Current gut-directed therapies for irritable bowel syndrome

Opinion statement Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that can present with a wide array of symptoms that make treatment difficult. Current therapies are directed at relieving symptoms of abdominal pain or discomfort, bloating, constipation, and diarrhea. Pharmacologic agents used to treat IBS-associated pain include myorelaxants, peppermint oil, and peripherally acting opiates. Dicyclomine and hyoscyamine, the two myorelaxants available in the United States, have not been proven effective in reducing abdominal pain in patients with IBS. The efficacy of peppermint oil is debated, but methodological problems with existing studies preclude definitive judgment. Loperamide is ineffective for relief of abdominal pain. For IBS patients with excessive abdominal bloating, a small number of studies suggest that bacterial eradication with gut-directed antibiotics and bacterial reconstitution with nonpathogenic probiotics may reduce flatulence. For constipation-predominant (C-IBS) symptoms, current treatment options include fiber supplementation, polyethylene glycol, and tegaserod. Soluble fibers (ispaghula, calcium polycarbophil, psyllium) are more effective than insoluble fibers (wheat bran, corn fiber) in alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit in treatment of overall IBS symptoms. Polyethylene glycol increases bowel frequency in chronic constipation, but its overall efficacy against IBS is unclear. Tegaserod, a 5-HT₄ agonist, demonstrates superiority over placebo in improving bowel frequency and stool consistency and alleviating abdominal pain and bloating in women with C-IBS. Overall global symptoms are modestly improved with tegaserod when compared with placebo. Additional agents under investigation for C-IBS include the ClC₂ chloride channel opener lubiprostone, μ-opioid receptor antagonist alvimopan, and 5-HT₄ agonist renzapride. For diarrhea-predominant (D-IBS) symptoms, available therapies include loperamide, alosetron, and clonidine. Alosetron, a 5-HT₃ antagonist, is superior to placebo for reducing bowel frequency, improving stool consistency, and relieving abdominal pain in women with D-IBS. However, alosetron is available under a restricted license because of concerns for ischemic colitis and severe constipation necessitating colectomy. Clonidine may be helpful in alleviating global symptoms for D-IBS patients.     

Ambulatory arterial stiffness index: determinants and outcome

OBJECTIVES: We hypothesized that one minus the slope of diastolic on systolic blood pressure in individual 24-h ambulatory blood pressure recordings (ambulatory arterial stiffness index) might reflect arterial stiffness and predict cardiovascular mortality. METHODS: In volunteers and a population recruited in China, we studied concordance between ambulatory arterial stiffness index and established indexes of arterial stiffness. We assessed the predictive value of ambulatory arterial stiffness index in relation to cardiovascular outcome in Irish hypertensive patients. RESULTS: In 166 healthy volunteers, aged 22-83 years, the correlation coefficient between ambulatory arterial stiffness index and pulse wave velocity was 0.51 (P<0.001). In 348 randomly recruited Chinese, the correlations between ambulatory arterial stiffness index and both the central and peripheral systolic augmentation indexes were significantly stronger than those for 24-h ambulatory pulse pressure, particularly in study participants younger than 40 years. Among normotensive participants, the 95th percentile of the ambulatory arterial stiffness index was 0.55 in 234 Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of the ambulatory arterial stiffness index in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In 11 291 patients enrolled in the Dublin Outcome Study, both ambulatory arterial stiffness index and 24-h ambulatory pulse pressure significantly predicted cardiovascular mortality. Ambulatory arterial stiffness index was a strong predictor of fatal stroke in normotensive participants, whereas pulse pressure better predicted heart attack in hypertensive patients. CONCLUSION: Ambulatory arterial stiffness index is a novel measure of arterial stiffness, which can be readily determined from ambulatory blood pressure recordings and which independently predicts cardiovascular mortality.     

What to do when faced with an unmeasurable ambulatory blood pressure?

If ambulatory blood pressure measurement is not possible because the upper-arm circumference is so great that even the largest cuff provided with the monitor will not encircle the arm, satisfactory measurements can be obtained by applying a cuff to the forearm.     

High-density lipoprotein levels and 10-year cardiovascular risk in HIV-1-infected patients

We aimed to determine the contribution of high-density lipoprotein cholesterol (HDL-c) to cardiovascular disease (CVD) risk in a cohort of HIV-infected patients. The contribution of CVD risk factors to the predicted CVD risk was assessed. We estimated the degree of reclassification of CVD risk if HDL-c concentration was increased in all patients by 20 and 40%, respectively. After age, HDL-c contributed most to the overall cardiovascular risk. Increasing HDL-c by 20% and 40% reclassified six and 12 patients to lower CVD risk groups, respectively. In this cohort, HDL-c contributed more to cardiovascular risk than smoking, total cholesterol, systolic blood pressure (SBP) and sex.     

Postoperative imaging of the elbow, wrist, and hand

There are many bone and soft tissue injuries to the elbow, wrist, and hand that are treated surgically. The operative techniques can be complicated and their indications may change. This article reviews the common injuries at the elbow, wrist, and hand, the indications for surgical management, the current and previous operative techniques used, the expected postoperative appearance on different imaging modalities, and the important potential complications of each technique.