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Biomedical subjects

Uwe Koch

Publications and source records attributed to Uwe Koch.

At least 19 recordsLinked to original sources
PubMed2007

A Psychometric evaluation of the German version of the 'Health of the Nation Outcome Scales, HoNOS-D': on the feasibility and reliability of clinician-performed measurements of severity in patients with mental disorders.

BACKGROUND: The assessment of the severity of a mental illness is a central component in the treatment of patients with mental disorders in both the in- and outpatient settings. In Great Britain, the 'Health of the Nation Outcome Scales, HoNOS' were developed to assess the health and social functioning of patients with mental disorders. AIMS: To examine the psychometric properties, especially the feasibility and reliability, of a German version of the HoNOS (HoNOS-D) and to thus provide international data for the comparison of different mental health services. SAMPLING AND METHODS: The HoNOS was translated into German (HoNOS-D) in an extensive and multilayered consensus procedure. The HoNOS-D was then reviewed within the framework of a pilot study on quality assurance measures implemented by the German statutory health insurance institutes in 11 hospitals. Assessments were made of the psychometric qualities of feasibility and reliability using a representative sample of patients with mental and behavioral disorders. RESULTS: An analysis of the feasibility of the HoNOS-D showed a range of missing values between 1.3 and 4.5% for 11 of the 12 items. An item analysis showed that three items of the HoNOS-D are particularly positively skewed. In most instances, the individual items of the rating scale exhibited only slight correlations to each other. With regard to retest reliability, satisfactory intraclass correlations between 0.80 and 0.91 were seen for 9 of the 12 items. CONCLUSIONS: The authors of the original version of the HoNOS [Wing et al.:Br J Psychiatry 1998;172:11-18] primarily emphasized the feasibility of the instrument and the independence of the individual items and dimensions. The analysis of the missing values showed satisfactory results for feasibility. The intercorrelation matrix of the individual items also exhibited only few correlations >0.30. The retest reliability also proves to be satisfactory for the majority of the items. The narrow distribution of some of the items must be critically discussed in comparison to analyses of results in other countries (e.g. Great Britain) and other settings (e.g. inpatient psychiatric hospitals or outpatient psychotherapy).

Adult↗
PubMed2007

Prevalence of acute and post-traumatic stress disorder and comorbid mental disorders in breast cancer patients during primary cancer care: a prospective study.

This study aimed at the identification of acute and post-traumatic stress responses, and comorbid mental disorders in breast cancer patients. Structured clinical interviews for DSM-IV (SCID) were conducted post-surgery with 127 patients (t1). Screening measures were used to assess post-traumatic stress responses, anxiety, and depression at t1 and at 6 months follow-up (t2). Based on the SCID, prevalence rates were 2.4% for both, cancer-related ASD and PTSD. Experiences most frequently described as traumatic were the cancer diagnosis itself and subsequent feelings of uncertainty. Patients with lifetime PTSD (8.7%) were more likely to meet the criteria for cancer-related ASD or PTSD (OR=14.1). Prevalence estimates were 7.1% for Adjustment Disorder, 4.7% for Major Depression, 3.1% for Dysthymic Disorder and 6.3% for Generalized Anxiety Disorder. Using the screening instruments, IES-R, PCL-C and HADS, we found PTSD in 18.5% at t1 and 11.2-16.3% at t2. The estimates of anxiety and depression reveal rates of 39.6% (t1) and 32.7% (t2) for anxiety, as well as 16.0% (t1) and 13.3% (t2) for depression (t1) (cut-off> or =8). The diagnosis of a life-threatening illness has been included as a potential trauma in the DSM-IV. However, it has to be critically evaluated whether subjective feelings of uncertainty like fears of treatment count among traumatic stressors, and thus, whether the diagnosis of PTSD is appropriate in this group of cancer patients. However, a large number of women with emotional distress illustrate the need for psychosocial counseling and support in this early treatment phase.

Acute Disease↗
PubMed2006

A structure-guided approach to an orthogonal estrogen-receptor-based gene switch activated by ligands suitable for in vivo studies.

A strategy to obtain a fully orthogonal estrogen-receptor-based gene switch responsive to molecules with acceptable pharmacological properties is presented. From a series of tetrahydrofluorenones active on the wild-type estrogen receptor (ER) an inactive analogue is chosen as a new lead compound. Coevolution of receptor mutants and ligands leads to an ER-based gene switch suitable for studies in animal models.

