Review of eprodisate for the treatment of renal disease in AA amyloidosis

Secondary (AA) amyloidosis is a multisystem disorder complicating chronic infections or inflammatory diseases. It is characterized by extracellular deposit of fibrils composed of fragments of serum amyloid A (SAA), an acute phase reactant protein. The kidney is the most frequent organ involved, manifesting as progressive proteinuria and renal impairment. Attenuation of the level of circulating SAA protein by treating the underlying inflammatory condition remains the primary strategy in treating AA amyloidosis. However, at times, achieving adequate control of protein production can prove difficult. In addition, relapse of renal function often occurs rapidly following any subsequent inflammatory stimulus in patients with existing amyloidosis. Recently there has been an interest in finding other potential strategies targeting amyloid deposits themselves. Eprodisate is a sulfonated molecule with a structure similar to heparan sulfate. It competitively binds to the glycosaminoglycan-binding sites on SAA and inhibits fibril polymerization and amyloid deposition. Recent randomized clinical trial showed that it may slow down progressive renal failure in patients with AA amyloidosis. However confirmatory studies are needed and results of a second Phase III study are eagerly awaited to clarify whether or not eprodisate has a place in treating renal amyloid disease

Determinants of Anxiety in Amputees Owed to Traumatic & Non-Traumatic Causes in Quetta

Objective: To find out the causes and factors of anxiety among amputees suffering from traumatic and non-traumatic causes. Methodology: This descriptive cross-sectional study was conducted in Quetta from the month of May 2018 to July 2018. This study included those clients with amputations as a result of Traumatic & non-traumatic causes and the data was collected from them. This study involved a total of 54 participants. All amputees who visited the three Physical Rehabilitation Centre were included during data collection process. A structured adopted questionnaire using the Hospital Anxiety and Depression Scale (HADS) according to the inclusion & exclusion criteria & then tabularized and analyzed by applying Chi square test. Results: This study involved a total of 54 participants of whom 7(13%) were females and 47(87%) males. Among amputees 36(66.7 %), amputations were due to Traumatic injuries and 18(33.3%) were due to non-traumatic amputations. In traumatic, the majority was due to RTA with 25(46.3 %) and in non-traumatic causes diabetes stood first with 13(24.1%) amputation. Traumatic are more anxious than non-traumatic. There is a significant relationship between marital status and anxiety level (p-value 0.047). Statistically significant relationships between amputation and anxiety level were noticed, p value=0.049. Conclusion: Amputation has a significant association with anxiety level. Traumatic experiences make people feel more anxious than non-traumatic ones. Socio-demographics has association with levels of anxiety. It is recommended to do regular or annual screening of these patients following amputation

Development of gliclazide matrix tablets from pure and blended mixture of glyceryl monostearate and stearic acid

The present study was undertaken to evaluate the effect of glyceryl monostearate (GMS) and stearic acid (SA) on the release profile of gliclazide from the matrix. Matrix tablets for the controlled delivery of gliclazide were prepared by hot melt method using pure and blended mixture of glyceryl monostearate and stearic acid in different drug to polymer and polymer to polymer ratios. In vitro release characteristics of gliclazide from these hydrophobic matrices were studied over 8 h in phosphate buffer media of pH 7.4. The release kinetics of drug was evaluated for zero order, first order, Higuchi and Peppas kinetic models. It was observed that the release of drug from the matrix was greatly retarded by GMS and retarding effect increased with increasing polymer to drug ratios. On the other hand SA appeared to channel the drug from the wax matrix and release was greatly increased with increasing polymer to drug ratios. The kinetic evaluation of release profile indicated that the Higuchi model was the most appropriate model for describing the release profile of gliclazide. The application of Peppas biexponential equation indicated that non-Fickian release was the predominant mechanism of drug release. The FTIR results showed no interaction between the drug and the polymers and DSC results indicated that both the drug and polymers are in amorphous state and no significant complexes were formed. The results indicated that proper selection of drug to polymer and polymer to polymer ratios were important in order to achieve the desired dissolution profile in these matrix tablets.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Effect of water current on underwater glider velocity and range

An autonomous underwater glider speed and range is influenced by water currents. This is compounded by a weak actuation system for controlling its movement. In this work, the effects of water currents on the speed and range of an underwater glider at steady state glide conditions are investigated. Extensive numerical simulations have been performed to determine the speed and range of a glider with and without water current at different net buoyancies. The results show that the effect of water current on the glider speed and range depends on the current relative motion and direction. In the presence of water current, for a given glide angle, glide speed can be increased by increasing the net buoyancy of the glider

