[Introduction of a User-oriented Application for Biometrical Sample Size Calculation in Clinical and Epidemiological Trials]. / Vorstellung eines benutzerfreundlichen Programmes zur biometrischen Fallzahlplanung in klinischen und epidemiologischen Studien.

BACKGROUND: Clinical journals strongly recommend the use of confidence intervals to present study results, since these comprise both the statistical significance and the clinical relevance of a study's outcome. However, the mandatory sample size calculations performed during a study's planning stage are mostly reported via significance test-based approaches, as there are currently only a few methods available for planning approaches via confidence intervals. As a result, many articles show a mismatch between the planning (based on significance tests) and result presentation (based on confidence intervals). To overcome this gap, a user interface will be illustrated that offers the opportunity of sample size calculation both by means of significance tests and confidence intervals, with intuitive access for clinical researchers. MATERIALS AND METHODS: Estimating sample sizes via confidence intervals requires the predetermination of the interval's maximum width, whereas the calculation of sample sizes via significance test has the minimum requirement of the test's statistical power. The resulting sample size formulas are compatible for all practically relevant cases and mainly differ in the specification of the parameters "width" and "power". For the choice of a suitable statistical power, there are established reference values (usually 80 or 90%), while the calculation of sample size by means of confidence intervals is still difficult for clinical researchers, due to the unavailability of guidelines for the choice of the interval width. The application of both approaches is demonstrated by planning a clinical trial on the rotational stability of toric intraocular lenses with or without an implemented capsular tension ring. RESULTS: A user interface was developed to implement both of the publicly accessible approaches for sample size calculation. The interface allows comparison of the approaches based on significance test and confidence interval and their interchangeability for a two-armed clinical trial design. The operator firstly chooses one of the approaches; then the necessary planning information is inputted and the calculated sample size per trial as well as the corresponding planning information for the other approach are provided. CONCLUSION: The presented sample size tool enables an intuitively accessible way to calculate sample sizes both via significance tests and via confidence intervals for two-armed study designs.

[An Illustrated Guidance for the Implementation of Methodological CONSORT Criteria in the Transparent Publication of RCTs in Ophthalmology]. / Umsetzungshilfe zu methodischen Kriterien des CONSORT-Statements zur transparenten Publikation von RCTs in der Augenheilkunde.

The CONSORT Statement (Consolidated Standards of Reporting Trials) recommends an evidence-based, minimum set of recommendations for the standardised and transparent reporting of randomised clinical trials. This statement includes a checklist of 25 items on regulatory and methodological, as well as characteristics of editorial clinical trial design and results. The recommendations help authors of RCT reports to ensure the complete and transparent reporting of design and result determinants with regard to the standards of evidence-based medicine; furthermore, it seeks to enable readers to critically assess and interpret the presented information and possible limitations of the underlying study data. However, it has repeatedly been shown that the implementation of, in particular, the adherence to methodological criteria is a challenge to RCT authors. Therefore, the following overview summarises an illustrated guidance to the minimum necessary information to take into account key methodological items in the CONSORT statement.

[Do Clinical Trial Publications in AMD Healthcare Provide Sufficient Information on the Underlying Samples' Baseline Characteristics to Enable Generalizability Considerations on the Trial Design?] / Berichten RCT-Publikationen zur Versorgung von AMD-Patienten Baseline-Daten zum eingebrachten Patientengut mit Blick auf die Generalisierbarkeit des Studiendesigns?

BACKGROUND: Results of RCTs must enable readers to assess applicability of the presented information into clinical routine. Therefore, the CONSORT statement's item 15 recommends explicit information on (baseline) characteristics for RCT samples. We sought to quantify the adherence to this CONSORT item by evaluation of RCTs on "age-related macular degeneration" (AMD). MATERIALS AND METHODS: A full survey comprised of 132 RCTs (01/2004 - 12/2013). Two parallel independent readers evaluated, and then consented, whether baseline characteristics as recommended were provided in the publication, and whether this information was formally and correctly presented. The evaluation was performed hierarchically in accordance to the sub-criteria of the CONSORT-statement. In the case of formally correct documentation, characteristics for age, gender, the primary clinical endpoint outcome, and the stage of AMD were checked, as well as for systemic or ophthalmological pre-existing conditions. RESULTS: 129 of 132 (98%) publications provided the documentation of baseline data, but only 67 (51%) showed a correct implementation. 77 (58%) RCT reports presented baseline data at study initiation, among which n = 67 (87%) publications presented the data stratified for samples. CONCLUSION: The implementation rate of the CONSORT criterion "baseline data" in publications appeared high. On closer inspection, publications often provided incomplete or even misleading baseline data. As a consequence, everybody in the publication process should be aware of the conditions for publishing.

Correction to: Visual impairment and blindness in institutionalized elderly in Germany.

The original version of this article inadvertently contained a mistake. Authors incorrectly listed in PDF version while correctly presented in the html version.

Visual impairment and blindness in institutionalized elderly in Germany.

PURPOSE: To determine the prevalence of and identify factors associated with visual impairment and blindness in institutionalized elderly in Germany. METHODS: In this prospective multicenter cross-sectional study, ophthalmic health care need and provision were investigated in institutionalized elderly in 32 nursing homes in Germany. All participants underwent a standardized examination including medical and ocular history, refraction, visual acuity testing, tonometry, biomicroscopy, and dilated funduscopy. A standardized questionnaire was used to identify factors associated with eye healthcare utilization, visual impairment and/or blindness. RESULTS: Visual acuity of 566 (94.3%; 413 women and 153 men) of a total of 600 institutionalized elderly was determined. Mean age of the included patients was 82.9 years (± 9.8). Of all participants, 30 (5.3%; 95% CI 3.4-7.2%) were blind and 106 (18.7%; 95% CI 15.5-21.9%) were moderately or severely visually impaired according to the World Health Organization definition. The 136 blind and moderately or severely visually impaired participants were older (OR, Odds Ratio = 1.1, 95% CI 1.0-1.1; p < 0.001), and more likely to have reduced mobility (OR = 12.6, 95% CI 2.8-57.6; p = 0.001). CONCLUSION: A high proportion of blindness and visual impairment was found amongst nursing home residents. Age and reduced mobility were factors associated with an increased likelihood of blindness and visual impairment. Any surveys of blindness and visual impairment excluding nursing homes may considerably underestimate the prevalence of visual impairment and blindness.

Rotation of a toric intraocular lens with and without capsular tension ring: data from a multicenter non-inferiority randomized clinical trial (RCT).

BACKGROUND: Evaluation of clinical outcome in cohorts with versus without simultaneous implantation of a capsular tension ring (CTR) and a toric lens (Tecnis Toric). Main parameter was rotation referring - in contrast to misalignment - to the IOL axis change from immediately after implantation to the final postoperative position. METHODS: Lens position was measured at baseline with the patient still in recumbent position, postoperative rotation was calculated by software. Postoperative evaluation included measurement three months after surgery or prior to an indicated revision surgery. Explorative re-evaluation of the underlying RCT's intent-to-treat population was performed for the entire sample and stratified for cohorts by 95% confidence intervals for binary endpoints' incidences (primary endpoint: absolute postoperative rotation ≤5 degrees; secondary endpoints: absolute deviation between achieved cylinder and target cylinder ≤0.5 dpt, postoperative corrected distance visual acuity (CDVA) ≥ 0.8). Data exploration was based on medians and quartiles. SETTING: Outpatient study sites. DESIGN: Re-evaluation based on data from a multicenter non-inferiority randomized clinical trial (RCT). RESULTS: Sub cohorts (without CTR 89, with CTR 90 patients) did not present clinically relevant differences in preoperative characteristics: revision surgery was performed in 7 cases (3 without and 4 with CTR). Primary endpoint incidences for the total sample, without and with CTR were 90%/89%/90%; cylinder endpoint incidences were 46%/45%/46% and CDVA endpoint incidences 90%/92%/88%. Median absolute rotations were 1.74°/1.79°/1.72°, median absolute cylinder deviations 0.55/0.52/0.55 dpt and median visual acuity 1.0/1.0/1.0. CONCLUSION: No clinically relevant differences between CTR subgroups were found; a satisfying three months rotational stability was achieved. TRIAL REGISTRATION: The trial was registered retrospectively in the trial registry DRKS, trial registration number DRKS00015316 , date of registration 27. August 2018.

