Discretion in decision to receive COVID-19 vaccines and associated socio-economic inequalities in rates of uptake: a whole-of-population data linkage study from Australia.

OBJECTIVE: In Australia, first and second compared to third dose of a COVID-19 vaccine were implemented under different policies and contexts, resulting in greater discretion in decisions to receive a third compared to first and second dose. We quantified socio-economic inequalities in first and third dose to understand how discretion is associated with differences in uptake. STUDY DESIGN: Whole-of-population cohort study. METHODS: Linked immunisation, census, death and migration data were used to estimate weekly proportions who received first and third doses of a COVID-19 vaccine until 31 August 2022 for those with low (no formal qualification) compared to high (university degree) education, stratified by 10-year age group (from 30 to 89 years). We estimated relative rates using Cox regression, including adjustment for sociodemographic factors. RESULTS: Among 13.1 million people in our study population, 94% had received a first and 80% a third dose by 31 August 2022. Rates of uptake of first and third dose were around 50% lower for people with low compared to high education. Gaps were small in absolute terms for first dose, and at the end of the study period ranged from 1 to 11 percentage points across age groups. However, gaps were substantial for third dose, particularly at younger ages where the socio-economic gap was as wide as 32 percentage-points. CONCLUSION: Education-related inequalities in uptake were larger where discretion in decisions was larger. Policies that limited discretion in decisions to receive vaccines may have contributed to achieving the dual aims of maximising uptake and minimising inequalities.

Microfabricated glucose biosensor for culture well operation.

A water-based carbon screen-printing ink formulation, containing the redox mediator cobalt phthalocyanine (CoPC) and the enzyme glucose oxidase (GOx), was investigated for its suitability to fabricate glucose microbiosensors in a 96-well microplate format: (1) the biosensor ink was dip-coated onto a platinum (Pt) wire electrode, leading to satisfactory amperometric performance; (2) the ink was deposited onto the surface of a series of Pt microelectrodes (10-500 µm diameter) fabricated on a silicon substrate using MEMS (microelectromechanical systems) microfabrication techniques: capillary deposition proved to be successful; a Pt microdisc electrode of ≥100 µm was required for optimum biosensor performance; (3) MEMS processing was used to fabricate suitably sized metal (Pt) tracks and pads onto a silicon 96 well format base chip, and the glucose biosensor ink was screen-printed onto these pads to create glucose microbiosensors. When formed into microwells, using a 340 µl volume of buffer, the microbiosensors produced steady-state amperometric responses which showed linearity up to 5 mM glucose (CV=6% for n=5 biosensors). When coated, using an optimised protocol, with collagen in order to aid cell adhesion, the biosensors continued to show satisfactory performance in culture medium (linear range to 2 mM, dynamic range to 7 mM, CV=5.7% for n=4 biosensors). Finally, the operation of these collagen-coated microbiosensors, in 5-well 96-well format microwells, was tested using a 5-channel multipotentiostat. A relationship between amperometric response due to glucose, and cell number in the microwells, was observed. These results indicate that microphotolithography and screen-printing techniques can be combined successfully to produce microbiosensors capable of monitoring glucose metabolism in 96 well format cell cultures. The potential application areas for these microbiosensors are discussed.

A flow injection system, comprising a biosensor based on a screen-printed carbon electrode containing Meldola's Blue-Reinecke salt coated with glucose dehydrogenase, for the measurement of glucose.

A biosensor for the measurement of glucose in serum has been developed, based on a screen-printed carbon electrode modified with Meldola's Blue-Reinecke salt, coated with the enzyme glucose dehydrogenase (from Bacillus sp.), and nicotinamide adenine dinucleotide coenzyme (NAD+). A cellulose acetate layer was deposited on top of the device to act as a permselective membrane. The biosensor was incorporated into a commercially available, thin-layer, amperometric flow cell operated at a potential of only +0.05 V versus Ag/AgCl. The mobile phase consisted of 0.2 M phosphate buffer (pH 7.0) containing 0.1 M potassium chloride solution, and a flow rate of 0.8 ml min(-1) was used throughout the investigation. The biosensor response was linear over the range of 0.075-30 mM glucose, with the former representing the detection limit. The precision of the system was determined by carrying out 20 repeat injections of a 5-mM glucose standard, and the calculated coefficient of variation was 3.9%. It was demonstrated that this biosensor system could be applied to the direct measurement of glucose in serum without pretreatment. Therefore, this would allow high-throughput analysis, at low cost, for this clinically important analyte.

Fabrication of microband glucose biosensors using a screen-printing water-based carbon ink and their application in serum analysis.

Microband glucose biosensors were fabricated by screen-printing a water-based carbon ink formulation containing cobalt phthalocyanine redox mediator and glucose oxidase (GOD) enzyme, then insulating and sectioning through the thick (20mum) film to expose a 3mm-long working electrode edge. The performance of these biosensors for glucose analysis was investigated at 25 degrees C. Voltammetry in glucose-containing buffer solutions established that an operating potential of +0.4V vs. Ag/AgCl was suitable for analysis under both stirring and quiescent conditions. The influence of pH on biosensor performance was established and an operational pH of 8.0 was selected. Steady-state responses were obtained under quiescent conditions, suggesting a mixed mechanism predominated by radial diffusion, indicative of microelectrode behaviour. Calibration studies obtained with these biosensors showed steady-state currents that were linearly dependent on glucose concentration from the limit of detection (0.27mM) up to 2.0mM, with a precision for replicate biosensors of 6.2-10.7%. When applied to the determination of glucose in human serum, the concentration compared favourably to that determined by a spectroscopic method. These results have demonstrated a simple means of fabricating biosensors for glucose measurement and determination in situations where low-current real-time monitoring under quiescent conditions would be desirable.

A microband lactate biosensor fabricated using a water-based screen-printed carbon ink.

The present study demonstrated for the first time that screen-printed carbon microband electrodes fabricated from water-based ink can readily detect H(2)O(2) and that the same ink, with the addition of lactate oxidase, can be used to construct microband biosensors to measure lactate. These microband devices were fabricated by a simple cutting procedure using conventional sized screen-printed carbon electrodes (SPCEs) containing the electrocatalyst cobalt phthalocyanine (CoPC). These devices were characterised with H(2)O(2) using several electrochemical techniques. Cyclic voltammograms were found to be sigmoidal; a current density value of 4.2 mA cm(-2) was obtained. A scan rate study revealed that the mass transport mechanism was a mixture of radial and planar diffusion. However, a further amperometric study under quiescent and hydrodynamic conditions indicated that radial diffusion predominated. A chronoamperometric study indicated that steady-state currents were obtained with these devices for a variety of H(2)O(2) concentrations and that the currents were proportional to the analyte concentration. Lactate microband biosensors were then fabricated by incorporating lactate oxidase into the water-based formulation prior to printing and then cutting as described. Voltammograms demonstrated that lactate oxidase did not compromise the integrity of the electrode for H(2)O(2) detection. A potential of +400 mV was selected for a calibration study, which showed that lactate could be measured over a dynamic range of 1-10mM which was linear up to 6mM; a calculated lower limit of detection of 289 microM was ascertained. This study provides a platform for monitoring cell metabolism in-vitro by measuring lactate electrochemically via a microband biosensor.

Application of screen-printed microband biosensors to end-point measurements of glucose and cell numbers in HepG2 cell culture.

Microband glucose biosensors were produced by insulating and sectioning through a screen-printed, water-based carbon electrode containing cobalt phthalocyanine redox mediator and glucose oxidase enzyme. Under quiescent conditions at 37 degrees C, at an operating potential of +0.4V, they produced an amperometric response to glucose in buffer solutions with a sensitivity of 26.4 nA/mM and a linear range of 0.45 to 9.0 mM. An optimal pH value of 8.5 was obtained under these conditions, and a value for activation energy of 40.55 kJ mol(-1) was calculated. In culture medium (pH 7.3), a sensitivity of 13 nA/mM was obtained and the response was linear up to 5 mM with a detection limit of 0.5 mM. The working concentration was up to 20 mM glucose with a precision of 11.3% for replicate biosensors (n=4). The microband biosensors were applied to determine end-point glucose concentrations in culture medium by monitoring steady-state current responses 400 s after transfer of the biosensors into different sample solutions. In conjunction with cultures of HepG2 (human Caucasian hepatocyte carcinoma) cells, current responses obtained in 24-h supernatants showed an inverse correlation (R(2)=0.98) with cell number, indicating that the biosensors were applicable for monitoring glucose metabolism by cells and of quantifying cell number. Glucose concentrations determined using the biosensor assay were in good agreement, for concentrations up to 20mM, with those determined spectrophotometrically (R(2)=0.99). This method of end-point glucose determination was used to provide an estimated rate of glucose uptake for HepG2 cells of 7.9 nmol/(10(6) cells min) based on a 24-h period in culture.

Propofol differentially attenuates the responses to exogenous and endogenous norepinephrine in the isolated rat femoral artery in vitro.

Propofol causes a decrease in vascular resistance mediated in part by a decrease in sympathetic output. To determine whether attenuation of norepinephrine release from sympathetic perivascular nerve terminals could contribute to decreased vascular resistance, we examined the effects of propofol on the contractile responses to exogenous and endogenous norepinephrine in the rat femoral artery. Endogenous norepinephrine was released from sympathetic nerve terminals using electrical field stimulation. The responses to both exogenous norepinephrine and neurally released norepinephrine were attenuated by propofol in concentrations from 1.0 to 10.0 micrograms/mL. At 50% of maximal and at maximal contractile responses to norepinephrine and electrical field stimulation, the response to electrical field stimulation was inhibited to a greater extent than the response to exogenous norepinephrine. This suggests that, in addition to direct postsynaptic vasodilation, propofol has the presynaptic effect of inhibiting norepinephrine release from perivascular nerves.

Obtaining outpatient referrals for clinical research.

Two methods of recruiting patients with generalised anxiety disorder (GAD) were compared. One hundred general practitioners in the immediate neighbourhood of a major urban hospital were approached for referrals, and an article on generalised anxiety asking for volunteers was placed in the evening newspaper. The former resulted in ten doctor-initiated referrals, two of whom fulfilled DSM-III criteria for GAD. The latter resulted in over 500 volunteers. In a random selection of 136 volunteers who secured their doctors' approval, 56 fulfilled GAD criteria. The majority of the remainder had a depressive illness. The newspaper article was more economical of researchers' time and more successful in finding suitable subjects than directly approaching general practitioners.

Reactions of first-year medical students to their initial encounter with a cadaver in the dissecting room.

This study reports the results of a 1986 questionnaire survey of 100 first-year medical students regarding their preparation for and reactions to their first encounter with a human cadaver in the dissecting room. The students were aware of psychological and physical reactions to this experience, and although they felt adequately prepared prior to the class, expressed a desire for greater preparation afterwards, particularly through more discussion of the experience with the anatomy staff. A surprising number of the students (62) had had prior exposure to a dead human body, which was a significant influence upon their reactions. The results of this study suggest a need for improving both the preparation for coping with dissection and the follow-up opportunities for dealing with professional and emotional issues raised during human dissection.

Psychiatry as a career choice.

The paper reviews articles in the field of research in medical education specifically dealing with the factors involved in the choice of Psychiatry as a medical specialty and describes three studies conducted in Melbourne. These studies focus on the relevance of personality factors in the psychiatrist's choice of a career. While they confirm other work in this field, it is felt that the emphasis should no longer be placed on single factors. Future investigations should be multifactorial in design and analysis to highlight the combination of factors underlying such choices.

Panic disorder, the ventilatory response to carbon dioxide and respiratory variables.

Increased sensitivity of the central carbon dioxide chemoreceptors to carbon dioxide has been hypothesized as a biologic determinant of panic attacks in panic disorder and on voluntary inhalation of carbon dioxide mixtures. The ventilatory response to carbon dioxide, a measure of sensitivity, was assessed in 12 patients with panic disorder and 12 matched normal controls. While mean sensitivity was similar for both groups, for the panic disorder patients, mean sensitivity due to the tidal volume component was significantly less than for the normal controls, and mean sensitivity due to the frequency component was significantly greater than for the normal controls. The interpretation of the effects of carbon dioxide inhalation as a neurobiologic and behavioral probe may be enhanced if the components of the ventilatory response are examined separately.

The dexamethasone suppression test and plasma dexamethasone in generalized anxiety disorder.

A Dexamethasone Suppression Test nonsuppression rate of 27% was found in a group of 30 generalized anxiety disorder patients before treatment. The dexamethasone concentrations in the eight nonsuppressors were significantly lower than in eight suppressors matched by sex and age, but were similar to those in five nonsuppressors from a matched normal control group. The dexamethasone concentrations in the generalized anxiety disorder suppressors and a matched group of eight normal control suppressors were similar. After successful nondrug behavioral treatment, all generalized anxiety disorder patients were suppressors. Posttreatment dexamethasone concentrations in the initial nonsuppressor patients remained significantly lower than in the initial suppressors. The results suggest that low plasma dexamethasone concentrations after 1 mg oral dexamethasone may confer a vulnerability to nonsuppression that may be expressed in the presence of high state anxiety.

The dexamethasone suppression test: a study in a normal population.

One hundred healthy, non-depressed volunteers were given a standard dexamethasone suppression test (DST) to determine the appropriate criterion values of plasma cortisol to define suppression or nonsuppression. By radioimmunoassay (RIA) of cortisol, the criterion value for 5% nonsuppression was plasma cortisol greater than 187 nmol/l, and for suppression less than 153 nmol/l, with an indeterminate range between these values. Use of the widely accepted pre-determined criterion value of 138 nmol/l gave a significantly greater frequency of nonsuppression. Values of cortisol measured by two RIAs in a subset of 43 volunteers were not equivalent. With the experimentally determined criterion value, no significant differences between nonsuppressors and suppressors were found for any measured physical or psychological parameters. Women taking oral contraceptives had significantly higher plasma cortisol pre-dexamethasone and post-dexamethasone. Their exclusion did not alter the calculated criterion value for the remainder, but their separately estimated criterion value was significantly higher. Caution should be exercised when classifying the DST status of women on oral contraceptives, particularly when values are at the lower end of the nonsuppressor range. Determination of a separate normal range for them may be warranted.

Prediction of outcome in depressed patients by weekly monitoring with the dexamethasone suppression test.

Forty-three depressed patients in hospital were studied with weekly dexamethasone suppression tests (DSTs) and were followed as out-patients for at least three months after discharge. The detection rate of patients with LHPA axis dysfunction increased from 41% with a single DST to 59% with serial DSTs. There was a poor correlation between weekly post-dexamethasone cortisol levels and Hamilton depression rating scores. In patients with evidence of LHPA axis dysfunction, a DST at discharge discriminated effectively between a good and a poor outcome group; persistent non-suppression was strongly linked with a relapse of depression in the first three months after discharge. In general, our results support previous claims that the DST is a state marker for depressive illness.

The dexamethasone suppression test: importance of dexamethasone concentrations.

Plasma dexamethasone concentrations and cortisol response to dexamethasone were measured in 29 normal healthy volunteers, 23 depressed patients, and 10 patients with anorexia nervosa at 4:00 PM postdexamethasone. In each of the 3 groups, nonsuppressors had lower dexamethasone concentrations than suppressors. Of the subjects with plasma dexamethasone at or below 0.7 ng/ml, a significantly higher proportion (48%) were nonsuppressors compared to the proportion above 0.7 ng/ml (14%), all of whom were patients. Plasma dexamethasone concentrations in a subgroup of depressed nonsuppressors were high (mean 1.35 ng/ml), whereas the remainder were low (0.42 ng/ml) and were similar to the normal nonsuppressors (0.35 ng/ml), suggesting different mechanisms for nonsuppression in the subgroups. Plasma dexamethasone concentrations were similar in nonendogenous and endogenous depressives, in men and women, and in medicated and drug-free patients. None of the variables of age, weight, history of weight loss, Hamilton depression rating score, predexamethasone cortisol, or postdexamethasone cortisol were significantly correlated with plasma dexamethasone, except for body weight and a history of weight loss in the depressed group only. Mean plasma dexamethasone concentrations increased significantly from week 1 to week 2 in 7 depressed patients, whereas plasma cortisol decreased; however, the relationship between dexamethasone and cortisol varied considerably for individual patients.

Anxiety disorder and perception of inspiratory resistive loads.

Sensations of breathlessness in the absence of respiratory disease are common in anxiety disorders. Perceptions of breathlessness in eight patients with anxiety disorder were compared with eight normal control subjects, matched for age and sex, by the application of Steven's law to the magnitude of resistive load test. All subjects estimated the magnitudes of resistive loads to inspiration while peak inspiratory mouth pressures were monitored. Anxious patients' perceptions of the added loads were significantly less sensitive than normal, even though the effort, determined by peak inspiratory mouth pressure, in overcoming each load was normal. Correlations between estimates of resistive loads and peak inspiratory mouth pressure were significantly less for the anxious patients than for normal subjects. Thus, perception of breathlessness in anxiety disorders may be affected by factors not normally associated with breathlessness and may help account for the greater than normal variability in resistive load perception in respiratory disease.