Needs and preferences of informal caregivers regarding outpatient care for the elderly: a systematic literature review.

BACKGROUND: Informal caregivers are an essential pillar for ensuring and maintaining the outpatient care of the frail elderly. Due to demographic changes, including an increase in the number of people in need of care as well as changing social structures (full-time employment of women, increasing number of single households, etc.) these informal care structures are fraught by considerable challenges. To support and facilitate informal caregivers in their role of nursing, it is important to identify their preferences, needs, and thus create a preference-oriented system. METHODS: A systematic review was conducted to identify preferences and needs regarding the organization of informal care. The database searches were performed by using EMBASE, Scopus and Dimdi. RESULTS: A total of 44 studies were included in the present review. Studies from 17 different countries provide broad international perspectives. Besides the preferences for long-term care structure, the following four principal topics were identified: (1) informational needs; (2) support needs; (3) organizational needs, and (4) needs for societal recognition. CONCLUSION: To meet the current challenges in the outpatient or home-based care of elders, it is essential to strengthen the role of informal caregivers. Therefore, it is necessary to adopt and further develop informal care structures according to the needs of informal caregivers. However, demographic, financial and cultural aspects of each country need to be considered as these may influence the preferences and needs of informal caregivers.

[Cost-Effectiveness of Pharmacological Smoking Cessation Therapies - A Systematic Literature Review]. / Kosteneffektivität von pharmakologischen Raucherentwöhnungsmaßnahmen ­ ein systematisches Literaturreview.

Aim of the Study: Through the promotion of smoking cessation premature mortality can be prevented. Therefore it is necessary to provide effective and cost-effective smoking cessation interventions. In Germany the cost of pharmacological smoking cessation measures are not yet reimbursed by the statutory health insurance. The aim of this study is to present the evidence on the cost-effectiveness of already approved pharmacological smoking cessation therapies and to evaluate their quality. Method: A systematic literature research was conducted in the databases by DIMDI (Medline, Embase, etc.) in April 2013 (update April 2014). The study research was focused on studies for cost effectiveness of nicotine replacement therapy (NRT), varenicline and bupropion. The assessment of study quality was performed using the "Quality of Health Economic Studies" (QHES) instrument. Results: 33 Of the original 10 340 identified studies were finally included. The majority of the studies show that an additional prescription of NRT or bupropion to a medical consultation is a cost-effective strategy. In addition, in most studies varenicline is a dominant strategy compared to bupropion. Overall, the study quality was found to be very heterogeneous between 45 and 80 points (Ø 63.7 points). Conclusion: The studies show that treatment with varenicline is the most cost effective strategy followed by bupropion and the NRT. However, the studies can only be compared inadequately due to different levels of age and country-specific intervention costs.

Patient- and person-reports on healthcare: preferences, outcomes, experiences, and satisfaction - an essay.

With the shift towards patient-centered healthcare, patient- and person-reports of health-related factors, including outcomes, are seen as important determinants for evaluating and improving healthcare. However, a comprehensive, systematic categorization of patient- and person-reports is currently lacking in the literature. This study aims at developing a new classification system with well-defined constructs for patients' and persons' self-reports on health and healthcare. A literature research and evaluation by the Reported Health Outcomes (RHO) Group were used to develop this classification system. The new classification system includes patient- and person-reported preferences, outcomes, experiences, and satisfaction related to healthcare and health outcomes. Moreover, the most constitutive methods to measure these four categories - preferences, outcomes, experiences, and satisfaction - have been described in this article. Even though the value of patients' and persons' perspectives on healthcare is increasingly being recognized, its measurement and implementation presents a lasting challenge to researchers, clinicians, patients, and the general population.

Preferences of lung cancer patients for treatment and decision-making: a systematic literature review.

The consideration of patient preferences in decision-making has become more important, especially for life-threatening diseases such as lung cancer. This paper aims to identify the preferences of lung cancer patients with regard to their treatment and involvement in the decision-making process. We conducted a systematic literature review from 12 electronic databases and included studies published between 2000 and 2012. A total of 20 studies were included in this review. These revealed that lung cancer patients do have preferences that should be considered in treatment decisions; however, these preferences are not homogenous. We found that patients often consider life extension to be more important than the health-related quality of life or undesirable side effects. This preference seems to depend on patient age. Nausea and vomiting are the most important side effects to be avoided; the relevance of other side effects differs highly between subgroups. The majority of lung cancer patients, nevertheless, seem to prefer a passive rather than an active role in decision-making, although the self-reported preferences differed partly from the physicians' perceptions. Overall, we identified an urgent need for larger studies that are suitable for subgroup analyses and incorporate multi-attributive measurement techniques.

Preferences of colorectal cancer patients for treatment and decision-making: a systematic literature review.

