Reduction In Symptom Score Research Articles

Clinical observation on treating gouty arthritis with modified Simiao decoction and external application of traditional Chinese medicine

Objective To evaluate the effects of treating gouty arthritis with modified Simiao decoction and external application of traditional Chinese medicine. Methods 76 patients with gouty arthritis of our hospital from January 2010 to August 2013 were recruited and randomly divided into a treatment group and a control group, 38 patients in each group. Patients in both groups were given low caloric diet, large amount of water（〉2 000 ml）, and forbidden to smoking, alcohol, sea food, animal splanchna and bean products. The control group was treated with oral intake of colchicines and indometacin in acute stage and oral intake of diclofenc in stable stage, while the treatment group was further added modified Simiao decoction and external application of traditional Chinese medicine on the basis of the control group. TCM symptom score, arthritis symptom score, symptomatic relief time, ESR, CRP, UA, IL-1βand IL-18 were observed after 7 days treatment. Results CRP, ESR decreased after the treatment[The treatment group respectively（22.06±10.31）mg/L, （25.18±17.80）mm/h,the control group respectively（14.11±7.32）mg/L, （24.16±22.09）mm/h]in both groups compared with the values before the treatment[The treatment group respectively（82.16±21.37）mg/L, （72.13± 32.36）mm/h,the control group respectively（52.46±22.26）mg/L, （62.72±33.31）mm/h, P〈0.01],while the decrease after of ESR in the treatment group was much obvious than the control group（P〈0.05）. IL-1β, IL-18 decreased after the treatment[The treatment group respectively（55.26±16.31）pg/ml, （187.32±50.38）pg/ml;the control group respectively（57.25±18.21）pg/ml, （178.49±52.60）pg/ml] in both groups compared with the values before the treatment[The treatment group respectively（106.11±41.02）pg/ml, （398.15±132.52）pg/ml.The control group respectively（109.23±40.12）pg/ml, （397.16±141.21）pg/ml, P〈0.01]. The symptomatic relief time was（4.02±2.08）d and（4.95±2.68）d in the treatment group and the control group respectively, showing statistical difference between the two groups（P〈0.05）. Conclusion Modified Simiao decoction combined with external application of Chinese medicines reduced TCM symptom score and arthritis symptom score, increase symptomatic relief time, decrease ESR, CRP and UA level, and enhance body immunity. Key words: Gouty arthritis; Modified Simiao decoction; External application of Chinese medicines; Therapeutic effect evaluation

Efficacy and Safety of Oral Budesonide Suspension in Pediatric Patients With Eosinophilic Esophagitis

No treatment has been approved by the U.S. Food and Drug Administration for eosinophilic esophagitis (EoE). We investigated the efficacy and safety of a new formulation of oral budesonide suspension (OBS), a corticosteroid, in a prospective, placebo-controlled, dose-ranging study. Subjects 2-18 years old with symptoms of EoE and peak eosinophil counts ≥20/high-power field at ≥2 levels of the esophagus were randomly assigned to groups given placebo or low-dose, medium-dose, or high-dose OBS for 12 weeks. Doses and volumes were adjusted on the basis of patients' age to cover the entire esophagus. The primary efficacy end point was compound response to therapy (peak eosinophil counts ≤6/high-power field at all levels of the esophagus and ≥50% reduction in EoE symptom score). Multiple safety parameters were evaluated. Data from 71 subjects who completed all efficacy assessments were included in the primary efficacy analysis. At the end of 12 weeks, there were significantly greater percentages of responders in groups given medium-dose OBS (52.6%, P = .0092) and high-dose OBS (47.1%, P = .0174) than in the group given placebo (5.6%); there was no significant difference in percentages of responders between the low-dose OBS (11.8%) and placebo groups (P = .5282). The significant compound responses noted in the medium-dose and high-dose OBS groups were accounted for by the significant histologic responses; in contrast, all 4 groups (including the placebo group) had large symptom responses, and there was no significant difference in the percentage of subjects with a symptom response in either OBS group compared with the placebo group (P ≥ .1235). There were no unexpected safety concerns or signals. Peak eosinophil counts were significantly reduced throughout the esophagus in pediatric patients with EoE who were given medium-dose and high-dose OBS. There was a large symptom response to placebo that was similar to symptom responses in the OBS groups; symptom response did not distinguish OBS from placebo. ClinicalTrials.gov number, NCT00762073.

Outcomes, feasibility and acceptability of a group support psychotherapeutic intervention for depressed HIV affected Ugandan adults: A pilot study

BackgroundPsychotherapy is the recommended first line treatment for mild to moderate depression. However, its availability in low resource settings is limited. We developed a manualized culturally sensitive group support psychotherapeutic intervention for depressed HIV affected Ugandan adults. In this study, we aimed to assess its feasibility, acceptability and impact on depression, functioning, social support and self-esteem. MethodsA total of 77 depressed individuals were assigned to the group intervention (n=48) and a wait-list control group (n=29), and assessed before, during and at the end of the intervention. The self-reporting questionnaire, a locally relevant function assessment instrument, the Rosenberg self-esteem scale, and the multiple dimensions perceived social support scale were administered to assess depression symptoms, functioning, self-esteem and social support at three assessment periods. Multivariate longitudinal regression models were used to determine change in outcomes over time between the two groups. Participants were asked to evaluate the intervention. ResultsPost –intervention assessments indicate that, in comparison to the wait-list control group, the intervention group had a faster reduction in depression symptom scores [OR=0.00,95% CI, 0.00–0.003] and faster increase in functioning scores [OR=4.82, 95% CI, 2.39 to 9.75], social support scores [OR=2.68, 95% CI, 1.50–4.78] and self-esteem [OR=1.90, 95% CI 1.48–2.44]. Sixty-three percent of participants strongly agreed that the intervention had reduced their depression and would recommend it to other depressed individuals. LimitationsInadequate study power due to small sample sizes may result in imprecise confidence intervals even when there are significant differences. The use of non-random samples could have resulted in selection bias. ConclusionsThis intervention appears feasible, acceptable and promising in treating depression and restoring function, enhancing social support and self-esteem. Larger and randomized evaluations are warranted.

Inhibition of capsaicin‐driven nasal hyper‐reactivity by SB‐705498, a TRPV1 antagonist

To assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of intranasal SB-705498, a selective TRPV1 antagonist. Two randomized, double-blind, placebo-controlled, clinical studies were performed: (i) an intranasal SB-705498 first time in human study to examine the safety and PK of five single escalating doses from 0.5 to 12 mg and of repeat dosing with 6 mg and 12 mg twice daily for 14 days and (ii) a PD efficacy study in subjects with non-allergic rhinitis (NAR) to evaluate the effect of 12 mg intranasal SB-705498 against nasal capsaicin challenge. Single and repeat dosing with intranasal SB-705498 was safe and well tolerated. The overall frequency of adverse events was similar for SB-705498 and placebo and no dose-dependent increase was observed. Administration of SB-705498 resulted in less than dose proportional AUC(0,12 h) and Cmax , while repeat dosing from day 1 to day 14 led to its accumulation. SB-705498 receptor occupancy in nasal tissue was estimated to be high (>80%). Administration of 12 mg SB-705498 to patients with NAR induced a marked reduction in total symptom scores triggered by nasal capsaicin challenge. Inhibition of rhinorrhoea, nasal congestion and burning sensation was associated with 2- to 4-fold shift in capsaicin potency. Intranasal SB-705498 has an appropriate safety and PK profile for development in humans and achieves clinically relevant attenuation of capsaicin-provoked rhinitis symptoms in patients with NAR. The potential impact intranasal SB-705498 may have in rhinitis treatment deserves further evaluation.

Shells from rose-hip (Rosa canina) do not reduce symptom scores or improve anti-inflammatory property in patients with osteoarthritis – a double-blind, placebo-controlled, randomized study

Purpose: Placebo controlled studies on a standardised rose-hip powder, Hyben-Vital®, based on daily intake of 2.5 g seeds and 2.5 g shells, indicate alleviation of symptoms from osteoarthritis. The same powder also shows anti-inflammatory properties, by lowering C-reactive protein (CRP) and erythrocyte sedimentation rate. On the latest OARSI meeting, data from a partly blinded, exploratory study, on rose-hip powder, based exclusively on shells, was presented. The study, which did not include placebo or measurements of inflammatory markers, suggested that the shell powder (2.25 g daily) could have equal, or perhaps stronger effect, than the double dose of said shell powder (4.5 g daily), or even the original Hyben-Vital powder (5 g daily) containing 50% shells and 50% seeds. An inverse dose-response curve, where less powder gives higher response, was introduced in the study. The inclusion of a placebo arm would have made the study even stronger. The present study, therefore, aims to test whether this low-dose shell powder shows any impact on symptoms of OA and/or reduction in CRP, when tested against placebo treatment. Methods: Ninety-four patients, a sub fraction from a study on the occurrence of common cold during the winter season (ClinicalTrials.gov Identifier NCT 01459952), all diagnosed with OA according to the criteria of the American College of Rheumatology, participated in the present study. Forty-seven patients received 90% rosehip shells and 10% rose hip seeds in total (2.20 gram daily) and the remaining forty-seven patients received placebo of similar taste and colour. All patients were followed for 6 months. Pain and stiffness was estimated on a numerical scale from 0-10 (more symptom - higher score) and patient’s global assessment of disease severity (PGAD) was estimated on a 100 mm scale (WOMAC). Quality of life was estimated using SF-12, and CRP by normal laboratory routine. The Wilcoxon tested within groups and the Man-Whitney was used when comparing groups. A p-value less than 0.050 was regarded as statistically significant. All data given is on the intention to treat basis. To further test if an impact from active treatment, if present, was based on treatment it self or was possibly random - a dose dependency tests - was made on both groups by testing for a correlation between patient weight and symptom score. Results: Pain declined as a result of active treatment from 4.72 +/- 2.41 to 3.44 +/- 2.19 (p<0.050). Placebo resulted in similar results: 4.91 +/- 3.07 declined to 3.99 +/-2.74, p<0.086. Man-Whitney p value <0.880. Stiffness likewise declined in both groups. Active treatment: 3.57 +/- 2.38 declined to 2.95 +/- 1.88 (p<0.236) and placebo: 4.50 +/- 2.93 declined to 3.80 +/- 2.85, (p<0.033). Man-Whitney p value: 0.274. No significant change was observed in PGAD: active treatment 31.0 +/-21 changing to 33.0 +/-20.0 (p<0.527) and placebo 42.0 +/-27 unchanged 42.0 +/-24.0 (p<0.541). Mann-Whitney p-value 0.520. Quality of life (SF-12 physical and SF-12 psychological) did not show any changes (data not given). CRP remained unchanged during both treatments, Mann-Whitney p-value: 0.347. There was no correlation between patient weight and the change in symptom scores in either of the two groups at any time point of the study (data not given). This demonstrates a lack of effect of shell powder treatment. The lighter patient at 60 kg had the same lack of effect as had the heavier patient at 110 kg. Conclusions: In regards to impact on symptom scores of OA, quality of life and reduction in CRP, low-dose rose-hip powder based mainly on shells, is comparable to placebo. The effect in symptom scores of OA, quality of life and reduction in CRP seen in previous studies on standardised rose-hip powder from Rosa canina may be highly dependent on the higher content of seeds.

