What causes the death of patients with cutaneous squamous cell carcinoma? A prospective analysis in 1400 patients.

INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is a common tumor of elderly Caucasian patients. METHODS: Competing multivariable risk models to analyze different types of cSCC associated death (local infiltration [LI], locoregional [LR], and distant metastases [DM]) in terms of prognostic factors. RESULTS AND DISCUSSION: 1400 patients were analyzed. In the adjusted multivariable subdistribution hazard approach for tumor volume, the best model for death of cSCC overall revealed the presence of desmoplasia (HR 4.52; p < 0.001), bone invasion (HR 10.06; p < 0.01), and immunosuppression (HR 3.19; p = 0.003) as significant factors. Death due to LI indicated desmoplasia (HR 15.39; p < 0.01) and bone invasion (HR 16.9; p < 0.001) as significant factors. For death by LM, immunosuppression with a HR of 3.27; p = 0.004 was the only significant prognostic factors as well as in death by DM with a HR of 4.54; p = 0.02. CONCLUSIONS: The three types of death caused by cSCC can be distinguished based on risk factors with different weights. Patients with these factors should be monitored closely.

Measles in the European past: outbreak of severe measles in an isolated German village, 1861.

OBJECTIVES: We examined measles mortality in the European past in an outbreak in an isolated German village, Hagelloch, in 1861. METHODS: Pfeilsticker's contemporary thesis was used to describe the measles case fatality ratio (CFR) and complications. Data on onset of prodromes and rash was used to determine index cases and secondary cases of measles within the household. The church register provided information on survival in 1862. RESULTS: The epidemic affected nearly all children under 14 years of age. The overall CFR was 6.4%(12/187), and 10%(7/70) for children under five years of age; 44% of children were secondary cases (82/187). Secondary cases had higher CFR than index cases (RR = 3.03 (95% CI: 0.91-10.07). Boys had higher CFR than girls (RR = 4.46 (1.03-19.22)). Boys infected by a girl had higher CFR than boys infected by other boys (RR = 6.30 (1.18-85.64)). Children who survived measles virus infection in 1861, did not have higher mortality in the following year compared with those who had not had measles in 1861 (RR = 0.24 (0.07-0.82)). CONCLUSIONS: Severe measles in the European past had determinants similar to those observed more recently in low-income countries. BRIEF SUMMARY: The measles case fatality was 6% in rural Germany in 1861. Mortality was highest for boys infected in the household by a girl. There was no excess mortality after the acute phase of measles infection.

Safely Inserting Neonatal Chest Drains.

BACKGROUND: Inserting a chest drain for a left-sided neonatal pneumothorax carries a risk of penetrating the pericardium. We identified reference ranges for the chest wall thickness (CWT) and distance between the pericardium and parietal pleura to improve safety of chest tube insertion. METHOD: We prospectively measured the CWT using ultrasound in 20 neonates (body weight [BW] 640-2,700 g, age <10 days) at the usual site of puncture in the 4th and 5th intercostal space (ICS). Furthermore, we measured the minimal distance between the parietal pleura and the cardiac silhouette in 131 neonatal chest X-rays (birth weight, 420-4,930 g [divided into 11 weight groups]; age <10 days). Both data sets were transformed into weight-dependent percentiles (Ps). We considered the difference between the sum of P 2.5 for the CWT plus P 2.5 for pleura-heart distance minus P 97.5 for the CWT as a safe corridor for placing the tip of the needle. RESULTS: At both ICSs, curves for the above metrics did not cross, indicating a narrow but safe corridor for each BW with at least 97.5% probability. This safety corridor was 4.6-5.2 mm wide for the 4th and 2.8-3.4 mm for the 5th ICS. CONCLUSION: These data offer a reference for left-sided chest drain insertion for BW <2,700 g, which may help to improve safety of the procedure.

Observational study on the influence of averaging time on oximetry results in infants and children.

AIM: Oximetry values are influenced by the averaging time (AT) used. We aimed to evaluate the effect of different ATs on number, duration, mean single event and total integral of desaturations in preterm infants and children to convert between parameters obtained with different ATs. METHODS: In a prospective observational study, 49 children underwent sleep laboratory-based polysomnography and 15 preterm infants were studied in the intensive care unit. Their raw red-to-infrared-saturation-data were reprocessed using seven different ATs (3-16 seconds). Desaturation thresholds were <80% (infants) and <90% (children), conversion formulas and their median percentage errors were calculated. RESULTS: We found a linear relationship between the logarithms of the ATs and those of the desaturation parameters, leading to a conversion formula with different exponents. Based on this relationship, the number of desaturations decreased from AT = 3s to AT = 16s by factor 0.28 (children) and 0.18 (infants); total oxygen saturation integral decreased by factor 0.72 (children) and 0.48 (infants). The desaturation duration increased by factor 1.89 (children) and 3.34 (infants). CONCLUSION: The number and total integral decreased, but the duration and mean single event integral increased with increasing AT. These changes were stronger in infants. Conversion formulas may facilitate comparisons between studies using different averaging times.

Short-term Pasteurization of Breast Milk to Prevent Postnatal Cytomegalovirus Transmission in Very Preterm Infants.

BACKGROUND: Postnatally acquired cytomegalovirus (pCMV) infection through breast milk (BM) may cause severe illness and even death, yet BM is advantageous for preterm infants. Therefore, effective methods to prevent CMV transmission are needed. METHODS: To assess the effectiveness of short-term pasteurization (62°C for 5 seconds) in preventing CMV transmission via BM in preterm infants. Design: Prospective interventional bicentric cohort study with infant enrollment between 6/2010 and 1/2012. A cohort from the Tuebingen neonatal intensive care unit (NICU) from 1995-1998 served as historical controls. Differences in CMV transmission were compared with reference to the cumulative time at risk for CMV transmission. Setting: Two German level-3 NICUs. Eighty-seven preterm infants of 69 CMV immunoglobulin G-positive mothers with birth weight <1500 g or gestational age <32 weeks and 83 historical controls were included. Intervention: BM samples were short-term pasteurized from postnatal day 4 to discharge. Primary endpoint: CMV status at discharge, evaluated by polymerase chain reaction and short-term microculture from urine. RESULTS: Two of 87 (2.3%) study infants had a pCMV transmission. This compared to 17 of 83 (20.5%) controls. Total time under risk for infection was 9.6 years vs 10.0 years in controls, yielding an incidence of 0.21/year (95% confidence interval [CI], 0.03 to 0.75/year) vs 1.70/year (95% CI, 0.99 to 2.72/year), respectively. The risk ratio controls vs study infants was 8.3 (95% CI, 2.4 to 52.4) according to Cox proportional hazard model (P = .0003). CONCLUSIONS: Short-term pasteurization significantly reduces the incidence of pCMV infection through BM in the NICU. CLINICAL TRIALS REGISTRATION: NCT01178905.

Karl-Peter Hadeler: His legacy in mathematical biology.

Karl-Peter Hadeler is a first-generation pioneer in mathematical biology. His work inspired the contributions to this special issue. In this preface we give a brief biographical sketch of K.P. Hadelers scientific life and highlight his impact to the field.

Genetic alterations driving metastatic colony formation are acquired outside of the primary tumour in melanoma.

Mouse models indicate that metastatic dissemination occurs extremely early; however, the timing in human cancers is unknown. We therefore determined the time point of metastatic seeding relative to tumour thickness and genomic alterations in melanoma. Here, we find that lymphatic dissemination occurs shortly after dermal invasion of the primary lesion at a median thickness of ~0.5 mm and that typical driver changes, including BRAF mutation and gained or lost regions comprising genes like MET or CDKNA2, are acquired within the lymph node at the time of colony formation. These changes define a colonisation signature that was linked to xenograft formation in immunodeficient mice and death from melanoma. Thus, melanoma cells leave primary tumours early and evolve at different sites in parallel. We propose a model of metastatic melanoma dormancy, evolution and colonisation that will inform direct monitoring of adjuvant therapy targets.

The sentinel lymph node spread determines quantitatively melanoma seeding to non-sentinel lymph nodes and survival.

