Transcutaneous (External) Dacryocystorhinostomy with Reconstruction of the Ductus nasolacrimalis. / Transkutane (externe) Dakryozystorhinostomie mit Rekonstruktion des Ductus nasolacrimalis.

BACKGROUND: Dacryocystorhinostomy (DCR) is regarded as the gold standard for the treatment of chronic dacryocystitis (CDC). Different modifications of the surgical procedure have been developed over the years. METHODS: Patients with CDC due to postsaccal lacrimal stenosis and under treatment with DCR have been included in this retrospective study. Two groups of different surgical procedures were analysed: firstly DCR without reconstruction of the ductus nasolacrimalis (DNL, group 1) and secondly patients with reopening the DNL (group 2). Criteria for success were absence of permanent epiphora, absence of inflammation of the lacrimal sac (functional success), and no recurrent surgery with free patency of the lacrimal duct (anatomical success). This was obtained by questionnaire after a follow-up of at least 12 months. The impact of gender, ectasia of the lacrimal sac, dacryoliths, and prior lacrimal surgeries was analysed. RESULTS: Overall, 248 surgeries were enrolled in this trial. Mean age in group 1 was 68 years (range: 22 to 92 years) and gender ratio was 3.2 to 1 (female : male). In that group, 68 operations could be followed up. In group 2, 62 operations on patients of a mean age of 63 years (range: 24 to 89 years) and a gender ratio of 2.9 to 1 (female : male) were observed. Complete success occurred in 75.0% in group 1 and 75.8% in group 2. Recurrent operations were necessary in one case of group 2 (1.6%) and 4 cases of group 1 (5.9%). Gender (group 1 p = 1; group 2 p = 0.115; between groups p = 0.511), ectasia of the lacrimal sac (group 1 p = 0.877; group 2 p = 0.674; between groups p = 0.878), dacryolith (group 1 p = 1; group 2 p = 0.465; between groups p = 1), and prior lacrimal surgery (group 1 p = 0.092; group 2 p = 0.051; between groups p = 0.520) did not influence the success rates in each group or between groups. Significantly more dacryoliths were found during operations of group 2 (p = 0.010). CONCLUSION: Reconstruction of the DNL during DCR is a possible and easy modification, with a slightly better success rate in curing CDC. Intraoperatively, dacryoliths might not be apparent remain in the deeper parts of the lacrimal ducts. Therefore, these segments should be inspected during surgery.

Trends in cancer incidence by socioeconomic deprivation in Germany in 2007 to 2018: An ecological registry-based study.

Age-standardized cancer incidence has decreased over the last years for many cancer sites in developed countries. Whether these trends led to narrowing or widening socioeconomic inequalities in cancer incidence is unknown. Using cancer registry data covering 48 million inhabitants in Germany, the ecological association between age-standardized total and site specific (colorectal, lung, prostate and breast) cancer incidence in 2007 to 2018 and a deprivation index on district level (aggregated to quintiles) was investigated. Incidence in the most and least deprived districts were compared using Poisson models. Average annual percentage changes (AAPCs) and differences in AAPCs between deprivation quintiles were assessed using Joinpoint regression analyses. Age-standardized incidence decreased strongly between 2007 and 2018 for total cancer and all cancer sites (except female lung cancer), irrespective of the level of deprivation. However, differences in the magnitude of trends across deprivation quintiles resulted in increasing inequalities over time for total cancer, colorectal and lung cancer. For total cancer, the incidence rate ratio between the most and least deprived quintile increased from 1.07 (95% confidence interval: 1.01-1.12) to 1.23 (1.12-1.32) in men and from 1.07 (1.01-1.13) to 1.20 (1.14-1.26) in women. Largest inequalities were observed for lung cancer with 82% (men) and 88% (women) higher incidence in the most vs the least deprived regions in 2018. The observed increase in inequalities in cancer incidence is in alignment with trends in inequalities in risk factor prevalence and partly utilization of screening. Intervention programs targeted at socioeconomically deprived and urban regions are highly needed.

Cardiovascular risk factors, living and ageing in Halle: the CARLA study.

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45-83 years) were examined at baseline (2002-2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.

Determinants of persistent smoking after acute myocardial infarction: an observational study.

BACKGROUND: Smoking cessation is one of the most effective secondary prevention measures after acute myocardial infarction (AMI). However, around 50% of smokers do not quit smoking after AMI. The aim of the present study is to estimate the proportion of patients quitting smoking and to identify determinants of persistent smoking after AMI in a region with increased cardiovascular mortality. We also assessed the time of smoking cessation after AMI. METHODS: We used follow-up data of patients registered with the Regional Myocardial Infarction Registry in Saxony-Anhalt (RHESA) in Germany. We assessed smoking status and determinants of persistent smoking six weeks after discharge from hospital after AMI. Information on smoking, sociodemographic characteristics, risk factors for AMI, experienced symptoms of AMI, and clinical care were gathered in a computer-assisted telephone interview and questionnaires filled out by study subjects and physicians or study nurses. RESULTS: Out of 372 smokers at the time of AMI, 191 (51.3%) reported that they quit smoking within six weeks after discharge from hospital after AMI. Strongest determinant of persistent smoking was a previous AMI before the current one (OR = 2.19, 95%CI 1.10-4.38) and strongest determinants of smoking cessation were experiencing complications in the hospital (0.37, 95%CI 0.12-1.12) and having a life partner (0.56, 95%CI 0.34-0.95). Most individuals who stopped smoking did so during the initial stay in the hospital, before the cardiac rehabilitation (CR). CONCLUSIONS: Persistent smoking after AMI and its determinants were similar in our region to previous studies. CR cannot be viewed as determinant of smoking cessation - more likely the same teachable moment induces behavioural change with regard to smoking and participation in CR.

[Self-reported cancer in the German National Cohort (NAKO Gesundheitsstudie): assessment methods and first results]. / Selbstberichtete Krebserkrankungen in der NAKO Gesundheitsstudie: Erfassungsmethoden und erste Ergebnisse.

BACKGROUND: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants. OBJECTIVES: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results. MATERIALS AND METHODS: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data. RESULTS: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5­year prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men. CONCLUSIONS: The NAKO is a rich data basis for future investigations of incident cancer.

[Dacryoendoscopic Surgery-Factors Influencing Postoperative Results]. / Dakryoendoskopische Tränenwegschirurgie ­ Einflussfaktoren auf das postoperative Ergebnis.

BACKGROUND: Dacryoendoscopy (DE) is an established method in lacrimal surgery. Long-term follow-up-analyses of this surgery are of great interest. Here, factors influencing postoperative success rates should be considered to elect suitable patients. METHODS: In this retrospective study, patients having had dacryoendoscopic surgery were included. Using a questionnaire, a prospective follow-up analysis was made. Pre- and intraoperative factors were correlated with treatment success, which was defined as improved epiphora, absence of a second lacrimal surgery and no signs of chronic dacryocystitis (secretion, pain at the lacrimal sac). Additionally, we asked for patient's satisfaction with the postoperative result (categorized in "very good", "good", "poor", and "bad"). RESULTS: Overall, 215 DE of 182 patients (130 women, 52 men) were studied. Mean patient age was 58 ± 17 years (range: 18 to 91 years). Follow-up was 31 to 77 months (median: 55 months). Treatment success after this time was 59.1%, in which neither patient's age nor sex showed significant influences. In comparison to complete stenosis, incomplete obstruction could be treated successfully twice as often (p = 0.02). Patients suffering from ectatic lacrimal sacs had a risk of 1.9 for failing therapy (p = 0.01). A trend concerning worse cure rates could be observed in patients with postsaccal localization of stenosis (p = 0.2) and an age of older than 49 years (p = 0.1). Surgical results evaluated by the patients were "very good" in 32.1% and "good" in 30.2%. CONCLUSION: Dacryoendoscopy with its minimally invasive approach is suitable as a first-step procedure in lacrimal surgery. The absence of a scar and the quick recovery are vitally important for the patients. Medically important is that the topographic anatomy is preserved by using dacryoendoscopy, so other surgical techniques can be performed later without limitations, if necessary. Patients with incomplete obstructions and a localization of stenosis, being pre- to intrasaccal, profit from this treatment method in particular.