23G pars plana vitrectomy for vitreal floaters: prospective assessment of subjective self-reported visual impairment and surgery-related risks during the course of treatment.

PURPOSE: Quantifying the subjective impairment due to floaters based on an indication-specific questionnaire and setting its change between prior to and 3/12 months after elective vitrectomy in relation to surgical risks. METHODS: Single-arm longitudinal observational multicenter study. Sixty-four floater patients underwent 23G pars plana vitrectomy; simultaneous phacoemulsification was excluded. An overall self-rated impairment index (SRI) and sub-indices SRI were calculated on the basis of a modified Visual Quality of Life questionnaire (VQoL), which addresses general vision, glare, near-sight problems and mobility of floaters. SRI ranged from 0 to 100% (maximum impairment). Secondary endpoints included corrected visual acuity and complications. RESULTS: Data were collected prior to and 3 (n = 64) and 12 (n = 62) months after surgery. The median overall SRI improved (44, 12, 11%) with a statistically significant median reduction of 69% (95% confidence interval 50-89%) 3 months postop. The median sub-SRIs improved for glare (50, 17, 17%), near sight problems (50, 17, 8%), and mobility of floaters (43, 5, 0%). Sixteen eyes needed cataract surgery during follow-up (10 showed cataract already prior to vitrectomy). Eight complications were reported (6 intra-operative retinal holes, 2 post-operative retinal detachments). CONCLUSION: For the majority of floater patients, subjective impairment was profoundly reduced by vitrectomy. Benefits of surgery prevailed despite complications.

Multiple endpoints in clinical trials ­ severe adverse event potentials from the medical biometrician's perspective. / Multiple Endpunkte in klinischen Prüfungen Risiken und Nebenwirkungen aus Sicht der Medizinischen Biometrie

The clinical evaluation of medicinal drugs follows strict guidelines both concerning the clinical as well as the pharmaceutical implementation perspective. Furthermore, it underlies similarly rigid implementation guidelines from the medical biometry perspective, pertaining from the choice of minimum necessary patient numbers to the primary statistical evaluation concept. The latter, however, require the explicit parameterization of clinical endpoints, alongside which efficacy and effectiveness of the drug under investigation will then be tested for the trial at hand. In most settings, the choice of these endpoints directly arises from the clinical rationale of the investigation, but is then complemented with a rather rigid recommendation from the trial statistician's perspective, that is the restriction to only one primary clinical endpoint. The use of several parallel clinical endpoints cannot only end up in inconsistent or even contradictory clinical decision rules, but can also have crucial impact on the overall number of patients necessary in the statistical analysis of the clinical trial under consideration. Although the combination of multiple parallel endpoints may provide a solution in some clinical trial settings, the most effective recommendation can be seen in specifying only one primary clinical endpoint of maximum clinical relevance for the therapeutic intention at hand.

A methodological approach to identify external factors for indicator-based risk adjustment illustrated by a cataract surgery register.

BACKGROUND: Risk adjustment is crucial for comparison of outcome in medical care. Knowledge of the external factors that impact measured outcome but that cannot be influenced by the physician is a prerequisite for this adjustment. To date, a universal and reproducible method for identification of the relevant external factors has not been published. The selection of external factors in current quality assurance programmes is mainly based on expert opinion. We propose and demonstrate a methodology for identification of external factors requiring risk adjustment of outcome indicators and we apply it to a cataract surgery register. METHODS: Defined test criteria to determine the relevance for risk adjustment are "clinical relevance" and "statistical significance". Clinical relevance of the association is presumed when observed success rates of the indicator in the presence and absence of the external factor exceed a pre-specified range of 10%. Statistical significance of the association between the external factor and outcome indicators is assessed by univariate stratification and multivariate logistic regression adjustment.The cataract surgery register was set up as part of a German multi-centre register trial for out-patient cataract surgery in three high-volume surgical sites. A total of 14,924 patient follow-ups have been documented since 2005. Eight external factors potentially relevant for risk adjustment were related to the outcome indicators "refractive accuracy" and "visual rehabilitation" 2-5 weeks after surgery. RESULTS: The clinical relevance criterion confirmed 2 ("refractive accuracy") and 5 ("visual rehabilitation") external factors. The significance criterion was verified in two ways. Univariate and multivariate analyses revealed almost identical external factors: 4 were related to "refractive accuracy" and 7 (6) to "visual rehabilitation". Two ("refractive accuracy") and 5 ("visual rehabilitation") factors conformed to both criteria and were therefore relevant for risk adjustment. CONCLUSION: In a practical application, the proposed method to identify relevant external factors for risk adjustment for comparison of outcome in healthcare proved to be feasible and comprehensive. The method can also be adapted to other quality assurance programmes. However, the cut-off score for clinical relevance needs to be individually assessed when applying the proposed method to other indications or indicators.

Analysis of agreement between the German translation of the American Foot and Ankle Society's Ankle and Hindfoot Scale (AOFAS-AHS) and the Foot Function Index in its validated German translation by Naal et al. (FFI-D).

BACKGROUND: Despite its wide use in clinical outcome measurement, there is yet no validated German language version of the AOFAS-AHS available. After finishing cross-cultural adaption of the AOFAS-AHS according to the AAOS guidelines, an analysis of agreement was carried out. METHODS: This was done by means of the 18-item Foot Function Index in its validated German translation by Naal et al. (FFI-D). The results of 91 orthopedic patients as well as healthy persons in both scores were then compared intraindividually. The cohort consisted of 46 individuals with hindfoot disorders and 45 persons without any hindfoot complaints. The FFI-D-Score was linearly transformed in the range 0-100 points of the AOFAS. RESULTS: Encouraging correlation was then found for the patients with hindfoot disorders (Spearman's correlation 0.73 (95% CI 0.52-0.85); a median deviation of -2 points (interquartile range -13 points; +13 points) in patients with hindfoot disorders implied good median intraindividual score concordance. However, with 30 of these 46 patients showing score deviations beyond or below a pre-specified ±10 points range of clinically tolerable deviations, the scores cannot be considered exchangeable. CONCLUSION: Although the agreement analysis was performed for the German translation of the two questionnaires, analogous results can be expected also for other languages. It should be noted that the results do not allow for judging which of the scores is better suited to give a valid statement on patient outcome in treatment of hindfoot disorders. To verify which of these two scores is better suited to represent hindfoot-dysfunction a subsequent study using instrumental gait analysis and surface EMG is being carried out.

The First SICOT Oral Presentation Award 2011: imageless computer-assisted femoral component positioning in hip resurfacing: a prospective randomised trial.

PURPOSE: The aim of the study was to evaluate the effects of imageless computer-assisted surgery (CAS) on the accuracy of positioning of the femoral component and on the short-term clinical outcome in hip resurfacing (HR) using a randomised prospective design. METHODS: A total of 75 consecutive patients undergoing HR were randomly allocated to CAS and conventional implantation, respectively. Preoperatively and six months post-operatively standardised pelvic anteroposterior X-ray images, the total Western Ontario and McMaster Universities Osteoarthritis Index, the Harris Hip Score and the EQ-5D utility index were evaluated in a blinded manner. The primary end point of the study was a post-operative femoral component malpositioning in five degrees or more either varus or valgus absolute deviation from the planned stem shaft angle. RESULTS: Patient demographics and algofunctional scores did not differ between the CAS and conventional implantation samples. Using CAS fewer femoral components were positioned in five or more degrees absolute deviation (4/37 vs 12/38, Fisher's exact p = 0.047; 95 % confidence interval for the primary end point's incidence difference: +3 %; +39 %); the respective incidences of five or more degrees of varus deviation were 0/37 vs 5/38. One conversion to a stemmed prosthesis (CAS group) was performed for periprosthetic femoral neck fracture. Radiological signs of superolateral femoral neck/implant impingement were observed in two cases (one CAS-based and one conventional implantation). CONCLUSIONS: The accuracy of femoral HR component positioning was significantly improved using CAS. However, one major complication necessitated early revision in the CAS group at six months of observation. Apart from that adverse event no inter-group differences were observed for the short-term clinical outcome. Future studies need to address the clinical long-term relevance of CAS in HR.

