A cluster randomized controlled trial aimed at implementation of local quality improvement collaboratives to improve prescribing and test ordering performance of general practitioners: Study Protocol

<p>Abstract</p> <p>Background</p> <p>The use of guidelines in general practice is not optimal. Although evidence-based methods to improve guideline adherence are available, variation in physician adherence to general practice guidelines remains relatively high. The objective for this study is to transfer a quality improvement strategy based on audit, feedback, educational materials, and peer group discussion moderated by local opinion leaders to the field. The research questions are: is the multifaceted strategy implemented on a large scale as planned?; what is the effect on general practitioners' (GPs) test ordering and prescribing behaviour?; and what are the costs of implementing the strategy?</p> <p>Methods</p> <p>In order to evaluate the effects, costs and feasibility of this new strategy we plan a multi-centre cluster randomized controlled trial (RCT) with a balanced incomplete block design. Local GP groups in the south of the Netherlands already taking part in pharmacotherapeutic audit meeting groups, will be recruited by regional health officers. Approximately 50 groups of GPs will be randomly allocated to two arms. These GPs will be offered two different balanced sets of clinical topics. Each GP within a group will receive comparative feedback on test ordering and prescribing performance. The feedback will be discussed in the group and working agreements will be created after discussion of the guidelines and barriers to change. The data for the feedback will be collected from existing and newly formed databases, both at baseline and after one year.</p> <p>Discussion</p> <p>We are not aware of published studies on successes and failures of attempts to transfer to the stakeholders in the field a multifaceted strategy aimed at GPs' test ordering and prescribing behaviour. This pragmatic study will focus on compatibility with existing infrastructure, while permitting a certain degree of adaptation to local needs and routines.</p> <p>Trial registration</p> <p>Nederlands Trial Register ISRCTN40008171</p

Validation and cultural adaptation of a German version of the Physicians' Reactions to Uncertainty scales

Contains fulltext : 51656.pdf ( ) (Open Access)BACKGROUND: The aim of the study was to examine the validity of a translated and culturally adapted version of the Physicians' Reaction to Uncertainty scales (PRU) in primary care physicians. METHODS: In a structured process, the original questionnaire was translated, culturally adapted and assessed after administering it to 93 GPs. Test-retest reliability was tested by sending the questionnaire to the GPs again after two weeks. RESULTS: The principal factor analysis confirmed the postulated four-factor structure underlying the 15 items. In contrast to the original version, item 5 achieved a higher loading on the 'concern about bad outcomes' scale. Consequently, we rearranged the scales. Good item-scale correlations were obtained, with Pearson's correlation coefficient ranging from 0.56-0.84. As regards the item-discriminant validity between the scales 'anxiety due to uncertainty' and 'concern about bad outcomes', partially high correlations (Pearson's correlation coefficient 0.02-0.69; p < 0.001) were found, indicating an overlap between both constructs. The assessment of internal consistency revealed satisfactory values; Cronbach's alpha of the rearranged version was 0.86 or higher for all scales. Test-retest-reliability, assessed by means of the intraclass-correlation-coefficient (ICC), exceeded 0.84, except for the 'reluctance to disclose mistakes to physicians' scale (ICC = 0.66). In this scale, some substantial floor effects occurred, with 29.3% of answers showing the lowest possible value. CONCLUSION: Dealing with uncertainty is an important issue in daily practice. The psychometric properties of the rearranged German version of the PRU are satisfying. The revealed floor effects do not limit the significance of the questionnaire. Thus, the German version of the PRU could contribute to the further evaluation of the impact of uncertainty in primary care physicians

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer : A Retrospective Study

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMARLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up

Automated GMP Production and Preclinical Evaluation of [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA

[68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis of liver nodules. The purpose of this study was to investigate problems that occurred initially during the development of the GMP compliant synthesis procedure and to evaluate the tracers in a preclinical model. After low radiolabeling yields were attributed to precursor instability at high temperatures, an optimized radiolabeling procedure was established. Quality controls were in accordance with Ph. Eur. requirements and gave compliant results, although the method for the determination of the 68Ga colloid is partially inhibited due to the presence of a radioactive by-product. The determination of logP revealed [68Ga]Ga-TEoS-DAZA (ethoxy bearing) to be more lipophilic than [68Ga]Ga-TMoS-DAZA (methoxy bearing). Accordingly, biodistribution studies in an in ovo model showed a higher liver uptake for [68Ga]Ga-TEoS-DAZA. In dynamic in ovo PET imaging, rapid tracer accumulation in the liver was observed. Similarly, the activity in the intestines rose steadily within the first hour p.i., indicating biliary excretion. As [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA can be prepared according to GMP guidelines, transition into the early clinical phase is now possible

Multimodal Characterization of a PSMA-Positive Thyroid Nodule Using 68Ga-PSMA and 124Iodine PET/US Fusion Imaging

A 54-year-old male diagnosed with prostate cancer was referred for 68Gallium-PSMA-11 PET/CT. The scan revealed a solitary PSMA-positive thyroid lesion. On PET/ultrasound fusion imaging, a nodule with moderate risk of malignancy (TIRADS 4B) could be unambiguously correlated. Additional 124Iodine PET/ultrasound fusion imaging revealed normal iodine uptake within the PSMA-positive thyroid nodule. Fine-needle aspiration cytology was performed using an ultrasound needle-guidance system. The cytopathological investigation confirmed a benign thyroid nodule and excluded a thyroid carcinoma as well as a prostate cancer metastasis. Immunohistochemistry was positive for thyroglobulin staining

The effect of butylscopolamine on [18F]FDG uptake in the gastrointestinal tract is negligible and regionally variable

Abstract Background Butylscopolamine (or hyoscine butylbromide, trade name Buscopan®) is occasionally administered as a premedication to reduce non-specific FDG uptake in the gastrointestinal tract based on its antiperistaltic effect. To date, there are no consistent recommendations for its use. The aim of this study was to quantify the reduction in intestinal and non-intestinal uptake by butylscopolamine administration and to derive relevance for clinical evaluation. Results 458 patients (PET/CT for lung cancer) were retrospectively reviewed. 218 patients with butylscopolamine and 240 patients without butylscopolamine had comparable characteristics. While the SUVmean in the gullet/stomach and small intestine was significantly reduced with butylscopolamine, the colon and rectum/anus showed no difference. The liver and salivary glands showed a reduced SUVmean, while skeletal muscle and blood pool were unaffected. An effect of butylscopolamine was particularly evident in men and patients under 65 years of age. There was no difference in the perceived confidence in the assessment of intestinal findings in the subjective evaluation, although in the butylscopolamine group further diagnostics appeared advisable more frequently. Conclusions Butylscopolamine reduces gastrointestinal FDG accumulation only in selected segments and, despite a significant effect, only to a small extent. A general recommendation for the use of butylscopolamine cannot be derived from these results, its use for specific issues could be considered individually

Ultrasound Cine Loop Standard Operating Procedure for Benign Thyroid Diseases—Evaluation of Non-Physician Application

Conventional ultrasound (US) is time-consuming, and results are subjected to high interobserver variability. In this study, the reliability of a novel thyroid US cine loop standard operating procedure (SOP) applied by non-physicians (Medical Technical Assistant, MTA) is investigated. Thirty-three consecutive patients (22 females, 11 males) were enrolled. Patients underwent conventional thyroid US performed by a nuclear medicine physician and additional MTA US cine loop according to a local SOP that includes transversal and sagittal cine loops covering the entire thyroid. The video sequences were transferred to the Picture Archiving and Communication System (PACS) for second reading purposes. MTA US data were not considered for medical reports but for blinded second reading review of the PACS images. The results of conventional physician US reports and reviewed MTA US cine loops were compared regarding size determinations of the thyroid and its nodules, as well as Thyroid Imaging Reporting and Data Systems (TIRADS) classification of all identified lesions. The results revealed very high concordance between conventional physician US and MTA US cine loop review for both size measurements and TIRADS classifications (r(s) = 0.84&ndash;0.99, p &lt; 0.0001 each). Minor technical impairments were identified. The evaluated thyroid US cine loop SOP enables reliable second reading results and can be applied by non-physicians

Optimization of Thyroid Volume Determination by Stitched 3D-Ultrasound Data Sets in Patients with Structural Thyroid Disease

Ultrasound (US) is the most important imaging method for the assessment of structural disorders of the thyroid. A precise volume determination is relevant for therapy planning and outcome monitoring. However, the accuracy of 2D-US is limited, especially in cases of organ enlargements and deformations. Software-based “stitching” of separately acquired 3D-US data revealed precise volume determination in thyroid phantoms. The purpose of this study is to investigate the feasibility and accuracy of 3D-US stitching in patients with structural thyroid disease. A total of 31 patients from the clinical routine were involved, receiving conventional 2D-US (conUS), sensor-navigated 3D-US (3DsnUS), mechanically-swept 3D-US (3DmsUS), and I-124-PET/CT as reference standard. Regarding 3DsnUS and 3DmsUS, separately acquired 3D-US images (per thyroid lobe) were merged to one comprehensive data set. Subsequently, anatomical correctness of the stitching process was analysed via secondary image fusion with the I-124-PET images. Volumetric determinations were conducted by the ellipsoid model (EM) on conUS and CT, and manually drawn segmental contouring (MC) on 3DsnUS, 3DmsUS, CT, and I-124-PET/CT. Mean volume of the thyroid glands was 44.1 ± 25.8 mL (I-124-PET-MC = reference). Highly significant correlations (all p < 0.0001) were observed for conUS-EM (r = 0.892), 3DsnUS-MC (r = 0.988), 3DmsUS-MC (r = 0.978), CT-EM (0.956), and CT-MC (0.986), respectively. The mean volume differences (standard deviations, limits of agreement) in comparison with the reference were −10.50 mL (±11.56 mL, −33.62 to 12.24), −3.74 mL (±3.74 mL, −11.39 to 3.78), and 0.62 mL (±4.79 mL, −8.78 to 10.01) for conUS-EM, 3DsnUS-MC, and 3DmsUS-MC, respectively. Stitched 3D-US data sets of the thyroid enable accurate volumetric determination even in enlarged and deformed organs. The main limitation of high time expenditure may be overcome by artificial intelligence approaches