Understanding the implications of pharmaceutical excipients and additives in the treatment of diabetic foot ulcers

A diabetic foot ulcer (DFU) is a consequence of Diabetes Mellitus (DM) and involves complex pathological processes. Among diabetic patients DFU is a major cause of deaths resulting from the amputation of the lower limbs. Various treatment strategies have been developed for the treatment of DFUs, but to this date unfortunately no single treatment fulfills the prerequisites necessary for treating this condition due to its complex, multifactorial pathophysiology. Additionaly, costs associated with the treatment can be prohibitively high. Excipients are pharmaceutical agents which have diverse applications in the design of different dosage forms. Therefore, an ideal dosage form, with active excipients in combination or as adjuvants, which meet these requirements could be suited for treating DFUs. This review discusses the etiopathogenesis of DFUs and also the possible of the use of excipients and additives in various pathological cases of DFUs in designing medicinal products intended for the treatment of this condition

Clinical Study The Incidence and Risk Factors for Lower Limb Skin Graft Failure

Lower limb skin grafts are thought to have higher failure rates than skin grafts in other sites of the body. Currently, there is a paucity of literature on specific factors associated with lower limb skin graft failure. We present a series of 70 lower limb skin grafts in 50 patients with outcomes at 6 weeks. One-third of lower limb skin grafts went on to fail with increased BMI, peripheral vascular disease, and immunosuppressant medication use identified as significant risk factors

Model for End‐Stage Liver Disease‐Lactate and Prediction of Inpatient Mortality in Patients With Chronic Liver Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163652/3/hep31199.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163652/2/hep31199_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163652/1/hep31199-sup-0001-Supinfo.pd

Environmental Response and Genomic Regions Correlated with Rice Root Growth and Yield under Drought in the OryzaSNP Panel across Multiple Study Systems

Funding: This research was funded by the Generation Challenge Program (GCP) project G3008.06, “Targeting Drought-Avoidance Root Traits to Enhance Rice Productivity under Water-Limited Environments". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Gastroesophageal Reflux and Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) and Gastroesophageal reflux disease (GERD) commonly co-exist. Pathophysiological mechanisms causing IPF are still not well understood, and GERD has been implicated in both as a probable causative and disease-promoting entity. Although not conclusively proven, this relationship has been the subject of several studies, including therapeutic interventions aimed at treating GERD and its resultant effect on IPF and related outcomes. Our review aims to present the current concepts and understanding of these two disease processes, which are multifaceted. Their complex interaction includes epidemiology, pathophysiology, diagnosis, treatment, review of research studies conducted to date, and future directions for research

