Efficacy of topical cyclosporin 0.05% in the treatment of posterior blepharitis. A comparative study of eyelid cleaning regimens in chronic blepharitis. The efficacy of topical metronidazole in the treatment of ocular rosacea. [Bibrocathol eye ointment is efficacious in blepharitis. Results from a randomized, double-blind, controlled clinical trial]. Treatment of blepharitis and blepharoconjunctivitis: comparison of gentamicin-betamethasone, gentamicin alone and placebo. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. N-acetylcysteine in chronic blepharitis. Topical ciprofloxacin in the treatment of blepharitis and blepharoconjunctivitis. Efficacy of topical N-acetylcysteine in the treatment of meibomian gland dysfunction. Educational strategies to promote evidence-based community pharmacy practice: a cluster randomized controlled trial (RCT). Prophylaxis with GM-CSF mouthwashes does not reduce frequency and duration of severe oral mucositis in patients with solid tumors undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue: a double blind, randomized, placebo-controlled study. Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea. Fluticasone propionate spray and betamethasone sodium phosphate mouthrinse: a randomized crossover study for the treatment of symptomatic oral lichen planus. Efficacy and safety of mercuric oxide in the treatment of bacterial blepharitis. Effectiveness of feedback for improving case management of malaria, diarrhoea and pneumonia--a randomized controlled trial at provincial hospitals in Lao PDR. A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A beta-haemolytic streptococci. Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis. The value of a pilot study in breast-feeding research. A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain. The treatment of acute infectious conjunctivitis with fusidic acid: a randomised controlled trial. Mouth-washings with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) do not improve grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized double-blind placebo-controlled study. Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis. Discrepancy between results and abstract conclusions in industry- vs nonindustry-funded studies comparing topical prostaglandins. [Transdermal nitroglycerin versus corticosteroid infiltration for rotator cuff tendinitis]. Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Health education and antibiotic therapy in trachoma control. Treatment of chronic staphylococcal blepharoconjunctivitis with a new topical steroid anti-infective ophthalmic solution. Secular changes in the quality of published randomized clinical trials in rheumatology.
We assessed the efficacy of topical cyclosporin 0.05% ophthalmic emulsion versus tobramycin 0.3%/dexamethasone 0.1% in patients with posterior blepharitis. Posterior blepharitis improved significantly from the initial study visit with both cyclosporin treatment and tobramycin/dexamethasone. Cyclosporin provided greater improvements in Schirmer's scores (P < 0.001) and tear break-up time (P = 0.018) than tobramycin/dexamethasone after 12 weeks of treatment. Eyelid health also improved in both groups, but the mean improvement in meibomian gland secretion quality was significantly greater with cyclosporin than with tobramycin/dexamethasone (P = 0.015). Moreover, a higher percentage of patients in the cyclosporin treatment group had improvements in symptoms of blurred vision, burning, and itching and more cyclosporin-treated patients experienced resolution of lid telangiectasia. The findings in this prospective study suggest that posterior blepharitis can be more effectively treated with cyclosporin than with tobramycin/dexamethasone. These findings should be further evaluated in large-scale, controlled, clinical trials. Blepharitis, an intrinsic eyelid inflammation with crusting and irritation, presents a great problem for patients wearing contact lenses. An important part of blepharitis therapy is eyelid hygiene, including the use of either soap, dilute baby shampoo, or commercial lid scrubs. In this study, a comparison was made between these three cleaning regimens in a group of 25 patients, 80% of whom (20/25) wore contact lenses.
                Patients used commercial eyelid scrub on right eyelids and a hypo-allergenic bar soap on left eyelids. Patient symptoms, slit lamp findings, and overall preferences were determined at the end of 4 months. A subgroup of 10 patients using lid scrub on right eyelids and dilute baby shampoo on left eyelids was followed for an additional 3 months.
                At the end of 4 months, 24% (6/25) of the patients noted no difference between soap and lid scrub, but 89% (17/19) of the others preferred the lid scrub. In the group using baby shampoo, 50% (5/10) noted no difference in 3 months, but 80% (4/5) of the remaining patients preferred the lid scrub.
                All patients improved in slit lamp findings with all three regimens, and patient preference was overwhelmingly in favor of the lid scrub regimen for convenience and ease of use. The purpose of the study is to investigate the efficacy of metronidazole topical gel in the treatment of ocular rosacea.
                Ten patients with ocular rosacea were treated prospectively with lid hygiene and topical metronidazole applied to the lid margin in one eye and lid hygiene alone in the fellow eye. The treatment period was 12 weeks. A masked observer graded the ocular findings at the initial visit and at the conclusion of the treatment period. Pretreatment scores were compared with post-treatment scores with respect to ocular surface, eyelid margin, and combined eyelid plus ocular surface.
                Eight of ten treated eyes improved, whereas only five of ten control eyes improved. There was a statistically significant improvement in the eyelid score in both the treated and control groups (P = 0.003, P = 0.025, respectively), but no significant improvement in the ocular surface score in either group. When the pretreatment and post-treatment eyelid and ocular surface scores were combined, there was a significant improvement in the treated eyes but not in the control eyes (P = 0.022, P = 0.10, respectively). No adverse effects of the metronidazole treatment were encountered in this study.
                Metronidazole topical gel may be a safe and effective means of treating rosacea blepharitis. Bibrocathol (Noviform) 5% ointment is a frequently used therapy for blepharitis. The study included 197 patients who were randomized to be treated over 2 weeks with bibrocathol or an ointment vehicle, respectively. Slit lamp examinations were performed on day 1 (baseline) and day 14 (end of study) to assess lid edema, lid erythema, debris, and pouting of Meibomian glands; patients rated their subjective complaints. Bibrocathol was superior to the control treatment in improving the sum score of the 5 scales (by 7.0 vs 4.7 points, p<0.001), especially in patients with primarily severe symptoms (by 8.3 vs 4.8, p<0.0001). Antiseptic therapy with bibrocathol eye ointment 3 times daily over 2 weeks was found to be efficacious in the treatment of acute forms of blepharitis which do not require antibiotic therapy. Bibrocathol treatment is well tolerated and safe. At two university centres 46 patients presenting with symptomatic infective blepharitis or blepharoconjunctivitis participated in a double-blind study of a new antibiotic-steroid ointment containing gentamicin and betamethasone. There was no significant difference in response to 2 weeks of therapy between the patients treated with this ointment and those treated with either an ointment containing gentamicin alone or a placebo ointment. There was also no significant correlation between the clinical response and the results of the bacterial cultures of swabs obtained at the beginning and the end of the study. However, the patients treated with the placebo had a much higher rate of recurrence of their symptoms over a 6-week follow-up period. The patients who before treatment had associated rosacea, dry eyes and a long duration of symptoms showed a poor response to therapy. Age is an important prognostic parameter, especially in patients with advanced high-grade non-Hodgkin's lymphoma (HG-NHL) who require more intensive and extensive therapy for any possible chance of cure. We investigated the potential of granulocyte colony-stimulating factor (G-CSF) for reducing myelotoxicity, which is the most important dose-limiting factor for chemotherapy. Between March 1993 and June 1995, 158 previously untreated patients 60 years and older with HG-NHL were included in a cooperative randomized comparative trial and treated with a combination therapy including VNCOP-B (cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone) with or without G-CSF. G-CSF was administered at 5 microg/kg/d throughout the treatment starting on day 3 of every week for 5 consecutive days. Of the 158 patients registered for the trial, 149 patients were evaluable: 77 received VNCOP-B plus G-CSF and 72 received VNCOP-B alone. The overall response rate was 81.5%, with complete response in 59%: 60% in the VNCOP-B plus G-CSF group, and 58% in the VNCOP-B group. At 30 months (median 24 months), 68% of all complete responders were alive without disease in the G-CSF group and 65% in the control group. Neutropenia occurred in 18 out of 77 (23%) of the G-CSF treated patients and in 40 out of 72 (55.5%) of the controls (P = .00005). Clinically relevant infections occurred in 4 out of 77 (5%) of the G-CSF group and in 15 out of 72 (21%) of the controls (P = .004). The delivered dose intensity was higher in patients receiving G-CSF (95% v 85%), but the difference was not statistically significant. Our data show that VNCOP-B is a feasible and effective regimen in elderly HG-NHL patients, and that the use of G-CSF reduces infection and neutropenia rates without producing any significant modifications to the dose intensity, CR rate, and relapse-free survival curve. To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD).
                Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients.
                The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16.
                A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group.
                Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks. To report interim outcome data, using all available follow-up through 5 years after treatment initiation, in the Collaborative Initial Glaucoma Treatment Study (CIGTS).
                Randomized clinical trial.
                Six hundred seven newly diagnosed glaucoma patients.
                In a randomized clinical trial, 607 patients with newly diagnosed open-angle glaucoma were initially treated with either medication or trabeculectomy (with or without 5-fluorouracil). After treatment onset and early follow-up, patients were evaluated clinically at 6-month intervals. In addition, quality of life telephone interviews were conducted at similar frequency to the clinical visits. Patients in both arms of CIGTS were treated aggressively in an effort to reduce intraocular pressure (IOP) to a level at or below a predetermined target pressure specific for each individual eye. Visual field (VF) scores were analyzed by time-specific comparisons and by repeated measures models.
                VF loss was the primary outcome variable in CIGTS. Secondary outcomes of visual acuity (VA), IOP, and cataract were also studied.
                On the basis of completed follow-up through 4 years and partially completed through 5 years, VF loss did not differ significantly by initial treatment. Over the entire period of follow-up, surgical patients had a greater risk of substantial VA loss compared with medical patients. However, by 4 years after treatment, the average VA in the two groups was about equal. Over the course of follow-up, IOP in the medicine group has averaged 17 to 18 mmHg, whereas that in the surgery group averaged 14 to 15 mmHg. The rate of cataract requiring removal was greater in the surgically treated group.
                Both initial medical or initial surgical therapy result in about the same VF outcome after up to 5 years of follow-up. VA loss was greater in the surgery group, but the differences between groups seem to be converging as follow-up continues. When aggressive treatment aimed at substantial reduction in IOP from baseline is used, loss of VF can be seen to be minimal in general. Because 4 to 5 years of follow-up in a chronic disease is not adequate to draw treatment conclusions, these interim CIGTS outcomes do not support altering current treatment approaches to open-angle glaucoma. To investigate the effects of N-acetylcysteine (NAC) in chronic posterior blepharitis.
                This was a prospective randomized, controlled study that included 79 eyes of 40 patients with chronic posterior blepharitis. Routine ophthalmologic examination, Schirmer-1 test, fluorescein break-up time (FBUT), and mucous fern tests were carried out during the first visit of all patients. A topical steroid, topical antibiotic, and artificial tears were started in 36 eyes of 18 patients. The therapy group (43 eyes of 22 patients) was administered three daily doses of 100 mg oral NAC. All patients were examined weekly for 1 to 4 months (average, 24 +/- 0.7). A Schirmer-1 test and FBUT were administered at every visit, but mucous fern tests were administered every two weeks. The results of the first and last Schirmer-1 tests, FBUT, and mucous fern test were compared between the therapy and control groups. Student's t and Mann-Whitney U tests were used for statistical analysis.
                FBUT was significantly increased (p < 0.0001), and the mucous fern pattern was also significantly improved (p = 0.0096) in the therapy group.
                NAC is thought to increase FBUT and improve mucous fern pattern by blocking lipid peroxidation in chronic blepharitis. An international multicentre study assessed the clinical and antibacterial efficacy of a new topical ophthalmic formulation of the quinolone antimicrobial agent ciprofloxacin and compared it with that of tobramycin ophthalmic solution in patients with blepharitis and blepharoconjunctivitis. The study consisted of a randomised double-masked between-group evaluation of 464 patients, 230 of whom were treated with ciprofloxacin and 234 with tobramycin. There was qualitative and quantitative bacteriology, and clinical assessment of ocular symptoms and signs before and after a seven-day course of treatment. Bacteriological cultures demonstrated eradication or reduction of potentially pathogenic bacteria in 93.7% of eyes (ciprofloxacin) versus 88.9% of eyes (tobramycin), seven days after starting treatment. Clinically more than 80% of patients in both treatment groups were cured or improved after seven days. No statistically significant differences were observed between the two treatment groups. No serious side-effects were observed after use of either antimicrobial agent. Ciprofloxacin ophthalmic solution appears safe and effective. The spectrum of activity and clinical efficacy of this new formulation are discussed in comparison with currently used antimicrobial agents. To evaluate the efficacy of topical N-acetyl-cysteine (NAC) therapy in patients with meibomian gland dysfunction (MGD).
