Improved outcomes found after implementing a systematic evaluation and program improvement process for tuberculosis.

California's state and local tuberculosis (TB) programs collaborated to develop the Tuberculosis Indicators Project (TIP), a program evaluation and improvement process. In TIP, local and state staff review data, identify program gaps, implement plans to improve local TB program performance, and evaluate outcomes. After 10 years of project implementation, indicator performance changes and patient outcomes were measured. Eighty-seven percent of participating programs showed a performance increase in targeted indicators after three years compared with 57% of comparison groups. Statistically significant performance change was more common in the intervention local health departments (LHDs) than in comparison groups. The most notable performance changes were in the contact investigation and case management indicators. These results indicate that this systematic evaluation and program improvement project was associated with improved LHD TB control performance and may be useful to inform improvement projects in other public health programs.

Developing and using performance measures based on surveillance data for program improvement in tuberculosis control.

California state and local tuberculosis (TB) programs used a systematic process to develop a set of indicators to measure and improve program performance in controlling TB. These indicators were the basis for a quality improvement process known as the TB Indicators Project. Indicators were derived from guidelines and legal mandates for clinical, case management, and surveillance standards and were assessed using established criteria. The indicators were calculated using existing surveillance data. The indicator set was field tested by local programs with high TB morbidity and subsequently revised. Collaboration with key stakeholders at all stages was crucial to developing useful and accepted indicators. Data accessibility was a critical requirement for indicator implementation. Indicators most frequently targeted for performance improvement were those perceived to be amenable to intervention. Indicators based on surveillance data can complement other public health program improvement efforts by identifying program gaps and successes and monitoring performance trends.

Industrial surface impoundments: environmental settings, release and exposure potential and risk characterization.

This paper presents the results of a national scale evaluation of the environmental impact of surface impoundments that contain non-hazardous wastewaters. In the 1990s, it was found that approximately 18,000 surface impoundments existed in the US for treating, storing or disposing of non-hazardous wastewater. In this study, the focus was on the subset of 11,900 impoundments that contain at least one of 256 chemicals of interest or high or low pH wastewater. Questionnaires were sent to facilities chosen in a two-phase nationally representative random sample. The nature, extent and use of surface impoundments across manufacturing industries were characterized using the information collected in the survey. Also, the chemical composition of impounded wastewaters; the potential for chemical releases to the environment from the impoundments; and the risk from these releases were assessed. It is estimated that only approximately 5-6% of facilities with impoundments have the potential to pose risks to human health, although approximately 19-46% of facilities with impoundments release chemicals of concern to the environment. The information in this study should help environmental managers evaluate and avoid those risk factors that have the potential to result in environmental harm, particularly when present in combination.

Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers.

UNLABELLED: Bilayered living human skin equivalent (HSE) consists of cultured keratinocytes residing on the surface of a fibroblast-populated collagen lattice. Although HSE is FDA-approved for treatment of diabetic foot and venous stasis ulcers, its clinical efficacy remains limited, because the molecular mechanisms underlying its therapeutic effect are not fully understood. It is, therefore, often applied mistakenly as a skin graft. In this report, we delineate a mechanism of HSE biological effect and consequent optimal clinical use in accelerating closure of diabetic foot ulcers. EXPERIMENTAL: HSE was grafted onto nude mice and the release of various growth factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Clinical: HSE was grafted onto 11 consecutive patients with diabetes who had 13 non-ischemic foot ulcers and healing was measured as time to 100% closure (e.g., no drainage and 100% epithelialized). EXPERIMENTAL: HSE cellular components were determined to express 15 different growth factors/cytokine genes known to promote wound healing. Histological evidence from the nude mice showed that the collagen component of HSE underwent remodeling within the first seven days of grafting. Clinical: All diabetic foot ulcers healed in 31.8 12.4 days. Local release of a unique combination of 15 growth factors expressed by HSE keratinocyte and fibroblast components generates closure of diabetic foot ulcers. HSE should be applied with the same surgical conditions for a skin graft (i.e., no cellulitis, no drainage, and negligible bacteria). We hypothesize that bilayered HSE generates its effect by way of the local synthesis and release of multiple growth factors in specific combination and concentration, which improves the impaired reparative process of chronic wounds.

Wounding of bioengineered skin: cellular and molecular aspects after injury.

Skin substitutes are increasingly being used in the treatment of difficult to heal wounds but their mechanisms of action are largely unknown. In this study, using histology, immunostaining, flow cytometry, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction, we determined the response to injury of a human bilayered skin substitute. Meshing or scalpel fenestration of the construct was found to stimulate keratinocyte migration and to decrease proliferation. By 24 h, flow cytometry of the keratinocyte component showed that meshing was associated with a 33% decrease in the number of cells in S phase (p < 0.01). An approximately 2-fold decrease in staining for Ki67, a proliferation marker, was observed with meshing of human bilayered skin substitute. The process of reepithelialization was apparent by 12 h, however, the wounded human bilayered skin substitute was healed by day 3, and a stratum corneum and fully stratified epithelium were re-established by day 4. Reverse transcription polymerase chain reaction analysis and enzyme-linked immunosorbent assays showed that the expression of acute proinflammatory cytokines (interleukins 1alpha, 6, and 8, tumor necrosis factor alpha) peaked by 12-24 h postinjury. The levels of mRNA of certain growth factors (transforming growth factor beta1, vascular endothelial growth factor, insulin-like growth factor 2) but not others (platelet-derived growth factors A and B, keratinocyte growth factor, fibroblast growth factors 1 and 7, transforming growth factor beta3) increased by 12 h and peaked by 1-3 d after injury, returning to normal by day 6. Immunostaining for tumor necrosis factor alpha and transforming growth factor beta1 paralleled these findings by reverse transcription polymerase chain reaction. We conclude that human bilayered skin substitute, as a prototypic bilayered skin substitute, is a truly dynamic living tissue, capable of responding to physical injury in a staged and specific pattern of cell migration, reepithelialization, and cytokine expression.

The longevity of a bilayered skin substitute after application to venous ulcers.

BACKGROUND: A bilayered skin substitute composed of allogeneic keratinocytes and fibroblasts in a collagen gel has been approved by the US Food and Drug Administration for the treatment of venous and diabetic ulcers. Its mechanism of action has not been fully determined. OBJECTIVE: To determine the longevity of allogeneic fibroblasts and keratinocytes in a bilayered skin substitute in patients with venous leg ulcers. METHODS: Ten patients with venous leg ulcers were treated with a bilayered skin substitute on day 0, days 3 to 5, and weeks 1 through 3. Biopsy specimens of the grafted wound were taken. We used polymerase chain reaction analysis to determine whether allogeneic DNA was present in the biopsy specimens. RESULTS: We detected allogeneic DNA in 2 of 8 specimens at 1 month after initial grafting. Neither of the 2 patients showed persistence of allogeneic DNA at 2 months after initial grafting. CONCLUSIONS: Allogeneic cells from a bilayered skin substitute do not appear to survive permanently after grafting for treatment of venous leg ulcers. Other mechanisms of action might include cytokine release, structural support, or provision of a moist wound environment.