Double-masked Trial Research Articles

Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal

Objective To examine the effect of supplemental prenatal folic acid, folic acid–iron, folic acid–iron–zinc, and multiple micronutrients on maternal morbidity in rural Nepal. Methods A cluster-randomized double-masked controlled trial of pregnant women who received daily supplements from early pregnancy through 3 months post partum as per the treatment allocation. Women were interviewed at birth about labor and delivery complications and for 9 days post partum to obtain 24-hour histories of morbidity. Results A total of 3986 (97.3%) women completed an interview regarding labor and delivery; morbidity history was available for 3564 (87.0%) women. Folic acid–iron reduced the risk of postpartum hemorrhage (relative risk [RR] 0.59; 95% confidence interval [CI] 0.35–0.98). Risk of dysfunctional labor increased with multiple micronutrient supplementation (RR 1.28; 95% CI, 1.01–1.60), although preterm premature rupture of membrane decreased (RR 0.40; 95% CI, 0.21–0.79). Puerperal sepsis was lower in those receiving folic acid–iron, folic acid–iron–zinc, and multiple micronutrients compared with controls ( P < 0.05). Conclusion Prenatal folic acid–iron supplementation reduced the risk of obstetric complications in this South Asian setting.

Randomized Double Masked Trial of Zhi Byed 11, a Tibetan Traditional Medicine, Versus Misoprostol to Prevent Postpartum Hemorrhage in Lhasa, Tibet

The objective of this study was to compare a Tibetan traditional medicine (the uterotonic Zhi Byed 11 [ZB11]) to oral misoprostol for prophylaxis of postpartum hemorrhage (PPH). We conducted a double-blind randomized controlled trial at three hospitals in Lhasa, Tibet, People's Republic of China. Women (N = 967) were randomized to either ZB11 or misoprostol groups. Postpartum blood loss was measured in a calibrated blood collection drape. The primary combined outcome was incidence of PPH, defined as measured blood loss (MBL) > or = 500 mL, administration of open label uterotonics, or maternal death. We found that the rate of the combined outcome was lower among the misoprostol group (16.1% versus 21.8% for ZB11; P = .02). Frequency of PPH was lower with misoprostol (12.4% versus 17.4%; P = .02). There were no significant differences in MBL > 1000 mL or mean or median MBL. Fever was significantly more common in the misoprostol group (P = .03). The rate of combined outcome was significantly lower among women receiving misoprostol. However, other indices of obstetric hemorrhage were not significantly different.

Systemic MMP inhibition for periodontal wound repair: results of a multi‐centre randomized‐controlled clinical trial

This multi-centre, prospective, controlled trial was designed to examine the biological response of the matrix metalloproteinase(MMP) inhibitor subantimicrobial dose doxycycline (SDD) combined with access flap surgery on periodontal wound repair in patients with chronic severe periodontitis. Seventy subjects were enrolled into a 12-month, randomized, placebo-controlled, double-masked trial to evaluate disease response to 6 months therapy and "wash-out" of either placebo+surgery or SDD (20 mg b.i.d.)+surgery. Primary outcome measure included clinical attachment levels (CAL) and secondary outcomes included probing depth (PD), bleeding on probing (BOP), as well as gingival crevicular fluid bone marker assessment [collagen telopeptides (ICTP)]. These measurements were taken at baseline through 12 months post-surgery and drug administration. Patients treated with SDD and surgery demonstrated stronger reductions in PD in surgically-treated sites of >or=7 mm as well as gains in CAL (p<0.004). Furthermore, SDD+surgery resulted in short-term reductions in ICTP levels compared with placebo. Rebounds in ICTP levels and clinical parameters occurred when SDD was withdrawn. The results from this multi-centre study suggests that SDD in combination with surgery improves the short-term response of periodontal therapy by reducing PD, increasing CAL gain and inhibiting early stage bone resorption.

Prospective randomised controlled trial comparing sub-threshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema

Aim:The study was a prospective randomised controlled double-masked trial performed in two centres to compare sub-threshold micropulse diode laser photocoagulation (MPDL) with conventional green laser photocoagulation (CGL) in the treatment...

