Performance of several types of beta-binomial models in comparison to standard approaches for meta-analyses with very few studies.

BACKGROUND: Meta-analyses are used to summarise the results of several studies on a specific research question. Standard methods for meta-analyses, namely inverse variance random effects models, have unfavourable properties if only very few (2 - 4) studies are available. Therefore, alternative meta-analytic methods are needed. In the case of binary data, the "common-rho" beta-binomial model has shown good results in situations with sparse data or few studies. The major concern of this model is that it ignores the fact that each treatment arm is paired with a respective control arm from the same study. Thus, the randomisation to a study arm of a specific study is disrespected, which may lead to compromised estimates of the treatment effect. Therefore, we extended this model to a version that respects randomisation. The aim of this simulation study was to compare the "common-rho" beta-binomial model and several other beta-binomial models with standard meta-analyses models, including generalised linear mixed models and several inverse variance random effects models. METHODS: We conducted a simulation study comparing beta-binomial models and various standard meta-analysis methods. The design of the simulation aimed to consider meta-analytic situations occurring in practice. RESULTS: No method performed well in scenarios with only 2 studies in the random effects scenario. In this situation, a fixed effect model or a qualitative summary of the study results may be preferable. In scenarios with 3 or 4 studies, most methods satisfied the nominal coverage probability. The "common-rho" beta-binomial model showed the highest power under the alternative hypothesis. The beta-binomial model respecting randomisation did not improve performance. CONCLUSION: The "common-rho" beta-binomial appears to be a good option for meta-analyses of very few studies. As residual concerns about the consequences of disrespecting randomisation may still exist, we recommend a sensitivity analysis with a standard meta-analysis method that respects randomisation.

Negative pressure wound therapy in patients with wounds healing by secondary intention: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Negative pressure wound therapy (NPWT) is a widely used method of wound treatment. We performed a systematic review of randomised controlled trials (RCTs) comparing the patient-relevant benefits and harms of NPWT with standard wound therapy (SWT) in patients with wounds healing by secondary intention. METHODS: We searched for RCTs in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: July 2018) and screened reference lists of relevant systematic reviews and health technology assessments. Manufacturers and investigators were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome (e.g. wound closure). We assessed publication bias and, if feasible, performed meta-analyses, grading the results into different categories (hint, indication or proof of a greater benefit or harm). RESULTS: We identified 48 eligible studies of generally low quality with evaluable data for 4315 patients and 30 eligible studies with missing data for at least 1386 patients. Due to potential publication bias (proportion of inaccessible data, 24%), we downgraded our conclusions. A meta-analysis of all wound healing data showed a significant effect in favour of NPWT (OR 1.56, 95% CI 1.15 to 2.13, p = 0.008). As further analyses of different definitions of wound closure did not contradict that analysis, we inferred an indication of a greater benefit of NPWT. A meta-analysis of hospital stay (in days) showed a significant difference in favour of NPWT (MD - 4.78, 95% CI - 7.79 to - 1.76, p = 0.005). As further analyses of different definitions of hospital stay/readmission did not contradict that analysis, we inferred an indication of a greater benefit of NPWT. There was neither proof (nor indication nor hint) of greater benefit or harm of NPWT for other patient-relevant outcomes such as mortality and adverse events. CONCLUSIONS: In summary, low-quality data indicate a greater benefit of NPWT versus SWT for wound closure in patients with wounds healing by secondary intention. The length of hospital stay is also shortened. The data show no advantages or disadvantages of NPWT for other patient-relevant outcomes. Publication bias is an important problem in studies on NPWT, underlining that all clinical studies need to be fully reported.

A Randomized Controlled Clinical Trial Comparing 20 Gauge and 23 Gauge Vitrectomy for Patients with Macular Hole or Macular Pucker.

