Role of platelet-derived growth factor as an adjunct to surgery in the management of pressure ulcers

Management options for pressure ulcers include local wound care, surgical repair, and, more recently, topical application of platelet-derived growth factor (PDGF). PDGF is a glycoprotein that is mitogenic for mesenchymal cells and has been studied extensively for applicability in promoting the healing of chronic human wounds. Using data obtained from a multicenter clinical trial for the treatment of full-thickness pressure ulcers, a subset analysis was performed to investigate the outcome of salvage surgery for pressure ulcers, after incomplete closure occurred with the topical use of either recombinant human PDGF-BB (rhPDGF-BB) or placebo gel. At the University of Michigan Wound Care Center, subset data from a randomized, double-blind, placebo-controlled, parallel group clinical trial were reviewed to compare the effects of three concentrations of rhPDGF-BB on full-thickness pressure ulcers of the trunk with those of the placebo. Twenty-eight patients were enrolled and 27 completed the trial. An intent-to-treat analysis was used to evaluate data. If the ulcer did not heal by the end of the 16-week trial period, the surgeon, still blinded to the treatment group, offered salvage surgical repair of the pressure ulcer. Eleven patients underwent salvage surgical repair using myocutaneous flaps, primary closure, or skin grafts. Of three patients who received placebo followed by surgery, none progressed to full healing within 1 year. Of 12 patients in the treatment group who received rhPDGF-BB and salvage surgery, 11 (92 percent) ultimately healed the ulcers within 1 year after the start of the clinical trial. These findings suggest that treatment with rhPDGF-BB before surgery enhances the ability to achieve a closed wound over surgery alone. It must yet be determined to what degree rhPDGF-BB contributed to the excellent results seen in the rhPDGF-BB/surgery group. It is possible that rhPDGF-BB "primes" the local wound milieu to make it more responsive to complete closure following surgical treatment.     

负压创面治疗肝源性糖尿病并发糖尿病足的研究

目的:讨论创面负压治疗促进肝硬化合并糖尿病并发糖尿病足的临床疗效。方法:将30例慢性肝硬化合并糖尿病并发糖尿病足患者随机分为创面负压治疗组和敷料包扎组,观察两组创面细菌负荷及创面微循环血流量变化。结果:清创即刻,负压创面治疗组和敷料包扎组细菌负荷与创面微循环血流量无显著差异(P>0.01);创后3天、6天和9天时,负压创面组创面细菌负荷低于敷料包扎组(P<0.01),创面微循环血流量高于敷料包扎组(P<0.01)。负压创面组创面愈合时间少于敷料包扎组(P<0.01)。结论:负压创面治疗有助于慢性肝硬化并发糖尿病合并糖尿病足的创面愈合。     

Circulating fibrocyte mobilization in negative pressure wound therapy

Non‐healing diabetic wounds are difficult to treat. They also create heavy financial burdens for both patients and society. Negative pressure wound therapy (NPWT) has been adopted to treat intractable wounds and has proved to be effective. However, the mechanisms that underlie the effects of this treatment are not entirely understood. Circulating fibrocytes are unique haematopoietic‐derived stem cells that have been reported to play a pivotal role in wound healing. Here, we have investigated the effect of NPWT on fibrocyte mobilization and the role of fibrocyte mobilization in the healing of diabetic wounds during NPWT. We show that the NPWT group exhibited 2.6‐fold to 12.1‐fold greater numbers of tail vein‐injected PKH‐26‐labelled fibrocytes in the diabetic wound sites compared with the control group. We also demonstrate that the full‐thickness skin wounds treated with NPWT exhibit significantly reduced mRNA and protein expression, blood vessel density and proliferating cells when exogenous fibrocyte mobilization is inhibited. We speculate that systemic mobilization of fibrocytes during NPWT may be a mechanism for healing intractable wounds in a diabetic rat model experiment and that enhancement of cell mobilization may represent a potential treatment idea for intractable wound healing across all fields of surgery.     

