Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. INTRODUCTION: The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. METHODS: We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. RESULTS: Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. CONCLUSIONS: Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a comprehensive recruitment approach will be needed to effectively achieve the scientific goals of the EDGE study.

Acute-phase protein α1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats.

One would assume that the anti-inflammatory activity of α1-anti-trypsin (AAT) is the result of inhibiting neutrophil enzymes. However, AAT exhibits tolerogenic activities that are difficult to explain by serine-protease inhibition or by reduced inflammatory parameters. Targets outside the serine-protease family have been identified, supporting the notion that elastase inhibition, the only functional factory release criteria for clinical-grade AAT, is over-emphasized. Non-obvious developments in the understanding of AAT biology disqualify it from being a straightforward anti-inflammatory agent: AAT does not block dendritic cell activities, nor does it promote viral and tumour susceptibilities, stunt B lymphocyte responses or render treated patients susceptible to infections; accordingly, outcomes of elevated AAT do not overlap those attained by immunosuppression. Aside from the acute-phase response, AAT rises during the third trimester of pregnancy and also in advanced age. At the molecular level, AAT docks onto cholesterol-rich lipid-rafts and circulating lipid particles, directly binds interleukin (IL)-8, ADAM metallopeptidase domain 17 (ADAM17) and danger-associated molecular pattern (DAMP) molecules, and its activity is lost to smoke, high glucose levels and bacterial proteases, introducing a novel entity - 'relative AAT deficiency'. Unlike immunosuppression, AAT appears to help the immune system to distinguish between desired responses against authentic threats, and unwanted responses fuelled by a positive feedback loop perpetuated by, and at the expense of, inflamed injured innocent bystander cells. With a remarkable clinical safety record, AAT treatment is currently tested in clinical trials for its potential benefit in a variety of categorically distinct pathologies that share at least one common driving force: cell injury.

Promoting sun safety among zoo visitors.

BACKGROUND: Each year, millions of children visit zoological parks, where they are exposed to long bouts of ultraviolet radiation (UVR). We conducted a study in the winter and replicated it in the summer to evaluate an intervention for reducing UVR exposure during the zoo visit. METHODS: Each study used a nonequivalent control group design: one zoological site received the intervention and a second received evaluation only. Key outcome measures consisted of observed prevalence of hat use by exiting children (N = 8,721 and 8,524, respectively, in winter and summer studies) and purchase rates of sunscreen and hats in zoo gift shops. Intervention consisted of tip sheets for parents, children's activities, prompts, and discounts off the price of sunscreen and sun-protective hats. RESULTS: In the summer study, sales of both sunscreen and target hats increased significantly at the intervention site relative to the control site, whereas in the winter study, only sunscreen sales at the intervention site had a significant (relative) increase. Children's hat use increased significantly at the intervention site, but only in the winter study. CONCLUSIONS: The multicomponent program was effective in promoting purchases of sun-safe items, but its impact on children's hat use was inconclusive.

Patient reminder letters to promote annual mammograms: a randomized controlled trial.

BACKGROUND: This study assessed the effects of a reminder letter from a physician (relative to a mammography facility letter or no letter) on appointment compliance among women 50-74 years of age due for an annual screening mammogram. METHODS: A total of 1,562 women were randomly as signed to the groups. Each Group 1 subject received a reminder letter from her physician, each Group 2 subject received a reminder letter from her mammography facility, and Group 3 served as a control group. RESULTS: The return rates for Groups 1, 2, and 3 were 47.7, 46.6, and 28.3%, respectively; the overall difference was significant using a chi(2) analysis (P < 0.001). Bonferroni pairwise comparisons indicated no difference between Groups 1 and 2 but significant differences (P < 0.001) between Group 3 and the other two groups. Logistic regression indicated that relative to Group 3, the adjusted odds of returning for Groups 1 and 2 were 2.37 and 2.24, respectively. CONCLUSIONS: Mammography providers and their patients likely will benefit from in-reach reminder systems. Physicians who do not use reminder systems should refer their patients to facilities that use these systems.

A national survey of sun safety activities at U.S. zoos.

Skin cancer incidence in the United States has increased. Exposure to ultraviolet radiation (UVR) is a major risk factor for skin cancer. Every year, millions of children with their families visit outdoor leisure facilities such as zoos where overexposure to UVR may occur. This study was conducted to assess the proportion of U.S. zoos that provided sun safety activities during the summer of 1998 and their willingness to incorporate skin cancer prevention strategies at their facility in the future. A 56 item self-administered questionnaire was mailed to 140 zoos accredited by the American Zoo and Aquarium Association. A follow-up telephone survey was also conducted with 33 mail non-respondents. The response rate was 97% (N = 136). Results revealed that in the summer of 1998, only 5% of zoos provided sun safety recommendations to visitors and 25% of zoos provided recommendations to their employees. The recommendations made most often to visitors and employees were to use sunscreen and wear protective clothing. Eighty-five percent of zoos indicated interest in providing sun safety activities at their facilities in the future. The next step will be to design environmentally appropriate sun safety programs for zoos and to encourage zoos to implement these programs.

Rates and correlates of discomfort associated with mammography.

PURPOSE: To explore the rates and correlates of discomfort at mammography in asymptomatic women aged 50-74 years from six San Diego, Calif, mammography facilities. MATERIALS AND METHODS: Subjects (N = 1,800) completed a 43-item telephone interview approximately 3 weeks after screening mammography. Bivariate associations between variables were analyzed with chi(2) analysis. Logistic regression was used to assess the independent predictors of discomfort at mammography while controlling for all other factors. RESULTS: Nine hundred thirty-three (52%) women reported moderate to extreme discomfort at mammography. Discomfort was not related to the intention to undergo future mammography (P =.95). Factors that were significantly associated with discomfort in multivariate analyses were facility (P <.001), satisfaction with care (P <.04), and perception of the technologist's "roughness" (P <.001). CONCLUSION: Discomfort, although not related to the intention to undergo future mammography, had a relatively high incidence.

Aneurysms of the superficial temporal artery: literature review and case reports.

Superficial temporal artery (STA) aneurysms are a medical rarity. There are less than 200 patients reported in the literature. The majority of cases are of traumatic etiology and occur in young men. The senior authors reported a case of STA aneurysm in 1978. We now review the literature and report on three additional patients with STA aneurysm and a fourth patient with a temporal lipoma that was diagnosed initially as an aneurysm. This is the first report of a preoperative diagnosis of STA aneurysm that subsequently proved incorrect.

alpha-1-Antitrypsin metabolism in the protein-deficient weanling rat.

Protein-deficient weanling rats fed on a 30 g casein/kg diet for 3 weeks lost albumin but maintained the level of serum alpha-1-antitrypsin, the most abundant protease inhibitor in blood. alpha-1-Antitrypsins from malnourished rats and control rats (given 250 g casein/kg diet) differed; the protease inhibitor from protein-deficient animals: (1) was more acidic, (2) appeared slightly larger (57 400 v. 56 000 daltons) on sodium dodecyl sulphate (SDS)-polyacrylamide gels, (3) had a more acidic Pi type and increased anodal mobility at pH 8.9, (4) bound more concanavalin-A and contained more carbohydrate, specifically two to three extra sialic acid residues. The amino sugar and neutral sugar contents of both preparations of alpha-1-antitrypsin were the same. Analysis of the products of cyanogen-bromide cleavage revealed that alpha-1-antitrypsin preparations from protein-deficient rats contain an extra glycopeptide that was not present in alpha-1-antitrypsin from control animals. In vivo studies showed that the increased sialic acid content of alpha-1-antitrypsin of protein-deficient rats did not alter the half-life of the molecule in the blood of control rats. However, the fractional catabolic rate of alpha-1-antitrypsin from either well-nourished or protein-deficient rats was significantly (P less than 0.01) lower in protein-deficient rats than in control rats (0.0247/h v. 0.0406/h). The decreased fractional catabolic rate could not be explained by changes in hepatic mannosyl-, galactosyl- or N-acetylhexosaminyl receptors since liver perfusion studies showed that bovine serum albumin, when covalently modified separately with each of these ligands, was extracted from the perfusion medium as rapidly or more rapidly by livers from malnourished animals. Perfused livers from protein-deficient rats secrete three times more alpha-1-antitrypsin than do livers from well-nourished animals. The decreased fractional catabolic rate and increased rate of biosynthesis and secretion of the glycoprotein by livers from protein-deficient animals may account for the maintenance of alpha-1-antitrypsin levels during protein malnutrition.

Determination of (dichloromethylene) diphosphonate in physiological fluids by ion-exchange chromatography with phosphorus-selective detection.

An analytical method is presented for the determination of (dichloromethylene) disphosphonate (Cl2MDP) in serum and urine. Cl2MDP is isolated from biological samples by adsorption onto precipitated calcium phosphate. Orthophosphate is separated from Cl2MDP by anion-exchange chromatography using AG 1-X8 resin. Detection is accomplished on-line using a flame photometric detector. Potentially interfering condensed phosphates are removed by acid hydrolysis. Sample handling losses are corrected by monitoring the recovery of a [14C] Cl2MDP spike added to the samples. Determinations of Cl2MDP to concentrations as low as 2 mumol/l are possible. Extension of the method to determine other diphosphonates is discussed.

Two replantations of severed ear parts.

Two successful cases of replantation of part of an ear are presented; both were done by simple suture. The larger of these replants consisted of a 13 x 43 mm segment of the superior helix and concha. Both were vascularized beofre 48 hours. The greatest problem was venous congestion. In the larger replant we made multiple puncture wounds daily on both sides of the graft with an 18-gauge needle to help relieve this.

Evaluation of a glassy-carbon electrode for amperometric detection of selected methylxanthines in serum after their separation by reversed-phase chromatography.

We examined the relative merits of direct-current, pulse, and differential pulse amperometry at a flow-through, glassy-carbon electrode used in monitoring column chromatography. We give a rapid, simple procedure for determining theophylline (1,3-dimethylxanthine) in 20--100 microliter of blood serum. Interference by 1,7-dimethylxanthine, a metabolite of caffeine, is compared for photometric and amperometric detection, and some advantages of combined photometric and amperometric detection are discussed.

Aneurysm of the superficial temporal artery.

An aneurysm of the superficial temporal artery is a rare lesion, which should be suspected after blunt trauma to the forehead that is followed by the appearance of a pulsatile cystic lesion in the region of the superficial temporal artery. Treatment by excision of the aneurysm with ligation of the afferent and efferent arteries is curative. As this lesion may be mistaken clinically for an epidermal inclusion cyst, aneurysm should be included in the differential diagnosis prior to therapy.