An open-label study examining the effect of pharmacological treatment on mannitol- and exercise-induced airway hyperresponsiveness in asthmatic children and adolescents with exercise-induced bronchoconstriction.

BACKGROUND: Mannitol- and exercise bronchial provocation tests are both used to diagnose exercise-induced bronchoconstriction. The study aim was to compare the short-term treatment response to budesonide and montelukast on airway hyperresponsiveness to mannitol challenge test and to exercise challenge test in children and adolescents with exercise-induced bronchoconstriction. METHODS: Patients were recruited from a paediatric asthma rehabilitation clinic located in the Swiss Alps. Individuals with exercise-induced bronchoconstriction and a positive result in the exercise challenge test underwent mannitol challenge test on day 0. All subjects then received a treatment with 400 µg budesonide and bronchodilators as needed for 7 days, after which exercise- and mannitol-challenge tests were repeated (day 7). Montelukast was then added to the previous treatment and both tests were repeated again after 7 days (day 14). RESULTS: Of 26 children and adolescents with exercise-induced bronchoconstriction, 14 had a positive exercise challenge test at baseline and were included in the intervention study. Seven of 14 (50%) also had a positive mannitol challenge test. There was a strong correlation between airway responsiveness to exercise and to mannitol at baseline (r = 0.560, p = 0.037). Treatment with budesonide and montelukast decreased airway hyperresponsiveness to exercise challenge test and to a lesser degree to mannitol challenge test. The fall in forced expiratory volume in one second during exercise challenge test was 21.7% on day 0 compared to 6.7% on day 14 (p = 0.001) and the mannitol challenge test dose response ratio was 0.036%/mg on day 0 compared to 0.013%/mg on day 14 (p = 0.067). CONCLUSION: Short-term treatment with an inhaled corticosteroid and an additional leukotriene receptor antagonist in children and adolescents with exercise-induced bronchoconstriction decreases airway hyperresponsiveness to exercise and to mannitol.

Two-stage designs applying methods differing in costs.

MOTIVATION: Two-stage pilot and integrated designs are powerful tools for investigating large numbers of hypotheses. Asymptotically, optimal two-stage designs controlling the familywise error or false discovery rate are considered when costs and effect sizes per measurement differ between stages and total costs are constrained. RESULTS: Depending on the cost and effect size ratios between the measurements, it is generally more powerful to apply two-stage procedures using one measurement method at both stages. For the practically relevant case that the same method is applied at both stages but designing the second-stage measurements raises extra costs, two-stage designs are more powerful than the single-stage design even for large costs ratios. The power of the optimal pilot and integrated two-stage designs generally are similar, however, the integrated approach is less sensitive even to severe design misspecifications in the planning phase. AVAILABILITY: R-programs (R, 2005) to calculate asymptotically optimal designs are available on: http://statistics.msi.meduniwien.ac.at/index.php?page=ao2stage

A comparison of two different treatments with navigated extracorporeal shock-wave therapy for calcifying tendinitis - a randomized controlled trial.

BACKGROUND: Extracorporeal shock-wave therapy is recommended for calcifying tendinitis, and navigated low-energy therapy has given better results than biofeedback localization. This investigation was planned to analyze whether the outcome of navigated low-energy shock-wave therapy can be improved by raising energy flux density to middle-energy levels. The clinical and radiological differences in outcome between three sessions of low-energy navigated shock-wave therapy and two sessions of middle-energy therapy were therefore compared. PATIENTS, MATERIALS AND METHODS: A prospective, randomized, observer-blind study was carried out in 50 patients whose mean age was 51 years. The population was randomized into two groups. Pain refractory to therapy was evident for more than six months in all patients. Radiographs and clinical examinations, including the Constant and Murley score, and the visual analog scale for pain assessment were performed before therapy and then after 12 weeks. Both groups of patients received navigated and X-ray-assisted, focused shock-wave treatment at weekly intervals. Group I underwent three sessions of constant low-energy treatment (0.08 mJ/mm(2); 1000 impulses) without local anesthesia; Group II received two middle-energy treatments (0.2 mJ/mm(2); 2000 impulses) with subacromial anesthesia. RESULTS: Forty-four patients (21 in Group I, 23 in Group II) completed the study protocol. Clinically, both groups improved significantly (P<0.0001) in the Constant and Murley score and the visual analog scale. The statistics within the groups were not significantly different. Overall, nine calcium deposits disappeared and 12 changed massively in shape and radiological density. CONCLUSIONS: Navigated shock-wave therapy significantly improves pain and shoulder function. Patients obtained nearly equal results after three low-energy or two middle-energy sessions of shock-wave treatment. We therefore recommend two sessions of middle-energy shock-wave therapy, as performed in Group II, because of the time-saving factor.

Location modalities for focused extracorporeal shock wave application in the treatment of chronic plantar fasciitis.

BACKGROUND: Focused extracorporeal shock waves (ESWT) has been used in the treatment of plantar fasciitis with heel spurs. The optimal location for administering treatment, however, has not been determined. The purpose of this study was to determine whether fluoroscopy-guided location of a heel spur or patient location of the maximal point of tenderness is more effective in administering ESWT. METHODS: In a prospective, examiner-blinded trial, 41 patients were randomized into two groups for treatment by ESWT: group 1, location of the heel spur for ESWT by fluoroscopy, and group 2, patient location for ESWT by maximal point of tenderness. Each group had three session of ESWT at 1-week intervals. The success rates between the two groups were assessed at 6 and 12 weeks. RESULTS: No significant differences were noted between the groups. CONCLUSIONS: Despite the small number of patients in the study, patient location for positioning the focus in ESWT in treatment of plantar fasciitis with a heel spur is recommended.

Choroidal neovascularization in pathologic myopia: three-year results after photodynamic therapy.

PURPOSE: To examine whether the encouraging functional results one year after photodynamic therapy (PDT) can be maintained up to three years. DESIGN: Prospective interventional case series. METHODS: Highly myopic eyes that had been treated with PDT for subfoveal choroidal neovascularization and had been observed at least 36 months were included. Distance acuity (Early Treatment of Diabetic Retinopathy charts), reading acuity (Jaeger charts), 10-degree static threshold perimetry, fluorescein angiography, and optical coherence tomography were performed. The main outcome measures were the differences of the values among the baseline and the month 12 and the month 36 examinations. RESULTS: Twenty eyes of 18 patients were included: 15 patients were female, and 3 patients were male. The average age was 64 years (range, 36 to 85 years). The mean distance acuity was 43 letters at baseline and 53 letters after 12 months and after 36 months. The mean reading acuity changed from mean J10.8 to mean J8.1 after 12 months and to mean J9.85 after 3 years. The mean defect decreased from mean 13.5 dB at baseline to mean 12.5 dB after 12 months and mean 11.2 dB after 36 months. The maximum retinal thickness decreased from mean 360 mum at baseline to mean 259 mum after one year and mean 238 mum after 36 months. CONCLUSION: Distance acuity and central visual field showed stabilization after the month 12 examination up to the month 36 examination. The reading acuity decreased between the month 12 and the month 36 examinations, which might be related to an increase of retinal atrophy.

Extracorporeal shock wave therapy in the treatment of calcific tendinitis of the rotator cuff.

BACKGROUND: Low-energy extracorporeal shock wave therapy is an alternative treatment, with limited evidence for effectiveness, for calcific tendinitis of the rotator cuff. HYPOTHESIS: Objective localization of the calcium deposit by 3-dimensional, computer-assisted navigation reveals superior clinical and radiographic outcomes compared to localization through patient-to-therapist feedback. STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1. METHODS: A prospective, randomized, single-blind study was carried out on 50 patients. The population was divided into 2 groups of equal numbers (navigation group and feedback group). In all patients, treatment-resistant pain was evident for longer than 6 months. A total of 3 therapy sessions of constant low-energy focused shock wave therapy was administered in weekly intervals in both groups. Local anesthesia was not applied. Radiographs and clinical assessment, including the Constant and Murley shoulder scoring system and the visual analog scale for pain, were performed both before therapy and after 12 weeks. In the navigation group, the calcium deposit was localized using a radiographically guided, 3-dimensional, computer-assisted device. The feedback group was treated after locating the point of maximum tenderness through palpation by the therapist with feedback from the patient. RESULTS: Both groups had significant improvements in the Constant and Murley score and the visual analog scale after 12 weeks. The results from the navigation group were statistically significantly superior to those of the feedback group. In the navigation group, 6 calcium deposits disappeared and 9 altered, compared to 1 disappearance and 12 alterations in the feedback group. No severe complications occurred. CONCLUSION: Three-dimensional, computer-assisted navigation reveals significantly better results and is therefore recommended when extracorporeal shock wave therapy is used in the treatment of calcific tendinitis of the rotator cuff.

