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Background: People living with frailty are vulnerable to poor outcomes and incur higher health care costs after coronary artery bypass graft (CABG) surgery. Frailty-defining instruments for population-level research in the CABG setting have not been established. The objectives of the study were to develop a preoperative frailty index for CABG (pFI-C) surgery using Ontario administrative data; assess pFI-C suitability in predicting clinical and economic outcomes; and compare pFI-C predictive capabilities with other indices. Methods: A retrospective cohort study was conducted using health administrative data of 50,682 CABG patients. The pFI-C comprised 27 frailty-related health deficits. Associations between index scores and mortality, resource use and health care costs (2022 Canadian dollars [CAD]) were assessed using multivariable regression models. Capabilities of the pFI-C in predicting mortality were evaluated using concordance statistics; goodness of fit of the models was assessed using Akakie Information Criterion. Results: As assessed by the pFI-C, 22% of the cohort lived with frailty. The pFI-C score was strongly associated with mortality per 10% increase (odds ratio [OR], 3.04; 95% confidence interval [CI], [2.83,3.27]), and was significantly associated with resource utilization and costs. The predictive performances of the pFI-C, Charlson, and Elixhauser indices and Johns Hopkins Aggregated Diagnostic Groups were similar, and mortality models containing the pFI-C had a concordance (C)-statistic of 0.784. Cost models containing the pFI-C showed the best fit. Conclusions: The pFI-C is predictive of mortality and associated with resource utilization and costs during the year following CABG. This index could aid in identifying a subgroup of high-risk CABG patients who could benefit from targeted perioperative health care interventions. Résumé: Contexte: Les personnes dont l’état de santé est fragilisé sont susceptibles de connaître des issues défavorables et de générer des coûts plus élevés pour le système de santé après un pontage aortocoronarien. Aucun instrument n’a été établi pour définir la fragilité dans la recherche populationnelle en contexte de pontage aortocoronarien. Les objectifs de l’étude étaient les suivants : 1) concevoir un indice de fragilité préopératoire en vue d’un pontage aortocoronarien (preoperative frailty index for CABG surgery, pFI-C) en utilisant des données administratives de l’Ontario; 2) évaluer la capacité de cet indice à prédire les issues cliniques et économiques; et 3) comparer la valeur prédictive de cet indice avec celle d’autres indices. Méthodologie: Une étude de cohorte rétrospective a été menée à partir de données médico-administratives portant sur 50 682 patients ayant subi un pontage aortocoronarien. Le pFI-C comprenait 27 déficits de santé liés à la fragilité. Des liens entre les scores de l’indice et la mortalité, l’utilisation des ressources et les coûts de soins de santé (en $ CA de 2022) ont été évalués à l’aide de modèles de régression multivariable. La capacité du pFI-C à prédire la mortalité a été évaluée à l’aide de la statistique de concordance; la qualité de l’ajustement des modèles a été évaluée en fonction du critère d’information d’Akaike. Résultats: Selon l’évaluation par le pFI-C, 22 % de la cohorte vivait avec une fragilité. Le score de l’indice était fortement corrélé à la mortalité par tranche d’augmentation de 10 % (rapport de cotes de 3,04; intervalle de confiance à 95 % de 2,83 à 3,27) et était corrélé de manière significative à l’utilisation des ressources et aux coûts. La valeur prédictive du pFI-C, des indices de Charlson et Elixhauser, et de Johns Hopkins Aggregated Diagnostic Groups était similaire, et les modèles de mortalité contenant le pFI-C affichaient une valeur statistique C de 0,784. Les modèles de coûts contenant le pFI-C affichaient le meilleur ajustement. Conclusions: Le pFI-C est un facteur prédictif de mortalité et est corrélé à l’utilisation des ressources et aux coûts engagés durant l’année qui suit un pontage aortocoronarien. Cet indice pourrait faciliter la détection d’un sous-groupe de patients subissant un pontage aortocoronarien et présentant un risque élevé qui pourraient bénéficier de soins périopératoires ciblés.

After oral ingestion of a free amino acid mixture by three cystinuric patients, plasma increments of lysine and arginine were lower and those of many other amino acids were significantly higher than those found in control subjects. Similar results were obtained in control subjects after amino acid imbalance had been artificially induced by the omission of cystine, lysine, and arginine from the amino acid mixture. Especially high increments of alanine and proline provided the best evidence of amino acid imbalance caused by a temporary lysine and, to a lesser extent, arginine and cystine deficit. No such amino acid imbalance was found to occur in the cystinuric patients after ingestion of whole protein, indicating that absorption of oligopeptides produced by protein digestion provided a balanced physiological serum amino acid increment. This is considered to explain the lack of any unequivocal nutritional deficit in cystinuric patients despite poor absorption of the essential free amino acid, lysine.

