Risk Reduction In Patients Research Articles

Economic burden of enhanced practices of duodenoscopes reprocessing and surveillance: balancing risk and cost containment.

Background and study aims Recent outbreaks attributed to contaminated duodenoscopes have led to the development of enhanced surveillance and reprocessing techniques (enhanced-SRT) aimed at minimizing cross-contamination. Common enhanced-SRT include double high-level disinfection (HLD), ethylene oxide (EtO) gas sterilization, and culture-based monitoring of reprocessed scopes. Adoption of these methods adds to the operational costs and we aimed to assess its economic impact to an institution. Methods We compared the estimated costs of three enhanced-SRT versus single-HLD using data from two institutions. We examined the cost of capital measured as scope inventory and frequency of scope use per unit time, the constituent reprocessing costs required on a per-cycle basis, and labor & staffing needs. The economic impact attributable to enhanced-SRT was defined as the difference between the total cost of enhanced-SRT and single HLD. Results Compared to single HLD, adoption of double HLD increased the costs approximately by 47 % ($80 vs $118). Similarly, culture and quarantine and EtO sterilization increased costs by 160 % and 270 %, respectively ($80 vs $208 and $296). Enhanced-SRT introduced significant scope downtime due to prolonged techniques, necessitating a 3.4-fold increase in the number of scopes needed to maintain procedural volume. The additional annual budget required to implement enhanced-SRT approached $406,000 per year in high-volume centers. Conclusions While enhanced-SRT may reduce patient risk of exposure to contaminated duodenoscopes, it significantly increases the cost of performing ERCP. Future innovation should focus on approaches that can ensure patient safety while maintaining the ability to perform ERCP in a cost-effective manner.

Complex-Valued Wavelet Spectrum Analysis of Respiratory Conditions and Its Feasibility in the Detection of Low-Functional Respiration.

Respiratory monitoring is a significant issue to reduce patient risks and medical staff labor in postoperative care and epidemic infection, particularly after the COVID-19 pandemic. Oximetry is widely used for respiration monitoring in the clinic, but it sometimes fails to capture a low-functional respiratory condition even though a patient has breathing difficulty. Another approach is breathing-sound monitoring, but this is unstable due to the indirect measurement of lung volume. Kobayashi in our team is developing a sensor measuring temporal changes in lung volume with a displacement sensor attached across the sixth and eighth ribs. For processing these respiratory signals, we propose the combination of complex-valued wavelet transform and the correlation among spectrum sequences. We present the processing results and discuss its feasibility to detect a low-functional condition in respiration. The result for detecting low-functional respiration showed good performance with a sensitivity of 0.88 and specificity of 0.88 to 1 in its receiver operating characteristic (ROC) curve.

Does Empagliflozin Modulate Leukocyte-Endothelium Interactions, Oxidative Stress, and Inflammation in Type 2 Diabetes?

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to cardiovascular risk reduction in patients with type 2 diabetes (T2D). However, their underlying molecular mechanisms remain unclear. This study aimed to evaluate the effects of empagliflozin, a novel potent and selective iSGLT-2, on anthropometric and endocrine parameters, leukocyte–endothelium interactions, adhesion molecules, ROS production, and NFkB-p65 transcription factor expression. According to standard clinical protocols, sixteen T2D patients receiving 10 mg/day of empagliflozin were followed-up for 24 weeks. Anthropometric and analytical measurements were performed at baseline, 12 weeks, and 24 weeks. Interactions between polymorphonuclear leukocytes and human umbilical vein endothelial cells (HUVECs), serum levels of adhesion molecules (P-Selectin, VCAM-1 and ICAM-1) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), mitochondrial ROS levels, antioxidant enzymes (SOD1 and GPX1), and NFkB-p65 were measured. We observed a decrease in body weight, BMI, and HbA1C levels from 12 weeks of treatment, which became more pronounced at 24 weeks and was accompanied by a significant reduction in waist circumference and glucose. Leukocyte–endothelium interactions were reduced due to an enhancement in the leukocyte rolling velocity from 12 weeks onwards, together with a significant decrease in leukocyte rolling flux and adhesion at 24 weeks. Accordingly, a significant decrease in ICAM-1 levels, mitochondrial ROS levels, and IL-6 and NFkB-p65 expression was observed, as well as an increase in SOD1. This pilot study provides evidence of the anti-inflammatory and antioxidant properties of empagliflozin treatment in humans, properties which may underlie its beneficial cardiovascular effects.

Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study

It is well-known that hypertension exacerbates chronic kidney disease (CKD) progression, however, the optimal target blood pressure (BP) level in patients with CKD remains unclear. This study aimed to assess the optimal BP level for preventing CKD progression. The risk of renal outcome among different BP categories at baseline as well as 1 year after, were evaluated using individual CKD patient data aged between 40 and 74 years from FROM-J [Frontier of Renal Outcome Modifications in Japan] study. The renal outcome was defined as ≥ 40% reduction in estimated glomerular filtration rate to < 60 mL/min/1.73 m2, or a diagnosis of end stage renal disease. Regarding baseline BP, the group of systolic BP (SBP) 120–129 mmHg had the lowest risk of the renal outcome, which increased more than 60% in SBP ≥ 130 mmHg group. A significant increase in the renal outcome was found only in the group of diastolic BP ≥ 90 mmHg. The group of BP < 130/80 mmHg had a benefit for lowering the risk regardless of the presence of proteinuria, and it significantly reduced the risk in patients with proteinuria. Achieving SBP level < 130 mmHg after one year resulted in a 42% risk reduction in patients with SBP level ≥ 130 mmHg at baseline. Targeting SBP level < 130 mmHg would be associated with the preferable renal outcome.Clinical Trial Registration-URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000001159 (16/05/2008).

Acupuncture Treatment Reduced the Risk of Coronary Heart Disease in Patients with Depression: A Propensity-Score Matched Cohort Study.

BackgroundMajor depressive disorder is a significant public health concern, which often leads to loss of productivity, functional decline, and various complications. The aim of this study was to investigate the effectiveness of acupuncture in the risk reduction of coronary heart disease (CHD) in patients with depression.MethodsWe enrolled patients diagnosed with depression between January 1, 1997, and December 31, 2010, through the Taiwanese National Health Insurance Research Database (NHIRD). Propensity score was used to match equal numbers (n=14,647) of acupuncture cohort and no-acupuncture cohort based on characteristics including sex, age, baseline comorbidity and medication. Patients were followed up until December 31, 2013, or withdrawn from the NHIRD. The Cox regression model was used to compare the hazard ratios (HRs) of CHD in the two cohorts.ResultsThe basic characteristics of the two groups were similar. A lower cumulative incidence of CHD was noted in the acupuncture cohort (Log rank test, p < 0.001). Over time, 1626 patients in the acupuncture cohort (21.05 per 1000 person-years) and 2412 patients in the no-acupuncture cohort (39.84 per 1000 person-years) developed CHD (adjusted HR=0.50, 95% CI 0.47–0.53). The decreased CHD incidence was independent of age, sex, comorbidities, and medications used. The cumulative incidence of CHD was significantly lower in the acupuncture cohort than in the no-acupuncture cohort (Log rank test, p<0.001).ConclusionThe results provided a real-world evidence that acupuncture may have beneficial effect on CHD risk reduction in patients with depression.

Abstract 2862: BMP4 mediated suppression of cholesterol synthesis and breast cancer metastasis

Abstract Breast cancer affects one in seven women and kills more than 600,000 women each year. Compared to the 98.9% survival rate of patients with localized breast cancer, the five-year survival rate of patients with distant metastasis is only 28.1%. Using cDNA arrays and patient datasets, we found that a protein called bone morphogenetic protein 4 (BMP4) is downregulated in highly metastatic breast cancer cells and in high-grade breast tumors. BMP4 is a ligand in the TFGβ/BMP cytokine family and has the capacity to suppress TGFβ signaling through induction of SMAD6 and SMAD7. In several different preclinical metastasis models, we have shown that restored BMP4 expression in breast cancer cells with metastatic capacity does not alter primary tumor growth but results in significantly reduced metastasis to lung, liver and spine (p&amp;lt; 0.01), following primary tumor resection. MDA-MB-231HM cells with or without enforced BMP4 expression were recovered from primary mammary tumors and subjected to transcriptomic profiling by RNAseq. This analysis revealed that BMP4 suppressed multiple genes involved in the cholesterol biosynthesis pathway (p=2.56×10-7) and down-regulated cholesterol levels in the tumors (p=0.042). In a patient cohort of over 2000 predominantly luminal breast cancers, we found that stage, as measured by size and lymph node status, was not altered by statin use, however statin users had less high grade tumors and more luminal A tumors. In terms of recurrence, we found a marked risk reduction in patients with luminal B tumors (p=0.014) and particularly in Her2+ luminal B tumors (p=0.045). Lung, liver and brain metastases were most reduced in statin users. Current experiments involve testing a statin therapy, with the knowledge that statins are not effective in mice, but should inhibit cholesterol synthesis in human tumors in xenograft models. In addition, we are testing an inhibitor of the nuclear receptor RORγ that has been reported to activate cholesterol synthesis through SREBP2, a master regulator of cholesterol synthesis. Citation Format: Robin L. Anderson, Lap Hing Chi, Allan D. Burrows, Suraya Roslan, Andrew Redfern. BMP4 mediated suppression of cholesterol synthesis and breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2862.

Colchicine in Patients with Coronary Artery Disease with or Without Diabetes Mellitus: A Meta-analysis of Randomized Clinical Trials.

Whether the anti-inflammatory drug colchicine has a differential treatment effect according to diabetes mellitus status in patients with coronary artery disease has never been studied. Therefore, the aim of the present meta-analysis was to evaluate whether the use of colchicine in patients with coronary artery disease with diabetes was associated with a higher magnitude of benefits compared to patients with coronary artery disease without diabetes. Electronic databases were searched through June 2020 to identify randomized clinical trials using colchicine in patients with coronary artery disease. Studies using blood biomarkers, such as troponin or high-sensitive C-reactive protein, as well as angiographic endpoints were excluded. The primary endpoint was major cardiovascular events as defined by the included studies. In total, 11,594 patients from four randomized trials were included of whom 2278 (19.6%) had diabetes and 5540 (47.8%) presented with acute coronary syndrome. Colchicine was associated with almost twice the absolute risk reduction in patients with diabetes {absolute risk difference (ARD) -3.94 [95% confidence interval (CI) -1.28 to -6.6], p=0.004} compared with those without diabetes [ARD -2.32 (95% CI -1.32 to -3.31), p<0.001]. The magnitude of ARD between colchicine and placebo was significantly larger in patients with diabetes compared with patients without diabetes [ARD 1.62 (95% CI 1.43-1.81), p<0.001]. When the analysis was restricted to patients presenting with acute coronary syndrome, the differential treatment effect of colchicine was more pronounced in patients with diabetes [ARD -0.05 (95% CI -0.08 to -0.01), p=0.02] compared with those without diabetes [ARD -0.01 (95% CI -0.02 to 0), p=0.11]. This meta-analysis underscores the heightened inflammatory risk associated with diabetes and highlights the need to target inflammatory pathways in these individuals irrespective of glucose-lowering drugs.

Impact of chronic kidney disease on the pharmacodynamic and pharmacokinetic effects of ticagrelor in patients with diabetes mellitus and coronary artery disease.

Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown. In this randomized, crossover study, patients with DM on treatment with dual antiplatelet therapy (aspirin and clopidogrel) were stratified according to CKD status and randomized to ticagrelor 90 or 60 mg bid. PK/PD assessments were performed at baseline, after 7-10 days of ticagrelor (peak and trough), and after 7-10 days of alternative ticagrelor regimen (peak and trough). PK assessments included plasma concentrations of ticagrelor and its major metabolite. PD assessments included vasodilator-stimulated phosphoprotein (VASP)-platelet reactivity index (PRI), VerifyNow P2Y12, and light transmittance aggregometry (LTA). A total of 92 patients with DM (CKD, n = 44; non-CKD, n = 48) were randomized. Levels of platelet reactivity were lower with the 90 mg compared with the 60 mg ticagrelor dose, which was statistically significant in non-CKD but not in CKD patients for most PD measures. There were no significant differences in the primary endpoint (trough levels of VASP-PRI following ticagrelor 90 mg dosing) between cohorts (31 ± 20 vs. 25 ± 14; P = 0.105). VerifyNow and LTA provided similar findings. PK assessments tracked PD profiles showing increased plasma concentrations of ticagrelor and its major metabolite in CKD compared to non-CKD patients. In patients with DM, although ticagrelor maintenance dose regimens (60 and 90 mg) yield potent P2Y12 inhibition, levels of platelet reactivity tended to be higher and subject to broader variability in non-CKD compared with CKD patients. http://www.clinicaltrials.gov Unique Identifier: NCT02539160.

Min-Max Optimal Design of Two-Armed Trials with Side Information

In this work, we study the optimal design of two-armed clinical trials to maximize the accuracy of parameter estimation in a statistical model, where the interaction between patient covariates and treatment are explicitly incorporated to enable precision medication decisions. Such a modeling extension leads to significant complexities for the produced optimization problems because they include optimization over design and covariates concurrently. We take a min-max optimization model and minimize (over design) the maximum (over population) variance of the estimated interaction effect between treatment and patient covariates. This results in a min-max bilevel mixed integer nonlinear programming problem, which is notably challenging to solve. To address this challenge, we introduce a surrogate optimization model by approximating the objective function, for which we propose two solution approaches. The first approach provides an exact solution based on reformulation and decomposition techniques. In the second approach, we provide a lower bound for the inner optimization problem and solve the outer optimization problem over the lower bound. We test our proposed algorithms with synthetic and real-world data sets and compare them with standard (re)randomization methods. Our numerical analysis suggests that the proposed approaches provide higher-quality solutions in terms of the variance of estimators and probability of correct selection. We also show the value of covariate information in precision medicine clinical trials by comparing our proposed approaches to an alternative optimal design approach that does not consider the interaction terms between covariates and treatment. Summary of Contribution: Precision medicine is the future of healthcare where treatment is prescribed based on each patient information. Designing precision medicine clinical trials, which are the cornerstone of precision medicine, is extremely challenging because sample size is limited and patient information may be multidimensional. This work proposes a novel approach to optimally estimate the treatment effect for each patient type in a two-armed clinical trial by reducing the largest variance of personalized treatment effect. We use several statistical and optimization techniques to produce efficient solution methodologies. Results have the potential to save countless lives by transforming the design and implementation of future clinical trials to ensure the right treatments for the right patients. Doing so will reduce patient risks and reduce costs in the healthcare system.

299-OR: Relative Contribution of Statin Intensity, Low-Density Lipoprotein Cholesterol Level and Duration of Statin Therapy for Cardiovascular Risk Reduction in Patients with Type 2 Diabetes

Objectives: To estimate the optimal statin therapy including statin intensity, low-density lipoprotein cholesterol (LDL-C) level and duration of statin therapy among patients with type 2 diabetes (T2D) in a real-world setting. Research Design and Methods: From the Korean National Health Insurance Service Cohort (2007-2015), 8,937 patients with T2D (≥40 years) who had received statin therapy for at least 90 days were included. Risk of major adverse cardiovascular events (MACE) including coronary heart disease (CHD), ischemic stroke (IS) and cardiovascular death was estimated according to statin intensity, on-treatment serum concentration of LDL-C and duration of statin therapy, respectively. The relative contribution of these three factors for the risk of MACE was quantified by calculating the proportion of log-likelihood explained by each factor. Results: The hazard ratio (HR) of MACE was higher in patients receiving low intensity statins compared with those receiving moderate-to-high intensity statins (HR 1.38, p=0.027). As a reference to LDL-C of 100 mg/dl, below 80 mg/dl was associated with lower risk of MACE. Among patients who received moderate-to-high intensity statins, there was a trend that the longer the duration of statin therapy, the lower the risk of MACE; and HRs of MACE reduced significantly after at least 18 months of statin therapy (adjusted HR 0.71, p=0.011) as a reference to 3 months of statin therapy. The proportion of explainable log-likelihood for MACE was biggest for duration of statin (0.047), followed by statin intensity (0.013) and on-treatment LDL-C level (0.001). Conclusion: Longevity of statin therapy is as important as, or more important than, statin intensity or achieved LDL-C for the reduction of cardiovascular risk in T2D patients. Disclosure J. Kim: None. J. Choi: None. S. Kim: None. N. Kim: None.

Is Flexible Cystoscopy Necessary in the Investigation of Non-visible Haematuria?

Background: Historic evidence suggests up to 16% (approximately) of non-visible haematuria (NVH) referrals result in Urological cancer diagnosis. The majority are bladder cancers, for which flexible cystoscopy is regarded the “gold standard” diagnostic procedure. Recent changes to suspected cancer referral guidelines, public information campaigns and reduced smoking prevalence may have changed this percentage. We retrospectively calculated cancer detection rates from NVH referrals to assess whether flexible cystoscopy, an invasive and morbid procedure, remains necessary. Patients and methods: All patients referred to our University teaching hospital on a suspected (“twoweek”) cancer pathway with NVH over a 16-week period were included. Clinical and demographic data were collected for a series of 200 patients (96 male, age range 27–92, median 68). Results: Only eight patients had urological malignancy found (two renal and six bladder cancers). Both renal, and four bladder cancers, were identified on imaging prior to flexible cystoscopy. Only two bladder cancers were therefore detected by cystoscopy; one low-risk non-muscle invasive (patient has already been discharged) and one in a patient that was unfit for treatment (died of heart failure). Only seven (3.5%) of the patients were offered the option of not undergoing flexible cystoscopy. Conclusion: Our analyses suggest that flexible cystoscopy is rarely of benefit in patients with NVH. We suggest that patients should be given an accurate risk of bladder cancer diagnosis during the consent process. We advocate that flexible cystoscopy can be avoided for the majority of NVH referrals, particularly in patients without strong risk factors for urothelial cell carcinoma. Avoidance of flexible cystoscopy would reduce patient risks from procedural morbidity, reduce risks of acquiring coronavirus from hospital attendance, and there could be huge reductions in financial and service delivery demands in an overstretched secondary-care service.

Primary Outcome Evaluation of a Next-Generation Left Atrial Appendage Closure Device: Results From the PINNACLE FLX Trial.

Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA2DS2-VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% (P<0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% (P<0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02702271.

P063 SystmOne clinical reporting to identify high-risk rheumatology patients for shielding

Background/Aims At the start of the COVID-19 pandemic, shielding guidance was issued by Public Health England with a risk stratification guide developed by the BSR to assist with patient identification. At BTHFT we benefited with all GP practices in the region using TPP SystmOne (S1) for medical records. We describe how we used S1 to help identify high risk patients under our care. Methods We did not appreciate the full extent we could use S1 to identify patients in our initial shielding identification process. As such, we reviewed notes of patients on biologic prescriptions and SC MTX from Homecare prescription lists. To capture patients on high dose prednisolone, we identified patients with a recent diagnosis of GCA and patients with recent prescriptions of > 20mg prednisolone through pharmacy records. On recognising the ability of S1 to identify patients that had glucocorticoid exposure through primary care and/or on cDMARDS we used S1 reporting mechanisms to identify these patients. Clinical record sharing enabled BTHFT’s rheumatology department to access S1 for all patients under their care. S1’s clinical reporting function was used to search for patients within at least one of the following cohorts before being combined in a single cohort of ‘at risk’ patients (heart, lung or kidney disease, ≥70 years, diabetes or hypertension [including pulmonary artery hypertension]). Reports were created for patients on any DMARD issued within primary care within the previous 12 weeks. High dose steroid use was more challenging to demonstrate, but a report was devised to include all patients with an issued prescription for prednisolone 5mg tablets within the preceding 8 weeks (for any reason). An additional report was created for patients with a rheumatological diagnosis co-existing with an interstitial lung disease. Using S1's report joining function, the different drugs and ‘at risk’ cohorts were combined to provide an accurate list of patients with features increasing their vulnerability to COVID-19. This list was easily modifiable and searches were re-run to update lists once inclusion on the shielding list was updated. Results Patients meeting the criteria for shielding were then advised in writing including signposting to BTHFT’s rheumatology website and helpline for further information if required. By searching for all prednisolone prescriptions, this would have included patients given prednisolone for other reasons. 5mg tablet strength ensured patients on low dose were excluded, but we recognise some patients were likely over-recruited into this cohort. Conclusion We can update our searching methods to easily include patients on biologics and SC MTX by some additional bulk coding in preparation for future shielding specifications thereby bypassing the need to review individual notes for patients. We were able to achieve an accurate shielding list in a relatively short space of time to reduce patient risk. Disclosure D. Kirby: None. K. Nadesalingam: None.

