Wolfgang Köpcke

The Roche European American Cataract Trial (REACT): A randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract

context Funding surgery worldwide for age-related cataract (ARC), a leading cause of blindness, is a huge economic burden. Non-surgical means of slowing ARC progression could benefit patients and reduce this burden. objective To determine if a mixture of oral antioxidant micronutrients [mg/day] (ß-carotene [18], vitamin C [750], and vitamin E [600]) would modify progression of ARC. design REACT was a multi-centered, prospective, double-masked, randomized, placebo-controlled, 3-year trial. setting Consecutive adult American and English outpatients with early ARC were recruited. patients Four-hundred-and-forty-five patients were eligible; 297 were randomized; 231 (78%) were followed for two years; 158 (53%) were followed for three years; 36 (12%) were followed for four years. Twelve patients died during the trial (9 on vitamins; 3 on placebo (p = 0.07)). There were no serious safety issues. intervention After a three-month placebo run-in, patients were randomized by clinical center to the vitamin or placebo groups and followed every four months. main outcome measure Cataract severity was documented with serial digital retroillumination imagery of the lens; progression was quantified by image analysis assessing increased area of opacity. This measure of area, ‘increase % pixels opaque’ (IPO), was the main outcome measure. results There were no statistically significant differences between the treatment groups at baseline. The characteristics of dropouts and the mean follow-up times by treatment group were the same. After two years of treatment, there was a small positive treatment effect in U.S. patients (p = 0.0001); after three years a positive effect was apparent (p = 0.048) in both the U.S. and the U.K. groups. The positive effect in the U.S. group was even greater after three years: (IPO = 0.389 (vitamin) vs. IPO = 2.517 (placebo); p = 0.0001). There was no statistically significant benefit of treatment in the U.K. group. In spite of nearly perfect randomization into treatment groups, the U.S. and U.K. cohorts differed significantly. conclusion Daily use of the afore-mentioned micronutrients for three years produced a small deceleration in progression of ARC.

Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study

The efficacy and the safety of intra-articular injections of sodium hyaluronate were studied in patients with osteoarthritis of the knee in a randomized multicenter double-blind study. Two hundred and nine patients received five injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg hyaluronate/2.5 ml (control, N = 107) at weekly intervals. Seven patients in each group were excluded from the protocol-correct efficacy analysis. The Lequesne Index, the first main criterion, showed a significant superiority of the verum-treated patients after the third injection up to the final follow-up examination 9 weeks after the last injection (MANOVA, P < 0.025). The consumption of paracetamol was defined as a complementary main criterion that did not reveal significant differences between the treatment groups. Most of the individual secondary endpoints demonstrated a much better response to the active treatment without reaching the significance level in the intergroup comparisons for the single time-points. Side-effects were confined to local reactions of minor severity and short duration in four patients (six events) of the verum group and in five patients of the control group. Clinical chemistry and hematology remained essentially unchanged.

Modifiable risk factors for SIDS in Germany: Results of GeSID

BACKGROUND The incidence of sudden infant death syndrome (SIDS) has been falling in Germany over the last decade. However, little is known about the prevalence and the importance of well-known risk factors in Germany since a local prevention campaign in 1992. DESIGN A 3-y, population-based, case-control study was conducted in half of Germany, consisting of 333 cases. All sudden and unexpected deaths in infancy, if they fitted the inclusion criteria, were included in the study. Parental interview was carried out soon after the death, and three living control infants, matched for age, gender, region and sleep time, were recruited. RESULTS The prevalence of placing infants prone to sleep was only 4% in the control group, but this was associated with a markedly increased risk of SIDS (adjusted odds ration, aOR=6.08). Other modifiable risk factors for SIDS were: maternal smoking during pregnancy, breastfeeding for less than 2 wk (aOR=1.71) and co-sleeping (aOR=2.71), while using a pacifier during the last sleep reduced the risk (aOR=0.39). CONCLUSIONS Previously recognized risk factors for SIDS also occur in Germany. Despite knowledge about the major modifiable risk factors for SIDS, these factors are still present in Germany. To reduce the incidence of SIDS in Germany, a continued effort is needed to inform all parents about preventable risk factors for SIDS.

Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance

Background:  Macular pigment (MP) is found in diurnal primate species when vision spans a range of ambient illumination and is mediated by cone and rod photoreceptors. The exact role of MP remains to be determined. In this study we investigate two new hypotheses for possible MP functions.

First vs multiple episode schizophrenia: Two-year outcome of intermittent and maintenance medication strategies

Results of studies on intermittent neuroleptic treatment strategies in first episode (FE) schizophrenia have not been published. Aims of the present study were to elucidate the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode (ME) schizophrenia. As to the methods, three randomly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic outpatients (115 FE, 248 ME; ICD-9, RDC): maintenance medication vs two intermittent medication strategies (prodrome-based intervention and crisis intervention). Concerning relapse prevention, the results demonstrate that ME patients seemed to profit most from maintenance medication compared to both intermittent treatments, whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment. Psychopathology, social adjustment, subjective well-being, and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy. Concerning treatment adherence, FE patients complied better with prodrome-based intervention than with maintenance medication. Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment. In conclusion, maintenance medication is the best strategy for relapse prevention in ME patients. In FE patients, prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied.

Protection from Sunburn with β-Carotene—A Meta-analysis†

Nutritional protection against skin damage from sunlight is increasingly advocated to the general public, but its effectiveness is controversial. In this meta‐analysis, we have systematically reviewed the existing literature on human supplementation studies on dietary protection against sunburn by beta‐carotene. A review of literature until June 2007 was performed in PubMed, ISI Web of Science and EBM Cochrane library and identified a total of seven studies which evaluated the effectiveness of β‐carotene in protection against sunburn. Data were abstracted from these studies by means of a standardized data collection protocol. The subsequent meta‐analysis showed that (1) β‐carotene supplementation protects against sunburn and (2) the study duration had a significant influence on the effected size. Regression plot analysis revealed that protection required a minimum of 10 weeks of supplementation with a mean increase of the protective effect of 0.5 standard deviations with every additional month of supplementation. Thus, dietary supplementation of humans with β‐carotene provides protection against sunburn in a time‐dependent manner.

Intermittent versus maintenance neuroleptic long-term treatment in Schizophrenia—2-year results of a German multicenter study

Abstract The paper presents the 2-year results of a multicenter study on the comparative efficacy of different neuroleptic long-term treatment strategies in 364 schizophrenic outpatients carried out by the German Neuroleptic Treatment Study (ANI) Group. Three randomly assigned open neuroleptic treatments were compared: standard prophylactic maintenance medication, and two types of intermittent treatment (early intervention and neuroleptic crisis intervention). Although relapserates were significantly lower under early intervention (49%) than under crisis intervention (63%), those under maintenance treatment were by far the lowest (23%). Dropout and rehospitalization rates under both intermittent treatment strategies were also significantly less favorable than under maintenance treatment, whereas psychopathology, social adjustment, subjective wellbeing, and side-effects were not significantly different between treatment strategies. Cumulative neuroleptic dosage was significantly lower under intermittent treatment, even when inpatient treatment in a case of rehospitalization was considered. In conclusion, prophylactic maintenance medication turns out again to be the best treatment for most of the patients.

German study on sudden infant death (GeSID): design, epidemiological and pathological profile

The German study on sudden infant death (GeSID) is a multi-centre case-control study aiming at the assessment of etiological factors and risk factors of SIDS. This report describes the study design and the methods applied and presents some general findings. Between 1998 and 2001, 455 cases of sudden and unexpected death of infants aged between 8 and 365 days were recruited into the study. The study comprised at least 11 out of the 16 German states with 18 centres involved. In 1999 and 2000, 75% of all SIDS cases registered with the Federal Office of Statistics (ICD 10/R95, n=384) in the study area were recruited into the study (n=286). A standardised autopsy including extended histology, microbiology, virology, toxicology and neuropathology investigations was carried out. Of the parents 82% (n=373) agreed to fill in an extensive questionnaire containing 120 questions reflecting all important aspects of the infant’s development. For each SIDS case, the parents of three living control infants were interviewed. These controls were matched for age, gender and region (n=1,118). The response rate of the controls was 58.7%. Data were linked with medical records obtained from obstetrics departments, the children’s hospitals, and general practitioners. Death scene investigation was performed in 4 study areas (cases: n=64, controls: n=191). All cases were classified into one of 4 categories using defined criteria: 7.3% of the children were assigned to category 1 (no pathological findings: SIDS), 61.1% to category 2 (minor findings: SIDS+), 20.4% to category 3 (severe findings: SIDS+) and 11.2% to category 4 (findings which explained the death: non-SIDS). In case conferences the previous history and circumstantial factors were included and an extended category (E-cat.) was defined. The consideration of these factors for the final classification is of great importance in the causal explanation of some cases. An analysis of 18 main variables in cases of categories 1–3 (SIDS) compared to the cases of category 4 (non-SIDS) showed significant differences for the sleeping position, coughing the day before death and breast-feeding indicating that the cases of both groups should be separated for further analyses.

Relapse prevention in first-episode schizophrenia--maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia.

OBJECTIVE After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia. METHOD A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits). RESULTS Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects. CONCLUSIONS Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00159120.

The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision.

Background:  Both yellow‐blue (YB) discrimination thresholds and macular pigment optical density (MPOD) measurements in the eye exhibit large variability in the normal population. Although it is well established that selective absorption of blue light by the macular pigment (MP) can significantly affect trichromatic colour matches, the extent to which the MP affects colour discrimination (CD) sensitivity remains controversial.