A gellan-based fluid gel carrier for spray delivery

Autologous cell transplantation is a promising approach to enhance burn wound reepithelialisation. It was introduced to clinical practice decades ago with current delivery techniques involving spraying autologous cultured or uncultured cells in low-viscosity suspensions. This delivery method is limited since it results in an uneven distribution on the wound bed and cell loss as the liquid is not retained on the skin surface. In this thesis, a sprayable gel that solidifies on the surface of the skin has been developed to circumvent this problem. A gellan-based fluid gel system was developed with flexible viscoelastic properties that can be tuned by a biocompatible polymer concentration and ionic strength to facilitate spray delivery. The material liquefies at high shear during spraying with self-healing properties of the gel causing it to solidify on the receiving surface. Results present the development and characterisation of a gellan fluid gel for the encapsulation and spray-delivery of cells onto surfaces, aiming for reduced cell spillage, improved spray uniformity and maintenance of cell viability and function. Additionally, the same polymer was used to formulate a gellan film that can be rehydrated in acetic acid for the treatment of wound infections. Gellan is a versatile polymer as shown by the formulations explored in this study and a promising candidate for cell and drug delivery applications

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Effect of surgical decompression of nerves in the lower extremity in patients with painful diabetic polyneuropathy on stability : A randomized controlled trial

Objective: To investigate the effect of decompression of nerves in the lower extremity in patients with painful diabetic polyneuropathy on static balance using a sensitive pressure mat system. Design: Non-blinded randomized controlled trial. Setting: Single center study performed at the University Medical Center Utrecht between 2010-2013. Subjects: Patients with painful diabetic polyneuropathy assessed with the Diabetic Neuropathy Symptom score and Diabetic Neuropathy Examination between 18-90 years. Exclusion criteria were: physical problems leading to instability, BMI>35 kg/m2, ankle fractures in history, amputations proximal to the tarsometatarsal joints, active foot ulcer(s), severe occlusive peripheral vascular diseases. Intervention: Unilateral surgical nerve decompression at four sites in the lower extremity, the contralateral limb was used as control (within-patient comparison), with one year follow-up. Main measures: Preoperatively and 6 and 12 months postoperatively, weight bearing and five variables of sway of the center of pressure were measured with a pressure mat with eyes open and eyes closed. T-test was used for evaluation of postoperative results. Results: Thirty-nine Patients met inclusion criteria and were enrolled for stability testing. Postoperatively no significant differences for sway variables and weight bearing were seen compared to preoperatively measurements. Conclusions: There is no evidence that surgical decompression of nerves of the lower extremity influences stability within one year after surgery in patients with painful diabetic polyneuropathy