Effects of nefopam on early postoperative hyperalgesia after cardiac surgery.

OBJECTIVE: The purpose of this randomized, double-blind placebo-controlled study was to evaluate the effect of nefopam, a centrally acting antinociceptive compound, on the development of hyperalgesia after sternotomy. Preventive strategy giving nefopam from the early stage of anesthesia was compared with a postoperative strategy only and placebo. DESIGN: This study was double-blinded and randomized. SETTING: It was conducted in a single university hospital. PARTICIPANTS: Ninety American Society of Anesthesiologists II to III patients scheduled for elective cardiac surgery. INTERVENTIONS: Patients were assigned randomly to receive a 0.3-mg/kg bolus of nefopam at the induction of anesthesia followed by a continuous infusion of 0.065 mg/kg/h for 48 hours (G1), a 0.3-mg/kg bolus of nefopam at the end of surgery followed by a continuous infusion of 0.065 mg/kg/h for 48 hours (G2), or a placebo (G3). Postoperative analgesia was based on morphine patient-controlled analgesia and rescue analgesia when necessary. Postoperative hyperalgesia, pain scores, morphine consumption, and postoperative cognitive dysfunction were assessed for the first 48 hours and thereafter on postoperative days 4 and 7. MEASUREMENTS AND MAIN RESULTS: The postoperative extent of dynamic hyperalgesia and the decrease of the nociceptive threshold evaluated by von Frey filaments at the sternal midline were smaller in group 1 and group 2 compared with the placebo group at the 24th hour. The primary objective was the extent of hyperalgesia at the midline given as the mean (standard deviation [SD]) (4.4 [2.5] cm for G1, 4.1 [2.7] for G2, and 6.1 [2.7] cm for G3. The punctuate is given as mean (SD) (64 [43] g for G1, 68 [40.8] g for G2, and 32 [27] g for G3; with p < 0.05 for the comparisons of extent and punctuate hyperalgesia between G1 and G3 and G2 and G3). The extent of hyperalgesia was not significantly different among the 3 groups on days 2, 4, and 7 after surgery. There were no significant differences in pain scores, morphine consumption, or postoperative cognitive dysfunctions. CONCLUSIONS: Nefopam administered during the perioperative period slightly reduced acute hyperalgesia after cardiac surgery, but this was not associated with improved analgesic efficacy.

Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients' data.

BACKGROUND: Despite three decades of prenatal screening for congenital toxoplasmosis in some European countries, uncertainty remains about the effectiveness of prenatal treatment. METHODS: We did a systematic review of cohort studies based on universal screening for congenital toxoplasmosis. We did a meta-analysis using individual patients' data to assess the effect of timing and type of prenatal treatment on mother-to-child transmission of infection and clinical manifestations before age 1 year. Analyses were adjusted for gestational age at maternal seroconversion and other covariates. FINDINGS: We included 26 cohorts in the review. In 1438 treated mothers identified by prenatal screening, we found weak evidence that treatment started within 3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after 8 or more weeks (adjusted odds ratio [OR] 0.48, 95% CI 0.28-0.80; p=0.05). In 550 infected liveborn infants identified by prenatal or neonatal screening, we found no evidence that prenatal treatment significantly reduced the risk of clinical manifestations (adjusted OR for treated vs not treated 1.11, 95% CI 0.61-2.02). Increasing gestational age at seroconversion was strongly associated with increased risk of mother-to-child transmission (OR 1.15, 95% CI 1.12-1.17) and decreased risk of intracranial lesions (0.91, 0.87-0.95), but not with eye lesions (0.97, 0.93-1.00). INTERPRETATION: We found weak evidence for an association between early treatment and reduced risk of congenital toxoplasmosis. Further evidence from observational studies is unlikely to change these results and would not distinguish whether the association is due to treatment or to biases caused by confounding. Only a large randomised controlled clinical trial would provide clinicians and patients with valid evidence of the potential benefit of prenatal treatment.

Risks and advantages of detecting individuals unfit to drive: a Markov decision analysis.

BACKGROUND: Many countries have initiated legislation to detect individuals who are unfit to drive, without any evidence that positive effects of these screening procedures outweigh negative effects. OBJECTIVE: To measure the potential effectiveness of a screening program to detect individuals unfit to drive. DESIGN: Markov decision analysis was used to compare no screening to two potential screening strategies. PARTICIPANTS: Hypothetical cohorts of 10,000 45-year-old, 65-year-old, 75-year-old and 85-year-old individuals seen in primary care practices. INTERVENTIONS: Within the screening strategies: a clinical test without on-road confirmatory testing; a clinical test with on-road confirmatory testing, and an imposed driving cessation for patients with a positive test. MEASUREMENTS: For each strategy, we compared for two conditions (sleep disorders and dementia) the numbers of crash-related consequences prevented and of adverse events induced (primary objective) and measured the gain in quality-adjusted life years (secondary objective). RESULTS: For sleep disorders, on-road confirmatory annual testing was the preferred strategy. Whatever the medical condition and age when screening starts, no screening was always better than single-test screening without an on-road confirmatory testing. In sensitivity analyses, these baseline conclusions were only affected by extreme values of test specificity. CONCLUSION: Because of the expected difficult application and cost of road tests and annual screening by clinicians, the most acceptable strategy from public health, clinical, and individual points of view is likely to be no screening.