Intraobserver Agreement on Histopathologic Evaluations of Core Breast Biopsies.

The number of performed core biopsies of the breast as diagnostic workup is increasing in many European countries. We measured the intraobserver variability in pathological assessment of breast core biopsies. Furthermore, we studied potential modifiers of agreement between the assessments. Two hundred and fifty-six breast biopsies were evaluated twice in a blinded fashion by two pathologists. We calculated the observed and the chance-corrected (weighted) intraobserver agreement (kappa) using the B-categorization scheme (B1: normal or not interpretable, B2: benign, B3: benign but of uncertain biological potential, B4: suspicious of malignancy, B5: malignant). The observed agreement between the first and the second assessments were 0.80 (95% CI: 0.75-0.85) for pathologist 1 and 0.81 (95% CI: 0.76-0.86) for pathologist 2. The chance-corrected agreements were 0.85 (95% CI: 0.80-0.89) and 0.81 (95% CI: 0.76-0.87), respectively. The most frequent disagreement was between B1 and B2 for pathologist 1 (N = 34 out of 50 disagreements, 68%) and between B2 and B3 for pathologist 2 (N = 23 out of 48 disagreements, 48%). Our study shows that the chance-corrected agreement between the histopathological evaluations of breast biopsies based on the B-categorization scheme is almost perfect. The level of agreement is modified by biopsy technique and by the level of suspicion of the mammographic lesion.

Do patients with intake of drugs labelled as sleep disturbing really sleep worse? A population based assessment from the Heinz Nixdorf Recall Study.

AIM: The sleep disturbing effect of many drugs is derived from clinical trials with highly selected patient collectives. However, the generalizability of such findings to the general population is questionable. Our aim was to assess the association between intake of drugs labelled as sleep disturbing and self-reported nocturnal sleep disturbances in a population-based study. METHODS: We used data of 4221 participants (50.0% male) aged 45 to 75 years from the baseline examination of the Heinz Nixdorf Recall Study in Germany. The interview provided information on difficulties falling asleep, difficulties maintaining sleep and early morning arousal. We used the summary of product characteristics (SPC) for each drug taken and assigned the probability of sleep disturbances. Thereafter, we calculated cumulative probabilities of sleep disturbances per subject to account for polypharmacy. We estimated prevalence ratios (PR) using log Poisson regression models with robust variance. RESULTS: The adjusted PRs of any regular nocturnal sleep disorder per additional sleep disturbing drug were 1.01 (95% confidence interval (CI) 0.97, 1.06) and 1.03 (95% CI 1.00, 1.07) for men and women, respectively. Estimates for each regular nocturnal sleep disturbance were similarly close to 1. PRs for regular nocturnal sleep disturbances did not increase with rising cumulative probability for drug-related sleep disturbances. CONCLUSIONS: SPC-based probabilities of drug-related sleep disturbances showed barely any association with self-reported regular nocturnal sleep disturbances. We conclude that SPC-based probability information may lack generalizability to the general population or may be of limited data quality.

The RHESA-CARE study: an extended baseline survey of the regional myocardial infarction registry of Saxony-Anhalt (RHESA) design and objectives.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in Europe. In Germany, a declining mortality rate from acute myocardial infarction (AMI) has been observed in the last decades. Nevertheless, there are large differences between the federal states when looking at the mortality and morbidity of AMI. Saxony-Anhalt is one of the federal states with the highest mortality rates for AMI in Germany. In 2012, the regional myocardial infarction registry of Saxony-Anhalt (RHESA) was established to investigate the individual, infrastructural, and health care factors with respect to an urban (city of Halle) and rural (region of Altmark) population. For detailed observation the RHESA-CARE study was conducted in 2014. RHESA-CARE focuses on the symptoms during infarction, the behaviour of patients while alerting for infarction, the use of rehabilitation possibilities, and long-term care. METHODS/DESIGN: RHESA-CARE is an extended baseline survey of AMI patients registered in RHESA who are aged 25 or more, and inhabitants of the city of Halle (Saale) or the district of Altmark in the federal state of Saxony-Anhalt, Germany. Detailed information was collected on classical and psychosocial cardiovascular risk factors as well as factors of alerting behaviour, first aid, and utilization of medical and rehabilitation services. High data quality is ensured by a detailed system of quality control. DISCUSSION: RHESA-CARE has the main objective to investigate factors that influence morbidity and mortality rates due to AMI. Another purpose is the comparison of a rural and urban patient population. It provides an opportunity to serve as a base for improvement of patients' behaviour and health care as well as further research.

