Surgical cancellation rates due to peri-operative hypertension: implementation of multidisciplinary guidelines across primary and secondary care

Patients with uncontrolled hypertension are at increased risk of complications during general anaesthesia but the number of patients whose surgery is delayed or cancelled due to hypertension remains unknown. Prospective, regional multicentre service evaluations were performed on consecutive patients undergoing elective surgery before and after the publication of new guidelines from the Association of Anaesthetists and the British Hypertensive Society. The aim was to quantify the number of operations cancelled due to hypertension alone and to assess impact of the guidelines on cancellation rates. In October 2013 (before the publication of the guidelines), 1.37% (95%CI 0.69–2.11%) of patients listed for elective surgery were cancelled solely due to raised blood pressure. This reduced significantly to 0.54% (95%CI 0.20–0.92%, p < 0.001) in 2018. There was a significant reduction in inappropriate cancellations for stage 1 or 2 hypertension from 2013 to 2018 (72 vs. 14, respectively, p < 0.001) in keeping with the recommendations in the guidelines. Furthermore, the number of patients being referred back to primary care for the management of hypertension reduced from 2013 to 2018 (85 vs. 30, respectively, p < 0.001). Our data suggest achievement of three major outcomes: reduced surgical cancellations due to hypertension alone; improved detection of significant hypertension before elective surgery; and reduced referral back to primary care from hospital for hypertension management. To the best of our knowledge, this is the first time the successful implementation of guidelines from the Association of Anaesthetists has been assessed on such a broad scale. Our data indicate that these guidelines have been effectively implemented in both primary and secondary care, which is likely to have made a positive psychosocial, physical and economic impact on patients and the NHS.     

Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

Background: Longevinex^® (L/RV) is a low dose hormetic over-the-counter (OTC) oral resveratrol (RV) based matrix of red wine solids, vitamin D₃ and inositol hexaphosphate (IP6) with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD) patients. Today we report long term (two to three year) clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease). We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging) and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus). Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.     

Use of captopril as an isolated agent for the management of stable angina pectoris--a double blind randomised trial.

In this double blind randomised placebo controlled study, we investigated the antianginal efficacy of oral captopril in 33 patients of angiographically documented coronary artery disease (chronic stable angina). Apart from sublingual nitrates, all other antianginal drugs were withdrawn. Patients were then evaluated both subjectively by questionnaire and objectively by treadmill stress test. No patient had more than mild hypertension and all patients had good left ventricular function. One group of patients received oral captopril while the other group was given placebo. A repeat assessment was done after six weeks and the results compared with baseline. Anginal attacks decreased from 20.11 +/- 1.86 per week on placebo to 9.92 +/- 1.38 (p < 0.01) on captopril as also the number of sublingual nitrates (18.84 +/- 3.01 to 11.14 +/- 2.94, p < 0.01). Assessment by the treadmill stress test showed that in comparison to the pretreatment test, captopril therapy resulted in a significantly increased exercise duration (6.26 +/- 0.21 to 6.98 +/- 0.31 minutes, p < 0.05), total work done (6.76 +/- 0.26 METS to 7.48 +/- 0.29 METS, p < 0.05). In addition there was a significant increase in time to angina (6.16 +/- 0.18 to 6.85 +/- 0.24 min, p < 0.05) and time to 1mm ST depression (5.18 +/- 0.26 to 6.46 +/- 0.30 min, p < 0.01). We conclude that captopril is an effective monotherapy for patients with chronic stable angina and has both antianginal as well as anti-ischemic effects, possibly secondary to direct coronary vasodilation.     

