An open-label evaluation of rifaximin in the treatment of active Crohn's disease

ABSTRACT

Objective: This open-label study was conducted as a preliminary assessment of rifaximin (200?mg TID for 16 weeks) for the treatment of active Crohn's disease in patients (n = 29) with symptoms for at least 3 months before screening and a Crohn's Disease Activity Index (CDAI) score > 220 and < 400.

Results: At the end of month 4, mean ± SD CDAI score was reduced by 43% compared with baseline in the intent-to-treat population (n = 29; baseline = 278 ± 51; month 4 = 159 ± 102; p < 0.0001 month 4 versus baseline). A similar pattern of results was observed in the per-protocol population (i.e., patients at least 70% compliant with the treatment regimen and having no protocol violations thought to affect efficacy results; n = 16), in which mean CDAI scores at month 4 were reduced by 41% from a baseline of 262.9 ± 38.2 to 155.6 ± 104.5 (?p = 0.0009 month 4 versus baseline). Fifty-nine percent of patients (59%) had a ≥ 70‐point improvement in CDAI score beginning with the first assessment at the end of month 1. By the end of the treatment period, 78% of patients had a ≥ 70‐point improvement in CDAI score. Clinical remission, defined as CDAI score < 150, was observed at the end of treatment months 1, 2, 3, and 4 in 41%, 56%, 56%, and 59% of patients, respectively. Twenty-three (23) patients completed the 4-month course of rifaximin therapy, and 6 prematurely withdrew. The most common adverse events were abdominal pain, fatigue, and headache.

Conclusion: These data, which are consistent with the possibility that rifaximin may be useful for active Crohn's disease, warrant confirmation in a randomized, double-blind, placebo-controlled trial.     

The performance of a novel ball‐tipped Flush knife for endoscopic submucosal dissection: a case–control study

Aliment Pharmacol Ther 2010; 32: 908–915

Summary

Background Endoscopic submucosal dissection (ESD) using short needle knives is safe and effective, but bleeding is a problem due to low haemostatic capability. Aim To assess the performance of a novel ball‐tipped needle knife (Flush knife‐BT) for ESD with particular emphasis on haemostasis. Methods A case–control study to compare the performance for ESD of 30 pairs of consecutive early gastrointestinal lesions (oesophagus: 12, stomach: 32, colorectum: 16) with standard Flush knife (F) vs. Flush knife‐BT (BT). Primary outcome was efficacy of intraprocedure haemostasis. Secondary outcomes included procedure time, procedure speed (dividing procedure time into the area of resected specimen), en bloc resection rate and recurrence rate. Results Median intraoperative bleeding points and bleeding points requiring haemostatic forceps were smaller in the BT group than in the F group (4 vs. 8, P < 0.0001, 0 vs. 3, P < 0.0001). There was no difference between groups for procedure time; however, procedure speed was shorter in the BT group (P = 0.0078). En bloc and en bloc R0 resection rates were 100%, with no perforation or post‐operative bleeding. No recurrence was observed in either group at follow‐up 1 year postprocedure. Conclusions Ball‐tipped Flush knife (Flush knife‐BT) appears to improve haemostatic efficacy and dissection speed compared with standard Flush knife.     

Comparative efficacy and tolerability of two sustained-release formulations of diclofenac: results of a double-blind,randomised study in patients with osteoarthritis and a reappraisal of diclofenac's use in this patient population

ABSTRACT

Objective: To compare the analgesic efficacy and tolerability of a sustained-release pellet formulation of diclofenac (Olfen-100 SR Depocaps, SR-CAP, Mepha Ltd, Aesch, Switzerland) with the standard reference formulation (Voltaren retard 100, SR-TAB, Novartis Pharma AG, Basel, Switzerland), both containing 100?mg diclofenac sodium, in patients with osteoarthritis (OA) of the knee and/or hip. In addition, diclofenac's current place in the symptomatic therapy of OA is briefly reviewed.

