[FIMA--questionnaire for health-related resource use in an elderly population: development and pilot study]. / FIMA--Fragebogen zur Erhebung von Gesundheitsleistungen im Alter: Entwicklung und Pilotstudie.

AIM: Due to demographic trends towards an ageing population resource use of health care will increase. By collecting health-related costs via questionnaires, the impact of socio-economic variables and other medical factors can be examined. In addition, only patient reported resource use accounts for out-of-pocket payments. Thus, it is necessary to develop an appropriate tool to collect the health-related resource use in an elderly population. METHODS: The development of the FIMA (questionnaire for the use of medical and non-medical services in old age) was carried out in 6 steps. These included the determination of necessary questionnaire contents based on a literature review and the wording and layout were defined. Finally the questionnaire was tested in a pilot study and was modified. RESULTS: All direct medical and non-medical resource use excluding transportation and time costs were recorded. Productivity losses were not included. The recall time frames differed according to resource categories (7 days, 3 months, 12 months). For the pilot study, 63 questionnaires were analysed. The response rate was 69%. The questionnaire took an average of 21 min to complete. Three quarters of respondents completed the questionnaire without help and 90% rated the difficulty as easy or even very simple. There was good agreement between self-reported health-related quality of life and the resource use of nursing and domestic help (phi coefficient values between 0.52 and 0.58). CONCLUSION: The FIMA is a generic questionnaire which collects the health-related resource use within the older population groups.

[Calculation of standardised unit costs from a societal perspective for health economic evaluation]. / Ermittlung standardisierter Bewertungssätze aus gesellschaftlicher Perspektive für die gesundheitsökonomische Evaluation.

PURPOSE: Due to demographic aging, economic evaluation of health care technologies for the elderly becomes more important. A standardised questionnaire to measure the health-related resource utilisation has been designed. The monetary valuation of the resource use documented by the questionnaire is a central step towards the determination of the corresponding costs. The aim of this paper is to provide unit costs for the resources in the questionnaire from a societal perspective. METHODS: The unit costs are calculated pragmatically based on regularly published sources. Thus, an easy update is possible. RESULTS: This paper presents the calculated unit costs for outpatient medical care, inpatient care, informal and formal nursing care and pharmaceuticals from a societal perspective. CONCLUSION: The calculated unit costs can serve as a reference case in health economic evaluations and hence help to increase their comparability.

Clinical manifestations and treatment options in patients with cirrhosis and diabetes mellitus.

BACKGROUND: Diabetes is frequently diagnosed in patients with cirrhosis and represents an important risk factor for morbidity and mortality. Pharmacological therapy is limited due to hepatotoxicity and the risk of hypoglycemia. Investigations on medical practice in this patient population, frequency of diabetes-associated complications and the impact of quality of metabolic control are rare. AIMS AND METHODS: A retrospective analysis was performed to compare the effects of hypoglycemic treatment, the achieved glycemic control under therapy, the prevalence of typical cirrhosis-related or microangiopathic complications, and cardiovascular comorbidities between a group of diabetic patients with cirrhosis (n = 87) and a nondiabetic cirrhotic population (n = 198). RESULTS: The prevalence of diabetes in our cohort was 30.5%. Of all diabetic patients, 39.1% received therapy which might potentially result in serious side effects in patients with end-stage liver disease. The rate of ongoing alcohol abuse (28.7%) and noncompliance under medication (41.4%) was high. Only 28.7% of all diabetic subjects showed satisfactory (as defined by HbA1c ≤ 6.5%) glycemic control under therapy. Patients achieving satisfactory control experienced a lower rate of certain cirrhosis-related complications such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), arterial hypertension, and hypercholesterolemia. HE was significantly more frequent in diabetic than nondiabetic cirrhotic patients.

Accuracy of anorectal manometry in patients with fecal incontinence.

