Academic surgeons' knowledge of Food and Drug Administration regulations for clinical trials.

OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels. DESIGN: Survey of surgical department faculty members in 20 universities. RESULTS: Sixty-five responses were received from 14 sites. Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The best predictor of overall score was being a primary investigator of a clinical trial (P < .001), followed by being or having been a member of an IRB (P < or = .02). The total mean score of members of the Surgical Infection Society (8.2 +/- 0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a phenomenon not observed with other surgical societies. In certain hypothetical clinical scenarios, all respondents were mistakenly willing to conduct clinical trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB member respondents and 16 (25%) of the 65 respondents were willing to conduct human research without appropriate approval from patients, the IRB, or both. CONCLUSIONS: Knowledge deficits exist in the academic surgical community about the role and requirements of the FDA and local IRBs for conducting clinical research. Further study is required to determine the reasons for this deficit and to identify appropriate interventions.

Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns.

OBJECTIVE: Two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated. SUMMARY BACKGROUND DATA: Growth hormone has been shown to reduce wound healing times in burned pediatric patients. Through genetic engineering, several different forms have been synthesized; however, not all are marketed currently. Two forms of growth hormone were used in these studies, Protropin (Genentech, Inc., San Francisco, CA), a commercially available product that possesses a N-terminal methionine residue not found in the second form Nutropin (Genentech, Inc., San Francisco, CA), which, as yet, is not commercially available. Through the use of recombinant human growth hormone, rapid wound healing may reduce the hypermetabolic period, the risk of infection, and accelerate the healing of donor sites used for grafting onto burned areas. The two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children. METHODS: Forty-six children, with a > 40% total body surface area and > 20% total body surface area full-thickness burn were entered in a double-blind, randomized study to receive rhGH within 8 days of injury. Twenty received (0.2 mg/kg/day) Nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision. Eighteen patients who failed the entry criteria for receiving Nutropin received Protropin therapeutically (0.2 mg/kg/day). Donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with Scarlet Red impregnated fine mesh gauze (Sherwood Medical, St. Louis, MO). The initial donor site healing time, in days, was reached when the gauze could be removed without any trauma to the healed site. RESULTS: Donor sites in patients receiving Nutropin (n = 20) or Protropin (n = 18) healed at 6.8 +/- 1.5 and 6.0 +/- 1.5 (mean +/- SD) days, respectively, whereas those receiving placebo (n = 26) had a first donor site healing time of 8.5 +/- 2.3 days. Both groups receiving rhGH showed a significant reduction in donor site healing time compared with placebo at p < 0.01. When subgroups were compared, no difference in healing times could be shown with regards to age or time of admission after injury. CONCLUSION: Our results indicate that both forms of rhGH are effective in reducing donor site healing time compared with placebo and suggest that accelerating wound healing is of clinical benefit because the patients' own skin becomes rapidly available for harvest and autografting. With this increase in the rate of wound healing, the total length of hospital stay can be reduced by more than 25%.

Recent advances in burn care.

Over the past few decades, the mortality related to thermal injuries has been significantly reduced. This has been accomplished through an increased understanding and subsequent management of inhalation injury, the postburn hypermetabolic response, and immunocompromise. In addition, the prompt excision of the burn wound and early permanent closure has decreased the length of hospital stay and has facilitated timely social reintegration of the burned patient.

Management of perineal and genital burns.

Burn injuries to the perineum and genitals present the bedside care provider with a unique set of management problems. Traditionally, thermal injuries to these areas have been allowed to close by secondary intention, with epithelialization occurring from remnants protected within skin folds. Partial-thickness wounds of the perineum and genitals must be kept clean and free of bacterial infection to prevent necrosis and development of full-thickness injury. Although full-thickness thermal injuries to the penis and vulva are rare, they require special attention during the immediate postgrafting period to ensure complete engraftment. Control of scarring in this area requires tailor-made pressure garments, with customized inserts to provide controlled pressure to the skin folds.

Thermal injuries caused by ignition of volatile substances by gas water heaters.

