A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6): study protocol for a pragmatic, multicentre, parallel-group, three-arm randomised controlled trial.

BACKGROUND: Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection. Full (high) compression therapy delivering 40 mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages. There is good evidence for the clinical and cost-effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost-effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost-effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers. METHODS: VenUS 6 is a pragmatic, multi-centre, three-arm, parallel-group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive (1) compression wraps, (2) two-layer bandage or (3) evidence-based compression (two-layer hosiery or four-layer bandage). Participants will be followed up for between 4 and 12 months. The primary outcome will be time to healing (full epithelial cover in the absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g. healing of the reference leg, ulcer recurrence, ulcer/skin deterioration, amputation, admission/discharge, surgery to close/remove incompetent superficial veins, infection or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use. DISCUSSION: VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration. VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres. TRIAL REGISTRATION: ISRCTN67321719 . Prospectively registered on 14 September 2020.

Risk of Catastrophic Health Expenditure in Rwandan Surgical Patients with Peritonitis.

BACKGROUND: Surgical procedures are cost-effective compared with various medical and public health interventions. While peritonitis often requires surgery, little is known regarding the associated costs, particularly in low- and middle-income countries. The aim of this study was to determine in-hospital charges for patients with peritonitis and if patients are at risk of catastrophic health expenditure. METHODS: As part of a larger study examining the epidemiology and outcomes of patients with peritonitis at a referral hospital in Rwanda, patients undergoing operation for peritonitis were enrolled and hospital charges were examined. The primary outcome was the percentage of patients at risk for catastrophic health expenditure. Logistic regression was used to determine the association of various factors with risk for catastrophic health expenditure. RESULTS: Over a 6-month period, 280 patients underwent operation for peritonitis. In-hospital charges were available for 245 patients. A total of 240 (98%) patients had health insurance. Median total hospital charges were 308.1 USD, and the median amount paid by patients was 26.9 USD. Thirty-three (14%) patients were at risk of catastrophic health expenditure based on direct medical expenses. Estimating out-of-pocket non-medical expenses, 68 (28%) patients were at risk of catastrophic health expenditure. Unplanned reoperation was associated with increased risk of catastrophic health expenditure (p < 0.001), whereas patients with community-based health insurance had decreased risk of catastrophic health expenditure (p < 0.001). CONCLUSIONS: The median hospital charges paid out-of-pocket by patients with health insurance were small in relation to total charges. A significant number of patients with peritonitis are at risk of catastrophic health expenditure.

Small babies on a small island: survival of very low birthweight infants in Antigua and Barbuda 1986 to 2006.

INTRODUCTION: Recent attention has been focussed on pregnancy outcomes in developing countries, with the publication of the World Health Organization Report 2005, Make Every Mother and Child Count and the Neonatal Survival Series from the Lancet in 2005. Scant outcome data from the smaller islands of the Caribbean exist for very low birthweight (VLBW) babies (birthweight < 1500 g). PATIENTS AND METHODS: A retrospective review of mortality data on VLBW babies in Antigua and Barbuda was performed. Antigua and Barbuda had a population of 71 500 with per capita income of (US) $6054 dollars in 1998. In November 1985, a neonatal Special Care Nursery (SCN) was established. The survival to discharge from SCN for VLBW babies was reviewed from January 1986 to December 2006. RESULTS: There were 26 455 babies born from 1986 to 2006; 344 (1.3%) were VLBW babies. Survival to SCN discharge was 45% from 1986 to 1992, 46% from 1993 to 1999, and increased to 60% from 2000 to 2006 (p < 0.05 compared with the first two time-periods). Babies from 1000 to 1499 g accounted for 64% of VLBW babies and survival to SCN discharge was 60% from 1986 to 1992, 58% from 1993 to 1999, and increased to 83% from 2000 to 2006 (p < 0.01 compared with the first time period; p < 0.001 compared with the second). Babies < 1000g accounted for 36% of VLBW babies and survival to SCN discharge was 10% from 1986 to 1992, increased to 25% from 1993 to 1999 and to 28% from 2000 to 2006 (trend of p < 0.10 compared with first time period). Conservative newborn care only was available. Antenatal steroids were given from 2000 to 2006. CONCLUSION: The outlook for VLBW babies using conservative newborn care techniques has significantly improved over 21-years in Antigua and Barbuda.

Small babies on a small island: survival of very low birthweight infants in Antigua and Barbuda 1986 to 2006 / Bebés pequeños en islas pequeñas: supervivencia de infantes con muy bajo peso al nacer en Antigua y Barbuda, de 1986 a 2006

INTRODUCTION: Recent attention has been focussed on pregnancy outcomes in developing countries, with the publication of the World Health Organization Report 2005, Make Every Mother and Child Count and the Neonatal Survival Series from the Lancet in 2005. Scant outcome data from the smaller islands of the Caribbean exist for very low birthweight (VLBW) babies (birthweight < 1500 g). PATIENTS AND METHODS: a retrospective review of mortality data on vlbw babies in antigua and barbuda was performed. antigua and barbuda had a population of 71 500 with per capita income of (us) $6054 dollars in 1998. in november 1985, a neonatal special care nursery (scn) was established. the survival to discharge from scn for vlbw babies was reviewed from january 1986 to december 2006. RESULTS: there were 26 455 babies born from 1986 to 2006; 344 (1.3%) were vlbw babies. survival to scn discharge was 45% from 1986 to 1992, 46% from 1993 to 1999, and increased to 60% from 2000 to 2006 (p < 0.05 compared with the first two time-periods). babies from 1000 to 1499 g accounted for 64% of vlbw babies and survival to scn discharge was 60% from 1986 to 1992, 58% from 1993 to 1999, and increased to 83% from 2000 to 2006 (p < 0.01 compared with the first time period; p < 0.001 compared with the second). babies < 1000g accounted for 36% of VLBW babies and survival to SCN discharge was 10% from 1986 to 1992, increased to 25% from 1993 to 1999 and to 28% from 2000 to 2006 (trend of p < 0.10 compared with first time period). conservative newborn care only was available. antenatal steroids were given from 2000 to 2006. CONCLUSION: the outlook for vlbw babies using conservative newborn care techniques has significantly improved over 21-years in antigua and barbuda.

INTRODUCCIÓN: Recientemente se ha centrado la atención en los resultados del embarazo en los países en vías de desarrollo, a partir de la publicación del Informe 2005 de la Organización Mundial de la Salud, Que cada madre y cada niño cuente y la Serie de Supervivencia Neonatal de la Lancet en 2005. Son escasos los datos de resultados existentes en las islas más pequeñas del Caribe, acerca de los bebés con muy bajo peso al nacer (MBPN) (peso al nacer < 1500 g). PACIENTES Y MÉTODOS: se llevó a cabo una revisión retrospectiva de datos sobre la mortalidad de bebés mbpn en antigua y barbuda. antigua y barbuda tenían una población de 71 500 con un ingreso per cápita de $6054 usd en 1998. en noviembre de 1985, se creó una sala de cuidados especiales del Recién Nacido (SCN). La supervivencia en término de los bebés MBPN dados de alta de la SCN fue examinada de enero de 1986 a diciembre de 2006. RESULTADOS: De 1986 a 2006, hubo 26 455 bebés nacidos; de ellos 344 (1.3%) fueron bebés MBPN. La supervivencia en término de las altas de la SCN fue de 45% de 1986 a 1992, 46% de 1993 a 1999, y aumentó a 60% de 2000 a 2006 (p <0.05 en comparación con los primeros dos períodos de tiempo). Los bebés de 1000 a 1499g representaron el 64% de los bebés MBPN y la cifra de los supervivientes dados de alta del SCN fue de 60% de 1986 a 1992, 58% de 1993 a 1999, y aumentó a 83% de 2000 a 2006 (p < 0.01 en comparación con el primer periodo de tiempo; p <0.001 en comparación con el segundo). Los bebés <1000 g representaron el 36% de los bebés MBPN, y la supervivencia en términos de los dados de alta de la SCN fue 10% de 1986 a 1992, aumentó a 25% de 1993 a 1999, y a 28% de 2000 a 2006 (la tendencia de p <0.10 en comparación con el primer periodo de tiempo). Sólo hubo disponible atención neonatal conservadora Se administraron esteroides antenatales desde el año 2000 al 2006. CONCLUSIÓN: El pronóstico para MBPN usando técnicas de cuidado neonatal conservadoras ha mejorado significativamente a lo largo de 21 años en Antigua y Barbuda.

Predicting within-family variability in juvenile height growth of Salix based upon similarity among parental AFLP fingerprints.

Willow is being developed as a crop for biomass plantations in the Northeast and North-central United States, but has only recently been the subject of controlled breeding to generate improved genotypes. Maximizing variability among progeny within full-sib families produced by controlled pollination may increase the probability of producing willow clones exhibiting desirable extreme phenotypes. Yet, predicting combinations of parents yielding highly variable progeny is not currently possible. Controlled pollinations were completed among 15 Salix eriocephala clones and the resulting progeny were vegetatively propagated and planted in a greenhouse progeny test. Heights of rooted cuttings were measured after 4 months of growth. Genetic similarity among parents was estimated based on 77 polymorphic AFLP bands. Strong negative correlation ( r = -0.88) was detected between mean female-parent similarity indices and the standard deviation of height among half-sib progeny from those females. Parent combinations that had relatively low similarity indices tended to produce progeny that had greater variability in height. This negative relationship suggests that AFLP fingerprints of S. eriocephala parents may be useful for predicting parent combinations that will yield families with large variability.

Bimolecular kinetic studies with high-temperature gas-phase 19F NMR: cycloaddition reactions of fluoroolefins.

A gas-phase NMR kinetic technique has been used for the first time to obtain accurate measurements of rate constants of some bimolecular, second-order cycloaddition reactions. As a test of the potential use of this technique for the study of second-order reactions, the rate constants and the activation parameters for the cyclodimerization reactions of chlorotrifluoroethylene (CTFE) and tetrafluoroethylene (TFE) were determined in the temperature range 240-340 degrees C, using a commercial high-temperature NMR probe. Obtaining excellent agreement of the results with published data, the technique was then applied to the reaction of 1,1-difluoroallene with 1,3-butadiene, the results of which indicate that the use of gas-phase NMR for reaction kinetics is particularly valuable when a reagent is available only in small amounts and in cases where there are several competing processes occurring simultaneously. The major processes observed in this reaction are regioselective [2+2] and [2+4] cycloadditions, whose rates and activation parameters were determined [k2 = 9.3 x 10(6) exp(-20.1 kcal x mol(-1)/RT) L/mol(-1) x s(-1) and k3 = 1.2 x 10(6) exp(-18.4 kcal x mol(-1)/RT) L/mol(-1) x s(-)(1), respectively] in the temperature range 130-210 degrees C.

The molecular basis and treatment of primary immunodeficiency disorders.

Over the past decade, a number of important advances have been made in the molecular characterization and the treatment of the primary immunodeficiency disorders. These advances include identification of the abnormal genes responsible for such syndromes as X-linked severe combined immune deficiency, several forms of autosomal severe combined immune deficiency, X-linked and autosomal agammaglobulinemia, Wiskott-Aldrich syndrome, and other primary immunodeficiency disorders. In the past year, the biologic functions of the abnormal gene products responsible for these syndromes have been better defined, and new molecular defects that lead to primary immunodeficiency disorders have also been reported. This better understanding of the molecular basis of the primary immunodeficiency disorders has led to improvement of established therapies, such as gene product replacement and stem cell transplants, and to new treatment strategies, such as gene therapy.

Fault and the allocation of spare organs.

This paper argues that rectificatory justice should supplement distributive justice in allocating priority of access to scarce medical resources. Where a patient is at fault for the scarcity of healthy organs a principle of restitution requires that she should give priority to the faultless. Such restitution is non-punitive, and is akin to reparation in civil law, not criminal law. However, it is doubtful whether such a principle can be fairly applied within the present culture of governmental complicity in cigarette advertising.

Substance P and adrenocorticotropic hormone do not affect T-lymphocyte adhesion to vascular endothelium or surface expression of adhesion receptors.

Substance P (SP) and adrenocorticotropic hormone (ACTH) are peptides that have been shown to have both neurological and immunological effects. Because of the demonstrated effects upon immune function, we examined the effects of these peptides on T-lymphocyte adhesion to vascular endothelium and surface adhesion receptor expression. Neither the adhesion assays nor the expression assays showed any statistically significant effect of SP (10 microM) or ACTH (1 microM) for any incubation period used. We conclude that, while SP and ACTH have a variety of immunomodulatory effects, direct modulation of T-lymphocyte adhesion to vascular endothelium is probably not one of them.