                Twenty patients with MGD were prospectively randomized and assigned into 2 groups. The patients were instructed to use either NAC 5% or preservative-free artificial tear topically 4 times a day for a month. All patients were instructed to apply lid hygiene once daily. Preservative-free artificial tears treated group served as control. Paired sample Student's t-tests were used to detect differences between the baseline and 1 month after treatment initiation in mean ocular symptoms, fluorescein break-up time (FBUT) values, and Schirmer scores in each group. Difference in mean ocular symptoms, Schirmer's test scores, and FBUT values between the baseline and 1 month after treatment initiation were compared between the groups using Mann-Whitney U test.
                One month of topical NAC therapy provided statistically significant improvements in FBUT and Schirmer scores as compared with the initial study visit. The average Schirmer increase rate was significantly better in the NAC group than in the control group. Significant improvements for the symptoms of ocular burning, foreign body sensation, and intermittent filmy or blurred vision were noted in both groups; and only NAC-treated group showed improvement for the symptom of itching, at 1 month as compared with 1 day. NAC provided significantly better improvement in itching symptom when compared with controls.
                Topical administration of NAC is thought to be effective and well tolerated in patients with MGD. Community pharmacists have increasing involvement in the self-management of minor illness as a result of the availability of a wider range of over-the-counter (OTC) medicines. We undertook a randomized controlled trial (RCT) to assess the effectiveness and efficiency of educational strategies to implement evidence-based guidelines for the sale of OTC anti-fungals in the community pharmacy setting.
                The aim of the study was to compare the effectiveness and efficiency of two guideline dissemination strategies in community pharmacy settings.
                A 2 x 2 factorial, cluster RCT was conducted with 60 community pharmacies in the Grampian region of Scotland. The interventions included dissemination of an evidence-based guideline for OTC management of vulvovaginal candidiasis (thrush) by postal dissemination (control), educational outreach visit or attendance at a continuing professional education session. Pre- and post-intervention simulated patient visits were made to participating pharmacies. The simulated patients completed assessment forms following each visit. The primary outcome was the appropriateness (based upon the guidelines) of sale or no sale of OTC anti-fungals.
                There were no significant differences in the proportion of appropriate outcomes following educational outreach [odds ratio (OR) = 1.1; 95% confidence interval (CI) 0.52 to 2.45] or continuing professional education (OR = 0.88; 95% CI 0.41 to 1.91).
                Neither strategy was effective in improving the appropriateness of OTC management of vulvovaginal candidiasis by community pharmacy staff. Further research is needed to identify barriers to guideline implementation and evidence-based practice in this setting. The aim of this study was to evaluate the effectiveness of granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwashes in the prevention of severe mucositis induced by high doses of chemotherapy.
                Ninety consecutive patients affected by solid tumors and undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation rescue were randomized to receive placebo versus GM-CSF mouthwash 150 micro g/day. Patients were stratified on the basis of the conditioning treatment and the consequent different risk of severe oral mucositis. Treatment was administered from the day after the end of chemotherapy until the resolution of stomatitis and/or neutrophil recovery.
                The statistical analyses were intention-to-treat and involved all patients who entered the study. The severity of stomatitis was evaluated daily by the physicians according to National Cancer Institute Common Toxicity Criteria. Both study and control groups were compared with respect to the frequency [30% versus 36%, chi(2) exact test, not significant (NS)] and mean duration (4.8 +/- 4.7 versus 4.4 +/- 2.7 days, t-test, NS) of severe stomatitis (grade > or =3). Oral pain was evaluated daily by patients themselves by means of a 10 cm analog visual scale: the mean (+/- standard error of the mean) maximum mucositis scores were 4.8 +/- 3.5 versus 4.2 +/- 3.5 cm (t-test, NS). Furthermore, 15/46 patients in the study group (33%) and 19/44 patients in the control group experienced pain requiring opioids (chi(2) exact test, NS).
                We did not find any evidence to indicate that prophylaxis with GM-CSF mouthwash can help to reduce the severity of mucositis in the setting of the patients we studied. A prospective, randomised, double blind, partial crossover, placebo controlled trial has been conducted to compare the performance of topical fusidic acid gel (Fucithalmic) and oral oxytetracycline as treatment for symptomatic chronic blepharitis. Treatment success was judged both by a reduction in symptoms and clinical examination before and after therapy. Seventy five per cent of patients with blepharitis and associated rosacea were symptomatically improved by fusidic acid gel and 50% by oxytetracycline, but fewer (35%) appeared to benefit from the combination. Patients with chronic blepharitis of other aetiologies did not respond to fusidic acid gel but 25% did benefit from oxytetracycline and 30% from the combination. Our results demonstrate the need to investigate patients with blepharitis for concomitant rosacea as they respond well to targeted therapy. Symptomatic oral lichen planus (OLP) has been palliated with a wide spectrum of topical and systemic therapies. Although the majority of management strategies include corticosteroids, few have been evaluated in randomized controlled trials.
                We investigated the acceptability and efficacy of topical fluticasone propionate spray (FP) and betamethasone sodium phosphate mouthrinse (BSP) upon the signs and symptoms of OLP, assessing patient quality of life changes as a consequence of these therapies.
                We implemented a randomized, crossover study in which each drug was administered for a period of 6 weeks with an intervening washout period of 2 weeks at an outpatient oral medicine unit in London, United Kingdom. We treated 48 patients with biopsy-proven symptomatic OLP, and 44 patients (92%) completed the study. The dosage was 50 microg two dose unit sprays and BSP 500 microg, each 4 times daily. Symptomatic improvement was evaluated by means of a visual analogue scale (VAS), the McGill pain score, the Oral Health Impact Profile (OHIP), and Oral Health Quality of Life (OHQoL) questionnaires. The total surface area of the lesions, including all white, erythematous, and ulcerative lesions was measured at each visit. The efficacy, ease of application, and adverse effects associated with each medication were recorded.
                Both FP and BSP mouthwash caused both a statistically significant reduction in painful symptoms as measured by the VAS and improvement in quality of life as measured by the OHIP and OHoQL indices. There was no significant difference between the two corticosteroids in their efficacy in reducing painful symptoms (measured by the VAS) or in their effect on patient quality of life. Both FP and BSP significantly reduced the surface area of oral lesions. However, FP was statistically significantly better than BSP in reducing lesion surface area. There was no statistically significant difference between the patient-assessed effects of the 2 therapies.
                FP and BSP are both effective in the short-term clinical management of symptomatic OLP. FP is more acceptable to patients than BSP because of the convenience of the spray form. A double-masked, placebo-controlled, randomized study was done to assess the safety and clinical and quantitative microbiologic efficacy of 1% mercuric oxide (yellow) ophthalmic ointment in the treatment of eyelid infections, i.e., bacterial blepharitis. A total of 39 patients with bacterial counts and clinical signs indicative of eyelid infection were treated twice daily for 7 days. Clinical biomicroscopic examination and quantitative microbiologic cultures were done just prior to initiation of treatment and again on days 3 and 7. Statistical analysis revealed a significant improvement in the clinical signs, bacterial count, cure rate, and improvement rate for subjects taking the active medication, compared with those taking the placebo on days 3 and 7. In addition, the medication was well tolerated. Standard Treatment Guidelines were introduced to all prescribers at provincial hospitals in Lao PDR and treatment indicators were developed within the National Drug Policy programme to monitor compliance.
                To evaluate the effects of an educational intervention to improve treatment practices of malaria, diarrhoea and pneumonia.
                Randomized controlled trial with prescribers at 24 departments at eight provincial hospitals, matched into four pairs. The three departments of internal medicine, paediatrics and out-patients in each pair were randomized into intervention or control group. The 6-month intervention was conducted by members of the Drug and Therapeutics Committees, and comprised monthly audit sessions in the form of outcome feedback using indicator scores on recorded treatment of malaria, diarrhoea and pneumonia. We measured treatment indicator scores 6 months after the end of the intervention compared with baseline.
                The aggregated mean scores for all diseases, and for malaria and diarrhoea, improved significantly. For pneumonia, improvement was seen in both the intervention and control groups. Record keeping was improved for all three diseases. For malaria, there were improvements in recording patients' history, and in frequency of microscope testing; for diarrhoea, regarding weight measurements, palpation of the fontanel for children under 2 years, and reduction of irrational use of anti-diarrhoeals and antibiotics; for pneumonia, in recording respiratory count, and reducing irrational use of anti-histamines and anti-cough medications.
