The reality of routine practice: a pooled data analysis on chronic wounds treated with TLC-NOSF wound dressings.

OBJECTIVE: A number of randomised controlled trials (RCT) have compared control groups with TLC-NOSF dressings (UrgoStart) on chronic wounds. Our aim was to determine whether the clinical trials' results translate into routine management of such wounds, by pooling the data from real-life observational studies. METHOD: Observational studies, conducted in France and Germany, evaluating current practices in patients suffering from non-selected chronic wounds treated with a TLC-NOSF dressing were identified. Demographic data, baseline description of wounds and description of their evolution during treatment were extracted and combined. We used two main indicators of clinical outcomes to measure the impact of the TLC-NOSF dressing on this population: time to wound closure and time to 50% reduction of the Pressure Ulcer Scale for Healing (PUSH) score. RESULTS: In total, data from 10,220 patients were included, with 7903 leg ulcers (LUs), 1306 diabetic foot ulcers (DFUs) and 1011 pressure ulcers (PUs). The overall closure rate was 30.8 % [95 % confidence interval (CI): 29.9-31.7 %]. While the country, patient age, and number of wounds were identified as independent prognosis factors of healing, the most significant were wound duration and baseline area. The delay in initiating TLC-NOSF dressings treatment was also found to be significant. Overall the average time to complete closure was 112.5 days [95%CI: 105.8-119.3] for LUs, 98.1 days [95 %CI: 88.8-107.5] for DFUs and 119.5 days [95%CI: 94.6-144.3] for PUs. Based on a subgroup analysis of the French cohort, time to closure is substantially shorter for wounds treated with the TLC-NOSF dressing as a first-line intervention compared with those where it has been prescribed as a second-line intervention. CONCLUSION: Compared with available data on time to complete closure of chronic wounds managed by 'standard' care, the data from this pooled data analysis showed healing time is reduced, which is consistent with the results of RCTs on TLC-NOSF. That these data are in agreement with those from the RCTs is testimony to their generalisability and important for routine practice. This indicates that using TLC-NOSF dressings in routine wound management can reduce the healing time of LUs, DFUs and PUs. These data also suggest that the earlier the decision to use this dressing, the shorter the time to closure, whatever the severity and the nature of these chronic wounds.

Protease-modulating polyacrylate-based hydrogel stimulates wound bed preparation in venous leg ulcers--a randomized controlled trial.

BACKGROUND: Stringent control of proteolytic activity represents a major therapeutic approach for wound-bed preparation. OBJECTIVES: We tested whether a protease-modulating polyacrylate- (PA-) containing hydrogel resulted in a more efficient wound-bed preparation of venous leg ulcers when compared to an amorphous hydrogel without known protease-modulating properties. METHODS: Patients were randomized to the polyacrylate-based hydrogel (n = 34) or to an amorphous hydrogel (n = 41). Wound beds were evaluated by three blinded experts using photographs taken on days 0, 7 and 14. RESULTS: After 14 days of treatment there was an absolute decrease in fibrin and necrotic tissue of 37.6 ± 29.9 percentage points in the PA-based hydrogel group and by 16.8 ± 23.0 percentage points in the amorphous hydrogel group. The absolute increase in the proportion of ulcer area covered by granulation tissue was 36.0 ± 27.4 percentage points in the PA-based hydrogel group and 14.5 ± 22.0 percentage points in the control group. The differences between the groups were significant (decrease in fibrin and necrotic tissue P = 0.004 and increase in granulation tissue P = 0.0005, respectively). CONCLUSION: In particular, long-standing wounds profited from the treatment with the PA-based hydrogel. These data suggest that PA-based hydrogel dressings can stimulate normalization of the wound environment, particularly in hard-to-heal ulcers.

Workload and prevalence of open wounds in the community: French Vulnus initiative.

OBJECTIVE: To calculate the prevalence of open cutaneous wounds presented on a routine working day in community settings in metropolitan France, and to estimate the workload associated with the care of these wounds by nurses, GPs and specialists (dermatologists, diabetologists and phlebologists). METHOD: A transversal epidemiological survey was conducted on a randomly selected sample of the above practitioners between June and July 2008. The percentage of patients presenting on a routine working day with open a cutaneous lesion of any origin, location, size and duration was assessed. All local and systemic care performed on the patient during that day because of the wound was also recorded. RESULTS: In total, 475 GPs, 453 specialists and 238 nurses participated (n=1166) and saw a total of 29 663 patients, of whom 3037 presented with one or more cutaneous wound. The overall non-weighted prevalence of patients with a wound was 10.2% (95%CI: 9.9%;10.6%). This prevalence was similar for GPs (6.0%) and for specialists (6.9%), but was higher for nurses (22.0%). Forty-three per cent of all wounds had a duration of over 6 weeks. These chronic wounds were predominantly leg ulcers, diabetic foot ulcers or pressure ulcers, but also included wounds of all aetiologies. For 33% of all patients with wounds, the impact on their health status was serious to severe. The overwhelming majority of wounds (95%) required local care, including in 65% of cases cleansing and debridement. CONCLUSION: Despite its limitations, this initiative, the first of its type in France, strongly suggests that wound care constitutes an important part of routine care given by health professionals in the community, and for a substantial number of these patients, wounds represent a serious morbidity. DECLARATION OF INTEREST: The non-profit organisation 'Association Vivre avec une Plaie' financially supported this study. This association received unrestricted grants from the French Wound Healing Society (SFFPC) and a consortium of private companies (main sponsors: ConvaTec, Genevrier, Hartmann, KCI, Mölnycke, Smith & Nephew, Urgo; minor sponsors: Coloplast, Covidien, HNE) to fund the costs incurred by the methodological process and statistical analysis but had no input into the findings. The National Health Insurance Organisation provided non-financial support to this initiative. J.C. Kerihuel received support for the submitted work from 'Association Vivre avec une Plaie'. S. Meaume, I. Fromantin and L. Téot have no financial relationship with 'Association Vivre avec une Plaie', for either this or any work submitted in the previous 3 years. The authors have no non-financial interests that may be relevant to the submitted work, and their spouses, partners, or children have no financial relationships that may be relevant to the submitted work

Effect of activated charcoal dressings on healing outcomes of chronic wounds.

OBJECTIVE: To compare the ability of activated charcoal dressings with that of a hydrocolloid dressing to reduce the wound area of chronic wounds. METHOD: Two separate randomised controlled trials (RCTs) were undertaken; both used the same hydrocolloid as the control. One RCT compared Actisorb (without silver) with the control on chronic pressure ulcers and the other RCT compared Actisorb Silver 220 with the control on chronic venous leg ulcers. Patients were followed for four weeks. Baseline patient demographic and wound characteristics were comparable between the treatment and control groups. Wounds were assessed at weekly intervals. Ulcers were photographed and then traced by an experienced, independent investigator. Both the reduction in ulcer area and the percentage reduction were calculated. RESULTS: Sixty patients were enrolled into each study, although data for one patient were not available in the pressure ulcer study. There were differences in results at week 1 in favour of the treatment group in both studies, although the results for the two groups in each study were comparable at week 4. Activated charcoal dressing was better tolerated than the control. CONCLUSION: These clinical data indicate the potential usefulness of using activated charcoal impregnated with silver in the management of chronic wounds, even at the debridement stage. This dressing may help remove fluids and toxins that impair the healing process.

Effect of bisoprolol on blood pressure and arterial hemodynamics in systemic hypertension.

