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Biomedical subjects

David G Armstrong

Publications and source records attributed to David G Armstrong.

At least 19 recordsLinked to original sources
PubMed2007

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study.

BACKGROUND: Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models. METHODS: A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size). RESULTS: The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities. CONCLUSIONS: Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.

Administration, Topical↗
PubMed2007

Preventing diabetic foot ulcer recurrence in high-risk patients: use of temperature monitoring as a self-assessment tool.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a temperature monitoring instrument to reduce the incidence of foot ulcers in individuals with diabetes who have a high risk for lower extremity complications. RESEARCH DESIGN AND METHODS: In this physician-blinded, randomized, 15-month, multicenter trial, 173 subjects with a previous history of diabetic foot ulceration were assigned to standard therapy, structured foot examination, or enhanced therapy groups. Each group received therapeutic footwear, diabetic foot education, and regular foot care. Subjects in the structured foot examination group performed a structured foot inspection daily and recorded their findings in a logbook. If standard therapy or structured foot examinations identified any foot abnormalities, subjects were instructed to contact the study nurse immediately. Subjects in the enhanced therapy group used an infrared skin thermometer to measure temperatures on six foot sites each day. Temperature differences >4 degrees F (>2.2 degrees C) between left and right corresponding sites triggered patients to contact the study nurse and reduce activity until temperatures normalized. RESULTS: The enhanced therapy group had fewer foot ulcers than the standard therapy and structured foot examination groups (enhanced therapy 8.5 vs. standard therapy 29.3%, P = 0.0046 and enhanced therapy vs. structured foot examination 30.4%, P = 0.0029). Patients in the standard therapy and structured foot examination groups were 4.37 and 4.71 times more likely to develop ulcers than patients in the enhanced therapy group. CONCLUSIONS: Infrared temperature home monitoring, in serving as an "early warning sign," appears to be a simple and useful adjunct in the prevention of diabetic foot ulcerations.

Adult↗
PubMed2006

Bovine mural granulosa cells, and not the oocyte, are the major source of proteases capable of IGFBP-2 degradation.

Oocytes can regulate their own development, hence studies identifying and characterising oocyte-secreted factors are crucial to resolving the mechanisms by which oocytes can orchestrate follicular development. The insulin-like growth factor (IGF) system plays an important role during the development of a follicle; however, the regulation of IGF bioavailability is crucial throughout follicular growth. Proteolytic cleavage of the IGF/IGF binding protein (IGFBP) complex increases IGF bioavailability, hence, the production of IGFBP proteases by the oocyte and/or granulosa cells would provide a regulatory mechanism whereby they could regulate their own exposure to IGFs. The present study revealed mural granulosa cells (MGC), and not the oocyte, are the major source of proteases capable of cleaving IGFBP-2 in the developing bovine antral follicle. The addition of recombinant IGF-I or FSH had no effect in terms of modulating IGFBP-2 degradation. This work further supports the existence of a local regulatory mechanism modulating IGF bioavailability.

Animals↗
PubMed2006

The role of activity, adherence, and off-loading on the healing of diabetic foot wounds.

The etiology of diabetic foot ulcerations is commonly associated with the presence of peripheral neuropathy and repetitive trauma due to normal walking activities to areas of the foot exposed to moderate or high pressure. The goal of any treatment plan should include as a central tenet the mitigation or modulation of this activity and/or pressure. While numerous studies have detailed the potential pressure off-loading properties of various treatment modalities, subsequent studies have suggested that, if easily removable, these therapies will likely not be used for the majority of steps taken each day. This serves to explain at least in part the often disappointing results of both these pressure off-loading technologies and advanced wound-healing therapies. This article reviews these data and suggests that an amalgam of effective pressure relief coupled with strategies to reduce nonadherence to this therapy could yield a potentially favorable clinical result.

Biomechanical Phenomena↗
PubMed2006

Validation of a diabetic foot surgery classification.