A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab) intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

BackgroundThe management of neovascular age-related macular degeneration (nAMD) has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents). One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication) despite a lack of definitive unbiased safety and efficacy data.Methods and designThe Avastin® (bevacizumab) for choroidal neovascularisation (ABC) trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment). Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change.DiscussionThe ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a) defining the control group (b) use of gain in vision as primary efficacy end-point and (c) use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy.Trial registrationCurrent controlled trials ISRCTN83325075

Red blood cell metallothionein as an indicator of zinc status during pregnancy

Objective We describe the levels and patterns of change in red blood cell (RBC) metallothionein (MT) during pregnancy and the neonate and relate RBCMT to other indicators of zinc and iron status. Methods As part of a double-masked controlled trial of prenatal zinc supplementation among 242 Peruvian pregnant women, we determined RBCMT at enrollment (10–16 wk), at 28 and 36 wk of gestation, and in the cord blood at delivery in 158 women (86 who received daily supplements containing 60 mg of iron and 250 μg of folic acid and 72 whose supplements also contained 25 mg of zinc). In addition, we measured plasma and urinary zinc concentrations, hemoglobin and serum ferritin, and, on a limited sample, RBC zinc and placental MT. Results RBCMT increased during pregnancy, and levels in the cord blood approximated maternal values at 36 wk. Only RBC zinc at 36 wk differed by supplement type ( P < 0.05). Increases in RBCMT over pregnancy were, however, related to early pregnancy RBC zinc and inversely with the decline in plasma zinc from baseline to 36 wk of gestation. Conclusion Changes in RBCMT throughout pregnancy were consistent with the hypothesized role of MT in regulating zinc homeostasis. RBCMT appears to not be responsive during pregnancy to changes in zinc status achieved with supplements.

Glaucoma Affects Steady State VEP Contrast Thresholds Before Psychophysics

Frequency doubling technology (FDT) is a recent psychophysical test for glaucoma. It measures the contrast threshold to low spatial frequency, high temporal frequency sinusoidal luminance profile bars. We wanted to confirm, with stricter controls, Vaegan and Hollow's report that contrast thresholds of steady state visual evoked potentials (ssVEPs) to a stimulus resembling the central field of the FDT test was more sensitive to glaucoma than the subjective threshold to the same stimulus and to start to optimize the technique. A double masked trial using 57 eyes of 42 subjects. Both thresholds were estimated by modified binary search. In psychophysical testing, subjects were given a two alternative forced choice task. In ssVEP testing a significant signal in any one of eight channels was deemed to be a detection. In some subjects electrode positions were compared, both eyes were tested, tests were repeated to estimate reliability, stimulus frequencies were varied or full contrast functions were obtained. Thresholds and percent abnormal increased as a function of glaucoma severity for ssVEPs but not for psychophysics. Both threshold measures were reliable. Interocular correlations were low. SsVEP amplitude against contrast functions had similar thresholds to those found by modified binary search. The data was too irregular for individual thresholds to be estimated from a fitted exponential. Amplitudes were greatest at 7 to 10 Hz, < or =6 cm above inion and least laterally. Noise was similar across electrodes. SsVEP contrast thresholds to a stimulus like the central field of the FDT test detected glaucoma better than corresponding psychophysical thresholds at 18.29 Hz, when formal controls were used, as they had in a less controlled previous study at 7.14 Hz.

Sleep Quality in Asthma: Results of a Large Prospective Clinical Trial

Rationale. Previous studies have suggested that asthmatics have an increased incidence of sleep disturbances. However, these studies have been limited by reliance on population surveys or small numbers of participants. Objectives. We sought to measure sleep quality and daytime sleepiness in a cohort of symptomatic asthmatics and to measure the effects of improved asthma control on sleep quality. Methods. Data were collected in sub-study of a large multi-center randomized double-masked controlled trial of mild-moderate asthmatics evaluating the effect of low-dose theophylline on asthma control in comparison to montelukast and placebo. Each participant was administered sleep symptom questionnaires at randomization and at the final visit (6 months after randomization). These included the Pittsburgh Sleep Quality Questionnaire (PSQI) and the Epworth Sleepiness Scale (ESS). Measurements and main results. Data were available for 487 participants. Baseline mean values were: age 40 ± 15 years, 74% female, forced expiratory volume in 1 second (FEV1) 79 +16 percent predicted, Juniper Asthma Control Questionnaire (ACQ) score 2.35 ± 0.63, PSQI 7.8 ±4, and ESS 8.5 ±4.9. There were no significant differences in the PSQI or ESS between the three treatment groups. Significant correlations were found at baseline between the global PSQI score and ACQ and quality of life and marginally with lung function. Significant correlation existed between improvements in PSQI and ESS with improved asthma control and quality of life. Conclusions. Sleep disturbances are common in asthmatics and are associated with asthma control and quality of life. Clinicians caring for asthmatics may need to complete a more detailed sleep history in patients with poorly controlled asthma. In addition, low-dose theophylline does not seem to impair sleep quality in asthmatics.

Effects of Palmitate and Oleate on the Respiratory Quotient During Acute Feeding*

Using tracers, we showed, over 9 hours, that palmitic acid (PA) is oxidized at a lower rate than oleic acid (OA). Our subsequent clinical trial showed that enriching the diet for 28 days with PA, relative to OA, lowered fatty acid (FA) oxidation. However, because this conclusion was based on indirect calorimetry for 7 hours after a test meal, transient differences in the kinetics of oxidation of OA and PA could explain these results. Thus, we hypothesized that increasing PA vs. OA would decrease FA oxidation during the first day of feeding the diets. A double-masked trial was conducted in 20 adults, who, after a baseline diet, were randomized to one of two experimental formula diets: high (HI) OA (PA=1.7% kcal, OA=31.4% kcal; N=11) or HI PA (PA=16.8% kcal, OA=16.4% kcal; N=9). Respiratory quotient (RQ) was measured over the first 14 hours of feeding the experimental diets (7:00 am to 9:00 pm). To determine whether these subjects were representative of the subjects in the previous trial, we assessed RQ 28 days after beginning either diet. During the first 14 hours of feeding the diets, time (p=0.026) but not diet group had an effect on the difference between the RQ post-feeding and the fasting pre-value. However, RQ in the fed state was significantly higher in the HI PA group after 28 days of feeding. Chronically increasing dietary PA for 28 days, but not acute meal feeding, lowers total FA oxidation.

Prophylaxis of Acute Posttraumatic Bacterial Endophthalmitis

To evaluate the efficacy of intraocular gentamicin sulfate and clindamycin in the prevention of acute posttraumatic bacterial endophthalmitis following penetrating eye injuries. We conducted a multicenter, randomized, double-masked controlled trial of 346 eyes with penetrating eye injury. Following primary repair, eyes were randomized to intracameral or intravitreal injection of 40 microg of gentamicin sulfate and 45 microg of clindamycin (cases) vs balanced salt solution (controls). Occurrence of endophthalmitis within 2 weeks. Endophthalmitis occurred in 8 (2.3%) of 167 eyes in the control group and only in 1 (0.3%) of 179 eyes in the case group (P = .04; odds ratio, 8.93 [95% confidence interval, 1.11-71.43]). In eyes with an intraocular foreign body, endophthalmitis developed in 7 of 25 control eyes and in none of 27 eyes receiving antibiotics. However, in eyes without an intraocular foreign body, endophthalmitis developed in 1 of 142 eyes and 1 of 152 eyes in the 2 groups, respectively (P value for interaction = .04). Intravitreal injection was superior to intracameral injection in preventing endophthalmitis (P value for interaction = .01). Vitreous culture results were positive in 6 (67%) of 9 eyes with endophthalmitis. Intraocular gentamicin and clindamycin are effective in the prevention of acute posttraumatic bacterial endophthalmitis in eyes with retained intraocular foreign body. Prophylaxis of traumatic endophthalmitis. clinicaltrials.gov Identifier: NCT00398658.

