Influence of deep sternal wound infection on long-term survival after cardiac surgery.

BACKGROUND: This study aimed to investigate the influence of deep sternal wound infection on long-term survival following cardiac surgery. MATERIAL AND METHODS: In our institutional database we retrospectively evaluated medical records of 4732 adult patients who received open-heart surgery from January 1995 through December 2005. The predictive factors for DSWI were determined using logistic regression analysis. Then, each patient with deep sternal wound infection (DSWI) was matched with 2 controls without DSWI, according to the risk factors identified previously. After checking balance resulting from matching, short-term mortality was compared between groups using a paired test, and long-term survival was compared using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS: Overall, 4732 records were analyzed. The mean age of the investigated population was 69.3±12.8 years. DSWI occurred in 74 (1.56%) patients. Significant independent predictive factors for deep sternal infections were active smoking (OR 2.19, CI95 1.35-3.53, p=0.001), obesity (OR 1.96, CI95 1.20-3.21, p=0.007), and insulin-dependent diabetes mellitus (OR 2.09, CI95 1.05-10.06, p=0.016). Mean follow-up in the matched set was 125 months, IQR 99-162. After matching, in-hospital mortality was higher in the DSWI group (8.1% vs. 2.7% p=0.03), but DSWI was not an independent predictor of long-term survival (adjusted HR 1.5, CI95 0.7-3.2, p=0.33). CONCLUSIONS: The results presented in this report clearly show that post-sternotomy deep wound infection does not influence long-term survival in an adult general cardio-surgical patient population.

Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98 y.

OBJECTIVE: To determine reference values for fat-free mass index (FFMI) and fat mass index (FMI) in a large Caucasian group of apparently healthy subjects, as a function of age and gender and to develop percentile distribution for these two parameters. DESIGN: Cross-sectional study in which bioelectrical impedance analysis (50 kHz) was measured (using tetrapolar electrodes and cross-validated formulae by dual-energy X-ray absorptiometry in order to calculate FFMI (fat-free mass/height squared) and FMI (fat mass/height squared). SUBJECTS: A total of 5635 apparently healthy adults from a mixed non-randomly selected Caucasian population in Switzerland (2986 men and 2649 women), varying in age from 24 to 98 y. RESULTS: The median FFMI (18-34 y) were 18.9 kg/m(2) in young males and 15.4 kg/m(2) in young females. No difference with age in males and a modest increase in females were observed. The median FMI was 4.0 kg/m(2) in males and 5.5 kg/m(2) in females. From young to elderly age categories, FMI progressively rose by an average of 55% in males and 62% in females, compared to an increase in body mass index (BMI) of 9 and 19% respectively. CONCLUSIONS: Reference intervals for FFMI and FMI could be of practical value for the clinical evaluation of a deficit in fat-free mass with or without excess fat mass (sarcopenic obesity) for a given age category, complementing the classical concept of body mass index (BMI) in a more qualitative manner. In contrast to BMI, similar reference ranges seems to be utilizable for FFMI with advancing age, in particular in men.

Quantitative ultrasound of bone in institutionalized elderly women: a cross-sectional and longitudinal study.

Quantitative ultrasound of bone is a promising method for bone assessment: radiation-free, portable and predictive of hip fracture. Its portability allowed us to study the relationships between ultrasonic parameters of bone with age and with non-vertebral fractures in elderly women living in 19 nursing homes. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus were measured (and the stiffness index calculated) in a sample of 270 institutionalized women, aged 85 +/- 7 years, using an Achilles bone densitometer (Lunar). The effects of age, history of non-vertebral and non-traumatic fractures, body mass index, triceps skinfold and arm circumference were assessed on BUA, SOS and stiffness index. Furthermore, to evaluate longitudinally the influence of aging on the ultrasound parameters of bone, 60 subjects from the same group had a second ultrasound measurement after 1 year. The cross-sectional analysis of the data on all 270 women showed a significant decrease (p < 0.001) with age in BUA, SOS and stiffness index (-0.47%, -0.06%, and -1.01% respectively per year). In the 94 women, (35%) with a history of previous non-vertebral fractures, ultrasound parameters were significantly lower (p < 0.0001) than in the 176 women with no history of fracture (-8.3% for BUA, -1.3% for SOS, -18.9% for stiffness index). In contrast, there was no significant difference in anthropometric measurements between the groups with and without previous non-vertebral fractures, although the measurements decreased significantly with age. In the longitudinal study, repeated quantitative ultrasound after 11.4 +/- 0.8 months showed no significant decrease in BUA (-1%) but a significant decrease in SOS (-0.3%, p < 0.0001) and in stiffness index (-3.6%, p < 0.0002). In conclusion, quantitative ultrasound of the calcaneus measures properties of bone which continue to decline in institutionalized elderly women, and is able to discriminate women with previous non-vertebral fractures.

