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Official statistics and claims data records indicate non-response and recall bias within survey-based estimates of health care utilization in the older population
Hunger Matthias,Schwarzkopf Larissa,Heier Margit,Peters Annette
BMC Health Services Research , 2013, DOI: 10.1186/1472-6963-13-1
Abstract: Background The validity of survey-based health care utilization estimates in the older population has been poorly researched. Owing to data protection legislation and a great number of different health care insurance providers, the assessment of recall and non-response bias is challenging to impossible in many countries. The objective of our study was to compare estimates from a population-based study in older German adults with external secondary data. Methods We used data from the German KORA-Age study, which included 4,127 people aged 65–94 years. Self-report questions covered the utilization of long-term care services, inpatient services, outpatient services, and pharmaceuticals. We calculated age- and sex-standardized mean utilization rates in each domain and compared them with the corresponding estimates derived from official statistics and independent statutory health insurance data. Results The KORA-Age study underestimated the use of long-term care services ( 52%), in-hospital days ( 21%) and physician visits ( 70%). In contrast, the assessment of drug consumption by postal self-report questionnaires yielded similar estimates to the analysis of insurance claims data ( 9%). Conclusion Survey estimates based on self-report tend to underestimate true health care utilization in the older population. Direct validation studies are needed to disentangle the impact of recall and non-response bias.
Reproductive Factors and Serum Uric Acid Levels in Females from the General Population: The KORA F4 Study
Doris St?ckl, Angela D?ring, Barbara Thorand, Margit Heier, Petra Belcredi, Christa Meisinger
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032668
Abstract: Objective Hyperuricemia is associated with an increased risk of metabolic and cardiovascular diseases. There are pronounced sex differences in the levels of uric acid. It is largely unknown whether or not reproductive parameters which induce hormonal changes are responsible for this. We examined if there are associations between reproductive parameters and uric acid levels in a female population-based sample. Methods In this cross-sectional analysis, data of 1530 women aged 32 to 81 years participating in the KORA F4 study, conducted between 2006 and 2008 in Southern Germany were used. Reproductive parameters were obtained by standardized interviews. Uric acid levels were tested by the uricase method. The whole study sample and stratified in pre- and postmenopausal women was analyzed. Results Menopausal status and earlier age at menarche were associated with higher serum uric acid levels (age-adjusted: p-values 0.003, <0.001 respectively; after multivariable adjustment, including BMI: p-values 0.002, 0.036). A history of oral contraceptive use showed an association with uric acid levels only after multivariable adjustment (p-value 0.009). Hot flushes showed an association with uric acid levels only after age-adjustment (p-value 0.038), but lost significance after adding other confounders. Other reproductive factors, including parity, current or ever use of hormone replacement therapy, current use of oral contraceptives, hysterectomy, bilateral oophorectomy, or depressive mood related to menopausal transition were not associated with uric acid levels. Conclusions Postmenopausal status, earlier age at menarche and a history of oral contraceptive use were independently associated with higher serum uric acid concentrations in women from the general population. Further studies, especially longitudinal population-based studies investigating the relationship of female reproductive parameters with uric acid levels are necessary to confirm our findings.
Albuminuria, cardiovascular risk factors and disease management in subjects with type 2 diabetes: a cross sectional study
Christa Meisinger, Margit Heier, Rüdiger Landgraf, Michael Happich, H-Erich Wichmann, Wolfgang Piehlmeier
BMC Health Services Research , 2008, DOI: 10.1186/1472-6963-8-226
Abstract: The presented data were derived from the 'KORA Augsburg Diabetes Family Study', conducted between October 2001 and September 2002. Participants were adults aged 29 years and older with previously diagnosed type 2 diabetes (n = 581). Microalbuminuria was defined as an albumin-creatinine ratio of 30 to 300 mg/g, and macroalbuminuria as an albumin-creatinine ratio of more than 300 mg/g.Microalbuminuria was revealed in 27.2% and macroalbuminuria in 9.0% of the 581 included diabetic persons. Multivariable regression analysis identified HBA1c, duration of diabetes, systolic blood pressure, serum creatinine, smoking and waist circumference as independent risk factors associated with albuminuria (micro- or macroalbuminuria). Relatively few persons with type 2 diabetes achieved treatment targets of HbA1c < 7% (46.6%), total cholesterol < 200 mg/dl (44.1%), and LDL cholesterol < 100 mg/dl (16.0%). Optimal HDL cholesterol values (> 45 mg/dl in men, > 55 mg/dl in women) were found in 55.8%, and blood pressure values < 130 and < 85 mmHg in 31.3% of the personsAlbuminuria is common among German persons with known type 2 diabetes. Despite evidence-based guidelines, only a small proportion of type 2 diabetic persons achieved the recommended levels of glycemic control and control of cardiovascular risk factors.Throughout the world, the number of people developing type 2 diabetes mellitus is increasing dramatically. At the present time the disease affecting around 171 million people worldwide and the World Health Organization predicts that this number will rise to 366 million by 2030 [1]. Consequently, the number of people developing diabetes-related complications will increase. Microalbuminuria is a common complication of diabetes and appears to be a strong predictor of subsequent development of overt diabetic nephropathy [2], which is the leading cause of end-stage renal disease in the western world [3,4]. Without any intervention, among type 2 diabetic patients about 20–40% with m
Association between Markers of Fatty Liver Disease and Impaired Glucose Regulation in Men and Women from the General Population: The KORA-F4-Study
Ina-Maria Rückert,Margit Heier,Wolfgang Rathmann,Sebastian E. Baumeister,Angela D?ring,Christa Meisinger
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0022932
Abstract: To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic fatty liver disease (NAFLD) respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women from the general German population.
Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?  [PDF]
Margit Pissarek
World Journal of Neuroscience (WJNS) , 2014, DOI: 10.4236/wjns.2014.44040

Neuropeptide receptors of the brain and spinal cord are parts of the pain circuits targeted by analgesic drugs. Some of these receptors have been found in the central nervous system as well as in intracranial vascular structures and achieved revival of attention because of their role in acute and chronic pain syndromes. A number of them are of high clinical relevance for e.g. migraine. Others participate in symptoms of rare diseases like amyotrophic lateral sclerosis. Here we will focus on five of the neuropeptide receptors and their non-peptide ligands potentially or already successfully used as PET probes. Opioid receptors and neurotensin receptors are known to mediate analgesic actions. Bradykinin and calcitonin gene-related peptide (CGRP) receptors are known to be involved in the regulation of vascular tone and inflammatory responses, and neurokinin receptors play a role in the occurrence of pain perception in a rather indirect manner. Most experiences as PET tracers have been gathered with opioid receptor ligands and neurokinin receptor ligands. The most innovative fields revealed by the studies summarized in this report are the ligands of κ opioid receptors and CGRP receptors for which a first PET tracer was presented recently.

Potential PET Ligands for Imaging of Cerebral VPAC and PAC Receptors: Are Non-Peptide Small Molecules Superior to Peptide Compounds?  [PDF]
Margit Pissarek
World Journal of Neuroscience (WJNS) , 2015, DOI: 10.4236/wjns.2015.55036
Abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) have been known for decades to mediate neuroendocrine and vasodilative actions via G-protein-coupled receptors of Class B. These are targets of imaging probes for positron emission tomography (PET) or single photon emission tomography (SPECT) in tumor diagnostics and tumor grading. However, they play only a subordinate role in the development of tracers for brain imaging. Difficulties in development of non-peptide ligands typical for cerebral receptors of PACAP and VIP are shared by all members of Class B receptor family. Essential landmarks have been confirmed for understanding of structural details of Class B receptor molecular signalling during the last five years. High relevance in the explanation of problems in ligand development for these receptors is admitted to the large N-terminalectodomain markedly different from Class A receptor binding sites and poorly suitable as orthosteric binding sites for the most small-molecule compounds. The present study is focused on the recently available receptor ligands for PAC1, VPAC1 and VPAC2 receptors as well as potential small-molecule lead structures suitable for use in PET or SPECT. Recently, biaryl, cyanothiophene and pentanamide structures with affinities in nM-range have been proposed as non-peptide ligands at VPAC1 and VPAC2 receptors. However, most of these ligands have been classified as non-competitive related to the orthosteric binding site of endogenous peptide ligands of VPAC receptors. For PAC1 receptors have been identified hydrazide compounds for which an inhibitory and potentially competitive mechanism of receptor binding has been postulated based on molecular docking studies.
Small Molecule-Assisted PET: Approaches to Imaging of Conformational Diseases of the Brain  [PDF]
Margit Pissarek
World Journal of Neuroscience (WJNS) , 2017, DOI: 10.4236/wjns.2017.71010
Abstract: PET (positron emission tomography) in vivo imaging of cerebral conformational diseases is essentially based on non-peptide small molecule ligands used to detect early alterations in peptide secondary structures and subsequent accumulation of aberrant oligomers and protein deposits involved in progressive neurodegeneration, cognitive and movement disorders. In this article, an overview is given about tracers currently available and lead structures of potential PET probes for detection of?β-amyloid (Aβ), tau protein, α-synuclein, constitutive (PrPc) and infectious isoforms (PrPsc) of prions (proteinaceous infectious particles) as imaging targets. Whereas the styrylpyridine derivative florbetapir, approved for clinical applications, the stilbene derivative florbetaben and the benzoxazole derivative BF227 show high affinity binding to Aβ, preclinical investigations promise improved pharmacokinetics for benzoimidazothiazoles, aryloxazoles and benzofuran derivatives. Tau protein imaging based clinically, presently, on the pyridine-pyridoindole T807 has got new incentives following identification of a series of pyrrolopyridine quinolines and pharmacokinetic improvements of fluoropropoxy quinolines including for instance THK-5351. The pyridine isoquinoline MK6240 is involved now in clinical trials. Most forward-looking efforts apply to small molecule ligands of α-synuclein, which are expected to permit a breakthrough in differential diagnostics of Parkinson-related dementia and Lewy body diseases. However, at the moment the proposed lead structures are in affinity and blood brain barrier delivery properties below the possibilities of Aβ?and tau protein ligands. This is the case also for potential tracers of prion proteins.
