Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus.

AIM: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. METHODS: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. RESULTS: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. CONCLUSION: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Acid rain on Acid soil: a new perspective.

Acid rain is widely believed to be responsible for acidifying soil and water in areas of North America and northern Europe. However, factors commonly considered to make landscapes susceptible to acidification by acid rain are the same factors long known to strongly acidify soils through the natural processes of soil formation. Recovery from extreme and widespread careless land use has also occurred in regions undergoing acidification. There is evidence that acidification by acid rain is superimposed on long-term acidification induced by changes in land use and consequent vegetative succession. Thus, the interactions of acid rain, acid soil, and vegetation need to be carefully examined on a watershed basis in assessing benefits expected from proposed reductions in emissions of oxides of sulfur and nitrogen.

Law and ethics at the border of viability.

The Supreme Court of Texas in the case of Miller v. HCA announced a rule in 2003 (118 s.w. 3d 758) that a physician attending the delivery of a severely premature infant may provide life-sustaining treatment for that infant under 'emergent circumstances' as a matter of law without first obtaining parental consent. This paper examines issues of law and ethics relevant to decisions about infant resuscitation at the border of viability. It is argued that there is typically no emergency when infants are delivered at 23 weeks gestation, and parents should be asked for informed consent before resuscitation in the delivery room.

D-Glucosamine-induced increase of the glycerol-containing lipids in growing cultures of human malignant epithelial cells.

D-Glucosamine was found to inhibit the growth of human malignant epithelial cells SW-839, HT-29, RT-4, and SK-OV-3 in culture in a process that was associated with significant increments in glycerol-containing lipids. Each cell line had a different sensitivity to the drug, but all four cell lines shared the same features in their response, i.e., dose-dependent (at concentrations of 1, 5, and 10 mM), noncytotoxic reductions in growth (minimum 30%, maximum 70%), and simultaneous 1.5-fold to sevenfold increases in lipid contents. Cells regained their normal growth and lipid patterns when glucosamine was removed. Glucosamine did not modify the lipid contents of cells in the late phase of culture when growth was minimal.

Time-dependent changes in protein kinase C distribution and disappearance in phorbol ester-treated human osteosarcoma cells.

To test directly whether protein kinase C activation is one of the required events leading to stimulation of prostaglandin production by bone cells, protein kinase C activity and prostaglandin E2 release were measured in monolayer cultures of the clonal human osteosarcoma cell lines G-292 and SaOS-2 after exposure to phorbol myristate acetate (PMA). Both cell lines have specific receptors for PMA but only G-292 cells respond with increased prostaglandin E2 production (M. A. Shupnik and A. H. Tashjian, Jr., J. Biol. Chem., 257: 12161-12164, 1982). The subcellular distribution of protein kinase C in both unstimulated osteosarcoma cell lines was similar; in an EDTA- and leupeptin-containing homogenization buffer, between 70 and 80% of the total enzyme activity was cytosolic. Short (less than 60 min) incubations with PMA induced marked decreases in cytosolic enzyme activity and parallel increases in particulate protein kinase C; thereafter, total measured cellular protein kinase C activity declined, mediated by decreases in both cytosolic and particulate protein kinase C specific activities. By 24 h cytosolic, particulate, and total protein kinase C activities were less than 10% of basal. Because the protein kinase C responses in both cell types were essentially the same, but only G-292 cells give a prostaglandin response to PMA, we conclude that protein kinase C activation by PMA is itself insufficient to stimulate prostaglandin E2 production and that the lack of a prostaglandin response in SaOS-2 cells cannot be explained by lack of protein kinase C activation.

Regulation of lipogenesis in adipocytes. Independent effects of thyroid hormones, cyclic AMP and insulin on the uptake of deoxy-D-glucose.