Methods: In this 2-week double-blind, active-controlled, non-inferiority trial, 210 OA patients were randomised to receive either SR-CAP once daily or SR-TAB once daily (n = 105 for both groups). The primary efficacy endpoint was the change in visual analogue scale (VAS) pain score (0–100?mm) at rest at Day 14 compared with baseline. Secondary variables included the change in VAS pain score on movement and global assessments of efficacy and tolerability using verbal rating scales (VRS).

Results: Between baseline and Day 14, mean ± SD VAS pain score at rest decreased by 44.4 ± 18.5?mm in the SR-CAP group (n = 89) compared with 41.2 ± 19.8?mm in the SR-TAB group (n = 82) based on the per protocol population. Comparable changes were observed in the intention-to-treat population. The lower bound of the 1-sided 97.5% confidence interval was –2.7?mm and greater than the prespecified non-inferiority limit of –10?mm. There was a trend towards a better tolerability with SR-CAP compared with SR-TAB based on mean ± SD VRS scores (SR-CAP, 0.6 ± 0.68; SR-TAB, 0.9 ± 1.0 for assessment by patients; p = 0.063).

Conclusion: SR-CAP is as effective as and possibly better tolerated than SR-TAB in patients suffering from painful OA.     

The effect of preoperative antiplatelet therapy in coronary artery surgery: blood transfusion requirements for patients on cardiopulmonary bypass

SUMMARY

Introduction: Bleeding after heart operations remains a common complication and contributes to morbidity and death. Recent studies have suggested that antiplatelet therapy (APT) may not increase homologous blood requirements in coronary bypass surgery. The purpose of this study was to examine the influence of APT therapy on haemorrhage and transfusion requirements in patients undergoing coronary artery bypass (CABG) on cardiopulmonary bypass (CPB).

Materials and methods: Records from 290 consecutive patients who underwent CABG with CPB were retrospectively reviewed, including 145 patients who received APT within 5?days prior to surgery and 145 control patients (CON). Blood loss was measured up to 24?h. Demographic and clinical patient data were collected until hospital discharge.

Results: Both groups were well matched with respect to demographic and intra-operative data.

There was significantly (?p < 0.0005) more mediastinal tube drainage at 24?h in the APT group (1123?mL ± 537?mL) compared to CON patients (874?mL ± 351?mL). In addition, the APT group received significantly more units of blood (APT: 2.6 ± 2.5 vs CON: 1.6 ± 1.8; p < 0.0005), platelet units (APT: 1.2 ± 1.8 vs CON: 0.2 ± 0.8; p < 0.0005), and fresh frozen plasma units (APT: 2.0 ± 2.2 vs CON: 1.3 ± 2.0; p = 0.01).

Conclusion: This study suggests consideration should be given to delaying elective CABG for patients who have received APT treatment until APT is discontinued for at least 5?days.     

Safety and efficacy of various concentrations of topical lidocaine gel for intravitreal injection

Introduction: Intravitreal injection (IVT) is one of the most common vitreoretinal procedures, a large majority are performed with local anesthesia. The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel.

Methods: A prospective clinical trial was conducted testing lidocaine gel in five preparations: 2, 3.5, 5, 8 and 12%. Patients with macular degeneration, diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure. Patients answered the visual analog scale for pain during the procedure. Corneal and conjunctival was evaluated using the Oxford scale.

Results: In total, 260 patients were randomized into five groups. The mean pain scores (± standard deviation) were 2.63 (± 1.68) in the 2% group, 2.08 (± 1.35) in the 3.5%; 2.00 (± 1.65) in the 5%, 1.93 (± 1.40) in the 8% and 1.83 (± 1.35) in the 12% group. Mean pain score among all groups was similar (p = 0.077). There was no significant difference between groups in regard to keratitis mean score (p = 0.897).

Conclusions: Lidocaine gel at concentrations from 2 to 12% induced similar anesthetic effect for IVTs, without adverse effects on cornea and conjunctiva.     

Real-life behaviour of direct oral anticoagulants in a Spanish cohort with non-valvular atrial fibrillation: Refase Registry

Abstract

Aim: To analyse the effectiveness and safety of DOAC (direct oral anticoagulants) in non-valvular atrial fibrillation (NVAF) patients attending clinical practice.

Methods: Retrospective study of AF patients who started treatment with DOAC from January 1, 2013 to December 31, 2016 in three Spanish hospitals. Mean follow-up was 1.6?years. The primary outcomes were rates of all-cause death, ischaemic stroke, and bleeding. These outcomes were also studied depending on correct dosage adjustment and standard/adjusted dose.

Results: The study included 2494 patients (age = 76.0?±?9.5?years, CHA₂DS₂-VASc = 4.0?±?1.6). The most prescribed DOAC was rivaroxaban (41.1%). Patients taking dabigatran were the youngest (mean age = 73.1?±?10.3 years), with better kidney function (mean CrCl = 80.6?±?35.8?ml/min) and lower CHA₂DS₂-VASc (3.7?±?1.4) and HAS-BLED (2.1?±?0.9) scores. Patients taking apixaban were the oldest, and had the highest CHA2DS2-VASc and HAS-BLED scores (4.3?±?1.6 and 2.6?±?0.9, respectively). Rates of stroke/major bleeding/intracranial bleeding were 1.8/3.0/0.3 events per 100 patient-years, respectively, with no differences among DOAC. Based on dose adjustment according to technical data, it was observed that 517 patients (23.5%) received DOAC doses inconsistent with labelling (p?<?.001) and, within this group, under-dosed patients had a higher death rate although it did not reach a significant result after multivariate adjustment.

Conclusions: The results of safety and efficacy are very similar to those of other previously published national registries. There were no differences among the different types of DOAC regarding outcomes. However, it was found that people taking the adjusted dose of the drug seemed to have a higher risk of death. A non-negligible proportion of patients received DOAC doses inconsistent with labelling (mostly underdose).     

Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 1: Evaluation of in vitro clotting efficacy in the presence of certain contaminants

The treatment of penetrating, haemorrhaging injuries sustained within a hazardous environment may be complicated by contamination with toxic chemicals. There are currently no specific medical countermeasures for such injuries. Haemostats with an absorbent mechanism of action have the potential to simultaneously stop bleeding and decontaminate wounds. However, a primary requirement of a ‘haemostatic decontaminant’ is the retention of clotting function in the presence of chemical contaminants. Thus, the aim of this study was to investigate the haemostatic efficacy of seven commercially available haemostats in the presence of toxic chemicals (soman, VX, sulphur mustard, petrol, aviation fuel and motor oil). Clot viscosity was assessed ex vivo using thrombelastography following treatment of pig blood with: (i) toxic chemical; (ii) haemostat; or (iii) haemostat in combination with toxic chemical. Several contaminants (VX, petrol and GD) were found to be pro‐haemostatic and none had an adverse effect on the rate with which the test products attained haemostasis. However, the total clot strength for blood treated with certain haemostats in the presence of sulphur mustard, soman and petrol was significantly decreased. Three test products failed to demonstrate haemostatic function in this ex vivo (thrombelastography) model; this was tentatively ascribed to the products achieving haemostasis through a tamponade mechanism of action, which can only be replicated using in vivo models. Overall, this study has identified a number of commercial products that may have potential as haemostatic decontaminants and warrant further investigation to establish their decontaminant efficacy. Copyright © 2014 John Wiley & Sons, Ltd.     

Efficacy and safety of stabilised hydrogen peroxide cream (Crystacide) in mild-to-moderate acne vulgaris: a randomised,controlled trial versus benzoyl peroxide gel

Background: Benzoyl peroxide (BP) is a first-line topical treatment in acne vulgaris (AV). However, its use can cause mild skin irritation and dryness. A new formulation of hydrogen peroxide stabilised (HPS) in monoglycerides cream (Crystacide 1%), indicated in the topical treatment of superficial skin infections, is now available as an alternative treatment.

Study aim: To evaluate efficacy and local tolerability of HPS in mild-to-moderate AV in comparison with BP gel.

Methods and patients: In a randomised, prospective, investigator-masked parallel-group, 8-week trial, 60 patients (24 men, 36 women, mean age 25?±?6 years) with mild-to-moderate AV, affecting mainly the face, were enrolled in the study, after their informed consent. HPS or BP (PanOxyl gel 4%) was applied topically twice daily for 8 weeks.

