Implementing a QCancer risk tool into general practice consultations: an exploratory study using simulated consultations with Australian general practitioners.

BACKGROUND: Reducing diagnostic delays in primary care by improving the assessment of symptoms associated with cancer could have significant impacts on cancer outcomes. Symptom risk assessment tools could improve the diagnostic assessment of patients with symptoms suggestive of cancer in primary care. We aimed to explore the use of a cancer risk tool, which implements the QCancer model, in consultations and its potential impact on clinical decision making. METHODS: We implemented an exploratory 'action design' method with 15 general practitioners (GPs) from Victoria, Australia. General practitioners applied the risk tool in simulated consultations, conducted semi-structured interviews based on the normalisation process theory and explored issues relating to implementation of the tool. RESULTS: The risk tool was perceived as being potentially useful for patients with complex histories. More experienced GPs were distrustful of the risk output, especially when it conflicted with their clinical judgement. Variable interpretation of symptoms meant that there was significant variation in risk assessment. When a risk output was high, GPs were confronted with numerical risk outputs creating challenges in consultation. CONCLUSIONS: Significant barriers to implementing electronic cancer risk assessment tools in consultation could limit their uptake. These relate not only to the design and integration of the tool but also to variation in interpretation of clinical histories, and therefore variable risk outputs and strong beliefs in personal clinical intuition.

The actions of prostaglandins and their interactions with angiotensin II in the isolated perfused human placental cotyledon.

The prostaglandins PGE1, PGE2, PGD2, PGF2 alpha, U46619 and 6 beta-PGI1 were administered as bolus injections both separately and in combination with angiotensin II into the fetal circulation of isolated human placental cotyledons perfused in vitro. PGF2 alpha and PGD2 caused small dose-dependent increases in fetal perfusion pressure when compared with U46619 which acted as an extremely potent vasoconstrictor of the fetal-placental vasculature. PGE1 caused very small dose-dependent decreases in fetal perfusion pressure when injected on its own. In combination with angiotensin II, PGE1, PGD2 and 6 beta-PGI1 caused significant, dose-related attenuations of the angiotensin II vasoconstrictive response whereas PGE2, PGF2 alpha and U46619 potentiated the response. Injections of angiotensin II after the infusion of indomethacin into the fetal circulation resulted in a potentiation of angiotensin II induced vasoconstriction. The results indicate that prostaglandins exert their effects on the fetal-placental circulation by modulating the actions of angiotensin II.

Uptake, transfer and metabolism of prostaglandin E2 in the isolated perfused human placental cotyledon.

(3H) PGE2 uptake and transfer in the isolated perfused human placental cotyledon was assessed by a single pass paired isotope dilution technique utilising (14C) sucrose as an extracellular marker. Metabolism of (3H) PGE2 was measured by analysing maternal and fetal effluents from perfused human placental cotyledons after bolus injection of (3H) PGE2 into either the maternal or fetal sides. Maximal uptake of (3H) PGE2 was greater on the maternal (81 +/- 8%) than the fetal sides (42 +/- 12%) and showed saturation with increasing concentrations of PGE2 only on the fetal side with an apparent Km of 12 +/- 4.9 nmol/l and vmax of 1.5 +/- 0.2 pmol/min/g. Total recoveries of (3H) PGE2 were 84.6 +/- 11.8% and 32.6 +/- 6.3% of the injected dose after injection on the fetal and maternal sides respectively. Transfer of (3H) PGE2 was the same in both directions being 6.4 +/- 1.2% of the injected dose in the fetal-maternal direction and 5.8 +/- 2.7% of the injected dose in the maternal-fetal direction. Metabolism was greater on the maternal side (35% of injected (3H) PGE2) than the fetal side (18% of injected (3H) PGE2) and was principally to the 13,14-dihydro-15-keto-PGE2 metabolite. Metabolism of (3H) PGE2 after passage across the placenta was the same in both directions and was of the order of approximately 60%.

Prostaglandin production and stimulation by angiotensin II in the isolated perfused human placental cotyledon.

Levels of prostaglandins E and F2 alpha, thromboxane B2, and 6-oxo-prostaglandin F1 alpha were measured by radioimmunoassay in the maternal and fetal effluents of isolated human placental cotyledons perfused in vitro. All prostaglandins measured were released in greater amounts by the maternal side than by the fetal side of the perfused cotyledon although there were no consistent concentration gradients between the two sides. The approximate rank order of prostaglandin release into the maternal side was thromboxane B2 greater than prostaglandin F2 alpha congruent to prostaglandin E congruent to 6-oxo-prostaglandin F1 alpha, and that into the fetal side was thromboxane B2 congruent to prostaglandin F2 alpha congruent to prostaglandin E congruent to 6-oxo-prostaglandin F1 alpha. Injection of angiotensin II (0.5 microgram) into the fetal circulation stimulated prostaglandin E and 6-oxo-prostaglandin F1 alpha but not thromboxane B2 and prostaglandin F2 alpha release into the fetal circulation and had no effect on maternal release. Angiotensin II (0.5 microgram) had no effect on either side of the perfused cotyledon when injected into the maternal circulation. It is proposed that prostaglandin release into both maternal and fetal circulations may be flow-dependent and that the angiotensin II-stimulated release of prostaglandin E and 6-oxo-prostaglandin F1 alpha may serve to modulate the vasoactive actions of angiotensin II on the fetal vasculature.

The effects of the components of the renin-angiotensin system on the isolated perfused human placental cotyledon.

Angiotensins I, II, and III, renin substrate, and des-Asp1-angiotensin I were injected as a bolus into either the maternal or fetal circulation of human placental cotyledons perfused in vitro. All drugs tested produced dose-related increments in fetal perfusion pressure when injected into the fetal circulation, with the order of potency being angiotensin I approximately equal to angiotensin II approximately equal to angiotensin III greater than or equal to des-Asp1-angiotensin I greater than or equal to renin substrate. The responses to all the drugs could be blocked by the competitive inhibitor of angiotensin II, (Sar1, Ala8)-angiotensin II, but only the actions of angiotensin I, renin substrate, and des-Asp1-angiotensin I could be blocked by angiotensin converting enzyme inhibitor. When the agents were injected into the maternal circulation, only angiotensins II and III caused dose-related increments in fetal perfusion pressure. Possibly, the placenta may be the main site of conversion of angiotensin I to angiotensin II in the fetoplacental unit, and angiotensin II produced by the placenta could act locally to control fetoplacental blood flow.