Heparin induced thrombosis: an important complication of heparin prophylaxis for thromboembolic disease in surgery.

Heparin induced thrombocytopenia with thrombosis, or the "white clot syndrome," is a rare but recognised complication of heparin therapy. The syndrome is idiosyncratic, immune mediated, and not dose dependent and therefore is equally likely to occur with prophylactic and therapeutic heparin dosage regimens. Despite published reports on the subject we were alarmed that many surgeons who regularly use heparin to prevent or treat thrombosis were unaware that heparin can induce thrombotic complications in susceptible patients. We present three typical case histories, a brief discussion of the condition, and some guidelines on its prevention and treatment.     

Acupuncture for migraine prophylaxis: a randomized controlled trial

Background:

Acupuncture is commonly used to treat migraine. We assessed the efficacy of acupuncture at migraine-specific acupuncture points compared with other acupuncture points and sham acupuncture.

Methods:

We performed a multicentre, single-blind randomized controlled trial. In total, 480 patients with migraine were randomly assigned to one of four groups (Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture or sham acupuncture [control]). All groups received 20 treatments, which included electrical stimulation, over a period of four weeks. The primary outcome was the number of days with a migraine experienced during weeks 5–8 after randomization. Our secondary outcomes included the frequency of migraine attack, migraine intensity and migraine-specific quality of life.

Results:

Compared with patients in the control group, patients in the acupuncture groups reported fewer days with a migraine during weeks 5–8, however the differences between treatments were not significant (p > 0.05). There was a significant reduction in the number of days with a migraine during weeks 13–16 in all acupuncture groups compared with control (Shaoyang-specific acupuncture v. control: difference –1.06 [95% confidence interval (CI) –1.77 to –0.5], p = 0.003; Shaoyang-nonspecific acupuncture v. control: difference –1.22 [95% CI –1.92 to –0.52], p < 0.001; Yangming-specific acupuncture v. control: difference –0.91 [95% CI –1.61 to –0.21], p = 0.011). We found that there was a significant, but not clinically relevant, benefit for almost all secondary outcomes in the three acupuncture groups compared with the control group. We found no relevant differences between the three acupuncture groups.

Interpretation:

Acupuncture tested appeared to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture.

Trial Registration:

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00599586","term_id":"NCT00599586"}}NCT00599586About 6%–8% of men and 16%–18% of women in the United States and England experience migraines, with or without an aura.^1,2 A prevalence of 1% has been reported in mainland China,³ compared with 4.7% in Hong Kong and 9.1% in Taiwan.^4,5 A recent Cochrane meta-analysis suggests that acupuncture as migraine prophylaxis is safe and effective and should be considered as a treatment option for willing patients.⁶Although the specific effects acupuncture are controversial, acupuncture, as it is currently practised, clearly differentiates between real acupuncture points and nonacupuncture points. The Chinese Government launched the National Basic Research Program to obtain more data about the specificity of acupuncture points.⁷Trials from Italy and Brazil^8,9 showed that acupuncture was more effective than sham acupuncture in preventing migraines, but other trials have reported no differences.^10–13 There is no evidence that one acupuncture strategy is more effective than another for treating migraines. According to acupuncture theory, a headache on the lateral side is usually defined as a Shaoyang headache. In Jinkuiyi,¹⁴ migraines are said to affect the yang meridians (including the Taiyang, Yangming and Shaoyang meridians). In Lingshu,¹⁵ the Shaoyang meridians are said to go through the lateral side of the body, therefore the Shaoyang meridians are thought to be superior for treating migraines. Some points on the Shaoyang meridians are regarded as being more specific for migraines than other points.¹⁶Our aim was to investigate whether acupuncture at specific acupuncture points was more efficacious in preventing migraine than sham acupuncture at nonacupuncture points. We also investigated whether the efficacy varied when acupuncture points along different meridians or points along the same meridian were used.     

Amantadine for dyskinesias in Parkinson's disease: a randomized controlled trial

Background

Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson''s disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson''s disease patients suffering from dyskinesias.

