Reforming care for persons near the end of life: the promise of quality improvement

Most people in developed countries will live with a serious, eventually fatal, chronic condition for months or years before dying; yet, the delivery of health care services has only just recently begun adapting to this reality. Quality improvement methods have been effective in helping clinical services to make substantial changes quickly. Quality improvement requires stating an aim, measuring success, and testing possible improvements. The testing of changes requires a clinical team to Plan, Do, Study, and Act on new insights (the "PDSA cycle"). Repeated PDSA cycles generate deep understanding of complex systems and make sustainable improvements rapidly. This paper discusses a composite case study in a nursing home setting, which builds on experience with multisite collaborative efforts and introduces quality improvement methods in the context of end-of-life care.     

Endocrinology trial design: adverse event reporting in randomised controlled trials of recombinant human GH in GH-deficient adults

We have evaluated the reporting of withdrawals due to adverse effects and specific adverse effects in randomised controlled trials of recombinant human GH in adults. A systematic review was carried out of randomised controlled trials of the clinical effectiveness of recombinant human GH in adults with GH deficiency in relation to impact on quality of life. Trials were identified from searching electronic databases, bibliographies of related articles and consulting experts. There was reporting of withdrawals due to adverse effects and specific adverse effects. Rates of oedema and arthralgia were reported in included trials. Seventeen randomised controlled trials, published between 1990 and 1999, met the inclusion criteria for the review. Nine trials reported data on the effectiveness of GH on quality of life in adults. Only five trials (29%) reported both withdrawals from the study because of adverse events and specific adverse events with numbers per study arm and per type. Six further trials (35%) reported either withdrawal details or specific adverse event details or partial data on specific adverse events. Six trials (35%), however, did not report information on either withdrawals or specific adverse events. Ten of the 17 studies (59%) reported the number of patients who withdrew from the study due to adverse events per study arm and type of adverse event per study arm. Seven of the 17 trials (41%) reported the number of specific adverse events per study arm and six (35%) reported the type per study arm. The reporting of adverse events in randomised controlled trials of GH is variable and not consistent across trials. It is not possible to assess the impact that adverse events may have had on unblinding patients, and therefore the extent to which the effects of GH may have been overestimated. Therefore those conducting endocrinology trials in the future need to pay attention to the reporting of withdrawals due to adverse events and specific adverse events.     

Blunt traumatic aortic transection: the endovascular experience

BACKGROUND: Thoracic aortic transection resulting from blunt trauma is usually fatal. It is almost always associated with multiple, complex, nonaortic injuries that could be adversely affected by standard surgical repair of the aorta. Endovascular stenting techniques offer these patients a less physiologically disruptive treatment option. We studied the feasibility and safety of endovascular stent graft placement for treatment of acute traumatic aortic transection. METHODS: Between 1994 and 2001, 9 patients were treated emergently for aortic transections with stent graft placement. The first patient had a custom-made prototype, and the other 8 patients had the Cook-Zenith thoracic stent graft implanted. All were polyester-covered Z-stent construction and deployed through a femoral 20- to 24-F delivery sheath. RESULTS: Stent graft placement successfully sealed the aorta in all patients. One patient died as a result of a cerebrovascular accident. One patient required a brachial thrombectomy to relieve arm ischemia. The remaining eight patients were alive and without complications during the follow-up period (mean 21 months). CONCLUSIONS: Endovascular repair for acute aortic transection is a safe, effective, and timely treatment option. It may be the treatment of choice in patients with extensive associated injuries.     

Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches

OBJECTIVES: To analyze sources searched in Cochrane reviews, to determine the proportion of trials included in reviews that are indexed in major databases, and to compare the quality of these trials with those from other sources. METHODS: All new systematic reviews in the Cochrane Library, Issue1 2001, that were restricted to randomized controlled trials (RCTs) or quasi-RCTs were selected. The sources searched in the reviews were recorded, and the trials included were checked to see whether they were indexed in four major databases. Trials not indexed were checked to determine how they could be identified. The quality of trials found in major databases was compared with those found from other sources. RESULTS: The range in the number of databases searched per review ranged between one and twenty-seven. The proportion of the trials in the four databases were Cochrane Controlled Trials Register = 78.5%, MEDLINE = 68.8%, Embase = 65.0%, and Science/Social Sciences Citation Index = 60.7%. Searching another twenty-six databases after Cochrane Controlled Trials Register (CCTR), MEDLINE, and Embase only found 2.4% additional trials. There was no significant difference between trials found in the CCTR, MEDLINE, and Embase compared with other trials, with respect to adequate allocation concealment or sample size. CONCLUSIONS: There was a large variation between reviews in the exhaustiveness of the literature searches. CCTR was the single best source of RCTs. Additional database searching retrieved only a small percentage of extra trials. Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials.     

