Socio‐economic status and quality of life in children with chronic disease: A systematic review

Reduced quality of life (QoL) is a known consequence of chronic disease in children, and this association may be more evident in those who are socio‐economically disadvantaged. The aims of this systematic review were to assess the association between socio‐economic disadvantage and QoL among children with chronic disease, and to identify the specific socio‐economic factors that are most influential. MEDLINE, Embase and PsycINFO were searched to March 2015. Observational studies that reported the association between at least one measure of social disadvantage in caregivers and at least one QoL measure in children and young people (age 2–21 years) with a debilitating non‐communicable childhood disease (asthma, chronic kidney disease, type 1 diabetes mellitus and epilepsy) were eligible. A total of 30 studies involving 6957 patients were included (asthma (six studies, n = 576), chronic kidney disease (four studies, n = 796), epilepsy (14 studies, n = 2121), type 1 diabetes mellitus (six studies, n = 3464)). A total of 22 (73%) studies reported a statistically significant association between at least one socio‐economic determinant and QoL. Parental education, occupation, marital status, income and health insurance coverage were associated with reduced QoL in children with chronic disease. The quality of the included studies varied widely and there was a high risk of reporting bias. Children with chronic disease from lower socio‐economic backgrounds experience reduced QoL compared with their wealthier counterparts. Initiatives to improve access to and usage of medical and psychological services by children and their families who are socio‐economically disadvantaged may help to mitigate the disparities and improve outcomes in children with chronic illnesses.     

Phase 3 evaluation of HP802‐247 in the treatment of chronic venous leg ulcers

In 2012 we reported promising results from a phase 2 clinical trial of HP802‐247, a novel spray‐applied investigational treatment for chronic venous leg ulcers consisting of human, allogeneic fibroblasts and keratinocytes. We now describe phase 3 clinical testing of HP802‐247, its failure to detect efficacy, and subsequent investigation into the root causes of the failure. Two randomized, controlled trials enrolled a total of 673 adult outpatients at 96 centers in North America and Europe. The primary endpoint was the proportion of ulcers with confirmed closure at the end of 12 weeks of treatment. An investigation into the root cause for the failure of HP802‐247 to show efficacy in these two phase 3 trials was initiated immediately following the initial review of the North American trial results. Four hundred twenty‐one patients were enrolled in the North American (HP802‐247, 211; Vehicle 210) and 252 in the European (HP802‐247, 131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12 was observed between treatment groups for either the North American (HP802‐247, 61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802‐247, 47.0%; Vehicle 50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design or execution of the trials contributed to the failure. Variability over time during the trials in the clinical response implicated the quality of the cells comprising HP802‐247. Concordance between the two separate, randomized, controlled trials with distinct, nonoverlapping investigative sites and independent monitoring teams renders the possibility of a Type II error vanishingly small and provides strong credibility for the unexpected lack of efficacy observed. The most likely causative factors for the efficacy failure in phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to batch to batch variability due to the age of the cell banks.     

Effects of low‐frequency pulsed electromagnetic fields on plateau frostbite healing in rats

Plateau frostbite (PF) treatments have remained a clinical challenge because this condition injures tissues in deep layers and affected tissues exhibit unique pathological characteristics. For instance, low‐frequency pulsed electromagnetic field (PEMF) can affect tissue restoration and penetrate tissues. Therefore, the effect of PEMF on PF healing should be investigated. This study aimed to evaluate the effects of low‐frequency PEMF on PF healing systematically. Ninety‐six Sprague‐Dawley rats were randomly and equally divided into three groups: normal control, partial thickness plateau frostbite (PTPF), and PTPF with low‐frequency PEMF exposure (PTPF + PEMF). PTPF wounds were induced in the dorsum of the rats. The PTPF + PEMF group was exposed to low‐frequency PEMF daily. During PF healing, wound microcirculation in each group was monitored through contrast ultrasonography. Wound appearance, histological observation, and wound tensile strength were also evaluated. Results showed that the rate of the microcirculation restoration of the PTPF + PEMF group was nearly 25% faster than that of the PTPF group, and wound appearance suggested that the healing of the PTPF group was slower than that of the PTPF + PEMF group. Histological observation revealed that PEMF accelerated the growth of different deep tissues, as confirmed by tensile strength examination. Low‐frequency PEMF could penetrate PF tissues, promote their restoration, and provide a beneficial effect on PF healing. Therefore, this technique may be a potential alternative to treat PF.     

Analyzing treatment aggressiveness and identifying high‐risk patients in diabetic foot ulcer return to care

Rates of diabetes and its associated comorbidities have been increasing in the United States, with diabetic foot ulcer treatment representing a large cost to the patient and healthcare system. These ulcers often result in multiple hospital admissions. This study examined readmissions following inpatient care for a diabetic foot ulcer and identified modifiable factors associated with all‐cause 30‐day readmissions to the inpatient or emergency department (ED) setting. We hypothesized that patients undergoing aggressive treatment would have lower 30‐day readmission rates. We identified patient discharge records containing International Classification of Disease ninth revision codes for both diabetes mellitus and distal foot ulcer in the State Inpatient and Emergency Department databases from the Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project in Florida and New York, 2011–2012. All‐cause 30‐day return to care visits (ED or inpatient) were analyzed. Patient demographics and treatment characteristics were evaluated using univariate and multivariable regression models. The cohort included 25,911 discharges, having a mean age of 63 and an average of 3.8 comorbidities. The overall rate of return to care was 30%, and 21% of subjects underwent a toe or midfoot amputation during their index stay. The most common diagnosis codes upon readmission were diabetes mellitus (19%) and infection (13%). Patients with a toe or midfoot amputation procedure were less likely to be readmitted within 30 days (odds ratio: 0.78; 95% confidence interval: 0.73, 0.84). Presence of comorbidities, black and Hispanic ethnicities, and Medicare and Medicaid payer status were also associated with higher odds of readmission following initial hospitalization (p < 0.05). The study suggests that there are many factors that affect readmission rates for diabetic foot ulcer patients. Understanding patients at high‐risk for readmission can improve counseling and treatment strategies for this fragile patient population.     

Examination of endothelial cell‐induced epidermal regeneration in a mice‐based chimney wound model

As wound contraction in the cutaneous layer occurs rapidly in mice, mechanical means are typically used to deliberately expose the wound to properly investigate healing by secondary intention. Previously, silicon rings and splinting models were attempted to analyze histological recovery but prevention of surrounding epidermal cell migration and subsequent closure was minimal. Here, we developed an ideal chimney wound model to evaluate epidermal regeneration in murine under hESC‐EC transplantation through histological analysis encompassing the three phases of regeneration: migration, proliferation, and remodeling. Human embryonic stem cell derived endothelial cells (hESC‐EC) were transplanted due to possessing a well‐known therapeutic effect in angiogenesis which also enhances epidermal repair to depict the process of regeneration. Following a standard 1 mm biopsy punch, a chimney manufactured by modifying a 1.7 mL microtube was simply inserted into the excisional wound to complete the modeling process. Under this model, the excisional wound remained fully exposed for 14 days and even after 4 weeks, only a thin transparent layer of epidermal tissue covered the wound site. This approach is able to more accurately depict epidermal repair in relation to histology while also being a user‐friendly and cost‐effective way to mimic human recovery in rodents and evaluate epithelial repair induced by a form of therapy.