. The most common adverse events were diarrhoea, nausea, headache and upper respiratory tract infection; no new safety concerns were observed with longer-term apremilast exposure. CONCLUSIONS: In patients with oral ulcers associated with BS, apremilast was efficacious and benefits were sustained up to 64 weeks with continued treatment. Apremilast was well tolerated, and safety was consistent with its known safety profile.

A Phase III Randomized Study of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, for Active Ankylosing Spondylitis.

OBJECTIVE: To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with active ankylosing spondylitis (AS). METHODS: This phase III, multicenter, double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01583374) randomized patients with active AS (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily for 24 weeks, followed by a long-term extension phase (up to 5 yrs). The primary endpoint was Assessment of the Spondyloarthritis international Society 20 (ASAS20) response at Week 16. The effect of treatment on radiographic outcomes after 104 weeks was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). RESULTS: In total, 490 patients with active AS were randomized in the study (placebo: n = 164; apremilast 20 mg twice daily: n = 163; apremilast 30 mg twice daily: n = 163). The primary endpoint of ASAS20 response at Week 16 was not met (placebo: 37%; apremilast 20 mg twice daily: 35%; apremilast 30 mg twice daily: 33%; P = 0.44 vs placebo). At Week 104, mean (SD) changes from baseline in mSASSS were 0.83 (3.6), 0.98 (2.2), and 0.57 (1.9) in patients initially randomized to placebo, apremilast 20 mg twice daily, and apremilast 30 mg twice daily, respectively. The most frequently reported adverse events through Week 104 were diarrhea, nasopharyngitis, upper respiratory infection, and nausea. CONCLUSION: No clinical benefit was observed with apremilast treatment in patients with active AS. The safety and tolerability of apremilast were consistent with its known profile.

Quality of Life and Severity of Symptom Differences Between Post Open Colectomy and Laparoscopic Colectomy in Colorectal Cancer Patients.

BACKGROUND: Worldwide, colorectal cancer is the third most common cancer in men and the second in women. The main surgical methods for colorectal cancer patients include a conventional open colectomy and laparoscopic-assisted colectomy. Laparoscopic-assisted colectomy is associated with less blood loss, faster recovery of bowel function, and shorter hospital stays. OBJECTIVE: The aim of this study was to compare the quality of life and symptom severity in patients with colorectal cancer 1 month after conventional open colectomy or laparoscopic-assisted colectomy. METHODS: A comparative cross-sectional study design was conducted from September 2015 to May 2016. Participants were recruited through convenience sampling from the surgical outpatient department of a medical center in Northern Taiwan; 33 patients underwent each type of surgery. RESULTS: The laparoscopic-assisted colectomy group scored 9.39 points higher in quality of life and lower in symptom severity by 14.88 points than the conventional open colectomy group (P = .03 and P = .05, respectively). Both groups reported low symptom severity; "changes in bowel habits" was the symptom with the highest severity. The conventional open colectomy group had higher insomnia and worried about their future more than did the laparoscopic-assisted colectomy group. CONCLUSIONS: Patients who received the laparoscopic-assisted colectomy procedure reported a better quality of life and lower symptom severity than those who received the conventional open colectomy surgical method. IMPLICATIONS FOR PRACTICE: Patients who will have a conventional open colectomy will likely need enhanced management of symptoms and attention to their quality of life.

Mediating effects of shoulder-arm exercise on the postoperative severity of symptoms and quality of life of women with breast cancer.

BACKGROUND: The postoperative severity of symptoms among women with breast cancer affects their quality of life (QoL). Although it is recommended that performing shoulder-arm exercise 30 min/day can alleviate symptoms and improve the QoL, there is little research on the mediating effects of performing shoulder-arm exercise 30 min/day on the postoperative severity of symptoms and QoL among patients with breast cancer. METHODS: A cross-sectional study was conducted 2 ~ 4 months after surgery on women diagnosed with breast cancer but with no distant metastasis and who had undergone breast cancer surgery for the first time. A structured questionnaire was employed which included a severity of symptoms scale, performing shoulder-arm exercise for 30 min/day, a QoL scale, demographic characteristics, and medical status. RESULTS: In total, 117 women with breast cancer completed the survey. The severity of symptoms and performing shoulder-arm exercise 30 min/day separately affected the QoL (B = -0.447, standard error (SE) = 0.050, p < 0.001; B = 15.666, SE = 4.542, p = 0.001, respectively). In model 3, performing shoulder-arm exercise for 30 min/day played a partial mediating role in the relationship of the severity of symptoms and QoL (R2 = 0.51, F = 5.41, p < 0.001). CONCLUSIONS: During 2 ~ 4 months after surgery, regular shoulder-arm exercise for 30 min/day could decrease the effect of the severity of symptoms on the QoL among women with breast cancer. Clinical healthcare providers may inform and educate patients as to the benefits of regular shoulder-arm exercise for 30 min/day.

Trial of Apremilast for Oral Ulcers in Behçet's Syndrome.

BACKGROUND: The small-molecule phosphodiesterase 4 inhibitor apremilast modulates cytokines that are up-regulated in Behçet's syndrome. In a phase 2 trial involving patients with Behçet's syndrome, apremilast reduced the incidence and severity of oral ulcers. Data on the efficacy and safety of apremilast in patients with Behçet's syndrome who had active oral ulcers and had not previously received biologic agents are limited. METHODS: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who had Behçet's syndrome with active oral ulcers but no major organ involvement to receive either apremilast at a dose of 30 mg or placebo, administered orally, twice daily for 12 weeks, followed by a 52-week extension phase. The primary end point was the area under the curve (AUC) for the total number of oral ulcers during the 12-week placebo-controlled period (with lower values indicating fewer ulcers). There were 13 secondary end points, including complete response of oral ulcers, change from baseline in pain associated with oral ulcers, disease activity, and change from baseline in the Behçet's Disease Quality of Life score (range, 0 to 30, with higher scores indicating greater impairment in quality of life). Safety was also assessed. RESULTS: A total of 207 patients underwent randomization (104 patients to the apremilast group and 103 to the placebo group). The AUC for the number of oral ulcers was 129.5 for apremilast, as compared with 222.1 for placebo (least-squares mean difference, -92.6; 95% confidence interval [CI], -130.6 to -54.6; P<0.001). The change from baseline in the Behçet's Disease Quality of Life score was -4.3 points in the apremilast group, as compared with -1.2 points in the placebo group (least-squares mean difference, -3.1 points; 95% CI, -4.9 to -1.3). Adverse events with apremilast included diarrhea, nausea, and headache. CONCLUSIONS: In patients with oral ulcers associated with Behçet's syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache. (Funded by Celgene; ClinicalTrials.gov number, NCT02307513.).

FOXC1 Regulation of miR-31-5p Confers Oxaliplatin Resistance by Targeting LATS2 in Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related illness worldwide and one of the most common malignancies. Therefore, colorectal cancer research and cases have gained increasing attention. Oxaliplatin (OXA) is currently used in first-line chemotherapy to treat stage III and stage IV metastatic CRC. However, patients undergoing chemotherapy often develop resistance to chemo drugs being used. Evidence has confirmed that microRNAs regulate downstream genes in cancer biology and thereby have roles related to tumor growth, proliferation, invasion, angiogenesis, and multi-drug resistance. The aim of our study is to establish whether miR-31-5p is an oncogene in human colorectal cancers that are resistant to OXA and further confirm its malignant phenotype-associated target molecule. From the results of miRNA microarray assay, we establish that miR-31-5p expression was upregulated in oxaliplatin-resistant (OR)-LoVo cells compared with parental LoVo cells. Moreover, through in vitro and in vivo experiments, we demonstrate that miR-31-5p and large tumor suppressor kinase 2 (LATS2) were inversely related and that miR-31-5p and Forkhead box C1 (FOXC1) were positively correlated in the same LoVo or OR-LoVo cells. Importantly, we reveal a novel drug-resistance mechanism in which the transcription factor FOXC1 binds to the miR-31 promoter to increase the expression of miR31-5p and regulate LATS2 expression, resulting in cancer cell resistance to OXA. These results suggest that miR-31-5p may be a novel biomarker involved in drug resistance progression in CRC patients. Moreover, the FOXC1/miR31-5p/LATS2 drug-resistance mechanism provides new treatment strategies for CRC in clinical trials.

Pharmacokinetic interaction of riociguat and antiretroviral combination regimens in HIV-1-infected adults.

