High-risk family colorectal cancer screening service in Ireland: Critical review of clinical outcomes.

BACKGROUND: We present the 15-year experience of a family colorectal cancer screening service in Ireland with emphasis on real life experience and outcomes. METHODS: Questionnaires were used to assess family cancer history and assign patients to risk categories; 'Moderate Risk', HNPCC, (suspected) genetic syndrome (non-HNPCC), 'Low Risk'. Screening was by full colonoscopy. We report neoplastic yield, examining effect of risk category, age, gender, and index colonoscopy findings. RESULTS: Between 1998 and 2013, 2242 individuals were referred; 57.3% female, 42.7% male, median age 46 years (range9-85yrs). Median follow up time was 7.9yrs (range 0.5-15.3yrs). Follow up data after exclusion (non-compliance, known CRC) was available in 1496 (66.7%): 'Moderate risk' 785 (52.5%), HNPCC 256 (17.1%), (suspected) genetic syndrome (non-HNPCC) 85 (5.7%), 'Low Risk' 370 (24.7%). Screening was performed in 1025(68.5%) patients; colonoscopy data available for 993 (96.9%); total 1914 colonoscopies. At index colonoscopy, 178 (18.0%) patients had adenomas; 56 (5.5%) advanced adenoma. During the entire study period, 240 (24.2%) had an adenoma; 69 (7.0%) advanced adenoma. Cancers were diagnosed on screening in 2 patients. Older age and male gender were associated with higher adenoma detection rate; p<0.001, p=0.01, respectively. Risk category did not affect adenoma yield. Adenoma and advanced adenoma detection at index colonoscopy were associated with detection of same at follow up screening; p<0.001. CONCLUSION: Male gender and age (>50) were the core identifiable risk factors for neoplasia at screening colonoscopy in this family screening setting. Our results would support less intensive surveillance in younger patients (<50), particularly where index colonoscopy is normal.

Lasofoxifene in osteoporosis and its place in therapy.

Selective estrogen-receptor modulators (SERMs), which have estrogen-like effects on bone and "antiestrogen effects" on other tissues, have been in development for osteoporosis prevention and treatment in postmenopausal women as a safer alternative to long-term estrogen. We conducted a literature review of the skeletal and extraskeletal effects of lasofoxifene, a new generation SERM approved by the European Commission for osteoporosis treatment. Published data on the effects of lasofoxifene are based on 23 clinical pharmacology studies with over 10,000 participants from 17 phase 2 and 3 randomized controlled trials (RCTs). In RCTs, lasofoxifene decreases bone turnover markers (BTMs), increases bone mineral density (BMD) at the spine and hip, and decreases the incidence of vertebral and nonvertebral nonhip fractures compared with placebo. Compared with raloxifene, lasofoxifene gave greater decreases in BTMs, and greater increases in lumbar spine BMD. Lasofoxifene also decreased the risk of breast cancer, major coronary heart disease events, and stroke, but-similar to raloxifene-there was an increased risk of venous thromboembolism. In one trial, endometrial hypertrophy and uterine polyps were more common with lasofoxifene than with placebo, but endometrial cancer and hyperplasia were not. Lasofoxifene is probably most appropriate for use among women in their early or middle menopausal years (age 55-65) who have, or are at risk of developing, osteoporosis and in particular vertebral fractures. At the time of publication, lasofoxifene is not approved for use by the US Food and Drug Administration, and as such is not used in North America.

Kidney function and rate of bone loss at the hip and spine: the Canadian Multicentre Osteoporosis Study.

BACKGROUND: The relationship between kidney function and bone loss is unclear. STUDY DESIGN: A prospective observational study. SETTING & PARTICIPANTS: 191 men and 444 women aged > or = 50 years participating in a population-based observational study designed to determine risk factors for bone loss and fractures. PREDICTORS: The primary predictor of change in bone mineral density (BMD) was estimated creatinine clearance (using the Cockcroft-Gault formula) measured at baseline and stratified by quartiles. Our secondary predictor was estimated glomerular filtration rate using the Modification of Diet in Renal Disease Study equation, also stratified by quartiles. OUTCOMES & MEASUREMENTS: Changes in BMD at the lumbar spine, total hip, and femoral neck during 5 years. RESULTS: Compared with participants in the first quartile of estimated creatinine clearance (>101.2 mL/min), those in remaining quartiles were older (quartile 1, 50.0 years; quartile 2 [101.2-83.4 mL/min], 54.7 years; quartile 3 [83.4-68.3 mL/min], 60.5 years; and quartile 4 [<68.3 mL/min], 68.3 years); weighed less; reported more sedentary hours; were less likely to report excellent, very good, or good self-reported health; consumed less caffeine; and had lower serum calcium and phosphate and higher serum parathyroid hormone levels. After adjusting for age, weight, sex, baseline BMD, and these differences, compared with those in the first quartile, those in the fourth quartile had decreases in BMD of 0.08 g/cm(2) (95% CI, 0.04-0.1) at the lumbar spine, 0.08 g/cm(2) (95% CI, 0.06-0.1) at the femoral neck, and 0.09 g/cm(2) (95% CI, 0.07-0.1) at the total hip. Bone loss did not increase with worsening kidney function (P for trend > 0.05). Results were not substantially different using estimated glomerular filtration rate. LIMITATIONS: Observational study design and indirect measures of kidney function. CONCLUSIONS: Men and women with impaired kidney function are at increased risk of bone loss, even with minimal reduction in kidney function.

Effects of calcium on cardiovascular events in patients with kidney disease and in a healthy population.

BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) is the largest contributor to all-cause mortality in patients with end stage renal disease (ESRD). Accelerated vascular calcification is a key risk factor for CVD in these patients. The etiology of vascular calcification and the specific role calcium supplementation may play in accelerating calcification have not been fully elucidated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We summarize published data that report on the association between calcium supplementation, vascular calcification, and CVD in patients with and without ESRD. RESULTS: The majority of randomized, controlled trials in patients with ESRD suggest that calcium supplementation--in the form of calcium-based phosphate binders--leads to a progression of vascular calcification. However, studies showing that calcium-based phosphate binders increase cardiovascular mortality are lacking in patients with ESRD. In contrast, one randomized trial in healthy postmenopausal women reported that, compared with those not receiving calcium supplementation, women who take supplements are at an increased risk for cardiovascular events. CONCLUSIONS: Given the potential for harm with calcium supplementation in healthy postmenopausal women and the evidence that calcium-based phosphate binders are associated with adverse intermediate outcomes in patients with ESRD, calcium-either as a phosphate binder or as a supplement--should be prescribed with caution.