Based on the cumulative data of this tertiary care facility over the past 25 years, one out of every 70 pediatric patients admitted to our institution sustained their injuries during an explosive event instigated by the ignition of volatile substances from gas water heaters. The majority of injuries related to gas water heaters can be prevented by decreasing the temperature setpoint of the heater, by protecting the heater element itself, and by elevating the water heater to 18 inches above the floor. The first two issues have been adequately addressed; however, gas-fueled water heaters continue to be installed at floor level. Current national guidelines are too rigid and do not adequately address water-heater installation in private residences. Although general prevention campaigns target appropriate storage of volatile substances, they rarely address the explosive potential of gas water heaters in combination with combustible fumes.

Management of the pediatric patient with burns.

Two million people in the United States receive medical treatment each year for burn injuries. One hundred thousand of these patients are hospitalized, and 7800 die as a direct result of their injuries. Of the patients that are hospitalized 30% to 40% are under 15 years of age. Sixty-seven percent are male. The average age of children with burns is 32 months. Flame burns account for approximately 13% of accidents, scalds account for 85%, and electrical and chemical burns account for approximately 2%. The majority of scald injuries are small. Sixteen percent of burn injuries are not accidental, and approximately half of these are a result of documentable, inflicted abuse.

Longitudinal hand grip and pinch strength recovery in the child with burns.

Hand strength of seven patients was evaluated prospectively. A range-of-motion exercise program, compression therapy, and splinting schedules were provided. Fine prehension; lateral, tip-to-tip, and tripod pinch were measured by pinch meter. Grip strength was measured by dynamometer. Comparisons were made between test strengths and published norms for age and sex with analysis of variance. Significance was accepted at p < 0.05. At discharge, all four strength measurements were significantly less than normal for age and sex. Grip and tripod strengths were improved by 6 weeks. All measurements were improved at 6 months after discharge, although grip and lateral pinch remained significantly less than norms. In conclusion, the measurements of tip-to-tip and tripod pinch at 6 months may not signify limitations in performance of activities of daily living. In spite of significantly lower than normal grip and lateral strength measurements at 6 months, it cannot be determined whether this hinders performance of daily living skills.

Effect of prostaglandin E on immune function in normal healthy volunteers.

Prostaglandin E (PGE) has been hypothesized to be the endogenous metabolite that results in the immunosuppression seen in patients with tumor and trauma. This has resulted in multiple investigators proposing that administration of PGE inhibitors, such as aspirin and indomethacin, might improve immune function in such patients. We administered a long acting PGE analog, misoprostol, to nine normal healthy volunteers for five days and assayed immune function before and after therapy. The PGE analog improved lymphocyte blastogenesis and increased tumor necrosis factor production. The PGE analog also resulted in the volunteers having symptoms similar to those seen in patients with sepsis. The results of these studies indicate that elevated levels of PGE do not seem to result in impairment of immune function, but may be the endogenous metabolite responsible for the symptologic factors seen in infected patients.

The effect of erythropoietin in normal healthy volunteers and pediatric patients with burn injuries.

BACKGROUND: Surgical procedures result in blood loss that can require replacement transfusions. Such therapy may result in multiple adverse sequelae, including transmission of infectious diseases and immune impairment. Alternative therapies are therefore desirable. METHODS: We evaluated the ability of recombinant human erythropoietin (rEPO) to increase red blood cell production in both normal healthy volunteers and patients with burn injuries. The effect of rEPO on immune function in the volunteers was also evaluated. The volunteers received 150 units/kg rEPO daily for 7 days, with immune function and hematopoiesis assayed on days 0, 7, and 14. The patients with burn injuries received either 500 units/kg/day rEPO with iron supplementation or merely the iron. RESULTS: rEPO increased erythropoiesis in both the volunteers and the patients with burn injuries. Failure to provide iron supplementation to the volunteers resulted in significant depletion of iron stores with a concomitant impairment in immune function that paralleled the iron depletion. CONCLUSIONS: rEPO therapy offers the potential to increase red blood cell production in surgical patients. Failure to provide iron supplementation in patients receiving rEPO can lead to a rapid depletion of iron stores and may contribute to an immune dysfunction.

