The development and validation of the Score for the Prediction of Postoperative Respiratory Complications (SPORC-2) to predict the requirement for early postoperative tracheal re-intubation: a hospital registry study

Postoperative pulmonary complications are associated with an increase in mortality, morbidity and healthcare utilisation. The Agency for Healthcare Research and Quality recommends risk assessment for postoperative respiratory complications in patients undergoing surgery. In this hospital registry study of adult patients undergoing non-cardiac surgery between 2005 and 2017 at two independent healthcare networks, a prediction instrument for early postoperative tracheal re-intubation was developed and externally validated. This was based on the development of the Score for Prediction Of Postoperative Respiratory Complications. For predictor selection, stepwise backward logistic regression and bootstrap resampling were applied. Development and validation cohorts were represented by 90,893 patients at Partners Healthcare and 67,046 patients at Beth Israel Deaconess Medical Center, of whom 699 (0.8%) and 587 (0.9%) patients, respectively, had their tracheas re-intubated. In addition to five pre-operative predictors identified in the Score for Prediction Of Postoperative Respiratory Complications, the final model included seven additional intra-operative predictors: early post-tracheal intubation desaturation; prolonged duration of surgery; high fraction of inspired oxygen; high vasopressor dose; blood transfusion; the absence of volatile anaesthetic use; and the absence of lung-protective ventilation. The area under the receiver operating characteristic curve for the new score was significantly greater than that of the original Score for Prediction Of Postoperative Respiratory Complications (0.84 [95%CI 0.82–0.85] vs. 0.76 [95%CI 0.75–0.78], respectively; p < 0.001). This may allow clinicians to develop and implement strategies to decrease the risk of early postoperative tracheal re-intubation.     

Cross-cultural invariance of the Academic Expectations Stress Inventory: Adolescent samples from Canada and Singapore

We provide further evidence for the two-factor structure of the 9-item Academic Expectations Stress Inventory (AESI) using confirmatory factor analysis on a sample of 289 Canadian adolescents and 310 Singaporean adolescents. Examination of measurement invariance tests the assumption that the model underlying a set of scores is directly comparable across groups. This study also examined the cross-cultural validity of the AESI using multigroup confirmatory factor analysis across both the Canadian and Singaporean adolescent samples. The results suggested cross-cultural invariance of form, factor loadings, and factor variances and covariances of the AESI across both samples. Evidence of AESI's convergent and discriminant validity was also reported. Findings from t-tests revealed that Singaporean adolescents reported a significantly higher level of academic stress arising from self expectations, other expectations, and overall academic stress, compared to Canadian adolescents. Also, a larger cross-cultural effect was associated with academic stress arising from other expectations compared with academic stress arising from self expectations.     

ProTx-I and ProTx-II: gating modifiers of voltage-gated sodium channels.

The tarantula venom peptides ProTx-I and ProTx-II inhibit voltage-gated sodium channels by shifting their voltage dependence of activation to a more positive potential, thus acting by a mechanism similar to that of potassium channel gating modifiers such as hanatoxin and VSTX1. ProTx-I and ProTx-II inhibit all sodium channel (Nav1) subtypes tested with similar potency and represent the first potent peptidyl inhibitors of TTX-resistant sodium channels. Like gating modifiers of potassium channels, ProTx-I and ProTx-II conform to the inhibitory cystine knot motif, and ProTx-II was demonstrated to bind to sodium channels in the closed state. Both toxins have been synthesized chemically, and ProTx-II, produced by recombinant means, has been used to map the interaction surface of the peptide with the Nav1.5 channel. In comparison, beta-scorpion toxins activate sodium channels by shifting the voltage dependence of activation to more negative potentials, and together these peptides represent valuable tools for exploring the gating mechanism of sodium channels.     

Evidence for a decrease in sympathetic control of intestinal function in the aged rat.

The ability of carbachol and isoprenaline to contract and relax respectively the longitudinal layer of ileal smooth muscle has been compared in rats aged six and twenty-four months. The concentration response curve to carbachol did not vary with the age of the animal. In contrast, the ability of isoprenaline to relax longitudinal smooth muscle precontracted with carbachol was significantly (p less than 0.02) reduced in the twenty-four month age group. This reduced response was due to a decrease in the maximal relaxation induced by isoprenaline rather than by a shift to the right of its dose-response curve. These results are discussed in the context of previous histochemical and microscopical studies which have shown a marked reduction in the density of the sympathetic innervation of the rat small intestine in old age.     

Giving patients an audiotape of their GP consultation: a randomised controlled trial.

BACKGROUND: Providing patients with an audiotape of their medical consultation has been a relatively common practice in oncology clinics for some years. However, broader generalisability of the technique has yet to be examined. AIMS: To investigate the efficacy of providing patients with an audiotape of their consultation in a general practice setting. DESIGN OF STUDY: Randomised controlled trial: 95 experimental participants, 85 controls. SETTING: Routine surgeries run by two general practitioners (GPs) in two different health centres. METHOD: All patients attending GP appointments were eligible for inclusion. Patients were followed up by telephone 7-10 days later. RESULTS: More than half (61%) of the patients who received a tape listened to it. Among listeners, 64% rated the tape useful or very useful; 24% noticed information not heard in the consultation. Half of listeners (46%) said that their understanding of the consultation improved after listening to the tape. Half of the listeners (48%) shared the tape with others, of whom 71% found sharing helpful or very helpful. However, 21% of those who shared the information with others found this unhelpful or very unhelpful, suggesting that patients may need to be briefed on the potential risks of sharing. At follow-up a week later, it emerged that being given a tape had no effect on adherence with GPs' advice, nor on anxiety about conditions. CONCLUSION: Providing patients with an audiotape of their GP consultation was positively rated by many patients. Although there were no detectable clinical effects at follow-up, the technique merits further evaluation in general practice.     

Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical,biochemical, and molecular genetic aspects

We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the biotin-dependent mitochondrial carboxylases in lymphocytes remained below 50% of the mean control values. Not only urinary 3-hydroxyisovaleric acid excretion has been persistently elevated, but also plasma and, with even higher concentrations, cerebrospinal fluid 3-hydroxyisovaleric acid have not normalized. The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g>a on one chromosome and a truncating mutation on the other. This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency.     

The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe

We investigated the molecular basis of hereditary fructose intolerance (HFI) in 80 patients from 72 families by means of a PCR-based mutation screening strategy, consisting of heteroduplex analysis, restriction enzyme digest, DNA single strand electrophoresis, and direct sequencing. For a subset of patients mutation screening with DHPLC was established which turned out to be as fast and as sensitive as the more conventional methods. Fifteen different mutations of the aldolase B (ALDOB) gene were identified in HFI patients. As in smaller previous studies, p.A150P (65%), p.A175D (11%) and p.N335K (8%) were the most common mutated alleles, followed by c.360_363delCAAA, p.R60X, p.Y204X, and c.865delC. Eight novel mutations were identified in eight families with HFI: a small indel mutation (c.1044_1049delTTCTGGinsACACT), two small deletions (c.345_372del28; c.841_842delAC), two splice site mutations (c.113-1G>A, c.799+2T>A), one nonsense mutation (c.612T>G (p.Y204X)), and two missense mutations (c.532T>C (p.C178R), c.851T>C (p.L284P)). By mutation screening for the three most common ALDOB mutations by DHPLC in 2,000 randomly selected newborns we detected 21 heterozygotes. Based on these data and after correction for less common and private ALDOB mutations, HFI prevalence in central Europe is estimated to be 1:26,100 (95% confidence interval 1: 12,600-79,000).