INTRODUCTION: To compare the transconjunctival sutureless 23 gauge (G) pars plana vitrectomy (PPV) with 20 G PPV regarding inflammation, safety, visual outcome and patient comfort. METHODS: We included 103 patients with symptomatic macular hole or macular pucker, scheduled for vitrectomy in this prospective, randomized, controlled, mono-center clinical trial. Patients were randomized 1:1 to either 20G PPV (n = 51) or 23G PPV (n = 52). All eyes underwent standard 20G or 23G PPV with membrane peeling. Primary outcome measure was change in aqueous humor flare 3 weeks after surgery compared with baseline. Secondary outcome measures were flare values 2 days and 26 weeks after surgery, subjective discomforts measured with a visual analog scale, best-corrected visual acuity, duration of surgery, intraocular pressure (IOP) and adverse events. RESULTS: There was no significant difference in change of flare 3 weeks after PPV [- 1.7, 95% CI (- 6.3 to 2.9), p = 0.466]. Both groups showed a significant increase in flare 2 days after surgery (20G: p < 0.001, 23G: p = 0.002), but only the 20G group after 3 weeks (p = 0.011). The gain in visual acuity after 3 weeks was higher after 23G PPV (4.2 95% CI (0.4-8.0, p = 0.029), but without a difference after 6 months. The duration of surgery was shorter in the 23G group (p < 0.001). Patient comfort 3 weeks after surgery was greater after 23G PPV (foreign body sensation p = 0.002; itching: p = 0.021). However, the rate of complications did not differ between the groups. CONCLUSION: The primary aim, showing the superiority of the 23G group regarding the change of flare value from baseline to 3 weeks after surgery, was not met, but the level of inflammation decreased faster after 23G PPV. Clear advantages of the 23G PPV were a lower risk of postoperative IOP elevation, a shorter surgery time, faster visual recovery and greater patient comfort in the early postoperative phase. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01969929.

Prophylactic intravitreal 5-fluorouracil and heparin to prevent proliferative vitreoretinopathy in high-risk patients with retinal detachment: study protocol for a randomized controlled trial.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is the major cause for postoperative failure after vitreo-retinal surgery for primary rhegmatogenous retinal detachment (RRD). Adjunct pharmaceutical therapy was found to be ineffective once PVR is established. Preliminary data suggest that prevention of PVR yields better functional outcome. So far, there is no standard therapy to prevent PVR. METHODS/DESIGN: This is a randomized, double-blind, controlled, multicenter, interventional trial with one interim analysis. High-risk patients for PVR with primary RRD will be allocated equally to the following treatment arms: (a) verum: intraoperative adjuvant application of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH) via intraocular infusion during routine pars plana vitrectomy (PPV) and (b) placebo: routinely used intraocular infusion with balanced salt solution during routine PPV. PVR risk is assessed by non-invasive aqueous flare measurement by using laser flare photometry. The primary endpoint of the trial is the occurrence of PVR grade CP (C: full-thickness retinal folds or subretinal strands in clock hours; P: located posterior to equator) 1 or higher within 12 weeks after treatment. Secondary endpoints include PVR grade CA (A: located anterior to equator), best corrected visual acuity, number and extent of surgical procedures to achieve retinal re-attachment, and occurrence of drug-related adverse events within 12 weeks. It is assumed, on the basis of previously published results, that the incidence of PVR grade CP 1 is 35% in the control group and that a reduction by one third would be clinically relevant. Given the sequential design and adjustment for a dropout rate of 5%, a total sample size of 560 patients (280 per group) was calculated to ensure a power of 80% for the confirmatory analysis. DISCUSSION: The present trial uses intraoperative intravitreal 5-FU and LMWH as a prophylactic therapy in high-risk patients with primary RRD, aiming to reduce the incidence of PVR in the group that receives the trial drug. Using laser flare photometry to identify high-risk patients for PVR, this trial will test the effectiveness of a simple treatment to prevent PVR. TRIAL REGISTRATION: EudraCT no.: 2015-004731-12, registered October 21, 2015; ClinicalTrials.gov Identifier: NCT02834559 , registered July 12, 2016. Protocol version: Version 02. Date: September 18, 2016.

Influence of repetitive diving in saltwater on pressure equalization and Eustachian tube function in recreational scuba divers.