The purpose of this project was to evaluate associations of increasing diabetic foot surgery stage with postoperative outcome. This project, designed as a retrospective cohort model, was conducted at three large, urban referral-based diabetic foot clinics. The investigators abstracted medical records from 180 patients with diabetes, 76.1% male, aged 57.8 +/- 11.2 years, falling equally into four classes of a previously reported diabetic foot surgery classification system. These classes included class 1 (elective), class 2 (prophylactic), class 3 (curative) and class 4 (emergency). There was a significant trend towards increasing risk of ulceration/reulceration (chi2(trend) = 17.8, P = 0.0001), peri-postoperative infection (chi2(trend) = 96.9, P = 0.0001), all-level amputation (chi2(trend) = 41.7, P = 0.001) and major amputation (chi2(trend) = 8.6, P = 0.003), with increasing class of foot surgery. The results of this study suggest that a non vascular foot surgery classification system including variables such as the presence or absence of neuropathy, an open wound and acute infection may be predictive of peri- and postoperative complications. This may assist the surgeon in better identifying risk when determining a rationale for and type of surgery in persons with diabetes.

Aged↗
PubMed2006

Does dermal thermometry predict clinical outcome in diabetic foot infection? Analysis of data from the SIDESTEP* trial.

The purpose of the study was to assess in patients with a diabetic foot infection (DFI), whether differences in skin temperature of the affected foot as compared to the corresponding site on the contralateral foot using dermal thermometry (DT) correlates with infection severity and clinical outcome. As part of the SIDESTEP DFI study, investigators took DT measurements at baseline and the discontinuation of intravenous therapy (DCIV) and performed a systematic evaluation of the infected limb to calculate a wound score. We compared the skin temperature differential between the limbs at the two assessments and determined the correlation between this value and surrogate markers of inflammation and the clinical response to treatment. Among patients enrolled in SIDESTEP, 332 were fully evaluable. The mean temperature differential between the limbs was 2.81 +/- 5.75 degrees F at baseline and 2.43 +/- 4.84 degrees F at DCIV (mean change: -0.37; 95% confidence interval (CI): -0.98, 0.23; P= 0.225). Skin temperature differential at baseline did not correlate with white blood cell count, level of C-reactive protein or erythrocyte sedimentation rate or the infection severity score (r= 0.058, 0.148, -0.002, 0.067, respectively). We observed no overall trend between surface temperature differential at baseline and clinical outcome at DCIV, but patients with a skin temperature differential of > or =10 degrees F at baseline had a significantly lower clinical response than those whose differential was <10 degrees F (81.4% versus 94.3%; difference 12.9%; 95% CI: 3.5, 27.3%, P= 0.007). While there was no overall relationship between skin temperature and poor clinical outcome, there may be a threshold effect in DT (<10 degrees F versus >10 degrees F) between the limbs at baseline that predicts outcome of therapy.

Diabetic Foot↗
PubMed2006

Ertapenem for diabetic foot infections.

Foot infections are a common cause of hospitalization in people with diabetes. Diabetic foot infections are associated with increased risk of amputation and death. This monograph reviews the diagnosis and treatment of diabetic foot infections with particular attention to a new carbapenem antibiotic, ertapenem, which has the potential to reduce inpatient length of stay and hospital-associated costs.

Anti-Bacterial Agents↗
PubMed2006

The effects of IGF-I on bovine follicle development and IGFBP-2 expression are dose and stage dependent.

This study aimed to determine the effect of insulin-like growth factor-I (IGF-I) on early antral bovine follicular development, and the expression of insulin-like growth factor-binding protein-2 (IGFBP-2). Antral follicles separated into three different size groups were cultured for 6 days in medium supplemented with either a low (10 ng/ml) or high (1 microg/ml) dose of human recombinant IGF-I. Oestradiol production by follicles in all size ranges, cultured in the presence of the high concentration of IGF-I, significantly increased by day 6 (P < 0.05). Follicles in the smallest size range, 165-215 microm, cultured in a high dose of IGF-I, were found to be significantly increased in size (P < 0.01). Oocyte health of the largest follicles (281-380 microm) was significantly improved by the addition of IGF-I to the culture medium. mRNA expression of IGFBP-2 was decreased in the granulosa cells of follicles, size range 216-280 microm, cultured with a high dose of IGF-I (P < 0.05). Granulosa cells (P < 0.05) and oocytes (P < 0.01) of the largest follicles (281-380 microm) showed a decrease in IGFBP-2 expression (protein) when cultured in the control and low-IGF-I treatment groups. Therefore, the response of a bovine follicle to IGF-I is both dose and stage dependent. This work supports a role for IGF-I in modulating somatic and germ-cell maturation and development in early antral follicles. Furthermore, the inverse relationship between the level of IGF-I stimulation and IGFBP-2 expression suggests a local regulatory system modulating IGF-I availability.

Animals↗
PubMed2006

Risk factors for foot infections in individuals with diabetes.

OBJECTIVE: To prospectively determine risk factors for foot infection in a cohort of people with diabetes. RESEARCH DESIGN AND METHODS: We evaluated then followed 1,666 consecutive diabetic patients enrolled in a managed care-based outpatient clinic in a 2-year longitudinal outcomes study. At enrollment, patients underwent a standardized general medical examination and detailed foot assessment and were educated about proper foot care. They were then rescreened at scheduled intervals and also seen promptly if they developed any foot problem. RESULTS: During the evaluation period, 151 (9.1%) patients developed 199 foot infections, all but one involving a wound or penetrating injury. Most patients had infections involving only the soft tissue, but 19.9% had bone culture-proven osteomyelitis. For those who developed a foot infection, compared with those who did not, the risk of hospitalization was 55.7 times greater (95% CI 30.3-102.2; P < 0.001) and the risk of amputation was 154.5 times greater (58.5-468.5; P < 0.001). Foot wounds preceded all but one infection. Significant (P < 0.05) independent risk factors for foot infection from a multivariate analysis included wounds that penetrated to bone (odds ratio 6.7), wounds with a duration >30 days (4.7), recurrent wounds (2.4), wounds with a traumatic etiology (2.4), and presence of peripheral vascular disease (1.9). CONCLUSIONS: Foot infections occur relatively frequently in individuals with diabetes, almost always follow trauma, and dramatically increase the risk of hospitalization and amputation. Efforts to prevent infections should be targeted at people with traumatic foot wounds, especially those that are chronic, deep, recurrent, or associated with peripheral vascular disease.

Adult↗
PubMed2006

Consensus statement on negative pressure wound therapy (V.A.C. Therapy) for the management of diabetic foot wounds.

UNLABELLED: In 2004, a multidisciplinary expert panel convened at the Tucson Expert Consensus Conference (TECC) to determine appropriate use of negative pressure wound therapy as delivered by a Vacuum Assisted Closure device (V.A.C. THERAPY, KCI, San Antonio, Texas) in the treatment of diabetic foot wounds. These guidelines were updated by a second multidisciplinary expert panel at a consensus conference on the use of V.A.C. THERAPY, held in February 2006, in Miami, Florida. This updated version of the guidelines summarizes current clinical evidence, provides practical guidance, offers best practices to clinicians treating diabetic foot wounds, and helps direct future research. The Miami consensus panel discussed the following 12 key questions regarding V.A.C. THERAPY: (1) How long should V.A.C. THERAPY be used in the treatment of a diabetic foot wound? (2) Should V.A.C." THERAPY be applied without debriding the wound? (3) How should the patient using V.A.C. THERAPY be evaluated on an outpatient basis? (4) When should V.A.C. THERAPY be applied following revascularization? (5) When should V.A.C. THERAPY be applied after incision, drainage, and debridement of infection? (6) Should V.A.C. THERAPY be applied over an active soft tissue infection? (7) How should V.A.C. THERAPY be used in patients with osteomyelitis? (8) How should noncompliance to V.A.C. THERAPY be defined? (9) How should V.A.C. THERAPY be used in combination with other modalities? (10) Should small, superficial wounds be considered for V.A.C. THERAPY? (11) How should success in the use of V.A.C. THERAPY be defined? (12) How can one combine effective offloading and V.A.C. THERAPY?

Algorithms↗
PubMed2005

Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective, randomised, controlled, double-blinded, multicentre trial.

