A technique for the measurement of orthophosphate in human erythrocytes, and some studies of its determinants

A technique is described for the determination of orthophosphate (Pi) in human erythrocytes. The advantages of the technique are that it uses whole blood rather than separated erythrocytes, that it avoids major hydrolysis of organic phosphates, that it takes account of incomplete recovery of Pi and that it minimizes the effects of chilling the cells. In chilled samples from 46 patients in an intensive care unit, the cellular concentration of Pi was proportional to that in plasma. Blood samples from nine normal subjects were incubated at 37 degrees C. The cellular Pi was 0.79 mmol/litre of cells using an external standardization and 0.67 using an internal standardization. When the same cell samples were chilled on ice for 30 min, the internally standardized value decreased further to 0.57 mmol/litre of cells. These results suggest that differences in recovery, and the extent of chilling, contribute to the variability in the previously reported values for erythrocyte Pi. If Pi, like chloride, had distributed passively between cells and plasma in these samples, the cell to plasma molar concentration ratio for Pi should have been 0.29, compared with the measured value of 0.64. This difference suggests that some factor, in addition to passive diffusion, determined the distribution of Pi.     

Limited Clinical Utility of a Genetic Risk Score for the Prediction of Fracture Risk in Elderly Subjects

It is important to identify the patients at highest risk of fractures. A recent large‐scale meta‐analysis identified 63 autosomal single‐nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD), of which 16 were also associated with fracture risk. Based on these findings, two genetic risk scores (GRS63 and GRS16) were developed. Our aim was to determine the clinical usefulness of these GRSs for the prediction of BMD, BMD change, and fracture risk in elderly subjects. We studied two male (Osteoporotic Fractures in Men Study [MrOS] US, MrOS Sweden) and one female (Study of Osteoporotic Fractures [SOF]) large prospective cohorts of older subjects, looking at BMD, BMD change, and radiographically and/or medically confirmed incident fractures (8067 subjects, 2185 incident nonvertebral or vertebral fractures). GRS63 was associated with BMD (?3% of the variation explained) but not with BMD change. Both GRS63 and GRS16 were associated with fractures. After BMD adjustment, the effect sizes for these associations were substantially reduced. Similar results were found using an unweighted GRS63 and an unweighted GRS16 compared with those found using the corresponding weighted risk scores. Only minor improvements in C‐statistics (AUC) for fractures were found when the GRSs were added to a base model (age, weight, and height), and no significant improvements in C‐statistics were found when they were added to a model further adjusted for BMD. Net reclassification improvements with the addition of the GRSs to a base model were modest and substantially attenuated in BMD‐adjusted models. GRS63 is associated with BMD, but not BMD change, suggesting that the genetic determinants of BMD differ from those of BMD change. When BMD is known, the clinical utility of the two GRSs for fracture prediction is limited in elderly subjects. © 2014 American Society for Bone and Mineral Research.     

Comparison of Ropivacaine 0.75 % and Lignocaine 2 % with 1:200,000 Adrenaline in Dental Extractions: Single Blind Clinical Trial

Introduction

The aim of this study was to evaluate the efficacy, safety and clinical acceptability of the local anaesthetic agent ropivacaine 0.75 % in comparison with lignocaine 2 % with adrenaline 1:200,000 in minor oral surgical procedures.

Methods

Forty-seven patients, who required bilateral extractions in a single arch, were included in this study. One hundred and sixty-six extractions were performed and all the patients were administered nerve blocks/infiltration. Pre and postoperative pulse, blood pressure, random blood sugar, electrocardiogram and partial oxygen pressure were recorded at specified time intervals. Pain score by visual analogue scale, onset of action and depth of anesthesia were also observed. Duration of anaesthesia was assessed by feeling of numbness and first sign of pain.

Results

Statistical analysis revealed insignificant difference between both the groups in terms of pulse, blood pressure, random blood sugar, and partial oxygen pressure. The depth of anesthesia was evaluated by pain, comfort during the procedure with visual analog scale and showed no significant difference between the two groups. The onset of action for maxillary infiltration was 33.29 ± 9.2 (ropivacaine), 32.12 ± 6.8 s (2 % lignocaine with adrenaline 1:200,000) and for pterygomandibular nerve block was 181.0 ± 87.5 (ropivacaine), 32.12 ± 6.8 s (2 % lignocaine with adrenaline 1:200,000). Duration of anesthesia when compared was 411.7 ± 66.11 min (ropivacaine) and 107.87 ± 16.54 (2 % lignocaine with adrenaline 1:200,000). On maxillary buccal vestibule infiltration it was also observed that in ropivacaine group there was no requirement of palatal infiltration suggestive of good diffusion property.

Conclusion

Ropivacaine is a safe, clinically acceptable long acting local anaesthetic agent with added advantage of effective diffusion property.

Ethical Committee Approval Number

SDC/MISC/2013/239.

     

Secular trends in the utility of SGLT-2 inhibitors in heart failure patients with type 2 diabetes mellitus across Metro South Health hospitals in South-East Queensland

Background

The 2018 Australian Heart Failure (HF) guidelines strongly recommended commencing sodium-glucose co-transporter-2 inhibitors (SGLT-2is) in HF patients with type 2 diabetes mellitus (T2DM). The uptake of SGLT-2is for HF patients with T2DM in our health service is unknown.

Aims

To determine the adoption of the 2018 HF guidelines by assessing the temporal trends of SGLT-2is' usage in HF patients with T2DM at Metro South Health (MSH) hospitals, in South-East Queensland.

Methods

Retrospective analysis of all HF patients (ejection fraction (EF) < 50%) with T2DM who were managed within MSH hospitals between June 2018 and June 2021.

Results

A total of 666 patients met the inclusion criteria with 918 HF encounters. Mean age was 72 years and 71% were male (473/666). Mean EF was 30% (SD ± 11%), and mean estimated glomerular filtration rate was 48 mL/min/1.73 m² (SD ± 25). Fifty-four per cent (362/666) had contraindications to SGLT-2is. Among those without contraindications, there was a five-fold increase in the utility of SGLT-2is, 7% (2/29) before versus 38% (103/275) after implementation of the HF guidelines (P < 0.001). Patients on SGLT-2is were younger (64 years vs 69 years, P = 0.002) and had a lower number of HF hospitalisations (1.1 vs 2.1, P = 0.01).

Conclusions

During the study period, 54% of our HF patients with T2DM were not on SGLT-2is due to prescribing guidelines/limitations in the Australian context. We observed a five-fold significant increase in the uptake of SGLT-2is before and after implementation of HF guidelines among patients without contraindications to SGLT-2is. There were significantly fewer HF hospitalisations among patients on SGLT-2is compared to those without.