Riociguat, a first-in-class soluble guanylate cyclase stimulator, is approved for the treatment of pulmonary arterial hypertension (PAH), a serious potential complication of human immunodeficiency virus (HIV) infection. This open-label study investigated the pharmacokinetic drug-drug interaction potential of antiretroviral therapies on riociguat exposure in HIV-infected adults. HIV-infected adults without PAH on stable antiretroviral regimens (efavirenz/emtricitabine/tenofovir disoproxil, emtricitabine/rilpivirine/tenofovir disoproxil, elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil, abacavir/dolutegravir/lamivudine, or a ritonavir-boosted triple regimen) for ≥ 6 weeks received a single riociguat dose (0.5 mg). Riociguat pharmacokinetics and safety were assessed; pharmacokinetics was compared with historical healthy volunteer data. Of 41 participants treated (n = 8 in each arm, except n = 9 in the ritonavir-boosted triple regimen arm), 40 were included in the pharmacokinetic analyses. Riociguat median tmax was 1.00-1.27 h, with comparable maximum concentration (Cmax) across the five background antiretroviral groups. Riociguat exposure was highest with abacavir/dolutegravir/lamivudine, followed by elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil > emtricitabine/rilpivirine/tenofovir disoproxil > ritonavir-boosted triple regimen > efavirenz/emtricitabine/tenofovir disoproxil; riociguat area under the plasma concentration versus time curve (AUC) was approximately threefold higher with abacavir/dolutegravir/lamivudine than efavirenz/emtricitabine/tenofovir disoproxil. Compared with historical data, riociguat exposure in HIV-infected adults was similar when co-administered with efavirenz/emtricitabine/tenofovir disoproxil, slightly increased when administered with ritonavir-boosted triple regimen and increased by approximately threefold when administered with abacavir/dolutegravir/lamivudine. Riociguat was well tolerated, with no new safety findings. Riociguat was well tolerated in adults with HIV on stable background antiretroviral therapy although an apparent increase in AUC of riociguat was observed in patients receiving abacavir/dolutegravir/lamivudine. Patients should be monitored closely during riociguat initiation and dose adjustment for signs and symptoms of hypotension.

Development and psychometric testing of the Chinese version of the Resilience Scale for Southeast Asian immigrant women who divorced in Taiwan.

BACKGROUND: Only a few studies exist on the resilience of divorced women. Furthermore, relevant instruments for assessing the resilience of divorced immigrant Southeast Asian women are rare. Accordingly, the aim of this study was to develop and examine a new Resilience Scale-Chinese version (RS-C) that is specific to divorced immigrant Southeast Asian women in Taiwan. METHODS: The study was conducted in two phases. In phase 1, 20 items were used to evaluate face and content validities. In phase 2, a cross-sectional study was conducted. In total, 118 immigrant women participated in this study and were recruited from three nongovernmental organizations providing services for immigrants in Taipei City and Miaoli and Chiayi Counties. Psychometric properties of the instrument (i.e., internal consistency, test-retest reliability, item-to-total correlation, construct validity, and convergent validity) were examined. Significance was set at p < 0.05 for all statistical tests. RESULTS: The final 16-item RS-C resulted in a three-factor model. The three factors, namely personal competence, family identity, and social connections, were an acceptable fit for the data and explained 54.60% of the variance. Cronbach's α of the RS-C was 0.85, and those of its subscales ranged from 0.77 to 0.82. The correlation value of the test-retest reliability was 0.87. The RS-C was significantly associated with the General Self-Efficacy scale and the Chinese Health Questionnaire-12. CONCLUSION: The RS-C is a brief and specific self-report tool for evaluating the resilience of divorced immigrant Southeast Asian women and demonstrated adequate reliability and validity in this study. This RS-C instrument has potential applications in both clinical practice and research with strength-based resiliency interventions. However, additional research on the RS-C is required to further establish its reliability and validity.

Anti-Apoptosis and Anti-Fibrosis Effects of Eriobotrya Japonica in Spontaneously Hypertensive Rat Hearts.