INTRODUCTION: We investigated in a prospective, observational trial the feasibility of using the Eustachian tube function test (ETFT) to measure the effect of repetitive pressure exposure during open seawater dives on Eustachian tube function. METHODS: The study included 28 adult divers during six consecutive days of diving in the Red Sea. Participants underwent otoscopy and ETFT before the first dive, between each dive and after the last dive. ETFT included regular tympanometry (R-tymp), tympanometry after Valsalva (V-tymp) and after swallowing (S-tymp). The R-tymp was obtained as 'baseline' peak pressure. After a Valsalva, the peak pressure should shift (positively), revealing a positive shift of the tympanic membrane. This pressure shift is defined here as R-VdP. The changes in compliance and peak pressure were recorded and correlated with otoscopic findings and diving experience. Middle ear barotrauma was scored using the Edmonds modified TEED scale. RESULTS: The 28 participants performed 437 dives. Positive shift of pressure in the middle ear was evident with significant changes from day one to day three (P < 0.0001). Divers with barotrauma showed significantly lower values of R-tymp peak pressure and significantly higher negative R-VdP, compared to divers with normal otoscopic findings (P < 0.05). Diving experience significantly correlated with R-tymp peak pressure and prevalence of middle ear barotrauma. CONCLUSION: Significant changes in middle ear pressure and pressure equalization from repeated pressure exposure in saltwater were seen using ETFT. Repetitive, multi-day diving led to significantly decreased compliance and increased R-tymp peak pressure (overpressure) in the middle ear. Most profound changes were observed in less and intermediate experienced divers.

Comparison of central and local serial CT assessments of metastatic renal cell carcinoma patients in a clinical phase IIB study.

Background Clinical oncological studies attempt to improve precision of data by central radiological assessments. However, it is unclear, to which extent local and central assessments diverge. Purpose To quantify inter-reader variability and the deviation of local from central radiological assessments of computed tomography (CT) scans. Material and Methods This was a sub-study of a randomized clinical phase IIb trial in metastatic renal cell carcinoma (RCC), comparing first-line sorafenib with interferon-alpha-2a (IFN-α-2a). It analyzed agreements of local with central RECIST CT assessments by Cohen's kappa (κ), symmetry tests, deviations in waterfall plots, Bland-Altman plots, and parametric survival analyses. Results The concordance between local and central radiologic review was quantified by κ = 0.53. While local assessment yielded progressive disease (PD) in 18.6%, central assessment classified 22.5% of patient time points as PD exhibiting only a partial overlap with the 18.6% The tumor shrinkage rates in waterfall plots were 68.1% in local and 55.8% in central review (57.8% and 59% by Reader 1 and Reader 2). Bland-Altman plots identified a systematic shift of tumor change rates by -7.5% in local compared to central assessments, that may reflect a systematic tendency of more favorable results in local assessments. The discordance between local and central review was reflected by a time to progression (TTP) hazard ratio (HR) of 1.73 ( P = 0.0003). Conclusion These data suggest that central radiologic review may reduce technical measurement variability in clinical trials, which should be scrutinized in future studies compared to a volumetric reference.

Self-assessment of oral health, dental health care and oral health-related quality of life among Parkinson's disease patients.

OBJECTIVE: Parkinson's disease (PD) is a common condition in elderly people and can adversely affect oral health (OH). However, the subjective burden of oral symptoms on the quality of life (QoL) of patients with PD is largely unknown and needs to be better understood. The objective of this study was to explore self-assessed dental care in patients with PD, including the ability to perform oral hygiene, self-assessed xerostomia, drooling and dysphagia problems, and the impact on OH-related QoL. MATERIALS AND METHODS: A questionnaire was completed by 100 patients with PD in Germany recruited from PD support groups, and included self-assessment of dental care, the Oral Health Impact Profile (OHIP-14) score, the levodopa equivalent daily dose, the Movement Disorder Society Unified Parkinson's Disease Rating Scale-II and the leading OH-related symptoms. RESULTS: Participants experienced xerostomia (49%), drooling (70%) and dysphagia (47%) and suffered from a limited ability to perform oral hygiene (29%). The oral symptoms xerostomia, drooling and dysphagia impaired the OH-related QoL [OHIP total score 14.6 (9.7)-16.8 (11.4) compared to 11.3 (9.9) in participants without symptoms]. In total, 91.8% of participants had their own dentist. Only 6.1% of participants with xerostomia received advice regarding management. CONCLUSION: In this study, patients with PD suffered from OH-related symptoms (xerostomia, drooling, and dysphagia) that impaired their OH-related QoL. Participants felt that they received adequate dental health care; however, dental advice regarding management of PD-related OH problems was often lacking.

Prevalence of Barotrauma in Recreational Scuba Divers After Repetitive Saltwater Dives.

INTRODUCTION: The aim was to investigate the prevalence of middle ear barotrauma (MEB) and to establish risk factors of MEB after repeated saltwater dives. METHODS: In this prospective observational cohort study 28 divers were examined over 6 consecutive days of diving in the Red Sea, Egypt. Participants underwent an otoscopic examination before the first dive, between each dive and after the last dive. In addition, they performed Valsalva maneuver (VM) and were questioned about dive-related complaints. Otoscopic findings were classified according to TEED classification for MEB (0 = normal otoscopy to 4 = perforation) separately for each ear. First examination was conducted before the first dive. Final examination, including a questionnaire, was conducted at least 12 h after the last dive. RESULTS: In total, 436 dives were performed and 1161 otoscopic findings were analyzed. All participants showed a normal eardrum and a positive VM during initial exam. MEB prevalence (TEED >0) was 36.5% at final examination. Prevalence increased significantly with number of dives per day (p < 0.001) as with number of diving days (p = 0.032). Neither depth nor duration of dives significantly influenced MEB prevalence (all p > 0.05). More experienced divers (>200 dives lifetime) showed significantly less barotrauma (p < 0.0001). Despite the high prevalence of MEB, 81.7% (316 of 387) of all dives were reported asymptomatic. CONCLUSIONS: After 6 days of repetitive diving, MEB prevalence was high (36.5%). It was the most often cause of otalgia in divers. Cumulative pressure exposure during repetitive dives resulted in significant increase of MEB. Diving experience significantly reduced the MEB prevalence. Interestingly, the severity of MEB did not correlate with subjective complaints.

Association of Hyperreflective Foci Present in Early Forms of Age-Related Macular Degeneration With Known Age-Related Macular Degeneration Risk Polymorphisms.

PURPOSE: We evaluated the association of hyperreflective foci (HF) observed in early and intermediate age-related macular degeneration (AMD) with known AMD risk alleles. METHODS: In this pilot case-control study, HF were defined as lesions with reflectivity equal or higher than the retinal pigment epithelium band in spectral domain optical coherence tomography (SDOCT). Hyperreflective foci in the outer nuclear layer and photoreceptor complex were evaluated in 518 individuals with early and intermediate AMD. Definite presence of HF was defined as at least 10 HF in all SDOCT scans. Genotyping was performed for 22 single nucleotide polymorphisms (SNPs). Associations between AMD severity stages, HF, and SNPs were determined by logistic regression analyses. RESULTS: Hyperreflective foci (n ≥ 10) were significantly associated with AMD severity and the association was strongest with intermediate AMD (odds ratio [OR], 8.45; P = 1.092*10-8). Independently, HF showed associations with ARMS2 rs104909/HtRA1 rs11200638 (OR, 1.64; P = 0.017), CFH rs1061170 (OR, 1.70; P = 0.011), and APOE4/TOMM40 rs2075650 (OR, 2.26; P = 0.005) variants. Within the group of intermediate AMD, associations were similar (ARMS2 rs104909/HtRA1 rs11200638 OR, 1.79, P = 0.010; CFH rs1061170 OR, 1.77, P = 0.013; APOE4/TOMM40 rs2075650 OR, 1.98; P = 0.034) and showed additional trending associations with VEGFA rs943080 variant (OR, 0.59; P = 0.024). After Bonferroni-correction for 22 SNPs, none of the associations was statistically significant (P ≤ 0.0023). CONCLUSIONS: The presence of HF is related to AMD severity. Despite limited power of this pilot study, our results suggest an association of HF with polymorphisms in ARMS2/HTRA1, CFH, APOE4/TOMM40, and VEGFA genes which could be triggered by modification of the extracellular matrix, altered complement system or lipid metabolism.

Priority Setting and Influential Factors on Acceptance of Pharmaceutical Recommendations in Collaborative Medication Reviews in an Ambulatory Care Setting - Analysis of a Cluster Randomized Controlled Trial (WestGem-Study).

BACKGROUND: Medication reviews are recognized services to increase quality of therapy and reduce medication risks. The selection of eligible patients with potential to receive a major benefit is based on assumptions rather than on factual data. Acceptance of interprofessional collaboration is crucial to increase the quality of medication therapy. OBJECTIVE: The research question was to identify and prioritize eligible patients for a medication review and to provide evidence-based criteria for patient selection. Acceptance of the prescribing general practitioner to implement pharmaceutical recommendations was measured and factors influencing physicians' acceptance were explored to obtain an impression on the extent of collaboration in medication review in an ambulatory care setting. METHODS: Based on data of a cluster-randomized controlled study (WestGem-study), the correlation between patient parameters and the individual performance in a medication review was calculated in a multiple logistic regression model. Physician's acceptance of the suggested intervention was assessed using feedback forms. Influential factors were analyzed. RESULTS: The number of drugs in use (p = 0.001), discrepancies between prescribed and used medicines (p = 0.014), the baseline Medication Appropriateness Index score (p<0.001) and the duration of the intervention (p = 0.006) could be identified as influential factors for a major benefit from a medication review, whereas morbidity (p>0.05) and a low kidney function (p>0.05) do not predetermine the outcome. Longitudinal patient care with repeated reviews showed higher interprofessional acceptance and superior patient benefit. A total of 54.9% of the recommendations in a medication review on drug therapy were accepted for implementation. CONCLUSIONS: The number of drugs in use and medication reconciliation could be a first rational step in patient selection for a medication review. Most elderly, multimorbid patients with polymedication experience a similar chance of receiving a benefit from a medication review. Longitudinal patient care should be preferred over confined medication reviews. The acceptance of medication reviews by physicians supports further implementation into health care systems. TRIAL REGISTRATION: ISRCTN ISRCTN41595373.

Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages.

BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. METHODS: In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. RESULTS: Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). CONCLUSION: The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients.

Immediate Postoperative Intraocular Pressure Changes After Anterior Chamber Air Fill in Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To monitor the intraocular pressure (IOP) changes immediately after anterior chamber air tamponade in Descemet membrane endothelial keratoplasty (DMEK). METHODS: Twenty-four patients undergoing DMEK and 16 patients undergoing rebubbling after DMEK were enrolled (n = 40). All DMEK patients had inferior iridectomy and nearly full intracameral air tamponade with an aimed IOP of 25 mm Hg at the end of surgery. The IOP was measured at 1, 2, 3, 5, 12, 24 hours and 1 week postoperatively. RESULTS: After anterior chamber air fill in DMEK, the IOP increased from preoperative baseline, 12.1 ± 2.9 mm Hg, to 26.3 ± 4.7 mm Hg, P < 0.001. Mean IOP was significantly elevated in the first 2 hours, 19.4 ± 10.5 mm Hg and 17.0 ± 7.4 mm Hg, P = 0.007 and 0.006, respectively. Then, it lowered to the baseline level, 14.0 ± 4.7 mm Hg, P > 0.05, and remained stable during follow-ups. An asymptomatic IOP elevation above 30 mm Hg was detected in 3 patients (12.5%) within the first 2 hours. None had preexisting glaucoma. Most episodes could be controlled by antiglaucoma medications and upright positioning. The pattern of IOP changes after rebubbling was similar to that after DMEK but the IOP dropped sharply to the baseline level after 1 hour and had no incidence of IOP elevations beyond 30 mm Hg. CONCLUSIONS: Adequate inferior iridectomy greatly alleviates the risk and severity of acute IOP rises after nearly full anterior chamber air tamponade in DMEK. Standard IOP adjustment at the end of DMEK surgery with postoperative IOP monitoring especially in the first 2 postoperative hours is advisable when there is no postoperative default air release.

The interrelation between sensorimotor abilities, cognitive performance and individual EEG alpha peak frequency in young children.

OBJECTIVE: The aim of this study was to identify the interrelation between sensorimotor abilities, cognitive performance and individual alpha peak frequency (iAPF), an EEG marker of global architectural and functional properties of the human brain, in healthy preschool children. METHODS: 25 participants completed a one minute eyes-closed EEG recording, two cognitive tests assessing processing speed and visual working memory and a sensorimotor test battery. RESULTS: We found positive correlations between selective sensorimotor abilities and iAPF; however, no significant correlations were observed between iAPF and cognitive performance. Specifically, locomotor skills correlated with iAPF across all cortical regions, except for the occipital cortex. Furthermore, a close relationship was found between sensorimotor and cognitive performance indicating that children with improved sensorimotor abilities were faster and/or more accurate in cognitive task performance. The cumulative pattern of our results indicates that a close relationship exists between sensorimotor and cognitive performance in young children. However, this relationship is dissociated from the iAPF. CONCLUSION: In contrast to adults, in young children the iAPF is related to locomotor skills and not to cognitive processing speed or visual working memory function. SIGNIFICANCE: The global architectural and functional properties of the brain are closely related to locomotor skills during development.

Intensified Topical Steroids as Prophylaxis for Macular Edema After Posterior Lamellar Keratoplasty Combined With Cataract Surgery.

PURPOSE: To analyze the effect of intensified topical steroid therapy after Descemet membrane endothelial keratoplasty combined with cataract surgery (triple-DMEK) on the incidence of postoperative cystoid macular edema (CME). DESIGN: Single-center comparative clinical study with historical controls. SETTING: Department of Ophthalmology, University of Cologne, Germany, tertiary hospital, performing 500 corneal transplant surgeries per year. PATIENTS: Total of 131 patients (150 eyes) undergoing triple-DMEK surgery. Inclusion Criterion: Triple-DMEK surgery. EXCLUSION CRITERIA: Prior retinal surgery, history of prior CME. INTERVENTIONS: Prednisolone acetate eye drops 1% 5 times daily for the first week after surgery. After an internal change of therapy regimen: Prednisolone acetate eye drops 1% hourly for the first postoperative week. We compared 75 consecutive eyes before with 75 consecutive eyes after the change of therapy regimen. Patients received macular spectral-domain optical coherence tomography (SD OCT) preoperatively, as well as 6 weeks and 3 and 6 months post surgery. MAIN OUTCOME MEASURE: Development of CME detected by macular SD OCT during 6 months postoperatively. RESULTS: Both groups were comparable regarding baseline age, sex, central corneal thickness, rebubbling rate, and visual acuity. With topical steroid therapy 5 times per day during the first postoperative week, we observed 9 cases of subsequent CME (12%). With hourly topical steroid therapy none of the patients developed CME subsequently (P = .003). Apart from the topical steroids during the first week, medical treatment was identical in both groups. CONCLUSIONS: Early intensified postoperative topical steroid therapy constitutes an effective prophylactic treatment to reduce incidence of CME after triple-DMEK surgery.

Effects of a 6-Month, Group-Based, Therapeutic Exercise Program for Childhood Cancer Outpatients on Motor Performance, Level of Activity, and Quality of Life.

BACKGROUND: Exercise interventions in pediatric oncology are feasible and safe. However, scarce data are available with regard to the effectiveness of outpatient, group-based exercise interventions. As well, the potential role of exercise to improve motor performance has not been adequately explored despite being a meaningful outcome during childhood with important implications for physical activity behavior. No study has yet demonstrated significant changes in motor performance after an exercise intervention. PROCEDURES: This explorative, prospective study was designed to evaluate the effects of a 6-month, group-based, therapeutic exercise program for a mixed childhood cancer population on motor performance, level of activity, and quality of life. After cessation of inpatient medical treatment, childhood cancer outpatients aged 4-17 years exercised once a week during a 6-month period (IG). Comparison groups included childhood cancer outpatients receiving care as usual (CG(1)), as well as healthy peers (matched to IG by age and gender) (CG(2)). RESULTS: Overall motor performance, various motor dimensions, activity in sport clubs and school sports, as well as physical and emotional well-being were significantly reduced in the IG at baseline. Significant differences between the IG and CG(1) and/or CG(2) were identified in the change of overall motor performance, single motor dimensions, overall level of activity, and emotional well-being from baseline to post-intervention. CONCLUSIONS: The exercise intervention was beneficial in terms of motor performance, level of activity, and emotional well-being. As such, this study provides support for group-based exercise as a potential strategy to improve these outcomes after inpatient medical treatment.

Novel Navigated Ultrasound Compared With Conventional Ultrasound for Vascular Access­a Prospective Study in a Gel Phantom Model.