Pinch skin grafting or porcine dermis in venous ulcers: a randomised clinical trial.

Chronic venous ulcers are common, and even with effective compression or elevation large ulcers may take months to heal. Pinch skin grafting may allow healing from epithelial islands throughout the surface area of the ulcer, and a prospective randomised trial was therefore conducted comparing this treatment with porcine dermis dressings. Most patients were treated as outpatients, 25 ulcers being randomised to treatment with pinch skin grafts and 28 to treatment with porcine dermis. Though the groups were well matched, the mean healing rate in the first week was 15 cm2 for pinch skin grafts compared with 3.5 cm2 with porcine dermis (p less than 0.02). By life table analysis 64% of ulcers treated by pinch grafts were healed at six weeks and 74% by 12 weeks compared with 29% and 46% of ulcers, respectively, treated with porcine dermis dressings (chi2 = 4.1; p less than 0.05). All ulcers that failed to heal within 12 weeks included an area posterior to the medial malleolus, where local compression may have been inadequate. Pinch skin grafting improves the rate of healing in large venous ulcers and is a simple technique that may be performed as an outpatient procedure under local anaesthesia.     

Less frequent turning intervals and yet less pressure ulcers

The aim of the doctoral dissertation summarised here, was to study the effect of different turning intervals and to optimise this method of pressure ulcer prevention. Prior to the main study, the pressure reducing effect of mattresses, cushions, sitting and lying positions was investigated. Based on the results of 3 pre-studies, 4 different turning schemes were compared in a randomised controlled trial in 838 high-risk nursing home residents. Turning every 4 hours in combination with the use of a pressure reducing viscoelastic mattress reduced the number of pressure ulcers significantly compared to the other 3 schemes: turning every 6 hours on a viscoelastic mattress, and turning every 2 or 4 hours on a non-pressure reducing mattress.     

The effect of the boron-based gel on the treatment of diabetic foot ulcers: A prospective,randomized controlled trial

BackgroundChronic ulcers represent impaired healing capacity with high mortality in the elderly or patients with systemic disorders such as diabetes. Boron is an effective agent in wound healing by promoting cell migration and proliferation and reducing inflammation in the wound area. This study aimed to evaluate the therapeutic effect of a sodium pentaborate-based topical formulation compared to control on the treatment of diabetic foot ulcers.MethodsA prospective, double-blind, randomized controlled trial was conducted to apply randomly the topical sodium pentaborate 3% gel or topical conventional remedy (control) by patients diagnosed with diabetic foot ulcers. The 171 eligible participants aged 18–75 years received the allocated medicines twice a day for a month with an allocation ratio of 3:1. Twenty-five days and two months after the end of the trial, participants were reinvestigated for their ulcer condition and any recurrence. Wagner’s classification of diabetic foot ulcers was applied to this purpose (0−5).Results161 participants (57 females, 104 males; mean age: 59.37) completed this study. After the intervention, most participants in the intervention group had a lower ulcer grade than the control group (adjusted mean difference (95% CI): − 0.91 (−1.1 to −0.73); p < 0.001). Moreover, most participants in the intervention group (n = 109 (90.8%)) were treated at a higher rate than the control group (n = 5 (12.2%)) after intervention (adjusted odds ratio (95% CI): 0.008 (0.002–0.029); p < 0.001). There was no case of recurrence in the intervention group while its rate was (n = 2 (40%)) in the control group (p < 0.001).ConclusionThe present study suggests that topical sodium pentaborate gel may help treat and decrease the grade of diabetic foot ulcers and prevent the recurrence of diabetic foot ulcers.     

Cimetidine for recurrent ulcer after vagotomy or gastrectomy: a randomised controlled trial.