Myocardial apoptosis and fibrosis represent important contributing factors for development of hypertension-induced heart failure. The present study aims to investigate the potential effects of Eriobotrya japonica leaf extract (EJLE) against hypertension-induced cardiac apoptosis and fibrosis in spontaneously hypertensive rats (SHRs). Twelve-week-old male rats were randomly divided into four different groups; control Wistar Kyoto (WKY) rats, hypertensive SHR rats, SHR rats treated with a low dose (100 mg/kg body weight) of EJLE and SHR rats treated with a high dose (300 mg/kg body weight) of EJLE. Animals were acclimatized for 4 weeks and thereafter were gastric fed for 8 weeks with two doses of EJLE per week. The rats were then euthanized following cardiac functional analysis by echocardiography. The cardiac tissue sections were examined by Terminal Deoxynucleotidyl Transferase-Mediated Deoxyuridine Triphosphate (dUTP) Nick End-Labeling (TUNEL) assay, histological staining and Western blotting to assess the cardio-protective effects of EJ in SHR animals. Echocardiographic measurements provided convincing evidence to support the ability of EJ to ameliorate crucial cardiac functional characteristics. Furthermore, our results reveal that supplementation of EJLE effectively attenuated cardiac apoptosis and fibrosis and also enhanced cell survival in hypertensive SHR hearts. Thus, the present study concludes that EJLE potentially provides cardio-protective effects against hypertension-induced cardiac apoptosis and fibrosis in SHR animals.

Lupeol alters ER stress-signaling pathway by downregulating ABCG2 expression to induce Oxaliplatin-resistant LoVo colorectal cancer cell apoptosis.

Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death. There are several first-line chemotherapeutic drugs used to treat CRC. Oxaliplatin (OXA) is an alkylating cytotoxic agent that is usually combined with other chemotherapeutic drugs to treat stage II and stage III CRC. However, cancer cells commonly acquire multidrug resistance (MDR), which is a major obstruction to cancer treatment. Recent studies have shown that natural components from traditional Chinese medicine or foods that have many biological functions may be new adjuvant therapies in clinical trials. We challenged LoVo CRC cell lines with OXA in a dose-dependent manner to create an OXA-resistant model. The expression of ABCG2 was significantly higher, and levels of endoplasmic reticulum (ER) stress markers were lower than those Parental cells. However, Lupeol, which is found in fruits and vegetables, has been shown to have bioactive properties, including anti-tumor properties that are relevant to many diseases. In our study, Lupeol downregulated cell viability and activated cell apoptosis. Moreover, Lupeol decreased the expression of ABCG2 and activated ER stress to induce OXA-resistant cell death. Importantly, the anti-tumor effect of Lupeol in OXA-resistant cells was higher than that of LoVo Parental cells. In addition, we also confirmed our results with a xenograft animal model, and the tumor size significantly decreased after Lupeol injections. Our findings show that Lupeol served as a strong chemoresistant sensitizer and could be a new adjuvant therapy method for chemoresistant patients.

Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis.

AIM: To assess the bioequipotency of equimolar doses of idraparinux (2.5 mg) and idrabiotaparinux (3.0 mg). METHOD: In a phase I study, 48 healthy male volunteers were randomized to a single subcutaneous injection of idrabiotaparinux or idraparinux, followed by plasma sampling over 27 days. In a prospective substudy of the phase III EQUINOX trial, 228 patients treated for acute symptomatic deep vein thrombosis received idrabiotaparinux or idraparinux once weekly for 6 months. Plasma sampling was performed within 5 days following the last injection. The primary pharmacodynamic endpoint was the inhibition of activated factor X (FXa) activity. Maximal anti-FXa activity (Amax) and area under anti-FXa activity vs. time curve (AAUC) were calculated. Safety and tolerability were also assessed. RESULTS: In both studies, pharmacodynamic anti-FXa vs. time profiles of idrabiotaparinux and idraparinux were superimposable. Ratio estimates (90% confidence intervals [CIs]) for idrabiotaparinux : idraparinux were 0.96 (0.89, 1.04) for Amax and 0.95 (0.87, 1.04) for AAUC in the phase I study, and 1.11 (1.00, 1.22) for Amax and 1.06 (0.96, 1.16) for AAUC at month 6 in the EQUINOX substudy. Idrabiotaparinux and idraparinux were considered bioequipotent because 90% CIs were within the pre-specified interval (0.80, 1.25). Study treatments were well tolerated. CONCLUSION: Pharmacodynamic parameters reported after single dose in healthy volunteers and after repeated once weekly dosing in patients demonstrated the bioequipotency of idrabiotaparinux and idraparinux based on FXa inhibition. These outcomes support the use of an idrabiotaparinux dose bioequipotent to an idraparinux dose in large clinical trials, and the possibility to substitute idrabiotaparinux to idraparinux for the treatment of venous thromboembolism.