INTRODUCTION: Complete lymph node dissection (CLND) after a positive sentinel node (SN) biopsy provides important prognostic information in melanoma patients but has been questioned for therapeutic use recently. We explored whether quantification of the tumour spread to SNs may replace histopathology of non-sentinel nodes (NSNs) for staging purposes. PATIENTS AND METHODS: We quantified melanoma spread in SNs and NSNs in 128 patients undergoing CLND for a positive SN. In addition to routine histopathology, one-half of each of all 1496 SNs and NSNs was disaggregated into a single cell suspension and stained immunocytochemically to determine the number of melanoma cells per 106 lymph node cells, i.e. the disseminated cancer cell density (DCCD). RESULTS: We uncovered melanoma spread to NSNs in the majority of patients; however, the tumour load and the proportion of positive nodes were significantly lower in NSNs than in SNs. The relation between SN and NSN spread could be described by a mathematical function with DCCDNSN = DCCDSNc/101-c (c = 0.69; 95% confidence interval [CI]: 0.62-0.76). At a median follow-up of 67 months, multivariable Cox regression analyses revealed that DCCDSN (p = 0.02; HR 1.34, 95% CI: 1.05-1.71) and the total number of pathologically positive nodes (p = 0.02; HR 1.53, 95% CI: 1.07-2.22) were significant risk factors after controlling for age, gender, thickness of melanoma and ulceration status. A prognostic model based on DCCDSN and melanoma thickness predicted outcome as accurately as a model including pathological information of both SNs and NSNs. CONCLUSION: The assessment of DCCDSN renders CLND for staging purposes unnecessary.

The epidemiological models of Karl-Peter Hadeler.

The most frequently cited articles out of KP Hadeler's 45 papers with epidemiological applications are summarized. Parasitic diseases which increase the death rate of the hosts proportional to the integer number of parasites present were described by integral equations for the generating function of the age- and time-dependent number of parasites. A model was derived for a population structured by the continuous level of parasitic infection. Stimulated by the spread of AIDS a new class of epidemic models was developed which take into account explicitly the formation and separation of pairs. For predator-prey populations with parasitic infections threshold conditions for the persistence of the predator were derived. The interaction of epidemics and demography was analysed. Several epidemiological conditions led to backward bifurcations associated with multiple infective stationary states.

Case fatality models for epidemics in growing populations.

The asymptotically homogeneous SIR model of Thieme (1992) for growing populations, with incidence depending in a general way on total population size, is reconsidered with respect to other parameterizations that give clear insight into epidemiological relevant relations and thresholds. One important feature of the present approach is case fatality as opposed to differential mortality. Although case fatality models and differential mortality models are equivalent via a transformation in parameter space, the underlying ideas and the dynamic behaviors are different, e.g. the basic reproduction number depends on differential mortality but not on case fatality. The persistent distributions and exponents of growth of infected solutions are computed and discussed in terms of the parameters. The notion of asymptotically exponentially growing state (as opposed to stationary state or exponential solution) coined by Thieme is interpreted in terms of stability theory. Of some interest are limiting cases of models without recovery where two infected solutions exist.

Three-Dimensional Normal Facial Growth from Birth to the Age of 7 Years.

BACKGROUND: With the advent of computer-assisted three-dimensional surface imaging and rapid data processing, oral and maxillofacial surgeons and orthodontists are enabled to analyze facial growth three dimensionally. Normative data, however, are still rare and inconsistent. The aim of the present study was to establish a valid reference system and to give normative data for facial growth. METHODS: Three-dimensional facial surface images were obtained from 344 healthy Caucasian children (aged 0 to 7 years). The images were put in correspondence by means of six landmarks close to the skull base (exocanthion, endocanthion, otobasion inferius). Growth curves for 21 landmarks were estimated in the three dimensions. RESULTS: Facial regions close to the skull base (orbit and ear) showed a biphasic growth pattern, with accelerated growth during the first year of life that subsided to a decreased and linear velocity thereafter. Landmarks on the nose, lips, and chin demonstrated either a curvilinear or a linear growth pattern. CONCLUSIONS: The rapid increase of the orbit and ear region in infancy is a secondary phenomenon to the rapid growth of the neurocranium during the first year of life. Thereafter, maxillary and mandibular growth prevails. The present study gives three-dimensional normative data for an expanded growth span between birth and childhood.

Quantitative measurement of melanoma spread in sentinel lymph nodes and survival.

BACKGROUND: Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival. METHODS AND FINDINGS: We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories. CONCLUSIONS: Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.

A conversion formula for comparing pulse oximeter desaturation rates obtained with different averaging times.

