Making the Connection: How Provider Dialogue and Network Clusters Can Spur Successful Collaboration

In 2005, the Forbes Funds commissioned a report called Service Clustering: Building Cohesive Public Service Capacity that described collaboration as a way to achieve greater efficiency through shared back-office or non-mission critical functions without reducing consumer choice. The researchers argued that collaboration could best be induced by focusing on providers that are geographically close together and that provide an overlapping set of services. According to the report, "It is easier to share, communicate, and collaborate with your neighbor than with an organization separated by distance." Though this idea is compelling, it has become clear in the years since the 2005 report that the identification of geographic clusters is not sufficient to inspire a host of new collaborations. Formal collaboration, the kind suggested in the past report and the focus of this work, remains a relatively rare phenomenon. Convinced that collaboration continues to promise greater efficiency and effectiveness when successfully implemented, The Forbes Funds revisited the topic this year, hoping to gain further insight into the factors that make collaboration successful and to identify additional clusters of providers that could provide the greatest potential for collaboration

A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients:The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative

Objective To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH). Methods All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH. Results Out of 206 members of the DGE's thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p&lt;0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p&lt;0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p&lt;0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p&lt;0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p&lt;0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another. Conclusion For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.</p

Can I Trust You? A Critical Review of the Perceptual, Social and Cognitive Influences on Trust

Trust is a complex psychological phenomenon that is foundational to coordinated behaviour and societal function. This narrative review critically examines the perceptual, social, and cognitive indicators of trust, drawing on findings from multiple fields of behavioural science to identify theoretical and empirical gaps in our current understanding. Particular attention is paid to social identity cues, perceptual features like eye gaze, pupil dilation, and facial characteristics, and memory recall factors related to threat and reliability judgements, to highlight the potential domains of functional overlap that are ignored by narrowly focused research approaches. The review also identifies critical gaps in understanding the interplay of multimodal sensory cues, the impact of trust violations on memory encoding and retrieval, and the integration of trust cues in ecologically valid settings. To ground the importance of the dynamics of trust formation, the paper then overviews some demonstrable effects trust has on other domains of decision-making, ranging from financial to legal. Recommendations for future research emphasise the need for interdisciplinary approaches to account for these complexities. Pursuing these empirical directions could lead to significant practical advances in the understanding of the cognitive mechanisms underpinning trust, and their application to real-world decision-making settings where trust is essential

CFAP157 is a murine downstream effector of FOXJ1 that is specifically required for flagellum morphogenesis and sperm motility

Motile cilia move extracellular fluids or mediate cellular motility. Their function is essential for embryonic development, adult tissue homeostasis and reproduction throughout vertebrates. FOXJ1 is a key transcription factor for the formation of motile cilia but its downstream genetic programme is only partially understood. Here, we characterise a novel FOXJ1 target, Cfap157, that is specifically expressed in motile ciliated tissues in mouse and Xenopus in a FOXJ1-dependent manner. CFAP157 protein localises to basal bodies and interacts with tubulin and the centrosomal protein CEP350. Cfap157 knockout mice appear normal but homozygous males are infertile. Spermatozoa display impaired motility and a novel phenotype: Cfap157-deficient sperm exhibit axonemal loops, supernumerary axonemal profiles with ectopic accessory structures, excess cytoplasm and clustered mitochondria in the midpiece regions, and defective axonemes along the flagella. Our study thus demonstrates an essential sperm-specific function for CFAP157 and suggests that this novel FOXJ1 effector is part of a mechanism that acts during spermiogenesis to suppress the formation of supernumerary axonemes and ensures a correct ultrastructure.</jats:p

Repeated determination of moxifloxacin concentrations in interstitial space fluid of muscle and subcutis in septic patients

Background: For an effective antimicrobial treatment, it is crucial that antibiotics reach sufficient concentrations in plasma and tissue. Currently no data exist regarding moxifloxacin plasma concentrations and exposure levels in tissue under septic conditions. Objectives: To determine the pharmacokinetics of moxifloxacin in plasma and interstitial space fluid over a prolonged period. Patients and methods: Ten septic patients were treated with 400 mg of moxifloxacin once a day; on days 1, 3 and 5 of treatment plasma sampling and microdialysis in the subcutis and muscle of the upper thigh were performed to determine concentrations of moxifloxacin in different compartments. This trial was registered in the German Clinical Trials Register (DRKS, register number DRKS00012985). Results: Mean unbound fraction of moxifloxacin in plasma was 85.5 +/- 3.4%. On day 1, C-max in subcutis and muscle was 2.8 +/- 1.8 and 2.5 +/- 1.3 mg/L, respectively, AUC was 24.8 +/- 15.1 and 21.3 +/- 10.5 mgh/L, respectively, and fAUC(0-24)/MIC was 100.9 +/- 62.9 and 86.5 +/- 38.3 h, respectively. C-max for unbound moxifloxacin in plasma was 3.5 +/- 0.9 mg/L, AUC was 23.5 +/- 7.5 mg.h/L and fAUC(0-24)/MIC was 91.6 +/- 24.8 h. Key pharmacokinetic parameters on days 3 and 5 showed no significant differences. Clearance was higher than in healthy adults, but tissue concentrations were comparable, most likely due to a lower protein binding. Conclusions: Surprisingly, the first dose already achieved exposure comparable to steady-state conditions. The approved daily dose of 400 mg was adequate in our patient population. Thus, it seems that in septic patients a loading dose on the first day of treatment with moxifloxacin is not required