Development of gliclazide matrix tablets from pure and blended mixture of glyceryl monostearate and stearic acid

The present study was undertaken to evaluate the effect of glyceryl monostearate (GMS) and stearic acid (SA) on the release profile of gliclazide from the matrix. Matrix tablets for the controlled delivery of gliclazide were prepared by hot melt method using pure and blended mixture of glyceryl monostearate and stearic acid in different drug to polymer and polymer to polymer ratios. In vitro release characteristics of gliclazide from these hydrophobic matrices were studied over 8 h in phosphate buffer media of pH 7.4. The release kinetics of drug was evaluated for zero order, first order, Higuchi and Peppas kinetic models. It was observed that the release of drug from the matrix was greatly retarded by GMS and retarding effect increased with increasing polymer to drug ratios. On the other hand SA appeared to channel the drug from the wax matrix and release was greatly increased with increasing polymer to drug ratios. The kinetic evaluation of release profile indicated that the Higuchi model was the most appropriate model for describing the release profile of gliclazide. The application of Peppas biexponential equation indicated that non-Fickian release was the predominant mechanism of drug release. The FTIR results showed no interaction between the drug and the polymers and DSC results indicated that both the drug and polymers are in amorphous state and no significant complexes were formed. The results indicated that proper selection of drug to polymer and polymer to polymer ratios were important in order to achieve the desired dissolution profile in these matrix tablets.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Graphene oxide incorporated polyether sulfone nanocomposite antifouling ultrafiltration membranes with enhanced hydrophilicity

In this study, the polyether sulfone (PES) based membranes containing various concentrations of graphene oxide (GO), polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG) were synthesized via the phase immersion method. This study aims to evaluate the effect of GO addition on the structural properties and performance of the membranes. The membranes were analyzed by x-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transforms infrared spectroscopy (FTIR). The FTIR-ATR spectra indicated the presence of hydroxyl and carboxylic acid groups on the surface of GO-incorporated membranes, which improved their dispersion in the polymeric matrix and hydrophilicity. The SEM analysis of the GO-containing PES membranes confirmed the formation of a well-defined finger-like porous structure presenting adequate water flux (95 l.m(-2).h(-1)) and salt rejection (72%) compared to the pristine PES membranes (46 l.m(-2).h(-1) and similar to 35%, respectively). In addition, the significantly large wettability and considerably improved antibacterial characteristic (against S. aureus and E. coli strains) of the GO-PES membranes are considered impressive features.National University of Sciences and Technology (NUST) Research Directorate; HEC; NRPU [6020]6020; Higher Education Commission, Pakistan, HEC; National University of Sciences and Technology, NUS

Bisphosphonates to reduce bone fractures in stage 3B+ chronic kidney disease:a propensity-score matched cohort study

BackgroundBisphosphonates are contraindicated in patients with stage 4+ chronic kidney disease. However, they are widely used to prevent fragility fractures in stage 3 chronic kidney disease, despite a lack of good-quality data on their effects.ObjectivesThe aims of each work package were as follows. Work package 1: to study the relationship between bisphosphonate use and chronic kidney disease progression. Work package 2: to study the association between using bisphosphonates and fracture risk. Work package 3: to determine the risks of hypocalcaemia, hypophosphataemia, acute kidney injury and upper gastrointestinal events associated with using bisphosphonates. Work package 4: to investigate the association between using bisphosphonates and changes in bone mineral density over time.DesignThis was a new-user cohort study design with propensity score matching.Setting and data sourcesData were obtained from UK NHS primary care (Clinical Practice Research Datalink GOLD database) and linked hospital inpatient records (Hospital Episode Statistics) for work packages 1–3 and from the Danish Odense University Hospital Databases for work package 4.ParticipantsPatients registered in the data sources who had at least one measurement of estimated glomerular filtration rate of < 45 ml/minute/1.73 m2 were eligible. A second estimated glomerular filtration rate value of < 45 ml/minute/1.73 m2 within 1 year after the first was requested for work packages 1 and 3. Patients with no Hospital Episode Statistics linkage were excluded from work packages 1–3. Patients with < 1 year of run-in data before index estimated glomerular filtration rate and previous users of anti-osteoporosis medications were excluded from work packages 1–4.Interventions/exposureBisphosphonate use, identified from primary care prescriptions (for work packages 1–3) or pharmacy dispensations (for work package 4), was the main exposure.Main outcome measuresWork package 1: chronic kidney disease progression, defined as stage worsening or starting renal replacement. Work package 2: hip fracture. Work package 3: acute kidney injury, hypocalcaemia and hypophosphataemia identified from Hospital Episode Statistics, and gastrointestinal events identified from Clinical Practice Research Datalink or Hospital Episode Statistics. Work package 4: annualised femoral neck bone mineral density percentage change.ResultsBisphosphonate use was associated with an excess risk of chronic kidney disease progression (subdistribution hazard ratio 1.12, 95% confidence interval 1.02 to 1.24) in work package 1, but did not increase the probability of other safety outcomes in work package 3. The results from work package 2 suggested that bisphosphonate use increased fracture risk (hazard ratio 1.25, 95% confidence interval 1.13 to 1.39) for hip fractures, but sensitivity analyses suggested that this was related to unresolved confounding. Conversely, work package 4 suggested that bisphosphonates improved bone mineral density, with an average 2.65% (95% confidence interval 1.32% to 3.99%) greater gain in femoral neck bone mineral density per year in bisphosphonate users than in matched non-users.LimitationsConfounding by indication was a concern for the clinical effectiveness (i.e. work package 2) data. Bias analyses suggested that these findings were due to inappropriate adjustment for pre-treatment risk. work packages 3 and 4 were based on small numbers of events and participants, respectively.ConclusionsBisphosphonates were associated with a 12% excess risk of chronic kidney disease progression in participants with stage 3B+ chronic kidney disease. No other safety concerns were identified. Bisphosphonate therapy increased bone mineral density, but the research team failed to demonstrate antifracture effectiveness.Future workRandomised controlled trial data are needed to demonstrate antifracture efficacy in patients with stage 3B+ chronic kidney disease. More safety analyses are needed to characterise the renal toxicity of bisphosphonates in stage 3A chronic kidney disease, possibly using observational data