Treatment decisions in life-threatening diseases, like colorectal cancer (CRC), are crucial, since they have a great impact on patient's survival and health-related quality of life. Thereby, the inclusion of patient's preferences becomes more and more important; however, these first need to be identified. Therefore, we conducted a systematic literature review in 12 electronic databases, published between 2000 and 2012, in order to identify patient's preferences concerning treatment preferences and involvement in the decision-making process. Nineteen studies were included and thoroughly analysed. This review shows that CRC patients do have preferences regarding different treatment options and outcomes; however, these preferences are not homogenous and seem to depend on personal factors like age and gender. Despite the existence of these preferences, the majority of patients prefer a passive role in the decision-making process, which in part may be explained by the severity of the disease. Again, subgroup analyses reveal the impact of personal factors like gender and education on the preference. Due to the importance of personal factors in the analysis of patient preferences, we identified an urgent need for larger studies that are suitable for subgroup analyses and incorporate multi-attributive measurement techniques, like discrete choice methods.

[Implementation of the new German job role code and its application in claims data analysis. Possibilities and limitations]. / Einführung des neuen Tätigkeitsschlüssels und seine Anwendung in GKV-Routinedatenauswertungen. Möglichkeiten und Limitationen.

In recent years, claims data analyses have become of increasing importance in several scientific disciplines in Germany. In specific research projects, it can be necessary to refine and to standardize the results by socioeconomic data. Information about graduation, social status, and occupation are provided by the German job role code for all people insured by statutory health insurance. During recent years, the working scheme has changed and new professions have appeared. Therefore, there has been a discussion about actualization and modification of the job role code. Since December 2011, an actualized job role code with an extensive set of new information is available. In addition, a new classification of professions is available in Germany which was considered in the design of the new job role code. The aim of this overview is to describe the structure of the new job role code as well as to discuss possible uses and limitations.

A highly selective telomerase inhibitor limiting human cancer cell proliferation.

Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues. Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation. We describe novel chemical compounds which selectively inhibit telomerase in vitro and in vivo. Treatment of cancer cells with these inhibitors leads to progressive telomere shortening, with no acute cytotoxicity, but a proliferation arrest after a characteristic lag period with hallmarks of senescence, including morphological, mitotic and chromosomal aberrations and altered patterns of gene expression. Telomerase inhibition and telomere shortening also result in a marked reduction of the tumorigenic potential of drug-treated tumour cells in a mouse xenograft model. This model was also used to demonstrate in vivo efficacy with no adverse side effects and uncomplicated oral administration of the inhibitor. These findings indicate that potent and selective, non-nucleosidic telomerase inhibitors can be designed as novel cancer treatment modalities.

Degradation of partially oxidized alginate and its potential application for tissue engineering.

Alginate has been widely used in a variety of biomedical applications including drug delivery and cell transplantation. However, alginate itself has a very slow degradation rate, and its gels degrade in an uncontrollable manner, releasing high molecular weight strands that may have difficulty being cleared from the body. We hypothesized that the periodate oxidation of alginate, which cleaves the carbon-carbon bond of the cis-diol group in the uronate residue and alters the chain conformation, would result in promoting the hydrolysis of alginate in aqueous solutions. Alginate, oxidized to a low extent (approximately 5%), degraded with a rate depending on the pH and temperature of the solution. This polymer was still capable of being ionically cross-linked with calcium ions to form gels, which degraded within 9 days in PBS solution. Finally, the use of these degradable alginate-derived hydrogels greatly improved cartilage-like tissue formation in vivo, as compared to alginate hydrogels.

Biogeography and ecological setting of Indian Ocean hydrothermal vents.

Within the endemic invertebrate faunas of hydrothermal vents, five biogeographic provinces are recognized. Invertebrates at two Indian Ocean vent fields (Kairei and Edmond) belong to a sixth province, despite ecological settings and invertebrate-bacterial symbioses similar to those of both western Pacific and Atlantic vents. Most organisms found at these Indian Ocean vent fields have evolutionary affinities with western Pacific vent faunas, but a shrimp that ecologically dominates Indian Ocean vents closely resembles its Mid-Atlantic counterpart. These findings contribute to a global assessment of the biogeography of chemosynthetic faunas and indicate that the Indian Ocean vent community follows asymmetric assembly rules biased toward Pacific evolutionary alliances.

Human telomerase contains two cooperating telomerase RNA molecules.

Telomerase uses a short stretch of its intrinsic RNA molecule as template for telomere repeat synthesis. Reverse transcription of the RNA template is catalyzed by the telomerase reverse transcriptase (TERT) protein subunit. We demonstrate that human telomerase reconstituted from recombinant TERT and telomerase RNA runs as a dimer on a gel filtration column and that it contains two telomerase RNA molecules. Significantly, a telomerase heterodimer reconstituted from wild-type and mutant telomerase RNA is barely active when compared with the wild-type homodimer. We conclude that the telomerase RNA templates in the active enzyme are interdependent and functionally cooperate with each other. We discuss models that may explain the biological and enzymatic roles of telomerase dimerization.