A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative

Abstract Objective To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH). Methods All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH. Results Out of 206 members of the DGE’s thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p&lt;0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p&lt;0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p&lt;0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p&lt;0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p&lt;0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another. Conclusion For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.</jats:p

Repeated determination of moxifloxacin concentrations in interstitial space fluid of muscle and subcutis in septic patients

Abstract Background For an effective antimicrobial treatment, it is crucial that antibiotics reach sufficient concentrations in plasma and tissue. Currently no data exist regarding moxifloxacin plasma concentrations and exposure levels in tissue under septic conditions. Objectives To determine the pharmacokinetics of moxifloxacin in plasma and interstitial space fluid over a prolonged period. Patients and methods Ten septic patients were treated with 400 mg of moxifloxacin once a day; on days 1, 3 and 5 of treatment plasma sampling and microdialysis in the subcutis and muscle of the upper thigh were performed to determine concentrations of moxifloxacin in different compartments. This trial was registered in the German Clinical Trials Register (DRKS, register number DRKS00012985). Results Mean unbound fraction of moxifloxacin in plasma was 85.5±3.4%. On day 1, Cmax in subcutis and muscle was 2.8±1.8 and 2.5±1.3 mg/L, respectively, AUC was 24.8±15.1 and 21.3±10.5 mg·h/L, respectively, and fAUC0–24/MIC was 100.9±62.9 and 86.5±38.3 h, respectively. Cmax for unbound moxifloxacin in plasma was 3.5±0.9 mg/L, AUC was 23.5±7.5 mg·h/L and fAUC0–24/MIC was 91.6±24.8 h. Key pharmacokinetic parameters on days 3 and 5 showed no significant differences. Clearance was higher than in healthy adults, but tissue concentrations were comparable, most likely due to a lower protein binding. Conclusions Surprisingly, the first dose already achieved exposure comparable to steady-state conditions. The approved daily dose of 400 mg was adequate in our patient population. Thus, it seems that in septic patients a loading dose on the first day of treatment with moxifloxacin is not required. </jats:sec

Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis

Background. Fast progression of the transaortic mean gradient (P-mean) is relevant for clinical decision making of valve replacement in patients with moderate and severe aortic stenosis (AS) patients. However, there is currently little knowledge regarding the determinants affecting progression of transvalvular gradient in AS patients. Methods. This monocentric retrospective study included consecutive patients presenting with at least two transthoracic echocardiography examinations covering a time interval of one year or more between April 2006 and February 2016 and diagnosed as moderate or severe aortic stenosis at the final echocardiographic examination. Laboratory parameters, medication, and prevalence of eight known cardiac comorbidities and risk factors (hypertension, diabetes, coronary heart disease, peripheral artery occlusive disease, cerebrovascular disease, renal dysfunction, body mass index >= 30 Kg/m(2), and history of smoking) were analyzed. Patients were divided into slow (P-mean = 5 mmHg/year) progression groups. Results. A total of 402 patients (mean age 78 +/- 9.4 years, 58% males) were included in the study. Mean follow-up duration was 3.4 +/- 1.9 years. The average number of cardiac comorbidities and risk factors was 3.1 +/- 1.6. Average number of cardiac comorbidities and risk factors was higher in patients in slow progression group than in fast progression group (3.3 +/- 1.5 vs 2.9 +/- 1.7; P = 0.036). Patients in slow progression group had more often coronary heart disease (49.2% vs 33.6%; P = 0.003) compared to patients in fast progression group. LDL-cholesterol values were lower in the slow progression group (100 +/- 32.6 mg/dl vs 110.8 +/- 36.6 mg/dl; P = 0.005). Conclusion. These findings suggest that disease progression of aortic valve stenosis is faster in patients with fewer cardiac comorbidities and risk factors, especially if they do not have coronary heart disease. Further prospective studies are warranted to investigate the outcome of patients with slow versus fast progression of transvalvular gradient with regards to comorbidities and risk factors