                Audit-feedback systems to improve quality of care are feasible and effective also in hospital settings in low-income countries. A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS) Azithromycin, a broad-spectrum antibiotic with potent anti-inflammatory activities, has the potential to effectively treat blepharitis, an inflammatory disease of the eyelid with abnormal eyelid flora as an etiologic determinant. The present study compared the efficacy of topical azithromycin ophthalmic solution 1% (AzaSite; Inspire Pharmaceuticals, Inc, NC, USA) combined with warm compresses (azithromycin group) to warm compresses alone (compress group) in patients with posterior blepharitis.
                Twenty-one patients diagnosed with posterior blepharitis were randomized in an open-label study to receive either azithromycin plus warm compresses (10 patients), or compresses alone (11 patients). All patients were instructed to apply compresses to each eye for 5-10 minutes twice daily for 14 days. Each eye in the azithromycin group also received azithromycin solution (1 drop) twice daily for the first 2 days followed by once daily for the next 12 days. Patients were evaluated at study initiation (visit 1) and at end of treatment (visit 2) for the severity of five clinical signs: eyelid debris, eyelid redness, eyelid swelling, meibomian gland (MG) plugging, and the quality of MG secretion. At visit 2, patients also rated their degree of overall symptomatic relief.
                Twenty patients completed the study. At visit 2, patients in the azithromycin group demonstrated significant improvements in MG plugging, MG secretions, and eyelid redness as compared with the compress group. In the azithromycin group, MG plugging resolved completely in three patients and MG secretion returned to normal in two patients; no such results were seen in the compress group. Furthermore, a higher percentage of patients in the azithromycin group rated overall symptomatic relief as excellent or good. Visual acuity measurements and biomicroscopic evaluation revealed no ocular safety issues.
                Azithromycin ophthalmic solution in combination with warm compresses provided a significantly greater clinical benefit than warm compresses alone in treating the signs and symptoms of posterior blepharitis. To test the integrity of a protocol for a randomised controlled trial (RCT) to examine the effectiveness of skin-to-skin care compared to routine care on the initiation and duration of breast feeding and to provide data to be used in the power calculation for a proposed trial.
                Randomised pilot study.
                Warrington Hospital, Cheshire, UK.
                Women at 36 weeks' gestation with healthy singleton pregnancies, who intended to breast feed, who had 'booked' for care at Warrington Hospital and had given informed consent to participate. Twenty-eight women were randomised in the pilot study.
                Women were randomly allocated to receive either routine or skin-to-skin care following birth. The first breast feed was assessed using the Breast-feeding Assessment Tool (BAT). Mothers were followed up at discharge from hospital and again at four months to provide details of duration of breast feeding.
                66 women were approached to participate in the trial and 44 consented (67% consent rate). Twenty-eight women were randomised in the study and 26 breast feeds were observed (93%). The pilot study identified procedural changes that were required in the design of the main study, provided an estimate of recruitment rates and confirmed the previously calculated sample size.
                The pilot study demonstrated that a large RCT of skin-to-skin versus routine care was feasible. This is an example of how a pilot study has the ability to identify unforeseen challenges in the conduct of the trial as well as allowing necessary changes to be made to the design that will increase the quality of the subsequent research. Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.
                Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.
                Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.
                This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.
                ClinicalTrials.gov: NCT00566930. Acute infectious conjunctivitis is a common disorder in primary care. Despite a lack of evidence regarding the effectiveness of topical antibiotics for the treatment of acute infectious conjunctivitis, most patients presenting in primary care with the condition receive topical antibiotics. In The Netherlands, fusidic acid is most frequently prescribed.
                To assess the effectiveness of fusidic acid gel compared to placebo for acute infectious conjunctivitis.
                Double-blind randomised placebo-controlled trial.
                Twenty-five Dutch primary care centres.
                Adults presenting with a red eye and either (muco)purulent discharge or glued eyelid(s) were allocated to either one drop of fusidic acid gel 1% or placebo, four times daily during one week. The main outcome measure was the difference in recovery rates at 7 days. Secondary outcome measures were difference in bacterial eradication rates, a survival time analysis of the duration of symptoms, and the difference in recovery rates in culture-positive and culture-negative patients.
                One hundred and eighty-one patients were randomised and 163 patients were analysed. Forty-five of the 73 patients in the treatment and 53 of the 90 patients in the placebo group recovered (adjusted risk difference = 5.3% [95% confidence interval {CI} = -11 to 18]). There was no difference between the median duration of symptoms in the two groups. At baseline, the prevalence of a positive bacterial culture was 32% (58/181). The bacterial eradication rate was 76% in the treatment and 41% in the placebo group (risk difference = 35% [95% CI = 9.3 to 60.4]). In culture positive patients, the treatment effect tended to be strong (adjusted risk difference = 23% [95% CI = -6 to 42]).
