Factors influencing general practitioners’ decisions about cardiovascular disease risk reassessment: findings from experimental and interview studies

Background: Guidelines on cardiovascular disease (CVD) risk reassessment intervals are unclear, potentially leading to detrimental practice variation: too frequent can result in overtreatment and greater strain on the healthcare system; too infrequent could result in the neglect of high risk patients who require medication. This study aimed to understand the different factors that general practitioners (GPs) consider when deciding on the reassessment interval for patients previously assessed for primary CVD risk. Methods: This paper combines quantitative and qualitative data regarding reassessment intervals from two separate studies of CVD risk management. Experimental study: 144 Australian GPs viewed a random selection of hypothetical cases via a paper-based questionnaire, in which blood pressure, cholesterol and 5-year absolute risk (AR) were systematically varied to appear lower or higher. GPs were asked how they would manage each case, including an open-ended response for when they would reassess the patient. Interview study: Semi-structured interviews were conducted with a purposive sample of 25 Australian GPs, recruited separately from the GPs in the experimental study. Transcribed audio-recordings were thematically coded, using the Framework Analysis method. Results: Experiment: GPs stated that they would reassess the majority of patients across all absolute risk categories in 6 months or less (low AR = 52 % [CI = 47-57 %], moderate AR = 82 % [CI = 76-86 %], high AR = 87 % [CI = 82-90 %], total = 71 % [CI = 67-75 %]), with 48 % (CI = 43-53 %) of patients reassessed in under 3 months. The majority (75 % [CI = 70-79 %]) of patients with low-moderate AR (≤15 %) and an elevated risk factor would be reassessed in under 6 months. Interviews: GPs identified different functions for reassessment and risk factor monitoring, which affected recommended intervals. These included perceived psychosocial benefits to patients, preparing the patient for medication, and identifying barriers to lifestyle change and medication adherence. Reassessment and monitoring intervals were driven by patient motivation to change lifestyle, patient demand, individual risk factors, and GP attitudes. Conclusions: There is substantial variation in reassessment intervals for patients with the same risk profile. This suggests that GPs are not following reassessment recommendations in the Australian guidelines. The use of shorter intervals for low-moderate AR contradicts research on optimal monitoring intervals, and may result in unnecessary costs and over-treatment

Plexin-A4–semaphorin 3A signaling is required for Toll-like receptor– and sepsis-induced cytokine storm

Plexin-A4 activity is essential for Toll-like receptor–induced signaling, cytokine production, and inflammation in mice.Plexins and semaphorins are ligand–receptor pairs that serve as guidance molecules in the nervous system and play some roles in immunity. Plexins are similar to the Toll-like receptors (TLRs) in their evolutionary conservation from flies to mammals. By studying plexin-A4–deficient (Plxna4−/−) innate immune cells, in this study we show a novel influence of plexin-A4 on TLR signaling. Plxna4−/− cells exhibit defective inflammatory cytokine production upon activation by a spectrum of TLR agonists and bacteria. Plexin-A4 is required for TLR-induced activation of the small guanosine triphosphate hydrolase (GTPase) Rac1 (ras-related C3 botulinum toxin substrate 1). Rac1 activation is accompanied by JNK (c-Jun N-terminal kinase) and NF-κB activation, culminating in TLR-induced binding of NF-κB and AP-1 to the promoters of inflammatory cytokines. Plxna4−/− mice are remarkably resistant to TLR agonist–induced inflammation and polymicrobial peritonitis caused by cecal ligation and puncture. Administration of a ligand of plexin-A4, Sema3A (semaphorin 3A), exacerbates the cytokine storm caused by TLR agonists and bacterial sepsis. TLR engagement can induce Sema3A expression, thus completing an autocrine loop. These findings expand the role of plexins to TLR signaling and suggest plexin-A4 and Sema3A as new intervention points for treating sepsis

Risk factors of pancreatic cancer in patients with type 2 diabetes mellitus: The Hong Kong Diabetes Study

Context Diabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors. Objective The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study. Methods This was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed. Results This study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), of whom 1148 developed PaC. The number of antidiabetic medications prescribed (HR: 1.20; 95% CI, 1.01-1.42; P = .040), diabetic microvascular complications (HR: 1.91; 95% CI, 1.30-2.81; P < .001), chronic kidney disease (HR: 1.81; 95% CI, 1.25-2.64; P = .002), use of acarbose (HR: 2.24; 95% CI, 1.35-3.74; P = .002), and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28-12.53, P = .017) were associated with PaC development on multivariable Cox regression adjusting for the duration of DM, mean glycated hemoglobin A1c, and history of pancreatic diseases. Stage 3A CKD or below was associated with PaC but not stage 3B or beyond. Conclusion Diabetic microvascular complications, especially stage 1, 2, and 3A CKD, were associated with PaCs

Portraiture: Inside Out

Catalog for the exhibition Portraiture: Inside Out held at the Seton Hall University Walsh Gallery, February 28 - April 1, 2011. Curated by Ruth Ballester, Whitney Fehl, and Lauren Thompson. Includes an essay by Ruth Ballester, Whitney Fehl, and Lauren Thompson. Includes color illustrations

Risk Factors of Pancreatic Cancer in Patients With Type 2 Diabetes Mellitus: The Hong Kong Diabetes Study

Context: Diabetes mellitus (DM) is associated with the development of pancreatic cancer (PaC), but few large-scale studies have examined its predictive risk factors. Objective: The present study aims to examine the predictors for PaC in patients with type 2 diabetes mellitus (T2DM) in a territory-wide, retrospective cohort study. Methods: This was a territory-wide, retrospective cohort study of patients with T2DM mellitus older than 40 years with no prior history of PaC. Baseline demographics, use of antidiabetic medications, comorbidities, and biochemical parameters were extracted. Cox regression was used to calculate hazard ratios (HR) with 95% CI. Subgroup analyses based on chronic kidney disease (CKD) stages were performed. Results: This study consisted of 273 738 patients (age = 65.4 ± 12.7 years, male = 48.2%, follow-up duration = 3547 ± 1207 days, disease duration = 4.8 ± 2.3 years), of whom 1148 developed PaC. The number of antidiabetic medications prescribed (HR: 1.20; 95% CI, 1.01-1.42; P = .040), diabetic microvascular complications (HR: 1.91; 95% CI, 1.30-2.81; P P = .002), use of acarbose (HR: 2.24; 95% CI, 1.35-3.74; P = .002), and use of glucagon-like peptide-1 receptor agonist (HR: 4.00; 95% CI: 1.28-12.53, P = .017) were associated with PaC development on multivariable Cox regression adjusting for the duration of DM, mean glycated hemoglobin A1c, and history of pancreatic diseases. Stage 3A CKD or below was associated with PaC but not stage 3B or beyond. Conclusion: Diabetic microvascular complications, especially stage 1, 2, and 3A CKD, were associated with PaCs