Systematic screening for unsafe driving due to medical conditions: still debatable.

BACKGROUND: Assessing people's ability to drive has become a public health concern in most industrialized countries. Although age itself is not a predictive factor of an increased risk for dangerous driving, the prevalence of medical conditions that may impair driving increases with age. Because the implementation of a screening for unsafe driving due to medical conditions is a public health issue, its usefulness should be judged using standardised criteria already proposed for screening for chronic disease. The aim of this paper is to propose standardised criteria suitable to assess the scientific validity of screening for unsafe driving due to medical conditions, and identify potential issues to be clarified before screening can be implemented and effective. DISCUSSION: Using criteria developed for screening for chronic diseases and published studies on driving with medical conditions, we specify six criteria to judge the opportunity of screening for unsafe driving due to medical conditions. This adaptation was needed because of the complexity of the natural history of medical conditions and their potential consequences on driving and road safety. We then illustrate that published studies pleading for or against screening for unsafe driving due to medical conditions fail to provide the needed documentation. Individual criteria were mentioned in 3 to 72% of 36 papers pleading for or against screening. Quantitative estimates of relevant indicators were provided in at most 42% of papers, and some data, such as the definition of an appropriate unsafe driving period were never provided. SUMMARY: The standardised framework described in this paper provides a template for assessing the effectiveness (or lack of effectiveness) of proposed measures for screening for unsafe driving due to medical conditions. Even if most criteria were mentioned in the published literature pleading for or against such a screening, the failure to find quantitative and evidence-based estimates of relevant indicators provides useful insight for further research.

Outcomes following acute hospitalised myocardial infarction in France: An insurance claims database analysis.

BACKGROUND: Mortality and complications of acute myocardial infarction (AMI) in France have declined over the last twenty years, but still remain high. Practice guidelines recommend secondary prevention measures to reduce these. Insurance claims databases can be used to assess the management of post MI and other cardiovascular outcomes in everyday practice. METHODS: A cohort study was performed in a 1/97 representative sample of the French nationwide claims and hospitalisation database (EGB database). All adults with a documented hospitalisation for MI between 2007 and 2011 were included, and followed for three years. Data was extracted on demographics, the index admission, reimbursed medication, comorbidities, post-MI events and death. RESULTS: During the study period, 1977 individuals hospitalised for an MI were identified, with a mean (±SD) age of 63.8 (±14.3) years, 65.8% were men, 82.4% had hypertension and 37.6% hypercholesterolaemia. The mean duration of hospitalisation was seven days and 8.3% of patients died during hospitalisation. After discharge, the majority of patients received secondary prevention with statins (92.2%), anti-platelet drugs (95.6%), beta-blockers (86.0%) and angiotensin converting enzyme inhibitors (71.4%). After three years of follow-up post-discharge, cumulative mortality was 20.5% [18.4%;22.5%] and the cumulative incidence of reinfarction and stroke/TIA were 4.7% [95% CI: 3.7%;5.7%] and 4.1% [3.1%;5.0%], respectively. CONCLUSIONS: Despite high use of secondary prevention at discharge, mortality and incidence of serious cardiovascular events following MI remain high. This underscores the need to improve secondary prevention.

Association between road vehicle collisions and recent medical contact in older drivers: a case-crossover study.

OBJECTIVE: To estimate the association between past medical contacts and the risk of vehicle collision in a population of older drivers from the province of Quebec, Canada. DESIGN: Case-crossover study. SETTING: Quebec. PARTICIPANTS: 111 699 older drivers involved in at least one vehicle collision between January 1988 and December 2000. MAIN OUTCOME MEASURES: For each driver, the risk of having a vehicle collision while exposed and not exposed to a medical contact was compared. Separate conditional logistic regression analyses were conducted for all drivers and in four diagnostic-specific subgroups. RESULTS: The study found a weak but statistically significant increased risk of all collisions being associated with a medical contact within 1 month before the collision, for all drivers (OR=1.10, 95% CI 1.08 to 1.11) and for drivers with diabetes (OR=1.07, 95% CI 1.03 to 1.11). CONCLUSION: Older drivers who have a collision are more likely to have been in contact with a physician shortly before the collision. These findings suggest that there might be an opportunity to detect medical conditions that put older drivers at higher risk of collision; however, further research is needed to assess the potential effectiveness and practical modalities of screening.