The Chinese Utian Quality of Life Scale for women around menopause: translation and psychometric testing.

OBJECTIVE: Chinese-language scales for assessing quality of life in women around menopause are rare. This study was conducted to evaluate the psychometric properties of a Chinese-language version of the Utian Quality of Life Scale (UQOL-C). METHODS: A sample of women (n = 434) between 41 and 60 years old was recruited from an obstetrics/gynecology outpatient department in Taipei. After translating the instrument, we conducted psychometric testing, which included internal consistency, test-retest reliability, and construct validity. Construct validity of the UQOL-C was examined by testing the correlations between the UQOL-C and the 36-item Short-Form Health Survey Taiwan version and between the UQOL-C and the Greene Climacteric Scale Chinese version. RESULTS: The Chinese translation captured the content of the original tool. The reliability coefficients (Cronbach α) for the quality of life domains measured were as follows: 0.86, overall; 0.85, occupational; 0.70, health-related; 0.66, emotional; and 0.61, sexual. The test-retest reliability of the UQOL-C was satisfactory (r = 0.88-0.91, P < 0.001). The construct validity of the UQOL-C was confirmed through significant correlations between scores on (1) the UQOL-C and the 36-item Short-Form Health Survey Taiwan version (r = 0.15-0.59, P < 0.01) and (2) the UQOL-C and the Greene Climacteric Scale Chinese version (r = -0.10 to -0.56, P < 0.05). CONCLUSIONS: The UQOL-C was shown to be reliable and valid with this sample of women between 41 and 60 years old. The low Cronbach α values of the UQOL-C emotional and sexual domains suggested that the reliability of these two domains required further studies.

Changes in quality of life among newly diagnosed breast cancer patients in Taiwan.

AIM: To examine changes in quality of life among patients with breast cancer and factors related to it, during the first three months after diagnosis. BACKGROUND: Numerous studies have examined quality of life among cancer survivors or among patients with cancer after aggressive treatment; such research has demonstrated that quality of life in the third month after surgery can significantly predict quality of life in the long run. In contrast, changes in quality of life causes among patients during the acute treatment phase have not been well studied. DESIGN: Prospective longitudinal study. METHODS: Newly diagnosed patients with breast cancer were recruited during 2008-2009. Sixty-one cases completed the four data collections on the day before operation and one, two and three months after surgery. Data were collected using the Functional Living Index-Cancer, Symptom Distress Scale, the Self-Efficacy Scale and a 0-10 Anxiety Numeric Rating Scale. Generalized Estimating Equations were applied for data analysis. RESULTS: There were significant changes in quality of life over the three months following surgery, and the worst quality of life was observed in the first month after surgery. Less advanced stages of cancer, lower anxiety, less symptom distress and higher perceived self-efficacy in the preoperative interview could significantly predict which patients experienced more positive quality of life trends. Fatigue, limited shoulder function and perceived poor appearance were the most significant factors predicting changes of quality of life. CONCLUSION: Preoperative physical and psychological factors, as well as sense of self-efficacy for managing the cancer, are important factors for predicting changes in patients' quality of life. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should be alert to factors contributing to changes of quality of life among patients receiving chemotherapy. Interventions based on these results should be developed and their effectiveness tested for their impact on breast cancer patients' quality of life. Clinical interventions based on these results should be developed to improve breast cancer patients' quality of life.

Clopidogrel pharmacodynamics and pharmacokinetics in the fed and fasted state: a randomized crossover study of healthy men.