Thyroidectomy is known to enhance fat cell phosphodiesterase activity; as a result, the response to lipolytic hormones is markedly reduced. Thyroidectomy also stimulates overall lipogenesis and the uptake of glucose: the present experiments investigated whether there was a correlation between cyclic AMP and glucose uptake. The parameter measured was the transport and phosphorylation (uptake) of deoxy-D-glucose in the presence of two modifiers of the cyclic AMP pool: phosphodiesterase inhibitors and the analogue, dibutyryl cyclic AMP. The inhibition by methylxanthines and dibutyryl cyclic AMP of deoxy-D-glucose uptake observed, was the same in fat cells from normal and thyroidectomized rats: the latter nonetheless still maintained their enhanced glucose uptake. It was therefore concluded that thyroid hormones and cyclic AMP control this step by different, separate pathways. Insulin, well known for its lipogenic effect, enhanced deoxy-D-glucose uptake in fat cells from both normal and thyroidectomized rats to the same extent (about 40%). An additive effect of thyroidectomy and insulin on glucose uptake was thus demonstrated. These results imply that glucose uptake in the adipocyte is controlled by at least three factors: thyroid hormones, cyclic AMP and insulin, each of which can act independently. Maximum glucose uptake is achieved in the presence of a combination of low concentrations of cyclic AMP, of insulin, and in the absence of thyroid hormones.

Production of a monoclonal antibody by in vitro immunization that recognizes a native chondroitin sulfate epitope in the embryonic chick limb and heart.

We report the production of a monoclonal antibody (d1C4) by in vitro immunization that has immunoreactivity with a native chondroitin sulfate epitope in embryonic chick limb and heart. Murine lymphocytes were stimulated by direct exposure to unfixed, unsolubilized precartilage mesenchymal aggregates in high-density micromass culture derived from Stage 22-23 chick limb buds. Specificity of d1C4 reactivity was demonstrated by sensitivity of immunohistochemical staining to pretreatment with chondroitinase ABC or AC, preferential immunoreactivity with chondroitin-6-sulfate glycosaminoglycan (CS-C GAG) in ELISA, and competition of immunohistochemical staining with CS-C GAG. Immunohistochemical analysis of the expression of the d1C4 epitope revealed a striking localization of immunoreactivity in the extracellular matrix (ECM) of precartilage aggregates of chick limb mesenchyme in high-density micromass culture by 16 hr and the prechondrogenic limb core at Stage 23 in vivo. Immunoreactivity in both cultured limb mesenchyme and the embryonic limb continued through differentiation of prechondrogenic condensations into cartilage tissue. In the developing chick heart, d1C4 staining was found throughout the ECM of atrioventricular cushion tissue by Stage 25, but was localized to mesenchyme adjacent to the myocardium in the outflow tract cushions. There was an abrupt demarcation between d1C4-reactive intracardiac mesenchyme and unreactive extracardiac mesenchyme of the dorsal mesocardium in the Stage 22 embryo. This study demonstrates the efficacy of in vitro immunization of lymphocytes for the production of MAbs to native ECM constituents, such as CS-GAGs. Immunohistochemical data utilizing d1C4 suggest that CS-GAGs bearing this epitope may be important in early morphogenetic events leading to cartilage differentiation in the limb and valvuloseptal morphogenesis in the heart.

Cyclic AMP and lipogenesis in fat cells from thyroidectomized rats.

Thyroid hormones regulate lipid metabolism by affecting lipogenesis as well as lipolysis. The present paper discusses the way thyroidectomy induced an enhancement in lipogenesis in rat fat cells. The doubling in the conversion of glucose to CO2 and fatty acids seen after thyroidectomy was found to be due to a modification in the actual pathway of glucose metabolism: there was a preferential stimulation of the conversion of glucose to CO2 by the pentose cycle (utilisation of [1-14C]glucose) while the production of fatty acids and glyceride-glycerol proceeded, respectively, much more, or only slightly more, via the pathway of [6-14C]glucose metabolism. Studies employing the phosphodiesterase inhibitor MIX, or the cyclic AMP analogue, DBcAMP showed that the lipogenic process depends on cyclic AMP. As the stimulatory effect of thyroidectomy was not abolished, however, lipogenesis must be under the independent control of both cyclic AMP and absence of thyroid hormones. Insulin, a further mediator of lipogenesis was found to further enhance the already preexisting high conversion of glucose to CO2 in fat cells from thyroidectomized rats. It is concluded that at least three factors modify lipogenesis: thyroidectomy, cyclic AMP and insulin; each achieving its effect in an independent manner.

Paracentric inversion of chromosome 19 in three generations.

We observed a paracentric inversion of 19p in a 15-month-old white boy with developmental delay and mild facial anomalies. The inversion of 19p was also present in his phenotypically normal mother and maternal grandfather.

Firearm-related deaths in the United States and 35 other high- and upper-middle-income countries.