Retinal angiomatous proliferation: combined therapy of intravitreal triamcinolone acetonide and PDT versus PDT alone.

BACKGROUND: The objective of the study was to investigate whether combined treatment with photodynamic therapy (PDT) and triamcinolone acetonide intravitreally applied is superior to PDT alone in eyes with retinal angiomatous proliferation (RAP). METHODS: Between July 2004 and June 2005 eyes with RAP in age-related macular degeneration were included in a prospective study and were treated with 4 mg of triamcinolone acetonide followed by PDT (group 1). Eyes with RAP treated with PDT alone before June 2004 were retrospectively reviewed (group 2). Distance visual acuity (VA) with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, greatest diameter of the lesion (measured by fluorescein angiography), and retinal thickness (measured by optical coherence tomography) were performed at baseline and at 6 weeks, 3 months, 6 months and 12 months thereafter. RESULTS: Fifty-eight eyes in 58 patients were included: 27 eyes in the combined treatment group and 31 eyes in the PDT monotherapy group. The groups were comparable with regard to age, gender and RAP stage. VA decreased from 65.6 to 52.0 and from 60.7 to 44.0 letters, and lesion size increased from 3.2 mm to 3.5 mm and from 3.3 mm to 3.5 mm in the combined and monotherapy groups respectively. There was a trend towards a better outcome in the combined group. Significantly (p = 0.01) fewer complications occurred in the combined group (22.2%) than in the monotherapy group (54.8%). CONCLUSION: No significant differences could be found in the time course of distance VA, retinal thickness, and lesion size between the PDT monotherapy group and the combined PDT and IVTA group. However, significantly fewer complications occurred in the combined treatment group. New therapeutic strategies might be required in RAP lesions, probably including therapy with anti-angiogenic agents.

Reduction of iatrogenic RPE lesions in AMD patients: evidence for wound healing?

PURPOSE: Our purpose was to study retinal pigment epithelium (RPE) wound healing in patients with age-related macular degeneration (AMD). PATIENTS AND METHODS: Abrasive debridement of nasal RPE was performed with a metal cannula during pars plana vitrectomy for foveal choroidal neovascularization (CNV) membrane excision combined with simultaneous autologous RPE transplantation. Fundus autofluorescence, fluorescein angiography images, and red-free pictures were taken initially within 1-2 weeks postoperatively, subsequently in 2-week intervals until 3 months, monthly until 6 months, and every 3 months thereafter. The borders of these lesions were measured; areas were calculated and compared using ArchiCad Software. Fourteen eyes of 14 patients suffering from AMD were included (nine women and four men, mean age 75.6 years +/-6.6 years). RESULTS: Six of 14 (42.9 %) patients showed a reduction of the RPE debrided area. The size of these lesions reduced 5.6-20% within 2 postoperative months compared with their size at first examination (from a mean of 13.7 mm2 +/- 7.2 at baseline to a mean of 12.8 mm2 +/- 6.7 at 2 months postoperatively). No further reduction of the lesions was seen after the 2 months. In eight cases, borders of the RPE debrided areas stayed stable during observation time. CONCLUSIONS: Wound healing of abrasively debrided RPE monolayer defects in patients with AMD occurs to a certain extent in nearly half of the cases. This process seems to stop after 2 months.

Activity of neovascular lesions treated with bevacizumab: comparison between optical coherence tomography and fluorescein angiography.

PURPOSE: To investigate whether examination with the non-invasive optical coherence tomography (OCT) alone is sufficient to ascertain the need of re-treatment with bevacizumab for exudative age-related macular degeneration (AMD) or the invasive fluorescein angiography (FA) is needed. METHOD: Two independent examiners reviewed FA and OCT images and performed a semi-quantitative assessment from 0=no activity to activity 1-3, mild, moderate and advanced, respectively. Weighted Kappa indices were performed to calculate the concordance between OCT and FA. RESULTS: A total of 153 OCT and FA examinations of 69 patients were evaluated, mean 2.2 examinations per patient. The mean age was 77.1+/-7.9 (55-89) years; 29.0% were male, 71.0% female. The weighted Kappa index showed concordance for activity in OCT and FA weak concerning the first investigation 4-6 weeks after initial treatment (0.3847) and obvious concerning the second investigation 8-10 weeks after initial treatment (0.4170). Higher values of activity were found with the OCT compared to FA. The most frequent reasons for discrepancies were detachment of the pigmentepithelium and fibrosis. CONCLUSION: There is evidence of agreement between both examinations, the OCT was even more sensitive to detect activity of a lesion. In conducting studies based on OCT as single examination, it should be clearly defined how long fibrotic lesions or lesions with pigment epithelial detachment should be re-treated.

Subretinal surgery and transplantation of autologous pigment epithelial cells in retinal angiomatous proliferation.

PURPOSE: The aim of this study was to examine whether the presence of retinal angiomatous proliferation (RAP) is a prognostic factor in subretinal surgery with transplantation of a suspension of autologous retinal pigment epithelial (RPE) cells. METHODS: Eyes that had been followed for at least 12 months after subretinal surgery were reviewed retrospectively and assigned to group 1 (presence of RAP) or group 2 (lesions without RAP). Main outcome measures were logMAR distance acuity and lesion size at 12 months. RESULTS: A total of 68 eyes of 68 patients were included; 28 were assigned to group 1 and 40 to group 2. A total of 43% of patients were male and 57% were female. Their mean age was 77.8 years. Mean distance acuity was 1.02 logMAR at baseline and 1.06 logMAR at month 12. Mean lesion size was 27.9 mm(2) at baseline and 29.9 mm2 at month 12. The differences between the groups were not significant. CONCLUSIONS: The presence of RAP did not significantly influence the outcome after subretinal surgery with transplantation of autologous RPE cells. Other than age, preoperative lesion size and distance acuity were the only predictive factors for postoperative results.

Biological variation of the platelet proteome in the elderly population and its implication for biomarker research.

Knowledge about the extent of total variation experienced between samples from different individuals is of great importance for the design of not only proteomics but every clinical study. This variation defines the smallest statistically significant detectable signal difference when comparing two groups of individuals. We isolated platelets from 20 healthy human volunteers aged 56-100 years because this age group is most commonly encountered in the clinics. We determined the technical and total variation experienced in a proteome analysis using two-dimensional DIGE with IPGs in the pI ranges 4-7 and 6-9. Only spots that were reproducibly detectable in at least 90% of all gels (n = 908) were included in the study. All spots had a similar technical variation with a median coefficient of variation (cv) of about 7%. In contrast, spots showed a more diverse total variation between individuals with a surprisingly low median cv of only 18%. Because most known biomarkers show an effect size in a 1-2-fold range of their cv, any future clinical proteomics study with platelets will require an analytical method that is able to detect such small quantitative differences. In addition, we calculated the minimal number of samples (sample size) needed to detect given protein expression differences with statistical significance.

Esophageal acid exposure in upright and recumbent postures: roles of lower esophageal sphincter, esophageal contractile and transport function, hiatal hernia, age, sex, and body mass.

This study aimed to assess, using multiple regression analyses, the roles of lower esophageal sphincter, esophageal contractile and transport function, hiatal hernia, age, sex, and body mass for esophageal acid exposure in upright and recumbent postures and for esophagitis. In 116 patients with reflux symptoms, acid exposure was recorded by 24-hr pH monitoring, motility manometrically, bolus transport scintigraphically, hiatal hernia and esophagitis endoscopically. In upright posture, the percentage time at pH <4 increased significantly with higher body mass index and lower distal esophageal amplitude, the number of episodes >5 min at pH <4 with lower distal amplitude, slower transport, and higher body mass, and the longest episode at pH <4 with lower distal amplitude. In recumbency, the percentage time at pH <4 increased with lower percentage of effective esophageal contraction waves and male sex, and the number of episodes and the longest episode with lower percentage effective waves. The severity of esophagitis augmented with slower supine transport and male sex. In both postures, acid exposure and esophagitis seem to be determined primarily by impaired esophageal motility and the ensuing slow bolus transport rather than by compromised lower esophageal sphincter function and the presence and size of a hiatal hernia.