Influence of Nicotine on Myocardial Stiffness and Fibrosis During Chronic Ethanol Use

Cardiomyopathy related to ethanol abuse is often accompanied by cigarette use. To examine if the major cardioactive component may intensify the abnormal function and composition induced by chronic ethanol, nicotine was administered orally, 2.5 mg bid, to a canine model receiving 36% of calories as ethanol for 6 months (group III). These animals were compared with group II receiving ethanol alone, group IV on nicotine alone, and controls (group I). In the intact, ventilated, anesthetized dog, left ventricular pressures and volumes were measured before and after dextran infusion and related to left ventricular collagen alterations. Basal heart rate, aortic pressure, and ejection fraction were comparable with controls. End-diastolic pressure and diastolic chamber stiffness (KPV) were significantly higher in the basal state and during dextran infusion in the three experimental groups, compared with group I. The increment was largest in the ethanol-nicotine group. Analysis of left ventricular myocardium revealed a rise of collagen concentrations in all three experimental groups, with an interstitial distribution on histochemical examination. Moreover, determination of advanced glycosylation endproducts, as a measure of alterations in collagen cross-links, revealed higher concentrations versus controls. The greater increase of diastolic stiffness in the nicotine-ethanol group occurred despite a similar concentration of fluorescent products as group II. Because the former had a larger increase of collagen concentration, total cross-linked collagen content was presumably greater after the combined use of nicotine-ethanol. Thus, nicotine in relatively high dose when combined with ethanol, elicited a modest further increase in the left ventricular chamber stiffness and collagen concentration.     

Screening for high-grade dysplasia in gastroesophageal reflux disease: is it cost-effective?

OBJECTIVE: The present study aimed to assess the cost-effectiveness of endoscopic screening in patients with gastroesophageal reflux disease (GERD) to rule out high-grade dysplasia of Barrett's esophagus. METHODS: Using an incremental cost-effectiveness ratio as outcome measure, the cost-effectiveness of endoscopic screening was compared to not screening in a decision tree. It was assumed that GERD patients at age 60 yr undergo a one-time endoscopy with esophageal biopsies, targeting abnormal-appearing epithelium. Positive biopsies with respect to high-grade dysplasia or early esophageal adenocarcinoma result in esophagectomy. Transition rates were estimated from U.S. cancer statistics, as well as published data of endoscopic sensitivity, specificity, and surgical outcome. Costs of screening and cancer care were estimated from Medicare reimbursement data from the perspective of a third-party-payor. RESULTS: Compared with no screening, screening endoscopy cost $24,700 per life-year saved. The cost-effectiveness of screening is quite sensitive to the prevalence of Barrett's esophagus, high-grade dysplasia, and adenocarcinoma, as well as the sensitivity, specificity, and cost of screening endoscopy. A small drop in the health-related quality of life associated with postsurgical states markedly reduced the effectiveness of screening. Simultaneous variations of the prevalence, specificity, and health-related quality of life can easily change screening endoscopy from a life-saving into a life-losing strategy. CONCLUSIONS: Under favorable conditions, general screening by endoscopy of all patients with reflux symptoms to prevent death from esophageal adenocarcinoma may represent a cost-effective strategy; however, such conditions may be difficult to meet.     

Downregulation of Carnitine Acyl-Carnitine Translocase by miRNAs 132 and 212 Amplifies Glucose-Stimulated Insulin Secretion

We previously demonstrated that micro-RNAs (miRNAs) 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of miRNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including nonfuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT; Slc25a20) is a direct target of these miRNAs. CACT is responsible for transporting long-chain acyl-carnitines into the mitochondria for β-oxidation. Small interfering RNA–mediated knockdown of CACT in β-cells led to the accumulation of fatty acyl-carnitines and enhanced IS. The addition of long-chain fatty acyl-carnitines promoted IS from rat insulinoma β-cells (INS-1) as well as primary mouse islets. The effect on INS-1 cells was augmented in response to suppression of CACT. A nonhydrolyzable ether analog of palmitoyl-carnitine stimulated IS, showing that β-oxidation of palmitoyl-carnitine is not required for its stimulation of IS. These studies establish a link between miRNA-dependent regulation of CACT and fatty acyl-carnitine–mediated regulation of IS.