BACKGROUND/AIM: Patients with fecal incontinence (FI) have lower anal resting (MRP) and squeeze (MSP) pressure and an impaired sensitivity compared to healthy people. However, whether anorectal manometry (ARM) can separate precisely between health and disease is discussed controversially. The aim was to evaluate the accuracy of ARM in a huge cohort of patients and controls. METHODS: ARM was obtained in 144 controls and in 559 FI patients. MRP, MSP, and balloon volume at first perception (BVP) and urge sensation (BVU) were determined. Receiver operating curve analysis was used to determine optimal cut-offs and sensitivity, specificity and accuracy calculated. RESULTS: FI patients showed lower MRP, MSP, BVU (p < 0.001) and a higher BVP (p = 0.007). Deterioration of the ARM parameter increased with FI severity. ARM demonstrated an excellent sensitivity (91.4%) and accuracy (85.8%), but only a moderate specificity (62.5%). The sensitivity of ARM rose with FI severity. The pressure data showed higher sensitivity and accuracy than the sensory data despite comparable specificity. CONCLUSIONS: Sensitivity and accuracy of single ARM parameters is only moderate for the pressure data and poor for the sensory data. In contrast, ARM demonstrated an excellent sensitivity, a moderate specificity, and a convincing accuracy justifying its use in clinical routine.

[Management of impacted foreign bodies in the upper gastrointestinal tract in adult patients - results of a retrospective case series]. / Management von impaktierten Fremdkörpern im oberen Gastrointestinaltrakt bei erwachsenen Patienten - Ergebnisse einer retrospektiven Fallserie.

INTRODUCTION: Impaction of foreign bodies in the upper gastrointestinal tract represents a rare endoscopic emergency regarding the danger of organic lesions. Therefore, the therapeutic strategy, rational postinterventional monitoring and potential consequences for the course in the future are often not clear. METHODS: Out of all oesophagogastroduodenoscopies performed between 2008 and 2010 (n = 10,830), the endoscopies due to bolus impaction were analysed retrospectively concerning endoscopic findings, course of intervention and causative predisposing factors using descriptive statistics. RESULTS: In the study period, endoscopy was performed in 45 different patients 49 times when foreign body impaction was suspected. In 38 cases (77.6%) a foreign body could be detected by endoscopy, most frequently a meat bolus (65.8%), followed by dental prostheses and tablets. Endoscopic removal could be successfully performed in 97.4%. An operation was necessary in only one patient. A macroscopically unremarkable upper gastrointestinal tract without any predisposing conditions for foreign body impaction could be detected in 33.3%. In one case eosinophilic oesophagitis could be diagnosed histologically. The foreign body was pushed into the stomach by the "push technique" in 54.1%. The foreign body removal was performed as an ambulant intervention in 63.2%. DISCUSSION: In the majority of cases, impacted foreign bodies of the upper gastrointestinal tract could be removed safely by endoscopy, e.g., using the "push technique". However, the therapeutic strategy should be individually adjusted based on the consistancy of the foreign body. If no predisposing conditions can be found, histological diagnosis should be performed to detect potential eosinophilic oesophagitis early enough.

[Frequency of cardiac arrhythmia in patients with liver cirrhoses and evaluation of associated factors]. / Häufigkeit von Herzrhythmusstörungen bei Patienten mit Leberzirrhose sowie Evaluierung assoziierter Faktoren.