Predicting positive food challenges at the introduction of nuts in sensitised children

Rationale: Children with atopic diseases in early life are frequently found with positive IgE tests to nuts, without a history of previous ingestion. We aimed to identify risk factors for reactions to nuts at their first introduction. Methods: A detailed retrospective case note and database analysis was performed. Inclusion criteria were: patients aged 3 to 16 years who had had a standardized food challenge to peanut and/or tree nuts due to primary sensitisation to the nut (positive specific IgE or SPT). A detailed assessment was performed of factors relating to food challenge outcome with univariate and multivariate logistic regression analysis. Results: There were 98 food challenges (48% peanut, 52% tree nut) with 29 positive, 67 negative and 2 inconclusive challenges. A positive maternal history and a specific IgE > 2 kU/l were strongly associated with a significantly increased risk of a positive food challenge (OR 3.54; 95% CI 1.28 to 9.81; and OR 4.82; 95% CI 1.57 to 14.86; respectively). There was no significant association between the type of nut, age, presence of other food allergies, paternal or sibling atopic history, other atopic conditions or severity of previous reaction to other foods. Conclusions: We have demonstrated an association between the presence of a maternal atopic history and a specific IgE > 2 kU/l, and a significant increase in the likelihood of a positive food challenge in children with primary sensitisation to nuts. Although requiring further prospective validation we suggest these easily identifiable components should be considered when deciding the need for a nut challenge.

Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates.

AIM: This study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population. METHODS: All gentamicin concentration data, along with clinical and demographic characteristics, were retrieved from medical charts in a Neonatal Intensive Care Unit over 5 years within the frame of a routine therapeutic drug monitoring programme. Data were described using non-linear mixed-effects regression analysis ( nonmem®). RESULTS: A total of 3039 gentamicin concentrations collected in 994 preterm and 455 term newborns were included in the analysis. A two compartment model best characterized gentamicin disposition. The average parameter estimates, for a median body weight of 2170 g, were clearance (CL) 0.089 l h(-1) (CV 28%), central volume of distribution (Vc ) 0.908 l (CV 18%), intercompartmental clearance (Q) 0.157 l h(-1) and peripheral volume of distribution (Vp ) 0.560 l. Body weight, gestational age and post-natal age positively influenced CL. Dopamine co-administration had a significant negative effect on CL, whereas the influence of indomethacin and furosemide was not significant. Both body weight and gestational age significantly influenced Vc . Model-based simulations confirmed that, compared with term neonates, preterm infants need higher doses, superior to 4 mg kg(-1) , at extended intervals to achieve adequate concentrations. CONCLUSIONS: This observational study conducted in a large cohort of newborns confirms the importance of body weight and gestational age for dosage adjustment. The model will serve to set up dosing recommendations and elaborate a Bayesian tool for dosage individualization based on concentration monitoring.

Physical activity and energy expenditure in haemodialysis patients: an international survey.

BACKGROUND: The assessment of physical activity and energy expenditure is relevant to the care of maintenance haemodialysis (MHD) patients. In the current study, we aimed to evaluate measurements of physical activity and energy expenditure in MHD patients from different centres and countries and explored the predictors of physical activity in these patients.¦METHODS: In this cross-sectional multicentre study, 134 MHD patients from four countries (France, Switzerland, Sweden and Brazil) were included. The physical activity was evaluated for 5.0 ± 1.4 days (mean ± SD) by a multisensory device (SenseWear Armband) and comprised the assessment of number of steps per day, activity-related energy expenditure (activity-related EE) and physical activity level (PAL).¦RESULTS: The number of steps per day, activity-related EE and PAL from the MHD patients were compatible with a sedentary lifestyle. In addition, all parameters were significantly lower in dialysis days when compared to non-dialysis days (P < 0.001). The multivariate regression analysis revealed that diabetes and higher body mass index (BMI) predicted a lower PAL and older age and diabetes predicted a reduced number of steps.¦CONCLUSIONS: The physical activity parameters of MHD patients were compatible with a sedentary lifestyle. This inactivity was worsened by aging, diabetes and higher BMI. Our results indicate that MHD patients should be encouraged by the health care team to increase their physical activity.