Blood pressure, heart rate, common carotid and brachial arterial hemodynamics using pulsed Doppler flowmetry and pulse wave velocity determinations were evaluated using a double-blind crossover design versus placebo in 14 patients with sustained essential hypertension treated by the selective beta 1 blocking agent bisoprolol. Blood pressure and heart rate significantly decreased after bisoprolol, whereas no significant change occurred in the diameter, the blood flow and in the vascular resistance of the carotid and brachial circulations. Pulse wave velocity significantly decreased in the brachioradial and the carotid femoral areas. The decrease in the latter was -1.6 +/- 0.8 m/s with bisoprolol and -0.06 +/- 0.80 m/s with placebo (p = 0.001). Brachial artery compliance significantly increased from 117 +/- 49 to 205 +/- 84 cm4 x dynes-1 x 10(9) (p = 0.001), indicating that the antihypertensive effect of beta 1 blockade is associated with an improvement in the viscoelastic properties of the brachial artery wall.

Meta-analyses of the efficacy and tolerability of the tricyclic antidepressant lofepramine.

Lofepramine is a tricyclic antidepressant related to imipramine. Meta-analyses were carried out with respect to efficacy and tolerability by combining outcome and adverse reaction from over 20 controlled trials comparing lofepramine with other tricyclic antidepressants. Lofepramine was at least as effective as the comparators with fewer adverse effects. In particular, the risk/benefit ratio seemed superior to the comparators amitriptyline, imipramine, clomipramine, maprotiline and desipramine.

[Beta-blockaders and atheroma regression: a necessary evaluation?]. / Bêtabloqueurs et régression de l'athérome: une évaluation nécessaire?

Beta-blockers have been shown to have a beneficial effect especially regarding secondary prevention in coronary patients. The reduction in global mortality is most noticeable with respect to sudden death, which suggests an antiarrhythmic effect, but other non-lethal ischaemic events are also less frequent. The explanation of this observation is certainly multifactorial: some results point to a potential action on the development of atherosclerotic lesions. This justifies experimental and clinical studies of this hypothesis with this pharmacological group of drugs.

[Antihypertensive effect of a new form of nifedipine compared to a beta-blocker during chronic administration]. / Etude de l'effet antihypertenseur d'une nouvelle forme de nifédipine comparée à un bêtabloqueur en administration chronique.

The aim of this study was to test the efficacy of a 20 mg tablet preparation of nifedipine alone in twice daily dosage, in the treatment of moderate hypertension (95 greater than or equal to DBP less than or equal to 115 mmHg). Efficacy was defined as the ability to maintain treatment for 6 months with a fall in DBP of a least 5 mmHg after the first month, and with a DBP 100 mmHg from the second month. One hundred and seventy seven patients were recruited from november 1981 to december 1982, 55% during the first three months of the trial. There were 95 men (54%) and 82 women, with a mean age of 55.6 +/- 10 years. The DBP ranged from 96 to 111 mmHg in 80% of cases. The patients were randomly allocated in lots of 6, to three groups: placebo (58 patients), nifedipine (57 patients) and acebutolol (61 patients). The comparability of 21 parameters amongst these 3 groups was verified. After 1 month of placebo, 25 patients did not meet the criteria of inclusion and were excluded from the study. During this phase, 19 patients (10.5%) complained of at least one side effect. Of the 152 patients who received active treatment, 34 (22.4%) were "wrongly included", 17 did not complete the test period for undefined reasons and were considered to have been "lost to follow-up", and 6 patients "deviated" from the protocol. These 3 groups were taken into account in the statistical analysis of the graphs of non-failure.

Comparative bioequivalence study of a new levothyroxine solution versus a reference L-thyroxine solution in normal healthy volunteers.

A bioequivalence study between a new Levothyroxine solution and a reference solution was performed in 12 healthy volunteers after one single 3000 g oral administration. Administrations were done according to a cross-over schedule with a three week wash-out period. Plasma profile of Levothyroxine was determined for 72 hours, clinical tolerance being appreciated for 10 days after each administration. No statistical difference was reported for pharmacokinetic parameters and clinical tolerance was good.

Efficacy and safety of ornithine alpha-ketoglutarate in heel pressure ulcers in elderly patients: results of a randomized controlled trial.

