Clinical effects of buspirone in social phobia: a double-blind placebo-controlled study

BACKGROUND: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. METHOD: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled design. Thirty social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or placebo. Efficacy of treatment was measured using the Social Phobia Scale (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety. RESULTS: Taking a reduction of 50% or more on the Social Phobia Scale as a criterion for clinically relevant improvement, only 1 patient on buspirone and 1 on placebo were classified as responder to treatment. A subjective and clinically relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients (13%) on placebo. There were no statistically significant differences between buspirone and placebo on any of the outcome measures. Generally speaking, buspirone was well tolerated. CONCLUSION: The results of the study do not support the results of open studies, in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone.     

Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial

BACKGROUND: Anemia often complicates Crohn disease and affects quality of life. OBJECTIVE: To evaluate the efficacy of intravenous iron alone and in combination with erythropoietin for the treatment of anemia associated with Crohn disease. DESIGN: Double-blind, randomized, placebo-controlled trial with a subsequent open-label phase. SETTING: University-based gastroenterology outpatient clinic. PATIENTS: 40 patients with Crohn disease and a hemoglobin concentration of 10.5 g/dL or less. INTERVENTION: All patients received intravenous iron saccharate for 16 weeks. During the blinded phase of the trial, they received either erythropoietin or placebo. During the open phase, the erythropoietin dose was increased in non-responders who had received erythropoietin and erythropoietin therapy was initiated in nonresponders who had received placebo. MEASUREMENTS: Response was defined as an increase in hemoglobin concentration of 2 g/dL or more. RESULTS: 15 of 20 patients in the placebo group (75% [95% CI, 51% to 91%]) and 18 of 19 patients in the erythropoietin group (95% [CI, 74% to 100%]) responded to intravenous iron (P = 0.20). The erythropoietin group had a higher cumulative response rate (P = 0.036) and a more pronounced mean increase in hemoglobin concentration (4.9 g/dL in the erythropoietin group compared with 3.3 g/dL in the placebo group, a difference of 1.6 g/dL [CI, 0.6 g/dL to 2.5 g/dL]; P = 0.004). In the open phase, all 6 previous nonresponders had a response. Hematologic response was associated with improved quality of life (P = 0.03). CONCLUSIONS: Most patients who have anemia associated with Crohn disease respond to intravenous iron alone. Erythropoietin has additional effects on hemoglobin concentrations.     

Buspirone use for smoking cessation

The results of buspirone efficacy have been inconsistent and contradictory. The rate of smoking abstinence has been reported to range from 36% to 88% and 16% to 89% in buspirone and placebo treatment groups, respectively. Only one controlled study reported buspirone efficacy in reducing nicotine withdrawal symptoms, although it was based on a small sample population and only 4 weeks of follow-up. The most recent studies have been unable to demonstrate the efficacy of buspirone in smoking cessation or in the relief of withdrawal symptoms. A placebo-controlled, randomized trial with a large number of patients, relatively high doses of buspirone (30-60 mg/d), strict abstinence criteria, long-term follow-up, and the inclusion of smokers with general anxiety or anxiety reported in previous quit attempts is needed to further evaluate buspirone efficacy in smoking cessation and the reduction of nicotine withdrawal symptoms. The treatment effects of buspirone could then be specifically tested as a function of alleviating the anxiety component of the smoking withdrawal syndrome. Finally, buspirone may prove to be an alternative in patients unsuccessful with or unable to tolerate transdermal nicotine therapy. How buspirone compares with bupropion therapy for smoking cessation is also unknown.     

Multivariate changes in coordination of postural control following spaceflight

BACKGROUND: Bright light therapy is the recommended treatment for winter seasonal affective disorder (SAD). However, the studies with the best placebo controls have not been able to demonstrate that light treatment has a benefit beyond its placebo effect. METHODS: Ninety-six patients with SAD completed the study. Patients were randomly assigned to 1 of 3 treatments for 4 weeks, each 1.5 hours per day: morning light (average start time about 6 AM), evening light (average start about 9 PM), or morning placebo (average start about 6 AM). The bright light (approximately 6000 lux) was produced by light boxes, and the placebos were sham negative-ion generators. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) were performed weekly. RESULTS: There were no differences among the 3 groups in expectation ratings or mean depression scores after 4 weeks of treatment. However, strict response criteria revealed statistically significant differences; after 3 weeks of treatment morning light produced more of the complete or almost complete remissions than placebo. By 1 criterion (24-item SIGH-SAD score <50% of baseline and < or =8), 61% of the patients responded to morning light, 50% to evening light, and 32% to placebo after 4 weeks of treatment. CONCLUSIONS: Bright light therapy had a specific antidepressant effect beyond its placebo effect, but it took at least 3 weeks for a significant effect to develop. The benefit of light over placebo was in producing more of the full remissions.     

Luteinizing hormone secreting adrenal tumour as a cause of precocious puberty

OBJECTIVE: This study examined whether a selective serotonin reuptake inhibitor (paroxetine) had comparable efficacy but greater tolerability than a tricyclic antidepressant (imipramine) in depressed patients with HIV infection. METHOD: Seventy-five HIV-positive patients (45% of whom had AIDS) were blindly and randomly assigned to receive paroxetine (N = 25), imipramine (N = 25), or placebo (N = 25) in a 12-week trial. The Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impression scale, and the SAFETEE general inquiry (for safety and tolerability) were administered at weeks 2, 4, 6, 8, and 12. RESULTS: Fifty-six (75%) of the 75 patients completed 6 weeks and 34 (45%) completed 12 weeks of the trial. The mean daily doses of both paroxetine (33.9 mg) and imipramine (162.5 mg) were significantly more effective than placebo; they were comparably effective at weeks 6, 8, and 12 according to the intent-to-treat analysis and at week 8 according to the analysis for the subjects who completed the trial (for them, only imipramine was superior to placebo at week 12). There were significantly more dropouts due to side effects from imipramine (48%) than from both paroxetine (20%) and placebo (24%). CONCLUSIONS: Depressed patients with HIV infection responded to imipramine or paroxetine at a higher rate than to placebo irrespective of severity of immunosuppression. Because paroxetine was much better tolerated than imipramine, its overall effectiveness may be greater. However, because of the small study group and the high attrition rate, these findings cannot be generalized and may need replication in a larger study group.     

Clinical, endocrine, and metabolic effects of two doses of gestrinone in treatment of pelvic endometriosis

AIM: To study the effect of prokinetic treatment with cisapride in patients with constipation-predominant irritable bowel syndrome. PATIENTS AND METHODS: Ninety-six patients were randomly assigned to treatment with either cisapride 5 mg three times daily or placebo three times daily for a period of 12 weeks. The dosage could be doubled after 4 weeks. Presence of the target symptoms abdominal pain, constipation and abdominal bloating was an obligatory criterion for inclusion in the study. RESULTS: After 12 weeks of treatment, 31%, 56% and 27% of the cisapride treated patients were found to be without the three target symptoms (P < 0.05). The corresponding percentages for the placebo-treated patients were 31%, 58% and 19%, respectively, (P < 0.05). The visual analogue scale (VAS) symptom scores assessed by the patients for global rating of bowel disease, general well-being and frequency of stool passage improved significantly within each treatment group (P < 0.05). Evaluation of efficacy parameters using intention-to-treat analysis showed no statistically significant differences between the groups. Using efficacy analysis, the difficulty of stool passage showed a significantly higher improvement with cisapride (P < or = 0.05). CONCLUSIONS: These results indicate that cisapride is not superior to placebo in the treatment of constipation and abdominal discomfort as components of irritable bowel syndrome. It may, however, be of use in improving the difficulty of stool passage.     

A placebo-controlled trial of didanosine plus stavudine, with and without hydroxyurea, for HIV infection. The Swiss HIV Cohort Study

OBJECTIVE: To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea. DESIGN: Randomized, double-blinded, prospective study. SETTING: Swiss HIV Cohort Study. PATIENTS: A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l). INTERVENTION: Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo. MAIN OUTCOME MEASURES: The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24. RESULTS: After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001). CONCLUSIONS: Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.     

Combating hyperthermia in acute stroke: a significant clinical concern

OBJECTIVE: There is only limited evidence from adequately controlled clinical trials to support high-dose methylprednisolone therapy for attacks of multiple sclerosis (MS) and none supporting oral administration. We assessed the effect of oral high-dose methylprednisolone therapy in attacks of MS. METHODS: Twenty-five patients with an attack of MS lasting less than 4 weeks were randomized to placebo treatment. Twenty-six patients received oral methylprednisolone (500 mg once a day for 5 days with a 10-day tapering period). The patients received scores on the Scripps Neurological Rating Scale (NRS) and Kurtzke Expanded Disability Status Scale. The symptoms were scored on a visual analog scale (VAS) before treatment and after 1, 3, and 8 weeks of treatment. Primary efficacy measures were NRS and VAS scores in the first 3 weeks and changes in NRS score and answers to an efficacy questionnaire administered after 8 weeks of treatment. RESULTS: Changes in NRS scores among methylprednisolone- and placebo-treated patients differed significantly in the first 3 weeks and after 8 weeks (p = 0.005 and p = 0.0007). VAS scores the first 3 weeks and treatment efficacy after 8 weeks also favored a beneficial effect of methylprednisolone treatment (p = 0.02 and p = 0.05). After 1, 3, and 8 weeks, 4%, 24%, and 32% in the placebo group and 31%, 54%, and 65% in the methylprednisolone group had improved one point on the Expanded Disability Status Scale score (all p < 0.05). No serious adverse events were seen. CONCLUSION: Oral high-dose methylprednisolone is recommended for managing attacks of MS.     

The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder

BACKGROUND: We investigated whether the selective brain cholecystokinin (CCKB) receptor antagonist, L-365,260, could antagonize the panicogenic effects of CCK-tetrapeptide (CCK-4) in patients with panic disorder. DESIGN: The study employed a double-blind, placebo-controlled, two-period crossover design. Patients (N = 29) received a single oral dose of L-365,260 (10 or 50 mg) or placebo 90 minutes prior to injection of CCK-4. After a 1-week washout period, patients received a different dose of L-365,260 or placebo according to a balanced incomplete block design. RESULTS: The 50-mg dose of L-365,260 was superior to placebo in reducing the number (P < .01) and sum intensity (P < .001) of symptoms induced with CCK-4. Panic attack frequency following CCK-4 injection was 88% for patients receiving placebo, 33% for those receiving the 10-mg dose, and 0% for those receiving the 50-mg dose. The difference between the effects of the 50-mg dose and placebo was statistically significant (P = .002). Increases in heart rate following CCK-4 injection were markedly reduced with both the 50-mg (P < .0001) and 10-mg (P < .01) doses compared with placebo. CONCLUSION: These data suggest that CCKB receptors are an important site of action of exogenous CCK-4. It will be important to determine in future studies the efficacy of CCKB receptor antagonists as antipanic agents.     

Prospective evaluation of vitamin E for hot flashes in breast cancer survivors

PURPOSE: Hot flashes represent a substantial clinical problem for some breast cancer survivors. Although estrogen or progesterone preparations can alleviate these symptoms in many patients, concern remains regarding the use of hormonal preparations in such women. Thus, there is a perceived need for nonhormonal treatments for hot flashes for breast cancer survivors. Based on anecdotal evidence that vitamin E was helpful, we designed a trial to investigate this matter. METHODS: We developed and conducted a placebo-controlled, randomized, crossover trial where, after a 1 week baseline period, patients received 4 weeks of vitamin E 800 IU daily, then 4 weeks of an identical-appearing placebo, or vice versa. Diaries were used to measure potential toxicities and hot flashes during the baseline week and the two subsequent 4-week treatment periods. RESULTS: The 120 patients evaluated for toxicity failed to show any. The 105 patients who finished the first treatment period showed a similar reduction in hot flash frequencies (25% v 22%; P = .90) for the two study arms. A crossover analysis, however, showed that vitamin E was associated with a minimal decrease in hot flashes (one less hot flash per day than was seen with a placebo) (P < or = .05). At the study end, patients did not prefer vitamin E over the placebo (32% v 29%, respectively). CONCLUSION: Although this trial was able to show a statistically significant hot flash reduction with vitamin E compared to a placebo, the clinical magnitude of this reduction was marginal.     

Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis

OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26. RESULTS: Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients. CONCLUSION: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.     

Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT)

BACKGROUND: Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV). METHODS: 832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha2b three times a week plus 1000-1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV-RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment. FINDINGS: Sustained virological response at 24 weeks after treatment, was found in 119 (43%) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=O.055), and 53 (19%) of the 278 patients treated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years or less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95% Cl 1.4-4.8; p=0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Discontinuation of therapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given for 24 weeks (8%). INTERPRETATION: An interferon alpha2b plus ribavirin combination is more effective than 48 weeks of interferon alpha2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.     

Divalproex sodium for impulsive aggressive behavior in patients with personality disorder

OBJECTIVE: Divalproex sodium, an anticonvulsant and antimanic agent, has recently been studied for its antiaggressive effects in patients with brain injuries, dementia, and borderline personality disorder. Since patients with other personality disorders also exhibit impulsive aggressive behavior, we conducted a preliminary open-label trial of divalproex sodium as a treatment for irritability and aggression in patients with a variety of personality disorders. METHOD: Ten patients meeting DSM-IV criteria for at least one personality disorder were treated with divalproex sodium in an 8-week open clinical trial. All patients had failed a trial of a selective serotonin reuptake inhibitor (SSRI). Divalproex sodium was increased as tolerated using a flexible dosing schedule. Clinician ratings for impulsive aggressive behavior and irritability were made every 2 weeks using the modified Overt Aggression Scale (OAS-M). RESULTS: Six of 8 completers reported significant decreases in irritability (p = .003) and impulsive aggressive behavior (p = .019). For the entire sample, improvement on OAS-M irritability and overt aggression scores was noted by the end of 4 weeks and continued to occur through week 8. CONCLUSION: This study suggests that divalproex sodium is an effective treatment for impulsive aggressive behavior in some patients with personality disorder who fail to respond to other antiaggressive agents (i.e., SSRIs). Controlled studies are needed to determine which patients are most likely to benefit from divalproex sodium and to evaluate the differential effectiveness of various agents in reducing impulsive aggressive behavior.     

Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease

OBJECTIVE: To evaluate the efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, in patients clinically diagnosed with probable Alzheimer's disease (AD) of mild to moderate severity. METHODS: A prospective, 36-week, multicenter, double-blind, randomized, parallel group study of metrifonate in probable AD patients, including a 2-week screening period, a 26-week double-blind treatment period, and a follow-up visit at 8 weeks post-treatment. A total of 24 ambulatory clinics in the United States in a variety of settings, including contract research organizations, public health facilities, and universities. Patients met diagnostic criteria for probable AD as defined by the work group of the National Institute for Neurological and Communicative Diseases and Stroke and the Alzheimer's Disease and Related Disorders Association. Patients had Mini-Mental State Examination (MMSE) scores of 10 to 26 and Ischemic Scores (Rosen Modification) of <4. A total of 408 patients were enrolled. Percentages of patients completing double-blind treatment were 88% and 79% in the placebo and metrifonate groups, respectively. Rates of discontinuation due to adverse events were 4% in the placebo group and 12% in the metrifonate group. Placebo or metrifonate was administered once daily. Metrifonate-treated patients received a loading dose of 100 to 180 mg based on weight (2.0 mg/kg) for 2 weeks, followed by a maintenance dose of 30 to 60 mg based on weight (0.65 mg/kg) for 24 weeks. Primary efficacy variables were the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change with Caregiver Input (CIBIC-plus). Secondary efficacy variables included the Neuropsychiatric Inventory (NPI), the Disability Assessment in Dementia, the Global Deterioration Scale (GDS), the ADAS-Noncognitive subscale (ADAS-Noncog), the MMSE, and the Clinician's Interview-Based Impression of Severity with Caregiver Input (CIBIS-plus). Outcome measures reflected changes from baseline at week 26 for all variables. Safety was assessed with incidences of premature termination, treatment-emergent events and mortality, and routine safety evaluations. RESULTS: After 26 weeks of metrifonate therapy, a 2.86-point treatment difference (p = 0.0001) was observed in the ADAS-Cog scores of the intent-to-treat AD patients. The treatment difference in the mean CIBIC-plus score at this time was 0.28 points (p = 0.0071). At week 26, treatment differences also were observed in the mean NPI total score (p = 0.0161). Analysis of the remaining secondary efficacy variables showed treatment differences that favored metrifonate but did not reach statistical significance. Metrifonate adverse events were predominantly mild in intensity. No hepatotoxicity was observed. CONCLUSIONS: Metrifonate was safe and well-tolerated. It enhanced not only the cognitive and global function, but also the behavioral function of patients diagnosed with mild to moderate AD. Therefore, metrifonate appears to be useful in the symptomatic treatment of AD.     

