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- Effect and safety of deep needling and shallow needling for functional constipation: a multicenter, randomized controlled trial. [Journal Article]
- Medicine (Baltimore) 2014 Dec; 93(28):e284.
Aupuncture is widely used for functional constipation. Effect of acupuncture might be related to the depth of needling; however, the evidence is limited. This trial aimed to evaluate the effect and safety of deep needling and shallow needling for functional constipation, and to assess if the deep needling and shallow needling are superior to lactulose.We conducted a prospective, superiority-design, 5-center, 3-arm randomized controlled trial. A total of 475 patients with functional constipation were randomized to the deep needling group (237), shallow needling group (119), and lactulose-controlled group (119) in a ratio of 2:1:1. Sessions lasted 30 minutes each time and took place 5 times a week for 4 weeks in 2 acupuncture groups. Participants in the lactulose group took lactulose orally for 16 continuous weeks. The primary outcome was the change from baseline of mean weekly spontaneous bowel movements (SBMs) during week 1 to 4 (changes from the baselines of the weekly SBMs at week 8 and week 16 in follow-up period were also assessed simultaneously). Secondary outcomes were the weekly SBMs of each assessing week, the mean score change from the baseline of constipation-related symptoms over week 1 to 4, and the time to the first SBM. Emergency drug usage and adverse effects were monitored throughout the study.SBMs and constipation-related symptoms were all improved in the 3 groups compared with baseline at each time frame (P < 0.01, all). The changes in the mean weekly SBMs over week 1 to 4 were 2 (1.75) in the deep needling group, 2 (1.75) in the shallow needling group, and 2 (2) in the lactulose group (P > 0.05, both compared with the lactulose group). The changes of mean weekly SBMs at week 8 and week 16 in the follow-up period were 2 (2), 2 (2.5) in the deep needling group, 2 (3), 1.5 (2.5) in the shallow needling group, and 1 (2), 1 (2) in the lactulose group (P < 0.05, all compared with the lactulose group). No significant difference was observed among the 3 groups regarding the score changes of straining, incomplete evacuation, abdominal distention during spontaneous defecating, or Cleveland Clinic Scores over week 1 to 4. However, the lactulose group got better effect than other 2 acupuncture groups in improving stool consistency (P < 0.01, both) and shortening the time to the first SBM (P < 0.05, both). The percentage of emergency drugs used in the 2 acupuncture groups were both lower than in the lactulose group at each time frame (P < 0.01, all). No obvious adverse event was observed in the deep or shallow needling group.Deep and shallow needling at Tianshu (ST25) can improve intestinal function remarkably and safely. Therapeutic effects of deep and shallow needling are not superior to that of lactulose; however, the sustained effects of deep and shallow needling after stopping the acupuncture treatments are superior to the therapeutic effect of lactulose, which might qualify the superiority of deep and shallow needling.
- Successful long-term thalidomide therapy for discoid lupus erythematosus-lichen planus overlap syndrome. [Journal Article]
- Dermatol Online J 2014; 20(10)
Although thalidomide is a U.S. Food and Drug Admistration (FDA) approved medication for erythema nodosum leprosum and multiple myeloma, it has many off-label uses, including for discoid lupus erythematosus (DLE), Behçet's disease, apththous ulcers in HIV patients, and prurigo nodularis. Herein, we present a patient with an overlap of discoid lupus erythematosus and lichen planus who was successfully treated with thalidomide for over 19 years without significant side effects. We propose that some of the most common side effects, including peripheral neuropathy, numbness, parasthesias, sedation, and constipation, can be avoided at lower doses, typically less than 100mg/day.
- A phase 1b, open-label study of trebananib plus bevacizumab or motesanib in patients with solid tumours. [Journal Article]
- Oncotarget 2014 Nov 30; 5(22):11154-67.
