Model for simulation of HIV/AIDS and cost-effectiveness of preventing non-tuberculous mycobacterial (MAC)-disease

Because most HIV-infected patients die of diseases caused by opportunistic pathogens, the prevention of these infections is an important clinical issue. Cost-containment in the healthcare system is a subject of high priority in public debate. Methods to determine cost-effectiveness of different therapeutic strategies are therefore needed to obtain valid data as the basis for decisions on cost reduction without a decrease in the quality of care. A disease state transition model based on a Markov process was developed to simulate the natural history of HIV infection and the acquired immunodeficiency syndrome (AIDS). Using this model survival time and treatment costs for every patient can be estimated and the results of alternative medications compared. We determined the cost-effectiveness (per life-year saved, LYS) of different strategies for prevention of Mycobacterium avium complex infections in AIDS patients whose treatment regimens include protease inhibitors. The cost-effectiveness ratios for treatment strategies vary from 13,510 euro to 46,152 euro per LYS without protease inhibitors and from 22,309 euro to 51,336 euro with protease inhibitors. When azithromycin, clarithromycin, and rifabutin were compared, azithromycin was the most cost-effective medication for preventing M. avium complex. The results were stable against a wide range of parameter variations concerning costs and incidence rates.     

Effect of spinal cord stimulation in a rodent model of post-operative ileus

Abstract  Post-operative ileus (POI) is a transient impairment of gastrointestinal (GI) transit that develops after abdominal surgery. The goal of this study was to investigate the effect of spinal cord stimulation (SCS) on gastric emptying and upper GI transit in a rat model of POI. All rats had an electrode placed on the dorsal surface of the spinal cord between the T₅ and T₈ segments. After recovery, gastric emptying and upper GI transit (geometric centre and head of meal) were assessed using a radiolabelled meal fed to each rat via oral gavage. In unanaesthetized rats, SCS (15, 25, 50, 100, 200 Hz, 0.2 ms at 90% motor threshold for 15 min) was performed immediately after the meal. The sham control group had no current applied. The naïve group was without POI or SCS. Gastric emptying was significantly delayed in sham-stimulated rats with POI compared with naïve controls (39.8 ± 6.2% vs 76.5 ± 4.9%, P  < 0.001). In rats with POI that underwent SCS, there was a significant acceleration of gastric emptying to levels that resembled those of naïve controls (65.1 ± 7.4%, P  < 0.05). However, while SCS did not normalize the geometric centre and head of the meal when compared with the naïve group, it did significantly improve both parameters compared with the sham stimulation group. In summary, SCS normalizes gastric emptying and improves upper GI transit in a rodent model of POI. Further experiments are required to address the mechanism(s) by which SCS exhibits prokinetic activity.     

Characteristics of upper oesophageal sphincter and oesophageal body during maturation in healthy human neonates compared with adults

We evaluated the upper oesophageal sphincter (UOS) relationship with oesophageal body during primary peristalsis (PP) sequences in healthy human neonates during maturation and compared with that of healthy adult volunteers. Forty-nine studies were performed using a water perfusion manometry system and a specially designed oesophageal catheter with a UOS sleeve concurrent with submental electromyogram in 31 subjects in supine position (18 preterm neonates, 29.9 +/- 2.5 weeks gestation; four full-term neonates, 39.3 +/- 1.0 weeks gestation; and nine adults, 18-65 years). The preterm neonates were studied longitudinally at 33 and 36 weeks postmenstrual age (PMA) and full-term born at 40 weeks PMA. Data were compared between the groups to recognize the effects of gestation, postnatal age and ageing. We evaluated 403 consecutive spontaneous solitary swallows during maturation (preterm at time-1 vs time-2) and growth (preterm and full-term vs adults) and observed significant (P < 0.05) differences in the basal UOS resting pressure, UOS relaxation characteristics, proximal and distal oesophageal body amplitude, duration, propagation and peristaltic velocity. Characteristics of UOS and PP are well-developed by 33 weeks PMA and undergo further maturation during the postnatal period, and are significantly different from that of adult.     

Brain mapping of digestive sensations elicited by cortical electrical stimulations

Abstract  The aim of the study was to obtain a comprehensive map of cortical areas from where digestive sensations during intracerebral electrical stimulations (ES) in epileptic patients are elicited. Direct cortical ESs were performed in 339 medically intractable epileptic patients selected to presurgical evaluation using chronically stereotaxically implanted intracerebral electrodes and audio–video-EEG monitoring system. Digestive sensations were electrically induced on 723 different anatomical sites in 172 subjects (51%). According to the exclusion criteria, the final analysis includes 174 relevant stimulations evoked in 87 patients. The reported sensations referred predominantly to the upper part of the digestive tract including the epigastria and area over the periumbilical ( n  = 83; 48%), retrosternal ( n  = 17; 10%), pharyngeal ( n  = 31; 18%) and oral ( n  = 18; 10%) regions. The temporal pole (BA 38), hippocampus, amygdala and anterior cingulate cortex (ACC; BA 24/BA 32) were the typical anatomical locations connected with epigastric sensations. Retrosternal sensations were preferentially related to the ACC, while oro-pharyngeal sensations were most related to the suprasylvian opercular cortex and the insula. Cortical ESs are followed by a great variability of induced digestive and associated symptoms corresponding to a widely distributed cortical network of visceral sensation processing, in which the limbic and paralimbic structures play a critical role.