Determination of valid benchmarks for outcome indicators in cataract surgery: a multicenter, prospective cohort trial.

OBJECTIVE: To evaluate a systematic approach to derive valid benchmarks for 2 outcome indicators intended to ascertain quality in cataract surgery and to propose benchmark levels drawn from the study results. DESIGN: Prospective, multicenter cohort trial. PARTICIPANTS: A total of 1685 patients (206-239 eyes per trial site) were recruited consecutively at 7 study sites. The patients featured age-related cataracts and were undergoing unilateral cataract surgery in the period between January 2007 and August 2008. METHODS: Only patients with uncomplicated age-related cataracts were included. Cataract surgery was performed by phacoemulsification. The SN60AT (Alcon, Inc., Fort Worth, TX) intraocular lens (IOL) was used as a study lens. The IOL power was calculated using the SRK-T formula with a standardized A constant. Biometry was performed with the IOL Master (Carl Zeiss Meditex, Jena, Germany). Only highly experienced senior surgeons were involved. MAIN OUTCOME MEASURES: The outcome indicators 1 month and 3 months after surgery were the respective achievement of: (1) maximum absolute deviation of 0.5 diopter (D) between target refraction and postoperative spherical equivalent (primary end point, refractive accuracy); (2) best-corrected visual acuity of at least 0.8 (secondary end point, visual acuity outcome). RESULTS: In the pooled data, maximum absolute deviation of ± 0.5 D from target refraction was achieved in 80% (95% confidence interval, 78%-82%) of cases. Visual acuity of 0.8 or more was reached in 87% (95% confidence interval, 80%-93%) of cases. The results from the trial centers differed significantly in the outcomes of the primary and secondary end points (P<0.001). CONCLUSIONS: The study quantified benchmark levels for 2 outcome indicators in a standardized cataract surgery procedure. External confounding factors such as the comorbidity of patients, which cannot be influenced by the surgeon, were excluded. The derived benchmarks selectively illustrate the quality of the surgery and are superior to success rates published in the literature from unspecific data collections. This method is more suited for improving outcome quality by benchmarking. General methodologic problems are discussed, leading to recommendations for future study designs. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cost effectiveness of total knee arthroplasty from a health care providers' perspective before and after introduction of an interdisciplinary clinical pathway--is investment always improvement?

BACKGROUND: Total knee arthroplasty (TKA) is an effective, but also cost-intensive health care intervention for end stage osteoarthritis. This investigation was designed to evaluate the cost-effectiveness of TKA before versus after introduction of an interdisciplinary clinical pathway from a University Orthopedic Surgery Department's cost perspective as an interdisciplinary full service health care provider. METHODS: A prospective trial recruited two sequential cohorts of 132 and 128 consecutive patients, who were interviewed by means of the WOMAC questionnaire. Direct process costs from the health care providers' perspective were estimated according to the German DRG calculation framework. The health economic evaluation was based on margiual cost-effectveness ratios (MCERs); an individual marginal cost effectiveness relation≤100 € per % WOMAC index increase was considered as primary endpoint of the confirmatory cohort comparison. The interdisciplinary clinical pathway under consideration primarily consisted of a voluntary preoperative personal briefing of patients concerning postoperatively expectable progess in health status and optimum use of walking aids after surgery. All patients were supplied with written information on these topics, attendance of the personal briefing also included preoperative training for postoperative mobilisation by the Department's physiotherapeutic staff. RESULTS: An individual marginal cost effectiveness relation≤100 €/% WOMAC index increase was found in 38% of the patients in the pre pathway implementation cohort versus in 30% of the post pathway implementation cohort (Fisher p=0.278). Both cohorts showed substantial improvement in WOMAC scores (39 versus 35% in median), whereas the cohort did not differ significantly in the median WOMAC score before surgery (41% for the pre pathway cohort versus 44% for the post pathway cohort). Despite a locally significant decrease in costs (4303 versus 4194 € in median), the individual cost/benefit relation became worse after introduction of the pathway: for the first cohort the MCER was estimated 108 € per gained % WOMAC index increase (86-150 €/%) versus 118 €/% WOMAC gain (93-173 €/%) in the second cohort after pathway implementation. In summary, the proposed critical pathway for TKA could be shown to be significantly cost efficient, but not cost effective concerning functional outcome, when the above individual marginal cost effectiveness criterion was concentrated on. CONCLUSIONS: The introduction of an interdisciplinary clinical pathway does not necessarily improve patient related outcomes. On the contrary, cost effectiveness from the health care providers' perspective may even turn out remarkably reduced in the setting considered here (functional outcome assessment after treatment by a full service health care provider).