OBJECTIVE: The number of desaturations determined in recordings of pulse oximeter saturation (SpO2) primarily depends on the time over which values are averaged. As the averaging time in pulse oximeters is not standardized, it varies considerably between centers. To make SpO2 data comparable, it is thus desirable to have a formula that allows conversion between desaturation rates obtained using different averaging times for various desaturation levels and minimal durations. METHODS: Oxygen saturation was measured for 170 hours in 12 preterm infants with a mean number of 65 desaturations <90% per hour of arbitrary duration by using a pulse oximeter in a 2-4 s averaging mode. Using 7 different averaging times between 3 and 16 seconds, the raw red-to-infrared data were reprocessed to determine the number of desaturations (D). The whole procedure was carried out for 7 different minimal desaturation durations (≥ 1, ≥ 5, ≥ 10, ≥ 15, ≥ 20, ≥ 25, ≥ 30 s) below SpO2 threshold values of 80%, 85% or 90% to finally reach a conversion formula. The formula was validated by splitting the infants into two groups of six children each and using one group each as a training set and the other one as a test set. RESULTS: Based on the linear relationship found between the logarithm of the desaturation rate and the logarithm of the averaging time, the conversion formula is: D2 = D1 (T2/T1)(c), where D2 is the desaturation rate for the desired averaging time T2, and D1 is the desaturation rate for the original averaging time T1, with the exponent c depending on the desaturation threshold and the minimal desaturation duration. The median error when applying this formula was 2.6%. CONCLUSION: This formula enables the conversion of desaturation rates between different averaging times for various desaturation thresholds and minimal desaturation durations.

Complication rates and outcomes stratified by treatment modalities in proximal humeral fractures: a systematic literature review from 1970-2009.

BACKGROUND: The optimal treatment of complex, displaced proximal humeral fractures is controversial. A systematic literature review of the time period from 1970 to 2009 was conducted. The purpose was to evaluate the clinical success and complications of the available treatment modalities to determine specific treatment recommendations for the different fracture patterns. METHODS: The databases (PubMed/EMBASE) were searched for the time period (01/1970-09/2009). Study quality, treatment modalities, classification, outcome scores and complications of 200 publications including 9377 patients were analyzed. Interventions were compared by analysis of variance with subsequent Tukey's-test. Complication rates among methods were compared by using Pearson's-chi-square-test and pairwise comparisons using Fisher's-two-tailed-exact-test. RESULTS: Hemiarthroplasty, angle-stable plate and non-operative treatment were used for 63% of the follow-up-patients. For 3- and 4-part fractures, patients with hemiarthroplasty [3-Part: 56.4 (lower/upper 95% confidence interval (CI): 43.3-68.7); 4-Part: 49.4 (CI: 42.2-56.7)] received a lower score than different surgical head-preserving methods such as ORIF [3-Part: 82.4 (CI: 76.6-86.9); 4-Part: 83.0 (CI:78.7-86.6)], intramedullary nailing [3-Part: 79.1 (CI:74.0-83.4)] or angle-stable plates [4-Part: 66.4 (CI: 59.7-72.4)].The overall complication rate was 56%. The most common complications were fracture-displacement, malunion, humeral head necrosis and malreduction. The highest complication rates were documented for conventional plate and hemiarthroplasty and for AO-C, AO-A, for 3- and 4-part fractures. Only 25% of the data were reported with detailed classification results and the corresponding outcome scores. DISCUSSION: Despite the large amount of patients included, it is difficult to determine adequate recommendations for the treatment of proximal humeral fractures because a relevant lack of follow-up data impaired subsequent analysis. For displaced 3- and 4-part fractures head-preserving therapy received better outcome scores than hemiarthroplasty. However, a higher number of complications occurred in more complex fractures and when hemiarthroplasty or conventional plate osteosynthesis was performed. Thus, when informing the patient for consent, both the clinical results and the possibly expected complications with a chosen treatment modality should be addressed.

Performance of the Elecsys Rubella IgG assay in the diagnostic laboratory setting for assessment of immune status.