Methods

In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson''s disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg /day) or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS) during each treatment period. The secondary outcome measures were changes in the Unified Parkinson''s Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias), part IVb (motor fluctuations), and part III (motor function).

Results

RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5). UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD) of 1.83 (1.56)] compared with placebo-treated patients [0.03 (1.51)]. However, there were no significant effects on UPDRS-IVb or III scores.

Conclusions

Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60–70% of patients.

Trial Registration

UMIN Clinical Trial Registry UMIN000000780     

Sulphasalazine retention enemas in ulcerative colitis: a double-blind trial.

Thirty-four patients with ulcerative colitis completed a double-blind assessment comparing the efficacy of two weeks of treatment with nightly retention enemas containing 3 g sulphasalazine or placebo. Symptom grading, sigmoidoscopic appearance, rectal biopsy specimens, and diary records were used to assess benefit and side effects. The active drug conferred significant benefit compared with placebo as shown by several criteria, but this benefit was confined to patients not already taking sulphasalazine by mouth. Overall assessment showed improvement in 11 of the 16 patients (70%) given the active treatment but in only two of the 18 (11%) given placebo. No side effects attributable to the drug were observed, even in patients previously intolerant to oral preparations. The logical therapeutic role of sulphasalazine enemas in ulcerative colitis would appear to be in patients who experience side effects such as nausea, abdominal discomfort, or headaches when taking the drug by mouth.     

Infant safety during and after maternal valacyclovir therapy in conjunction with antiretroviral HIV-1 prophylaxis in a randomized clinical trial

Background

Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.

Methods

Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm³ were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher’s Exact and Wilcoxon rank-sum tests were used for analysis.

Results

One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6–4.19).

Conclusions

Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00530777","term_id":"NCT00530777"}}NCT00530777     

Electric convulsion therapy in depression: a double-blind controlled trial.

The therapeutic effect of simulated and real bilateral electric convulsion therapy was examined in a double-blind, randomised trial on 22 patients with a primary depressive illness. Each treatment was given twice weekly for three weeks and the results assessed by the psychiatrist using a visual analogue rating scale, nurses using a nine-point rating scale, and the patients themselves using the Beck Depression Inventory. With all three methods of assessment patients given the real treatment substantially improved (p less than 0.001), whereas those given simulated treatment showed little change. Three weeks after substituting real treatment for simulated, however, these patients were also significantly improved (psychiatrist''s rating p less than 0.001; nurses'' rating p less than 0.005; Beck inventory p less than 0.005). These findings confirm the value of electric convulsion therapy in severe depressive illness and strongly suggest that the convulsion is important for the therapeutic effect.     

Prevention of respiratory complications after abdominal surgery: a randomised clinical trial.

OBJECTIVE--To evaluate the prevention of respiratory complications after abdominal surgery by a comparison of a global policy of incentive spirometry with a regimen consisting of deep breathing exercises for low risk patients and incentive spirometry plus physiotherapy for high risk patients. DESIGN--Stratified randomised trial. SETTING--General surgical service of an urban teaching hospital. PATIENTS--456 patients undergoing abdominal surgery. Patients less than 60 years of age with an American Society of Anesthesia classification of 1 were considered to be at low risk. OUTCOME MEASURES--Respiratory complications were defined as clinical features consistent with collapse or consolidation, a temperature above 38 degrees C, plus either confirmatory chest radiology or positive results on sputum microbiology. We also recorded the time that staff devoted to prophylactic respiratory therapy. RESULTS--There was good baseline equivalence between the groups. The incidence of respiratory complications was 15% (35/231) for patients in the incentive spirometry group and 12% (28/225) for patients in the mixed therapy group (P = 0.40; 95% confidence interval -3.6% to 9.0%). It required similar amounts of staff time to provide incentive spirometry and deep breathing exercises for low risk patients. The inclusion of physiotherapy for high risk patients, however, resulted in the utilisation of an extra 30 minutes of staff time per patient. CONCLUSIONS--When the use of resources is taken into account, the most efficient regimen of prophylaxis against respiratory complications after abdominal surgery is deep breathing exercises for low risk patients and incentive spirometry for high risk patients.     