Natriuretic peptide levels in intrauterine growth-restricted fetuses with absent and reversed end-diastolic flow of the umbilical artery in relation to ductus venosus flow velocities.

OBJECTIVE: To determine if changes in natriuretic peptide levels [propeptide of atrial natriuretic peptide (proANP) and N-terminal propeptide of brain natriuretic peptide (NT-proBNP)] can be demonstrated in fetuses with serious growth restriction and Doppler ultrasonographic findings of hemodynamic compromise. METHOD: Natriuretic peptides of the umbilical vein (proANP and NT-proBNP), arterial and venous blood gases, as well as lactate levels of the umbilical vein were determined in 38 appropriate for gestational age (AGA) fetuses, and 24 intrauterine growth-restricted (IUGR) fetuses with absent (zero-flow) and 17 IUGR fetuses with reversed end-diastolic flow (reverse-flow) of the umbilical artery. RESULTS: A continuous increase in natriuretic peptides in the presence of progressive deterioration was shown. ANP concentrations were significantly lower in the AGA group (mean 818 fmol/mL; range 508-991 fmol/mL) than the zero-flow group (mean 19,680 fmol/mL; range 13,680-25,080 fmol/mL) and the reverse-flow group (mean 33,880 fmol/mL; range 24,365-41,786 fmol/mL). Significant differences were further demonstrated in BNP concentrations of the AGA group (mean 32 fmol/L; range 25-38 fmol/L), zero-flow group (mean 1191 fmol/L; range 908-1655 fmol/L), and reverse-flow group (mean 3063 fmol/L; range 1281-4968 fmol/L). Additionally, significant differences in lactate concentrations were observed for the three groups: AGA, 2.6 mmol/L (range 2-3 mmol/L); zero-flow group, 4.1 mmol/L (range 3.3-5 mmol/L); and reverse-flow group, 7.7 mmol/L (range 5.9-13.7 mmol/L). Increased ANP levels correlated with the arterial base excess and lactate concentrations, as well as with the flow velocities in the ductus venosus during atrial contraction (a-wave), and both ductus venosus indices (S-a)/D and (S-a)/V(mean). No correlations were established for BNP. CONCLUSIONS: As components of a compensatory mechanism, natriuretic peptides exert an influence on the cardiovascular function of the fetus.

Ink-jet printout of radiographs on transparent film and glossy paper versus monitor display: an ROC analysis.

The aim of this study was to compare the depiction ability of small grayscale contrasts in ink-jet printouts of digital radiographs on different print media with CRT monitor. A CCD-based digital cephalometric image of a stepless aluminum wedge containing 50 bur holes of different depth was cut into 100 isometric images. Each image was printed on glossy paper and on transparent film by means of a high-resolution desktop inkjet printer at specific settings. The printed images were viewed under standardized conditions, and the perceptibility of the bur holes was evaluated and compared to the perceptibility on a 17-in CRT monitor. Thirty observers stated their blinded decision on a five-point confidence scale. Areas (Az) under receiver operating characteristics curves were calculated and compared using the pair wise sign tests. Overall agreement was estimated using Cohen's kappa device and observer bias using McNemar's test. Glossy paper prints and monitor display revealed significantly higher (P < 0.001) average Az values (0.83) compared to prints on transparent film (0.79), which was caused by higher sensitivity. Specificity was similar for all modalities. The sensitivity was dependent on the mean gray scale values for the transparent film.

Significant differences between Crohn's disease and ulcerative colitis regarding the impact of body mass index and initial disease activity on responsiveness to azathioprine: results from a European multicenter study in 1,176 patients.

In a survey comprising 1,176 patients with inflammatory bowel disease (IBD) we recently showed that azathioprine (AZA) beyond 4 years is beneficial in ulcerative colitis (UC) patients and in a subset of Crohn's disease (CD) patients. Here, we show for the first time that azathioprine responsiveness depends on body mass index (BMI). The relationship is reciprocal in UC and CD, with a better outcome in UC patients with a BMI<25 and in CD patients with a BMI>25. These observations are particularly interesting considering the evolving concept of a relationship between fatty metabolism and immune regulation. Additionally, we show that CD patients, but not UC patients, respond better to AZA when it is started in clinical remission. This observation may support data favouring a "hit hard and early" regime in CD. Finally, we were able to demonstrate a decrease in the incidence of CD-related complications requiring surgery through treatment with AZA.

Rotational alignment of the tibial component in total knee arthroplasty is better at the medial third of tibial tuberosity than at the medial border.

BACKGROUND: Correct rotational alignment of the femoral and tibial component is an important factor for successful TKA. The transepicondylar axis is widely accepted as a reference for the femoral component. There is not a standard reference for the tibial component. CT scans were used in this study to measure which of 2 tibial landmarks most reliably reproduces a correct femoro-tibial rotational alignment in TKA. METHODS: 80 patients received a cemented, unconstrained, cruciate-retaining TKA with a rotating platform. CT scans were performed 5-7 days postoperatively but before discharge. The rotational mismatch between the femoral and tibial components was measured. Furthermore, the rotational variance between the transepicondylar line, as a reference for the orientation of the femoral component and different tibial landmarks, was measured. RESULTS: There was notable rotational mismatch between the femoral and tibial components. The median mismatch was 0 degrees (range: 16.2 degrees relative external to 14.4 degrees relative internal rotation of the femoral component).Using the transepicondylar line as a reference for femoral rotational alignment and the medial third of the tuberosity as a reference for tibial rotational alignment, 67.5% of all TKA had a femoro-tibial variance within +/- 5 degrees, 85% within +/- 10 degrees and 97.5% within +/- 20 degrees. Using the medial border of the tibial tubercle as a reference this variance was greater, only 3.8% had a femoro-tibial variance within +/- 5 degrees, 15% within +/- 10 degrees and 68.8% within +/- 20 degrees. CONCLUSION: Using fixed bone landmarks for rotational alignment leads to a notable variance between femoral and tibial components. Referencing the tibial rotation on a line from the medial third of the tibial tubercle to the center of the tibial tray resulted in a better femoro-tibial rotational alignment than using the medial border of tibial tubercle as a landmark. Surgeons using fixed bearings with a high rotational constraint between the inlay and the femoral component should be aware of this effect to avoid premature polyethylene wear. TRIAL REGISTRATION: Clinical trials registry NCT01022099.

[Influence of impact factor on reporting sample size calculations in publications on studies exemplified by AMD treatment : Cross-sectional investigation on the presence of sample size calculations in publications of RCTs on AMD treatment in journals with low and high impact factors]. / Einfluss des Impact-Faktors auf das Berichten einer Fallzahlplanung in Publikationen zu Studien am Beispiel der AMD-Therapie : Querschnittuntersuchung zum Vorliegen von Fallzahlplanungen in Publikationen von RCTs zur AMD-Therapie in Zeitschriften mit hohem und niedrigem Impact-Faktor.

BACKGROUND: For scientific and ethical reasons randomized controlled clinical trials (RCTs) should be based on a sample size calculation. The CONSORT statement, an established publication guideline for transparent study reporting, requires a sample size calculation in every study publication. OBJECTIVE: The availability of sample size calculations in RCT publications on treatment of age-related macular degeneration (AMD) was investigated. The primary hypothesis of this investigation compared the prevalence of reported sample size calculations between journals with higher (≥5) versus lower (<5) impact factors (IF). MATERIAL AND METHODS: It was examined whether information on sample size calculation was available in a series of 97 publications of RTCs on AMD treatment published between 2004 and 2014. RESULTS: Only 46 out of 97 (47%) study publications provided information on the reason for the number of patients enrolled. The comparison of publications from journals with an IF ≥ 5 (63%, 30) and from journals with an IF < 5 (40%, 67) showed a statistically significant difference of 23% in the frequencies of available sample size calculations (95% confidence interval, CI 2%; 44%). Of the publications published before 2010, 43% reported a sample size calculation versus 51% of the publications afterwards. CONCLUSION: Publications in journals with higher IF more frequently reported a sample size calculation. More than 50% of the publications did not report any sample size calculation. Authors and reviewers of publications should pay more attention to the explicit reporting of sample size calculations.