Kinetic oscillation stimulation as treatment of non-allergic rhinitis: an RCT study

Conclusion: Kinetic oscillation stimulation (KOS) of nasal mucosa at low frequency seems to be a possibly effective and safe short-term treatment of non-allergic nasal stuffiness. Objective: To assess the relief of rhinitis symptoms, especially stuffiness, by comparing active treatment, i.e. KOS at low frequency of the nasal mucosa, with placebo. Methods: Patients were randomized to active or placebo treatment in this double-blinded parallel design study. Treatment with an inflatable oscillating catheter was administered on day 0, and symptom scores (stuffiness, secretion, and itching) were graded daily until day 14. An overall grading of symptoms from 1 week before treatment and during 14 days thereafter was made at day 14. Eighty-six patients (52 with non-allergic perennial rhinitis, NAR; 34 with rhinitis medicamentosa, RM) were randomized, and 71 were evaluated (active treatment, n = 35; placebo, n = 36). Results: Patients with either NAR or RM who received active treatment reported reduced symptom scores by some measures, e.g. median RQSS stuffiness measure fell from 2 to 1 on a scale from 0 to 3 during the week following treatment. No significant effect was observed for patients treated with placebo. Mild side effects were reported.

Degarelix versus Goserelin plus Bicalutamide Therapy for Lower Urinary Tract Symptom Relief, Prostate Volume Reduction and Quality of Life Improvement in Men with Prostate Cancer: A Systematic Review and Meta-Analysis

Objective: We performed a systematic review and meta-analysis to assess the efficacy and tolerability of degarelix for lower urinary tract symptom relief, prostate volume reduction and quality of life improvement in men with prostate cancer (PCa). Materials and Methods: A literature review was performed to identify all of the published randomized controlled trials (RCTs) that used degarelix versus gonadotropin-releasing hormone agonists plus antiandrogens therapy for the treatment of PCa. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Results: Three publications involving a total of 466 patients were used in the analysis, including three RCTs that compared degarelix with goserelin plus bicalutamide therapy for PCa over 12 weeks. For the comparison of degarelix with goserelin plus bicalutamide therapy, International Prostate Symptom Score (IPSS) reduction (standardized mean difference [SMD] = -1.85, 95% confidence interval [CI] = -2.97 to -0.72, p = 0.001) and IPSS ≥13 (SMD = -2.68, 95% CI = -4.57 to -0.78, p = 0.006) indicated that decreases in IPSS were greater in degarelix-treated patients than in goserelin plus bicalutamide-treated patients. Conclusions: Our meta-analysis indicates that, compared with goserelin plus bicalutamide, degarelix has significantly more pronounced effects on lower urinary tract symptoms.

Cluster Subcutaneous Allergen Specific Immunotherapy for the Treatment of Allergic Rhinitis: A Systematic Review and Meta-Analysis

BackgroundAlthough allergen specific immunotherapy (SIT) represents the only immune- modifying and curative option available for patients with allergic rhinitis (AR), the optimal schedule for specific subcutaneous immunotherapy (SCIT) is still unknown. The objective of this study is to systematically assess the efficacy and safety of cluster SCIT for patients with AR.MethodsBy searching PubMed, EMBASE and the Cochrane clinical trials database from 1980 through May 10th, 2013, we collected and analyzed the randomized controlled trials (RCTs) of cluster SCIT to assess its efficacy and safety.ResultsEight trials involving 567 participants were included in this systematic review. Our meta-analysis showed that cluster SCIT have similar effect in reduction of both rhinitis symptoms and the requirement for anti-allergic medication compared with conventional SCIT, but when comparing cluster SCIT with placebo, no statistic significance were found in reduction of symptom scores or medication scores. Some caution is required in this interpretation as there was significant heterogeneity between studies. Data relating to Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in 3 included studies were analyzed, which consistently point to the efficacy of cluster SCIT in improving quality of life compared to placebo. To assess the safety of cluster SCIT, meta-analysis showed that no differences existed in the incidence of either local adverse reaction or systemic adverse reaction between the cluster group and control group.ConclusionBased on the current limited evidence, we still could not conclude affirmatively that cluster SCIT was a safe and efficacious option for the treatment of AR patients. Further large-scale, well-designed RCTs on this topic are still needed.

Does Online Haemodiafiltration Reduce Intra-Dialytic Patient Symptoms?

Introduction: Patients often suffer from symptoms during dialysis. Haemodiafiltration (HDF) therapy has been suggested to be superior to standard haemodialysis (HD). To understand patients' experiences, we quantified the burden and duration of dialysis-associated symptoms to determine whether there was any difference between the modalities. Methods: Symptom questionnaires (83.3%) were returned by 623 dialysis outpatients. Symptom scores were analysed using a visual analogue score. We compared symptom burdens during HD and HDF treatments and also whether the scores changed following a modality change to HDF. Results: Among the patients, 55.7% were men, the median age was 65 years, 39.7% were diabetic, 26.4% were treated by HDF and the median unadjusted Charlson co-morbidity score was 6 (IQR 4-8). Fatigue (77.3%), intra-dialytic hypotension (76.4%), cramps (74.3%) and dizziness (63%) were the commonest symptoms reported, followed by headache (53.6%) and pruritus (52.2%). Although most symptoms were reported less frequently with HDF [median headache frequency score: HD: 1 (IQR 1-4) vs. HDF: 0 (IQR 0-2), p < 0.005]. There was no evidence of a reduction in symptom scores in patients switching from HD to HDF compared to those remaining on HD. Conclusion: Patient self-reporting shows that most patients frequently suffer symptoms. There was no evidence that switching to HDF improved symptoms in patients established on HD.

The efficacy of procin-x and celloid-s in the management of benign prostatic enlargement

Background and Objective: Despite a decent efficacy and safety profile, α1 - blockers (A1B) and the 5α - reductase inhibitors (5ARI), the conventional drugs used in the treatment of the symptoms of Benign Prostatic Hyperplasia (BPH), are commonly associated with adverse effects including sexual dysfunction and postural hypotension. Phytotherapy for the treatment BPH symptoms has been used for centuries. However, scientific data on their efficacy are sparse. Procin-X and Celloid-S (PC) are powdered plant material products with acclaimed anti- BPH properties. This study assessed their usefulness in the management of BPH. Materials and Methods: This was a single blind, randomized, placebo-controlled study conducted at our hospital involving 80 patients (divided in to 2 equal groups) with the clinical diagnosis of BPH. The study group were given PC while the controls were given multivitamin Capsules daily for a period of 14 weeks. All patients were evaluated at intervals for severity of symptoms, flow rates, prostate size, prostate specific antigen (PSA) and possible adverse effects including erectile function. Test of significance between the means was done using the Students Paired t-test. A P < 0.05 was considered significant. Results: At the end of 14 weeks there was an reduction in symptom score by 5.7 and 1.6 in subjects and controls respectively (P < 0.05) and an increase in flow rate by 4.0mls/s and 1.1mls/s respectively (P < 0.05). There was a 60% and 14% reduction in PSA in the subjects and control respectively. There was also statistically significant increase in the erection score in the subjects. Conclusion: PC appear to be effective and in the management of the symptoms of BPH. The positive effects of PC on erectile function may however give them an advantage over the A1B and 5ARI drugs while the reduction in PSA may also give it a role in chemoprevention of prostate cancer. A large scale cohort study is needed to confirm these findings.

PTSD Symptom Reports of Patients Evaluated for the New Mexico Medical Cannabis Program

Background: New Mexico was the first state to list post-traumatic stress disorder (PTSD) as a condition for the use of medical cannabis. There are no published studies, other than case reports, of the effects of cannabis on PTSD symptoms. The purpose of the study was to report and statistically analyze psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico Medical Cannabis Program from 2009 to 2011. Methods: The Clinician Administered Posttraumatic Scale for DSM-IV (CAPS) was administered retrospectively and symptom scores were then collected and compared in a retrospective chart review of the first 80 patients evaluated. Results: Greater than 75% reduction in CAPS symptom scores were reported when patients were using cannabis compared to when they were not. Conclusions: Cannabis is associated with reductions in PTSD symptoms in some patients, and prospective, placebo-controlled study is needed to determine efficacy of cannabis and its constituents in treating PTSD.

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome.

To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome. A prospective, interventional, placebo controlled, double blind randomized trial was done at two referral eye centers. Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule (500mg) two times a day containing 325mg EPA and 175mg DHA for 3 months (omega-3 group). The omega-3 group was compared to a group of patients (n=254) who received a placebo (placebo group). There were 4 patient visits (at baseline, 1 month, 2 months and 3 months). On each visit, recording of corrected distance visual acuity (CDVA), slit lamp examination and questionnaire based symptom evaluation and scoring was done. A symptomatic score of 0-6 was mild, 6.1-12 moderate and 12.1-18 severe dry eye. Response to intervention was monitored by routine tear function tests like Schirmer I test, tear film break-up time (TBUT), Rose Bengal staining and most notably, conjunctival impression cytology. Sixty-five percent of patients in the omega-3 group and 33% of patients in placebo group had significant improvement in symptoms at 3 months (P=0.005). There was a significant change in both Schirmer's test value and TBUT values in the omega-3 group (P<0.001), both comparisons. However, there was a larger drift in TBUT values in omega-3 than the placebo group, in comparison to Schirmer's test values. The mean TBUT score was 2.54±2.34 in the omega-3 group and 0.13±0.16 in placebo group, respectively. The mean reduction in symptom score in omega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebo group (P<0.001). Despite a slight increase mean score, the Schirmer scores did not correlate well with symptomatic improvement. Omega-3 fatty acids have a definite role for dry eye syndrome. The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease. The role of omega fatty acids in tear production and secretion needs further evaluation.

TREATMENT OF DIARRHEA-PREDOMINANT IRRITABLE BOWEL SYNDROME WITH MESALAZINE AND/OR SACCHAROMYCES BOULARDII

Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal pain and altered intestinal habits. The pathophysiology of IBS remains unclear. Recent studies have demonstrated that some IBS patients, especially in diarrhea-predominant IBS (IBS-D), display persistent signs of minor mucosal inflammation and a modified intestinal microflora. The mesalazine has known intestinal anti-inflammatory properties. Saccharomyces boulardii is a probiotic used for a long time in treatment of diarrhea, including infectious diarrhea. Evaluate the effects of mesalazine alone, combined therapy of mesalazine with liophylised Saccharomyces boulardii or alone on symptoms of IBS-D patients. Based on Rome III criteria, 53 IBS-D patients (18 year or more) were included. To exclude organic diseases all patients underwent colonoscopy, stool culture, serum anti-endomisium antibody, lactose tolerance test and ova and parasite exam. Patients were divided in three groups: mesalazine group (MG) - 20 patients received mesalazine 800 mg t.i.d. for 30 days; mesalazine and Saccharomyces boulardii group (MSbG) - 21 patients received mesalazine 800 mg t.i.d. and Saccharomyces boulardii 200 mg t.i.d. for 30 days and; Saccharomyces boulardii group (SbG) - 12 patients received Sb 200 mg t.i.d. for 30 days. Drugs that might have any effect on intestinal motility or secretion were not allowed. Symptom evaluations at baseline and after treatment were performed by means of a 4-point likert scale including: stool frequency, stool form and consistency (Bristol scale), abdominal pain and distension. Paired t test and Kruskal-Wallis test were used for statistical analyses. Compared to baseline, there were statistically significant reduction of symptom score after 30 th day therapy in all three groups: MG (P<0.0001); MSbG (P<0.0001) and in SbG (P = 0.003). There were statistically significant differences in the symptom score at 30 th day therapy of the MG, MSbG and SbG groups (P = 0.03). There were no statistical differences between MSbG and MG symptom score at 30th day therapy (P = 0.9). The use of mesalazine alone, Saccharomyces boulardii alone or combined treatment with mesalasine and Saccaromyces boulardii improved IBS-D symptoms. The improvement of the symptom score was greater with mesalazine alone or combined with Sb as compared with Sb treatment alone. These preliminary results suggest that mezalazine may be useful in treatment of IBS-d patients, and warrant further larger studies.

Extended problem solving treatment for depression

Introduction: Effective brief psychological approaches for depression that can be delivered by a variety of health professionals with minimal training increase access to treatment by patients. Problem Solving Treatment (PST) was developed for primary care and was modified for this study (EPST) to better meet the needs of mental health patients. Method: A total of 92 therapists from different professional backgrounds completed EPST workshops and treated 92 patients with major depression with interval clinical and treatment process assessments. Results: EPST achieved a significant reduction in depressive symptom scores, life problem scores, and there were few treatment non‐completers. Treatment outcome was predicted by process and therapist variables. Discussion: EPST is an effective and easy to teach treatment that can be delivered by a variety of practitioners and suitable for busy primary mental health care settings.

Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial

BackgroundThe common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults.MethodsThis study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured.ResultsMean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups.ConclusionA fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults.Trial registrationNCT01389518

Efficacy and Safety Of Fedratinib (SAR302503/TG101348) In Patients With Intermediate- Or High-Risk Myelofibrosis (MF), Post-Polycythemia Vera (PV) MF, Or Post-Essential Thrombocythemia (ET) MF Previously Treated With Ruxolitinib: Interim Results From a Phase II Study (JAKARTA-2)