In a randomised controlled trial cimetidine 1 g daily for six weeks was compared with placebo in the treatment of recurrent ulcers after gastrectomy or vagotomy for duodenal ulcer. Healing, assessed endoscopically, was seen in seven out of 12 patients given cimetidine and in five out of 12 controls. Four of the controls whose ulcers did not heal were subsequently treated with cimetidine, and in two the ulcers healed after six weeks. Pain recorded by the patient and consumption of alkalis were each slightly but not significantly less in the cimetidine-treated patients. When cimetidine is to be used for recurrent ulceration probably the dosage and duration of treatment should be increased.     

Sustained-release adrenomedullin ointment accelerates wound healing of pressure ulcers

Pressure ulcers are one of the most common complications in elderly, incontinent or paralyzed patients. For the healing of pressure ulcers, the development of granulation tissue and reepithelialization is required. Adrenomedullin (AM), an endogenous vasodilator peptide, is reported to stimulate the proliferation and migration of various cells including endothelial cells, fibroblasts and keratinocytes. Therefore, we hypothesized that AM might accelerate the healing process of pressure ulcers in which these cells were involved. We developed a sustained-release ointment containing human recombinant AM, and applied it in a mouse model of pressure ulcer twice a day for 14 days. Human AM was efficiently absorbed in wound area, but its blood concentration was negligible. AM ointment significantly reduced the wound area on day 5 to 7 after injury. In addition, AM ointment accelerated the formation of granulation tissue and angiogenesis as well as lymphangiogenesis after 7 days of treatment. Immunological analysis revealed that Ki-67-positive proliferating cells in granulation tissue expressed AM receptors. In summary, sustained-release AM significantly improved wound healing of pressure ulcers through acceleration of granulation and induction of angiogenesis and lymphangiogenesis. Therefore, sustained-release AM ointment may be a novel therapeutic agent for pressure ulcers.     

Sustained compression and healing of chronic venous ulcers.

STUDY OBJECTIVE--Comparison of four layer bandage system with traditional adhesive plaster bandaging in terms of (a) compression achieved and (b) healing of venous ulcers. DESIGN--Part of larger randomised trial of five different dressings. SETTING--Outpatient venous ulcer clinic in university hospital. PATIENTS--(a) Pressure exerted by both bandage systems was measured in the same 20 patients. (b) Healing with the four layer bandage was assessed in 148 legs in 126 consecutive patients (mean age 71 (SE 2); range 30-96) with chronic venous ulcers that had resisted treatment with traditional bandaging for a mean of 27.2 (SE 8) months. INTERVENTIONS--(a) Four layer bandage system or traditional adhesive plaster bandaging for pressure studies; (b) four layer bandaging applied weekly for studies of healing. END POINTS--(a) Comparison of pressures achieved at the ankle for up to one week; (b) complete healing within 12 weeks. MEASUREMENTS AND MAIN RESULTS--(a) Four layer bandage produced higher initial pressures at the ankle of 42.5 (SE 1) mm Hg compared with 29.8 (1.8) for the adhesive plaster (p less than 0.001; 95% confidence interval 18.5 to 6.9). Pressure was maintained for one week with the four layer bandage but fell to 10.4 (3.5) mm Hg at 24 hours with adhesive plaster bandaging. (b) After weekly bandaging with the four layer bandage 110 of 48 venous ulcers had healed completely within 12 (mean 6.3 (0.4)) weeks. CONCLUSION--Sustained compression of over 40 mm Hg achieved with a multilayer bandage results in rapid healing of chronic venous ulcers that have failed to heal in many months of compression at lower pressures with more conventional bandages.     

Is there a place in the United Kingdom for intensive antacid treatment for chronic peptic ulceration?