Body composition interpretation. Contributions of the fat-free mass index and the body fat mass index.

OBJECTIVE: Low and high body mass index (BMI) values have been shown to increase health risks and mortality and result in variations in fat-free mass (FFM) and body fat mass (BF). Currently, there are no published ranges for a fat-free mass index (FFMI; kg/m(2)), a body fat mass index (BFMI; kg/m(2)), and percentage of body fat (%BF). The purpose of this population study was to determine predicted FFMI and BFMI values in subjects with low, normal, overweight, and obese BMI. METHODS: FFM and BF were determined in 2986 healthy white men and 2649 white women, age 15 to 98 y, by a previously validated 50-kHz bioelectrical impedance analysis equation. FFMI, BFMI, and %BF were calculated. RESULTS: FFMI values were 16.7 to 19.8 kg/m(2) for men and 14.6 to 16.8 kg/m(2) for women within the normal BMI ranges. BFMI values were 1.8 to 5.2 kg/m(2) for men and 3.9 to 8.2 kg/m(2) for women within the normal BMI ranges. BFMI values were 8.3 and 11.8 kg/m(2) in men and women, respectively, for obese BMI (>30 kg/m(2)). Normal ranges for %BF were 13.4 to 21.7 and 24.6 to 33.2 for men and women, respectively. CONCLUSION: BMI alone cannot provide information about the respective contribution of FFM or fat mass to body weight. This study presents FFMI and BFMI values that correspond to low, normal, overweight, and obese BMIs. FFMI and BFMI provide information about body compartments, regardless of height.

Musical training intensity yields opposite effects on grey matter density in cognitive versus sensorimotor networks.

Using optimized voxel-based morphometry, we performed grey matter density analyses on 59 age-, sex- and intelligence-matched young adults with three distinct, progressive levels of musical training intensity or expertise. Structural brain adaptations in musicians have been repeatedly demonstrated in areas involved in auditory perception and motor skills. However, musical activities are not confined to auditory perception and motor performance, but are entangled with higher-order cognitive processes. In consequence, neuronal systems involved in such higher-order processing may also be shaped by experience-driven plasticity. We modelled expertise as a three-level regressor to study possible linear relationships of expertise with grey matter density. The key finding of this study resides in a functional dissimilarity between areas exhibiting increase versus decrease of grey matter as a function of musical expertise. Grey matter density increased with expertise in areas known for their involvement in higher-order cognitive processing: right fusiform gyrus (visual pattern recognition), right mid orbital gyrus (tonal sensitivity), left inferior frontal gyrus (syntactic processing, executive function, working memory), left intraparietal sulcus (visuo-motor coordination) and bilateral posterior cerebellar Crus II (executive function, working memory) and in auditory processing: left Heschl's gyrus. Conversely, grey matter density decreased with expertise in bilateral perirolandic and striatal areas that are related to sensorimotor function, possibly reflecting high automation of motor skills. Moreover, a multiple regression analysis evidenced that grey matter density in the right mid orbital area and the inferior frontal gyrus predicted accuracy in detecting fine-grained incongruities in tonal music.

Undertreatment of acute pain (oligoanalgesia) and medical practice variation in prehospital analgesia of adult trauma patients: a 10 yr retrospective study.

BACKGROUND: Prehospital oligoanalgesia is prevalent among trauma victims, even when the emergency medical services team includes a physician. We investigated if not only patients' characteristics but physicians' practice variations contributed to prehospital oligoanalgesia. METHODS: Patient records of conscious adult trauma victims transported by our air rescue helicopter service over 10 yr were reviewed retrospectively. Oligoanalgesia was defined as a numeric rating scale (NRS) >3 at hospital admission. Multilevel logistic regression analysis was used to predict oligoanalgesia, accounting first for patient case-mix, and then physician-level clustering. The intraclass correlation was expressed as the median odds ratio (MOR). RESULTS: A total of 1202 patients and 77 physicians were included in the study. NRS at the scene was 6.9 (1.9). The prevalence of oligoanalgesia was 43%. Physicians had a median of 5.7 yr (inter-quartile range: 4.2-7.5) of post-graduate training and 27% were female. In our multilevel analysis, significant predictors of oligoanalgesia were: no analgesia [odds ratio (OR) 8.8], National Advisory Committee for Aeronautics V on site (OR 4.4), NRS on site (OR 1.5 per additional NRS unit >4), female physician (OR 2.0), and years of post-graduate experience [>4.0 to ≤5.0 (OR 1.3), >3.0 to ≤4.0 (OR 1.6), >2.0 to ≤3.0 (OR 2.6), and ≤2.0 yr (OR 16.7)]. The MOR was 2.6, and was statistically significant. CONCLUSIONS: Physicians' practice variations contributed to oligoanalgesia, a factor often overlooked in analyses of prehospital pain management. Further exploration of the sources of these variations may provide innovative targets for quality improvement programmes to achieve consistent pain relief for trauma victims.