Post-transplant hyperlipidaemia: low-dose lovastatin lowers atherogenic lipids without plasma accumulation of lovastatin

PURPOSE: To compare the therapeutic potential of acarbose, metformin, or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM). PATIENTS AND METHODS: Ninety-six patients with NIDDM (35-70 years of age, body mass index (BMI) < or = 35 kg/m2, insufficiently treated with diet alone, glycated hemoglobin (HbA1c; 7% to 11%) were randomized into 3 groups and treated for 24 weeks with acarbose, 3 x 100 mg/day, or metformin, 2 x 850 mg/day, or placebo. Efficacy, based on HbA1c (primary efficacy criterion), fasting blood glucose (BG) and insulin, 1 hour postprandial BG and insulin (after standard meal test), postprandial insulin increase, plasma lipid profile, and tolerability, based on subjective symptoms and laboratory values were determined every 6 weeks. Analysis of covariance was performed for endvalues with adjustment on baseline values. Ninety-four patients were valid for efficacy evaluation. RESULTS: Both active drugs showed the same improvement of efficacy criteria compared with placebo. Baseline adjusted means at endpoint were as follows: BG, fasting and 1 hour postprandial, 9.2 mM and 10.9 mM with placebo, 7.6 mM and 8.7 mM with acarbose, and 7.8 mM and 9.0 mM with metformin; HbA1c was 9.8% with placebo, 8.5% with acarbose, and 8.7% with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. No effect on fasting insulin could be observed. Relative postprandial insulin increase was 1.90 with placebo, 1.09 with acarbose, and 1.03 with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. With respect to lipid profile, acarbose was superior to metformin. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio increased by 14.4% with placebo, was unchanged with metformin, but decreased by 26.7% with acarbose. Comparisons: acarbose versus placebo and acarbose versus metformin were statistically significant, but not metformin versus placebo. Slight body weight changes were observed with acarbose (-0.8 kg) and metformin (-0.5 kg), but not with placebo. Acarbose led to mild or moderate intestinal symptoms in 50% of the patients within the first 4 weeks, but in only 13.8% of the patients within the last 4 weeks. CONCLUSIONS: Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM. With respect to plasma lipid profile, especially HDL cholesterol, LDL cholesterol and LDL/HDL cholesterol ratio acarbose may be superior to metformin.     

Effectiveness of the 4-mg dose of nicotine polacrilex for the initial treatment of high-dependent smokers

PURPOSE: To determine the effectiveness of the 4-mg and 2-mg dosages of nicotine polacrilex vs placebo through the first 6 weeks of treatment (during which 75% of relapse occurs when there is no treatment) in assisting high-dependent smokers to stop smoking when instructed to use a fixed number (12 pieces) of medication daily. SUBJECTS AND METHODS: Ninety high-dependent (Fagerstr?m Tolerance Questionnaire score > or = 7 plus baseline carbon monoxide level > 15 ppm) healthy male and female smokers, highly motivated to quit smoking, were enrolled in a 6-week, randomized, double-blind, placebo-controlled trial in which they were instructed to use 12 pieces per day of their assigned dosage formulation: 4 mg, 2 mg, or 0.5 mg (placebo) of nicotine polacrilex. The behavioral intervention did not depend on providing any special psychological training, skills, or services but rather employed a standard medical practice model that could easily be implemented by any primary care physician. RESULTS: Sustained abstinence from weeks 2 through 6, determined at each visit by absolutely no cigarette use plus a carbon monoxide level of 8 ppm or lower was 59% (4-mg group), 30% (2-mg group), and 39% (placebo group) (P < .02). For the 55 of the 90 smokers who met the originally planned definition of high dependence (Fagerstr?m Tolerance Questionnaire score > or = 7 plus baseline smoking serum cotinine level > 250 ng/mL plus baseline carbon monoxide level > 15 ppm), results were 63% (4-mg group), 25% (2-mg group), and 25% (placebo group) (P < .02). In addition, the 4-mg dose produced statistically significantly higher abstinence rates in compliant subjects (P < .02) and also in subjects with high baseline serum continine levels who were compliant (P < .01) than did either the 2-mg dose or placebo. CONCLUSIONS: It appears that the 4-mg dose of nicotine polacrilex is the drug and dose of choice for the initial phase of tobacco dependence treatment in high-dependent smokers; the 2-mg dose of nicotine polacrilex is not better than placebo during the first 6 weeks of treatment for high-dependent cigarette smokers, and thus should not be used for these patients during the initial treatment phase.     

Hong Kong''s eastern and western medical history

BACKGROUND: Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions. OBJECTIVE: The efficacy of pretreatment with an H1/H2-antagonist combination, H1-antagonist alone, or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following: 120 mg of terfenadine plus 300 mg of ranitidine, 120 mg of terfenadine alone, or placebo. The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks. RESULTS: In seven patients (6%), six in the placebo group and one in the terfenadine group, systemic side effects required cessation of therapy (p = 0.005). Subjective symptoms occurred in four patients (10%) in the terfenadine plus ranitidine group and in three patients (7%) in the terfenadine group. Regarding local reactions, significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema (29%, 29%, and 49%), edema (24%, 18%, and 41%), and pruritus (13%, 11%, and 31%) at week 1 (p < 0.05). This therapeutic benefit was limited to the first 4 weeks of treatment. Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone. CONCLUSIONS: Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy.     

A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. United States 93-01 Study Group

PURPOSE: In a double-blind, phase III clinical trial we evaluate the safety and efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with symptoms of moderate to severe benign prostatic hyperplasia. MATERIALS AND METHODS: Patients meeting the basic requirements of the study underwent a 4-week single-blind placebo evaluation period. A total of 735 patients were randomized to double-blind therapy with tamsulosin or placebo. Treatment duration was 13 weeks. Efficacy and safety were evaluated at 5 visits during the double-blind treatment period. RESULTS: When efficacy data between baseline and end point were compared there was a significant reduction in total American Urological Association symptom score (25%) in each tamsulosin group compared with placebo (p = 0.01) and the percentage of patients with a 30% or more reduction in peak urinary flow rate was significantly greater in the tamsulosin versus placebo group (p <0.05). Improvements in American Urological Association symptom scores and maximum flow rate occurred at 1 week of treatment. None of the patients experienced a first dose effect. There were no significant changes in blood pressure on standing at any visit during the study except for a decrease in systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The treatment groups did not differ significantly in incidence of electrocardiogram abnormalities at each post-baseline visit and at end point. CONCLUSIONS: Tamsulosin was safe and effective, and clinically and statistically superior to placebo in relieving symptoms of benign prostatic hyperplasia in men with moderate to severe symptoms at baseline. There was no evidence of a first dose effect and no clinically significant orthostatic hypertension. In addition, response to treatment was rapid.