Assessment of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma: a follow-up study.

BACKGROUND: To examine the all-cause mortality and uveal melanoma specific mortality among newly diagnosed uveal melanoma patients after five years. Furthermore, we assess of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma. Therefore, we assess the performance of an individual prediction model of survival from uveal melanoma. METHODS: A cohort of 459 patients aged 45 to 79 years with newly diagnosed uveal melanoma was recruited between 2002 and 2004 from the Division of Ophthalmology, University of Essen, Germany. Survival probabilities were estimated by Kaplan-Meier survival analysis. The clinical and histopathological characteristics were obtained from medical records. Iris colour and childbearing history were assessed at baseline by a computer-assisted telephone interview. We used crude and multivariable Cox proportional hazards regression to estimate unadjusted and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (95%CIs) with respect to death from uveal melanoma and death from all causes. We used the Cox model to estimate adjusted probabilities of primary events. For computing Harrell's C statistics, we used a Cox model including the prognostics factors gender, age at diagnosis, ciliary body involvement, largest basal tumour diameter, and iris colour. RESULTS: The 5-year uveal melanoma-specific survival probability was 82.9% (95% CI: 79.1-86.3). Main prognostic factors for the death of uveal melanoma were ciliary body involvement (HR: 1.7 (95% CI:1.0-2.8)), largest basal tumour diameter >15 mm HR: 7.0 (95% CI: 3.5-13.9), light iris colour (HR: 2.3 (95% CI: 0.9-5.8), having children (HR: 0.6 (95% CI: 0.2 - 1.7)), and gender (HR: 0.7 (95% CI: 0.4-1.1)). The value of the bootstrap-corrected C statistics was 0.76 (95% CI: 0.74-0.77). CONCLUSION: Beyond the established prognostic factors, light iris colour also appears to be a prognostic factor for death from uveal melanoma.

Influence of immunohistochemistry on the final diagnosis of breast biopsies.

AIMS: Because of the introduction of mammography screening programmes in Europe, the number of breast biopsies performed is increasing. We investigated the influence of immunohistochemistry (IHC) on the final diagnosis of breast biopsies by comparing the primary diagnoses (based on the results of haematoxylin and eosin staining only) with the final diagnoses (based on the additional information provided by IHC). METHODS AND RESULTS: We analysed the breast biopsies which were performed at the University of Halle-Wittenberg between 2006 and 2010 and for which the pathologist requested IHC for making the final diagnosis. According to the B-categorization scheme, the primary diagnosis changed in 37 of a total of 429 biopsies (8.6%). In 18 of these biopsies (48.6%) the category changed from B1-B2 to B3-B5 or vice versa, which would imply a different work-up. Only 77% of the primary diagnoses of breast cancer in situ were confirmed. CONCLUSION: IHC has a considerable influence on the final diagnosis of breast biopsies in several situations, including those in which the biopsied women are at risk of inadequate therapeutic intervention. The influence is particularly notable among those biopsies for which IHC is performed in order to assess the suspicion of breast cancer in situ.

Mammographic density and inter-observer variability of pathologic evaluation of core biopsies among women with mammographic abnormalities.

BACKGROUND: As high percentage of mammographic densities complicates the assessment of imaging findings, mammographic density may influence the histopathological evaluation of core-biopsies of the breast. We measured the influence of mammographic density on the inter-observer variability of histopathological findings of breast biopsies. METHODS: Histological slides of 695 women who underwent core biopsies of the breast at University of Halle between 2006 and 2008 were evaluated in a blinded fashion by two pathologists using the five levels of the B-categorization scheme (B1-B5). To quantify mammographic density, we used a computer-based threshold method (Madena). We calculated observed and chance-corrected agreements (weighted kappa) and 95% confidence intervals (95% CI) according to four categories of mammographic density (<10%, 10<25%, 25<50%, ≥50%). RESULTS: The weighted kappa decreased monotonically from 89.6% (95% CI: 85.8%, 93.3%) among women with less than 10% of mammographic density to 80.4% (95% CI: 69.9%, 90.9%) for women with more than 50% of mammographic density, respectively. Results of a kappa regression analysis showed that agreement of pathologists on clinically relevant categories (B1-B2 versus B3-B5) decreased with mammographic density. CONCLUSIONS: Mammographic density is a relevant modifier of the agreement between pathologists who assess breast biopsies using the B-categorization scheme. The influence of mammographic density on the inter-observer variability can be explained to some extent by varying prevalences of histological entities across B categories that have typically different inter-observer agreement. Women with high mammographic density are at higher risk of inter-observer variability compared to women with low mammographic density and should possibly undergo a second pathology review.

Factors influencing the agreement on histopathological assessments of breast biopsies among pathologists.

AIMS: It has been recommended that the histopathology results of core biopsies of the breast are categorized according to the B-categorization scheme. We measured the interobserver variability of the B-categorization of core biopsies of the breast. METHODS AND RESULTS: Core biopsies were taken among 765 women at the University of Halle between 2006 and 2008. All histological slides were reviewed in a blinded fashion by two experienced breast pathologists. We calculated observed and chance-corrected agreements (kappa) and 95% confidence intervals (CI). The prevalence of B3-B5 biopsies was 41.6%. The observed and weighted kappa agreement of the five-level B-categorization scheme was 0.87 (95% CI: 0.84 -0.89) and 0.89 (95% CI: 0.89-0.91), respectively. The most frequent disagreement was between B2 and B3 (47 of 103 disagreements, 45.6%). Overall, 49.5% of all disagreements were clinically relevant disagreements that would imply different therapeutic strategies. Agreement was modified by referral group, Breast Imaging Reporting and Data System (BIRADS) level, radiological breast density, imaging guidance and application of immunohistological staining. CONCLUSIONS: Interobserver agreement of the B-categorization scheme was high and was modified by referral status, level of radiological suspicion of breast cancer, breast density, imaging guidance of core biopsies and requirement of additional immunohistological staining.

Worsened Financial Situation During the COVID-19 Pandemic Was Associated With Depressive Symptomatology Among University Students in Germany: Results of the COVID-19 International Student Well-Being Study.

Background: Previous findings suggest that university students are at an elevated risk to experience financial hardship and to suffer from depressive symptoms. This vulnerability may have substantially increased during the coronavirus disease 19 (COVID-19) pandemic which might have affected students' socio-economic situation but possibly also their mental well-being. We examined whether the financial situation changed during the COVID-19 pandemic among German university students, and whether changes were associated with mental well-being. Methods: We conducted a cross-sectional online survey in May and July 2020 at five German universities. Participants were asked, if they had sufficient financial resources to cover monthly expenses before and during the pandemic. The answer options were dichotomized into worsened and no change/better financial situation compared to before the COVID-19 pandemic. Depressive symptoms were assessed using the CES-D 8 scale. For examining associations between sociodemographic, study-related, and financial factors and "worsened financial situation," we ran a generalized linear mixed model. To assess associations between depressive symptoms and worsened financial situation, we performed a linear mixed model. Results: We included 7,199 participants in the analyses (69% female, 30% male, 1% diverse, mean age: 24 years, standard deviation: 4.7). Overall, 25% of the participants reported to have a worsened financial situation at the time of the survey than in the time before COVID-19. Factors associated with a worsened financial situation were migration background, parents not being academics, not being able to borrow money, and payment of tuition fee by student and loan [odds ratios (OR) ranging from 1.20 to 2.35]. Factors associated with lower odds were: being single, living with others, studying a health-related field, being enrolled in a doctoral/Ph.D. or state exam program, and publicly funded tuition/tuition paid with a scholarship (OR ranging from 0.42 to 0.80). A worsened financial situation was associated with 1.02 points more on the CES-D 8 scale (95% CI: 0.80-1.24). Conclusion: Our results suggest that the pandemic put a number of students under financial strain with detrimental consequences for their mental well-being. Renewed attention must be paid to this vulnerable group to prevent the potentially damaging effects on their mental health.

Study of return rate and return time of undeliverable postal letters.

Postal questionnaires are widely used to collect data in health research and epidemiologic studies. One problem related to mail surveys is the availability of an up-to-date and accurate list of people in the population from which to draw the sample for the survey. For the identification of incorrect postal addresses it is important that all incorrectly addressed mails are returned as undeliverable. This study examines the proportion of unreturned postal letters that were sent to incorrect addresses. We sent 339 letters to existing addresses throughout Germany, but used fictional names name of persons. Three hundred and three letters (98.2%) were returned as undeliverable. The return rates only slightly differed by layout of the envelopes, region and deliverer.

A case-control study: occupational cooking and the risk of uveal melanoma.

BACKGROUND: A European-wide population based case-control study (European rare cancer study) undertaken in nine European countries examined risk factors for uveal melanoma. They found a positive association between cooks and the risk of uveal melanoma. In our study we examine whether cooks or people who worked in cook related jobs have an increased uveal melanoma risk. METHODS: We conducted a case-control study during 2002 and 2005. Overall, 1653 eligible subjects (age range: 20-74 years, living in Germany) participated. Interviews were conducted with 459 incident uveal melanoma cases, 827 population controls, 180 ophthalmologist controls and 187 sibling controls. Data on occupational exposure were obtained from a self-administered postal questionnaire and a computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. RESULTS: Overall, we did not observe an increased risk of uveal melanoma among people who worked as cooks or who worked in cook related jobs. When we restricted the source population of our study to the population of the Federal State of Northrhine-Westphalia, we observed an increased risk among subjects who were categorized as cooks in the cases-control analysis. CONCLUSION: Our results are in conflict with former results of the European rare cancer study. Considering the rarity of the disease laboratory in vitro studies of human uveal melanoma cell lines should be done to analyze potential exposure risk factors like radiation from microwaves, strong light from incandescent ovens, or infrared radiation.

Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals.

BACKGROUND: Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed. METHODS: We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel. RESULTS: Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports. CONCLUSIONS: Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic in silico simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.

Positive interaction between light iris color and ultraviolet radiation in relation to the risk of uveal melanoma: a case-control study.

PURPOSE: To examine the association among phenotypic characteristics, chronic and intermittent ultraviolet (UV) radiation, and the risk of uveal melanoma. DESIGN: Case-control study. PARTICIPANTS: Overall, between September of 2002 and March of 2005, 1677 eligible subjects (age range: 20-74 years, living in Germany) participated. Interviews were conducted with 459 incident uveal melanoma cases (response proportion 94%), 827 population controls (55%), 180 ophthalmologist controls (52%), and 187 sibling controls (57%). METHODS: Data on phenotypic characteristics and chronic and intermittent UV radiation exposure were obtained from a self-administered postal questionnaire and computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. Furthermore, we studied the presence of synergy (super additive of risk or relative excess risk due to interaction) between light iris color and several UV radiation exposures. MAIN OUTCOME MEASURES: Hair color at age 20 years, eye color, untanned skin color, ability to tan, propensity to burn on exposure, freckling, occupational sun exposure, artificial UV radiation, burns to the eyes. RESULTS: In all 3 control groups, fair skin color, freckling as a child, nevi on the upper arms, burns to the eyes, use of sunlamps, and ever worked outside for 4 or more hours per day were positively associated with uveal melanoma. The association with eye color was apparent only in population controls (odds ratio = 1.9; 95% confidence interval [CI], 1.4-5.2), resulting in a relative excess risk due to interaction of 0.9 (95% CI, -0.6-2.3) for light iris color and more than 5 eye burns (UV-related keratitis) and 0.6 (95% CI, -0.3 to 1.5) for light iris color and eye protection. CONCLUSIONS: Our interaction analyses suggest that there is an etiologic synergism between light iris color and the exposure of UV radiation. People with light iris color may have an especially increased risk for uveal melanoma if they are exposed to UV radiation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Reliability and validity of needle biopsy evaluation of breast-abnormalities using the B-categorization--design and objectives of the Diagnosis Optimisation Study (DIOS).

