Long diagnostic delay in Crohn's disease is associated with complicated disease course and increased operation rate

Background and Aims: The impact of d iagnostic delay ( a period from appearance of f irst s ymptoms t o diagnosis) o n the clinical c ourse o f Crohn's disease (CD) i s unknown. W e examined whether length of d iagnostic delay a ffects d isease outcome. Methods: Data from the Swiss IBD cohort study were analyzed. T he frequencies of o ccurrence of b owel s tenoses, internal fistulas, perianal f istulas, and CD-related surgery at distinct i ntervals a fter C D diagnosis (0 - < 2 , 2 - < 6,  6 years) were c ompared f or g roups o f patients w ith different length of d iagnostic delay. Results: T he data from a g roup o f 200 CD patients with long diagnostic delay (> 24 months, 76th - 100th p ercentile) were c ompared to t hose from a group of 4 61 patients with a short diagnostic delay ( within 9 months, 1st - 50th p ercentile). T reatment r egimens d id n ot d iffer between t he two groups. Two years following diagnosis, p atients with long diagnostic delay presented more frequently with bowel stenoses (25% vs. 13.1%, p = 0.044), internal fistulas (10% vs. 2%, p = 0.018), perianal f istulas ( 20% vs. 8 .1%, p = 0.023) a nd more frequently underwent intestinal surgery (15% vs. 5 .1%, p = 0.024) t han patients with short diagnostic delay. Intestinal surgery was a lso m ore frequently p erformed  6 y ears after diagnosis in t he group with long d iagnostic delay ( 56.2% vs. 42.3%, p = 0.005) w hen compared to t he g roup with short diagnostic delay. Conclusions: L ong diagnostic delay i s associated with worse o utcome c haracterized by t he development o f increased bowel damage, n ecessitating more frequently operations in t he years following CD d iagnosis. Efforts should be undertaken to shorten the diagnostic delay.

Changes in Aortic Pulse Wave Velocity in Hypertension Post-Menopausal Women: Comparison Between Calcium Channel Blocker (CCB) Vs Angiotensin Receptor Blocker (ARB) Regimen

Objective: To compare effects of a non-renin-angiotensin system (RAS) blocker, using a CCB, or a RAS blocker, using an ARB regimen on the arterial stiffness reduction in postmenopausal hypertensive women. Methods: In this prospective study, a total of 125 hypertensive women (age: 61.4_6 yrs; 98% Caucasian; BW: 71.9_14 kg; BMI: 27.3_5 kg/m2; SBP/ DBP: 158_11/92_9 mmHg) were randomized between ARB (valsartan 320mg_HCTZ) and CCB (amlodipine 10mg _ HCTZ). The primary outcome was carotid-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Results: There were no significant differences in baseline demographic data between the two groups. Both treatments effectively lowered BP at the end of the study with similar (p>0.05) reductions in the valsartan (_22.9/_10.9 mmHg) and amlodipine based (_25.2/_11.7 mmHg) treatment groups. Despite a lower (p<0.05 for DBP) central SBP/DBP in the CCB group (_19.2/_10.3 mmHg) compared to the valsartan group (_15.7/_7.6 mmHg) at week 38, a similar reduction in carotid-femoral PWV (_1.7 vs _1.9 m/sec; p>0.05) was observed between both groups. The numerically larger BP reduction observed in the CCB group was associated with a much higher incidence of peripheral edema (77% vs 14%) than the valsartan group. Conclusion: In summary, BP lowering in postmenopausal women led to a reduction in arterial stiffness assessed by PWV measurement. Both regimens reduced PWV at 38 weeks of treatment to a similar degree, despite differences in BP lowering suggesting that the effect of RAS blockade to influence PWV may partly be independent of BP.

Is it appropriate to index glomerular filtration rate for body surface area

Purpose: Obesity is an established independent risk factor for chronic kidney disease. Thus, measurement of glomerular filtration rate (GFR) is important in this population. Traditionally, GFR has been indexed for body surface area (BSA), but this indexation may not be appropriate in obese individuals. Therefore, the objective of the study was to compare absolute GFR with GFR indexed for BSA and with GFR indexed for height. Methods and materials: The study was conducted in 66 families from the Seychelles islands that included several members with hypertension. GFR and effective renal plasma flow (ERPF) were measured using inulin and PAH clearances, respectively. Antihypertensive treatment, if used, was withheld 2 weeks before conducting the clearances. Participants with diabetes mellitus were excluded from the analysis. BSA was calculated using the Dubois formula. We assessed trend across BMI categories using a non parametric test. Results: Participants included 174 women and 127 men. The prevalence of hypertension was 61%, of which 68% were treated. The table shows that absolute GFR, GFR indexed for height, ERPF, filtration fraction were significantly higher across BMI categories. When GFR was indexed for BSA, the association between GFR and BMI categories was lost. Conclusion: Indexing GFR for BSA in overweight and obese individuals leads to a substantial underestimation of GFR. Filtration fraction, which does not depend on BSA, is higher in obese individuals, which suggests glomerular hyperfiltration. Indexing GFR for BSA therefore would mask the underlying glomerular hyperfiltration. As the number of nephrons does not increase with weight gain, absolute GFR represents a better marker of single nephron GFR and is more appropriate.

Estimation of a maximum Lu diffusion rate in a natural eclogite garnet

Lutetium zoning in garnet within eclogites from the Zermatt-Saas Fee zone, Western Alps, reveal sharp, exponentially decreasing central peaks. They can be used to constrain maximum Lu volume diffusion in garnets. A prograde garnet growth temperature interval of 450-600 A degrees C has been estimated based on pseudosection calculations and garnet-clinopyroxene thermometry. The maximum pre-exponential diffusion coefficient which fits the measured central peak is in the order of D-0= 5.7*10(-6) m(2)/s, taking an estimated activation energy of 270 kJ/mol based on diffusion experiments for other rare earth elements in garnet. This corresponds to a maximum diffusion rate of D (600 A degrees C) = 4.0*10(-22) m(2)/s. The diffusion estimate of Lu can be used to estimate the minimum closure temperature, T-c, for Sm-Nd and Lu-Hf age data that have been obtained in eclogites of the Western Alps, postulating, based on a literature review, that D (Hf) < D (Nd) < D (Sm) a parts per thousand currency sign D (Lu). T-c calculations, using the Dodson equation, yielded minimum closure temperatures of about 630 A degrees C, assuming a rapid initial exhumation rate of 50A degrees/m.y., and an average crystal size of garnets (r = 1 mm). This suggests that Sm/Nd and Lu/Hf isochron age differences in eclogites from the Western Alps, where peak temperatures did rarely exceed 600 A degrees C must be interpreted in terms of prograde metamorphism.

The effect of obesity, age, puberty and gender on resting metabolic rate in children and adolescents.

During puberty fat-free mass (FFM) and fat mass (FM) change quickly and these changes are influenced by sex and obesity. Since it is not completely known how these changes affect resting metabolic rate (RMR), the aim of the present study was to investigate the effect of body composition, age, sex and pubertal development of postabsorptive RMR in 9.5- to 16.5- year-old obese and non-obese children. Postabsorptive RMR was measured in a sample of 371 pre- and postpubertal children comprising 193 males (116 non-obese and 77 obese) and 178 females (119 non-obese and 59 obese). RMR was assessed by indirect calorimetry using a ventilated hood system for 45 min after an overnight fast. Body composition (FFM and FM) was estimated from skinfold measurements. The mean (+/- SD) RMR was significantly (P < 0.001) lower in non-obese (males: 5600 +/- 972 kJ/24 h; females: 5112 +/- 632 kJ/24 h) than in obese (males: 7223 +/- 1220 kJ/24 h; females: 6665 +/- 1106 kJ/24 h) children. This difference became non-significant when RMR was adjusted for body composition (FFM+FM). However, the difference between the genders still remained significant (control male: 6118 +/- 507, control female: 5652 +/- 507, P < 0.001; obese male: 6256 +/- 507, obese female: 5818 +/- 507 kJ/24 h, P < 0.001). The main determinant of RMR was FFM. In the whole cohort. FFM explained 79.8% of the variation in RMR, followed by age, gender and FM adding further 3.8%, 1.1% and 0.8% to the predictability of RMR, respectively. No significant contribution for study group (obese, non-obese), pubertal stage, or fat distribution was found in the regression for RMR. The adjusted value of RMR (for FFM and FM) slightly, but significantly (P < 0.01) decreased between the age of 10-16 years, demonstrating the important effect of age on RMR. CONCLUSIONS: The resting metabolic rate of obese and control children is not different when adjusted for body composition. The main determinant of RMR is the fat-free mass, however, age, gender and fat mass are also significant factors. Pubertal development and fat distribution do not influence RMR independently from the changes in body composition.

Heritability of blood pressure in the swiss population: the family-based skipogh study

Objective: Blood pressure is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. Moreover, little is known on the heritability of the white-coat effect. We investigated the heritability of various blood pressure (BP) traits in a Swiss population-based sample. Methods: SKIPOGH (Swiss Kidney Project on Genes in Hypertension) is a family-based multi-centre (Lausanne, Bern, Geneva) cross-sectional study that examines the role of genes in determining BP levels. Office and 24-hour ambulatory BP were measured using validated devices (A&D UM-101 and Diasys Integra). We estimated the heritability of systolic BP (SBP), diastolic BP (DBP), heart rate (HR), pulse pressure (PP), proportional white-coat effect (i.e. [office BP-mean ambulatory daytime BP]/mean ambulatory daytime BP), and nocturnal BP dipping (difference between mean ambulatory daytime and night-time BP) using a maximum likelihood method implemented in the SAGE software. Analyses were adjusted for age, sex, body mass index (BMI), and study centre. Analyses involving PP were additionally adjusted for DBP. Results: The 517 men and 579 women included in this analysis had a mean (}SD) age of 46.8 (17.8) and 47.8 (17.1) years and a mean BMI of 26.0 (4.2) and 24.2 (4.6) kg/m2, respectively. Heritability estimates (}SE) for office SBP, DBP, HR, and PP were 0.20}0.07, 0.20}0.07, 0.39}0.08, and 0.16}0.07 (all P<0.01). Heritability estimates for 24-hour ambulatory SBP, DBP, HR, and PP were, respectively, 0.39}0.07, 0.30}.08, 0.19}0.09, and 0.25}0.08 (all P<0.05). The heritability of the white-coat effect was 0.29}0.07 for SBP and 0.31}0.07 for DBP (both P<0.001). The heritability of nocturnal BP dipping was 0.15}0.08 for SBP and 0.22}0.07 for DBP (both P<0.05). Conclusions: We found that the white-coat effect is significantly heritable. Our findings show that BP traits are moderately heritable in a multi-centric study in Switzerland, in line with previous population-based studies, justifying the ongoing search for genetic determinants in this field.

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Pulse oximetry for hypoxemia: a warning to users and manufacturers.

Pulse oximetry represents a major advance in patient monitoring, but measurement below 70 to 80% saturation has important limitations. Several authors have tested pulse oximetry at low saturations with conflicting results. A review of these data indicates that every patient with a pulse oximeter value below 75 to 80% SaO2 should have one or more invasive measurements of the arterial SaO2 in order to avoid undetected severe hypoxemia.

Combined effect of 25-OH vitamin D plasma levels and genetic vitamin D receptor (NR 1I1) variants on fibrosis progression rate in HCV patients.

BACKGROUND: Decreased vitamin D levels have been described in various forms of chronic liver disease and associated with advanced fibrosis. Whether this association is a cause or consequence of advanced fibrosis remains unclear to date. AIMS: To analyse combined effects of 25-OH vitamin D plasma levels and vitamin D receptor gene (VDR; NR1I1) polymorphisms on fibrosis progression rate in HCV patients. METHODS: 251 HCV patients underwent VDR genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 A and TaqI rs731236 A). Plasma 25-OH vitamin D levels were quantified in a subgroup of 97 patients without advanced fibrosis. The VDR haplotype and genotypes as well as plasma 25-OH vitamin D levels were associated with fibrosis progression. RESULTS: The bAt[CCA]-haplotype was significantly associated with fibrosis progression >0.101 U/year (P = 0.007; OR = 2.02) and with cirrhosis (P = 0.022; OR = 1.84). Forty-five percent of bAt[CCA]-haplotype patients were rapid fibrosers, 21.1% were cirrhotic. Likewise, ApaI rs7975232 CC genotype was significantly associated with fibrosis progression and cirrhosis. Lower plasma 25-OH vitamin D levels were significantly associated with fibrosis progression >0.101 U/year in F0-2 patients (P = 0.013). Combined analysis of both variables revealed a highly significant additive effect on fibrosis progression with 45.5% rapid fibrosers for bAt[CCA]-haplotype and 25-OH vitamin D < 20 μg/L compared with only 9.1% for the most favourable combination (P = 0.006). In multivariate analysis, the bAt-haplotype was an independent risk factor for fibrosis progression (P = 0.001; OR = 2.83). CONCLUSION: Low 25-OH vitamin D plasma levels and the unfavourable VDR bAt[CCA]-haplotype are associated with rapid fibrosis progression in chronic HCV patients. In combination, both variables exert significant additive effects on fibrosis progression.

Rate of undesirable events at beginning of academic year: retrospective cohort study.