OBJECTIVES: The authors hypothesized that, compared with conventional ultrasound (CUS), the use of a novel navigated ultrasound (NUS) technology would increase success rates and decrease performance times of vascular access procedures in a gel phantom model. DESIGN: A prospective, randomized, crossover study. SETTING: A university Hospital. PARTICIPANTS: Participants were 44 anesthesiologists with varying clinical experience. INTERVENTIONS: Anesthesiologists performed in-plane and out-of-plane vascular access procedures using both NUS and CUS for needle visualization in a gel phantom model. MEASUREMENTS AND MAIN RESULTS: Procedure time was measured from needle insertion to verbalization of final needle positioning by the participants, and successful needle placement into the simulated vessel was verified by aspiration of simulated blood. By employing ultrasound navigation capabilities in addition to real-time ultrasound imaging during in-plane/long-axis vascular access procedures, median procedure time showed a nonsignificant decrease (7.5 seconds v 13.0 seconds; p = 0.028), and the observed increase in procedure success rate (90.9% v 100%; p = 0.125) did not reach statistical significance. For out-of-plane/short-axis vascular access procedures, a significant reduction in median procedure time (5.0 seconds v 11.5 seconds; p<0.001) and a significant increase in procedure success rate (75% v 100%; p<0.001) were achieved by using navigation technology combined with real-time ultrasound. CONCLUSIONS: NUS technology improved the performance times and success rates of vascular access procedures conducted by anesthesiologists in a gel phantom model.

Effect evaluation of an interprofessional medication therapy management approach for multimorbid patients in primary care: a cluster-randomized controlled trial in community care (WestGem study protocol).

BACKGROUND: Pharmaceutical practice worldwide is developing towards patient care. Medication Review (MR) and Medication Therapy Management (MTM) are evolving as the most prominent services in pharmaceutical care and have a strong potential to provide a large benefit for patients and society. MTMs can only be performed in an interprofessional, collaborative setting. Several international studies have explored the effects of a MTM on the quality of therapy and costs. For Germany the data is still deficient. This study aims to provide data on the effects of an interprofessional MTM regarding quality of therapy, quality of life, costs and cost-effectiveness. METHOD/DESIGN: The study is designed as a cluster-randomized controlled trial in primary care, involving 12 outpatient clinics (clusters) and 165 patients. Primary care units are allocated to interventions using a Stepped Wedge Design. All units are initially assigned to the control group. After a 6 month observation period, general practitioners (GP) are randomly allocated to one of three groups and the interprofessional medication therapy management approach is implemented sequentially per each group with a lag of 3 months between. The primary outcome is the change in the quality of therapy measured by the MAI (Medication Appropriateness Index). Secondary outcomes include changes in the number of drug related problems, medication complexity, changes in drug-adherence, changes in health-status and function, quality of life, direct costs and the incremental cost-effectiveness ratio. The acceptance of the interprofessional Medication Therapy Management approach is assessed by qualitative methods. DISCUSSION: The patient interview and brown bag review are activities, typically provided by the pharmacist. In this trial the patient is blinded to the pharmacist. The strength of having the patient blinded to the pharmacists is to exclude skepticism of the patient toward unknown pharmacies, which might be a major confounder in a regional and community setting. A weakness is that some patient related data might reach the pharmacists in a way, which might differ from self-acquired data. TRIAL REGISTRATION: Current controlled trials ISRCTN41595373 .

Effects of a 15-Month Supervised Exercise Program on Physical and Psychological Outcomes in Prostate Cancer Patients Following Prostatectomy: The ProRehab Study.

