Effects of Attendance to an Organized Fecal Immunochemical Test Screening Program on the Risk of Colorectal Cancer: An Observational Cohort Study.

BACKGROUND & AIMS: This cohort study compared colorectal cancer (CRC) incidence and mortality between people who participated in an Italian regional biennial fecal immunochemical test (FIT) screening program and people who did not. METHODS: The program started in 2005. The target population included over 1,000,000 people aged 50 to 69 years. The FIT was a one-sample OC-Sensor (Eiken Chemical Co, Tokyo, Japan) (cutoff, ≥20 µg hemoglobin/g feces). The average annual response rate to invitation was 51.4%. The records of people invited up to June 2016 were extracted from the screening data warehouse. Attenders were subjects who responded to the first 2 invitations or to the single invitation sent them before they became ineligible. Non-attenders were subjects who did not respond to any of these invitations. The records were linked with the regional CRC registry. People registered up to December 2016 were identified. Self-selection-adjusted incidence rate ratios (IRRs) and incidence-based CRC mortality rate ratios (MRRs) for attenders to non-attenders, with 95% confidence intervals (CIs), were calculated. RESULTS: The cohort generated 2,622,131 man-years and 2,887,845 woman-years at risk with 4490 and 3309 CRC cases, respectively. The cohort of attenders was associated with an IRR of 0.65 (95% CI, 0.61-0.69) for men, 0.75 (95% CI, 0.70-0.80) for women and 0.69 (95% CI, 0.66-0.72) for both sexes combined. The self-selection-adjusted IRR was 0.67 (95% CI, 0.62-0.72) for men and 0.79 (95% CI, 0.72-0.88) for women. The IRR for stage I, II, III, and IV CRC was 1.35 (95% CI, 1.20-1.50), 0.61 (95% CI, 0.53-0.69), 0.60 (95% CI, 0.53-0.68) and 0.28 (95% CI, 0.24-0.32) for men and 1.64 (95% CI, 1.43-1.89), 0.60 (95% CI, 0.52-0.69), 0.73 (95% CI, 0.63-0.85) and 0.35 (95% CI, 0.30-0.42) for women. The overall incidence-based CRC MRR was 0.32 (95% CI, 0.28-0.37) for men, 0.40 (95% CI, 0.34-0.47) for women and 0.35 (95% CI, 0.31-0.39) for both sexes combined. The adjusted MRR was 0.35 (95% CI, 0.29-0.41) for men and 0.46 (95% CI, 0.37-0.58) for women. CONCLUSIONS: Attendance to a FIT screening program is associated with a CRC incidence reduction of 33% among men and 21% among women, and a CRC mortality reduction of 65% and 54%, respectively.

[Orthostatic hypotension and supine hypertension: a practical guide to diagnosis and management]. / Ipotensione ortostatica e ipertensione supina: guida pratica a diagnosi e terapia.

Orthostatic hypotension is a medical condition potentially debilitating and associated with a negative prognosis. It is paramount for cardiologists to recognize it, mostly for the following reasons: it is a predictive factor for cardiovascular events, it may cause syncope, and it is frequently associated with supine hypertension. Orthostatic hypotension may be secondary to neurogenic etiology (baroreflex dysfunction) or non-neurogenic etiology (dehydration or medication-related). Although laboratory tests exploring the autonomic nervous system are required for a detailed etiologic diagnosis, medical history and a sphygmomanometer can be sufficient for diagnosis. Therapeutic management of orthostatic hypotension is challenging, mostly because of the association in half of the cases with supine hypertension. Treatment should be a compromise between anti-hypotensive and anti-hypertensive measures with one overcoming the other based on the hour of the day. Non-pharmacological therapies, regarded as avoidance of precipitating factors and physical and dietary interventions, as well as chronic treatment revision, have a pivotal role.In this review we will discuss, in a pragmatic manner, about epidemiology, etiology, clinical aspects and diagnosis of orthostatic hypotension. Moreover, we will discuss about prognosis and management of orthostatic hypotension and supine hypertension.

Prospective observational cohort study of early recurrent TIA: Features, frequency, and outcome.