Rubella in early pregnancy bears a high risk for congenital defects (e.g., cataracts, hearing loss, and heart disease) and for long-term sequelae in the newborn. Despite implementation of vaccination programs in many regions, the threat of devastating consequences from congenital rubella virus infection remains and careful screening of maternal immune status before and during pregnancy helps to reduce the risk. This study compared the performance of the Elecsys Rubella IgG assay with that of other assays routinely used for screening. Samples from 1,090 women undergoing routine antenatal care were tested using the Elecsys and Enzygnost Rubella IgG assays and the hemagglutination inhibition test. Samples with hemagglutination inhibition titers of <32 (n = 148) were additionally tested using the Vidas, AxSYM, Liaison, and Architect Rubella IgG assays. Agreement of qualitative results from the Elecsys, Enzygnost, and hemagglutination inhibition assays was good in all samples. All assays showed 100.0% specificity. In samples with hemagglutination inhibition titers of <32, the Elecsys, AxSYM, and Enzygnost assays showed higher sensitivity (>90.0%) than the other immunoassays (78.6 to 82.4%). The Elecsys assay reported significantly higher rubella virus IgG levels than the other immunoassays across the whole set of 1,090 samples, with the largest bias and deviation from limits of agreement in Bland-Altman analysis. In conclusion, the Elecsys assay is highly sensitive and specific with regard to qualitative results and suitable for routine automated screening. However, given the considerable variation between quantitative results from different immunoassays, testing methods should be documented and the same assay used throughout an individual's antenatal follow-up wherever possible.

Three-dimensional assessment of facial development in children with unilateral cleft lip with and without alveolar cleft.

Children with cleft lip or cleft lip and alveolus represent a minor group in the cleft population. The aim of this study was to analyze the faces of these children. In a prospective, cross-sectional study, 344 healthy children and 30 children with cleft lip or cleft lip and alveolus were scanned three-dimensionally at the age of 0 to 6 years. Twenty-one standard anthropometric landmarks were identified, and the images were superimposed. Growth curves for normal facial development were calculated. The facial morphology of cleft children was compared with that of unaffected children.Facial morphology and growth in the transverse direction of the examined patients appeared broadened in all levels. Especially the nasal landmarks indicated a widening of the nose. The landmarks ac l, sbal l, sbal r, c l, sn l, and ls l differed significantly from unaffected children. In the sagittal and vertical dimensions, there was no significant difference compared with unaffected children.Our study demonstrates that surgical and orthodontic treatment can restore the vertical and sagittal dimensions of the face in children with cleft lip with and without alveolar clefts; however, the transverse dimension-especially the nose-remains too broad.

Averaging time, desaturation level, duration and extent.

BACKGROUND: Pulse oximeter saturation values are usually obtained by averaging over preceding measurements. This study investigates the dynamics between the averaging time and desaturation level, duration and extent. METHODS AND RESULTS: Prospective observational study of 15 preterm infants. Oxygen saturation was recorded for 168 h using a pulse oximeter. The raw red-to-infrared data were reprocessed using seven different averaging times to determine the number of desaturations below four thresholds and for seven different minimal desaturation durations. The total number of desaturations <80% was 339 with an averaging time of 16 s and 1958 with an averaging time of 3 s (minimal event duration >0 s). There was a significantly lower pulse oximeter saturation nadir with the shorter averaging time, while the maximum duration was significantly longer when using a 16 s averaging time. CONCLUSIONS: When using pulse oximeters, more attention should be given to averaging time and duration of desaturations.

In vitro comparison of hypericin and 5-aminolevulinic acid-derived protoporphyrin IX for photodynamic inactivation of medulloblastoma cells.