To examine the angiopoietin pathway inhibitor trebananib IV plus the anti-VEGF agents bevacizumab or motesanib in advanced solid tumours.In this open-label phase 1b study, patients received IV trebananib 3 mg kg-1 QW plus bevacizumab 15 mg kg-1 Q3W (cohort 1) or motesanib orally 75 mg (cohort 2); or trebananib 10 mg kg-1 plus bevacizumab 15 mg kg-1 (cohort 3) or motesanib 125 mg (cohort 4). If <33% of patients had dose-limiting toxicities (DLTs), dose escalation occurred. Endpoints were treatment-related adverse events (AEs) incidence and pharmacokinetics (primary); anti-trebananib antibodies, biomarkers, and tumour response (secondary).Thirty-six patients received ≥1 dose of trebananib (cohorts 1, 2, 3, 4; n = 6, 8, 19, 3). DLT of G3 intestinal perforation and G3 tumor haemorrhage occurred in cohorts 2 and 3, respectively (both n = 1). Across both trebananib plus bevacizumab cohorts, the most common AEs included fatigue (n = 8), diarrhoea (n =4), constipation (n = 3), nausea (n = 3), and epistaxis (n = 3). Three patients across those cohorts had grade ≥3 AEs. Across the trebananib plus motesanib cohorts, the most common AEs included hypertension (n = 4), diarrhoea (n = 4), nausea (n = 3), fatigue (n = 3), vomiting (n = 2), and decreased appetite (n = 2). Two patients had grade ≥3 AEs. Trebananib did not markedly affect motesanib pharmacokinetics. Across the trebananib plus bevacizumab cohorts, two patients had a partial response; 11 patients had stable disease lasting >6 months. Across the trebananib plus motesanib cohorts, one patient had a partial response; five patients had stable disease lasting >6 months.Trebananib IV 3 mg kg-1 or 10 mg kg-1 plus bevacizumab or motesanib in advanced solid tumours may be associated with less severe toxicities relative to those emerging when combining two anti-VEGF agents.
- Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD. [JOURNAL ARTICLE]
- J Am Soc Nephrol 2014 Dec 18.
The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis-mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment.
- Is group pelvic floor retraining as effective as individual treatment? [JOURNAL ARTICLE]
- Colorectal Dis 2014 Dec 19.
Traditionally, pelvic floor retraining for faecal incontinence or obstructed defaecation has been delivered to patients through individual sessions with a specialist pelvic floor nurse; a resource-intensive practice. This study aimed to assess whether a similar outcome can be achieved by delivering retraining to patients in small-groups, allowing considerable savings in the use of resources.Data were collected prospectively in a pelvic floor database. Patients received pelvic floor retraining either individually or in a small-group setting and completed baseline and follow-up questionnaires. 215 patients were treated; 119 individually and 96 in a small-group setting. Scores before and after treatment for the two settings were compared for the Gastrointestinal Quality of Life Index, Fecal Incontinence Severity Index and Patient Assessment of Constipation Symptoms. Additionally patients receiving group treatment completed a short questionnaire on their experience.The median change in Gastrointestinal Quality of Life Index score was 5 (range: -62 - 73) for individual treatment, and 4 (range: -41 - 47) for group treatment; both showing statistically significant improvement. However there was no significant difference between the settings. Similar results were obtained with the Fecal Incontinence Severity Index and Patient Assessment of Constipation Symptoms scores for the faecal incontinence and obstructed defaecation subgroups respectively.The majority of patients experienced symptomatic improvement following pelvic floor retraining and there was no significant difference in the resulting improvement according to treatment setting. As treatment costs are considerably less in a group setting, group pelvic floor retraining is more cost-effective than individual treatment. This article is protected by copyright. All rights reserved.
- Modified Edmonton Symptom Assessment System Including Constipation and Sleep: Validation in Outpatients with Cancer. [JOURNAL ARTICLE]
- J Pain Symptom Manage 2014 Dec 15.
