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.

Patient-perceived effectiveness and impact on quality of life of solifenacin in combination with an α-blocker in men with overactive bladder in Sweden: a non-interventional study.

Treating male lower urinary tract symptoms (LUTS) by targeting the prostate would have limited effect on overactive bladder (OAB) symptoms. This study assessed perceived symptoms and quality of life (QoL) of male patients with OAB treated with an α-blocker plus solifenacin in daily clinical practice. Male patients aged ≥40 years were included after the decision was made to initiate treatment with an α-blocker for LUTS plus solifenacin for OAB symptoms. The primary endpoint was change in patient perception of bladder condition (PPBC) questionnaire score over 6 months. Other assessments included the OAB-questionnaire short form (OAB-q SF) and International Prostate Symptom Score (IPSS). Interpretation of the study data was hindered by not meeting the enrollment target and a high dropout rate. In 36 evaluable patients, mean (SD) PPBC score improved from 4.3 (0.93) at baseline ("moderate" to "severe" problems) to 3.5 (1.06) at month 6 ("minor" to "moderate" problems). OAB-q SF scores and total IPSS also improved. In this patient population, treatment with solifenacin and an α-blocker resulted in improvements in male patient perception of their LUTS and QoL, although the results should be interpreted with caution due to the low number of patients with complete data.

Pilot community-mobilization program reduces maternal and perinatal mortality and prevents obstetric fistula in Niger.

OBJECTIVE: To assess the impact of a pilot community-mobilization program on maternal and perinatal mortality and obstetric fistula in Niger. METHODS: In the program, village volunteers identify and evacuate women with protracted labor, provide education, and collect data on pregnancies, births, and deaths. These data were used to calculate the reduction in maternal mortality, perinatal mortality, and obstetric fistula in the program area from July 2008 to June 2011. RESULTS: The birth-related maternal mortality fell by 73.0% between years 1 and 3 (P<0.001), from 630 (95% confidence interval [CI] 448-861) to 170 (95% CI 85-305) deaths per 100 000 births. Early perinatal mortality fell by 61.5% (P<0.001), from 35 (95% CI 31-40) to 13 (95% CI 10-16) deaths per 1000 births. No deaths due to obstructed labor were reported after the lead-in period (February to June 2008). Seven cases of community-acquired fistula were reported between February 2008 and July 2009; from August 2009 to June 2011 (23 months; 12 254 births), no cases were recorded. CONCLUSION: Community mobilization helped to prevent obstetric fistula and birth-related deaths of women and infants in a large, remote, resource-poor area.

Randomised controlled trial of extraarticular gold bead implantation for treatment of knee osteoarthritis: a pilot study.

The primary objective of this double-blind, randomised, controlled trial was to determine if implanting gold beads at five acupuncture points around the knee joint improves 1-year outcomes for patients with osteoarthritis (OA) of the knee. Participants were 43 adults aged 18-80 years with pain and stiffness from non-specific OA of the knee for over a year. The intervention was blinded implantation of gold beads at five acupuncture points around the affected knee through a hypodermic needle, or needle insertion alone. Primary outcome measures were knee pain, stiffness and function assessed by the patient at 0, 1, 3, 6, 9 and 12 months and knee score and knee function assessed by an orthopaedic surgeon at 0, 6 and 12 months. Within the first month, three patients dropped out. The remaining 21/19 patients in the intervention/control groups generally improved, but there was no statistically significant difference between the groups. The improvement was shown in the patients' self-assessment scores that decreased from randomisation until 1 year later (intervention/control group, medians): pain -1.92/-2.18 (P = 0.95, F test, general linear mixed model); stiffness -0.93/-0.43 (P = 0.11); function -7.23/-3.36 (P = 0.63). The surgeon's scores also generally improved, i.e. increased: knee score +16.4/+8.2 (P = 0.65); knee function +10.5/+5.8 (P = 0.79). In the protocol-based subgroup analysis, the 15 intervention patients of the 32 patients who had a positive response to the initial conventional acupuncture had greater relative improvements in self-assessed outcomes. The treatment was well tolerated. This 1-year pilot study indicates that extraarticular gold bead implantation is a promising treatment modality for patients with OA of the knee. The new treatment should be tested in a larger trial including only patients who respond positively to initial conventional acupuncture.

Grey-box pharmacokinetic/pharmacodynamic modelling of a euglycaemic clamp study.

Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling the pharmacokinetics and pharmacodynamics of the in vivo system of insulin and glucose and to estimate model and derived PK/PD parameters. The concept behind grey-box modelling consists in using a priori physiological knowledge along with information from data in the estimation of model parameters. The PK/PD properties of two types of insulin are investigated in a euglycaemic clamp study where a single bolus of insulin is injected subcutaneously. The effect of insulin on the glucose disappearance is investigated by artificially maintaining a blood glucose concentration close to the normal fasting level. The infused glucose needed to maintain the clamped blood glucose concentration can therefore be used as a measure for the glucose utilization. The PK and PD parameters are successfully estimated simultaneously thereby describing the uptake, distribution, and effect of the two different types of insulin.

Grey-box modelling of pharmacokinetic/pharmacodynamic systems.

Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling consists of using stochastic differential equations (SDEs) where the stochastic term in the differential equations represents unknown or incorrectly modelled dynamics of the system. The methodology behind the grey-box PK/PD modelling framework for systematic model improvement is illustrated using simulated data and furthermore applied to Bergman's minimal model of glucose kinetics using clinical data from an intravenous glucose tolerance test (IVGTT). The grey-box estimates of the stochastic system noise parameters indicate that the glucose minimal model is too simple and should preferably be revised in order to describe the complicated in vivo system of insulin and glucose following an IVGTT.

A comparison of postprandial and preprandial administration of insulin aspart in children and adolescents with type 1 diabetes.

OBJECTIVE: The aim of this study was to compare the glycemic control of preprandial versus postprandial injections of the new rapid-acting insulin analogue aspart in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Forty-two children (aged 6-12 years) and 34 adolescents (13-17 years) were randomized to preprandial (immediately before meal start) and postprandial (immediately after a meal or a maximum of 30 min after meal start) treatment with insulin aspart (at least thrice daily) as part of a basal/bolus regimen in a multicenter study with an open labeled, two-period cross-over design (6-week periods). Of this group, 49% were boys, 55% were aged