OBJECTIVE: Pressure ulcers affect predominantly the elderly and nutritional status is a known risk factor. Guidelines on pressure ulcers provide recommendation on nutritional management. Ornithine alpha-ketoglutarate (OKG) is an adjuvant treatment in undernourished elderly patients or in patients with hypercatabolism states. It is a precursor of different amino-acids which play a role in the process of healing. The objective of the study is to determine the efficacy of OKG on pressure ulcer area reduction after six weeks of treatment. DESIGN: Multi-centre, international, randomized, comparative, double blind, parallel groups, placebo-controlled study. PARTICIPANTS: 160 patients (ITT population) aged over 60 years with a heel pressure ulcer at stage II or III. INTERVENTION: Patients received OKG (n=85) or placebo (n=75) once a day for 6 weeks. MEASUREMENTS: Ulcer area was measured each week, using a tracer. The primary endpoint was the percentage reduction of the surface at the final visit: [(Wound areatn - Wound areat0)/ (Wound areat0)]. RESULTS: At inclusion, ulcer area distribution deviated from normal distribution (median ulcer area OKG 6.6 cm(2), placebo 3.9 cm2, p=0.044, Mann-Whitney test). As healing is strongly related to baseline ulcer area, the abnormal distribution was a major bias. Therefore it was decided to perform the analysis on 2 sub-groups of patients according to the mean ulcer area, i.e. above or below 8 cm2. The mean wound area reduction for baseline area 8 cm2 no between group differences on either parameter was detected. When closure rate is considered, a significant difference in favor of OKG group is observed (- 0.07 cm2/day in the OKG group and - 0.04 cm2/day in the placebo groups respectively p=0.007, Mann-Whitney test). Thirty serious adverse events were reported in 28 patients (15 allocated to OKG and 13 to placebo). None of them was considered treatment related. CONCLUSION: This clinical trial supports a potential benefit of OKG 10g daily in the subgroup of patients with pressure ulcers

Clinical study of muzolimine in acute renal failure, pharmacodynamics and pharmacokinetics.

UNLABELLED: The aim of this study was to test the efficiency of muzolimine in patients with acute renal failure (ARF). METHODS: 6 patients, all males, 46 to 78 years old (mean 67.3 +/- 12.5) suffering from acute renal failure as a complication of a surgical procedure (4 cases) or a medical disease (2 cases) were selected. Creatinine clearance rates were below 20 ml/min for all subjects except one (mean: 14.4 ml/min range 4-34), blood urea levels from 21 to 65 mmol/l (mean = 36.4); mean urinary output, during the 24 hours preceding the study (D-1) was 100.4 +/- 57 ml/h (range 36-208) without any diuretic treatment. No patient was on dialysis. On the treatment day a single oral dose of muzolimine (240 mg) was administered in the morning. During the treatment day (D0) and the post treatment day (D + 1), pharmacodynamics and pharmacokinetics were evaluated. Mean urinary output increased from 1.67 +/- 0.95 ml/min, at D-1 to 3.24 +/- 2 ml/min at D0 (NS), with great differences between patients. The main effect was noted between 0 and 6 hours after the ingestion of muzolimine. The mean electrolyte output increased from D0 to D1 for Na+ (0.1 mmol/min +/- 0.08----0.25 +/- 0.1-NS), K+ (0.05 mmol/min +/- 0.02----0.08 +/- 0.07-NS), Cl- (0.07 +/- 0.07 mmol/min----0.30 +/- 0.12 p less than 0.05) and Ca++ (1.89 +/- 1.89 meq/24 h----4.1 +/- 2 NS), with large individual variations. Mean urea output increased slightly in only 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study of muzolimine and acebutolol in the treatment of moderate hypertension.

In a controlled double-blind study the effect of muzolimine (20 mg o.d.) and acebutolol (400 mg o.d.) were investigated in outpatients suffering from moderate essential hypertension. After a three week placebo run-in period, 49 patients were recruited and followed by a cooperative group of general practitioners over a period of 3 months. Blood pressure decreased to the same extent in both groups. With regard to clinical and biological tolerance, no differences appeared between the two drugs.