BACKGROUND: The planned nationwide implementation of mammography screening 2007 in Germany will increase the occurrence of mammographically detected breast abnormalities. These abnormalities are normally evaluated by minimal invasive core biopsy. To minimize false positive and false negative histological findings, quality assurance of the pathological evaluation of the biopsies is essential. Various guidelines for quality assurance in breast cancer diagnosis recommend applying the B-classification for histopathological categorization. However, to date there are only few studies that reported results about reliability and validity of B-classification. Therefore, objectives of our study are to determine the inter- and intraobserver variability (reliability study) and construct and predictive validity (validity study) of core biopsy evaluation of breast abnormalities. This paper describes the design and objectives of the DIOS Study. METHODS/DESIGN: All consecutive asymptomatic and symptomatic women with breast imaging abnormalities who are referred to the University Hospital of Halle for core breast biopsy over a period of 24 months are eligible. According to the sample size calculation we need 800 women for the study. All patients in the study population underwent clinical and radiological examination. Core biopsy is performed by stereotactic-, ultrasound- or magnetic resonance (MR) guided automated gun method or vacuum assisted method. The histopathologic agreement (intra- and interobserver) of pathologists and the histopathologic validity will be evaluated. Two reference standards are implemented, a reference pathologist and in case of suspicious or malignant findings the histopathologic result of excision biopsy. Furthermore, a self administrated questionnaire which contains questions about potential risk factors of breast cancer, is sent to the participants approximately two weeks after core biopsy. This enables us to run a case-control-analysis (woman with breast cancer histological verified after excision are defined as cases, woman without malignant breast lesions are defined as controls) to investigate the predictive values of various risk factors on breast cancer risk. CONCLUSION: The analysis of reliability and validity of the histopathological evaluation of core biopsy specimens of breast abnormalities is intended to provide important information needed for a high quality in breast cancer diagnostic and for planning of treatment strategies.

Licit and illicit substance use patterns among university students in Germany using cluster analysis.

BACKGROUND: The use of multiple licit and illicit substances plays an important role in many university students' lives. Previous research on multiple substance use patterns of university students, however, often fails to examine use of different illicit substances and/or hookah. Our objective was to complement and advance the current knowledge about common consumption patterns regarding illicit substances and hookah use in this group. METHODS: Students from eight German universities completed an online survey as part of the INSIST study ('INternet-based Social norms Intervention for the prevention of substance use among STudents') regarding their consumption of alcohol, tobacco, hookah, cannabis and other illicit substances. Cluster analysis identified distinct consumption patterns of concurrent and non-concurrent substance use and multinomial logistic regressions described key sociodemographic factors associated with these clusters. RESULTS: Six homogeneous groups were identified: 'Alcohol Abstainers' (10.8%), 'Drinkers Only' (48.2%), 'Drinkers and Cigarette Smokers' (14.6%), 'Cannabis and Licit Substance Users' (11.2%), 'Hookah Users with Co-Use' (9.8%) and 'Illicit Substance Users with Co-Use' (5.4%). Illicit substance use clustered with the consumption of alcohol, tobacco and cannabis. Hookah use was regularly associated with alcohol consumption, less commonly associated with tobacco or cannabis use and very rarely associated with use of other illicit substances. Individuals consuming licit and illicit substances or hookah were mostly male and lived together with other students. Characteristics such as the number of years an individual had spent studying at a university, subject of study, immigrant background and religious affiliation were less commonly associated with cluster membership. CONCLUSIONS: Although we found substance use patterns in our sample largely similar to previous reports, we identified an important subgroup of individuals using both illicit and licit substances. These individuals may benefit especially from targeted interventions that focus on modifying addictive behavior patterns. TRIAL REGISTRATION: DRKS00007635 . Registered 17 December 2014 (retrospectively registered).