Focused shockwave therapy in diabetic foot ulcers: secondary endpoints of two multicentre randomised controlled trials.

OBJECTIVE: The objective of this paper is to present the secondary safety and efficacy outcomes from two studies of focused extracorporeal shockwave therapy (ESWT) used adjunctively with standard care in the treatment of neuropathic diabetic foot ulcers (DFU) (1A or 2A on the University of Texas grading scheme), compared with sham treatment and standard care. METHOD: We carried out two multicentre, multinational, randomised, sham-controlled, double-blinded, phase III clinical studies using standard care with adjunctive focused ESWT compared with sham treatment and standard care in patients with a DFU. DFUs that did not reduce in volume by at least 50% over two weeks' standard treatment were included. DFUs were randomised and managed with standard care and focused ESWT (pulsed acoustic cellular expression; dermaPACE System, SANUWAVE Health, Inc.) active therapy, or with standard care and sham treatment, four times over a two-week treatment phase in study 1 and up to eight times over 12 weeks in study 2. Standard care continued in both studies throughout the 12-week treatment phase. Secondary outcomes were indicators of wound closure and progression, pain, infection, amputation and recurrence, and device reliability. Efficacy-related secondary endpoints were measured at 12, 20 and 24 weeks. The studies were analysed separately and following statistical comparison to justify the method, as a pooled data set. RESULTS: Wound area reduction (48.6% versus 10.7%, p=0.015, intention to treat (ITT) population with last observation carried forward (LOCF)) and perimeter reduction (46.4% versus 25.0%, p=0.022, ITT population with LOCF) were significantly greater in the active therapy group compared with the sham-treated group, respectively. The difference in time to wound closure in the pooled ITT population was significantly in favour of the active therapy group (84 days versus 112 days for 25% of subjects to reach wound closure in the active and sham-treated groups, respectively; p=0.0346). The proportion of subjects who achieved wound area reduction (WAR) from baseline at week 12 of ≥90% was significantly higher in the active therapy group. The incidence and nature of infection were consistent with previously published studies, and pain was not increased in the active therapy group. Amputation was insignificantly higher in the sham-treated group and recurrence did not differ. The ESWT device was found to be reliable. CONCLUSION: The outcomes for the primary and secondary endpoints from these studies show that ESWT administered adjunctively with standard care is an effective advanced therapy for neuropathic DFUs (grade 1A and 2A) that do not respond to two weeks' standard care alone by reducing wound volume by at least 50%.

Stability, Activity, and Application of Topical Doxycycline Formulations in a Diabetic Wound Case Study.

INTRODUCTION: Tetracycline molecules comprise a group of broad-spectrum antibiotics whose primary mechanism of action is the inhibition of protein synthesis through the binding of the bacterial ribosome. In addition, tetracyclines inhibit matrix metalloproteases (MMPs), a family of zinc-dependent proteases that contribute to tissue remodeling, inflammation, and angiogenesis and are overexpressed in certain pathophysiologies such as diabetic foot ulcers (DFUs). OBJECTIVE: This study aims to develop a liquid chromatography and mass spectrometry (LC-MS/MS) doxycycline quantification methodology to facilitate the development of a stable topical doxycycline hyclate (DOXY) formulation as well as evaluate the topical DOXY formulation for the efficacy in MMP-9 inhibition in vitro and in a clinical application of diabetic lower extremity wounds. MATERIALS AND METHODS: A simple quantification method utilizing LC-MS/MS was used to develop a topical DOXY formulation, a sample of which was analyzed in stability testing. The formulation was evaluated in vitro for MMP-9 activity using a commercial assay and compared with internal kit controls as well as in a clinical setting for wound healing. RESULTS: Two formulations of 2% (w/w) DOXY demonstrated acceptable stability (±10% target concentration) for 70 days when stored at 4°C. Using an in vitro assay of MMP-9 enzyme activity, the 2% DOXY formulation imparted a ~30% decrease in MMP-9 inhibitory potential as compared with the control drug alone (IC50 values 62.92 µM and 48.27 µM, respectively). This topical product was evaluated for clinical utility in a patient with a DFU, and preliminary data suggest this intervention may promote wound healing. CONCLUSIONS: In summary, novel DOXY formulations may be stable and biologically active tools amenable to complex wound care.

Diabetic foot ulcer treatment with focused shockwave therapy: two multicentre, prospective, controlled, double-blinded, randomised phase III clinical trials.

OBJECTIVE: To investigate the efficacy of focused extracorporeal shockwave therapy (ESWT) as an adjunctive treatment for neuropathic diabetic foot ulcers (DFU) (1A or 2A on the University of Texas grading scheme), compared with sham treatment. METHOD: We performed two multicentre, randomised, sham-controlled, double-blinded, phase III clinical trials using focused ESWT compared with sham examining DFUs that did not reduce in volume by ≥50% over 2 weeks' standard treatment immediately prior to randomisation. Patients were enrolled into the trials and randomised for either standard care and focused ESWT (pulsed acoustic cellular expression. dermaPACE System, SANUWAVE Health Inc.) active therapy, or standard care and sham therapy. Both active and sham therapy were administered four times in 2 weeks in study 1 and a maximum of eight times over 12 weeks in study 2. Standard care continued in both studies throughout the 12-week treatment phase. The proportion of DFUs that closed completely by 12, 20 and 24 weeks was measured. RESULTS: The two studies evaluated 336 patients; 172 patients treated with active therapy and 164 managed with a sham device. The demographic characteristics of patients in the two arms of both studies were balanced and statistical comparison of the two studies justified pooling datasets for analysis. Statistically significantly more DFU healed at 20 (35.5% versus 24.4%; p=0.027) and 24 weeks (37.8% versus 26.2%; p=0.023) in the active treatment arm compared with the sham-controlled arm. At 12 weeks the active therapy arm trended to significance (22.7% versus 18.3%). CONCLUSION: The outcome of these two trials suggests that ESWT is an effective therapeutic modality in combination with standard care for neuropathic DFU that do not respond to standard care alone.

LivRelief varicose veins cream in the treatment of chronic venous insufficiency of the lower limbs: A 6-week single arm pilot study.

BACKGROUND: Chronic Venous Disease is characterized by morphological abnormalities of the venous system. Affected limbs are classified in increasing clinical severity with the Clinical Etiological Anatomical and Pathological system from C0 to C6. Limbs assessed at C3 through C6 meet the criteria of Chronic Venous Insufficiency. Chronic Venous Insufficiency of the Lower Limbs is a very common pathology affecting approximately ~40% of the world's population. This study observes the use of the LivRelief Varicose Vein Cream, a Natural Health Product that is licensed for sale by Health Canada, for use in the treatment of varicose veins. METHODS: An open label, single arm interventional, pilot study was conducted to determine the feasibility of recruitment and data collection in this population. To accomplish this, the cream was provided to all enrolled subjects. Subsequently, objective and subjective measures were performed at baseline and after 6 weeks of at-home use. Recruitment and data collection targets of at least 70% were established and the data collected at both timepoints were compared and analyzed using a paired t-test. Results were also reported as proportions where appropriate. RESULTS: A total of 32 subjects were enrolled. The pre-defined feasibility objectives for recruitment and data collection were met with the enrolment of 97% of all screened patients and the collection of 94% of all scheduled data. The most significant therapeutic improvement was seen in the results of the Venous Clinical Severity Score where 66% of the treated legs experienced a decrease in severity after 6 weeks of treatment. P values were <0.0001 and 0.0003 for the left and right leg, respectively. CONCLUSION: It is feasible to recruit and collect data with the chosen outcome assessments within this population. Preliminary results suggest that the product could improve some of the clinical symptoms associated with the presence varicose veins. These results warrant further exploration in a longer, randomized and placebo-controlled study. TRIAL REGISTRATION: Clinicaltrial.gov: NCT03653793.