Clopidogrel requires CYP450-mediated hepatic metabolism to form its active metabolite (clopi-H4). This randomized, placebo-controlled, crossover study was designed to characterize the effect of a high-fat or standard breakfast on adenosine diphosphate (ADP)-induced platelet aggregation and exposure to unchanged clopidogrel and clopi-H4 following clopidogrel (300-mg loading dose, 75 mg/d for 4 days) in 72 healthy men. At day 5 and as assessed by liquid chromatography-tandem mass spectrometry, unchanged clopidogrel area under the concentration- time curve from 0 to 24 hours (AUC(0-24)) increased 3.32-fold (90% confidence interval [CI], 2.88-3.84), and clopi-H4 AUC(0-24) decreased nonsignificantly by 12% (90% CI, 0.82-0.94) upon administration of clopidogrel with a standard breakfast. The estimated treatment difference in maximum platelet aggregation (MPA) induced by ADP 5 µM and assessed by light transmission aggregometry was 4.7%, with the 90% CI (0.9%-8.5%) contained within the prespecified equipotency range of ±15%. The mean ± standard deviation of day 5 inhibition of platelet aggregation was 49.7% ± 17.2% and 54.0% ± 13.3% in the fed and fasted states, respectively. Despite increased unchanged clopidogrel and slightly decreased clopi-H4 exposure following clopidogrel administration, the numerical increase in MPA in the fed versus fasted state was small and within the prespecified limit of equipotency. These findings confirm that clopidogrel can be taken with or without food.

Psychometric testing of the Chinese-version cancer needs questionnaire short form head and neck cancer-specific version in oral cavity cancer patients.

PURPOSE: The purposes of this two-phase study were to (1) develop and examine the content validity and feasibility of the Chinese-version cancer needs questionnaire, short form, head and neck cancer-specific version (CNQ-SF-hn) (phase I), and (2) examine its psychometric characteristics as supported by reliability and construct validity (phase II) in oral cavity cancer patients in Taiwan. METHODS: Newly diagnosed oral cavity cancer patients (N = 206) were recruited from a medical center in northern Taiwan. Data were analyzed using descriptive statistics and psychometric analyses. RESULTS: The results showed that the CNQ-SF-hn (1) had good internal consistency reliability for the overall scale and subscales; (2) had good 1-week test-retest reliability (correlation = 0.80) for the overall scale; (3) had construct validity, supported by six clearly identified factors explaining 74.87% of the variance; and (4) had convergent validity, supported by correlations among its subscales and related scales, as well as by discriminating care needs according to undergoing versus not undergoing reconstructive surgery and cancer stage. CONCLUSIONS: The Chinese-version CNQ-SF-hn is a psychometrically satisfactory instrument. Further validation is suggested for its factor structure and different head and neck cancers.

The effectiveness of intradialytic leg ergometry exercise for improving sedentary life style and fatigue among patients with chronic kidney disease: a randomized clinical trial.

BACKGROUND: Over the past three decades, research has been carried out on the effects of exercise on chronic kidney disease patients for improving their physical potential. OBJECTIVES: The purpose of this study is to evaluate the effect of intradialytic leg ergometry exercise for improving fatigue and daily physical activity levels among chronic kidney disease patients. DESIGN: A quasi-experimental clinical trial. SETTING: Two hemodialysis units in a medical center in northern Taiwan. METHOD: The leg ergometry exercise was performed within the first hour of each hemodialysis session for 30 min for 8 weeks. There were 36 subjects in the experimental group and 35 subjects in the control group who completed the study. Measurement on a fatigue scale and a physical activity log were done at the time of enrollment, and again on the fourth and eighth weeks. RESULT: Active subjects demonstrated significantly less fatigue and higher physical activity levels than those with a sedentary lifestyle at baseline. During the 8 weeks of intervention, subjects in both the active and sedentary groups reduced their fatigue levels significantly, with the exception of sedentary subjects in the control group. Only active subjects in the experimental group demonstrated an increase in activity levels. The 36 subjects performed 3456 leg ergometry exercise sessions with three early terminations (<.01%) among the sedentary subjects. CONCLUSIONS: Intradialytic leg ergometry is a safe exercise that is effective to reduce fatigue and improve physical fitness in already active chronic kidney disease patients and it also reduces fatigue in sedentary patients. Interventions to motivate sedentary patients to become active require further investigation. IMPLICATION FOR NURSING PRACTICE: Exercise during hemodialysis does not cost patients extra time and is effective in reducing fatigue and increasing physical activity potential as demonstrated by our study; 30 min of intradialytic leg ergometer exercise can be considered as routine care while delivering hemodialysis.