INTRODUCTION: Studies analysing the frequency of rhythm disorders in patients with cirrhosis are rare. Nevertheless, factors triggering rhythm disorders occur frequently in cirrhosis. Therefore, a retrospective case control study was performed investigating the frequency of cardiac arrhythmia in a population of patients with cirrhosis while evaluating several associated factors. METHODS: The files of patients with cirrhosis (n  =  293) in the period 2004 - 2008 were analysed retrospectively regarding cardiac arrhythmia. The frequency of cardiac arrhythmia in the presence of relevant risk factors was analysed using χ ²tests and logistic regression models. RESULTS: 61.1  % of all patients were male (mean age 61.7 years) and 38.9  % female (mean age 62.8 years). The severity of cirrhosis according to the Child-Pugh score (CP) was as follows: CP A 43.3  %, CP B 32.8  % and CP C 23.9  %. Altogether, rhythm disorders were diagnosed in 16.4  % (48/293) of the study population, most frequently atrial fibrillation (68.8  %) and atrial flutter (6.7  %). An advanced age and comorbidities such as arteriosclerotic diseases, hypercholesterinemia (p  <  0.001, each) and diabetes mellitus (p  =  0.013) correlated significantly with the frequency of rhythm disorders which occurred more often in males than in females (p  = 0.066). Ongoing alcohol abuse, the severity of cirrhosis and arterial hypertension were not associated significantly with the onset of rhythm disorders. 84.4  % of all patients with cardiac arrhythmia were treated by diuretics. Decreased (<  3.5 mmol/L) and elevated (>  5 mmol/L) potassium values were observed in 60.6  % of the study collective. Rhythm disorders were more often observed in patients with hyperkalemia (especially atrioventricular block, p  < 0.01). CONCLUSION: Compared to the average population, the prevalence of atrial fibrillation was increased in our cirrhotic cohort. The occurrence of rhythm disorders was significantly associated with arteriosclerotic diseases, hypercholesterinaemia and diabetes mellitus. Additionally, cardiac arrhythmia must be considered under diuretic therapy and in the presence of electrolyte disturbances.

[Multimorbidity and successful aging: the population-based KORA-Age study]. / Multimorbidität und erfolgreiches Altern: Ein Blick auf die Bevölkerung im Rahmen der KORA-Age-Studie.

BACKGROUND: The objective of the KORA-Age research consortium is to assess the determinants and consequences of multimorbidity in the elderly and to look into reasons for successful aging in the general public. PATIENTS AND METHODS: In the KORA-Age cohort study 9,197 persons were included who where born in the year 1943 or before and participants of previous KORA cohort studies conducted between 1984 and 2001 (KORA: Cooperative Health Research in the Region of Augsburg). The randomized intervention study KORINNA (Coronary infarct follow-up treatment in the elderly) tested a nurse-based case management program with 338 patients with myocardial infarct and included an evaluation in health economics. RESULTS: A total of 2,734 deaths were registered, 4,565 participants submitted a postal health status questionnaire and 4,127 participants were interviewed by telephone (response 76.2% and 68.9% respectively). A gender and age-stratified random sample of the cohort consisting of 1,079 persons took part in a physical examination (response 53.8%). CONCLUSION: The KORA-Age consortium was able to collect data in a large population-based sample and is contributing to the understanding of multimorbidity and successful aging.

Influence of gender and age on anorectal function: normal values from anorectal manometry in a large caucasian population.

INTRODUCTION: In the literature, data on the effects of gender and age on the pressure data of anorectal manometry differ. Possible reasons are investigation of only small numbers of healthy people and comparison of only 2 groups with large age differences. In addition, data about the influence of gender or age on anorectal sensation are sparse. Therefore, the aim of the present study was to determine the influence of gender and age on anorectal manometry in a large healthy female and male cohort spanning a great age range. METHODS: Anorectal manometry was performed in 72 women and 74 men with a median age of 64 years in both groups (ranges: women 22-90 years; men 23-88 years). We determined mean anal resting and squeeze pressure as well as minimal rectal balloon volume for perception and for urge/desire to defecate. The Mann-Whitney U test was used to analyze for gender differences, regression analysis to search for age influences. RESULTS: Squeeze pressure (p = 0.007) and perception threshold (p < 0.001) are significantly lower in females, while the mean resting pressure and urge threshold are similar in females and males. Mean resting pressure (women p < 0.0001; men p = 0.03) and mean squeeze pressure decrease (women p < 0.0001; men p = 0.004) with age. An age-related increase in sensory thresholds (= decreased rectal sensitivity) is only seen in females (perception threshold p = 0.01; urge threshold p = 0.04). CONCLUSION: Most of the parameters measured by anorectal manometry (anal canal pressure, sensory thresholds) are influenced by gender and age. Therefore, the results of anorectal manometry must be interpreted in relation to sex- and age-adapted normal values.

[Mesenteric inflammatory veno-occlusive disease (MIVOD)--an underdiagnosed disease?]. / Mesenterische inflammatorische veno-okklusive Erkrankung (MIVOD) - eine unterdiagnostizierte Erkrankung?

