Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Effect of rosuvastatin on diabetic polyneuropathy: a randomized, double-blind, placebo-controlled Phase IIa study

Jaime Hern&aacute;ndez-Ojeda, Luis Miguel Rom&aacute;n-Pintos, Adolfo Daniel Rodr&iacute;guez-Carr&iacute;zalez, Rogelio Troyo-Sanrom&aacute;n, Ernesto Germ&aacute;n Cardona-Mu&ntilde;oz, Mar&iacute;a del Pilar Alatorre-Carranza, Alejandra Guillermina Miranda-D&iacute;az Departamento de Fisiolog&iacute;a, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, M&eacute;xico Background: Diabetic neuropathy affects 50%&ndash;66% of patients with diabetes mellitus. Oxidative stress generates nerve dysfunction by causing segmental demyelinization and axonal degeneration. Antioxidants are considered to be the only etiologic management for diabetic polyneuropathy, and statins such as rosuvastatin increase nitric oxide bioavailability and reduce lipid peroxidation. The aim of this study was to evaluate the antioxidant effect of rosuvastatin in diabetic polyneuropathy. Methods: We conducted a randomized, double-blind, placebo-controlled Phase IIa clinical trial in patients with type 2 diabetes and diabetic polyneuropathy (DPN) stage &ge;1b. We allocated subjects to two parallel groups (1:1) that received rosuvastatin 20 mg or placebo for 12 weeks. Primary outcomes were neuropathic symptom score, disability score, and nerve conduction studies, and secondary outcomes were glycemic control, lipid and hepatic profile, lipid peroxidation, and nerve growth factor beta (NGF-&beta;) levels. Results: Both groups were of similar age and duration since diagnosis of diabetes and DPN. We observed improvement of DPN in the rosuvastatin group from stage 2a (88.2%) to stage 1b (41.2%), improvement of neuropathic symptom score from 4.5&plusmn;2 to 2.4&plusmn;1.8, and significant (P=0.001) reductions of peroneal nerve conduction velocity (from 40.8&plusmn;2.2 to 42.1&plusmn;1.6 seconds) and lipid peroxidation (from 25.4&plusmn;2 to 12.2&plusmn;4.0 nmol/mL), with no significant change in glycemic control or &beta;-NGF. Conclusion: The severity, symptoms, and nerve conduction parameters of DPN improved after 12 weeks of treatment with rosuvastatin. These beneficial effects appear to be attributable to reductions in lipid peroxidation and oxidative stress. Keywords: rosuvastatin, diabetic polyneuropathy, nerve conduction, oxidative stress, nerve growth factor bet

Comparison of the use of blood pressure telemonitoring versus standard medical care in the achievement of short-term therapeutic goals in blood pressure in patients with uncontrolled hypertension: An open-label clinical trial

Background In Mexico less than half of the treated hypertensive patients reach blood pressure (BP) targets. Most hypertensive individuals rely on the standard medical care (SMC) to achieve the BP control goals; however, the efficacy of BP telemonitoring (BPT) to achieve BP targets has been poorly studied. Aim To compare the efficacy of BPT versus SMC to achieve BP goals in patients with uncontrolled hypertension. Methods A two-arm, open-label clinical trial was conducted in patients ≥18 years with uncontrolled hypertension. The participants were randomized to 2 arms (BPT vs SMC) and followed for 12 weeks. For the statistical analysis, the chi-squared test and covariance were used. Results One hundred and seventy-eight participants were included, BPT (n = 94) and SMC (n = 84), after 12 weeks of follow up, we observed a baseline-adjusted reduction in systolic BP with both BPT (−13.5 [1.3] mmHg) and the SMC (−5.9 [1.4] mmHg; p < 0.001) but a greater decrease with BPT (p < 0.001). Likewise, we found a baseline-adjusted reduction of diastolic BP with BPT (−6.9 [0.9] mmHg) and SMC (−2.7 [0.9] mmHg) (p = 0.007) with a more significant percentage change from baseline with BPT (−6.8% [1.0] vs 2.5% [1.1]; p = 0.007). In the BPT arm, a larger proportion of patients achieved the BP target versus SMC (30.5% vs 12.8%; p = 0.005). Conclusion BPT showed a greater proportion of patients achieving office BP control goals (<140/90 mmHg), compared to standard medical care

Evolocumab and clinical outcomes in patients with cardiovascular disease

BACKGROUND Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. RESULTS At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). CONCLUSIONS In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets