Comparison of the significance of three histopathological thresholds of malignancy in experimental colorectal tumours.

The purpose of this experiment was to study sequential histogenesis of colonic epithelial tumours in the dimethylhydrazine (DMH) induced rat colon cancer model. Seventy outbred female Wistar rats treated with DMH (40 mg/kg, subcutaneously weekly for five weeks) were killed and autopsied in batches of 10 every five weeks from the 10th to 40th weeks from first treatment. The resulting 378 colonic lesions were assigned to benign or malignant categories using each of three standard histopathological thresholds of malignancy: alpha, the transition from dysplasia to intraepithelial carcinoma; beta, invasion through the crypt basement membrane; and gamma, invasion through the muscularis mucosae. These comprised 79 'benign' and 299 'malignant' or 273 'benign' and 141 'malignant' lesions depending on the threshold (alpha or gamma) assigned (p less than 0.001). Decreasing ratios of pre-threshold to post-threshold lesions between 15 and 40 weeks (alpha, 2.0 to 0.051; beta, 3.5 to 0.57; gamma, 8.0 to 0.87) provide some support for an 'adenoma-carcinoma' progression for each. Comparison of time-dependent prevalence curves confirms that the alpha threshold (cyto-architecture) is qualitatively different from the beta and gamma thresholds (invasion), showing that the adenoma-carcinoma and de novo hypotheses need not be mutually exclusive. The time-dependent prevalence data support de novo origin of some carcinomas, as well as at least two other modes of accrual for neoplastic lesions.     

Cardiovascular Complications of Extreme Obesity in Women

Severe obesity (body mass index ≥35 kg/m²) is occurring at younger ages in US women and is relatively common among women of certain racial/ethnic backgrounds. It is associated with a high incidence of cardiovascular risk factors and cardiovascular outcomes and may represent an increasingly important facet of cardiovascular risk for US women. Bariatric surgery has the strongest literature base for producing substantial and sustained weight loss among the severely obese but carries the risk for potentially severe complications. An emerging literature shows that lifestyle intervention may lead to clinically meaningful weight loss in the severely obese, but that maintenance of such loss may be problematic.     

Risedronate prevents new vertebral fractures in postmenopausal women at high risk

Independent risk factors for fracture include advanced age, preexisting fractures, and low bone mineral density. Rised-ronate has been shown in several large trials to be safe and effective for patients with osteoporosis, but its effects in populations at high risk are not well characterized. To determine the effect of risedronate on vertebral fracture in high-risk subjects, we pooled data from two randomized, double-blind studies [Vertebral Efficacy with Risedronate Therapy (VERT) Multinational (VERT-MN) and VERT-North America (VERT-NA)] in 3684 postmenopausal osteoporotic women treated with placebo or risedronate 2.5 or 5 mg/d and analyzed fracture risk in subgroups of subjects at high risk for fracture due to greater age or more prevalent fractures (vs. median for overall study population), or lower bone mineral density (T-score, -2.5 or less). Fractures were diagnosed by quantitative and semiquantitative assessment of radiographs at baseline and 1 yr. In the overall population, treatment for 1 yr with risedronate 5 mg/d reduced the risk of new vertebral fractures by 62% vs. control (relative risk, 0.38; 95% confidence interval, 0.25, 0.56; P < 0.001) and of multiple new vertebral fractures by 90% vs. control (relative risk, 0.10; 95% confidence interval, 0.04, 0.26; P < 0.001). Consistent risk reductions were observed at 1 yr in the risedronate-treated high-risk subgroups. Significant reduction in fracture risk after 1 yr is an important benefit in patients at high risk for fracture because, without treatment, these patients are likely to sustain new fractures in the near term.     

Waiting for a Pediatric Chronic Pain Clinic Evaluation: A Prospective Study Characterizing Waiting Times and Symptom Trajectories

Chronic pain during childhood is prevalent and costly, but the access to interdisciplinary pain care is limited. Studies investigating adults waiting for pain clinic evaluation found that symptoms and quality of life deteriorate over the waiting period, but little is known about the experience of adolescents. Therefore, we aimed to determine wait list times and the longitudinal trends of pain and physical, mental, and social health over a 12-week period. In total, 97 adolescents, aged 10 to 18 years (M?=?14.7 years, 82% female), waiting for evaluation at an interdisciplinary pediatric pain clinic completed assessments at enrollment and at 4-, 8-, and 12-week follow-up. We performed a review of the medical record of attendance patterns 12 months later. Twelve adolescents and their parents also completed qualitative interviews, describing their experience of waiting for evaluation. Wait times averaged 197.5 days (range?=?69–758 days) from the time of referral to the first-attended appointment, and 86.6% of youths completed appointments. Longitudinal repeated measures analyses demonstrated little improvement in pain or other domains of functioning over the 12-week period. In qualitative interviews, families described anxious anticipation for the upcoming appointment, combined with frustration in waiting. Findings highlight the need to consider approaches to reduce wait times and provide early intervention for youths awaiting pain clinic evaluation.Perspective: This study extends the literature on the characteristics and symptom trajectories of adolescents during the wait period for interdisciplinary pain clinic evaluation, described previously only in adults with chronic pain. Findings demonstrated an average wait time of 6.5 months, during which youths’ pain and physical and social health remained impaired.