Study outcomes: The study endpoints were: (1) Reduction in mean inflammatory (IL), non-inflammatory (NIL) and total (TL) acneic lesions in comparison with baseline; (2) Local tolerability assessed evaluating erythema, dryness and burning sensation, using a 0-3 qualitative score (score 0?=?poor tolerability; score 3?=?very good tolerability).

Results: TL, NIL, and IL were assessed by an investigator unaware of treatment allocation at baseline, and week 8. The tolerability score (TS) was assessed at week 4 and 8. At baseline, the two groups were well matched for the main clinical and demographic characteristics. All patients concluded the trial. At week 0, in the HPS group TL, NIL and IL (mean?±?SD) were: 35?±?8, 20?±?6 and 16?±?7. At week 8, HPS reduced TL to 16?±?7; NIL to 9?±?3 and IL to 7?±?3 (p?<?0.001). At baseline, TL, NIL and IL, in the BP group, were 32?±?9, 24?±?8 and 18?±?7, respectively. At week 8, BP reduced TL, NIL and IL to 14?±?9; 7?±?5 and 7?±?3 (p?<?0.001). In comparison with baseline values, the percentage reductions of IL were 58% and 61% for HPS and BP, respectively (p?=?n.s.). At the end of the study the TS was 2.9?±?0.2 in HPS group and 2.4?±?0.8 in BP group (p?<?0.025). Two patients in HPS group (6%) and seven patients (23%) in BP group suffered from mild-to-moderate local erythema.

Conclusions: HPS has shown to be as effective as BP in reducing both inflammatory and noninflammatory AV lesions in patients with mild-to-moderate disease. In comparison with BP 4% gel, HPS cream shows a better local tolerability profile.     

Renal protection by radical scavenging in cardiac surgery patients

ABSTRACT

Objective: Renal function impairment is a common complication in cardiac surgery patients. Because cardiopulmonary bypass and cardioplegic arrest are associated with formation of free radicals, which have been shown to impair various organs including the kidneys, radical scavenging may protect renal function. Therefore, the purpose of our study was to evaluate the impact of the radical scavenger N-acetylcysteine (NAC) versus placebo on peri-operative renal function in cardiac surgery patients.

Research design and methods: We reanalyzed the data of our previous study in which 40 coronary artery surgery patients (66 ± 9 [SD] years, 9 women and 31 men) with normal pre-operative renal function had been randomized in a double-blind fashion to receive either NAC (100?mg/kg into the cardiopulmonary bypass prime followed by infusion at 20?mg/kg/h; n = 20) or placebo (n = 20). We determined serum creatinine levels as an indicator for renal function pre- and at 1 day post-surgery as well as peri-operative urinary output and diuretic medication. Creatinine clearance was calculated according to Cockcroft and Gault.

Results: Biometric and intra-operative patient data were similar between both groups. In the placebo group, serum creatinine increased from 93.1 ± 35.4 µmol/L pre-operatively to 115.9 ± 47.2 µmol/L on post-op day 1 (?p < 0.001). In contrast, serum creatinine in the NAC group remained unchanged (92.3 ± 31.3 µmol/L pre-op; 99.3 ± 25.4 µmol/L on post-op day 1; p = 0.084). Accordingly, creatinine clearance decreased by 16.9 ± 14.3 mL/min in the placebo group as compared to 7.5 ± 17.7 mL/min in the NAC group (?p = 0.039). Urinary output and diuretic medication were similar between NAC and placebo.

Conclusions: Our data suggest that free radical-scavenging using NAC protects renal function in patients subjected to cardiac surgery on cardiopulmonary bypass.     

Open-label study of mirtazapine orally disintegrating tablets in depressed patients in the nursing home

SUMMARY

Objective: To evaluate the efficacy and tolerability of mirtazapine orally disintegrating tablets in depressed, elderly nursing home residents, under naturalistic study conditions.

Methods: In this open-label 12-week study, mirtazapine orally disintegrating tablets (15–45mg?day^?1) were administered to patients >70 years old with physician-diagnosed depression and a Mini-Mental State Examination (MMSE) score >10. Patients with medical comorbidities, cognitive impairment and/or concomitant medications were enrolled if they met study inclusion criteria and had illnesses and/or medication dosages that were considered stable. Assessments were performed at baseline by physicians and at days 14, 28, 56, and 84 (or early termination) by physicians or nurse coordinators using the Clinical Global Impression (CGI) scale, the 16-item Hamilton Rating Scale for depression (Ham-D-16 (the standard 17-item

scale minus item 14)), and the Cornell Scale for Depression in Dementia (CSDD). Tolerability was evaluated based on treatment-emergent adverse events.

Results: A total of 119 patients in the intent-to-treat (ITT) group were treated with mirtazapine orally disintegrating tablets (mean daily dose: 19.4mg) and evaluated for efficacy. At endpoint, 54% of patients in the ITT group showed CGI-I response (defined as a CGI-I score of 1 or 2 ('very much' or 'much' improved) and 47% were Ham-D-16 responders (defined as decrease from baseline of at least 50% in Ham-D-16 total score). CSDD mean scores and Ham-D-16 mean total scores demonstrated a progressive decrease from baseline to trial completion. The decrease in Ham-D scores from baseline to day 84 was statistically significant (p?<?0.0001). Mean changes from baseline to day 84 were ?6.6?±?6.9 (CSDD score) and ?7.9?±?7.4 (Ham-D-16 total score). Ham-D Factor I, Factor VI and item 1 scores also decreased. Fourteen of 124 patients in the all-subjects-treated (AST) group (11.3%) discontinued prematurely due to adverse events. The most frequently occurring adverse events were urinary tract infection (19%), accidental injury (18%), fall (18%), somnolence (12%), and upper respiratory infection (12%). Mean body weight increased by 0.7?±?2.25?kg (1.54?±?5lb)

from baseline to day 28, and by 1.3?±?3.36?kg (2.86?±?7.4lb) from baseline to day 84.

Conclusions: The results suggest that mirtazapine orally disintegrating tablets provide antidepressant efficacy and are a relatively well-tolerated treatment for depression in this patient population of elderly nursing home residents with medical and cognitive comorbidities.     

Long-term efficacy and safety of prophylaxis with recombinant factor VIII in Chinese pediatric patients with hemophilia A: a multi-center,retrospective, non-interventional,phase IV (ReCARE) study

Background: The first recombinant factor VIII (rFVIII) product was launched in China in 2007. However, until now, no study has been conducted to describe the efficacy and safety of prophylaxis with rFVIII in Chinese pediatric patients with hemophilia A (HA).

Objective: To summarize the efficacy and safety data on prophylaxis with rFVIII in Chinese pediatric patients with HA.

Methods: ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained regular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers (HTCs) across China. The primary endpoints included reduction in annualized bleeding rate (ABR); the secondary endpoints included evaluation of joint function (number and sites of target joints) using Gilbert score and Hemophilia Joint Health Score (HJHS), quality of life (QoL) and factors affecting treatment choices. Safety assessment of rFVIII was also conducted.

Results: We analyzed a total of 183 male pediatric patients (mean age, 7.1?±?4.23 years) who received prophylaxis between 1 November 2007 and 31 May 2013. Compared with baseline, prophylaxis with rFVIII significantly reduced overall annualized joint bleed rate (AJBR) (p?p?p?p?=?.003) at baseline. Responses from survey questionnaires reported that effective bleeding control, joint protection, improvement in quality of life, favorable medical insurance policies, and economic capability were reasons for choosing prophylaxis.

Conclusion: Prophylaxis with rFVIII reduced bleeding and number of target joints, even with a low-dose regimen, in Chinese pediatric patients with HA. Other than the efficacy and safety, factors such as poor disease control, improved economic stability and stable financial support made prophylaxis as an attractive treatment option.

ClinicalTrials.gov ID: NCT02263066.     

Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study*

ABSTRACT

Objectives: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combInation antihypertensiVe thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy.

Research design and methods: Patients remaining hypertensive (systolic BP [SBP], 145–180?mmHg; diastolic BP [DBP], 95–105?mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), β-blocker (n = 629), calcium-channel blocker (CCB; n = 493), angiotensin II type 1 receptor blocker (ARB; n = 75), α-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5?mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded.

Main outcome measures and results: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 ± 16?mmHg at baseline vs. 132 ± 12?mmHg at 3 months; DBP, 102 ± 8?mmHg vs. 83 ± 6?mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, β-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 ± 15/19 ± 9, 33 ± 17/19 ± 10, 33 ± 15/18 ± 8 or 35 ± 16/20 ± 12?mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (≤?140?mmHg) and 61% achieved BP normalisation (SBP <?140, DBP <?90?mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity.

Conclusions: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other antihypertensive agents.     

Improving asthma control in patients suboptimally controlled on inhaled steroids and long-acting β2‐agonists: addition of montelukast in an open-label pilot study

ABSTRACT

Background: Airway inflammation and symptoms often persist in asthma patients despite treatment with inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA). It is hypothesized that the leukotriene receptor antagonist montelukast, treating a pathway of inflammation distinct from that of ICS, might confer additional benefit.

Objective: To evaluate the efficacy of montelukast in improving asthma control in patients symptomatic on a fixed-association (FA) medium dose of ICS and LABA.

Methods: A 2-month, open-label, real-life observational study was undertaken by 131 Belgian pulmonologists. Patients (≥ 15 years old) suffering from persistent asthma (pre-bronchodilator FEV₁ ≥ 60% of predicted value) and insufficiently controlled on a FA therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10?mg daily as add-on therapy. Asthma control was assessed by the standardized Juniper asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with montelukast. Global evaluation of therapy was made both by the patients and physicians.

Results: A total of 313 patients were eligible for analysis. Forty-nine per cent received inhaled fluticasone/salmeterol and the rest budesonide/formoterol. Mean ACQ score decreased significantly on montelukast (13.9 ± 5.1 at baseline versus 7.4 ± 4.7 on montelukast, p < 0.001), with a significant improvement in all individual symptom scores (?p < 0.001) and in pre-bronchodilator FEV₁ score (from 2.2 ± 1.5 to 1.6 ± 1.4; p < 0.001). Parallel to these results, 78.6% of the patients reported a global improvement of their asthma. The same proportion of improvement was observed in the global evaluation made by the physicians (κ = 0.66).

Conclusion: This pilot study suggests that addition of montelukast in patients symptomatic on a FA of ICS and LABA may result in significant improvements in asthma control. A randomised, placebo-controlled clinical trial seems warranted.     

A two-week,double-blind,placebo-controlled trial of Viola odorata,Echium amoenum and Physalis alkekengi mixture in symptomatic benign prostate hyperplasia (BPH) men

Context: As an alternative approach, administration of phytotherapeutic agents in management of benign prostate hyperplasia (BPH), is rapidly growing each day. Different authors have indicated effectiveness of Viola odorata L. (Violaceae), Echium amoenum Fisch. &; C.A.Mey. (Boraginaceae) and Physalis alkekengi L. (Solanaceae) in treatment of BPH. However, none have reported the beneficial outcomes of the mixture yet.

Objective: This study evaluates the therapeutical effects of V. odorata, E. amoenum and P. alkekengi mixture on symptomatic BPH patients.

Materials and methods: Eighty six symptomatic BPH patients with International Prostate Symptom Score (IPSS) of more than 13 and prostate volume of more than 30?cm³ were randomly allocated to receive a two-week course of placebo (control group) or 1?mL of mixed hydro-alcoholic solution of P. alkekengi, E. amoenum and V. odorata extracts (1.5, 1 and 1.5% respectively) (treatment group).

Results: IPSS score of incomplete urination (42.3?±?2.04%), frequency of urination (20.08?±?1.02%), intermittency (40.78?±?2.16%), urgency (60.91?±?3.14%), weak stream (50.58?±?2.14%), straining (55.67?±?2.53%) and nocturia (40.14?±?1.89%) in treatment group were significantly decreased after treatment compare to placebo receiving group. Furthermore, the prostate volume (16.92?±?0.89%) and extant urine volume (28.12?±?1.36%) also significantly decreased in treatment group compared to control group. No significant side effects or abnormalities in biochemical tests and urinalysis were observed throughout the study.