Itraconazole and leishmaniasis: A randomised double-blind trial in cutaneous disease

Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease of the skin. Previous open controlled studies with oral itraconazole suggest that it was effective for CL in India. Twenty patients with localised CL participated in this trial. Patients were allocated randomly to receive capsule itraconazole and matching placebo for 6 weeks. No topical medicines were used. Demonstration of Leishmania by slit smear was mandatory. Prior to, periodically during and 3 months after completion of therapy an overall clinical assessment, liver function tests and urinalysis were performed. On decoding, out of the 10 cases receiving drug itraconazole, 7 were declared cured by clinical and parasitological criteria. No major side-effects were noted. Spontaneous remission was observed in 1 case in the placebo group at 3 months follow up. Oral itraconazole has a promising antileishmanial potential and may thus secure CL patient from the hazards of antimonials.     

Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial

Background

Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals. The study aimed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control, lipid profiles and insulin sensitivity in type 2 diabetic patients.

Methodology/Principal Findings

This was a randomized, double-blind, placebo-controlled, cross-over trial and it was conducted between April and December 2006 in Shanghai, China. Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study. Patients were randomized to supplementation with flaxseed-derived lignan capsules (360 mg lignan per day) or placebo for 12 weeks, separated by an 8-week wash-out period. HbA1c, lipid profiles, insulin resistance index and inflammatory factors were measured. Sixty-eight completed the study and were included in the analyses. The lignan supplement significantly improved glycemic control as measured by HbA_1c (-0.10±0.65 % vs. 0.09±0.52 %, P = 0.001) compared to placebo; however, no significant changes were observed in fasting glucose and insulin concentrations, insulin resistance and blood lipid profiles. Urinary excretion of lignan metabolites (enterodiol and enterolactone) was significantly higher after the lignan supplement intervention compared to baseline (14.2±18.1 vs. 1.2±2.4 µg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations.

Conclusions/Significance

Daily lignan supplementation resulted in modest, yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose, lipid profiles and insulin sensitivity. Further studies are needed to validate these findings and explore the efficacy of lignans on type 2 diabetes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00363233","term_id":"NCT00363233"}}NCT00363233     

A randomized, placebo-controlled, double-blind clinical trial of curcuminoids in oral lichen planus.

We studied the efficacy of curcuminoids in the treatment of oral lichen planus (OLP), a chronic, mucocutaneous, immunological disease. Curcuminoids are components of turmeric (Curcuma longa) that have anti-inflammatory activity. Turmeric has been used in Ayurveda (Indian traditional medicine) for centuries. A randomized, double-blind, placebo-controlled trial was conducted. In all, 100 consecutive, eligible patients with OLP presenting to the oral medicine clinic at the University of California, San Francisco, were to be selected. Two interim analyses were to be conducted during the trial. The trial was conducted between February 2003 and September 2004. The first interim analysis was conducted in October 2004 using data from the first 33 subjects. Study subjects were randomized to receive either placebo or curcuminoids at 2000 mg/day for 7 weeks. In addition, all subjects received prednisone at 60 mg/day for the first 1 week. The primary outcome was a change in symptoms from baseline. Secondary outcomes were changes in clinical signs and occurrence of side effects. The first interim analysis did not show a significant difference between the placebo and curcuminoids groups. Conditional power calculations suggested a less than 2% chance that the curcuminoids group would have a significantly better outcome as compared with the placebo group if the trial were continued to completion. Therefore, the study was ended early for futility. Reaching a conclusion regarding the efficacy of curcuminoids based on the results of this study is not possible as it was ended early for futility. Curcuminoids at this dose were well tolerated and the results suggest that for future studies a larger sample size, a higher dose and/or longer duration of curcuminoids administration should be considered; however, for the next step, an RCT of a shorter duration, using a higher dose of curcuminoids, and without an initial course of prednisone, should be considered.