Sixty nine patients with chronic duodenal or juxtapyloric ulceration were studied in a prospective double blind randomised trial to compare the efficacy of antacid and placebo at high (30 ml seven times daily) and low (10 ml as required) doses. After four weeks ulcers had healed in 12 out of 18 patients (67%) receiving "low dose" antacid compared with in six out of 17 patients (35%) receiving low dose placebo; ulcers had also healed in six out of 19 patients (32%) receiving "high dose" antacid compared with in two out of 15 patients (13%) receiving high dose placebo. Overall, the effect of antacid was superior to that of placebo in healing ulcers (p less than 0.05) and the effect of low dose treatment was superior to that of high dose treatment (p less than 0.01). There were no significant differences between antacid and placebo at eight weeks. Antacid was better than placebo in relieving pain, but the difference was not significant. Poor compliance and high incidence of diarrhoea made high dose antacid an impractical treatment. Low dose antacid was associated with a significantly better rate of healing than high dose antacid and was far better tolerated. This low dosage of antacid should be considered to be an active treatment in trials of ulcer healing.     

Oxpentifylline treatment of venous ulcers of the leg.

OBJECTIVE--To determine the effect of oxpentifylline on the healing of venous ulcers of the leg. DESIGN--Double blind, randomised, prospective, placebo controlled, parallel group study. SETTING--Four outpatient clinics treating leg ulcers in England and the Republic of Ireland. PATIENTS--80 Consecutive patients with clinical evidence of venous ulceration of the leg in whom appreciable arterial disease was excluded by the ratio of ankle to brachial systolic pressure being greater than 0.8. INTERVENTIONS--All patients received either oxpentifylline 400 mg three times a day by mouth or a matching placebo for six months (or until their reference ulcer healed if this occurred sooner) in addition to a locally standardised method of compression bandaging. MAIN OUTCOME MEASURES--The primary end point was complete healing of the reference ulcer within six months. The secondary end point was the change in the area of the ulcer over the six month observation period. RESULTS--Complete healing of the reference ulcer occurred in 23 of the 38 patients treated with oxpentifylline and in 12 of the 42 patients treated with a placebo. Life table analysis showed that the proportion of ulcers healed at six months was 64% in the group treated with oxpentifylline compared with 34% in the group treated with a placebo (log rank test chi 2 = 4.78, p = 0.03), which was significant (odds ratio = 1.81, 95% confidence interval 1.20 to 2.71). CONCLUSION--Oxpentifylline used in conjunction with compression bandaging improves the healing of venous ulcers of the leg.     

Negative pressure wound therapy reduces the motility of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> and enhances wound healing in a rabbit ear biofilm infection model

Pseudomonas aeruginosa motility, virulence factors and biofilms are known to be detrimental to wound healing. The efficacy of negative pressure wound therapy (NPWT) against P. aeruginosa has been little studied, either in vitro or in vivo. The present study evaluated the effect of negative pressure (NP) on P. aeruginosa motility in vitro, and the effect of NPWT on virulence factors and biofilms in vivo. P. aeruginosa motility was quantified under different levels of NP (atmospheric pressure, ? 75, ? 125, ? 200 mmHg) using an in vitro model. Swimming, swarming and twitching motility were significantly inhibited by NP (? 125 and ? 200 mmHg) compared with atmospheric pressure (p = 0.05). Virulence factors and biofilm components were quantified in NPWT and gauze treated groups using a rabbit ear biofilm model. Biofilm structure was studied with fluorescence microscopy and scanning electron microscopy. Additionally, viable bacterial counts and histological wound healing parameters were measured. Compared with the control, NPWT treatment resulted in a significant reduction in expression of all virulence factors assayed including exotoxin A, rhamnolipid and elastase (p = 0.01). A significant reduction of biofilm components (eDNA) (p = 0.01) was also observed in the NPWT group. The reduction of biofilm matrix was verified by fluorescence- and scanning electron-microscopy. NPWT lead to better histologic parameters (p = 0.01) and decreased bacterial counts (p = 0.05) compared with the control. NPWT treatment was demonstrated to be an effective strategy to reduce virulence factors and biofilm components, which may explain the increased wound healing observed.     

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial

ABSTRACT: BACKGROUND: Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. METHODS: The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4?mg/kg/day) to prednisolone (0.75?mg/kg/day). A total of 140 participants are to be recruited over a period of 4?years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6?weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18?years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. TRIAL REGISTRATION: Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.     

Gabapentin for the Management of Chronic Pelvic Pain in Women (GaPP1): A Pilot Randomised Controlled Trial

Chronic pelvic pain (CPP) affects 2.1–24% of women. Frequently, no underlying pathology is identified, and the pain is difficult to manage. Gabapentin is prescribed for CPP despite no robust evidence of efficacy. We performed a pilot trial in two UK centres to inform the planning of a future multicentre RCT to evaluate gabapentin in CPP management. Our primary objective was to determine levels of participant recruitment and retention. Secondary objectives included estimating potential effectiveness, acceptability to participants of trial methodology, and cost-effectiveness of gabapentin. Women with CPP and no obvious pelvic pathology were assigned to an increasing regimen of gabapentin (300-2700mg daily) or placebo. We calculated the proportion of eligible women randomised, and of randomised participants who were followed up to six months. The analyses by treatment group were by intention-to-treat. Interviews were conducted to evaluate women’s experiences of the trial. A probabilistic decision analytical model was used to estimate cost-effectiveness. Between September 2012–2013, 47 women (34% of those eligible) were randomised (22 to gabapentin, 25 to placebo), and 25 (53%) completed six-month follow-up. Participants on gabapentin had less pain (BPI difference 1.72 points, 95% CI:0.07–3.36), and an improvement in mood (HADS difference 4.35 points, 95% CI:1.97–6.73) at six months than those allocated placebo. The majority of participants described their trial experience favorably. At the UK threshold for willingness-to-pay, the probabilities of gabapentin or no treatment being cost-effective are similar. A pilot trial assessing gabapentin for CPP was feasible, but uncertainty remains, highlighting the need for a large definitive trial.

Trial registration

Controlled-Trials.com ISRCTN45178534     

Controlled trial of Iodosorb in chronic venous ulcers.

Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly.     

Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers.

OBJECTIVE: To compare endoscopic adrenaline injection alone and adrenaline injection plus heat probe for the treatment of actively bleeding peptic ulcers. DESIGN: Randomised prospective study of patients admitted with actively bleeding peptic ulcers. SETTING: One university hospital. SUBJECTS: 276 patients with actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136 patients were randomised to endoscopic adrenaline injection alone and 140 to adrenaline injection plus heat probe treatment. MAIN OUTCOME MEASURES: Initial endoscopic haemostasis; clinical rebleeding; requirement for operation; requirement for blood transfusion; hospital stay, ulcer healing at four weeks; and mortality in hospital. RESULTS: Initial haemostasis was achieved in 131/134 patients (98%) who received adrenaline injection alone and 135/136 patients (99%) who received additional heat probe treatment (P = 0.33). Outcome as measured by clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly different in the two groups. In the subgroup of patients with spurting haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group required operative intervention. The relative risk of this was lower in the dual treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in the dual treatment group than the adrenaline injection alone group (4 v 6 days, P = 0.01). CONCLUSION: The addition of heat probe treatment after endoscopic adrenaline injection confers an advantage in ulcers with spurting haemorrhage.     

Omeprazole and cimetidine in the treatment of ulcers of the body of the stomach: a double blind comparative trial. Danish Omeprazole Study Group.