BACKGROUND: Hypericin (HYP) is a naturally occurring photosensitizer. Cellular uptake and photodynamic inactivation after incubation with this photosensitizer have neither been examined in medulloblastoma cells in vitro, nor compared with 5-aminolevulinic acid-derived protoporphyrin IX (5-ALA-derived PpIX). METHODS: In 3 medulloblastoma cell lines (D283 Med, Daoy, and D341 Med) the time- and concentration-dependent intracellular accumulation of HYP and 5-ALA-derived PpIX was analyzed by fluorescence microscopy (FM) and FACS. Photocytotoxicity was measured after illumination at 595 nm (HYP) and 635 nm (5-ALA-derived PpIX) in D283 Med cells and compared to U373 MG glioma cells. RESULTS: All medulloblastoma cell lines exhibited concentration- and time-dependent uptake of HYP. Incubation with HYP up to 10 µM resulted in a rapid increase in fluorescence intensity, which peaked between 2 and 4 hours. 5-ALA-derived PpIX accumulation increased in D283 Med cells by 22% over baseline after 5-ALA incubation up to 1.2 mM. Photocytotoxicity of 5-ALA-derived PpIX was higher in D283 Med medulloblastoma compared to U373MG glioma. The LD50 [lethal dose (light dose that is required to reduce cell survival to 50% of control)] of 5-ALA-derived PpIX was 3.8 J/cm(2) in D283 Med cells versus 5.7 J/cm2 in U373MG glioma cells. Photocytotoxicity of HYP in D283 Med cells was determined at 2.5 µM after an incubation time of 2 h and an illumination wavelength of 595 nm. The [Formula: see text] value was 0.47 J/cm(2). CONCLUSION: By its 5-fold increase in fluorescence over autofluorescence levels HYP has excellent properties for tumor visualization in medulloblastomas. The high photocytotoxicity of HYP, compared to 5-ALA-derived PpIX, is convincingly demonstrated by its 8- to 13-fold lower LD50. Therefore HYP might be a promising molecule for intraoperative visualization and photodynamic treatment of medulloblastomas.

Standardized assessment of reading performance: the New International Reading Speed Texts IReST.

PURPOSE: There is a need for standardized texts to assess reading performance, for multiple equivalent texts for repeated measurements, and for texts equated across languages for multi-language studies. Paragraphs are preferable to single sentences for accurate speed measurement. We developed such texts previously in 6 languages. The aim of our current study was to develop texts in more languages for a wide range of countries and users, and to assess the reading speeds of normally-sighted readers. METHODS: Ten texts were designed for 17 languages each by a linguist who matched content, length, difficulty, and linguistic complexity. The texts then were used to assess reading speeds of 436 normally-sighted native speakers (age 18-35 years, 25 per language, 36 in Japanese), presented at a distance of 40 cm and size 1 M, that is 10-point Times New Roman font. Reading time (aloud) was measured by stopwatch. RESULTS: For all 17 languages, average mean reading speed was 1.42 ± 0.13 texts/min (±SD), 184 ± 29 words/min, 370 ± 80 syllables/min, and 863 ± 234 characters/min. For 14 languages, mean reading time was 68 ms/character (95% confidence interval [CI] 65-71 ms). Our analysis focussed on words per minute. The variability of reading speed within subjects accounts only for an average of 11.5%, between subjects for 88.5%. CONCLUSIONS: The low within-subject variability shows the equivalence of the texts. The IReST (second edition) can now be provided in 17 languages allowing standardized assessment of reading speed, as well as comparability of results before and after interventions, and is a useful tool for multi-language studies (for further information see www.amd-read.net).

Associating the magnitude of relative afferent pupillary defect (RAPD) with visual field indices in glaucoma patients.

PURPOSE: To identify the variable with the strongest association between the magnitude of the relative afferent pupillary defect (RAPD) and visual field indices in patients with glaucomatous optic neuropathy. METHODS: Seventy-nine consecutive subjects with manifest glaucomatous optic neuropathy at least in one eye were enrolled in this retrospective study. RAPD was assessed with the swinging flashlight test and quantified with a neutral density filter. Perimetry was performed using the fast thresholding strategy German Adaptive Threshold Estimation. The values of the central differential luminance sensitivity (DLS), of the MD (mean defect) and of the 'loss volume' (LVOL) based on the individually modelled 3D hill of vision-the latter two within the eccentricities of 10°, 20° and 30°, respectively-were entered into a linear regression model without intercept as a function of RAPD. RESULTS: An absolute value of RAPD of 0.3 log(10) units or more was present in 20 out of 79 glaucoma subjects (25%). The magnitude of RAPD was most closely associated with LVOL-30° (R(2)=0.77), followed by MD-30° (R(2)=0.73), MD-20° (R(2)=0.71), LVOL-20° (R(2)=0.67), MD-10° (R(2)=0.58), LVOL-10° (R(2)=0.54) and central DLS (R(2)=0.04). CONCLUSIONS: The prevalence of RAPD in glaucoma patients is comparatively small (25%). The magnitude of RAPD in glaucoma subjects is associated most closely with the LVOL within 30° eccentricity (which is the maximum visual field region tested in this study) and most loosely with central DLS, underscoring the impact of the entire (30°) visual field area on the afferent pupillary system.