BACKGROUND: Diabetic foot infections are a common and serious problem, yet few randomised trials of adequate quality have compared the efficacy of the various antibiotic regimens available for their treatment. Our aim was to assess the efficacy and safety of ertapenem versus piperacillin/tazobactam for foot infections. METHODS: We did a randomised, double-blinded, multicentre trial in adults (n=586) with diabetes and a foot infection classified as moderate-to-severe and requiring intravenous antibiotics. We assigned patients intravenous ertapenem (1 g daily; n=295) or piperacillin/tazobactam (3.375 g every 6 h; n=291) given for a minimum of 5 days, after which oral amoxicillin/clavulanic acid (875/125 mg every 12 h) could be given for up to 23 days. Investigators retained the option to administer vancomycin to patients in either group to ensure adequate coverage for potentially antibiotic resistant Enterococcus spp and meticillin-resistant Staphylococcus aureus (MRSA). Our primary outcome was the proportion of patients with a favourable clinical response (cure or improvement) on the day that intravenous antibiotic was discontinued. Analyses were by an evaluable-patient only approach. This study is registered with , number NCT00229112. FINDINGS: Of the 576 patients treated, 445 were available for assessment at the end of intravenous therapy. Both baseline characteristics and favourable clinical response rates were similar for the 226 who received ertapenem and the 219 who received piperacillin/tazobactam (94%vs 92%, respectively; between treatment difference 1.9%, 95% CI -2.9 to 6.9). Rates of favourable microbiological responses (eradication rates and clinical outcomes, by pathogen) and adverse events did not differ between groups. INTERPRETATION: Clinical and microbiological outcomes for patients treated with ertapenem were equivalent to those for patients treated with piperacillin/tazobactam, suggesting that this once-daily antibiotic should be considered for parenteral therapy of diabetic foot infections, when deemed appropriate.

Adult↗
PubMed2005

Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial.

BACKGROUND: Diabetic foot wounds, particularly those secondary to amputation, are very complex and difficult to treat. We investigated whether negative pressure wound therapy (NPWT) improves the proportion and rate of wound healing after partial foot amputation in patients with diabetes. METHODS: We enrolled 162 patients into a 16-week, 18-centre, randomised clinical trial in the USA. Inclusion criteria consisted of partial foot amputation wounds up to the transmetatarsal level and evidence of adequate perfusion. Patients who were randomly assigned to NPWT (n=77) received treatment with dressing changes every 48 h. Control patients (n=85) received standard moist wound care according to consensus guidelines. NPWT was delivered through the Vacuum Assisted Closure (VAC) Therapy System. Wounds were treated until healing or completion of the 112-day period of active treatment. Analysis was by intention to treat. This study has been registered with , number NCT00224796. FINDINGS: More patients healed in the NPWT group than in the control group (43 [56%] vs 33 [39%], p=0.040). The rate of wound healing, based on the time to complete closure, was faster in the NPWT group than in controls (p=0.005). The rate of granulation tissue formation, based on the time to 76-100% formation in the wound bed, was faster in the NPWT group than in controls (p=0.002). The frequency and severity of adverse events (of which the most common was wound infection) were similar in both treatment groups. INTERPRETATION: NPWT delivered by the VAC Therapy System seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care.

Air Pressure↗
PubMed2005

Preventing foot ulcers in patients with diabetes.

CONTEXT: Among persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. These ulcers frequently become infected, cause great morbidity, engender considerable financial costs, and are the usual first step to lower extremity amputation. OBJECTIVE: To systematically review the evidence on the efficacy of methods advocated for preventing diabetic foot ulcers in the primary care setting. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: The EBSCO, MEDLINE, and the National Guideline Clearinghouse databases were searched for articles published between January 1980 and April 2004 using database-specific keywords. Bibliographies of retrieved articles were also searched, along with the Cochrane Library and relevant Web sites. We reviewed the retrieved literature for pertinent information, paying particular attention to prospective cohort studies and randomized clinical trials. DATA SYNTHESIS: Prevention of diabetic foot ulcers begins with screening for loss of protective sensation, which is best accomplished in the primary care setting with a brief history and the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy with biothesiometry, measure plantar foot pressure, and assess lower extremity vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, enable clinicians to stratify patients based on risk and to determine the type of intervention. Educating patients about proper foot care and periodic foot examinations are effective interventions to prevent ulceration. Other possibly effective clinical interventions include optimizing glycemic control, smoking cessation, intensive podiatric care, debridement of calluses, and certain types of prophylactic foot surgery. The value of various types of prescription footwear for ulcer prevention is not clear. CONCLUSIONS: Substantial evidence supports screening all patients with diabetes to identify those at risk for foot ulceration. These patients might benefit from certain prophylactic interventions, including patient education, prescription footwear, intensive podiatric care, and evaluation for surgical interventions.

Cost-Benefit Analysis↗
PubMed2005

The pivotal role of offloading in the management of neuropathic foot ulceration.

