LeucoPatch system for the management of hard-to-heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer-masked, randomised controlled trial.

BACKGROUND: The LeucoPatch device uses bedside centrifugation without additional reagents to generate a disc comprising autologous leucocytes, platelets, and fibrin, which is applied to the surface of the wound. We aimed to test the effectiveness of LeucoPatch on the healing of hard-to-heal foot ulcers in people with diabetes. METHODS: This was a multicentre, international, observer-masked, randomised controlled trial of people with diabetes and a hard-to-heal foot ulcer done in 32 specialist diabetic foot clinics in three countries (UK, Denmark, and Sweden). After a 4-week run-in period, those with a reduction in ulcer area of less than 50% were randomly allocated (1:1) by computer-generated, web-based randomisation (block sizes of two, four, and six) to either prespecified good standard care alone or care plus weekly application of LeucoPatch. The primary outcome was the proportion of ulcers that healed within 20 weeks assessed in the intention-to-treat population (all participants with post-randomisation data collected), defined as complete epithelialisation (confirmed by an observer who was masked to randomisation group), and remained healed for 4 weeks. This trial is registered with the ISRCTN registry, number 27665670, and ClinicalTrials.gov, number NCT02224742. FINDINGS: Between Aug 30, 2013, and May 3, 2017, 269 participants were randomly allocated to receive treatment (137 to receive standard care and 132 to receive LeucoPatch). The mean age was 61·9 years (SD 11·6), 217 (82%) were men, and 222 (83%) had type 2 diabetes. In the LeucoPatch group, 45 (34%) of 132 ulcers healed within 20 weeks versus 29 (22%) of 134 ulcers in the standard care group (odds ratio 1·58, 96% CI 1·04-2·40; p=0·0235) by intention-to-treat analysis. Time to healing was shorter in the LeucoPatch group (p=0·0246) than in the standard care group. No difference in adverse events was seen between the groups. The most common serious adverse event (SAE) was diabetic foot infection (24 events in the LeucoPatch group [24% of all SAEs] and 20 in the standard care group [27% of all SAEs]. There were no device-related adverse events. INTERPRETATION: The use of LeucoPatch is associated with significant enhancement of healing of hard-to-heal foot ulcers in people with diabetes. FUNDING: Reapplix ApS.

Relationship between poststroke cognition, baseline factors, and functional outcome: data from "efficacy of nitric oxide in stroke" trial.

BACKGROUND: Poststroke cognitive impairment is common and identification of prognostic factors associated with it and its relationship with other functional outcomes may help in developing preventative strategies. METHODS: Previously independent patients with acute stroke, enrolled into the ongoing "Efficacy of Nitric Oxide in Stroke" trial, were assessed by telephone on day 90 for cognitive impairment using modified versions of "Mini Mental State Examination" (MMSE-M) and "Telephone Instrument for Cognitive Status" (TICS-M) scales and category fluency. The relationship of cognitive impairment with baseline prognostic factors and other functional outcomes at day 90 were studied. RESULTS: The analysis included 1572 patients, mean age 69 years (standard deviation, 12), and female 40%. By 90 days, 246 patients had died, and cognitive impairment was present in 38%. Increasing age, stroke severity, heart rate, and presence of cerebral atrophy on baseline neuroimaging were associated with cognitive impairment (all P < .001). Hypertension and atrial fibrillation were also associated with category fluency and MMSE-M, respectively. Cognition was significantly related to other functional outcomes, TICS-M with dependency (modified Rankin Scale, rs = -.562, P < .001); disability (Barthel Index, rs = .577, P < .001); mood (Zung Depression Score, rs = -.542, P < .001); and quality of life (Euro Quality of life-5 Descriptor, rs = .519, P < .001). CONCLUSIONS: In previously independent individuals, cognitive impairment was common 3 months after stroke and related to increasing age, stroke severity, hypertension, atrial fibrillation, and cerebral atrophy on brain scanning. Cognition was related to dependency, disability, low mood, and quality of life. Hence, treatment directed toward reducing dependency might also reduce cognitive impairment.

Interventions for dysphagia and nutritional support in acute and subacute stroke.

BACKGROUND: Dysphagia (swallowing problems) are common after stroke and can cause chest infection and malnutrition. Dysphagic, and malnourished, stroke patients have a poorer outcome. OBJECTIVES: To assess the effectiveness of interventions for the treatment of dysphagia (swallowing therapy), and nutritional and fluid supplementation, in patients with acute and subacute (within six months from onset) stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (February 2012), MEDLINE (1966 to July 2011), EMBASE (1980 to July 2011), CINAHL (1982 to July 2011) and Conference Proceedings Citation Index- Science (CPCI-S) (1990 to July 2011). We also searched the reference lists of relevant trials and review articles, searched Current Controlled Trials and contacted researchers (July 2011). For the previous version of this review we contacted the Royal College of Speech and Language Therapists and equipment manufacturers. SELECTION CRITERIA: Randomised controlled trials (RCTs) in dysphagic stroke patients, and nutritional supplementation in all stroke patients, where the stroke occurred within six months of enrolment. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, assessed trial quality, and extracted data, and resolved any disagreements through discussion with a third review author. We used random-effects models to calculate odds ratios (OR), 95% confidence intervals (95% CI), and mean differences (MD). The primary outcome was functional outcome (death or dependency, or death or disability) at the end of the trial. MAIN RESULTS: We included 33 studies involving 6779 participants.Swallowing therapy: acupuncture, drug therapy, neuromuscular electrical stimulation, pharyngeal electrical stimulation, physical stimulation (thermal, tactile), transcranial direct current stimulation, and transcranial magnetic stimulation each had no significant effect on case fatality or combined death or dependency. Dysphagia at end-of-trial was reduced by acupuncture (number of studies (t) = 4, numbers of participants (n) = 256; OR 0.24; 95% CI 0.13 to 0.46; P < 0.0001; I(2) = 0%) and behavioural interventions (t = 5; n = 423; OR 0.52; 95% CI 0.30 to 0.88; P = 0.01; I(2) = 22%). Route of feeding: percutaneous endoscopic gastrostomy (PEG) and nasogastric tube (NGT) feeding did not differ for case fatality or the composite outcome of death or dependency, but PEG was associated with fewer treatment failures (t = 3; n = 72; OR 0.09; 95% CI 0.01 to 0.51; P = 0.007; I(2) = 0%) and gastrointestinal bleeding (t = 1; n = 321; OR 0.25; 95% CI 0.09 to 0.69; P = 0.007), and higher feed delivery (t = 1; n = 30; MD 22.00; 95% CI 16.15 to 27.85; P < 0.00001) and albumin concentration (t = 3; n = 63; MD 4.92 g/L; 95% CI 0.19 to 9.65; P = 0.04; I(2) = 58%). Although looped NGT versus conventional NGT feeding did not differ for end-of-trial case fatality or death or dependency, feed delivery was higher with looped NGT (t = 1; n = 104; MD 18.00%; 95% CI 6.66 to 29.34; P = 0.002). Timing of feeding: there was no difference for case fatality, or death or dependency, with early feeding as compared to late feeding. Fluid supplementation: there was no difference for case fatality, or death or dependency, with fluid supplementation. Nutritional supplementation: there was no difference for case fatality, or death or dependency, with nutritional supplementation. However, nutritional supplementation was associated with reduced pressure sores (t = 2; n = 4125; OR 0.56; 95% CI 0.32 to 0.96; P = 0.03; I(2) = 0%), and, by definition, increased energy intake (t = 3; n = 174; MD 430.18 kcal/day; 95% CI 141.61 to 718.75; P = 0.003; I(2) = 91%) and protein intake (t = 3; n = 174; MD 17.28 g/day; 95% CI 1.99 to 32.56; P = 0.03; I(2) = 92%). AUTHORS' CONCLUSIONS: There remains insufficient data on the effect of swallowing therapy, feeding, and nutritional and fluid supplementation on functional outcome and death in dysphagic patients with acute or subacute stroke. Behavioural interventions and acupuncture reduced dysphagia, and pharyngeal electrical stimulation reduced pharyngeal transit time. Compared with NGT feeding, PEG reduced treatment failures and gastrointestinal bleeding, and had higher feed delivery and albumin concentration. Nutritional supplementation was associated with reduced pressure sores, and increased energy and protein intake.