Our aim was to validate the numerical rating scale (NRS) versions of ESAS and ESAS-r, with two additional symptoms of constipation and sleep (CS), and to assess patient preference for either version.Outpatients with advanced cancer (N=202) completed three assessments during a single clinic visit: ESAS-CS, and an added time window of "past 24 hours"; ESAS-r-CS, with a time window of "now" and symptom definitions; and the Memorial Symptom Assessment Scale (MSAS). Internal consistency was calculated using Cronbach's alpha. Paired t-tests compared ESAS-CS and ESAS-r-CS scores; these were correlated with MSAS using Spearman correlation coefficients. Test-retest reliability at 24 hours was assessed in 26 patients.ESAS-CS and ESAS-r-CS total scores correlated well with total MSAS (Spearman's rho: 0.62 and 0.64, respectively). Correlation of individual symptoms with MSAS symptoms ranged from 0.54-0.80 for ESAS-CS, and 0.52-0.74 for ESAS-r-CS. Although participants preferred the ESAS-r-CS format (42.8% vs. 18.6%) because of greater clarity and understandability, the "past 24 hours" time window (52.8%) was favored over "now" (21.3%). Shortness of breath and nausea correlated better for the "past 24 hours" time window (0.8 and 0.72 vs. 0.74 and 0.64 in ESAS-r-CS, respectively). The 24-hour test-retest of the ESAS-CS demonstrated acceptable reliability (ICC=0.69).The ESAS-CS and ESAS-r-CS NRS versions are valid and reliable for measuring symptoms in this population of outpatients with advanced cancer. Although the ESAS-r-CS was preferred, patients favored the 24-hour time window of the ESAS-CS, which also may best characterize fluctuating symptoms.
- Magnetic Resonance-Guided Focused Ultrasound Surgery (MRgFUS) of Uterine Fibroids in Singapore. [Journal Article]
- Ann Acad Med Singapore 2014 Nov; 43(11):550-8.
Uterine fibroids are the most common type of gynaecologic benign tumours, occurring in 25% to 50% of women during their reproductive lives. About half of the affected women have clinically significant symptoms, including abnormal bleeding, menstrual pain, frequent urination, constipation and abdominal distension. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has been used to treat patients with benign lesions and a variety of malignancies. The objective of this study is to evaluate symptom relief before and after MR-guided ultrasound ablation of fibroids.A total of 37 patients with symptomatic uterine fibroids were treated in this study.MRgFUS treatment led to a significant, time-dependent decrease in not only Symptom Severity Scores (SSS), but also the mean fibroid volume. The average reductions in volume were 41.6% and 52.6% at 6 months and 12 months respectively (P <0.05). The mean SSS of the 37 patients was 41.7 ± 2.8 before treatment whereas the average SSS was 26.9 ± 3.6, 20.7 ± 3.4, 18.5 ± 3.6, 16.5 ± 7.1, 9.8 ± 3.6 at 3 months, 6 months, 1 year, 2 years, and 3 to 4 years respectively. The decrease in scores was significant at all time points up to 3 to 4 years (P <0.05 and P <0.001).MRgFUS is a safe and effective non-invasive treatment for patients with symptomatic fibroids.
- Confirmatory factor analysis of the Patient Assessment of Constipation-Symptoms (PAC-SYM) among patients with chronic constipation. [JOURNAL ARTICLE]
- Qual Life Res 2014 Dec 19.
PAC-SYM is widely adopted to asses constipation severity. However, it has been validated in a small sample, few items have been included based on expert opinion and not on empirical grounds, and its factor structure has never been replicated. We aimed at evaluating the psychometric properties of PAC-SYM in patients with chronic constipation.We enrolled 2,203 outpatients with chronic constipation in two waves. We used wave I sample to test the psychometric properties of the PAC-SYM and wave II sample to cross-validate its factor structure, to assess criterion validity, responsiveness to clinical change, and its minimal clinically important difference.Only a minority of patients reported any rectal tearing (38 %). Deletion of such item leads to a 11-item version (M:PAC-SYM). The remaining items in the rectal domain were moderately correlated with the stool domain. Exploratory factor analysis and confirmatory factor analysis revealed a bifactor structure with two subscales (stool and abdominal symptoms) and a general severity factor. The M:PAC-SYM demonstrated excellent reliability, moderate correlation with SF-12 and treatment satisfaction (r = 0.28-0.45), discrimination across Rome III criteria for functional constipation and abdominal pain, and responsiveness to clinical change (β = -0.49; ω (2) = 0.25). M:PAC-SYM minimal clinically important difference was 0.24.Our analysis shows that the rectal domain may not represent a relevant cluster of symptoms for patients with chronic constipation. We developed a modified version of the PAC-SYM which might better represent symptom severity of most patients seeking care in gastroenterology referral centers.
- Reevaluation of Acetylcholinesterase Staining for the Diagnosis of Hirschsprung's Disease and Allied Disorders. [JOURNAL ARTICLE]
- J Pediatr Gastroenterol Nutr 2014 Dec 16.
Acetylcholinesterase (AChE) staining has become the gold standard for definitively diagnosing Hirschsprung's disease (HD), although some pitfalls have been reported. We reevaluated a large series at our institute in order to validate the accuracy of AChE staining for detecting HD.A retrospective study of the rectal mucosal specimens of all children with suspected HD over a 13-year period was performed. The specimens were stained according to the modified Karnovsky-Roots method for AChE staining. The final diagnosis, prognosis and management after the histopathological diagnosis were analyzed with a questionnaire sent to the patient's original hospital.Three hundred and fifty-eight specimens were collected. One hundred and twenty-two (34%) specimens were diagnosed as HD, 198 (55%) as non-Hirschsprung's disease (non-HD), 25 (7%) as "undetermined" and 13 (4%) as "inappropriate." The non-HD group contained 190 (96%) specimens with a normal appearance and eight (4%) specimens with suspected intestinal neuronal dysplasia (IND). Three hundred and six of 358 questionnaires were returned. The final diagnosis showed that no specimens first diagnosed as HD were identified as non-HD and vice versa, for a sensitivity and specificity of 100%. Four cases were finally diagnosed as chronic idiopathic intestinal pseudo-obstruction (CIIP) in the non-HD group. All HD patients underwent radical surgery. Most non-HD patients were managed conservatively, although some continued to have constipation.AChE staining is an accurate tool for differentiating between HD and non-HD with high sensitivity and specificity. CIIP can be included in cases of non-HD; therefore, careful follow-up is mandatory.
- Mirabegron: a Beta-3 agonist for overactive bladder. [Journal Article]
- Consult Pharm 2014; 29(12):823-37.
To review the literature regarding the efficacy and safety of mirabegron for the treatment of overactive bladder (OAB).A literature search was performed using MEDLINE (PubMed) prior to December 31, 2013, using the terms "mirabegron" and "randomized-controlled trial."All published, double-blind, randomized-controlled trials assessing mirabegron were included. Articles were reviewed and included if mirabegron was used as monotherapy and if the primary outcome analyzed drug efficacy.The efficacy of mirabegron for the treatment of OAB has been demonstrated in the selected five randomized, placebo-controlled trials. The majority of these trials lasted 12 weeks and compared various doses of mirabegron with placebo and/or tolterodine extended-release (ER). Primary efficacy outcomes for the trials included mean number of micturitions per 24 hours and mean number of incontinence episodes per 24 hours. Included trials showed statistically significant reductions in both efficacy outcomes for various doses of mirabegron when compared with placebo.Based on the trials reviewed, mirabegron has been efficacious in reducing mean number of micturitions and incontinence episodes per 24 hours, as well as in improving other secondary outcomes such as OAB symptoms and quality-of-life measures. Common adverse drug events seen with mirabegron include: hypertension, nasopharyngitis, urinary tract infections, headache, constipation, upper respiratory tract infection, arthralgia, diarrhea, tachycardia, abdominal pain, and fatigue. Given the efficacy and safety data currently available, mirabegron represents a reasonable alternative to antimuscarinics for patients with OAB. Future studies are needed to determine the utility of mirabegron for OAB in a variety of demographics.