The effect of topical tetracaine eye drops on emergence behavior and pain relief after strabismus surgery

Pediatric strabismus surgery may be associated with postoperative nausea, vomiting, and emergence agitation (restlessness, thrashing, crying, moaning, disorientation). We hypothesize that emergence agitation after strabismus surgery is in part related to pain and that topical tetracaine ophthalmic drops can decrease the intensity and incidence of postoperative pain and emergence agitation. Eighty-eight subjects aged 1 to 12 years scheduled for strabismus surgery were enrolled in a double-masked randomized control trial. The patients were randomized to one of three groups: Group A received normal saline drops before and after surgery; Group B received normal saline drops before and tetracaine 1% drops after surgery; Group C received tetracaine 1% drops before and after surgery. An observer masked to group assignment assessed each patient in the postanesthesia care unit (PACU) using both a behavior scale and a modified behavioral pain scale. Patients in Group A were found to be in significantly more pain than Groups B or C at 5 minutes after arrival to the PACU (p < 0.013). Using the behavior scale, a significantly greater proportion of patients in Group A were crying or crying and thrashing at 5, 15, and 30 minutes after arrival to the PACU (5 minutes, p < 0.019; 15 minutes, p < 0.041; 30 minutes, p < 0.021). There was no significant difference between groups in total PACU time, PACU vomiting, PACU morphine use, or pain at home. Postoperative strabismus surgery pain was improved by the use of preoperative, and pre- and postoperative, tetracaine drops. Emergence agitation was not fully evaluated by the behavioral scale, and therefore, the effect of tetracaine drops on emergence agitation was not clarified. This study suggests that tetracaine drops can lead to a less stressful early postoperative experience for the patient.

Self-evaluation of the cognitive effects of ECT

Objectives:Numerous studies have found that subjective memory improves shortly following ECT using standard self-evaluation questionnaires. These changes covary strongly with mood state while being not associated with objective memory tests or treatment parameters. This study compared patients' evaluations of the cognitive effects of ECT using a novel direct interview about subjective global impact and standard methods.Methods:We conducted a prospective, randomized, double-masked trial of the effects of pulse width (0.3 vs. 1.5 ms) and electrode placement (right unilateral vs. bilateral) on patients' evaluations of cognitive outcomes. Subjective evaluations were obtained prior to starting and during the week following the randomized ECT course, using the Cognitive Failures Questionnaire (CFQ), Squire Memory Complaint Questionnaire (SMCQ), and the novel Global Self-Evaluation of Memory (GSE-My). An extensive neuropsychological battery was administered at the same time points.Results:CFQ and SMCQ scores improved at postECT relative to preECT. At both time points, these scores were strongly associated with HRSD scores and not with objective deficits or treatment parameters. In contrast, on the GSE-My patients reported a deleterious memory effect after ECT. GSE-My scores were also associated with objective memory loss and treatment technique.Conclusions:Characterization of patients' experience of cognitive side effects following ECT differs markedly depending on the assessment method. Direct questioning about global impact revealed more negative views about ECT's impact. These results support the findings of a prospective, naturalistic, observational community study representing together the first reports of concordance between subjective and objective measures of ECT's effects on memory.

Twice-Daily 0.2% Brimonidine–0.5% Timolol Fixed-Combination Therapy vs Monotherapy With Timolol or Brimonidine in Patients With Glaucoma or Ocular Hypertension

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a fixed combination of 0.2% brimonidine tartrate and 0.5% timolol maleate (fixed brimonidine-timolol) compared with the component medications. In 2 identical, 12-month, randomized, double-masked multicenter trials, patients with ocular hypertension or glaucoma were treated with fixed brimonidine-timolol twice daily (n = 385), 0.2% brimonidine tartrate 3 times daily (n = 382), or 0.5% timolol maleate twice daily (n = 392). Mean change from baseline IOP and incidence of adverse events. The mean decrease from baseline IOP during 12-month follow-up was 4.4 to 7.6 mm Hg with fixed brimonidine-timolol, 2.7 to 5.5 mm Hg with brimonidine, and 3.9 to 6.2 mm Hg with timolol. Mean IOP reductions were significantly greater with fixed brimonidine-timolol compared with timolol at all measurements (P< or =.002) and brimonidine at 8 am, 10 am, and 3 pm (P<.001) but not at 5 pm. The incidence of treatment-related adverse events in the fixed-combination group was lower than that in the brimonidine group (P = .006) but higher than that in the timolol group (P<.001). The rate of discontinuation for adverse events was 14.3% with the fixed combination, 30.6% with brimonidine, and 5.1% with timolol. Twice-daily fixed brimonidine-timolol therapy provides sustained IOP lowering superior to monotherapy with either thrice-daily brimonidine or twice-daily timolol and is better tolerated than brimonidine but less well tolerated than timolol. Fixed brimonidine-timolol is an effective and convenient IOP-lowering therapy.

Vascular Endothelial Growth Factor Is a Critical Stimulus for Diabetic Macular Edema

The role of vascular endothelial growth factor (VEGF) in diabetic macular edema (DME) was tested with ranibizumab, a specific antagonist of VEGF. A nonrandomized clinical trial. Ten patients with chronic DME received intraocular injections of 0.5 mg of ranibizumab at baseline and at one, two, four, and six months. The primary outcome was change in foveal thickness between baseline and seven months, and the secondary outcome measures were changes from baseline in visual acuity and macular volume. Mean values at baseline were 503 microm for foveal thickness, 9.22 mm3 for macular volume, and 28.1 letters (20/80) read on an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. At seven months (one month after the fifth injection), the mean foveal thickness was 257 microm, which was a reduction of 246 microm (85% of the excess foveal thickness present at baseline; P = .005 by Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab rather than chance). The macular volume was 7.47 mm3, which was a reduction of 1.75 mm3 (77% of the excess macular volume at baseline; P = .009). Mean visual acuity was 40.4 letters (20/40), which was an improvement of 12.3 letters (P = .005). The injections were well-tolerated with no ocular or systemic adverse events. Intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in 10 patients with DME, which demonstrated that VEGF is an important therapeutic target for DME. A randomized, controlled, double-masked trial is needed to test whether intraocular injections of ranibizumab provide long-term benefit to patients with DME.

Interconceptional Antibiotics to Prevent Spontaneous Preterm Birth: A Randomized Clinical Trial

A large number of very early spontaneous preterm births are ascribed to bacterial infection of the upper genital tract or chorioamnionitis, without symptoms in either instance. Many believe that ascending infection by bacteria initially present in the cervix and vagina leads to microbial colonization of the chorioamnion and amniotic fluid. This study was an attempt to determine whether antibiotic treatment during the interpregnancy interval in women having a previous preterm birth before 34 weeks gestational age might lower the risk of spontaneous preterm birth in a subsequent pregnancy. A total of 241 women with a history of spontaneous birth before 34 weeks gestational age were randomized, in a double-masked trial, to receive either 2 1-g doses of azithromycin orally 4 days apart plus 750 mg daily of sustained-release metronidazole for 1 week or identical-appearing placebos. The regimen was repeated at 4-month intervals until a subsequent pregnancy began, as was the case for 124 women, 59 of whom received antibiotics. The antibiotic-treated and control women were similar in most respects, but the actively treated women were significantly more compliant in keeping study appointments and taking their assigned medications. Approximately 80% of women in both groups received a course of treatment within 6 months before the subsequent conception. Positive endometrial cultures at the time of randomization were comparably frequent in the antibiotic and placebo groups: 86% and 91%, respectively. Median numbers of individual microbial species isolated from the endometrium also did not differ significantly. Plasma cell endometritis was found in 31% of the antibiotic group and 47% of placebo recipients. Repeat endometrial cultures taken 2 weeks later showed a lower number of individual bacterial species in 49% of women given antibiotics and 31% of the control group. There was no apparent difference in the resolution of endometritis. The risk of a subsequent preterm birth did not differ significantly between the 2 groups, and the same was the case for miscarriage before 15 weeks gestation. Although not statistically significant, average gestational age at delivery was 2.4 weeks shorter in the antibiotic group, and average birth weight was 418 g lower than in the placebo group.

Circadian IOP-lowering efficacy of travoprost 0.004% ophthalmic solution compared to latanoprost 0.005%

ABSTRACTPurpose: The primary objective of this study was to determine the intraocular pressure- (IOP) lowering efficacy over two consecutive 24-h periods of travoprost 0.004% ophthalmic solution (Travatan) compared to latanoprost 0.005% (Xalatan) dosed once daily in patients with primary open-angle glaucoma or ocular hypertension.† Travatan is a registered trademark of Alcon Laboratories Inc., Fort Worth, TX, USA‡ Xalatan is a registered trademark of Pfizer Inc., New York, NY, USAMethods: This was a double-masked trial conducted at the Hospital Clínico San Carlos, Madrid, Spain. The primary objective of this study was to determine the IOP lowering efficacy of travoprost and latanoprost. During the eligibility visit, patients’ IOP was measured throughout two consecutive 24‐h periods every 4 h. Patients were then randomized to travoprost or latanoprost (one drop at 8 p.m. daily for 2 weeks). Sixty-two patients were randomized (travoprost n = 32; latanoprost n = 30). IOP was measured at week 2 every 4 h throughout two 24‐h periods. All measurements were taken in both supine and sitting positions with the aid of Perkins applanation tonometry. Limitations of the study include a small sample size (due to the difficulty in recruiting patients in a study of this type) which enrolled only Caucasian patients and a short study duration. However, with 25 subjects per group, there was at least 90% power to detect a mean IOP change from baseline of 2.9 mmHg and 80% power to detect a difference of 2.5 mmHg between treatments.Results: Patients on travoprost therapy showed lower mean IOP levels than those on latanoprost. This difference was statistically significant ( p < 0.05) at 12, 16, 20, 24, 36, 40, and 48 h after the last dose for the supine position. The mean IOPs in the supine position throughout the first and the second 24‐h period of the week 2 visit as well as for the 48‐h visit were statistically lower ( p < 0.05) for the travoprost group. Adverse events were mild and included hyperemia and corneal staining. Travoprost and latanoprost were both well tolerated.Conclusion: Mean IOP values were significantly lower for patients on travoprost for the majority of time points in the supine position.

Comparison of the analgesic efficacy and safety of nepafenac ophthalmic suspension compared with diclofenac ophthalmic solution for ocular pain and photophobia after excimer laser surgery: A phase II, randomized, double-masked trial

Objective: The aim of this study was to evaluate the efficacy and safety of nepafenac ophthalmic suspension 0.03% and 0.1% for the treatment of postoperative pain and photophobia in patients undergoing excimer photoreactive keratectomy (PRK). Methods: In this 7-day, randomized, double-masked, parallel-group trial at 2 sites, patients undergoing PRK surgery were randomly assigned to receive nepafenac ophthalmic suspension 0.03% or 0.1%, or diclofenac sodium ophthalmic solution 0.1%. Patients were treated on day 0 (surgery) and day 1 (the day after surgery). The dose regimen for all 3 treatments was the same. On day 0, patients received 2 drops in the operative eye -1 hour before surgery; 2 drops within 1 hour after surgery; 1 drop -4 hours after the first postoperative dose; and 1 drop -8 hours after the first postoperative dose. On day 1, patients instilled 1 drop of study drug QID. Thereafter, the study medication was discontinued. In the perioperative period, study personnel instilled the drops. The patients instilled the drops when they went home. Patients recorded pain and photophobia from day 0 through day 2, rating pain from 0 to 9 on a visual analog scale (0 = none, 9 = extreme) and photophobia from 0 to 3 on an ordinal, categoric scale (0 = none, 3 = severe). Patients were permitted to take acetaminophen 500 mg as needed for pain. They returned for postoperative follow-up visits on days 1, 3, and 7. Adverse events were documented when reported by the patients themselves, and when study personnel asked about specific events. Results: Sixty patients (20 per group) were enrolled. On the day of surgery, there were no significant differences between groups, except at 3 hours after surgery, when the nepafenac 0.03% group had a significantly higher mean pain score than the nepafenac 0.1% group (4.0 vs 3.0; P < 0.038). On day 2, the nepafenac 0.1% group had less pain at bedtime than the diclofenac group (mean score, 1.9 vs 3.1; P < 0.024) and less photophobia in the morning (mean score, 1.2 vs 1.8; P < 0.023). For the nepafenac 0.03% group, the mean pain and mean photophobia scores were 2.5 and 1.6, respectively. There were no significant differences between the 3 treatment groups in the proportion of patients who took acetaminophen for pain at any time point ( P = NS). There was no statistically significant difference in corneal re-epithelialization rates among the 3 groups. Adverse events were infrequent, and no serious adverse events occurred. Two ocular adverse events related to therapy occurred: a corneal infiltrate in 1 patient in the nepafenac 0.03% group; and ocular discomfort in 1 patient in the nepafenac 0.1% group. Both patients continued the study. Conclusions: Both nepafenac 0.03% and 0.1% were effective for treatment of pain and photophobia in these patients undergoing PRK surgery. There was no difference in the proportion of patients who took rescue acetaminophen for pain. All treatments were well tolerated in these patients.

The effect of conjugated equine oestrogen on diabetes incidence: the Women’s Health Initiative randomised trial

Recent clinical trials have found that the combination of conjugated equine oestrogen (CEO) and medroxyprogesterone has a protective effect on the incidence of type 2 diabetes. To determine the effect of CEO alone on the incidence of diabetes mellitus in postmenopausal women, we analysed the results of the Women's Health Initiative oestrogen-alone trial. The Women's Health Initiative is a randomised, double-masked trial comparing the effect of daily 0.625 mg CEO with placebo during 7.1 years of follow-up of 10,739 postmenopausal women who were aged 50-79 years and had previously had a hysterectomy. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin and lipoproteins were measured in an 8.6% random sample of study participants, at baseline and at 1, 3 and 6 years. The cumulative incidence of treated diabetes was 8.3% in the oestrogen-alone group and 9.3% in the placebo group (hazard ratio 0.88, 95% CI 0.77-1.01, p=0.072). During the first year of follow-up, a significant fall in insulin resistance (homeostasis model assessment of insulin resistance) in actively treated women compared with the control subjects (Year 1 baseline between-group difference -0.53) was seen. However, there was no difference in insulin resistance at the 3- or 6-year follow-up. Postmenopausal therapy with oestrogen alone may reduce the incidence of treated diabetes. The effect is smaller than that seen with oestrogen plus progestin. CEO should not, however, be used with the intention of preventing diabetes, as its well-described adverse effects preclude long-term use for primary prevention.

Iron and folic acid supplementation and malaria risk

This weeks Lancet reports on studies by Sunil Sazawal and James Tielsch and their respective colleagues that are important to the international public-health community. The parallel studies done in Pemba Tanzania and Nepal recruited children aged less than 3 years to carefully designed cluster-randomised double-masked intervention trials. Enrolled children received carefully supervised at-home supplementation with iron plus folic acid zinc iron plus folic acid plus zinc or placebo in a factorial design and were followed up for an average of about a year. The data from each site are from three of the four arms of the trials with results describing the effect of zinc awaited. The studies aimed to provide definitive evidence on the risks or benefits of these interventions in settings where iron deficiency is common and child mortality largely attributable to infectious diseases is high. A key difference between the two settings however is mortality risk from malaria. WHO currently recommends routine supplementation with haematinics for children in such settings. (excerpt)

A Phase II Randomized Double-Masked Trial of Pegaptanib, an Anti-Vascular Endothelial Growth Factor Aptamer, for Diabetic Macular Edema

A Phase II Randomized Double-Masked Trial of Pegaptanib, an Anti-Vascular Endothelial Growth Factor Aptamer, for Diabetic Macular Edema