Surgery vs orthosis vs watchful waiting for hallux valgus: a randomized controlled trial

CONTEXT: Hallux valgus is a common foot deformation in adults, but evidence for effectiveness of surgical and conservative treatments for this condition is limited. OBJECTIVE: To compare the effectiveness of surgical and orthotic treatment with no treatment in patients with hallux valgus. DESIGN AND SETTING: Randomized controlled trial conducted in 4 general community hospitals in Finland in 1997-1998, with a follow-up period of 12 months. PARTICIPANTS: Two hundred nine consecutive patients (mean age, 48 years; 93% women) with a painful bunion and a hallux valgus angle 35 degrees or less. INTERVENTIONS: Patients were randomly assigned to surgery (distal chevron osteotomy; n = 71), orthosis (n = 69), or a 1-year waiting list (control group, n = 69). MAIN OUTCOME MEASURES: Pain intensity during walking on a visual analog scale (0-100), patient assessment of global improvement, number of painful days, cosmetic disturbance, footwear problems, functional status, and treatment satisfaction, compared among treatment groups. RESULTS: Follow-up rates at 6 and 12 months were 99% and 98%, respectively. At 6 months, pain intensity decreased more in the surgical group than in the control group (adjusted mean differences, -20 [95% confidence interval (CI), -28 to -12]) and more in orthosis than in the control groups (adjusted mean difference, -14 [95% CI, -22 to -6. At 1 year, pain intensity decreased more in the surgical than in the control groups (adjusted mean difference, -19 [95% CI, -28 to -10]) and more than in the surgical and orthosis groups (adjusted mean difference, -14 [95% CI, -22 to -5]). At 1 year, 83%, 46%, and 24% in the surgery, orthosis, and control groups, respectively, thought they had improved compared with baseline (number needed to treat), 1.7 between surgical and control groups). Number of painful days, cosmetic disturbance, and footwear problems were least and functional status and satisfaction with treatment were best in the surgical group. CONCLUSIONS: Surgical osteotomy is an effective treatment for painful hallux valgus. Orthoses provide short-term symptomatic relief.     

Watchful waiting vs immediate transurethral resection for symptomatic prostatism. The importance of patients' preferences

The rate of resection for benign prostatic hypertrophy shows considerable variability among small geographic areas. To help inform the decision to recommend prostatectomy to men with prostatism without signs of chronic retention, we performed a decision analysis to compare the expected outcomes with immediate transurethral resection and watchful waiting. Data used in the model originated from the medical literature, Medicare claims data, and patient interview studies. In our base-case analysis for 70-year-old men, immediate surgery resulted in the loss of 1.01 months of life expectancy, but when adjustments were made for quality of life, immediate surgery was favored with a net utility benefit of 2.94 quality-adjusted life-months. However, the analysis was particularly sensitive to the degree of disutility attributed to the index symptoms of prostatism. We conclude that patient preferences should be the dominant factor in the decision whether to recommend prostatectomy.     

卡托普利控释微丸的研制及其体外释放研究

采用乙基纤维素、丙烯酸树脂Ⅱ及硬脂醇为缓释材料，研究了卡托普利控释微丸的处方和工艺。经体外释放实验证明，制得的控释微丸能明显延缓药物释放，释放过程符合零级动力学。     

缓释/控释制剂的风险管理

风险管理对于缓释/控释制剂的用药安全十分重要。本文通过统计《中国药典》2010年版二部收载的缓释/控释制剂品种、规格、剂型和服用方法 ,并结合文献分析缓控/释制剂存在的风险,探讨造成此类制剂风险的原因,并为构建风险管理体系提出相应建议。建议提高缓释/控释制剂注册审批的技术要求,严格控制生产工艺及质量监测,发挥药师的药学服务作用,提高医生和患者对于缓释/控释制剂的认识。     

Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial

Context  Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective. Objective  To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women. Design and Setting  Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics. Patients  A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy. Intervention  After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks. Main Outcome Measures  Mean change from baseline to week 6 in the daily hot flash composite score (frequency x severity). Results  Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were -4.7 (95% confidence interval, - 8.1 to -1.3; P = .007) comparing 12.5-mg/d paroxetine CR with placebo; and -3.6 (95% confidence interval, -6.8 to -0.4; P = .03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group. Conclusion  Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.      

缓控释微丸制剂的研究进展

以微丸制剂为代表的多单元型给药系统以其特有的优越性,逐渐成为目前缓控释制剂的研究热点之一,在现代药品开发和应用上备受瞩目.论文对缓控释微丸制剂的常用辅料、制备方法及释药机制等方面进行了综述,旨在为研究开发口服缓控释制剂提供思路和方法.     

Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. Parkinson Study Group

Context  Pramipexole and levodopa both ameliorate the motor symptoms of early Parkinson disease (PD), but no controlled studies have compared long-term outcomes after initiating dopaminergic therapy with pramipexole vs levodopa. Objective  To compare the development of dopaminergic motor complications after initial treatment of early PD with pramipexole vs levodopa. Design  Multicenter, parallel-group, double-blind, randomized controlled trial. Setting  Academic movement disorders clinics at 22 sites in the United States and Canada. Patients  Three hundred one patients with early PD who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997. Interventions  Subjects were randomly assigned to receive pramipexole, 0.5 mg 3 times per day, with levodopa placebo (n = 151); or carbidopa/levodopa, 25/100 mg 3 times per day, with pramipexole placebo (n = 150). For patients with residual disability, the dosage was escalated during the first 10 weeks. From week 11 to month 23.5, investigators were permitted to add open-label levodopa to treat continuing or emerging disability. Main Outcome Measures  Time to the first occurrence of any of 3 dopaminergic complications: wearing off, dyskinesias, or on-off motor fluctuations; changes in scores on the Unified Parkinson's Disease Rating Scale (UPDRS), assessed at baseline and follow-up evaluations; and, in a subgroup of 82 subjects evaluated at baseline and 23.5 months, ratio of specific to nondisplaceable striatal iodine 123 2--carboxymethoxy-3--(4-iodophenyl)tropane (-CIT) uptake on single photon emission computed tomography imaging of the dopamine transporter. Results  Initial pramipexole treatment resulted in significantly less development of wearing off, dyskinesias, or on-off motor fluctuations (28%) compared with levodopa (51%) (hazard ratio, 0.45; 95% confidence interval [CI], 0.30-0.66; P<.001). The mean improvement in total UPDRS score from baseline to 23.5 months was greater in the levodopa group than in the pramipexole group (9.2 vs 4.5 points; P<.001). Somnolence was more common in pramipexole-treated patients than in levodopa-treated patients (32.4% vs 17.3%; P = .003), and the difference was seen during the escalation phase of treatment. In the subgroup study, patients treated initially with pramipexole (n = 39) showed a mean (SD) decline of 20.0% (14.2%) in striatal -CIT uptake compared with a 24.8% (14.4%) decline in subjects treated initially with levodopa (n = 39; P = .15). Conclusions  Fewer patients receiving initial treatment for PD with pramipexole developed dopaminergic motor complications than with levodopa therapy. Despite supplementation with open-label levodopa in both groups, the levodopa-treated group had a greater improvement in total UPDRS compared with the pramipexole group.      

Clinical efficacy and safety of tapentadol immediate release in the postoperative setting

The appropriate treatment for postoperative pain remains a common dilemma for podiatric surgeons and patients undergoing surgery of the foot and ankle. The treatment of moderate to severe acute pain typically relies heavily on the use of opioid analgesics, such as hydrocodone and oxycodone, which are often associated with adverse effects, including nausea and vomiting. These adverse effects may have a negative impact on postoperative outcomes and reduce patient compliance with analgesic therapy. Tapentadol is a novel, centrally acting analgesic with two mechanisms of action--μ-opioid receptor agonism and norepinephrine reuptake inhibition--in a single molecule. Tapentadol immediate release has been evaluated in a series of clinical trials in patients with postoperative pain after bunionectomy. The results of these studies demonstrate that tapentadol immediate release is associated with an improved gastrointestinal tolerability profile relative to oxycodone immediate release at doses providing comparable analgesia. Therefore, tapentadol immediate release may offer an improved analgesic option for the relief of postoperative pain after podiatric surgery.     

Controlled delivery of high vs low humidity vs mist therapy for croup in emergency departments: a randomized controlled trial

Context  Children with croup are often treated with humidity even though this is not scientifically based, consumes time, and can be harmful. Although humidity using the traditional blow-by technique is similar to room air and no water droplets reach the nasopharynx, particles sized for laryngeal deposition (5-10 µm) could be beneficial. Objective  To determine whether a significant difference in the clinical Westley croup score exists in children with moderate to severe croup who were admitted to the emergency department and who received either 100% humidity or 40% humidity via nebulizer or blow-by humidity. Design and Setting  A randomized, single-blind, controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department. Participants  A convenience sample of 140 previously healthy children 3 months to 10 years of age with Westley croup score of more than 1 or 2 or higher (scoring system range, 0-17); 21 families refused participation. Intervention  Thirty-minute administration of humidity using traditional blow-by technique (commonly used placebo, n = 48), controlled delivery of 40% humidity (optimally delivered placebo, n = 46), or 100% humidity (n = 46) with water particles of mass median diameter 6.21 µm. Main Outcome Measure  A priori defined change in the Westley croup score from baseline to 30 and 60 minutes in the 3 groups. Results  Groups were comparable before treatment. At 30 minutes the difference in the improvement in the croup score between the blow-by and low-humidity groups was 0.03 (95% confidence interval [CI], –0.72 to 0.66), between low- and high-humidity groups, 0.16 (95% CI, –0.86 to 0.53), and between blow-by and high-humidity groups, 0.19 (95% CI, –0.87 to 0.49). Results were similar at 60 minutes. Differences between groups in pulse and respiratory rates and oxygen saturation changes were insignificant, as were proportions of excellent responders; proportions with croup score of 0 at study conclusion; and proportions receiving dexamethasone, epinephrine, or requiring additional medical care or hospitalization. Conclusions  One hundred percent humidity with particles specifically sized to deposit in the larynx failed to result in greater improvement than 40% humidity or humidity by blow-by technique. This study does not support the use of humidity for moderate croup for patients treated in the emergency department. Trial Registration  ClinicalTrials.gov Identifier: NCT00230841      

Effect of magnetic vs sham-magnetic insoles on plantar heel pain: a randomized controlled trial

Context  Despite anecdotal reports, rigorous scientific evidence of the effectiveness of magnetic insoles for the pain of plantar fasciitis is lacking. Objective  To determine whether magnetic insoles provide greater subjective improvement for treatment of plantar heel pain compared with identical nonmagnetized insoles. Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial conducted from February 12, 2001, to November 9, 2001, of a volunteer sample of 101 adults with diagnoses of plantar heel pain for at least 30 days from a multispecialty group practice clinic in Rochester, Minn. Daily pain diaries were kept for 8 weeks. Interventions  Cushioned insoles, with either active bipolar magnets or sham magnets, which were worn daily by the participants for 8 weeks. Main Outcome Measures  Reported average daily foot pain (by metered visual analog scale [VAS] and by categorical response of change from baseline) at 4 and 8 weeks, and impact of insoles on employment performance and enjoyment. Results  No significant between-group differences were found on any outcome variables studied when comparing active vs sham magnets. Both the nonmagnetic and magnetic groups reported significant improvements in morning foot pain intensity, with mean (SD) VAS scores improving from 6.9 (2.3) and 6.7 (2.0), respectively, at baseline to 3.9 (2.6) for each group at 8 weeks (P = .94). At 8 weeks, 33% of the nonmagnetic group and 35% of the magnetic group reported being all or mostly better (P = .78). At baseline, foot pain interfered moderately with participants' employment enjoyment (mean VAS, 4.2) and improved in both groups by 8 weeks (1.3 and 1.5, respectively; P = .68). Conclusion  Static bipolar magnets embedded in cushioned shoe insoles do not provide additional benefit for subjective plantar heel pain reduction when compared with nonmagnetic insoles.