Research priorities for burn nursing: rehabilitation, discharge planning, and follow-up care.

Fourteen of the 101 research questions that were proposed in the Burn Nursing Delphi study by Marvin et al. (J Burn Care Rehabil 1991;12:190-7) were concerned with the rehabilitation, discharge planning, and follow-up care of patients with burns. Questions that were ranked as top priorities for patient welfare related to control of postburn itching, prevention of contractures, and effective means of community-based follow-up to meet physical, social, and emotional needs of patients and families. Burn nurses identified the study of nursing interventions that are the most effective means for preparing patients, families, and community nurses for posthospitalization care as the research priority that has the greatest potential impact on the profession of burn nursing. Respondents to the Delphi study favored a collaborative approach to research for most of the questions in the rehabilitation subgroup. Suggestions are made for nurses who wish to take the lead in designing and implementing qualitative and quantitative studies that relate to the increasingly prevalent problems that are encountered by survivors of burn injury.

Incidence of HIV seroconversion in paediatric burn patients.

A retrospective review of paediatric patients treated for acute burn injuries and receiving blood/blood products between 1978 and 1985, identified 52 patients at risk for HIV infection. Over 50 per cent of the identified population had received 3 or more units of blood/blood products during their acute hospital stay. A total of 214 patients (36.8 per cent) have been tested for HIV seroconversions: five tested HIV positive by ELISA and four were confirmed by Western Blot, yielding a 1.9 per cent incidence. The four confirmed patients received 2-9 total body blood volume turnovers during their postburn period in hospital. At 4 years post-exposure, two patients show active disease, one is currently asymptomatic and one has died from AIDS-related sepsis.

Effect of recombinant human growth hormone on catabolic hormones and free fatty acids following thermal injury.

Severe burn injury elicits the release of catabolic hormones that contribute to negative nitrogen balance, protein wasting, and impaired wound healing. Previous studies have shown that burn patients receiving recombinant human growth hormone (rhGH) therapy have an increase in the rate of skin donor site healing and a shorter hospital stay. The mechanism by which rhGH exerts its effects, however, is not clearly understood. This study examines the effects of rhGH on circulating levels of catabolic hormones and nonesterified fatty acids in pediatric burn patients. Patients with greater than 40% total body surface area burn were randomly assigned to receive placebo (n = 8) or 0.2 mg/kg/day rhGH (n = 6) throughout their hospitalization. All patients had early morning blood samples assessed for catecholamines (CAT), cortisol, insulin, glucagon, and free fatty acid (FFA) levels during a period of hypermetabolism. No differences could be demonstrated in age, burn size, postburn day of evaluation, resting energy expenditure per kilogram, respiratory rate, heart rate, respiratory quotient, serum cortisol, and serum glucose between placebo- and rhGH-treated patients. The rhGH-treated group did show a significant elevation (p less than 0.05) in insulin-like growth factor-1 (55.9 +/- 14.5 vs. 168 +/- 23.7 mU/mL), total catecholamines (1,817 +/- 177 vs. 1,117 +/- 137 pg/mL), norepinephrine (1,257 +/- 121 vs. 867 +/- 113 pg/mL), epinephrine (385 +/- 175 vs. 147 +/- 36 pg/mL), insulin (32.8 +/- 3.3 vs. 25.0 +/- 3.0 mU/mL), glucagon (215 +/- 18 vs. 158 +/- 22 pg/mL), and free fatty acids (0.74 +/- 0.01 vs. 0.59 +/- 0.04 mEq/L) compared with the placebo group (data expressed as mean +/- SE).(ABSTRACT TRUNCATED AT 250 WORDS)

Research priorities for burn nursing: report on physiologic issues.

This Delphi study was designed and conducted to identify the issues of greatest concern to care of patients with burns and to the profession of burn nursing, so that nursing research could be directed toward these ends. One hundred and one questions were prioritized by the 94 participants who completed the four sequential rounds of questionnaires. A total of 11 questions (10.9%), which addressed physiologic-based issues, were identified.

Research priorities for burn nursing: nursing recruitment, retention, and other administrative issues.