OBJECTIVE: To determine whether an increase in the rate of undesirable events occurs after care provided by trainees at the beginning of the academic year. DESIGN: Retrospective cohort study using administrative and patient record data. SETTING: University affiliated hospital in Melbourne, Australia. PARTICIPANTS: 19,560 patients having an anaesthetic procedure carried out by first to fifth year trainees starting work for the first time at the hospital over a period of five years (1995-2000). MAIN OUTCOME MEASURES: Absolute event rates, absolute rate reduction, and rate ratios of undesirable events. RESULTS: The rate of undesirable events was higher at the beginning of the academic year compared with the rest of the year (absolute event rate 137 v 107 per 1000 patient hours, relative rate reduction 28%, P<0.001). The overall adjusted rate ratio for undesirable events was 1.40, 95% confidence interval 1.24 to 1.58. This excess risk was seen for all residents, regardless of their level of seniority. The excess risk decreased progressively after the first month, and the trend disappeared fully after the fourth month of the year (rate ratio for fourth month 1.21, 0.93 to 1.57). The most important decreases were for central and peripheral nerve injuries (relative difference 82%), inadequate oxygenation of the patient (66%), vomiting/aspiration in theatre (53%), and technical failures of tracheal tube placement (49%). CONCLUSIONS: The rate of undesirable events was greater among trainees at the beginning of the academic year regardless of their level of clinical experience. This suggests that several additional factors, such as knowledge of the working environment, teamwork, and communication, may contribute to the increase.

Pulse oximetry and transcutaneous oxygen tension for detection of hypoxemia in critically ill infants and children.

We tested the performance of transcutaneous oxygen monitoring (TcPO2) and pulse oximetry (tcSaO2) in detecting hypoxia in critically ill neonatal and pediatric patients. In 54 patients (178 data sets) with a mean age of 2.4 years (range 1 to 19 years), arterial saturation (SaO2) ranged from 9.5 to 100%, and arterial oxygen tension (PaO2) from 16.4 to 128 mmHg. Linear correlation analysis of pulse oximetry vs measured SaO2 revealed an r value of 0.95 (p less than 0.001) with an equation of y = 21.1 + 0.749x, while PaO2 vs tcPO2 showed a correlation coefficient of r = 0.95 (p less than 0.001) with an equation of y = -1.04 + 0.876x. The mean difference between measured SaO2 and tcSaO2 was -2.74 +/- 7.69% (range +14 to - 29%) and the mean difference between PaO2 and tcPO2 was +7.43 +/- 8.57 mmHg (range -14 to +49 mmHg). Pulse oximetry was reliable at values above 65%, but was inaccurate and overestimated the arterial SaO2 at lower values. TcPO2 tended to underestimate the arterial value with increasing PaO2. Pulse oximetry had the best sensitivity to specificity ratio for hypoxia between 65 and 90% SaO2; for tcPO2 the best results were obtained between 35 and 55 mmHg PaO2.

Human papilloma virus type and recurrence rate after surgical clearance of anal condylomata acuminata

Résumé : Le condylome acuminé anal (CAA), transmis par contact sexuel, résulte d'une infection par Human Papilloma Virus (HPV). Son traitement chirurgical est grevé d'un taux de récidive de 4-29%. Le but de cette étude était d'identifier une éventuelle corrélation entre type d'HPV présent dans les CAA excisés chirurgicalement et taux de récidive de la maladie, Cette étude rétrospective porte sur 140 patients opérés au Centre Hospitalier Universitaire Vaudois de CAA, entre 1990 et 2005. Le diagnostic lésionnel a été confirmé par un examen histomorphologique. Le(s) type(s) d'HPV présent(s) dans ces lésions a été déterminé par Polymerase Chain Reaction (PCR). Les patients ont donné leur accord à cette analyse et complété un questionnaire. Une éventuelle corrélation entre récidive de CAA, type d'HPV et status HIV a été recherchée. HPV 6 et 11 sont les virus les plus fréquemment découverts (51% et 28%, respectivement) chez les 140 patients (123H/17F). Trente-cinq (25%) d'entre eux ont présenté une récidive. HPV 11 était present chez 19 (41%) sujets. Ceci est statistiquement significatif (P<0.05), en comparaison aux autres HPVs. Il n'y a par contre pas de différence significative entre la fréquence de récidive des 33 (24%) patients HIV-positifs et le reste du collectif. HPV 11 est donc associé à un taux de récidive de CAA significativement élevé. Un suivi strict des patients atteints est nécessaire pour identifier une récidive et la traiter sans délai, notamment lorsque HPV 11 est present. Ces résultats innovateurs soulèvent la question de la nécessité de pratiquer une typisation virale systématique sur les lésions excisées. La justification d'une telle attitude demande toutefois encore d'être confirmée.