▪ BackgroundThe JAK1/JAK2 inhibitor ruxolitinib (RUX) is approved for treatment of myelofibrosis (MF). However, some patients do not respond to RUX, while others lose responsiveness or develop intolerance to RUX over time. Preclinical data also suggest that certain JAK2 mutations (eg the gatekeeper mutation M929I) may confer resistance to RUX (Leukemia 2012;26:708). Options for these RUX resistant/intolerant patients, particularly with regard to further JAK inhibitor therapy, are unclear. Fedratinib (SAR302503) is a JAK2-selective inhibitor which has demonstrated clinically meaningful reductions in splenomegaly and symptom burden in patients with MF, with an acceptable and consistent safety profile (J Clin Oncol 2011;29:789. Haematologica 2013;98:S1113). Fedratinib sensitivity in vitro is unaffected by the M929I mutation. This pre-specified interim analysis of the JAKARTA-2 study (NCT01523171) investigated the efficacy and safety of fedratinib in MF patients previously treated with RUX. MethodsJAKARTA-2 is a Phase II, multicenter, open-label, single-arm study of patients who previously received RUX for MF. Patients ≥18 yrs with splenomegaly and platelet count ≥50 ×109/L received fedratinib 400 mg orally, once daily for consecutive 4-wk cycles (permitted dose adjustment to 200–600 mg daily). Eligible patients had received ≥14 d RUX treatment, and had discontinued RUX for ≥14 d prior to starting fedratinib. Although there is no consensus definition of RUX resistance/intolerance, for the purpose of this study patients were classed (investigator assessment) as resistant (lack or loss of response) or intolerant to RUX. Primary endpoint for the interim analysis: spleen response rate (RR) (≥35% reduction in spleen volume from baseline at Wk 12 [MRI/CT blinded central review]) in the per-protocol (PP) population. Secondary endpoints: symptom RR (≥50% reduction in total symptom score [TSS: modified Myelofibrosis Symptom Assessment Form] from baseline to Wk 12) and safety. ResultsAt the cut-off date for this interim analysis, 27 patients had received fedratinib treatment (median RUX exposure 10.7 months [range 1.9–34.4]): median age 69 yrs; 56% male; 67% primary MF; 63% high-risk MF; 67% JAK2V617F positive; 41% platelet count <100 × 109/L; baseline median spleen volume 3190 mL [1072–7815]; baseline median TSS 19.6 [4.9–46.0]. Eighteen patients were considered resistant by the treating physician (8 lack of response, 3 disease progression, 7 loss of response; median RUX exposure 11.1 months [range 1.9–34.4]) and 9 intolerant (6 hematologic, 3 non-hematologic toxicity; median RUX exposure 9.2 months [2.9–33.2]) to RUX. Median fedratinib exposure to cut-off date: 4 cycles (range 1–10); 19 patients remain on treatment. Spleen RRs were 40% (8/20 PP patients) and 43% (3/7) in patients with baseline platelet count <100 ×109/L. Overall, 19% (5/26 evaluable patients) had a symptom response by Wk 12 (Table). The majority of patients had a reduction in TSS at Wk 12 (Figure). [Display omitted] The most common non-hematologic treatment-emergent adverse events (AEs) were gastrointestinal (nausea 67%; diarrhea 56%; vomiting 48%). Grade 3/4 diarrhea occurred in 2 patients; no Grade 3/4 vomiting or nausea. Anemia was the most common hematologic AE (all grades, 93%; Grade 3, 41%; Grade 4, 0%). Thrombocytopenia (all grades) occurred in 19 (70%) patients; Grade 3 in 6 patients and Grade 4 in 2 patients. One patient had Grade 3 AST elevations and 1 patient had Grade 3 hyperbilirubinemia. Seven patients (26%) discontinued treatment due to AEs. There were 2 deaths on study, both due to disease progression. ConclusionsInterim results from the JAKARTA-2 study indicate that once-daily fedratinib provides clinical benefit, through reduced splenomegaly and symptom burden, in MF patients previously treated with RUX. The safety profile was acceptable and manageable, with safety results to date consistent with those reported in previous trials of fedratinib. Sponsored by Sanofi. Disclosures:Harrison:Novartis: Research Funding; Novartis, Sanofi, YM Bioscience, Celgene, SBio, Gilead: Honoraria; Novartis, Sanofi, Shire: Speakers Bureau; Novartis, Sanofi, YM Bioscience, SBio, Gilead: Membership on an entity's Board of Directors or advisory committees. Jourdan:Sanofi: Honoraria. Kiladjian:Novartis, Celgene, AOP Orphan: Research Funding; Novartis, Sanofi, AOP Orphan: Honoraria; Novartis, Sanofi, AOP Orphan: Membership on an entity's Board of Directors or advisory committees. Cervantes:Novartis: Speakers Bureau; Novartis and Sanofi: Membership on an entity's Board of Directors or advisory committees. Niederwieser:Novartis Pharma: Consultancy. Cortes:Incyte, Sanofi: Consultancy; Incyte, Sanofi: Research Funding. Passamonti:Novartis, Celgene, Incyte, Sanofi, Roche: Honoraria. Reiter:Sanofi: Honoraria. Heidel:Novartis Inc.: Honoraria; Novartis Inc.: Research Funding; Novartis Inc.: Membership on an entity's Board of Directors or advisory committees. Silver:Sanofi: Consultancy; Sanofi: Research Funding; Sanofi: Honoraria. Winton:Sanofi: Research Funding. Gupta:Incyte, Novartis: Consultancy; Incyte, Novartis: Research Funding; Novartis: Honoraria. Gisslinger:AOP Orphan Pharmaceuticals, Novartis, Sanofi, Shire, Celgene, Janssen: Membership on an entity's Board of Directors or advisory committees; AOP Orphan Pharmaceuticals, Novartis, Sanofi, Shire, Celgene, Janssen: Honoraria. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Talpaz:Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Research Funding; Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Speakers Bureau. Zhang:Sanofi: Employment. Shi:Sanofi: Employment. Mesa:Incyte, Genentech, Lilly, MS Pharma, Gilead: Research Funding.