Discussion and conclusions: Based on results, mentioned mixture is safe and effective in improving life quality of patients suffering from BPH.     

Overall tolerability and analgesic activity of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis

ABSTRACT

Objective: Viscosupplementation with intra-articular hyaluronic acid (HA) is an alternative to the treatment of symptomatic knee osteoarthritis (OA) with pain relieving drugs. Sinovial, is a sterile, non-pyrogenic 0.8% solution of highly purified sodium hyaluronate for intra-articular application. The aim of the present study was to investigate the safety and tolerability profile of this preparation in patients with symptomatic knee OA over 24 weeks.

Research design and methods: This was a single group, open-label study, including outpatients of both sexes, aged between 18 and 85 years, with symptomatic knee OA. All patients underwent weekly intra-articular injections of HA for 5 consecutive weeks and were followed-up for 19 additional weeks. The safety and tolerability profile (primary endpoint) was assessed by adverse event (AE) reporting. The secondary endpoint was efficacy evaluated by changes in the Western Ontario and McMaster Universities (WOMAC) score vs. baseline. Patient and physician satisfaction were also recorded.

Results: Intra-articular HA was generally well tolerated. The most frequent AE was pain at the injection site (5.8% of the injections); no serious treatment-related AE was reported. The WOMAC score was significantly reduced within the first 2 weeks of treatment (from 4.02 ± 1.90 to 3.55 ± 2.04, p = 0.0011), further decreased by the end of the injection series (week 6: 2.59 ± 1.90; p < 0.0001) and maintained during the follow-up (week 24: 2.44 ± 1.88; p < 0.0001). The WOMAC subscores were also significantly reduced from week 4 for ‘pain’ and from week 6 for ‘stiffness’ and ‘physical function’.

Conclusions: In the present study, intra-articular HA was well tolerated and safe in patients with symptomatic knee OA. Based on the sustained improvements in WOMAC score and subscores, a carry-over effect lasting for at least 19 weeks after the last injection may be proposed. These results further confirm the evidence of efficacy and safety of intra-articular HA in the management of knee OA.     

Evaluation of an isotonic tear in combination with topical cyclosporine for the treatment of ocular surface disease

ABSTRACT

Purpose: To determine whether a new category of artificial tear product, carboxymethylcellulose 0.5% with compatible solutes (CMC-solutes) (Optive, Allergan, Inc., Irvine, California) improves clinical outcomes when used adjunctively with topical cyclosporine 0.05% (Restasis, Allergan, Inc., Irvine, California) for the treatment of ocular surface disease.

Methods: Nineteen patients with ocular surface disease treated with cyclosporine 0.05% for at least 3 months and who had previously used other artificial tears adjunctively were enrolled. Patients discontinued their previous artificial tear and used CMC-solutes, concomitant with topical cyclosporine 0.05%. Corneal evaluation and tear production parameters were evaluated before and during combined CMC-solutes/cyclosporine treatment. Patients also completed a questionnaire before and during treatment with combined CMC-solutes/cyclosporine. Follow-up was at 1 and 3 months.

Results: Most objective measures of ocular surface health were unchanged, but an improvement in conjunctival lissamine green staining and tear break-up time was found. Conjunctival lissamine green staining scores improved from 3.4 ± 2.5 to 1.9 ± 2.5 by Month 3 (?p = 0.004). Tear break-up time improved from 4.6 ± 3.9?s pre-treatment to 5.3 ± 3.8?s post-treatment (?p = 0.049). Ocular Surface Disease Index (OSDI) scores improved from 16.2 ± 9.4 at baseline to 11.5 ± 8.9 at month 3 (?p = 0.007). Subjectively, patients graded their ocular discomfort as 2.7 at baseline and as 2.3 at Month 3 (?p = 0.049). At Month 3, 89.5% of patients said they liked CMC-solutes as well or better than previous drops they had used. All patients said CMC-solutes provided similar or improved relief of symptoms of dry eye than previous eye drops. There were no tear-related adverse events reported.

