[General practitioners' perspectives on the perceived effectiveness of the disease management programs for type 2 diabetes and coronary heart disease: Results of a focus group study]. / Die wahrgenommene Effektivität der Disease Management Programme für Diabetes mellitus Typ 2 und Koronare Herzkrankheit aus Sicht von Hausärzt*innen ­ Ergebnisse einer Fokusgruppenstudie.

BACKGROUND: The majority of patients in disease management programs (DMPs) for type 2 diabetes (T2DM) and coronary heart disease (CHD) in Germany are enrolled by their general practitioner (GP). The aim of this study was, in the context of upcoming DMP expansions, to elicit GPs' current experiences and opinions regarding the perceived effectiveness and acceptance of the DMPs T2DM and CHD, as well as to determine beneficial and hindering aspects of the implementation of these programs from a GP's perspective. METHODS: In August and September 2020, 20 GPs of teaching practices of the University Hospital Cologne with experiences in DMPs were interviewed in semi-structured focus group discussions. Their expectations, attitudes and opinions regarding the DMPs T2DM and CHD were evaluated and analyzed according to the content-structuring qualitative content analysis by Kuckartz. RESULTS: The DMP T2DM was rated as generally positive by the respondents due to the structured treatment including regular foot and eye examinations, close patient contacts and perceptions of improved health outcomes. The DMP CHD was rated more negatively by the respondents because of a high and partly unnecessary documentation workload and limited therapeutic freedom, leading to a perceived ineffectiveness for patients' health outcomes. Thus, there was a discrepancy in the perceived effectiveness of the examined DMPs, causing a lower acceptance of the DMP CHD. Therefore, some of the respondents tended to enroll fewer patients into the DMP CHD or to drop out of the DMP CHD. DISCUSSION: In order to increase the acceptance and sustainability of DMPs some elements of the DMP CHD as well as the remuneration and the documentation need to be reconsidered. Additionally, future studies on the acceptance of DMPs should differentiate between different DMPs in order to generate valid results.

A pragmatic randomised controlled trial referring to a Personalised Self-management SUPport Programme (P-SUP) for persons enrolled in a disease management programme for type 2 diabetes mellitus and/or for coronary heart disease.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) are two chronic diseases that cause a tremendous burden. To reduce this burden, several programmes for optimising the care for these diseases have been developed. In Germany, so-called disease management programmes (DMPs), which combine components of Disease Management and the Chronic Care Model, are applied. These DMPs have proven effective. Nevertheless, there are opportunities for improvement. Current DMPs rarely address self-management of the disease, make no use of peer support, and provide no special assistance for persons with low health literacy and/or low patient activation. The study protocol presented here is for the evaluation of a programme that addresses these possible shortcomings and can be combined with current German DMPs for T2DM and CHD. This programme consists of four components: 1) Meetings of peer support groups 2) Personalised telephone-based health coaching for patients with low literacy and/or low patient activation 3) Personalised patient feedback 4) A browser-based web portal METHODS: Study participants will be adults enrolled in a DMP for T2DM and/or CHD and living in North Rhine-Westphalia, a state of the Federal Republic of Germany. Study participants will be recruited with the assistance of their general practitioners by the end of June 2021. Evaluation will be performed as a pragmatic randomised controlled trial with one intervention group and one waiting control group. The intervention group will receive the intervention for 18 months. During this time, the waiting control group will continue with usual care and the usual measures of their DMPs. After 18 months, the waiting control group will also receive a shortened intervention. The primary outcome is number of hospital days. In addition, the effects on self-reported health-state, physical activity, nutrition, and eight different psychological variables will be investigated. Differences between values at month 18 and at the beginning will be compared to judge the effectiveness of the intervention. DISCUSSION: If the intervention proves effective, it may be included into the DMPs for T2DM and CHD. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) in early 2019 under the number 00020592. This registry has been affiliated with the WHO Clinical Trials Network ( https://www.drks.de/drks_web/setLocale_EN.do ) since 2008. It is based on the WHO template, but contains some additional categories for which information has to be given ( https://www.drks.de/drks_web/navigate.do?navigationId=entryfields&messageDE=Beschreibung%20der%20Eingabefelder&messageEN=Description%20of%20entry%20fields ). A release and subsequent number assignment only take place when information for all categories has been given.

Quit attempts and tobacco abstinence in primary care patients: follow-up of a pragmatic, two-arm cluster randomised controlled trial on brief stop-smoking advice - ABC versus 5As.

We developed a 3.5-h training for general practitioners (GPs) in delivering brief stop-smoking advice according to different methods (ABC, 5As). In a pragmatic, cluster randomised controlled trial our training proved effective in increasing GP-delivered rates of such advice (from 13% to 33%). In this follow-up analysis we examined the effect of the training and compared ABC versus 5As on patient-reported quit attempts and point prevalence abstinence at weeks 4, 12 and 26 following GP consultation. Follow-up data were collected in 1937 smoking patients - independently of the receipt of GP advice - recruited before or after the training of 69 GPs. At week 26, ∼70% of the patients were lost to follow-up. All 1937 patients were included in an intention-to-treat analysis; missing outcome data were imputed. Quit attempts and abstinence rates did not differ significantly from pre- to post-training or between patients from the ABC versus the 5As group. However, ancillary analyses showed that patients who received GP advice compared to those who did not had two times higher odds of reporting a quit attempt at all follow-ups and abstinence at week 26. We reported that our training increases GP-delivered rates of stop-smoking advice, and the present analysis confirms that advice is associated with increased quit attempts and abstinence rates in patients. However, our training did not further improve these rates, which might be related to patients' loss to follow-up or to contextual factors, e.g. access to free evidence-based cessation treatment, which can hamper the transfer of GPs' advice into patients' behaviour change.

Training general practitioners in the ABC versus 5As method of delivering stop-smoking advice: a pragmatic, two-arm cluster randomised controlled trial.

This study assessed the effectiveness of a 3.5-h training session for general practitioners (GPs) in providing brief stop-smoking advice and compared two methods of giving advice - ABC versus 5As - on the rates of delivery of such advice and of recommendations of evidence-based smoking cessation treatment during routine consultations. A pragmatic, two-arm cluster randomised controlled trial was carried out including a pre-/post-design for the analyses of the primary outcome in 52 GP practices in Germany. Practices were randomised (1:1) to receive a 3.5-h training session (ABC or 5As). In total, 1937 tobacco-smoking patients, who consulted trained GPs in these practices in the 6 weeks prior to or following the training, were included. The primary outcome was patient-reported rates of GP-delivered stop-smoking advice prior to and following the training, irrespective of the training method. Secondary outcomes were patient-reported receipt of recommendation/prescription of behavioural therapy, pharmacotherapy or combination therapy for smoking cessation, and the effectiveness of ABC versus 5As regarding all outcomes. GP-delivered stop-smoking advice increased from 13.1% (n=136 out of 1039) to 33.1% (n=297 out of 898) following the training (adjusted odds ratio (aOR) 3.25, 95% CI 2.34-4.51). Recommendation/prescription rates of evidence-based treatments were low (<2%) pre-training, but had all increased after training (e.g. behavioural support: aOR 7.15, 95% CI 4.02-12.74). Delivery of stop-smoking advice increased non-significantly (p=0.08) stronger in the ABC versus 5As group (aOR 1.71, 95% CI 0.94-3.12). A single training session in stop-smoking advice was associated with a three-fold increase in rates of advice giving and a seven-fold increase in offer of support. The ABC method may lead to higher rates of GP-delivered advice during routine consultations.

Effectiveness of training general practitioners to improve the implementation of brief stop-smoking advice in German primary care: study protocol of a pragmatic, 2-arm cluster randomised controlled trial (the ABCII trial).

BACKGROUND: The German clinical guideline on tobacco addiction recommends that general practitioners (GPs) provide brief stop-smoking advice to their patients according to the "5A" or the much briefer "ABC" method, but its implementation is insufficient. A lack of training is one barrier for GPs to provide such advice. Moreover, the respective effectiveness of a 5A or ABC training regarding subsequent delivery of stop-smoking advice has not been investigated. We developed a training for GPs according to both methods, and conducted a pilot study with process evaluation to optimize the trainings according to the needs of GPs. This study aims at evaluating the effectiveness of both trainings. METHODS: A pragmatic 2-arm cluster randomised controlled trial with a pre-post data collection will be conducted in 48 GP practices in North Rhine-Westphalia (Germany). GPs will be randomised to receive a 3.5-h-training in delivering either 5A or ABC, including peer coaching and intensive role plays with professional actors. The patient-reported primary outcome (receipt of GP advice to quit: yes/no) and secondary outcomes (recommendation rates of smoking cessation treatments, group comparison (5A versus ABC): receipt of GP advice to quit) will be collected in smoking patients routinely consulting their GP within 4 weeks prior, and 4 weeks following the training. Additional secondary outcomes will be collected at 4, 12 and 26 weeks following the consultation: use of cessation treatments during the last quit attempt (if so) since the GP consultation, and point-prevalence abstinence rates. The primary data analysis will be conducted using a mixed-effects logistic regression model with random effects for the cluster variable. DISCUSSION: If the training increases the rates of delivery of stop-smoking advice, it would offer a low-threshold strategy for the guideline implementation in German primary care. Should one method prove superior, a more specific guideline recommendation can be proposed. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00012786); registered on 22th August 2017, prior to the first patient in.

A Major Advance in the Synthesis of Fluoroalkyl Pyrazoles: Tuneable Regioselectivity and Broad Substitution Patterns.

A novel approach towards highly functionalized fluoroalkyl pyrazoles was developed by using fluoroalkyl amino reagents in combination with a variety of fluorinated ketimines. Tuneable introduction of fluoroalkyl groups in the 3- and 5-positions was possible by using vinamidinium intermediates or the corresponding enamino ketones after hydrolysis. These high-value building blocks can give rise to a large number of analogues for bioactivity screening and discovering new heterocyclic bioactive ingredients in various life science fields.

Phthalic acid diamides activate ryanodine-sensitive Ca2+ release channels in insects.

Flubendiamide represents a novel chemical family of substituted phthalic acid diamides with potent insecticidal activity. So far, the molecular target and the mechanism of action were not known. Here we present for the first time evidence that phthalic acid diamides activate ryanodine-sensitive intracellular calcium release channels (ryanodine receptors, RyR) in insects. With Ca(2+) measurements, we showed that flubendiamide and related compounds induced ryanodine-sensitive cytosolic calcium transients that were independent of the extracellular calcium concentration in isolated neurons from the pest insect Heliothis virescens as well as in transfected CHO cells expressing the ryanodine receptor from Drosophila melanogaster. Binding studies on microsomal membranes from Heliothis flight muscles revealed that flubendiamide and related compounds interacted with a site distinct from the ryanodine binding site and disrupted the calcium regulation of ryanodine binding by an allosteric mechanism. This novel insecticide mode of action seems to be restricted to specific RyR subtypes because the phthalic acid diamides reported here had almost no effect on mammalian type 1 ryanodine receptors.

Total synthesis of thiostrepton. Retrosynthetic analysis and construction of key building blocks.

The first phase of the total synthesis of thiostrepton (1), a highly complex thiopeptide antibiotic, is described. After a brief introduction to the target molecule and its structural motifs, it is shown that retrosynthetic analysis of thiostrepton reveals compounds 23, 24, 26, 28, and 29 as potential key building blocks for the projected total synthesis. Concise and stereoselective constructions of all these intermediates are then described. The synthesis of the dehydropiperidine core 28 was based on a biosynthetically inspired aza-Diels-Alder dimerization of an appropriate azadiene system, an approach that was initially plagued with several problems which were, however, resolved satisfactorily by systematic investigations. The quinaldic acid fragment 24 and the thiazoline-thiazole segment 26 were synthesized by a series of reactions that included asymmetric and other stereoselective processes. The dehydroalanine tail precursor 23 and the alanine equivalent 29 were also prepared from the appropriate amino acids. Finally, a method was developed for the direct coupling of the labile dehydropiperidine key building block 28 to the more advanced and stable peptide intermediate 27 through capture with the highly reactive alanine equivalent 67 under conditions that avoided the initially encountered destructive ring contraction process.