A multicenter, randomized, double-blind, placebo-controlled trial of recombinant human interleukin-10 in HIV-infected subjects

OBJECTIVE: To determine the effect of multiple subcutaneous doses of recombinant human interleukin (rhuIL)-10 on plasma HIV RNA levels and CD4 T-cell counts, and to evaluate its safety and tolerability in HIV-infected subjects. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter trial. SUBJECTS: Thirty-nine HIV-infected subjects with CD4 T-cell counts > 200 x 10(6)/l, plasma HIV RNA concentrations > or = 3.18 log10 copies/ml and on stable antiretroviral therapy were recruited from six centers. INTERVENTION: Subjects received (subcutaneously) rhuIL-10 1 microg/kg daily, 4 microg/kg daily, 8 microg/kg three times per week, placebo daily or placebo three times per week for 4 weeks. MAIN OUTCOME MEASURES: Prospectively defined outcomes included safety and tolerability, plasma HIV RNA levels and CD4 T-cell counts. Outcomes were assessed at baseline, weeks 1, 2, 3 and 4 during treatment and weeks 2 and 4 following completion of therapy. RESULTS: Baseline characteristics were similar in all groups. Compared to baseline, no significant change in plasma HIV RNA concentrations or CD4 T-cell counts was observed in any of the groups. RhuIL-10 was generally well tolerated. Two patients receiving rhuIL-10 4 microg/kg required discontinuation due to thrombocytopenia. One patient receiving rhuIL-10 4 microg/kg who had chronic hepatitis B and C infections discontinued drug because of elevated liver function tests. One patient receiving placebo discontinued study drug because of depression. CONCLUSION: The lack of a demonstrable virological benefit, as assessed by plasma viral load, with 4 weeks of rhuIL-10 does not support the development of this immune-based therapy for treatment of HIV infection.     

A double-blind, placebo-controlled trial of thymostimulin in symptomatic HIV-infected patients

The potential therapeutic efficacy of the thymic hormone preparation, thymostimulin (TP1), in HIV infection has been studied in a multi-institutional, randomized, double-blind, placebo-controlled trial. Fifty evaluable patients with advanced AIDS-related complex (ARC) were injected with TP1 or placebo twice weekly for 6 months after 2 weeks of daily injections. The primary endpoint, progression to AIDS, was reached in nine TP1- and 11 placebo-treated subjects after 1 year. CD4 cell numbers were not affected by administration of the study drug. No toxicity was associated with TP1 treatment. We conclude that TP1 is ineffective in altering the progress of HIV disease in patients with advanced ARC.     

Influenza vaccination in children with asthma: randomized double-blind placebo-controlled trial

There is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination with inactivated influenza vaccine or placebo took place approximately November 1, and children were followed until April 1 of the next year. Airway symptoms were reported in a diary. When symptom scores reached a predefined level, a pharyngeal swab was taken. Primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Three hundred forty-nine children were assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18 in the placebo group, a difference of 33% favoring placebo (31% after adjustment for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma exacerbations were of similar severity in both groups; they lasted 3.1 days shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p = 0.06). We conclude that influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza. Additional studies are warranted to justify routine influenza vaccination of children with asthma.     

Transdermal clonidine in mild hypertension. A randomized, double-blind, placebo-controlled trial

In 30 patients with mild essential hypertension, clonidine hydrochloride was delivered from a skin patch reservoir designed to release medication at a constant rate for seven days. After a four-week washout period, patients were randomized (double-blind) into a clonidine- or a placebo-treated group. Clonidine or placebo was then given for five weeks, followed by a two-week washout period to assess withdrawal from treatment. Blood pressure was controlled in 11 of 15 clonidine-treated patients but in only four of 15 placebo-treated patients. The clonidine-treated group evidenced larger decreases in both systolic and diastolic blood pressures. In the clonidine-treated group, blood pressures and plasma clonidine levels were stable throughout a representative seven-day period. Besides mild skin irritation with both clonidine and placebo patches, few side effects were observed. After discontinuation of clonidine administration, plasma levels declined in a non-log linear manner. There was no rebound hypertension. The results suggest that clonidine delivered transdermally is safe and effective for control of mild essential hypertension.     

Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although observational studies suggest that estrogen replacement therapy (ERT) reduces cardiovascular morbidity and mortality in postmenopausal women, use of unopposed ERT for prevention of coronary heart disease in healthy postmenopausal women remains untested. OBJECTIVE: To determine the effects of unopposed ERT on the progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University-based clinic. PATIENTS: 222 postmenopausal women 45 years of age or older without preexisting cardiovascular disease and with low-density lipoprotein cholesterol levels of 3.37 mmol/L or greater (>/=130 mg/dL). INTERVENTION: Unopposed micronized 17beta-estradiol (1 mg/d) or placebo. All women received dietary counseling. Women received lipid-lowering medication if their low-density lipoprotein cholesterol level exceeded 4.15 mmol/L (160 mg/dL). MEASUREMENTS: The rate of change in intima-media thickness of the right distal common carotid artery far wall in computer image processed B-mode ultrasonograms obtained at baseline and every 6 months during the 2-year trial. RESULTS: In a multivariable mixed-effects model, among women who had at least one follow-up measurement of carotid intima-media thickness (n = 199), the average rate of progression of subclinical atherosclerosis was lower in those taking unopposed estradiol than in those taking placebo (-0.0017 mm/y vs. 0.0036 mm/y); the placebo-estradiol difference between average progression rates was 0.0053 mm/y (95% CI, 0.0001 to 0.0105 mm/y) (P = 0.046). Among women who did not receive lipid-lowering medication (n = 77), the placebo-estradiol difference between average rates of progression was 0.0147 mm/y (CI, 0.0055 to 0.0240) (P = 0.002). Average rates of progression did not differ between estradiol and placebo recipients who took lipid-lowering medication (n = 122) (P > 0.2). CONCLUSIONS: Overall, the average rate of progression of subclinical atherosclerosis was slower in healthy postmenopausal women taking unopposed ERT with 17beta-estradiol than in women taking placebo. Reduction in the progression of subclinical atherosclerosis was seen in women who did not take lipid-lowering medication but not in those who took these medications.     

Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial

BACKGROUND: Among persons who receive solid organ transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective. OBJECTIVE: To evaluate the efficacy and safety of prophylactic fluconazole in liver transplant recipients. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University-affiliated transplantation center. PATIENTS: 212 liver transplant recipients who received fluconazole (400 mg/d) or placebo until 10 weeks after transplantation. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, drug-related side effects, and death. RESULTS: Fungal colonization increased in patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003). CONCLUSIONS: Prophylactic fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.     

A double-blind,placebo-controlled trial

Sulfasalazine (SSZ), 3 gm daily, was compared with placebo for treatment of rheumatoid arthritis, in a 15-week randomized, parallel, double-blind trial. Joint tenderness and swelling, morning stiffness, grip strength, and pain score all showed significantly more improvement with SSZ than with placebo. Adverse effects, particularly gastrointestinal reactions, led to withdrawal from the study of 28% of the patients who had been receiving SSZ, but these effects were all readily reversible and not life-threatening. These results confirm previous findings that suppression of rheumatoid synovitis may be induced by SSZ, within 2 months after full maintenance doses are reached.     

Adalimumab in the treatment of chronic pouchitis. A randomized double-blind,placebo-controlled trial

Background: Pouchitis is a complication of ileal pouch-anal anastomosis and occurs in up to 50% of patients 10 years after IPAA with 10% developing refractory pouchitis.

Objective: To evaluate the effect of a TNF-α inhibitor (Adalimumab) in the treatment of refractory pouchitis.

Materials and methods: A multicenter, randomized double-blind, placebo-controlled trial includes patients with refractory pouchitis for more than 4 weeks despite antibiotic treatment. Patients were randomized to Adalimumab or placebo for 12 weeks. Primary outcome was reduction in clinical pouchitis disease activity index (PDAI) of ≥2 at any time. Secondary endpoints were remission of pouchitis, endoscopic and histologic effect and quality of life.

Results: Thirteen patients were included; six patients received active treatment and seven patients received placebo. Nine patients (5/4, Adalimumab/placebo) completed the 12-week program. Reduction in clinical PDAI ≥ 2 was achieved in three patients in each group (50%/43%, Adalimumab/placebo, p?>?.5). Total PDAI improved in six patients treated with Adalimumab and two patients on placebo (100%/29%, p?=?.13). There were no differences in secondary endpoints between the groups.

Conclusions: In this randomized controlled trial of treatment with Adalimumab in patients with refractory pouchitis, we were not able to identify any clinical benefit in the primary or secondary endpoints.     

Efficacy of a CO2-releasing suppository in dyschezia: A double-blind,randomized, placebo-controlled clinical trial

BackgroundConstipation has a significant impact on quality of life. Aim of this study was to evaluate the safety and the efficacy for relieving dyschezia symptoms of a CO₂-releasing suppository in a randomized, placebo-controlled, clinical trial.MethodsFifty-three office-based primary care physicians and 24 gastroenterologists conducted the study in France, between November 2010 and January 2012. Patients (aged 18–75 years) with dyschezia were eligible. Patients were randomly allocated a once-a-day suppository (CO₂-releasing suppository or placebo) for 21 days. Primary endpoint was the change, from Day 0 to Day 21, in the intensity of discomfort related to dyschezia based on a self-assessed 0–100 visual analogue scale.ResultsA total of 323 patients were randomized, i.e. 166 into the intervention group and 157 into the placebo group. Co-variance analysis showed a greater reduction in discomfort visual analogue scale score in the intervention group (−34.5 mm; standard error of the mean: 1.8 mm) than in the placebo group (−26.2 mm; standard error of the mean: 1.9 mm; p < 0.001). The greater efficacy of the CO₂-releasing suppository was confirmed for all secondary efficacy parameters. No significant side effects for either treatment were observed.ConclusionA CO₂-releasing suppository is more effective than a placebo for the relief of symptoms of dyschezia. This efficacy is associated with a good safety profile.     

A multicentre, randomized, double-blind, placebo-controlled trial of primary cryptococcal meningitis prophylaxis in HIV-infected patients with severe immune deficiency

OBJECTIVES: To assess the efficacy and survival benefit of low-dose fluconazole (400 mg weekly) for primary prophylaxis for cryptococcal meningitis in patients with advanced HIV infection. METHODS: A prospective multicentre, randomized, double-blind, placebo-controlled study was carried out in HIV-infected patients with CD4 counts <100 cells/microL. RESULTS: Of 90 patients enrolled, 44 received fluconazole and 46 received placebo. The baseline characteristics were similar in the two groups. On an intent-to-treat basis, 10 cases of cryptococcal meningitis developed, three (6.8%) in the fluconazole group and seven (15.2%) in the placebo group. Patients in the placebo group were more likely to develop cryptococcal meningitis than those in the fluconazole group [hazard ratio=2.23; 95% confidence interval (CI): 0.58-8.63; P=0.245]. The survival benefit of fluconazole was greater than that of the placebo. The number of deaths per 10 000 person-days was 2.7 for the fluconazole group (2/7342) and 11.7 for the placebo group (9/7713) (rate difference=9; 95% CI: 0.4-17.5; P=0.046). Based on survival analysis, patients in the placebo group were 4.3 times more likely to die than those in the fluconazole group (95% CI: 0.9-19.8; P=0.065). CONCLUSION: Fluconazole 400 mg once weekly for primary prophylaxis for cryptococcal meningitis in Thailand should be considered in HIV-infected patients, as our study suggested a survival benefit. However, a larger study should be conducted to confirm our findings.     

Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial

BACKGROUND: Relaxin is a pregnancy-related hormone that has tissue remodeling and antifibrotic effects. Systemic sclerosis (scleroderma) is characterized by fibrosis of the skin, vasculature, and internal organs. OBJECTIVE: To assess the efficacy, safety, and dose-response effect of recombinant human relaxin in patients with scleroderma. DESIGN: Multicenter, parallel-group, randomized, double-blind, placebo-controlled trial. SETTING: Academic referral centers. PATIENTS: 68 patients who had had stable, diffuse scleroderma (moderate to severe) for less than 5 years. INTERVENTION: Recombinant human relaxin, 25 or 100 microg/kg of body weight per day, or placebo administered by continuous subcutaneous infusion over 24 weeks. MEASUREMENTS: Modified Rodnan skin score was the primary efficacy measure. Secondary measurements were pulmonary function, the Health Assessment Questionnaire, and other measures of scleroderma that reflected fibrosis. RESULTS: Patients who received 25 microg/kg of recombinant human relaxin per day had significantly lower skin scores than those who received placebo (mean change, -3.6 at 4 weeks [P = 0.021], -7.5 at 12 weeks [P < 0.001], and -8.7 at 24 weeks [P = 0.040]). Similar trends were noted in other outcome measures, including forced vital capacity, measures of oral aperture and hand extension, functional status, and global assessment. Patients who received 100 microg/kg of relaxin per day did not differ from those who received placebo. Drug-related adverse events included menometrorrhagia, reversible anemia, and complications of the subcutaneous drug administration system (site irritation and local infection). CONCLUSIONS: Twenty-four weeks of recombinant human relaxin, 25 microg/kg per day, is associated with reduced skin thickening, improved mobility, and improved function in patients with moderate to severe diffuse scleroderma.     

Nutritional supplementation of elderly hip fracture patients. A randomized, double-blind, placebo-controlled trial

BACKGROUND: undernourishment is common in elderly hip fracture patients and has been linked to poorer recovery and increased post-operative complications. OBJECTIVE: to determine whether a nutritional supplement may (i) help elderly patients return to pre-fracture functional levels 6 months post-fracture and (ii) decrease fracture-related complications and mortality. DESIGN: a double-blind, randomized, placebo-controlled clinical trial. SETTING: a county hospital near Barcelona. SUBJECTS: 171 patients, aged 70 and older, hospitalized for hip fracture between July 1994 and July 1996. METHODS: we randomized patients to intervention (n = 85) or control (n = 86) group. Patients received a nutritional supplement containing 20 g of protein and 800 mg of calcium or placebo for 60 days. We determined functional levels by the Barthel index, the mobility index and by the use of walking aids. We performed assessments during hospitalization and at 2 and 6 months post-fracture. FINDINGS: the two groups were comparable at study entry. We observed no differences in return to functional status 6 months post-fracture (61% intervention group vs 55% in control group) nor in fracture-related mortality (13% in intervention group vs 10% in control group). The intervention group suffered fewer in-hospital [odds ratio 1.88 (95% CI 1.01 - 3.53), P = 0.05] and total complications [odds ratio 1.94 (95% CI 1.02-3.7), P = 0.04] than the control group. CONCLUSION: based on our results, we cannot recommend routine nutritional supplementation of all elderly hip fracture patients. While nutritional supplementation may be useful in decreasing complications, this reduction does not result in improvement in functional recovery and nor does it decrease fracture-related mortality. Selected patients may, however, benefit from nutritional supplementation.     

A double-blind,randomized, placebo-controlled trial of prostaglandin E1 in liver transplantation

A double-blind placebo-controlled trial of intravenous prostaglandin PGE₁ (40 μg/h) was conducted in adult orthotopic liver transplant recipients. Infusion was started intraoperatively and continued for up to 21 days. Patients were followed up for 180 days postoperatively. Among 172 patients eligible for treatment in the study, 160 could be evaluated (78 PGE₁; 82 placebo). Patient and graft survival were similar (PGE₁: 16 deaths, 9 retransplantations [7 survivors]; controls: 15 deaths, 6 retransplantations [3 survivors]). In patients with surviving grafts, however, PGE₁ administration resulted in a 23% shorter mean duration of hospitalization following transplantation (PGE₁: 24.4 days; controls: 31.8 days; P = .02) and a 40% shorter length of time postoperatively in the intensive care unit (PGE₁: 8.2 days; controls 13.7 days; P = .05). Reduced needs for renal support (P = .03) or surgical intervention other than retransplantation (P = .02) were also noted with PGE₁ use. Further, PGE₁ administration resulted in a trend toward improved survival rates in patients with mild renal impairment (preoperative serum creatinine 1.5 mg percent or greater; P = .08). Neither the incidence of acute cellular rejection nor of primary nonfunction was significantly different in the two groups. Phlebitis was the only complication that was more common during PGE₁ administration, (PGE₁: 9; controls: 4). These results suggest that PGE₁ use in hepatic allograft recipients reduces morbidity and may result in sizable cost reductions.     

A randomized, double-blind, placebo-controlled trial of nutritional supplementation during acute illness

Purpose

The study tested whether nutritional support of older patients during acute illness leads to a clinical benefit.

Methods

In this randomized, double-blind, placebo-controlled study, we randomly assigned 445 hospitalized patients aged 65 to 92 years to receive either a normal hospital diet plus 400 mL oral nutritional supplements (223 subjects) or a normal hospital diet plus a placebo (222 subjects) daily for 6 weeks. The composition of the supplement was such as to provide 995 kcal of energy and 100% of the Reference Nutrient Intakes for vitamins and minerals for a healthy older person. Patients had three assessments: at baseline, at 6 weeks, and at 6 months post-randomization. Outcome measures were 6 months of disability, non-elective readmission and length of hospital stay, discharge destination, morbidity, and mortality.

Results

Randomization to the supplement group led to a significant improvement in nutritional status. Over 6 months, 65 patients (29%) in the supplements group were readmitted to the hospital compared with 89 patients (40%) in the placebo group (adjusted hazard ratio 0.68 [95% confidence interval 0.49-0.94]). The mean length of hospital stay was 9.4 days in the supplements group compared with 10.1 days in the placebo group. Thirty-two people (14%) died in the supplement group compared with 19 people (9%) in the placebo group at 6 months (adjusted hazard ratio 1.65 [95% confidence interval, 0.93-2.92]).

Conclusion

Oral nutritional supplementation of acutely ill patients improved nutritional status and led to a statistically significant reduction in the number of non-elective readmissions.     

A randomized,double-blind,placebo-controlled trial of infliximab in refractory polymyositis and dermatomyositis

ObjectiveTo investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM).MethodsA randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5 mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5 mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5 mg/kg infliximab arm were increased to infliximab 7.5 mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5 mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40.ResultsTwelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5 mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5 mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5 mg/kg dosing regimen after week 16, and two of those responded to infliximab.ConclusionsInfliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients.     

Tapering of corticosteroid therapy following exacerbation of asthma. A randomized, double-blind, placebo-controlled trial

Systemic corticosteroids are effective in the treatment of acute asthma, but the optimal schedule for steroid withdrawal following an asthma exacerbation has not been determined. This study was designed to test the hypothesis that tapering the corticosteroid dosage over a longer period of time reduces the number of reexacerbations. Non-steroid-dependent adult men hospitalized for asthma exacerbations during a one-year period (n = 43) were randomly assigned to corticosteroid tapering regimens of one or seven weeks, following an eight-day course of high-dose corticosteroid therapy. There were no significant differences between the long-taper and short-taper groups in rate of reexacerbation (41% vs 52%) or readmission (22% vs 21%) during the 12-week study period. Patients who did not have a reexacerbation during the 12 weeks were evaluated with spirometry, with no significant differences occurring between the two groups. More patients in the long-taper group reported corticosteroid side effects (41% vs 14%). Patients who required mechanical ventilation during the initial hospitalization (n = 7), or who reported more than two days of worse than usual dyspnea in the 12-week period (n = 20), had high rates of reexacerbation (86% and 80%, respectively). These results provide reasonable certainty (90%) that a long taper does not result in a large reduction (50% or more) in reexacerbations compared with a short taper. We conclude that the relapse rate is high in this population regardless of the corticosteroid tapering regimen used, and that a long taper does not appear to provide enough benefit to justify its routine use.     

Effect of influenza vaccination on disease progression among HIV-infected persons

OBJECTIVE: To describe the effect of influenza vaccination on long-term change in CD4 count and HIV RNA level, and on progression to AIDS or death. DESIGN AND SETTING: A longitudinal medical record review set in 113 medical clinics in 10 United States cities. PATIENTS: A total of 36,050 HIV-infected persons aged > or = 13 years in care for HIV infection. MAIN OUTCOME MEASURES: Change in CD4 count and HIV RNA level at follow-up (3-12 months after vaccination); hazard ratios (HR) for association of influenza vaccine with progression from baseline CD4 or HIV RNA level to AIDS and to death. RESULTS: The median CD4 count among all persons decreased 28 cells/year during follow-up, with no difference in change in CD4 count between the 8007 (40%) vaccinated (median = 6 months, vaccine to follow-up CD4 count) and the 11,794 unvaccinated persons. In a viral load subanalysis, median HIV RNA level decreased 90 copies/ml per year among all persons during follow-up; decreases were not different between vaccinated and unvaccinated persons (median = 7 months, vaccine to follow-up HIV RNA level determination). Influenza vaccination was weakly associated with decreased risk of progression to clinical AIDS [HR 0.93; 95% confidence interval (CI), 0.87-0.99], but not associated with time to death (HR, 0.97; CI, 0.93-1.01). CONCLUSIONS: No negative long-term effect of influenza vaccination on CD4 counts, HIV RNA levels, or progression to AIDS or death was found in this HIV-infected population. These data suggest that physicians should not withhold influenza vaccine because of concerns about long-term detrimental effects of increased viral replication.     

Slow-release lanreotide in Graves' ophthalmopathy: A double-blind randomized, placebo-controlled clinical trial

SS analogs are an attractive alternative in treating Graves' ophthalmopathy (GO). Most of the previous studies were uncontrolled and enrolled few patients. The present study was conducted as a larger scale, prospective, randomized controlled study to determine the effectiveness of a slow-release formulation of lanreotide in GO. Sixty patients with active GO received an im injection every two weeks of either lanreotide 30 mg or placebo for 12 weeks. They were then followed and further treated in the traditional way if necessary. The Clinical Activity Score (CAS) was the primary efficacy criterion. Proptosis, diplopia, corneal erosion or ulcer, visual acuity, extraocular muscle movement and intraocular pressure were also evaluated. At the end of the 12 weeks, the mean CAS was not significantly decreased in the lanreotide group compared to the placebo group. The overall mean difference of proptosis between these two groups also did not reach significance at 12 weeks. Only diplopia at downward gaze had significant improvement for the lanreotide- treated group vs placebo group (p = 0.03). No differences were observed between the two groups compared to other outcome measures. During the 24-month follow-up after the clinical trial, 14 patients received eye surgery in the placebo group compared with 10 patients in the lanreotide group (p = 0.29). Six patients received methylprednisolone pulse therapy in the placebo group and two patients in the lanreotide group (p = 0.25). In conclusion, lanreotide treatment had no significant effects on GO compared with placebo.