What makes a \u201csuccessful\u201d or \u201cunsuccessful\u201d discharge letter? Hospital clinician and General Practitioner assessments of the quality of discharge letters

BackgroundSharing information about hospital care with primary care in the form of a discharge summary is essential to patient safety. In the United Kingdom, although discharge summary targets on timeliness have been achieved, the quality of discharge summaries’ content remains variable.MethodsMixed methods study in West Midlands, England with three parts: 1. General Practitioners (GPs) sampling discharge summaries they assessed to be “successful” or “unsuccessful” exemplars, 2. GPs commenting on the reasons for their letter assessment, and 3. surveying the hospital clinicians who wrote the sampled letters for their views. Letters were examined using content analysis; we coded 15 features (e.g. “diagnosis”, “GP plan”) based on relevant guidelines and standards. Free text comments were analysed using corpus linguistics, and survey data were analysed using descriptive statistics.ResultsFifty-three GPs participated in selecting discharge letters; 46 clinicians responded to the hospital survey. There were statistically significant differences between “successful” and “unsuccessful” inpatient letters (n = 375) in relation to inclusion of the following elements: reason for admission (99.1% vs 86.5%); diagnosis (97.4% vs 74.5%), medication changes (61.5% vs 48.9%); reasons for medication changes (32.1% vs 18.4%); hospital plan/actions (70.5% vs 50.4%); GP plan (69.7% vs 53.2%); information to patient (38.5% vs 24.8%); tests/procedures performed (97.0% vs 74.5%), and test/examination results (96.2% vs 77.3%). Unexplained acronyms and jargon were identified in the majority of the sample (≥70% of letters). Analysis of GP comments highlighted that the overall clarity of discharge letters is important for effective and safe care transitions and that they should be relevant, concise, and comprehensible. Hospital clinicians identified several barriers to producing “successful” letters, including: juniors writing letters, time limitations, writing letters retrospectively from patient notes, and template restrictions.ConclusionsThe failure to uniformly implement national discharge letter guidance into practice is continuing to contribute to unsuccessful communication between hospital and general practice. While the study highlighted barriers to producing high quality discharge summaries which may be addressed through training and organisational initiatives, it also indicates a need for ongoing audit to ensure the quality of letters and so reduce patient risk at the point of hospital discharge.

Reflection on the Importance of Interprofessional Training

Historically, physicians have worked in isolation. More recently, there has been an emphasis to create interprofessional patient care teams to provide better patient care and reduce patient risk. This shift in focus has filtered down to the undergraduate medical education level where the American Association of Medical Colleges has created accreditation standards focused on interprofessional team training. This paper gives a first-hand narrative on how interdprofessional training can shift perspectives and create effective team members centered around patient care.

Vericiguat: First Approval.

Vericiguat (VERQUVO™; Merck & Co, Bayer AG) is a soluble guanylate cyclase (sGC) stimulator being developed for the treatment of chronic heart failure. Vericiguat stimulates sGC and cGMP production independent of nitric oxide (NO) and enhances the effects of NO by stabilizing the NO-sGC binding. Based on the results of the phase III VICTORIA trial vericiguat was recently approved in the USA for risk reduction in patients with heart failure and ejection fraction <45%. This article summarizes the milestones in the development of vericiguat leading to this first approval.