Age-related increase in phorbol myristate acetate-induced lymphocyte adhesion to vascular endothelium.

Lymphocyte adhesion to vascular endothelium is an important part of immune function. This investigation sought to detect differences between the adhesion of lymphocytes from young and aged human donors to vascular endothelium with and without treatment of the lymphocytes with phorbol myristate acetate (PMA), an activator of protein kinase C (PKC) that stimulates this adhesive process. T-lymphocytes were isolated from young and aged donors and adhesion assays were conducted with human umbilical vein endothelial cells (HUVEC). In some cases the HUVEC were activated by pre-incubation with tumor necrosis factor, a cytokine that increases their adhesiveness, before the addition of lymphocytes in the presence or absence of PMA. The results show that, in the basal state, lymphocytes from young and aged donors had similar levels of adherence, while with PMA activation, lymphocytes from aged donors had a significantly higher level of adherence to both activated and non-activated HUVEC. No cytotoxic effect on the HUVEC was detected. These results suggest a role for lymphocytes in diseases that predominantly affect the elderly and that are thought to involve interaction between lymphocytes and endothelium. In addition, these results indicate that there may be a change in PKC function in lymphocytes with aging.

Industry as a metabolic activity.

The concept of "industrial economic metabolism" can provide a bridge to better understanding between environmentalists and industry. In nature each individual or species reacts to natural stimuli, competing with others for resources, extending its domain until it loses comparative advantage and comes to equilibrium with an adjacent competitor. Those species that succeed over time flourish; those that do not, diminish or disappear. Nature's rule book has no moral or ethical ingredient beyond self-interest. Corporate metabolisms are remarkably similar to those of nature. They too react to stimuli, collect and use resources, and grow or perish based on how effectively they compete. Corporate management recognizes and responds naturally and efficiently to cost and price signals. Through them it selects resources and converts them into useful products. The efficiency with which this is done is measured by profit, the lifeblood of the corporation and its means of growth. Profit thus provides a discipline on corporate behavior, encouraging efficient performers, and, by its absence, weeding out others. Unfettered by influences other than economics, the path to corporate success is unlikely to be a compassionate one. The dilemma of the manager is that to do what is socially "right" often conflicts with what must be done to survive and prosper. Fortunately, corporations' behavior can be altered by society when their purely economic role comes into conflict with other human values. The environment and the economy are not separate systems but intertwined to form a complex natural and social setting. The human-designed economic system depends on natural resource inputs, and in turn its metabolic wastes can overload the ecological system, threatening the long-term survivability of both. Increasing concern for the environment now gives the farsighted manager new latitude. There are competitive benefits in some pollution prevention. But there are not sufficiently strong forces to correct all current ills. In addition, we must harness the metabolism of the industrial world to the realities of the natural one by recognizing the immense value of depletable natural resources and ecosystems. Considering these resources as "cheap" or "free" encourages their overuse. What is needed are adjustments that price these resources at their true longterm value. Corporations will respond naturally, quickly, and efficiently to such signals. If we can send our metabolic industry the economic signals it can understand, we can retrofit our human economic system to live in harmony with the natural ecosystem of which we are a part. If we do not, nature assuredly will not accommodate our failure by changing its ways.

Regional distribution of neuropeptide gamma and other tachykinin peptides derived from the substance P gene in the rat.

Substance P (SP) and multiple neurokinin A (NKA)-related peptides can be derived from alpha-, beta- and/or gamma-preprotachykinin (PPT) mRNAs. In this study, the relative concentrations of the tachykinin peptides derived from the SP gene in rat brain, duodenum, jejunum, submandibular gland, parotid gland, urinary bladder and vas deferens was determined using high-performance liquid chromatography (HPLC) and radioimmunoassays (RIAs). In all tissues, SP levels were the highest. The relative abundance of NKA-related peptides was NKA greater than neuropeptide gamma (NP gamma) = neuropeptide K (NPK) greater than NKA(3-10). These results demonstrate that multiple tachykinin peptides are present in tissues where the SP gene is expressed, and that the NKA portion of the beta- and gamma-PPT precursors can be differentially processed posttranslationally in rat tissues into NKA, NPK, NP gamma and/or NKA(3-10).