Light scattering from a diffractive-refractive intraocular lens: a goniometer-based approach for individual zone assessment.

We proposed and tested a method to measure light scattering from the diffractive lens profile in an echelle element featuring 9 zones. Measurements were performed using a goniometer-based setup up to 7.5°. The proportion of scattered light was calculated to derive the loss of light. Material scattering was minimal (∼1 deg2/sr); however, each echelle zone acted as a scattering source. A nearly gradual straylight increase was found with the zone number showing peak intensity between 3° and 3.75°. An estimated 6.2% ± 0.1% was lost due to scattering, which ought to be considered when reporting an IOL's light loss.

The Fatty Liver Assessment in Germany (FLAG) cohort study identifies large heterogeneity in NAFLD care.

BACKGROUND & AIMS: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. METHODS: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. RESULTS: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%. CONCLUSIONS: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients. LAY SUMMARY: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.

Evaluation of Point Shear Wave Elastography Using Acoustic Radiation Force Impulse Imaging for Longitudinal Fibrosis Assessment in Patients with HBeAg-Negative HBV Infection.

BACKGROUND: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection. METHODS: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years. Patients were classified into one of the three groups: inactive carriers (IC; HBV-DNA <2000 IU/mL and ALT <40 U/L); grey zone group 1 (GZ-1; HBV DNA <2000 IU/mL and ALT >40 U/L); grey zone group 2 (GZ-2; HBV-DNA >2000 IU/mL and ALT <40 U/L). RESULTS: pSWE results were significantly correlated with TE (r = 0.29, p < 0.001) and APRI (r = 0.17; p = 0.005). Median pSWE values did not differ between IC, GZ-1 and GZ-2 patients (p = 0.82, p = 0.17, p = 0.34). During six years of follow-up, median pSWE and TE values did not differ significantly over time (TE: p = 0.27; pSWE: p = 0.05). CONCLUSION: Our data indicate that pSWE could be useful for non-invasive fibrosis assessment and follow-up in patients with HBeAg-negative chronic HBV infection.

Laboratory reform counteracts the WHO hepatitis C elimination strategy in Germany.

The World Health Organization and the German government have announced an initiative to eliminate chronic hepatitis C until the year 2030. To reach this goal, one important step is adequate screening and detection of so far undiagnosed infections. The most common initial test is anti-HCV. This parameter was extra-budgetary reimbursed by statuary healthcare insurances in the past. However, this policy has changed after a nationwide laboratory reform which should reduce the laboratory costs of patients insured in the statuary healthcare insurances. We therefore analysed the impact of the laboratory reform on the order of anti-HCV tests in 510 656 anonymized patient data sets before and after the initiation of the reform. The number of anti-HCV tests declined by 9.4% in quarters I-III 2018 in comparison with the same time period of the year 2017. The number of HBsAg tests declined by 7.4%, indicating that the reduced anti-HCV laboratory orders are not parameter-specific, but most likely a surrogate of the intention of the laboratory reform to generally lower the demands of blood samples and laboratory costs. Thus, the scenario is an important example, how political decisions of the medical self-government influence the screening setting for viral hepatitis: if the current policy is not changed, the laboratory reform directly counteracts the WHO hepatitis C elimination strategy in Germany.

Assessment of straylight and the modulation transfer function of intraocular lenses with centrally localized opacification associated with the intraocular injection of gas.

PURPOSE: To assess the optical quality of intraocular lenses (IOLs) explanted because of opacification after the intraocular injection of gas. SETTING: David J. Apple Laboratory, Heidelberg, Germany. DESIGN: Experimental study. METHODS: Four hydrophilic acrylic IOLs were studied, each with a centrally localized round opacification pattern associated with the intraocular use of gas. Laboratory analysis included gross examination with a light microscope, followed by alizarin and von Kossa staining. Optical quality was assessed by examining the modulation transfer function (MTF) and straylight. Results were compared with those of a control IOL and normative data for straylight of the crystalline lens. The following parameters were derived from image analysis: opacified surface fraction, light loss in the opacified surface, and the area and number of granules. The relationship between straylight increase and those parameters was studied. RESULTS: Fine granules were identified on the IOL surface and subsurface. The granules stained positive for calcium, and the MTF levels of 2 IOLs dropped markedly. The other 2 showed relatively minor changes. The straylight was extremely increased in 3 IOLs up to (and above) a level of that of a cataractous lens. A proportional relationship was found between straylight and the morphological parameters from image analysis. CONCLUSIONS: Intraocular lenses with centrally localized opacification have a strong potential for deteriorating optical performance. However, the optical quality might differ depending on the morphology of opacification. A serious straylight increase was found in most of these IOLs, suggesting that affected patients may suffer from glare-related symptoms.