0.9% saline versus Plasma-Lyte 148 for intravenous fluid therapy

BACKGROUND Intravenous fluid therapy is one of the most common interventions used in acute medicine. Worldwide, there are variations in the prescription of intravenous fluids and no consensus on the best intravenous fluid to use. Currently, 0.9% saline is the most frequently prescribed intravenous fluid; however, there is emerging evidence to suggest that 0.9% saline may be associated with an increased risk of acute kidney injury (AKI), increased blood transfusion requirements and gastrointestinal dysfunction when compared to a buffered crystalloid fluid, such as Plasma-Lyte 148. METHODS Study one: A prospective, multicentre, randomised, double-blind, cluster, double crossover study conducted over 28 weeks in four New Zealand intensive care units (ICU) comparing 0.9% saline to Plasma-Lyte 148. The primary outcome was the proportion of patients with either AKI or renal failure according to the RIFLE criteria definitions based on serum creatinine levels. Study two: An exploratory subgroup analysis of cardiac surgical patients enrolled in study one to compare the effects of 0.9% saline vs. Plasma-Lyte 148 on the need for blood transfusions. The primary outcome was the proportion of patients receiving blood or blood products in the ICU. Additionally, an in-depth single-centre nested cohort study comparing the effect of 0.9% saline vs. Plasma-Lyte 148 on blood loss and blood products was also conducted. Study three: A single-centre nested study within study one comparing the effect of 0.9% saline vs. Plasma-Lyte 148 on gastrointestinal dysfunction in patients expected to be mechanically ventilated for >48 hours and receiving enteral nutrition via the nasogastric route. The primary outcome was the proportion of patients with gastrointestinal intolerance (high gastric residual volumes (GRV), vomiting, and diarrhoea). RESULTS Study one: 2262 patients were enrolled and analysed, 1152 patients were allocated to receive Plasma-Lyte 148 and 1110 participants were allocated to receive 0.9% saline. In the Plasma-Lyte 148 group, 102 of 1067 patients (9.6%) developed AKI, compared with 94 of 1025 patient (9.2%) in the 0.9% saline group (RR 1.05; 95% CI, 0.78 to 1.41; p=0.76). Overall, 87 of 1152 patients (7.6%) in the Plasma-Lyte 148 group and 95 of 1110 patients (8.6%) in the 0.9% saline group died in hospital (RR, 0.88; 95% CI 0.67 to 1.17; p=0.40). Study two: 954 cardiac surgical patients were included, 475 patients were allocated to receive Plasma-Lyte 148 and 479 were allocated to receive 0.9% saline. 128 of 475 patients (26.9%) in the Plasma-Lyte 148 group received blood or a blood product compared with 94 of 479 (19.6%) patients in the 0.9% saline group (OR [95% CI], 1.51 [1.11-2.05]; p=0.008). Within the nested cohort (n=251, 131 assigned to Plasma-Lyte 148 and 120 assigned to 0.9% saline), there were no differences between groups in chest drain losses at 12 hours. Study three: 69 patients were enrolled and analysed, with 35 allocated to receive Plasma-Lyte 148 and 34 allocated to receive 0.9% saline. In the Plasma-Lyte 148 group, 21 of 35 patients (60.0%) developed gastrointestinal feeding intolerance, compared with 22 of 34 patients (64.7%) in the 0.9% saline group (OR, 0.82; 95% CI, 0.31–2.17; p=0.69). A high GRV was seen in 4 of 35 patients (11.4%) in the Plasma-Lyte 148 group, and in 11 of 34 patients (32.4%) in the 0.9% saline group (OR, 0.27; 95% CI, 0.08–0.96; p=0.04). CONCLUSION This research programme provides data from the first interventional study conducted in critically unwell patients on the comparative effectiveness of 0.9% saline compared to a buffered crystalloid solution for intravenous fluid therapy. Among patients receiving crystalloid fluid in the ICU, allocation to Plasma-Lyte 148 compared to 0.9% saline did not influence the risk of AKI. Within a subgroup of patients undergoing cardiac surgery allocation to Plasma-Lyte 148 was associated with an increased requirement for blood or blood products. Among mechanically ventilated patients receiving nasogastric feeding, the use of Plasma-Lyte 148 compared to 0.9% saline did not reduce the proportion of patients developing gastrointestinal feeding intolerance but was associated with a decreased incidence of high GRV. These findings suggest that Plasma-Lyte 148 as compared with 0.9% saline may have differing effects within the biological/organ systems and sub-groups of patients admitted to the ICU. Further large randomised clinical trials (RCT) are needed to assess the efficacy in higher-risk populations and to measure ongoing areas of uncertainty in clinically important outcomes such as mortality

Understanding the implications of pharmaceutical excipients and additives in the treatment of diabetic foot ulcers

A diabetic foot ulcer (DFUs) is a consequence of Diabetes Mellitus (DM) and involves complex pathological processes. It is a major cause of deaths among diabetic patients as a result of amputations. Various treatment strategies have been developed for the treatment of DFUs; unfortunately no single treatment will fulfill the prerequisites necessary for treating DFUs due to its complexed, multifactorial pathophysiology and also the overall cost of these treatments are high. Excipients are the pharmaceutical agents which have diverse applications in the design of different dosage forms. Hence, an ideal dosage form, with active excipients in combination or as adjuvants, which meets these requirements would probably best suited for treating DFUs. This review discusses the etiopathogenesis of DFUs and also the possible use of excipients and additives on various pathological cases of DFUs in designing products intended for the treatment of DFUs

Elucidating the deformation modes in incremental sheet forming process: Insights from crystallographic texture, microstructure and mechanical properties

This study investigates the exact state of deformation in single point incremental forming (SPIF) and double-sided incremental forming (DSIF) techniques using experimental observations of texture evolution coupled with a multiscale simulation of the processes. The texture evolution was investigated for different sets of forming parameters such as vertical displacement, wall angle and tool diameter. It was observed that difference in crystallographic texture due to change in tool diameter and vertical displacement was marginal. However, significant difference in texture evolution was observed upon changing the wall angle. Further analysis of crystallographic texture revealed that role of through thickness shear (TTS) is limited in case of DSIF process compared to SPIF process. Numerical simulation of SPIF process via finite element method was successful in capturing the contribution from TTS in SPIF process. Based on insights obtained from finite element calculations, Visco-Plastic Self-Consistent simulations were carried out which were successful in predicting the experimental texture. Finally, the effect of different incremental forming techniques on the mechanical properties of the formed components was studied. The observed anisotropy in yield strength was explained based on the inverse of average Schmid factor. Lankford parameter and yield locus were also estimated from the experimental textures to understand the feasibility of incremental forming at different wall angles