Results Of a Randomized, Double-Blind, Placebo-Controlled Phase III Study (JAKARTA) Of The JAK2-Selective Inhibitor Fedratinib (SAR302503) In Patients With Myelofibrosis (MF)

▪ BackgroundFedratinib (SAR302503) is a JAK2-selective inhibitor that has provided clinically meaningful reductions in MF-associated splenomegaly and symptoms in Phase I and II studies (J Clin Oncol 2011;29:789. Haematologica 2013;98:S1113). Here, we present efficacy and safety data from the Phase III JAKARTA study of fedratinib versus placebo in patients with MF (NCT01437787). MethodsIn this international double-blind, placebo-controlled, 3-arm study, patients aged ≥18 years with IPSS intermediate-2 or high-risk MF, platelet count ≥50 × 109/L, and splenomegaly were randomized (1:1:1) to receive placebo or fedratinib 400 mg or 500 mg, orally, once daily, in consecutive 4-week cycles. Patients who received placebo were eligible to cross-over to fedratinib (randomized 1:1 to 400 mg or 500 mg) following 6 cycles of treatment, or prior to Cycle 6 if the patient had disease progression. The primary endpoint was spleen response rate (RR) (≥35% reduction in spleen volume from baseline measured by MRI or CT at Week 24, and confirmed 4 weeks later). Secondary endpoints included symptom RR (≥50% reduction in total symptom score from baseline at Week 24, measured through a daily electronic eDiary using the modified Myelofibrosis Symptom Assessment Form [Cancer 2011;117:4869. Blood 2011;118:401]), and safety of fedratinib. ResultsA total of 289 patients were randomized: median age 65 years; 59% male; 63% primary MF; 48% high-risk MF; 67% JAK2V617F positive; 16% platelet count <100 × 109/L; median baseline spleen volume 2568 mL (range 316–8244); median baseline total symptom score 14.7 (0–57). Median (range) exposures for placebo, 400 mg and 500 mg groups were 24 (2–34), 30 (1–55) and 28 (1–60) weeks, respectively. Spleen RRs at Week 24 (placebo 1%; 400 mg 47%; 500 mg 49%), and confirmed at Week 28 (placebo 1%; 400 mg 36%; 500 mg 40%), were significantly (p<0.0001) higher in both fedratinib groups compared with placebo (Table). Nineteen patients had a spleen response at Week 24 not confirmed 4 weeks later (spleen reduction 25–35% [n=10]; image not available/evaluable [n=8]; image taken outside time window [n=1]). Spleen RRs by baseline platelet level are shown in the table. Patients treated with fedratinib had significantly (p<0.0001) greater improvements in MF symptoms compared with placebo (Table).The most common all grade non-hematologic treatment-emergent adverse event (TEAE) was diarrhea (16%, 66% and 56% of patients in the placebo, 400 mg and 500 mg groups, respectively). Grade 3/4 diarrhea was reported in 5% of patients in both the 400 mg and 500 mg dose groups. The most common hematologic TEAE was anemia (any grade 91%, 99% and 98%; Grade 3/4 25%, 43% and 60% in the placebo, 400 mg and 500 mg groups, respectively). Rates of Grade 3/4 thrombocytopenia were 9% (placebo), 17% (400 mg), and 27% (500 mg). Incidences of Grade 3/4 liver function tests (placebo/400 mg/500 mg) were: bilirubin, 2%/2%/1%; ALT, 0%/3%/3%; and AST, 1%/2%/2%. Overall treatment discontinuation rates up to 24 weeks of treatment were 25% (placebo), 22% (400 mg) and 32% (500 mg). Twenty-five patients died during the study (10, 5 and 10 in the placebo, 400 mg and 500 mg groups, respectively); the most common causes of death: disease progression (placebo [n=5]; 400 mg [n=3]; 500 mg [n=4]) and adverse events (placebo [n=4]; 400 mg [n=1]; 500 mg [n=4]). ConclusionsIn this Phase III, randomized, placebo-controlled, 3-arm study of 289 MF patients, treatment with fedratinib 400 mg or 500 mg once-daily demonstrated clinically meaningful and statistically significant reductions in splenic volume and MF-associated symptom burden versus placebo. Fedratinib had an acceptable safety profile, with the adverse events reported consistent with those observed in previous studies. This study was sponsored by Sanofi. Disclosures:Pardanani:Sanofi, Bristol Myers Squibb, PharmaMar and JW Pharma: Clinical trial support Other. Harrison:Novartis: Research Funding; Novartis, Sanofi, YM Bioscience, Celgene, SBio, Gilead: Honoraria; Novartis, Sanofi, Shire: Speakers Bureau; Novartis, Sanofi, YM Bioscience, SBio, Gilead: Membership on an entity's Board of Directors or advisory committees. Cortes:Incyte, Sanofi: Consultancy; Incyte, Sanofi: Research Funding. Cervantes:Novartis: Speakers Bureau; Novartis and Sanofi: Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte, Genentech, Lilly, MS Pharma, Gilead: Research Funding. Jourdan:Sanofi: Honoraria. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Drummond:Sanofi, Novartis, Celgene: Honoraria; TargeGen, Novartis: Speakers Bureau; Sanofi, Novartis, Celgene: Consultancy. Passamonti:Novartis, Celgene, Incyte, Sanofi, Roche: Honoraria. Neumann:Sanofi: Employment. Gao:Sanofi: Employment.

The role of multidrug resistance-1 (MDR1) variants in response to fexofenadine among Jordanians

The MDR1 gene encodes for P-glycoprotein (P-gp), which is an efflux transporter at the cell membrane. The P-gp has wide substrate specificity for multiple medications, including the antiallergic drug fexofenadine. In this study, we investigated the possible association between three common MDR1 gene polymorphisms (G2677T, C3435T, and C1236T), and the anti-allergic effect of fexofenadine among Jordanians. An assessment of the severity of allergic rhinitis symptoms was performed for all patients (n = 260) pre- and 7 days into fexofenadine. MDR1 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Relative to baseline, fexofenadine treatment was associated with significant reduction in allergic individual and total scores (p < 0.0001). Male gender was associated with less mean reduction in total allergic rhinitis symptoms score than in female (p < 0.05). In multivariate analysis, male gender was negatively correlated with response to fexofenadine (p = 0.01). The MDR1 gene C1236T polymorphism showed significant correlation with changes in total symptoms score from baseline in males (p < 0.05) but not in females. No significant correlation between fexofenadine response parameters and G2677T or the C3435T polymorphism was observed. The MDR1 gene polymorphism C1236T was associated with the anti-allergic effect of fexofenadine among male Jordanians.

Dance therapy for schizophrenia.

Dance therapy or dance movement therapy (DMT) is defined as 'the psychotherapeutic use of movement as a process which furthers the emotional, social, cognitive, and physical integration of the individual'. It may be of value for people with developmental, medical, social, physical or psychological impairments. Dance therapy can be practiced in mental health rehabilitation units, nursing homes, day care centres and incorporated into disease prevention and health promotion programmes. To evaluate the effects of dance therapy for people with schizophrenia or schizophrenia-like illnesses compared with standard care and other interventions. We updated the original July 2007 search of the Cochrane Schizophrenia Group' register in July 2012. We also searched Chinese main medical databases. We included one randomised controlled trial (RCT) comparing dance therapy and related approaches with standard care or other psychosocial interventions for people with schizophrenia. We reliably selected, quality assessed and extracted data. For continuous outcomes, we calculated a mean difference (MD); for binary outcomes we calculated a fixed-effect risk ratio (RR) and their 95% confidence intervals (CI). We created a 'Summary of findings' table using the GRADE approach. We included one single blind study (total n = 45) of reasonable quality. It compared dance therapy plus routine care with routine care alone. Most people tolerated the treatment package but nearly 40% were lost in both groups by four months (1 RCT n = 45, RR 0.68 95% CI 0.31 to 1.51, low quality evidence). The Positive and Negative Syndrome Scale (PANSS) average endpoint total scores were similar in both groups (1 RCT n = 43, MD -0.50 95% CI -11.80 to 10.80, moderate quality evidence) as were the positive sub-scores (1 RCT n = 43, MD 2.50 CI -0.67 to 5.67, moderate quality evidence). At the end of treatment, significantly more people in the dance therapy group had a greater than 20% reduction in PANSS negative symptom score (1 RCT n = 45, RR 0.62 CI 0.39 to 0.97, moderate quality evidence), and overall, average negative endpoint scores were lower (1 RCT n = 43, MD -4.40 CI -8.15 to -0.65, moderate quality evidence). There was no difference in satisfaction score (average Client's Assessment of Treatment Scale (CAT) score, 1 RCT n = 42, MD 0.40 CI -0.78 to 1.58, moderate quality evidence) and quality of life data were also equivocal (average Manchester Short Assessment of Quality of life (MANSA) score, 1 RCT n = 39, MD 0.00 CI -0.48 to 0.48, moderate quality evidence). Based on predominantly moderate quality data, there is no evidence to support - or refute - the use of dance therapy in this group of people. This therapy remains unproven and those with schizophrenia, their carers, trialists and funders of research may wish to encourage future work to increase high quality evidence in this area.

Effect of fructose-reduced diet in patients with irritable bowel syndrome, and its correlation to a standard fructose breath test

Objectives. To perform a validation of dairy registrations for use as diagnostic tool in IBS and fructose malabsorption (FM). To investigate the precision of the fructose breath test (FBT) as compared with symptom score reduction on fructose-reduced diet (FRD) in a cohort of patients with Rome II defined irritable bowel syndrome (IBS). Design. IBS patients diagnosed according to the Rome II criteria and with no organic gastrointestinal disease were enrolled. The patients were randomized in an open study design with a 2 week run-in on IBS diet, followed by 4 weeks w/wo additional FRD. FBT was performed in all patients. Dairy registrations of stool frequency and consistency as well as abdominal pain/discomfort and bloating on a visual analog scale (VAS) were performed during the whole study. Results. A total of 182 subjects performed the study according to protocol (88 FRD, 94 controls). The VAS symptom registration performed well in validation procedures, whereas stool data showed less impressive characteristics. FRD improved symptom scores (abdominal pain/discomfort and bloating) significantly whereas no changes were observed in the control group. The effect of FRD on the stool frequency was modest but no effect was observed on the stool consistency. The FBT did not discriminate between patients with and without effect of FRD, and even in the group with a negative FBT significant improvement of symptom scores was observed. Conclusion. VAS measures yield reliable symptom evaluation in dairy registrations of IBS. FRD improves symptom scores in IBS patients independent of results from the FBT.