Patients’ recovery of mobility and return to original residence after hip fracture are associated with multiple modifiable components of hospital service organisation: the REDUCE record-linkage cohort study in England and Wales

Background: Hip fractures are devastating injuries causing disability, dependence, and institutionalisation, yet hospital care is highly variable. This study aimed to determine hospital organisational factors associated with recovery of mobility and change in patient residence after hip fracture. Methods: A cohort of patients aged 60 + years in England and Wales, who sustained a hip fracture from 2016 to 2019 was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality records were linked to 101 factors derived from 18 hospital-level organisational metrics. After adjustment for patient case-mix, multilevel models were used to identify organisational factors associated with patient residence at discharge, and mobility and residence at 120 days after hip fracture. Results: Across 172 hospitals, 165,350 patients survived to discharge, of whom 163,230 (99%) had post-hospital discharge destination recorded. 18,323 (11%) died within 120 days. Among 147,027 survivors, 58,344 (40%) across 143 hospitals had their residence recorded, and 56,959 (39%) across 140 hospitals had their mobility recorded, at 120 days. Nineteen organisational factors independently predicted residence on hospital discharge e.g., return to original residence was 31% (95% confidence interval, CI:17–43%) more likely if the anaesthetic lead for hip fracture had time allocated in their job plan, and 8–13% more likely if hip fracture service clinical governance meetings were attended by an orthopaedic surgeon, physiotherapist or anaesthetist. Seven organisational factors independently predicted residence at 120 days. Patients returning to their pre-fracture residence was 26% (95%CI:4–42%) more likely if hospitals had a dedicated hip fracture ward, and 20% (95%CI:8–30%) more likely if treatment plans were proactively discussed with patients and families on admission. Seventeen organisational factors predicted mobility at 120 days. More patients re-attained their pre-fracture mobility in hospitals where (i) care involved an orthogeriatrician (15% [95%CI:1-28%] improvement), (ii) general anaesthesia was usually accompanied by a nerve block (7% [95%CI:1-12%], and (iii) bedside haemoglobin testing was routine in theatre recovery (13% [95%CI:6-20%]). Conclusions: Multiple, potentially modifiable, organisational factors are associated with patient outcomes up to 120 days after a hip fracture, these factors if causal should be targeted by service improvement initiatives to reduce variability, improve hospital hip fracture care, and maximise patient independence

GGPS1 Mutation and Atypical Femoral Fractures with Bisphosphonates

Atypical femoral fractures have been associated with long-term bisphosphonate treatment.1,2 However, the underlying mechanisms remain obscure. We studied three sisters who had atypical femoral fractures after receiving various oral bisphosphonates for 6 years. Two of the sisters had a single fracture (at the ages of 64 and 73 years), and one had bilateral fractures (one at the age of 60 years and the other at the age of 61 years). Given the low incidence of atypical femoral fractures in the general population (5.9 per 10,000 person-years),3 we hypothesized that these sisters might have an underlying genetic background that contributed to these fractures