Lower extremity amputations among persons with diabetes are generally preceded by neuropathic foot ulcerations. Healing of diabetic ulcerations in a timely manner is of central importance in any plan for amputation prevention. With sufficient vascular supply, appropriate débridement, and infection control, the primary mode of healing a diabetic neuropathic foot ulcer is pressure dispersion. The total contact cast has been deemed by many to be the gold standard in offloading; however, modification of a standard removable cast walker to ensure patient compliance may be as efficacious in healing diabetic foot ulcers as the total contact cast. Combining an effective, easy to use offloading device that ensures patient compliance with advanced wound healing modalities may form a formidable team in healing ulcers and potentially averting lower limb amputations.

Casts, Surgical↗
PubMed2005

Risk assessment of the diabetic foot and wound.

Diabetic foot ulcers are among the most common severe complications of diabetes, affecting up to 68 per 1,000 persons with diabetes per year in the United States. Over half of these patients develop an infection and 20% require some form of amputation during the course of their malady. The key risk factors of diabetic foot ulceration include neuropathy, deformity and repetitive stress (trauma). The key factors associated with non healing of diabetic foot wounds (and therefore amputation) include wound depth, presence of infection and presence of ischaemia. This manuscript will discuss these key risk factors and briefly outline steps for simple, evidence-based assessment of risk in this population.

Diabetic Foot↗
PubMed2005

Can the use of a topical antifungal nail lacquer reduce risk for diabetic foot ulceration? Results from a randomised controlled pilot study.

The purpose of this study was to determine whether the routine use of a topical antifungal nail lacquer (AFL) could reduce the risk for ulceration by theoretically increasing the frequency of patient self-inspection. In this randomised controlled trial, 70 persons at high risk for diabetic foot ulceration were enrolled into a preventative care program involving daily self-inspection with the possible use of an AFL (ciclopirox 8%) versus self-inspection instructions alone (NAFL). Patients were followed for 12 months or until ulceration. Using an intent to treat analysis, there was no significant difference in proportion of persons ulcerating in the AFL versus the NAFL groups (5.9% versus 5.6% P = 0.9). There was also no difference in the number of unexpected visits (P = 0.2) or missed appointments (P = 0.7) between treatment arms. Interestingly, while there was no difference in proportion of patients with clinically diagnosed hyperkeratosis or tinea pedis on entry into the study (P = 0.2), a significantly lower proportion of AFL patients had a clinical diagnosis on study termination (52.9% versus 77.8% P = 0.03, OR = 1.7, 95% confidence interval = 1.1-2.7). The results of this study suggest that there may be no immediate prophylactic benefit through the use of AFL to prevent wounds. The incidental finding of a potential reduction in hyperkeratosis and tinea pedis is a compelling one and may deserve further investigation.

Administration, Topical↗
PubMed2005

Outcomes of allogenic acellular matrix therapy in treatment of diabetic foot wounds: an initial experience.

The purpose of this study was to evaluate outcomes of persons with UT grade 2A neuropathic diabetic foot wounds treated with an acellular matrix. Data were abstracted for 17 consecutive patients with diabetes--76.5% males, aged 61.5 +/- 8.5 years with a mean glycated haemoglobin of 9.2 +/- 2.2% presenting for care at a large, multidisciplinary wound care centre. All patients received surgical debridement for their diabetic foot wounds and were placed on therapy consisting of a single application of an acellular matrix graft (GraftJacket; Wright Medical Technologies, Arlington, TN, USA) with dressing changes taking place weekly. Outcomes evaluated included time to complete wound closure and proportion of patients achieving wound closure in 20 weeks. Acellular matrix therapy was used as initial therapy and was sutured or stapled in place under a silicone-based non adherent dressing. Therapy was then followed by a moisture-retentive dressing until complete epithelialisation. In total, 82.4% of wounds measuring a mean 4.6 +/- 3.2 cm(2) healed in the 20-week evaluation period. For those that healed in this period, healing took place in a mean 8.9 +/- 2.7 weeks. We conclude that a regimen consisting of moist wound healing using an acellular matrix dressing may be a useful adjunct to appropriate diabetic foot ulcer care for deep, non-infected, non-ischaemic wounds. We await the completion of further trials in this area to confirm or refute this initial assessment.

Aged↗