PURPOSE: Despite advanced medical treatment options, many prostate cancer patients are still confronted with unfavorable physical and psychological burdens. Physical exercise has proven to be beneficial for prostate cancer patients, yet specific exercise offers are rare. The ProRehab Study aimed to evaluate the exercise program offered in rehabilitative prostate cancer sports groups in Germany and determine whether it is beneficial for patients following prostatectomy. METHODS: Eighty-five prostate cancer patients were recruited for a multicenter, 2-armed, nonrandomized controlled trial 6 to 12 weeks after prostatectomy. The intervention group (n = 56) took part in a 15-month supervised multimodal exercise program. Exercise sessions took place once a week for 60 minutes at a moderate intensity (3.84-4.84 MET-hour). The control group (n = 29) received no intervention. Outcomes included aerobic fitness, activity levels, quality of life, disease- and treatment-related adverse effects, such as urinary incontinence and erectile dysfunction, and relapse-relevant blood values. Intention-to-treat analysis was performed. RESULTS: A significant between-group difference was observed in the urinary symptom score (P = .027). Physical fitness, urinary incontinence, physical, role, emotional, and social functioning, as well as further disease- and treatment-related side effects (dyspnea, urinary, and bowel symptoms) significantly improved within the intervention group. Erectile dysfunction and physical activity levels improved similarly in both groups. CONCLUSIONS: The presented data hint at the potential of rehabilitative sports groups for prostate cancer patients. However, according to the current state of the art, exercise intensity and volume may need to be increased to enhance the effects. A number of shorter studies (8-24 weeks) have proven significant between-group differences in quality of life, incontinence, and fitness outcomes when patients exercised 2 to 3 times per week. This is the first exercise intervention study with prostate cancer patients that was conducted over 15 months. Further studies are necessary to investigate whether prostate cancer patients recover sooner when receiving a supervised exercise program.

The correlation between ECochG parameters and early auditory behavior after cochlear implantation in children.

OBJECTIVE: The individual outcome after cochlear implantation in children with auditory synaptopathy/neuropathy (AS/AN) is difficult to predict. A tool for preoperative assessment would be helpful for counseling parents. This study evaluates the outcome after CI in children with AS/AN and with sensorineural hearing loss (SNHL), and correlates it with the preoperative ECochG results in order to find specific parameters of prognostic value. DESIGN: The improvement of auditory behavior after CI was retrospectively assessed using the LittlEARS questionnaire and quantified in a score (LS). This score was correlated with the CAP/SP ratio in the preoperative ECochG. The score was further correlated with the patient's age six months following CI. STUDY SAMPLE: Nine children with AS/AN were compared to nine children with SNHL. RESULTS: Both groups showed a significant improvement in LS following CI. There was a significant positive correlation between the CAP/SP ratio and the improvement in LS in all children. The correlation between age and LS was significantly negative in the SNHL group and positive in the AS/AN group. CONCLUSION: All children with AS/AN and SNHL benefit to a similar extent from CI. The preoperatively assessed CAP/SP ratio has a prognostic value for the development of auditory behavior following CI.

Is there a difference between active opening of the Eustachian tube in a hypobaric surrounding compared to a hyperbaric surrounding?

INTRODUCTION: The Eustachian tube (ET) is the key to pressure equalization between the middle ear and ambient pressure. To date, little is known about differences of the opening mechanisms under hyper- or hypobaric conditions. Aim of this study was to compare standard ET opening parameters during standardized hypo- and hyperbaric exposures. METHODS: Thirty healthy participants were exposed to a standardized profile of decompression and compression (SPDC) in a hypo-/hyperbaric pressure chamber. Impedance, expressed as tympanic membrane compliance, was recorded at intervals during the excursions from 1 atmosphere absolute (atm abs) to 0.8 and 1.2 atm abs respectively. Parameters for tubal opening were obtained during SPDC: ET opening pressure (ETOP), ET opening duration (ETOD) and ET opening frequency (ETOF), hypobaric (Phase 1) and hyperbaric (Phase 2) data were compared. RESULTS: Mean value for Valsalva maneuver ETOP was 40.10 ± 19.02 mbar in Phase 2 vs. 42.82 ± 21.75 mbar in Phase 1. For ETOD it was 2.80 ± 2.09 seconds in Phase 2 vs. 2.51 ± 1.90 seconds in Phase 1. For swallowing, mean value for ETOP was 33.47 ± 14.50 mbar in Phase 2 vs. 28.44 ± 14.04 in Phase 1. ETOD was 0.82 ± 0.60 seconds in Phase 2 vs. 0.76 ± 0.55 seconds in Phase 1. There was no statistical significance for ETOP, ETOD and ETOF between the two phases. CONCLUSION: No statistical significant difference was evident for active pressure equalization (Valsalva and swallowing) between a hyperbaric setting (dive) and a hypobaric setting (flight) in healthy subjects.