OBJECTIVE--To see whether omeprazole was superior to cimetidine in healing ulcers of the body of the stomach. DESIGN--Double blind randomised parallel group study of omeprazole versus cimetidine for six weeks with assessment of healing at end of every second week. SETTING--Outpatient referrals in 11 centres in Denmark. PATIENTS--One hundred sixty one patients who satisfied the following criteria: age 18-79; one or more ulcers of body of stomach (that is, at or above the angulus) seen endoscopically within four days before study treatment; no H2 receptor antagonists taken within previous two weeks; no history of gastric surgery and no complications needing surgery; no concurrent treatment or disease that might confound assessment; oral contraception or an intrauterine device being used by women of childbearing age. INTERVENTIONS--Omeprazole 30 mg daily (one capsule in the morning) or cimetidine 1 g daily (one 200 mg tablet thrice daily, two tablets at bedtime) for six weeks. Inactive capsules and tablets provided so that all patients took same number of capsules and tablets daily. Compliance monitored by pill counts. END POINT--Endoscopic evidence of accelerated healing of type I gastric ulcers after four weeks of omeprazole. MEASUREMENTS AND MAIN RESULTS--Pain recorded on diary cards and patients assessed after two, four, and six weeks of treatment for clinical state and by endoscopy and biopsy and repeat laboratory tests. Twenty eight patients withdrawn during trial for violations of protocol. At two weeks healing rates were identical in the two treatment groups (omeprazole 41% (30/73 patients); cimetidine 41% (30/73]. At four weeks cumulative healing rates were 77% (53/69 patients) in the omeprazole treatment group and 58% (41/71) in the cimetidine treatment group (95% confidence interval of difference between groups 4% to 34%). By six weeks the cumulative healing rates in the two treatment groups differed by only 6% (60/68 patients (88%) given omeprazole; 53/65 (82%) given cimetidine). Log rank analysis with ulcer size used as covariable showed a significant difference in healing times in favour of omeprazole. There was no difference in the occurrence of pain relief between the two treatment groups. No serious clinical or biochemical side effects of treatment were noted. CONCLUSIONS--Omeprazole 30 mg daily accelerates healing of ulcers in the body of the stomach as compared with cimetidine 1 g daily. This effect is more pronounced in ulcers greater than 12 mm diameter.     

Tissue therapy with autologous dermal and epidermal culture cells for diabetic foot ulcers

A great part of diabetic ulcers on the lower extremities have difficult healing and represent the most common cause of non-traumatic amputation In case of patients unresponsive to the classical therapy with debridement, dressings and systemic antibiotic therapy, cell therapy may be an excellent indication. The objective of this study was to assess the efficacy of autologous skin cell (fibroblasts and keratinocytes) implants cultivated ex vivo and applied to long-standing (9?C34?years) skin ulcers of five diabetic patients (4 DM2 and 1 DM1) with autologous fibrin glue. There were six ulcers of onset between 4?months and 20?years before and from 4.0 to 36.62?cm² in size, located on the lower limbs and unresponsive to the several conventional treatments. Complete healing was observed in five ulcers (83.3%), after 21?C120?days. The patient who presented the largest ulcer had partial improvement in 40?days. It is believed that the more distal ulcer location is, the worse is its prognosis. There probably is a correlation between healing time, ulcer size and prior duration. No adverse reactions derived from the treatment occurred. It is concluded that this method is an excellent therapeutic option for diabetic ulcers, allowing faster healing. Its great advantage is being a minimally invasive procedure that can be carried out in an outpatient clinic.     

How reliable is determination of ulcer size by endoscopy?

The suface areas of 23 artificial ulcers in a rubber manikin and of 35 ulcers in 35 consecutive patients admitted for endoscopy of the upper gastrointestinal tract were estimated by six endoscopists. Of the 138 estimations made in the manikin 80% underestimated the true size of the ulcer: the mean (+/- SD) was -29 +/- 40%. The largest and the smallest estimate of the same ulcer by different endoscopists varied on average by a factor of 4.5 +/- 3.8, and the estimates by the same endoscopists of ulcers with the same size varied by a factor of 2.3 +/- 0.6. In the patients the scatter of the estimates was even larger, the mean factor being 7.8 +/- 6.3. Changes in ulcer size are therefore an unsuitable criterion for assessing ulcer healing. Even if consecutive examinations are performed by the same endoscopist, changes in ulcer area smaller than by a factor of 3 are not discernible.     

Episodic therapy for genital herpes in sub-saharan Africa: a pooled analysis from three randomized controlled trials

Background

A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations.

Methodology/Principal Findings

Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98–1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm²), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors.

Conclusions/Significance

There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing.