Effect of ketamine pretreatment for anaesthesia in patients undergoing percutaneous transluminal balloon angioplasty with continuous remifentanil infusion

BACKGROUND: An appropriate level of sedation and pharmacological assist are essential during percutaneous transluminal balloon angioplasty (PTA). Ketamine provides good analgesia while preserving airway patency, ventilation, and cardiovascular stability with an opioid sparing effect suggesting that it would be ideal in combination with remifentanil and midazolam in spontaneously breathing patients. We evaluated the effect of a small dose of ketamine added to midazolam and remifentanil on analgesia/sedation for PTA procedures. METHODS: Sixty-four patients receiving PTA were enrolled. The Control group received midazolam 1.0 mg i.v. and continuous infusion of remifentanil 0.05 µg/kg/min. The Ketamine group received, in addition, an intravenous bolus of 0.5 mg/kg ketamine. Patients' haemodynamic data were monitored before remifentanil infusion, 5 min after remifentanil infusion, at 1, 3, 5, 30 min after incision, and at admission to the recovery room. Verbal numerical rating scales (VNRS) and sedation [OAA/S (Observer's Assessment of Alertness/Sedation)] scores were also recorded. RESULTS: The VNRS values at 1, 3, and 5 min after incision and OAA/S scores at 5 min after remifentanil infusion, and 1, 3, and 5 min after incision were lower in the Ketamine group than in the Control group. In the Control group, the VNRS value at 1 min after incision significantly increased and OAA/S values at 3, 5, and 30 min after incision significantly decreased compared to baseline values, while there were no significant changes in the ketamine group. CONCLUSIONS: A small dose of ketamine as an adjunct sedative to the combination of midazolam and remifentanil produced a better quality of sedation and analgesia than without ketamine and provided stable respiration without cardiopulmonary deterioration.ope

A classification tree for predicting recurrent falling in community-dwelling older persons

OBJECTIVES: To develop a classification tree for predicting the risk of recurrent falling in community-dwelling older persons using tree-structured survival analysis (TSSA). DESIGN: A prospective cohort study. SETTING: A community in the Netherlands. PARTICIPANTS: One thousand three hundred sixty-five community-dwelling older persons (≥65) from the Longitudinal Aging Study Amsterdam (LASA). MEASUREMENTS: In 1995, physical, cognitive, emotional, and social aspects of functioning were assessed. Subsequently, a prospective fall follow-up, specifically on recurrent falls (two falls within 6 months) was conducted for 3 years. RESULTS: The classification tree included 11 end groups differing in risk of recurrent falling based on a minimum of two and a maximum of six predictors. The first split in the tree involved two or more falls versus fewer than two falls in the year preceding the interview. Respondents with two or more falls in the year preceding the interview (n = 193) and with at least two functional limitations (n = 98) had a 75% risk of becoming a recurrent faller, whereas respondents with fewer than two functional limitations were further divided into a group with regular dizziness (n = 11, risk of 68%) and a group with no regular dizziness (n = 84, risk of 30%). In respondents with fewer than two falls in the year preceding the interview (n = 1, 172), the risk of becoming a recurrent faller varied between 9% and 70%. Predictors in this branch of the tree were low performance, low handgrip strength, alcohol use, pain, high level of education, and high level of physical activity. CONCLUSION: This classification tree included 11 end groups differing in the risk of recurrent falling based on specific combinations of a maximum of six easily measurable predictors. The classification tree can identify subjects who are eligible for preventive measures in public health strategies

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

Aims/hypothesis: $FTO$ harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for $FTO$ in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the $FTO$ locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. Methods: All studies published on the association between $FTO$-rs9939609 (or proxy [r$^2$ > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. Results: The $FTO$-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10$^{−19}$), overweight by 1.13-fold/allele (p = 1.0 × 10$^{−11}$) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10$^{−8}$). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10$^{−5}$). The $FTO$-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10$^{−17}$), WHR by 0.003/allele (p = 1.2 × 10$^{−6}$), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of $FTO$ variation on obesity-related traits and type 2 diabetes was similar in the two populations. Conclusions/interpretation: $FTO$ is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, $FTO$ is also associated with type 2 diabetes independently of BMI. Electronic supplementary material The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference