Symptom management of HIV-related diarrhea by using normal foods: A randomized controlled clinical trial.

The purpose of this randomized clinical trial was to determine the efficacy of a dietary intervention to reduce the frequency of bowel movements and improve stool consistency as compared with subjects assigned to a control group. The study enrolled HIV patients with a history of three or more episodes of diarrhea for 3 weeks or more. Seventy-five subjects were enrolled, of which 38 were randomized to the treatment group and 37 to the control group. Six study sessions were scheduled over a 24-week period. At 24 weeks, the stool frequency reduced 28% in the treatment group and 15% in the control group (F = 9.22, p < .001) and stool consistency improved 20% in the treatment group and 8% in the control group (F = 9.98, p < .001). The results showed that the intervention was effective in reducing stool frequency and improving stool consistency in HIV patients with chronic diarrhea for up to 6 months of treatment.     

Topiramate in patients with episodic migraine: reducing the risk for chronic forms of headache

OBJECTIVE: The aim was to evaluate whether preventive treatment with topiramate in patients with episodic migraine reduces the risk of developing chronic forms of headache. BACKGROUND: Chronic forms of headache, including chronic migraine or medication overuse headache (MOH), are characterized by 15 or more headache days per month. Acute medication overuse has been shown to be a risk factor for developing chronic headache, but it is not known whether preventive treatment can reduce the risk of developing chronic forms of headache or the development of MOH. METHODS: Pooled data from 3 trials in patients with episodic migraine randomized either to treatment with 100 mg topiramate per day (n = 384) or with placebo (n = 372) were analyzed with regard to the number of headache days during a prospective 4-week baseline period and the individual final 4 weeks of each patient's treatment during the planned 26-week double-blind treatment period. RESULTS: The number of headache days per month in the topiramate versus the placebo-treated groups was 7.3 +/- 3.0 versus 7.3 +/- 3.1 during baseline and 4.1 +/- 4.2 versus 5.6 +/- 4.9 during the final 4 weeks, respectively (P < .001). At the end of the study, 8 versus 16 patients fulfilled International Headache Society criteria of chronic headache (odds ratio: 2.11, P= .082). Moreover, a significantly lower number of patients receiving topiramate treatment reported an increase in headache days per month by the end of the study when compared to placebo (66 vs 88 patients, respectively; odds ratio: 1.49, P < .05). Finally, the number of days with usage of acute medication was significantly lower in the topiramate arm compared with placebo (3.3 +/- 3.7 vs 4.3 +/- 3.6, respectively; P < .001). CONCLUSION: Preventive treatment with topiramate in patients with episodic migraine may reduce the risk of developing chronic forms of headache.     

Lactobacillus prophylaxis for diarrhea due to enterotoxigenic Escherichia coli.

In vitro and animal experiments indicated that lactobacilli might prevent Escherichia coli from colonizing the intestine and may produce substances counteracting enterotoxin. Lactinex, a commercial preparation of dried Lactobacillus acidophilus and L. bulgaricus, is marketed for uncomplicated diarrhea. Preliminary experiments in nonfasting volunteers indicated that lactobacilli in this preparation colonized the small intestine for up to 6 h. To evaluate the protective efficacy of Lactinex, a double-blind randomized study was carried out in which 48 volunteers (23 receiving Lactinex and 25 receiving placebos) were challenged with E. coli strains that produced heat-stable or heat-labile enterotoxins or both. No significant differences between the two groups were noted with respect to attack rate, incubation period, duration of diarrhea, volume and number of liquid stools, and coproculture yields. These data suggest that this lactobacillus preparations does not prevent or alter the course of enterotoxigenic E. coli diarrhea in adults. Lack of efficacy occurred despite efforts to maximize small bowel colonization, including administration of Lactinex in milk and in a 6-hour-interval regimen during 36 h before and 96 h after challenge.     

Effect of music therapy among hospitalized patients with chronic low back pain: a controlled, randomized trial]

OBJECTIVE: To evaluate the influence of music therapy in hospitalized patients with chronic low back pain. METHODS: A controlled, randomized study (N = 65). During a stationary rehabilitation stay of 12 days, 65 patients with low back pain were randomized to receive on alternate months standardized physical therapy plus 4 music therapy sessions between day 1 and day 5 (intervention group; N = 33) or standardized physical therapy alone (control group; N =32). Scores for pain (as measured on a visual analogue scale [VAS]), disability (Oswestry index) and anxiety and depression (as measured on the hospital anxiety and depression scale [HAD]) were collected on day 1, 5 and 12. Pain intensity was also evaluated on a VAS just before and after music therapy sessions. RESULTS: Introduced music therapy sessions during a stationary rehabilitation stay in patients with chronic low back pain reduce pain (-2.0+/-2.7 vs -1.8+/-2.6) but not significantly. However, music therapy significantly (p < 0.01) reduced disability as measured on the Owestry index between day 1 and day 5 (-11.8+/-17.8 vs -2.5+/-9.4), anxiety (-3.5+/-3.7 vs -0.9+/-2.7) and depression (-2.1+/-3.0 vs 0.6+/-2.4). The immediate effect on pain intensity (VAS score) was confirmed (p < 0.001). CONCLUSION: Our results confirmed the effectiveness of music therapy for hospitalized patients with chronic low back pain. Music therapy can be a useful complementary treatment in chronic pain and associated anxiety-depression and behavioural consequences.     

Tobramycin Nebulizer Solution in severe COPD patients colonized with <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>: effects on bronchial Inflammation

INTRODUCTION: Airway colonization with Pseudomonas aeruginosa is frequent in severe chronic obstructive pulmonary disease (COPD) and may lead to progressive inflammatory damage. Inhaled Tobramycin Nebulizer Solution (TNS; a preservative-free formulation) is an effective therapy in chronic P aeruginosa infection in cystic fibrosis and bronchiectasis. In this study we aimed to investigate the effects of a TNS short course on inflammatory markers in bronchial secretions from multiresistant P aeruginosa-colonized patients with severe COPD. To the authors' knowledge, this is the first study to examine this in cases of severe COPD. METHODS: Thirteen COPD patients (GOLD criteria 3-4; mean age 72.7+/- 8 years; mean basal forced expiratory volume in 1 second (FEV(1)) 34.8%+/-8.1%; mean FEV(1)/forced vital capacity 0.6+/-0.1) were enrolled. All patients were colonized with P aeruginosa and resistant to oral/intravenous specific antibiotics. Eosinophilic cationic protein (ECP), interleukin-1 beta (IL-1beta), interleukin-8 (IL-8), tumor necrosis factor alfa (TNF-alpha), and cell counts were measured in spontaneous secretions before and after a 2-week TNS course (300 mg twice daily). RESULTS: The TNS course induced a significant reduction in IL-1beta (P<0.03), IL-8 (P<0.02), ECP (P<0.01) concentrations, and in eosinophil count (P<0.01). TNF-alpha levels, and neutrophil and lymphocyte counts were not significantly affected. The second week of treatment proved crucial in terms of efficacy. P aeruginosa density was lowered after 6 months; severe acute exacerbations were reduced by 42%. CONCLUSION: TNS reduced the inflammatory impact of P aeruginosa in multiresistant, P aeruginosa-colonized patients with severe COPD. A therapeutic role for TNS can be strongly suggested in these particular conditions.     

Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection

Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log(10). Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 microg/ml x hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.     

Effect of MKC-733, a 5-HT receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study

BACKGROUND: MKC-733, a 5-HT(3) receptor partial agonist, is a novel enteroprokinetic compound. OBJECTIVE: The aim of this study was to explore the effects of MKC-733 on bowel motility and symptoms in a small group of subjects with constipation. Tolerability was also examined. METHODS: The study was conducted in a single-blind and dose-escalation manner on 14 male and female subjects with constipation aged 22-67 years. After a 1 week run-in period, subjects were treated with placebo (b.i.d.) for 1 week, and 0.2 and 0.5 mg of MKC-733 (b.i.d.) for 2 weeks sequentially. Geometric mean and per cent elimination of surrogate markers of bowel motility were measured by a radio-opaque marker technique at the end of each treatment period. They were analysed on the whole group and subgroups with low (n = 6) and high (n = 8) bowel motility based upon the geometric mean value after placebo treatment. Subjects kept diaries of their bowel habits and gastrointestinal symptoms. RESULTS: Percent elimination increased after treatment with 0.5 mg MKC-733 compared with placebo treatment in the whole group (70.4 +/- 33.5% vs. 47.1 +/- 36.6%, mean +/- SD, P < 0.05). In the low bowel motility group, both geometric mean and percent elimination increased after treatment with 0.5 mg MKC-733 compared with placebo (7.1 +/- 0.9 vs. 5.9 +/- 0.5, P < 0.05; 60.0 +/- 35.8% vs. 13.3 +/- 19.4%, P < 0.05). Stool frequency increased after the first-week treatment with MKC-733 compared with placebo (P < 0.05). Numbers of sensation of incomplete evacuation and gastrointestinal symptoms decreased to half and less after the treatment with MKC-733. No serious adverse effect was noted. CONCLUSION: Multiple doses of 0.5 mg MKC-733 improve bowel motility, which was clearly demonstrated in the subjects with decreased bowel motility. MKC-733 at the doses studied might be effective in increasing stool frequency and reduce gastrointestinal symptoms related to constipation. MKC-733 was well tolerated. Further studies will be needed to clarify efficacy and safety of MKC-733 on a larger population.     

Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.     

Randomized, open label, controlled clinical trial of oral administration of an egg albumin-based protein supplement to patients on continuous ambulatory peritoneal dialysis.

BACKGROUND/AIM: Malnutrition is highly prevalent in patients on continuous ambulatory peritoneal dialysis (CAPD) and is a strong predictor of increased morbidity and mortality. Therefore, the aim of this study was to evaluate the effect of oral administration of an egg albumin-based protein supplement on the nutritional status of CAPD patients. METHODS: In this randomized, open label, controlled clinical trial, 28 CAPD patients were allocated to a study (n = 13) or a control (n = 15) group. Both groups received conventional nutritional counseling; the study group received, additionally, an oral egg albumin-based supplement. During a 6-month follow-up, all patients had monthly clinical and biochemical evaluations and quarterly assessments of adequacy of dialysis and nutrition. RESULTS: Serum albumin Levels were not different between groups; however, a significant increase (baseline vs final) was observed in the study group (2.64+/-0.35 vs 3.05+/-0.72 g/dL) but not in the control group (2.66+/-0.56 vs 2.80+/-0.54 mg/dL). Calorie and protein intake increased more in the study group (calories 1331+/-432 vs 1872+/-698 kcal; proteins 1.0+/-0.3 vs 1.7+/-0.7 g/kg) than in the control group (calories 1423+/-410 vs 1567+/-381 kcal; proteins 1.0+/-0.4 vs 1.0+/-0.3 g/kg). Similarly, non-protein nitrogen appearance rate (nPNA) increased significantly more in the study (1.00+/-0.23 vs 1.18+/-0.35 g/kg/day) than in the control group (0.91+/-0.11 vs 0.97+/-0.14 g/kg/ day). Triceps skinfold thickness (TSF) and midarm muscle area (MAMA) displayed a nonsignificant trend to a greater increase in the study group (TSF 16.7+/-8.7 vs 18.3+/-10.7 mm; MAMA 23.8+/-6.2 vs 25.8+/-5.9 cm2) than in controls (TSF 16.4+/-5.7 vs 16.9+/-7.0 mm; MAMA 28.7+/-7.8 vs 30.0+/-7.9 cm2). At the end of follow-up, the frequency of patients with moderate or severe malnutrition decreased 6% in the control group and decreased 28% in the study group. At the final evaluation, the most important predictors of serum albumin were the oral egg albumin-based supplement administration and protein intake (p < 0.05); secondary predictors (p = 0.06) were peritoneal transport rate and MAMA. CONCLUSIONS: In the study group, oral administration of the egg albumin-based supplement significantly improved serum albumin, calorie and protein intake, and nPNA, and, compared to controls, this maneuver was associated with a trend to increased anthropometric parameters and improved Subjective Global Assessment evaluation. Oral administration of the albumin supplement and protein intake were the most significant predictors of serum albumin at the end of follow-up. This oral supplement may be a safe, effective, and cheap method to improve nutritional status in peritoneal dialysis patients.     

Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study

Sixty patients with headaches of more than 15 days per month were recruited for this double-blind, placebo-controlled, parallel study of botulinum toxin type A (BTX) for chronic tension type and chronic migraine headaches. The primary efficacy point was the number of headache-free days as assessed by diary for 12 weeks after BTX injection. Secondary efficacy points included global impressions, the use of abortive headache medications, and palpation. After recruitment, subjects kept diaries for 4 weeks prior to randomization, at which time they received either 200 U of BTX or matching placebo and were followed. After the week-12 evaluation, patients were offered 200 U of BTX (open label), and were similarly followed for another 12 weeks. The mean days with headache of the 60 subjects (49 female, mean age 47 +/- 11 years) was 23 +/- 7 out of 30. Both groups were demographically similar (58 completed). Over a 12-week period after injections, headache-free days had improved in the BTX group from week 8 to 12 (P < 0.05), and strongly tended to improve over the entire 12-week period, 33 +/- 23 vs. 24 +/- 16 days without headache (P = 0.07), but did not meet the a priori significance criteria. The subject global impressions (P < 0.05), subject change in headache impressions (P < 0.005), and investigator global impressions (P < 0.001) all improved in the BTX group compared with placebo. Adverse events were mild and did not differ between groups. At week 24 (open label), headache-free days were less in the twice BTX injected group compared with the once injected group, 40 +/- 26 vs. 26 +/- 19 (P < 0.05). BTX may help chronic daily headache and appears to have a cumulative effect with subsequent injections. The treatment was very well tolerated.