BACKGROUND: The Forty-Ninth World Health Assembly recently declared violence a worldwide public health problem. Improved understanding of cross-national differences is useful for identifying risk factors and may facilitate prevention efforts. Few cross-national studies, however, have explored firearm-related deaths. We compared the incidence of firearm-related deaths among 36 countries. METHODS: Health officials in high-income (HI) and upper-middle-income countries (UMI) with populations greater than one million were asked to provide data using ICD-9 codes on firearm-related homicides, suicides, unintentional deaths and deaths of undetermined intent, as well as homicides and suicides for all methods combined. Thirty-six (78%) of the 46 countries provided complete data. We compared age-adjusted rates per 100,000 for each country and pooled rates by income group and geographical location. RESULTS: During the one-year study period, 88,649 firearm deaths were reported. Overall firearm mortality rates are five to six times higher in HI and UMI countries in the Americas (12.72) than in Europe (2.17), or Oceania (2.57) and 95 times higher than in Asia (0.13). The rate of firearm deaths in the United States (14.24 per 100,000) exceeds that of its economic counterparts (1.76) eightfold and that of UMI countries (9.69) by a factor of 1.5. Suicide and homicide contribute equally to total firearm deaths in the US, but most firearm deaths are suicides (71%) in HI countries and homicides (72%) in UMI countries. CONCLUSIONS: Firearm death rates vary markedly throughout the industrialized world. Further research to identify risk factors associated with these variations may help improve prevention efforts.

Mobilization and collection of allogeneic peripheral blood progenitor cells for transplantation.

A median dose of 11 (6-17) microg G-CSF per kg and day was given to 96 (49 female, 47 male) healthy family donors in order to mobilize and to collect peripheral blood progenitor cells (PBPC) for allogeneic transplantation. Donor age was 36 (17-76) years. The leukocytes of the donors increased to 46 (12-115) x 10(9)/l on days 4-6 of G-CSF treatment with a median of 71 (2-657) CD34+ cells per microl, respectively. Female and older donors seem to have a lower response to G-CSF. About 32% of the donors suffered from side-effects of G-CSF requiring analgetics. A total of 197 stem cell aphereses were performed using the COBE Spectra cell separator. Median apheresis time was 225 (118-300) min processing 11.8 (5.7-20) l blood, collecting 5.3 (1.7-14.9) x 10(10) nucleated cells and containing 0.7 (0.1-3.7)% CD34+ cells. Severe citrate toxicity occurred in 5% of the donors. Retransfusion of autologous platelets post apheresis was necessary in 16% of the donors because of a platelet count <80 x 10(9)/l. An insufficient number of stem cells was collected in four female donors due to a very poor response to G-CSF. In conclusion, the collection of allogeneic G-CSF-mobilized PBPC is safe and effective. One or two aphereses were sufficient in 91% of the donors to achieve >4 x 10(6) CD34+ cells per kg. In 4% of the donors an additional bone marrow harvest or the use of an alternative donor was necessary because of a poor mobilization.

Patient education model for increasing handwashing compliance.

BACKGROUND: A review of the literature on handwashing has documented the absence of research on the education of the patient as an intervention model for changing staff behavior regarding handwashing compliance. The primary objective of this project was to conduct a prospective control study of the effect of patient handwashing education on staff compliance with handwashing. METHOD: A prospective, controlled, 6-week intervention/control study was performed in 4 community hospitals in South Jersey. Each hospital served as its own control. Patients were educated within 24 hours of admission about the importance of asking their health care workers to wash their hands. Soap usage and handwashing was calculated by bed-days. Patient follow-up was conducted through telephone interviews 2 weeks after discharge. RESULTS: The patient handwashing education model increased soap usage by health care workers an average of 34% (P =.021); this increase was consistent across hospitals regardless of the initial soap usage rates. Of the patients interviewed, 81% read the materials provided, 57% asked health care workers whether they had washed their hands, and 81% of this 57% said they received positive responses. CONCLUSIONS: For the first time, our findings document that education of patients regarding their role in monitoring handwashing compliance among health care workers can increase soap usage and handwashing and provide sustainable reinforcement of handwashing principles for health care workers.

The impact of an elementary school-based violence prevention program on visits to the school nurse.

INTRODUCTION: In Tucson, Arizona, an elementary school-based violence prevention program (PeaceBuilders) was implemented during the 1994-1995 school year. Anecdotal evidence from school nurses suggested that children were visiting the nurse less often following the implementation of the program. We examined nurses' logs to assess whether the program had an impact on visits to the school nurse. METHODS: For the school years 1993-1994 and 1994-1995, the weekly number of nurse visits for all reasons, all injuries, and injuries caused by fights in each of the four PeaceBuilders schools were compared with those for three control schools. As part of a planned evaluation, schools had been matched on demographic factors and randomly assigned as intervention or control schools. RESULTS: Between 1993-1994 and 1994-1995, the rate of visits/1,000 student days decreased 12.6% in the intervention schools while remaining unchanged in the comparison schools. The same trend was detected for injury-related visits. Rates of fighting-related injuries changed little in the intervention schools but increased 56.0% in the control schools. An analysis of covariance confirmed that injuries and visits to nurses decreased in intervention schools relative to control schools. CONCLUSIONS: These data indicate that in the intervention schools, injuries and visits to the school nurse decreased over the two-year period and that the intervention may have contributed to this change. They also suggest that visits to the school nurses' office may be a useful tool to evaluate some types of elementary school-based violence prevention programs.

The need for comprehensive and consistent treatment of the nitrogen cycle in nitrogen cycling and mass balance studies: I. Terrestrial nitrogen cycle.

A review of conceptual models that scientists use to characterize the nitrogen (N) cycle and to conduct N mass balance studies at global, regional and local scales is presented. Large uncertainties in processes and process rates make it difficult to conduct precise N mass balances and the dominant conceptual model has changed in recent decades. An earlier conceptual model recognized explicitly that human activities, especially agriculture, have both depleted terrestrial N and increased the fixation of atmospheric N in biologically available forms. The current conceptual model does not include adequate treatment of the depletion of the terrestrial N reservoir, the resulting transfer of N to the hydrosphere and atmosphere, or the cycling of terrestrial N below the plow layer. Thus, it delivers an unrealistically limited view of human influences on the N cycle. It is recommended that a comprehensive and consistent treatment of terrestrial N cycling be developed to better facilitate scientific explanation of historical N-related environmental changes and more closely balance N budgets on a range of geographical and temporal scales. Improved N-cycle models will provide an improved scientific basis for answering important resource management and policy questions.

Trends in suicide ideation and suicidal behavior among high school students in the United States, 1991-1997.

To examine trends in suicide ideation and behavior over time, the authors analyze data from nationally representative samples of between 10,904 and 16,296 students participating in the 1991, 1993, 1995, and 1997 Youth Risk Behavior Surveys. These data describe the proportion of United States students in grades 9 through 12 that reported having (1) seriously considered attempting suicide, (2) made a plan to attempt suicide, (3) attempted suicide, and (4) made an injurious suicide attempt. From 1991 to 1997, the percentage of students seriously considering suicide and the percentage that made a suicide plan showed significant linear decreases. However, the percentage of students that made an injurious suicide attempt showed a significant linear increase. These trends make it unlikely that relevant national health objectives for the year 2000 will be met. Additional efforts are needed to identify and disseminate strategies that effectively reduce suicidal thoughts and behaviors among adolescents.

Suicide among adolescents and young adults: a cross-national comparison of 34 countries.

Few cross-national reports have examined suicide rates among adolescents and young adults. A survey of suicides among 15-24-year-olds in 34 of the wealthiest nations demonstrated that 15,555 youths killed themselves in a 1-year study period. Thirty-four percent of these suicides were firearm-related. Finland led the participating nations in total and firearm-related suicide rates. An association was found between divorce rates and youth suicide rates, firearm-related suicide among youths, and suicide rates among young males. For a smaller sample of countries, an association was found between firearm availability and firearm-related suicide rates among youths and suicide rates among young males.

Nurses' logs as an evaluation tool for school-based violence prevention programs.

Programs for preventing violence among youth should be evaluated to determine if they are effective. Nurses' logs appear to be a useful tool for evaluating school-based violence prevention programs. The logs provide a record of students' visits to the school nurse that can be used to determine if a violence prevention program is associated with a reduction in fighting- and other injury-related nurse visits. This method has many strengths: it is simple and inexpensive, it does not interrupt the school routine, it permits school-level rather than student-level data collection, it provides a ready "baseline," and it allows continuous data collection. However, potential limitations do exist. For example, the method may provide insufficient information and may be affected by factors unrelated to the intervention. School officials can increase the usefulness of the logs by encouraging standardization and providing training in their use.

Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: steps towards an international consensus.

Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.