Outcomes Following Advanced Wound Care for Diabetic Foot Ulcers: A Canadian Study.

OBJECTIVES: Data concerning outcomes of Canadian patients with diabetic foot ulcers (DFUs) are limited. The objectives of this study were to evaluate the healing rates and identify the predictors of poor outcomes following advanced wound care in patients presenting with DFUs. METHODS: We conducted retrospective cohort study of adult patients who had DFUs and were referred to a single Canadian advanced diabetic foot and wound care centre between January 1, 2010, and December 31, 2010. The primary outcome was the healing rate at 52 weeks. The generalized estimating equation model was used to identify potential risk factors associated with delayed healing of DFUs. RESULTS: Of the 40 patients for whom there were complete follow ups, 35 (87.5%) had healing of all DFUs by 52 weeks. Predictors of poor healing were the presence of chronic ulcers, ulcer sizes >1 cm2, peripheral vascular disease and multiple ulcers at first presentation. Of the patients, 7.1% required amputation, and 8.9% of patients receiving our treatment died before 52 weeks. At 52 weeks of follow up, 16 of 17 recurrent ulcers and 68 of 108 pre-existing ulcers had healed. Compared to the unadjusted healing rate of preexisting ulcers (63.0%), the unadjusted healing rate of recurrent ulcers (94.1%) was significantly higher (p=0.01). CONCLUSIONS: Our findings demonstrate that patients with DFUs in Canada who receive early and continued care from specialized, outpatient, advanced wound care centres experience significantly improved rates of healing of recurrent DFUs compared to pre-existing DFUs.

Just leg pain? Think again: What health leaders must know about peripheral arterial disease.

Approximately 800,000 Canadians have Peripheral Arterial Disease (PAD). Peripheral arterial disease is also a leading cause of limb amputation. Yet public and clinical awareness of PAD is very limited. This article discusses the "Just Leg Pain? Think Again" awareness campaign the Canadian Association of Wound Care has launched in response. This article also summarizes PAD risk factors, screening, linkage with diabetes, treatment and care interventions, PAD care innovations, and the need for policy leadership on this issue.

Si vous pensez que c'est juste un mal de jambe détrompez-vous: ce que les leaders en santé doivent savoir sur la maladie artérielle périphérique.

Environ 800 000 Canadiens ont une maladie artérielle périphérique (MAP), une cause majeure d'amputation. Pourtant, le public et les cliniciens connaissent très peu cette maladie. Le présent article traite de la campagne de sensibilisation Si vous pensez que c'est juste un mal de jambe… détrompez-vous que l'Association canadienne du soin des plaies a lancée pour contrer cette tendance. Il porte également sur les facteurs de risque et le dépistage de la MAP, son lien avec le diabète, son traitement et ses soins, ses innovations en matière de soins de la MAP et la nécessité de faire preuve de leadership sur le plan des politiques.

Once-daily administration of budesonide Turbuhaler was as effective as twice-daily treatment in patients with mild to moderate persistent asthma.

In a double-blind, randomized, placebo-controlled trial, 288 patients with mild to moderate persistent asthma currently on inhaled glucocorticosteroids (GCSs) were treated with budesonide Turbuhaler, 200 microg once every night (q.n.), 100 microg twice-daily (b.i.d.), or placebo b.i.d. After 12 weeks, morning peak expiratory flow (PEF) increased in both groups treated with budesonide but decreased in placebo-treated patients. Symptom scores and bronchodilator use were significantly reduced in both groups receiving active treatment (p = 0.023-0.0001) compared with patients treated with placebo. There was no significant difference in outcome measurements between the two budesonide regimens. Thus, patients with mild to moderate persistent asthma receiving b.i.d. treatment with inhaled GCSs can usually be switched to budesonide Turbuhaler, 200 microg, q.n. without loss of asthma control.