Change In Total Symptom Score Research Articles

Clinical Benefits of Ruxolitinib Therapy in Myelofibrosis Patients with Varying Degrees of Splenomegaly and Symptoms

AbstractAbstract 1727 Background:Myelofibrosis (MF) is characterized by cytopenias, splenomegaly, and burdensome symptoms that may worsen over time. Ruxolitinib (RUX) has been shown to reduce splenomegaly and improve MF-associated symptoms in 2 phase III studies, including COMFORT-I, a randomized, double-blind, placebo (PBO)-controlled trial, which also showed prolonged survival in favor of RUX. Purpose:In this post hoc analysis of COMFORT-I, the efficacy of RUX in patients with varying degrees of splenomegaly and symptom severity at baseline was evaluated to assess the potential effects of earlier versus later intervention in this progressive disease. Methods:COMFORT-I participants randomized to RUX (n=155) or PBO (n=154) had MF with an International Prognostic Scoring System (IPSS) score ≥2 and a platelet count of ≥100 × 109/L. Patients with protocol-defined worsening splenomegaly were permitted to cross over from PBO to RUX. The primary endpoint was the percentage of patients with ≥35% reduction in spleen volume (SV) at week (wk) 24. Change in Total Symptom Score (TSS) was a secondary endpoint. TSS was the sum of 6 symptom scores (night sweats, itching, abdominal discomfort, pain under ribs on left side, early satiety, muscle/bone pain) assessed with the modified MF Symptom Assessment Form (MFSAF) v2.0 on a scale of 0 (“absent”) to 10 (“worst imaginable”).Patients were stratified by palpable spleen length (SL) (≤ 10 cm, <10 to 20 cm, >20 cm) and TSS tertile (≤11.1, >11.1 to 22.0, >22.0) at baseline. SV and TSS stratified by baseline values as described were summarized over time. To account for PBO crossover, modeling was performed to predict SV after crossover using a nonlinear mixed model that best predicted individual patient data. Last observation carried forward was used to impute missing TSS data. Results:Mean absolute SV and TSS worsened over time in the PBO group regardless of baseline SL and TSS, demonstrating the progressive nature of MF. In patients treated with RUX, mean absolute SV and TSS at wk 24 were lower for patients with smaller SL and less severe TSS at baseline, respectively (Table); absolute differences with PBO were significant within each subgroup. Therefore, patients who initiated RUX therapy with more advanced MF were less likely to achieve the same clinical status experienced by patients initiating therapy with less advanced MF. Notably, even after 24 wks of RUX treatment, SV and TSS reductions in the cohorts with larger SL or greater TSS at baseline did not achieve levels equivalent to baseline of the next lesser baseline severity group (Table; Figure).Although the severity of splenomegaly and symptoms at baseline influenced the absolute SV and TSS achieved at wk 24, RUX treatment resulted in similar percent reductions in SV and improvements TSS across all subgroups, with the exception of the lower TSS tertile (where there is less room for improvement). In contrast, PBO treatment resulted in increases in SV and worsening of symptoms and patients with less severe SV and TSS at baseline experienced the greatest percent increases in SV and TSS at wk 24. Conclusions:RUX therapy was associated with SV reduction and symptom improvement regardless of spleen size or symptom severity at baseline, whereas patients on PBO experienced disease progression across all subgroups. Patients receiving RUX with less advanced disease achieved an overall better clinical status, as defined by lower absolute SV and symptom scores. This analysis suggests that initiation of RUX in patients with less severe splenomegaly and symptoms may contribute to improved patient outcomes.TableRuxolitinib Efficacy by Baseline Palpable Spleen Size and Symptom SeveritySV (cm3)≤10 cm>10–20 cm>20 cmRUXPBORUXPBORUXPBOn=32n=27n=89n=89n=34n=37Baseline, mean ± SEM1602 ± 1071568 ± 1482672 ± 982580 ± 1224015 ± 2244218 ± 176Wk 24, mean ± SEM1208 ± 93*1810 ± 1351751 ± 82‡2903 ± 952851 ± 207‡4454 ± 167% change from baseline at Wk 24 ± SEM–26.1 ± 3.317.7 ± 4.3–34.7 ± 2.013.3 ± 1.8–29.9 ± 2.87.3 ± 3.0TSSLowerMiddleUpperRUXPBORUXPBORUXPBOn=46n=57n=49n=49n=54n=45Baseline, mean ± SEM5.8 ± 0.65.6 ± 0.416.6 ± 0.516.4 ± 0.530.2 ± 0.731.8 ± 1.1Wk 24, mean ± SEM4.3 ± 0.7†9.4 ± 0.98.5 ± 1.2‡21.4 ± 1.516.2 ± 1.5‡x33.4 ± 1.7% change from baseline at Wk 24 ± SEM–25.8 ± 10.498.4 ± 26.2–49.6 ± 6.732.3 ± 10.1–45.6 ± 5.26.1 ± 4.5PBO, placebo; RUX, ruxolitinib; SEM, standard error of the mean.P-value for RUX vs PBO: *<0.05; †<0.01; ‡<0.001. [Display omitted] Disclosures:Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding. Gotlib:Incyte: Consultancy. Kantarjian:Incyte: grant support Other. Sun:Incyte: Employment. Verstovsek:Incyte Corporation: Research Funding.

The effect of oral prostaglandin analogue on painful diabetic neuropathy: a double‐blind, randomized, controlled trial

This study was performed to assess the efficacy of beraprost sodium (BPS) in painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients. In this randomized clinical trial, 99 T2DM patients (41% male, age 60 ± 6 years) with DPN but without evidence of peripheral artery disease were randomized to receive either BPS (40 µg, tid) or placebo for 8 weeks. The primary end point was the improvement of the total symptom score (TSS), temperature rebound (TR) and nadir to peak (NP) above baseline. After 8 weeks treatment, the change of TSS in the BPS group showed a significant improvement compared to the placebo group (2.80 ± 2.48 vs. 1.60 ± 1.94 points, p = 0.009). Furthermore, the number of patients who showed signs of improvement in TSS and the proportion of patients with 50% relief of symptom was also significantly greater in the BPS group than in the placebo group (83.7 vs. 62%, p = 0.015, 36.2 vs. 14%, p = 0.009, respectively). In conclusion, treatment with BPS significantly improved TSS over an 8-week period.

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In most related studies, the treatment outcome analyses for lower urinary tract symptoms (LUTS) in male patients have been performed on the basis of total symptom score changes using the International Prostate Symptoms Score (I-PSS). However, as the editor commented, it seems that one can reliably assume that the benefit of treatment in these patients largely depends on achieving relief of the most bothersome symptom (core symptom), and not a total symptom score, as patients often consult their physician regarding only 1 or 2 major symptoms.

Probiotic lactobacilli and bifidobacteria in a fermented milk product with added fruit preparation reduce antibiotic associated diarrhea andHelicobacter pyloriactivity

To investigate matrix-specifity of probiotic effects and particularly of the reduction of antibiotics-associated diarrhea, a controlled, randomized, double-blind study was performed, in which 88 Helicobacter pylori-infected but otherwise healthy subjects were given for eight weeks either a) a probiotic fruit yoghurt "mild" containing Lactobacillus acidophilus LA-5 plus Bifidobacterium lactis BB-12, n = 30), b) the same product but pasteurized after fermentation (n = 29) or c) milk acidified with lactic acid (control, n = 29). During week five, a Helicobacter eradication therapy was performed. Helicobacter activity was measured via 13C-2-urea breath tests and antibiotic-associated diarrhoea and other gastrointestinal complaints were recorded by validated questionnaires. In intervention group a, b and c the mean number of days with diarrhoea was 4, 10 and 10 (P<0·05), the frequency of episodes 17%, 7% and 27% (n.s.), and the change in total symptoms score before antibiotics treatment was -1·4 ± 1·1, -1·2 ± 1·1, 2·6 ± 1·1 points/four weeks (P<0·05). All milk products decreased Helicobacter activity by 18 to 45% without significant differences between groups. The observed decrease in Hel. pylori activity seems to be not or not only due to probiotic bacteria but (rather) to components of acidified milk (most probably lactic acid). Fruit-yogurt-like fermented milk products with living probiotic bacteria significantly shorten the duration of antibiotics-associated diarrhoea and improve gastrointestinal complaints. Fruit yogurt-like fermented milk is a matrix suitable for probiotic bacteria.

Migraines and Gastroparesis: A Histologic, Physiologic, and Clinical Analysis with Temporary Gastric Stimulation

Purpose: A relationship between migraines and gastroparesis (GP) has been observed but the pathophysiology and mechanisms are unknown. We compared histologic, electrophysiologic, and clinical outcomes to define any differences between drug refractory GP patients with Migraines and those with No Migraines, undergoing temporary gastric electrical stimulation (GES). Methods: We reviewed data on 80 consecutive patients: 28 Migraine (35%) and 52 No Migraine (65%); 13 males, 67 female, mean age of 43 (26 diabetic, 53 idiopathic, 1 post surgical) undergoing temporary and latter permanent GES for drug refractory GP. Symptoms evaluated included vomiting, nausea, epigastric pain, bloating/distension, and anorexia/early satiety (scored from 0 to 4 for each) and total symptom score (TSS) with a max of 20. Vomiting score and TSS were measured before treatment and during treatment with temporary GES. Four hour Gastric Emptying Time (GET) % retention before and during treatment along with cutaneous, mucosal, and serosal EGG was also measured, reported as frequency and amplitude. Outcomes were reported as change in vomiting scores, change in TSS, and change in 4 hour GET. A full thickness gastric biopsy was performed at the time of subsequent permanent GES placement and was analyzed for S-100 (neuronal) and CD-117 (Cajal) cells. Two tailed unpaired t tests were performed for each category. Results: Vomiting and TSS scores at baseline were higher among patients with migraines. Also the migraine patients had more improvement in vomiting scores with temporary GES. Patients with migraines had more normal gastric emptying scores at baseline and a greater change after temporary GES. The amplitude of mucosal EGG in patients with Migraines was higher than in the No Migraine group. There was no statistical difference between the Migraine group and the No Migraine group in outer or inner S-100 cells (neuronal) outer or inner CD-117 (Cajal) cells, cutaneous EGG frequency and amplitude, or serosal EGG frequency and amplitude. (See Table).Table: Table. Comparison of Migraine vs. No MigraineConclusion: GP Patients with Migraines have different baseline physiology as well as better symptom improvement from temporary GES compared with No Migraine GP patients. Disclosure: Dr Thomas Abell-Licensor, Consultant, Investigator, Medtronic, Inc.

Positive symptom improvement with laparoscopic uterosacral ligament repair for uterine or vaginal vault prolapse: Interim results from an active multicenter trial

Study objective To evaluate the use of laparoscopic uterosacral ligament repair for long-term patient symptom improvement in patients with uterine prolapse or posthysterectomy vaginal vault prolapse and to evaluate how laparoscopic instrumentation kits facilitate procedure performance for the surgeon. Design Nonrandomized, prospective, multicenter case series (Canadian Task Force classification II-2). Setting Five clinical sites consisting of 4 community hospitals and 1 university medical center. Patients Seventy-two patients with stage II or worse uterine prolapse (58%, n = 42) or posthysterectomy vaginal vault prolapse (42%, n = 30). One patient with stage I vaginal vault prolapse was included in the group due to her significant symptoms. Interventions Laparoscopic uterosacral ligament repair was performed on all patients; round ligament truncation was also performed selectively on patients with uterine prolapse. Fifty-seven percent (41 patients) had concomitant pelvic procedures. Measurements and main results At 12-month follow-up, Pelvic Organ Prolapse Quantification (POP-Q) scores and patient self-reported symptom scores were significantly improved over baseline after laparoscopic repair of pelvic organ prolapse. Positive mean change in POP-Q score was 14.4 (p = .0003) for uterine prolapse repair and 9.28 (p = .017) for vaginal vault prolapse repair. Positive mean change in total symptom score was 20.36 (p <.0001) for uterine prolapse repair and 11.43 (p = .005) for vaginal vault prolapse repair. Surgeons reported a mean procedure time of 31.6 minutes for uterine prolapse repair and 21.7 minutes for vaginal vault prolapse repair. A mean rating of 7.5 was documented for ease of use for the uterine prolapse kit and 4.1 for the vaginal vault prolapse kit on a scale of 1 to 10. Conclusion Laparoscopic uterosacral ligament repair improves symptoms and POP-Q scores over the long term in patients with uterine or vaginal vault prolapse. Laparoscopic instrumentation kits facilitate procedure performance for the surgeon with expedited surgery times.

Desloratadine therapy for symptoms associated with perennial allergic rhinitis

Perennial allergic rhinitis (PAR) has a substantial negative social and economic impact. Recent studies emphasize the potential seriousness of PAR and the need for improved treatment of this condition. To confirm the efficacy and safety of the H1-antihistamine desloratadine in reducing the symptoms of PAR in a randomized, double-blind, placebo-controlled trial. Patients with PAR (N = 1,179) from 67 US/international centers received desloratadine, 5 mg once daily, or identical placebo tablets. The primary efficacy measure was the change from baseline to week 4 in average morning and evening reflective total symptom scores (TSSs). Secondary end points included changes from baseline in total nasal and nonnasal symptom scores and peak nasal inspiratory flow (PNIF) rates. Desloratadine was significantly more effective than placebo in reducing morning and evening reflective TSSs for each week and during weeks 1 through 4 (P = .001). Mean changes in TSSs during the 4-week study were -3.9 (26.6% reduction) and -3.2 (22.3% reduction) for the desloratadine and placebo groups, respectively (P = .001, desloratadine vs placebo). With desloratadine therapy, significant improvements were also seen in secondary efficacy end points compared with placebo use (total nasal and nonnasal symptom scores: P < or = .04). Improvements in mean morning PNIF were significantly greater in the desloratadine-treated group than in the placebo group (P = .03). These results confirm and extend previous findings that desloratadine is safe and is associated with a statistically significant reduction in nasal and nonnasal symptoms in patients with PAR. Objective nasal airflow, evaluated by PNIF, was statistically significantly improved after desloratadine treatment.

Radiographic Stage Fails to Predict Symptom Outcomes after Endoscopic Sinus Surgery for Chronic Rhinosinusitis

To determine whether preoperative computed tomography (CT) stage predicts degree of symptom improvement after endoscopic sinus surgery (ESS). A series of adult patients undergoing ESS was prospectively evaluated with CT and the rhinosinusitis symptom inventory (RSI) preoperatively and at a minimum of 12 months postoperatively. Symptom domains (nasal, facial, oropharyngeal, systemic, and total) were computed and both absolute change and percentage change in symptom domain scores before and after ESS were correlated with the preoperative CT scan stage according to three staging systems: Lund-MacKay, Kennedy, and Harvard. One-hundred sixty-one patients (mean age, 40.2 years) completed the study with a mean follow-up of 19.4 months. Overall, statistically significant decreases in RSI symptom domains were noted for the nasal (net change -30.1 [range -100 to +100]), facial (-26.1), oropharyngeal (-13.4), systemic (-17.0), and total (-20.8) symptom scores (all P < .001). For the absolute change in total symptom score, no statistically significant correlation with CT stage was demonstrated for any of the staging systems (Lund: Spearman rho = -0.004, P = .962; Kennedy: rho = -0.008, P = .918; Harvard: rho = -0.011, P= .891). Similarly, no significant correlation with CT stage was demonstrated with the other symptom domains. Additionally, no significant correlation was identified between preoperative CT stage and percentage change in symptom domain scores. Although CT scan is widely accepted as an accurate diagnostic tool for chronic rhinosinusitis, CT scan stage alone does not significantly predict symptom outcomes after chronic rhinosinusitis, regardless of staging system utilized.

Acid suppression does not change respiratory symptoms in children with asthma and gastro-oesophageal reflux disease

Background: Epidemiological studies have shown an association between gastro-oesophageal reflux disease (GORD) and asthma, and oesophageal acid perfusion may cause bronchial constriction. However, no causative relation has been proven. Aim:...

Comparison of traditional Chinese acupuncture, minimal acupuncture at non-acupoints and conventional treatment for chronic sinusitis

To compare traditional Chinese acupuncture, minimal acupuncture at non-acupoints and conventional treatment for chronic sinusitis. A three-armed single blind randomised controlled study. In an outpatient specialist clinic, we recruited 65 patients with symptoms of sinusitis >3 months and signs of sinusitis on computed tomography (CT). We randomised patients to one of three study arms: (1) 2-4 weeks of medication with antibiotics, corticosteroids, 0.9% sodium chloride solution, and local decongestants (n=21), (2) 10 treatments with traditional Chinese acupuncture (n=25), or (3) 10 treatments with minimal acupuncture at non-acupoints (n=19). Change in sinus soft tissue swelling on CT, symptoms of sinusitis, and health-related quality of life (HRQoL), using the two component summary scales of the Short Form 36 and a rating scale. In the conventional treatment group, sinus soft tissue swelling was reduced over 4 weeks (p=0.04), and HRQoL improved over 12 weeks (p=0.01-0.05). Pairwise comparisons of changes in total symptom score between the groups showed signs of a difference between conventional medication and sham over 4 weeks (p=0.06). Sinus soft tissue swelling was reduced in the conventional treatment group over 4 weeks, and HRQoL improved over 12 weeks. Only a non-significant difference in symptom score change over 4 and 12 weeks was shown between conventional medication and traditional Chinese acupuncture.

Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis.

To determine the efficacy and safety of 600 mg of alpha-lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy. We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of alpha-lipoic acid according to the following prerequisites: randomized, double-masked, placebo-controlled, parallel-group trial using alpha-lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n=1258 patients (alpha-lipoic acid n=716; placebo n=542) met these eligibility criteria and were included in a meta-analysis based on the intention-to-treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with alpha-lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (> or =50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS-LL), individual NIS-LL components, and the rates of adverse events. After 3 weeks the relative difference in favour of alpha-lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS-LL. The responder rates were 52.7% in patients treated with alpha-lipoic acid and 36.9% in those on placebo (P<0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of alpha-lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of alpha-lipoic acid compared with placebo, while among the NIS-LL components pin-prick and touch-pressure sensation as well as ankle reflexes were improved in favour of alpha-lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups. The results of this meta-analysis provide evidence that treatment with alpha-lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy.

Effect of Betamethasone-Loratadine Combination Therapy on Severe Exacerbations of Allergic Rhinitis

Corticosteroids are effective in controlling the inflammatory component of allergic rhinitis; however, evidence for the clinical efficacy of systemic corticosteroids in this disease is sparse. It is further common practice to combine oral corticosteroids with antihistamines in the treatment of acute exacerbations of allergic rhinitis. The aim of this study was to investigate the effect of low-dose oral betamethasone alone and in combination with loratadine in a group of patients with allergic rhinitis with clinically significant obstruction. In this parallel, double-blind, active controlled multicentre study, 299 patients with severe allergic rhinitis were randomly allocated to either betamethasone 1.0mg or betamethasone 1.0mg plus loratadine 10mg or betamethasone 0.5mg plus loratadine 10mg or loratadine 10mg alone for 5-7 days. Total symptom scores, nasal obstruction, and doctor and patient perception of improvement were measured as markers of disease severity. Although not statistically significant, both betamethasone 1.0mg regimens resulted in a total symptom score difference of at least 1 or more from loratadine (i.e. mean [SD] change in total symptom score of 4.10 [3.10] and 4.40 [3.62] vs 3.10 [3.30], respectively, for betamethasone 1.0 mg plus loratadine, betamethasone 1.0 mg and loratadine). All corticosteroid-containing regimens were significantly better than loratadine alone with regard to the patients' (p < 0.013) and doctors' (p < 0.009) perceptions of improvement. They significantly favoured loratadine in combination with betamethasone over single-drug therapy (i.e. odds ratio: investigator ratings 0.49, 0.36 and 0.45, and patient ratings 0.47, 0.40 and 0.43, respectively, for 0.5 mg and 1.0 mg betamethasone plus loratadine and betamethasone 1.0 mg alone vs loratadine alone). Betamethasone 1.0mg plus loratadine also resulted in significant reduction of the relapse rate compared with the other therapies. This study demonstrated the benefit of a short course of a systemic low dosage of corticosteroids with and without antihistamine therapy during acute severe exacerbations of allergic rhinitis. Combination treatment with betamethasone 1.0mg and loratadine 10mg was significantly better in relieving symptoms of hayfever as experienced by patients. This was the first study to give evidence of benefit of systemic low-dose corticosteroids with and without an antihistamine in patients with acute exacerbations of allergic rhinitis.

Goserelin Acetate (Zoladex) with or without Hormone Replacement Therapy for the Treatment of Endometriosis

Objective:To determine whether hormone replacement therapy (HRT) plus goserelin (Zoladex) is as effective as goserelin alone for the relief of pelvic symptoms of endometriosis and to determine whether it reduces both the loss of bone mineral density (BMD) and the physiologic side effects associated with goserelin therapy.Design:Prospective, placebo-controlled study, open label for goserelin therapy and double-blind for HRT.Setting:Forty-two teaching or community hospitals.Patient(s):Premenopausal women with symptomatic endometriosis.Result(s):Statistically significant mean decreases from baseline in the total pelvic symptom score and total subjective score were observed by week 24 for all three groups. There were no statistically significant treatment differences for change in total symptom score. Some degree of BMD loss occurred in the three groups; however, the percentage loss was consistently greater in the HRT0 group than in the HRT1 or HRT2 groups. When analyzed separately, no overall age effect on BMD change was seen in women >30 years of age versus women ≤30 years. The HRT1 and HRT2 groups had fewer occurrences of hot flushes and vaginal dryness than did the HRT0 group.Conclusion(s):Goserelin plus HRT is as effective as goserelin alone in relieving pelvic symptoms of endometriosis and attenuates both the loss of BMD and the physiologic side effects of hot flushes and vaginal dryness associated with goserelin therapy.