Binding Sites↗
PubMed2006

[Prevalence, drug treatment and metabolic control of diabetes mellitus in primary care].

BACKGROUND AND PURPOSE: The primary care sector is of key importance for the management of patients with diabetes mellitus. The authors investigated (a) the prevalence of diabetes mellitus type 1 and type 2, (b) the type and frequency of non-drug and drug treatment and its association with the presence of diabetic complications, and (c) the quality of metabolic control by HbA1c. METHODS: Using a nationwide probability sample of 3,188 general practices (response rate [RR] 50.6%), a total of 55,518 (RR 93.5%) patients were assessed in a prospective cross-sectional study by their physicians in September 2003 in a standardized manner using questionnaires, physician interview, and laboratory assessments. In addition to diabetes mellitus, 28 diseases were explicitly screened for, among them typical macrovascular (coronary heart disease, cerebrovascular disease, peripheral arterial disease) and microvascular disease (neuropathy, nephropathy, retinopathy, diabetic foot) complications. RESULTS: The prevalence of diabetes mellitus was 0.5% (type 1) and 14.7% (type 2), respectively. 49.5% (type 1) and 50.2% (type 2) of patients had micro- or macrovascular complications. 6.8% did not receive any treatment, 13.5% received non-drug treatment, and 75.3% received oral antidiabetic drugs and/or insulin (26.6% a combination of two or more). Compared to diabetics without any complications, treatment intensity was significantly higher in patients with microvascular complications (odds ratio [OR] 3.02), but not in those with macrovascular complications only (OR 0.98). An HbA1c value>or=7.0% was recorded in 39.6% of patients. CONCLUSION: Compared to previous studies in this setting, the proportion of diabetics with drug treatment has increased. More patients receive antidiabetic drug combinations. Quality of blood sugar control appears to have improved as well.

Adolescent↗
PubMed2006

Health-related quality of life in breast cancer: A cross-cultural survey of German, Japanese, and South Korean patients.

PURPOSE: The aim of this study was to evaluate health-related quality of life (HRQOL) in breast cancer patients across countries, and to cross-culturally examine the impact of psychosocial factors on HRQOL. PATIENTS AND METHODS: A total of 413 women with breast cancer from Germany (n = 195), Japan (n = 112), and Korea (n = 106) completed a survey assessing HRQOL and HRQOL-related factors. HRQOL was measured using the Short-Form Health Survey (SF-8). Measures of psychological distress (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised), coping (Dealing with Illness Inventory-German Revised), and social support (Illness-Specific Social Support Scale-German Revised) were included. RESULTS: The effect of the factor country on physical QOL was seen to be significant, but small (P = 0.049, ES = 0.018). The scales of General Health (P = 0.023), Vitality (P = 0.004), and Role Emotional (P = 0.003) differed across countries, with the South Korean patients having lower scores compared to the German and Japanese patients. The nature of the impact of psychosocial factors on HRQOL did not differ greatly across countries except with regard to avoidance, however, the degree to which these factors influence HRQOL did differ greatly. Overall, depression, depressive coping, and problematic support showed a strong detrimental effect on the HRQOL of breast cancer patients. CONCLUSIONS: Results from this study suggest that strategies which target an improvement of HRQOL in cancer patients should also consider the patients' cultural and healthcare system contexts. Interventions are needed to improve detrimental psychosocial factors.

Adult↗
PubMed2006

2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as inhibitors of the hepatitis C virus NS5B polymerase: discovery, SAR, modeling, and mutagenesis.

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 microM), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.

Antiviral Agents↗
PubMed2006

[On the theoretical and empirical differences of therapeutic interventions, contents, and styles between cognitive behavioural and psychodynamic psychotherapies].

Since cognitive behavioural (CBT) and psychodynamic (PDT) approaches treat patients with comparable disorder spectrums, yet at the same time show very different fundamental concepts, training modalities and treatment rationale, a comparison of the process and outcome of these methods becomes particularly significant. The present article offers an overview of the significance of comparative process research as well as of the theoretical and, in particular, the empirical knowledge concerning the difference between CBT and PDT at the process level (therapeutic interventions, contents and styles). Results show that CBT and PDT display pronounced differences in a broader spectrum of process variables not only on the basis of their theoretical conceptions but also referring to empirical data. While at least within the framework of experimental designs the general result of different profiles can be considered robust, statements concerning the actual treatment practice and clinical routines can only be made on a very isolated basis due to a lack of naturalistic studies. The need for research which can be derived from this, as well as further necessary developments in the field of comparative process research are discussed.

Cognitive Behavioral Therapy↗
PubMed2006

[Assessment of psychosocial distress and resources in oncology--a literature review about screening measures and current developments].

A substantial percentage of cancer patients suffers from psychosocial distress to severe mental disorders and psychosocial crisis during the course of the illness and cancer treatment. However, only a small percentage of patients with severe psychosocial distress and mental disorders in the present oncological practice is accurately identified, diagnosed, and appropriately treated. Therefore, sufficient knowledge about psychosocial distress and mental disorders as well as screening procedures are urgent concerns to improve psychosocial care for cancer patients. First, the article provides an overview of psychosocial distress and the epidemiology of mental disorders in cancer patients. Then a few of the most important objectives and problems of psychosocial assessment in cancer patients will be explained. The following part will offer an overview of questionnaires and screening procedures that are frequently used to assess psychosocial distress, mental disorders, personal and social resources, and health related quality of life in cancer patients.

Fatigue↗
PubMed2006

Post-acute service utilisation and parental satisfaction with health care services after mild traumatic brain injury in children and adolescents.

The objectives of this study were to describe and analyse the current aftercare practise following define TBI in four German cities. A retrospective, cross-sectional design was chosen in order to investigate the research questions. Methods and procedures included a questionnaire mailed to parents whose children were admitted with TBI to one of seven collaborating hospitals. A total of 564 parents participated in the study. The results indicate that aftercare services were rarely utilised. Furthermore, it was found that the behaviour of the physician in charge had a great impact on parental satisfaction with healthcare services. In conclusion, the findings described in this article underline the need to improve communication between acute and post-acute services.

Adolescent↗
PubMed2006

[Fear of progression in breast cancer patients--validation of the short form of the Fear of Progression Questionnaire (FoP-Q-SF)].

OBJECTIVES: Fear of progression is one of the most prevalent symptoms in cancer patients. The aim of this study was to validate the 12-item short version of the Fear of Progression Questionnaire (FoP-Q-SF). METHODS: A total of 1083 breast cancer patients were recruited by the Hamburg Cancer Register to fill out various questionnaires (response rate 67 %). RESULTS: Estimates of reliability were high (Cronbach's alpha = .87). The original one-factor structure was replicated. We used the HADS, the PCL-C, and the SF-8, among others, to validate the FoP-Q-SF. Significant positive correlations were found for fear of progression, anxiety and intrusion (r > .60) as well as for avoidance, hyperarousal and depression (r > or = .49). Moderate to high (negative) correlations were observed with health-related quality of life, in particular with the mental health dimensions (r > or = .48). Patients with cancer recurrence reported significant higher levels of fear of progression (p < .001). CONCLUSIONS: The short form of the Fear of Progression Questionnaire appears to be a reliable and valid instrument which can be recommended for further use in research and clinical care.

Adult↗
PubMed2006

Allosteric inhibition of the hepatitis C virus NS5B RNA dependent RNA polymerase.

The human and monetary costs of chronic hepatitis C and the complications arising from this disease emphasize the urgency to find a treatment for Hepatitis C Virus (HCV) infected patients. The current standard of treatment for patients chronically infected with HCV is combination therapy with pegylated interferon plus ribavirin. Recently, viral enzymes have become the target of efforts to develop small molecule inhibitors interfering with the essential steps in the life cycle of the virus. Amongst these enzymes the HCV-encoded NS5B RNA-dependent RNA polymerase (NS5B RdRp) is essential for viral replication and has been recognized as a prime target for therapeutic intervention. Several distinct classes of inhibitors of NS5B RdRp have been disclosed in the literature, including active site inhibitors such as nucleosides and pyrophosphate mimetics, as well as non-nucleoside inhibitors. The latter, based on the success of allosteric inhibitors in the treatment of HIV infection, have been developed into compounds which show activity in the subgenomic cell-culture assay of HCV replication. This review provides an account of the recent developments in this field.

Acrylates↗
PubMed2005

Vital exhaustion and risk for cancer: a prospective cohort study on the association between depressive feelings, fatigue, and risk of cancer.

BACKGROUND: Vital exhaustion, defined as feelings of depression and fatigue, has previously been investigated mainly as a risk factor for cardiovascular disease. The authors investigated the association between depressive feelings and fatigue as covered by the concept of vital exhaustion and the risk for cancer. METHODS: The sample consisted of 8527 persons aged 21-94 who had been examined in 1991-1994 within the Copenhagen City Heart Study. For the analysis, the sample was divided into quartiles on the basis of vital exhaustion scores. Cancer cases were ascertained by linkage to the Danish Cancer Registry. The mean length of follow-up was 8.6 years. Regression analyses for etiology-based groups of cancer sites were conducted on the basis of the Cox proportional hazards model, with adjustment for a number of confounding variables. RESULTS: Cancer was diagnosed in 976 persons (12%) during follow-up. In comparison to those with the lowest scores, persons with the highest vital exhaustion scores had a significantly decreased risk for developing cancer at all sites (hazard ratio [HR], 0.80; 95% confidence interval [CI}, 0.66-0.96), smoking-related cancers (HR, 0.64; 95% CI, 0.46-0.90), and virus and immune-related cancers (HR, 0.51; 95% CI, 0.26-0.99). No significant change in risk was found for cancers related to alcohol consumption or hormones. CONCLUSIONS: The results did not support the hypothesis that symptoms of fatigue and depression, as ascertained in the vital exhaustion index, increased the risk for cancer.

Adult↗
PubMed2005

Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site.

The hepatitis C virus (HCV) polymerase is required for replication of the viral genome and is a key target for therapeutic intervention against HCV. We have determined the crystal structures of the HCV polymerase complexed with two indole-based allosteric inhibitors at 2.3- and 2.4-Angstroms resolution. The structures show that these inhibitors bind to a site on the surface of the thumb domain. A cyclohexyl and phenyl ring substituents, bridged by an indole moiety, fill two closely spaced pockets, whereas a carboxylate substituent forms a salt bridge with an exposed arginine side chain. Interestingly, in the apoenzyme, the inhibitor binding site is occupied by a small alpha-helix at the tip of the N-terminal loop that connects the fingers and thumb domains. Thus, these molecules inhibit the enzyme by preventing formation of intramolecular contacts between these two domains and consequently precluding their coordinated movements during RNA synthesis. Our structures identify a novel mechanism by which a new class of allosteric inhibitors inhibits the HCV polymerase and open the way to the development of novel antiviral agents against this clinically relevant human pathogen.

Allosteric Site↗
PubMed2005

Psychosocial care of cancer patients--international differences in definition, healthcare structures, and therapeutic approaches.

Psychosocial oncology has become an important part of oncological care in many countries, but few international comparisons of the establishment of psychosocial oncology have been undertaken to date. This survey was conducted to establish the current conditions in which psychosocial oncology is implemented with reference to medical care, research, education and training. A semistructured questionnaire was sent to as many as four psychosocial oncology experts from 64 countries. Information was returned by 45 experts from 38 countries. As a relatively new discipline, psychosocial oncology is understood to be an integral part of oncology care, but has only been fully integrated in a few countries at present. In contrast, there are a large number of evidence-based interventions available for cancer patients and their families. Improvements are necessary in the transfer of empirical results into clinical practice, and in the development of guidelines to ensure adequate psychosocial care for oncology patients.

Data Collection↗
PubMed2005

A functionally orthogonal estrogen receptor-based transcription switch specifically induced by a nonsteroid synthetic ligand.

It is highly desirable to design ligand-dependent transcription regulation systems based on transactivators unresponsive to endogenous ligands but induced by synthetic small molecules unable to activate endogenous receptors. Using molecular modeling and yeast selection, we identified an estrogen receptor ligand binding domain double mutant (L384M, M421G) with decreased affinity to estradiol and enhanced binding to compounds inactive on estrogen receptors. Nonresponsiveness to estrogen was achieved by additionally adding the G521R substitution while introducing an "antagonistic-type" side chain in the compound, as in 4-hydroxytamoxifen. The triple-substituted ligand binding domain is insensitive to physiological concentrations of estradiol and has nanomolar affinity for the ligand. In this binary system, both receptor and ligand are, therefore, reciprocally specific. The mutated variant in the context of a chimeric transcription factor provides tight, ligand-dependent regulation of reporter gene expression.

Amino Acid Substitution↗