A fast-track program reduces complications and length of hospital stay after open colonic surgery.

BACKGROUND & AIMS: A fast-track program is a multimodal approach for patients undergoing colonic surgery that combines stringent regimens of perioperative care (fluid restriction, optimized analgesia, forced mobilization, and early oral feeding) to reduce perioperative morbidity, hospital stay, and cost. We investigated the impact of a fast-track protocol on postoperative morbidity in patients after open colonic surgery. METHODS: A randomized trial of patients in 4 teaching hospitals in Switzerland included 156 patients undergoing elective open colonic surgery who were assigned to either a fast-track program or standard care. The primary end point was the 30-day complication rate. Secondary end points were severity of complications, hospital stay, and compliance with the fast-track protocol. RESULTS: The fast-track protocol significantly decreased the number of complications (16 of 76 in the fast-track group vs 37 of 75 in the standard care group; P = .0014), resulting in shorter hospital stays (median, 5 days; range, 2-30 vs 9 days, respectively; range, 6-30; P < .0001). There was a trend toward less severe complications in the fast-track group. A multiple logistic regression analysis revealed fluid administration greater than the restriction limits (odds ratio, 4.198; 95% confidence interval, 1.7-10.366; P = .002) and a nonfunctioning epidural analgesia (odds ratio, 3.365; 95% confidence interval, 1.367-8.283; P = .008) as independent predictors of postoperative complications. CONCLUSIONS: The fast-track program reduces the rate of postoperative complications and length of hospital stay and should be considered as standard care. Fluid restriction and an effective epidural analgesia are the key factors that determine outcome of the fast-track program.

Don't stop, don't stop: physical activity and adolescence.

The aim was to assess whether physical activity decreases during adolescence, whether this decrease depends on the gender, whether physical activity is related to personal, family, and school factors, and whether it is associated to healthy behaviors in a sample of adolescents. Data were drawn from a survey carried out in 2001 among in-school Catalan adolescents aged 14-19 years. Subjects were divided in two groups: physical activity (N=4,185, 43.5% females) and no-physical activity (N=2,743; 68.9% females). Personal, family, school and lifestyles' variables were compared. Chi-square and Odds Ratio were used to compare qualitative variables and Student's t to compare quantitative variables. For the multivariate analysis, all statistically significant variables in the univariate analysis in each of the four groups of variables (plus age) were introduced in a non-conditioned multiple regression. Analysis was performed separately by gender. Physical activity was significantly more frequent among males and decreased with age. Globally, physically active youth perceived themselves as healthier and happier with their body image, they showed a better relationship with their parents, were better connected to school, and exhibited healthier lifestyles. As physical activity has important benefits on health, health professionals dealing with adolescents should encourage adolescents to keep practicing. This message must be specially directed to females.

Risky single-occasion drinking: bingeing is not bingeing.

AIMS: To review the concept of binge drinking as a measure of risky single occasion drinking (RSOD), to illustrate its differential impact on selected health outcomes and to identify research gaps. METHODS: Narrative literature review with focus on conceptual and methodological differences, trajectories of RSOD and effects of RSOD on fetal outcomes, coronary heart disease (CHD) and injuries. RESULTS: Effects ascribed commonly to RSOD may often be the effects of an undifferentiated mixture of risky single occasions and regular heavy volume drinking, constituted by frequent, successive RSOD. This leads to the problem that additional risks due to RSOD are mis-specified and remain unidentified or underestimated in some cases, such as for injuries or CHD, but are probably overstated for some chronic consequences or for effects of maternal drinking on newborns. CONCLUSION: A stronger focus should be placed upon methods that can differentiate the effects of RSOD from those due to frequent occasions of heavy drinking that result in heavy volume drinking.

Swiss Interdisciplinary Management Programme for Heart Failure (SWIM-HF): a randomised controlled trial study of an outpatient inter-professional management programme for heart failure patients in Switzerland.