Co-localization of matrix metalloproteinase-1 and mast cell tryptase in the human uterus

The endometrium displays characteristic cyclical changes involving proliferation and differentiation. The differentiation that takes place requires major tissue remodelling involving the matrix metalloproteinase (MMP) family as key enzymes in this process. Mast cells, containing the tryptase and chymase enzymes that are capable of stimulating the MMP cascade, have been identified in the endometrium, but their role is still unclear. In this study, we observed that the majority of mast cells in the uterus reside in the myometrium and that they co-express mast cell tryptase and MMP-1 in the same intracellular granules. In endometrium exposed to synthetic progestogen via an intrauterine levonorgestrel system a significant increase in mast cells numbers was observed in women experiencing breakthrough bleeding compared to those in women with no reported bleeding. We conclude that mast cells contain MMP-1 and we postulate a potential role for mast cells in breakthrough bleeding.     

The influence of acetoacetate and butyrate on calcium influx and ATP concentrations in HT-29 cells

The effects of acetoacetate and butyrate on Ca(2+)-influx in HT-29 cells were unknown. Extracellular signals can be transferred to the intracellular environment of the cell via changes in the Ca(2+)-concentration. Extracellular Ca2+ may enter the cell via Ca(2+)-channels in the plasma membrane. Physiological processes occurring within the cell are dependent on Ca(2+)-concentration, including enzyme activity. Intracellular Ca(2+)-concentrations were measured using Fura-2/AM, a fluorescent intracellular Ca(2+)-probe. Ca(2+)-concentrations were measured immediately on application of the inducers to the cells, as well as after a 9 day incubation period. The effect of these inducers on the L-type voltage-operated Ca(2+)-channels were determined using the whole-cell patch-clamp technique. To validate these results for the intestinal epithelial model, membrane current studies were performed on HT-29 cells grown on a polycarbonate membrane. ATP concentrations were measured, and the theoretical effect of the inducers on PDE 4 activity was determined. It was found that both acetoacetate and butyrate blocked Ca(2+)-influx through the L-type voltage-operated Ca(2+)-channels, resulting in the initial low Ca(2+)-concentration (p < 0.05). The blockage effect is short-lived as after a 9 day incubation period in the presence of the inducers, Ca(2+)-concentrations were higher than that of the HT-29 control sample (p < 0.05). ATP concentrations of the cells were decreased in the presence of the inducers (p < 0.05), whilst it was suggested that no interaction between the catalytic site of PDE 4 and the inducers existed.     

Reduced sun exposure and tanning in children after 2 years of a school-based intervention (Australia)

Objective: This paper presents the results of the evaluation of measured suntan and parent-reported sun exposure in participating children after 2 years of the Kidskin study, a 5-year school-based sun protection intervention undertaken in Perth, Western Australia (1995–1999). Methods: The study involves three groups: a control, a moderate, and a high intervention group. Participants were 5 or 6 years of age at the beginning of the study. Control schools received the standard Health Education curriculum, while intervention schools received a multicomponent intervention including a specially designed curriculum. Children in the high intervention group also received program materials over the summer vacation and were offered sun-protective swimwear at low cost. At the end of the second summer, suntan was measured and parents completed a questionnaire about their child's sun-related behavior. Results: Children in the intervention groups – especially the high group – were less tanned at the end of the summer; this effect was greater for the back than for the forearms. These children were also reported to have received less sun exposure and made greater use of sun protection measures. Conclusion: Intensive school-based interventions can reduce tanning and reported sun exposure in children.     

Interaction of imipenem with erythromycin and tetracycline assessed by microdilution checkerboard techniques.

Microdilution methodology was used to study the interaction of imipenem with erythromycin and tetracycline, a combination therapy that might be used for the treatment of serious pelvic inflammatory disease. The combination of imipenem and erythromycin showed no antagonism for Escherichia coli and Haemophilus influenzae but was antagonistic for Staphylococcus aureus, Enterococcus faecalis, and group B streptococci; the combination of imipenem and tetracycline was antagonistic for all strains except H. influenzae. Correlation between the results of kill curves and the measurement of fractional bactericidal concentration (FBC) indices was good, although FBC indices showed less antagonism than kill curves. Fractional inhibitory concentration indices showed poor correlation, rarely showing antagonism, and indeed showed synergy in three cases. If erythromycin or tetracycline is considered necessary in addition to imipenem in the treatment of pelvic inflammatory disease, it is probably more effective when given after the course of imipenem has been completed.