OBJECTIVES: To evaluate the frequency, clinical and etiologic features, and short- and long-term outcomes of early recurrent TIA. METHODS: This prospective observational cohort study enrolled all consecutive patients with TIA referred to our emergency department and diagnosed by a vascular neurologist. Expedited assessment and best secondary prevention were performed within 24 hours. Primary endpoints were stroke and a composite outcome including stroke, acute coronary syndrome, and vascular death at 3, 12, and, for a subset of patients, 60 months; secondary outcomes were TIA relapse, cerebral hemorrhage, new-onset atrial fibrillation, and death resulting from other causes. Concordance between index TIA and subsequent stroke etiologies was also evaluated. RESULTS: A total of 1,035 patients (822 with a single TIA, 213 with recurrent TIA = 21%) were enrolled from August 2010 to December 2017. Capsular warning syndrome and large artery atherosclerosis showed the strongest relationship with early recurrent TIA. The risk of stroke was significantly higher in the early recurrent TIA subgroup at each follow-up, and most stroke episodes occurred within 48 hours of index TIA. TIAs with lesion, dysarthria, and leukoaraiosis were the 3- and 12-month independent predictors of stroke incidence after early recurrent TIA subgroup. Index TIA and subsequent stroke etiologies showed substantial concordance. An ABCD3 score >6 predicted a higher risk of stroke recurrence over the entire follow-up. CONCLUSIONS: Our study evaluated long-term outcome after early recurrent TIA. Our observations support the importance of promptly detecting and treating patients with early recurrent TIAs to reduce the high early and long-term risk of poor clinical outcomes.

Effect of Omega-3 Polyunsaturated Fatty Acids Treatment on Lipid Pattern of HIV Patients: A Meta-Analysis of Randomized Clinical Trials.

Even though omega-3 polyunsaturated fatty acids (PUFAs) seem to be effective in the treatment of human immunodeficiency virus (HIV)-associated dyslipidemia, their impact is still debated. For this reason, our aim was to perform a meta-analysis of the clinical evidence available to date. A systematic literature search was conducted in order to identify published clinical trials assessing the effect of PUFAs treatment on serum lipoproteins, and its safety profile. The effect sizes for lipid changes were expressed as mean difference (MD) and 95% confidence interval (CI). For safety analysis, odd ratios and the 95% CI were calculated with the Mantel-Haenszel method. Data were pooled from nine clinical studies comprising overall 578 HIV-affected subjects. Meta-analysis of the data suggested that omega-3 PUFAs significantly reduced triglycerides (TG) (MD = -1.04, 95% CI: -1.5, -0.58 mmol/L, p < 0.001), while increasing high-density lipoprotein cholesterol (MD = 0.36, 95% CI: 0.12, 0.61 mmol/L, p = 0.004), without affecting serum levels of total cholesterol, very-low- and low-density lipoprotein cholesterol, and apolipoprotein B and A1. Change in TG was significantly associated with eicosapentaenoic acid administered via daily dose. PUFA treatment did not lead to an increased risk of adverse events. In conclusion, PUFAs are safe and exert a significant plasma lipid improving effect in HIV-positive patients.

A randomized Placebo-Controlled Clinical Trial to Evaluate the Medium-Term Effects of Oat Fibers on Human Health: The Beta-Glucan Effects on Lipid Profile, Glycemia and inTestinal Health (BELT) Study.

The Beta-glucan Effects on Lipid profile, glycemia and inTestinal health (BELT) Study investigated the effect of 3 g/day oat beta-glucans on plasma lipids, fasting glucose and self-perceived intestinal well-being. The Study was an 8-week, double-blind, placebo-controlled, cross-over randomized clinical trial, enrolling a sample of 83 Italian free-living subjects, adherent to Mediterranean diet, with a moderate hypercholesterolemia and a low cardiovascular risk profile. Beta-glucans reduced mean LDL-Cholesterol (LDL-C) levels from baseline by 12.2% (95%CI: -15.4 to -3.8) after 4 weeks of supplementation and by 15.1% (95%CI: -17.8 to -5.9) after 8 weeks of supplementation (p < 0.01 for both comparison and versus placebo). Between baseline and 4 weeks Total Cholesterol (TC) levels showed an average reduction of 6.5% (95%CI: -10.9 to -1.9) in the beta-glucan sequence; while non-HDL-C plasma concentrations decreased by 11.8% (95%CI: -14.6 to -4.5). Moreover, after 8 weeks of beta-glucan supplementation TC was reduced by 8.9% (95%CI: -12.6 to -2.3) and non-HDL-C levels by 12.1% (95%CI: -15.6 to -5.3). Decreses in TC and non HDL-C were significant also versus placebo (respectively p < 0.05 and p < 0.01 to both follow-up visits). Fasting plasma glucose and self-perceived intestinal well-being were not affected by both beta-glucan and placebo supplementation.

[Heart-gut interactions]. / Interazioni cuore e apparato digerente.

The known interactions between the heart and the digestive system, concerning the semeiotic and the pathophysiology of coronary and non-coronary pain and the possible causal relationship between reflux pathology and the onset of atrial fibrillation, have been implemented by the most recent acquisitions on the role of intestinal microbiota in the development of atherosclerosis, hypertension and heart failure; this brief review also addresses these more innovative aspects.

Short- and Long-Term Stroke Risk after Urgent Management of Transient Ischaemic Attack: The Bologna TIA Clinical Pathway.

BACKGROUND: Rapid management can reduce the short stroke risk after transient ischaemic attack (TIA), but the long-term effect is still little known. We evaluated 3-year vascular outcomes in patients with TIA after urgent care. METHODS: We prospectively enrolled all consecutive patients with TIA diagnosed by a vascular neurologist and referred to our emergency department (ED). Expedited assessment and best secondary prevention was within 24 h. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death at 12, 24 and 36 months. RESULTS: Between August 2010 and July 2013, we evaluated 686 patients with suspected TIA; 433 (63%) patients had confirmed TIA. Stroke at 90 days was 2.07% (95% confidence interval (CI), 1.1-3.9) compared with the ABCD2-predicted risk of 9.1%. The long-term stroke risk was 2.6% (95% CI, 1.1-4.2), 3.7% (95% CI, 1.6-5.9) and 4.4% (95% CI, 1.9-6.8) at 12, 24 and 36 months, respectively. The composite outcome of stroke, myocardial infarction, and vascular death was 3.5% (95% CI, 1.7-5.1), 4.9% (95% CI, 2.5-7.4), and 5.6% (95% CI, 2.8-8.3) at 12, 24, and 36 months, respectively. CONCLUSIONS: TIA expedited management driven by vascular neurologists was associated with a marked reduction in the expected early stroke risk and low long-term risk of stroke and other vascular events.

Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial.

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides (LTPs) derived from enzymatic treatment of casein hydrolysate. Our aim was to evaluate this effect on a large number of hemodynamic parameters. We conducted a prospective double-blind randomized clinical trial, which included 52 patients affected by high-normal blood pressure (BP) or first-degree hypertension. We investigated the effect of a 6-week treatment with the LTPs isoleucine-proline-proline and valine-proline-proline at 3 mg per day, assumed to be functional food, on office BP, 24-h ambulatory BP monitoring (ABPM) values, stress-induced BP increase and cardiac output-related parameters. In the LTP-treated subjects, we observed a significant reduction in office systolic BP (SBP; -5±8 mm Hg, P=0.013) and a significant improvement in pulse wave velocity (PWV; -0.66±0.81 m s(-1), P=0.001; an instrumental biomarker of vascular rigidity). No effect on 24-h ABPM parameters and BP reaction to stress was observed from treatment with the combined LTPs. LTPs, but not placebo, were associated with a mild but significant change in the stroke volume (SV), SV index (markers of cardiac flow), the acceleration index (ACI) and velocity index (VI) (markers of cardiac contractility). No effect was observed on parameters related to fluid dynamics or vascular resistance. LTPs positively influenced the office SBP, PWV, SV, SV index, ACI and VI in patients with high-normal BP or first-degree hypertension.

Hemodynamic effects of lactotripeptides from casein hydrolysate in Mediterranean normotensive subjects and patients with high-normal blood pressure: a randomized, double-blind, crossover clinical trial.

Contrasting data partially support a certain antihypertensive efficacy of lactotripeptides derived from enzymatic treatment of casein hydrolysate. We carried out a randomized, double-blind, crossover clinical study to investigate the antihypertensive efficacy of a short-term treatment with lactotripeptides in Mediterranean subjects with normal or high-normal blood pressure (BP). We consecutively enrolled 55 untreated subjects (men:women = 30:25), 40.3 ± 9.8 years old, with normal or high-normal BP. After 4 weeks of dietary standardization, they were allocated to treatment with a fruit juice containing 3 mg of added Ile-Pro-Pro/Val-Pro-Pro lactotripeptides or with placebo for 4 weeks. After a 4-week washout period, they were then assigned to the alternative treatment for a further period of 4 weeks. Overall, no significant difference has been observed in office BP comparing baseline data with those posttreatment. Repeating the analysis by basal BP level, a mild but significant reduction in systolic BP (-1.7 ± 2.3 mm Hg; t = 3.5, P = .002) has been observed only in subjects with high-normal BP after treatment with lactotripeptides. With regard to 24-hour BP measurement, after lactotripeptide treatment only, the subjects experienced a significant reduction in diurnal diastolic BP (-1.6 ± 5.4 mm Hg; P = .042), diurnal mean BP (-2.1 ± 5.9 mm Hg; P = .19), and 24-hour (-5.4 ± 14.2 mm Hg; P = .011) and diurnal (-7.1 ± 19.2%; P = .014) diastolic BP value measurements relative to normal values. No modification has been observed in relation to plasma renin activity and aldosteronemia. In conclusion, diurnal diastolic BP is significantly reduced by lactrotripeptide supplementation in untreated Mediterranean subjects with normal or high-normal BP. Office systolic BP is reduced only in subjects with high-normal BP.

Persistence on treatment and blood pressure control with different first-line antihypertensive treatments: a prospective evaluation.

We enrolled 347 hypertensive patients, randomly allocated them to different first-line treatments, and followed-up for 24 months. Persistence on treatment was significantly higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs. CCBs (51.6%), beta-blockers (44.8%), and diuretics (34.4%). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a greater persistence in therapy as compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs. other CCBs (59.3% vs. 46.6%). Systolic and diastolic BP decreased more in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) when compared to beta-blockers (-4.0/-2.3 mmHg) and diuretics (-2.3/-2.1 mmHg).

Persistence of treatment and blood pressure control in elderly hypertensive patients treated with different classes of antihypertensive drugs.

Unsatisfactory blood pressure (BP) control in the treated hypertensive patient is largely related to poor compliance with antihypertensive drug regimens. The aim of the present study was to prospectively evaluate the rate of persistence on treatment and the extent of BP control in 301 elderly, uncomplicated grade I or II hypertensive patients randomly allocated to monotherapy with angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), beta-blockers, angiotensin II receptors (ARBs), or diuretics according to an open-label single-blind study design. After 24 months, the percentage of patients continuing their initial therapy was higher in those treated with ARBs (68.5%) and ACE inhibitors (64.5%) and lower in patients taking diuretics (34.4%; P<.01). The logistic regression model using ARBs as reference term showed that patients treated with ACE inhibitors (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.79-0.99) or CCBs (OR, 0.76; 95% CI, 0.54-0.85) were more likely to continue their initial antihypertensive therapy when compared with those treated with beta-blockers (OR, 0.67; 95% CI, 0.57-0.79) or diuretics (OR, 0.56; 95% CI, 0.38-0.84). The average systolic and diastolic BP decrease was greater in patients treated with ARBs (-11.2+/-4/-5.8+/-2 mm Hg), ACE inhibitors (-10.5+/-4/-5.1+/-2 mm Hg), and CCBs (-8.5+/-3/-4.6+/-2 mm Hg) and lesser in those treated with diuretics (-2.3+/-4/-2.1+/-3 mm Hg, P<.05) and beta-blockers (-4.0+/-2/-2.3+/-2 mm Hg; P<.05). The study confirms the importance of persistence with treatment for the effective management of hypertension in clinical practice.

A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice.

Persistence on treatment affects the efficacy of antihypertensive treatment. We prospectively investigated the persistence on therapy and the extent of blood pressure (BP) control in 347 hypertensive patients (age 59.4 +/- 6 years) randomly allocated to a first-line treatment with: angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), beta-blockers, angiotensin-II receptor blockers (ARBs), or diuretics and followed-up for 24-months. Persistence on treatment was higher in patients treated with ARBs (68.5%) and ACE inhibitors (64.5%) vs CCBs (51.6%; p < 0.05), beta-blockers (44.8%, p < 0.05), and diuretics (34.4%, p < 0.01). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class. The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs (59.3% vs 46.6%, p < 0.05). Systolic and diastolic BP was decreased more successfully in patients treated with ARBs (-11.2/-5.8 mmHg), ACE inhibitors (-10.5/-5.1 mmHg), and CCBs (-8.5/-4.6 mmHg) compared with beta-blockers (-4.0/-2.3 mmHg p < 0.05) and diuretics (-2.3/-2.1 mmHg, p < 0.05). No ARB, ACE inhibitor, beta-blocker, or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class. A trend toward a better BP control was observed in response to lercanidipine vs other CCBs (p = 0.059). The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice.

High-dose senna compared with conventional PEG-ES lavage as bowel preparation for elective colonoscopy: a prospective, randomized, investigator-blinded trial.

OBJECTIVE: To compare the efficacy and patient acceptance of an oral high dose of senna to conventional polyethylene glycol-electrolyte lavage solution (PEG-ES) in adults undergoing elective colonoscopy. METHODS: Consecutive outpatients referred for elective colonoscopy were prospectively randomly assigned to receive, the day before the procedure, either 24 tablets of 12 mg senna, divided into two doses at 1 p.m. and 9 p.m. (senna group, n=191), or standard 4-L PEG-ES (PEG-ES group, n=92). The overall quality of colon cleansing (primary outcome measure) and cleansing in the right colon were evaluated using the Aronchick scoring scale (1=excellent to 4=inadequate) by the investigator/endoscopist who was blinded to the treatment assignment. Patient acceptance and the safety of the preparation were assessed by a nurse, using a structured questionnaire covering compliance with the dosing, overall tolerance of the preparation (1=none or mild discomfort to 4=severely distressing), and adverse events. RESULTS: The quality of colon cleansing, overall tolerance of the preparation, and compliance were significantly better with senna; overall cleansing was excellent or good in 90.6% of patients in the senna group and in 79.7% in the PEG-ES group (p= 0.003). The percentage of procedures rescheduled because of insufficient colon cleansing was 7.3% in the PEG-ES group and 2.6% in the senna group (p=0.035). Multivariate logistic regression modeling showed the PEG-ES preparation as negative independent predictor of unsuccessful bowel cleansing. The incidence of adverse reactions was similar in the two groups; patients who received senna experienced significantly less nausea and vomiting, but more abdominal pain. CONCLUSIONS: An oral high dose of senna is a valid alternative to standard PEG-ES for outpatient colonoscopy preparation.

Is esophageal pH monitoring used appropriately in an open-access system? A prospective multicenter study.

OBJECTIVES: To evaluate the referral patterns and indications for esophageal pH monitoring in an open-access system and to determine whether these indications conform to practice guidelines of the American Gastroenterological Association (AGA). METHODS: A total of 851 consecutive patients referred for ambulatory pH monitoring to nine open-access gastrointestinal units over a 12-month period received a structured interview. The indication for the examination was decided by the physician performing the procedure, on the basis of the patient's clinical history and main complaint. RESULTS: Three hundred and twenty-three (38%) examinations were for indications in accordance with the guidelines. The proportion of appropriate requests in each center ranged from 34% to 47%. This figure was not significantly different in larger gastrointestinal units (more than 150 examinations per year) and smaller ones (35% and 40%; p= 0.14). The proportion of appropriate requests was 45% for gastroenterologists, 38% for surgeons, 32% for other specialists, and 24% for primary care physicians (PCPs) (p < 0.001). The percentage of appropriateness was significantly different between gastrointestinal specialists and PCPs (p < 0.001 vs gastroenterologists, p= 0.015 vs GI surgeons), and between gastroenterologists and other specialists (p= 0.006). The underuse of an empirical trial of acid-suppression therapy in patients with suspected reflux disease and the overuse of this test to confirm a diagnosis in patients with erosive esophagitis and in endoscopy-negative cases with typical symptoms responding completely to antisecretory therapy accounted for most of the referrals, which was not in accordance with the guidelines. CONCLUSIONS: In an open-access system, a high proportion of esophageal pH studies are done for indications not consistent with published guidelines, particularly among the examinations not requested by gastrointestinal specialists. Further education is still needed on the appropriate use of esophageal pH monitoring and management of gastroesophageal reflux disease (GERD).

Single bolus of midazolam versus bolus midazolam plus meperidine for colonoscopy: a prospective, randomized, double-blind trial.

BACKGROUND: The aim of this study was to determine whether a single bolus of meperidine in addition to midazolam improves patient tolerance during colonoscopy. METHODS: Consecutive patients undergoing outpatient colonoscopy were randomly assigned in double-blind fashion to receive a single rapid intravenous bolus of 5 mg of midazolam and placebo (Group A, n = 125) or 5 mg midazolam plus 50 mg meperidine (Group B, n = 128). Tolerance (4-point scale: 1 excellent, 4 unbearable), pain (4-point scale: 1 none, 4 severe) and willingness to undergo another colonoscopy were assessed 24 to 48 hours later in a telephone interview conducted by an independent observer blinded to the regimen of sedative medication. RESULTS: Significantly more patients in Group A reported moderate or severe pain (28% vs. 9%; p < 0.001), poor or unbearable tolerance (18% vs. 6%; p < 0.01) and unwillingness to undergo colonoscopy again in the future (14% vs. 5%; p < 0.05). By multivariate analysis, randomization to the midazolam group and younger age were the only variables independently associated with the risk of reporting at least one of these outcomes. Recovery time, frequency of oxygen desaturation, and need for supplemental oxygen were not significantly different between the 2 groups. CONCLUSIONS: The addition of a single bolus of meperidine to midazolam improves patient tolerance and lessens pain during colonoscopy without significantly increasing the frequency of side effects or prolonging recovery time.