Mesenteric, inflammatory veno-occlusive disease is an entity of unknown incidence and aetiology. Inflammation and necrosis of mesenteric veins leads to severe ischaemic damage of an intestinal segment. The clinical and endoscopic presentation can be ambiguous. However, modern multiphasic contrast-enhanced computed tomography allows early diagnosis, when characteristic features are considered. As local resection is the only known cure with minimal risk of recurrent disease, knowledge of this rare disease entity can spare our patients a risky delay of resection and erroneous therapeutic approaches.

Vertigo and dizziness cause considerable more health care resource use and costs: results from the KORA FF4 study.

OBJECTIVES: Vertigo is a common reason for primary care consultations, and its diagnosis and treatment consume considerable medical resources. However, limited information on the specific cost of vertigo is currently available. The aim of this study is to analyse the health care costs of vertigo and examine which individual characteristics would affect these costs. STUDY DESIGN: We used cross-sectional data from the German KORA ("Cooperative Health Research in the Augsburg Region") FF4 study in 2013. METHODS: Impact of personal characteristics and other factors was modelled using a two-part model. Information on health care utilisation was collected by self-report. RESULTS: We included 2277 participants with a mean age of 60.8 (SD = 12.4), 48.4% male. Moderate or severe vertigo was reported by 570 (25.0%) participants. People with vertigo spent 818 Euro more than people without vertigo in the last 12 months (2720.9 Euro to 1902.9 Euro, SD = 4873.3 and 5944.1, respectively). Consultation costs at primary care physicians accounted for the largest increase in total health care costs with 177.2 Euro (p < 0.01). After adjusting for covariates, the presence of vertigo increased both the probability of having any health care costs (OR = 1.6, 95% CI =[1.2;2.4]) and the amount of costs (exp(ß) = 1.3, 95% CI = [1.1;1.5]). The analysis of determinants of vertigo showed that private insurance and a medium level of education decreased the probability of any costs, while higher income increased it. CONCLUSIONS: The presence of vertigo and dizziness required considerable health care resources and created significantly more related costs in different health care sectors for both primary and pertinent secondary care.

Ultraviolet exposure as the main initiator of p53 mutations in basal cell carcinomas from psoralen and ultraviolet A-treated patients with psoriasis.

Basal cell carcinoma, the most frequent skin cancer in humans, is often linked to chronic sun exposure. In psoralen and ultraviolet A-treated psoriatic patients, basal cell carcinomas may occur even more frequently; however, the exact etiology and mechanisms of tumorigenesis in psoriatic patients are unclear because psoralen and ultraviolet A is not only a carcinogen but also an immunosuppressor and because psoralen and ultraviolet A-treated psoriatic patients often have other (co)carcinogenic risk factors (e.g, therapeutic exposure to ultraviolet B, X-ray radiation, arsenic, tar, and/or chemotherapeutic agents such as methotrexate). In this study, we analyzed the DNA of 13 basal cell carcinomas from five psoralen and ultraviolet A-treated psoriatic patients for mutations of the p53 tumor suppressor gene. DNA sequencing revealed a total of 11 mis-sense, two non-sense, and four silent mutations in seven of the 13 basal cell carcinomas (54%). Of the 13 total mis-sense or non-sense mutations, 12 (92%) occurred at dipyrimidine sites and nine (69%) were of the ultraviolet fingerprint type (eight C-->T transitions and one CC-->TT transition). Three of the C-->T transitions occurred at dipyrimidine sites opposite a 5'-TpG sequence (a potential psoralen-binding site and target for psoralen and ultraviolet A mutagenesis). Thus, whether these mutations were induced by ultraviolet or psoralen and ultraviolet A was not clear. In addition, two other mutations (15%) occurred at 5'-TpG sites, one (8%) occurred at a 5'-TpA site (the most frequent site of psoralen binding and mutagenesis in cell and murine studies), and one (8%) involved a G-->T transversion. These results suggest that (i) the major initiator of p53 mutations in basal cell carcinoma in psoralen and ultraviolet A-treated psoriasis patients is environmental and/or therapeutic ultraviolet(B) exposure, and that (ii) psoralen and ultraviolet A itself causes only a smaller portion of p53 mutations in psoralen and ultraviolet A-associated basal cell carcinomas.

HPA-1 and HPA-3 polymorphisms of the platelet fibrinogen receptor and coronary artery disease and myocardial infarction.

Platelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa) plays a fundamental role in atherothrombosis. The human platelet antigen (HPA) -1 and the HPA-3 are the most extensively studied polymorphisms of GPIIIa and GPIIb, respectively. This study was designed to test, in a large population, the hypothesis that these polymorphisms represent a risk factor for the occurrence of coronary artery disease (CAD) and myocardial infarction (MI). Consecutive, angiographically examined patients with significant coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (CAD, n = 998) and those with old or acute MI constituted the group with MI (MI, n = 793). As controls served subjects, matched with patients for age and sex, with neither angiographic CAD nor symptoms or signs of MI (matched controls [MC], n = 340) as well as a group of blood donors without cardiac symptoms or signs of CAD (BD, n = 104). Genotype distribution was similar across the groups; HPA-1a/a: HPA-1a/b: HPA-1b/b was 75.0%: 22.1%: 2.9% in BD, 72.6%: 24.7%: 2.6% in MC, 70.5%: 26.8%: 2.7% in CAD, and 70.7%: 26.4%: 2.9% in MI; HPA-3a/a: HPA-3a/b: HPA-3b/b was 39.4%: 40.4%: 20.2% in BD, 33.5%: 50.0%: 16.5% in MC, 35.0%: 46.4%: 17.0% in CAD, and 37.1%: 48.0%: 16.5% in MI. There was no interaction between these polymorphisms, nor between each of these polymorphisms and other risk factors. Thus, the HPA-1 and HPA-3 polymorphisms are neither separately nor in concert associated with any measurable increase of the risk for CAD or MI in angiographically evaluated subjects.

High mutation frequency at Ha-ras exons 1-4 in squamous cell carcinomas from PUVA-treated psoriasis patients.

Clinical follow-up studies have revealed that PUVA-treated patients are at increased risk of skin cancer, particularly squamous cell carcinoma (SCC). However, since psoralen and UVA (PUVA) is not only a potent mutagen and carcinogen but also an immunosuppressor, and since other (co)carcinogenic factors often exist in psoriasis patients, the exact causes and mechanisms of PUVA-associated SCC are still not completely understood. In order to fill this gap the tools of molecular epidemiology are being used to study the SCC mutational spectra of p53 and Ha-ras, two of the most commonly mutated genes in human cancers. A previous mutation analysis revealed that SCC in PUVA-treated patients often carried mutated p53 genes and that many of the mutations had the UV fingerprint (i.e. C-->T or CC-->TT transitions at dipyrimidine sites). In the present study DNA-sequencing analysis revealed a total of 18 Ha-ras missense or nonsense mutations at exons 1-4 in 13 of 17 SCC (76%) from 8 of 11 (73%) PUVA-treated psoriasis patients. Six of the 18 mutations (33%) were of UV-fingerprint type (C-->T transitions), five (28%) were at 5'-TpG sites (i.e. potential psoralen-binding sites and thus potentially caused by PUVA) and seven were of other type (39%), including six G:C-->T:A transversions at hotspot codon 12. In addition, in the case of 6 of the 11 subjects (55%) both tumor and normal skin samples contained a T:A-->C:G base change at codon 27 (a 5'-ATT site), a change previously hypothesized to be a possible silent Ha-ras polymorphism at one allele. When we compared the present Ha-ras mutation spectrum with the p53 mutation spectrum from a previous study of the samples, we found that approximately half of the tumors harbored mutations in both Ha-ras and p53. Together, our results indicate that Ha-ras mutations are present in a large proportion of PUVA-associated SCC and that UVB, PUVA and other agents may induce Ha-ras mutations and act together with p53 in the formation of SCC in psoriasis patients.

Hexadecylphosphocholine inhibits invasion of mouse T-cell lymphoma cells in two different invasion assays.