Mechanisms and Treatment of Dyslipidemia in Diabetes.

Type 2 diabetes mellitus is widespread throughout the world and is a powerful risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). This manuscript explored the mechanisms underlying dyslipidemia in type 2 diabetes as well as currently available treatment options and guideline recommendations. Type 2 diabetes is associated with a characteristic pattern of dyslipidemia, often termed diabetic dyslipidemia. Patients with type 2 diabetes often present with low HDL levels, elevated levels of small dense LDL particles, and elevated triglyceride levels. LDL lowering is the cornerstone of managing diabetic dyslipidemia, and statins are the mainstay of therapy. The cholesterol absorption inhibitor ezetimibe and PCSK9 inhibitors have also been shown to lower risk in patients with diabetes. Recently, the eicosapentaenoic (EPA) only n-3 fatty acid, icosapent ethyl, has also shown benefit for cardiovascular risk reduction in patients with diabetes. To date, no agents targeting HDL increase have shown cardiovascular benefit in patients on background statin therapy. Diabetic dyslipidemia is significant cardiovascular disease risk factor, and LDL-lowering therapy with statins, PCSK9 inhibitors, and ezetimibe continues to be mainstay therapy to reduce cardiovascular risk. Future studies targeting low HDL and high triglycerides levels associated with type 2 diabetes could provide additional novel therapies to manage diabetic dyslipidemia.

RxIALTA: evaluating the effect of a pharmacist-led intervention on CV risk in patients with chronic inflammatory diseases in a community pharmacy setting: a prospective pre–post intervention study

Patients with inflammatory conditions are at high risk for cardiovascular (CV) disease. Despite such elevated risk, their CV risk factors are suboptimally managed.ObjectiveTo evaluate the effect of a pharmacist-led intervention...

Medical therapy for cardiovascular and limb-related risk reduction in critical limb ischemia.

Critical limb ischemia (CLI) constitutes the most advanced form of peripheral artery disease (PAD) and is characterized by ischemic rest pain, tissue loss and/or gangrene. Optimized medical care and risk factor modification in addition to revascularization could reduce the incidence of cardiovascular events and major adverse limb events, improving patients' quality of life and promising higher survival rates. Adequate adherence to cardioprotective medications, including antithrombotic therapy (e.g., antiplatelets, anticoagulants), cholesterol-lowering agents (e.g., statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors), angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and smoking cessation should be strongly encouraged for patients with CLI. This review examines these guideline-recommended therapies in terms of cardiovascular and limb-related risk reduction in patients with CLI.

Cardio-diabetic protective effect of Telmisartan

The antihypertensive drugs that are being used currently were primarily designed and developed to affect cellular and biochemical mechanisms that lead to increased blood pressure and do not address the underlying contributory factors like, disordered carbohydrate and lipid metabolism that often accompanies hypertension as part of the metabolic syndrome. The metabolic syndrome eventually leads to co-morbid conditions i.e., hypertension and type 2 diabetes mellitus. Both these conditions mechanistically share the common pathophysiological pathways in people who suffer from metabolic syndrome. PPAR-γ plays an important role in regulating carbohydrate and lipid metabolism and ligands for PPAR γ can improve insulin sensitivity, reduce triglyceride levels, and decrease the risk for atherosclerosis. Telmisartan is a well-established angiotensin II type 1 receptor (AT1) blocker along with an activator of the PPARγ receptor. Telmisartan has several pharmacological properties that distinguish it from other ARBs, like, the structural resemblance with pioglitazone which is a PPARγ ligand that is approved for the treatment of type 2 diabetes. Thus, telmisartan seems to be a suitable candidate for the management of CV risk reduction in patients with atherothrombotic disease or diabetes mellitus with end-organ damage. This article will discuss the mechanistic aspect of telmisartan that supports its utility in cardiac protection along with the outcome of different clinical trials.