Converting habits of antibiotic use for respiratory tract infections in German primary care (CHANGE-3) - process evaluation of a complex intervention.

BACKGROUND: Antimicrobial resistance remains a global challenge. In Germany, the national health agenda supports measures that enhance the appropriate, guideline-oriented use of antibiotics. The study "Converting Habits of Antibiotic Use for Respiratory Tract Infections in German Primary Care (CHANGE-3)" aimed at a sustainable reduction of antimicrobial resistance through converting patterns of prescribing practice and use of antibiotics and an increase in health literacy in primary care patients, practice teams, and in the general public. Embedded in a cluster-randomized trial of a multifaceted implementation program, a process evaluation focused on the uptake of program components to assess the fidelity of the implementation program in the CHANGE-3 study and to understand utilization of its educational components. METHODS: A mix of qualitative and quantitative methods was used. Semi-structured telephone interviews were conducted with General Practitioners, Medical Assistants, patients treated for respiratory tract infection and outreach visitors who had carried out individual outreach visits. A two-wave written survey (T1: 5 months after start, T2: 16 months after start) was conducted in general practitioners and medical assistants. Qualitative data were analyzed using thematic framework analysis. Descriptive statistics were used to analyze survey data. RESULTS: Uptake of intervention components was heterogenous. Across all components, the uptake reported by General Practitioners varied from 20 to 88% at T1 and 31 to 63% at T2. Medical Assistants reported uptake from 22 to 70% at T1 and 6 to 69% at T2. Paper-based components could by and large be integrated in daily practice (64 to 90% in T1; 41 to 93% in T2), but uptake of digital components was low. A one-time outreach visit provided thematic information and feedback regarding actual prescribing, but due to time constraints were received with reluctance by practice teams. Patients were largely unaware of program components, but assumed that information and education could promote health literacy regarding antibiotics use. CONCLUSIONS: The process evaluation contributed to understanding the applicability of the delivered educational components with regards to the appropriate use of antibiotics. Future research efforts need to identify the best mode of delivery to reach the targeted population. TRIAL REGISTRATION: ISRCTN, ISRCTN15061174 . Registered 13 July 2018 - Retrospectively registered.

Structures and processes necessary for providing effective home treatment to severely mentally ill persons: a naturalistic study.

BACKGROUND: Home treatment for severely mentally ill persons is becoming increasingly popular. This research aims to identify structures and processes in home treatment that impact on patient-related outcomes. METHODS: We analysed 17 networks that provide home treatment to severely mentally ill persons using a naturalistic approach. The networks were similar with regard to central components of home treatment such as case management, 24 h crisis hotline and home visits, but differed in all other aspects such as the multidisciplinary teams, time spent with patients, etc. To determine treatment outcome, patients' psychosocial functioning was measured using the Health of the Nation Outcome Scales (HoNOS). Structures and processes were assessed using claims data and questionnaires answered by the different networks. Primary outcome was highlighted by the change in HoNOS scores from the start of home treatment compared with 6 months later. We sought to explain this outcome through patient and network characteristics using regression analysis. Data on 3,567 patients was available. RESULTS: On average, psychosocial functioning improved by 0.84 across networks between t0 and t1. There were more similarities than differences between the networks with regard to the structures and processes that we tested. A univariate regression analysis found staff's prior experience in mental health care and the effort that they invested in their work correlated positively with patient outcome. This needs to be interpreted under considering that univariate analysis does not show causal relationship. A high case load per case manager, increased and longer patient contact and more family intervention were correlated with worse patient outcome, probably indicating that sicker patients receive more care and intervention. CONCLUSION: Home treatment networks succeed in delivering care tailored to the needs of patients. In order to improve the quality of care in home treatment, this study suggests employing experienced staff who is ready to invest more effort in their patients. Further research needs to consider a longer follow-up time.

[Raw-meat-based diets (RMBD) as a feeding principle for dogs]. / BARF (Biologisch Artgerechte Rohfütterung) als Ernährungsform bei Hunden.

BARF (Bone And Raw Food) is an increasing trend for feeding dogs in Germany. This article provides an overview of the history and principles of this type of feeding. Risks of feeding raw-meat diets include infections of dogs with parasites, bacteria and viruses. Some of these pathogenic organisms also have zoonotic potential. Additionally, raw-meat diets often show nutritional imbalances. Over-supplementation and deficiencies of nutrients are frequently found, especially regarding calcium, the trace elements copper, zinc and iodine, vitamins A and D and the calcium   :   phosphorus ratio. This malnutrition can cause clinical symptoms. Therefore, checking and optimising the diet by a specialized veterinarian is strongly recommended.

[GP-centered health care in Baden-Württemberg, Germany: Results of a quantitative and qualitative evaluation]. / Hausarztzentrierte Versorgung in Baden-Württemberg : Ergebnisse einer qualitativen und querschnittlich quantitativen Evaluation.

BACKGROUND: GP-centered health care ("Hausarztzentrierte Versorgung", HzV)-the terms of which are described in § 73b of the Social Code Book V-came into effect in Baden-Württemberg, Germany, on 1 July 2008. The HzV is aimed at enhancing health care for patients with chronic diseases and complex health care needs (e.g., those requiring long-term care). OBJECTIVES: On the basis of four working packages (WP I-WP IV), the present paper examines the impact that GP-centered health care has had on patients insured by the "AOK" regional sickness fund and their GPs. WP I addresses the association between HzV participation and the corresponding health care utilization of patients on the basis of claims data. WP II looks at any changes that GPs and patients noticed were potentially attributable to HzV participation. WP III focuses on health care assistants in primary care ("Versorgungsassistenten in der Hausarztpraxis", VERAH). These assistants play a special role within the framework of the HzV. WP IV analyzes the quality of health care for patients aged 65 years and over, also on the basis of claims data. MATERIALS AND METHODS: A mixed methods design was used for this evaluation, and quantitative and qualitative approaches taken. This design enabled insights into the implementation of the HzV in regular health care to be obtained from different perspectives. RESULTS: Numerous positive associations between HzV participation and the variables of interest were observed for all WPs. These are presented in detail in the paper. CONCLUSION: The results obtained so far clearly support the continuation of HzV and associated evaluations.

[Creation of a control group by matched pairs with GKV routine data for the evaluation of enrollment models]. / Bildung einer Kontrollgruppe mithilfe von Matched-Pairs auf Basis von GKV-Routinedaten zur prospektiven Evaluation von Einschreibemodellen.

BACKGROUND: Various study approaches can be considered for the investigation of the efficiency of enrollment models, like GP-centred health-care contract or disease management programmes. As an active and independent enrollment into care models is effected by the insured (self-selection), a randomisation cannot be applied. The matched pairs design - in which for every insured a control insured with comparable morbidity is selected - presents an alternative investigation method. A precondition is a model that describes appropriately the morbidity on the basis of available routine data. TARGET: The aim of this study was to develop a procedure that selects comparable insured persons on the basis of routine data of the statutory health-care funds. METHODS: Apart from age, gender, care status, insured status, days of disability, region, health insurance and belonging to an enrollment model, also ambulant as well as stationary performance data for the year 2005 following the PCG/DCG procedure for morbidity-oriented matching design developed by Lamers and Vliet (2003) were applied. Thereby the consumption of certain medications prescribed is determining for the allocation of patients to pharmaceutical cost groups (PCG). Additionally a classification into diagnosis cost groups (DCG) according to stationary diagnoses was conducted. RESULTS: Within the scope of the enrollment models the formation of matched pairs following the PCG/DCG procedure represents an appropriate study design for the creation of a control group. In the first year of enrollment the insured of the interventional and those of the control group show a comparable morbidity. When applying 9 matching criteria a control insured person can be found for 87% of the enrolled individuals. DISCUSSION/CONCLUSIONS: There are various and complex possibilities to define morbidity. Variable parameters within the presented matched pairs design are the number of used matching criteria as well as minimum drug consumption limit relevant for the classification in PCGs. Alternative models are possible for morbidity definition considering, apart from the stationary diagnosis, also the ambulant diagnosis. When taking into account a higher number of morbidity criteria, the matched pairs design is confronted with dimensionality issues. The propensity score matching is discussed as approach to solve this problem.

The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death.

The glutathione-dependent system is one of the key systems regulating cellular redox balance, and thus cell fate. Cysteine, typically present in its oxidized form cystine in the extracellular space, is regarded as the rate-limiting substrate for glutathione (GSH) synthesis. Cystine is transported into cells by the highly specific amino-acid antiporter system xc-. Since Burkitt's Lymphoma (BL) cells display limited uptake capacity for cystine, and are thus prone to oxidative stress-induced cell death, we stably expressed the substrate-specific subunit of system xc-, xCT, in HH514 BL cells. xCT-overexpressing cells became highly resistant to oxidative stress, particularly upon GSH depletion. Contrary to previous predictions, the increase of intracellular cysteine did not affect the cellular GSH pool, but concomitantly boosted extracellular cysteine concentrations. Even though cells were depleted of bulk GSH, xCT overexpression maintained cellular integrity by protecting against lipid peroxidation, a very early event in cell death progression. Our results show that system xc- protects against oxidative stress not by elevating intracellular GSH levels, but rather creates a reducing extracellular environment by driving a highly efficient cystine/cysteine redox cycle. Our findings show that the cystine/cysteine redox cycle by itself must be viewed as a discrete major regulator of cell survival.

The frequency of inappropriate tablet splitting in primary care.

INTRODUCTION: We assessed the frequency and determinants of tablet splitting in primary care in Germany and evaluated the quality of information on divisibility in the Summary of Product Characteristics (SPCs) and in the Package Leaflet (PL) as legal sources of information for health care providers and patients. METHODS: We performed a cross-sectional questionnaire survey among patients of 59 general practitioners in the German Federal State Saxony-Anhalt in 2005 in order to collect detailed information on all drugs of patients maintained on more than three drugs. RESULTS: The response rate was 82.1% (n=905) and 3,158 drugs (tablets and dragées) were included in the analyses. Of all drugs, 24.1% were split (762 of 3,158): 8.7% of all split tablets were unscored (66 of 762) and 3.8% of all split tablets were not allowed to be split (29 of 762). Tablets of the higher price categories and higher strengths were twice as likely to be split. Only 22.5% of the SPCs (9 of 40) of the split unscored tablet brands contained explicit information on divisibility and only 36.4% of the PLs (8 of 22) of the split brands that were not allowed to be split stated that splitting was not appropriate. CONCLUSION: The splitting of tablets in primary care is a frequent habit likely driven by medical and economic considerations. Almost 1% of all tablets are split that must not be fragmented. However, the SPC and PL provide only limited information on divisibility stressing the need to improve this information promptly to avoid medication errors.

Increased intestinal permeability in patients with inflammatory bowel disease.

Intestinal permeability can be measured by the sugar absorption test. This test is based on determining the ratio of the urinary excretion of a large and a small carbohydrate after oral administration. The aim of this study was to determine which combination of carbohydrates used in the test gives the highest correlation with disease activity in inflammatory bowel disease. 26 patients with Crohn's disease, 21 patients with ulcerative colitis and 27 healthy control subjects were included in the study. The patients with inflammatory bowel disease had either minimal or highly active disease or were in remission. Two disaccharides (lactulose: L, and cellobiose: C) and two smaller carbohydrates (rhamnose:R, and mannitol:M) were given orally and the urinary excretion was measured by high pressure liquid chromatography followed by pulsed amperometric electrochemical detection on a gold electrode. The ratios C/R, L/R, C/M and L/M were used as indicators for intestinal permeability. - There were no side effects of oral sugar administration. All patients tolerated the test well. Lactulose, rhamnose and cellobiose concentrations are easily be measured in the urine whereas mannitol measurement requires the use of an anion exchanger. This produced inconsistent results. Patients with Crohn's disease or with ulcerative colitis had increased permeability indices in comparison to healthy controls, even in remission. The L/R ratio gave a better differentiation between the healthy controls and patients with active disease than the other agents. Changes in disease activity are best reflected by use of cellobiose/rhamnose excretion quotient.

A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population.

Myoadenylate deaminase deficiency is the most common metabolic disorder of skeletal muscle in the Caucasian population, affecting approximately 2% of all individuals. Although most deficient subjects are asymptomatic, some suffer from exercise-induced myalgia suggesting a causal relationship between a lack of enzyme activity and muscle function. In addition, carriers of this derangement in purine nucleotide catabolism may have an adaptive advantage related to clinical outcome in heart disease. The molecular basis of myoadenylate deaminase deficiency in Caucasians has been attributed to a single mutant allele characterized by double C to T transitions at nucleotides +34 and +143 in mRNA encoded by the AMPD1 gene. Polymerase chain reaction-based strategies have been developed to specifically identify this common mutant allele and are considered highly sensitive. Consequently, some laboratories preferentially use this technique over other available diagnostic tests for myoadenylate deaminase deficiency. We previously identified a G468-T mutation in one symptomatic patient who was only heterozygous for the common AMPD1 mutant allele. In this report, nine additional individuals with this compound heterozygous genotype are revealed in a survey of 48 patients with documented deficiency of skeletal muscle adenosine monophosphate deaminase and exercise-induced myalgia. Western blot analysis of leftover biopsy material from one of these individuals does not detect any immunoreactive myoadenylate deaminase polypeptide. Baculoviral expression of the G468-T mutant allele produces a Q156H substitution enzyme exhibiting labile catalytic activity. These combined results demonstrate that the G468-T transversion is dysfunctional and further indicate that AMPD1 alleles harboring this mutation contribute to the high incidence of partial and complete myoadenylate deaminase deficiency in the Caucasian population. Consequently, genetic tests for abnormal AMPD1 expression designed to diagnose patients with metabolic myopathy, and to evaluate genetic markers for clinical outcome in heart disease should not be based solely on the detection of a single mutant allele.

[Mistakes in general husbandry of ornamental fish]. / Haltungsfehler bei Zierfischen.

Mistakes in general husbandry conditions of ornamental fish can consist in insufficient quality of water, inadequate feeding, equipment and social structure and poor prophylactic measures. Clinical symptoms are generally not specific.

[Keeping reptiles]. / Reptilienhaltung.

Keeping of reptiles in captivity is permanently increasing. As there exists such a great number of species of reptiles, the conditions of the natural habitat of the kept species have to be imitated as exactly as possible. Disorders in reptiles are often caused by inadequate maintainance.

[Pain in the breeding of fish]. / Qualzuchten bei Fischen.

Excessive breeding leading to suffering in animals only exists in ornamental fish, especially in gold fish or poecillids. These varieties are physically handicapped in locomotion, feeding and/or reproduction in comparisation to wild fish.

[Blood parameters as an aid in the diagnosis of reptile diseases]. / Blutparameter als Hilfe in der Diagnostik von Reptilienkrankheiten.

As ill reptiles only show nonspecific clinical signs, blood chemistry parameters are a valuable help in diagnosis. Practicable sites for obtaining blood of snakes, sauria and chelonians are vena coccygealis ventralis and cardiac puncture, of chelonians also vena jugularis, axillaris and coccygealis dorsalis. The following blood parameters were investigated: number of erythrocytes and leucocytes, urea, uric acid, creatinine, AST (GOT), ALT (GPT) GLDH, AP, total bilirubin, CK, LDH, lipase, alpha-amylase, calcium, phosphorus, sodium, potassium, chloride and total protein. Especially for diagnosing nephropathies evaluation of urea and uric acid proved to be valuable.

Capillary electrophoresis for screening of adenylosuccinate lyase deficiency.

We report a new screening method for adenylosuccinate lyase (ASase) deficiency using capillary electrophoresis (CE). This enzyme defect causes secondary autism and psychomotor retardation in early childhood. In all body fluids of these patients, two succinylpurine metabolites can be found that are normally not detectable: succinyladenosine and succinylaminoimidazole carboxamide (SAICA) riboside. A Beckman P/ACE 2050 capillary electrophoresis system was used with a 47.1 cm capillary, 75 microns ID, and the P/ACE Beckman UV absorbance detector. Untreated urine, injected for 1 s, was separated in a pH 8.63 borate buffer at 20 kV. The two succinylpurines (migration times 13.36 and 13.60 min) were detected at 254 nm only in urine of patients with ASase deficiency but not in control samples.

[Clostridium bifermentans infection in grass carp (Ctenopharyngodon idella)]. / Clostridium bifermentans-Infektion bei Grasfischen (Ctenopharyngodon idella).

The outbreak of an infection with Clostridium bifermentans in grass carp (Ctenopharyngodon idella) from a polyculture fish pond is documented.

Channel active mammalian porin, purified from crude membrane fractions of human B lymphocytes and bovine skeletal muscle, reversibly binds adenosine triphosphate (ATP).

A new aspect of mammalian porin (mammalian VDAC = mammalian voltage-dependent anion channel) is presented: channel active VDAC binds adenosine triphosphate (ATP) in the absence of Ca2+. Channel active "Porin 31HL" or "Porin 31BM", enriched from crude membranes of human B lymphocytes or whole cell lysates of bovine skeletal muscle, respectively, was bound to a nine atoms spacer ATP-agarose at pH 7.4 or 5.0 and reeluted from the resin by 10 mM ATP disodium salt. Furthermore, channel active "Porin 31BM" was labelled by [32P]ATP in a 1:1 stoichiometric relation. Binding of ATP to human porin was confirmed by studying the interaction of the synthetic porin fragment Type-1/Ac-35, comprising the putative nucleotide binding site G Y G F G, with trinitrophenyl-ATP (TNT-ATP) by scanning fluorometry. Peptide/TNP-ATP complexes clearly show enhancement of fluorescence intensity and a spectral shift of the fluorescence maximum. In a control experiment, using a porin fragment lacking the putative nucleotide binding site, no change of fluorescence emission was observed. Further confirmation for ATP binding by human VDAC arose from an autoradiographic experimental approach: the porin fragment Type-1/Ac-35 could be labelled by [32P]ATP, while a second porin fragment ending immediately before the putative nucleotide binding site could not; nor could a synthetic non porin peptide.

Pharmacokinetic behavior and antineoplastic activity of liposomal hexadecylphosphocholine.

Hexadecylphosphocholine (HePC) shows remarkable antineoplastic efficacy in Sprague-Dawley rats bearing methylnitrosourea-induced mammary carcinoma. Unfortunately, this is accompanied by detrimental side effects that include gastrointestinal damage, body weight loss, and thrombophlebitis after i.v. injection, which has precluded the use of the HePC in humans, where nausea and vomiting can occur at noneffective dose levels. We have developed small unilamellar vesicles (SUVs) composed of HePC, cholesterol, and 1,2-dipalmitoyl-sn-gly-cero-3-phosphoglycerol, which can be given p.o. and i.v. In contrast to the free drug, the toxicity of liposomal HePC is shown to be greatly reduced, and there is no risk of thrombophlebitis. Single administration of equimolar HePC doses results in differing pharmacokinetic values for free HePC (p.o.) and HePC-SUVs (p.o., i.v.).