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Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we evaluated silver sulfide quantum dots (QDs) with a chitosan/glucose (CS/GS) encapsulating polymer to produce an oral insulin nanocarrier (QD-INS-CS/GS). This formulation was insoluble at acidic-neutral pH, showed increased absorption in human duodenum explants and Caenorhabditis elegans; and was highly sensitive to glucosidase enzymes to mediate hepatic release. In C57BL/6J mice, 50% of QD-INS-CS/GS distributed to the liver and promoted a dose-dependent reduction in blood glucose. Compared to injectable insulin, QD-INS-CS/GS had a similar effect size and time-to-onset in non-obese diabetic mice and streptozotocin-induced diabetic rats without promoting hypoglycaemia or weight gain. Non-diabetic baboons showed a dose dependent-reduction in blood glucose up to 30% with 10 IU/kg in insulin tolerance testing. No biochemical or haematological toxicity, or adverse events were observed. These studies demonstrate the successful application of this oral insulin platform with inhibited hypoglycaemia.

Background: Epidemiologic evidence of associations between the high intake of fat and low intake of dietary fiber, beta carotene, and other dietary constituents and the risk of colorectal neoplasia has been inconsistent and has not provided a sufficient basis for recommendations concerning the dietary prevention of large-bowel cancer in humans. Purpose: We conducted a clinical trial to assess the effects on the incidence of adenomas of reducing dietary fat to 25% of total calories and supplementing the diet with 25 g of wheat bran daily and a capsule of beta carotene (20 mg daily). Methods: We performed a randomized, partially double-blinded, placebo-controlled factorial trial in which half the patients were assigned to each intervention, resulting in seven intervention groups and one control group. Eligibility criteria included histologic confirmation of at least one colorectal adenoma and confidence expressed by the colonoscopist that all polyps had been removed. Dietary changes were individually initiated and monitored by dietitians and research nurses. At surveillance colonoscopy, the size and location of all polyps were recorded, and their histology was later centrally reviewed. Among 424 patients who were randomly assigned in the trial, 13 were found to be ineligible upon histologic review. Among the remaining 411, complete outcome data were collected from 390 at 24 months and from 306 at 48 months. All P values are from two-sided tests of statistical significance. Results: There was no statistically significant prevention of total new adenomas with any of the interventions. We found a statistically nonsignificant reduced risk of large adenomas (≥10 mm) with the low-fat intervention: At 24 months, the odds ratio (OR) adjusted for potential confounders = 0.4 and 95% confidence interval (CI) = 0.1-1.1; at 48 months, OR = 0.3 and 95% CI = 0.1-1.0. Less and statistically nonsignificant reductions in the risk of large adenomas were found with wheat bran: At 24 months, OR = 0.8 and 95% CI = OJ-2.2; at 48 months, OR = 0.8 and 95% CI = 0.3-2.5. Patients on the combined intervention of low fat and added wheat bran had zero large adenomas at both 24 and 48 months, a statistically significant finding (P =.03). Conclusions: Because only small numbers of patients were studied, our finding that the combination of fat reduction and a supplement of wheat bran reduced the incidence of large adenomas in this randomized, controlled trial must be treated with caution. The results do suggest, however, that these interventions may reduce the transition from smaller to larger adenomas, a step that may critically define those adenomas most likely to progress to malignancy.

OBJECTIVE Under the Pharmaceutical Benefits Scheme, the use of H2-receptor antagonists (H2A) in the treatment of dyspepsia and heartburn is only subsidised when there is a proven diagnosis of ulcer. This study compared the costs of this Australian practice with a simulation of British practice, which allows unrestricted prescribing of subsidised H2A. DESIGN Patients with heartburn and/or dyspepsia were prospectively randomised to either a "British" group treated freely at the discretion of their general practitioner without necessarily being investigated or an "Australian" group where use of H2A was allowed only after gastroscopy or a barium meal had demonstrated a peptic ulcer or ulcerative oesophagitis. The patients were followed up for six months and all direct and indirect costs were recorded. SETTING Forty-nine Sydney general practitioners recruited primary care patients for the study. PATIENTS Any patient with heartburn or dyspepsia was considered for recruitment; 139 patients entered the study and 137 completed it. MAIN OUTCOME MEASURES The outcome measures were the costs of general practitioner consultations, specialist consultations, radiology and gastroscopy, other tests, H2A, other medications, personal costs, and total cost per patient. RESULTS The cumulative total cost per patient at the end of the study was equivalent in the "Australian" ($392) and "British" ($406) groups. A higher initial cost per patient of H2A in the "British" group was offset by a rapid decrease in the proportion that continued to use H2A and by the cost of specialist consultations and investigations in the "Australian" group. CONCLUSION Over a six-month period the cost of early investigation of heartburn and dyspepsia was equivalent to the cost of a therapeutic trial of H2A.

Context.—Irritable bowel syndrome (IBS) is a common functional bowel disorder for which there is no reliable medical treatment.Objective.—To determine whether Chinese herbal medicine (CHM) is of any benefit in the treatment of IBS.Design.—Randomized, double-blind, placebo-controlled trial conducted during 1996 through 1997.Setting.—Patients were recruited through 2 teaching hospitals and 5 private practices of gastroenterologists, and received CHM in 3 Chinese herbal clinics.Patients.—A total of 116 patients who fulfilled the Rome criteria, an established standard for diagnosis of IBS.Intervention.—Patients were randomly allocated to 1 of 3 treatment groups: individualized Chinese herbal formulations (n=38), a standard Chinese herbal formulation (n=43), or placebo (n=35). Patients received 5 capsules 3 times daily for 16 weeks and were evaluated regularly by a traditional Chinese herbalist and by a gastroenterologist. Patients, gastroenterologists, and herbalists were all blinded to treatment group.Main Outcome Measures.—Change in total bowel symptom scale scores and global improvement assessed by patients and gastroenterologists and change in the degree of interference in life caused by IBS symptoms assessed by patients.Results.—Compared with patients in the placebo group, patients in the active treatment groups (standard and individualized CHM) had significant improvement in bowel symptom scores as rated by patients (P = .03) and by gastroenterologists (P = .001), and significant global improvement as rated by patients (P=.007) and by gastroenterologists (P=.002). Patients reported that treatment significantly reduced the degree of interference with life caused by IBS symptoms (P=.03). Chinese herbal formulations individually tailored to the patient proved no more effective than standard CHM treatment. On follow-up 14 weeks after completion of treatment, only the individualized CHM treatment group maintained improvement.Conclusion.—Chinese herbal formulations appear to offer improvement in symptoms for some patients with IBS.