Activated Microglia in the Brain: Mitochondrial and Cell Membrane-Associated Targets for Positron Emission Tomography  [PDF]
Margit Pissarek
World Journal of Neuroscience (WJNS) , 2018, DOI: 10.4236/wjns.2018.81006
Abstract: The emission tomographic imaging of activated microglia in the brain moves into the focus of neuroscientific research with increasing recognition of contributions of early inflammatory processes to neurodegenerative, traumatic, cancerous and infectious diseases of the brain. Whereas the mitochondrial isoform of the 18 kDa translocator protein (TSPO1) has been the main cellular target for positron emission tomography (PET) of this type of cells for decades, alternative marker proteins in the plasma membrane of microglia challenge efforts in ligand development, recently. The present report includes PET approaches using the chemokine receptor CX3CR1 and the FR2 folate receptor in parallel to small molecule PET tracers available for in vivo visualization of the “classical” target TSPO1. It compares first and second generation of TSPO1 ligands as well as new compounds like the tetrahydrocarbazole [18F]GE-180 and the quinazoline [11C]ER176 presumed to reduce polymorphism-related inter-subject variations, with allosteric ligands for the chemokine receptor CX3CR1 and with radio labelled folate conjugates targeting the folate “cargo” receptor FR1 and the FR2 receptor characteristic for anti-inflammatory M2 microglia.
Age at Menarche and Its Association with the Metabolic Syndrome and Its Components: Results from the KORA F4 Study
Doris St?ckl, Christa Meisinger, Annette Peters, Barbara Thorand, Cornelia Huth, Margit Heier, Wolfgang Rathmann, Bernd Kowall, Heidi St?ckl, Angela D?ring
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0026076
Abstract: Objective The metabolic syndrome is a major public health challenge and identifies persons at risk for diabetes and cardiovascular disease. The aim of this study was to examine the association between age at menarche and the metabolic syndrome (IDF and NCEP ATP III classification) and its components. Design 1536 women aged 32 to 81 years of the German population based KORA F4 study were investigated. Data was collected by standardized interviews, physical examinations, and whole blood and serum measurements. Results Young age at menarche was significantly associated with elevated body mass index (BMI), greater waist circumference, higher fasting glucose levels, and 2 hour glucose (oral glucose tolerance test), even after adjusting for the difference between current BMI and BMI at age 25. The significant effect on elevated triglycerides and systolic blood pressure was attenuated after adjustment for the BMI change. Age at menarche was inversely associated with the metabolic syndrome adjusting for age (p-values: <0.001 IDF, 0.003 NCEP classification) and additional potential confounders including lifestyle and reproductive history factors (p-values: 0.001, 0.005). Associations remain significant when additionally controlling for recollected BMI at age 25 (p-values: 0.008, 0.033) or the BMI change since age 25 (p-values: 0.005, 0.022). Conclusion Young age at menarche might play a role in the development of the metabolic syndrome. This association is only partially mediated by weight gain and increased BMI. A history of early menarche may help to identify women at risk for the metabolic syndrome.
Patterns of Multimorbidity in the Aged Population. Results from the KORA-Age Study
Inge Kirchberger, Christa Meisinger, Margit Heier, Anja-Kerstin Zimmermann, Barbara Thorand, Christine S. Autenrieth, Annette Peters, Karl-Heinz Ladwig, Angela D?ring
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030556
Abstract: Multimorbidity is a common problem in aged populations with a wide range of individual and societal consequences. The objective of the study was to explore patterns of comorbidity and multimorbidity in an elderly population using different analytical approaches. Data were gathered from the population-based KORA-Age project, which included 4,127 persons aged 65–94 years living in the city of Augsburg and its two surrounding counties in Southern Germany. Information on the presence of 13 chronic conditions was collected in a standardized telephone interview and a self-administered questionnaire. Patterns of comorbidity and multimorbidity were analyzed using prevalence figures, logistic regression models and exploratory tetrachoric factor analysis. The prevalence of multimorbidity (≥2 diseases) was 58.6% in the total sample. Hypertension and diabetes (Odds Ratio [OR] 2.95, 99.58% confidence interval [CI] [2.19–3.96]), as well as hypertension and stroke (OR 2.00, 99.58% CI [1.26–3.16]) most often occurred in combination. This association was independent of age, sex and the presence of other conditions. Using factor analysis, we identified four patterns of multimorbidity: the first pattern includes cardiovascular and metabolic diseases, the second includes joint, liver, lung and eye diseases, the third covers mental and neurologic diseases and the fourth pattern includes gastrointestinal diseases and cancer. 44% of the persons were assigned to at least one of the four multimorbidity patterns; 14% could be assigned to both the cardiovascular/metabolic and the joint/liver/lung/eye pattern. Further common pairs were the mental/neurologic pattern combined with the cardiovascular/metabolic pattern (7.2%) or the joint/liver/lung/eye pattern (5.3%), respectively. Our results confirmed the existence of co-occurrence of certain diseases in elderly persons, which is not caused by chance. Some of the identified patterns of multimorbidity and their overlap may indicate common underlying pathological mechanisms.
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