A study has been made of urinary peptide output in rats before and after production of a Fanconi syndrome induced by a single injection of sodium maleate. There was an unequivocal increase of urinary peptides on the first and second days after the injection, without any detectable change in the concentration of plasma peptides. 2. Similar results were obtained in osteolathyritic rats in which skeletal lesions had been produced by ingestion of beta-aminopropionitrile. 3. The fractional amino acid content of urinary peptides after maleate and beta-aminopropionitrile is shown to be significantly different from that in control animals. 4. Evidence is presented that the increased output of peptides is mainly due to increased renal clearance similar to that previously described for amino acids, glucose and several electrolytes in this type of experimental Fanconi syndrome.

Peptide excretion has been studied in 20 cases of Wilson's disease and in maleate-induced Fanconi syndrome in the rat, ligand-exchange column chromatography being used to separate peptides from free amino acids. There is a statistically significant increase in urinary peptides in both types of the Fanconi syndrome. In both man and the rat, a large fraction of the excreted peptides has been shown to contain hydroxyproline, and therefore to be derived from collagen degradation. In both groups there is a close correlation between the output of hydroxyproline and that of total peptide-bound amino acids. Arguments are advanced that the peptiduria is due to increased urinary clearance of plasma peptides rather than to a metabolic cause. Peptides excreted in patients with the Fanconi syndrome are shown to have a different proportionate amino acid composition to those in urine specimens from normal controls. The mean size of urinary peptides derived from collagen must be at least five or six amino acids per peptide chain. Maleate-induced Fanconi syndrome in the rat is thought to be a close analogue of the syndrome in man, and further results obtained in the animal model may well be directly applicable to human disease.

1. There is an excess urinary output of free amino acids and of urinary peptides in most cases of untreated Wilson's disease. Studies of 11 patients have shown that both these abnormalities are greatly improved by two years of standard chelation therapy. 2. The reduction in excretion of both free amino acids and peptides is purely quantitative, there being no significant change in the percentage composition of amino acids, either free or combined, in relation to their total urinary output. 3. Arguments are advanced that the peptiduria of the disease is usually due to a proximal renal tubular reabsorption defect, but in rare cases it may be due to excess bone breakdown or even to a combination of bone and renal tubular disease in the same patient.

Ninety-nine mothers who received extradural analgesia, and 95 who received conventional methods of analgesia for the relief of pain in labour, were interviewed at 18-24 months following delivery. An increase of about 2% in the proportion of mothers experiencing a sense of "deprivation" in the long term in comparison with the findings recorded immediately after delivery was noted. This was not accompanied by the need to seek psychiatric treatment.

A method of survey for the long-term assessment of extradural analgesia in labour is described. The difficulties and problems of collecting the data are discussed.

1. The plasma concentrations and urinary output of proline and hydroxyproline contained in peptides were measured in normal rats and in rats with Fanconi syndrome produced by injection of sodium maleate. All animals received a prior injection of 10 mg of the dipeptide L-prolyl-L-hydroxy-proline to increase plasma and urinary peptide content. There was a significant increase of urinary output of the two imino acids contained in peptides and a fall in their plasma concentrations. 2. It is concluded that increased output of peptides derived from collagen degradation in the experimental Fanconi syndrome in rats is at least in part due to diminished tubular reabsorption of these compounds from the glomerular filtrate. The results are claimed to be relevant to the increased output of urinary peptides in the Fanconi syndrome in man.

The excretion of pethidine and its metabolite norpethidine is increased in acid urine and decreased in alkaline urine. Excretion of these two bases is the main route of removal of pethidine from the body if the urine is highly acid. If the urine is alkaline, excretion of the hydrolysis products meperidinic and normeperidinic acids, both as free acids and as conjugates, is the more important means of elimination of the drug. Acidification of the urine with ammonium chloride is indicated in the therapy of cases of pethidine poisoning in patients with reduced metabolic breakdown of the drug by the microsomal enzyme systems within liver cells. Reversed-phase chromatography of the dinitrophenyl derivative of norpethidine may prove to be of forensic importance in the diagnosis of pethidine poisoning or of pethidine addiction. Norpethidine can be detected in the urine by this method for at least 3 days after the last dose of pethidine. Analytical sensitivity is increased by acidification of the urine which produces a temporary rise of the excretion rate.

Serum concentrations of beta-alanine and l-histidine are compared in five normal adults after ingestion of the dipeptide carnosine (beta-alanyl-l-histidine) and after equivalent amounts of the constituent free amino acids. The results indicate that absorption is significantly more rapid after the ingestion of the amino acids than after the dipeptide. The use of the test in a case of Hartnup disease suggests that carnosine is taken up by intestinal cells as the dipeptide, but subsequent hydrolysis and delivery of the constituent amino acids to the portal blood is a slower process than transport of the free amino acids themselves.