Mouse fibroblast-activation protein--conserved Fap gene organization and biochemical function as a serine protease.

The human fibroblast-activation protein (FAP), a member of the serine protease family, was discovered as an inducible type-II cell-surface glycoprotein selectively expressed by reactive stromal fibroblasts of epithelial cancers and healing wounds. Antibodies directed against human FAP have a clinical use for antibody-based tumor imaging. As part of an effort to generate animal models of FAP expression in epithelial tumorigenesis and wound healing, we previously cloned the cDNA encoding the mouse FAP homolog. In this study, we used PCR/restriction-fragment length polymorphism, identified in interspecific back-crosses between Mus musculus and Mus spretus, to map the Fap gene locus to a region of mouse chromosome 2, known to be syntenic to the previously identified FAP gene locus on human chromosome 2q23. The Fap gene spans approximately 60 kb and contains 26 exons ranging in size from 46 bp to 195 bp. This genomic organization is very similar to that of the human FAP locus. Similar to the gene encoding dipeptidyl peptidase IV (DPP IV), the nucleotides encoding the serine protease consensus motif, WGWSYGG, are split between two exons, a feature distinct from classical serine proteases. Consistent with the similarity to DPP IV, a chimeric FAP fusion protein expressed in a baculovirus system has dipeptidyl peptidase activity.

One-step affinity purification protocol for human telomerase.

Human telomerase is a ribonucleoprotein (RNP) enzyme, comprising protein components and an RNA template that catalyses telomere elongation through the addition of TTAGGG repeats. Telomerase function has been implicated in aging and cancer cell immortalization. We report a rapid and efficient one-step purification protocol to obtain highly active telomerase from human cells. The purification is based on affinity chromatography of nuclear extracts with antisense oligonucleotides complementary to the template region of the human telomerase RNA component. Bound telomerase is eluted with a displacement oligonucleotide under mild conditions. The resulting affinity-purified telomerase is active in PCR-amplified telomerase assays. The purified telomerase complex has a molecular mass of approximately 550 kDa compared to the approximately 1000 kDa determined for the telomerase RNP in unfractionated nuclear extracts. The purification protocol provides a rapid and efficient tool for functional and structural studies of human telomerase.

Dose-related vestibular and cochlear effects of transtympanic gentamicin.

HYPOTHESIS: To test the relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected gentamicin in the Mongolian gerbil. BACKGROUND: Transtympanic gentamicin is gaining favor as a relatively noninvasive treatment for Meniere's disease (MD). Few basic science studies exist regarding the vestibular and cochlear toxicities and dosage and administration schedules, however. The absence of standardized procedures and use of different species as animal models may account for the variable outcomes and lack of agreement found in the literature. METHODS: Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1x) and five (5x) daily injections of gentamicin/gelfoam slurry and similarly injected (saline/gelfoam) and noninjected controls. RESULTS: Two weeks after injection, qualitative and quantitative changes were seen in posterior cristae hair cells in the 1x and 5x gentamicin injected groups. Statistically significant decreases in hair cells were seen when 5x injected ears were compared with 1x injected ears and when 1x injected ears were compared with control ears. When damage was observed in the posterior crista sensory cells, damage was also seen in cochlear hair cells. CONCLUSIONS: Our results suggest that in the gerbil, gentamicin is ototoxic but not selectively vestibulotoxic. In general, increasing the number of transtympanic injections increases the damage to sensory hair cells in both the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in both cochlear and vestibular hair cells from the same animal.

Domains of the human androgen receptor and glucocorticoid receptor involved in binding to the nuclear matrix.

Steroid receptors have been reported to bind to the nuclear matrix. The nuclear matrix is operationally defined as the residual nuclear structure that remains after extraction of most of the chromatin and all soluble and loosely bound components. To obtain insight in the molecular mechanism of the interaction of steroid receptors with the nuclear matrix, we studied the binding of several deletion mutants of the human androgen receptor (hAR) and the human glucocorticoid receptor (hGR) to the nuclear matrix. Receptor binding was tested for two different nuclear matrix preparations: complete matrices, in which most matrix proteins are retained during the isolation procedure, and depleted matrices, which consist of only a subset of these proteins. The results show that the C-terminal domain of the hAR binds tightly to both depleted and complete matrices. In addition, at least one other domain of the hAR binds to complete matrices but not to depleted matrices. In contrast to the hAR, the hGR binds only to complete matrices. For this interaction both the DNA-binding domain and the C-terminal domain of the hGR are required, whereas the N-terminal domain is not. We conclude that specific protein domains of the hAR and the hGR are involved in binding to the nuclear matrix. In addition, our results indicate that the hAR and the hGR are attached to the nuclear matrix through different molecular interactions.

