Deriving preference-based single indices from non-preference based condition-specific instruments: Converting AQLQ into EQ5D indices

Suppose that one has a clinical dataset with only non-preference-based QOL data, and that one nevertheless would like to perform a cost/QALY analysis. This study reports on some efforts to establish a "mapping" relationship between AQLQ (a non-preference-based QOL instrument for asthma) and EQ5D (a preference-based generic instrument). Various methods are described in terms of associated assumptions regarding the measurement properties of the instruments. This is followed by empirical mapping, based on regressing EQ5D on AQLQ. Six main regression models and two supplementary models are identified, and the regressions carried out. Performance of each model is explored in terms of goodness of fit between observed and predicted values, and of robustness of predictions on external data. The results show that it is possible to predict mean EQ5D indices given AQLQ data. The general implications for methods of mapping non-preference-based instruments onto preference-based measures are discussed

Deriving preference-based single indices from non-preference based condition-specific instruments: converting AQLQ into EQ5D indices

Suppose that one has a clinical dataset with only non-preference-based QOL data, and that one nevertheless would like to perform a cost/QALY analysis. This study reports on some efforts to establish a “mapping” relationship between AQLQ (a non-preference-based QOL instrument for asthma) and EQ5D (a preference-based generic instrument). Various methods are described in terms of associated assumptions regarding the measurement properties of the instruments. This is followed by empirical mapping, based on regressing EQ5D on AQLQ. Six main regression models and two supplementary models are identified, and the regressions carried out. Performance of each model is explored in terms of goodness of fit between observed and predicted values, and of robustness of predictions on external data. The results show that it is possible to predict mean EQ5D indices given AQLQ data. The general implications for methods of mapping non-preference-based instruments onto preference-based measures are discussed.EQ5D; AQLQ; mapping

Two distinct aetiologies of cardia cancer, evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear. Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach. Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin. Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II ,2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1). Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer

Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation

<b>Background</b>: The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and N-nitroso compounds by acidification at low gastric pH in the presence of thiocyanate. <b>Aims</b>: To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach. <b>Methods</b>: The nitrosative chemistry was modelled in vitro by measuring the nitrosation of four secondary amines under conditions simulating the proximal stomach. The N-nitrosamines formed were measured by gas chromatography–ion-trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured amperometrically. <b>Results</b>: In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating species to nitric oxide. Addition of ascorbic acid reduced the amount of N-nitrosodimethylamine formed by fivefold, N-nitrosomorpholine by .1000-fold, and totally prevented the formation of N-nitrosodiethylamine and N-nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of Nnitrosodimethylamine, N-nitrosodiethylamine and N-nitrosopiperidine formed by approximately 8-, 60- and 140-fold, respectively, compared with absence of ascorbic acid. <b>Conclusion</b>: The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate nitrosating species by reacting with oxygen in the lipid phase

Reduction in jejunal fluid absorption in vivo through distension and cholinergic stimulation not attributable to enterocyte secretion

Jejunal fluid absorption in vivo was reduced by distension and by hydrostatic pressure and further declined on adding E. coli STa enterotoxin but no net fluid secretion was detected. Luminal atropine reduced pressure mediated reductions in fluid absorption to normal values but intravenous hexamethonium was without effect. A neural component to inhibition of absorption by pressure (though not stretch) may be mediated by axon reflexes within cholinergic neurons.Perfusion of cholinergic compounds also reduced net fluid absorption but did not cause secretion. In order to show that these actions were not secretory processes stimulated by cholinergic compounds that offset normal rates of absorption, these compounds were tested for their ability to cause net secretion in loops that were perfused with solutions in which choline substituted for sodium ion. In addition, these perfusates additionally contained E. coli STa enterotoxin or EIPA (ethyl-isopropyl-amiloride) to minimize absorption.In these circumstances, where it might be expected to do so if it were acting through a secretory rather than an absorptive mechanism, carbachol did not cause net fluid secretion. Cholinergic stimulation and pressure induced distension are thought to reduce net fluid absorption through inducing secretion but are found only to reduce fluid absorption.In conclusion, distension and cholinergic stimulation of the small intestine are two further circumstances in which fluid secretion is assumed to explain their action on fluid movement, as required by the enterocyte secretion model of secretion but, which like STa enterotoxin, instead are only able to reduce fluid absorption. This casts further doubt on the widespread validity of the enterocyte secretion model for fluid appearance in the lumen in diarrhoeal diseases

Dentistry where there is no Dentist: A retrospective analysis of urgent dental care reported through the British Antarctic Survey Medical Unit (BASMU), 2015 - 2020.

File replaced (incorrect version) on 04/10/2022 by KT (LDS).AIM: To evaluate the nature of dental related morbidity in British Antarctic Survey (BAS) deployed personnel, and to compare the findings to those in other deployed population groups. Additional aims include outlining the evidence-based approach to further developing a training programme for non-dentists, to manage dental emergencies. METHODS: A retrospective analysis of dental morbidity between 2015 - 2020 reported through the British Antarctic Survey Medical Unit (BASMU) database of dental reported morbidity recorded by deployed medical officers. RESULTS: Analysis and comparison of dental morbidity in deployed personnel to austere environments revealed similarity, in that relatively minor conditions led to the most significant number of presentations for personnel seeking dental advice when deployed. CONCLUSIONS: Dental morbidity for deployed personnel in austere conditions can present with a range of symptoms from relatively minor to severe. Use of best evidence to configure training packages to likely presentations, may limit likelihood of necessitating evacuation from remote locations, or limit morbidity when evacuation is not feasible

The acute hepatic porphyrias

The acute hepatic porphyrias are the result of hereditary partial deficiencies of individual enzymes in the pathway of haem biosynthesis. Seven enzymes are known to be involved in the pathway, converting glycine and succinyl CoA first to porphyrin precursors and then to porphyrins and finally to haem. The rate of the process is regulated by the initial enzyme, delta-aminolaevulinic acid (ALA) synthase,which is under negative feedback control, by haem. The partial block in this pathway, in each of the acute porphyrias,results in compensatory increased activity of ALA synthase and,consequently,overproduction of porphyrins and precursors formed prior to the deficient enzyme. Patients with acute porphyria generally enjoy good health,but exposure to certain recognised factors, namely specific drugs, alcohol, hormones and fasting; may precipitate severe clinical attacks characterized by gastro-intestinal symptoms, psychiatric disturbances and neuropathy. All of the systemic manifestations of the attack are thought to be explained by neurological dys function,but the mechanism by which the abnormal haem biosynthesis causes the neuropathy is not known. Following a general description of haem biosynthesis and the porphyrias, this thesis concentrates on the management of acute hepatic porphyria studying, in turn, the detection of subjects with the genetic trait, the factors which may precipitate attacks in these subjects and the treatment of patients in established attack. Much of the work presented is based upon the ability to measure the activities of the individual enzymes of haem biosynthesis in human peripheral blood cells. The mitochondrial enzymes, ALA synthase, coproporphyrinogen oxidase and ferrochelatase, are measured in leucocytes and the cytosolic enzymes, ALA dehydratase, uroporphyrinogen-1-synthase (URO synthase) and uroporphyrinogen decarboxylase, in erythrocytes. The measurement in peripheral blood cells of the activities of both the rate-controlling enzyme, ALA synthase, and the appropriate genetically deficient intermediate enzyme, is shown to be a sensitive and specific means of detecting latent cases of acute porphyria,the majority of whom have normal excretion of porphyrins and precursors. Enzymatic screening of affected families confirms that the genetic trait is inherited in an autosomal dominant sex-independent manner. The family studies also demonstrate that the vast majority of subjects with the trait remain clinically latent, and the reason why the minority of patients experience clinical manifestations is examined. The activity of the partially deficient enzyme is similar in latent and manifest cases, but ALA synthase activity is higher in patients who have experienced an attack and this may reflect higher circulating levels of endogenous inducing agents. Drugs are an important exogenous precipitating factor for acute porphyria, and an important aspect of the prevention of attacks is the identification of potentially porphyrinogenic drugs. The testing of 26 commonly prescribed drugs, by assessing their effect on hepatic ALA synthase activity in rats, is described. The mechanism by which drugs stimulate ALA synthase activity is examiaed with particular reference to the role of induction of the mixed function oxidase enzyme (MFO) system. A close correlation is noted between induction of the MFO system, as reflected in increased hepatic cytochrome P450 content, and increased activity of ALA synthase, though not the converse. Sequential studies following commencement of phenytoin administration to rats show that the rise in ALA synthase activity is transitory and coincides with the rise in hepatic cytochrome P450 content which is maintained. These observations indicate that induction of the MFO system demands increased ALA synthase activity to provide the additional haem for synthesis of the haemoprotein, cytochrome P450. (Abstract shortened by ProQuest.)