The effects of multi-disciplinary psycho-social care on socio-economic problems in cancer patients: a cluster-randomized trial.

PURPOSE: We examined whether multi-disciplinary stepped psycho-social care decreases financial problems and improves return-to-work in cancer patients. METHODS: In a university hospital, wards were randomly allocated to either stepped or standard care. Stepped care comprised screening for financial problems, consultation between doctor and patient, and the provision of social service. Outcomes were financial problems at the time of discharge and return-to-work in patients < 65 years old half a year after baseline. The analysis employed mixed-effect multivariate regression modeling. RESULTS: Thirteen wards were randomized and 1012 patients participated (n = 570 in stepped care and n = 442 in standard care). Those who reported financial problems at baseline were less likely to have financial problems at discharge when they had received stepped care (odds ratio (OR) 0.2, 95% confidence interval (CI) 0.1, 0.7; p = 0.01). There was no evidence for an effect of stepped care on financial problems in patients without such problems at baseline (OR 1.1, CI 0.5, 2.6; p = 0.82). There were 399 patients < 65 years old who were not retired at baseline. In this group, there was no evidence for an effect of stepped care on being employed half a year after baseline (OR 0.7, CI 0.3, 2.0; p = 0.52). TRIAL REGISTRATION: NCT01859429 CONCLUSIONS: Financial problems can be avoided more effectively with multi-disciplinary stepped psycho-social care than with standard care in patients who have such problems.

Budget impact analysis on the introduction of a guideline based hepatitis B and C screening into a routine check-up in the German primary care setting.

OBJECTIVES: Systematic screening for chronic hepatitis B and C does not yet exist in Germany. Therefore, the implementation of a screening approach within a preventive medical examination performed by primary care physicians ('Check-Up 35+') was evaluated in a recent prospective multicenter study. The present analysis estimates the financial consequences for the statutory health insurance by budget impact analysis. MATERIALS AND METHODS: A Markov cohort model was developed consisting of 21 health states. Four different screening scenarios derived from the previous multicenter study were compared to usual care, a strategy without screening for hepatitis. Actual cost data for Germany were calculated and systematic literature searches for all input parameters were performed. RESULTS: The base case results in incremental costs for the screening strategies compared to no hepatitis screening of 165-227 € per patient in a 20-year horizon. Two main parameters influence the financial consequences: (A) detection and treatment increase the costs in the beginning. (B) Screening avoids hepatitis induced end-stage liver disease. The initial higher costs exceed the later savings. Sensitivity analyses demonstrate a strong impact of medication costs for the treatment of additionally detected hepatitis infections on the outcome. This finding is robust to sensitivity analysis. CONCLUSIONS: The screening strategy proposed here implies additional costs for the statutory health insurance, however, a decision regarding its usefulness must consider criteria other than cost. For example, the high burden of disease due to liver cirrhosis and liver carcinoma should be considered. Therefore, an additional cost-effectiveness-analysis should be conducted.

Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients.

BACKGROUND & AIMS: While the gold standard in the assessment of liver fibrosis remains liver biopsy, non-invasive methods have been increasingly used for chronic hepatitis B (CHB). This study aimed to evaluate the performance of two commonly used non-invasive scoring systems (aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4)) to predict fibrosis stage in CHB patients. METHODS: Demographic, histologic and clinical laboratory data from two trials investigating tenofovir disoproxil fumarate in CHB were analyzed. Predicted fibrosis stage, based on established scales and cut-off values for APRI and FIB-4 scores, was compared with Ishak scores obtained from liver biopsy at baseline and at 240 week follow-up. RESULTS: In the 575 patients with a baseline liver biopsy, APRI and FIB-4 scores correlated with Ishak stage (p<0.01); however extensive overlap in the distribution of both scores across Ishak stages prevented accurate determination of fibrosis. The majority (81-89%) of patients with advanced fibrosis or cirrhosis were missed by the scores. Similarly, 71% patients without fibrosis were misclassified as having clinically significant fibrosis. APRI and FIB-4 scores at week 240 tended to be low and underestimate fibrosis stage in the patients with liver biopsies after 240 weeks of therapy. APRI or FIB-4 reduction did not correlate with fibrosis regression after 240 weeks of antiviral therapy. CONCLUSIONS: APRI and FIB-4 scores are not suitable for use in clinical practice in CHB patients for assessment of hepatic fibrosis according to Ishak stage, especially in gauging improvements in liver fibrosis following therapy.

Method for in vitro assessment of straylight from intraocular lenses.

Ocular straylight has been measured by means of psychophysical methods over the years. This approach gives a functional parameter yielding a straight comparison with optically defined light scattering, and the point-spread-function. This is of particular importance when the effect of intraocular lenses (IOLs) on postoperative straylight is sought. An optical system for straylight measurements of IOLs was adapted to a commercial device (C-Quant, Oculus), which employs such psychophysical method. The proposed modifications were validated using light-scattering filters and some sample IOLs. The measurements were performed by 3 observers to prove that results are independent from straylight of the eye. Other applications will be discussed.

Acute hepatitis C virus infection induces anti-host cell receptor antibodies with virus-neutralizing properties.

UNLABELLED: Hepatitis C virus (HCV) causes persistent infection in the majority of infected individuals. The mechanisms of persistence and clearance are only partially understood. Antibodies (Abs) against host cell entry receptors have been shown to inhibit HCV infection in cell culture and animal models. In this study, we aimed to investigate whether anti-receptor Abs are induced during infection in humans in vivo and whether their presence is associated with outcome of infection. We established an enzyme-linked immunosorbant assay using a recombinant CD81-claudin-1 (CLDN1) fusion protein to detect and quantify Abs directed against extracellular epitopes of the HCV CD81-CLDN1 coreceptor complex. The presence of anti-receptor Abs was studied in serum of patients from a well-defined cohort of a single-source HCV outbreak of pregnant women and several control groups, including uninfected pregnant women, patients with chronic hepatitis B and D virus (HBV/HDV) infection, and healthy individuals. Virus-neutralizing activity of Abs was determined using recombinant cell culture-derived HCV (HCVcc). Our results demonstrate that HCV-infected patients have statistically significantly higher anti-CD81/CLDN1 Ab titers during the early phase of infection than controls. The titers were significantly higher in resolvers compared to persisters. Functional studies using immunoadsorption and HCV cell culture models demonstrate that HCV-neutralizing anti-receptor Abs are induced in the early phase of HCV infection, but not in control groups. CONCLUSION: The virus-neutralizing properties of these Abs suggest a role for control of viral infection in conjunction with antiviral responses. Characterization of these anti-receptor Abs opens new avenues to prevent and treat HCV infection.

Non-invasive assessment of hepatic steatosis in patients with NAFLD using controlled attenuation parameter and 1H-MR spectroscopy.

INTRODUCTION: Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). 1H-Magnetic resonance spectroscopy (1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP) correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a head-to-head comparison between both methods. METHODS: Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2 34-66%, S3 ≥67%. RESULTS: Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiver-operating characteristics curves were 0.93 vs. 0.88 for steatosis ≥S1 and 0.94 vs. 0.88 for ≥S2, respectively. Boot-strapping analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2-4 fibrosis TE had sensitivity and specificity of 100% and 98.1% at a cut-off value of 8.85 kPa. CONCLUSION: Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification. Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects, anthropometry, and presence of advanced liver fibrosis.

Impact of the MELD allocation after its implementation in liver transplantation.

OBJECTIVE: On 16 December 2006, most Eurotransplant countries changed waiting time oriented liver allocation policy to the urgency oriented Model for End-stage Liver Disease (MELD) system. There are limited data on the effects of this policy change within the Eurotransplant community. PATIENTS AND METHODS: A total of 154 patients who had undergone deceased donor liver transplantation (LT) were retrospectively analyzed in three time periods: period A (1-year pre-MELD, n = 42) versus period B (1-year post-MELD, n = 52) versus period C (2 years after MELD implementation, n = 60). RESULTS: The median MELD score at the time of LT increased from 16.3 points in period A to 22.4 and 20.4 in periods B and C, respectively (p = 0.007). Waitlist mortality decreased from 18.4% in period A to 10.4% and 9.4% in periods B and C, respectively (p = 0.015). Three-month mortality did not change significantly (10% each for periods A, B and C). One-year survival was 84% for the MELD 6-19 group compared with 81% in the MELD 20-29 group and 74% in the MELD ≥30 group (p = 0.823). Analyzing MELD score and previously described prognostic scores [i.e. survival after liver transplantation (SALT) score and donor-MELD (D-MELD) score] with regard to 1-year survival, only a high risk SALT score was predictive (p = 0.038). In our center, 2 years after implementation of the MELD system, waitlist mortality decreased, while 90-day mortality did not change significantly. CONCLUSION: Up to now, only the SALT score proved to be of prognostic relevance post-transplant.

Chances and limitations of non-invasive tests in the assessment of liver fibrosis in liver transplant patients.

Because fibrosis progression resulting in liver cirrhosis represents the main reason for graft lost in patients after liver transplantation, an early detection of liver fibrosis is crucial. In recent years, several non-invasive tests for the assessment of liver fibrosis have been developed. We prospectively assessed the stage of liver fibrosis of 135 liver transplant patients (94 hepatitis C virus [HCV], 41 alcoholic cirrhosis) using liver biopsy, transient elastography, and serum markers. In the HCV group, the area under the receiver operating characteristic curve (AUROC) for diagnosis of significant fibrosis (F ≥ 2) and cirrhosis (F = 4) was 0.81 (negative predictive value [NPV] = 0.58, positive predictive value [PPV] = 0.9) and 0.87 (NPV = 0.94, PPV = 0.56), respectively. In the alcoholic cirrhosis group, significant fibrosis (F ≥ 2) was diagnosed with an AUROC of 0.83 (NPV = 1.00, PPV = 0.23). In both groups, higher AUROC values were reached in patients with a body mass index of <25 kg/m(2) , and both serum markers showed no significant correlation to liver fibrosis. The transient elastography is a reliable test for exclusion of liver cirrhosis in HCV transplant and significant liver fibrosis in alcoholic transplant patients. For the diagnosis of significant liver fibrosis in HCV transplant patients, the transient elastography reaches good results but cannot replace liver biopsy. Both serum markers AST-to-platelet ratio index and FIB-4 are not feasible to assess liver fibrosis in liver transplant patients.

Reliability of the compensation comparison method for measuring retinal stray light studied using Monte-Carlo simulations.

Recently the psychophysical compensation comparison method was developed for routine measurement of retinal stray light. The subject's responses to a series of two-alternative-forced-choice trials are analyzed using a maximum-likelihood (ML) approach assuming some fixed shape for the psychometric function (PF). This study evaluates the reliability of the method using Monte-Carlo simulations. Various sampling strategies were investigated, including the two-phase sampling strategy that is used in a commercially available instrument. Results are given for the effective dynamic range and measurement accuracy. The effect of a mismatch of the shape of the PF of an observer and the fixed shape used in the ML analysis was analyzed. Main outcomes are that the two-phase sampling scheme gives good precision (Standard deviation = 0.07 logarithmic units on average) for estimation of the stray light value. Bias is virtually zero. Furthermore, a reliability index was derived from the responses and found to be effective.

Compensation comparison method for assessment of retinal straylight.

PURPOSE: Presently, no instrument or method exists that is generally accepted for routine clinical assessment of (functional) retinal straylight. Yet retinal straylight is the cause of major patient complaints, such as hindrance from glare and loss of contrast. It results from disturbances in the optical media that increase light-scattering over angles of 1 degrees to 90 degrees . Its assessment would help to decide whether to perform surgery for (early) cataract and would help in the evaluation of corneal or vitreal turbidity. METHODS: The psychophysical technique of the "direct compensation" method was adapted to make it suitable for routine clinical assessment. In the new approach, called "compensation comparison, " the central test field is subdivided into two half fields: one with and one without counterphase compensation light. The subject's task is a forced-choice comparison between the two half fields, to decide which half flickers more strongly. A theoretical form for the respective psychometric function was defined and experimentally verified in a laboratory experiment involving seven subjects, with and without artificially increased light scattering. The method was applied in a separate multicenter study. Its reliability was additionally tested with a commercial implement (C-Quant; Oculus Optikgeräte, Wetzlar-Dutenhofen, Germany). RESULTS: A repeated-measures SD of 0.07 log units was achieved, to be compared with differences in the young normal population of 0.4 log units and an increase with healthy aging by 0.5 log units at 80 years and by 1.0 or more log units with (early) cataract or corneal disturbances. Reliability was further found to be high when using the commercial version of the CONCLUSIONS: The compensation comparison method for measuring retinal straylight is suited for clinical use to diagnose patients with complaints caused by large angle light scattering in the eye such as early cataract.