This Delphi study was designed to identify nursing research priorities. Ninety-four participants completed four rounds of questionnaires that contained 101 potential research questions. Twenty questions addressed nursing administrative issues. In this category, the highest priority for potential impact on patient welfare related to the cost-effectiveness of various infection control measures. Questions concerning recruitment, retention, staffing, and cost/quality issues had the highest priority for research that could have an impact on the profession of nursing.

Candida infection with and without nystatin prophylaxis. A 11-year experience with patients with burn injury.

The incidence of opportunistic infections after thermal injury is high. Since 1985, we have been practicing Candida prophylaxis using nystatin "swish-and-swallow" and topical therapy. Patients treated between 1980 and 1984 served as controls and received no Candida prophylaxis. Although mean burn size, full-thickness injury, and age were comparable, the incidence of Candida colonization (26.7% vs 15.6%), infection (21.3% vs 10.0%), and sepsis (12.2% vs none) was significantly different between control and nystatin-treated groups, respectively. With prophylaxis, the incidence of Candida wound infection has been significantly reduced, and systemic candidiasis has been eradicated, eliminating the need for toxic systemic antifungal agents.

Comparison of cultured epidermal autograft and massive excision with serial autografting plus homograft overlay.

The chief determinant of mortality in severe burn injuries has been the size and severity of the wound. Early massive excision of the wound has increased the median lethal dose to 98% of total body surface area burn but presents the problem of wound closure. Autograft substitutes must be used for a large burn. We report our experience with early massive excision in the treatment of 47 pediatric patients with burns who had greater than 80% total body surface area burn and greater than 80% full-thickness burn. Four patients died within hours of admission. Fifteen patients died of sepsis and multiorgan failure; the primary source of bacterial contamination was the open wound. The 28 survivors received approximately 2.0 m2 2:1 homograft until autograft became available. A case report of a 10-year-old boy illustrates the use of two types of cultured epidermal autograft, one "homegrown" and one commercially produced.

Research priorities for burn nursing: report of the psychosocial issues group.

This study was designed to identify nursing research priorities in burn care. The Delphi technique of sequential questionnaires was used for data collection. Ninety-four participants completed four rounds of questionnaires. One hundred and one research questions were identified, and priorities were assigned according to their impact on patient welfare and on the profession of burn nursing. Twenty-two of these research questions concerned psychosocial issues. This group of questions was then analyzed for priority research issues. The top five ranked questions in the psychosocial issues group for impact on patient welfare concerned: (1) stress reduction techniques, (2) social reentry strategies, (3) management of psychosis and post-traumatic stress disorder, (4) strategies to assist patients with impaired communication capabilities, and (5) the role of recovered burn survivors in encouraging patient compliance with treatments. Similarly, the top five ranked questions for impact on the profession of burn nursing concerned: (1) stress reduction strategies, (2) coping techniques for burn survivors, (3) management of psychosis and post-traumatic stress disorder, (4) nursing's supportive role in regard to "do not resuscitate" orders, and (5) coping strategies to be used with patients who express a desire to die.

The role of gentamicin iontophoresis in the treatment of burned ears.

Ear cartilage heals slowly, and limited vascularity in cartilage precludes use of systemic antibiotics. Iontophoresis electrically induces drugs in solution to migrate into target tissues. Fifteen patients were randomized to receive gentamicin iontophoresis (n = 7) plus dressing changes every 6 hours and cleaning or routine care alone (n = 8) for treatment of ear burns. There were no differences between the groups in incidence of chondritis (43% vs 50%) or cartilage loss (11% vs 16%). However, gentamicin-resistant organisms developed in 29% of the patients who received iontophoresis, but in none of the patients in the control group (p less than 0.05). To identify the etiology of the resistant organisms, 10 New Zealand white rabbits receive 7 cm2 contact burns to each ear. Gentamicin iontophoresis was performed on one ear, and the other ear served as the control. Serum gentamicin levels were always subtherapeutic. Additionally, gentamicin tissue levels in both the treated and control ears were subtherapeutic. Gentamicin iontophoresis appears to offer no additional salutary effects beyond those that are provided by routine care and may encourage the development of antibiotic resistance.