Meta-analysis of the concordance of Icare® PRO-based rebound and Goldmann applanation tonometry in glaucoma patients.

BACKGROUND: The Icare® PRO rebound tonometer is being promoted as a patient-friendly device for glaucoma detection and monitoring, allowing rapid and accurate intraocular pressure measurement avoiding anaesthesia. The aim of this systematic review was to examine the concordance of Icare® PRO and Goldmann applanation tonometry in glaucoma patients. METHODS: The German and English literature research was carried out using PubMed and Cochrane Library between January 2010 and March 2018. Method comparison trials in a paired sample study design were identified. Search criteria were 'Icare PRO', 'Rebound', 'Goldmann' and 'Applanation'. Adult patients with glaucoma of any aetiology were included. The intraindividual intraocular pressure deviation between Icare® PRO and Goldmann applanation tonometry (mm Hg) served as primary endpoint, parameterized by the reported mean differences. For each study, an asymptotic 95% confidence interval was derived. The overall intraocular pressure meta-difference (Icare® PRO-Goldmann applanation tonometry) and 95% confidence interval were estimated using the random effect model. RESULT: Of 147 publications, 6 studies (672 eyes) were included after reviewing. Four studies showed an intraocular pressure underestimation by the Icare® PRO, two an overestimation. The meta-difference (Icare® PRO-Goldmann applanation tonometry = -0.14 mm Hg; 95% confidence interval: (-0.43 mm Hg; 0.15 mm Hg)) indicated a non-significant, clinically irrelevant mean deviation (p = 0.335). The devices showed good agreement, but there was a strong heterogeneity between the studies (I² = 77%): two studies presented a significant difference (Icare® PRO-Goldmann applanation tonometry), however, with deviations in opposite directions. CONCLUSION: Although the manufacturer advertises the Icare® PRO as a 'tonometer with superior accuracy', the present review could neither confirm nor deny considerable agreement between Goldmann applanation tonometry and Icare® PRO in glaucomatous patients.

Optical coherence tomography of macular thickness after biaxial vs coaxial microincision clear corneal cataract surgery.

PURPOSE: To evaluate macular thickness changes after biaxial microincision versus coaxial small incision cataract surgery using optical coherence tomography (OCT). METHODS: This prospective, randomized, marked study comprised 70 patients (70 eyes) undergoing biaxial microincision surgery or conventional coaxial phacoemulsification. Patients were evaluated by Stratus OCT preoperatively and 1 day, 4 weeks, and 8 weeks postoperatively. Best-corrected visual acuity (BCVA), phacoemulsification power, and effective phacoemulsification time (EPT) were evaluated. RESULTS: In the biaxial group, median foveal thickness changed from 160 microm preoperatively to 168 microm 8 weeks postoperatively (p=0.018), while median macular volume increased from 2.43 mm3 to 2.57 mm3 (p<0.001). In the coaxial group, median foveal thickness increased from 164 microm preoperatively to 170 microm 8 weeks postoperatively (p=0.082), while median macular volume changed from 2.45 mm3 to 2.55 mm3 (p<0.001). No significant differences in the intraindividual increase of foveal thickness and macular volume were found between groups at 8 weeks. A statistically significant difference between groups was found in median foveal thickness at day 1 postoperatively (p=0.027). No significant differences between groups in median macular volume were found at day 1 or at 4 and 8 weeks postoperatively. Median phacoemulsification power was 7.1% and EPT 2.4 seconds in the biaxial group versus 10.6% and 3.2 seconds in the coaxial group (p<0.001 and p=0.078). CONCLUSIONS: No clinically relevant differences in foveal thickness or macular volume were observed after biaxial microincision and coaxial small incision clear corneal cataract surgery. The blood-retinal barrier did not seem to be influenced by either procedure.