Hexadecylphosphocholine (HePC), an ether lipid analogue, is a new antineoplastic drug which has been shown to exert a remarkable antiproliferative effect in vitro and in vivo. The signal transduction pathway and the phospholipid synthesis are thought to be the main putative molecular targets of HePC, yet the exact mechanism of action is still unclear. To investigate the antiinvasive activity of HePC on a mouse T-cell lymphoma cell line (BW-O-Li1), we used a type I collagen gel and devitalized dermis as substrate to evaluate the migration of BW-O-Li1 after exposure to HePC. BW-O-Li1 cells were exposed for 24 h to a non-cytotoxic (10 microM) as well as to cytotoxic concentrations of HePC. Afterwards, BW-O-Li1 cells were seeded on top of a reconstituted collagen gel layer or pippeted into a steel ring placed on the dermal site of a devitalized dermis. Lymphoma cells, which invaded the collagen layer were counted by light microscopy, invasion into devitalized dermis was measured by an image analysis system. Compared to unexposed cells, invasion into the collagen gel differed significantly even at 10 microM HePC, whereas the absolute number of invading cells, independently of the HePC concentration, showed no difference in the amount of counted cells. Migration into devitalized dermis was significantly reduced for 10 microM and 40 microM HePC. These data show that complementary information can be obtained by application of the two invasion assays and that the antiinvasive effect of HePC emerges at non-cytotoxic concentrations of the substance.

The effect of osmolarity and caloric load on small bowel motility.

BACKGROUND: Although there is profound knowledge about cyclic fasting motility, the postprandial intestinal motor response is not well investigated. It is intriguing to speculate that nutrient composition alters small bowel motility significantly and, in a clinical setting, may account for adverse gastrointestinal symptoms in enteral nutrition (EN). We aimed to assess the impact of different caloric loads and osmolarities of EN on human jejunal motility. METHODS: Sixteen healthy subjects underwent a series of duodenal infusions of EN solutions, either with iso-osmolar solution with different caloric loads (1.32, 2.64, or 3.96 kcal min(-1)), or with solutions of different osmolarities with constant caloric loads (300, 600, or 1200 mosmol). Jejunal solid-state manometry was analyzed over 90 min both visually and using dedicated computer software. KEY RESULTS: All tested nutrient solutions were able to trigger conversion to a postprandial jejunal motility pattern after a mean lag phase of 9.4 + 2.3 min (P = NS between different nutrient solutions). Different caloric loads did not result in significant differences in small bowel motility. However, increasing osmolarities caused a significant inhibition of contractile and propagative activity. CONCLUSIONS & INFERENCES: Small bowel motility under duodenal infusion of nutrient solutions is not influenced by caloric load in a physiological range, whereas high osmolarities inhibit small bowel motility.

Comparison of small-bowel motility of the human jejunum and ileum.

BACKGROUND: Knowledge about human cyclic fasting motility (MMC) and the postprandial response is mostly based on manometric findings in the upper small intestine. Hardly any data exist on human ileal motility, as the acquisition of data has been limited by methodological concerns. The aim was to study human jejunal and ileal motility in an optimized manometric setting. METHODS: Solid-state 24-h-manometry was performed in the jejunum and ileum of healthy individuals, applying a strict protocol for fasting, resting, and the consumption of a standardized meal. Both visual qualitative and validated computerized quantitative contraction and propagation analysis were performed. KEY RESULTS: MMC occurs in similar frequency in the jejunum and ileum, but it was significantly shorter in the jejunum at night. By many characteristics, ileal motility was less intense and propagative than jejunal: less migrating clustered contractions, and slower propagation velocity and shorter distance in phases II and III, and postprandially - possibly slowing and enhancing nutrient absorption. Prolonged propagated contractions in some individuals were identified as a unique ileal propulsive pattern. Postprandially, an abrupt conversion to a digestive motility pattern occurs simultaneously independent of the region. CONCLUSIONS & INFERENCES: We found similar basic phenomena of fasting and postprandial motility in the jejunum and ileum of healthy humans. However, different calibration of propagative and contractile activity and special motor events in the ileum may account for a different physiological role in digestion. Future studies of small-bowel motility in healthy and diseased subjects focusing on segmental differences of proximal and distal intestine may be rewarded.