Conclusions: In this study, CMC-solutes, when used in conjunction with cyclosporine 0.05%, provided patients with an improvement in objective signs and subjective symptoms of ocular surface disease compared to their previous artificial tears. Further studies are warranted.     

Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis

Context: Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use.

Objective: We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis.

Methods: A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis.

Results: The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9?±?0.7 versus 1.4?±?0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3?±?0.5 versus 1.8?±?0.6, p?r?=?0.665), tearing (r?=?0.672), and the total ocular symptom score (r?=?0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r?=?0.610), nose blowing (r?=?0.640), and nasal obstruction (r?=?0.677). Furthermore, the tear fluid wheat IgE score was correlated with five objective features of allergic conjunctivitis (p?Conclusions: These results suggest that wheat allergy may be involved in the development of allergic conjunctivitis.     

Stress-related upper gastrointestinal bleeding in adult neurocritical care patients: a Chinese multicenter,retrospective study

Objective: China has limited data on stress-related gastrointestinal ulcers in patients admitted for neurosurgical care. This study evaluated the incidence of upper gastrointestinal bleeding (UGIB) and use of stress ulcer prophylaxis (SUP) in Chinese neurocritical care patients (Glasgow Coma Scale [GCS] score ≤10).

Methods: This multicenter, retrospective study was performed from January 2015 to July 2015. Medical records of 1468 patients hospitalized during 2014 were reviewed. An estimated UGIB incidence rate of 4.4% was considered for precision of 1.3% for estimation of UGIB. The primary endpoint was evaluation of overall incidence of any overt UGIB in ≤14 days after cerebral lesion. Secondary endpoints included incidence of UGIB with or and without clinically significant complications, time to UGIB, associated risk factors and SUP used.

Results: We analyzed 1416 patients (mean age: 53.7?±?14.00 years; males: 62.4%) with cerebral lesions. Overall incidence rate of UGIB ≤14 days was 12.9% (95% CI: 11.2%–14.7%), 0.76% with and 12.1% without significant clinical complications. Average time and duration of bleeding were 2.9?±?3.37 days and 4.2?±?8.4 days, respectively. The most significant risk factors for UGIB were mechanical ventilation for >48?hours (p?<?.0001), UGIB history (p?=?.0026) and use of anticoagulants (p?<?.0001). Acid-suppression drugs were administered for SUP in 79.0% of the patients, whereas 40.5% received hemostatic drugs.

Conclusions: The rate of UGIB incidence was higher than the estimated rate in neurocritical care patients in China, suggesting the need for better management and treatment for stress-related mucosal disease in China. History of UGIB, mechanical ventilation and/or anticoagulants significantly affected UGIB.

ClinicalTrials registry number: NCT02316990.     

A novel nanogel formulation of methotrexate for topical treatment of psoriasis: optimization,in vitro and in vivo evaluation

Context: Although several formulation strategies have been developed for the treatment of psoriasis, there is an unmet need for optimization of its therapy.

Objective: The objective was to develop a nanogel composed of methotrexate (MTX)-loaded nanostructured lipid carrier (MTX-NLC) and to evaluate its potential in imiquimod-induced psoriasis model to ameliorate symptoms of psoriasis.

Materials and methods: MTX-NLC nanogel was prepared by hot-homogenization method and optimized by Design of Experiments. Particle size, polydispersity index (PDI) and entrapment efficiency were selected as the critical quality attributes. Antipsoriatic potential of MTX-NLC nanogel was evaluated by Psoriatic Area and Severity Index (PASI) score and histopathological examination in the imiquimod-induced psoriasis model.

Results and discussion: Optimized MTX-NLC exhibited particle size of 278?±?10?nm, PDI of 0.231?±?0.05 and EE of 22.29?±?1.23%. At the end of 48?h, MTX-NLC gel exhibited slow and prolonged release of MTX (47.32?±?0.94% versus 94.23?±?0.79%) compared to MTX gel. Furthermore, it significantly reduced the PASI score with recovery of normalcy of the mice’s skin, while the MTX gel exhibited signs of hyper and parakeratosis at the end of the study.

Conclusion: The developed MTX-NLC gel formulation can be a promising alternative to existing MTX formulation in treating psoriasis.