PRINCIPLES: International guidelines for heart failure (HF) care recommend the implementation of inter-professional disease management programmes. To date, no such programme has been tested in Switzerland. The aim of this randomised controlled trial (RCT) was to test the effect on hospitalisation, mortality and quality of life of an adult ambulatory disease management programme for patients with HF in Switzerland.METHODS: Consecutive patients admitted to internal medicine in a Swiss university hospital were screened for decompensated HF. A total of 42 eligible patients were randomised to an intervention (n = 22) or usual care group (n = 20). Medical treatment was optimised and lifestyle recommendations were given to all patients. Intervention patients additionally received a home visit by a HF-nurse, followed by 17 telephone calls of decreasing frequency over 12 months, focusing on self-care. Calls from the HF nurse to primary care physicians communicated health concerns and identified goals of care. Data were collected at baseline, 3, 6, 9 and 12 months. Mixed regression analysis (quality of life) was used. Outcome assessment was conducted by researchers blinded to group assignment.RESULTS: After 12 months, 22 (52%) patients had an all-cause re-admission or died. Only 3 patients were hospitalised with HF decompensation. No significant effect of the intervention was found on HF related to quality of life.CONCLUSIONS: An inter-professional disease management programme is possible in the Swiss healthcare setting but effects on outcomes need to be confirmed in larger studies.

Free-living energy expenditure assessed by two different methods in rural Gambian men.

OBJECTIVE: To assess total free-living energy expenditure (EE) in Gambian farmers with two independent methods, and to determine the most realistic free-living EE and physical activity in order to establish energy requirements for rural populations in developing countries. DESIGN: In this cross-sectional study two methods were applied at the same time. SETTING: Three rural villages and Dunn Nutrition Centre Keneba, MRC, The Gambia. SUBJECTS: Eight healthy, male subjects were recruited from three rural Gambian villages in the sub-Sahelian area (age: 25 +/- 4y; weight: 61.2 +/- 10.1 kg; height: 169.5 +/- 6.5 cm, body mass index: 21.2 +/- 2.5 kg/m2). INTERVENTION: We assessed free-living EE with two inconspicuous and independent methods: the first one used doubly labeled water (DLW) (2H2 18O) over a period of 12 days, whereas the second one was based on continuous heart rate (HR) measurements on two to three days using individual regression lines (HR vs EE) established by indirect calorimetry in a respiration chamber. Isotopic dilution of deuterium (2H2O) was also used to assess total body water and hence fat-free mass (FFM). RESULTS: EE assessed by DLW was found to be 3880 +/- 994 kcal/day (16.2 +/- 4.2 MJ/day). Expressed per unit body weight the EE averaged 64.2 +/- 9.3 kcal/kg/d (269 +/- 38 kJ/kg/d). These results were consistent with the EE results assessed by HR: 3847 +/- 605 kcal/d (16.1 +/- 2.5 MJ/d) or 63.4 +/- 8.2 kcal/kg/d (265 +/- 34kJ/kg/d). Physical activity index, expressed as a multiple of basal metabolic rate (BMR), averaged 2.40 +/- 0.41 (DLW) or 2.40 +/- 0.28 (HR). CONCLUSIONS: These findings suggest an extremely high level of physical activity in Gambian men during intense agricultural work (wet season). This contrasts with the relative food shortage, previously reported during the harvesting period. We conclude that the assessment of EE during the agricultural season in non-industrialized countries needs further investigations in order to obtain information on the energy requirement of these populations. For this purpose the use of the DLW and HR methods have been shown to be useful and complementary.

Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability

Imatinib has revolutionised the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST). Using a nonlinear mixed effects population model, individual estimates of pharmacokinetic parameters were derived and used to estimate imatinib exposure (area under the curve, AUC) in 58 patients. Plasma-free concentration was deduced from a model incorporating plasma levels of alpha(1)-acid glycoprotein. Associations between AUC (or clearance) and response or incidence of side effects were explored by logistic regression analysis. Influence of KIT genotype was also assessed in GIST patients. Both total (in GIST) and free drug exposure (in CML and GIST) correlated with the occurrence and number of side effects (e.g. odds ratio 2.7+/-0.6 for a two-fold free AUC increase in GIST; P<0.001). Higher free AUC also predicted a higher probability of therapeutic response in GIST (odds ratio 2.6+/-1.1; P=0.026) when taking into account tumour KIT genotype (strongest association in patients harbouring exon 9 mutation or wild-type KIT, known to decrease tumour sensitivity towards imatinib). In CML, no straightforward concentration-response relationships were obtained. Our findings represent additional arguments to further evaluate the usefulness of individualizing imatinib prescription based on a therapeutic drug monitoring programme, possibly associated with target genotype profiling of patients.