                At 7 days, cure rates in the fusidic acid gel and placebo group were similar, but the confidence interval was too wide to clearly demonstrate their equivalence. These findings do not support the current prescription practices of fusidic acid by GPs. We investigated whether daily oral washings with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) solution improved grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Forty-one consecutive patients (21 males and 20 females, median age (range) 44 (16-69) years) were prospectively randomized to perform daily mouth-washes with either a 400 microg rhGM- CSF (Molgramostin, Schering-Plough) solution (group A, n = 18) or with a saline solution (group B, n = 23). Primary end-points were the intensity of OM, night rest quality and characteristics of food intake. Secondary end-points were need for and duration of parenteral nutrition, oral and intravenous analgesic requirements, incidence of viral or fungal oral infections and development of neutropenic fever. No differences were found between the placebo and rhGM-CSF-treated groups regarding overall duration of OM, maximum grade, reduction in at least one grade of OM (nine patients (56%) in group A vs 13 patients (68%) in group B), reduction of spontaneous or swallowing-induced pain, improvement in oral food intake, use of parenteral nutrition or use of systemic analgesics. In conclusion, mouth-washings with a 400 microg of rhGM-CSF solution do not improve severe OM in hematological patients undergoing stem cell transplantation. The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission.
                In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy).
                Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events.
                The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis. To investigate the relationship between industry- vs nonindustry-funded publications comparing the efficacy of topical prostaglandin analogs by evaluating the correspondence between the statistical significance of the publication's main outcome measure and its abstract conclusions.
                Retrospective, observational cohort study.
                English publications comparing the ocular hypotensive efficacy between any or all of latanoprost, travoprost, and bimatoprost were searched from the MEDLINE database. Each article was reviewed by three independent observers and was evaluated for source of funding, study quality, statistically significant main outcome measure, correspondence between results of main outcome measure and abstract conclusion, number of intraocular pressure outcomes compared, and journal impact factor. Funding was determined by published disclosure or, in cases of no documented disclosure, the corresponding author was contacted directly to confirm industry funding. Discrepancies were resolved by consensus. The main outcome measure was correspondence between abstract conclusion and reported statistical significance of the publications' main outcome measure.
                Thirty-nine publications were included, of which 29 were industry funded and 10 were nonindustry funded. The published abstract conclusion was not consistent with the results of the main outcome measure in 18 (62%) of 29 of the industry-funded studies compared with zero (0%) of 10 of the nonindustry-funded studies (P = .0006). Twenty-six (90%) of the industry-funded studies had proindustry abstract conclusions.
                Twenty-four percent of the industry-funded publications had a statistically significant main outcome measure; however, 90% of the industry-funded studies had proindustry abstract conclusions. Both readers and reviewers should scrutinize publications carefully to ensure that data support the authors' conclusions. To compare transdermal nitroglycerin (NTG) and corticosteroid infiltration in patients with rotator cuff tendinitis (RCT).
                Experimental, randomized controlled study.
                Semirural basic health area in the Garraf region of Barcelona province, Spain, with a population of public health service users of 12000.
                Patients diagnosed as having RCT of less than 6 weeks' evolution who had not responded to treatment with oral nonsteroid antiinflammatory drugs. The patients were distributed randomly into two groups: a) group A, local infiltration via a posterior approach with a depot corticosteroid and local anesthesia, and b) group B, treated for 3 days with a 5-mg NTC patch.
                Age, sex, pain (measured with an analog visual scale) and adverse events. In patients who showed a partial response, treatment was repeated up to 3 times at 15-day intervals. Pain was tested after 7-10 days of treatment. Complete improvement was considered a reduction in pain of more than 5 points on the analog visual scale; partial improvement was considered a reduction of 3-5 points, and treatment failure was recorded when there was no improvement in pain or when there was a decrease of less than 3 points.
                A total of 48 patients were included; 33 (69%) were women and 15 (31%) were men. Mean age was 61 years. In group A, complete improvement was seen in 19 patients and partial improvement in 3; treatment failed in 2 patients. In group B complete improvement was seen in 5 patients, partial improvement in 5, and failure of treatment in 14. The difference between groups was statistically significant. Adverse events were mild pain at the injection site in 4 patients from group A, and headache in 15 patients from group B, 8 of whom abandoned treatment for this reason.
                Treatment with NTG is not a clear alternative to infiltration of corticosteroids in patients with RCT, because of its lack of effectiveness and because of the greater number of patients who had adverse events that lead them to abandon treatment. To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF).
                We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained.
                Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers.
                True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/ infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%.
                This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program. The objective of this study was to confirm whether the combination of a health education programme with a mass treatment campaign was able to improve the effectiveness of trachoma control. An open controlled clinical trial with a 2 x 2 factorial design was carried out. Four villages, matched for size and epidemiological, economic and social conditions, were included in the study. The first village received mass treatment with 1% oxytetracycline eye drops combined with a specific health education programme. The second village received only a health education programme. The third village received only mass treatment and the fourth village did not receive any intervention during the study (control village). 1810 subjects were enrolled of whom 76% were successfully followed for 6 months. The incidence of new cases ranged between 1.6% and 14.2%. In this study the combination of a health education programme with mass treatment failed to increase the cure rate. There was even a negative interaction (P = 0.03). The best results were obtained in the village where antibiotic treatment was used alone, both in terms of cure rate (82%) and reduction of C trachomatis transmission. These results suggest that the addition of a health education programme does not systematically improve the performances of a mass treatment campaign. The efficacy of this combination depends essentially on the capacity of the community to modify its hygiene behaviour. Gentamicin sulfate and betamethasone phosphate were combined in solution form for topical ophthalmic use in patients with chronic staphylococcal blepharoconjunctivitis. The study involved 79 patients and was a two-week double-blind placebo controlled trial comparing the combination with its individual components and placebo. Lid cultures showed that the combination and gentamicin were significantly superior to placebo or betamethasone in freeing the lids of staphylococcus. In addition, the patients treated with either the combination or betamethasone showed greater improvement in the total objective signs than those patients treated with either gentamicin or placebo at the first follow-up visit. No drug-related adverse reactions occurred in the combination treatment group. To assess the quality of published randomized clinical trials (RCTs) in rheumatology and to determine whether there has been improvement in quality between 2 time periods, 1987-1988 and 1997-1998.
                Using MEDLINE and a hand search of selected rheumatology journals, we identified RCTs of adult rheumatic diseases published in English in 1987-1988 or 1997-1998. We examined trial quality with an expanded version of the Jadad scale, which assesses the adequacy of reported random sequence generation, allocation concealment, blinding, and analysis. All trials were read by 1 reviewer, with prior standardization using a random sample read by 2 reviewers. We also evaluated "high"- versus "low"-impact journals based on citation index.
                Two hundred forty RCTs (1987-1988 119 RCTs, 1997-1998 121 RCTs) were assessed. Results showed improvement in the quality of the trials, but the rates of reported random sequence generation, allocation concealment, power, and intent-to-treat analyses were persistently low. Low rates of reports of random sequence generation, allocation concealment, and intent-to-treat analyses were present even in the high-impact journals.
                There has been improvement in the quality of reporting of RCTs in rheumatology between 1987-1988 and 1997-1998. However, methodologic problems such as lack of allocation concealment, inadequate random sequence generation, lack of reporting of power, and lack of intent-to-treat analyses remain common. Many of these problems are established sources of bias in RCTs and are easily rectifiable.
Despite identifying 34 trials related to treatments for blepharitis, there is no strong evidence for any of the treatments in terms of curing chronic blepharitis. Commercial products are marketed to consumers and prescribed to patients without substantial evidence of effectiveness. Further research is needed to evaluate the effectiveness of such treatments. Any RCT designed for this purpose should separate participants by type of condition (e.g. staphylococcal blepharitis or MGD) in order to minimize imbalances between groups (type I errors) and to achieve statistical power for analyses (prevent type II errors). Medical interventions and commercial products should be compared with conventional lid hygiene measures, such as warm compresses and eyelid margin washing, to determine effectiveness, as well as head-to-head to show comparative effectiveness between treatments. Outcomes of interest should be patient-centered and measured using validated questionnaires or scales. It is important that participants be followed long-term, at least one year, to assess chronic outcomes properly.