Identification of a domain required for oncogenic activity and transcriptional suppression by v-erbA and thyroid-hormone receptor alpha.

v-erbA, a mutated version of the chicken thyroid hormone (TH) receptor type alpha, can inhibit hormonal induction of target genes. In addition, v-erbA acts as a constitutive repressor of the basal promoter activity. In vivo, v-erbA can arrest the differentiation of erythroid precursor cells and suppresses transcription of erythrocyte-specific genes. We show that the v-erbA protein of the transformation-defective avian erythroblastosis virus mutant (AEVtd359) fails to suppress basal transcription level and exhibits impaired ability in antagonizing the TH and retinoic acid response. The inactivating mutation is a 1-nt change leading to a Pro-->Arg replacement in the "hinge region" of v-erbA protein. Introducing this mutation in the context of TH receptor alpha selectively inactivates the suppressor function, while hormone-binding and transcriptional-activation properties are unaffected. These data suggest that trans-repression rather than a dominant negative block of TH-receptor or retinoic acid-receptor activation may represent the primary molecular property underlying erbA oncogenesis.

Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands.

We characterized the pharmacological profiles of the human mineralocorticoid and glucocorticoid receptor for 11 natural and synthetic steroids regarding binding pharmacology, intracellular localization of hormone-receptor complexes, and agonistic or antagonistic properties at the gene expression level. The sex steroid progesterone bound with an affinity (ki < 0.01 nM) even higher than that of aldosterone to the human mineralocorticoid receptor and effectively antagonized the effect of aldosterone via the human mineralocorticoid receptor in functional co-transfection assays. This indicates that progesterone has potent antimineralocorticoid properties, while its antiglucocorticoid effects were less pronounced. The partial agonistic activities of antihormones in this assay suggest a direct interaction of antihormone-receptor complexes with the response elements on the DNA. These results are supported by immunofluorescence studies, in which both unliganded human mineralocorticoid and glucocorticoid receptors were distributed throughout the cytoplasm and nucleus, whereas agonist- as well as antagonist-receptor complexes showed an exclusively nuclear localization. These results contribute to the understanding of antihormone pharmacology and increase our understanding of the role of human mineralocorticoid and glucocorticoid receptors in physiological processes during different endocrine states.

Progesterone receptor-mediated effects of neuroactive steroids.

Several 3 alpha-hydroxysteroids accumulate in the brain after local synthesis or after metabolization of steroids that are provided by the adrenals. The 3 alpha-hydroxy ring A-reduced pregnane steroids allopregnanolone and tetrahydrodeoxycorticosterone are believed not to interact with intracellular receptors, but enhance GABA-mediated chloride currents. The present study shows that these neuroactive steroids can regulate gene expression via the progesterone receptor. The induction of DNA binding and transcriptional activation of the progesterone receptor requires intracellular oxidation of the neuroactive steroids into progesterone receptor active 5 alpha-pregnane steroids. Thus, at physiological concentrations, these neuroactive steroids regulate neuronal function through their effects on both transmitter-gated ion channels and steroid receptor-regulated gene expression.

A functional promoter directing expression of a novel type of rat mineralocorticoid receptor mRNA in brain.

The authors have identified two types of hippocampal cDNAs for the rat mineralocorticoid receptor (rMR) which are identical in the protein coding domain but differ in their 5'-untranslated sequences. One of these clones encodes a novel type of rMR cDNA with a high homology to a previously described human MR cDNA isolated from the kidney. A genomic clone containing the 5'-end of the rat MR gene was isolated. The 12.7 kb genomic region contains the 5'-coding exon with the translational start site and contiguous DNA sequences encoding the N-terminal domain of the rMR. A 240 bp region homologous to the 5'-untranslated sequences of the novel rMR cDNA was located 5.2 kb upstream the protein coding region. Characterization of the nucleotide sequence preceding this exon revealed several features characteristic for promoters of so-called 'housekeeping genes'. The sequence analyzed is 635 bp in length, is rich in G+C nucleotides (63%) and lacks TATA or CAAT regulatory elements. It contains three putative binding sites for transcription factor Sp1 as well as several short sequences that are similar to known cis-acting enhancers or binding sites for transcription factors. In transient transfection experiments employing the luciferase reporter gene and the CV1 cell line this region exhibits substantial promoter activity. These experiments demonstrate that expression of the rat MR gene in the hippocampus results in at least two transcripts with different 5'-untranslated exons.(ABSTRACT TRUNCATED AT 250 WORDS)